ADVANCING FRONTIERS IN REACTIVE AND SELECTIVE IRIDIUM C H BORYLATION CATALYSIS AND TARGETED SILSESQUIOXANE SYNTHESIS By Jonathan E. Dannatt A DISSERTATION Submitted to Michigan State University in partial fulfillment of the requirements for the degree of Chemistry Doctor of Philosophy 2019 ABSTRACT ADVANCING FRONTIERS IN REACTIVE AND SELECTIVE IRIDIUM C H BORYLATION CATALYSIS AND TARGETED SILSESQUIOXANE SYNTHESIS By Jonathan E. Dannatt The studies in this dissertation are aimed at uncovering reactive and selective Ir - catalyzed C H borylation (CHB) catalysts. Due to the high versatility of organoboron species, green methodology to produce the C B bond is poised to support a myriad of subs equent transformations. These transformations include Suzuki couplings, aminations, oxidations, halogenations, cyanations, and trifluoromethylations. Typical iridium catalyzed CHBs proceed through an iridium trisboryl with a bidentate ligand such as bipyr idine or 1,10 - phenanthroline. The selectivity of these standard catalysts is generally driven by sterics; however, many methods of overcoming the steric bias have been developed in the two decades since the first thermal catalytic C H activation borylation . These methods include both inner - and outer - sphere directed mechanisms. Outer - sphere directed borylations have been accomplished by leveraging hydrogen bonding, Lewis acid - base, and ion - pairing as directing elements. In general this reactivity is activat ed by precise design of the bidentate ligand framework. Herein is reported a subtle electrostatic interaction to direct ortho - borylation of phenols by simply switching boron source from the common B 2 pin 2 (pin = pinacolate) to B 2 eg 2 (eg = ethyleneglycolate ). This electrostatic interaction was revealed by a careful computational analysis of key C H activation transition states. Understanding gained by the computational studies led to the redesign of the boron source which enabled by selectivities of >99% ort ho borylation. This methodology was extended to the highly selective ortho - borylation of anilines, and the underlying mechanism has been interrogated. Currently, iridium based catalysts have been generated to borylate ortho, meta, and even para to a variet y of classes of substrates; however, control of selectivity can breakdown in many fluorinated arenes without a directing group. These substrates are challenging because the fluoro moiety being similar in size to a hydrogen offers little in the way of steri c bias. While working to overcome these challenges, a serendipitously discovered hydrazone based ligand was discovered. Exploration of the catalysts generated by this ligand revealed not only impressive activity rivaling dtbpy but also incredible selectivi ty for meta to a fluoro group. In general iridium CHB catalysts selectively activate sp 2 C - H bonds leaving all sp 3 C - H bonds intact; however , a method to turn on sp 3 C - H activation would be desirable. It was reasoned that a directing group able to increas e the effective concentration of the iridium catalyst near a C(sp3) - H bond may enable this transformation. Indeed , it was discovered that catalysts able to accept amide directing groups were able to selectively borylate compounds with amide N - methyl substituents. Copyright by J ONATHAN E. DANNATT 2019 v To Hailey and Josiah this experience vi A CKNOWLEDGMENTS As I write this final section, my time left in Michigan is numbered in days and hours rather than years and months. conclusion. My experience in graduate school and Michigan can only be described as transformative. Philosophie s and opinions I thought were immovable in my mind have been significantly refined and in some cases even reversed. How I think, approach problems, read and process information, write, conduct myself professionally, view the world as a scientist, interact with colleagues, manage time, deal with stress, mentor, and teach have all been enhanced over the last five years . However, t his type of transformation did not occur because I worked at a lab bench or in a hood. It occurred because of the people surrounding said bench and hood. To them I will be forever grateful. graduate school as well as the individuals that made my time in Michigan such a positive experience . To start I need to thank my family. To my parents, Shaunda and Elvin : Your constant belief in me made all the difference. To my siblings, Brienna , Gabriel , and Devon (even if you are from another mother): closer friends than you guys . To my grandparents, Gene, Brenda, Kathy, and Steve: Y ou will never know how much I have learned from your wisdom thank you. To the rest of my family, Heather, Harlan, Ernie, George, Dorjea n ne, Rob, Baelynn, Byron, Jen, Eric, Heather, Chase, Blaze, an d Brittany: the importance of your support and love over the years can never be stated. vii I want to also thank my colleagues and friends. To my labmates, Hoa Li, Damith Perera , Aaron Baker , Suzi Miller , Ruwi Jayasundara , Fangyi Shen , Badru - Deen Barr y, Pepe Montero , Emmanuel Maloba , Thomas Oleskey , and Arzoo Chhabra , Tim Shannon , Kristen Gore , Behnaz Ghaffari , Dmitry Shabashov , Ryan Fornwald , Alex l, Seokjoo Lee , Anshu Yadav , Chris Peruzzi , Pauline Mansour , Cash Jowers , David Vogelsang , and Aditya Patil : Working with you guys has been an honor and I dearly hope to keep in close contact over the years. To my close friends within the department, Aritra Sarkar , Gracielou Klinger , Aliakbar Mohammadlou , Saeedeh Torabikohlbouni , Po - Jen Hsiao , and B ryan Paulus : in and outside the realm of science I could never ask for a better group of friends . To a handful of the many academic advisors and mentors that have supported me over the years . To Rob Maleczka: Your guidan ce and continued support has . To Mitch Smith: I have always admired and hope to emulate your dedication to quality science and your passion for your students. To Babak B orhan: I recognize you play so many roles, but I have never met a PI that better encompasses the term mentor. To Bill Wulff : Your dedication to the field and thoroughness in reading and mechanisms has changed how I read think about problems . To key undergr aduate professors: Anthony Grafton, Barry Gehm, David Pace, Jeremy Chapman, Megan Powell, and Tharanga Wijetunge: I would have never entered graduate school without your guidance and support . viii TABLE OF CONTENTS LIST OF TABLES ................................ ................................ ................................ ........... xi LIST OF FIGURES ................................ ................................ ................................ ......... xii LIST OF SCHEMES ................................ ................................ ................................ ...... xiii Chapter 1: An Introduction ................................ ................................ ........................... 1 1.1: Background ................................ ................................ ................................ ..................... 1 1.2: Identity of FG x ................................ ................................ ................................ .................. 2 1.3: C - H activation borylation the initial discovery ................................ ................................ ... 4 1.4 Mechanism of iridium catalyzed C - H activation borylation ................................ ................ 4 1.5: Regioselectivity of iridium C - H Borylation ................................ ................................ ........ 6 1.6: Directing the iridium catalyst ................................ ................................ ............................ 7 1.7: Conclusions ................................ ................................ ................................ .................... 10 REFERENCES ................................ ................................ ................................ ...................... 11 Chapter 2: Directed C(sp 3 ) H activation borylation ................................ ................. 16 2.1: Introduction ................................ ................................ ................................ ..................... 16 2.2: Optimization of amide directed C(sp 3 ) H borylation ................................ ........................ 20 2.3: Substrate scope of amide directed C(sp 3 ) H borylation ................................ .................. 22 2.4: Kinetic Isotope Effect in amide dir ected C(sp 3 ) H borylation ................................ .......... 24 2.5: Proposed catalytic cycle ................................ ................................ ................................ . 25 2.6: Conclusions ................................ ................................ ................................ .................... 26 2.7: Experimental details ................................ ................................ ................................ ....... 27 2.8: Not es: ................................ ................................ ................................ ............................. 65 APPENDIX ................................ ................................ ................................ ............................ 66 REFERENCES ................................ ................................ ................................ .................... 107 Chapter 3: Ortho Selective Borylation of Phenols ................................ ................. 113 3.1: Introduction ................................ ................................ ................................ ................... 113 3.2: An Unusual Selectivity in Phenol Borylations ................................ ................................ 115 3.3: Substrate Scope of Phenol Borylation with B 2 pin 2 ................................ ......................... 116 3.4: Theoretical Investigation of the Directing Effect i n Phenol Borylations .......................... 118 3.5 Experimental Support for Electrostatic Directing Effect ................................ .................. 120 ix 3.6: Strategy to Increase Ortho Selectivity ................................ ................................ ........... 121 3.7: Experimentally Testing Computational Results with B 2 eg 2 ................................ ............ 124 3.8: Understanding the Optimal Borylation Conditions with B 2 eg 2 ................................ ........ 125 3.9: Conclusions ................................ ................................ ................................ .................. 129 3.10: Experimental Details ................................ ................................ ................................ ... 130 3.11: Notes ................................ ................................ ................................ .......................... 184 APPENDIX ................................ ................................ ................................ .......................... 185 REFERENCES ................................ ................................ ................................ .................... 297 Chapter 4: Ortho Selective Borylation of Anilines ................................ ................. 303 4.1: Introduction ................................ ................................ ................................ ................... 303 4.2: Aniline B orylation with B 2 eg 2 ................................ ................................ ......................... 307 4.3: Substrate scope of Aniline Borylation with B 2 eg 2 ................................ .......................... 308 4.4: Theoretical Investigation of the Directing Effect in Aniline Borylations .......................... 310 4.5: Experimentally Probing the Directing Element in Aniline CHB ................................ ...... 313 4.6: Computational study of N - Methylaniline borylation ................................ ....................... 315 4.7: Conclusions ................................ ................................ ................................ .................. 316 4.8: Experimental Details ................................ ................................ ................................ ..... 318 4.9: N otes ................................ ................................ ................................ ............................ 326 APPENDIX ................................ ................................ ................................ .......................... 328 REFERENCES ................................ ................................ ................................ .................... 351 Chapter 5: Exploration of Hydrazone Derived Ir C H Borylation Catalysts with Selectivit y for C H bonds in Similar Steric Environments ................................ .... 356 5.1: Introduction ................................ ................................ ................................ ................... 356 5.2: Prior studies in borylations of fluoro - containing arenes ................................ ................. 357 5.3: Activity of dmadphz generated catalyst ................................ ................................ ......... 362 5.4: Selectivity of dmadphz generated catalyst: A well plate study ................................ ....... 364 5.5: Substrate scope ................................ ................................ ................................ ............ 367 5.6: Effect of boron source ................................ ................................ ................................ ... 369 5.7: Structural adjustments to dmadphz and the effects ................................ ...................... 370 5.8: Conclusions ................................ ................................ ................................ .................. 372 5.9: Experimental Details ................................ ................................ ................................ ..... 373 5.10: Notes ................................ ................................ ................................ .......................... 454 APPENDIX ................................ ................................ ................................ .......................... 455 REFERENCES ................................ ................................ ................................ .................... 464 x Chapter 6: Synthesis and Study of Double - Decker Shaped Silsesquioxanes ..... 467 6.1: Background and introduc tion ................................ ................................ ........................ 467 6.2: Selecting a DDSQ target ................................ ................................ .............................. 468 6.3: Synthesis of compound 1 ................................ ................................ ............................. 470 6.4: Tuning melting points to disperse DDSQ additives ................................ ....................... 474 6.5: Separation and identification of DDSQ cis/trans isomers ................................ .............. 475 6.6: Thermal behavior of DDSQ isomers ................................ ................................ ............. 477 6.7: Solid - liquid phase equilibrium of compound 1 ................................ ............................... 4 77 6.8: Conclusions ................................ ................................ ................................ .................. 478 6.9 Experimental Details ................................ ................................ ................................ ...... 479 6.10: Notes ................................ ................................ ................................ .......................... 486 APPENDIX ................................ ................................ ................................ .......................... 487 REFERENCES ................................ ................................ ................................ .................... 496 xi LIST OF TABLES Table 1: Optimization of N,N - dimethylacetamide borylation ................................ .......... 21 Table 2: Substrate scope of C(sp 3 ) H borylation ................................ .......................... 23 Table 3: Ortho borylation of Substituted Phenols wit h B 2 pin 2 ................................ ...... 117 Table 4: ortho - Borylation of Phenols with B 2 eg 2 ................................ .......................... 124 Table 5: Ortho Borylation of Substituted Anilines with B 2 eg 2 ................................ ....... 309 Table 6: Ligand Electronic effect on selectivity ................................ ............................ 358 Table 7: Selectivity for the borylation of 1,3 - chlorofluorobenzene ............................... 360 Table 8: Ligand comparison between prior work and dmadphz ................................ .. 361 Table 9: Borylation of electron rich aromatics to gauge activity. ................................ .. 362 Table 10: Well plate analysis of common borylation ligands ................................ ....... 365 Table 11: Well plate analysis of 1,3 - difluorobenzene ................................ .................. 366 Table 12: Scale up of well plate reactions ................................ ................................ ... 367 Table 13: Substrate comparison between dmadphz and dtbpy ................................ ... 368 Table 14: Effect of boron source ................................ ................................ ................. 369 Table 15: Importance of free amino group on dmadphz ................................ .............. 370 Table 16 : Nickel catalyzed Sonogashira cross - coupling ................................ ............. 472 Table 17 : Characteristics of crystal structures of individual isomers ........................... 476 Table 18 : Experimental values obtained from cis and trans DDSQ - 2((Me)(R)) by DSC. m m /T m ................................ ................................ ................................ .............. 477 xii LIST OF FIGURES Figure 1: C H Borylation of 4 - Substituted Phenols and Anisoles ................................ 116 Figure 2: Transition state structures for borylation of 4 - MeO - C 6 H 4 OBpin´ with (bpy)Ir(Beg) 2 (Bpin´). ................................ ................................ ................................ .... 119 Figure 3: Calculated electrostatic potential surfaces for TS3 - anti (left) and TS3 - OMe anti (right). ................................ ................................ ................................ .............. 120 Figure 4: Ligand Effects on Borylation Selectivity ................................ ....................... 121 Figure 5: Calculated inner coordination spheres, selected metrical parameters, and natural bond orders for TS3 - OBpin´ anti and TS3 - OMe anti (left) and TS5 - OBeg an ti and TS5 - F (right). ................................ ................................ ................................ ............... 122 Figure 6: Transition states for borylation of 4 - F - C 6 H 4 OBeg with (dtbpy)Ir(Beg) 3 . ........ 123 Figure 7: Key Controls with B 2 pin 2 ................................ ................................ .............. 128 Figure 8: Proposed Transition States for Ortho Borylations of Anilines and Phenols. . 306 Figure 9: Computed transition states for Ir - catalyzed CHB of PhN(H)Beg with B 2 eg 2 . 311 Figure 10: Proposed Transition States for Ortho Borylations of Anilines. .................... 312 Figure 11: Computed transition states for Ir - catalyzed CHB of PhN(CH 3 )Beg with B 2 eg 2 . ................................ ................................ ................................ ................................ .... 315 Figure 12: Fluorinated pharmaceuticals ................................ ................................ ...... 373 Figure 13 . Structure of cis/trans - DDSQ - 2(R 1 R 2 ) and POSS - R 1 where R are inert organic moieties and R 1 and R 2 are active functional groups ................................ .................. 467 Figure 14 : 29 Si NMR peaks representing the isomers after separation; a) cis - 1, b) trans - 1 ................................ ................................ ................................ ................................ .. 476 Figure 15 : a) DSC curves for compound 3. ................................ ................................ . 478 xiii LIST OF SCHEMES Scheme 1: General C - H activation/functionalization scheme with key aspirations .......... 1 Scheme 2: Utility of versatile functional groups in C - H activation/functionalization ......... 2 Scheme 3: The versatility of boronic esters and acids ................................ .................... 3 Scheme 4: First thermal catalytic C - H activation borylation ................................ ............ 4 Scheme 5: Mechanism s of iridium catalyzed C - H activation borylation. .......................... 5 Scheme 6: Examples of sterically selective borylations ................................ .................. 7 Scheme 7: Why directing groups do not direct with dtbpy based boryalton catalysts ..... 7 Scheme 8: Monodentate homogeneous ligand for directed C - H activation ..................... 8 Scheme 9: A) Hemilabile ligand strategy B) Heterogeneous monodentate ligand design ................................ ................................ ................................ ................................ ........ 9 Scheme 10: Relay directed borylation and bidentate monoanionic ligand design. .......... 9 Scheme 11: Outer - sphe re direction via appended acceptor group. .............................. 10 Scheme 12: Reaction of generic boronic acid and generic diol. ................................ .... 16 Scheme 13: A) Interaction between Bortezomib and yeast 20S proteasome. This is adapted from reference 21. B) Select examples of b iologically active alpha - aminoboronic compounds. ................................ ................................ ............................ 17 Scheme 14: Relay directed iridium catalyzed C(sp 3 ) H borylations. ............................. 19 Scheme 15: Prior chelate directed C(sp 3 ) H activation borylation ................................ 20 Scheme 16: Competitive KIE study ................................ ................................ ............... 25 Scheme 17: Proposed catalytic cyc le ................................ ................................ ............ 26 Scheme 18: Selected Mechanisms for Directed Borylation ................................ ......... 114 xiv Scheme 19: Phenol Borylation with Traceless Protection ................................ ........... 115 Scheme 20: Minimizing B(OAryl) 3 Formation ................................ .............................. 126 Scheme 21: NMR Tube Reaction Showing ArylOBeg Species ................................ ... 128 Scheme 22: Boron Reagent Effects on Borylation of 4 - Fluorophenol ......................... 129 Scheme 23: Comparison of the Kanai - Kuninobu CHB of N - Acylated Anilines to This Work ................................ ................................ ................................ ............................ 305 Scheme 24 :Aniline CHBs with B 2 pin 2 and B 2 eg 2 . ................................ ........................ 308 Scheme 25: Aniline CHBs of PhN(H)Bpin with B 2 eg 2 and PhN(H)Beg with B 2 pin 2 . .... 313 Scheme 26: Borylation of N - Methylaniline ................................ ................................ ... 314 Scheme 27: Regiochemical consequences of Beg and Bpin reagents in aniline CHBs. ................................ ................................ ................................ ................................ .... 316 Scheme 28: Mechanistic reasons for steric selectivity ................................ ................ 356 Scheme 29: A pallet of ligands organized by basicity and steric hindrance ................ 359 Scheme 30: A) Prior work and limitations B) Synthetic route leading to the discovery of dmadphz ................................ ................................ ................................ ..................... 361 Scheme 31: A) Slow N - borylation with HBpin B) Fast N - borylation with Hbpin and iridium source C) No evidence of N,N - diborylation ................................ ...................... 372 Scheme 32 - 1) B) Structure of Phenyl POSS and designed DDSQ additive 1 ................................ ......... 470 Scheme 33 : Retrosynthetic analysis of compound 1 ................................ ................... 471 Scheme 34 : Palladium catalyzed Sonogashira ................................ ........................... 472 Scheme 35 : Synthesis of dichlorosilane 2 ................................ ................................ ... 473 Scheme 36 : Synthesis of compound 1 ................................ ................................ ........ 473 Scheme 37 : Condensation of 3 with two equivalents of organo - dichlorosilanes ......... 474 xv K EY TO ABBREVIATIONS Ac a cetate Ar a ryl B 2 pin 2 b is(pinacolato)diboron HBpin p inacoleborane NMR n uclear magnetic resonance GC g as chromatography GCMS g as chromatography mass spectrometry THF t etrahydrofuran Bpin 4,4,5,5 - Tetramethyl - 1,3,2 - dioxaborolane CHB C H activation borylation Cp c yclopentadienyl Cat c atecholate Ir ir idium Dmpe b is(dimethylphosphino)ethane dppe 1,2 - Bis(diphenylphosphino)ethane dtbpy - di - tert - butyl - - bip yridine bpy - bipyridine tmp 3,4,7,8 - tetramethylphenanthroline COD c yclooctadiene COE c yclooctene Pd(PPh 3 ) 2 Cl 2 b is(triphenylphosphine)palladium(II) dichloride xvi MgSO 4 m agnesium sulphate EtOAc e thyl acetate KOtBu p otassium tert - butoxide eg ethylene glycol DoM directed ortho metalation Bn b enzyl Boc tert - butyloxycarbonyl CPME c yclopentylmethyl ether CDCl 3 deuterated chloroform CH 2 Cl 2 dichloromethane DDSQ double decker silsesquioxan e DMAc N,N - dimethylacetamide DMF N,N - dimethylformamide DPM dipyridylmethane DSC differential scanning calorimetry GCI Green Chemistry Institute h hour mg milligrams mL milliliter mmol millimole mp melting point N 2 nitrogen NASA National Aeronautics and Space Administration xvii NiCl 2 (PPh 3 ) 2 dichlorobis(triphenylphosphine)nickel(II) POSS polyhedral oligomeric silsesquioxanes ppm parts per milli on rt room temperature SMAP silicon - constrained monodentate trialkylphosphine T d temperature of decomposition T g glass transition temperature TGA thermogravimetric analysis TLC thin layer chromatography equiv equivalents mp melting point Bozo - b is - 2 - oxazoline Bnbozo - b is[(4S) - 4 - benzyl - - 2 - oxazoline] t - Bu t ertiary Butyl, or tert - Butyl °C Degrees Celsius Cp Cyclopentadiene or Cyclopentadienyl Cp* Pentamethyl Cyclopentadien yl kcal kilocalorie Cy c yclohexane delta, NMR Chemical shift d doublet, double peak in NMR spectrum dd doublet of doublets DCM d ichloromethane xviii 4 - DMAP 4 - d imethylaminopyridine dmadpm d imethylaminodipyridyl m ethane dpm d ipyridyl m ethane EAS e lectrophilic a romatic s ubstitution FG f unctional g roup GC g as c hromatograph GC - FID g as c hromatograph with f lame i onizing d etector GC - MS g as c hromatograph with m ass s pectrometer Hz h ertz (cycles per second) H e nthalpy, or c hange in e nthalpy J NMR c oupling c onstant KIE k inetic i sotope e ffect L l igand LDA l ithium d iisopropyl a mine m m ultiplet peak in NMR spectrum M+ m olecular i on peak in m ass s pectrum m/z m ass divided b y c harge of an ion Me m ethyl MeCN a cetonitrile MHz m ega h ertz mol m ole Ph p henyl xix s singlet peak in NMR spectrum 1 Chapter 1: An Introduction 1.1: Background C - H activation/functionalization is a powerful synthetic technique that not only uniquely enables targeted synthesis 1 but also allows rapid late stage diversification of chemical matter. 2 Such a powerful tool has of course been extensively reviewed with over - The extensive nature in which the community has studied this topic highlights both the broad utility and the significant chemical challenges inherent in the field. Scheme 1 : General C - H activation/functionalization scheme with key aspirations As is well recognized, C - H bonds are not only ubiquitously distributed over organic - H activation/functionalization is to activate any C - H bond selectively followed by the installation of any desired functional group (scheme 1). To achieve this lofty goal first predictable selectivity for the activation of relatively inert C - H bonds must be achieved. Ideally at this point a user would si mply plug - and - play with desired functional groups. Unfortunately, ideality and reality are often quite disparate. Changing the functional group often requires a reoptimization of the system and in many cases requires the development of a new catalyst. This - H activation a new 2 methodology may be needed not just for every type of desired C - H bond but also for each type of functional group. Given these challenges our group purposely decouples the broad functional group trans formations from the C - H activation by using C - H activation to install a versatile functional group (FG x ). This versatile group can then be converted into a myriad of other functionalities (scheme 2). With this strategy, the focus of the research is narrowe d to one - overall C - H to C - FG can be accomplished through a two step process C - H to C - FG x followed by C - FG x to C - FG. Scheme 2 : Utility of versatile functional group s in C - H activation/functionalization 1.2: Identity of FG x The strategy described above is predicated on the identity of FG x . Methodologies must be in place to support transformations from FG x to a diverse array of other moieties. Furthermore, this functional group should be stable, isolatable, and preferably instill little to no toxicity to the parent organic compound. Finally, the installation of FG x should be broadly functional group tolerant . 3 Scheme 3 : The versatility of boronic esters and acids Boronic esters meet many if not all of these requirements. Organoboron containing materials are extraordinarily versatile building blocks a nd undergo a diverse array of transformations. 3 As an example the Nobel prize winning Suzuki cross - coupling reaction forms carbon carbon bonds from C - B precursors. This powerful transformation is among the most utilized carbon carbon bond forming reactions in medicinal chemistry, 4,5 which is likely due to the well known stability and safety of organoboron containing compounds. 6 That being said carbon boron intermediates support more than just the Suzuki reaction. For example, ani mations, 7,8 oxidations, 9 halogenations, 10,11 cyanations, 12,13 trifluoromethylations, 14 thiotrifluoromethylations 15 and other transformations have all been achieved wit h C - B starting materials. 4 1.3: C - H activation borylation the initial discovery With an appealing functional group selected the strategy in scheme 2 requires a catalytic system to activate C - H bonds followed by installing the C - B bond. Currently, there are a number of C - H borylation catalysts including Fe, 16,17 Co, 18 20 Ni, 21, 22 Zn, 23 Rh, 24 Pt, 25,26 Pd, 27,28 and Ir 29 based catalysts; however, the iridium based systems are by far the most studied. The first thermal catalytic C - H borylation was disclosed by Smith and co - workers in 1999 (Scheme 4). 30 Scheme 4 : First thermal catalytic C - H activation borylation This result while groundbreaking did not reveal a catalyst active enough to be broadly applied. However, efforts by the Smith and Maleczka collaboration produced the first synthetically applicable C - H activation borylation system. In 2002 they communicated a L 2 ligand framework that generated an active catalyst from an iridium precur sor, demonstrated significantly higher turnover numbers (50 - 5000), showed the first C - H activation borylation of a heterocycle, for the first time telescoped C - H activation borylation/Suzuki cross - coupling reaction, and proposed an Ir III/V catalytic cycle. 31 This seminal work brought the transformation from an interesting observation to a synthetically powerful tool. 1.4 Mechanism of iridium catalyzed C - H activation borylation Since the initial discove ry many research teams have significantly contributed to the field both in terms of fundamental understanding and advancing the catalysis. 5 Ishiyama, Hartwig, and Miyaura disclosed an extradinarliy active catalyst with 4,4´ - di - t Bu - 2,2´ - bipyridine (dtbpy) as a ligand which is still used today. 32 This system has been rigorously studied computationally confirming the initial Ir III/V proposal. 33 Careful kinetic analysis has experimentally validated the computational study. The mechanism in accordance with these findings is shown in scheme 5. Scheme 5 : Mechanisms of iridium catalyzed C - H activation borylation. Ishiyama, Miyaura, and Hartwig isolated and crystalized an [Ir(Bpin) 3 (dtbpy)(coe)] complex which they proposed was a potential intermediate in the catalysis. 34 Hartwig and co - wo rkers discovered a more robust method to isolate this complex and used it in a careful kinetic analysis of the catalysis. 35 They found reversible dissociation of the COE ligand generates the active cat alyst (complex I from scheme 5). This 16e - complex oxidatively adds to an arene C - H bond yielding an Ir V intermediate complex II . Reductive elimination of the carbon boron material leaves Ir III complex III . Regeneration of complex I can then occur with eit her B 2 pin 2 B 2 pin 2 . It is proposed that complex III oxidatively adds to boron - boron bond in B 2 pin 2 6 providing complex IV as a tetraborylmonohydride that can reductively eliminate HBpin regenerating the trisbo ryl catalyst I . There are a few points worth commenting regarding the mechanism. First, the turnover limiting step is C - H activation. This is supported by a high primary kinetic isotope effect of 5 in the borylation of benzene vs benzene - d 6 . 35 The transition state for C - H activation is shown in scheme 5. Calculations from our group in collaboration with Professor Singleton have revealed that the higher negative charge character on the arene in the transition state the lower the barrier. 36 Second, while the trisboryl has been shown to be active in C - H activation, it is not unreasonable that the diborylmonohydride IrIII complex can also C - H activate and reductively eliminate borylate products. Smith and Maleczka found compelling evidence for this process with a phosphine ligand system where 31 P NMR revealed many potentially simultaneously active catalysts. 37 1.5: Regioselectivity of iridium C - H B orylation In general iridium borylations are sterically selective. 29 This empirical observation can be rationalized by the mechanism in scheme 5. Since C - H activation is the turnover limiting ste p and irreversible to understand the selectivity we must consider complex I . In order for borylation to occur, the aromatic C - H bond must approach the vacant site on the iridum center. This approach is readily inhibited by large groups near the C - H bond. Some examples of this selectivity are shown in scheme 6. Sterically directed CHBs offer selectivities that complement traditional chemistries such as directed ortho metalation (D o M) and electrophilic aromatic substitution reactions (EAS). 38 7 Scheme 6 : Examples of sterically selective borylations 1.6: Directing the iridium catalyst As stated above, the ideal situation would be for a user to predictably select any C - H bond to activate then functionalize with any functional group. Since borylated compounds can undergo many functional group transformations, research in this space focuse s on developing methods for selective C - H activation. While the field is far from the ability to selectively activate any desired C - H bond, significant efforts to expand the number of C - H bonds available for activation/borylation is seen in the literature. Some selected methods for iridium catalysts are discussed below. One technique to achieve selectivity is to utilize a d irecting group. This group would in some way interact with the catalyst and direct it to a specific C - H bond. Unfortunately, with traditional sterically controlled CHB catalysts directing groups are inoperative. This can be rationalized by considering comp lex I (scheme 7). If a directing group chelated to the metal center, the catalyst would have no open sites available to C - H activate (scheme 7). Scheme 7 : Why directing group s do not direct with dtbpy based boryalton catalysts To overcome this limitation a number of strategies have been developed. One strategy is to design a catalyst such that the metal can coordinate both the directing group and have a second vacant site for C - H activation. This necessitates a second coordination site which can be achieved by using a monodentate ligand (Scheme 8). This strategy has 8 been used for ortho selective C - H borylations of esters, amides, and ketones with triarylphosphines, 39 triarylarsines, 40 or pyridines 41 monodentate ligands. Unfortunately, the rate of disassociate for monodentate ligands is much higher for bidentate ligands. This can translate to both a lower catalytic activity since the unligated metal is usually inactive and poorer selectivity if two monodentate ligands coordinate to one metal center. Sche me 8 : Monodentate homogeneous ligand for directed C - H activation Both Lassaletta and Sawamura offered unique solutions to overcome the issues generated by ligand disassociation. Lassaletta and co - workers cleverly designed a bidentate ligand framework where one arm only weakly coordinated to the iridium. 42 In this system it was proposed that after the directing group coordinates one arm of the bidentate ligand dissociates leaving an open site on the metal for C - H activation. Sawamura and co - workers generated heterogeneous catalysts by covalently linking the monodentate ligand to a silica support. 43,44 Due to the pa rticle size of the silica support, two ligands could not bind the same metal center meaning only 14e - iridium species were present. 9 Scheme 9 : A) Hemilabile ligand strategy B) Heterogeneous monode ntate ligand design Hartwig approached this issue with different strategy. He noticed that silanes could in situ replace a boryl ligand on the metal center, so he installed silanes on the arene as 45 The Smith and Maleczka groups also contributed in this space. Rather than using the silane as a directing group, they installed the silane on the ligand generating a bidentate, monoanionic liga nd framework. 46 This framework supported 14e - iridium complexes without the increased disassociate issue of simple monodentate ligands. Scheme 10 : Relay directed borylation and bidentate monoanionic ligand design. Each of the directing strategies discussed thus far are inner - sphere where an interaction between the directing group and metal controls the selectivity. Outer - sphere directing stra tegies have also been explored. The conceptually simplest outer - sphere directing strategies explored is to append some form of acceptor to the bipyridine ligand 10 framework (scheme 11). The acceptor would interact with a group on the substrate and direct the iridium catalyst to a specific C - H bond. This has been successful for both ortho and meta selective borylations with interactions such as Lewis acid - base, 47 hydrogen bonding, 48 50 and ion pairing. 51 53 The strategies listed herein have significantly advanced the type of C - H bonds able to be activated with iridium borylation catalysts. Scheme 11 : Outer - sphere direction via appended acceptor group. 1.7: Conclusions Overall, C - H activation/functionalization has changed the landscape for how to think about building or diversifying molecules. In this space, iridium catalyzed C - H activation/borylation offers a distinct strategy in that the borylated compounds are extraordinarily versatile building blocks with methodologies that support a myriad of further functionalizations. Thus the challenge with iridium borylations is to develop methods to select a desired C - H bond for activation. Some of the techniques to establish this control over the iridium catalysts discussed in the preceding se ctions include both inner and outer - directed strategies. Subtler variants of the outer - sphere directing strategy and methods to extend C - H activation to include sp 3 C - H bonds are explored in detail in the following chapters. 11 REFERENCES 12 REFERENCES (1) Abrams, D. J.; Provencher, P. A.; Sorensen, E. J. Chem. Soc. Rev. 2018 , 47 (23), 8925. (2) Wencel - Delord, J.; Glorius, F. Nat. Chem. 2013 , 5 (5), 369. (3) Hall, D. G. Boronic Acids: Preparation, Applications in Organic Synthesis and Medicine ; John Wiley & Sons, 2006. (4) Roughley, S. D.; Jordan, A. M. J. Med. Chem. 2011 , 54 (10), 3451. (5) Brown, D. G.; Boström, J. J. Med. Chem. 2016 , 59 (10), 4443. (6) Suzuki, A. J. Organomet. Chem. 1999 , 576 (1), 147. (7) Chan, D. M. T.; Monaco, K. L.; Wang, R. - P.; Winters, M. P. Tetrahedron Letters . 1998, pp 2933 2936. (8) Hardouin Duparc, V.; Bano, G. L.; Schaper, F. ACS Catal. 2018 , 8 (8), 7308. (9) Kuivila, H. G.; Armour, A. G. J. Am. Chem. Soc. 1957 , 79 (21), 5 659. (10) Vints, I.; Gatenyo, J.; Rozen, S. J. Org. Chem. 2013 , 78 (23), 11794. (11) Szumigala, R. H., Jr; Devine, P. N.; Gauthier, D. R., Jr; Volante, R. P. J. Org. Chem. 2004 , 69 (2), 566. (12) Kim, J.; Choi, J.; Shin, K.; Chang, S. J. Am. Chem. Soc. 2012 , 134 (5), 2528. (13) Dai, J. - J.; Zhang, W. - M.; Shu, Y. - J.; Sun, Y. - Y.; Xu, J.; Feng, Y. - S.; Xu, H. - J. Chem. Commun. 2016 , 52 (41), 6793. (14) Liu, T.; Shen, Q. Org. Lett. 2011 , 13 (9), 2342. (15) Shao, X.; Liu, T.; Lu, L.; Shen, Q. Org. Lett. 2014 , 16 (18), 4738. (16) Hatanaka, T.; Ohki, Y.; Tatsumi, K. Chem. Asian J. 2010 , 5 (7), 1657. (17) Yan, G.; Jiang, Y.; Kuang, C.; Wang, S.; Liu, H.; Zhang, Y.; Wang, J. Chem. Commun. 2010 , 46 (18), 3170. (18) Obligacion, J. V.; Semproni, S. P.; Chirik, P. J. J. Am. Chem. Soc. 2014 , 136 (11), 4133. 13 (19) Palmer, W. N.; Obligacion, J. V.; Pappas, I.; Chirik, P. J. J. Am. Chem. Soc. 2016 , 138 (3), 766. (20) Obligacion, J. V.; Semproni, S. P.; Pappas, I.; Chirik, P. J. J. Am. Chem. Soc. 2016 , 138 (33), 10645. (21) Furukawa, T.; Tobisu, M.; Chatani, N. Chem. Commun. 2015 , 51 (30), 6508. (22) Zhang, H.; Hagihara, S.; Itami, K. Chem. Lett. 2015 , 44 (6), 779. (23) Bose, S. K.; Deißenberger, A.; Eichhorn, A.; Steel, P. G.; Lin, Z.; Marder, T. B. Angew. Chem. Int. Ed Engl. 2015 , 54 (40), 11843. (24) Esteruelas, M. A.; Oliván, M.; Vélez, A. Organometallics 2015 , 34 (10), 1911. (25) Takaya, J.; Ito, S.; Nomoto, H.; Saito, N.; Kirai, N.; Iwasawa, N. Chem. Commun. 2015 , 51 (100), 17662. (26) Furukawa, T.; Tobis u, M.; Chatani, N. J. Am. Chem. Soc. 2015 , 137 (38), 12211. (27) He, J.; Jiang, H.; Takise, R.; Zhu, R. - Y.; Chen, G.; Dai, H. - X.; Dhar, T. G. M.; Shi, J.; Zhang, H.; Cheng, P. T. W.; Yu, J. - Q. Angew. Chem. Int. Ed. 2016 , 55 (2), 785. (28) He, J.; Shao, Q.; Wu, Q.; Yu, J. - Q. J. Am. Chem. Soc. 2017 , 139 (9), 3344. (29) Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.; Murphy, J. M.; Hartwig, J. F. Chem. Rev. 2010 , 110 (2), 890. (30) Iverson, C. N.; Smith, M. R. J. Am. Chem. Soc. 1999 , 121 (33), 7696. (31) Maleczka, R. E., Jr.; Smith, M. R., III. Science 2002 , 295 . (32) Ishiyama, T.; T akagi, J.; Hartwig, J. F.; Miyaura, N. Angew. Chem. Int. Ed. 2002 , 41 (16), 3056. (33) Tamura, H.; Yamazaki, H.; Sato, H.; Sakaki, S. J. Am. Chem. Soc. 2003 , 125 (51), 16114. (34) Ishiyama, T.; Takagi, J.; Ishida, K.; Miyaura, N.; Anastasi, N. R.; Hartwig, J. F. J. Am. Chem. Soc. 2002 , 124 (3), 390. (35) Boller, T. M.; Murphy, J. M.; Hapke, M.; Ishiyama, T.; Miyaura, N.; Hartwig, J. F. J. Am. Chem. Soc. 2005 , 127 (41), 14263. (36) Britt A. Vanchura, I. I.; Preshlock, S. M.; Roosen, P. C.; Kallepalli, V. A.; Staples, 14 R. J.; Maleczka, R. E., Jr; Singleton, D. A.; Milton R. Smith, I. Chem. Commun. 2010 , 46 (41), 7724. (37) Ghaffari, B.; Vanchura, B. A.; Chotana, G. A.; Staples, R. J.; Holmes, D.; Maleczka, R. E.; Smith, M. R. Organometallics . 2015, 4740. (38) Hurst, T. E.; Macklin, T. K.; Becker, M.; Hartmann, E.; Kügel, W.; Parisienne - La Salle, J. - C.; Batsanov, A. S.; Marder, T. B.; Snieckus, V. Chem. Eur. J. 2010 , 16 (27), 8155. (39) Ishiyama, T.; Isou, H.; Kikuchi, T.; Miyaura, N. Chem. Commun. 2010 , 46 (1), 159. (40) Itoh, H.; Kikuchi, T.; Ishiyama, T.; Miyaura, N. Chem. Lett. 2011 , 40 (9), 1007. (41) Unpublished work by Shabashov, D.; Shannon, T. M .; Oppenheimer, J.; Maleczka, R. E., Jr.; Smith, M. R. III. (42) Ros, A.; Estepa, B.; López - Rodríguez, R.; Álvarez, E.; Fernández, R.; Lassaletta, J. M. Angew. Chem. Int. Ed. 2011 , 50 (49), 11724. (43) Yamazaki, K.; Kawamorita, S.; Ohmiya, H.; Sawamura, M. Org. Lett. 2010 , 12 (18), 3978. (44) Kawamorita, S.; Ohmiya, H.; Hara, K.; Fukuoka, A.; Sawamura, M. J. Am. Chem. Soc. 2009 , 131 (14), 505 8. (45) Boebel, T. A.; Hartwig, J. F. J. Am. Chem. Soc. 2008 , 130 (24), 7534. (46) Ghaffari, B.; Preshlock, S. M.; Plattner, D. L.; Staples, R. J.; Maligres, P. E.; Krska, S. W.; Maleczka, R. E., Jr; Smith, M. R., 3rd. J. Am. Chem. Soc. 2014 , 136 (41), 14345. (47) Li, H. L.; Kuninobu, Y.; Kanai, M. Angew. Chem. Int. Ed. 2017 , 56 (6), 1495. (48) Kuninobu, Y.; Ida, H.; Nishi, M.; Kanai, M. Nat. Chem. 2015 , 7 (9), 712. (49) Roosen, P. C.; Kallepalli, V. A.; Chattopadhyay, B.; Singleton, D. A.; Maleczka, R. E., Jr; Smith, M. R., 3rd. J. Am. Chem. Soc. 2012 , 134 (28), 11350. (50) Preshlock, S. M.; Plattner, D. L.; Maligres, P. E.; Krska, S. W.; Maleczka, R. E.; Smith, M. R. Angew. Chem. Int. Ed. 2013 , 52 (49), 12915. (51) Mihai, M. T.; Davis, H. J.; Genov, G. R.; Phipps, R. J. ACS Ca tal. 2018 , 8 (5), 3764. 15 (52) Davis, H. J.; Genov, G. R.; Phipps, R. J. Angew. Chem. Int. Ed. 2017 , 56 (43), 13351. (53) Davis, H. J.; Mihai, M. T.; Phipps, R. J. J. Am. Chem. Soc. 2016 , 138 (39), 12759. 16 Chapter 2: Directed C(sp 3 ) H activation borylation 2.1: Introduction Alkylbononic acids and esters are an important class of compounds both for the versatile reactivity of the C B intermediate 1 5 and for inherent biological activity. 6 11 Boron containing compounds have been shown to act as sensors for saccharides, 12 14 enzyme inhibitors, 15,16 and neutron capture agents for cancer therapy. 17,18 This diverse range of therapeutic interest is directly related to physical properties of the boron containing compounds. For example, boronic acids are known to readily form boronic esters in the presence of diols; thus, depending on the framework containing the boronic acid, biologically relevant saccharides can be targeted (Scheme 1 2 ). The targeted saccharide would react with the boronic acid to form a boronic ester allowing boronic acids in a way to mim ic antibodies. 12,19 Scheme 12 : Reaction of generic boronic acid and generic diol. In terms of enzyme inhibition, alpha - aminoboronic acids are key pharmacophores in potent protease inhibitors. Bortezomib, which contains the alpha - aminoboronic moiety, was the first protease inhibitor to be studied in humans and is currently FDA approved 20 for the treatment of multiple myeloma and mantle cell lymphoma. A crystal structure of bortezomib in a yeast proteasome revealed a covalent bond between the boron and a threonine amino acid in the proteasome (Scheme 13 A). 21 The therapeutic success of Bortezomib has inspired a significant study of the alpha - aminoboronic moiety and many active compounds have been identified including Ixazomib which is an orally viable, FDA approve d treatment for multiple myeloma (Scheme 13 B). 22 17 Scheme 13 : A) Interaction between Bortezomib and yeast 20S proteasome. This is adapted from reference 21. B) Select examples of biologically active alpha - aminoboronic compounds. Given the biological relevance and subsequent reactivity of these boronic compounds synthetic methods to generate the C B bond has garnered significant attention. Tradit ionally, alkylboronic compounds are prepared by trapping alkylmagnesium 23,24 or alkyllithium 25,26 reagents with boron electrophiles. While these classical routes have low functional group tolerance, more recent transition metal based 18 methods such as alkene or enone hydroboration, 27 29 addition across C - heteroatom doubl e bonds, 30 32 and Miyaura - type borylations 33,34 largely overcome this issue. 35 However, each of these methods require the starting organic material to be prefunctionalized in preparation of the C B bond forming reaction. This is where C H activation has a distinct advantage. Not only is C H activation atom efficient, it als o requires little preparation of the starting organics. To this end, it has been demonstrated that Co, 36 Ru, 37 Rh, 38 42 Pd, 43 W, 44 Re, 45 and Ir 46 49 are capable of C(sp 3 ) H activation borylation. 50 While recent advances in palladium 51 53 and cobalt 54 catalyzed borylations have shown interesting reactivity, the iridium based catalysts for C(sp 3 ) H borylation are by far the most extensively studied. These can be divided into three major categories: 1) borylation of activated C H bonds, such as benzylic, 46,55 cyclopro pyl, 48,49,56 and alpha - silyl, 57 61 2) directed CHB, 62 69 and 3) methane borylation. 70 72 Despite significant advances in directed iridium C(sp 2 ) H borylations, similar advances in sp 3 borylations have yet to be rea lized. The most used directing strategy in iridium catalyzed sp 3 borylations is the relay directed method whereby a silane on the substrate will displace a spectating boryl ligand (Scheme 14 ). Unfortunately, this requires the presence of a silane in the starting organic which in most cases must be installed. 19 Scheme 14 : Relay directed iridium catalyzed C(sp 3 ) H borylations. Pioneering work by Sawamura and co - workers with solid - supported phosphine ligands offers an alternative directing strategy where presumably a coordinatively unsaturated metal center can accept donor directing groups. This was demonstrated in both iridium catalyzed CHB of 2 - alkylpyridines with Si - SMAP ligands, and amide directed rhodium catalyzed CHB with an analogous immobilized phosphine ligand, Si - TRIP (Scheme 15 ). Unfortunately, this methodology is limited in that the ligand synthesis requires multiple steps along with specialized silica and the starting materials are used in excess to limit borylation. The excess substrate is undesirable for late - stage applications. Clearly immobilization of the ligand is necessary for the C(sp 3 ) H activation to occur; however, it is unclear if the immobilization accomplished more than strictl y control the metal to neutral ligand ratio (Scheme 15 ). If the immobilization only enforced the metal to neutral ligand ratio, we hypothesized that well defined homogeneous catalysts could achieve similar directed C(sp 3 ) H activation borylation while avoi ding the aforementioned limitations. 20 Scheme 15 : Prior chelate directed C(sp 3 ) H activation borylation With this in mind we set out to test if amide directed C(sp 3 ) H borylation could be achieved with homogeneous iridium catalysts from readily available ligands. Importantly, during the preparation of this chapter, the Clark group published an excellent proof of principle study demonstrating with limited scope, four substrates, that amide directed CHB is possible with homogeneous catalysts. 73 2.2 : Optimization of amide directed C(sp 3 ) H borylation We initiated our study with the borylation of N,N - dimethylacetamide ( 1a ) under various conditions (Table 1). As it has been shown that sp 3 CHB can occur without addition of ligand, 69 - tert - butyl - - bipyridine, tmphen = 3,4,7,8 - tetramethyl - 1,10 - phe nanthroline) are common CHB ligands, we started by screening 1.5 mol % [Ir(OMe)cod)] 2 , 1.2 equiv B 2 pin 2 , with no ligand (entry 1), and with 3 mol % dtbpy (entry 2) or tmphen (entry 3, Table 1). Unfortunately, no reaction occurred without ligand added and b oth dtbpy and tmphen provided a complex mixture of products in the 1 H NMR. Ligand L1 , which has been used for ortho - selective borylations of arylimines, 74 provided low conversion to 2a , and increased r eaction temperature provided no additional conversion (entries 4 and 5). 21 Table 1 : Optimization of N,N - dimethylacetamide borylation Conditions: 1 (1 equiv, 0.5 mmol), Boron source (1.2 equiv, 0.6 mm ol), [Ir(OMe)(cod)] 2 (1.5 mol %, 0.0075 mmol), ligand (3 mol %, 0.015 mmol) in 2 mL THF. a Based on 1 H NMR. b Reaction time 7.5 h. c 2 equiv HBpin. d 0.75 mol % [Ir(OMe)(cod)] 2 , 1.5 mol % L3 . pin = pinacolate, eg = ethylene glycolate Given the low reactivity of L1 and that Sawamura demonstrated immobilization of the phosphine ligand was necessary for the C(sp 3 ) H activation to occur, we thought a stronger control of the neutral ligand to metal ratio may provide greater reactivity. In 2014, we publis hed silyl phosphorus and nitrogen based bidentate, monoanionic ligand frameworks for iridium catalyzed ortho selective borylations. 75 The anionic silyl ligand replaces a spectating boryl, and due to th e bidentate nature, the metal to neutral donor ligand ratio is well controlled. Satisfyingly, previously reported silyl - nitrogen ligand L2 provided 60% conversion to the 2a (entry 6). With this result, we sought to optimize the structure of this ligand 22 fra mework. Cognizant that better donors have been shown to increase rates of CHB catalysis, we prepared pyridine based ligand L3 which gave nearly full conversion to the desired product. Additional donation ( L4 ) and decreasing the sterics around the silyl sit e ( L5 ) both provided inferior results (entries 8 and 9); however, by simply increasing the reaction temperature to 80 °C, full conversion to the product was achieved in 7.5 hours (entry 10). Adjusting the boron source to either pinacol borane or B 2 eg 2 (eg = ethylene glycol), which has been used in ortho - selective CHB of phenols 76 and anilines, 77 had a negative impact on the reaction (entry 11 and 12 ). Finally, lowering the catalyst loading slowed the reaction. With optimum reaction conditions in hand, we sought to explore substrate scope. 2.3 : Substrate scope of amide directed C(sp 3 ) H borylation We first selected a number of acyclic and cyclic alk yl dimethyl amides ( 1a - i ). Notably, perfect N - methyl regioselectivity was observed for compounds 1b and 1c where two primary C(sp 3 ) H bonds are equidistant from the directing carbonyl and could potentially be activated. The increased sterics in the alkyl region for 1c had no adverse effect on the reaction. Moreover, increased chain length and cyclic alkyls ( 1d - f ) were also tolerated. Cyclic amides 1g - i proceeded smoothly; however, the reactivity of 1g was significantly attenuated. We attribute the low reactivity to the increased distance of the N - methyl C H bond from the directing carbonyl the in the 5 - membered ring compared to the 6 - and 7 - membered rings. Where both primary and secondary C H bonds are available, the catalyst displays high regioselectivity for the sterically least hindered C H bond ( 2j ). Excitingly, other amide like moieties such as a carbamate and urea directed the C (sp 3 ) H borylation ( 1k - l ) as well. Product 2k is a promising result as carbamates can be 23 readily generated from the corresponding amines using standard protecting group protocols. 78 Iridium based bory lation catalysts are notably active toward C(sp 2 ) H bonds; 79 thus, we wondered at regioselectivity of N,N - dimethylbenzamide ( 1m ). Interestingly, the C(sp 2 ) H borylation was significantly favored; howev er, increasing the distance between the directing amide and the C(sp 2 ) H bonds by two methylene linkers ( 1n ) yielded perfect selectivity for the C(sp 3 ) H bond ( 2n ). This important result demonstrates the tolerance of aromatic C H bonds. Table 2 : Substrate scope of C(sp 3 ) H borylation 24 a Yields are conversions based on 1H NMR. Yields in parenthesis are isolated material. There were also a number of instructive substrates with no observed reactivity. Trifluoromethyl substituted compound 1o showed no evidence of borylation. We propose this is due to a weaker interaction between the carbonyl oxygen and iridium vacant site. Interestingly addition of a methylene spacer between the directing amide carbonyl and the electron withdrawing trifluoromethyl group did not increase the reactivity ( 1p ), which demonstrates an overall electronic sensitivity. Finally, while compound 1j showed the high selectivity for primary methyl C H bonds, in cases with only secondary C H bonds no reaction occurs ( 1q ). 2.4 : Kinetic Isotope Effect in amide directed C(sp 3 ) H borylation Mechanistically C H activation is the turnover - limiting step for traditional iridium catalyzed aromatic C H borylations. As such a large primary kinetic isotope effect (5.0) is observed for the borylation of benzene. 80 Primary isotope effects are reported in the literature for iridium catalyzed C(sp 3 ) H borylations as well; however, the magnitude is often lower with 2.2, 55 2.4, 47 2.6 63 and 2.9 47 being recorded. The lowest KIE (2.2) was observed for iridium catalyzed benzy lic borylations with a modified phenanthroline ligand and Et 3 SiBpin as boron source. A diboryl monosilyl ligated complex was isolated and demonstrated to be the resting state of the catalytic cycle. Interestingly, DFT calculations suggested that C H activa tion is not the turnover limiting step. Rather an isomerization after C H activation where the hydride on the Ir(V) intermediate is exchanged between the boryl ligands is turnover limiting. Albeit distinct our proposed active catalyst also is a diboryl mo nosilyl complex; thus we wondered if the turnover limiting step was C H activation. To gain insight, a 25 competitive kinetic isotope study between dimethylacetamide ( 1a ) and dimethylacetamide - d 6 ( 1a - d 6 ) with limiting B 2 pin 2 was conducted (Scheme 16 ). This study revealed a large primary isotope effect of 5.0. Thus, C H activation is the likely turnover limiting step. Scheme 16 : Competitive KIE study 2.5 : Proposed cat alytic cycle A proposed mechanism for amide borylation is presented in Scheme 17 . Upon mixture of iridum precatalyst, ligand L3 and B 2 pin 2 complex I is generated. This 14 electron complex can readily coordinate amide substrate 1 generating 16 electron comp lex II . This initial coordination event explains the lack of reactivity observed in electron deficient substrates as they will only weakly coordinate. Complex II then proceeds through the turnover limiting step activating the amide N - methyl C(sp 3 ) H bond generating complex III . This intermediate must then reductively eliminate the C - B bond and lose the product from the coordination sphere. The loss of product from the coordination sphere is likely assisted by a strong interaction between the carbonyl oxygen and boron in the boronic ester. This interaction is supported by a sharp boron peak in the 11 B NMR observed for all C(sp 3 ) borylated products. Finally, regeneration of complex I from complex IV can occur through oxidative addition of B 2 pin 2 followed by reductive elimination of HBpin. 26 Scheme 17 : Proposed catalytic cycle 2.6 : Conclusions In conclusion, a silyl - pyridine based bidentate, monoanionic ligand generates a highly active homogeneous amide directed C(sp 3 ) H borylation catalyst. Selectivity for the amide N - methyl C H bond was observed. Importantly, over - borylated by - products were not formed under these reaction conditions; thus, enabling the substrate to be used as limiting reagent unli ke the prior heterogeneous rhodium system. This improvement provides potential for late stage amide directed functionalization. Other directing groups such as the urea and carbamate functional groups were capable of C(sp 3 ) H activation borylation. Importan tly, C(sp 3 ) H borylation occurred selectively in the presence of sp 2 C H bonds; however, in a competitive experiment between directed sp 2 and sp 3 C H activation, the sp 2 CHB was favored. Mechanistically the high KIE suggests C H activation as the rate dete rmining step, and a catalytic cycle was proposed. Overall, this 27 methodology is a significant improvement to the current art and provides a direct route to biologically relevant alpha - amidoboronic compounds. 2.7 : Experimental details General Information All commercially available chemicals were used as received unless otherwise indicated. Bis(pinacolato)diboron (B 2 pin 2 ) and tetrahydroxydiboron (B 2 (OH) 4 ) were generously supplied by BoroPharm, Inc., and pinacolborane (HBpin) was purchased from A nderson Chemical Company. Bis( 4 - 1,5 - cyclooctadiene) - di - - methoxy - diiridium(I) [Ir(OMe)(cod)] 2 was prepared per literature procedure . 81 Tetrahydrofuran (THF) was refluxed over a sodium/benzophenone ketyl, distilled, and degassed before use. Column chromato graphy was performed on Silia P - Flash silica gel. Thin layer chromatography was performed on 0.25 mm thick aluminum - backed silica gel plates and visualized with standard staining techniques. Sublimations were conducted with a water - cooled cold finger. 1 H, 13 C, 11 B and 19 F NMR spectra were recorded on 500 MHz NMR spectrometers. The boron bearing carbon atom was not observed due to quadrupolar relaxation. All coupling constants are apparent J values measured at the indicated field strengths in Hertz (s = singlet, d = doublet, t = triplet, q = quartet, dd = doublet of doublets, ddd = doublet of doublet of doublets, bs = broad singlet). High - resolution mass spectra (HRMS) were obtained at the Michigan State University Mass Spectrometry Service Center using electrospray ionization (ESI+ or ESI - ). 82 Melting points were measured in a ca pillary melting point apparatus and are uncorrected. 28 Ligand Preparation Preparation of Ligand L2 Ligand L2 was prepared in similar yield following the previously reported procedure. 75 Preparation of Ligand L3 To an oven dried 250 mL round bottom flask equipped with a stir bar, under nitrogen was added THF (40 mL) and diisopropylamine (1.1 equiv, 15.9 mmol, 2.25 mL) which was freshly distilled over calcium hydride. This solution was cooled to - 78 C in an acetone dry ice bath. Then n - butyllithium (2.5 M in hexanes, 1.1 equiv, 15.9 mmol, 6.36 mL) was added dropwise. This solution was allowed to stir for 5 min after which 2 - methylpyridine (1.0 equiv, 14.5 mmol, 1.43 mL) which was fr eshly distilled over calcium hydride was slowly added dropwise. This addition took approximately 5 min after which a reddish - orange solution was observed. In a separate oven dried 250 mL round bottom flask equipped with a stir bar, under nitrogen was added THF (20 mL) and diisopropylchlorosilane (1 equiv, 14.5 mmol, 2.47 mL) which was freshly distilled over calcium hydride. This solution was cooled to - 78 C in an acetone dry ice bath. The contents of the flask containing the lithiated 2 - methylpyridine were then slowly cannula 29 transferred into the second flask containing the chlorosilane. This cannula transfer took approximately 20 min. Upon completion the resulting solution was allowed to stir at - 78 C for 30 min after which an aliquot was removed, quenche d with methanol, and GCMS was collected. The GCMS revealed 2 products in a 9:1 ratio with masses corresponding to the desired monosilylated product and undesired disilyated product. The entire reaction mixture was then quenched by the addition of methanol (5 mL), solvents were removed under reduced pressure and a DCM/H 2 O extraction was performed. The resulting material was further purified by distillation (oil bath temperature: 60 - 80 C; vacuum: 0.01 torr). This provided L3 as a clear colorless liquid in 58 % yield (1.743 g). 1 H NMR (500 MHz, CDCl 3 ): H 8.4 2 ( d , J = 4.88 Hz, 1H), 7.48 (td, J = 7.7, 1.9 Hz, 1H), 7.05 (d, J = 7.9 Hz, 1H), 6.96 (dd, J = 7.4, 5.0 Hz, 1H), 3.71 3.58 ( s , 1H), 2.43 (d, J = 3.7 Hz, 2H), 0.99 (s, 1 4 H). 13 C NMR (125 MHz, CDCl 3 ): C 161.45, 149.10, 135.91, 122.61, 119.39, 22.08, 18.70, 18.56, 10.60. 2 9 Si NMR (99 MHz, CDCl 3 Si 7.32. 30 Preparation of Ligand L4 To an oven dried 250 mL round bottom flask equipped with a stir bar, under nitrogen was added THF (50 mL) and diisopropylamine (1.1 equiv, 9.2 mmol, 1.3 mL) which was freshly distilled over calcium hydride. This solution was cooled to - 78 C in an acetone dry ice bath. Then n - butyllithium (2.5 M in hexanes, 1.1 equiv, 9.2 mmol, 3.7 mL) was added dropwise. This solution was allowed to stir for 10 min after which 2 - methoxy - 6 - methylpyridine (1.0 equiv, 8.4 mmol, 1.02 mL) which was placed over 4 Å molecular sie ves 24 h before use was slowly added dropwise. This addition took approximately 5 min after which an orange - yellow solution was observed. The solution was allowed to stir for 30 min after which diisopropylchlorosilane (1 equiv, 8.4 mmol, 1.4 mL) freshly di stilled over calcium hydride was added. This mixture stirred for 1 h then quenched by the addition of methanol (5 mL). Solvents were removed under reduced pressure and a DCM/H 2 O extraction was performed. The resulting material was further purified by silic a column with a DCM/Hexanes (1:9) solvent system. This provided L4 as a clear colorless liquid in 38% yield (0.754 g). 1 H NMR (500 MHz, CDCl 3 ): H 7.38 (t, J = 7.4 Hz, 1H), 6.63 (d, J = 7.2 Hz, 1H), 6.43 (d, J = 8.1 Hz, 1H), 3.88 (s, 3H), 3.59 (bs, 1H), 2.34 (d, J = 3.2 Hz, 2H), 1.02 (s, 14H). 13 C NMR (125 MHz, CDCl 3 ): C 163.31, 159.32, 138.52, 114.93, 105.64, 53.12, 21.47, 18.75, 18.58, 10.67. 29 Si NMR (99 MHz, CDCl 3 Si 7.04. 31 Preparation of Ligand L5 To an oven dried 250 mL round bottom flask equipped with a stir bar, under nitrogen was added THF (50 mL) and diisopropylamine (1.1 equiv, 14.5 mmol, 2.05 mL) which was freshly distilled over calcium hydride. This solution was cooled to - 78 C in an aceton e dry ice bath. Then n - butyllithium (2.5 M in hexanes, 1.1 equiv, 14.5 mmol, 5.8 mL) was added dropwise. This solution was allowed to stir for 10 min after which 2 - methylpyridine (1.0 equiv, 13.1 mmol, 1.3 mL) which was freshly distilled over calcium hydri de was slowly added dropwise. This addition took approximately 5 min after which a bright rex - orange solution was observed. In a separate oven dried 250 mL round bottom flask equipped with a stir bar, under nitrogen was added THF (20 mL) and dimethylchloro silane (1 equiv, 13.1 mmol, 1.46 mL) which was freshly distilled over calcium hydride. This solution was cooled to - 78 C in an acetone dry ice bath. The contents of the flask containing the lithiated 2 - methylpyridine were then slowly cannula transferred i nto the second flask containing the chlorosilane. This cannula transfer took approximately 20 min. Upon completion the resulting solution was allowed to stir at - 78 C for 30 min after which the reaction was quenched by addition of silica. The silica was t hen rinsed with THF (250 mL) then volatiles were removed under reduced pressure. A DCM/H 2 O extraction was performed. The 1 H NMR at this point showed 95% conversion to the desired product. Unusually, at ambient temperature over a week the product slowly con verted back into the starting pyridine. To remove the starting materials and silicon byproducts, the 32 compound was distilled twice with a short - path distillation head (oil bath temperature: 60 - 80 C; vacuum: 0.01 torr). This provided L5 as a clear colorless liquid in 22% yield (0.436 g). Unfortunately, this purified compound also slowly decomposed in a nitrogen filled glove box at ambient temperature. 1 H NMR (500 MHz, CDCl 3 ): H 8.44 (d, J = 5.0 Hz, 1H), 7.51 (td, J = 7.7, 1.9 Hz, 1H), 7.04 6.93 (m, 2H), 4.02 (m, J = 3.6 Hz, 1H), 2.42 (d, J = 3.6 Hz, 2H), 0.10 (d, J = 3.6 Hz, 6H). 13 C NMR (125 MHz, CDCl 3 ): C 160.88, 149.17, 136.03, 122.28, 119.42, 27.56, - 4.50. Data for Table 1 Table 1 Entry 1 In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (4.97 mg, 0.0075 mmol, 1.5 mol %) and B 2 pin 2 (152.4 mg, 0.6 mmol, 1.2 equiv) were weighed into separate test tubes and N,N - dimethylacetamide (43.5 mg, 0.5 mmol, 1 equiv) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.3 mL THF. The resulting solution was then transferred into the test tube containing B 2 pin 2 . The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B 2 pi n 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was then transferred into the 5 mL conical vial followed by a similar rinsing procedure described above. The conical vial was then sealed and placed in a pre - heated aluminum block and allo wed to stir for 24 h. The vial was then opened and crude 1 H NMR was collected. Only starting amide was observed. 33 Table 1 Entry 2 In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (4.97 mg, 0.0075 mmol, 1.5 mol %), dtbpy (4.0 mg, 0.015 mmol, 3 mol %), and B 2 pin 2 (152.4 mg, 0.6 mmol, 1.2 equiv) were weighed into separate test tubes and N,N - dimethylacetamide (43.5 mg, 0.5 mmol, 1 equiv) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B 2 pin 2 . The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to t he B 2 pin 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was then transferred into the test tube containing dtbpy and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the r insing procedure. The conical vial was then sealed and placed in an aluminum block pre - heated to 60 o C and allowed to stir for 24 h. The vial was then opened and crude 1 H NMR was collected. A complex mixture of products was observed. 34 Table 1 Entry 3 In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (4.97 mg, 0.0075 mmol, 1.5 mol %), tmphen (3.5 mg, 0.015 mmol, 3 mol %), and B 2 pin 2 (152.4 mg, 0.6 mmol, 1.2 equiv) were weighed into separate test tubes and N,N - dimethylacetamide (43.5 mg, 0.5 mmol, 1 equiv) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B 2 pin 2 . The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B 2 pin 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was then transferred into the test tube containing tmphen and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre - heated to 60 o C and allowed to stir for 24 h. The vial was then opened and crude 1 H NMR was collected. A complex mixture of products was observed. 35 Table 1 Entry 4 In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (4.97 mg, 0.0075 mmol, 1.5 mol %), L1 (2.2 mg, 0.015 mmol, 3 mol %), and B 2 pin 2 (152.4 mg, 0.6 mmol, 1.2 equiv) were weighed into separate test tubes and N,N - dimethylacetamide (43.5 mg, 0.5 mmol, 1 equiv) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B 2 pin 2 . The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B 2 pin 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was then transferred into the test tube containing L1 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing p rocedure. The conical vial was then sealed and placed in an aluminum block pre - heated to 60 o C and allowed to stir for 24 h. The vial was then opened and crude 1 H NMR was collected. A conversion to the desired product of 10% was observed. 36 Table 1 Entry 5 In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (4.97 mg, 0.0075 mmol, 1.5 mol %), L1 (2.2 mg, 0.015 mmol, 3 mol %), and B 2 pin 2 (152.4 mg, 0.6 mmol, 1.2 equiv) were weighed into separate test tubes and N,N - dimethylacetamide (43.5 mg, 0.5 mmol, 1 equiv) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B 2 pin 2 . The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B 2 pin 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was then transferred into the test tube containing L1 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre - heated to 80 o C and allowed to stir for 24 h. The vial was then opened and crude 1 H NMR was collected. A conversion to the desired product of 10% was observed. 37 Table 1 Entry 6 In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (4.97 mg, 0.0075 mmol, 1.5 mol %), L2 (3.7 mg, 0.015 mmol, 3 mol %), and B 2 pin 2 (152.4 mg, 0.6 mmol, 1.2 equiv) were weighed into separate test tubes and N,N - dimethylacetamide (43.5 mg, 0.5 mmol, 1 equiv) was weighed into a 5 mL conical via l equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B 2 pin 2 . The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B 2 pin 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was then transferred into the test tube containing L2 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre - heated to 60 o C and allowed to stir for 24 h. The vial was then opened and crude 1 H NMR was collected. A conversion to the desired product of 60% was observed. 38 Table 1 Entry 7 In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (4.97 mg, 0.0075 mmol, 1.5 mol %), L3 (3.1 mg, 0.015 mmol, 3 mol %), and B 2 pin 2 (152.4 mg, 0.6 mmol, 1.2 equiv) were weighed into separate test tubes and N,N - dimethylacetamide (43.5 mg, 0.5 mmol, 1 equiv) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.2 mL THF. T he resulting solution was then transferred into the test tube containing B 2 pin 2 . The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B 2 pin 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was then t ransferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre - h eated to 60 o C and allowed to stir for 24 h. The vial was then opened and crude 1 H NMR was collected. A conversion to the desired product of 91% was observed. 39 Table 1 Entry 8 In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (4.97 mg, 0.0075 mmol, 1.5 mol %), L4 (3.6 mg, 0.015 mmol, 3 mol %), and B 2 pin 2 (152.4 mg, 0.6 mmol, 1.2 equiv)were weighed into separate test tubes and N,N - dimethylacetamide (43.5 mg, 0.5 mmol, 1 equiv) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B 2 pin 2 . The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B 2 pin 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was then transferred into the test tube containing L4 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed b y the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre - heated to 60 o C and allowed to stir for 24 h. The vial was then opened and crude 1 H NMR was collected. A complex mixture of products was observed. 40 Table 1 Entry 9 In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (4.97 mg, 0.0075 mmol, 1.5 mol %), L5 (2.3 mg, 0.015 mmol, 3 mol %), and B 2 pin 2 (152.4 mg, 0.6 mmol, 1.2 equiv)were weighed into separate test tubes and N,N - dimethyla cetamide (43.5 mg, 0.5 mmol, 1 equiv) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B 2 pin 2 . The co ntents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B 2 pin 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was then transferred into the test tube containing L5 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre - heated to 60 o C and allowed to stir for 24 h . The vial was then opened and crude 1 H NMR was collected. A conversion to the desired product of 11% was observed. 41 Table 1 Entry 10 In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (4.97 mg, 0.0075 mmol, 1.5 mol %), L3 ( 3.1 mg, 0.015 mmol, 3 mol %), and B 2 pin 2 (152.4 mg, 0.6 mmol, 1.2 equiv) were weighed into separate test tubes and N,N - dimethylacetamide (43.5 mg, 0.5 mmol, 1 equiv) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B 2 pin 2 . The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B 2 pin 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre - heated to 80 o C and allowed to stir for 7.5 h. The vial was then opened and crude 1 H NMR was collected. Full conversion to the desired product was observed. 42 Table 1 Entry 11 In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (4.97 mg, 0.0075 mmol, 1.5 mol %), L3 (3.1 mg, 0.015 mmol, 3 mol %), and HBpin (128.0 mg, 1.0 mmol, 2.0 equiv) were weighed into separate test tubes and N,N - dimethylacetamide (43.5 mg, 0.5 mmol, 1 equiv) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir (OMe)(cod)] 2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing HBpin. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the HBpin containing test tube. The solution of [I r(OMe)(cod)] 2 and HBpin was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre - heated to 80 o C and allowed to stir for 24 h. The vial was then opened and crude 1 H NMR was collected. A complex mixture of products was observed. 43 Table 1 Entry 12 In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (4.97 mg, 0.0075 mmol, 1.5 mol %), L3 (3.1 mg, 0.015 mmol, 3 mol %), and B 2 eg 2 (85.0 mg, 0.6 mmol, 1.2 equiv) were weighed into separate test tubes and N,N - dimethylacetamide (43.5 mg, 0.5 mmol, 1 equiv) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B 2 eg 2 . The contents of the first test tube were rinsed three times (~0. 2 mL/rinse) and added to the B 2 pin 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 eg 2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre - heated to 80 o C and allowed to stir for 24 h. The vial was then opened and crude 1 H NMR was collected. Only starting amide was observed. 44 Table 1 Entry 13 For the procedure see below. A conversion to the desired product of 85% was observed after 24 h. Effect of Catalyst Loading Stock solutions of [Ir(OMe)cod] 2 and ligand L3 were prepared to ensure accuracy in the amount of catalyst added. The procedure for the preparation of each stock solution is provided below. Preparation of [Ir(OMe)cod] 2 stock solution : In a test tube was weighed 66.3 mg of [Ir(OMe)cod] 2 . Then THF was used to transfer this compound from the test tube to a 4 mL volumetric flask. The flask was shaken until no solids were observed then filled with THF to exactly 4 mL. Preparation of ligand L3 stock solution: To a 2 mL volumetric flask was a dded 62.2 mg of ligand L3 . Then 1.5 mL THF was added and the flask was shaken to ensure the solution was well mixed. The flask was then filled with THF to exactly 2 mL. Ligand Loading 1.5 mol % [Ir(OMe)cod] 2 In a nitrogen filled glove box, B 2 pin 2 (152.3 mg, 0.6 mmol, 1.2 equiv) was weighed into a test tube and N,N - dimethylacetamide (43.5 mg, 0.5 mmol, 1.0 equiv) was weighed into a 5 mL conical reaction vial equipped with a stir bar. Added to the test tube was [Ir(OMe)cod] 2 (0.3 mL from the stock solution, 1.5 mol %) and ligand L3 (0.1 mL from the 45 stock solution, 3 mol %) with a microsyringe. The resulting solution was then transferred to the 5 mL reaction vial followed by rinsing the test tube with approximately 0.4 mL of T HF three times. The reaction vials were then sealed and placed in an aluminum block pre - heated to 80 C and allowed to stir. Aliquots were removed at 1 h, 4 h, and 7.5 h, 10 h, and 24 h. Proton NMR of each aliquot was obtained and the conversion of starting material to product was calculated. This data is displayed in the scheme above. Ligand Loading 1.0 mol % [Ir(OMe)cod] 2 In a nitrogen filled glove box, B 2 pin 2 (152.3 mg, 0.6 mmol, 1.2 equiv) was weighed into a test tube and N,N - dimethylacetamide (43.5 mg, 0.5 mmol, 1.0 equiv) was weighed into a 5 mL conical reaction vial equipped with a stir bar. Added to the test tube was [Ir(OMe)cod] 2 (0.2 mL from the stock solution, 1.0 mol %) and ligand L3 (0.066 mL from the stock solution, 2 mol %) with a microsyringe. The resulting solution was then transferred to the 5 mL reaction vial followed by rinsing the test tube with approximately 0.4 mL of THF three times. The reaction vials were then sealed and placed in an aluminum block pre - heated to 80 C and allowed to stir. Aliquots were removed at 1 h, 4 h, and 7.5 h, 10 h, and 24 h. Proton NMR of each aliquot was obtained and the conversion of starting material to product was calculated. This data is displayed in the scheme above. 46 Ligand Loading 0.75 mol % [Ir(OMe)cod] 2 In a nitrogen filled glove box, B 2 pin 2 (152.3 mg, 0.6 mmol, 1.2 equiv) was weighed into a test tube and N,N - dimethylacetamide (43.5 mg, 0.5 mmol, 1.0 equiv) was weighed into a 5 mL conical reaction vial equipped with a stir bar. Added to the test tube was [Ir(OMe)cod] 2 (0.15 m L from the stock solution, 0.75 mol %) and ligand L3 (0.05 mL from the stock solution, 1.5 mol %) with a microsyringe. The resulting solution was then transferred to the 5 mL reaction vial followed by rinsing the test tube with approximately 0.4 mL of THF three times. The reaction vials were then sealed and placed in an aluminum block pre - heated to 80 C and allowed to stir. Aliquots were removed at 1 h, 4 h, and 7.5 h, 10 h, and 24 h. Proton NMR of each aliquot was obtained and the conversion of starting m aterial to product was calculated. This data is displayed in the scheme above. Ligand Loading 0.5 mol % [Ir(OMe)cod] 2 In a nitrogen filled glove box, B 2 pin 2 (152.3 mg, 0.6 mmol, 1.2 equiv) was weighed into a test tube and N,N - dimethylacetamide (43.5 mg, 0.5 mmol, 1.0 equiv) was weighed into a 5 mL conical reaction vial equipped with a stir bar. Added to the test tube was [Ir(OMe)cod] 2 (0.10 mL from the stock solution, 0.5 mol %) and ligand L3 (0.033 mL from 47 the stock solut ion, 1 mol %) with a microsyringe. The resulting solution was then transferred to the 5 mL reaction vial followed by rinsing the test tube with approximately 0.4 mL of THF three times. The reaction vials were then sealed and placed in an aluminum block pre - heated to 80 C and allowed to stir. Aliquots were removed at 1 h, 4 h, and 7.5 h, 10 h, and 24 h. Proton NMR of each aliquot was obtained and the conversion of starting material to product was calculated. This data is displayed in the scheme above. Data for Table 2 Borylation of N,N - dimethylacetamide (1a) In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B 2 pin 2 (1.5 mmol, 1.5 equiv, 380.9 mg) were we ighed into separate test tubes and N,N - dimethylacetamide (1 mmol, 1 equiv, 87.1 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.2 mL THF. The resulting solution was then transferre d into the test tube containing B 2 pin 2 . The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B 2 pin 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre - heated to 80 o C and allowed to stir for 24 h. The vial was then opened and 48 crude 1 H NMR was collected. The desired product was observed in 100% conversion. The crude reaction mixture was passed through deactivated silica (35% H 2 O w/w) with a gradient solvent system of 10% to 15% MeOH in EtOAc. T his afforded 132.7 mg (62% , mp: 116 - 121 o C ) of isolated 2 a which matched previously reported spectra. 42 1 H NMR (500 MHz, CDCl 3 H 3.07 (s, 1H), 2.40 (s, 1H), 2.14 ( s , 1H), 1.19 (s, 4H). Borylation of N,N - dimethylpropionamide (1b) In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B 2 pin 2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and N,N - dimethylpropionamide (1 mmol, 1 equiv, 101.2 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B 2 pin 2 . The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B 2 pin 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was then transferred into the test tube containing L3 and the rinsing procedure was r epeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre - heated to 80 o C and allowed to stir for 24 h . The vial was then opened and c rude 1 H NMR was collected. The desired product was observed in 100% conversion. The crude reaction mixture was passed through deactivated silica (35% H 2 O 49 w/w) with a gradient solvent system of 10% to 15% MeOH in EtOAc. This afforded 174. 9 mg (77% , mp = 118 - 120 o C ) of isolated 2 b . 1 H NMR (500 MHz, CDCl 3 H 3.05 (s, 3H), 2.43 2.36 (m, 4H), 1.21 (t, J = 7.6 Hz, 3H), 1.19 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C . 177.48, 79.88, 35.51, 25.13, 22.07, 8.70. 11 B NMR (176 MHz, CDCl 3 B 12.2 (s) Borylation of N,N - dimethylisobutyramide (1c) In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B 2 pin 2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and N,N - dimethylisobutyramide (1 mmol, 1 equiv, 115.2 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.2 mL TH F. The resulting solution was then transferred into the test tube containing B 2 pin 2 . The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B 2 pin 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was th en transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block p re - heated to 80 o C and allowed to stir for 24 h. The vial was then opened and crude 1 H NMR was collected. The desired product was observed in 75% conversion. The crude reaction mixture was passed through deactivated silica (35% H 2 O 50 w/w) with a gradient sol vent system of 10% to 15% MeOH in EtOAc. This afforded 132.6 mg (55% , mp = 81 - 85 o C ) of isolated 2c . 1 H NMR (500 MHz, CDCl 3 H 3.09 (s, 3H), 2.77 (hept, J = 6.8 Hz, 1H), 2.40 (s, 2H), 1.27 (s, 3H), 1.20 (s, 3H), 1.19 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C . 180.15, 79.75, 35.42, 27.36, 25.12, 18.47. 11 B NMR (176 MHz, CDCl 3 B 12.37 (s) Borylation of N,N - dimethylpentanamide (1d) In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B 2 pin 2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and N,N - dimethylpentanamide (1 mmol, 1 equiv, 129.2 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B 2 pin 2 . The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B 2 pi n 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing pro cedure. The conical vial was then sealed and placed in an aluminum block pre - heated to 80 o C and allowed to stir for 24 h. The vial was then opened and crude 1 H NMR was collected. The desired product was observed in 100% conversion. The crude reaction mixt ure was passed through deactivated silica (35% H 2 O 51 w/w) with a gradient solvent system of 10% to 15% MeOH in EtOAc. This afforded 202.8 mg (80% , mp = 104 - 106 o C ) of isolated 2d . 1 H NMR (500 MHz, CDCl 3 H 3.05 (s, 1H), 2.38 (s, 2H), 2.36 (t, J = 8.0 Hz, 2H), 1.65 (p, J = 7.8 Hz, J = 7.4 Hz, 2H), 1.37 (h, J = 7.4 Hz, 2H), 1.18 (s, 12H), 0.91 (t, J = 7.4 Hz, 3H). 13 C NMR (125 MHz, CDCl 3 C 176.93, 79.78, 35.67, 28.15, 26.55, 25.13, 22.28, 13.57. 11 B NMR (176 MHz, CDCl 3 B 12.44 (s) Borylation of N,N - dimethylcyclopentanecarboxamide (1e) In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B 2 pin 2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and N,N - dimethylcyclopentanecarboxamide (1 mmol, 1 equiv, 141.2 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B 2 pin 2 . The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B 2 pin 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then seal ed and placed in an aluminum block pre - heated to 80 o C and allowed to stir for 24 h. The vial was then opened and crude 1 H NMR was collected. The desired product was observed 52 in 100% conversion. The crude reaction mixture was passed through deactivated sil ica (35% H 2 O w/w) with a gradient solvent system of 10% to 15% MeOH in EtOAc. This afforded 210.2 mg (79% , mp = 98 - 99 o C ) of isolated 2e . 1 H NMR (500 MHz, CDCl 3 H 3.06 (s, 3H), 2.83 (p, J = 8.0 Hz, 1H), 2.37 (s, 2H), 1.91 1.71 (m, 6H), 1.65 1.51 (m, 2H), 1.16 (s, 12H). 13 C NMR (125 MHz, CDCl 3 C 179.79, 79.72, 37.39, 35.59, 29.79, 25.87, 25.13. 11 B NMR (176 MHz, CDCl 3 B 12.31 (s) Borylation of N,N - dimethylcyclohexanecarboxamide (1f) In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B 2 pin 2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and N,N - dimethylcyclohexanecarboxamide (1 mmol, 1 equiv, 155.2 mg) was weighed int o a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B 2 pin 2 . The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B 2 pin 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL co nical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre - heated to 80 o C and allowed to stir for 24 h. The vial was then opened and crude 1 H NMR was collected. The desired product was observed 53 in 100% conversion. The crude reaction mixture was passed through deactivated silica (35% H 2 O w/w) with a gradient solvent system of 10% to 15% MeOH in EtOAc. This afforded 225.1 mg (80% , mp = 139 - 140 o C ) of isolated 2f . 1 H NMR (500 MHz, CDCl 3 H 3.07 (s, 3H), 2.44 (tt, J = 11.6, 3.5 Hz, 1H), 2.37 (s, 2H), 1.87 1.67 (m, 5H), 1.61 1.51 (m, 2H), 1.32 1.21 (m, 3H), 1.18 (s, 12H). 13 C NMR (125 MHz, CDCl 3 C 179.21, 79.68, 37.00, 35.43, 28.21, 25.34, 25.32, 25.14. 11 B NMR (176 MHz, CDCl 3 B 12.38 (s) Borylation of 1 - methylpyrrolidin - 2 - one (1g) In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B 2 pin 2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weig hed into separate test tubes and 1 - methylpyrrolidin - 2 - one (1 mmol, 1 equiv, 99.1 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.2 mL THF. The resulting solution was then transferr ed into the test tube containing B 2 pin 2 . The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B 2 pin 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre - heated to 80 o C and allowed to stir for 24 h. T he vial was then opened and crude 1 H NMR was collected. The desired product was observed in 33% conversion . 54 Borylation of 1 - methylpiperidin - 2 - one (1h) In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B 2 pin 2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and 1 - methylpiperidin - 2 - one (1 mmol, 1 equiv, 113.2 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B 2 pin 2 . The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B 2 pin 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre - heated to 80 o C and allowed to stir for 24 h. The vial was then opened and crude 1 H NMR was collected. The desired product was observed in 100% conversion. The crude reaction mixture was passed through deactivated silica (35% H 2 O w/w) with a gradient solv ent system of 10% to 15% MeOH in EtOAc. This afforded 107.1 mg (70% , mp = 127 - 131 o C ) of isolated 2h . 1 H NMR (500 MHz, CDCl 3 H 3.31 (t, J = 5.7 Hz, 2H), 2.49 (t, J = 6.2 Hz, 2H), 2.34 (t, J = 1.6 Hz, 2H), 1.90 1.75 (m, 4H), 1.19 (s, 12H). 13 C NMR (125 MHz, CDCl 3 C 173.93, 79.91, 47.82, 26.43, 25.15, 21.99, 19.45. 11 B NMR (176 MHz, CDCl 3 B 12.68 (s) 55 Borylation of 1 - methylazepan - 2 - one (1i) In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B 2 pin 2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and 1 - methylazepan - 2 - one (1 mmol, 1 equiv, 127.2 mg) was weighed into a 5 mL conical vial equipped with a sti r bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B 2 pin 2 . The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B 2 pin 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing proced ure. The conical vial was then sealed and placed in an aluminum block pre - heated to 80 o C and allowed to stir for 24 h. The vial was then opened and crude 1 H NMR was collected. The desired product was observed in 100% conversion. The crude reaction mixture was passed through deactivated silica (35% H 2 O w/w) with a gradient solvent system of 10% to 15% MeOH in EtOAc. This afforded 176.6 mg (70% , mp = 110 - 113 o C ) of isolated 2i which matched previously reported spectra. 42 1 H NMR (500 MHz, CDCl 3 H 3. 45 3.34 (m, 2H), 2.61 2.52 (m, 2H), 2.49 (s, 2H), 1.77 1.68 (m, 2H), 1.67 1.60 (m, 4H), 1.15 (s, 12H). 13 C NMR (125 MHz, CDCl 3 C 179.46, 79.83, 50.37, 31.19, 29.77, 26.32, 25.11, 22.11. 56 11 B NMR (176 MHz, CDCl 3 B 12.52 (s) Borylation of N - ethyl - N - methylacetamide (1j) In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B 2 pin 2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and N - ethyl - N - methylacetamide (1 mmol, 1 equiv, 101.2 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.2 mL TH F. The resulting solution was then transferred into the test tube containing B 2 pin 2 . The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B 2 pin 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was th en transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block p re - heated to 80 o C and allowed to stir for 24 h. The vial was then opened and crude 1 H NMR was collected. The desired product was observed in 100% conversion. The crude reaction mixture was passed through deactivated silica (35% H 2 O w/w) with a gradient so lvent system of 10% to 15% MeOH in EtOAc. This afforded 161.2 mg (71% , 149 - 153 o C ) of isolated 2j . 1 H NMR (500 MHz, CDCl 3 H 3.37 (q, J = 7.3 Hz, 2H), 2.36 (d, J = 1.5 Hz, 2H), 2.13 (t, J = 1.2 Hz, 3H), 1.20 (t, J = 7.4 Hz, 3H), 1.17 (s, 12H). 13 C NMR (125 MHz, CDCl 3 C 173.70, 79.86, 43.65, 25.12, 15.40, 12.65. 57 11 B NMR (176 MHz, CDCl 3 ): B 12.41 (s) Borylation of tert - butyl dimethylcarbamate (1k) In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B 2 pin 2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and tert - butyl dimethylcarbamate (1 mmol, 1 equiv, 145.2 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B 2 pin 2 . The contents of the first test tube were rinsed three times (~0.2 mL /rinse) and added to the B 2 pin 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical via l followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre - heated to 80 o C and allowed to stir for 24 h. The vial was then opened and crude 1 H NMR was collected. The desired product was observed in 47% convers ion. Crude 1 H NMR matched previous spectra. 83 Borylation of 1,3 - dimethyltetrahydropyrimidin - 2(1 H ) - one (1l) 58 In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B 2 pin 2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and 1,3 - dimethyltetrahydropyrimidin - 2(1 H ) - one (1 mmol, 1 equiv, 128.2 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B 2 pin 2 . The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B 2 pin 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing proce dure. The conical vial was then sealed and placed in an aluminum block pre - heated to 80 o C and allowed to stir for 24 h. The vial was then opened and crude 1 H NMR was collected. The desired product was observed in 100% conversion. The crude reaction mixtur e was passed through deactivated silica (35% H 2 O w/w) with a gradient solvent system of 10% to 15% MeOH in EtOAc. This afforded 227.4 mg (89% , mp = 165 - 172 o C ) of isolated 2l which matched previously reported spectra. 42 1 H NMR (500 MHz, CDCl 3 H 3.34 3.14 (m, 4H), 2.98 (s, 2H), 2.34 (s, 2H), 1.96 (p, J = 5.95, 2H), 1.18 (s, 12H). 13 C NMR (125 MHz, CDCl 3 C 159.52, 79.56, 46.55, 44.64, 36.01, 25.15, 20.93. 11 B NMR (176 MHz, CDCl 3 B 11.53 (s) 59 Borylation of N,N - dimethylbenzamide (1m) In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B 2 pin 2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and N,N - dimethylbenzamide (1 mmol, 1 equiv, 149.2 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B 2 pin 2 . The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B 2 pin 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre - heated to 80 o C and allowed to stir for 2 4 h. The vial was then opened and crude 1 H NMR was collected. The starting material was 100% consumed with the major product being the ortho borylated product. The spectra for 2m was in accordance with a previous report. 75 The spectra also showed diborylated mater ial in 1.2:1 ratio of mono:di - borylated. 60 Borylation of N,N - dimethyl - 3 - phenylpropanamide (1n) In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B 2 pin 2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and N,N - dimethyl - 3 - phenylpropanamide (1 mmol, 1 equiv, 177.3 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B 2 pin 2 . The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B 2 pin 2 containing test tube. T he solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial w as then sealed and placed in an aluminum block pre - heated to 80 o C and allowed to stir for 24 h. The vial was then opened and crude 1 H NMR was collected. The desired product was observed in 85% conversion. The crude reaction mixture was passed through deactivated silica (35% H 2 O w/w) with a gradient solvent system of 10% to 15% MeOH in EtOAc. This afforded 191.0 mg (63% , mp = 98 - 103 o C ) of isolated 1n . 1 H NMR (500 MHz, CDCl 3 H 7.34 7.27 (m, 2H), 7.24 7.22 (m, 1H), 7.21 7.15 (m, 2H), 3.0 5 2.97 (m, 2H), 2.93 (s, 3H), 2.71 2.60 (m, 2H), 2.39 (s, 2H), 1.21 (s, 12H). 13 C NMR (125 MHz, CDCl 3 C 175.84, 139.69, 128.72, 128.28, 126.64, 79.96, 35.54, 30.75, 30.59, 25.17. 61 11 B NMR (176 MHz, CDCl 3 B 13.09 (s) Borylation of 2,2,2 - trifluoro - N,N - dimethylacetamide (1o) In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (0.0075 mmol, 1.5 mol %, 4.9 mg), L3 (0.015 mmol, 3 mol %, 3.1 mg), and B 2 pin 2 (0.6 mmol, 1.2 equiv, 152.4 mg) were weighed into separate test tubes and 2,2,2 - trifluoro - N,N - dimethylacetamide (0.5 mmol, 1 equiv, 70.5 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was add ed ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B 2 pin 2 . The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B 2 pin 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an alu minum block pre - heated to 80 o C and allowed to stir for 21 h. The vial was then opened and crude 1 H NMR was collected. Only starting material was observed. Borylation of 3,3,3 - trifluoro - N,N - dimethylpropanamide (1p) 62 In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (0.0075 mmol, 1.5 mol %, 4.9 mg), L3 (0.015 mmol, 3 mol %, 3.1 mg), and B 2 pin 2 (0.6 mmol, 1.2 equiv, 152.4 mg) were weighed into separate test tubes and 3,3,3 - trifluoro - N,N - dimethylpropanamide (0.5 mmol, 1 equiv, 75.6 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B 2 pin 2 . The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B 2 pin 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre - heated to 80 o C and allowed to stir for 21 h. The vial was then opened and crude 1 H NMR was collected. Some starting material was consumed but the products were unclear. The spectra are shown in the final appendix. Borylation of N,N - diethylacetamide (1q) In a nitrogen filled glove box, [Ir(OMe)(cod)] 2 (0.0075 mmol, 1.5 mol %, 4.9 mg), L3 (0.015 mmol, 3 mol %, 3.1 mg), and B 2 pin 2 (0.75 mmol, 1.5 equiv, 190.5 mg) were weighed into separate test tubes and N,N - diethylacetamide (0.5 mmol, 1 equiv, 57.6 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)] 2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube 63 containing B 2 pin 2 . The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B 2 pin 2 containing test tube. The solution of [Ir(OMe)(cod)] 2 and B 2 pin 2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing p rocedure. The conical vial was then sealed and placed in an aluminum block pre - heated to 80 o C and allowed to stir for 21 h. The vial was then opened and crude 1 H and 11 B NMR were collected. In the 1 H NMR spectrum, starting material, B 2 pin 2 and borates mad e up most the material; however, some new peaks with complex multiplicity did appear. The 11 B NMR showed only two peaks corresponding to B 2 pin 2 at 30 ppm and borates at 22 ppm. Based on this data it was concluded that no product like material was formed un der these reaction conditions. Competitive Kinetic Isotope Effect Stock solutions of each of the reagents were used for these reactions, and the reaction was carried out in triplicate to ensure accuracy. The procedure for the preparation of each stock solution is provided below. Preparation of [Ir(OMe)cod] 2 stock solution : In a test tube was weighed 59.7 mg of [Ir(OMe)cod] 2 . Then THF was used to transfer this compound from the test tube to a 2 64 mL volumetric flask. The flask was shaken until no solids were observed then filled with THF to exactly 2 mL. Preparation of ligand L3 stock solution: To a 2 mL volumetric flask was a dded 37.3 mg of ligand L3 . Then 1.5 mL THF was added and the flask was shaken to ensure the solution was well mixed. The flask was then filled with THF to exactly 2 mL. Preparation of B 2 pin 2 stock solution : In a test tube was weighed 634.9 mg of B 2 pin 2 . Th en THF was used to transfer this compound from the test tube to a 5 mL volumetric flask. The flask was shaken until no solids were observed then filled with THF to exactly 5 mL. Preparation of N,N - dimethylacetamide 1 a stock solution : To a 2 mL volumetric f lask was added 261.4 mg of N,N - dimethylacetamide 1 a . Then 1.5 mL THF was added and the flask was shaken to ensure the solution was well mixed. The flask was then filled with THF to exactly 2 mL. Preparation of N,N - dimethylacetamide - d 6 1 a - d 6 stock solution: To a 2 mL volumetric flask was added 106.2 mg of N,N - dimethylacetamide - d 6 1 a - d 6 . Then 1.5 mL THF was added and the flask was shaken to ensure the solution was well mixed. The flask was then filled with THF to exactly 2 mL. In a nitrogen filled g love box, [Ir(OMe)cod] 2 (0.1 mL from the stock solution, 1.5 mol %) and B 2 pin 2 (0.2 mL from the stock solution, 0.1 mmol, 1 equiv) were added to three separate 3 mL conical reaction vials equipped with stir bars. To these solutions was then added ligand L3 (0.1 mL from the stock solution, 3 mol %). Then to each of the three reaction vessels was added N,N - dimethylacetamide 1 a (0.1 mL from the stock solution, 0.15 mmol, 1.5 equiv) and N,N - dimethylacetamide - d 6 1 a - d 6 (0.263 mL, 0.15 mmol, 1.5 equiv). The reacti on vials were then sealed and placed in an aluminum block pre - heated 65 to 60 o C and allowed to stir. Aliquots from each reaction vessel were removed at 2 h, 3 h, and 4 h and the ratio of 2 a to 2 a - d 5 was obtained by GC/MS analysis. The average of these data points is 5.0. 2.8: Notes: Anshu Yadav is thanked for significant contributions to this project. 66 APPENDIX 67 1 H NMR (500 MHz, CDCl 3 ) 68 13 C NMR (125 MHz, CDCl 3 ) 69 29 Si NMR (99 MHz, CDCl 3 ) 70 1 H NMR (500 MHz, CDCl 3 ) 71 13 C NMR (125 MHz, CDCl 3 ) 72 29 Si NMR (99 MHz, CDCl 3 ) 73 1 H NMR (500 MHz, CDCl 3 ) 74 13 C NMR (125 MHz, CDCl 3 ) 75 1 H NMR (CDCl 3 , 500 MHz) 76 1 H NMR (CDCl 3 , 500 MHz) 77 13 C NMR (CDCl 3 , 126 MHz) 78 11 B NMR (CDCl 3 , 160 MHz) 79 1 H NMR (CDCl 3 , 500 MHz) 80 13 C NMR (CDCl 3 , 126 MHz) 81 11 B NMR (CDCl 3 , 160 MHz) 82 1 H NMR (CDCl 3 , 500 MHz) 83 11 B NMR (CDCl 3 , 160 MHz) 84 13 C NMR (CDCl 3 , 126 MHz) 85 1 H NMR (CDCl 3 , 500 MHz) 86 11 B NMR (CDCl 3 , 160 MHz) 87 13 C NMR (CDCl 3 , 126 MHz) 88 1 H NMR (CDCl 3 , 500 MHz) 89 11 B NMR (CDCl 3 , 160 MHz) 90 13 C NMR (CDCl 3 , 126 MHz) 91 1 H NMR (CDCl 3 , 500 MHz) 92 11 B NMR (CDCl 3 , 160 MHz) 93 13 C NMR (CDCl 3 , 126 MHz) 94 1 H NMR (CDCl 3 , 500 MHz) 95 13 C NMR (CDCl 3 , 126 MHz) 96 11 B NMR (CDCl 3 , 160 MHz) 97 1 H NMR (CDCl 3 , 500 MHz) 98 13 C NMR (CDCl 3 , 126 MHz) 99 11 B NMR (CDCl 3 , 160 MHz) 100 1 H NMR (CDCl 3 , 500 MHz) 101 13 C NMR (CDCl 3 , 126 MHz) 102 11 B NMR (CDCl 3 , 160 MHz) 103 1 H NMR (CDCl 3 , 500 MHz) 104 13 C NMR (CDCl 3 , 126 MHz) 105 11 B NMR (CDCl 3 , 160 MHz) 106 1 H NMR (CDCl 3 , 500 MHz) 107 REFERENCES 108 REFERENCES (1) Boronic acids: preparation and applications in organic synthesis and medicine ; Wiley - VCH Verlag GmbH: Weinheim, 2005. (2) Miyaura, N.; Suzuki, A. Chem. Rev. 1995 , 95 (7), 2457. (3) Jana, R.; Pathak, T. P.; Sigman, M. S. Chem. Rev. 2011 , 111 (3), 1417. (4) Scott, H. K.; Aggarwal, V. K. Chemistry 2011 , 17 (47), 13124. (5) Doucet, H. Eur. J. O rg. Chem. 2008 , 2008 (12), 2013. (6) Borissenko, L.; Groll, M. Chem. Rev. 2007 , 107 (3), 687. (7) Touchet, S.; Carreaux, F.; Carboni, B.; Bouillon, A.; Boucher, J. - L. Chem. Soc. Rev. 2011 , 40 (7), 3895. (8) Trippier, P. C.; McGuigan, C. Med. Chem. Commun. 2010 , 1 (3), 183. (9) Baker, S. J.; Ding, C. Z.; Akama, T.; Zhang, Y. - K.; Hernandez, V.; Xia, Y. Future Med. Chem. 2009 , 1 (7), 1275. (10) Baker, S. J.; Tomsho, J. W.; Benkovic, S. J. Chem. Soc. Rev. 2011 , 40 (8), 4279. (11) Das, B. C.; Thapa, P.; Karki, R.; Schinke, C.; Das, S.; Kambhampati, S.; Banerjee, S. K.; Van Veldhuizen, P.; Verma, A.; Weiss, L. M.; Evans, T. Future Med. Chem. 2013 , 5 (6), 653. (12) James, T. D.; Sandanayake, K. R. A. S.; Shinkai, S. An gew. Chem. Int. Ed Engl. 1996 , 35 (17), 1910. (13) Fossey, J. S.; James, T. D. In Reviews in Fluorescence 2007 ; Geddes, C. D., Lakowicz, J. R., Eds.; Springer New York: New York, NY, 2009; pp 103 118. (14) In Supramolecular Chemistry ; Gale, P. A., Steed, J. W., Eds.; John Wiley & Sons, Ltd: Chichester, UK, 2012; Vol. 35, p 1911. (15) Myung, J.; Kim, K. B.; Crews, C. M. Med. Res. Rev. 2001 , 21 (4), 245. (16) Smoum, R.; Rubinstein, A.; Dembitsky, V. M.; Srebnik, M. Chem. Rev. 2012 , 112 (7), 4156. (17) Soloway, A. H.; Tjarks, W.; Barnum, B. A.; Rong, F. - G.; Barth, R. F.; Codogni, I. 109 M.; Wilson, J. G. Chem. Rev. 1998 , 98 (4), 1515. (18) Barth, R. F.; Mi, P.; Yang, W. Cancer Commun. 2018 , 38 (1), 35. (19) Yang, W.; Gao, X.; Wa ng, B. Med. Res. Rev. 2003 , 23 (3), 346. (20) Bross, P. F.; Kane, R.; Farrell, A. T.; Abraham, S.; Benson, K.; Brower, M. E.; Bradle y, S.; Gobburu, J. V.; Goheer, A.; Lee, S. - L.; Leighton, J.; Liang, C. Y.; Lostritto, R. T.; McGuinn, W. D.; Morse, D. E.; Rahman, A.; Rosario, L. A.; Verbois, S. L.; Williams, G.; Wang, Y. - C.; Pazdur, R. Clin. Cancer Res. 2004 , 10 (12 Pt 1), 3954. (21) Groll, M.; Berkers, C. R.; Ploegh, H. L.; Ovaa, H. Structure 2006 , 14 (3), 451. (22) Gentile, M.; Offidani, M.; Vigna, E.; Corvatta, L.; Recchia, A. G.; Morabito, L.; Morabito, F.; Gentili, S. E xpert Opin. Investig. Drugs 2015 , 24 (9), 1287. (23) Snyder, H. R.; Kuck, J. A.; Johnson, J. R. J. Am. Chem. Soc. 1938 , 60 (1), 105. (24) Brown, H. C.; Bhat, N. G.; Somayaji, V. Organometallics 1983 , 2 (10), 1311. (25) Brown, H. C.; Cole, T. E. Organ ometallics 1983 , 2 (10), 1316. (26) Brown, H. C.; Srebnik, M.; Cole, T. E. Organometallics 1986 , 5 (11), 2300. (27) Burgess, K.; Ohlmeyer, M. J. Chem. Rev. 1991 , 91 (6), 1179. (28) Semba, K.; Fujihara, T.; Terao, J.; Tsuji, Y. Tetrahedron 2015 , 71 (15), 2183. (29) Smith, J. R.; Collins, B. S. L.; Hesse, M. J.; Graham, M. A.; Myers, E. L.; Aggarwal, V. K. J. Am. Chem. Soc. 2017 , 139 (27), 9148. (30) Beenen, M. A.; An, C.; Ellman, J. A. J. Am. Chem. Soc. 2008 , 130 (22), 6910. (31) Laitar, D. S.; Tsui, E. Y.; Sad ighi, J. P. J. Am. Chem. Soc. 2006 , 128 (34), 11036. (32) Zhou, N.; Yuan, X. - A.; Zhao, Y.; Xie, J.; Zhu, C. Angew. Chem. Int. Ed Engl. 2018 , 130 (15), 4054. (33) Yang, C. - T.; Zhang, Z. - Q.; Tajuddin, H.; Wu, C. - C.; Liang, J.; Liu, J. - H.; Fu, Y.; Czy zewska, M.; Steel, P. G.; Marder, T. B.; Liu, L. Angew. Chem. Int. Ed Engl. 2012 , 124 (2), 543. (34) Bose, S. K.; Brand, S.; Omoregie, H. O.; Haehnel, M.; Maier, J.; Bringmann, G.; Marder, T. B. ACS Catal. 2016 , 6 (12), 8332. 110 (35) Neeve, E. C.; Geier, S. J.; Mkhalid, I. A. I.; Westcott, S. A.; Marder, T. B. Chem. Rev. 2016 , 116 (16), 9091. (36) Palmer, W. N.; Obligacion, J. V.; Pappas, I.; Chirik, P. J. J. Am. Chem. Soc. 2016 , 138 (3), 766. (37) Murphy, J. M.; Lawrence, J. D.; Kawamura, K.; Incarvito, C.; Hartwig, J. F. J. Am. Chem. Soc. 2006 , 128 (42), 13684. (38) Chen, H.; Schlecht, S.; Semple, T. C.; Hartwig, J. F. Science 2000 , 287 (5460), 1995. (39) Angew. Chem. Int. Ed. 2001 , 40 (11), 2168. (40) Lawrence, J. D.; Takahashi, M.; Bae, C.; Hartwig, J. F. J. Am. Chem. Soc. 2004 , 126 (47), 15334. (41) Hartwig, J. F.; Cook, K. S.; Hapke, M.; Incarvito, C. D.; Fan, Y.; Webster, C. E.; Hall, M. B. J. Am. Chem. Soc. 2005 , 127 (8), 2538. (42) Kawamorita, S.; Miyazaki, T.; Iwai, T.; Ohmiya, H.; Sawamura, M. J. Am. Chem. Soc. 2012 , 134 (31), 12924. (43) Ishiyama, T. ; Ishida, K.; Takagi, J.; Miyaura, N. Chem. Lett. 2001 , 30 (11), 1082. (44) Waltz, K. M.; Hartwig, J. F. J. Am. Chem. Soc. 2000 , 122 (46), 11358. (45) Chen, H.; Hartwig, J. F. Angew. Chem. Int. Ed. 1999 , 38 , 3391. (46) Boebel, T. A.; Hartwig, J. F. Organometallics 2008 , 27 (22), 6013. (47) Li, Q.; Liskey, C. W.; Hartwig, J. F. J. Am. Chem. Soc. 2014 , 136 (24), 8755. (48) Murakami, R.; Tsunoda, K.; Iwai, T.; Sawamura, M. Chem. Eur. J. 2014 , 20 (41), 13127. (49) Miyamura, S.; Araki, M.; Suzuki, T.; Yamaguchi, J.; Itami, K. Angew. Chem. Int. Ed. 2015 , 54 (3), 846. (50) Xu, L.; Wang, G.; Zhang, S.; Wang, H.; Wang, L.; Liu, L.; Jiao, J.; Li, P. Tetrahedron 2017 , 73 (51), 7123. (51) He, J.; Shao, Q.; Wu, Q.; Yu, J. - Q. J. Am. Chem. Soc. 2017 , 139 (9), 3344. (52) He, J.; Jiang, H.; Takise, R.; Zhu, R. - Y.; Chen, G.; Dai, H. - X.; Dhar, T. G. M.; Shi, J.; Zhang, H.; Cheng, P. T. W.; Yu, J. - Q. Angew. Chem. Int. Ed. 2016 , 55 (2), 785. (53) Zhang, L. - S.; Chen, G.; Wang, X.; Guo, Q. - Y.; Zhang, X. - S.; Pan, F.; Chen, K.; 111 Shi, Z. - J. Angew. Chem. Int. Ed. 2014 , 53 (15), 3899. (5 4) Jayasundara, C. R. K.; Sabasovs, D.; Staples, R. J.; Oppenheimer, J.; Smith, M. R., III; Maleczka, R. E., Jr. Organometallics 2018 , 37 (10), 1567. (55) Larsen, M. A.; Wilson, C. V.; Hartwig, J. F. J. Am. Chem. Soc. 2015 , 137 (26), 8633. (56) Liskey, C. W.; Hartwig, J. F. J. Am. Chem. Soc. 2013 , 135 (9), 3375. (57) Ohmura, T.; Torigoe, T.; Suginome, M. J. Am. Chem. Soc. 2012 , 134 (42), 17416. (58) Huang, G.; Kalek, M.; Liao, R. - Z.; Himo, F. Chem. Sci. 2015 , 6 (3), 1735. (59) O hmura, T.; Sasaki, I.; Torigoe, T.; Suginome, M. Organometallics 2016 , 35 (11), 1601. (60) Torigoe, T.; Ohmura, T.; Suginome, M. J. Org. Chem. 2017 , 82 (6), 2943. (61) Ohmura, T.; Torigoe , T.; Suginome, M. Organometallics 2013 , 32 (21), 6170. (62) Iwai, T.; Harada, T.; Hara, K.; Sawamura, M. Angew. Chem. Int. Ed. 2013 , 52 (47), 12322. (63) Liskey, C. W.; Hartwig, J. F. J. Am. Chem. Soc. 2012 , 134 (30), 12422. (64) Cho, S. H.; Hartwig, J. F. Chem. S ci. 2014 , 5 (2), 694. (65) Cho, S. H.; Hartwig, J. F. J. Am. Chem. Soc. 2013 , 135 (22), 8157. (66) Larsen, M. A.; Cho, S. H.; Hartwig, J. J. Am. Chem. Soc. 2016 , 138 (3), 762. (67) Wang, G.; Liu, L.; Wang, H.; Ding, Y. - S.; Zhou, J.; Mao, S.; Li, P. J. Am. Chem. Soc. 2017 , 139 (1), 91. (68) Kawamorita, S.; Murakami, R.; Iwai, T.; Sawamura, M. J. Am. Chem. Soc. 2013 , 135 (8), 2947. (69) Mita, T.; Ikeda, Y.; Michigami, K.; Sato, Y. Chem. Commun. 2013 , 49 (49), 5601. (70) Cook, A. K.; Schimler, S. D.; Matzger, A. J.; Sanford, M. S. Science 2016 , 351 (6280), 1421. (71) Smith, K. T.; Berritt, S.; González - Moreiras, M.; Ahn, S.; Smith, M. R., 3rd; Baik, M. - H.; Mindiola, D. J. Science 2016 , 351 (6280), 1424. 112 (72) Ahn, S.; Sorsche, D.; Berritt, S.; Gau, M. R.; Mindiola, D. J.; Baik, M. - H. ACS Catal. 2018 , 8 (11), 10021. (73) Hyland, S. N.; Meck, E. A.; Tortosa, M.; Clark, T. B. Tetrahedron Lett. 2019 , 60 (16), 1096. (74) Bisht, R.; Chattopadhyay, B. J. Am. Chem. Soc. 2016 , 138 (1), 84. (75) Ghaffari, B.; Preshlock, S. M.; Plattner, D. L.; Staples, R. J.; Maligres, P. E.; Krska, S. W.; Maleczka, R. E., Jr.; Smith, M. R., III J . Am. Chem. Soc. 2014 , 136 (41), 14345. (76) Chattopadhyay, B.; Dannatt, J. E.; Andujar - De Sanctis, I. L.; Gore, K. A.; Maleczka, R. E., Jr.; Singleton, D. A.; Smith, M. R., III J. Am. Chem. Soc. 2017 , 139 (23), 7864. (77) Smith, M. R., III; Bisht, R.; Haldar, C.; Pandey, G.; Dannatt, J. E.; Ghaffari, B.; Maleczka, R. E., Jr.; Chattopadhyay, B. ACS Catal. 2018 , 8 (7), 6216. (78) ; Wiley - Interscience, 2006. (79) Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.; Murphy, J. M.; Hartwig, J. F. Chem. Rev. 2010 , 110 (2), 890. (80) Boller, T. M.; Murphy, J. M.; Hapke, M.; Ishiyama, T.; Miyaura, N.; Hartwig, J. F. J. Am. Chem. Soc. 2005 , 127 (41), 14263. (81) Uson, R.; Oro, L. A.; Cabeza, J. A. Inorg. Synth. 1985 , 23 , 126 - 130. (82) The MSU Mass Spectrometry facility are thanked for obtaining ESI+ HRMS. (83) Lima, F.; Sharma, U. K.; Grunenberg, L.; Saha, D.; Johannsen, S.; Sedelmeier, J.; Vander Eycken, E. V.; Ley, S. V. Angew. Chem. Int. Ed. 2017 , 56, 15136 - 15140. 113 Chapter 3: Ortho Selective Borylation of Phenols 3.1: Introduction Catalytic C H functionaliza tion is a powerful synthetic tool that offers innate synthetic advantages in terms of step, atom and redox economy, provided that the catalytic functionalization is both active and selective. 1 Simultan eously obtaining both high activity and high selectivity, however, can be challenging. It might be supposed that strong catalyst - substrate interactions are best for obtaining selectivity. However, strong work, for example, has demonstrated that the involvement of highly stable metallacycle intermediates significantly limits the range of reactive substrates; weak coordination leads to higher reactivity, providing access to a large variety of functionalizat ions. 2,3 Weak interactions can be fully sufficient of 2.7 kcal/mol is sufficient for 99:1 selectivity at 25 °C. C H functionalizations using non - covalent direction for uncharged substrates have been identified in hydrophobic hydrophobic interactions between cyclodextrins and steroids in C H hydroxylations , 4 7 host - guest size - differentiated C H activations, 8,9 and hydrogen bond directed C H functionalizations. 10 14 Hydrogen bonding has also proven effective in directing the hydroformylation of alkenes 15,16 and the hydrometalation of unsymmetrical a lkynes. 17,18 Recently, significant progress has been made in demonstrating the viability of anion - 19,20 though experimental quantification of these interactions is challenging. 21 The importance of non - covalent interactions is routinely seen in organocatalysis and biological systems. 22,23 The regioselectivity of metal catalyzed C H borylations (CHBs) of the sp 2 - hybridized C H bonds in arenes is usually sterically determined. 24 To comple ment this selectivity, the direction of CHBs toward sterically encumbered positions has been of 114 great interest. 25 27 The most common approach makes use of strong substrate - catalyst interactio ns, particularly chelation of a directed metalating group (DMG) to the metal center to achieve ortho borylation (Scheme 1 8 ). This has been accomplished using surface supported phosphines, 28 certain mon odentate ligands, 29 hemilabile bidentate ligands, 30 and P,Si - N,Si - and N,B - bidentate anionic ligands. 31,32 Alternative approaches to ortho borylation shown in Scheme 1 8 include relay direction with silanes, 33 which is also useful in directed C H silylations. 34,35 Scheme 18 : Selected Mechanisms for Directed Borylation Weaker interactions have been exploited in CHBs as well. For example, the N H protons in aniline carbamates can hydrogen bond to the oxygen atoms of Bpin ligands, favoring ortho borylation. Similar interactions were exploited in traceless ortho borylations of ani lines and aminopyridines. 36,37 Recently, meta - selective borylations of imines have been proposed to proceed via a related outer - sphere mechanism. 38 These hydrogen bonding concepts have been extended to meta - selective CHBs where pendant ureas on dipyridyl ligands function as dual hydrogen bond donors (Scheme 1 8 ). 39 115 Kanai and coworkers descri bed ortho borylation of aryl thioethers directed by a Lewis acid - base interaction between the thiol ether in the substrate and a boron glycolate linked to the bipyridine ligand. 40,41 Interestingly , high meta selectivity was achieved only rely on interactions between pendant groups on the bipyridine ligand with matching functionality in the substrate to direct CH B to the desired site. While extending traceless protection chemistry to phenols, where the OH group would be converted to OBpin prior to C H borylation, enhanced ortho borylation was observed. In this paper, experimental and computational results implica te a subtle electrostatic attraction between O Bglycolate and bipyridyl groups as the origin for ortho direction (Scheme 1 8 ). Calculated stabilizations of ortho transition states were sensitive to the steric nature of the boryl ligand; thus, greatly enhanc ed selectivities resulted by redesigning the diboron reagent. 3.2: An Unusual Selectivity in Phenol Borylations We first examined the borylation of phenol with two equivalents of HBpin, expecting that C 6 H 5 OBpin would form rapidly, and the ensuing borylatio n of this intermediate would afford a mixture of m - and p - HOC 6 H 4 Bpin upon workup (Scheme 19 ). Scheme 19 : Phenol Borylation with Traceless Protection Using the commonly employed ligand/precatalyst combination dtbpy/[Ir(OMe)(cod)] 2 (dtbpy = 4,4´ - tert - butyl - 2,2´ - bipyridine, cod = 1,5 - cyclooctadiene), 42 a striking amount of ortho borylation was found (o:m+p = 15:85). This was sur prising since 116 anisole affords only 4% of the ortho borylation product and an OBpin group is sterically larger than an OMe group. The propensity for borylation ortho to OBpin was more apparent in comparisons between 4 - substituted phenols and 4 - substituted a nisoles. Chart 1 clearly shows preference for borylation ortho to OBpin relative to OMe. 43 Borylation of 4 - chlorophenol was highly ortho selective, while the CHB for 4 - cyanophenol was not. Despite the low selectivity for CHB in 4 - cyanophenol ortho to OBin was more pronounced than CHB ortho to OMe. For both the phenol and anisole borylation ortho to F predominated, although borylation ortho to OBpin increased slightly. With these results in hand, we knew that some favorable interaction between the OBpin and the catalyst was occuring; however, the general synthetic utility and nature of this interaction was unknown. CHB for a range of phenols was surveyed to get a sense of the synthetic utility of this tra nsformation. Figure 1 : C H Borylation of 4 - Substituted Phenols and Anisoles 3.3: Substrate Scope of Phenol Borylation with B 2 pin 2 The yields for the products in Table 3 range from excellent to mo derate. This process is operationally simpler than the relay - directed approach highlighted in Scheme 1 8 33,44 as the relay directed approach requires (i) catalyzed O silylation of the phenol with 117 Et 2 SiH 2 to generate ArOSiEt 2 H, (ii) conversion of Bpin intermediates to BF 3 K salts, and (iii) removal of the O SiEt 2 H directing groups affording high yields of pure BF 3 K phenols. The Bpin to BF 3 K conversion was required because protodeboronation 45 of C Bpin occurred concomitantly with Si O cleavage. Table 3 : Ortho borylation of Substituted Phe nols with B 2 pin 2 a a For details see section 3.10, yields are isolated. b Entry 1a was obtained in 74% yield on a 2 g scale using 1.5 mol % Ir - catalyst, 3.0 mol % dtbpy and 0.7 equiv B 2 pin 2 . c The Bpin product was converted to the BF 3 K salt for isolation. d Conversion and isomer ratio based on GC - FID. e Approximately 18% diborylated product was observed. The loadings in Table 3 are higher than we normally employ because the reactions were run at small scale (see secti on 3.10 for details). To test for scalability at lower catalyst loadings compound 1a was prepared from 2.0 g of 4 - chorophenol, 1.1 equiv 118 HBpin, and 0.7 equiv B 2 pin 2 , using 1.5 mol % [Ir(OMe)(cod)] 2 and 3 mol % dtbpy. After workup, 2.9 g (74% yield) of 1a w as isolated as a colorless solid. With the exception of products 1c , 1o , and 1p , ortho selectivity is high (>99%) and is not degraded by substitution ortho to OH. However, the substrates in Table 3 where high selectivity is observed have substituents at th e 4 - position that are larger than CN or F. While the traceless CHB transformation in Table 3 - directed ortho CHBs of phenols, the ortho selectivity for their protocol was high for all substrates, including phenol. This motiva ted us to better identify features that contribute to the selectivities in the traceless reaction. The reaction of 4 - methoxyphenol is particularly perplexing because the catalyst exclusively selects the position ortho to OBpin yielding 1d when given a choi ce of CHB ortho to the smaller OMe substituent. To gain further insight into this unusual directing effect, we turned to theory. 3.4: Theoretical Investigation of the Directing Effect in Phenol Borylations Our initial computational model substrate was 4 - MeO - C 6 H 4 OBpin´ ( 3 ), where pin´ = meso - butylene glycolate. The OBpin´ model was chosen because its methyl groups can partially reflect the steric interactions present in the full catalytic system. A series of transition structures for the bo rylation of 3 with (bpy)Ir(Beg) 2 (Bpin´) were located in M06 calculations employing an SDD basis set on Ir and a 6 - 31G* basis set on the other atoms. The lowest - energy structures for borylation ortho to OBpin´ ( TS3 - OBpin´ anti ) and ortho to OMe ( TS3 - OMe anti ) refers to the arrangement of the methyl or Bpin´ groups relative to the bpy ligand; a structure with the Bpin´ syn to the bpy was higher in energy. A striking observation was that TS3 - OBpin ´ anti is enthalpically favored over TS3 - OMe anti by 5.2 kcal/mol. The steric 119 interaction of the two pin´ groups in TS3 - OBpin´ ant i restricts their motion, so that TS3 - OMe anti is entropically favored, but TS3 - OBpin´ anti remains favored in free - energy by 1.8 kcal/mol. From the model, the isomer ratio is predicted to be 92:8, favoring 1d . Since the minor isomer is not experimentally detected in borylation of 4 - methoxyphenol, the model underestimates G rel for TS3 - OMe . Figu re 2 : Transition state structures for borylation of 4 - MeO - C 6 H 4 OBpin´ with (bpy)Ir(Beg) 2 (Bpin´). We sought to identify the structural effect responsible for the stunning enthalpic preference for TS3 - OBpin´ anti over TS3 - OMe anti . An unusual feature of both structures is a rotation of the OBpin´ or OMe groups out of the plane of the aromatic ring when ortho to the C H insertion. The B27 O26 C ipso C a and the C Me O30 C ipso C a dihedral angles in TS3 - OBpin´ anti and TS3 - OMe anti 90°. This rotation is not present in the ground state of 4 - MeO - C 6 H 4 OBpin´ nor when the OBpin or OMe groups are meta to the C H insertion. In the orthogonal orientations, the dipoles associated with the B27 O26 C ipso , 120 B27 - O43 - C, and C Me O30 C ipso angles are oriented towards the proximal bpy pyridine ring, suggesting an electrostatic interaction. To assess the role of this electrostatic interaction in the selectivity, the NPA (Natural Population Analysis) charges were calculated with selected values given in Figure 1 (see section 3.10 for full listing). The NPA charges on O43 and O26 in TS3 - OBpin´ anti are significantly more negative than O30 in TS3 - OMe anti , and O43 has the shortest contacts to H47 and H49, which are partially positively charged. Figure 3 : Calculated electrostatic potential surfaces for TS3 - anti (left) and TS3 - OMe anti (right). Electrostatic potential maps were calculated and are shown in Figure 2. From the maps, O43 is best positioned to maximize attraction to the positive charge of H47 and H49, while it is expected that O26 and O30 offer similar degrees of electrostatic stabili zation to their respective transition states. 3.5 Experimental Support for Electrostatic Directing Effect If the electrostatic model is correct, electronic alteration of the bipyridine ligand should affect selectivities. To test this, borylations of phen ol were performed with 4,4´ - substituted bipyridines 4a d . As shown in Chart 2, there is a clear trend for increasing ortho selectivity as the bipyridine ligand is made more electron deficient. Moreover, high 121 linearity was observed when plotting the energy vs Hammett parameters of the R groups on the bipyridines. Figure 4 : Ligand Effects on Borylation Selectivity Although this provides experimental evidence to the proposed electrostatic interactions, the improved ortho selectivity for 4d comes at the expense of catalytic activity. 42 Thus, we sought another solution for improving borylation selectivities that provided synthetically useful reactivit y and selectivity for substrates like 4 - fluorophenol. 3.6: Strategy to Increase Ortho Selectivity A closer inspection of the calculated TSs revealed significant distortions of the arene geometries for TS3 - OBpin´ anti and TS3 - OMe anti (Figure 3). Specifically , steric pressure from the Bpin´ groups pushes the arene away from the activating Beg group in TS3 - OBpin´ anti . This results in elongation of H act act in TS3 - OBpin´ anti (2.360 Å) relative to TS3 - OMe anti (2.159 Å), which translates to a 23% reduction in the natural bond order between H act and B act . 122 Figure 5 : Calculated inner coordination spheres, selected metrical parameters, and natural bond orders for TS3 - OBpin´ anti and TS3 - O Me anti (left) and TS5 - OBeg anti and TS5 - F (right). Since Beg is the smallest glycolatoboryl ligand, we hypothesized that transition states with Beg ligands should be less distorted, allowing for TS stabilization by removing the steric clash between Bpin gr oups, which simultaneously would allow for maximum TS stabilization from H act act interactions. To test this hypothesis, 4 - F - C 6 H 4 OBeg was chosen to assess borylation ortho to OBeg or F, which is the smallest non - hydrogen substituent. TSs for borylation or tho to F ( TS5 - F ) and ortho to OBeg ( TS5 - OBeg anti ) were calculated and are shown in Figure 4. The geometries of the inner coordination sphere for borylation ortho to OBeg or F are nearly identical as seen by the equivalent C ipso - Ir - B act angles for TS5 - OBeg a nti and TS5 - F (Figure 3). This indicates that the reduced repulsion between Beg groups restores the H act act interaction in TS5 - OBeg anti . Further, TS5 - OBeg anti has short contacts between O31 H43 and O31 H54 (Figure 4). The OBeg B to pyridine centroid dist ance in TS5 - OBeg anti is 0.3 shorter than the corresponding distance in TS3 - OBpin´ anti , thus increasing the strength of the electrostatic interaction and further stabilizing TS5 - OBeg anti . Interestingly, TS5 - OBeg syn , where the OBeg is directly below a pyridine ring in 123 the dtbpy ligand, is 1.6 kcal/mol above the anti configuration. We attribute this to the significant distortion of the bipyridine ligand which is seen in the 22.2° dihedral between the dtbpy nitrogens c ompared to the 5.6° dihedral in TS5 - OBeg anti . This twisting of the dtbpy ligand results in a small elongation of the Ir N bond (0.03 ), but more importantly, N8 has poorer overlap with the Ir center. Stabilizing Lewis acid/base interactions between a bory l ligand and the substrate were considered as well. Figure 6 : Transition states for borylation of 4 - F - C 6 H 4 OBeg with (dtbpy)Ir(Beg) 3 . There is a distance of 3.22 between an O of B act and B of the OBeg group in TS5 - OBeg anti . The energy of this interaction is below the 0.05 kcal/mol threshold for second order perturbation theory analysis of the Fock matrix in the NBO basis. Although a TS was located (Figure 4, TS5 - OBeg syn - Beg , between O26 in the OB eg group and B14 in a spectator boryl ligand, it lies 2.3 kcal/mol above TS5 - OBeg anti . Despite searching, no Lewis acid/base interaction could be found which provided a lower TS than TS5 - OBeg anti . Overall, TS5 - OBeg anti is favored over TS5 - F by 1.5 kcal/mol a 93:7 isomer ratio favoring borylation ortho to OBeg at 25 °C. 124 3.7: Experimentally Testing Computational Results with B 2 eg 2 We tested the computational prediction by preparing B 2 eg 2 from B 2 (OH) 4 and ethylene glycol. The room temperature rates were too slow for direct comparison to the 4 ). The Beg products were converted to pinacolate esters, which were easier to purify. Most importantly, CHB with B 2 eg 2 as the boron source provided exclusively ortho borylated products. Such exclusive regiochemical outcomes, validated the theoretically driven decision to employ B 2 eg 2 in these reactions. That said, we were not disappointed by the fact that that the experimentally observed ortho borylation of 4 - fluorophenol ( 1r ) was higher than that predicted by theory. Table 4 : ortho - Borylation of Phenols with B 2 eg 2 a a For details see section 3.10. Yields are isolated mono - borylated products. Diborylated products were not isolated. b Mono:o,o´ - diborylation = 82:18. c B 2 eg 2 used as 1.2 equiv, mono:o,o´ - diborylation = 89:11. d Mono:o,o ´ - diborylation = 81:19. e Mono:o,o´ - diborylation = 85:15. Diborylated side products were observed for some of the substrates but were readily separable by chromatography. Given the previously reported difficulties in isolating ortho borylated phenols, the yields here of pure products are highly satisfactory. 125 Remarkably, toluene was an excellent solvent for the reactions, as competing solvent borylation was not observed. 3.8: Understanding the Optimal Borylation Conditions with B 2 eg 2 In addition to a change in the boron sources, the Table 4 conditions include the addition of triethylamine, without which CHB conversions for all phenols plateaued at 50%. Unlike HBpin, which is the most stable HBgly (gly = glycolate) compound, HBeg rapidly disproportionates at room temperature to B 2 H 6 and B 2 eg 3 (Scheme 20 ). However, Shore showed that HBeg reacts with NMe 3 3 , which is stable at room temperature. 46,47 Our initial hypothesis was that HBeg generated during the formation of ArylOBeg rapidly disproportionated, and the B 2 H 6 produced converted free ArylOH to B(OAryl) 3 and H 2 , as shown in red in Scheme 20 . Aryl borates rapidly hydrolyze to the corresponding phenol and boric acid upon work - up, which would account for the recovery of unreacted phenols (Scheme 20 ). It is noteworthy that XBeg compounds (X = halogen) are not stable. They associate in solution, which has been attributed to Lewis acid - interactions. 48 Acid - catalyzed side reactions of B 2 H 6 or HBeg could be deleterious. If this is the case, triethylamine could trap these reactive species as their NEt 3 adducts before they wreak havoc on the desired borylation pathway (Scheme 20 ). 126 Scheme 20 : Minimizing B(OAryl) 3 Formation Given the low stability of HBeg, its addition to phenols to form ArylOBeg species is not synthetically applicable. Thus, an important question is Are ArylOBeg intermediates formed in the reaction? Owing to the stability of HBpin, we generate ArylOBpin and clearly demonstrate they are competent in the B 2 pin 2 ortho CHBs of phenols (Table 3 ). However, we wished to show that ArylOBpin species form without the addition of pinacolborane. To demo nstrate this, [Ir(dtbpy)(COE)(Bpin) 3 ] (COE = cyclooctene) in cyclohexane - d 12 was added to 4 - FC 6 H 4 OH which provided quantitative conversion to 4 - FC 6 H 4 OBpin by 19 F, 11 B and 1 H NMR. Proton resonances closely matching previously reported [Ir(dtbpy)(H)(Bpin) 2 (C OE)] were also observed. 49 This shows that even without pinacolborane, ArylOBpin species form under the reaction conditions. This indicated that HBpin pregeneration of ArylOBpin is an unnecessary step used in Table 3 . However, it should be noted that an extra equivalent of boron is needed as the first borylation will occur at the phenolic hydrogen. More pertinent to the original question, these data provide support that ArylOBeg species form without HBe g addition because it is assumed borylations with B 2 eg 2 proceed through a similar trisboryl species, [Ir(dtbpy)Beg 3 ]. To conclusively determine if the ArylOBeg species forms and assess whether formation of B(OAryl) 3 led to the low conversions, we prepared 2 - F - C 6 H 4 OBeg from 2 - 50 the 11 B{ 1 H} NMR spectrum of the product is typical for B(OR) 3 species. However, 11 B NMR is not well - suited for quantifying how many B(OR) 3 species are present. In contrast, 19 F is an s = ½ nucleus with a broad NMR spectral window. As such, by employing a 127 fluorinated phenol as our substrate we could use 19 F NMR to determine the number of B(OR) 3 species. In practice the 19 132.6) in the 19 F{ 1 H} spectrum prepared b y - maximum) and low levels of impurities these impurities could deactivate the CHB catalyst and/or catalyze detrimental s ide - reactions. Thus, we sought an alternative means for generating ArylOBeg species. Based on our previous result with the isolated trisboryl catalyst and the fact that iridium is known to readily form Ir Bgly species, we theorized that [Ir(cod)(OMe)] 2 cou ld catalyze the formation of ArylOBeg with B 2 eg 2 and phenol. Excitingly, full conversion to 2 - FC 6 H 4 OBeg was achieved with 1 mol % [Ir(cod)(OMe)] 2 and B 2 eg 2 . With a facile route to ArylOBeg species, 4 - FC 6 H 4 OBeg was generated and spectra were collected. To test if this species is formed under the reaction conditions 4 - fluorophenol was added to an NMR tube containing a toluene - d 8 solution of B 2 eg 2 , [Ir(OMe)(cod)] 2 , and dtbpy (Scheme 21 ). As judged by 19 F NMR, this resulted in rapid, quantitative conversion to 4 - F - C 6 H 4 OBeg at room temperature. Interestingly, the 11 B NMR spectrum displayed a doublet at 28.9 ppm, which collapsed in the 11 B{ 1 H} spectrum. This is consistent with generation of HBeg. Ultimately, these experiments confirmed two key pieces of informati on: (i) ArylOBeg species are rapidly formed under the reaction conditions and (ii) diborane does not consume phenol substrates as we had originally hypothesized. As, B 2 eg 3 and B 2 H 6 , the disproportionation products from HBeg, are not known to be active for CHB, we conclude amine stabilized HBeg participate in Ir - catalyzed borylation. 128 Scheme 21 : NMR Tube Reaction Showing ArylOBeg Species Although our experiments supported the role of triethylamine as an HBeg stabilizer, we recognize that the change in conditions between Tables 3 and 4 may also affect the selectivities. As a control, the borylation of 4 - fluorophenol with B 2 pin 2 as the boron source was carried out in toluene with and without triethylamine (Chart 3). In toluene without triethylamine, the meta product was more pronounced (m/o 97:3) than that observed in cyclohexane (m/o 90:10). Given that the addition of triethylamine actually pushed the reaction further toward the meta product, the selectivities in Table 4 must solely be due to the change in the boron source and not a change in the conditions (i.e. solvent or additives). Figure 7 : Key Controls with B 2 pin 2 B 2 eg 2 was critical to the high ortho selectivity as selectivities for some substrates in Table 4 with B 2 pin 2 were poor. The directing difference between Bpin and Beg is best illustrated by the selectivity for 4 - fluorophenol where borylation with B 2 pin 2 gives a 9:1 ratio favoring borylation ortho to F, while B 2 eg 2 gives exclusive borylation ortho to O (Scheme 22 ). Theory predicts the same trend. 129 Scheme 22 : Boron Reagent Effects on Borylation of 4 - Fluorophenol It is important to recognize that disentangling the directing effect of substituents on the phenols and the electrostatic interactions proposed herein is challenging. However, the borylation of phenol itself is instructional as phenol bears no other substituent to affect regiochemical outcomes, and it is a substrate where the calculated electrostatic interaction should be maximized. Yet, borylation with B 2 eg 2 provided only orth o borylated products ( 1q ), whereas with B 2 pin 2 a ratio of 15:85 (o:m+p) was observed. - systems are well established. - system interacts with a positively charge partner. 51 Nevertheless, - systems can be stabilizing. 21,52 Moreover, in neutral pyridine - 2,6 - dicarboxylic acid dimers , the interaction of the electron - rich carboxylic acid group of one pyridine with the electron - - system of its partner, is stabilizing by - 7.3 kcal/mol. 53 This further supports our h ypothesis that electrostatic interactions dictate the regioselectivity observed experimentally and supported by computational studies. 3.9: Conclusions To summarize, iridium - catalyzed ortho directed borylation of phenols using the most commonly employed li gand/precatalyst combination dtbpy/[Ir(OMe)(cod)] 2 is 130 reported. After traceless protection of phenols with Bpin, CHB ortho to OBpin occurred in a higher than expected portion. This phenomenon was explored in various phenol substrates that showed the requir ement for a substrate larger than fluorine in the 4 - position for good ortho selectivity. To further understand the origins of this ortho selectivity, we turned to calculations, which revealed an electrostatic interaction between the partially positive bipy ridine ligand and partially negative OBpin in the substrate. Seeking experimental evidence for this calculated interaction, electron rich through electron poor bipyridine ligands were used in the borylation of phenol. Electron poor ligands produced higher ortho selectivity thus supporting the calculations; however, the electron poor ligands provided low reactivity. Further study of the calculations suggested that a steric interaction from the methyl groups on the OBpin species distorted the transition state geometries, but by changing to OBeg these geometries significantly restored. Thus, borylations with B 2 eg 2 were conducted and high ortho selectivity was achieved. Overall, by simply changing the boron source high ortho selectivity was achieved which we att ribute to a unique electrostatic interaction between the bipyridine ligand and OBeg group. While the interactions revealed here are fortuitous, the demonstration that they can be both sterically and electronically modulated augurs favorably for deploying t hem in specifically designed catalysts. Efforts towards this end are underway in our laboratories. 3.10: Experimental Details General Information All commercially available chemicals were used as received unless otherwise indicated. Bis(pinacolato)diboron (B 2 pin 2 ) and tetrahydroxydiboron (B 2 (OH) 4 ) were generously supplied by BoroPharm, Inc., and pinacolborane (HBpin) was purchased from 131 Anderson Chemical Company. Bis( 4 - 1,5 - cyclooctadiene) - di - µ - methoxy - diiridium(I) [Ir(OMe)(cod)] 2 was prepared per literature procedure. 54 Cyclohexane (CyH) and tetrahydrofuran (THF) were refluxed over sodium/benzophenone ketyl, distilled and degassed. Column chromatography was performed on Silia P - Flash silica gel. Thin layer chromatography was perfo rmed on 0.25 mm thick aluminum - backed silica gel plates and visualized with ultraviolet light ( = 254 nm) and iodine. Sublimations were conducted with a water - cooled cold finger. 1 H, 13 C, 11 B and 19 F NMR spectra were recorded on 500 MHz NMR spectrometers. The boron bearing carbon atom was not observed due to quadrupolar relaxation unless otherwise reported . All coupling constants are apparent J values measured at the indicated field strengths in Hertz (s = singlet, d = doublet, t = triplet, q = quartet, dd = doublet of doublets, ddd = doublet of doublet of doublets, bs = broad singlet). High - resolution mass spectra (HRMS) were obtained at the Michigan State University Mass Spectrometry Service Center using electrospray ionization (ESI+ or ESI - ). 55 Melting points were measured in a capillary melting point apparatus and are uncorrected. Borylation of Anisole: The reaction was conducted using a modified version of a previously reported procedure. 56 In a glovebox, a 5 mL conical vial was charged with anisole (435 µ L, 4.0 132 mmol), [Ir(OMe)(cod)] 2 (10 mg, 1.5 mol %, 0.015 mmol), dtbpy (8 mg, 3 mol %, 0.03 mmol), B 2 Pin 2 (254 mg, 1.0 mmol, 0.25 equiv), and dry cyclohexane (3 mL). The vial was sealed and placed in a preheated aluminum block at 80°C for 16 h. The volatiles were then removed on the rotary evaporator, and the conversion and isomer ratios were determined by GC /FID. The results are shown in the scheme. Borylation of 4 - Chloroanisole with B 2 pin 2 (2a): In a glovebox, a 5 mL conical vial was charged with [Ir(OMe)(cod)] 2 (10 mg, 1.5 mol %, 0.015 mmol), dtbpy (8 mg, 3.0 mol %, 0.03 mmol), and B 2 pin 2 (127 mg, 0.25 equiv, 0.5 mmol). Dry cyclohexane (3 mL, 0.33 M) was added under an inert atmosphere and stirred for 5 min at room temperature. To this mixture, 4 - chloroanisole ( 285 mg, 2.0 mmol) was added. The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C and was stirred for 4 h. GC analysis showed that conversion of the starting material was 47% based on the consumption of the an isole and the borylation results 57 are as follows: mono/di = 92/08, ortho/meta (wrt OMe) = 71/29. Borylation of 4 - Fluoroanisole with B 2 pin 2 (2c): 133 In a glovebox, a 5 mL conical vial was charged with [Ir(OMe)(cod)] 2 (10 mg, 1.5 mol %, 0.015 mmol), dtbpy (8 mg, 3.0 mol %, 0.03 mmol), and B 2 pin 2 (127 mg, 0.25 equiv). Dry cyclohexane (3 mL) was added under an inert atmosphere and stirred for 5 min at room temperature. To this mixture, 4 - fluoroanisole (252 mg, 2.0 mmol) was added. The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C and was stirred for 4 h. GC analysis showed that conversion of the starting material was 49% based on the consumption of the anisole and the bory lation results are as follows: mono/di = 93/07, ortho/meta (wrt OMe) = 06/94. Borylation of 4 - Chlorophenol with limiting B 2 pin 2 (1a) In a glovebox, a 5 mL conical vial was charged with 4 - chlorophenol (257 mg, 2.0 mmol) and pinacolborane (319 µ L, 1.1 equ iv) and stirred for 5 min at room temperature. To this mixture, [Ir(OMe)(cod)] 2 (10 mg, 1.5 mol %, 0.015 mmol), dtbpy (8 mg, 3.0 mol %, 0.03 mmol), and B 2 pin 2 (127 mg, 0.25 equiv) was charged. Dry cyclohexane (3 mL, 0.33 M) was added under an inert atmosphere. The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C. The reaction mixture was stirred for 4 h. The boryla tion results are shown in the scheme above and the results are based on GC and 1 H NMR data. Borylation of 4 - Cyanophenol with limiting B 2 pin 2 (1b) 134 In a glovebox, a 5 mL conical vial was charged with 4 - cyanophenol (238 mg, 2.0 mmol) and pinacolborane (319 L, 1.1 equiv) and stirred for 5 min at room temperature. To this mixture, [Ir(OMe)(cod)] 2 (10 mg, 1.5 mol %, 0.015 mmol), dtbpy (8 mg, 3.0 mol %, 0.03 mmol), and B 2 pin 2 (127 mg, 0.25 equiv) was charged. Dry cyclohexane (3 mL, 0.33 M) was added under an in ert atmosphere. The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C. The reaction mixture was stirred for 4 h. The borylation results are shown in the scheme and the results are based on the 1 H NMR d ata of cr ude material . Borylation of 4 - Fluorophenol with limiting B 2 Pin 2 (1c) In a glovebox, a 5 mL conical vial was charged with 4 - fluorophenol (224 mg, 2.0 mmol) and pinacolborane (319 µ L, 1.1 equiv) and stirred for 5 min at room temperature. To this mixture, [Ir(OMe)(cod)] 2 (10 mg, 1.5 mol %, 0.015 mmol), dtbpy (8 mg, 3.0 mol %, 0.03 mmol), and B 2 pin 2 (127 mg, 0.25 equiv) was charged. Dry cyclohexane (3 mL, 0.33 M) was added under an inert atmosphere. The vial was capped with a teflon pressure cap 135 and placed into a pre - heated aluminum block at 80 o C. The reaction mixture was stirr ed for 4 h. The borylation results are shown in the scheme and the results are based on GC data. General Procedure for the Synthesis of Pinacolborane (Bpin) Protected Phenols: In a glovebox, under a N 2 atmosphere phenols (0.5 mmol) and HBpin (0.55 mmol) w ere charged in a 2 mL vial, and stirred at room temperature for 1 - 30 min until the reaction was complete (quantitative conversion). The product was characterized by 1 H, 13 C, and 11 B NMR in air - free, screw cap NMR tubes. Preparation of 2 - (4 - chlorophenoxy) - 4 ,4,5,5 - tetramethyl - 1,3,2 - dioxaborolane: The Bpin protected 4 - chlorophenol was prepared as described in the general procedure using 4 - chlorophenol (0.5 mmol, 64 mg) and HBpin (80 µ L, 0.55 mmol). 1 H NMR (500 MHz, CDCl 3 ): H 7.22 - 7.19 (m, 2H), 7.03 6.99 (m, 2H), 1.30 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C 152.0, 129.2, 128.1, 120.8, 83.7, 24.6. 11 B NMR (176, MHz, CDCl 3 ): B 21.7 (s). Preparation of 2 - (4 - bromophenoxy) - 4,4,5,5 - tetramethyl - 1,3,2 - dioxaborolane: 136 The Bpin protected 4 - bromophenol was prepared as described in the general procedure using 4 - bromophenol (87 mg, 0.5 mmol) and HBpin (80 µ L, 0.55 mmol). 1 H NMR (500 MHz, CDCl 3 ): H 7.37 7.33 ( m , 2H), 6.97 6.95 (m, 2H), 1.29 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C 152.6, 132.2, 121.4, 115.7, 83.8, 24.6. 11 B NMR (176, MHz, CDCl 3 ): B 21.7 (s). Preparation 4,4,5,5 - tetramethyl - 2 - (p - tolyloxy) - 1,3,2 - dioxaborolane: The Bpin protected p - cresol was prepared as described in the general procedure using the p - cresol (54 mg, 0.5 mmol) and HBpin (80 µ L, 0.55 mmol). 1 H NMR (500 MHz, CDCl 3 ): H 7.07 - 7.03(m, 2H), 6.97 6.93 (m, 2H), 2.27 (s, 3H) 1.29 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C 151.2, 132.4, 129.8, 119.2, 83.5, 24.6, 20.7 11 B NMR (176, MHz, CDCl 3 ): B 21.7 (s). Preparation of 2 - (4 - (tert - butyl)phenoxy) - 4,4,5,5 - tetramethyl - 1,3,2 - dioxaborolane: The Bpin protected 4 - tert - butylphenol was prepared as described in the general procedu re using 4 - tert - butylphenol (75 mg, 0.5 mmol) and HBpin (80 µ L, 0.55 mmol). 137 1 H NMR (500 MHz, CDCl 3 ): H 7.28 - 7.25 (m, 2H), 7.01 6.98 (m, 2H), 1.30 (s, 12H), 1.30 (s, 9H) . 13 C NMR (125 MHz, CDCl 3 ): C 151.0, 145.6, 126.1, 118.8, 83.5, 34.2, 31.5, 24.6. 11 B NMR (176, MHz, CDCl 3 ): B 21.7 (br s). Preparation of 4,4,5,5 - tetramethyl - 2 - (4 - (trifluoromethyl)phenoxy) - 1,3,2 - dioxaborolane: The Bpin protected 4 - trifluorophenol was prepared as described in the general procedure using 4 - trifluorophenol (81 mg, 0.5 mmol) and HBpin (80 µ L, 0.55 mmol). 1 H NMR (500 MHz, CDCl 3 ): H 7.55 (d, J = 8.8 Hz, 2H), 7.21 (d, J = 8.8 Hz, 2H), 1.34 (s, 12H) . 13 C NMR (125 MHz, CDCl 3 ): C 156.0, 126.8 (q, 3 J C - F = 3.9 Hz), 125.3 (q, 2 J C - F = 32 Hz), 124.2, (q, 1 J C - F = 271 Hz), 119.8, 83.9, 24.6. 11 B NMR (176, MHz, CDCl 3 ): B 21.7 (s). Preparation of ethyl 4 - ((4,4,5,5 - tetramethyl - 1,3,2 - dioxaborolan - 2 - yl)oxy)benzo ate: 138 The Bpin protected ethyl 4 - hydroxybenzoate was prepared as described in the general procedure using ethyl 4 - hydroxybenzoate (83 mg, 0.5 mmol) and HBpin (80 µ L, 0.55 mmol). 1 H NMR (500 MHz, CDCl 3 ): H 7.98 - 7.94 (m, 2H), 7.14 7.10 (m, 2H), 4.32 (q, J = 7.1 Hz, 2H), 1.34 (t, J = 7.2 Hz, 3H), 1.30 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C 166.2, 157.2, 131.3, 125.4, 119.4, 83.9, 60.7, 24.6, 14.3. 11 B NMR (176, MHz, CDCl 3 ): B 21.7 (br s). Preparation of 2 - ( 4 - bromo - 2 - chlorophenoxy) - 4,4,5,5 - tetramethyl - 1,3,2 - dioxaborolane: The Bpin protected 4 - bromo - 2 - chlorophenol was prepared as described in the general procedure using 4 - bromo - 2 - chlorophenol (104 mg, 0.5 mmol) and HBpin (80 µ L, 0.55 mmol). 1 H NMR (500 MHz , CDCl 3 ): H 7.52 (d, J = 2.4 Hz, 1H), 7.31 (dd, J = 8.6, 2.5 Hz, 1H), 7.07 (d, J = 8.6 Hz, 1H), 1.29 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C 148.9, 132.7, 130.7, 126.4, 122.6, 115.9, 84.2, 24.6. 11 B NMR (176, MHz, CDCl 3 ): B 21.6 (s). Preparation of 2 - (2,4 - dichlorophenoxy) - 4,4,5,5 - tetramethyl - 1,3,2 - dioxaborolane: 139 The Bpin protected 2,4 - dichlorophenol was prepared as described in the general procedure using 2,4 - dichlorophenol (82 mg, 0.5 mmol) and HBpin (80 µ L, 0.55 mmol). 1 H NMR (50 0 MHz, CDCl 3 ): H 7.35 ( J = 2.4 Hz, 1H), 7.14 (dd, J = 8.6, 2.6 Hz, 1H), 7.08 (d, J = 8.8 Hz, 1H), 1.29 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C 148.5, 129.8, 127.8, 126.0, 122.1, 117.1, 84.2, 24.6. 11 B NMR (176, MHz, CDCl 3 ): B 21.6 (s). Preparation of 2 - (3,4 - d i methylphenoxy) - 4,4,5,5 - tetramethyl - 1,3,2 - dioxaborolane: The Bpin protected 3,4 - dimethylphenol was prepared as described in the general procedure using 3,4 - dimethylphenol (61 mg, 0.5 mmol) and HBpin (80 µ L, 0.55 mmol). 1 H NMR (500 MHz, CDCl 3 ): H 7.03 (d, J = 8.3 Hz, 1H), 6.87 (d, J = 2.5 Hz, 1H), 6.84 (dd, J = 8.2, 2.6 Hz, 1H), 2.21 (s, 3H), 2.17 (s, 3H), 1.29 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C 151.4, 137.6, 131.2, 130.2, 120.7, 116.6, 83.4, 24.6, 19.9, 19.0. 11 B NMR (176, MHz, CDCl 3 ): B 21.8 (s). 140 Preparation of 2 - (4 - chloro - 3 - methylphenoxy) - 4,4,5,5 - tetram ethyl - 1,3,2 - dioxaborolane: The Bpin protected 4 - chloro - 3 - methylphenol was prepared as described in the general procedure using 4 - chloro - 3 - methylphenol (71 mg, 0.5 mmol) and HBpin (80 µ L, 0.55 mmol). 1 H NMR (500 MHz, CDCl 3 ): H 7.19 (d, J = 8.6 Hz, 1H), 6.93 (d, J = 3.0 Hz, 1H), 6.85 (dd, J = 8.7, 3.1 Hz, 1H), 2.31 (s, 3H), 1.30 (s, 12H) 13 C NMR (125 MHz, CDCl 3 ): C 151.9, 136.9, 129.5, 128.4, 121.9, 118.3, 83.7, 24.6, 20.2 11 B NMR (176, MHz, CDCl 3 ): B 21.7 (s). Preparation of 2 - (2 - methox y - 4 - methylphenoxy) - 4,4,5,5 - tetramethyl - 1,3,2 - dioxaborolane: 141 The Bpin protected 2 - methoxy - 4 - methylphenol was prepared as described in the general procedure using 2 - methoxy - 4 - methylphenol (69 mg, 0.5 mmol) and HBpin (80 µ L, 0.55 mmol). 1 H NMR (500 MHz, C DCl 3 ): H 6.95 ( J = 8.1 Hz, 1H), 6.72 (s, 1H), 6.67 (d, 1H, J = 8.2 Hz), 3.83 (s, 3H), 2.31 (s, 3H), 1.30 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C 149.7, 140.7, 133.5, 121.1, 120.1, 113.0, 83.4, 55.6, 24.5, 21.3. 11 B NMR (176, MHz, CDCl 3 ): B 21.9 (s). Preparation of ethyl 3 - ((4,4,5,5 - tetramethyl - 1,3,2 - dioxaborolan - 2 - yl)oxy)benzoate: The Bpin protected ethyl 3 - hydroxybenzoate was prepared as descr ibed in the general procedure using ethyl 3 - hydroxybenzoate (83 mg, 0.5 mmol) and HBpin (80 µ L, 0.55 mmol). 1 H NMR (500 MHz, CDCl 3 ): H 7.77 - 7.74 (m, 2H), 7.35 (t, J = 8.0 Hz, 1H), 7.30 7.27 (m, 1H), 4.37 (q, J = 7.0 Hz, 2H), 1.39 (t, J = 7.0 Hz, 3H), 1.33 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C 166.2, 153.4, 131.8, 129.2, 124.3, 124.1, 120.7, 83.8, 61.0, 24.6, 14.3. 11 B NMR (176, MHz, CDCl 3 ): B 21.7 (s). 142 Preparation of 4,4,5,5 - tetramethyl - 2 - (o - tolyloxy) - 1,3,2 - dioxaborolane: The Bpin protected o - cresol was prepared as described in the general procedure using o - cresol (54 mg, 0.5 mmol) and HBpin (80 µ L, 0.55 mmol). 1 H NMR (500 MHz, CDCl 3 ): H 7.18 - 7.12 (m, 2H), 7.09 7.08 (m, 1H), 6.99 (ddd, J = 7.3, 7.3, 1.2 Hz, 1H), 2.25 (s, 3H), 1.33 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C 151.9, 130.9, 128.4, 126.7, 123.3, 119.4, 83.5, 24.6, 16.4 11 B NMR (176, MHz, CDCl 3 ): B 21.7 (s). Preparation of 4,4,5,5 - tetramethyl - 2 - phenoxy - 1 ,3,2 - dioxaborolane: The Bpin protected phenol was prepared as described in the general procedure using phenol (47 mg, 0.5 mmol) and HBpin (80 µ L, 0.55 mmol) and stirring for ten minutes. 1 H NMR (500 MHz, CDCl 3 ): H 7.29(t, J = 7.7 Hz, 2H) , 7.11 ( d, J = 7.9 Hz, 2H), 7.06 (t, J = 7.0 Hz, 1H), 1.33 (s, 12H) 13 C NMR (125 MHz, CDCl 3 ): C 153.4, 129.3, 123.1, 119.5, 83.5, 24.6. 11 B NMR (176, MHz, CDCl 3 ): B 21.7 (s). 143 Preparation of 2 - (3 - methoxyphenoxy) - 4,4,5,5 - tetramethyl - 1,3,2 - dioxaborolane: The Bpin prot ected 3 - methoxyphenol was prepared as described in the general procedure using 3 - methoxyphenol (62 mg, 0.5 mmol) and HBpin (80 µ L, 0.55 mmol). 1 H NMR (500 MHz, CDCl 3 ): H 7.15 (t, J = 8.2 Hz), 6.72 (ddd, J = 8.0, 2.3, 0.87 Hz, 1H), 6.68 (t, J = 2.3 Hz, 1H) , 6.63 (ddd, J = 8.3, 2.4, 0.87 Hz, 1H), 3.76 (s, 3H), 1.30 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C 160.5, 154.5, 129.7, 111.9, 108.6, 105.9, 83.6, 55.3, 24.6 11 B NMR (176, MHz, CDCl 3 ): B 21.7 (s). Preparation of 2 - (3 - chlorophenoxy) - 4,4,5,5 - tetramethyl - 1,3,2 - dioxaborolane: The Bpin protected 3 - chlorophenol was prepared as described in the general procedure using 3 - chlorophenol (64.3 mg, 0.5 mmol) and HBpin (80 µ L, 0.55 mmol). 1 H NMR (500 MHz, CDCl 3 ): H 7.17 (t, J = 8.2 Hz, 1H), 7.10 (t, J = 2.4 Hz, 1H), 7.02 (ddd, J = 7.8, 3.0, 1.0 Hz, 1H), 6.97 (ddd, J = 8.3 Hz, 3.0 Hz, 1.0 Hz, 1H), 1.30 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C 154.1, 134.4, 130.0, 123.4, 120.1, 117.9, 83.8, 24.6. 11 B NMR (176, MHz, CDCl 3 ): B 21.7 (s). 144 Preparation of 4,4,5,5 - tetramethyl - 2 - (naphthalen - 2 - yloxy) - 1,3,2 - dioxaborolane: The Bpin protected 2 - naphthol was prepared as described in the general procedure using 2 - naphthol (72 mg, 0.5 mmol) and HBpin (80 µ L, 0.55 mmol). 1 H NMR (500 MHz, CDCl 3 ): H 7.78 (m, 3H), 7.49 (d, J = 2.4 Hz, 1H), 7.42 (ddd, J = 8.1, 5.9, 1.3 Hz, 1H), 7.36 (ddd, J = 8.2, 6.0, 1.4 Hz, 1H), 7.26 (dd, J = 8.8, 2.5 Hz, 1H), 1.33 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C 151.3, 134.2, 130.1, 129.3, 127.6, 127.2, 126.3, 124.5, 120.7, 115.2, 83.7, 24.6. 11 B NMR (176, MHz, CDCl 3 ): B 21.9 (s). Preparation of the Authentic Boronic Esters for Phenols: 2 - (2 - Hydroxyphenyl)1,3,2 - dioxaborolane from 2 - hydroxyphenylboronic acid and ethylene glycol: A 5 mL conical vial was charged with 2 - hydroxyphenylboronic acid (276 mg, 2.0 mmol), ethylene glycol (122 mg, 2.0 mmol) and molecular seives (3 Å , 1.0 gm). Dry TH F (3.0 mL) was added and the vial was capped with a teflon pressure cap and stirred at room temperature. After 30 min, the reaction mixture was filtered immediately through a short pad of celite under an inert atmosphere, which was then evaporated under re duced 145 pressure to afford 265.0 mg of the boronic ester (80%) as oil. The compound is highly air sensitive and decomposed rapidly. 1 H NMR (500 MHz, CDCl 3 ): H 7.64 (dd, J = 7.5, 1.5 Hz, 1H), 7.61 (s, 1H), 7.39 - 7.42 (m, 1H), 6.90 - 6.93 (m, 2H), 4.42 (s, 4H). 13 C NMR (125 MHz, CDCl 3 ): C 163.4, 135.8, 134.1, 119.7, 115.6, 65.9. 11 B NMR (160 MHz, CDCl 3 ): B 31.3 ( bs ). HRMS (ESI) m/z calcd for C 8 H 8 BO 3 [M - H] - 163.0568, found 163.0568. 2 - (3 - Hydroxyphenyl)1,3,2 - dioxaborolane from 3 - hydroxyphenylboronic acid and ethylene glycol: A 5 mL conical vial was charged with 3 - hydroxyphenylboronic acid (276 mg, 2.0 mmol), ethylene glycol (122 mg, 2.0 mmol) and molecular seives (3 Å , 1.0 gm). Dry TH F (3.0 mL) was added and the vial was capped with a teflon pressure cap and stirred at room temperature. After 30 min, the reaction mixture was filtered immediately through a short pad of celite under an inert atmosphere, which was then evaporated under re duced pressure to afford 255 mg of the boronic ester (77%) as white solid (mp = 128 - 129 o C). The compound is highly air sensitive and decomposed rapidly. 1 H NMR (500 MHz, CDCl 3 ): H 7.39 (d, J = 7.5 Hz, 1H), 7.20 - 7.34 (m, 2H), 6.98 (dd, J = 7.5, 2.0 Hz, 1H), 5.50 ( bs ., 1H), 4.39 (s, 4H). 13 C NMR (125 MHz, CDCl 3 ): C 155.2, 128.9, 126.6, 120.5, 119.2, 66.1. 146 11 B NMR (160 MHz, CDCl 3 ): B 31.5 ( bs ). HRMS (ESI) m/z calcd for C 8 H 8 BO 3 [M - H] - 163.0568, found 163.0568. 2 - (4 - Hydroxyphenyl)1,3,2 - dioxaborolane from 4 - hydroxyphenylboronic acid and ethylene glycol: A 5 mL conical vial was charged with 3 - hydroxyphenylboronic acid (276 mg, 2.0 mmol), ethylene glycol (122 mg, 2.0 mmol) and molecular seives (3 Å , 1.0 gm). Dry TH F (3.0 mL) was added and the vial was capped with a teflon pressure cap and stirred at room temperature. After 30 min, the reaction mixture was filtered immediately through a short pad of celite under an inert atmosphere, which was then evaporated under re duced pressure to afford 260 mg of the boronic ester (79%) as white solid (mp = 131 - 132 o C). The compound is highly air sensitive and decomposed rapidly. 1 H NMR (500 MHz, CDCl 3 ): H 7.73 (d, J = 8.5 Hz, 2H), 6.85 (d, J = 8.5 Hz, 2H), 5.35 (s, 1H), 4.37 (s, 4H). 13 C NMR (125 MHz, CDCl 3 ): C 158.5, 136.9, 115.0, 66.0. 11 B NMR (160 MHz, CDCl 3 ): B 31.5 ( bs ). HRMS (ESI) m/z calcd for C 8 H 8 BO 3 [M - H] - 163.0568, found 163.0568. 147 2 - (2 - Hydroxyphenyl) - 4,4,5,5 - tetramethyl - 1,3,2 - dioxaborolane from 2 - hydroxyphe nylboronic acid and pinacol: A 5 mL conical vial was charged with 2 - hydroxyphenylboronic acid (276 mg, 2.0 mmol), pinacol (236 mg, 2.0 mmol) and molecular seives (3 Å , 1.0 g). Dry THF (3.0 mL) was added and the vial was capped with a teflon pressure cap and stirred at room temperature. After 30 min, the reaction mixture was filtered immediately through a short pad of celite under inert atmosphere, which was then evaporated under reduced pressure to afford 330 mg of the boronic ester (80%) as colorless oil. The NMR data of this compound were in accordance with the literature reported compound. 58 2 - (3 - Hydroxyphenyl) - 4,4,5,5 - tetramethyl - 1,3,2 - dioxaborolane This compound is commercially available and was purchased from Sigma - Aldrich and used witho ut any further purification. 2 - (4 - Hydroxyphenyl) - 4,4,5,5 - tetramethyl - 1,3,2 - dioxaborolane from 4 - hydroxyphenylboronic acid and pinacol: A 5 mL conical vial was charged with 4 - hydroxyphenylboronic acid (276 mg, 2.0 mmol), pinacol (236 mg, 2.0 mmol) and mol ecular seives (3 Å , 1.0 g). Dry THF (3.0 mL) was 148 added and the vial was capped with a teflon pressure cap and stirred at room temperature. After 30 min, the reaction mixture was filtered immediately through a short pad of celite under an inert atmosphere, w hich was then evaporated under reduced pressure to afford 341 mg of the boronic ester (78%) as white solid (mp = 102 - 105 o C). The NMR data of this compound were in accordance with the literature reported compound. 59 Synthesis of 2,2' - bi(1,3,2 - dioxaborolane ) from Tetrahydroxydiboron: This compound was synthesized by modifying the previously reported procedure. 60 A 100 mL round bottom flask was charged with tetrahydroxydiboron (1.0 g, 11.2 mmol, 1 equiv), dry MgSO 4 (1.61 g, 1 .2 equiv) and dry THF (~20 mL) then sealed with a septa. To this solution was added freshly distilled ethylene glycol (1.31 mL, 23.4 mmol, 2.1 equiv). After stirring for 24 h at room temperature, the reaction mixture was filtered through a medium glass fri t using approximately 30 mL THF to aid transfer and wash the MgSO 4 . The THF solution was evaporated under reduced pressure to afford a white solid. The solid was dried under highvac to yield 1.53 g of pure B 2 eg 2 (97%). It should be noted that if further pu rification is necessary B 2 eg 2 sublimes at 0.01 mm Hg pressure and 65 - 70 o C. (mp = 159 - 160 o C). 1 H NMR (500 MHz, CDCl 3 H 4.21 (s, 4H). 13 C NMR (125 MHz, CDCl 3 C 65.3. 11 B NMR (160 MHz, CDCl 3 B 30.9 ( bs ). 149 HRMS (ESI) m/z calcd for C 4 H 9 B 2 O 4 [M + H] + 143.0687, found 143.0685. Borylation of 4 - Chlorophenol with B 2 pin 2 (1a): In a glovebox, a 5 mL conical vial was charged with 4 - chlorophenol (129 mg, 1.0 mmol) and pinacolborane (160 µ L, 1.1 equiv) and stirred for 5 min at room temperature. To this mixture, [Ir(OMe)(cod)] 2 (20 mg, 3.0 mol %, 0.03 mmol), dtbpy (16 mg, 6.0 mol %, 0.06 mmol), and B 2 pin 2 (254 mg, 1.0 equiv) was charged. Dry cyclohexane (3 mL, 0.33 M) was added under an inert atmosphere. The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C. The reaction mixture was stirre d for 3 h. After completion (judged by GC), the cyclohexane was removed under reduced pressure and chromatographic separation with silica gel (chloroform as eluent) gave 203 mg of the ortho - borylated product (80%) as a white solid (mp = 59 - 60 o C). The NMR data w ere in accordance with the literature reported data . 58 1 H NMR (500 MHz, CDCl 3 H 7.77 (s, 1H), 7.56 (d, J = 2.5 Hz, 1H), 7.31 (dd, J = 9.0, 2.5 Hz, 1H), 6.82 (d, J = 9.0 Hz, 1H), 1.38 (s, 12H). 13 C NMR (125 MHz, CDCl 3 C 162.1, 134.8, 133.6, 124. 5, 117.1, 84.9, 24.8. 11 B NMR (160 MHz, CDCl 3 B 30.7 ( bs ). 150 Gram Scale Borylation of 4 - Chlorophenol (1a): In a glovebox, a 100 mL air free flask was charged with 4 - chlorophenol (2.0 g, 15.5 mmol) and HBpin (2.18 g, 17.05 mmol). After stirring for 5 minutes, a solid had formed. Then, [Ir(OMe)cod] 2 (150 mg, 1.5 mol %, 0.226 mmol), dtbpy (125 mg, 3 mol %, 0.465 mmol), B 2 Pin 2 (2.75 g, 10.85 mmol), and dry cyclohexane (25 mL) were added. The flask was sealed and heated at 80°C. After 3 h, the reaction was complete (judged by GC/FID), and the volatiles were removed under reduced pressure. Purification by column chromatography with chloroform as the eluent afforded 2.92 g of the analytically pure ortho - borylated product (74%) as a white solid. Borylation of 2 - Chloro - 5 - hydroxypyridine with B 2 pin 2 (1b): In a glovebox, a 5 mL conical vial was charged with 2 - chloro - 5 - hydroxypyridine (129 mg, 1.0 mmol) and pinacolborane (160 µ L, 1.1 equiv) in THF (1.5 mL) and stirred for 5 min at room temperature. To this mixture, [Ir(OMe)(cod)] 2 (10 mg, 1.5 mol %, 0.015 mmol), dtbpy (8 mg, 3.0 mol %, 0.03 mmol), and B 2 pin 2 (127 mg, 0.5 equiv) was charged. Additional THF (1.5 mL) was added under an inert atmosphere. The vial was capped with a teflo n 151 pressure cap and placed into a pre - heated aluminum block at 80 o C. The reaction mixture was stirred for 5 hours. The reaction was then cooled to room temperature and transferred to a round bottom flask. It was washed in with additional THF (3 mL). The so lution was cooled to 0 o C and degased with N 2 for 5 minutes. Then, KHF 2 (2.2 mL, 8.8 mmol, 4.0 M in H 2 O) was added via syringe dropwise. The reaction was allowed to stir at 0 o C for 10 minutes, then the ice bath was removed and the reaction warmed to room temperature. After stirring at room temperature for 16 h, the reaction was filtered, and the recovered solid washed with THF to afford the organotrifluoroborate product (87%) as a white solid (mp = 226 230 o C dec). 1 H NMR (500 MHz, (CD 3 ) 2 CO): H 7.65 (s, 1H), 7.47 (q, 1H, J =11.4 Hz), 7.15 (br, 1H) 13 C NMR (125 MHz, (CD 3 ) 2 SO): C 156.18, 140.18, 135.58, 127.59 (q, 1.88 Hz) 11 B NMR (160 MHz, (CD 3 ) 2 CO): B 2.65 (q, J = 51.5 Hz) HRMS (ESI) m/z calcd for C 5 H 3 BClF 3 NO [M - K] - 195.9955, found 195.9948 Bor ylation of 4 - Fluorophenol with B 2 pin 2 (1c): In a glovebox, a 5 mL conical vial was charged with 4 - fluorophenol (112 mg, 1.0 mmol) and pinacolborane (160 µ L, 1.1 equiv) and stirred for 5 min at room temperature. To this mixture, [Ir(OMe)(cod)] 2 (20 mg, 3.0 mol %, 0.03 mmol), dtbpy (16 mg, 6.0 mol %, 0.06 mmol), and B 2 pin 2 (178 mg, 0.7 equiv) was charged. Dry cyclohexane (3 mL, 0.33 M) was added under an inert atmosphere. The vial was capped with a teflon pressure cap and 152 placed into a pre - heated aluminum block at 80 o C. The reaction mixture was stirre d for 24 h. GC - FID showed 100% conversion of the starting material. The ratio of products w ere 10:90 (ortho:meta wrt to OH), and 82:18 (monoborylation:diborylation). Borylation of 4 - methoxyphenol with B 2 pin 2 (1d): In a glovebox, a 5 mL conical vial was c harged with 4 - methoxyphenol (124 mg, 1.0 mmol) and pinacolborane (160 µ L, 1.1 equiv) and stirred for 5 min at room temperature. To this mixture, [Ir(OMe)(cod)] 2 (20 mg, 3.0 mol %, 0.03 mmol), dtbpy (16 mg, 6.0 mol %, 0.06 mmol), and B 2 pin 2 (178 mg, 0.7 equ iv) was charged. Dry cyclohexane (3 mL, 0.33 M) was added under an inert atmosphere. The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C. The reaction mixture was stirred for 24 h. After completion (judged by GC), the ratio of ortho/meta (wrt OH) borylated product was found to be 65/35. The cyclohexane was removed under reduced pressure and chromatographic separation with silica gel (chloroform as eluent) gave 144.0 mg of the ortho - borylated product (58%) as a colorless oil. NMR data were in accordance with the literature reported data. 58 1 H NMR (500 MHz, CDCl 3 ): H 7.52 (s, 1H), 7.10 (d, J = 3.0 Hz, 1H), 6.97 (dd, J = 9.5, 3.0 Hz, 1H), 6.83 (d, J = 9.5 Hz, 1H), 3.78 (s, 3H), 1.37 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C 157.9, 152.6, 121.3, 118.0, 116.5, 84.5, 55.8, 24.8. 11 B NMR (160 MHz, CDCl 3 ): B 31.1 ( bs ). 153 Borylation of 4 - bromolphenol with B 2 pin 2 (1e): In a glovebox, a 5 mL conical vial was charged with 4 - bromophenol (173 mg, 1.0 mmol) and pinacolborane (160 µ L, 1.1 equiv) and stirred for 5 min at room temperature. To this mixture, [Ir(OMe)(cod)] 2 (20 mg, 3.0 mol %, 0.03 mmol), dtbpy (16 mg, 6.0 mol %, 0.06 mmol), and B 2 pin 2 (178 mg, 0.7 equiv) was charged. Dry cyclohexane (3 mL, 0.33 M) was added under an inert atmosphere. The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C. The reaction mixture was stirred for 24 h. After completion (judged by GC), the cyclohexane was removed under reduced pressure and chromatographic separation with silica gel (chloroform as eluent) gave 188 mg of the ortho - borylate d product (63%) as a yellow solid (mp = 68 - 69 o C). 1 H NMR (500 MHz, CDCl 3 ): H 7.78 (s, 1H), 7.70 (d, J = 3.0 Hz, 1H), 7.44 (dd, J = 9.0, 2.5 Hz, 1H), 6.78 (d, J = 9.0 Hz, 1H), 1.37 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C 162.6, 137.8, 136.4, 117.6, 111.9, 84.9, 24.8. 11 B NMR (160 MHz, CDCl 3 ): B 30.6 ( bs ). HRMS (ESI) m/z calcd for C 12 H 15 BBrO 3 [M - H] - 297.0300, found 297.0299. 154 Borylation of 4 - methylphenol with B 2 pin 2 (1f): In a glovebox, a 5 mL conical vial was charged with 4 - methylphenol (108 mg, 1.0 mmol) and pinacolborane (160 µ L, 1.1 equiv) and stirred for 5 min at room temperature. To this mixture, [Ir(OMe)(cod)] 2 (20 mg, 3.0 mol %, 0.03 mmol), dtbpy (16 mg, 6.0 mol %, 0.06 mmol), and B 2 pin 2 (178 mg, 0.7 equiv) was charged. Dry cyclohexane (3 mL, 0.33 M) was added under an inert atmosphere. The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C. The reaction mixture was stirre d for 24 h. After completion (judged by GC), cyclohexane was removed under reduced pressure and chromatographic separation with silica gel (chloroform as eluent) gave 199 mg of the borylated product (85%) as a pale yellow solid (mp = 35 - 36 o C). The NMR dat a were in accordance with the literature reported data . 58 1 H NMR (500 MHz, CDCl 3 ): H 7.66 (s, 1H), 7.42 (d, J = 1.5 Hz, 1H), 7.20 (dd, J = 8.5, 2.0 Hz, 1H), 6.81 (d, J = 8.5 Hz, 1H), 2.27 (s, 3H), 1.38 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C 161.5, 135.6, 134.6, 128.5, 115.3, 84.4, 24.8, 20.3. 11 B NMR (160 MHz, CDCl 3 ): B 31.0 ( bs ). 155 Borylation of 4 - tertbutylphenol with B 2 pin 2 (1g): In a glovebox, a 5 mL conical vial was charged with 4 - tertbutylphenol (150 mg, 1.0 mmol) and pinacolborane (1 60 µ L, 1.1 equiv) and stirred for 5 min at room temperature. To this mixture, [Ir(OMe)(cod)] 2 (20 mg, 3.0 mol %, 0.03 mmol), dtbpy (16 mg, 6.0 mol %, 0.06 mmol), and B 2 pin 2 (178 mg, 0.7 equiv) was charged. Dry cyclohexane (3 mL, 0.33 M) was added under an inert atmosphere. The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C. The reaction mixture was stirred for 24 h. After comp letion (judged by GC), cyclohexane was removed under reduced pressure and chromatographic separation with silica gel (chloroform as eluent) gave 233 mg of the borylated product (84%) as a white solid (mp = 78 - 79 o C). 1 H NMR (500 MHz, CDCl 3 ): H 7.76 (s, 1 H), 7.60 (d, J = 2.5 Hz, 1H), 7.42 (dd, J = 8.5, 2.5 Hz, 1H), 6.83 (d, J = 8.5 Hz, 1H), 1.37 (s, 12H), 1.31 (s, 9H). 13 C NMR (125 MHz, CDCl 3 ): C 161.5, 141.9, 131.9, 131.2, 115.0, 84.4, 34.0, 31.5, 24.8. 11 B NMR (160 MHz, CDCl 3 ): B 30.6 ( bs ). HRMS (ESI ) m/z calcd for C 16 H 24 BO 3 [M - H] - 275.1822, found 275.1825. 156 Borylation of 4 - trifluoromethylphenol with B 2 pin 2 (1h): In a glovebox, a 5 mL conical vial was charged with 4 - trifluoromethylphenol (162 mg, 1.0 mmol) and pinacolborane (160 µ L, 1.1 equiv) and stirred for 20 min at room temperature. To this mixture, [Ir(OMe)(cod)] 2 (20 mg, 3.0 mol %, 0.03 mmol), dtbpy (16 mg, 6 .0 mol %, 0.06 mmol), and B 2 pin 2 (178 mg, 0.7 equiv) was charged. Dry cyclohexane (3 mL, 0.33 M) was added under an inert atmosphere. The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C. The reaction mixture was stirred for 24 h. After completion (judged by GC), cyclohexane was removed under reduced pressure and chromatographic separation with silica gel (chloroform as eluent) gave 188 mg of the borylated product (63%) as a white solid (mp = 75 - 76 o C) 1 H NMR ( 500 MHz, CDCl 3 ): H 8.16 (s, 1H), 7.89 (d, J = 1.5 Hz, 1H), 7.61 (dd, J = 9.0, 1.5 Hz, 1H), 6.96 (d, J = 9.0 Hz, 1H), 1.39 ( bs ., 12H). 13 C NMR (125 MHz, CDCl 3 ): C 166.1, 133.2 (q, J = 3.7 Hz), 130.7 (q, J = 3.1 Hz), 124.5 (q, J = 271.8 Hz), 121.9 (q, J = 33.0 Hz), 116.0, 85.1, 24.8. 11 B NMR (160 MHz, CDCl 3 ): B 30.6 ( bs ). HRMS (ESI) m/z calcd for C 13 H 15 BF 3 O 3 [M - H] - 287.1069, found 287.1072. 157 Borylation of 4 - carboethoxyphenol with B 2 pin 2 (1i): In a glovebox, a 5 mL conical vial was charged with 4 - carboethoxyphenol (166 mg, 1.0 mmol) and pinacolborane (160 µ L, 1.1 equiv) and stirred for 5 min at room temperature. To this mixture, [Ir(OMe)(cod)] 2 (20 mg, 3.0 mol %, 0.03 mmol), dtbpy (16 mg, 6.0 mo l %, 0.06 mmol), and B 2 pin 2 (178 mg, 0.7 equiv) was charged. Dry cyclohexane (3 mL, 0.33 M) was added under an inert atmosphere. The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C. The reaction mixture was s tirred for 10 h. After completion (judged by GC), cyclohexane was removed under reduced pressure and chromatographic separation with silica gel (chloroform as eluent) gave 144 mg of the borylated product (51%) as a white solid (mp = 106 - 107 o C). 1 H NMR (5 00 MHz, CDCl 3 ): H 8.33 (d, J = 2.5 Hz, 1H), 8.25 (s, 1H), 8.0 (dd, J = 9.0, 2.5 Hz, 1H), 6.91 (d, J = 9.0 Hz, 1H), 4.35 (q, J = 7.3 Hz, 2H), 1.36 - 1.40 (m, Bpin 12H and ester 3H overlapped). 13 C NMR (125 MHz, CDCl 3 ): C 167.3, 166.3, 138.1, 135.4, 122.1, 115.6, 84.9, 60.6, 24.8, 14.5; 11 B NMR (160 MHz, CDCl 3 ): B 30.8 ( bs ). HRMS (ESI) m/z calcd for C 15 H 22 BO 5 [M + H] + 293.1563, found 293.1565. 158 Borylation of 4 - bromo - 2 - chlorophenol with B 2 pin 2 (1j): In a glovebox, a 5 m L conical vial was charged with 4 - bromo - 2 - chlorophenol (207 mg, 1.0 mmol) and pinacolborane (160 µ L, 1.1 equiv) and stirred for 5 min at room temperature. To this mixture, [Ir(OMe)(cod)] 2 (20 mg, 3.0 mol %, 0.03 mmol), dtbpy (16 mg, 6.0 mol %, 0.06 mmol), and B 2 pin 2 (178 mg, 0.7 equiv) was charged. Dry cyclohexane (3 mL, 0.33 M) was added under an inert atmosphere. The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C. The reaction mixture was stirred for 24 h. After comp letion (judged by GC), cyclohexane was removed under reduced pressure and chromatographic separation with silica gel (chloroform as eluent) gave 250 mg of the borylated product (75%) as a brown solid (mp = 109 - 110 o C). 1 H NMR (500 MHz, CDCl 3 ): H 8.28 (s, 1H), 7.62 (d, J = 2.4 Hz, 1H), 7.57 (d, J = 2.4 Hz, 1H), 1.38 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C 157.9, 136.3, 136.1, 121.8, 111.5, 85.4, 24.8. 11 B NMR (160 MHz, CDCl 3 ): B 30.0 (bs) HRMS (ESI) m/z calcd for C 12 H 14 BBrClO 3 [M - H] - 330.9910, found 330.9910. 159 Borylation of 2,4 - dichlorophenol with B 2 pin 2 (1k): In a glovebox, a 5 mL conical vial was charged with 2,4 - dichlorophenol (163 mg, 1.0 mmol) and pinacolborane (160 µ L, 1.1 equiv) and stirred for 5 min at room temperature. To this mixture, [Ir(OMe)(cod)] 2 (20 mg, 3.0 mol %, 0.03 mmol), dtbpy (16 mg, 6.0 mol %, 0.06 mmol), and B 2 pin 2 (178 mg, 0.7 equiv) was charged. Dry cyclohexane (3 mL, 0.33 M) was added under an inert atmosphere. The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C. The reaction mixture was st irred for 8 h. After completion (judged by GC), cyclohexane was removed under reduced pressure and chromatographic separation with silica gel (chloroform as eluent) gave 141 mg of the borylated product (49%) as a yellow solid (mp = 108 - 109 o C). 1 H NMR (50 0 MHz, CDCl 3 ): H 8.26 (s, 1H), 7.47 (d, J = 2.5 Hz, 1H), 7.43 (d, J = 2.5 Hz, 1H), 1.38 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C 162.3, 157.4, 133.4, 124.7, 121.5, 85.3, 24.8. 11 B NMR (160 MHz, CDCl 3 ): B 31.1 ( bs ). HRMS (ESI) m/z calcd for C 12 H 14 BCl 2 O 3 [M - H] - 287.0415, found 287.0418. 160 Borylation of 3,4 - dimethylphenol with B 2 pin 2 (1l): In a glovebox, a 5 mL conical vial was charged with 3,4 - dimethylphenol (122 mg, 1.0 mmol) and pinacolborane (160 µ L, 1.1 equiv) and stirred for 5 min at room temperature. To this mixture, [Ir(OMe)(cod)] 2 (20 mg, 3.0 mol %, 0.03 mmol), dtbpy (16 mg, 6.0 mol %, 0.06 mmol), and B 2 pin 2 (178 mg, 0.7 equiv) was charged. Dry cyclohexane (3 mL, 0.33 M) was added under an inert atmosphere. The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C. The reaction mixture was st irred for 24 h. After completion (judged by GC), cyclohexane was removed under reduced pressure and chromatographic separation with silica gel (chloroform as eluent) gave 169 mg of the borylated product (68%) as an oil. 1 H NMR (500 MHz, CDCl 3 ): H 7.60 (s , 1H), 7.36 (s, 1H), 6.72 (s, 1H), 2.25 (s, 3H), 2.19 (s, 3H), 1.38 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C 161.9, 143.2, 136.0, 127.5, 116.5, 84.2, 24.8, 20.3, 18.5. 11 B NMR (160 MHz, CDCl 3 ): B 30.8 ( bs ). HRMS (ESI) m/z calcd for C 14 H 20 BO 3 [M - H] - 247.1508, found 247.1509. 161 Borylation of 4 - chloro - 3 - methylphenol with B 2 pin 2 (1m): In a glovebox, a 5 mL conical vial was charged with 4 - chloro - 3 - methylphenol (143 mg, 1.0 mmol) and pinacolborane (160 µ L, 1.1 equiv) and stirred for 20 min at roo m temperature. To this mixture, [Ir(OMe)(cod)] 2 (20 mg, 3.0 mol %, 0.03 mmol), dtbpy (16 mg, 6.0 mol %, 0.06 mmol), and B 2 pin 2 (178 mg, 0.7 equiv) was charged. Dry cyclohexane (3 mL, 0.33 M) was added under an inert atmosphere. The vial was capped with a t eflon pressure cap and placed into a pre - heated aluminum block at 80 o C. The reaction mixture was stirred for 20 h. After completion (judged by GC), cyclohexane was removed under reduced pressure and chromatographic separation with silica gel (10% ethylace tate in hexane as eluent) gave 159 mg of the ortho - borylated product (59%) as a red liquid. 1 H NMR (500 MHz, CDCl 3 ): H 7.67 (s, 1H), 7.54 (s, 1H), 6.78 (s, 1H), 2.34 (s, 3H), 1.37 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C 162.0, 142.0, 135.2, 125.1, 117.9, 84.7, 24.7, 20.6. 11 B NMR (160 MHz, CDCl 3 ): B 30.5 ( bs ). HRMS (ESI) m/z calcd for C 13 H 17 BClO 3 [M - H] - 267.0962, found 267.0964. 162 Borylation of 2 - methoxy - 4 - methylphenol with B 2 pin 2 (1n): In a glovebox, a 5 mL conical vial was charged with 2 - methoxy - 4 - methylphenol (138 mg, 1.0 mmol) and pinacolborane (160 µ L, 1.1 equiv) and stirred for 5 min at room temperature. To this mixture, [Ir(OMe)(cod)] 2 (20 mg, 3.0 mol %, 0.03 mmol), dtbpy (16 mg, 6 .0 mol %, 0.06 mmol), and B 2 pin 2 (178 mg, 0.7 equiv) was charged. Dry cyclohexane (3 mL, 0.33 M) was added under an inert atmosphere. The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C. The reaction mixture was stirred for 20 h. After completion (judged by GC), cyclohexane was removed under reduced pressure and chromatographic separation with silica gel (10% ethylacetate in hexane as eluent) gave 175 mg of the ortho - borylated product (66%) as a pale yellow oi l. 1 H NMR (500 MHz, CDCl 3 ): H 7.61 (s, 1H), 7.02 (d, J = 1.0 Hz, 1H), 6.82 (d, J = 1.5 Hz, 1H), 3.87 (s, 3H), 2.28 (s, 3H), 1.36 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C 150.8, 147.1, 129.0, 126.6, 116.7, 84.4, 56.0, 24.8, 20.8. 11 B NMR (160 MHz, CDCl 3 ): B 30.5 ( bs ). HRMS (ESI) m/z calcd for C 14 H 22 BO 4 [M + H] + 265.1614, found 265.1603. 163 Borylation of 3 - carboethoxyphenol with B 2 pin 2 (1o): In a glovebox, a 5 mL conical vial was charged with 3 - carboethoxyphenol (166 mg, 1.0 mmol) and pinacolborane (160 µL, 1.1 equiv) and stirred for 5 min at room temperature. To this mixture, [Ir(OMe)(cod)] 2 (20 mg, 3.0 mol %, 0.03 mmol ), dtbpy (16 mg, 6.0 mol %, 0.06 mmol ), and B 2 pin 2 (1.0 equiv) was charged. Dry cyclohexane (3 mL, 0.33 M) was added under an inert atmosphere. The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C. The reaction mixture was stirred for 5 h. GC - FID showed a 100% conversion of the starting material. The ratio of products was 18:82 (ortho:meta wrt OH). Borylation of ortho - cresol with B 2 pin 2 (1p): In a glovebox, a 5 mL conical vial was charged with ortho - cresol (108 mg, 1.0 mmol) and pinacolborane (160 µ L, 1.1 equiv) and stirred for 5 min at room temperature. To this mixture, [Ir(OMe)(cod)] 2 (10 mg, 1.5 mol %, 0.015 mmol ), dtbpy (8 mg, 3.0 mol %, 0.03 mmol ), and B 2 pin 2 (178 mg, 0.7 equiv) was charged. Dry cyclohexane (3 mL, 0.33 M) was added under an inert atmosphere. The vial was capped with a teflon pressure cap and 164 placed into a pre - heated aluminum block at 80 o C. The reaction mixture was stirred for 4 h. GC - FID showed a 100% conversion of the starting material. The ratio of products was 1:99 (ortho:meta wrt OH). Borylation of phenol with B 2 eg 2 (1q): In a glovebox, a 5 mL conical vial was charged with [Ir(OMe)(cod)] 2 (10 mg, 1.5 mol %, 0.015 mmol), dtbpy (8 mg, 3.0 mol %, 0.03 mmol), B 2 eg 2 (213 mg, 1.5 equiv, 1.5 mmol), p henol (94 mg, 1.0 mmol), dry PhMe (2.5 mL) and Et 3 N (209 µ L, 1.5 equiv, 1.5 mmol). The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C for 2 h. The solvent was evaporated under reduced pressure and dry chloroform (10 mL) was added. To this mixture, pinacol (354 mg, 3.0 equiv) was added and stirred at room temperature for 40 min. Upon completion (judged by GC), the crude mixture was passed through a short pad of silica gel (chloroform as eluent) to afford the 142 mg of the ortho - borylated product (65%) as a colorless oil. The ratio of mono/ o,o - di borylated product was found to be 82/18 by the GC - FID and the diborylated product was assigned by the crude NMR spectra, but was not isolated. The NMR data were i n accordance with the literature reported data. 58 165 Borylation of 4 - Fluorophenol with B 2 eg 2 (1r): In a glovebox, a 5 mL conical vial was charged with [Ir(OMe)(cod)] 2 (10 mg, 1.5 mol %, 0.015 mmol), dtbpy (8 mg, 3.0 mol %, 0.03 mmol), B 2 eg 2 (170.07 mg, 1.2 equiv, 1.2 mmol), 4 - fluorophenol (112 mg, 1.0 mmol), dry PhMe (2.5 mL) and Et 3 N (209 µ L, 1.5 equiv, 1.5 mmol). The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C for 2 h. Solvent was evaporated under reduced pressure and dry chloroform (10 mL) was added. To this mixture, pinacol (354 mg, 3.0 equiv) was added and stirred at room temperature for 40 min. Upon completion (judged by GC), the crude mixture was passed through a short pad of silica gel (chloroform as eluent) to afford the 118 mg of the ortho - borylated product (50%) as a brown oil. The ratio of mono/ o,o - di borylated product was found to be 89/11 by the GC - FID and the di - borylated product was assigned by the crude NMR spectra, but not isolated. The NMR data of the isolated product were in accordance with the literature reported data. 58 1 H NMR (500 MHz, CDCl 3 ): H 7.65 (s, 1H), 7.25 - 7.27 (m, OH and ArH overlapped, 2H), 7.06 (dt, J = 8.5, 3.5 Hz, 1H), 6.83 (dd, J = 8.5, 3.5 Hz, 1H), 1.38 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C 159.6 (d, J = 1.9 Hz), 156.3 (d, J = 237.6 Hz), 120.6 (d, J = 21.2 Hz), 120.4, 116.7 (d, J = 7.2 Hz), 84.8, 24.8. 11 B NMR (160 MHz, CDCl 3 ): B 30.4 ( bs ). 19 F NMR (470 MHz, CDCl 3 ): F - 126.0 (td, J = 21.5, 13.3, 5.1 Hz). 166 Borylation of 3 - carboethoxyphenol with B 2 eg 2 (1s) In a glovebox, a 5 mL conical vial was charged with [Ir(OMe)(cod)] 2 (10 mg, 1.5 mol %, 0.015 mmol), dtbpy (8 mg, 3.0 mol %, 0.03 mmol), B 2 eg 2 (213 mg, 1.5 equiv, 1.5 mmol), 3 - carboethoxyphenol (166 mg, 1.0 mmol), dry PhMe (2.5 mL) and Et 3 N (209 µ L, 1.5 equiv, 1.5 mmol). The vial was capped with a teflon pre ssure cap and placed into a pre - heated aluminum block at 80 o C for 2 h. Solvent was evaporated under reduced pressure and dry chloroform (10 mL) was added. To this mixture, pinacol (354 mg, 3.0 equiv) was added and stirred at room temperature for 40 min. U pon completion (judged by GC), the crude mixture was passed through a short pad of silica gel (chloroform as eluent) to afford the 163 mg of the ortho - borylated product (56%) as colorless oil. In this reaction, no di - borylation was observed. 1 H NMR (500 MHz, CDCl 3 ): H 7.89 (s, 1H), 7.67 (d, J = 8.0 Hz, 1H), 7.51 - 7.56 (m, 2H), 4.37 (q, J = 7.5 Hz, 2H), 1.38 - 1.41 (m, Bpin 12H and ester 3H overlapped, 15H). 13 C NMR (125 MHz, CDCl 3 ): C 166.3, 163.4, 135.7, 135.3, 120.2, 116.4, 84.9, 61.1, 24.8, 14.3. 11 B NMR (160 MHz, CDCl 3 ): B 30.6 ( bs ). HRMS (ESI) m/z calcd for C 15 H 20 BO 5 [M - H] - 291.1407, found 291.1403. 167 Borylation of ortho - cresol with B 2 eg 2 (1t): In a glovebox, a 5 mL conical vi al was charged with [Ir(OMe)(cod)] 2 (10 mg, 1.5 mol %, 0.015 mmol), dtbpy (8 mg, 3.0 mol %, 0.03 mmol), B 2 eg 2 (213 mg, 1.5 equiv, 1.5 mmol), o - cresol (108 mg, 1.0 mmol), dry PhMe (2.5 mL) and Et 3 N (209 µ L, 1.5 equiv, 1.5 mmol). The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C for 2.5 h. Solvent was evaporated un der reduced pressure and dry chloroform (10 mL) was added. To this mixture, pinacol (354 mg, 3.0 equiv) was added and stirred at room temperature for 40 min. Upon completion (judged by GC), the crude mixture was passed through a short plug of silica gel (c hloroform as eluent) to afford the 172 mg of the ortho - borylated product (73%) as a solid (mp = 51 - 52 o C). No di - borylation was found in this reaction. 1 H NMR (500 MHz, CDCl 3 ): H 8.02 (s, 1H), 7.49 (dd, J = 7.5, 1.5 Hz, 1H), 7.26 (dd, J = 7.5, 1.5 Hz, 1H) , 6.83 (t, J = 7.5 Hz, 1H), 2.27 (s, 3H), 1.39 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C 161.8, 134.9, 133.2, 124.4, 119.4, 84.4, 24.8, 16.0. 11 B NMR (160 MHz, CDCl 3 ): B 30.9 ( bs ). HRMS (ESI) m/z calcd for C 13 H 18 BO 3 [M - H] - 233.1351, found 233.1354. 168 Borylation of 3 - methoxyphenol with B 2 eg 2 (1u): In a glovebox, a 5 mL conical vial was charged with [Ir(OMe)(cod)] 2 (10 mg, 1.5 mol %, 0.015 mmol), dtbpy (8 mg, 3.0 mol %, 0.03 mmol), B 2 eg 2 (213 mg, 1.5 equiv, 1.5 mmol), 3 - metho xyphenol (124 mg, 1.0 mmol), dry PhMe (2.5 mL) and Et 3 N (209 µ L, 1.5 equiv, 1.5 mmol). The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C for 2 h. Solvent was evaporated under reduced pressure and dry chloro form (10 mL) was added. To this mixture, pinacol (354 mg, 3.0 equiv) was added and stirred at room temperature for 40 min. Upon completion (judged by GC), the crude mixture was passed through a short pad of silica gel (chloroform as eluent) to afford 199 m g of the ortho - borylated product (80%) as a colorless oil. The ratio of mono/ o,o - di borylated product was found to be 81/19 by the GC - FID and the di - borylated product was assigned by the crude NMR spectra, but it was not isolated. 1 H NMR (500 MHz, CDCl 3 ): H 7.91 (s, 1H), 7.52 (d, J = 8.5 Hz, 1H), 6.48 (dd, J = 8.5, 2.5 Hz, 1H), 6.43 (d, J = 2.5 Hz, 1H), 3.81 (s, 3H), 1.37 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C 165.5, 164.5, 136.8, 107.0, 100.1, 84.2, 55.2, 24.8. 11 B NMR (160 MHz, CDCl 3 ): B 30.8 ( bs ). HRMS (ESI) m/z calcd for C 13 H 18 BO 4 [M - H] - 249.1301, found 249.1303. 169 Borylation of 3 - chlorophenol with B 2 eg 2 (1v): In a glovebox, a 5 mL conical vial was charged with [Ir(OMe)(cod)] 2 (10 mg, 1.5 mol %, 0.015 mmol), dtbpy (8 mg, 3.0 mol %, 0.03 mmol), B 2 eg 2 (213 mg, 1.5 equiv, 1.5 mmol), 3 - chlorophenol (129 mg, 1.0 mmol), dry PhMe ( 2.5 mL) and Et 3 N (209 µ L, 1.5 equiv, 1.5 mmol). The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C for 2 h. Solvent was evaporated under reduced pressure and dry chloroform (10 mL) was added. To this mixture , pinacol (354 mg, 3.0 equiv) was added and stirred at room temperature for 40 min. Upon completion (judged by GC), the crude mixture was passed through a short pad of silica gel (chloroform as eluent) to afford 199 mg of the ortho - borylated product (60%) as a white solid (mp = 62 - 63 o C). The ratio of mono/ o,o - di borylated product was found to be 85/15 by the GC - FID and the di - borylated product was assigned by the crude NMR spectra, but was not isolated. 1 H NMR (500 MHz, CDCl 3 ): H 7.92 (s, 1H), 7.53 (d, J = 8.5 Hz, 1H), 6.91 (d, J = 1.5 Hz, 1H), 6.88 (dd, J = 8.5, 1.5 Hz, 1H), 1.38 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C 164.3, 139.4, 136.6, 120.1, 115.9, 84.7, 24.8. 11 B NMR (160 MHz, CDCl 3 ): B 30.6 ( bs ). HRMS (ESI) m/z calcd for C 12 H 15 BClO 3 [M - H] - 253.0805, found 253.0808. 170 Borylation of 2 - methoxyphenol with B 2 eg 2 (1w): In a glovebox, a 5 mL conical vial was charged with [Ir(OMe)(cod)] 2 (10 mg, 1.5 mol %, 0.015 mmol), dtbpy (8 mg, 3.0 mol %, 0.03 mmol), B 2 eg 2 (213 mg, 1.5 equiv, 1.5 mmol), 2 - methoxyphenol (124 mg, 1.0 mmol), dry PhMe (2.5 mL) and Et 3 N (209 µ L, 1.5 equiv, 1.5 mmol). The vial was capped with a teflon pressure cap and place d into a pre - heated aluminum block at 80 o C for 2 h. Solvent was evaporated under reduced pressure and dry chloroform (10 mL) was added. To this mixture, pinacol (354 mg, 3.0 equiv) was added and stirred at room temperature for 40 min. Upon completion (jud ged by GC), the crude mixture was purified by passing it through a short pad of silica gel (chloroform as eluent) followed by kugelrohr distillation (20 mm Hg/ 100 o C) to afford 183 mg of the ortho - borylated product (73%). NMR data of the isolated product were in accordance with the literature reported data. 61 Borylation of 2 - naphthol with B 2 eg 2 (1x): In a glovebox, a 5 mL conical vial was charged with [Ir(OMe)(cod)] 2 (10 mg, 1.5 mol %, 0.015 mmol), dtbpy (8 mg, 3.0 mol %, 0.03 mmol), B 2 eg 2 (213 mg, 1.5 e quiv, 1.5 mmol), 2 - naphthol (144 mg, 1.0 mmol), dry PhMe (2.5 mL) and Et 3 N (209 µ L, 1.5 equiv, 1.5 171 mmol). The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C for 3 h. Solvent was evaporated under reduced pres sure and dry chloroform (10 mL) was added. To this mixture, pinacol (354 mg, 3.0 equiv) was added and stirred at room temperature for 40 min. Upon completion (judged by GC), the crude mixture was passed through a short pad of silica gel (chloroform as elue nt) to afford the 181 mg of the ortho - borylated product (67%) as a colorless oil. The NMR data were in accordance with the literature reported data . 61 1 H NMR (500 MHz, CDCl 3 ): H 8.27 (s, 1H) 7.79 - 7.81 (m, OH and ArH overlapped, 2H), 7.70 (d, J = 8.5 Hz, 1H), 7.46 (dt, J = 7.5, 1.0 Hz, 1H), 7.30 (dt, J = 7.5, 1.0 Hz, 1H), 1.44 (s, 12H). 13 C NMR (125 MHz, CDCl 3 ): C 159.2, 138.2, 137.3, 128.6, 128.0, 127.8, 126.4, 123.2, 109.4, 8 4.8, 24.9. 11 B NMR (160 MHz, CDCl 3 ): B 30.7 ( bs ). Evidence for 2 - (4 - fluorophenoxy) - 1,3,2 - dioxaborolanephenols formation under the reaction conditions: In a glove, [Ir(OMe)(cod)] 2 (0.001g, 1.5 mol %) was dissolved in 0.05 mL deuterated toluene, B 2 eg 2 (0.021g, 0.15mmol, 1.5 equiv) was dissolved in 0.4 mL deuterated toluene, dtbpy (0.0008 g, 3 mol %) was dissolved in 0.05 mL, and 4 - fluorophenol (0.0112 g, 0.1 172 mmol, 1 equiv) was disso lved in 0.2 mL deuterated toluene. The [Ir(OMe)(cod)] 2 , B 2 eg 2 , and dtbpy solutions were transferred to a J - Young tube and C 6 F 6 (3 µL) was added as a reference. The 4 - fluorophenol was sealed in an air tight flask with a septa. The NMR tube was taken to a sp ectrometer and the 4 - fluorophenol was injected into the NMR tube. The tube was inverted once for mixing and inserted into the spectrometer. 19 F NMR was collected. The time between addition of the phenol and the last scan for the 19 F NMR was ~2 minutes. The only observable product in 19 F NMR was the 2 - (4 - fluorophenoxy) - 1,3,2 - dioxaborolane which is shown below. 173 Control for effects of toluene on borylation selectivity : In a glovebox, a 3 mL conical vial was charged with [Ir(OMe)(cod)] 2 (10 mg, 1.5 mol %, 0 .015 mmol), dtbpy (8 mg, 3.0 mol %, 0.03 mmol), B 2 pin 2 (304.7 mg, 1.2 equiv, 1.2 mmol), 4 - fluorophenol (112 mg, 1.0 mmol), and dry PhMe (2.5 mL). The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C for 2 h. S olvent was evaporated under reduced pressure and crude 19 F, 1 H, 11 B NMR were recorded. The ratio of products, 97:3 m:o (with respect to OH), and conversion, 45%, was judged based on integration of 19 F NMR. Control for effects of toluene and triethylamine on borylation selectivity: In a glovebox, a 3 mL conical vial was charged with [Ir(OMe)(cod)] 2 (10 mg, 1.5 mol %, 0.015 mmol), dtbpy (8 mg, 3.0 mol %, 0.03 mmol), B 2 pin 2 (304.7 mg, 1.2 equiv, 1.2 mmol), 4 - fluorophenol (112 mg, 1.0 mmol), dry PhMe (2.5 mL) and Et 3 N (0.209 mL, 1.5 equiv, 1.5 mmol). The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C for 2 h. Solvent was evapor ated under reduced pressure and 174 crude 19 F, 1 H, 11 B NMR were recorded. The conversion, 45%, was judged based on integration of 19 F NMR. It should be noted that no borylation ortho to OH was detected. Example of effects of triethylamine on B 2 eg 2 reaction: In a glovebox, a 3 mL conical vial was charged with [Ir(OMe)(cod)] 2 (10 mg, 1.5 mol %, 0.015 mmol), dtbpy (8 mg, 3.0 mol %, 0.03 mmol), B 2 eg 2 (212 mg, 1.5 equiv, 1.5 mmol), 4 - fluorophenol (112 mg, 1.0 mmol), dry PhMe (2.5 mL) and Et 3 N (0.209 mL, 1.5 equiv, 1.5 mmol). The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C for 2 h. Solvent was evaporated under reduced pressure and dry chloroform (10 mL) was added. To this mixture, pinacol (354 mg, 3.0 equiv) was added and stirred at room temperature for 40 min after which crude 19 F NMR was collected. The spectra showed full conversion and a 89:11 monoborylation:diborylation ratio. In a glovebox, a 3 mL conical vial was charged with [Ir(OMe)(cod)] 2 (10 mg, 1.5 mol %, 0.015 mmol), dtbpy (8 mg, 3.0 mol %, 0.03 mmol), B 2 eg 2 (212 mg, 1.5 equiv, 1.5 mmol), 4 - fluorophenol (112 mg, 1.0 mmol) and dry PhMe (2.5 mL). The vial was capped with a 175 tefl on pressure cap and placed into a pre - heated aluminum block at 80 o C for 2 h. Solvent was evaporated under reduced pressure and dry chloroform (10 mL) was added. To this mixture, pinacol (354 mg, 3.0 equiv) was added and stirred at room temperature for 40 min after which crude 19 F NMR was collected. The spectra showed 35% conversion and a 85:15 monoborylation:diborylation ratio. Synthesis of 2 - (4 - fluorophenoxy) - 4,4,5,5 - tetramethyl - 1,3,2 - dioxaborolane from 4 - fluorophenol and the isolated trisboryl Ir cataly st: In a glove, isolated trisboryl catalyst (0.0022g, 1 equiv) was dissolved in 0.4 mL deuterated cyclohexane and 4 - fluorophenol (0.0003g, 1 equiv) was dissolved in 0.3 mL deuterated cyclohexane. The isolated trisboryl cat alyst and 4 - fluorophenol solutions were transferred into a J - Young tube and one drop of C 6 F 6 was added as a reference. The tube was sealed with a J - Young valve and 19 F, 11 B, 1 H NMR were collected. Analysis : Observed in the proton NMR, as shown below, is a n iridium hydride species at - 4.61 and the methyl groups on the Bpin of the phenol. The fluorine NMR shows the correct chemical shift at - 121.8 ppm. Finally, the boron NMR showed the correct shift for the ArOBpin species at 21.7 ppm. Overall, this clearly demonstrates ArOB(OR) 2 species can form from the iridium trisboryl catalyst. 176 177 Borylation of phenol with Ligand 4a: In a glovebox, a 5 mL conical vial was charged with phenol (188 mg, 2.0 mmol, 1.0 equiv) and pinacolborane (0.320 mL, 282 mg, 2.2 mmol, 1.1 equiv) and stirred for 5 min at room temperature. To this mixture, [Ir(OMe)(cod)] 2 (20 mg, 0.03 mmol, 1.5 mol %), 4,4' - Bis( N,N - dimethylamino) - 2,2 - bipyridine ( 4a ) (14.5 mg, 0.06 mmol, 3.0 mol %), and B 2 pin 2 (127 mg, 0.5 mmol, 0.25 equiv) was charged. Dry cyclohexane (3 mL, 0.66 M) was added under an inert atmosphere. The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C. The reaction mixture was stirred for 2 h. GC - FID showed 98% conversion (based on B 2 pin 2 ). The ratio of products was 6:94 of o:(m+p) and 98:2 monoborylation:diborylation. Bory lation of phenol with Ligand 4b: In a glovebox, a 5 mL conical vial was charged with phenol (188 mg, 2.0 mmol, 1.0 equiv) and pinacolborane (0.320 mL, 282 mg, 2.2 mmol, 1.1 equiv) and stirred for 5 min at room temperature. To this mixture, [Ir(OMe)(cod)] 2 (20 mg, 0.03 mmol, 1.5 mol %), dtbpy ( 4b ) (16.1 mg, 0.06 mmol, 3.0 mol %), and B 2 pin 2 (127 mg, 0.5 mmol, 0.25 equiv) was charged. Dry cyclohexane (3 mL, 0.66 M) was added under an inert atmosphere. The vial was 178 capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C. The reaction mixture was stirred for 2 h. GC - FID showed 92% conversion (based on B 2 pin 2 ). The ratio of products was 15:85 of o:(m+p) and 98:2 monoborylation:diborylati on. Borylation of phenol with Ligand 4c: In a glovebox, a 5 mL conical vial was charged with phenol (188 mg, 2.0 mmol, 1.0 equiv) and pinacolborane (0.320 mL, 282 mg, 2.2 mmol, 1.1 equiv) and stirred for 5 min at room tem perature. To this mixture, [Ir(OMe)(cod)] 2 (20 mg, 0.03 mmol, 1.5 mol %), - bis(trifluoromethyl) - - bipyridine ( 4c ) (17.5 mg, 0.06 mmol, 3.0 mol %), and B 2 pin 2 (127 mg, 0.5 mmol, 0.25 equiv) was charged. Dry cyclohexane (3 mL, 0.66 M) was added under an inert atmosphere. The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C. The reaction mixture was stirred for 24 h. GC - FID showed 68% conversion (based on B 2 pin 2 ). The ratio of products was 35:65 of o:(m+p). Borylation of phenol with Ligand 4d: In a glovebox, a 5 mL conical vial was charged with phenol (94.1 mg, 1.0 mmol, 1.0 equiv) and pinacolborane (0.160 mL, 141 mg, 1.1 mmol, 1.1 equiv) and stirred for 5 min at room 179 temperature. To this mixture, [Ir(OMe)(cod)] 2 - bipyridine] - - dicarbonitrile ( 4d ) (6.2 mg, 0.03 mmol, 3.0 mol %), and B 2 pin 2 (63.5 mg, 0.25 mmol, 0.25 equiv) was charged. Dry cyclohexane (3 mL, 0.33 M) was added under an inert atmosphere. The vial was capped with a teflon pressure cap and placed into a pre - heated aluminum block at 80 o C. The reaction mixture was stirred for 24 h. GC - FID showed 26% conversion (based on B 2 pin 2 ). The ratio of products was 44:56 of o:(m+p) . Analysis: Below is a chart summing up the data and the equation used to calculate the energy. This data was graphed , and a strong linear correlation was observed. R group Hammett Value o rtho meta+para Energy at 80 (kcal/mol) NMe2 - 0.83 6 94 1.93086827 tBu - 0.2 15 85 1.217242651 CF3 0.54 35 65 0.434405897 CN 0.66 44 55 0.156589232 2 - (4 - fluorophenoxy) - 1,3,2 - dioxaborolane from 4 - fluorophenol following Route B: y = - 1.1506x + 0.9837 R² = 0.9949 0 0.5 1 1.5 2 2.5 -1 -0.5 0 0.5 1 Energy (kcal/mol) Hammett sigma value Hammett plot 180 In a glove, [Ir(OMe)(cod)] 2 (0.0006g, 1 mol %) was dissolved in 0.05 mL deuterated toluene, 4 - fluorophenol (0.0112g, 0.1 mmol, 1 equiv) was dissolved in 0.3 mL deuterated toluene, and B 2 eg 2 (0.0141g, 0.1mmol, 1 equiv) was d issolved in 0.35 mL deuterated toluene then these three solutions were transferred to a J - Young tube and C 6 F 6 (3 µL) was added as a reference. The tube was sealed with a J - Young valve the J - Young tube was then heated at 80 o C for 12 hours. After ~30 minute s the solution turned from a yellow to a black color and black sediment was observed. After heating 19 F, 11 B, 1 H NMR were collected. It should be noted that this compound was not isolated. Further evidence that this reaction produces the ArOBeg species can be found in the experiments with 2 - fluorophenol. 1 H NMR (500 MHz, toluene - D 8 H 6.79 - 6.84 (m, 2H), 6.57 - 6.63 (m, 2H), 3.83 (s) 11 B NMR (176 MHz, toluene - D 8 B 22.6 (s). 19 F NMR (470 MHz, toluene - D 8 F - 120.80 (m) 2 - (2 - fluorophenoxy) - 1,3,2 - dioxaborolane from 2 - fluorophenol Route A: This procedure was adapted from a previous reported procedure. 62 To a flask under argon was added borane dimethylsulfide (1 mL, 10.5 mmol, 1 equiv). The flask was in an ice bath, connected to a bubbler, and 2 - fluorophenol (3.1 mL, 34.7 mmol, 3.3 equiv) was added slowly. The reaction was allowed to warm to room temperature and stirred for 12 hours after which the dimethyl sulfide was distilled off via a sho rt - path distillation head. 181 After the distillation, the product was a solid that still contained 2 - fluorophenol. To remove the excess 2 - fluorophenol, the product was heated to 100 o C and exposed to vacuum (0.1 mBar). At this temperature, the product liquefi es. After cooling, back to room temperature, the product was obtained in 92% yield (3.36 g). 1 H NMR (500 MHz, CDCl 3 H 7.26 - 7.30 (m, 1H), 7.16 - 7.20 (m, 1H), 7.07 - 7.14 (m, 2H) 13 C NMR (125 MHz, CDCl 3 C 154.56, 152.60, 140.61, 140.52, 124.81 124.65 (m), 124.47 124.32 (m), 122.38, 116.53, 116.39 11 B NMR (176 MHz, CDCl 3 B 16.47 (s). 19 F NMR (470 MHz, CDCl 3 F - 132.27 (m) In a flask under argon was charged tris(2 - fluorophenyl) borate (2.75 g, 8 mmol, 1 equiv) and ethylene glycol (0.497 g, 8 mmol, 1 equiv). The reaction mixture was heated to 110 o C in an oil bath and stirred under argon for 12 hours. The mixture was then dis tilled under vacuum to remove excess 2 - fluorophenol. The resulting product was a yellow oil which was pure by 19 F NMR and 11 B NMR. However, the product contained extra glycol peaks in the 1 H NMR and could not be fully purified in our hands. The spectra are shown below. 1 H NMR (500 MHz, CDCl 3 H 7.15 - 7.19 (m, 1H), 7.09 - 7.13 (m, 1H), 7.04 - 7.07 (m, 2H), 4.33 (s, 4H) 11 B NMR (176 MHz, CDCl 3 B 22.88 (s). 19 F NMR (470 MHz, CDCl 3 F - 132.62 (m) 1 H NMR 182 11 B NMR 183 2 - (2 - fluorophenoxy) - 1,3,2 - dioxaborolane from 2 - fluorophenol Route B: This route follows previously reported work. 63 In a flask under argon wa s BCl 3 (20 mL of 1 M solution in CH 2 Cl 2 , 20 mmol, 1 equiv) and ethylene glycol (1.24 g, 20 mmol, 1 equiv). The flask was connected to a bubbler and the ethylene glycol was added slowly at - 78 o C. After addition, the reaction was allowed to stir until the b ath had warmed to room temperature. The reaction mixture was then distilled under vacuum at room temperature, removing CH 2 Cl 2 . The resulting product was distilled at 75 o C to give a viscus oil (0.424 g, 20%) that turned a reddish brown upon warming to room temperature. The low yield is likely due to the fact that the boron trichloride solution was no longer 1 M. In a flask under argon wa s added 2 - chloro - 1,3,2 - dioxaborolane (0.424g, 4 mmol, 1 equiv), CH 2 Cl 2 (5 mL), and 2 - fluorophenol (0.447g, 4mmol, 1 equiv) dropwise at room temperature. The reaction mixture was sampled for NMR without isolation. 19 F, 11 B, 1 H NMR were collected. It should be noted that this compound was not isolated. 2 - (2 - fluorophenoxy) - 1,3,2 - dioxaborolane from 2 - fluorophenol Route C: In a glove, [Ir(OMe)(cod)] 2 (0.0006g, 1 mol %) was dissolved in 0.05 mL deuterated chloroform, 2 - fluorophe nol (0.0112g, 0.1 mmol, 1 equiv) was dissolved in 0.3 mL 184 deuterated chloroform, and B 2 eg 2 (0.0141g, 0.1mmol, 1 equiv) was dissolved in 0.35 mL deuterated chloroform then these three solutions were transferred to a J - Young tube and C 6 F 6 (3 µL) was added as a reference. The tube was sealed with a J - Young valve the J - Young tube was then heated at 80 o C for 12 hours. After ~30 minutes the solution turned from a yellow to a black color and black sediment was observed. After heating 19 F, 11 B, 1 H NMR were collecte d. It should be noted that this compound was not isolated. Comparison between route A and B to 2 - (2 - fluorophenoxy) - 1,3,2 - dioxaborolane 3.11: Notes Parts of this chapter were reprinted with permission from Chattopadhyay, B.; Dannatt, J. E.; Andujar - De Sanctis, I. L.; Gore, K. A.; Maleczka, R. E., Jr.; Singleton, D. A.; Smith, M. Ir - Catalyzed ortho - Electrostatic Interactions: A Combined Experimental/ in Silico Strategy for Optimizing Weak Interactions J. Am. Chem. Soc. 2017 , 139 , 7864. The work presented in this chapter was not all conducted by Dannatt, J. E. Credit for the substrate exploration belongs to Chattopadhyay and Gore. Calculations were con ducted by Andujar - De Sanctis, Singleton, and Smith. 185 APPEND IX 186 1 H - NMR (500 MHz, CDCl 3 ) 187 13 C - NMR (125 MHz, CDCl 3 ) 188 1 H - NMR (500 MHz, CDCl 3 ) 189 13 C NMR (125 MHz, CDCl 3 ) 190 1 H - NMR (500 MHz, CDCl 3 ) 191 13 C - NMR (125 MHz, CDCl 3 ) 192 1 H - NMR (500 MHz, CDCl 3 ) 193 13 C - NMR (125 MHz, CDCl 3 ) 194 1 H - NMR (500 MHz, CDCl 3 ) 195 13 C - NMR (125 MHz, CDCl 3 ) 196 1 H - NMR (500 MHz, CDCl 3 ) 197 13 C - NMR (125 MHz, CDCl 3 ) 198 1 H - NMR (500 MHz, CDCl 3 ) 199 13 C - NMR (125 MHz, CDCl 3 ) 200 1 H - NMR (500 MHz, CDCl 3 ) 201 13 C - NMR (125 MHz, CDCl 3 ) 202 1 H - NMR (500 MHz, CDCl 3 ) 203 13 C - NMR (125 MHz, CDCl 3 ) 204 1 H - NMR (500 MHz, CDCl 3 ) 205 13 C - NMR (125 MHz, CDCl 3 ) 206 1 H - NMR (500 MHz, CDCl 3 ) 207 13 C NMR (125 MHz, CDCl 3 ) 208 1 H - NMR (500 MHz, CDCl 3 ) 209 13 C - NMR (125 MHz, CDCl 3 ) 210 1 H - NMR (500 MHz, CDCl 3 ) 211 13 C - NMR (125 MHz, CDCl 3 ) 212 1 H - NMR (500 MHz, CDCl 3 ) 213 13 C - NMR (125 MHz, CDCl 3 ) 214 1 H - NMR (500 MHz, CDCl 3 ) 215 13 C - NMR (125 MHz, CDCl 3 ) 216 1 H - NMR (500 MHz, CDCl 3 ) 217 13 C - NMR (125 MHz, CDCl 3 ) 218 1 H - NMR (500 MHz, CDCl 3 ) 219 13 C - NMR (125 MHz, CDCl 3 ) 220 1 H - NMR (500 MHz, CDCl 3 ) 221 13 C - NMR (125 MHz, CDCl 3 ) 222 1 H - NMR (500 MHz, CDCl 3 ) 223 13 C NMR (125 MHz, CDCl 3 ) 224 1 H - NMR (500 MHz, CDCl 3 ) 225 13 C - NMR (125 MHz, CDCl 3 ) 226 1 H - NMR (500 MHz, CDCl 3 ) 227 13 C NMR (125 MHz, CDCl 3 ) 228 1 H - NMR (500 MHz, CDCl 3 ) 229 13 C NMR (125 MHz, CDCl 3 ) 230 1 H - NMR (500 MHz, CDCl 3 ) 231 13 C - NMR (125 MHz, CDCl 3 ) 232 1 H - NMR (500 MHz, CDCl 3 ) 233 13 C NMR (125 MHz, CDCl 3 ) 234 1 H - NMR (500 MHz, CDCl 3 ) 235 13 C - NMR (125 MHz, CDCl 3 ) 236 1 H - NMR (500 MHz, (CD 3 ) 2 CO) 237 13 C - NMR (125 MHz, CDCl 3 ) 238 1 H - NMR (500 MHz, CDCl 3 ) 239 13 C - NMR (125 MHz, CDCl 3 ) 240 1 H - NMR (500 MHz, CDCl 3 ) 241 13 C - NMR (125 MHz, CDCl 3 ) 242 1 H - NMR (500 MHz, CDCl 3 ) 243 13 C - NMR (125 MHz, CDCl 3 ) 244 1 H - NMR (500 MHz, CDCl 3 ) 245 13 C - NMR (125 MHz, CDCl 3 ) 246 1 H - NMR (500 MHz, CDCl 3 ) 247 13 C - NMR (125 MHz, CDCl 3 ) 248 1 H - NMR (500 MHz, CDCl 3 ) 1 H - NMR (500 MHz, CDCl 3 ) 249 13 C - NMR (125 MHz, CDCl 3 ) 250 1 H - NMR (500 MHz, CDCl 3 ) 251 13 C - NMR (125 MHz, CDCl 3 ) 252 1 H - NMR (500 MHz, CDCl 3 ) 253 13 C - NMR (125 MHz, CDCl 3 ) 254 1 H - NMR (500 MHz, CDCl 3 ) 255 13 C - NMR (125 MHz, CDCl 3 ) 256 1 H - NMR (500 MHz, CDCl 3 ) 257 13 C - NMR (125 MHz, CDCl 3 ) 258 1 H - NMR (500 MHz, CDCl 3 ) 259 13 C - NMR (125 MHz, CDCl 3 ) 260 1 H - NMR (500 MHz, CDCl 3 ) 261 13 C - NMR (125 MHz, CDCl 3 ) 262 1 H - NMR (500 MHz, CDCl 3 ) 263 13 C - NMR (125 MHz, CDCl 3 ) 264 1 H - NMR (500 MHz, CDCl 3 ) 265 13 C - NMR (125 MHz, CDCl 3 ) 266 1 H - NMR (500 MHz, CDCl 3 ) 267 13 C - NMR (125 MHz, CDCl 3 ) 268 1 H - NMR (500 MHz, CDCl 3 ) 269 13 C - NMR (125 MHz, CDCl 3 ) 270 Computational procedures and results for chapter 3 General Calculations of structures, energies, and frequencies employed default procedures in Gaussian09 63 - 65 unless otherwise noted. Complete structures and energetics are provided in sections below. All absolute energies are in Hartrees. All relative energies are presented in kcal/mol. NPA charges were calculated with NBO 5.9. 66 Guide to Structures, Structure Titles and Their Organization The sections below are divided into reactants and transition structures, then divided into specific structures and given a descriptive title. The first line after the title for a structure is a file name for the original calculation file, so that this file can always be located even if the file title changes. The second line after the title shows the method and - - that the iridium atom was given an SDD basis, while the remaining atoms were given a 6 - while the rema ining atoms were given a 6 - 31G* basis set. Alternative conformations for important structures are given, along with a short structures were obtained but are not incl uded here. lowest - energy structures were not modeled. Rather, structures were chosen that would include the steric interactions present with the full Bpin group. 271 Calculated Structures, Energies, and Selected NPA Charges Reactants: 4 - MeO - C 6 H 4 - 31+G** (3) MeOPhOBpinprimeM06PS M06/6 - 31+G** E(RM06) = - 753.634700207 Zero - point correction= 0.253860 (Hartree/Particle) Thermal correction to Energy= 0.267961 Thermal correction to Enthalpy= 0.268905 Thermal correction to Gibbs Free Energy= 0.212837 Sum of electronic and ZPE= - 753.380840 Sum of electronic and th ermal Energies= - 753.366739 Sum of electronic and thermal Enthalpies= - 753.365795 Sum of electronic and thermal Free Energies= - 753.421863 E CV S KCal/Mol Cal/Mol - K Cal/Mol - K Total 168.148 55.651 118.005 C,0,0.8989574659,0.04675157, - 1.2528236824 C,0,0.147143111,0.1420022159, - 0.0894033793 C,0,0.7797232518,0.0740133624,1.153879395 C,0,2.1556642021, - 0.0927360474,1.213870955 C,0,2.9156662173, - 0.193500707,0.0462397102 C,0,2.281038254, - 0.1233342107, - 1.1944 523496 B,0, - 2.1972793913,0.1988215786,0.6560508735 O,0, - 2.0720714699, - 0.2448591683,1.9522671682 C,0, - 3.3523459901, - 0.0416729816,2.5702695706 C,0, - 4.3226602953,0.0302616351,1.3737083774 O,0, - 3.489971759,0.504499287,0.3100543971 C,0, - 4.9448597992, - 1.2858673487,0.9605237132 H,0, - 5.1048369947,0.7791788472,1.5561270504 H,0, - 3.321650894,0.9464845268,3.0576723802 C,0, - 3.6125201939, - 1.1063594599,3.6031111688 H,0,0.1954779439,0.1427025846,2.0661936029 H,0,2.6689036733, - 0.1486676044 ,2.1708643992 O,0,4.2561818668, - 0.3567643838,0.2184561241 H,0,2.8434880167, - 0.1968272326, - 2.1206776068 H,0,0.3867903425,0.1086675615, - 2.2099337028 O,0, - 1.2016976858,0.3322974235, - 0.2511374308 H,0, - 5.6471226071, - 1.6570626456,1.7159535436 H,0, - 5.488273 4114, - 1.1518053506,0.0201685962 H,0, - 4.1717181058, - 2.048116592,0.7988636411 H,0, - 2.8542415077, - 1.0586443948,4.3908437469 H,0, - 4.596103354, - 0.9638965788,4.0667167182 H,0, - 3.576536222, - 2.1061307352,3.1569519391 C,0,5.0548242612, - 0.4767511146, - 0.9330270354 H,0,6.0835984256, - 0.5935424629, - 0.5863129735 H,0,4.7730559866, - 1.3575107137, - 1.5287183578 H,0,4.9885746627,0.4204641401, - 1.5658245525 4 - MeO - C 6 H 4 - 31G* (3) MeOPhOBpinprimeM06SB M06/6 - 31G* E(RM06) = - 753.592046918 Zero - point correction= 0.255470 (Hartree/Particle) Thermal correction to Energy= 0.270366 Thermal correction to Enthalpy= 0.271310 Thermal correction to Gibbs Free Energy= 0.211998 Sum of electronic and ZPE= - 753.336577 Sum of electronic and thermal Energies= - 753.321681 Sum of electronic and thermal Enthalpies= - 753.320737 Sum of electronic and thermal Free Energies= - 753.380049 E CV S KCal/Mol Cal/Mol - K Cal/Mol - K Total 169.657 57.193 124.831 C,0,0.8747774221,0.0088138081, - 1.2385701465 C,0,0.1360719232,0.2037328314, - 0.0798276431 C,0,0.7799555824,0.2171098778,1.1584454789 C,0,2.1508460814,0.026550814,1.2186764748 C,0,2.8980997939, - 0.1747570698,0.0559974198 C,0,2.2524837197, - 0.1819041538, - 1.1797593432 B,0, - 2.1973888152,0.2417507813,0.6676592578 O,0, - 2.0575074242, - 0.2500796355,1.9436105073 C,0, - 3.3305541474, - 0.0761560441,2.5764281788 C,0, - 4.3101520839,0.039675822,1.3908261121 O,0, - 3.4911801659,0.55768277 18,0.3417832092 C,0, - 4.9259073437, - 1.2638635438,0.930457812 H,0, - 5.0977650826,0.77466331,1.6091949449 H,0, - 3.303383084,0.8915704284,3.1055886022 C,0, - 3.5777815934, - 1.1840022239,3.5673828847 H,0,0.2053203954,0.3660764677,2.0681642402 H,0,2.6750233928, 0.0322175465,2.1724561333 O,0,4.2347796131, - 0.3524414377,0.2310663836 H,0,2.8059058824, - 0.3340357167, - 2.1030769348 H,0,0.3532498384,0.0100333698, - 2.1937112326 O,0, - 1.2088109288,0.4156175841, - 0.24063455 H,0, - 5.6257335193, - 1.6696018618,1.6719080663 H,0 , - 5.4701506443, - 1.0993878456, - 0.0060958567 H,0, - 4.1457320846, - 2.0140924012,0.7400413153 H,0, - 2.8144828499, - 1.1629141176,4.3533803059 H,0, - 4.5608685196, - 1.0710057412,4.0426703873 H,0, - 3.5337808713, - 2.1657759073,3.0813284388 C,0,5.02069274, - 0.5296510024, - 0.9173126076 H,0,6.0529677434, - 0.640556183, - 0.5744372205 H,0,4.7289689949, - 1.4326876604, - 1.4763973618 H,0,4.957234035,0.3395121331, - 1.5907672566 272 4 - F - C 6 H 4 OBeg M06/6 - 31+G** pFPhOBegM06PS M06/6 - 31+G** E(RM06) = - 659.807029462 Zero - point correction= 0.157604 (Hartree/Particle) Thermal correction to Energy= 0.168384 Thermal correction to Enthalpy= 0.169328 Thermal correction to Gibbs Free Energy= 0.118827 Sum of electronic and ZPE= - 659.649425 Sum of electronic and thermal Energies= - 659.638646 Sum of electronic and thermal Enthalpies= - 659.637701 Sum of electronic and thermal Free Energies= - 659.688203 E CV S KCal/Mol Cal/Mol - K Cal/Mol - K Total 105.662 40.352 106.288 C,0,1.3598666814,1.714778561, - 1.5472203797 C,0,2.5449651157,1.0073793838, - 1.7390209685 C,0,3.6953658017,1.4270035763, - 1.0948937266 C,0,3.7082877172,2.5345330629, - 0.2616070565 C,0 ,2.5253961893,3.2381074405, - 0.0717265177 C,0,1.3547237096,2.8299793695, - 0.7102211815 F,0,4.8384961115,0.7401591254, - 1.2838816112 O,0,0.2454532531,3.5917500885, - 0.45999687 B,0, - 1.0352785675,3.4152682273, - 0.8628633734 O,0, - 1.5044358381,2.4174249292, - 1.6851934107 C,0, - 2.9251026767,2.5416394605, - 1.7172129857 C,0, - 3.2012820295,3.9382198488, - 1.1423768757 O,0, - 2.0106667214,4.2828297056, - 0.4465640645 H,0,2.5799587486,0.134044 5037, - 2.3843164931 H,0,4.6321464033,2.8325842198,0.2257839224 H,0,2.488477073,4.1127612439,0.5722091666 H,0, - 3.3819092294,4.6817385642, - 1.9301593551 H,0, - 4.0499155876,3.9547729178, - 0.4508208509 H,0, - 3.3612390382,1.7438185463, - 1.1020972688 H,0, - 3.2791 635372,2.420687702, - 2.7459258146 H,0,0.4485484214,1.400272523, - 2.0446782849 4 - F - C 6 H 4 OBeg M06/6 - 31G* FPhOBeg M06/6 - 31G* with ultrafine grid E(RM06) = - 659.770268208 Zero - point correction= 0.158255 (Hartree/Particle) Thermal correction to Energy= 0.169057 Thermal correction to Enthalpy= 0.170001 Thermal correction to Gibbs Free Energy= 0.119105 Sum of electronic and ZPE= - 659.612013 Sum of electronic and th ermal Energies= - 659.601211 Sum of electronic and thermal Enthalpies= - 659.600267 Sum of electronic and thermal Free Energies= - 659.651163 E CV S KCal/Mol Cal/Mol - K Cal/Mol - K Total 106.085 40.185 107.120 C,0,1.3945375918,1.8285285449, - 1.6838374867 C,0,2.5602509421,1.083825301, - 1.8323626913 C,0,3.6758082436,1.4061660193, - 1.0781647546 C,0,3.6630346293,2.4574856908, - 0.1748389782 C,0,2.499043982,3.1991522201, - 0.0267814409 C,0,1.3663216693,2.8848231647, - 0.7750776405 F,0,4.7946780634,0.6862629708, - 1.225562134 O,0,0.2756195208,3.6863790958, - 0.575847866 B,0, - 1.0161224662,3.4578297504, - 0.9123534728 O,0, - 1.50351012,2.3526009144, - 1.5660111882 C,0, - 2.9197117672,2.4735356294, - 1.5817039763 C,0, - 3.1898749047,3.9323152411, - 1.1787985793 O,0, - 1.9777872596,4.3789440505, - 0.5960144407 H,0,2.6120833385,0.2529971319, - 2.5321285674 H,0,4.5587104413,2.683166155 9,0.3987963588 H,0,2.4469664161,4.0337696117,0.6688992634 H,0, - 3.4260212191,4.5641690132, - 2.0472601419 H,0, - 4.0072242137,4.0295571739, - 0.4542724168 H,0, - 3.3451696107,1.7574616944, - 0.8645276452 H,0, - 3.2987062248,2.2252674576, - 2.5800632646 H,0,0.509764 9482,1.5855161683, - 2.264872937 4 - F - C 6 H 4 OBpin M06/6 - 31+G** pFPhOBPINrM06PS M06/6 - 31+G** E(RM06) = - 816.965258089 Zero - point correction= 0.268270 (Hartree/Particle) Thermal correction to Energy= 0.284168 Thermal correction to Enthalpy= 0.285112 Thermal correction to Gibbs Free Energy= 0.224703 Sum of electronic and ZPE= - 816.696988 Sum of electronic and thermal Energies= - 816.681091 Sum of electronic and thermal Enthalpies= - 816.680146 Sum of electronic and thermal Free Energies= - 816.740555 E CV S KCal/Mol Cal/Mol - K Cal/Mol - K Total 178.318 63.299 127.141 273 C,0,1.3113529024,1.5205835616, - 1 .3280876739 C,0,2.552358047,1.0802699327, - 1.7781183977 C,0,3.6974899786,1.6807852908, - 1.2818861015 C,0,3.6474023102,2.7040274395, - 0.3495372323 C,0,2.4042113473,3.1413886274,0.0951052399 C,0,1.240521335,2.5569666925, - 0.3986096007 F,0,4.8979334084,1.25 38992845, - 1.7194793262 O,0,0.0511522748,3.0013935726,0.1137027324 B,0, - 1.0944119708,3.1638832652, - 0.6016402162 O,0, - 1.1914423981,3.0808424051, - 1.9672369749 C,0, - 2.6059079235,3.0707301946, - 2.2690089317 C,0, - 3.2161996147,3.7881866977, - 1.0218214946 O,0, - 2.27956574,3.4434567612,0.0219482739 H,0,2.638985579,0.2778070797, - 2.5053107756 H,0,4.5705224362,3.1436571265,0.0174802413 H,0,2.3183511341,3.9381313147,0.8293504742 C,0, - 3.211696971,5.3049367752, - 1.143444443 C,0, - 4.5932744318,3.3009582781, - 0.6219097537 C,0, - 3.0180664446,1.6099515155, - 2.3827735989 C,0, - 2.8286985103,3.7797940689, - 3.5878079683 H,0,0.3971202568,1.0709776017, - 1.7070970401 H,0, - 4.9390524394,3.859323641,0.2550411286 H,0, - 5.3134077442,3.46390924 58, - 1.4341835954 H,0, - 4.588804932,2.2381219799, - 0.3629166898 H,0, - 3.4560188455,5.7355388728, - 0.1662657599 H,0, - 2.2270923224,5.6826646057, - 1.4430066066 H,0, - 3.9545825991,5.6541697602, - 1.8704326764 H,0, - 3.9012523454,3.865702324, - 3.8050882275 H,0, - 2.3881214492,4.780935561, - 3.5896750492 H,0, - 2.363967761,3.2055045153, - 4.3970114646 H,0, - 4.0665444845,1.5060888859, - 2.6860673184 H,0, - 2.3926681988,1.1283287435, - 3.1432772757 H,0, - 2.8767248835,1.07399537 92, - 1.4361728976 4 - F - C 6 H 4 OBpin M06/6 - 31G* FPhOBpinrM06SB M06/6 - 31G* E(RM06) = - 816.916040347 Zero - point correction= 0.269582 (Hartree/Particle) Thermal correction to Energy= 0.285516 Thermal correction to Enthalpy= 0.286460 Thermal correction to Gibbs Free Energy= 0.224280 Sum of electronic and ZPE= - 816.646458 Sum of electronic and thermal Energies= - 816.630524 Sum of electronic and thermal Enthalpies= - 816.629580 Sum of electr onic and thermal Free Energies= - 816.691760 E CV S KCal/Mol Cal/Mol - K Cal/Mol - K Total 179.164 63.046 130.869 C,0,1.6140981727,2.4483414201, - 1.8641145904 C,0,2.8761069565,1.9881362459, - 2.2266412086 C,0,3.81926 26177,1.7370023393, - 1.2445935013 C,0,3.5389051341,1.9338492271,0.0986100565 C,0,2.2794417272,2.3920713703,0.4592034099 C,0,1.3168504358,2.6463994847, - 0.5163395443 F,0,5.0318809535,1.2945954038, - 1.6005193389 O,0,0.1155988205,3.1128149747, - 0.0603945436 B,0, - 1.0676078249,3.2060920498, - 0.7193559525 O,0, - 1.2940461351,2.8936638382, - 2.0372066522 C,0, - 2.7285532996,2.9127855006, - 2.2111017857 C,0, - 3.1848507742,3.8713703728, - 1.0684078667 O,0, - 2.1822332045,3.6485689138, - 0.0598182958 H,0,3.1365371714,1.8232732036, - 3.2696366342 H,0,4.304678786,1.7279823543,0.8426210985 H,0,2.018839622,2.562004695,1.5015909706 C,0, - 3.105925745,5.3407509526, - 1.4576127653 C,0, - 4.5475563178,3.5609070577, - 0. 4856686777 C,0, - 3.2144735786,1.483699401, - 2.0209875512 C,0, - 3.0468470646,3.3902961257, - 3.6118528066 H,0,0.8617283092,2.6465760772, - 2.6217546956 H,0, - 4.783274219,4.2828472212,0.3059421694 H,0, - 5.3263283609,3.6368600836, - 1.2574457969 H,0, - 4.5833847329, 2.558060551, - 0.0472935026 H,0, - 3.2243072621,5.9507160191, - 0.5539885622 H,0, - 2.1338987109,5.5862056737, - 1.9049931574 H,0, - 3.896073604,5.6173525576, - 2.1676284205 H,0, - 4.1321264651,3.501516229, - 3.7442563678 H,0, - 2.5671374051,4.3493701612, - 3.834069308 H, 0, - 2.690953561,2.6555355321, - 4.3448356694 H,0, - 4.2903431849,1.3917616907, - 2.2179303947 H,0, - 2.6792115307,0.8312758186, - 2.7215134082 H,0, - 3.0148967255,1.1242284542, - 1.0032457066 (bpy)Ir(Beg) 3 M06/BS1 hartwigbpyIrBeg3 M06/gen E(RM06) = - 1361.09051610 Zero - point correction= 0.370807 (Hartree/Particle) Thermal correction to Energy= 0.396820 Thermal correction to Enthalpy= 0.397764 Thermal correction to Gibbs Free Energy= 0.312274 Sum of electronic and ZPE= - 1360.719709 Sum of electronic and thermal Energies= - 1360.693696 Sum of electronic and thermal Enthalpies= - 1360.692752 Sum of electronic and thermal Free Energies= - 1360.778242 E CV S KCal/Mol Cal/Mol - K Cal/Mol - K 274 Total 249.008 96.26 9 179.929 B,0,1.692786538,12.8875448334,5.6407656346 B,0,1.9813407921,11.0298443329,3.7297630086 B,0,2.5173353617,10.5405820385,6.2661351842 C,0, - 0.313858819,11.4863345859,8.3591765148 H,0,0.7578461528,11.4258263238,8.536344993 C,0, - 1.213996062 3,11.7020569535,9.3945373931 H,0, - 0.8554876842,11.8022225559,10.4145743272 C,0, - 2.5663027972,11.7930745875,9.086367329 C,0, - 2.9677323752,11.6680411218,7.7627857913 C,0, - 2.0055334431,11.4458336439,6.7760237953 C,0, - 2.3443384128,11.3246805757,5.3389888575 C,0, - 3.6597886399,11.2669859103,4.877493239 H,0, - 4.4937107382,11.2768093166,5.5730802863 C,0, - 3.8982838978,11.1824670144,3.5117633314 C,0, - 2.8193721186,11.1636806168,2.6362122535 H,0, - 2.9611748436,11.1070408649,1.5610692923 C,0, - 1.5341434789,11.2137389003,3.1644467089 H,0, - 0.641687234,11.210616385,2.5372942534 C,0,2.8456097582,14.8196181 405,5.3001008243 C,0,2.4661738637,14.6921788455,6.776041294 C,0,3.721511406,10.674745681,2.2824305398 C,0,2.6229038522,11.4663456143,1.5761223675 C,0,4.6495345825,10.4053582545,7.0468070627 C,0,3.9951349957,9.0272958918,7.1353288773 Ir,0,0.8049060841 ,11.1320867066,5.382676982 N,0, - 0.6976375434,11.3548694517,7.0856429012 N,0, - 1.303435399,11.28464317,4.4814613811 O,0,2.5223113011,13.5545856727,4.7468952648 O,0,1.5077292852,13.6453799433,6.7996429221 O,0,3.325246147,10.6691859361,3.6422147631 O,0,1 .5055506585,11.3549988938,2.4456980143 O,0,3.564516933,11.2883921813,6.8107521722 O,0,2.7735711824,9.1765045249,6.4302732749 H,0, - 4.0190809885,11.7588583445,7.5064017687 H,0, - 4.9181772896,11.1331424297,3.1381252705 H,0, - 3.3037344439,11.9669904327,9.8659669906 H,0,3.9106673422,15.0304681471,5.1475994242 H,0,2.0303885932,15.6086920765,7.1919229211 H,0,2.260272192,15.6002563754,4.7902101051 H,0,3.3297327658,14.400087285 8,7.3923367112 H,0,5.1779455984,10.6965289354,7.9628417092 H,0,3.7842218503,8.7369388026,8.176870744 H,0,3.7832275041,9.6382493623,1.9159221903 H,0,2.3702681998,11.0699632013,0.5850799403 H,0,4.7122539856,11.1346044837,2.1837074623 H,0,2.8891374413,1 2.5289093149,1.4724844531 H,0,5.3505372492,10.4673992771,6.2006598375 H,0,4.5984865931,8.2362790618,6.6737666376 (bpy)Ir(Beg) 2 bypIRBeg2BpinprimeM06SB M06/gen E(RM06) = - 1439.60530524 Zero - point correction= 0.428507 (Hartree/Particle) Thermal correction to Energy= 0.457180 Thermal correction to Enthalpy= 0.458124 Thermal correction to Gibbs Free Energy= 0.366862 Sum of electronic and ZPE= - 1439.176799 Sum of electronic and thermal Energies= - 1439.148125 Sum of electronic and thermal Enthalpies= - 1439.147181 Sum of electronic and thermal Free Energies= - 1439.238443 E CV S KCal/ Mol Cal/Mol - K Cal/Mol - K Total 286.885 106.972 192.077 B,0,1.7292028143,12.8794869661,5.6177213404 B,0,1.9828687113,10.9924072899,3.7534100062 B,0,2.5122670622,10.5715560996,6.2906498292 C,0, - 0.3305631132,11.6179680635,8.355687241 H,0,0.7436 274806,11.6093684422,8.5303988905 C,0, - 1.2389279101,11.8494695936,9.3797482848 H,0, - 0.8854428638,12.016097121,10.3939230327 C,0, - 2.5925335339,11.8695331394,9.0698441354 C,0, - 2.9884689129,11.6617175927,7.7559350467 C,0, - 2.0188351467,11.4297620414,6.780 4739034 C,0, - 2.3511970005,11.2289204694,5.3513933961 C,0, - 3.6607354299,11.0849074062,4.8953429955 H,0, - 4.4942275743,11.0738360368,5.5930651128 C,0, - 3.8945596561,10.9424631032,3.5344646341 C,0, - 2.8178054615,10.9509761138,2.6579764591 H,0, - 2.9580593013,10.8521707973,1.5845177477 C,0, - 1.5368371807,11.081625397,3.1814531143 H,0, - 0.6439271763,11.096868748,2.5544673045 C,0,2.9368193346,14.7661970532,5.2403861523 C,0,2.5725336914,14.6612756511,6.7221238379 275 C,0,3.7340146658,10.5719051112,2.3346689648 C,0,2.6458455262,11.370992553,1.6017745808 C,0,4.6431022825,10.4729840244,7.0706777069 C,0,4.0312684054,9.0708178518,7 .1003115071 Ir,0,0.8007923544,11.1424236928,5.3968949342 N,0, - 0.7086431741,11.4077630145,7.0918701411 N,0, - 1.3100154545,11.2093924036,4.4938370398 O,0,2.5553779653,13.515655717,4.6991596892 O,0,1.5743866924,13.6586490375,6.7655348106 O,0,3.3393972124 ,10.6743683255,3.6956766643 O,0,1.5101761779,11.2356355253,2.451822982 O,0,3.5413645077,11.3332022032,6.8508888606 O,0,2.7931087498,9.2114191872,6.4319165246 H,0, - 4.0431852962,11.7004848042,7.4961854645 H,0, - 4.9117959329,10.8281887646,3.1648308369 H, 0, - 3.3373146639,12.0534705754,9.8416291827 H,0,4.0087171988,14.9339780609,5.0745207238 H,0,2.1871155889,15.5994957208,7.1421457453 H,0,2.3803246483,15.5710988427,4.7333789723 H,0,3.4346997897,14.3327553405,7.3240032786 H,0,5.1526754802,10.7435047002,8.005143512 H,0,3.858270685,8.7166020837,8.1298134033 C,0,3.833348728,9.1072463928,1.9579040043 C,0,2.3134767367,10.9422327345,0.1940812472 H,0,4.7154844886,11.0556528809,2.2151544149 H,0,2.9376962102,12.4364051772,1.60 54447768 H,0,5.35868521,10.5848428477,6.2408518238 H,0,4.6518918045,8.3254143862,6.5853488015 H,0,4.5124978392,8.5998473597,2.6531595784 H,0,2.8508878793,8.6215801921,2.0397829585 H,0,4.2118201956,8.9671376682,0.9364224366 H,0,1.5208689929,11.5780557 2, - 0.2185116115 H,0,3.1911316078,11.0251963796, - 0.4611910083 H,0,1.9614770648,9.9030675958,0.172548588 (bpy)Ir(Beg) 2 bypIRBeg2BpinprimeM06PS M06/gen E(RM06) = - 1439.66858895 Zero - point correction= 0.426348 (Hartree/Particle) Thermal correction to Energy= 0.455049 Thermal correction to Enthalpy= 0.455994 Thermal correction to Gibbs Free Energy= 0.365325 Sum of electronic and ZPE= - 1439.242241 Sum of electronic and thermal Energies= - 1439.213540 Sum of electronic and thermal Enthalpies= - 1439.212595 Sum of electronic and thermal Free Energies= - 1439.303264 E CV S KCal/ Mol Cal/Mol - K Cal/Mol - K Total 285.548 107.503 190.828 B,0,1.708738587,12.8786923147,5.5963203156 B,0,1.9979558507,10.9676236296,3.7441294316 B,0,2.5402411653,10.5796465499,6.3047574858 C,0, - 0.309034201,11.5540828632,8.3621601343 H,0,0.763486 1549,11.533598095,8.5429954138 C,0, - 1.2180972074,11.7718539863,9.3895387956 H,0, - 0.8647947396,11.9188687031,10.405728112 C,0, - 2.5724170684,11.8022456802,9.0785211538 C,0, - 2.9671066281,11.6195614997,7.7597566827 C,0, - 1.9958659297,11.4038583228,6.780496 2777 C,0, - 2.3295368768,11.2344050427,5.3469408724 C,0, - 3.6432655882,11.1385087658,4.886333207 H,0, - 4.4784146975,11.1493873821,5.5802298066 C,0, - 3.8790019523,11.019857265,3.522621428 C,0, - 2.7991379252,11.0055854627,2.6481937949 H,0, - 2.9390311985,10.9248055455,1.574205832 C,0, - 1.5156371391,11.0924345966,3.1759392147 H,0, - 0.6237600248,11.0914764809,2.5484874113 C,0,2.8863053172,14.7888307001,5.2208878817 C,0,2.5172342471,14.6821731052,6.7011432925 C,0,3.7315498582,10.5201309369,2.3032168183 C,0,2.6625088531,11.3631259324,1.5912646839 C,0,4.6783358293,10.4908552201,7.0772321654 C,0,4.0221991776,9.1233943199,7.2611254179 Ir,0,0.8227334328,11.1152869642 ,5.3946822829 N,0, - 0.6859146006,11.368942824,7.0931569567 N,0, - 1.2874321809,11.1962767815,4.4910738173 O,0,2.5347283696,13.5238436442,4.6839911163 O,0,1.5315998965,13.6619129802,6.7398871134 O,0,3.343852731,10.6075666922,3.6707664483 O,0,1.5264094102 ,11.243458085,2.4470844897 O,0,3.5925416124,11.3588360288,6.7953661688 O,0,2.796179502,9.2282306014,6.5557157611 H,0, - 4.0208411979,11.6619039697,7.5011493839 H,0, - 4.8974211993,10.9424777113,3.1498108801 H,0, - 3.316702665,11.9738197888,9.8521540254 H,0 ,3.9541464592,14.9770193448,5.058022682 H,0,2.1120912396,15.6129132841,7.1162027824 H,0,2.3120029162,15.575178999,4.7072222577 H,0,3.3784230346,14.364784555,7.3083049858 H,0,5.2161229811,10.838792212,7.9676151936 H,0,3.8171540573,8.9040087163,8.3210553778 C,0,3.7953878682,9.061729745,1.8954091239 C,0,2.3118186598,10.9733499011,0.1768795085 H,0,4.7232560748,10.9831246895,2.191895763 H,0,2.9823466173,12.4193686328,1.6155869238 H,0,5.3715508405,10.4964034238,6.2 222453296 H,0,4.6201863425,8.3008845265,6.8503551477 H,0,4.4736541089,8.5267900018,2.5682619593 H,0,2.8057239849,8.5939678412,1.9782124116 H,0,4.158711119,8.9394506042,0.867377184 H,0,1.5402454091,11.6426056534, - 0.2188301844 H,0,3.1898958463,11.04298 36792, - 0.4776165859 H,0,1.9282444662,9.9471597184,0.1354000661 (bpy)Ir(Bpin) 3 M06/BSsmall bpyIrBPIN3M06SB M06/gen E(RM06) = - 1832.47310358 Zero - point correction= 0.706376 (Hartree/Particle) Thermal correction to Energy= 0.748008 Thermal correction to Enthalpy= 0.748952 Thermal correction to Gibbs Free Energy= 0.633777 Sum of electronic and ZPE= - 1831.766728 Sum of electronic and thermal Energies= - 1831.725095 276 Sum of electronic and thermal Enthalpies= - 1831.724151 Sum of electronic and thermal Free Energies= - 1831.839326 E CV S KCal/Mol Cal/Mol - K Cal/Mol - K Total 469.38 2 164.337 242.407 B,0,1.7486487866,12.8651667202,5.6436466567 B,0,1.9830539063,11.0359387379,3.6889461925 B,0,2.4691757191,10.5218527746,6.3058612124 C,0, - 0.3090934882,11.5581839099,8.317279416 H,0,0.7663765691,11.5533320052,8.4936564246 C,0, - 1 .2197329071,11.7780809625,9.3419771424 H,0, - 0.8670974295,11.9386371893,10.3575064553 C,0, - 2.5738383881,11.7948757785,9.032022593 C,0, - 2.967635046,11.5925422707,7.717088089 C,0, - 1.9972237259,11.3678108224,6.7411714087 C,0, - 2.3330730153,11.1610282988,5.3141766808 C,0, - 3.6412129582,10.9778993967,4.8674179371 H,0, - 4.4697768575,10.9437507891,5.5703521419 C,0, - 3.8800639162,10.820265845,3.5089187739 C,0, - 2.810120496,10.851873 8952,2.6249348467 H,0, - 2.9549574487,10.7387408195,1.5536150849 C,0, - 1.5300746492,11.0221182427,3.1385853242 H,0, - 0.6426709304,11.0560483323,2.5046108061 C,0,2.8592936883,14.8204745746,5.2573736617 C,0,2.2573215111,14.8343671816,6.6928686772 C,0,3.7103469338,10.6228821308,2.2256797264 C,0,2.6194991877,11.4795923125,1.5186102629 C,0,4.468574594,10.4341223494,7.4118931106 C,0,3.958479434,8.9880422786,7.1434015516 Ir,0,0.8114281091,11.1390028756,5 .3472340106 N,0, - 0.6864035418,11.3517132171,7.0519106765 N,0, - 1.2979024999,11.167077682,4.4483156474 O,0,2.7882880966,13.4312718604,4.9117751009 O,0,1.3164152995,13.752221378,6.6314634745 O,0,3.3323097153,10.7142794212,3.5984330504 O,0,1.4963297866,1 1.325624533,2.4002587977 O,0,3.2786620142,11.2112615329,7.2161278646 O,0,2.9032053627,9.2018995114,6.2017991861 H,0, - 4.0219707215,11.6284186225,7.4547501786 H,0, - 4.8961933392,10.6728634839,3.1481702403 H,0, - 3.3195010111,11.9711573564,9.8047404054 C,0 ,4.3011996185,15.2761294082,5.1561503735 C,0,1.5204003704,16.1062137773,7.0644196005 C,0,2.0045909609,15.5834015693,4.2508428038 C,0,3.2781847524,14.4949454043,7.7707570673 C,0,4.9957381147,10.6804260143,8.8118625933 C,0,3.3437245028,8.335298002,8.3753427187 C,0,3.6591790042,9.1501118408,1.837476744 C,0,2.2316303896,11.0060356438,0.1315361402 C,0,5.127580316,11.1449348016,2.0827970092 C,0,2.9623814377,12.9636189738,1.4818573151 C,0,5.4842553706,10.9122596447,6.38 05577703 C,0,4.9850940687,8.0618873943,6.5212432503 H,0,5.3141459582,11.7271966489,8.90783357 H,0,4.2327562438,10.4904460043,9.5753323494 H,0,5.8680134,10.0443040222,9.0215763649 H,0,2.8252919594,7.4191188404,8.0656575647 H,0,4.1007457777,8.0673199805,9.1253450726 H,0,2.6043568767,8.9986989772,8.8446877782 H,0,4.5463634329,7.0660850967,6.3764024728 H,0,5.3061671309,8.4336117637,5.5413474194 H,0,5.8678022097,7.9555518446,7.168 6752448 H,0,5.6538584824,11.9868402828,6.531393116 H,0,6.4495378338,10.397401646,6.4839307084 H,0,5.1037688008,10.7751158776,5.3591445441 H,0,4.2964231804,8.5843287431,2.5287176031 H,0,2.6398760124,8.7521155606,1.9249479304 H,0,4.0194350779,8.9797247 591,0.8133840183 H,0,5.8186930988,10.4709903061,2.6074175704 H,0,5.4341122298,11.1916284465,1.0274955808 H,0,5.2311617403,12.1410891228,2.5293737038 H,0,1.4647954185,11.6721697319, - 0.285882882 H,0,3.0964771166,11.0247005681, - 0.5474871836 H,0,1.8234897436,9.9891549888,0.14687194 H,0,2.0714932386,13.5218564218,1.1636574521 H,0,3.2461807356,13.3192823624,2.4808613662 H,0,3.7746489623,13.1789215186,0.7739289255 H,0,2.7424580089,14.3109732033,8 .7118770056 H,0,3.824142395,13.5777904346,7.5193668081 H,0,3.9888176626,15.3169516103,7.9337283593 H,0,1.1301202063,16.0184177182,8.0867361238 H,0,2.1950723884,16.9742011898,7.0349473062 H,0,0.673579444,16.2972147858,6.3962021507 H,0,4.6353765964,15. 2082377245,4.1118467429 H,0,4.4086167202,16.3219859426,5.4787928511 H,0,4.9665958375,14.6511285636,5.7610002292 H,0,2.3678251583,15.3668739179,3.2381459409 H,0,0.9542709754,15.2679133089,4.3049840102 H,0,2.0554596951,16.669497519,4.4076320459 (bpy)Ir (Bpin) 3 M06/BS1 bpyIrBPIN3M06PS M06/gen E(RM06) = - 1832.56850386 Zero - point correction= 0.702334 (Hartree/Particle) Thermal correction to Energy= 0.744053 Thermal correction to Enthalpy= 0.744997 Thermal correction to Gibbs Free Energy= 0.629418 Sum of electronic and ZPE= - 1831.866170 277 Sum of electronic and thermal Energies= - 1831.824451 Sum of electronic and thermal Enthalpies= - 1831.823507 Sum of electronic and thermal Free Energies= - 1831.939 086 E CV S KCal/Mol Cal/Mol - K Cal/Mol - K Total 466.900 165.113 243.258 B,0,1.702656396,12.81576038,5.629151248 B,0,1.9907846418,10.9705100756,3.6862387279 B,0,2.4847626304,10.462190892,6.3036486155 C,0, - 0.279 7684939,11.4783651155,8.3204529209 H,0,0.7935219563,11.4144638053,8.4971923378 C,0, - 1.17585085,11.737269258,9.3494956722 H,0, - 0.8134727557,11.8669502086,10.3649678841 C,0, - 2.5287150892,11.8308863731,9.0421983669 C,0, - 2.9338555516,11.668370084,7.724355 3641 C,0, - 1.9769049769,11.4047521575,6.7430354132 C,0, - 2.3250061564,11.2477601425,5.3120507786 C,0, - 3.6443790777,11.1742707873,4.8631043474 H,0, - 4.4729318695,11.1946964594,5.5649242952 C,0, - 3.8945517716,11.059560052,3.5016037415 C,0, - 2.8233537973,11.0250241139,2.6171767633 H,0, - 2.9748161052,10.9442087212,1.5448429533 C,0, - 1.5336983374,11.0893122821,3.1330136711 H,0, - 0.647293054,11.0715219421,2.497804681 C,0,2.7879195409,14.79058156 98,5.2458118742 C,0,2.1898397111,14.790533439,6.6847297254 C,0,3.7408429711,10.6066965416,2.2271796147 C,0,2.6275176965,11.4316830506,1.5128539037 C,0,4.4916264785,10.4281721124,7.4111046142 C,0,4.0098240523,8.9676172461,7.1600557767 Ir,0,0.815336571,11.0605584375,5.3462184806 N,0, - 0.6691764905,11.3070766058,7.0524494766 N,0, - 1.2914755228,11.1920914615,4.4457559842 O,0,2.7247012316,13.401301857,4.8899910355 O,0,1.2629460459,13.6924269636 ,6.6228009483 O,0,3.3452521745,10.6730021654,3.5983100081 O,0,1.5048456201,11.255277218,2.3949971653 O,0,3.2858920839,11.1802142682,7.2011673693 O,0,2.942986086,9.1493790369,6.2205229793 H,0, - 3.9841606241,11.7640484177,7.4653439874 H,0, - 4.9176991845, 10.9987453435,3.1388471727 H,0, - 3.2621885236,12.0374643922,9.8176083211 C,0,4.2277381809,15.2534226683,5.1434098069 C,0,1.432621266,16.0491735662,7.0610652426 C,0,1.9253322846,15.5518687787,4.2448281496 C,0,3.2170290489,14.4644437431,7.7618638906 C,0,5.0082371019,10.701092152,8.8105140934 C,0,3.4131377961,8.3144256547,8.4008688619 C,0,3.7453585289,9.1347391822,1.8322492939 C,0,2.2549735323,10.9372727402,0.1283894238 C,0,5.1397753098,11.1816757621,2. 1061891211 C,0,2.9298534183,12.9243334004,1.4642914159 C,0,5.5013739831,10.9165126318,6.3778421803 C,0,5.0506840221,8.0552810209,6.5407843596 H,0,5.3126192294,11.7518248756,8.8918073667 H,0,4.2437000316,10.5125005929,9.5711490161 H,0,5.8857435152,10. 0785531909,9.0321607731 H,0,2.9082464795,7.3895972336,8.0988832208 H,0,4.1794502503,8.0640793884,9.1457674228 H,0,2.6667380531,8.9682191089,8.8698618887 H,0,4.6255435114,7.0539719772,6.4033933692 H,0,5.364633176,8.4252168813,5.5591344092 H,0,5.934252 0276,7.966242607,7.1878080141 H,0,5.6598228448,11.9915410453,6.5295266367 H,0,6.4699442911,10.4100973302,6.4799693911 H,0,5.1191622874,10.779487087,5.3581919822 H,0,4.3954740436,8.5914550756,2.5279501092 H,0,2.7410684553,8.7014573042,1.9103434005 H,0,4.120168713,8.9812768805,0.8119045328 H,0,5.8461949581,10.5297029562,2.635533224 H,0,5.4572575503,11.2466600974,1.0563191601 H,0,5.1973076896,12.1772909315,2.560804177 H,0,1.4674168874,11.5760545181, - 0.2897138239 H,0,3.1190631923,10.9827953234, - 0 .5484881727 H,0,1.8828993079,9.9081107759,0.1492641755 H,0,2.0303517729,13.4523639335,1.1234468252 H,0,3.1836398323,13.3007281214,2.4623793155 H,0,3.7485634406,13.1509281292,0.7691861659 H,0,2.6828016088,14.2697560742,8.7004775896 H,0,3.7807401799,13 .5582654416,7.5133742074 H,0,3.9103185438,15.2993189599,7.9266783828 H,0,1.0514058296,15.952207172,8.0846217311 H,0,2.0911917837,16.9278983695,7.0273096883 H,0,0.5792354242,16.2234878381,6.3986029941 H,0,4.5560626699,15.1959796065,4.0979175764 H,0,4. 3315779317,16.2953859827,5.4755156275 H,0,4.8960373227,14.6246678035,5.7392864108 H,0,2.2927289862,15.3446274713,3.2329340955 H,0,0.8799086422,15.2236444643,4.2962921773 H,0,1.9654124076,16.6361421739,4.4083928807 (tbut - bpy)Ir(Beg) 3 M06/BSsmall tbutbpyIrBeg3M06SB M06/gen E(RM06) = - 1675.28804397 Zero - point correction= 0.597715 (Hartree/Particle) Thermal correction to Energy= 0.634805 Thermal correction to Enthalpy= 0.635749 Thermal correction to Gibbs Free Energy= 0.525333 Sum of electronic and ZPE= - 1674.690329 Sum of electronic and thermal Energies= - 1674.653239 Sum of electronic and thermal Enthalpies= - 1674.652295 Sum of electronic and thermal Free Energies= - 1674.762 711 E CV S KCal/Mol Cal/Mol - K Cal/Mol - K Total 398.346 139.305 232.391 278 B,0,1.8548885546,12.8827177365,5.6759359686 B,0,2.0314072582,11.1044058525,3.6960525868 B,0,2.5769118175,10.5153153442,6.205558954 C,0, - 0.230485539,11.5267347784,8.3526470903 H,0,0.8428043385,11.4808370377,8.5286450327 C,0, - 1.1288038401,11.7258127962,9.3860733413 H,0, - 0.7485607827,11.8213078145,10.4012932711 C,0, - 2.4981126425,11.8125687762,9.1147827168 C,0, - 2.8759010311,11.6889063559,7.7797567543 C,0, - 1.9194847739,11.479579329,6.7851499193 C,0, - 2.2702834828,11.3627659603,5.3494364881 C,0, - 3.5815631783,11.2775600419,4.8961184422 H,0, - 4.397595482,11.2572117423,5.6153180288 C,0, - 3.8668065915,11.200889 6939,3.5291719012 C,0, - 2.7752183466,11.2218648796,2.6637387478 H,0, - 2.9035099071,11.1764655877,1.5857396493 C,0, - 1.4853687225,11.2933008609,3.1768419828 H,0, - 0.604535897,11.3155949167,2.5327117508 C,0,3.0694090369,14.7792510066,5.3692670709 C,0,2.687 304143,14.6369238496,6.8443760017 C,0,3.7510934595,10.7627584803,2.2265269518 C,0,2.6489873105,11.573901015,1.5451672412 C,0,4.7069973409,10.285172731,6.9559995413 C,0,4.0186841732,8.9208257244,6.9719258187 Ir,0,0.8779232505,11.1893665068,5.36274925 N,0, - 0.610033675,11.3981132199,7.0771262403 N,0, - 1.2316409449,11.3541678187,4.4861227906 O,0,2.6937311477,13.5464309075,4.7877061271 O,0,1.7122829426,13.6115595784,6.8584014928 O,0,3.365967227,10.7185186481,3.5843007217 O,0,1.5477598772,11.4769141595,2.4292699432 O,0,3.6465916359,11.2057690087,6.7824103867 O,0,2.7985441092,9.1381933877,6.2910810334 H,0, - 3.9234231621,11.7729938175,7.505174743 C,0, - 5.309998858,11.0923003743,3.0522956035 C,0, - 3.4940507871,12.0459710505,10.2429314898 H,0,4.1430911606,14.9525781326,5.2207398672 H,0,2.2729393969,15.558678084,7.2741368345 H,0,2.5192862509,15.598828941 4,4.8789658505 H,0,3.548312285,14.3261935089,7.4569685314 H,0,5.2548650238,10.5071344851,7.8814591649 H,0,3.81377006,8.5775928135,7.999905078 H,0,3.8137130745,9.7368222657,1.828051258 H,0,2.37633814,11.1867337201,0.5540691713 H,0,4.7422484993,11.2252 096718,2.1298684424 H,0,2.9318825846,12.6328504323,1.435998992 H,0,5.4049559076,10.3754061576,6.1083095654 H,0,4.6011531906,8.1409026249,6.4642301004 C,0, - 4.9364014307,12.095325208,9.7444204578 C,0, - 3.3747884966,10.9064798347,11.261756251 C,0, - 3.1736 787507,13.3817310739,10.9241974671 H,0, - 5.6115157468,12.2671050972,10.5931296872 H,0, - 5.0951118857,12.9134631792,9.0279594486 H,0, - 5.2392662975,11.151806202,9.2690145655 H,0, - 4.0964755703,11.0536009725,12.0775079662 H,0, - 3.5833795315,9.9346976233,10.7 937393948 H,0, - 2.3741935418,10.8555097516,11.7097135951 H,0, - 3.8801383024,13.5631221997,11.7464008248 H,0, - 2.1603479246,13.3985300714,11.3453597838 H,0, - 3.2554272415,14.2158593719,10.2140119526 C,0, - 5.4082207392,11.0447844925,1.529515461 C,0, - 5.9279863572,9.8072974531,3.6161925863 C,0, - 6.1033689365,12.3069578441,3.5477454649 H,0, - 6.4621012123,10.9632065577,1.2323327367 H,0, - 5.0036572267,11.9542093434,1.0644190934 H,0, - 4.8797433449,10.177168 1998,1.1113500589 H,0, - 7.1431593905,12.243736187,3.197577939 H,0, - 6.1272233064,12.3700251763,4.6434153341 H,0, - 5.6725684537,13.2426908522,3.1661616486 H,0, - 6.9678519598,9.7096557619,3.2742247525 H,0, - 5.3734648865,8.9215801545,3.2775048663 H,0, - 5.9370590187,9.7979917653,4.7139727339 Transition Structures: TS3 - anti M06/BSsmall OBegleftantimetaOMeM06SB M06/gen E(RM06) = - 2193.18937429 Zero - point correction= 0.682041 (Hartree/Particle) Thermal correction to Energy= 0.725667 Thermal correction to Enthalpy= 0.726611 Thermal correction to Gibbs Free Energy= 0.606528 Sum of electronic and ZPE= - 2192.507333 Sum of electronic and thermal Energies= - 2192.463707 Sum of electronic and thermal Enthalpies= - 2192.462763 Sum of electronic and thermal Free Energies= - 2192.582846 E CV S KCal/Mol Cal/Mol - K Cal/Mol - K Total 455.36 3 167.968 252.736 279 C,0,3.5609557514,0.2010813501,2.9702170343 C,0,2.3465361305,0.0880035865,2.2927747296 N,0,2.2785030042, - 0.5593437922,1.1114144307 C,0,3.3751864716, - 1.1156840926,0.5873894674 C,0,4.6124161331, - 1.0392028647,1.2127062384 C,0,4.7035759076, - 0.3617700765,2.4211864776 C,0,1.0737926044,0.615122503,2.8329982715 N,0, - 0.0304918251,0.3263492787,2.1234092939 C,0, - 1.2273265207,0.6959912613,2.5770541401 C,0, - 1.3847311775,1.4150204918,3 .7547369653 C,0, - 0.2502850977,1.7520638692,4.479116308 C,0,0.994101251,1.34167461,4.0207930673 Ir,0,0.3087544863, - 0.5309623767,0.0197824122 B,0,0.7738968876, - 1.3277477366, - 1.7892584164 O,0,0.1284718577, - 1.0325753194, - 2.9860353036 C,0,0.9155757334, - 1.5097201279, - 4.0592145519 C,0,1.9085305223, - 2.4744777515, - 3.4082496763 O,0,1.9052664266, - 2.1064389012, - 2.0389726012 C,0,1.0234849562,1.439992062, - 0.7199690365 C,0,2.0869216554,1.41598836 62, - 1.6264929268 C,0,2.8718296207,2.5399166592, - 1.8960164162 C,0,2.5928304302,3.750844512, - 1.268278799 C,0,1.5134823733,3.8082964088, - 0.3906657056 C,0,0.7434749023,2.6849863014, - 0.1323809168 O,0,3.8902590717,2.3473552054, - 2.7824285857 O,0, - 0.32303745 55,2.8308628155,0.7393401607 B,0, - 1.5569078861,3.0221671987,0.2117843534 O,0, - 1.7960010473,3.3177764995, - 1.1052267737 C,0, - 3.2044581235,3.1733475604, - 1.297976995 C,0, - 3.4588015882,1.8341669761, - 1.9546834044 B,0,0.0269850742, - 2.4545261453,0.8632607737 O,0,0.8465310391, - 3.5434628176,0.6311548739 C,0,0.4365612398, - 4.6050009427,1.4780822161 C,0, - 0.9457924521, - 4.1804325253,1.9668086668 O,0, - 0.9509735364, - 2.7715314549,1.8080241884 B,0, - 1.5592702547, - 1.3159565562, - 0.380964026 O,0, - 2.7564788645, - 0.811703 5008,0.1444859143 C,0, - 3.7383286868, - 1.8405281725, - 0.0046317547 C,0, - 5.1299591556, - 1.2695284492, - 0.0990509759 O,0, - 1.8205613661, - 2.4765891897, - 1.1085996381 C,0, - 3.2317410506, - 2.6304234433, - 1.2155481861 C,0, - 3.6802930951, - 2.1145147072, - 2.5672369741 O,0, - 2.6915029246,2.9426850216,0.9808773805 C,0, - 3.7719421155,3.3359960681,0.1303808355 C,0, - 5.0017217722,2.5318096878,0.4640572318 H,0, - 0.3598928704,0.6331571773, - 0.9590140192 H,0, - 2.0738497859,0.4205231241,1.9483813811 H,0,1.8895428896,1.5936413519,4.5833189521 H,0, - 2.3780978599,1.7211411528,4.0719988135 H,0, - 0.3283530404,2.3308489026,5.397650439 H,0,3.6173041265,0.7196243619,3 .9235151109 H,0,5.6564681832, - 0.2764588765,2.9402466784 H,0,5.4812775667, - 1.5021671394,0.7522072949 H,0,3.2297740775, - 1.6359907567, - 0.3603493538 H,0, - 3.6669096511, - 2.4907230598,0.8859922402 H,0, - 3.4761725298, - 3.6990579171, - 1.114752638 H,0,2.367420677 5,0.4966150828, - 2.1420287669 H,0,3.1830905191,4.6435123143, - 1.4611741205 H,0,1.2487905956,4.7441636811,0.1000083868 H,0, - 1.1428811751, - 4.4431884111,3.013485509 H,0, - 1.7470120138, - 4.6103862966,1.3420716943 H,0,1.153650664, - 4.7087007114,2.3075629061 H, 0,0.4260850614, - 5.5461981336,0.9151738293 H,0,2.9240739484, - 2.388137208, - 3.8161155951 H,0,1.5892874738, - 3.5236901721, - 3.5001300643 H,0,1.4257541738, - 0.6591151487, - 4.5399500128 H,0,0.2771828525, - 1.9930139444, - 4.8101653761 H,0, - 3.9639734093,4.4074743969,0.3136280686 H,0, - 3.5494529819,3.9919680109, - 1.9460222242 H,0, - 5.8265425306,2.7641044999, - 0.2223714833 H,0, - 4.7774527469,1.4597888464,0.4008802046 H,0, - 5.3327447793,2.7522039 543,1.4857143879 H,0, - 4.5179346576,1.7016025862, - 2.216193131 H,0, - 2.8618814582,1.7622991541, - 2.8721315992 H,0, - 3.1528474969,1.0161780839, - 1.2853168724 H,0, - 5.3883935402, - 0.7344461457,0.82306409 H,0, - 5.2187500462, - 0.5700726755, - 0.9401640523 H,0, - 5.866 4497944, - 2.0721794215, - 0.2412872894 H,0, - 4.7560001344, - 2.2638124763, - 2.7306460373 H,0, - 3.4491883916, - 1.0438718442, - 2.6623153015 H,0, - 3.1306628636, - 2.6399397457, - 3.3567870067 C,0,4.6995672201,3.4500417737, - 3.0827743924 H,0,5.4486848823,3.1023880944, - 3. 8001961523 H,0,4.1223670522,4.2706259896, - 3.5380899383 H,0,5.2140022584,3.8367411961, - 2.188206327 Natural Atom No Charge ------------------- C 1 - 0.24646 C 2 0.21581 N 3 - 0.49138 C 4 0.07661 C 5 - 0.27386 C 6 - 0.19795 C 7 0.19519 N 8 - 0.49548 C 9 0.08336 C 10 - 0.24989 280 C 11 - 0.20403 C 12 - 0.24513 Ir 13 - 0.02514 B 14 1.01502 O 15 - 0.80561 C 16 - 0.139 51 C 17 - 0.14019 O 18 - 0.81237 C 19 - 0.27611 C 20 - 0.26647 C 21 0.31015 C 22 - 0.34025 C 23 - 0.24705 C 24 0.28632 O 25 - 0.56346 O 26 - 0.75724 B 27 1.36734 O 28 - 0.77518 C 29 0.06467 C 30 - 0.74261 B 31 0.93793 O 32 - 0.77879 C 33 - 0.14178 C 34 - 0.14238 O 35 - 0.78516 B 36 0.94922 O 37 - 0.82952 C 38 0.06238 C 39 - 0.72201 O 40 - 0.80472 C 41 0.06468 C 42 - 0.72889 O 43 - 0.78107 C 44 0.06465 C 45 - 0.72546 H 46 0.21114 H 47 0.27152 H 48 0.24550 H 49 0.26014 H 50 0.25431 H 51 0.24890 H 52 0.25604 H 53 0.26212 H 54 0.27939 H 55 0.22554 H 56 0.23221 H 57 0.24850 H 58 0.24898 H 59 0.24937 H 60 0.22786 H 61 0.21055 H 62 0.21174 H 63 0.229 37 H 64 0.21083 H 65 0.22834 H 66 0.22748 H 67 0.21050 H 68 0.22483 H 69 0.23531 H 70 0.24705 H 71 0.25191 H 72 0.25572 H 73 0.23931 H 74 0.26683 H 75 0.25790 H 76 0.25045 H 77 0.24391 H 78 0.24995 H 79 0.23929 H 80 0.24840 H 81 0.25973 C 82 - 0.33347 H 83 0.23551 H 84 0.21064 H 85 0.20817 TS3 - anti M06/BS1 OBegleftantimetaOMeM06PS M06/gen E(RM06) = - 2193.29319812 Zero - point correction= 0.676815 (Hartree/Particle) Thermal correction to Energy= 0.721187 Thermal correction to Enthalpy= 0.722131 Thermal correction to Gibbs Free Energy= 0.598260 Sum o f electronic and ZPE= - 2192.616383 Sum of electronic and thermal Energies= - 2192.572011 Sum of electronic and thermal Enthalpies= - 2192.571067 Sum of electronic and thermal Free Energies= - 2192.694938 E CV S KCal/Mol Cal/Mol - K Cal/Mol - K Total 452.552 169.542 260.708 C 3.52785 - 0.44173 2.98803 C 2.31424 - 0.38682 2.29983 N 2.19639 - 0.93317 1.0722 9 C 3.23827 - 1.55786 0.51249 C 4.4707 - 1.64999 1.1462 C 4.61621 - 1.07307 2.4021 C 1.09118 0.21617 2.87585 N - 0.02488 0.10954 2.13372 C - 1.18575 0.55881 2.61249 C - 1.28906 1.17461 3.85324 C - 0.13791 1.32424 4.615 29 C 1.06629 0.83342 4.12755 Ir 0.25694 - 0.61537 - 0.02621 B 0.67073 - 1.32159 - 1.88756 O 0.07846 - 0.88065 - 3.068 C 0.83486 - 1.36114 - 4.1 6591 C 1.69028 - 2.48193 - 3.57457 O 1.71963 - 2.1953 - 2.18324 C 1.17154 1.32868 - 0.59632 C 2.24253 1.27269 - 1.49391 C 3.14903 2.32385 - 1.65122 C 2.9938 3.49589 - 0.91401 C 1.90764 3.59094 - 0.04559 C 1.01273 2.54125 0.09551 O 4.15532 2.105 - 2.548 07 O - 0.05743 2.72906 0.95705 B - 1.24405 3.1205 0.43125 281 O - 1.41391 3.54554 - 0.86189 C - 2.82721 3.59367 - 1.08884 C - 3.22778 2.35081 - 1 .8531 B - 0.24399 - 2.56345 0.65302 O 0.43811 - 3.72095 0.32577 C - 0.0918 - 4.79059 1.09805 C - 1.42036 - 4.24897 1.61904 O - 1.25678 - 2.83821 1.57415 B - 1.68431 - 1.12912 - 0.5156 O - 2.82572 - 0.52399 0.02681 C - 3.92229 - 1.41329 - 0.21589 C - 5.2332 - 0.67313 - 0.28525 O - 2.06603 - 2.191 24 - 1.33442 C - 3.48399 - 2.16655 - 1.47639 C - 3.83635 - 1.50577 - 2.79367 O - 2.39983 3.1299 1.17394 C - 3.40465 3.72006 0.33899 C - 4.73389 3 .05739 0.59075 H - 0.25968 0.67617 - 0.91419 H - 2.04707 0.43299 1.95736 H 1.97214 0.93755 4.71738 H - 2.25093 1.54785 4.19174 H - 0.17278 1.81744 5.5838 H 3.62486 - 0.00098 3.97536 H 5.56669 - 1.11961 2.9283 H 5.293 - 2.16298 0.65643 H 3.05388 - 1.99014 - 0.47138 H - 3.95035 - 2.13111 0.62335 H - 3.8534 - 3.2027 - 1.45882 H 2.43068 0.38214 - 2.09352 H 3.67933 4.33258 - 1.0 1355 H 1.73501 4.50098 0.52605 H - 1.65543 - 4.56742 2.64112 H - 2.25949 - 4.52882 0.96116 H 0.60602 - 5.02793 1.91507 H - 0.20319 - 5.68081 0.4688 H 2.71203 - 2.50256 - 3.97234 H 1.23725 - 3.47255 - 3.72655 H 1.45184 - 0.54074 - 4.56521 H 0.1636 - 1.70622 - 4.96162 H - 3.46211 4.7894 7 0.60184 H - 3.04842 4.49609 - 1.67502 H - 5.50214 3.44506 - 0.08943 H - 4.6468 1.97405 0.44874 H - 5.06024 3.24381 1.6191 H - 4.28616 2.3753 - 2.1433 H - 2.61978 2.27468 - 2.76136 H - 3.04693 1.45199 - 1.24629 H - 5.44348 - 0.17857 0.66963 H - 5.22234 0.08719 - 1.07502 H - 6.05427 - 1.37132 - 0.49194 H - 4.91735 - 1.51373 - 2.98098 H - 3.4775 - 0.46798 - 2.80923 H - 3.33714 - 2.03763 - 3.6 1022 C 5.09153 3.13364 - 2.74241 H 5.80622 2.768 - 3.4834 H 4.61608 4.04909 - 3.12501 H 5.63051 3.37345 - 1.81333 TS3 - OMe anti M06/BSsmall OMeleftmetaOBegM06SB M06/gen E(RM06) = - 2193.18032628 Zero - point correction= 0.680323 (Hartree/Particle) Thermal correction to Energy= 0.724912 Thermal correction to Enthalpy= 0.725856 Thermal correction to Gibbs Free Energy= 0.600324 Sum of electronic and ZPE= - 2192.500003 Sum of electronic and thermal Energies= - 2192.455414 Sum of electronic and thermal Enthalpies= - 2192.454470 Sum of electronic and thermal Free Energies= - 2192.580 003 E CV S KCal/Mol Cal/Mol - K Cal/Mol - K Total 454.889 168.996 264.206 C,0,0.1350037065,3.9521785187, - 2.0247472636 C,0,0.6320295662,2.8802586274, - 1.2827690245 N,0,0.4322300422,1.6097705979, - 1.6898525329 C,0, - 0.2167112834,1.3745450672, - 2.8364237057 C,0, - 0.7278956633,2.3973701198, - 3.6231808553 C,0, - 0.5568388559,3.7085639664, - 3.2013167176 C,0,1.4333112059,3.0649709536, - 0.0537637292 N,0,1.8658400457,1.9434036159,0.5481338894 C,0,2.64605194,2.0341776383,1.6266508773 C,0,3.0305898306,3.2540291534,2.1666970173 C,0,2.5740000423,4.4191755886,1.5658906332 C,0,1.7680216624,4.3266351824,0.4415730055 Ir,0,1.078892252, - 0.0530044932, - 0.3156286583 B,0,0.3140025812, - 1.6807475583, - 1.2 541496525 282 O,0, - 0.0464597142, - 2.8692332877, - 0.6253082288 C,0, - 0.5113503982, - 3.7774861939, - 1.6035363552 C,0, - 0.8390913405, - 2.8971161035, - 2.8095025576 O,0, - 0.0907894271, - 1.7131786009, - 2.5905479048 C,0, - 0.8215318789,0.2674045179,0.7953206497 C,0, - 2.0219202518,0.1005268496,0.0932900507 C,0, - 3.2360726228,0.5462220175,0.6064807567 C,0, - 3.2987837371,1.1590454337,1.8546762795 C,0, - 2.1245706933,1.2965953812,2.5832732013 C,0, - 0.9098295615,0.8530493656 ,2.0655274157 O,0, - 4.3421767608,0.4040964488, - 0.1976170765 B,0, - 5.5872074828,0.0695228773,0.2111761407 O,0, - 5.9730235708, - 0.1958040418,1.5031451732 C,0, - 7.3009799598, - 0.7242696162,1.4242887782 C,0, - 7.2338041952, - 2.2307401879,1.5449405264 O,0,0.221065 2035,1.0128089397,2.8416936486 B,0,2.8448463717, - 0.2389572339, - 1.4664358679 O,0,2.9335940172, - 0.7042654419, - 2.7652741989 C,0,4.2779268473, - 0.5822217476, - 3.1995318129 C,0,5.0702260667, - 0.3505102956, - 1.9138215624 O,0,4.1060015115,0.1319602474, - 0.9933524 976 B,0,2.4047735416, - 1.3501694255,0.5713783075 O,0,2.9420456896, - 1.1005451322,1.8358784424 C,0,3.9937802723, - 2.0406194747,2.0487258864 C,0,4.118131785, - 2.3540888167,3.5187949849 O,0,2.9295415639, - 2.5302510423,0.0575206862 C,0,3.6166821266, - 3.1969995956,1.1131426995 C,0,2.6909916319, - 4.2363729841,1.7115861415 O,0, - 6.6098837847, - 0.0375074456, - 0.6985747763 C,0, - 7.8042552271, - 0.1922237517,0.0669617718 C,0, - 8.7974886007, - 1.0453969996, - 0.6801535762 H,0,0.344000105, - 0.819501 2334,0.9337408212 H,0,2.9608164328,1.0838237045,2.0566865733 H,0,1.4125894113,5.2315117575, - 0.0437598576 H,0,3.6698734702,3.2811980633,3.0455563648 H,0,2.8457871161,5.395384526,1.9632407186 H,0,0.2863983012,4.9742452424, - 1.6890986673 H,0, - 0.9515889934,4.5379140638, - 3.7851072367 H,0, - 1.2522006801,2.1597436207, - 4.5451233919 H,0, - 0.3132125448,0.3237502923, - 3.1104880616 H,0,4.9315213458, - 1.5840077109,1.681417791 H,0,4.5151392243, - 3.67837118 57,0.6988151811 H,0, - 2.0374393412, - 0.3739165719, - 0.8900103775 H,0, - 4.2515888415,1.5011308176,2.251267877 H,0, - 2.1324009476,1.7573017646,3.5711888268 H,0,5.8826254649,0.3784232789, - 2.0260042425 H,0,5.4976668424, - 1.2894002993, - 1.5232043522 H,0,4.360880 0984,0.2678343245, - 3.8949110725 H,0,4.5800346113, - 1.4912942691, - 3.7339672073 H,0, - 1.9116802338, - 2.646556922, - 2.8539975791 H,0, - 0.5528905027, - 3.3486109103, - 3.767722346 H,0, - 1.3819851713, - 4.3264556382, - 1.2225403351 H,0,0.2821170793, - 4.5070075748, - 1.8309156399 H,0, - 7.8883502761, - 0.3022085297,2.2519819066 H,0, - 8.2319965403,0.8137742925,0.2230952868 H,0,4.3791434538, - 1.4475300381,4.0782663665 H,0,3.1684327368, - 2.733401 0991,3.9169738372 H,0,4.8986285316, - 3.104813098,3.7010400124 H,0,3.1907902319, - 4.8424079188,2.4790052789 H,0,1.8091237787, - 3.753899347,2.158086744 H,0,2.3318995812, - 4.9003931953,0.9169367812 H,0, - 8.2338969359, - 2.6821327312,1.56204412 H,0, - 6.671554648 4, - 2.6606247119,0.7044442225 H,0, - 6.7141090425, - 2.5020561992,2.4706185886 H,0, - 9.7185576215, - 1.1787422716, - 0.097679456 H,0, - 9.0587407209, - 0.5662066795, - 1.6302987924 H,0, - 8.377981328, - 2.0333085814, - 0.9049672067 C,0,0.4556152675, - 0.0696025032,3.71337495 56 H,0,1.3800349812,0.1483616948,4.2607378143 H,0, - 0.3745900026, - 0.192873577,4.4286449396 H,0,0.5994438126, - 1.0123082851,3.1600454055 Natural Atom No Charge ------------------- C 1 - 0.24506 C 2 0.20934 N 3 - 0.49068 C 4 0.07025 C 5 - 0.27175 C 6 - 0.19725 C 7 0.20317 N 8 - 0.49267 C 9 0.08546 C 10 - 0.27154 C 11 - 0.20119 C 12 - 0.24587 Ir 13 - 0.01380 B 14 1.02034 O 15 - 0.804 26 C 16 - 0.13931 C 17 - 0.14001 O 18 - 0.81375 C 19 - 0.28572 C 20 - 0.27053 C 21 0.31916 C 22 - 0.30656 C 23 - 0.26173 C 24 0.27756 O 25 - 0.73960 B 26 1.36437 O 27 - 0.78529 C 28 0.06148 C 29 - 0.73800 O 30 - 0.61056 B 31 0.91988 O 32 - 0.77739 C 33 - 0.14375 C 34 - 0.14243 O 35 - 0.78760 B 36 0.95018 O 37 - 0.82101 C 38 0.06262 C 39 - 0.723 56 O 40 - 0.79617 C 41 0.06315 C 42 - 0.73021 O 43 - 0.77113 C 44 0.05978 C 45 - 0.72887 H 46 0.21838 H 47 0.26997 H 48 0.24609 H 49 0.25839 283 H 50 0.25445 H 51 0.24889 H 52 0.25633 H 53 0.26295 H 54 0.28001 H 55 0.22215 H 56 0.23251 H 57 0.24622 H 58 0.26164 H 59 0.25123 H 60 0.21309 H 61 0.22314 H 62 0.22567 H 63 0.21808 H 64 0.21130 H 65 0.22824 H 66 0.22580 H 67 0.21240 H 68 0.23867 H 69 0.22701 H 70 0.25390 H 71 0.24896 H 72 0.24544 H 73 0.23968 H 74 0.249 97 H 75 0.26006 H 76 0.24859 H 77 0.24762 H 78 0.26491 H 79 0.24804 H 80 0.26317 H 81 0.25064 C 82 - 0.30788 H 83 0.22626 H 84 0.19996 H 85 0.20860 TS3 - OMe anti M06/BS1 OMeleftmetaOBegM06PS M06/gen E(RM06) = - 2193.28495198 Zero - point correction= 0.676488 (Hartree/Particle) Thermal correction to Energy= 0.721357 Thermal correction to Enthalpy= 0.722302 Thermal correction to Gibbs Free Energy= 0.595063 Sum of el ectronic and ZPE= - 2192.608464 Sum of electronic and thermal Energies= - 2192.563595 Sum of electronic and thermal Enthalpies= - 2192.562650 Sum of electronic and thermal Free Energies= - 2192.689889 E CV S KCal/Mol Cal/Mol - K Cal/Mol - K Total 452.659 169.934 267.795 C 0.25942 4.36579 - 0.88391 C 0.72454 3.12581 - 0.44183 N 0.52873 2.01339 - 1.17944 C - 0.08343 2.10286 - 2.36705 C - 0.56373 3.30665 - 2.86539 C - 0.39797 4.45573 - 2.1024 C 1.48874 2.96302 0.81432 N 1.90429 1.71658 1.10061 C 2.65728 1.5062 2.18275 C 3.02719 2.53139 3.04377 C 2.58228 3.81934 2.77294 C 1.80569 4.04094 1.64475 Ir 1.11316 0.03486 - 0.27628 B 0.35212 - 1.27232 - 1.63187 O - 0.04762 - 2.57644 - 1.35151 C - 0.46142 - 3.19181 - 2.55836 C - 0.75565 - 2.01828 - 3.49127 O - 0.00199 - 0.94505 - 2.94355 C - 0.80931 0.09313 0.84431 C - 1.99376 0.13772 0.09635 C - 3.2142 0.46517 0.6783 C - 3.30366 0.74089 2.04018 C - 2.1466 0.66259 2.80678 C - 0.92482 0.33592 2.22035 O - 4.29997 0.56037 - 0.16225 B - 5.56119 0.15298 0.10524 O - 5.99624 - 0.43244 1.27143 C - 7.32608 - 0.90784 1.01513 C - 7.2725 - 2.39546 0.74599 O 0.18672 0.26957 3.03801 B 2.91318 0.11262 - 1.39505 O 3.03897 0.00184 - 2.76797 C 4.40009 0.21413 - 3.11763 C 5.15285 0.06461 - 1.797 O 4.16464 0.31338 - 0.80673 B 2.36737 - 1.49497 0.28732 O 2.87741 - 1.59375 1.58372 C 3.89616 - 2.59584 1.57234 C 3.97466 - 3.27471 2.91674 O 2.86814 - 2.52759 - 0.49683 C 3.51074 - 3.46462 0.36687 C 2.54466 - 4.59394 0.6628 O - 6.55454 0.29586 - 0.834 C - 7.77881 - 0.03285 - 0.1712 C - 8.75547 - 0.64366 - 1.14257 H 0.32783 - 1.00684 0.70101 H 2.96094 0.47397 2.3496 H 1.45735 5.04365 1.41744 H 3.64361 2.31442 3.91129 H 2.83957 4.64721 3.42931 H 0.40914 5.25784 - 0.28405 H - 0.76885 5.41558 - 2.45355 H - 1.0594 3.33133 - 3.83125 H - 0.17718 1.16689 - 2.91696 H 4.85443 - 2.09259 1.34885 H 4.4065 - 3.85011 - 0.14141 H - 1.99259 - 0.06951 - 0.97448 H - 4.26045 0.99154 2.49004 H - 2.17426 0.8587 3.87771 H 5.98326 0.77119 - 1.68382 H 5.54119 - 0.95802 - 1.66231 H 4.51137 1.22195 - 3.54506 H 4.70575 - 0.51722 - 3.87454 H - 1.82363 - 1.74924 - 3.48637 H - 0.44737 - 2.19749 - 4.52785 H - 1.33601 - 3.82686 - 2.37417 284 H 0.35477 - 3.82427 - 2.93999 H - 7.93698 - 0.70391 1.90463 H - 8.19903 0.90551 0.22882 H 4.25322 - 2.55033 3.68995 H 3.00546 - 3.70729 3.19182 H 4.72577 - 4.07438 2.91137 H 3.01032 - 5.38677 1.26109 H 1.66225 - 4.21588 1.19744 H 2.19478 - 5.02536 - 0.28062 H - 8.27581 - 2.81581 0.61053 H - 6.68126 - 2.60683 - 0.1541 H - 6.79554 - 2.90316 1.59008 H - 9.69101 - 0.91393 - 0.63783 H - 8.9886 0.07389 - 1.93532 H - 8.33655 - 1.54098 - 1.61094 C 0.38649 - 1.00342 3.61846 H 1.29733 - 0.94393 4.22374 H - 0.46359 - 1.2852 4.25931 H 0.53656 - 1.77637 2.8481 TS3 - syn M06/BSsmall OBegleftsynmetaOMeM06SB M06/gen E(RM06) = - 2193.18274050 Zero - point correction= 0.681553 (Hartree/Particle) Thermal correction to Energy= 0.725715 Thermal correction to Enthalpy= 0.726659 Thermal correction to Gibbs Free Energy= 0.603579 Sum of electronic and ZPE= - 2192.501187 Sum of electronic and thermal Energies= - 2192.457026 Sum of electronic and thermal Enthalpies= - 2192.456082 Sum of ele ctronic and thermal Free Energies= - 2192.579162 E CV S KCal/Mol Cal/Mol - K Cal/Mol - K Total 455.393 168.455 259.044 C,0, - 1.9371764833,0.8726555481,3.5723254207 C,0, - 1.2119773504,0.2968032091,2.5300470881 N,0, - 0.0883935347,0.8736659486,2.0559265617 C,0,0.3612136411,1.9975253131,2.6274752422 C,0, - 0.301594063,2.6116420554,3.681843972 C,0, - 1.4787613652,2.0458860699,4.1528286933 C,0, - 1.6276103723, - 0.9659717072,1.8924837321 N,0, - 1.1157993623, - 1.2095151257,0.6729906071 C,0, - 1.4611233017, - 2.3288340647,0.0340149622 C,0, - 2.3131441678, - 3.2743304099,0.5930320634 C,0, - 2.8122320014, - 3.0505881388,1.8688655437 C,0, - 2.4695110899, - 1.877388031,2.5288045272 Ir,0,0.8124757461,0.008617 4257,0.179568634 B,0,2.5838263409,0.9790406313,0.0831000963 O,0,3.4415221986,1.016126597, - 1.0075740401 C,0,4.5960686627,1.7485825844, - 0.6467072554 C,0,4.1642980508,2.5508219931,0.5804325713 O,0,3.0409240454,1.8444606253,1.0814985735 C,0, - 0.1841498541,1.6523320326, - 0.9376682403 C,0,0.3333764476,2.9424011973, - 0.7929805062 C,0, - 0.3260227974,4.0736744263, - 1.2786900702 C,0, - 1.5260518635,3.9309102222, - 1.9691110936 C,0, - 2.0463486391,2.65228995 03, - 2.1501835511 C,0, - 1.3936240373,1.5387812543, - 1.6382335448 O,0,0.2873860503,5.2680629959, - 1.0360262706 O,0, - 1.903244475,0.2765711163, - 1.8848967873 B,0, - 3.1793487326, - 0.057963546, - 1.6004780935 O,0, - 4.1247779914,0.7862698731, - 1.0637589948 C,0, - 5.263 4595848, - 0.0142370863, - 0.7512977138 C,0, - 5.2817347584, - 0.2634165717,0.7407702707 B,0,1.8230448978, - 1.3920154677,1.4055325636 O,0,3.0425529219, - 1.1843471506,2.0259724891 C,0,3.4855578122, - 2.4228737965,2.5512439007 C,0,2.2205035654, - 3.277972363,2.625587 469 O,0,1.3206320751, - 2.6532621451,1.7227818675 B,0,1.6876812848, - 1.4320011356, - 1.0148368224 O,0,0.9618350786, - 2.1001319625, - 2.0000603721 C,0,1.779296857, - 3.156192585, - 2.5047391257 C,0,1.4879623103, - 3.3910671048, - 3.9656179124 O,0,2.9872696892, - 1.917028597, - 0.9695048359 285 C,0,3.2006462943, - 2.7044951552, - 2.138606313 C,0,3.900674683, - 1.8478229356, - 3.1733131751 O,0, - 3.659489163, - 1.3254483019, - 1.8400872504 C,0, - 5.0692445372, - 1.2670124 747, - 1.6344517182 C,0, - 5.57148449, - 2.5767377317, - 1.0806597072 H,0,0.7558533086,0.419258734, - 1.4051236286 H,0, - 1.0172469029, - 2.4611109051, - 0.9522726342 H,0, - 2.8329222434, - 1.6829554053,3.535426706 H,0, - 2.5682317296, - 4.1698038717,0.0310467167 H,0, - 3.462 1534303, - 3.7801383659,2.3493665679 H,0, - 2.8659672962,0.4156750947,3.9062969707 H,0, - 2.0364525814,2.5131545724,4.9621766649 H,0,0.1012305896,3.5253921621,4.1112896579 H,0,1.2929572042,2.3905318618,2.2204063494 H,0,1.5412651405, - 4.0681918229, - 1.9275146143 H,0,3.8293522269, - 3.5666144302, - 1.8703872932 H,0,1.282250609,3.1119764092, - 0.2818224157 H,0, - 2.0562535409,4.7872672803, - 2.3782787989 H,0, - 2.9774964054,2.5200703443, - 2.6983469065 H,0,1.7796768877, - 3.2799793 104,3.6348586184 H,0,2.3864334871, - 4.3204100613,2.3252178349 H,0,3.9625648402, - 2.2690215425,3.5275607353 H,0,4.2308553369, - 2.8548744361,1.8650521611 H,0,3.8575790538,3.5752626222,0.3112770187 H,0,4.9405754183,2.6161367726,1.3529288243 H,0,4.9155755781,2.3816458628, - 1.4842010108 H,0,5.412476731,1.0473240441, - 0.4124897729 H,0, - 6.1662822349,0.536910931, - 1.0524003971 H,0, - 5.5416500565, - 1.0822431801, - 2.6151116991 H,0, - 6.6583062759, - 2.549871859 7, - 0.9275681687 H,0, - 5.3439497456, - 3.3880657605, - 1.781940978 H,0, - 5.0857575495, - 2.8085857521, - 0.1246074748 H,0, - 6.1769324729, - 0.8156282354,1.0548597412 H,0, - 4.3926507112, - 0.835144366,1.0429581461 H,0, - 5.2606093688,0.6973153564,1.268877419 H,0,0.44162 16598, - 3.6891439974, - 4.0995336164 H,0,1.6529572046, - 2.4762673074, - 4.5473623156 H,0,2.1271638283, - 4.186231485, - 4.3726777133 H,0,4.1573608262, - 2.4190446696, - 4.0753104454 H,0,3.2702762683, - 0.9933029717, - 3.4565740727 H,0,4.8215734075, - 1.4409438762, - 2.7392 279068 C,0, - 0.335204604,6.4220819448, - 1.5280829899 H,0,0.2960202356,7.2674475373, - 1.2389702513 H,0, - 0.426075284,6.4019857507, - 2.6258739611 H,0, - 1.3394909132,6.5607488518, - 1.095835761 TS3 - syn M06/BS1 OBegleftsynmetaOMeM06PS M06/gen E(RM06) = - 2193.28699673 Zero - point correction= 0.677046 (Hartree/Particle) Thermal correction to Energy= 0.721590 Thermal correction to Enthalpy= 0.722534 Thermal correction to Gibbs Free Energy= 0.598428 Sum of electronic and ZPE= - 2192.609951 Sum of electronic and thermal Energies= - 2192.565407 Sum of electronic and thermal Enthalpies= - 2192.564463 Sum of electronic and thermal Free Energies= - 2192.688569 E CV S KCal/Mol Ca l/Mol - K Cal/Mol - K Total 452.805 169.793 261.203 C,0, - 2.1172927325,0.7460120366,3.4172143456 C,0, - 1.3246651789,0.1933950911,2.4098566473 N,0, - 0.2094535381,0.8191202329,1.9773583305 C,0,0.1535296281,1.9772375874,2.5433435662 C,0, - 0.5847723294, 2.5761900929,3.5555802059 C,0, - 1.745973402,1.9518862936,3.9943535183 C,0, - 1.6547714133, - 1.0903744413,1.7616235462 N,0, - 1.0655232311, - 1.3208230571,0.5754699288 C,0, - 1.314361967, - 2.4665963584, - 0.0633260952 C,0, - 2.1417907932, - 3.4509848111,0.4619274308 C,0, - 2.730243614, - 3.2345100863,1.7011388502 C,0, - 2.4930614539, - 2.0343216979,2.3586862898 Ir,0,0.8192535401,0.0024363882,0.1501779479 B,0,2.5715726953,1.0132177663,0.191071887 O,0,3.5451368904,1.0383046592, - 0.7968148191 C,0,4.6729853198,1.7319915739, - 0.2900702826 C,0,4.1105123231,2.5681664539,0.856988646 O,0,2.9198251097,1.8861516166,1.2275890352 C,0, - 0.1757910802,1.6372202678, - 0.9856158349 C,0,0.3815481602,2.9186054212, - 0 .9364485256 C,0, - 0.2678874704,4.0422772941, - 1.4520466385 C,0, - 1.5026509474,3.9008371592, - 2.0794800573 C,0, - 2.0676873122,2.6288974406, - 2.1628154967 C,0, - 1.4226345359,1.5249563619, - 1.6201810693 O,0,0.3911636303,5.230151736, - 1.3053712077 O,0, - 1.98616570 02,0.2688121406, - 1.7601221272 B,0, - 3.2621991572, - 0.0154182654, - 1.4272603294 O,0, - 4.1898993054,0.8805221026, - 0.9403230377 C,0, - 5.3401919909,0.1261201351, - 0.5488871235 C,0, - 5.3624876102,0.0183009315,0.9603324565 B,0,1.8647449685, - 1.403166961,1.355721984 5 O,0,3.1063455188, - 1.2156810861,1.9413147014 C,0,3.5619577741, - 2.468237009,2.4291602811 C,0,2.2949736854, - 3.3179922141,2.5294021166 O,0,1.3702689954, - 2.6710165792,1.6632977737 B,0,1.7433156374, - 1.3725626693, - 1.0904470655 O,0,1.0364390744, - 2.007698484, - 2.1117715144 C,0,1.8440434043, - 3.0820759763, - 2.5987173754 C,0,1.5797143147, - 3.3164189795, - 4.0645149425 O,0,3.0381411172, - 1.8666001688, - 1.033508143 C,0,3.2652807493, - 2.6594627 946, - 2.1988681426 C,0,4.0149551163, - 1.8263027718, - 3.217991615 O,0, - 3.7648026769, - 1.2912534553, - 1.5503249227 C,0, - 5.1707073097, - 1.2047515522, - 1.3171202001 C,0, - 5.6655411483, - 2.4544564386, - 0.6332984894 H,0,0.832791435,0.4295717951, - 1.4171912137 H,0, - 0. 8179481379, - 2.5814550589, - 1.0258155926 H,0, - 2.9291038092, - 1.8478960901,3.3367359407 H,0, - 2.3139555668, - 4.3670905455, - 0.0958435385 H,0, - 3.3677999593, - 3.9902976855,2.1549201417 H,0, - 3.0297982585,0.2446344662,3.7289475472 H,0, - 2.3597356967,2.3987530485,4 .7727003114 H,0, - 0.2501064561,3.5179560119,3.980225459 H,0,1.0777227467,2.4110968497,2.1668302918 H,0,1.575690863, - 3.9863447497, - 2.0219734448 H,0,3.8651384705, - 3.5349160216, - 1.910504156 286 H,0,1.3601863814,3.0874152496, - 0.487162532 H,0, - 2.0285831157,4.7476412992, - 2.510787028 H,0, - 3.028707722,2.4983012012, - 2.6550921762 H,0,1.8833973937, - 3.3341653548,3.5497888901 H,0,2.4437542836, - 4.3541028318,2.2027628504 H,0,4.0692785292, - 2.3313971916,3.3914250125 H,0,4.2806968373, - 2.8890881522,1.7102028946 H,0,3.8555836172,3.5902383084,0.5343596253 H,0,4.7850457579,2.6325167861,1.7187200584 H,0,5.1285365747,2.3364775071, - 1 .0830261067 H,0,5.4142290925,0.9997132364,0.0650341501 H,0, - 6.2337232035,0.6613782311, - 0.8987487754 H,0, - 5.6631191848, - 1.1077916072, - 2.299447601 H,0, - 6.7476610588, - 2.4055909234, - 0.4614184865 H,0, - 5.4565502093, - 3.3274009021, - 1.2606521738 H,0, - 5.160374 4036, - 2.60081145,0.3292975376 H,0, - 6.2691098571, - 0.4836363411,1.3185622405 H,0, - 4.4870623803, - 0.5407313108,1.3182029628 H,0, - 5.3254640483,1.0229900147,1.3944087361 H,0,0.5356630433, - 3.6083330828, - 4.2179588914 H,0,1.7620865807, - 2.4041974787, - 4.64324103 66 H,0,2.2220369843, - 4.115591864, - 4.4552673018 H,0,4.2786324816, - 2.4114333479, - 4.1076498567 H,0,3.416538227, - 0.959479839, - 3.5268713487 H,0,4.9363242169, - 1.4460503864, - 2.7650772824 C,0, - 0.2135205119,6.3793495933, - 1.8400391351 H,0,0.4585380547,7.2140958935, - 1.6274389191 H,0, - 0.3497094413,6.2967796065, - 2.9287303556 H,0, - 1.1905591713,6.5778681921, - 1.3737433707 TS3 - OMe Conformer B M06/BSsmall OMerightmetaOBegM06SBb M06/gen E(RM06) = - 2193.17982496 Zero - point correction= 0.680847 (Hartree/Particle) Thermal correction to Energy= 0.725458 Thermal correction to Enthalpy= 0.726402 Thermal correction to Gibbs Free Energy= 0.599436 Sum of electronic and ZPE= - 2192.49897 8 Sum of electronic and thermal Energies= - 2192.454367 Sum of electronic and thermal Enthalpies= - 2192.453423 Sum of electronic and thermal Free Energies= - 2192.580389 E CV S KCal/Mol Cal/Mol - K Cal/Mol - K Total 455 .231 168.824 267.222 C,0,1.4628911864, - 3.7854332846, - 2.221047007 C,0,1.2190755196, - 2.4879756268, - 1.768441026 N,0,1.6803437954, - 2.074290212, - 0.5730753639 C,0,2.3968575101, - 2.9104771621,0.1839191809 C,0,2.6726185926, - 4.2137299958, - 0.2041456833 C,0,2.1914946387, - 4.6583648925, - 1.4282148817 C,0,0.4952806855, - 1.4912460736, - 2.5860458473 N,0,0.5388825524, - 0.2183818887, - 2.1524802498 C,0, - 0.0342050774,0.7437631408, - 2.8798007869 C,0, - 0.7200986993,0.48092 94424, - 4.0591060312 C,0, - 0.8129771685, - 0.8353848172, - 4.4900394311 C,0, - 0.1906866504, - 1.831828517, - 3.7523905051 Ir,0,1.2211784857,0.0316035264,0.0498017853 B,0,1.9255026815, - 0.0027853286,1.9504998608 O,0,1.3207906707,0.5471406554,3.0726342112 C,0,2.22 24648665,0.4648513112,4.1554151917 C,0,3.2419592139, - 0.5928447,3.725936671 O,0,3.1137534045, - 0.6514867095,2.3168159728 C,0, - 0.8282299371, - 0.6697251799,0.5655027674 C,0, - 1.018406071, - 1.6345159693,1.5682215624 C,0, - 2.271266562, - 2.2036773946,1.7908735276 C,0, - 3.3710224913, - 1.8345101825,1.0232747885 C,0, - 3.200787938, - 0.8831299105,0.0265978867 C,0, - 1.9495049075, - 0.3143648618, - 0.1891345025 O,0,0.0823366883, - 2.0447875945,2.2818081871 O,0, - 4.2208459298, - 0.487079978, - 0.8081058676 B,0, - 5.5091838379, - 0.2910512548, - 0.4473803689 O,0, - 6.0171930987, - 0.3911984588,0.8256653865 C,0, - 7.4356167864, - 0.2677340932,0.699340252 C,0, - 8.0110471685,0.4224576503,1.9094411497 B,0,3.2152708816,0.4783671 023, - 0.4908716524 O,0,3.9164243988, - 0.3349597945, - 1.3790450491 287 C,0,5.2549421724,0.1272984592, - 1.4578324452 C,0,5.2067476807,1.5307454053, - 0.8550992026 O,0,4.0133368445,1.5455556755, - 0.0929100892 B,0,1.3952846998,2.0820081344,0.1197853234 O,0,1.308099 3885,2.857651065, - 1.042991114 C,0,1.771840966,4.1647094746, - 0.7082643028 C,0,1.108443333,5.2021614518, - 1.5792579916 O,0,1.5921194141,2.8930327749,1.221768336 C,0,1.5202210337,4.251418552,0.8050889683 C,0,0.1737447104,4.8187799675,1.2063738171 O,0, - 6. 4492308233,0.0564642923, - 1.3862198462 C,0, - 7.6197341443,0.4350680692, - 0.6619513329 C,0, - 7.6893846019,1.9461560035, - 0.6026877407 H,0, - 0.0295681847,0.704971807,0.8571658437 H,0,0.0739166575,1.7527222467, - 2.4811153583 H,0, - 0.2594102592, - 2.8676354231, - 4.0 742932278 H,0, - 1.1828369632,1.2941401155, - 4.6124467258 H,0, - 1.3649205032, - 1.0883027513, - 5.3931991349 H,0,1.1072879947, - 4.1072767207, - 3.196000611 H,0,2.3919219093, - 5.6714870284, - 1.7716369603 H,0,3.2620300893, - 4.8579294581,0.4433312306 H,0,2.7652370962, - 2.4958422197,1.1218588622 H,0,2.8627840626,4.1808307192, - 0.8801476609 H,0,2.3266572266,4.8119171182,1.3009336743 H,0, - 2.3969882866, - 2.9637398981,2.560700242 H,0, - 4.3490534517, - 2.2734060135 ,1.2049048694 H,0, - 1.8732824727,0.4492402555, - 0.9661089476 H,0,5.1490811151,2.3101274082, - 1.6320372874 H,0,6.065640446,1.7553166046, - 0.2102618112 H,0,5.5928668373,0.1168655621, - 2.5018933915 H,0,5.9064445299, - 0.546206183, - 0.8798303783 H,0,3.0190357849, - 1.5838244656,4.1582337313 H,0,4.2735236026, - 0.3337045625,3.9972253965 H,0,1.6854465841,0.1939041655,5.0754278766 H,0,2.694068,1.4474693363,4.3127803095 H,0,1.3621672127,5.0295435197, - 2.6321700413 H,0,0.0164494621,5.1580802966, - 1.482 7574978 H,0,1.4406658491,6.2140239826, - 1.3108547738 H,0,0.0939124057,5.8898573994,0.977330705 H,0, - 0.6367072623,4.2872148338,0.6880491669 H,0,0.0273613881,4.6806273491,2.2836085877 H,0, - 8.498190628,0.0365592427, - 1.1894499876 H,0, - 7.8510421724, - 1.2877359574,0.6266703241 H,0, - 9.099856889,0.5296501939,1.8179231366 H,0, - 7.7982491429, - 0.1627301461,2.8111301055 H,0, - 7.5704925367,1.4177968071,2.0422442026 H,0, - 8.6104429006,2.2937220366, - 0.1177821116 H,0, - 6.8302385726,2.35013922 19, - 0.0491270769 H,0, - 7.6564212322,2.3536916544, - 1.6192306398 C,0, - 0.1082095948, - 2.2775341258,3.6536086966 H,0,0.8878017252, - 2.4096841992,4.0926365855 H,0, - 0.6047087441, - 1.4186799257,4.1308114198 H,0, - 0.689146304, - 3.1918400716,3.8521771502 TS3 - OMe sy n M06/BS1 OMerightmetaOBegM06PS OMerightmetaOBeg M06/gen E(RM06) = - 2193.28635803 Zero - point correction= 0.677703 (Hartree/Particle) Thermal correction to Energy= 0.722240 Thermal correction to Enthalpy= 0.723185 Thermal correction to Gibbs Free Energy= 0.597612 Sum of electronic and ZPE= - 2192.608655 Sum of electronic and thermal Energies= - 2192.564118 Sum of electronic and thermal Enthalpies= - 2192.563173 Sum of electronic and thermal Free Energies= - 2192.688746 E CV S KCal/Mol Cal/Mol - K Cal/Mol - K Total 453.213 169.542 264.289 C,0.441931, - 3.483352, - 2.593041 C,0.569712, - 2.219001, - 2.012722 N,1.304915, - 2.037812, - 0.899794 C,1.941635, - 3.078836, - 0.351353 C,1.84752, - 4.363455, - 0.868896 C,1.078883, - 4.567769, - 2.008924 C, - 0.053175, - 1.014903, - 2.602687 N,0.337962,0.168807, - 2.094312 C, - 0.144866,1.298631, - 2.620387 C, - 1.0757 95,1.305149, - 3.653109 C, - 1.523234,0.08748, - 4.15011 C, - 0.997864, - 1.08649, - 3.627976 Ir,1.342365,0.021732,0.008517 B,2.193419, - 0.398287,1.805126 O,1.837814,0.151095,3.028325 C,2.406098, - 0.638776,4.051962 C,3.548116, - 1.383376,3.362119 O,3.180735, - 1.380168,1.989194 C, - 0.735637, - 0.389684,0.697306 C, - 0.979249, - 1.51212,1.513585 C, - 2.277024, - 1.961409,1.749392 C, - 3.375272, - 1.302817,1.189936 C, - 3.152812, - 0.186258,0.397569 C, - 1.850114,0.262629,0.175145 O,0.122805, - 2.139778,2.026237 O, - 4.149224,0.538924, - 0.217417 B, - 5.489138,0.409264, - 0.121391 O, - 6.180866, - 0.464669,0.689051 C, - 7.558306, - 0.370193,0.302323 C, - 8.455729, - 0.600759,1.490228 B,3.348387,0.146697, - 0.659894 O,3.938289, - 0.899368, - 1.371456 C,5.333954, - 0.648709, - 1.460511 C,5.460162,0.847328, - 1.18977 O,4.276572,1.166993, - 0.472849 B,1.830157,2.000624,0.306581 O,1.610522,2.951516, - 0.69566 C,2.318562,4.133472, - 0.31423 C,1.645084,5.361788, - 0.873062 O,2.366915,2.602992,1.427057 C,2.400609,4.012018,1.215487 C,1.260451,4.652152,1.981354 O, - 6.316684,1.204994, - 0.8798 C, - 7.645057,1.006008, - 0.38792 C, - 8.015064,2.163418,0.514379 H,0.34055,0.78813,1.027782 H,0.235093,2.217943, - 2.17519 288 H, - 1.340451, - 2.046632, - 4.002109 H, - 1.45147,2.248361, - 4.03898 H, - 2.27283,0.048404, - 4.936553 H, - 0.134401, - 3.617955, - 3.502977 H,0.986126, - 5.55789, - 2.448891 H,2.378177, - 5.179689, - 0.387184 H,2.541751, - 2.850707,0.528519 H,3.338413,4.047501, - 0.725603 H,3.363719,4 .395287,1.582659 H, - 2.459995, - 2.835051,2.37019 H, - 4.383085, - 1.657342,1.380934 H, - 1.732546,1.162926, - 0.429547 H,5.487619,1.43354, - 2.120787 H,6.339636,1.108945, - 0.590038 H,5.704836, - 0.946715, - 2.448235 H,5.854028, - 1.24633, - 0.69643 H,3.670846, - 2.415391,3.716146 H,4.509468, - 0.861601,3.479142 H,1.64316, - 1.335191,4.439382 H,2.741868, - 0.001809,4.879028 H,1.658593,5.3352, - 1.968026 H,0.600631,5.421832, - 0.545975 H,2.164108,6.272913, - 0.549717 H,1.282566,5.746592,1.909367 H,0.294325,4.29322,1.602747 H,1.329972,4.370607,3.036847 H, - 8.326673,0.964564, - 1.248334 H, - 7.737644, - 1.15378, - 0.452471 H, - 9.510331, - 0.517411,1.200892 H, - 8.291409, - 1.603734,1.896437 H, - 8.252257,0.125398,2.284721 H, - 9.052419,2.090659,0.861062 H, - 7.355658,2.2 00247,1.391132 H, - 7.899025,3.103607, - 0.033637 C, - 0.049692, - 3.308671,2.779816 H,0.95543, - 3.648934,3.05208 H, - 0.626676, - 3.12387,3.69914 H, - 0.548411, - 4.098811,2.196411 TS5 - OBeg anti M06/BSsmall OBegleftantimetaFM06SB M06/gen E(RM06) = - 2335.05183674 Zero - point correction= 0.753989 (Hartree/Particle) Thermal correction to Energy= 0.801889 Thermal correction to Enthalpy= 0.802833 Thermal correction to Gibbs Free Energy= 0.671652 Sum of electronic and ZPE= - 2334.297848 Sum of electronic and thermal Energies= - 2334.249948 Sum of electronic and thermal Enthalpies= - 2334.249004 Sum of electronic and thermal Free Energies= - 2334.380 184 E CV S KCal/Mol Cal/Mol - K Cal/Mol - K Total 503.193 183.507 276.093 C,0,2.4882205871, - 0.5833960495,3.4863387563 C,0,1.4708755934, - 0.3563479925,2.5582308882 N,0,1.3957136511, - 1.0726067019,1.4208943513 C,0, 2.3074362671, - 2.0269957264,1.196182081 C,0,3.3383897843, - 2.2926083052,2.0802447458 C,0,3.4570395356, - 1.5570623087,3.2633443447 C,0,0.3911427701,0.6285172553,2.7917434801 N,0, - 0.6138104586,0.6198564805,1.8960914871 C,0, - 1.6667182521,1.4031839916,2.1101608158 C,0, - 1.754159566,2.2716554863,3.1906867295 C,0, - 0.7048994109,2.3487073487,4.102176749 C,0,0.3748025125,1.4877315173,3.8850018556 Ir,0, - 0.1721018927, - 0.4986024731, - 0.0855457346 B,0,0.3811955957, - 1.6061521515, - 1.6945357983 O,0,0.0884537048, - 1.3084328389, - 3.0190933483 C,0,0.622623656, - 2.3274175773, - 3.8414359374 C,0,1.6626278374, - 3.0142108966, - 2.9582184924 O,0,1.2639309046, - 2.6886001185, - 1.6365404019 C,0,1.2531379732,1.1032669029, - 0.6748029831 C,0,2.4712558331,0.6843808376, - 1.228024404 C,0,3.5417859115,1.5557477432, - 1.341380413 C,0,3.4583732317,2.879394433, - 0.9431927793 C,0,2.2486644328,3.3243125843, - 0 .4259690457 C,0,1.168942559,2.4535689913, - 0.3081836698 F,0,4.6988791148,1.1007336913, - 1.8495172386 O,0,0.0063091341,2.9785199392,0.2229007878 B,0, - 1.0917892705,3.161943271, - 0.5515425342 O,0, - 1.1428436582,2.9393762256, - 1.9014159059 C,0, - 2.4819898175,3 .1539342893, - 2.3114020428 C,0, - 3.1838421319,3.7678547142, - 1.0819765917 O,0, - 2.2605003395,3.6395966925, - 0.0154753708 B,0, - 1.3431552376, - 2.1141975935,0.6145882779 O,0, - 1.0015232475, - 3.4521177744,0.5371327638 C,0, - 1.9892152445, - 4.212349028,1.2143141646 C,0, - 3.1594179059, - 3.244946594,1.3806708229 O,0, - 2.5685886992, - 1.9611708158,1.2685820277 B,0, - 2.044482374, - 0.4653113492, - 0.9356636061 O,0, - 2.9733625609,0.5506275604, - 0.6666464361 C,0, - 4.249840163,0.0675140727, - 1.055787118 C,0, - 3.9310853602, - 1.0053069464, - 2.0895858538 O,0, - 2.6291055198, - 1.4352654596, - 1.7416517688 H,0, - 0.1841402114,0.6611414192, - 1.2586512465 H,0, - 2.4560342563,1.3439715263,1.3625501668 H,0,1.2169709776,1.49920521,4.5737457204 289 H,0, - 2.6355782388,2.90078991 98,3.2780733345 C,0, - 0.695239987,3.3043538078,5.2880397464 H,0,2.5100205595,0.003850669,4.3988382783 C,0,4.592409912, - 1.8416685112,4.2376958392 H,0,4.0461883079, - 3.0816740351,1.832901933 H,0,2.1823740213, - 2.579943494,0.2652789656 H,0, - 4.7556834312, - 0.3556270203, - 0.1735547965 H,0, - 4.861051701,0.8894642073, - 1.4539786841 H,0, - 4.6271706137, - 1.8534731594, - 2.0635255781 H,0, - 3.9203073119, - 0.5987812477, - 3.1141319854 H,0,2.6144859623, - 0.34438 31985, - 1.5616203672 H,0,4.3169628933,3.5374590559, - 1.0528137501 H,0,2.1198894112,4.359022886, - 0.111883335 H,0, - 3.674041999, - 3.3413509055,2.3448015005 H,0, - 3.9042641585, - 3.3674197464,0.5761530417 H,0, - 1.5894885265, - 4.5493218754,2.1834794093 H,0, - 2.244 7057537, - 5.1002968633,0.6231984157 H,0,2.6762926037, - 2.6192314548, - 3.1386573672 H,0,1.691965322, - 4.1037553618, - 3.0827710735 H,0,1.051839757, - 1.8894220908, - 4.7512912172 H,0, - 0.18350589, - 3.0167152763, - 4.1373294383 H,0, - 3.4218411188,4.8319992079, - 1.2253112059 H,0, - 4.1141161926,3.2440051563, - 0.8255245903 H,0, - 2.9204712864,2.1883192158, - 2.5961524181 H,0, - 2.4945078102,3.8180679411, - 3.1847461149 C,0, - 1.9626544506,4.153903 5474,5.3486789716 C,0, - 0.5910210445,2.5000714004,6.5888743531 C,0,0.5082350833,4.2459827012,5.1636289662 H,0, - 1.9068230464,4.8353066171,6.2082061339 H,0, - 2.086007687,4.7673509828,4.4457910887 H,0, - 2.8637967675,3.5377638897,5.4740532458 H,0, - 0.5970262 496,3.1786435429,7.4535827491 H,0, - 1.4382738246,1.8082981095,6.692881192 H,0,0.3328818462,1.908974143,6.6376058695 H,0,0.527314361,4.9457404368,6.0112086988 H,0,1.4620762771,3.7025989804,5.1587101333 H,0,0.4520994035,4.8323348126,4.2365512729 C,0,4.5 473514094, - 0.9351861337,5.4649033846 C,0,4.4950444631, - 3.2978432964,4.7083944072 C,0,5.9299044542, - 1.6214461123,3.5206350623 H,0,5.3087093303, - 3.5213698007,5.4127640697 H,0,3.5407517481, - 3.4841484668,5.2200042544 H,0,4.5725468917, - 4.0070390822,3.87455 00392 H,0,5.3863881298, - 1.1759573483,6.1308784958 H,0,4.6355183399,0.1258779679,5.1929327349 H,0,3.620694648, - 1.0714440052,6.039890967 H,0,6.7633097401, - 1.8218558308,4.2086379745 H,0,6.0461840278, - 2.2846190799,2.6539679146 H,0,6.0213821967, - 0.5861062848,3.1651461832 TS5 - OBeg anti M06/BS1 OBegleftantimetaFM06PS M06/gen E(RM06) = - 2335.16879005 Zero - point correction= 0.749172 (Hartree/Particle) Thermal correction to Energy= 0. 797412 Thermal correction to Enthalpy= 0.798357 Thermal correction to Gibbs Free Energy= 0.666667 Sum of electronic and ZPE= - 2334.419619 Sum of electronic and thermal Energies= - 2334.371378 Sum of electronic and thermal Enthalpies= - 2334.370433 Sum of electronic and thermal Free Energies= - 2334.502123 E CV S KCal/Mol Cal/Mol - K Cal/Mol - K Total 500.384 184.801 277.165 C,0, - 3.4125366695, - 0.4555369491, - 0.575360218 C,0, - 2.0575237021, - 0.1564738736, - 0.7230683852 N,0, - 1.1420138504, - 1.1319793852, - 0.8637726401 C,0, - 1.5536611731, - 2.4019142591, - 0.9546866483 C,0, - 2.8857397604, - 2.7586148628, - 0.830717915 C,0, - 3.8545968791, - 1.7 77303304, - 0.5947916647 C,0, - 1.5374354563,1.2301498421, - 0.7234656596 N,0, - 0.1973510803,1.3566962693, - 0.6745458498 C,0,0.3301458263,2.5767974172, - 0.7355494895 C,0, - 0.4420173349,3.730053872, - 0.8110496071 C,0, - 1.8314041488,3.634851158, - 0.833111025 C,0, - 2.3678054619,2.3431461803, - 0.8012004549 Ir,0,0.9596025115, - 0.6028140536, - 0.2411062057 B,0,1.7611134847, - 2.4502390584,0.0477288608 O,0,2.740303165, - 2.7622322458,0.9838106552 C,0,3.0729560721, - 4.133008578 8,0.8500682453 C,0,1.8766472534, - 4.7337649157,0.1146729853 O,0,1.2805674035, - 3.6224428665, - 0.541183528 C,0,0.046346605, - 0.6390965672,1.7856535501 C,0, - 0.4859443393, - 1.8721307713,2.193626596 C,0, - 1.4205678872, - 1.9427302946,3.2114901833 C,0, - 1.84492210 79, - 0.8245994102,3.909375472 C,0, - 1.2889477263,0.4000026617,3.5563760016 C,0, - 0.3537925641,0.4828615202,2.5262291823 F,0, - 1.9406772423, - 3.1494829649,3.5361142763 O,0,0.101315222,1.7481949549,2.2199167843 B,0,1.3982805596,2.1197489058,2.3568278964 O,0,2.3808844624,1.3564064041,2.9266849546 C,0,3.5852894114,2.1076469026,2.882069457 C,0,3.21788631,3.4248988856,2.1643108645 O,0,1.814068213,3.3641505268,1.9554371774 B,0,1.5683579628, - 0.6515706496, - 2.27135 82251 O,0,1.487867336, - 1.7497340072, - 3.1068837129 C,0,1.8664747967, - 1.35102013, - 4.4178087949 C,0,2.5756967304, - 0.0154730593, - 4.2086307543 O,0,2.0664329002,0.4537990548, - 2.9674958769 B,0,2.9054623267,0.0410951558, - 0.4040581208 O,0,3.2791451151,1.37300 46461, - 0.1755632624 C,0,4.5565745024,1.5607057427, - 0.7712873167 C,0,5.1462823762,0.1556949069, - 0.8111993847 O,0,4.0063519541, - 0.6858628237, - 0.8444952851 H,0,1.5663632239, - 0.4404959099,1.2723338139 H,0,1.4168584874,2.6286605767, - 0.6926488657 H,0, - 3.44 52504547,2.2059775169, - 0.8452854938 H,0,0.0657141612,4.6893134416, - 0.8290849515 C,0, - 2.7535223514,4.846288392, - 0.8910708062 H,0, - 4.1175900002,0.3519851349, - 0.4085091583 C,0, - 5.3006715341, - 2.1723739764, - 0.3308522262 H,0, - 3.1494727876, - 3.8121329468, - 0.8 816209482 H,0, - 0.7640673073, - 3.1401477729, - 1.094380947 H,0,4.4183672555,1.9719687345, - 1.7832489621 H,0,5.1512871177,2.2687658357, - 0.178309358 H,0,5.771432979, - 0.0266909677, - 1.693206579 290 H,0,5.7397677558, - 0.0687018138,0.08913323 H,0, - 0.2077882124, - 2.7999887562,1.6937368583 H,0, - 2.5747774312, - 0.9196146961,4.7084164214 H,0, - 1.5716554848,1.3135050144,4.075072739 H,0,2.376686595,0.7179532442, - 4.9985220828 H,0,3.6665535143, - 0.1460639679, - 4.1169034298 H,0,0.9651903496, - 1.2475186915, - 5.0400689282 H,0,2.5099735985, - 2.1168264659, - 4.8654064698 H,0,1.1471869451, - 5.1749037099,0.8125583362 H,0,2.1549306408, - 5.4952491929, - 0.6229914881 H,0,3.2400254085, - 4.5753635283,1.8392035704 H,0,4.00089270 13, - 4.2241843888,0.2657094553 H,0,3.4562257122,4.3133753824,2.7616143022 H,0,3.7132827755,3.511242477,1.1885993795 H,0,4.343789081,1.5339619364,2.3345081222 H,0,3.9411597256,2.2701089451,3.9072740326 C,0, - 1.9729424945,6.1589413586, - 0.9194326425 C,0, - 3.6164373383,4.7692879796, - 2.1569897374 C,0, - 3.6552436452,4.8484550616,0.35040222 H,0, - 2.6750705977,7.0004428453, - 0.9658640217 H,0, - 1.3601118822,6.2890222692, - 0.018536688 H,0, - 1.3178314814,6.2265182181, - 1.7974897474 H,0, - 4.277891239,5.6437714882, - 2.2129247802 H,0, - 2.9916756085,4.7559564544, - 3.0592197583 H,0, - 4.2493561457,3.8739102733, - 2.1729919425 H,0, - 4.3129182276,5.7274500207,0.3349021976 H,0, - 4.2921895023,3.9571386004,0.4000753587 H,0, - 3.0559130104,4.88420915 21,1.2688365179 C,0, - 6.21211543, - 0.9597325729, - 0.147800551 C,0, - 5.8361684526, - 3.001862509, - 1.5039049794 C,0, - 5.3365693323, - 3.0049023179,0.9583381466 H,0, - 6.8793168113, - 3.2855439661, - 1.3134688981 H,0, - 5.8050674923, - 2.4278131489, - 2.4389779481 H,0, - 5.26 64655884, - 3.9257337651, - 1.656549293 H,0, - 7.2387242629, - 1.3008525317,0.0333302968 H,0, - 5.9153134927, - 0.3475717609,0.713633755 H,0, - 6.2311324724, - 0.3214868097, - 1.0412511477 H,0, - 6.3710673292, - 3.2845098658,1.1969772299 H,0, - 4.7497112709, - 3.9265649975,0.8 675925581 H,0, - 4.9285574733, - 2.435369299,1.8035451707 TS5 - F M06/BSsmall leftFmetaOBegM06SBa leftFmetaOBeg M06/gen E(RM06) = - 2335.04360634 Zero - point correction= 0.753465 (Hartree/Particle) Thermal correction to Energy= 0.802253 Thermal correction to Enthalpy= 0.803197 Thermal correction to Gibbs Free Energy= 0.665879 Sum of electronic and ZPE= - 2334.290142 Sum of electronic and thermal Energies= - 2334.241353 Sum of electronic and th ermal Enthalpies= - 2334.240409 Sum of electronic and thermal Free Energies= - 2334.377727 E CV S KCal/Mol Cal/Mol - K Cal/Mol - K Total 503.421 183.894 289.011 C, - 0.845406,2.979139,1.338458 C, - 0.965807,1.711894,0.765132 N, - 0.246797,0.671115,1.225768 C,0.563816,0.85923,2.274973 C,0.711092,2.089906,2.88993 C,0.006442,3.200261,2.41651 C, - 1.898403,1.427404, - 0.34821 N, - 1.844981,0.184525, - 0.86121 C, - 2.690102, - 0.143243, - 1.836638 C, - 3.624369,0.745765 , - 2.352321 C, - 3.703757,2.04142, - 1.846456 C, - 2.811804,2.365234, - 0.82184 Ir, - 0.322738, - 1.269151,0.093399 B,1.013388, - 2.395263,1.125825 O,1.731534, - 3.465959,0.606282 C,2.543539, - 4.010026,1.627367 C,2.598612, - 2.913483,2.692442 O,1.477513, - 2.093773,2.408837 C,2.562803, - 0.220007, - 0.608098 C,1.303115, - 0.449642, - 1.176614 C,1.103949,0.104125, - 2.439541 C,2.047613,0.877443, - 3.096319 C,3.27741,1.116539, - 2.494535 C,3.528908,0.551302, - 1.247905 F, - 0.054254, - 0.133665, - 3.088518 O,4.705315,0. 755887, - 0.564903 B,5.93864,0.874615, - 1.103894 O,6.251674,0.789462, - 2.439064 C,7.635861,1.075057, - 2.559038 C,8.175776,1.002372, - 1.121253 O,7.027441,1.093996, - 0.298072 B, - 1.848609, - 1.889095,1.419085 O, - 1.705718, - 2.114265,2.776283 C, - 2.979367, - 2.413344,3.3225 53 C, - 3.845497, - 2.72595,2.104266 O, - 3.177482, - 2.084675,1.031467 B, - 1.130479, - 3.056528, - 0.537744 291 O, - 1.798829, - 3.167318, - 1.757291 C, - 2.532358, - 4.380365, - 1.74114 C, - 1.847743, - 5.213279, - 0.65975 O, - 1.206021, - 4.254983,0.161173 H,0.56003, - 1.843099, - 1.173815 H, - 2.598151, - 1.163325, - 2.209445 H, - 2.843767,3.358682, - 0.380219 H, - 4.282107,0.405756, - 3.147706 C, - 4.700095,3.077412, - 2.351682 H, - 1.419053,3.803664,0.926975 C,0.181564,4.562684,3.073166 H,1.390189,2.17123,3.736417 H,1.097922, - 0.027439,2.616867 H, - 3.581311, - 4.163178, - 1.482124 H, - 2.507513, - 4.847311, - 2.733558 H, - 2.552366, - 5.805925, - 0.061764 H, - 1.093714, - 5.896956, - 1.07935 H,1.813894,1.276797, - 4.081458 H,4.036499,1.711186, - 2.99522 H, - 4.873307, - 2.351131,2.18884 H, - 3.886394, - 3.809788,1.902371 H, - 3.351508, - 1.539475,3.88047 H, - 2.89648, - 3.25465,4.021657 H,3.519214, - 2.311738,2.616122 H,2.527733, - 3.300723,3.716701 H,3.531121, - 4.267964,1.223888 H,2.078437, - 4.930992,2.011883 H,8.106258,0.348221, - 3.23206 4 H,7.75906,2.076465, - 2.99681 H,8.870872,1.816942, - 0.88305 H,8.686757,0.048891, - 0.922198 C, - 5.589536,2.522902, - 3.462077 C, - 5.600106,3.523939, - 1.193729 C, - 3.93506,4.284742, - 2.905969 H, - 6.333122,4.261457, - 1.55015 H, - 6.150591,2.671956, - 0.772016 H, - 5.029701,3.990794, - 0.380337 H, - 6.291365,3.29974, - 3.793591 H, - 5.004484,2.210888, - 4.338182 H, - 6.183771,1.664277, - 3.120275 H, - 4.641449,5.041013, - 3.276615 H, - 3.306347,4.762206, - 2.143304 H, - 3.284198,3.988843, - 3.739974 C, - 0.6645 64,5.643946,2.405399 C, - 0.235104,4.464986,4.54571 C,1.654623,4.97805,2.981455 H, - 0.116616,5.44137,5.036676 H, - 1.287338,4.16286,4.63868 H,0.372736,3.738006,5.099537 H,1.797946,5.962745,3.448463 H,2.317249,4.268044,3.492341 H,1.980709,5.046048,1.934685 H, - 0.49985,6.604359,2.911625 H, - 0.397038,5.779585,1.348093 H, - 1.738937,5.420639,2.466845 H,2.821056, - 0.634925,0.367615 TS5 - OBeg syn M06/BSsmall This structure is the higher - energy syn conformer of TS5 - OBeg anti given above and discussed in the main text. OBegleftsynmetaFM06SB OBegleftsynmetaF M06/gen E(RM06) = - 2335.04787486 Zero - point correction= 0.753268 (Hartree/Particle) Thermal correction to Energy= 0.801596 Thermal correction to Enthalpy= 0.802540 Thermal correction to Gibbs Free Energy= 0.670267 Sum of electronic and ZPE= - 2334.294606 Sum of electronic and thermal Energies= - 2334.246279 Sum of electronic and thermal Enthalpies= - 2334.245335 Sum of electronic and thermal Free Energies= - 2334 .377608 E CV S KCal/Mol Cal/Mol - K Cal/Mol - K Total 503.009 183.823 278.393 C,2.223685,2.047328, - 1.180309 C,1.335335,1.022238, - 0.855648 N,0.004653,1.175812, - 0.979581 C, - 0.45803,2.327777, - 1.483367 C,0.374624,3.373629, - 1.840251 C,1.758321,3.263082, - 1.673131 C,1.801767, - 0.290493, - 0.370643 N,0.898562, - 1.02648,0.303854 C,1.270512, - 2.227496,0.747492 C,2.537832, - 2.756877,0.525793 C,3.480811, - 2.030718, - 0.19869 C,3.081292, - 0.76 5285, - 0.640756 Ir, - 1.335654, - 0.357138, - 0.009288 B, - 3.16104,0.266252, - 0.617222 O, - 4.373948, - 0.060271, - 0.030852 C, - 5.374563,0.797334, - 0.544512 C, - 4.7452,1.409382, - 1.795929 O, - 3.350471,1.246479, - 1.595488 C, - 1.47155,1.050736,1.718001 C, - 2.251592,2.206745,1.553 8 C, - 2.198406,3.243275,2.469484 C, - 1.404308,3.185751,3.602045 C, - 0.648714,2.038556,3.80063 C, - 0.688967,0.997276,2.876769 292 F, - 2.946632,4.338386,2.253879 O,0.036206, - 0.142546,3.167339 B,1.383209, - 0.131444,3.09499 O,2.137733,0.914396,2.614865 C,3.496542,0.5293 43,2.680285 C,3.493958, - 0.884286,3.306371 O,2.134313, - 1.195442,3.530101 B, - 1.265917, - 1.539255, - 1.7666 O, - 1.898844, - 1.24402, - 2.960733 C, - 1.561983, - 2.238317, - 3.913374 C, - 0.972618, - 3.372913, - 3.078065 O, - 0.562519, - 2.742371, - 1.876305 B, - 2.19167, - 2.207306,0.311071 O, - 1.650857, - 3.102415,1.233941 C, - 2.211075, - 4.378581,0.973208 C, - 3.496129, - 4.065702,0.213325 O, - 3.254181, - 2.793802, - 0.361401 H, - 2.064466, - 0.412089,1.462508 H,0.505452, - 2.781538,1.291307 H,3.757002, - 0.157028, - 1.240147 H,2.759627, - 3.744492,0.920772 C,4.866981, - 2.563137, - 0.544554 H,3.286091,1.890845, - 1.011311 C,2.673656,4.429505, - 2.017917 H, - 0.074542,4.28324, - 2.234411 H, - 1.538994,2.385208, - 1.604919 H, - 1.507573, - 4.960456,0.353979 H, - 2.375541, - 4.915961,1.915105 H, - 3.720439, - 4.796137, - 0.57475 H, - 4.367435, - 4.002175,0.883011 H, - 2.903713,2.33066,0.688996 H, - 1.395339,4.013746,4.306578 H, - 0.021993,1.933274,4.685523 H, - 0.119408, - 3.872048, - 3.554777 H, - 1.73093, - 4.136981, - 2.83838 H, - 0.830392, - 1.826792, - 4.626499 H, - 2.456518, - 2.535232, - 4.474471 H, - 4.982784,2.473147, - 1.925694 H, - 5.041128,0.874198, - 2.710825 H, - 5.616773,1.563277,0.210292 H, - 6.287469,0.226891, - 0.75726 H,3.920044,0.533054,1.663284 H,4.055324, 1.257417,3.283623 H,4.039955, - 0.923824,4.258759 H,3.932256, - 1.637242,2.631041 C,5.127463, - 3.931208,0.080827 C,4.972817, - 2.697449, - 2.068964 C,5.943264, - 1.592728, - 0.044587 H,5.957917, - 3.099517, - 2.345378 H,4.203977, - 3.379259, - 2.457053 H,4.851564, - 1.731236, - 2. 576301 H,6.139768, - 4.268484, - 0.178861 H,5.058811, - 3.899717,1.17757 H,4.42219, - 4.688925, - 0.286584 H,6.940192, - 1.96391, - 0.320404 H,5.833958, - 0.589381, - 0.477133 H,5.915171, - 1.493995,1.049851 C,4.143287,4.106543, - 1.760743 C,2.507558,4.777761, - 3.502025 C,2.286384,5.638724, - 1.1586 H,3.167044,5.615869, - 3.767747 H,2.769421,3.922567, - 4.140128 H,1.479361,5.075221, - 3.74465 H,2.936009,6.492785, - 1.396765 H,1.248765,5.951808, - 1.330967 H,2.395143,5.413685, - 0.088979 H,4.761637,4.976818, - 2.017581 H,4.330859,3.868409, - 0.704362 H,4.490324,3.263057, - 2.374261 TS5 - OBeg syn Conformer B M06/BSsmall This structure is another higher - energy syn conformer of TS5 - OBeg syn given above and discussed in the main text. In this conformer, the OBeg on the FPhOBeg is oriented for a Lewis acid/base interaction with a Beg on the Ir, but this does not lead to low - energy structure. OBegrightsynmetaFM06SB M06/gen E(RM06) = - 2335.05 155106 Zero - point correction= 0.754817 (Hartree/Particle) Thermal correction to Energy= 0.802154 Thermal correction to Enthalpy= 0.803098 Thermal correction to Gibbs Free Energy= 0.675357 Sum of electronic and ZPE= - 2334.296734 Sum of electron ic and thermal Energies= - 2334.249397 Sum of electronic and thermal Enthalpies= - 2334.248453 Sum of electronic and thermal Free Energies= - 2334.376194 E CV S KCal/Mol Cal/Mol - K Cal/Mol - K Total 503.359 183.278 268.853 C,0, - 3.0888518229, - 0.8771872378, - 0.0163867506 C,0, - 1.7751561363, - 0.4188488598, - 0.1205278109 N,0, - 0.7278011301, - 1.2598331506, - 0.0324881026 C,0, - 0.9696431732, - 2.568092179,0.1193253236 C,0, - 2.251940873, - 3.0825325712,0.2029638739 C,0, - 3.3593160156, - 2.2316565957,0.1572604141 C,0, - 1.4629196442,0.9949930509, - 0.4223489037 N,0, - 0.2189089636,1.228236 2649, - 0.8787356398 C,0,0.0961539186,2.4595982945, - 1.2749737428 293 C,0, - 0.7812610297,3.5327843266, - 1.1619048192 C,0, - 2.0392927132,3.3403714618, - 0.5932036514 C,0, - 2.3795485221,2.0269246573, - 0.2562384969 Ir,0,1.3335567521, - 0.3814666693, - 0.1907953656 B,0,2. 4655921684, - 1.9431344833,0.4227613833 O,0,1.9419594721, - 3.2329501551,0.6252920922 C,0,3.0419590493, - 4.1043548702,0.8481725333 C,0,4.1473441436, - 3.1704754821,1.3211088702 O,0,3.8111163998, - 1.9222975293,0.743120183 C,0,1.1242521328,0.5377126924,1.846722 8469 C,0,0.6759591045,1.8609445036,1.9775114842 C,0,0.2554854877,2.3664434695,3.1946643529 C,0,0.2918327676,1.6122931643,4.35406579 C,0,0.7828498061,0.316626401,4.2597929008 C,0,1.1997447008, - 0.2001778822,3.0352566422 F,0, - 0.1983925439,3.6341720834,3.2505595323 O,0,1.740632477, - 1.471041084,3.0427818278 B,0,0.9595956734, - 2.5683259311,3.1586959322 O,0, - 0.4140076378, - 2.5629983136,3.0553318542 C,0, - 0.8493167967, - 3.866672465, 3.3952458672 C,0,0.4176127729, - 4.7251365696,3.3015397537 O,0,1.4804255309, - 3.8037050729,3.4660019422 B,0,1.4294712042, - 1.2063280626, - 2.1338447959 O,0,1.5558471019, - 2.5477900741, - 2.4514341212 C,0,1.5225226841, - 2.685862855, - 3.8626429597 C,0,1.715261915 5, - 1.2636970919, - 4.387547107 O,0,1.3571357535, - 0.4346840691, - 3.2954826837 B,0,2.9806577025,0.3165388634, - 1.2155690968 O,0,3.1139171511,1.6753117992, - 1.5107335151 C,0,4.1328144311,1.8076428323, - 2.4891742188 C,0,4.9277267512,0.5093412012, - 2.3728400668 O,0,4.0181505532, - 0.403298067, - 1.7860752729 H,0,2.345747816,0.4542811917,0.7964108811 H,0,1.1151380348,2.5808487852, - 1.645165392 H,0, - 3.3504573774,1.8155127761,0.1874115489 H,0, - 0.4481119737,4.517775631, - 1.4775063696 C,0, - 2.99793398,4.4799201078, - 0.2805046626 H,0, - 3.9025069416, - 0.1636631851, - 0.1092595839 C,0, - 4.7702420857, - 2.7939398732,0.2661543711 H,0, - 2.3737543702, - 4.1605085943,0.3009850008 H,0, - 0.0852136361, - 3.2027740788,0.1718501021 H,0,3.6668654612,1.9121562013, - 3.4823830455 H,0,4.7302490624,2.7055249848, - 2.2885132602 H,0,5.2699994696,0.1249088873, - 3.3425216854 H,0,5.8052241171,0.617997241 5, - 1.717220622 H,0,0.6508940854,2.5327971597,1.1202999224 H,0, - 0.0402869591,2.0379796747,5.2977337968 H,0,0.8570742293, - 0.3123357603,5.1463922811 H,0,1.0903836718, - 1.0316532553, - 5.2591075041 H,0,2.7671017196, - 1.0687313052, - 4.6558727308 H,0,0.55331898 6, - 3.1121512692, - 4.1655501266 H,0,2.3131478187, - 3.3740782438, - 4.1863133354 H,0,5.1478375797, - 3.4796570895,0.993428775 H,0,4.1446933885, - 3.0771561006,2.418677772 H,0,3.2981549199, - 4.6021376387, - 0.10044476 H,0,2.7737036035, - 4.8621762258,1.5940101107 H, 0,0.4722891993, - 5.5024669765,4.0733021811 H,0,0.5073524958, - 5.2058918908,2.3131233199 H,0, - 1.6400559708, - 4.1860077505,2.7021334222 H,0, - 1.2675077575, - 3.8553354226,4.413169097 C,0, - 2.4450241523,5.8322374732, - 0.7241174343 C,0, - 4.3363191549,4.2502527251, - 0.9896957263 C,0, - 3.2099446116,4.5157745894,1.2395286233 H,0, - 3.1688335175,6.6216088874, - 0.4819366274 H,0, - 1.5052800226,6.0781836973, - 0.2111476541 H,0, - 2.2692800858,5.8672110558, - 1.8084595025 H,0, - 5.0319732256,5.0672823842, - 0.7522532128 H,0, - 4.2069295014,4.2206743663, - 2.08044356 H,0, - 4.8146033383,3.3112544101, - 0.6821409067 H,0, - 3.8342619885,5.3781740324,1.5128248783 H,0, - 3.7142868568,3.6109521342,1.6038520998 H,0, - 2.2520000543,4.595535675 9,1.7717752197 C,0, - 5.8339069088, - 1.6987901046,0.2601604425 C,0, - 5.0283080138, - 3.7279135068, - 0.9219019858 C,0, - 4.8985045058, - 3.5803273016,1.5763759472 H,0, - 6.0415690229, - 4.1491862256, - 0.8581900138 H,0, - 4.9436204446, - 3.1859957123, - 1.873753359 H,0, - 4.3188195281, - 4.5650384131, - 0.9485278903 H,0, - 6.8287376473, - 2.1531388383,0.3585153198 H,0, - 5.705068143, - 0.9993462004,1.0979602734 H,0, - 5.8282998721, - 1.1244331902, - 0.676667127 H,0, - 5.9234757618, - 3.9609988012,1.6873002652 H,0, - 4.2215483289, - 4.4441 571053,1.6079805412 H,0, - 4.6747605531, - 2.9432833176,2.4434251365 TS for (bpy)IrBpin 3 + 4 - FC 6 H 4 OBpin, meta to F, M06/BSsmall BPINrOBPINMetaFM06SB M06/gen E(RM06) = - 2649.38481910 Zero - point correction= 0.975237 (Hartree/Particle) Thermal correction to Energy= 1.032493 Thermal correction to Enthalpy= 1.033437 Thermal correction to Gibbs Free Energy= 0.888855 Sum of electronic and ZPE= - 2648.409582 Sum of electronic and t hermal Energies= - 2648.352326 Sum of electronic and thermal Enthalpies= - 2648.351382 Sum of electronic and thermal Free Energies= - 2648.495964 E CV S KCal/Mol Cal/Mol - K Cal/Mol - K Total 647.899 230.480 304.299 294 C,0, - 3.6033436224,3.9399971904,0.7077285974 C,0, - 2.2900682983,4.1052814719,0.3012719059 C,0, - 1.4609911873,3.0309867374,0.0275122365 C,0, - 1.9165675995,1.7119045868,0.1743406612 C,0, - 3.2573856145,1.5564868861,0.549338526 C,0, - 4.0837960653,2.6417621285 ,0.822492881 Ir,0, - 0.3239777333,0.1848843964,0.3195707614 N,0, - 1.470751972, - 0.8744721546,2.0202936829 C,0, - 1.301436118, - 0.3898713484,3.2623462567 C,0, - 2.0069497914, - 0.9189057537,4.3447019481 C,0, - 2.8857299785, - 1.9707011829,4.1307187749 C,0, - 3.0336109236, - 2.4774695053,2.8472192466 C,0, - 2.3032198211, - 1.8967578421,1.8187018246 C,0, - 0.3208117291,0.7080076463,3.4107039592 N,0,0.2424871173,1.1791713471,2.2796224728 C,0,1.1633667904,2.148290703 ,2.3449555758 C,0,1.5699670366,2.7037164042,3.550195175 C,0,0.9976503953,2.2310610628,4.7243674006 C,0,0.0458839442,1.2253743241,4.654953224 B,0,1.4094695156, - 0.9031262053,0.8468788904 O,0,1.4124047719, - 2.0544906314,1.626065689 C,0,2.7257544851, - 2.20 37000539,2.1911272195 C,0,3.6124703113, - 1.4130510709,1.1852628693 O,0,2.6979060869, - 0.4218930078,0.6909075034 B,0, - 0.1406998732, - 1.4628961228, - 0.9108293833 O,0,0.9961700995, - 1.9075061292, - 1.58175316 C,0,0.6206688074, - 3.0074835871, - 2.4177079553 C,0, - 0 .5875469452, - 3.5900696555, - 1.642526381 O,0, - 1.1698275949, - 2.4003274171, - 1.0760405123 B,0,0.8517144824,1.1320489461, - 1.0434472597 O,0,1.6699987975,2.2226678821, - 0.7246481865 C,0,2.2270047321,2.7465969103, - 1.9430594444 C,0,2.1201749169,1.520714557, - 2.8926351829 O,0,0.943780961,0.8670036706, - 2.4029212442 H,0, - 1.5075342633,0.5362670811, - 0.8071145115 H,0, - 2.3845016057, - 2.2427370167,0.7889505252 H,0, - 1.8865289744, - 0.5126934733,5.3453394438 H,0, - 3.7140596326, - 3.2968410019,2.6301620313 H,0, - 3.4496146497, - 2.3875287881,4.963224353 H,0, - 0.3988944121,0.8383689974,5.5676500092 H,0,1.2915704046,2.63750546 12,5.6902326922 H,0,2.3206631489,3.4897222941,3.5591126225 H,0,1.5799207624,2.4617985427,1.3872963232 C,0, - 0.1763096485, - 4.4828102841, - 0.4780603271 C,0, - 1.6074114881, - 4.3063682865, - 2.5025963388 C,0,1.7958896669, - 3.9508065799, - 2.5735458965 C,0,0.23881 57156, - 2.4284234168, - 3.7751670517 H,0, - 0.4342967045,3.2387287156, - 0.2714300283 O,0, - 3.8063116974,0.2932291304,0.6591393023 H,0, - 4.2273856326,4.8070293985,0.9097925851 F,0, - 1.7995327125,5.3495202498,0.1741581891 H,0, - 5.114451607,2.4501309383,1.11761599 78 C,0,2.6833568341, - 1.5696841505,3.5761406587 C,0,3.0472224274, - 3.6802358953,2.3078718248 C,0,4.8078733423, - 0.7068177622,1.7932205628 C,0,4.049915206, - 2.2536197221, - 0.0052464643 C,0,1.3547517101,3.9137997306, - 2.3848290622 C,0,3.63953661,3.222308707, - 1.6705348218 C,0,1.9323068431,1.8519705472, - 4.3586793933 C,0,3.276600749,0.5417305551, - 2.7192607445 H,0, - 1.058784253, - 4.6695352124,0.1487040473 H,0,0.2085383541, - 5.4527256043, - 0.8222132479 H,0,0.5813089466, - 3.9950927982,0.1510532725 H,0, - 2.4130725557, - 4.7047493585, - 1.8713350134 H,0, - 2.054592086, - 3.6430259066, - 3.2524300043 H,0, - 1.1420423077, - 5.1556686336, - 3.0235979053 H,0,1.5222230455, - 4.8143448216, - 3.1967118294 H,0,2.6252916619, - 3.4247 048239, - 3.0656303008 H,0,2.1577978303, - 4.3235825943, - 1.6081418347 H,0, - 0.0146102092, - 3.2132657637, - 4.501052878 H,0, - 0.6071542495, - 1.7344428906, - 3.6848892706 H,0,1.0889850847, - 1.8539212748, - 4.1659347947 H,0,4.0777359312, - 3.8320114708,2.6605232545 H,0,2.3686301139, - 4.1508436156,3.0312715388 H,0,2.9269662623, - 4.1977311245,1.3486758261 H,0,3.6249892831, - 1.7124361826,4.1237308945 H,0,2.4761281803, - 0.4918817387,3.5149097841 H,0,1.8740668443, - 2.037222867, 4.1534252183 H,0,4.521072683, - 1.6002481224, - 0.7510861407 H,0,4.773400564, - 3.0282724811,0.2829120869 H,0,3.1813287995, - 2.7223910675, - 0.4831804656 H,0,5.3470592848, - 0.1639647475,1.0055305244 H,0,4.5079892351,0.0228830769,2.5548960044 H,0,5.5044162565, - 1.4269325881,2.2467147227 H,0,1.7674801091,4.4178860682, - 3.2693357538 H,0,0.3342110738,3.581129559, - 2.6165862231 H,0,1.2942011387,4.6490444049, - 1.5710105377 H,0,4.1377558564,3.5250717111, - 2.6028383737 H,0,3.6174444659,4.0940292568, - 1.0031548543 H,0,4.237595965,2.4408772902, - 1.1881854629 H,0,1.8748147314,0.9208153247, - 4.9381700175 H,0,1.0081791956,2.4132674222, - 4.5355035324 H,0,2.7807032523,2.4374127533, - 4.7418916113 H,0,3.0064470457, - 0.4047751836, - 3.2064016312 H,0,4.2063753369, 0.9186282273, - 3.1680446457 H,0,3.4444052129,0.3239114777, - 1.655812737 B,0, - 4.3254564282, - 0.278224786, - 0.4579177178 O,0, - 4.7588830171, - 1.5790835177, - 0.4678036582 C,0, - 5.4599609302, - 1.7468725111, - 1.7169295788 C,0, - 4.8221804934, - 0.6392480662, - 2.615097858 3 295 O,0, - 4.4911562772,0.3769388484, - 1.650157253 C,0, - 3.5129900136, - 1.0697380707, - 3.259067711 C,0, - 5.7520599491, - 0.047592686, - 3.6536730139 C,0, - 5.2496710991, - 3.1615464036, - 2.2098452913 C,0, - 6.9360248232, - 1.5054703024, - 1.4325454078 H,0, - 5.2160372786,0.71 29061002, - 4.2349481096 H,0, - 6.0995225014, - 0.8239778832, - 4.3497782783 H,0, - 6.6243255089,0.4316246007, - 3.1962343984 H,0, - 3.0185042871, - 0.1811866843, - 3.6736541518 H,0, - 2.8342865924, - 1.515598745, - 2.5183667782 H,0, - 3.6752517152, - 1.7876512563, - 4.0757928771 H,0, - 7.5582661283, - 1.7042820328, - 2.31497213 H,0, - 7.2538670067, - 2.1801574722, - 0.6280733767 H,0, - 7.1198658435, - 0.4749314376, - 1.1022103733 H,0, - 5.6717576634, - 3.2908835669, - 3.2164576465 H,0, - 4.1853867199, - 3.417674365, - 2.2360778264 H,0, - 5.7535965831, - 3.8687956174, - 1.5384677256 TS for (bpy)IrBpin 3 + 4 - FC 6 H 4 OBpin, ortho to F, M06/BSsmall BPINrOBPINOrthoFM06SB M06/gen E(RM06) = - 2649.37950521 Zero - point correction= 0.973595 (Hartree/Parti cle) Thermal correction to Energy= 1.031712 Thermal correction to Enthalpy= 1.032657 Thermal correction to Gibbs Free Energy= 0.883138 Sum of electronic and ZPE= - 2648.405911 Sum of electronic and thermal Energies= - 2648.347793 Sum of electron ic and thermal Enthalpies= - 2648.346849 Sum of electronic and thermal Free Energies= - 2648.496367 E CV S KCal/Mol Cal/Mol - K Cal/Mol - K Total 647.409 231.471 314.688 C,0, - 4.5208730853, - 1.7804610393, - 1.0824915935 C,0, - 4.174144836, - 0.7330082956, - 0.2338484134 C,0, - 2.8460893054, - 0.3440726602, - 0.0921111697 C,0, - 1.8103840699, - 0.9985624288, - 0.7713668438 C,0, - 2.199296949, - 2.0219097104, - 1.6317220835 C,0, - 3.5153252293, - 2.4 244760299, - 1.7948707507 Ir,0,0.2537168566, - 0.6588217127, - 0.0691798185 N,0,0.7451793556, - 2.9116547165, - 0.2825591348 C,0,0.5350754301, - 3.6796456165,0.7999325408 C,0,0.9158775742, - 5.0230342302,0.8183758826 C,0,1.5259028261, - 5.569783627, - 0.2999534679 C,0 ,1.7441709555, - 4.763945868, - 1.4097790938 C,0,1.3357786682, - 3.4381978116, - 1.3571967572 C,0, - 0.0827284851, - 3.0158190222,1.9682392663 N,0, - 0.296945788, - 1.6876662389,1.8704270169 C,0, - 0.8130303937, - 1.0192004669,2.9093640504 C,0, - 1.1561552917, - 1.6468437756 ,4.0989085669 C,0, - 0.9557506967, - 3.0164620214,4.2089658792 C,0, - 0.4129748912, - 3.7060134284,3.1355551356 B,0,2.0883627848, - 0.4033702025,0.9471181011 O,0,3.1191122544, - 1.3408135973,0.9377070684 C,0,3.9498335323, - 1.084249954,2.0815080037 C,0,3.7066127015,0.4308478483,2.328173466 O,0,2.3536950991,0.5916327167,1.8733713533 B,0,1.6295298516,0.0275895759, - 1.4377606728 O,0,2.5373652685,1.0704556483, - 1.2973824228 C,0,3.1549041541,1.2928082549, - 2.5 713939699 C,0,3.0640296081, - 0.1176125571, - 3.2142110367 O,0,1.8285581991, - 0.6083937139, - 2.6646532446 B,0, - 0.0839334676,1.2970193887,0.3526000234 O,0, - 0.5247848291,1.7627647989,1.5932284398 C,0, - 0.7869127577,3.1726889919,1.4855323756 C,0,0.0624323502,3 .5645258346,0.2424781332 O,0,0.0231323642,2.3618542209, - 0.532786479 H,0, - 0.597079713, - 0.2414051427, - 1.4241834015 296 H,0,1.4862730908, - 2.7522274624, - 2.1903021331 H,0,0.749953451, - 5.6389811254,1.6984587803 H,0,2.2247745431, - 5.1489342973, - 2.3058832739 H,0,1.8318674027, - 6.6143780408, - 0.3002646272 H,0, - 0.2538819408, - 4.7782980774,3.2076937774 H,0, - 1.2185101643, - 3.5468450637,5.1221653413 H,0, - 1.5745097803, - 1.0647252821,4.9159783799 H,0, - 0.9325947356,0.05455 63081,2.762479351 C,0,4.1661334172, - 1.0553010686, - 2.7359630344 C,0,2.9789429291, - 0.1299861776, - 4.7257909152 C,0,4.5598683193,1.817714485, - 2.3577868564 C,0,2.3178233786,2.3366621488, - 3.3007316794 H,0, - 2.6266820131,0.4763404951,0.5929517418 O,0, - 5.1027986833, - 0.0848623851,0.5447184059 H,0, - 5.5620560303, - 2.07594221, - 1.1945155071 F,0, - 1.2590275206, - 2.6600035012, - 2.3597971749 H,0, - 3.7407039668, - 3.2370392107, - 2.4831031203 C,0,3.4215848167, - 1.96070 04439,3.2123063469 C,0,5.3795135709, - 1.4622411097,1.7533761744 C,0,3.7903915125,0.8698374433,3.7756909832 C,0,4.5850822034,1.3188720765,1.4584101237 C,0, - 2.2829910818,3.3428057821,1.259972048 C,0, - 0.3732978889,3.8429158793,2.7805738817 C,0, - 0.4954250 889,4.7061139074, - 0.582432482 C,0,1.5267187244,3.8271259766,0.5809760755 H,0,3.9359993895, - 2.0751067699, - 3.0737159697 H,0,5.14827705, - 0.7772991507, - 3.142489563 H,0,4.2209651461, - 1.0701135352, - 1.6371769164 H,0,2.9236424177, - 1.1646401258, - 5.088533581 H ,0,2.09006517,0.3987142959, - 5.08617258 H,0,3.8709079231,0.3359886693, - 5.1689335188 H,0,5.06559421,1.9891473576, - 3.3189846264 H,0,4.5118668666,2.7754906053, - 1.8213090624 H,0,5.1707647529,1.1299231682, - 1.7621841775 H,0,2.7648520937,2.6227169539, - 4.26271 86676 H,0,1.2966611452,1.9746966998, - 3.4741507835 H,0,2.2459089876,3.2329285871, - 2.6699441978 H,0,6.0557559068, - 1.1977227618,2.5791122876 H,0,5.4489146234, - 2.5459539889,1.5928064303 H,0,5.7285754755, - 0.9642440947,0.8416463679 H,0,4.0284297295, - 1.8704213836,4.1235807499 H,0,2.3809936249, - 1.7011061235,3.4566190975 H,0,3.4414278958, - 3.0100949877,2.8873144592 H,0,4.2201359304,2.3527835232,1.5201986821 H,0,5.6343148994,1.3016753874,1.7833144473 H,0,4.522388042,1.0141810738,0.4066925565 H,0,3.5867234259,1.9468738103,3.8427329768 H,0,3.0559321974,0.3509177398,4.4019217837 H,0,4.7949530859,0.6888158787,4.1849 631664 H,0, - 2.5798217881,4.400546406,1.264239381 H,0, - 2.5951923369,2.8953726807,0.306926484 H,0, - 2.826023976,2.8320697236,2.0664096304 H,0, - 0.4555879758,4.9367545838,2.7025774516 H,0, - 1.0307858497,3.5137050633,3.5961696906 H,0,0.6564732185,3.58320991 8,3.0510755986 H,0,0.1608470708,4.8877945172, - 1.4439242833 H,0, - 1.4963924292,4.4780803164, - 0.9650311998 H,0, - 0.5454548901,5.6323657889,0.0082060462 H,0,2.1007755581,3.857425798, - 0.3557677361 H,0,1.662148085,4.7823095572,1.1073191294 H,0,1.9405102342, 3.010359217,1.1885239007 B,0, - 6.3378948075,0.2889985336,0.1309585265 O,0, - 7.2601893957,0.7661247686,1.0262651964 C,0, - 8.3417951555,1.2957640449,0.2391709162 C,0, - 8.2130094582,0.4889704575, - 1.0891851198 O,0, - 6.7953251536,0.2458658034, - 1.1628160686 C,0, - 8.8885799417, - 0.8744733093, - 1.0255535213 C,0, - 8.6537406993,1.2290252571, - 2.3342735792 C,0, - 9.6419669024,1.0899047572,0.9886032651 C,0, - 8.0760458277,2.7844822645,0.0590903642 H,0, - 8.5356210955,0.580788 5249, - 3.211503037 H,0, - 9.7130828243,1.5130383928, - 2.2620559629 H,0, - 8.0578644154,2.1318275964, - 2.5037589239 H,0, - 8.5673072471, - 1.4659131303, - 1.8922343148 H,0, - 8.6027254903, - 1.4204884659, - 0.1165519465 H,0, - 9.9830009585, - 0.7920192863, - 1.0515441257 H,0, - 10.499176501,1.4015658644,0.3751909282 H,0, - 9.7812785002,0.0444002964,1.2834935192 H,0, - 9.6408839782,1.6982867557,1.9015825341 H,0, - 8.9037908616,3.2880243757, - 0.4573868454 H,0, - 7.9579698951,3.2418260304,1.048937268 H,0, - 7.1519283115,2.96265 66119, - 0.5060670832 297 REFERENCES 298 REFERENCES (1) Gutekunst, W. R.; Baran, P. S. Chem. Soc. Rev. 2011 , 40 (4), 1976. (2) Engle, K. M.; Mei, T. - S.; Wasa, M.; Yu, J. - Q. Acc. Chem. Res. 2012 , 45 (6), 788. (3) Li, G.; Wan, L.; Zhang, G.; Leow, D.; Spangler, J.; Yu, J. - Q. J. Am. Chem. Soc. 2015 , 137 (13), 4391. (4) Breslow, R.; Zhang, X.; Huang, Y. J. Am. Chem. Soc. 1997 , 119 (19), 4535. (5) Breslow, R.; Huang, Y.; Zhan g, X.; Yang, J. Proc. Natl. Acad. Sci. U. S. A. 1997 , 94 (21), 11156. (6) Yang, J.; Breslow, R. Angew. Chem. Int. Ed. 2000 , 39 (15), 2692. (7) Yang, J.; Gabriele, B.; Belvedere, S.; Huang, Y.; Breslow, R. J. Org. Chem. 2002 , 67 (15), 5057. (8) Leung, D. H.; Bergman, R. G.; Raymond, K. N. J. Am. Chem. Soc. 2006 , 128 (30), 9781. (9) Brown, C. J.; Toste, F. D.; Bergman, R. G.; Raymond, K. N. Chem. Rev. 2015 , 115 (9), 3012. (10) Das, S.; Incarvito, C. D.; Crabtree, R. H.; Brudvig, G. W. Science 2006 , 312 (5782), 1941. (11) Das, S.; Brudvig, G. W.; Crabtree, R. H. J. Am. Chem. Soc. 2008 , 130 (5), 1628. (12) Dydio, P.; Reek, J. N. H. Chem. Sci. 2014 , 5 (6), 2135. (13) Davis, H. J.; Phipps, R. J. Chem. Sci. 2017 , 8 (2), 864. (14) Butts, C. P.; Filali, E.; Lloyd - Jones, G. C.; Norrby, P. - O.; Sale, D. A.; Schramm, Y. J. Am. Chem. Soc. 2009 , 131 (29), 9945. (15) Angew. Chem. Int. Ed. 2008 , 47 (2), 311. (16) Dydio, P.; Dzik, W. I.; Lutz, M.; de Bruin, B.; Reek, J. N. H. Angew. Chem. Int. Ed Engl. 2011 , 50 (2), 396. (17) Rummelt, S. M.; Fürstner, A. Angew. Chem. Int. Ed Engl. 2014 , 53 (14), 3626. 299 (18) Rummelt, S. M.; - A.; Fürstner, A. J. Am. Chem. Soc. 2015 , 137 (16), 5506. (19) Zhao, Y.; Domoto, Y.; Orentas, E.; Beuchat, C.; Emery, D.; Mareda, J.; Sakai, N.; Matile, S. Angew. Chem. Int. Ed Engl. 2013 , 52 (38), 9 940. (20) Zhao, Y.; Cotelle, Y.; Sakai, N.; Matile, S. J. Am. Chem. Soc. 2016 , 138 (13), 4270. (21) Giese, M.; Albrecht, M.; Rissanen, K. Chem. Commun. 2016 , 52 (9), 1778. (22) Wheeler, S. E.; Seguin, T. J.; Guan, Y.; Doney, A. C. Acc. Chem. Res. 2016 , 49 (5), 1061. (23) Persch, E.; Dumele, O.; Diederich, F. Angew. Chem. Int. Ed. 2015 , 54 (11), 3290. (24) Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.; Murphy, J. M.; Hartwig, J. F. Chem. Rev. 2010 , 110 (2), 890. (25) Ros, A.; Fernández, R.; Lassaletta, J. M. Chem. Soc. Rev. 2014 , 43 (10), 3229. (26) Saito, Y.; S egawa, Y.; Itami, K. J. Am. Chem. Soc. 2015 , 137 (15), 5193. (27) Haines, B. E.; Sa ito, Y.; Segawa, Y.; Itami, K.; Musaev, D. G. ACS Catal. 2016 , 6 (11), 7536. (28) Kawamorita, S.; Ohmiya, H.; Hara, K.; Fukuoka, A.; Sawamura, M. J. Am. Chem. Soc. 2009 , 131 (14), 5058. (29) Ishiyama, T.; Isou, H.; Kikuchi, T.; Miyaura, N. Chem. Commun. 2010 , 46 (1), 159. (30) Ros, A.; Estepa, B.; López - Rodríguez, R.; Álvarez, E.; Fernández, R.; Lassaletta, J. M. Angew. Chem. Int. Ed. 2011 , 50 (49), 11724. (31 ) Ghaffari, B.; Preshlock, S. M.; Plattner, D. L.; Staples, R. J.; Maligres, P. E.; Krska, S. W.; Maleczka, R. E., Jr; Smith, M. R., III J. Am. Che m. Soc. 2014 , 136 (41), 14345. (32) Wang, G.; Liu, L.; Wang, H.; Ding, Y. - S.; Zhou, J.; Mao, S.; Li, P. J. Am. Chem. Soc. 2017 , 139 (1), 91. (33) Boebel, T. A.; Hartwig, J. F. J. Am. Che m. Soc. 2008 , 130 (24), 7534. (34) Ghavtadze, N.; Melkonyan, F. S.; Gulevich, A. V.; Huang, C.; Gevorgyan, V. Nat. Chem. 2014 , 6 (2), 122. 300 (35) Simmons, E. M.; Hartwig, J. F. Nature 2012 , 483 (7387), 70. (36) Roosen, P. C.; Kallepalli, V. A.; Chattopadhyay, B.; Singleton, D. A.; Maleczka, R. E., Jr; Smith, M. R., 3rd. J. Am. Chem. Soc. 2012 , 134 (28), 11350. (37) Preshlock, S. M.; Plattner, D. L.; Maligres, P. E.; Krska, S. W.; Maleczka, R. E., Jr.; Smith, M. R. III Angew. Chem. Int. Ed. 2013 , 52 (49), 12915. (38) Bisht, R.; Chattopadhyay, B. J. Am. Chem. Soc. 2016 , 138 (1), 84. (39) Kuninobu, Y.; Ida, H.; Nishi, M.; Kanai, M. Nat. Chem. 2015 , 7 (9), 712. (40) Davis, H. J.; Mihai, M. T.; Phipps, R. J. J. Am. Chem. Soc. 2016 , 138 (39), 12759. (41) Li, H. L.; Kuninobu, Y.; Kanai, M. Angew. Chem. Int. Ed Engl. 2017 , 56 (6), 1495. (42) Ishiyama, T.; Takagi, J.; Hartwig, J. F.; Miyaura, N. Angew. Chem. Int. Ed. 2002 , 41 (16), 3056. (43) Chotana, G. A.; Rak, M. A.; Sm ith, M. R. J. Am. Chem. Soc. 2005 , 127 (30), 10539. (44) Yamazaki, K.; Kawamorita, S.; Ohmiya, H.; Sawamura, M. Org. Lett. 2010 , 12 (18), 3978. (45) Cox, P. A.; Leach, A. G.; Campbell, A. D.; Lloyd - Jones, G. C. J. Am. Chem. Soc. 2016 , 138 (29), 9145. (46) Rose, S. H.; Shore, S. G. Inorg. Chem. 1962 , 1 (4), 744. (47) McAchran, G. E.; Shore, S. G. Inorg. Chem. 1966 , 5 (11), 2044. (48) Shore, S. G.; Crist, J. L.; Lockman, B.; Long, J. R.; Coon, A. D. J. Chem. Soc. Dalton Trans. 197 2 , 11 , 1123. (49) Boller, T. M.; Murphy, J. M.; Hapke, M.; Ishiyama, T.; Miyaura, N.; Hartwig, J. F. J. Am. Chem. Soc. 2005 , 127 (41), 14263. (50) Blau, J. A.; Gerrard, W .; Lappert, M. F. J. Chem. Soc. 1957 , 4116 - 4120 . (51) Salonen, L. M.; Ellermann, M.; Diederich, F. Angew. Chem. Int. Ed Engl. 2011 , 50 (21), 4808. (52) Gamez, P.; Mooibroek, T. J.; Teat, S. J.; Reedijk, J. Acc. Chem. Res. 2007 , 40 (6), 435. 301 (53) Mirzaei, M.; Eshtiagh - Mague, J. T.; Bauzá, A.; Frontera, A. CrystEngComm 2014 , 16 (24), 5352. (54) Uson, R.; Oro, L. A.; Cabeza, J . A. Inorg. Synth. 1985, 23, 126 - 130. (55) Ms. Yu - Ling Lien and the MSU Mass Spectrometry facility are thanked for obtaining ESI+ HRMS. (56) Ishiyama, T.; Takagi, J.; Ishida, K.; Miyaura, N.; Anastasi, N. R.; Hartwig, J. F. J. Am. Chem. Soc. 2002, 12 4, 390 - 391. (57) Cheng, C.; Hartwig, J. F. Science 2014, 343, 853 - 857. (58) Friedman, A. A.; Panteleev, J.; Tsoung, J.; Huynh, V.; Lautens, M. Angew. Chem. Int. Ed. 2013, 52, 9755 9758. (59) Huang, W.; Su, L.; Bo, Z. J. Am. Chem. Soc. 2009, 82, 870 - 8 78. (60) Welch, C. N.; Shore, S. G. Inorg. Chem. 1968, 7, 225 - 230. (61) Sumida, Y.; Kato, T.; Hosoya, T. Org. Lett. 2013, 15, 2806 2809. (62) a) Pineschi, M.; Bertolini, F.; Haak, R. M.; Crotti, P.; Macchia, F. Chem. Commun., 2005, 1426 - 1428. b) Laurent, J - P.; Comptes Rendus Hebdomadaires - 868. (63) Blau, J. A.; Gerrard, W.; Lappert, M. F.; J. Chem. Soc. 1957, 4116 - 4119. Gaussian 09, Revision A.02, Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M. ; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, Jr., J. A.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Nor mand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, N. J.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; C ammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian, Inc., Walli ngford CT, 2009. (64) Gaussian 09, Revision B.01, Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; 302 Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, Jr., J. A.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, N. J.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adam o, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö .; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian, Inc., Wallingford CT, 2009. (65) Gaussian 09, Revision D.01, Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; M ennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Naka i, H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M .; Rega, N.; Millam, N. J.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Vot h, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian, Inc., Wallingford CT, 2009. (66) NBO 5.9. E. D. Glendening, J. K. Badenhoop, A. E. Reed, J. E. Carpe nter, J. A. Bohmann, C. M. Morales, and F. Weinhold (Theoretical Chemistry Institute, University of Wisconsin, Madison, WI, 2011); http://www.chem.wisc.edu/~nbo5 303 Chapter 4: Ortho Selective Borylation of Anilines 4.1: Introduction Anilines are chemicals with important dye, pharmaceutical, agrochemical, and polymer applications. 1 Aniline is commercially prepared by benzene nitration followed by hydrogenation of the nitrobenzene intermediate. Most commercially available substituted anilines are prepared by derivatizing aniline, often through electrophilic aromatic substitution (EAS). 2 The NH 2 group is classified as a strong ortho/para director; 3 even so traditional nitration of aniline provides 32 49% meta - nitroaniline along with the major para isomer. 4 ortho - selective examples are for anilines substituted at C4. For anilines that are unsubstituted at C4, EAS generates significant quantities of para isomers e ven in some of the most ortho - selective methods. 5 The best traditional synthetic method for ortho functionalization of aniline is directed ortho metalation (DoM) with carbamate derivatives, followed by subsequent addition of an electrophile to the ortho carbanion. 6 This approach requires conversion of the aniline to the carbamate, which is then removed after the reaction, if aniline products are des ired. Even though directed ortho metalation reactions are remarkably powerful, 7 catalytic methods can exhibit complementary selectivities and increased functional group tolerance. 8 There are several examples of catalytic ortho functionalizations of aniline. Most require the installation of a directing group prior to C H functionalization, and removal of said directing group to restore the nitrogen functionality. 9 11 While the NH 2 group would be untouched in ideal catalytic ortho functionalization of primary anilines, the next most desirable process is one where there is no trace in the product of any in situ modification of the amino group during catalysis. 304 The traceless Ir - catalyzed C H borylation (CHB) of primary anilines has been described in the literature. 12 C H borylation is a synthetic method where sp 2 , sp 3 , and sp C H bonds are converted to C B bonds. 13 15 With few exceptions, 16,17 most examples requir e a catalyst, and metal - catalyzed CHBs have been reported for a number of transition metals. 13,18 20 Some of the earliest reports of metal - catalyzed CHBs of arene C(sp 2 ) H bonds indicate d that the least hindered C H bonds were generally more reactive. 21 23 This feature became a hallmark of Ir - catalyzed CHBs because regioselectivities can complement those found in EAS and DoM , as well as the regioselectivities in early examples of catalytic intra - and intermolecular ortho selective C H functionalizations. 24,25 The first report of catalytic ortho CHBs relied on classic chelate - directed mechanisms where a substrate functional group binds to a vacant metal site. 26 28 - 29 Other inner sphere approaches, like relay - directed ortho CHBs of silylated phenols and anilines, where reversible Si H oxidative addition to Ir was proposed to direct borylation, were also developed. 30 Directing strategies for ortho CHBs have been proposed where the metal center is not a directing element. 31,32 - 29,33 Examples of outer - sphere direction in ortho CHBs include Lewis acid - base, 34 36 hydrogen bonding, 12,33,37 electrostatic interactions, 38 and an example where both inner - and outer - sphere mechanisms are plausi ble. 39 The electrostatic mechanism is a more subtle variant of the ion - pairing mechanisms proposed by Phipps and co - workers in recently designed meta - selective CHBs, 40 which 305 complements other meta - selective CHBs where outer - sphere mechanisms are proposed to account for selectivity. 34,37,41 Kanai and Kuninobu recently disclosed ortho CH Bs of aniline and phenol derivatives (Scheme 23 ). 36 The bipyridine ligand with the best selectivity is not commercially available (ligand A in scheme 23) . It has an electron - withdrawing aryl group at t he bipyridine 5 - position and was synthesized from commercially available precursors . 42 To achieve ortho CHB of primary anilines thiomethyl methylene (CH 2 SMe) and acyl groups must be attached to the aniline nitrogen. While this approach provides excellent o rtho selectivities, ligand synthesis and if ortho - borylated primary anilines are the desired product, the additional synthetic steps to add and subsequently remove functional groups on aniline nitrogen are unappealing. Scheme 23 : Comparison of the Kanai - Kuninobu CHB of N - Acylated Anilines to This Work. 36 , 43,44 The previously reported traceless CHBs of primary anilines built on an initial repo rt of ortho CHBs of N - Boc anilines. 12,33 For these aryl carbamates, experiment and theory were consistent with an outer - sphere mechanism involving N H···O hydrogen bonding between the aniline su bstrate and an Ir Bpin ligand giving rise to the ortho selectivity. 33 As shown in Figure 5 , previous CHBs required C4 substituents larger than H to achieve high ortho selectivity. 12,33 Additionally, substitution at C2 was deleterious to ortho 306 selectivity. Given that C B bonds can be readily converted to a host of functional groups, and the aforementioned limited scope of previous ortho - direc ted CHBs of anilines, a method overcoming these shortcomings would be highly desirable. Figure 8 : Proposed Transition States for Ortho Borylations of Anilines and Phenols. Traceless, ortho - directed CHB of phenols was recently described. 38 The initial CHB substrates were phenol O - boronate esters ArylOBpin (pin = pinacolate). Experimental and computational studies pointed to transit ion state stabilization arising from electrostatic interactions between the bipyridine bound to Ir and OBpin of the phenol boronate ester. Like previous aniline borylations, 4 - substituents larger than H were necessary to achieve synthetically useful ortho selectivity. An in silico redesign of the catalyst predicted that the ortho CHB transition state could be significantly stabilized if the Bpin groups on Ir and the phenolboronate ester were replaced with Beg (eg = ethylene glycolate). Indeed, this led to exquisite ortho selectivities for Ir - catalyzed CHBs of phenols when the diboron reagent B 2 eg 2 was used in lieu of HBpin. This raised the question as to whether ortho selectivities for aniline CHBs could be similarly improved using B 2 eg 2 . If ortho selectivi ties indeed improve, another question arises. Is transition state stabilization due to electrostatic interactions or enhanced 307 hydrogen bonding? This chapter addresses these questions using experiment and theory synergistically. 4.2: Aniline Borylation wit h B 2 eg 2 Ir - catalyzed CHB of aniline with B 2 eg 2 was used to optimize reaction conditions. First, a THF solution of aniline, 0.5 equiv of B 2 eg 2 , and 0.5 mol % [Ir(OMe)(cod)] 2 was briefly heated to generate PhN(H)Beg, which was verified by 11 B/ 1 H NMR spectros copy. Then NEt 3 , dtbpy (dtbpy = 4,4´ - di - t Bu - 2,2´ - bipyridine), additional B 2 eg 2 and [Ir(OMe)(cod)] 2 were added, and the resulting solution was heated at 80 °C until borylation ceased. The best results were obtained with a 2.5 mol % loading of [Ir(OMe)(cod)] 2 , 5 mol % dtbpy, 2.0 equiv B 2 eg 2 , and 2.0 equiv of NEt 3 . When CHB was complete, the eg group was transesterified by treating the reaction mixture with 3.0 equiv of pinacol, and the more stable Bpin product was purified and isolated in 67% yield. Conversion to products suffered at lower catalyst loadings; howev er, high regioselectivity was still achieved. The regioselectivities for aniline CHBs with B 2 pin 2 and B 2 eg 2 are compared in Scheme 24 . To avoid significant diborylation, the control reaction used less B 2 pin 2 and a shorter reaction time. Notably, the 2.7:1. 8:1 ortho:meta:para isomer ratio for CHB with B 2 pin 2 is similar to the ratio previously reported for Ir - catalyzed aniline CHB with HBpin (ortho:meta:para = 2.3:1.5:1). 12 While the major regioisomer is the ortho product, which suggests some favorable interactions for ortho CHB with B 2 pin 2 , substantial quantities of meta and para CHB products dampen the synthetic utility. In contrast, B 2 eg 2 , which is easily prepared from commercially available (OH) 2 B B(O H) 2 and ethylene glycol, provides exquisite ortho selectivity. 308 Scheme 24 : Aniline CHBs with B 2 pin 2 and B 2 eg 2 . 4.3: Substrate scope of Aniline Borylation with B 2 eg 2 We next assessed the substrate scope with B 2 eg 2 for ortho selectivity. Table 5 lists the results for twenty - four substrates. The catalyst loadings in Table 5 are (6 mol % Ir) higher than we usually use for borylations because the reactions were run with 0.5 mmol of aniline sub strates, using weighed amounts of the [Ir(OMe)(cod)] 2 . When CHB of aniline was performed on a 5 mmol scale with 0.25 and 0.75 mol % of the precatalyst (2 mol % Ir) in steps 1 and 2 in Scheme 24 , ortho - borylated product 2a was isolated in 75% yield. The ave rage isolated yield is 71(±4)% for substrates in Table 5 . For substrate 1q , 20% diborylation contributed to the low yield of monoborylated product. The only diborylated isomers detected were 2,6 - regioisomers. Substrate 1s had the lowest yield, but it is th e first metal - catalyzed CHB of a nitro - containing substrate that gives more than trace quantities. In crude reaction mixtures, CHB was only detected at sites ortho to NH 2 . Gratifyingly, CHBs of meta - substituted anilines 1j - 1m did not generate 5 - borylated p roducts, as had been found for Ir - catalyzed CHBs of anilines 1k - 1m with HBpin. 12 The yields of ortho - borylated products from CHBs anilines 1k , 1l , and 1m increased over those previously reported from CHBs with HBpin by 46%, 24%, and 55%, respectively. Furthermore, this methodology outperforms previously reported CHB of N - Boc anilines. 309 Table 5 : Ortho Borylation of Substituted Anilines with B 2 eg 2 . a a All reactions were carried out on a 0.5 mmol scale, and yields are reported for isolated materials after column chromatographic separation. b The other o - borylated isomer was observed, but underwent rapid proto - deboronation . c 20% o,o - diborylation was observed. d Isolated yield: 20%; GC conversion: 50%. No CHBs of 2 - substituted N - Boc anilines have been reported, and ortho selectivity eroded for substrates that lacked blocking groups at the 4 - position. For example, CHB of 3 - ch loro - N - Boc - aniline provided 92% yield but exhibited an ortho:meta selectivity of only 2:1. 33 In addition, this yield does not include removal of the Boc group. On the other hand, substrate 1k provided only the ortho borylated product, 2k, and was isolated in 88% yield. Substrates 1b - i underwent CHB with B 2 eg 2 at C6 exclusively, yielding ortho - borylated products 2b - 2i . This stands in sharp contrast to previously reported CHBs of 2 - substituted 310 a nilines with HBpin, where ortho borylation was not observed. 12 Borylation of quinoline 1x proceeded smoothly providing the 7 - borylated product 2x in 71% isolated yield. Indole CHB with either B 2 eg 2 or B 2 pin 2 provides the 2 - borylated products in comparable yields. 45 Compounds 2c - i , 2r , and 2u - v are new. Of these, 2g is the only structure whose boronic acid has been reported in the primary literature. 46 Significantly, the transformations in Table 5 do no t require installing and removing a directing group and use dtbpy, the most commonly used ligand in Ir - catalyzed CHBs. 4.4: Theoretical Investigation of the Directing Effect in Aniline Borylations The improved selectivity raises the interesting question as to whether the molecular origins arise from ligand/substrate electrostatic interactions or hydrogen bonding (Scheme 2 4 ). To tackle this question, we turned to theory. DFT calculations used the M06 functional with a 6 - 31G* basis set for light atoms and an SDD basis set and core potential for Ir. The polarizable continuum model was the self - consistent reaction field method applied for the THF solvent. Compared to other systems that we have studied, transition state location was challenging. Low energy imagin ary frequencies associated with Me group rotations in dtbpy ligands plagued calculations on the full system. Replacing bipyridine tBu with Me groups made the problem more manageable. Ultimately, TSs with a single imaginary frequency corresponding to C H sc ission were located. The maximum atom displacement in all calculated TSs exceeded software convergence thresholds. In addition, the RMS displacement exceeded the software convergence defaults in approximately half of the calculated TSs. Atomic Cartesian co ordinates and energies for these TSs are included in the experimental section 4.8. Four transition states ( TS1 - 4 ) were located for ortho borylation. Figure 6 depicts TS1 is analogous to the lowest energy 311 transition state for phenol ortho borylation. 38 In the other three TSs, the PhN(H)Beg H is hydrogen bonded to a Beg O. The H···O distances in TS2 , TS3 , and TS4 are 2.07, 2.28, and 2.49 Å, respectively . Figure 9 : Computed transition states for Ir - catalyzed CHB of PhN(H)Beg with B 2 eg 2 . The N H hydrogen and the C H hydrogen in the bond bei ng cleaved are yellow. Dashed orange lines indicate hydrogen bonding interactions. G rel and H rel values relative to TS1. G values for TS2 - 4 relative to TS1 are given as G rel in Figure 6 . The hydrogen - bonded TSs TS2 , TS3 , and TS4 are stabilized by 1.9, 2.6, and 1.7 kcal/mol 1 , respectively, relative to TS1 . Notably, the starting geometry for TS4 was similar to that for TS1 except that the Beg moiety is syn to the 4,4´ - dimethylpyridine lig and (Figure 7 ). The syn PhOBeg TS has short (~3.0 Å) contacts between the Beg group and the bipyridine - stacking. 38 An analogous TS was not found for PhN(H)Beg. Instead , the N(H)Beg group rotated about the N C ipso bond to engage in hydrogen bonding between the aniline proton and an Ir Beg oxygen ( TS4 , Figure 6 ). However, a TS analogous to the syn geometry for PhOBeg was located for CHB of PhN(Me)Beg ( TS8 , vide infra). 312 Figure 10 : Proposed Transition States for Ortho Borylations of Anilines. The highest energy hydrogen - bonded TS ( TS4 ) has the longest H···O distance, but it is only 0.2 kcal·mol 1 less stable than TS2 , where the H···O distance is 0.42 Å shorter. The number of heavy atoms in TS1 - 4 is too large to easily apply the level of theory that is typically used to quantify stabilization from hydrogen bonding. 47 - H values for N H vibrations of the N(H)Beg group in TS2 (3533 cm 1 ), TS4 (3541 cm 1 ), and TS3 (3557 cm 1 ) do not correlate with distance, which is not surprising since Beg O lone pair interactions with the aniline H differ with Beg ligand orientation. Howev er, the - H values in TS2 - 4 are 62 - 38 cm 1 lower than that calculated for PhN(H) - H = 3595 cm 1 ) at the same level of theory. Based on the infrared shift, H···O distance, and N - H lengthening, the hydrogen bonding interaction is classified as a weak hydrogen bond which are mostly electrostatic in nature. 48 The TS for para CHB ( TS5 all of the hydrogen - bonding TSs, and was separated from the lowest energy TS ( TS3 ) by 1.0 kcal·mol 1 G value of 1.0 kcal·mol 1 between TS3 and TS5 predicts an ortho:para ratio of 8.2:1. While the ortho:para ratio of 26:1 predicted from predictions fall short of observed experimental selectivity. 313 4.5: Experimentally Probing the Directing Element in Aniline CHB The computational results predict that Beg outperforms Bpin because the N(H)Beg substituent and Beg ligands can adopt optimal hydrogen bonding configurations with minimal steri c interference. CHBs of PhN(H)Bpin with B 2 eg 2 and PhN(H)Beg with B 2 pin 2 were performed as an experimental test of this hypothesis (Scheme 25 ). If an electrostatic interaction was key for the high selectivity, then the selectivity in the CHB of PhN(H)Bpin w ith B 2 eg 2 should more negatively impact ortho - borylation as the boryl group on the substrate is responsible for the selectivity. However, if the hydrogen bonding controls the selectivity as the computational results suggest, then changing the boryl ligands on the iridium to Bpin should have a larger effect in the selectivity as increasing the sterics around the hydrogen bond acceptor should have the larger impact. Scheme 25 : Aniline CHBs of PhN(H)Bpin with B 2 eg 2 and PhN(H)Beg with B 2 pin 2 . CHB of PhN(H)Bpin exhibits the same high ortho selectivity when B 2 eg 2 is the borylating agent as is observed for CHB of aniline with B 2 eg 2 . When the NBeg in the structure of TS3 is converted to NBpin and the syn bipyridine Me is converted to tBu, the closest C···C contact (4.31 Å) is longer than the closest C···C contact (3.96 Å) in the crystal structure of Ir(Bpin)3(dtbpy)(coe) (coe = cyclooctene). 23 Con sequently, retention of high ortho selectivity for the NBpin/B 2 eg 2 combination is not surprising. 314 In contrast, ortho selectivity erodes when PhN(H)Beg is borylated with B 2 pin 2 , although the ortho:meta:para ratio of 11:1.2:1 is better than the 2.5:1.5:1 rat io for Ir - catalyzed CHB of aniline with HBpin. 12 The TSs for the PhN(H)Beg/Ir Bpin structures are not calculated. However, it is not unreasonable to expect that the calculated steric destabilization f rom changing Beg to Bpin in phenol ortho CHB transition states would translate to aniline CHBs. 38 The experiments in Scheme 25 demonstrate that the B substituents on the boryl ligands, and thus the CH B reagent, have the greater influence on ortho selectivity. Overall, these results support the hydrogen bonding controlled selectivity suggested by the calcuaiotns as PhN(H)Bpin would have a larger impact on selectivity if the electrostatic directing effec t controlled the selectivity. Meta and para CHB of N - methylaniline would further support the hypothesis that hydrogen - bonding is responsible for the high ortho selectivity of B 2 eg 2 in aniline CHBs since PhN(Me)Beg lacks an NH moiety. Remarkably, CHB on PhN(H)Me yields only the ortho isomer, albeit at only 24% conversion. In operando NMR spectroscopy shows that PhN(H)Me is fully converted to PhN(Me)Beg before CHB ensues. Even though the conversion of PhN(Me)Beg to borylated products is low, the ortho product is the only CHB isomer detected. Scheme 26 : Borylation of N - Methylaniline 315 4.6: Computational study of N - Methylaniline b orylation This surprising result raises an obvious question. Would calculations also favor ortho CHB when hydrogen bonding is not an option? The calculated TS structures for meta CHB ( TS6 ) and ortho CHB with anti ( TS7 ) and syn ( TS8 ) dispositions of the Beg group relative to bipyridine ligand are shown in Figure 8 . Unfortunately, both TS5 and TS7 value between of - 0.3 kcal/mol 1 value predicts a higher ortho:meta ratio of 4.1:1. Although the ortho isomer is predicted to be major, the actual selectivity is much higher. While the trend in the computed ratio correlates with the experimental results, future studies at a higher level of theory may be warranted. Overall, the experimental findings show that hydrogen bonding is not required for ortho selectivity for N - methyl aniline when the CHB reagent is switched from B 2 pin 2 to B 2 eg 2 . Figure 11 : Computed transition states for Ir - catalyzed CHB of PhN(CH 3 )Beg with B 2 eg 2 . The hydrogen in the C H bond being cleaved is pale yellow. G rel and H rel are G H values relative to TS6. 316 4.7: Conclusions In addition to removin g previous limitations for ortho CHBs of anilines with B 2 pin 2 and HBpin, CHBs with B 2 eg 2 can complement selectivities for aniline CHBs with commonly used boron reagents. Scheme 27 shows two examples highlighting the most dramatic differences in CHB selecti vities. Scheme 27 : Regiochemical consequences of Beg and Bpin reagents in aniline CHBs. The important findings of this study are listed below. By changing the boron reagent from HBpin or B 2 pin 2 to bis - (ethyleneglycolato)diboron (B 2 eg 2 ), ortho CHBs can now be accomplished wide variety of anilines. Substrates whose previously poor (or altered) regioselectivity is now overcome include (i) anilines with no substituents at the 4 - position, (ii) 2 - substituted anilines, (iii) 3 - substituted anilines, and (iv) N - methylaniline. 317 The substituents on the Ir boryl ligands have the greatest impact on selectivity . The ortho - borylated isomer is the only product observed in the Ir - catalyzed CHB of N - methylaniline with B 2 eg 2 . 1 H NMR studies show that PhN(H)Me is fully converted to PhN(Beg)Me before CHB ensues. Thus, hydrogen bonding in the TS cannot accou nt for ortho selectivity. For Ir - catalyzed CHB of PhN(H)Beg, computational studies revealed three NH···O hydrogen bonding transition states where the aniline N(Beg)H interacted with an Ir - CHB TS that lacks hydrogen bonding. of PhN(H)Beg. Of three TSs calculated for Ir - catalyzed CHB of PhN(Me)Beg, the ortho TS where the Beg moiety is anti to the bipyridine ligand TS closely resembled the favored TS for CHB ortho to the OBeg of 4 - F - C 6 H 4 OBeg, where selectivity is proposed to arise from electrostatic interactions between the OBeg unit and the proximal pyridine ring of the bipyridine ligand. In summary, the diboron reagent B 2 eg 2 lifts the limitations seen in Ir - catalyzed CHBs of anilines with HBpin. Experiment and theory are consistent with stabilization of hydrogen bonding TSs when Bpin Ir boryl ligands are replaced by less sterically encumbered Beg ligands. 318 4.8: Experimental Details General information All commercially available chemicals were used as received unless otherwise indicated. Pinacolborane (HB p in) and bis(pinacolato)diboron (B 2 p in 2 ) were procured from Sigma - A ldrich and A. K. Scientific respectively and used directly. B 2 eg 2 was produced as previously reported from B 2 (OH) 4 and ethylene glycol. 49 Bis( 4 - 1,5 - cyclooctadiene) - di - - methoxy - diiridium(I) [Ir(OMe)COD] 2 was procured from Sigma - Aldrich. Tetrahydrofuran (THF) were refluxed over sodium/benzophenone ketyl, distilled and degassed twice before borylation. Column chromatography was performed on flash silica gel (ACME, India). Thin layer chromatography was perfo rmed on 0.25 mm thick aluminum - backed silica gel plates purchased from Merck and visualized with ultraviolet light ( = 254 nm). All borylations were conducted in an argon - filled glovebox, unless otherwise stated. 1 H, 13 C, and 11 B NMR spectra collected at the Centre of Biomedical Research (CBMR, Lucknow) were recorded on Bruker 400 MHz, 600 MHz and 800 MHz NMR spectrometers . 1 H, 13 C, and 11 B NMR spectra collected at Michigan State University were recorded on Varian 500 MHz NMR spectrometers. The boron bear ing carbon atom was not observed due to quadrupolar relaxation. All coupling constants are apparent J values measured at the indicated field strengths in Hertz (s = singlet, d = doublet, t = triplet, q = quartet, dd = doublet of doublets, bs = broad single t, dt = doublet of triplet, td = triplet of doublet, ttt = triplet of triplet of triplet). High - resolution mass spectra (HRMS) were obtained at the Centre of Biomedical Research Mass Spectrometry Service Center using a Waters GCT Premier instrument run on electron ionization (EI) direct probe or a Waters 319 QTOF Ultima instrument run on electrospray ionization (ESI+). GC - MS (Agilent Technology) was obtained from Centre of Biomedical Research. Ortho - borylation of N - methylaniline same conditions as Table 5 : In a glove box, a 5.0 mL Wheaton microreactor was charged with [Ir(cod)(OMe)] 2 (3.3 mg, 0.5 mol %), B 2 eg 2 (70.8 mg, 0.5 equiv.), N - methylaniline (107.2 mg, 1.0 mmol, 1 equiv), dry THF (1.0 mL) and stirred in a preheated aluminum block at 80 °C for 10 min. The microreactor was charged again with [Ir(cod)(OMe)] 2 (16.5 mg, 2.5 mol %), dtbpy (13.4 mg, 5.0 mol %), B 2 eg 2 (283.0 mg, 2.0 equiv.), Et 3 N (202.3 mg, 2.0 equiv.) and dry THF (4.0 mL). The microreactor was cap ped with a Teflon pressure cap and placed into a preheated aluminum block at 80 °C. After 12 h, THF was removed under reduced pressure using dry CHCl 3 as transferring solvent and transesterification was performed using dry CHCl 3 (4.0 mL) and pinacol (355.0 mg, 3.0 equiv.) at room temperature for 1h. Removal of solvent under reduced pressure and chromatographic separation with silica gel (1% EtOAc in hexane to 5% EtOAc in hexane as eluent) gave 49.3 mg of ortho - borylated N - methyl aniline (21%) as a solid. Spe ctra data are in accordance with reported data. 50 It should be noted that by GC ortho - borylation is the only mono - borylated product and conversion was 24%. A trace amount of diborylated material was observed on the GCMS. The remainder of the mass was unrea cted starting material. 320 Ortho - borylation of N - methylaniline ( scheme 26 ): In a glove box, a 5.0 mL Wheaton microreactor was charged with [Ir(cod)(OMe)] 2 (1.7 mg, 0.5 mol %), B 2 eg 2 (70.8 mg, 1.0 equiv.), dtbpy (1.3 mg, 1 mol %) N - methylaniline (53.5 mg, 0.5 mmol, 1 equiv), dry THF (1.0 mL) and stirred in a preheated aluminum block at 80 °C for 1 h. The microreactor was charged again with [Ir(cod)(OMe)] 2 (8.3 mg, 2.5 mol %), dtbpy (6 .7 mg, 5.0 mol %), B 2 eg 2 (141.7 mg, 2.0 equiv.), Et 3 N (101.2 mg, 2.0 equiv.) and dry THF (3.0 mL). The microreactor was capped with a Teflon pressure cap and placed into a preheated aluminum block at 80 °C. After 12 h, THF was removed under reduced pressur e using dry CHCl 3 as transferring solvent and transesterification was performed using dry CHCl 3 (4.0 mL) and pinacol (177.2 mg, 3.0 equiv.) at room temperature for 1h. GC showed only the ortho - borylated product in 29% conversion and a trace of diborylation . The remainder of the mass was unreacted starting material. 321 N - Borylation of N - methylaniline with dtbpy: 1 H NMR (25 °C, 500 MHz, THF) In a nitrogen filled glove box, a stock solution of [Ir(OMe)(cod)] 2 was prepared by di ssolving 3.3 mg in 0.5 mL THF and a stock solution of dtbpy was prepared by dissolving 2.7 mg in 0.5 mL THF. N - Methylaniline (10.7 mg, 0.1 mmol, 1.0 equiv) and B 2 eg 2 (7.1 mg, 0.05 mmol, 0.5 equiv) were dissolved in 0.4 mL deuterated THF respectively. The N - methylaniline and B 2 eg 2 were transferred to a J - Young tube after which 0.05 mL of the stock [Ir(OMe)(cod)] 2 (0.5 mol %) and stock dtbpy (1 mol %) was added. Finally, three drops of THF - d8 was added to enable locking. The J - Young tube sealed and removed from the glove box. 1 H NMR was immediately collected. The NMR tube was then heated 322 at 20 min increments after w hich NMR was collected. The 1 H spectra show a new N - Methyl peak growing at 3.06 ppm as a singlet and in the 11 B NMR N B bond formation via a broad singlet at 25.27 ppm. Over 1 h this conversion was complete. N - Borylation of N - methylaniline with table 5 conditions: 1 H NMR (25 °C, 500 MHz, THF) In a nitrogen filled glove box, a stock solution of [Ir(OMe)(cod)] 2 was prepared by dissolving 3.3 mg in 0.5 mL THF. N - Methylaniline (10.7 mg, 0.1 mmol, 1.0 equiv) and B 2 eg 2 (7.1 mg , 0.05 mmol, 0.5 equiv) were dissolved in 0.4 mL deuterated THF respectively. The N - methylaniline and B 2 eg 2 were transferred to a J - Young tube after which 0.05 mL of the stock [Ir(OMe)(cod)] 2 (0.5 mol %). Finally, three drops of THF - d8 was added to enable locking. The J - Young tube sealed and removed from the glove box. 1 H and 11 B NMR were immediately collected. The NMR tube was then heated at 80 o C for 12 h after which NMR was collected. The 1 H spectra show a new N - Methyl peak growing at 3.06 ppm as a singlet and in the 11 B NMR N B bond formation via a broad 323 singlet at 25.27 ppm; however, even after 12 h of heating the conversion was incomplete at only 41% based on 1 H NMR integration. C H borylation of aniline wi th B 2 pin 2 In a glove box, a 5.0 mL Wheaton microreactor was charged with [Ir(cod)(OMe)] 2 (1.65 mg, 0.5 mol %), B 2 pin 2 (64.0 mg, 0.5 equiv.), aniline (47 mg, 0.5 mmol), dry THF (0.5 mL) and stirred in a preheated aluminum b lock at 80 o C for 10 min. The microreactor was charged again with [Ir(cod)(OMe)] 2 (8.28 mg, 2.5 mol %), dtbpy (6.7 mg, 5.0 mol %), B 2 pin 2 (127.0 mg, 1.0 equiv.), Et 3 N (101 mg, 2.0 equiv.) and dry THF (2.0 mL). The microreactor was capped with a teflon pres sure cap and placed into a preheated aluminum block at 80 o C and heated for 30 min. The GC (the aliquot taken from reaction mixture was treated with methanol prior to injection in to GC) showed a mixture of monoborylated products (2.7:1.8:1 o:m:p). 324 Synthesis of 4,4,5,5 - tetramethyl - N - phenyl - 1,3,2 - dioxaborolan - 2 - amine (PhN(H)Bpin) This synthesis was adapted from a previous reported procedure. 51 In a nitrogen filled glove box, a 50 mL Schlenk flask was charged with anil ine (1 g, 10.7 mmol, 1 equiv), HBpin (1.374 g, 10.7 mmol, 1 equiv), and dry THF (10 mL). The Schlenk flask was removed from the glove box and allowed to stir under nitrogen for 24 h. After removing the volatiles under reduced pressure, 2.33 g (99%) of a wh ite solid was obtained. It should be noted that this compound is highly hygroscopic and should not be exposed to air. 1 H NMR (500 MHz, CDCl 3 t , J = 8. 0 Hz , 2H), 7.11 7.05 ( d , J = 8.0 Hz, 2H), 6.85 (t, J = 7.3 H z, 1H), 4.62 (bs, 1H), 1.31 (s, 12H). 13 C NMR (126 MHz, CDCl 3 11 B NMR (160 MHz, CDCl 3 325 Regioselectivity of C H borylation of PhN(H)Bpin with B 2 eg 2 In a nitrogen filled glove box, a 3.0 mL conical vial was charged with aniline - N - Bpin (110 mg, 0.5 mmol, 1.0 equiv), [Ir(cod)(OMe)] 2 (3.3 mg, 1 mol %), dtbpy (2.68 mg, 2.0 mol %), B 2 eg 2 (70.8 mg, 0.5 mmol, 1.0 equiv), Et 3 N (101.1 mg, 1 mmol, 2 equiv) and dry THF (1.5 ml). The vial was capp ed with a teflon pressure cap and was taken out of the glove box and placed into a preheated aluminum block at 80 º C and heated for 3 h after which the volatiles were removed under reduced pressure. Pinacol (177 mg, 1.5 mmol, 3 equiv) and CHCl 3 (5.0 mL) we re added to the reaction vial and stirred at room temperature for 30 min. After which 1 H NMR showed 57% conversion to the ortho - borylated product with a 9.7:1 ratio of mono:diborylation. Synthesis of N - phenyl - 1,3,2 - dioxaborolan - 2 - amine (PhN(H)B eg ) In a nitrogen filled glove box, a 3.0 mL conical vial was charged with [Ir(cod)(OMe)] 2 (3.3 mg, 0.5 mol %), B 2 eg 2 (70.9 mg, 0.5 equiv), aniline (93.0 mg, 1.0 mmol, 1.0 equiv), and dry THF (1.0 ml). The vial was capped with a teflon pressure cap, brought out of the glove box and placed into preheated aluminum block at 80 ºC for 15 minutes. After bringing the 326 vial back into the glove box solvent was removed and an aliquot of the black solid was dissolved in C 6 D 6 . 1 H NMR (500 M Hz, C 6 D 6 7.08 (m, 2H), 7.06 7.02 (m, 2H), 6.78 (ddd, J = 8.5, 6.6, 1.2 Hz, 1H), 4.44 (s, 1H), 3.53 (s, 4H). 11 B NMR (160 MHz, C 6 D 6 Regioselectivity of C H borylation of PhN(H)Beg with B 2 pin 2 In a nitrogen filled glove box, a 3.0 mL conical vial was charged with [Ir(cod)(OMe)] 2 (1.65 mg, 0.5 mol %), B 2 eg 2 (35.75 mg, 0.5 equiv), aniline (46.5 mg, 0.5 mmol, 1.0 equiv), and dry THF (0.5 ml). The vial was capped wit h a teflon pressure cap, brought out of the glove box and placed into a preheated aluminum block at 80 º C for 15 minutes then the vial was taken to the glove box and volatiles were removed under reduced pressure and vial was charged with [Ir(cod)(OMe)] 2 (3 .3 mg, 1.0 mol %), dtbpy (2.68 mg, 2.0 mol %), B 2 pin 2 (127.0 mg, 1.0 equiv), and dry THF (1.5 ml). The vial was capped with a teflon pressure cap and was taken out of the glove box and placed into a preheated aluminum block at 80 º C and heated for 3 h. The GC (the aliquot taken from reaction mixture was treated with methanol prior to injection in to GC) showed 80% conversion (58% mono - borylated aniline o : m : p (11.0 : 1.16 : 1) and 22% of diborylated products). 4.9: Notes Parts of this chapter were reprinted with permission from Smith, M. R., III; Bisht, R.; Haldar, C.; Pandey, G.; Dannatt, J. E.; Ghaffari, B.; Maleczka, R. E., Jr.; Chattopadhyay, 327 - H Borylations by Modifying Boron ACS Catal. 2018 , 8 , 6216. The work presented in this chapter was not all conducted by Dannatt, J. E. Credit for the substrate exploration belongs to Bisht, Haldar, Pandey, and Chattopadhyay. Calculations were conducted by Smith. 328 APPENDIX 329 1 H NMR (CDCl 3 , 500 MHz) 330 1 H NMR (CDCl 3 , 500 MHz) 331 13 C NMR (CDCl 3 , 126 MHz) 332 11 B NMR (CDCl 3 , 160 MHz) 333 1 H NMR (CDCl 3 , 500 MHz) 334 11 B NMR (CDCl 3 , 160 MHz) 335 Computational procedures and results for c hapter 4 General Calculations of structures, energies, and frequencies emplo yed default procedures in Gaussian09 51 - 53 with the following exceptions and all calculations were performed at the Department of Chemistry, Michigan State University. For transition state optimizations, (i) the maximum step size was set to 0.01 Bohr (MaxStep=1), (ii) the 2 - electron integral accur acy was set to 10 12 (acc2e=12), and (iii) superfine (PhN(H)Beg) or ultrafine (PhN(Me)Beg) grids were used for integration . DFT calculations were performed using the M06 functional with a split 6 - 31G*/SDD basis set for the light and Ir atoms. An SDD core potential was used for Ir. Complete structures and energetics are provided in sections below. All absolute energies are in Hartrees. All relative energies are presented in kcal/mol. The default self - consistent reaction filed (SCRF) and parameters for THF were used for all calculations. Guide to structures, structure titles and their organization The sections below are divided into reactants and transition structures, then divided into specific structures. The first line after the title for a structure is a file name for the original calculation file, so that this file can always be located even if the file title changes. 336 Calculated Structures, Energies, and Selected NPA Charges Reactants: PhN(H)Beg PhN(H)Beg_superfine_grid E(RM06) = - 579.973272280 Item Value Threshold Converged? Maximum Force 0.000035 0.000450 YES RMS Force 0.000010 0.000300 YES Maximum Displacement 0.000627 0.001800 YES RMS Displacement 0.000216 0.001200 YES Zero - point correction = 0.206810 (Hartree/Particle) Thermal correction to Energy= 0.222466 Thermal correction to Enthalpy= 0.223585 Thermal correction to Gibbs Free Energy= 0.158549 Sum of electronic and zero - point Energies= - 579.766462 Sum of electronic and thermal Energies= - 579.750806 Sum of electronic and thermal Enthalpies= - 579.749688 Sum of electronic and thermal Free Energies= - 579.814723 E (Thermal ) CV S KCal/Mol Cal/Mol - Kelvin Cal/Mol - Kelvin Total 139.600 51.547 115.561 C, - 3.483286, - 0.775444, - 0.003278 C, - 3.696065,0.599968,0.008356 C, - 2.593915,1.450565,0.013842 C, - 1.29 8053,0.948532,0.008065 C, - 1.08329, - 0.435629, - 0.003604 C, - 2.193232, - 1.289649, - 0.009255 B,1.480243, - 0.377108, - 0.00584 O,2.621715, - 1.142154, - 0.065399 C,3.719889, - 0.254488,0.11683 C,3.131497,1.142553, - 0.10883 O,1.725131,0.972747,0.057677 H, - 4.706597,1.003553,0.013276 H, - 0.44578,1.623315,0.012648 H,3.49943,1.883592,0.609132 H,3.326915,1.515251, - 1.123599 H,4.516817, - 0.500909, - 0.593582 H,4.114578, - 0.375744,1.135246 N,0.19934, - 0.989126, - 0.010122 H, - 2.740862,2.52987 9,0.022964 H, - 2.035077, - 2.368945, - 0.018555 H,0.207509, - 2.002847, - 0.020572 H, - 4.329564, - 1.460917, - 0.007888 PhN(Me)Beg MeOPhOBpinprimeM06SB E(RM06) = - 540.7031200 Item Value Threshold Converged? Maximum Force 0.000047 0.000450 YES RMS Force 0.000008 0.000300 YES Maximum Displacement 0.002886 0.001800 NO RMS Displacement 0.000699 0.001200 YES Zero - point correction = 0.178465 (Hartree/Particle) Thermal correction to Energy = 0.192327 Thermal correction to Enthalpy = 0.193445 Thermal correction to Gibbs Free Energy = 0.132344 Sum of electronic and zero - point Energies = - 540.524655 Sum of electronic and thermal Energies = - 540.510794 Sum of electronic and thermal Enthalpies = - 540.509675 Sum of electronic and thermal Free Energies = - 540.570776 E (Thermal) CV S KCal/Mol Cal/Mol - Kelvin Cal/Mol - Kelvin Total 120.687 45.867 108.570 C, - 3.46457, - 0.67753,0.278879 C, - 3.626669,0.676532,0.016203 C, - 2.500686,1.434807, - 0.29594 C, - 1.240002,0.857372, - 0.345606 C, - 1.066057, - 0.508477, - 0.070315 C, - 2.204525, - 1.267112,0.23692 B,1.452855, - 0.425579, - 0.015991 O,2.651473, - 1.09613 7, - 0.125878 C,3.681122, - 0.171589,0.204081 337 C,3.005311,1.200395,0.129559 O,1.611635,0.919601,0.222329 H, - 4.613169,1.134739,0.048959 H, - 0.377667,1.465489, - 0.600664 H,3.30026,1.869238,0.945552 H,3.20439,1.708409, - 0.824068 H,4.513235, - 0.277377, - 0.50085 H,4.052783, - 0.394221,1.213973 N,0.206758, - 1.110982, - 0.128334 H, - 2.602686,2.496697, - 0.516336 H, - 2.11666, - 2.328101,0.455686 H, - 4.327568, - 1.295254,0.523809 C,0.248152, - 2.565277, - 0.208955 H, - 0.055222, - 3.040687,0.735103 H, - 0.417097 , - 2.926885, - 1.004126 H,1.266754, - 2.885282, - 0.436185 (4,4´ - dimethyl - 2,2´ - bipyridine)Ir(Beg) 3 - Me2 - bipyridine_Ir_(Beg)3_superfine_grid E(RM06) = - 659.807029462 Zero - point correction = 0.426357 (Hartree/Particle) Thermal corre ction to Energy = 0.466553 Thermal correction to Enthalpy = 0.467671 Thermal correction to Gibbs Free Energy = 0.343220 Sum of electronic and zero - point Energies = - 1439.201607 Sum of electronic and thermal Energies = - 1439.161411 Sum o f electronic and thermal Enthalpies = - 1439.160293 Sum of electronic and thermal Free Energies = - 1439.284744 E (Thermal) CV S KCal/Mol Cal/Mol - Kelvin Cal/Mol - Kelvin Total 292.766 125.248 221.136 C, - 3.916953,1.421993, - 0.117558 C, - 2.711242,0.724928, - 0.101524 N, - 1.528843,1.374512, - 0.07018 C, - 1.529066,2.714237, - 0 .041438 C, - 2.693942,3.464353, - 0.045913 C, - 3.927697,2.814985, - 0.093126 C, - 2.647857, - 0.755708, - 0.111396 N, - 1.418778, - 1.297853, - 0.218154 C, - 1.3024, - 2.631257, - 0.214439 C, - 2.388861, - 3.483085, - 0.114942 C, - 3.671917, - 2.943824, - 0.007427 C, - 3.783755, - 1.555828, - 0.001 458 Ir,0.376829,0.110811, - 0.307007 B,1.841447,1.517676, - 0.288722 O,3.182763,1.378074, - 0.662476 C,3.894652,2.524468, - 0.228329 C,2.815911,3.585306, - 0.03976 O,1.625681,2.835,0.152463 B,1.208185, - 0.412052,1.410607 O,2.223293,0.248167,2.104654 C,2.387958, - 0.387804,3.363128 C,1.699598, - 1.738253,3.18998 O,0.772254, - 1.524649,2.137131 B,1.877122, - 1.061094, - 0.962767 O,2.120262, - 1.186331, - 2.339379 C,3.115088, - 2.180235, - 2.535874 C,3.759867, - 2.33792, - 1.162973 O,2.766291, - 1.8 81363, - 0.258201 H, - 0.285993, - 3.015174, - 0.283899 H, - 4.769809, - 1.108202,0.101441 H, - 2.237051, - 4.560939, - 0.116854 C, - 4.874452, - 3.826335,0.091934 H, - 4.864661,0.889691, - 0.158802 C, - 5.207442,3.586574, - 0.131928 H, - 2.639501,4.551223, - 0.017142 H, - 0.543057,3.177634, - 0.004941 H,2.640506, - 3.114909, - 2.875033 H,3.823737, - 1.858292, - 3.308991 H,4.037141, - 3.373492, - 0.930202 H,4.658633, - 1.7089, - 1.062231 H,1.177266, - 2.077797,4.092822 H,2.415814, - 2.518928,2.888022 H,1.908338,0.220419,4.146027 H,3.454362, - 0.476493,3.603857 H,2.707558,4.224023, - 0.930777 H,2.996849,4.234797,0.82562 H,4.653305,2.805518, - 0.96933 H,4.406796,2.295121,0.719957 H, - 6.07549,2.943955,0.051508 H, - 5.206061,4.391136,0.613579 H, - 5.341862,4.060532, - 1.113587 H, - 5.779245, - 3.25547 3,0.327507 H, - 5.045526, - 4.354373, - 0.855743 H, - 4.737592, - 4.593529,0.864191 338 Transition structures: TS1 - dimethylbipyridine_Ir(Beg)3_ superfine_grid E(RM06) = - 1980.29036773 Item Value Threshold Converged? Maximum Force 0.000010 0.000450 YES RMS Force 0.000003 0.000300 YES Maximum Displacement 0.015452 0.001800 NO RMS Displacement 0.00217 6 0.001200 NO Zero - point correction = 0.600770 (Hartree/Particle) Thermal correction to Energy = 0.656449 Thermal correction to Enthalpy = 0.657567 Thermal correction to Gibbs Free Energy = 0.499537 Sum of electronic and zero - point Energies = - 1979.689598 Sum of electronic and thermal Energies = - 1979.633919 Sum of electronic and thermal Enthalpies = - 1979.632801 Sum of electronic and thermal Free Energies = - 1979.790830 E (Thermal) CV S KCal/Mol Cal/Mol - Kelvin Cal/Mol - Kelvin Total 411.928 176.449 280.802 C, - 4.117407,0.388126, - 0.733646 C, - 2.724633,0.376213, - 0.66984 N, - 2.05852, - 0.726826, - 0.27129 C, - 2.75437, - 1.825 669,0.049393 C, - 4.137176, - 1.873754,0.004914 C, - 4.852497, - 0.741289, - 0.386524 C, - 1.900778,1.537215, - 1.074707 N, - 0.568704,1.349474, - 1.065205 C,0.22414,2.332466, - 1.50075 C, - 0.264694,3.554232, - 1.936694 C, - 1.639559,3.789568, - 1.913364 C, - 2.458372,2.75157, - 1.474256 Ir,0.167856, - 0.559577,0.025916 B,0.578367, - 2.298693,0.983977 O,1.582906, - 2.476199,1.935326 C,1.562276, - 3.824441,2.377133 C,0.181534, - 4.327742,1.970488 O, - 0.212104, - 3.450729,0.923106 C, - 0.386794,0 .385637,1.972138 C, - 1.119969, - 0.434334,2.845988 C, - 1.896833,0.07705,3.882259 C, - 1.935237,1.451552,4.097871 C, - 1.158418,2.281711,3.301592 C, - 0.371948,1.764053,2.264744 B,1.838667,2.606731,1.382896 O,2.644144,1.690739,2.01736 C,3.97748,1.922624,1.590577 C,3. 906884,3.164884,0.679848 O,2.531846,3.511202,0.609539 B,0.413452, - 1.509675, - 1.855348 O,0.061046, - 2.815843, - 2.158954 C,0.240764, - 3.022576, - 3.556438 C,1.132657, - 1.866027, - 3.989625 O,0.919728, - 0.874564, - 2.992049 B,2.142954, - 0.562997, - 0.561238 O,2.817641,0.600735, - 0.944415 C,3.990189,0.209756, - 1.646336 C,4.253007, - 1.208511, - 1.157233 O,2.974808, - 1.66711, - 0.738876 H,1.078667,0.023777,1.258146 H,1.2924,2.122095, - 1.470472 H, - 3.535267,2.904774, - 1.449952 H,0.426365,4.325616, - 2.272956 C, - 2.214422,5.092 711, - 2.369881 H, - 4.646583,1.279241, - 1.063528 C, - 6.346919, - 0.747727, - 0.429657 H, - 4.655472, - 2.792312,0.274865 H, - 2.156176, - 2.684862,0.351921 H,3.7882,0.237265, - 2.728433 H,4.811761,0.905014, - 1.427624 H,4.651365, - 1.86862, - 1.936924 H,4.945505, - 1.228078, - 0.30105 1 H, - 1.12483, - 1.514887,2.685978 H, - 2.540653,1.872785,4.899381 H, - 1.129652,3.356392,3.488558 H,0.882161, - 1.466607, - 4.97922 H,2.197954, - 2.148728, - 3.987835 H, - 0.739546, - 2.997365, - 4.055668 H,0.691276, - 4.006176, - 3.732443 H, - 0.542117, - 4.251013,2.797983 H,0.18421 1, - 5.363924,1.611991 339 H,1.735721, - 3.868983,3.459034 H,2.366371, - 4.385301,1.876339 H,4.47528,4.013083,1.08465 H,4.278001,2.956563, - 0.332595 H,4.339429,1.036525,1.052609 H,4.615708,2.080564,2.469458 N,0.434235,2.668725,1.531779 H, - 0.03317,3.507337,1.207078 H, - 2.47379, - 0.597888,4.514 H, - 6.744739,0.166689, - 0.883138 H, - 6.720816, - 1.60777, - 0.999289 H, - 6.76257, - 0.831103,0.58333 H, - 3.214053,5.262342, - 1.953841 H, - 1.570644,5.933634, - 2.085985 H, - 2.305043,5.111275, - 3.464613 TS2 PhN(H)Beg_H - dimethylbipyridine_Ir(Beg)3_superfine_grid E(RM06) = - 1980.29476162 Item Value Threshold Converged? Maximum Force 0.000004 0.000450 YES RMS Force 0.000002 0.000300 YES Maximum Displacement 0.003496 0.001800 NO RMS Displacement 0.000651 0.001200 YES Zero - point correction = 0.601453 Thermal correction to Energy = 0.656979 Thermal correction to Enthalpy = .658098 Thermal correction to Gibb s Free Energy = 0.500930 Sum of electronic and zero - point Energies = - 1979.693309 Sum of electronic and thermal Energies = - 1979.637782 Sum of electronic and thermal Enthalpies = - 1979.636664 Sum of electronic and thermal Free Energies = - 1979.793832 E (Thermal) CV S KCal/Mol Cal/Mol - Kelvin Cal/Mol - Kelvin Total 412.261 176.182 279.270 C,2.120282,2.287515,1.81476 C,1.005112,1.758526,1.169163 N,0.843423,0.42474,1.047222 C,1.747738, - 0.390761,1.598788 C,2.871951,0.075002,2.261167 C,3.089388,1.448203,2.360342 C, - 0.079748,2.608886,0.630271 N, - 1.154868,1.964389,0.137644 C, - 2.189817,2.683664, - 0.30637 C, - 2.195181,4.069936, - 0.310879 C, - 1.079548,4.759997,0.161837 C, - 0.014595,4.000649,0.64135 Ir, - 0.840499, - 0.306323, - 0.224634 B, - 0.354568, - 2.268219, - 0.227309 O, - 0.008135, - 2.990858,0.916852 C,0.678003, - 4.172219,0.50958 C,0.250198, - 4.362767, - 0.938793 O, - 0.104666, - 3.049134, - 1.362618 C,0.381377,0.433265, - 1.958022 C, - 0.087299,1.526666, - 2.697745 C,0.738369,2.28871, - 3.521358 C,2.080795,1.943733, - 3.641668 C,2.562926,0.824016, - 2.975668 C,1.726475,0.056751, - 2.155033 B,3.486845, - 1.248293, - 0.874333 O,4.488886, - 0.303558, - 0.823623 C,5.481466, - 0.798823,0.064353 C,5.146248, - 2.285494,0.242281 O,3.793778, - 2.403876, - 0.179304 B, - 1.86416, - 0.770847,1.572141 O, - 1.551705, - 0.125777,2.765068 C, - 2.316854, - 0.70872,3.815311 C, - 3.411794, - 1.491913,3.096387 O, - 2.912742, - 1.66262,1.775399 B, - 2.743471, - 0.86168, - 0.787723 O, - 3.813192,0.031383, - 0.747207 C, - 5.010424, - 0.711221, - 0.942562 C, - 4.543281, - 2.022526, - 1.572622 O, - 3.160888, - 2.09788, - 1.254008 H, - 0.993968, - 0.60181, - 1.816058 340 H, - 3.035922,2.105207, - 0.676786 H,0.868916,4.513027 ,1.015806 H, - 3.061398,4.608666, - 0.691079 C, - 1.038484,6.254591,0.181101 H,2.243844,3.363841,1.911339 C,4.310458,2.00632,3.017677 H,3.571157, - 0.635494,2.700858 H,1.545359, - 1.457073,1.506686 H, - 5.491077, - 0.875317,0.03392 H, - 5.702369, - 0.146882, - 1.578816 H, - 5.067433, - 2.898159, - 1.171304 H, - 4.662857, - 2.022592, - 2.666268 H, - 1.139479,1.808235, - 2.610227 H,2.748585,2.52558, - 4.276034 H,3.601841,0.51767, - 3.092918 H, - 4.359627, - 0.934215,3.053339 H, - 3.610342, - 2.470466,3.549054 H, - 2.7090 99,0.07813,4.470376 H, - 1.666673, - 1.362911,4.414406 H, - 0.627359, - 5.019428, - 1.029769 H,1.049024, - 4.756134, - 1.578275 H,0.404262, - 5.00952,1.161167 H,1.763106, - 3.996823,0.591202 H,5.779684, - 2.928408, - 0.385671 H,5.242446, - 2.62136,1.2821 H,5.41976, - 0.248176,1.016 173 H,6.47782, - 0.633587, - 0.36194 N,2.25375, - 1.097324, - 1.539797 H,1.577523, - 1.852039, - 1.45088 H,0.3335,3.141659, - 4.065444 H, - 0.009204,6.630678,0.190639 H, - 1.557644,6.678801, - 0.68632 H, - 1.539469,6.641447,1.079096 H,4.077426,2.904282,3.602213 H,4.783074,1.27152,3.679463 H,5.052391,2.297702,2.261058 TS3 PhN(H)Beg_H···O - dimethylbipyridine_Ir(Beg)3_superfine_grid E(RM06) = - 1980.29368534 Item Value Threshold Converged? Maximu m Force 0.000002 0.000450 YES RMS Force 0.000001 0.000300 YES Maximum Displacement 0.007538 0.001800 NO RMS Displacement 0.000925 0.001200 YES Zero - point correction = 0.601689 (Hartree/Particle) Thermal correction to Energy = 0.657309 Thermal correction to Enthalpy = 0.658428 Thermal correction to Gibbs Free Energy = 0.498707 Sum of electronic and zero - point Energies = - 1979.691997 Sum of electronic and thermal Energies = - 1979.636376 Sum of electronic and thermal Enthalpies = - 1979.635258 Sum of electronic and thermal Free Energies = - 1979.794978 E (Thermal) CV S KCal/Mol Cal/Mol - Kelvin Cal/Mol - Kelvin Total 412.468 175.978 283.806 C,1.074012,3.008629,2.02546 C,0.290603,2.147028,1.259553 N,0.526668,0.817728,1.248695 C,1.512301,0.331483,2.015692 C,2.325784,1.137916,2.79313 C,2.121578,2.517605,2.799766 C, - 0.864955,2.621415,0.467254 N, - 1.601948,1.671797, - 0.137534 C, - 2.695435,2.038674, - 0.814024 C, - 3.093297,3.359912, - 0.939356 C, - 2.330134,4.365059, - 0.34485 C, - 1.202056,3.970999,0.369175 Ir, - 0.678227, - 0. 447734, - 0.17803 B,0.265161, - 2.243706, - 0.048929 O,1.138529, - 2.598184,0.984924 C,1.897031, - 3.730615,0.567939 C,1.087256, - 4.310275, - 0.585954 O,0.308476, - 3.214531, - 1.047273 C,0.54667,0.373273, - 1.881109 C, - 0.072105,1.156614, - 2.863924 C,0.641592,1.882377, - 3.81466 C,2.030767,1.816224, - 3.80496 C,2.683713,1.035801, - 2.859657 341 C,1.960227,0.310377, - 1.90199 B,4.008411, - 0.552004, - 0.597591 O,5.062448,0.082706, - 1.213055 C,6.253383, - 0.421321, - 0.615435 C,5.781529, - 1.09 2297,0.678031 O,4.396981, - 1.339933,0.468487 B, - 1.882513, - 1.010414,1.474209 O, - 1.511311, - 1.817681,2.536625 C, - 2.577174, - 1.840119,3.482154 C, - 3.776199, - 1.316725,2.701111 O, - 3.195604, - 0.5652,1.641477 B, - 2.333053, - 1.508872, - 0.802393 O, - 3.302941, - 0.934685, - 1.62 2814 C, - 4.454498, - 1.770847, - 1.587669 C, - 3.914194, - 3.121475, - 1.132819 O, - 2.71012, - 2.798929, - 0.447215 H, - 0.542884, - 0.849288, - 1.753334 H, - 3.253561,1.223411, - 1.273878 H, - 0.588598,4.73355,0.84373 H, - 3.990192,3.605371, - 1.505693 C, - 2.722574,5.803721, - 0.454756 H,0 .870943,4.077009,2.033539 C,2.994884,3.43128,3.597883 H,3.115284,0.687386,3.392285 H,1.641242, - 0.750076,1.988047 H, - 5.175798, - 1.356506, - 0.866013 H, - 4.926475, - 1.799479, - 2.576316 H, - 4.595544, - 3.653595, - 0.458466 H, - 3.681731, - 3.781144, - 1.981846 H, - 1.163956,1.189043, - 2.890329 H,2.615953,2.368, - 4.540098 H,3.770752,0.983147, - 2.851492 H, - 4.442423, - 0.68086,3.295361 H, - 4.37093, - 2.137454,2.268246 H, - 2.320994, - 1.189468,4.331636 H, - 2.718016, - 2.859533,3.859251 H,0.417813, - 5. 118488, - 0.254564 H,1.71235, - 4.693421, - 1.40103 H,2.018971, - 4.425585,1.406732 H,2.8934, - 3.38823,0.248256 H,6.301931, - 2.034164,0.885431 H,5.901139, - 0.432202,1.549663 H,6.955477,0.401615, - 0.440719 H,6.723206, - 1.13752, - 1.304205 N,2.640998, - 0.458164, - 0.948718 H, 2.010782, - 0.924775, - 0.303188 H,0.116568,2.47973, - 4.559149 H,3.915825,3.660807,3.04459 H,2.49545,4.382221,3.8146 H,3.29438,2.969188,4.545867 H, - 3.602157,6.013145,0.16884 H, - 1.915895,6.470221, - 0.13025 H, - 2.992778,6.062126, - 1.485938 TS4 - dimethylbipyridine_ Ir(Beg)3_superfine_grid E(RM06) = - 1980.29519479 Item Value Threshold Converged? Maximum Force 0.000003 0.000450 YES RMS Force 0.000001 0.000300 YES Maximum Displacement 0.003225 0.001800 NO RMS Displacement 0.000385 0.001200 YES Zero - point correction = 0.601723 (Hartree/Particle) Thermal correction to Energy = 0.657028 Ther mal correction to Enthalpy = 0.658146 Thermal correction to Gibbs Free Energy = 0.501778 Sum of electronic and zero - point Energies = - 1979.693472 Sum of electronic and thermal Energies = - 1979.638167 Sum of electronic and thermal Enthalpies = - 1979.637049 Sum of electronic and thermal Free Energies = - 1979.793417 E (Thermal) CV S KCal/Mol Cal/Mol - Kelvin Cal/Mol - Kelvin Total 412.291 176.033 277.850 C,0.822272,3.506792, - 1.614067 C,0.52764,2.194915, - 1.250156 N, - 0.67837,1.869756, - 0.737962 C, - 1.606477,2.826492, - 0.611223 C, - 1.374461,4.145971, - 0.963014 C, - 0.126937,4.514771, - 1.464991 C,1.477463,1.080379, - 1.461397 342 N,1.020555, - 0.149545, - 1.155809 C,1.772886, - 1.207305, - 1.462604 C,3.030477, - 1.09669, - 2.037119 C,3.562587,0.168186, - 2.277084 C,2.750252,1.266366, - 1.995572 Ir , - 0.907087, - 0.18232,0.158108 B, - 2.647821,0.034211,1.177242 O, - 2.986452, - 0.643706,2.34746 C, - 4.283216, - 0.230757,2.754037 C, - 4.508284,1.077789,2.004254 O, - 3.614705,1.002256,0.900294 C,0.276903,0.673572,1.841672 C, - 0.257762,1.793192,2.491014 C,0.507255,2.60873,3.322267 C,1.842881,2.285868,3.543887 C,2.388601,1.148144,2.963845 C,1.615253,0.331121,2.127445 B,3.510866, - 1.174153,1.313632 O,4.593221, - 0.340243,1.491889 C,5.755061, - 1.117543,1.221993 C,5.231317, - 2.326457, 0.4445 O,3.8567, - 2.40658,0.794377 B, - 1.989532, - 0.820858, - 1.553822 O, - 3.270063, - 0.438249, - 1.918725 C, - 3.573968, - 1.017474, - 3.184475 C, - 2.52957, - 2.114542, - 3.350164 O, - 1.466329, - 1.710605, - 2.495488 B, - 1.214579, - 2.217369,0.211243 O, - 0.131524, - 3.099207,0.197215 C , - 0.635858, - 4.398658, - 0.095463 C, - 2.108554, - 4.314051,0.288452 O, - 2.408936, - 2.924843,0.207972 H, - 0.531811, - 0.793206,1.623178 H,1.348439, - 2.177192, - 1.205323 H,3.126225,2.265765, - 2.203927 H,3.598095, - 1.996167, - 2.270859 C,4.951381,0.350148, - 2.80087 H,1.79649,3 .758481, - 2.027106 C,0.180676,5.933844, - 1.820549 H, - 2.165737,4.883795, - 0.842863 H, - 2.561652,2.500076, - 0.201547 H, - 0.50608, - 4.596895, - 1.170992 H, - 0.078294, - 5.153337,0.470145 H, - 2.763133, - 4.876076, - 0.387915 H, - 2.288264, - 4.663808,1.315554 H, - 1.305819,2.054599,2.32217 H,2.460366,2.906579,4.192414 H,3.422022,0.871435,3.16429 H, - 2.167851, - 2.222379, - 4.379252 H, - 2.906709, - 3.092246, - 3.008715 H, - 3.490876, - 0.246402, - 3.964873 H, - 4.602501, - 1.39621, - 3.182603 H, - 4.247793, 1.953015,2.620347 H, - 5.536786,1.202625,1.646028 H, - 4.315636, - 0.114104,3.843718 H, - 5.016841, - 0.999388,2.467549 H,5.320367, - 2.175857, - 0.643922 H,5.739535, - 3.261644,0.705231 H,6.221228, - 1.410763,2.173644 H,6.477173, - 0.520251,0.653542 N,2.164148, - 0.850685,1.60 1638 H,1.467904, - 1.494966,1.234468 H,0.062166,3.48489,3.792734 H, - 0.684509,6.425392, - 2.281071 H,0.436015,6.507945, - 0.919438 H,1.030229,6.00466, - 2.508942 H,5.31921, - 0.558758, - 3.290855 H,5.008542,1.179982, - 3.515464 H,5.640812,0.58581, - 1.977812 TS meta PhN(H)Beg_left_meta_4,4´ - Me2 - bipyridine_Ir_(Beg)3_ superfine_grid E(RM06) = - 1980.29107739 Item Value Threshold Converged? Maximum Force 0.000010 0.000450 YES RMS Force 0.000003 0.000300 YES Maximum Displacement 0.061559 0.001800 NO RMS Displacement 0.011491 0.001200 NO Zero - point correction = 0.601119 (Hartree/Particle) Thermal correction to Energy = 0.657013 Thermal cor rection to Enthalpy = 0.658131 Thermal correction to Gibbs Free Energy = 0.496329 Sum of electronic and zero - point Energies = - 1979.689958 Sum of electronic and thermal Energies = - 1979.634065 Sum of electronic and thermal Enthalpies = - 1979.632946 Sum of electronic and thermal Free Energies = - 1979.794748 E (Thermal) CV S KCal/Mol Cal/Mol - Kelvin Cal/Mol - Kelvin Total 412.282 176.298 287.505 343 C,0.599247,2.867861,2.439927 C,0.175882,2.047881,1.395216 N, - 0.609373,0.975851,1.630255 C, - 0.983675,0.707654,2.888249 C, - 0.591641,1.48417,3.965408 C,0.226047,2.594312,3.752548 C,0.529684,2.314423, - 0.016553 N, - 0.018723,1.494677, - 0.93212 C,0.2 33633,1.709562, - 2.227708 C,1.060805,2.729666, - 2.670334 C,1.659726,3.579552, - 1.739429 C,1.375961,3.35609, - 0.394832 Ir, - 1.120218, - 0.352218, - 0.10463 B, - 2.057621, - 1.889794,0.828633 O, - 2.067593, - 3.214063,0.389708 C, - 2.834511, - 3.992099,1.295588 C, - 2.912445, - 3.13 2499,2.55347 O, - 2.657025, - 1.813308,2.089765 C,0.869696, - 1.277326,0.250662 C,1.062545, - 2.108106,1.365519 C,2.347954, - 2.458443,1.771727 C,3.471807, - 2.024801,1.077061 C,3.303995, - 1.221763, - 0.056307 C,2.007012, - 0.867564, - 0.452498 B,5.783414, - 0.975986, - 0.671566 O,6.67697, - 0.369932, - 1.526832 C,7.959436, - 0.909754, - 1.231147 C,7.791727, - 1.581949,0.13606 O,6.386089, - 1.769026,0.275767 B, - 2.956597,0.699994, - 0.280218 O, - 4.012358,0.666619,0.616024 C, - 4.995179,1.608313,0.196425 C, - 4.62544,1.9 1072, - 1.250681 O, - 3.246261,1.571595, - 1.333089 B, - 2.156811, - 0.919877, - 1.796988 O, - 1.655217, - 0.683077, - 3.077922 C, - 2.71869, - 0.869074, - 4.00449 C, - 3.712772, - 1.744343, - 3.251197 O, - 3.420961, - 1.496103, - 1.88141 H, - 0.314504, - 1.57667, - 0.838242 H, - 0.250854,1.017631, - 2.917024 H,1.831249,4.002321,0.352437 H,1.243086,2.857854, - 3.736028 C,2.550828,4.699882, - 2.171696 H,1.222855,3.736468,2.241272 C,0.688205,3.446855,4.890362 H, - 0.926437,1.224735,4.968241 H, - 1.627342, - 0.163551,3.007763 H, - 3.150921,0.112134, - 4.256379 H, - 2.33951, - 1.329996, - 4.923773 H, - 4.758361, - 1.490124, - 3.462012 H, - 3.56653, - 2.813629, - 3.46511 H,0.206016, - 2.474466,1.934332 H,4.470463, - 2.31097,1.397533 H, - 4.774414,2.960148, - 1.530206 H, - 5.189186,1.279052, - 1.956261 H, - 4.935668 ,2.502971,0.834166 H, - 5.995991,1.174642,0.305079 H, - 2.14271, - 3.413241,3.290021 H, - 3.890405, - 3.174002,3.047567 H, - 2.347844, - 4.960211,1.465594 H, - 3.829744, - 4.179013,0.864059 H,8.300235, - 2.550235,0.202618 H,8.150197, - 0.944958,0.956759 H,8.706566, - 0.107914, - 1. 223106 H,8.23554, - 1.631246, - 2.013204 N,4.389311, - 0.760532, - 0.811536 H,2.481422, - 3.089132,2.651363 H,1.095322,4.402617,4.542298 H, - 0.130859,3.651341,5.590533 H,1.476202,2.935122,5.459285 H,3.175097,5.062308, - 1.347341 H,3.205596,4.39183, - 2.995605 H,1.954495,5.548025, - 2.534766 H,1.896439, - 0.248919, - 1.348275 H,4.118707, - 0.178757, - 1.596751 TS5 - Me2 - bipyridine_Ir_(Beg)3_ superfine_grid E(RM06) = - 1980.29037111 Item Value Thresh old Converged? Maximum Force 0.000003 0.000450 YES RMS Force 0.000001 0.000300 YES Maximum Displacement 0.010812 0.001800 NO RMS Displacement 0.001474 0.001200 NO 344 Zero - point correcti on = 0.601098 (Hartree/Particle) Thermal correction to Energy = 0.656941 Thermal correction to Enthalpy = 0.658060 Thermal correction to Gibbs Free Energy = 0.496976 Sum of electronic and zero - point Energies = - 1979.689273 Sum of electronic and thermal Ene rgies = - 1979.633430 Sum of electronic and thermal Enthalpies = - 1979.632311 Sum of electronic and thermal Free Energies = - 1979.793395 E (Thermal) CV S KCal/Mol Cal/Mol - Kelvin Cal/Mol - Kelvin Total 412.237 176.297 286.228 C,0.310189,2.976566,2.35232 C, - 0.199857,2.148224 ,1.353734 N, - 0.331497,0.820732,1.555415 C,0.034715,0.301762,2.734704 C,0.550898,1.074051,3.761369 C,0.702457,2.449182,3.579041 C, - 0.647298,2.667252,0.042183 N, - 1.195657,1.769732, - 0.796538 C, - 1.651267,2.185553, - 1.983679 C, - 1.56203,3.503761, - 2.399545 C, - 0.97 7521,4.450811, - 1.556456 C, - 0.522498,4.009417, - 0.317641 Ir, - 1.046706, - 0.437648, - 0.159874 B, - 0.816852, - 2.311393,0.578156 O, - 0.520008, - 3.444243, - 0.181691 C, - 0.45638, - 4.5694,0.68057 C, - 0.282186, - 3.965133,2.070251 O, - 0.775033, - 2.638449,1.936556 C,1.066418, - 0.401184, - 0.831356 C,2.03659, - 1.136161, - 0.132835 C,3.402468, - 0.937034, - 0.310461 C,3.861567,0.006357, - 1.236651 C,2.91261,0.727086, - 1.96917 C,1.551416,0.520179, - 1.770449 B,6.377424, - 0.333797, - 0.867578 O,7.637059,0.0 95405, - 1.222753 C,8.562854, - 0.775573, - 0.584019 C,7.740604, - 1.495126,0.490703 O,6.386633, - 1.33161,0.077933 B, - 2.993614, - 0.301362,0.681379 O, - 3.392144, - 0.827887,1.899941 C, - 4.723629, - 0.397946,2.167022 C, - 5.235197,0.085506,0.815635 O, - 4.051562,0.393728,0.0893 48 B, - 2.469722, - 1.268346, - 1.40081 O, - 2.771929, - 0.720268, - 2.648463 C, - 3.992666, - 1.298392, - 3.093897 C, - 4.096032, - 2.595474, - 2.300733 O, - 3.299277, - 2.357967, - 1.146938 H, - 0.294176, - 1.096534, - 1.456382 H, - 2.095809,1.410427, - 2.608463 H, - 0.062852,4.726326,0.35916 H, - 1.941088,3.79188, - 3.37872 C, - 0.858667,5.882917, - 1.970147 H,0.402269,4.047543,2.186599 C,1.271421,3.315168,4.656781 H,0.831265,0.604458,4.702658 H, - 0.108583, - 0.773944,2.83545 H, - 4.821577, - 0.612609, - 2.858384 H, - 3.962553, - 1.450 927, - 4.178929 H, - 5.122924, - 2.837769, - 2.001953 H, - 3.685829, - 3.4527, - 2.855432 H,1.725076, - 1.889045,0.595126 H, - 5.87966,0.969712,0.882029 H, - 5.783904, - 0.7063,0.28011 H, - 4.700927,0.410373,2.913277 H, - 5.307674, - 1.229445,2.578126 H,0.776958, - 3.929708,2.371674 H, - 0.842111, - 4.497176,2.848498 H,0.375169, - 5.221993,0.387877 H, - 1.390647, - 5.145732,0.598739 H,7.975743, - 2.562578,0.567046 H,7.868632, - 1.040047,1.482842 H,9.392837, - 0.193648, - 0.16731 H,8.970546, - 1.475558, - 1.327171 N,5.224113,0.240182, - 1.459265 H,4.119415, - 1.5 18031,0.265878 H,1.115833,4.379247,4.447605 H,0.821501,3.082539,5.629714 H,2.352382,3.147437,4.755525 345 H, - 0.286501,6.469853, - 1.243353 H, - 0.367232,5.970083, - 2.947412 H, - 1.851125,6.341918, - 2.070567 H,0.848947,1.100188, - 2.373482 H,5.406421,0.941084, - 2.168621 H,3.249893,1.455628, - 2.709542 TS6 PhN(Me)Beg_anti_meta_4,4´ - Me2 - bipyridine_Ir_(Beg)3_ ultrafine_grid E(RM06) = - 2019.56206022 Item Value Threshold Converged? Maximum Force 0.000010 0 .000450 YES RMS Force 0.000004 0.000300 YES Maximum Displacement 0.007165 0.001800 NO RMS Displacement 0.001371 0.001200 NO Zero - point correction = 0.629879 (Hartree/Particle) Thermal correction to Energy = 0.687155 Thermal correction to Enthalpy = 0.688274 Thermal correction to Gibbs Free Energy = 0.527023 Sum of electronic and zero - point Energies = - 2018.932181 Sum of electronic and thermal Energies = - 2018.874905 Sum of electronic and thermal Enthalpies = - 2018.873787 Sum of electronic and thermal Free Energies = - 2019.035037 E (Thermal) CV S KCal/Mol Cal/Mol - Kelvin Cal/Mol - Kelvin Total 431.1 96 181.762 286.524 C,0.083109,3.447338,1.843978 C, - 0.16724,2.374169,0.989868 N, - 0.889004,1.312027,1.403478 C, - 1.36416,1.297137,2.656259 C, - 1.14282,2.330659,3.550271 C, - 0.399937,3.441937,3.148918 C,0.31234,2.346697, - 0.409736 N, - 0 .11651,1.318878, - 1.164194 C,0.252202,1.259572, - 2.448389 C,1.087098,2.1991, - 3.032262 C,1.574554,3.255611, - 2.261068 C,1.159735,3.323484, - 0.933392 Ir, - 1.166829, - 0.393751, - 0.03171 B, - 2.053463, - 1.785845,1.147142 O, - 1.939091, - 3.167215,0.984386 C, - 2.710718, - 3.811768,1.985953 C, - 2.926372, - 2.732795,3.042101 O, - 2.738206, - 1.513543,2.335628 C,0.851035, - 1.054823,0.622795 C,1.032318, - 1.586725,1.905347 C,2.314264, - 1.708171,2.439674 C,3.437019, - 1.329041,1.715455 C,3.289737, - 0.832829,0.412683 C,1.995169, - 0.713849, - 0.11055 B,5.727548, - 0.947092, - 0.200425 O,6.777898, - 0.474837, - 0.959839 C,7.895343, - 1.31302, - 0.695249 C,7.518379, - 2.064967,0.584662 O,6.102255, - 1.948822,0.665867 B, - 3.045637,0.459139, - 0.537831 O, - 4.144703,0.582089,0.29 6941 C, - 5.153254,1.322146, - 0.384684 C, - 4.724168,1.272471, - 1.845653 O, - 3.324822,1.024916, - 1.784944 B, - 2.040084, - 1.383583, - 1.617283 O, - 1.469817, - 1.380128, - 2.891118 346 C, - 2.450678, - 1.844155, - 3.810918 C, - 3.442636, - 2.607828, - 2.940431 O, - 3.253056, - 2.064612, - 1.639996 H, - 0.23284, - 1.674598, - 0.443294 H, - 0.143551,0.410807, - 3.007054 H,1.519591,4.139726, - 0.310754 H,1.365291,2.102516, - 4.080442 C,2.528822,4.254909, - 2.832513 H,0.651581,4.307117,1.496685 C, - 0.135364,4.575501,4.087041 H, - 1.552531,2 .270938,4.557102 H, - 1.944117,0.41469,2.925537 H, - 2.922263, - 0.978187, - 4.301074 H, - 1.978585, - 2.465364, - 4.580818 H, - 4.484604, - 2.469559, - 3.253259 H, - 3.228457, - 3.686687, - 2.918045 H,0.171403, - 1.887984,2.50557 H,4.427998, - 1.422183,2.150441 H, - 4.921092,2.202078, - 2 .392017 H, - 5.207871,0.441493, - 2.384737 H, - 5.174139,2.350895,0.00514 H, - 6.133882,0.866322, - 0.205897 H, - 2.183671, - 2.799487,3.853191 H, - 3.926739, - 2.756808,3.490258 H, - 2.173938, - 4.688057,2.36917 H, - 3.661749, - 4.154284,1.549984 H,7.80048, - 3.123532,0.559219 H,7.9 67277, - 1.60899,1.478426 H,8.79859, - 0.702421, - 0.582816 H,8.04274, - 1.994436, - 1.545161 N,4.409879, - 0.42919, - 0.349686 H,2.443563, - 2.096386,3.450548 H,0.355639,5.414538,3.582134 H, - 1.067519,4.940011,4.536674 H,0.511846,4.251633,4.91284 H,2.591579,5.157384, - 2.214454 H,3.53842,3.824967, - 2.897273 H,2.23897,4.546733, - 3.849066 H,1.868543, - 0.344239, - 1.126991 C,4.170039,0.508089, - 1.438603 H,3.672902,0.035645, - 2.299342 H,3.533928,1.337963, - 1.096685 H,5.124101,0.915614 , - 1.781992 TS para - Me2 - bipyridine_Ir_(Beg)3_ ultrafine_grid E(RM06) = - 2019.55943016 Item Value Threshold Converged? Maximum Force 0.000008 0.000450 YES RMS Force 0.000002 0.000300 YES Maximum Displacement 0.018462 0.001800 NO RMS Displacement 0.002295 0.001200 NO Zero - point correction = 0.629662 (Hartree/Particle) Thermal correction to Energy = 0.687168 Thermal correction to Enthalpy = 0.688286 Thermal correction to Gibbs Free Energy = 0.524533 Sum of electronic and zero - point Energies = - 2018.929768 Sum of electronic and thermal Energies = - 2018.872262 Sum of electronic and thermal Enthalpies = - 2018.871144 Sum of electronic and thermal Free Energies = - 2019.034898 E (Thermal) CV S KCal/Mol Cal/Mol - Kelvin Cal/Mol - Kelvin Total 431.204 181.874 290.973 C,0.3980 59,2.794752,2.49018 C, - 0.172871,2.041472,1.464882 N, - 0.368362,0.714242,1.607 C, - 0.011192,0.123033,2.754957 C,0.560511,0.818973,3.806122 C,0.781491,2.191479,3.684001 C, - 0.61839,2.644301,0.189003 N, - 1.204777,1.811262, - 0.689708 C, - 1.66167,2.305533, - 1.845596 C, - 1.537943,3.64177, - 2.189473 C, - 0.917164,4.523592, - 1.30293 C, - 0.45922,4.000363, - 0.097338 Ir, - 1.168272, - 0.426827, - 0.155646 B, - 1.038078, - 2.341332,0.499981 O, - 0.860717, - 3.460369, - 0.314867 347 C, - 0.829345, - 4.621262,0.500227 C, - 0.5457 95, - 4.087289,1.900799 O, - 0.949036, - 2.725462,1.841853 C,0.934025, - 0.485646, - 0.858669 C,1.87218, - 1.317018, - 0.226038 C,3.240198, - 1.197491, - 0.438847 C,3.749203, - 0.233602, - 1.321902 C,2.826044,0.579501, - 1.990608 C,1.457665,0.445754, - 1.762716 B,6.165177, - 0.520656 , - 0.667918 O,7.497403, - 0.322784, - 0.967222 C,8.254766, - 0.968297,0.048289 C,7.253706, - 1.203005,1.182195 O,5.977766, - 1.123259,0.555877 B, - 3.101107, - 0.206689,0.697911 O, - 3.548238, - 0.784787,1.87543 C, - 4.846881, - 0.27692,2.166409 C, - 5.30853,0.33657,0.85014 O, - 4.0 99021,0.604293,0.151141 B, - 2.642039, - 1.118552, - 1.422793 O, - 2.904051, - 0.507469, - 2.650467 C, - 4.158991, - 0.986959, - 3.117049 C, - 4.348258, - 2.302556, - 2.372419 O, - 3.544598, - 2.157101, - 1.207849 H, - 0.466822, - 1.069091, - 1.488508 H, - 2.137977,1.580419, - 2.505887 H,0.026838,4.665393,0.613093 H, - 1.920089,3.994345, - 3.146076 C, - 0.768177,5.974455, - 1.633542 H,0.548245,3.86524,2.370233 C,1.406892,2.974555,4.793492 H,0.83213,0.291801,4.719095 H, - 0.206676, - 0.947745,2.809008 H, - 4.942244, - 0.257 316, - 2.856785 H, - 4.136347, - 1.100854, - 4.206984 H, - 5.389789, - 2.491068, - 2.086281 H, - 3.988196, - 3.162821, - 2.956473 H,1.531595, - 2.0909,0.466078 H, - 5.885538,1.260037,0.976096 H, - 5.910219, - 0.372262,0.258323 H, - 4.771786,0.473072,2.968063 H, - 5.49462, - 1.089442,2.5152 95 H,0.526532, - 4.136858,2.148918 H, - 1.10371, - 4.610632,2.686344 H, - 0.058716, - 5.313699,0.140028 H, - 1.802596, - 5.132662,0.445899 H,7.369107, - 2.181657,1.661406 H,7.319713, - 0.427456,1.95836 H,9.09581, - 0.331358,0.344913 H,8.658026, - 1.9112, - 0.347907 N,5.135617, - 0.112679, - 1.562964 H,3.924468, - 1.864748,0.078421 H,1.405011,4.04972,4.584 H,0.877921,2.80607,5.740002 H,2.447685,2.661434,4.949664 H, - 0.114775,6.488787, - 0.920293 H, - 0.355065,6.109126, - 2.640939 H, - 1.744537,6.477118, - 1.618925 H,0.78125,1.098673, - 2.319357 H,3.165283,1.331879, - 2.699691 C,5.536376,0.581201, - 2.77875 H,5.353598,1.664407, - 2.718716 H,6.604602,0.428028, - 2.947189 H,4.985541,0.1902, - 3.644769 TS7 - dimethylbipyridine_Ir_(Beg)3_ ultrafine_ grid E(RM06) = - 2019.56349599 Item Value Threshold Converged? Maximum Force 0.000006 0.000450 YES RMS Force 0.000002 0.000300 YES Maximum Displacement 0.006201 0.001800 NO RMS Displacement 0.001434 0.001200 NO Zero - point correction = 0.629878 (Hartree/Particle) Thermal correction to Energy = 0.686928 Thermal correction to Enthalpy = 0.688046 Thermal correction to Gibbs Free Energy = 0.528049 Sum of electron ic and zero - point Energies = - 2018.933618 Sum of electronic and thermal Energies = - 2018.876568 Sum of electronic and thermal Enthalpies = - 2018.875450 Sum of electronic and thermal Free Energies = - 2019.035447 E (Thermal) CV S KCal/Mol Cal/Mol - Kelvin Cal/Mol - Kelvin Total 431.054 181.648 284.297 348 C, - 4.150198,0.57305, - 0.407393 C, - 2.760405,0.482579, - 0.479227 N, - 2.119479, - 0.648631, - 0.120977 C , - 2.842248, - 1.707573,0.26776 C, - 4.224398, - 1.683324,0.342814 C, - 4.91045, - 0.513317,0.014957 C, - 1.917892,1.590013, - 0.981658 N, - 0.586652,1.420122, - 0.885222 C,0.218317,2.367665, - 1.378119 C, - 0.258594,3.52071, - 1.980065 C, - 1.635458,3.723276, - 2.085305 C, - 2.464907,2.730058, - 1.574129 Ir,0.133008, - 0.608657, - 0.011447 B,0.541852, - 2.471387,0.68014 O,1.645146, - 2.820317,1.458761 C,1.589553, - 4.210365,1.737118 C,0.137819, - 4.587428,1.461829 O, - 0.327269, - 3.563951,0.591471 C, - 0.144345, 0.097388,2.095667 C, - 0.760273, - 0.827421,2.957548 C, - 1.299643, - 0.467831,4.188936 C, - 1.200975,0.8504,4.622332 C, - 0.544751,1.775262,3.822559 C, - 0.007122,1.414108,2.580282 B,2.052723,2.313499,1.524635 O,2.862463,1.284172,1.950534 C,4.170279,1.530151,1.459911 C ,4.056939,2.812797,0.614284 O,2.724538,3.268992,0.791354 B,0.138266, - 1.328439, - 2.006087 O, - 0.339381, - 2.560856, - 2.425019 C, - 0.303131, - 2.60242, - 3.84822 C,0.629446, - 1.459047, - 4.227951 O,0.582887, - 0.588227, - 3.104043 B,2.040767, - 0.652623, - 0.789974 O,2.765318,0.506696, - 1.082124 C,3.834984,0.14129, - 1.944119 C,4.036313, - 1.340852, - 1.663672 O,2.764733, - 1.772403, - 1.198939 H,1.185101, - 0.205136,1.181487 H,1.286203,2.178566, - 1.277027 H, - 3.542731,2.847235, - 1.662268 H,0.442315,4. 259061, - 2.366796 C, - 2.190488,4.959246, - 2.718559 H, - 4.656166,1.498185, - 0.674392 C, - 6.399688, - 0.433833,0.120622 H, - 4.764382, - 2.573332,0.661388 H, - 2.267132, - 2.599987,0.513291 H,3.533638,0.32064, - 2.988055 H,4.722055,0.75106, - 1.726372 H,4.326497, - 1.915355, - 2.55 1268 H,4.789274, - 1.512089, - 0.878282 H, - 0.855082, - 1.868859,2.643533 H, - 1.608334,1.152255,5.586331 H, - 0.419069,2.800359,4.172249 H,0.320849, - 0.924328, - 5.133668 H,1.666015, - 1.807316, - 4.365503 H, - 1.320195, - 2.453792, - 4.24101 H,0.05543, - 3.582589, - 4.183055 H, - 0.4683, - 4.58256,2.382125 H,0.026015, - 5.567392,0.983081 H,1.894575, - 4.39928,2.773514 H,2.284756, - 4.744389,1.071148 H,4.756409,3.594159,0.938736 H,4.227578,2.61687, - 0.45284 H,4.501621,0.668696,0.86533 H,4.85613,1.648127,2.309 925 N,0.676789,2.418659,1.836778 H, - 1.792934, - 1.218004,4.806569 H, - 6.794813,0.46429, - 0.366615 H, - 6.87495, - 1.312602, - 0.332554 H, - 6.711075, - 0.409311,1.173534 H, - 3.273998,4.889228, - 2.86516 H, - 1.991537,5.839037, - 2.091994 H, - 1.721314,5.148751, - 3.692099 C, - 0.056 159,3.644512,1.577818 H, - 0.212652,4.245782,2.486739 H,0.497889,4.259743,0.861643 H, - 1.044579,3.417145,1.150034 TS8 - dimethylbipyridine_Ir_(Beg)3_ ultrafine_grid E(RM06) = - 2019.56240728 Item Value Threshold Converged? Maximum Force 0.000004 0.000450 YES RMS Force 0.000002 0.000300 YES Maximum Displacement 0.003059 0.001800 NO RMS Displacement 0.000449 0.001200 YES Zero - point correction = 0.629836 (Hartree/Particle) 349 Thermal correction to Energy = 0.686751 Thermal correction to Enthalpy = 0.687869 Thermal correction to Gibbs Free Energy = 0.531128 Sum of electronic and zero - point Energies = - 201 8.932572 Sum of electronic and thermal Energies = - 2018.875656 Sum of electronic and thermal Enthalpies = - 2018.874538 Sum of electronic and thermal Free Energies = - 2019.031279 E (Thermal) CV S KCal/Mol Cal/Mol - Kelvin Cal/Mol - Kelvin Total 430.943 181.769 278.512 C, - 2.299356,1.489658,2.530213 C, - 1.429737,0.719902,1.759689 N, - 0.185761,1.150664,1.469616 C,0.229663,2.31632,1.984083 C, - 0.576445,3.110797,2.780948 C, - 1.88542,2.709801,3.055059 C, - 1.810669, - 0.606348,1.235625 N, - 1.039689, - 1.105672,0.25173 C, - 1.334209, - 2.313329, - 0.237167 C, - 2.399206, - 3.074484,0.223408 C, - 3.197178, - 2.585516,1.256016 C, - 2.880805, - 1 .325867,1.762923 Ir,0.942375,0.054946, - 0.147649 B,2.69005,1.080397, - 0.18001 O,3.546534,1.203475, - 1.273126 C,4.671108,1.980177, - 0.889899 C,4.219174,2.691517,0.382552 O,3.137141,1.902123,0.858566 C,0.022471,1.575977, - 1.508543 C,0.564861,2.872446, - 1.443863 C, - 0.075334,3.988596, - 1.974459 C, - 1.289728,3.837443, - 2.634687 C, - 1.827068,2.564298, - 2.75994 C, - 1.190631,1.443114, - 2.213425 B, - 3.076244, - 0.104558, - 1.85738 O, - 3.687261,0.699168, - 0.913605 C, - 4.921161,0.098373, - 0.562732 C, - 4.99169, - 1.209185, - 1.377357 O, - 3.818653, - 1.226222, - 2.171117 B,1.748585, - 1.219011,1.348917 O,2.659471, - 0.843951,2.322673 C,2.855405, - 1.942289,3.208218 C,2.298825, - 3.137656,2.44443 O,1.39374, - 2.559843,1.511275 B,2.023328, - 1.504181, - 0.966658 O,1.430631, - 2. 469698, - 1.780688 C,2.324063, - 3.57303, - 1.872001 C,3.681388, - 2.977595, - 1.51719 O,3.361749, - 1.821954, - 0.752763 H,1.015856,0.271944, - 1.770067 H, - 0.671742, - 2.67499, - 1.02302 H, - 3.465337, - 0.922248,2.588578 H, - 2.601267, - 4.047846, - 0.220698 C, - 4.339943, - 3.372225,1.8 1672 H, - 3.31864,1.150062,2.706208 C, - 2.794735,3.556866,3.886112 H, - 0.189903,4.049485,3.174257 H,1.252848,2.596514,1.736927 H,2.015839, - 4.343905, - 1.14777 H,2.285768, - 4.004634, - 2.878725 H,4.307759, - 3.654862, - 0.924227 H,4.247305, - 2.67616, - 2.411167 H,1.515167, 3.031507, - 0.932479 H, - 1.803768,4.696283, - 3.063915 H, - 2.76455,2.410181, - 3.295525 H,1.775049, - 3.859244,3.081906 H,3.087459, - 3.671135,1.889322 H,2.305782, - 1.756542,4.14308 H,3.920215, - 2.040655,3.448689 H,3.858956,3.712223,0.175947 H,5.003056,2.753892,1.14649 H,4.941957,2.672417, - 1.696327 H,5.52811,1.314461, - 0.70602 H, - 5.004782, - 2.099892, - 0.730904 H, - 5.875397, - 1.250958, - 2.027453 H, - 5.744906,0.784907, - 0.79981 H, - 4.938175, - 0.089859,0.522467 N, - 1.824593,0.183381, - 2.432233 H,0.38129,4.97 3085, - 1.874726 H, - 3.814145,3.15652,3.909722 H, - 2.430285,3.618192,4.920183 H, - 2.835781,4.583541,3.501172 H, - 5.217968, - 2.733775,1.982747 H, - 4.629225, - 4.192502,1.149661 H, - 4.073464, - 3.810515,2.787977 C, - 1.180577, - 0.71155, - 3.377342 H, - 0.217898, - 1.084353, - 2.997 402 350 H, - 1.829138, - 1.574883, - 3.561789 H, - 1.002456, - 0.200959, - 4.336533 351 REFERENCES 352 REFERENCES (1) Travis, A. S. In The Chemistry of Anilines ; Rappoport, Z., Ed.; John Wiley & Sons, Ltd: Chichester, UK, 2007; pp 715 782. (2) Berliner, E. Progress in Physical Organic Chemistry 1964 . (3) Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry ; OUP Oxford, 2012 . (4) Holleman, A. F.; Hartogs, J. C.; Van der Linden, T. Ber. Dtsch. Chem. Ges. 1911 , 44 (1), 704. (5) Shen, H.; Vollhardt, K. P. C. Synlett 2012 , 2012 (02), 208. (6) Takagishi, S.; Katsoulos, G.; S chlosser, M. Synlett 1992 , 1992 (04), 360. (7) Whisler, M. C.; MacNeil, S.; Snieckus, V.; Beak, P. Angew. Chem. Int. Ed Engl. 2004 , 43 (17), 2206. (8) Hurst, T. E.; Macklin, T. K. ; Becker, M.; Hartmann, E.; Kügel, W.; Parisienne - La Salle, J. - C.; Batsanov, A. S.; Marder, T. B.; Snieckus, V. Chem. Eur. J. 2010 , 16 (27), 8155. (9) Tischler, M. O.; Tóth, M. B.; Novák, Z. Chem. Rec. 2017 , 17 (2), 184. (10) Fang, H.; Dou, Y.; G e, J.; Chhabra, M.; Sun, H.; Zhang, P.; Zheng, Y.; Zhu, Q. J. Org. Chem. 2017 , 82 (20), 11212. (11) Allu, S.; Ravi, M.; Kumara Swamy , K. C. Eur. J. Org. Chem. 2016 , 2016 (34), 5697. (12) Preshlock, S. M.; Plattner, D. L.; Maligres, P. E.; Krska, S. W.; Maleczka, R. E., Jr.; Smith, M. R., III Angew. Chem. Int. Ed. 2013 , 52 (49), 12915. (13) Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.; Murphy, J. M.; Hartwig, J. F. Chem. Rev. 2010 , 110 (2), 890. (14) Hartwig, J. F. Acc. Chem. Res. 2012 , 45 (6), 864. (15) Lee, C. - I.; Zhou, J.; Ozerov, O. V. J. Am. Chem. Soc. 2013 , 135 (9), 3560. (16) Del Grosso, A.; Singleton, P. J.; Muryn, C. A.; Ingl eson, M. J. Angew. Chem. Int. Ed. Engl. 2011 , 50 (9), 2102. 353 (17) Légaré, M. - A.; Courtemanche, M. - A.; Rochette, É.; Fontaine, F. - G. Science 2015 , 349 (6247), 513. (18) Mazzacano, T. J.; Mankad, N. P. J. Am. Chem. Soc. 2013 , 135 (46), 17258. (19) Obligacion, J. V.; Semproni, S. P.; Chirik, P. J. J. Am. Chem. Soc. 2014 , 136 (11), 4133. (20) Furukawa, T.; Tobisu, M.; Chatani, N. Chem. Commun. 2015 , 51 (30), 6508. (21) Cho, J. - Y.; Iverson, C. N.; Smith, M. R., III J. Am. Chem. Soc. 2000 , 122 (51), 12868. (22) Cho, J. - Y.; Tse, M. K.; Holmes, D.; Maleczka, R. E., Jr.; Smith, M. R., III Scie nce 2002 , 295 (5553), 305. (23) Ishiyama, T.; Takagi, J.; Ishida, K.; Miyaura, N.; Anastasi, N. R.; Hart wig, J. F. J. Am. Chem. Soc. 2002 , 124 (3), 390. (24) Jones, W. D.; Kosar, W. P. J. Am. Chem. Soc. 1986 , 108 (18), 5640. (25) Murai, S.; Kakiuchi, F.; Sekine, S.; Tanaka, Y.; Kamatani, A.; Sonoda, M.; Chatani, N. Nature 1993 , 366 , 529. (26) Kawamorita, S.; Ohmiya, H.; Hara, K.; Fukuoka, A.; Sawamura, M. J. Am. Chem. Soc. 2009 , 131 (14), 5058. (27) Ishiyama, T.; Isou, H.; Kikuchi, T.; Miyaura, N. Chem. Commun. 2010 , 46 (1), 159. (28) Ros, A.; Fernández, R.; Lassaletta, J. M. Chem. Soc. Rev. 2014 , 43 (10), 3229. (29) Taube, H.; Posey, F. A. J. Am. Chem. Soc. 1953 , 75 (6), 1463. (30) Boebel, T. A.; Hartwig, J. F. J. Am. Chem. Soc. 2008 , 130 (24), 7534. (31) Davis, H. J.; Phipps, R. J. Chem. Sci. 2017 , 8 (2), 864. (32) Haldar, C.; Hoque, E.; Bisht, R.; Chattopadhyay, B. Tetrahedron Lett. 2018 , 59 (14), 1269. (33) Roosen, P. C.; Kallepalli, V. A.; Chattopadhyay, B.; Singleton, D. A.; Maleczka, R. E., Jr.; Smith, M. R., III J. Am. Chem. Soc. 2012 , 134 (28), 11350. (34) Bisht, R.; Chattopadhyay, B. J. Am. Chem. Soc. 2016 , 138 (1), 84. (35) Li, H. L.; Kuninobu, Y.; Kanai , M. Angew. Chem. Int. Ed Engl. 2017 , 56 (6), 1495. 354 (36) Li, H. L.; Kanai, M.; Kuninobu, Y. Org. Lett. 2017 , 19 (21), 5944. (37) Davis, H. J.; Genov, G. R.; Phipps, R. J. Angew. Chem. Int. Ed. 20 17 , 56 (43), 13351. (38) Chattopadhyay, B.; Dannatt, J. E.; Andujar - De Sanctis, I. L.; Gore, K. A.; Maleczka, R. E., Jr.; Singleton, D. A.; Smith, M. R., III J. Am. Chem. So c. 2017 , 139 (23), 7864. (39) Yamamoto, T.; Ishibashi, A.; Suginome, M. Org. Lett. 0 (0), null. (40) Davis, H. J.; Mihai, M. T.; Phipps, R. J. J. Am. Chem. Soc. 2016 , 138 (39), 12759. (41) Kuninobu, Y.; Ida, H.; Nishi, M.; Kanai, M. Nat. Chem. 2015 , 7 (9), 712. (42) The l igand for the Kanai - Kuninobu o rtho CHB of a nil ine i s p repared via a Suzuki c ross - c oupling of 5 - b romo - 2,2´ - b ipyridine ($14,000/mol) with 1 - Bpin - 4 - (trifluoromethyl)benzene ( $ 870/mol) in 73% y ield. B 2 pin 2 ($50/mol) i s the b orylating a gent. Prices are the lowes t per mole values of all commercial sources listed by SciFinder Scholar on 05/01/19. (43) The y ields for d eprotection a re giv en in an e ndnote in r ef. 35. The p roducts a re n ot s pecified and e xperimental d etails w ere n ot r eported. We p resume t hat the d eprotected c ompounds a re N - a cylated since a ll ArN(Ac)(CH 2 SMe) r eactants w ere p rep ared from ac ylated a nilines. (44) The Ir l igand u sed in t his w ork i s d tbpy ( $ 2,300/mol). B 2 eg 2 i s p repared from B 2 (OH) 4 ( $ 51/mol) and e thylene g lycol ($ 0.22/mol) in 91% y ield. (45) Robbins, D. W.; Hartwig, J. F. Org. Lett. 2012 , 14 (16), 4266. (46) Bartlett, R. K.; Turner, H. S.; Warne, R. J.; Young, M. A.; Lawrenson, I. J. J. Chem. Soc. A 1966 , 0 (0), 479. (47) Thanthiriwatte, K. S.; Hohenstein, E. G.; Burns, L. A.; Sherrill, C. D. J. Chem. Theory Comput. 2011 , 7 (1), 88. (48) Parthasarathi, R.; Subramanian, V. In Hydrogen Bonding New Insights ; Grabowski, S. J., Ed.; Springer Netherlands: Dordrecht, 2006 ; pp 1 50. (49) Chattopadhyay, B.; Dannatt , J. E.; Andujar - De Sanctis, I. L.; Gore, K. A.; Maleczka, R. E., Jr.; Singleton, D. A.; Smith, M. R., III J. Am. Chem. Soc. 2017 , 139, 7864. (50) Lam, H.; Tsoung, J.; Lautens, M. J. Org. Chem., 2017 , 82 , 6089. 355 (51) Romero, E. A.; Peltier, J. L.; Jazzar, R.; Bertrand, G. Chem. Commun. 2016 , 52 , 10563. Gaussian 09, Revision A.02, Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Peter sson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, Jr., J. A.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Milla m, N. J.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador , P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian, Inc., Wallingford CT, 2009. (52) Gaussian 09, Revision B.01, Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G . E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Ha segawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, Jr., J. A.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, N. J.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochte rski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian, Inc., Wallingford CT, 2009. (53) Gaussian 09, Revision D.01, Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Blo ino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brother s, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, N. J.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Go mperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö.; Foresman, J. B.; Orti z, J. V.; Cioslowski, J.; Fox, D. J. Gaussian, Inc., Wallingford CT, 2009. 356 Chapter 5: Exploration of Hydrazone Derived Ir C H Borylation Catalysts with Selectivity for C H bonds in Similar Steric Environments 5.1: Introduction The selectivity in the irid ium C H borylation (CHB) literature is often dictated by the steric parameters of the substrate. 1 This selectivity can be rationalized by a close examination of the mechanism. It has been shown that C H activation is the turnover limiting step. Indeed a high primary kinetic isotope effect of 5.0 is observed in the CHB of benzene vs benzene - d 6 . 2 As such the selectivity in the final product is completely dictated by the rate of C H activation between sites. These rates are determined by the transition state barrier of the C H activating step. Conside r for example the activation of H a and H b shown in scheme 28 . Each of these transition states lead to a different product; however, the barrier for path B is much higher due to significant steric clash between the substrate and catalyst. The difference in these transition states remains high enough that only one product is observed as long as the R group is sufficiently large. Scheme 28 : Mechanistic reasons for steric selectivity This steric sel ectivity can of course be overruled by careful catalyst design and properly paired directing elements. 3 For example, it has been shown that hydrogen 357 bonding, 4 7 Lewis acid/base interactions, 8,9 ion pairing, 10,11 and electrostatic interactions 12 can direct C H borylation to ortho, meta, and even para positions. 13 However, despite this superb level of control in many classes of substrates, there are still significant challenges in selective borylation. For example 1,3 - disubstituted substrates without an inherent directing group that also contain at least one small substituent are difficult to selectively borylate. This is because the difference in energy between the two transition states from path A and path B in scheme 28 is no longer large enough to provide only one product. One such small substituent is the fluo ro group. Given the dramatic effects fluorine can instill in medicinal products 14,15 and the growth of fluorinated pharmaceuticals on the market, 16 we recognize the importance of selective functionalization of fluorinated arenes. Recently, a variety of ligand frameworks were examined to locate 1) a method to borylate ortho or meta to fluorine and 2) to gain an empirical understanding of what fa ctors effect these selectivities. 17 5.2: Prior studies in borylations of fluoro - containing arenes Cognizant that regiochemical outcome of borylations is significantly impacted by both the electronic an d steric nature of the ligand, we sought to build a predictive model around these parameters. As a model substrate, 1,3 - chlorofluorobenzene was selected since the C H bonds ortho and meta to fluorine are sterically accessible. To understand the electronic effects on selectivity, the electronic nature of the bipyridine framework was - position. Interestingly, an electronic trend was revealed (Table 6 ). Electron donating groups provide a catalyst with a slight pref erence for meta to fluorine borylation 1a and electron withdrawing groups inverted this selectivity favoring 1b . 358 Table 6 : Ligand Electronic effect on selectivity Significant computational work has been conducted to elucidate selectivity trends. For example, the Houk group correlated selectivity with Ir C bond dissociation energy, 18 the stronger the intermediate Ir - C bond t he lower the transition state, and our group in collaboration with Professor Singleton has shown the higher negative charge character on the arene in the transition state the lower the barrier; 19 howev er, these studies do not provide obvious insights into the underlying electronic trend in Table 6 . One hypothesis for this trend stems from the interaction between the fluoro group and the bipyridine ligand. The fluoro group which carries significant parti al negative character may be repelled by or attracted by the ligand in an electrostatic interaction. If the ligand has a donating group, this would somewhat repel the partially negative fluoro group thus raising the transition state for ortho to fluoro C H activation. Evidence for electrostatic interactions controlling regioselectivities in iridium catalyzed CHB has been previously demonstrated. 12 We next considered the steric parameters for this class of substrates. Though fluorine is similar in size to hydrogen, it is still slightly larger; thus a more sterically 359 demanding ligand around the C H activating site should favor a steric product 1a as opposed to an electronic product 1b . Scheme 29 : A pallet of ligands organized by basicity and steric hindrance With this theory and the electronic trend from table 6 , various ligands were selected and ranked in terms of steric hinderan ce and basicity and are presented in scheme 2 9 . Ligands dpm and dmadpm both have a methylene linker between the donating pyridines, and will form puckered 6 - membered metalacycles when bound to the iridium. These puckered metalocycles are predicted to be th e most sterically demanding ligands. Conversely, the least sterically demanding ligand, bozo, will form a 5 - membered metalocycle and is a smaller heterocycle compared to pyridine. It is expected that a benzyl group on the bnbozo ligand points toward the C H activation site thus increasing the steric interactions significantly. 360 In terms of basicity, the most basic ligand has dimethylamino donating groups, dmadpm. As a reference 2 - methyloxazolium, 20 2,4 - dimethylpyridinium, 21 and N,N - dimethyl - 4 - aminopyridinium 22 have pK a s of 5.5, 6.7, and 9.7 respectively. Although not a direct comparison, this provides a general indication of basicity. Notice all suggested ligands follow the trend of increased basicity and sterics except bnbozo which has a high steric demand but low basi city. Because of this, predicting its selectivity apriori is challenging at best. To see if the predicted trend is followed and where bnbozo falls the borylation of 1 with this ligand pallet was carried out (Table 7 ). Table 7 : Sel ectivity for the borylation of 1,3 - chlorofluorobenzene With the ligands in scheme 29 , the substrate scope of was expanded to include ten other substrates following the same motif of having two open borylation sites. 17 In every case, higher selectivity than dtbpy, the most common CHB ligand, was observed. Unfortunately, despite the improved selectivity the overall reactivity was poor in comparison to dtbpy. Thus, a ligan d that produces dtbpy - like activity, but retains selectivity would be highly desirable scheme 3 0 A. A serendipitous discovery potentially provided one such ligand. 361 Scheme 30 : A) Prior work and limitations B) Synthetic route leading to the discovery of dmadphz In the synthetic route to dmadpm, a ketone intermediate is reduced to the methylene bridge via the Wolf - Kishner, scheme 3 0 B. During this reduction, the hydrazone intermediate was found to b e persistent. This is likely due to the internal hydrogen bonding between the pyridyl ring and the hydrazone amino group. Table 8 : Ligand comparison between prior work and dmadphz 362 Given this pers istence it was isolated and used as a ligand in a test reaction for the borylation of 1,3 - dicyanobenzene table 8 . Amazingly, this reaction was complete within 1 hour with a 16:1 ratio! This d i m ethyl a mino d i p yridyl h ydra z one (dmadphz) seemed to produce the d esired activity and selectivity. The exploration of this ligand framework and the catalysts provided is the topic of the remainder of this chapter. 5 .3: Activity of dmadphz generated catalyst The first aim of this project is to explore the activity of the dmadphz generated catalyst in comparison to other highly active ligands namely dtbpy and tmphen. Electron rich substrates are less active toward iridium CHB and generally require elevated temperatures. Thus three electron rich substrates, 1,3 - dimethoxyben zene, 1,3 - diisopropylbenzene, and 3 - dimethylaminotoluene, were chosen to compare ligand activity see table 9 . Table 9 : Borylation of electron rich aromatics to gauge activity. 363 a Temperature: 80 o C, time: 16 h Each of these substrates has only one sterically available borylation site so that only reactivity is probed. It should be noted that the reaction conditions were purposely set to facilitate incomplete conversion. In other words, these reactions can likely be pushed to completion by increasing reaction time and/or temperature; however, a better understanding of catalyst activity could be derived at low conversion. Finally, pinacolborane, HBpi n, is a less active boron source in comparison to bis(pinacolato)diboron, B 2 pin 2 1 . Despite the lower reactivity, borylations with HBpin are more atom efficient and economical 18 ; thus, it is the preferred boron source for industrial applications. Excitingly , in all cases dmadphz either matches or outperforms dtbpy. Tmphen, on the other hand, is more reactive for these electron rich substrates. For 1,3 - dimethoxybenzene dmadphz is comparable to tmphen. Indeed this initial screen demonstrates that dmadphz is at minimum as active as dtbpy with pinacolborane as a boron source. 364 5 .4: Selectivity of dmadphz generated catalyst: A well plate study The second goal of this project is to explore the selectivity of dmadphz generated catalysts in comparison to other common borylation ligands in the literature. An initial well - plate screen was conducted with three substrates, five ligands and two solvents. The ligands in the study were dmadphz ( L1 L2 , L3 ) 13,15 ligand ( L4 ), and dtbpy ( L5 ). L igands L2 , L3 , and L4 have never been tested against the substrate class shown in table 10 . In fact, Lassaletta claims that his ligand produces a catalyst that is inactive for C H borylation unless a directing effect facilitates the reaction 13 . Given these factors, we wanted to know if dmadphz was able to outperform both dtbpy and these other ligands reported in the literature. The solvents, THF and cyclohexane, were chosen to probe the polarity effects on reactivity and selectivity. It should be noted that due to poor solubility 1,3 - dicyanobenzene was not tested in cyclohexane. These experiments were conducted in a well plate at a 0.1 mmol scale and each reaction was duplicated within the same well - plate. The averaged results are shown in table 10 . As a ge neral trend, dmadpz and dtbpy are the most active ligands; furthermore, dmadpz generates the most selective catalyst in a polar solvent. Ligands L2 , L3 , L4 , and L5 benefit in terms of reactivity by switching to a less polar solvent however in most cases this erodes selectivity. Ligand L3 is more reactive than L2 , which correlates to the theory that a more electron rich catalyst is more active. It also matches with li terature 15 , but despite the increased activity, L3 still was not as active or as selective as dmadphz in THF. 365 Table 10 : Well plate analysis of common borylation ligands a L4 , was the second most selective in THF, but the least reactive. The reactivity improved significantly in cyclohexane at the cost of selectivity. Finally, it should be noted that in the well plate the overall reactivity and selectivity observed is lower than reac tions at a larger scale. For example, compare 1,3 - dicyanobenzene with dmadphz in table 9 with table 10 . This difference could be due to the small scale or poor stirring, but will effect all reactions equally so the trends should hold. Interestingly, dmadph z has the ability to selectively borylate a small, small motif such as 1,3 - difluorobenzene, table 11 . Consider the fact that in 1,3 - difluorobenzene all C H bonds are sterically available for activation; moreover, after the first borylation, every 366 isomer ha s the ability to diborylate. This makes 1,3 - difluorobenzene an extraordinarily challenging substrate to selectively borylate via iridium catalyzed C H activation. In the borylation of 1,3 - difluorobenzene, dmadphz is both the most reactive and selective in THF. The selectivity is dramatically decreased in cyclohexane. Excitingly, the ratio of borylation meta to fluorine versus all borylation ortho to fluorine is 4.2:1 with dmadphz, and this does not correct for the fact that there are three times as many C H bonds ortho to fluorine! Every other ligand considered has poor reactivity with the exception of dtbpy in which case the selectivity is poor, 1.4:1 meta:ortho to fluorine. Table 11 : Well plate analysis of 1,3 - difluorobenzene Ultimately this study shows that despite structural similarities, dmadphz is more active than the other hydrazone and imine derived ligands that are previously reported in the literature and has higher selectivity in every case. It also demonstrates the importance of a polar solvent since both activity and selectivity drop in cyclohexane. Finally, the dmadphz ligand generates a catalyst that can selectivity borylate even in a small, small motif like 1,3 - difluorobenzene where every C H bond is sterically available. 367 5 .5: Substrate scope Given that the data in the well plate may have been effected by the scale and stirring, the reactions with dmadphz were repeated at 1 mmol scale. In all cases the reaction s went to complete conversion with the exception of 3 - fluorotoluene. Overall, the trends in reactivity compared well for the reactions at both scales; however, the selectivities did not track as well. Table 12 : Scale up of well plate reactions a 1 equiv HBpin. b Solvent: cyclohexane. c ratio is meta product to all ortho products. d 4 fold excess of substrate For instance , dicyanobenzene borylation was more selective at the larger scale, but the chlo rofluorobenzene selectivity decreased. Note the selectivity for 1,3 - difluorobenzene is shown as 4:1 this is the meta borylated product to all other borylated isomers. Just for reference out of the four borylated products observed about 75% is meta - borylate d. For this substrate the selectivity tracked well and the reactivity increased. It should be noted that the data in entry 5 was collected after 2 hours and with more time the amount of borylated products increased. It is likely that if the reaction was al lowed to completely diborylate the ratio of the 2,5 - diborylated material would be high. Interestingly, 368 the ratio does not change if the reaction is run with a 4 - fold excess of substrate to boron source; however, the amount of diborylated materials did decr ease. Next, two heterocycle were tested and compared against dtbpy, table 13 . Pyridines help facilitate borylation para to the nitrogen. This seems to hold as in entry 1 the selectivity is 36:1! Table 13 : Substrate comparison between dmadphz and dtbpy a 1.5 mol % [Ir(Ome)cod]2, 3 mol % ligand. b 4 - fold excess of substrate. This is due to an electronic effect of the pyridine nitrogen. Evidence for this electronic effect is apparent wh en considering 1,3 - chlorofluorobenzene has a selectivity of 5:1. This demonstrates the strength of this pyridine electronic effect. In entry 2, this electronic effect is pitted against dmadphz in that borylation meta to fluorine is generally favored. As ex pected the selectivity is low, 1.7:1. Notice though the selectivity is reversed 369 for dtbpy, 1:1.6. Finally, a comparison of CHB ortho to fluorine or ortho to cyano is demonstrated by 1,4 - fluorocyanobenzene. Interestingly, both dmadphz and dtbpy have the sa me selectivity for borylation ortho to fluorine. 5 .6 : Effect of boron source In general, B 2 pin 2 is considered the more active boron source. It was originally postulated that this was because the B B bond strength is weaker than the B H bond strength in HB pin; however, high level calculations have shown that this is not the case. 23 The true driving force for the increased activity of B 2 pin 2 is likely the differences in the stoichiometric byproducts. If the reaction is conducted with B 2 pin 2 the byproduct is HBpin. Alternatively, if the reaction is conducted with HBpin the byproduct is H 2 . Since the BDE for HBpin is calculated to be 7 kcal/mol stronger than H 2 , the reaction that produces HBpin provides a larger thermodynamic driving force to the overall transformation. To test the difference in selectivity and activity with B 2 pin 2 the borylation of 1,3 - chlorofluorobenzene was conducted (Table 14 ). While the activity remains constant, the selecti vity is dramatically decreased with the use of B 2 pin 2 . This unusual phenomenon has been observed before with the dmadpm ligand framework. 17 Table 14 : Effect of boron source This result does not match with the standard Ir III/V trisboryl catalytic cycle. In the standard cycle C H activation is rate limiting and occurs before the boron source enters 370 the cycle. 2 Thus the source of boron should have no effect on selectivity. This is assuming that the iridium trisboryl species is the active catalyst with both boron sources. It is not unreasonable to imagine an Ir III bisboryl monohydride species is a ctive in C H borylation. If this iridium hydride species leads to a different selectivity than the trisboryl, this could explain the unusual result because using HBpin as the boron source should favor the iridium hydride more than using B 2 pin 2 as the sourc e. 5 .7 : Structural adjustments to dmadphz and the effects To test the necessity of the free amino group on dmadphz, the N - methyl and N,N - dimethyl hydrazones were prepared. In general, both ligands produced a less active and less selective catalyst. Table 15 : Importance of free amino group on dmadphz Consider 1,3 - dicyanobenzene neit her the methylated (entry 5) or dimethylated (entry 1) hydrazone push this reaction to completion, and a selectivity of 4:1 was observed which is a dramatic decrease from the 16:1 selectivity with the free amino moiety. For 1,3 - chlorofluorobenzene, entries 2 and 4, the reactions went nearer to complete conversion, 371 but both cases took longer reaction time and had lower selectivity when compared to dmadphz. Finally , when considering 3 - fluorotoluene, a substrate that was less active with dmadphz, with the dime thylhydrazone ligand a similar trend is seen. Overall, this brief study showed that the free amino group in dmadphz is vital to both selectivity and reactivity. Since it has been previously demonstrated that the amino group in aniline will N - borylate under standard reaction conditions, 6 we wondered if this was operative with a hydrazone free NH 2 moiety. To explore this possibility, NMR tube reactions with HBpin and dmadphz were conducted (scheme 31 ). It was observed that without addition of iridium HBpin react with dmadphz to form a N - Bpin species over the course of 6 days at room temperature. Notably in the 11 B NMR, the observed peak was sharp. This indicates the boron is tetracoordinate. We propose one of the pyridine nitrogens coordinates to the boron forming a 6 - membered ring. However , reactions conducted with this ligand framework are at full conversion by 6 days, so this may not be a major component in the borylations. To assess this, we added 1.0 mol % of [Ir(OMe)(cod)] 2 to see if the i ridium helps catalyze this transformation. Under these conditions, the reaction was complete within 30 minutes, which indicates at least mono - borylation of the ligand NH 2 has occurred during the catalysis. We were also curious if bis N - borylation could occ ur. To test this 1.5 equiv of HBpin, 1.0 mol % [Ir(OMe)(cod)]2 and dmadphz was allowed to react in an NMR tube at room temperature for 12 h. At this point it was observed by 11 B NMR that only 1 equiv of HBpin was consumed. 372 Scheme 31 : A) Slow N - borylation with HBpin B) Fast N - borylation with Hbpin and iridium source C) No evidence of N,N - diborylation 5 .8 : Conclusions A new ligand framework was discovered to be active in iridium catalyzed C H borylations. This hydrazone based ligand, dmadphz, was tested against the most common borylation ligands used in the literature, dtbpy and tmphen, with electron rich substrates, and it was found that dmadphz was at least as active as dtbpy under the reacti on conditions. Excitingly, dmadphz generated a more active and selective catalyst with pinacolborane as the boron source. A well plate to screen dmadphz against other common ligands seen in the literature, two of which are also hydrazone derived, was run w ith four substrates and two solvents. The well - plate clearly indicated dmadphz generates the most active and selective catalyst in THF. These reactions were repeated at larger 373 scale. In all cases the reactivity increased; however , in some substrates, namel y 1,3 - difluorobenzene, the observed selectivity dropped. Despite the drop in selectivity, this is an exciting result as literature offers relatively few methods of borylation meta to fluorine. Given the increase in fluorinated aromatics in pharmaceuticals 3 1 , three relevant and recently approved examples shown in figure 9 , methods for late stage functionalization would be a powerful synthetic tool. Figure 12 : Fluorinated pharmaceuticals 5 .9: Experime ntal Details Materials and methods All reactions were carried out in oven - dried glassware under an atmosphere of nitrogen, with magnetic stirring, and monitored by 1 H - NMR and 19 F - NMR. Tetrahydrofuran was freshly distilled from sodium/benzophenone under nitrogen. 1 H, 13 C{ 1 H}, 11 B, and 19 F NM R spectra were recorded on an Agilent DirectDrive2 500 MHz NMR spectrometer equipped with an OneProbe operating at 499.7 MHz for 1 H NMR, 125.7 MHz for 13 C NMR, 470.1 MHz for 19 F NMR and 160.3 MHz for 11 B NMR. General Borylation procedure: 374 In a nitrogen a tmosphere glove box the substrate was weighed into a 20 mL vial containing a magnetic stir bar. [Ir(OMe)cod] 2 , ligand, and boron source were weighed into three test tubes separately each being diluted with 0.5 mL THF. The test tube containing the boron sou rce solution was transferred into the test tube containing [Ir(OMe)cod] 2 . This mixture was stirred by shaking the test tube until a golden yellow clear solution was obtained (~30s). Next the solution containing the [Ir(OMe)cod] 2 and boron source was transf erred into the test tube containing the ligand, and upon stirring by shaking the test tube the resulting solution turned a dark brown - red color. Finally, the contents of the test tube with the pre - generated catalyst were transferred into 20mL vial containi ng the substrate and magnetic stir bar. To ensure little to no transfer loss, 0.5 mL THF was added to test tube one then transferred to test tube two then to test tube three and finally to the reaction mixture. This procedure was repeated 3 times. This via l was then sealed. The reaction mixture stirred for at room temperature for a variable amount of time depending on the substrate, after which the vial was taken out of the glove box. The solvent of the crude reaction mixture was then removed by rotary evap oration and NMR spectra were collected . Experimental for Table 8 : A ll data except entry 6 can be found in a recent work. 17 Table 8 : Entry 6 375 [Ir(OMe)cod] 2 (9.9 mg, 0.015 mmol), HBpin ( 256 mg, 2 mmol), and dmadphz (8.5 mg, 0.03 mmol) were added into three separate test tubes. 1,3 - dicyanobenzene (128 mg , 1 mmol) was charged into a 20 ml vial equipped with a stir bar. To each test tube 0.5 mL THF was added. The HBpin solution was then transferred into the [Ir(OMe)cod] 2 and stirred by shaking the test tube until a golden yellow clear solution was obtained (~30s). Next, the solution containing the [Ir(OMe)cod] 2 and HBpin was transferred into the test tube conta ining the dmadphz solution, and upon stirring by shaking the test tube the resulting solution turned a dark brown - red color. Finally, the contents of the test tube with the pre - generated catalyst were transferred into 20mL vial containing the substrate and magnetic stir bar. To ensure little to no transfer loss, 0.5 mL THF was added to test tube one then transferred to test tube two then to test tube three and finally to the reaction mixture. This procedure was repeated 3 times. The vial was then sealed. T he reaction mixture stirred for at room temperature for 1 hour, after which the vial was taken out of the glove box. The solvent of the crude reaction mixture was removed by rotary evaporation leaving a dark, blackish oil. By the 1 H NMR conversion was dete rmined to be >99% with a ratio of 16:1. This was consistent with previously reported NMR spectra . Experimental for Table 9 : Table 9 : Entry 1 [Ir(OMe)cod] 2 (5 mg, 0.0075 mmol), HBpin (128 mg, 1 mmol), and dmadphz (4.7 mg, 0.015 mmol) were added into three separate test tubes. 1,3 - dimethoxybenzene (69 376 mg , 0.5 mmol) was charged into a 3 mL V - shaped vial equipped with a stir bar. To each test tube 0.25 mL THF was added. The HBpin solution was then transferred into the [Ir (OMe)cod] 2 and stirred by shaking the test tube until a golden yellow clear solution was obtained (~30s). Next, the solution containing the [Ir(OMe)cod] 2 and HBpin was transferred into the test tube containing the dmadphz solution, and upon stirring by sha king the test tube the resulting solution turned a dark brown - red color. Finally, the contents of the test tube with the pre - generated catalyst were transferred into 3 mL vial containing the substrate and magnetic stir bar. To ensure little to no transfer loss, 0.25 mL THF was added to test tube one then transferred to test tube two then to test tube three and finally to the reaction mixture. This procedure was repeated 3 times. This vial was then sealed. The vial was removed from the glove box and placed into a preheated oil bath at 65 . The reaction mixture stirred for 22 hours, after which the vial was removed from the oil bath and opened. The solvent of the crude reaction mixture was then removed by rotary evaporation leaving a dark, blackish oil. T he 1 H NMR was consistent with previous reports and conversion was determined to be 61%. Table 9 : Entry 2 [Ir(OMe)cod] 2 (5 mg, 0.0075 mmol), HBpin (128 mg, 1 mmol), and dtbpy (4 mg, 0.015 mmol) were added into three separate test tubes. 1,3 - dimethoxybenzene (69 mg , 0.5 mmol) was charged into a 3 mL V - shaped vial equipped with a stir bar. To each test tube 0.25 mL THF was added. The HBpin solution was then transferred into the 377 [Ir(OMe)cod] 2 and stirred by shaking the test tube until a golden yellow clear solution was obtained (~30s). Next, the solution containing the [Ir(OMe)cod] 2 and HBpin was transferred into the test tube containing the dtbpy solution, and upon stirring by shaking the test tube the resulting solution turned a dark brown - red color. Finally, the contents of the test tube with the pre - generated catalyst were transferred into 3 mL vial containing the substrate and magnetic stir bar. To ensure little to no transfer loss, 0.25 mL THF was added to test tube one then transferred to test tube two then to test tube three and finally to the reaction mixture. This procedure was repeated 3 times. This vial was then sealed. The vial was removed from the glove box and placed into a preheated oil bath at 65 . The reaction mixture stirred for 22 hours, after which the vial was removed from the oil bath and opened. The solvent of the crude reaction mixture was then removed by rotary evaporation leaving a dark, blackish oil. T he 1 H NMR was consistent with previous reports and conversion was determined to be 3 1%. Table 9 : Entry 3 [Ir(OMe)cod] 2 (5 mg, 0.0075 mmol), HBpin (128 mg, 1 mmol), and tmphen (3.5 mg, 0.015 mmol) were added into three separate test tubes. 1,3 - dimethoxybenzene (69 mg, 0.5 mmol) was charged into a 3 mL V - shaped vial equipped with a stir bar. To each test tube 0.25 mL THF wa s added. The HBpin solution was then transferred into the [Ir(OMe)cod] 2 and stirred by shaking the test tube until a golden yellow clear solution was obtained (~30s). Next, the solution containing the [Ir(OMe)cod] 2 and HBpin was 378 transferred into the test t ube containing the tmphen solution, and upon stirring by shaking the test tube the resulting solution turned a dark brown - red color. Finally, the contents of the test tube with the pre - generated catalyst were transferred into 3 mL vial containing the subst rate and magnetic stir bar. To ensure little to no transfer loss, 0.25 mL THF was added to test tube one then transferred to test tube two then to test tube three and finally to the reaction mixture. This procedure was repeated 3 times. This vial was then sealed. The vial was removed from the glove box and placed into a preheated oil bath at 65 . The reaction mixture stirred for 22 hours, after which the vial was removed from the oil bath and opened. The solvent of the crude reaction mixture was then rem oved by rotary evaporation leaving a dark, blackish oil. T he 1 H NMR was consistent with previous reports and conversion was determined to be 64 %. Table 9 : Entry 4 [Ir(OMe)cod] 2 (5 mg, 0.0075 mmol), HBpin (128 mg, 1 mmol), and dmadphz (4.7 mg, 0.015 mmol) were added into three separate test tubes. 1,3 - diisopropylbenzene (81 mg , 0.5 mmol) was charged into a 3 mL V - shaped vial equipped with a stir bar. To each test tube 0.25 mL TH F was added. The HBpin solution was then transferred into the [Ir(OMe)cod] 2 and stirred by shaking the test tube until a golden yellow clear solution was 379 obtained (~30s). Next, the solution containing the [Ir(OMe)cod] 2 and HBpin was transferred into the te st tube containing the ligand solution, and upon stirring by shaking the test tube the resulting solution turned a dark brown - red color. Finally, the contents of the test tube with the pre - generated catalyst were transferred into 3 mL vial containing the s ubstrate and magnetic stir bar. To ensure little to no transfer loss, 0.25 mL THF was added to test tube one then transferred to test tube two then to test tube three and finally to the reaction mixture. This procedure was repeated 3 times. This vial was then sealed. The vial was removed from the glove box and placed into a preheated oil bath at 80 . The reaction mixture stirred for 16 hours, after which the vial was removed from the oil bath and opened. The solvent of the crude reaction mixture was then removed by rotary evaporation leaving a dark, blackish oil. T he 1 H NMR was consistent with previous reports and conversion was determined to be 27 %. Table 9 Entry 5 [Ir(OMe)cod] 2 (5 mg, 0.0075 mmol), HBpin (128 mg, 1 mmol), and dtbpy (4 mg, 0.015 mmol) were added into three separate test tubes. 1,3 - diisopropylbenzene (81 mg , 0.5 mmol) was charged into a 3 mL V - shaped vial equipped with a stir bar. To each test tube 0.25 mL THF wa s added. The HBpin solution was then transferred into the [Ir(OMe)cod] 2 and stirred by shaking the test tube until a golden yellow clear solution was 380 obtained (~30s). Next, the solution containing the [Ir(OMe)cod] 2 and HBpin was transferred into the test t ube containing the ligand solution, and upon stirring by shaking the test tube the resulting solution turned a dark brown - red color. Finally, the contents of the test tube with the pre - generated catalyst were transferred into 3 mL vial containing the subst rate and magnetic stir bar. To ensure little to no transfer loss, 0.25 mL THF was added to test tube one then transferred to test tube two then to test tube three and finally to the reaction mixture. This procedure was repeated 3 times. This vial was then sealed. The vial was removed from the glove box and placed into a preheated oil bath at 80 . The reaction mixture stirred for 16 hours, after which the vial was removed from the oil bath and opened. The solvent of the crude reaction mixture was then rem oved by rotary evaporation leaving a dark, blackish oil. T he 1 H NMR was consistent with previous reports and conversion was determined to be 16 %. Table 9 : Entry 6 [Ir(OMe)cod] 2 (5 mg, 0.0075 mmol), HBpin (128 mg, 1 mmol) , and tmphen (3.5 mg, 0.015 mmol) were added into three separate test tubes. 1,3 - diisopropylbenzene (81 mg , 0.5 mmol) was charged into a 3 mL V - shaped vial equipped with a stir bar. To each test tube 0.25 mL THF was added. The HBpin solution was then tran sferred into the [Ir(OMe)cod] 2 and stirred by shaking the test tube until a golden yellow clear solution was 381 obtained (~30s). Next, the solution containing the [Ir(OMe)cod] 2 and HBpin was transferred into the test tube containing the ligand solution, and u pon stirring by shaking the test tube the resulting solution turned a dark brown - red color. Finally, the contents of the test tube with the pre - generated catalyst were transferred into 3 mL vial containing the substrate and magnetic stir bar. To ensure lit tle to no transfer loss, 0.25 mL THF was added to test tube one then transferred to test tube two then to test tube three and finally to the reaction mixture. This procedure was repeated 3 times. This vial was then sealed. The vial was removed from the gl ove box and placed into a preheated oil bath at 80 . The reaction mixture stirred for 16 hours, after which the vial was removed from the oil bath and opened. The solvent of the crude reaction mixture was then removed by rotary evaporation leaving a dark, blackish oil . T he 1 H NMR was consistent with previous reports and conversion was determined to be 60 %. Table 9 : Entry 7 [Ir(OMe)cod] 2 (5 mg, 0.0075 mmol), HBpin (128 mg, 1 mmol), and dmadphz (4.7 mg, 0.015 mmol) we re added into three separate test tubes. N,N ,3 - trimethylananline (67 mg , 0.5 mmol) was charged into a 3 mL V - shaped vial equipped with a stir bar. To each test tube 0.25 mL THF was added. The HBpin solution was then transferred into the [Ir(OMe)cod] 2 and stirred by shaking the test tube until a golden yellow clear solution was 382 obtained (~30s). Next, the solution containing the [Ir(OMe)cod] 2 and HBpin was transferred into the test tube containing the ligand solution, and upon stirring by shaking the test tube the resulting solution turned a dark brown - red color. Finally, the contents of the test tube with the pre - generated catalyst were trans ferred into 3 mL vial containing the substrate and magnetic stir bar. To ensure little to no transfer loss, 0.25 mL THF was added to test tube one then transferred to test tube two then to test tube three and finally to the reaction mixture. This procedure was repeated 3 times. This vial was then sealed. The vial was removed from the glove box and placed into a preheated oil bath at 65 . The reaction mixture stirred for 22 hours, after which the vial was removed from the oil bath and opened. The solvent of the crude reaction mixture was then removed by rotary evaporation leaving a dark, blackish oil. T he 1 H NMR was consistent with previous reports and conversion was determined to be 13 %. Table 9 : Entry 8 [Ir(OMe)cod] 2 (5 mg, 0.0075 mmol), HBpin (128 mg, 1 mmol), and dtbpy (4 mg, 0.015 mmol) were added into three separate test tubes. N,N, 3 - trimethylananline (67 mg , 0.5 mmol) was charged into a 3 mL V - shaped vial equipped wi th a stir bar. To each test tube 0.25 mL THF was added. The HBpin solution was then transferred into the [Ir(OMe)cod] 2 and stirred by shaking the test tube until a golden yellow clear solution was 383 obtained (~30s). Next, the solution containing the [Ir(OMe) cod] 2 and HBpin was transferred into the test tube containing the ligand solution, and upon stirring by shaking the test tube the resulting solution turned a dark brown - red color. Finally, the contents of the test tube with the pre - generated catalyst were transferred into 3 mL vial containing the substrate and magnetic stir bar. To ensure little to no transfer loss, 0.25 mL THF was added to test tube one then transferred to test tube two then to test tube three and finally to the reaction mixture. This proc edure was repeated 3 times. This vial was then sealed. The vial was removed from the glove box and placed into a preheated oil bath at 65 . The reaction mixture stirred for 22 hours, after which the vial was removed from the oil bath and opened. The sol vent of the crude reaction mixture was then removed by rotary evaporation leaving a dark, blackish oil. T he 1 H NMR was consistent with previous reports and conversion was determined to be 13 %. Table 9 : Entry 9 [Ir(OMe)cod] 2 (5 mg, 0.0075 mmol), HBpin (128 mg, 1 mmol), and tmphen (3.5 mg, 0.015 mmol) were added into three separate test tubes . N,N ,3 - trimethylananline (67 mg , 0.5 mmol) was charged into a 3 mL V - shaped vial equipped with a stir bar. To each test tube 0.25 mL THF was added. The HBpin solution was then transferred into the [Ir(OMe)cod] 2 and stirred by shaking the test tube until a golden yellow clear solution was 384 obtained (~30s). Next, the solution containing the [Ir(O Me)cod] 2 and HBpin was transferred into the test tube containing the ligand solution, and upon stirring by shaking the test tube the resulting solution turned a dark brown - red color. Finally, the contents of the test tube with the pre - generated catalyst we re transferred into 3 mL vial containing the substrate and magnetic stir bar. To ensure little to no transfer loss, 0.25 mL THF was added to test tube one then transferred to test tube two then to test tube three and finally to the reaction mixture. This p rocedure was repeated 3 times. This vial was then sealed. The vial was removed from the glove box and placed into a preheated oil bath at 65 . The reaction mixture stirred for 22 hours, after which the vial was removed from the oil bath and opened. The solvent of the crude reaction mixture was then removed by rotary evaporation leaving a dark, blackish oil. T he 1 H NMR was consistent with previous reports and conversion was determined to be 33 %. Experimental for table 10 Entry L1 - A The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A phot o redox - catalysis 96 well plate was filled with 96 shell 385 vials (0.75 mL 8 x 30mm). Vials in the wells were equi pped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL THF. A 6.25 mM stock solution of L1 was prepared by dissolving 35.6 mg L1 in 20 mL THF. A 500 mM stock solution of 1,3 - dicyanobenzene was prepared by dissolving 640 mg 1,3 - dicyanobenzene into 10 mL THF. These were all prepared in a nitrogen atmosphere glove box. the selected wells 12.5 mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was al lowed to stir for - dicyanobenzene was added into the same well as the previous reagents. After all reagents were added, a plastic liner was placed over the wells and the top of th e plate was screwed shut. The well plate was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL eth yl acetate for GC analysis. The rest of the crude material was dissolved in CDCl 3 for NMR analysis. Crude 1 H NMR ratios were determined to be 10:1 and conversion was determined to be 71% as an average of the two runs. Entry L2 - A 386 The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL THF. A 25 mM stock solution of L2 was prepared by dissolving 37.7 mg L2 in 5 mL THF. A 500 mM stock solution of 1,3 - dicyanobenzene was prepared by dissolving 640 mg 1,3 - dicyanobenzene into 10 mL THF. These were all prepared in a nitrogen atmosphere glove box. p mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for appro - dicyanobenzene was added into the same well as the previous reagents. After all reagents were added, a plastic liner was placed over the wells and the top of the plate was screwed shu t. The well plate was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analy sis. The rest of the crude material 387 was dissolved in CDCl3 for NMR analysis. Crude 1H NMR ratios were determined to be 3:1 and conversion was determined to be 38% as an average of the two runs. Entry L3 - A The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equi pped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL THF. A 25 mM stock solution of L3 was prepared by dissolving 43.1 mg L3 in 5 mL THF. A 500 mM stock solution of 1,3 - dicyanobenzene was prepared by dissolving 640 mg 1,3 - dicyanobenzene into 10 mL THF. These were all prepared in a nitrogen atmosphere glove box. lected wells by mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for - dicyanobenzene was added into the same well as the previous reagents. After all reagents were added, a plastic liner was placed over the wells and the top of the plat e 388 was screwed shut. The well plate was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl ace tate for GC analysis. The rest of the crude material was dissolved in CDCl3 for NMR analysis. Crude 1 H NMR ratios were determined to be 5:1 and conversion was determined to be 68% as an average of the two runs. Entry L4 - A The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars . Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL THF. A 25 mM stock solution of L4 was prepared by dissolving 35 mg L4 in 5 mL THF. A 500 mM stock s olution of 1,3 - dicyanobenzene was prepared by dissolving 640 mg 1,3 - dicyanobenzene into 10 mL THF. These were all prepared in a nitrogen atmosphere glove box. mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for 389 appr - dicyanobenzene was added into the same well as the previous reagents. After all reagents were added, a plastic liner was placed over the wells and the top of the plate was screwed sh ut. The well plate was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC anal ysis. The rest of the crude material was dissolved in CDCl3 for NMR analysis. Crude 1 H NMR showed only the starting material and the steric product 2a, but this could be due to the low conversion. Conversion was determined to be 14% as an average of the tw o runs. Entry L5 - A The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL THF. A 25 mM stock solution of L5 was prepared b y dissolving 33.6 mg L5 in 5 mL THF. A 500 mM stock solution of 1,3 - dicyanobenzene was prepared by dissolving 640 mg 1,3 - dicyanobenzene into 10 mL THF. These were all prepared in a nitrogen atmosphere glove box. 390 as added into the selected wells by mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for - dicyanobenzene was added into the same well as the previous reagents. After all reagents were added, a plastic liner was placed over the wells and the top of the plate was screwed shut. The well plate was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material was dissolved in CDCl3 for NMR analysis. Crude 1 H NMR ratios were determined to be 3:1 and conversion was determined to be 72% as an average of the two runs. Entry L1 - B The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell 391 vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL THF. A 6.25 mM stock solution of L1 was prepared by dissolving 35.6 mg L1 in 20 mL THF. These were all prepared in a nitrogen atmosphere glove box. 12.5 mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for - chlorofluorobenzene was added into the same well as the previous reagents. After all reagents were added, a plastic liner was placed over the wells and the top of the plate was screwed shut. The well plate was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis . The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material was dissolved in CDCl3 for NMR analysis. Crude 19 F NMR ratios were determined to be 6.2:1 and conversion was determined to be 80% as an average of the two runs. Th e NMR data was consistent with the previous report ed data . Entry L2 - B 392 The ratio and conversion were determined from a well plate screen and ar e an average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL THF. A 25 mM stock solution of L2 was prepared by dissolving 37.7 mg L2 in 5 mL THF. These were all prepared in a nitrogen atmosphere glove box. 25 mM L2 stock was added into the selected wells by mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for - chlorofluorobenzene was added into the same well as the previous reagents. After all reagents were added, a plastic liner was placed over the wells and the t op of the plate was screwed shut. The well plate was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material 393 was dissolved in CDCl3 for NMR analysis. Crude 19 FNMR ratios were determined to be 2:1 and conversion was determined to be 15% as an average of the two runs. Entry L3 - B The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well pla te was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)c od] 2 in 5 mL THF. A 25 mM stock solution of L3 was prepared by dissolving 43.1 mg L3 in 5 mL THF. These were all prepared in a nitrogen atmosphere glove box. pipettor. The THF mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for - chlorofluorobenzene was added into the same well as the previous reagents. After all reagents were added, a plastic liner was placed over the wells and the to p of the plate was screwed shut. The well plate was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. 394 The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material was dissolved in CDCl3 for NMR analysis. Crude 19 F NMR ratios were determined to be 2.5:1 and conversion was determined to be 18% as an average of the two runs. Entry L4 - B The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL THF. A 25 mM stock solution of L4 was prepared by dissolving 35.1 mg L4 in 5 mL THF . These were all prepared in a nitrogen atmosphere glove box. mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for - chlorofluorobenzene was added into the same well as the previous rea gents. After all reagents were added, a plastic liner was placed over the wells and the top of the plate was screwed shut. The well plate was 395 allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The conte nts of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material was dissolved in CDCl3 for NMR analysis. Crude 19 F NMR ratios were determined to be 2.9:1 and conve rsion was determined to be 14% as an average of the two runs. Entry L5 - B The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was f illed with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL THF. A 25 mM stock solution of L5 was prepared by dissolving 33.6 mg L5 in 5 mL THF. These were all prepared in a nitrogen atmosphere glove box. pipettor. The THF solvent mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for approximately 5 minutes. Fin - chlorofluorobenzene was added into the 396 same well as the previous reagents. After all reagents were added, a plastic liner was placed over the wells and the top of the plate was screwed shut. The well plate was allowed to stir in the g love box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material was dissol ved in CDCl3 for NMR analysis. Crude 19 F NMR ratios were determined to be 2.5:1 and conversion was determined to be 69% as an average of the two runs. Entry L1 - C The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL THF. A 6.25 mM stock solution of L1 was prepared by dissolving 35.6 mg L1 in 20 mL THF. These were al l prepared in a nitrogen atmosphere glove box. 397 12.5 mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for - fluorotoluene was added into the same well as the previous reagents. After all re agents were added, a plastic liner was placed over the wells and the top of the plate was screwed shut. The well plate was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well wer e analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material was dissolved in CDCl3 for NMR analysis. Crude 19 F NMR ratios were determined to be 4.3:1 and conversion was determined to be 35% as an average of the two runs. Th e NMR data was consistent with previous reported data . Entry L2 - C The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A pho toredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by di ssolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL THF. A 25 mM stock solution of L2 was prepared by dissolving 37.7 mg L2 in 5 mL THF. These were all prepared in a nitrogen atmosphere glove box. 398 ed wells by mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for - fluorotoluene was added into the same well as the previous reagents. After all reagents were added, a plastic liner was placed over the wells and the top of the plate was screwed shut. The well plate was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material was dissolved in CDCl3 for NMR analysis. Crude 19 FNMR ratios were determined to be 0.75:1 and conversion was determined to be 2% as an average of the two runs. Entry L3 - C The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL THF. A 25 mM 399 stock solution of L3 was prepared by dissolving 43.1 mg L3 in 5 mL THF. These were all p repared in a nitrogen atmosphere glove box. mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for - fluorotoluene was added into the same well as the previous reagents. After all reagents were added, a plastic liner was placed over the wells and the top of the plate was screwed shut. The well plate was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were anal yzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material was dissolved in CDCl3 for NMR analysis. The crude 19 F NMR ratios were inconsistent between the two runs one being 0.86:1 and the other being 1.36:1, but given the conversion was determined to be 2% as an average of the two runs the ratio was reported as NA. Entry L4 - C 400 The ratio and conversion were determined from a well plate screen and are a n average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock sol ution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL THF. A 25 mM stock solution of L4 was prepared by dissolving 35.1 mg L4 in 5 mL THF. These were all prepared in a nitrogen atmosphere glove box. mM L4 stock was added into the selected wells by stock solution of [Ir(OMe)cod] 2 was ad ded. This mixture was allowed to stir for - fluorotoluene was added into the same well as the previous reagents. After all reagents were added, a plastic liner was placed over the wells and the top of the plate was screwed shut. The well plate was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acet ate for GC analysis. The rest of the crude material was dissolved in CDCl3 for NMR analysis. Crude 19 F NMR ratios were determined to be 2:1 and conversion was determined to be 2% as an average of the two runs. 401 Entry L5 - C The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equi pped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL THF. A 25 mM stock solution of L5 was prepared by dissolving 33.6 mg L5 in 5 mL THF. These were all prepared in a nitrogen atmosphere glove box. stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for - fluorotoluene was added into the same well as the previous reagents. After all reagents were added, a plastic liner was placed over the wells and the top of the plate was screwed shut. The well plate was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The co ntents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material 402 was dissolved in CDCl3 for NMR analysis. Crude 19 F NMR ratios were determined to be 1.4:1 and co nversion was determined to be 25% as an average of the two runs. Entry L1 - D The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL cyclohexane. A 6.25 mM stock solution of L1 was prepared by dissolving 35.6 mg L1 in 20 mL THF. These were all prepared in a nitrogen atmosphere glove box. stock was added into the selected wells of 12.5 mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir - chlorofluorobenzene was added into the same well as the previous reagents. After all reagents were added, a plastic liner was placed over the wells and the top of the plate was screwed shut. The well plate was 403 allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material was dissolved in CDCl3 for NMR analysis. Crude 19 F NMR ratios were determined to be 1.9:1 and conversion was determined to be 69% as an average of the two runs. Entry L2 - D The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh mic ro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL cyclohexane. A 25 mM stock solution of L2 was prepared by dissolving 37.7 mg L2 in 5 mL cyclohexane. These were all prepared in a nitrogen atmosphere glove box. 12.5 mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for - chlorofluorobenzene was added into the 404 same well as the previous reagents. After all reagents were added, a plastic liner was placed over the wells and the top of the plate was screwed shut. The well plate was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR anal ysis. The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material was dissolved in CDCl3 for NMR analysis. Crude 19 FNMR ratios were determined to be 1.6:1 and conversion was determined to be 53% as an average of the two runs. Entry L3 - D The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL cyclohexane. A 6.25 mM stock solution of L3 was prepared by dissolving 43.1 mg L3 in 20 mL cylcohexane. These were all prepared in a nitrogen atmosphere glove box. selected wells 405 of 12.5 mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was a llowed to stir - chlorofluorobenzene was added into the same well as the previous reagents. After all reagents were added, a plastic liner was placed over the wells and the top of the plate was screwed sh ut. The well plate was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC anal ysis. The rest of the crude material was dissolved in CDCl3 for NMR analysis. Crude 19 F NMR ratios were determined to be 3:1 and conversion was determined to be 58% as an average of the two runs. Entry L4 - D The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL cyclohexane. A 25 mM stock solution of L4 was prepared by dissolving 35.1 mg L4 in 5 mL cyclohexane. These were al l prepared in a nitrogen atmosphere glove box. 406 12.5 mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for - chlorofluorobenzene was added into the same well as the previous reagents. Aft er all reagents were added, a plastic liner was placed over the wells and the top of the plate was screwed shut. The well plate was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material was dissolved in CDCl3 for NMR analysis. Crude 19 F NMR ratios were determined to be 1.6:1 and conversion was d etermined to be 40% as an average of the two runs. Entry L5 - D The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL cyclo hexane. A 407 25 mM stock solution of L5 was prepared by dissolving 33.6 mg L5 in 5 mL cyclohexane. These were all prepared in a nitrogen atmosphere glove box. pipettor. The solven 12.5 mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for approximately 5 min - chlorofluorobenzene was added into the same well as the previous reagents. After all reagents were added, a plastic liner was placed over the wells and the top of the plate was screwed shut. The well plate was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material w as dissolved in CDCl3 for NMR analysis. Crude 19 F NMR ratios were determined to be 2:1 and conversion was determined to be 90% as an average of the two runs. Entry L1 - E The ratio and conversion were determined from a well plate screen and are an average of two separat e runs. A photoredox - catalysis 96 well plate was filled with 96 shell 408 vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 w as made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL cyclohexane. A 6.25 mM stock solution of L1 was prepared by dissolving 35.6 mg L1 in 20 mL THF. These were all prepared in a nitrogen atmosphere glove box. stock was added into the selected wells of 12.5 mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir - fluorotoluene was added into the same well as the previous reagents. After all reagents were added, a plastic liner was placed over the wells and the top of the pla te was screwed shut. The well plate was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl ac etate for GC analysis. The rest of the crude material was dissolved in CDCl3 for NMR analysis. Crude 19 F NMR ratios were determined to be 1.3:1 and conversion was determined to be 53% as an average of the two runs. Entry L2 - E 409 The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL cyclohexane. A 25 mM stock solution of L2 was prepared by dissolving 37.7 mg L2 in 5 mL cyclohe xane. These were all prepared in a nitrogen atmosphere glove box. 12.5 mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for - fluorotoluene was added into the same well as the previous rea gents. After all reagents were added, a plastic liner was placed over the wells and the top of the plate was screwed shut. The well plate was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material was dissolved in CDCl3 for NMR analysis. Crude 19 F NMR ratios were determined to be 0.75:1 and conversion was determined to be 44% as an average of the two runs. 410 Entry L3 - E The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 9 6 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL cyclohexane. A 6.25 mM stock solution of L3 was prepared by dissolving 43.1 mg L3 in 20 mL cyclohexane. These were all prepared in a nitrogen atmosphere glove box. ected wells of 12.5 mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allo wed to stir - fluorotoluene was added into the same well as the previous reagents. After all reagents were added, a plastic liner was placed over the wells and the top of the plate was screwed shut. The wel l plate was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. 411 The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The r est of the crude material was dissolved in CDCl3 for NMR analysis. Crude 19 F NMR ratios were determined to be 1.5:1 and conversion was determined to be 17% as an average of the two runs. Entry L4 - E The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL cyclohexane. A 25 mM stock solution of L4 was prepared by dissolving 35.1 mg L4 in 5 mL cyclohexane. These were all prepared in a nitrogen atmosphere glove box. 12.5 mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for - fluorotoluene was added into the same well as the previous reagents. After all reagents were added, a plastic liner was placed over 412 the wells and the top of the plate was screwed shut. The well plate was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material was dissolved in CDCl3 for NMR analysis. Crude 19 F NMR ratios were determined to be 1.3:1 and conversion was determined to be 12% as an average of the two runs. Entry L5 - E The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL cyclohexane. A 25 mM stock solution of L5 was prepared by dissolving 33.6 mg L5 in 5 mL cyclohexane. These were all prepared in a nitrogen atmosphere glove box. 12.5 mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for - fluorotoluene was added into the same well 413 as the previous reagents. After all reagents were added, a plastic liner was placed over the wells and the top of the plate was screwed shut. The well plate was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material was dissolved in CDCl3 for NMR analysis. Crude 19 F NMR ratios were determined to be 1:1 and conversion wa s determined to be 93% as an average of the two runs. Experimental for Table 11 Entry L1 - THF The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL THF. A 6.25 mM 414 stock solution of L1 was prepared by dissolving 35.6 mg L1 in 20 mL THF. These were al l prepared in a nitrogen atmosphere glove box. 12.5 mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for - difluorobenzene was added into the same well as the previous reagents. After all reagents were added, a plastic liner was placed over the wells and the top of the plate was screwed shut. The well plate was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material was dissolved in CDCl3 for NMR analysis. Crude 19 F NMR ratios were determined to be 43: 9.9: 1: 4.5: 0.37 (a:b:c:d:e ) and conversion was determined to be 85% as an average of the two runs. Th e NMR data was consistent with previously reported data. Entry L2 - THF 415 The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solut ion of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL THF. A 25 mM stock solution of L2 was prepared by dissolving 37.7 mg L2 in 5 mL THF. These were all prepared in a nitrogen atmosphere glove box. pipettor. The THF solv mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for approximately 5 minutes. - difluorobenzene was added into the same well as the previous reagents. After all reagents were added, a plastic liner was placed over the wells and the top of the plate was screwed shut. The well plate was allowed to 416 stir in the glo ve box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material was dissolve d in CDCl3 for NMR analysis. Crude 19 F NMR ratios were determined to be 2.1: 1.2: 1: 0: 0 (a:b:c:d:e) and conversion was determined to be 8% as an average of the two runs. Entry L3 - THF The ratio and conversion were det ermined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL THF. A 25 mM 417 stock solution of L3 was prepared by dissolving 43.1 mg L3 in 5 mL THF. These were all prepared in a nitrogen atmosphere glove box. 12.5 mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for - difluorobenzene was added into the same well as the previous reagents. After all reagents were added, a plastic liner w as placed over the wells and the top of the plate was screwed shut. The well plate was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were analyzed separately. One drop of t he crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material was dissolved in CDCl3 for NMR analysis. Crude 19 F NMR ratios were determined to be 11: 4.1: 1: 0: 0 (a:b:c:d:e) and conversion was determined to be 10% as an average of the two runs. Entry L4 - THF 418 The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL THF. A 25 mM stock solution of L4 was prepared by dissolving 35 mg L4 in 5 mL THF. These were all pre pared in a nitrogen atmosphere glove box. mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for - difluorobenzene was added into the same well as the previous reagents. After all reagent s were added, a plastic liner was placed over the wells and the top of the plate was screwed shut. The well plate was allowed to 419 stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material was dissolved in CDCl3 for NMR analysis. Crude 19 F NMR ratios were determined to be 8.2: 3 : 0: 0: 0 (a:b:c:d:e) and conversion was determined to be 8% as an average of the two runs. Entry L5 - THF The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photo redox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by diss olving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL THF. A 25 mM stock solution of L5 was prepared by dissolving 33.6 mg L5 in 5 mL THF. These were all prepared in a nitrogen atmosphere glove box. 420 wells by mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to st ir for - difluorobenzene was added into the same well as the previous reagents. After all reagents were added, a plastic liner was placed over the wells and the top of the plate was screwed shut. The well plat e was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material was dissolved in CDCl3 for NMR analysis. Crude 19 F NMR ratios were determined to be 4.7: 2.6: 1: 1.2: 0.1 (a:b:c:d:e) and conversion was determined to be 58% as an average of the two runs. Entry L1 - Cyclohexane 421 The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equi pped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL cyclohexane. A 6.25 mM stock solution of L1 was prepared by dissolvi ng 35.6 mg L1 in 20 mL THF. These were all prepared in a nitrogen atmosphere glove box. and of 12.5 mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir - difluorobenzene was added into the s ame well as the previous reagents. After all reagents were added, a plastic liner was placed over the wells and the top of the plate was screwed shut. The well plate was 422 allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material was dissolved in CDCl3 for NMR analysis. Crude 19 F NMR ratios were dete rmined to be 2: 1.6: 1: 0: 0 (a:b:c:d:e). Entry L2 - Cyclohexane The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was filled wit h 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL cyc lohexane. A 25 mM stock solution of L2 was prepared by dissolving 37.7 mg L2 in 5 mL cyclohexane. These were all prepared in a nitrogen atmosphere glove box. 423 pipettor. The solv 12.5 mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for approximately 5 m - difluorobenzene was added into the same well as the previous reagents. After all reagents were added, a plastic liner was placed over the wells and the top of the plate was screwed shut. The well plate was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material was dissolved in CDCl3 for NMR analysis. Crude 19 F NMR ratios were determined to be 1.3: 1.1: 1: 0: 0 (a:b:c:d:e). Entry L3 - Cyclohexane 424 The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL cyclohexane. A 6.25 mM stock solution of L3 was prepared by dissolving 43.1 mg L3 in 20 mL cyclohexan e. These were all prepared in a nitrogen atmosphere glove box. 12.5 mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for - difluorobenzene was added into the same well as the previous re agents. After all reagents were added, a plastic liner was placed over the wells and the top of the plate was screwed shut. The well plate was allowed to stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The cont ents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material was dissolved in CDCl3 for NMR analysis. Crude 19 F NMR ratios were determined to be 4.1: 1.7: 1: 0 : 0 (a:b:c:d:e). 425 Entry L4 - Cyclohexane The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 o r 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL cyclohexane. A 25 mM stock solution of L4 was prepared by dissolving 35 mg L4 in 5 mL cyclohexane. These were all prepared in a ni trogen atmosphere glove box. 12.5 mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for - difluorobenzene was added into the same well as the previous reagents. After all reagents were ad ded, a plastic liner was placed over the wells and the top of the plate was screwed shut. The well plate was allowed to 426 stir in the glove box for 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material was dissolved in CDCl3 for NMR analysis. Crude 19 F NMR ratios were determined to be 11.8: 13: 1: 0: 0 (a:b:c:d:e). Entry L5 - Cyclohexane The ratio and conversion were determined from a well plate screen and are an average of two separate runs. A photoredox - catalysis 96 well plate was filled with 96 shell vials (0.75 mL 8 x 30mm). Vials in the wells were equipped with fresh micro stir bars. Reagents were prepared in 5 or 10 mL volumetric flasks. A 12.5 mM stock solution of [Ir(OMe)cod] 2 was made by dissolving 41.5 mg of [Ir(OMe)cod] 2 in 5 mL cyclohexane. A 25 mM stock solution of L5 was prepared by dissolving 33.6 mg L5 in 5 mL cyclohexane. These were all prepared in a nitrogen atmosphere glove box. 427 pipettor. The solvent was allowed t 12.5 mM stock solution of [Ir(OMe)cod] 2 was added. This mixture was allowed to stir for approximately 5 minutes. Finally, - difluorobenzene was added into the same well as the previous reagents. After all reagents were added, a plastic liner was placed over the wells and the top of the plate was screwed shut. The well plate was allowed to stir in the glove box fo r 24 hours then the reactions were removed for GC and NMR analysis. The contents of each well were analyzed separately. One drop of the crude material was placed in 1.5 mL ethyl acetate for GC analysis. The rest of the crude material was dissolved in CDCl 3 for NMR analysis. Crude 19 F NMR ratios were determined to be 2.2: 3.3: 1: 1: 0.1 (a:b:c:d:e). Experimental for table 12 Entry 1 [Ir(OMe)cod] 2 (6.6 mg, 0.01 mmol), HBpin ( 256 mg, 2 mmol), and dmadphz (5.7 mg, 0.02 mmol) were added into three separate test tubes. 1,3 - dicyanobenzene (128 mg , 1 mmol) was charged into a 20 ml vial equipped with a stir bar. To each test tube 0.5 mL THF was added. T he HBpin solution was then transferred into the [Ir(OMe)cod] 2 and 428 stirred by shaking the test tube until a golden yellow clear solution was obtained (~30s). Next, the solution containing the [Ir(OMe)cod] 2 and HBpin was transferred into the test tube contai ning the dmadphz solution, and upon stirring by shaking the test tube the resulting solution turned a dark brown - red color. Finally, the contents of the test tube with the pre - generated catalyst were transferred into 20mL vial containing the substrate and magnetic stir bar. To ensure little to no transfer loss, 0.5 mL THF was added to test tube one then transferred to test tube two then to test tube three and finally to the reaction mixture. This procedure was repeated 3 times. This vial was then sealed. T he reaction mixture stirred for at room temperature for 1 hour, after which the vial was taken out of the glove box. The solvent of the crude reaction mixture was then removed by rotary evaporation leaving a dark, blackish oil. By the 1 H NMR conversion was determined to be >99% with a ratio of 16:1. Entry 2: [Ir(OMe)cod] 2 (6.6 mg, 0.01 mmol), HBpin (256 mg, 2 mmol), and dmadphz (5.7 mg, 0.02 mmol) were added into three separate test tubes. 1,3 - chlorofluorobenzene (130 mg, 1 mmol) was charged into a 20 ml vial equipped with a stir bar. To each test tube 0.5 mL THF was added. The HBpin solution was then transferred into the [Ir(OMe)cod] 2 and stirred by shaking the test tube until a golden yellow clear solution was obtained (~3 0s). Next, the solution containing the [Ir(OMe)cod] 2 and HBpin was transferred into the test 429 tube containing the dmadphz solution, and upon stirring by shaking the test tube the resulting solution turned a dark brown - red color. Finally, the contents of the test tube with the pre - generated catalyst were transferred into 20mL vial containing the substrate and magnetic stir bar. To ensure little to no transfer loss, 0.5 mL THF was added to test tube one then transferred to test tube two then to test tube three and finally to the reaction mixture. This procedure was repeated 3 times. This vial was then sealed. The reaction mixture stirred for at room temperature for 5 hours, after which the vial was taken out of the glove box. The solvent of the crude reaction mixture was then removed by rotary evaporation leaving a dark, blackish oil . By the 1 H NMR conversion was determined to be >99% with a ratio of 5:1. Entry 3: [Ir(OMe)cod] 2 (6.6 mg, 0.01 mmol), HBpin (128 mg, 1 mmol), and d madphz (5.7 mg, 0.02 mmol) were added into three separate test tubes. 3 - fluorotoluene (110 mg , 1 mmol) was charged into a 20 ml vial equipped with a stir bar. To each test tube 0.5 mL THF was added. The HBpin solution was then transferred into the [Ir(OMe )cod] 2 and stirred by shaking the test tube until a golden yellow clear solution was obtained (~30s). Next, the solution containing the [Ir(OMe)cod] 2 and HBpin was transferred into the test tube containing the dmadphz solution, and upon stirring by shaking the test tube the resulting solution turned a dark brown - red color. Finally, the contents of the test tube with 430 the pre - generated catalyst were transferred into 20mL vial containing the substrate and magnetic stir bar. To ensure little to no transfer loss , 0.5 mL THF was added to test tube one then transferred to test tube two then to test tube three and finally to the reaction mixture. This procedure was repeated 3 times. This vial was then sealed. The reaction mixture stirred for at room temperature for 24 hours, after which the vial was taken out of the glove box. The solvent of the crude reaction mixture was then removed by rotary evaporation leaving a dark, blackish oil. By the 19 F NMR conversion was determined to be 76% with a ratio of 3.7:1. Entry 4 : [Ir(OMe)cod] 2 (6.6 mg, 0.01 mmol), HBpin (128 mg, 1 mmol), and dmadphz (5.7 mg, 0.02 mmol) were added into three separate test tubes. 3 - fluorotoluene (110 mg , 1 mmol) was charged into a 20 ml vial equipped with a stir bar. To each test tube 0.5 mL cyclohexane was adde d. The HBpin solution was then transferred into the [Ir(OMe)cod] 2 and stirred by shaking the test tube until a golden yellow clear solution was obtained (~30s). Next, the solution containing the [Ir(OMe)cod] 2 and HBpin was transferred into the test tube co ntaining the dmadphz solution, and upon stirring by shaking the test tube the resulting solution turned a dark brown - red color. Finally, the contents of the test tube with the pre - generated catalyst were transferred into 20mL vial containing the substrate and magnetic stir bar. To ensure little to no transfer loss, 0.5 mL cyclohexane was added to 431 test tube one then transferred to test tube two then to test tube three and finally to the reaction mixture. This procedure was repeated 3 times. This vial was th en sealed. The reaction mixture stirred for at room temperature for 24 hours, after which the vial was taken out of the glove box. The solvent of the crude reaction mixture was then removed by rotary evaporation leaving a dark, blackish oil. By the 19 F NMR conversion was determined to be 70% with a ratio of 2:1. Entry 5: [Ir(OMe)cod] 2 (6.6 mg, 0.01 mmol), HBpin (256 mg, 2 mmol), and dmadphz (5.7 mg, 0.02 mmol) were added into three separate test tubes. 1,3 - difluorobenzene (114 mg , 1 mmol) was charged into a 20 ml vial equipped with a stir bar. To each test tube 0.5 mL THF was added. T he HBpin solution was then transferred into the [Ir(OMe)cod] 2 and stirred by shaking the test tube until a golden yellow clear solution was obtained (~30s). Next, the solution containing the [Ir(OMe)cod] 2 and HBpin was transferred into the test tube contai ning the dmadphz solution, and upon stirring by shaking the test tube the resulting solution turned a dark brown - red color. Finally, the contents of the test tube with 432 the pre - generated catalyst were transferred into 20mL vial containing the substrate and magnetic stir bar. To ensure little to no transfer loss, 0.5 mL THF was added to test tube one then transferred to test tube two then to test tube three and finally to the reaction mixture. This procedure was repeated 3 times. This vial was then sealed. T he reaction mixture stirred for at room temperature for 2 hours, after which the vial was taken out of the glove box. The solvent of the crude reaction mixture was then removed by rotary evaporation leaving a dark, blackish oil. By the 19 F NMR conversion w as determined to be >99% with a ratio of 16.97: 3.5:1:0.77 (a:b:c:d). This corresponds to 3.89:1 of the ortho:meta to fluorine. Interestingly if the reaction is allowed to run for 3 hours the ratio becomes 7.89:2.05:1:9.24:0.71. It is likely that the react ion can be pushed to the diborylated products with isomer d highly favored. Entry 6: [Ir(OMe)cod] 2 (10 mg, 0.015 mmol), HBpin (128 mg, 1 mmol), and dmadphz (85 mg, 0.03 mmol) were added into three separate test tubes. 1,3 - difluorobenzene (456 mg , 4 mmol) was charged into a 20 ml vial equipped with a stir bar. To each test tube 0.5 433 mL THF was added. The HBpin solution was then transferred into the [Ir(OMe)cod] 2 and stirred by shaking the test tube until a golden yellow cle ar solution was obtained (~30s). Next, the solution containing the [Ir(OMe)cod] 2 and HBpin was transferred into the test tube containing the dmadphz solution, and upon stirring by shaking the test tube the resulting solution turned a dark brown - red color. Finally, the contents of the test tube with the pre - generated catalyst were transferred into 20mL vial containing the substrate and magnetic stir bar. To ensure little to no transfer loss, 0.5 mL THF was added to test tube one then transferred to test tube two then to test tube three and finally to the reaction mixture. This procedure was repeated 3 times. This vial was then sealed. The reaction mixture stirred for at room temperature for 2 hours, after which the vial was taken out of the glove box. The so lvent of the crude reaction mixture was then removed by rotary evaporation leaving a dark, blackish oil. By the 19 F NMR conversion was determined to be >99% with a ratio of 22.32: 4.76:1:0.31 (a:b:c:d). This corresponds to 3.94:1 of the ortho:meta to fluor ine. Experimental for table 13 : Entry 1: [Ir(OMe)cod] 2 (3.3 mg, 0.005 mmol), HBpin (128 mg, 1 mmol), and dmadphz (2.8 mg, 0.01 mmol) were added into three separate test tubes. 2,6 - chlorofluoropyridine (66 mg , 1 mmol) was charged into a 20 ml vial equipped with a stir bar. To each test tube 434 0.25 mL THF was added. The HBpin solution was then transferred into the [Ir(OMe)cod] 2 and stirred by shaking the test tube until a golden ye llow clear solution was obtained (~30s). Next, the solution containing the [Ir(OMe)cod] 2 and HBpin was transferred into the test tube containing the dmadphz solution, and upon stirring by shaking the test tube the resulting solution turned a dark brown - red color. Finally, the contents of the test tube with the pre - generated catalyst were transferred into 20mL vial containing the substrate and magnetic stir bar. To ensure little to no transfer loss, 0.25 mL THF was added to test tube one then transferred to test tube two then to test tube three and finally to the reaction mixture. This procedure was repeated 3 times. This vial was then sealed. The reaction mixture stirred for at room temperature for 2 hours, after which the vial was taken out of the glove bo x. The solvent of the crude reaction mixture was then removed by rotary evaporation leaving a dark, blackish oil. By the 19 F NMR conversion was determined to be >99% with a ratio of 120:1.The NMR spectra matched the reported values. Entry 3: [Ir(OMe)cod] 2 (3.3 mg, 0.005 mmol), HBpin (128 mg, 1 mmol), and dmadphz (2.8 mg, 0.01 mmol) were added into three separate test tubes. 2 - chloro - 3 - fluoropyridine (66 mg , 1 mmol) was charged into a 20 ml vial equipped with a stir bar. T o each test tube 0.25 mL THF was added. The HBpin solution was then transferred into the [Ir(OMe)cod] 2 and stirred by shaking the test tube until a golden yellow clear solution was obtained 435 (~30s). Next, the solution containing the [Ir(OMe)cod] 2 and HBpin was transferred into the test tube containing the dmadphz solution, and upon stirring by shaking the test tube the resulting solution turned a dark brown - red color. Finally, the contents of the test tube with the pre - generated catalyst were transferred int o 20mL vial containing the substrate and magnetic stir bar. To ensure little to no transfer loss, 0.25 mL THF was added to test tube one then transferred to test tube two then to test tube three and finally to the reaction mixture. This procedure was repea ted 3 times. This vial was then sealed. The reaction mixture stirred for at room temperature for 2 hours, after which the vial was taken out of the glove box. The solvent of the crude reaction mixture was then removed by rotary evaporation leaving a dark, blackish oil. By the 19 F NMR conversion was determined to be 95% with a ratio of 1.7:1. The NMR spectra matched the reported values. Entry 5: [Ir(OMe)cod] 2 (3.3 mg, 0.005 mmol), HBpin (64 mg, 0.5 mmol), and dmadphz (2.8 mg, 0.01 mmol) were added into three separate test tubes. 1,4 - cyanofluorobenzene (242 mg , 2 mmol) was charged into a 20 ml vial equipped with a stir bar. To each test tube 0.5 mL THF was add ed. The HBpin solution was then transferred into the [Ir(OMe)cod] 2 and stirred by shaking the test tube until a golden yellow clear solution was obtained (~30s). Next, the solution containing the [Ir(OMe)cod] 2 and HBpin was transferred into the test tube c ontaining the dmadphz solution, and upon stirring by shaking the test tube the 436 resulting solution turned a dark brown - red color. Finally, the contents of the test tube with the pre - generated catalyst were transferred into 20mL vial containing the substrate and magnetic stir bar. To ensure little to no transfer loss, 0.5 mL THF was added to test tube one then transferred to test tube two then to test tube three and finally to the reaction mixture. This procedure was repeated 3 times. This vial was then seal ed. The reaction mixture stirred for at room temperature for 24 hours, after which the vial was taken out of the glove box. The solvent of the crude reaction mixture was then removed by rotary evaporation leaving a dark, blackish oil. By the 19 F NMR conver sion was determined to be >99% with a ratio of 1:9 a:b. The NMR spectra matched the reported values. Experimental for table 14 : Entry 2: [Ir(OMe)cod] 2 (3.3 mg, 0.005 mmol), B2pin2 (254 mg, 1 mmol), and dmadphz (2.8 mg, 0.01 mmol) were added into three separate test tubes. 1,3 - chlorofluorobenzene (65.3mg , 0.5 mmol) was charged into a 20 ml vial equipped with a stir bar. To each test tube 0.25 mL THF was added. The HBpin solution was then transferred into the [Ir(OMe)cod] 2 and stirred by shaking the test tube until a golden yellow clear solution was obtained (~30s). Next, the solution containing the [Ir(OMe)cod] 2 and HBpin was transferred into the test tu be containing the dmadphz solution, and upon stirring by shaking the test tube the resulting solution turned a dark brown - red color. Finally, the 437 contents of the test tube with the pre - generated catalyst were transferred into 20mL vial containing the subst rate and magnetic stir bar. To ensure little to no transfer loss, 0.25 mL THF was added to test tube one then transferred to test tube two then to test tube three and finally to the reaction mixture. This procedure was repeated 3 times. This vial was then sealed. The reaction mixture stirred for at room temperature for 2.5h hour, after which the vial was taken out of the glove box. The solvent of the crude reaction mixture was then removed by rotary evaporation leaving a dark, blackish oil. By the 19 F NMR conversion was determined to be >99% with a ratio of 2.1:1. Synthesis of hydrazone ligands: All hydrazone ligands are derived from a central ketone intermediate shown below. This ketone is derived from dimethylaminopyridi ne (dmap) over 2 steps. Initial routes to the ketone involved installing a bromine in the 2 - position of dmap. This 2 - bromodmap was isolated then reacted with n - BuLi for a lithium halogen exchange and trapped with half an equivalent of ethyl chloroformate. This last step has always been quite problematic giving extremely low yields and difficult to work up6. 438 Due to the problematic last step route 2 was proposed as a viable alternative. This route skips the bromination and goes instead to an ester. This ester when added to the lithiated dmap produces the desired ketone is decent yield. It should be noted that t he shown yields are the best over multiple runs. Most often the yields average to around 55% for both the first and second steps. Evidence suggests that using fresh ethyl chloroformate and sec - butyl lithium as opposed to n - butyl lithium may offer a one - ste p route to the desired ketone from dmap, but further exploration is necessary. Finally, phosgene may offer a one - step route as well, but to date the exotherm upon addition of lithiated dmap to phosgene has not been controlled. The experimental details for route 2 will be provided below, but this route can likely be optimized further. 439 Synthesis of ethyl 4 - (dimethylamino)picolinate To a 500 mL 3 - neck round bottom flask DMAP (3 g, 24.5 mmol) was added. The left neck was sealed with a rubber septum, through the middle neck was a mechanical stirrer, and a low temperature thermometer was in the right neck. Argon was flushed through the system for approximately 5 minutes. Approximately 200 m L THF from a sodium benzophenone dry still was added such that the thermometer was under the solvent level even when the stirring was vigorous. This solution was sparged for 10 minutes. The sparging was stopped, but positive pressure of argon was in place throughout the reaction. At this point BF 3 2 (3.7 mL,30 mmol) was added. Upon addition the clear 440 solution turned cloudy for an instant then went clear again. The temperature also rose approximately 5 C. This mixture was allowed to stir for approximatel y 30 min before being placed in an acetone dry ice bath. A s the solution temperature approached - 78 the solution turned cloudy white. After reaching - 78 , n - BuLi (18.25 mL of 1.6 M in hexanes, 29 mmol) was added drop wise taking care that all drops ent ered the solution and that the temperature never rose above - 73 . This process took about 25 minutes. After the addition of n - BuLi the solution looked opaque or cloudy light yellow. This solution was allowed to stir at - 78 for 1.5 hours. At this point the ethyl chloroformate (2.35 mL, 24.5 mmol) was added rapidly to the reaction. The addition took about 3 seconds. A large exotherm was observed the temperature increased by 15 then cooled back to - 78 . The reaction was then allowed to stir for 3.5 h ours after which 1 mL ethanol was added to the stirring reaction to quench it. Upon warming to room temperature, two phases separated, a bright yellow solid phase and liquid phase. The reaction was filtered through a medium frit using dry THF to aid transf er. The collected yellow solid is the BF 3 salt of the ester and is insoluble in THF making it difficult to use in the next step. BF 3 removal: The salt was dissolved in a minimum amount of water and transferred to a 250 mL sepratory funnel. Dilute HCl was added to bring the pH to approximately 2. If the NMR of the BF 3 salt showed impurity extract with DCM. If not, bring the pH up to 8 using dilute NaOH. It is important not to go above pH 8 because above pH 8 the extraction with DCM forms three layers. After bringing the solution to pH 8, DCM was used to extract the ester from the water layer. Concentration of the combined organic layers gave the 2 - dmap ethyl ester as a yellow liquid in 65% yield (3.1g). NMR are not known in the literature: 441 1 H NMR (500 MHz, c = 7.2, 3.0 Hz, 1H), 4.57 (q, J = 7.2 Hz, 2H), 3.33 (s, 6H), 1.54 (t, J = 7.1 Hz, 3H). 13 38.96, 14.18. S ynthesis of bis(dimethylaminopyridyl)methanone: To a 250 mL 3 - neck round bottom flask DMAP (1.36 g, 11.1 mmol) was added. The left neck was sealed with a rubber septum, through the middle neck was a mechanical stirrer, and a low temperature thermometer was in the right neck. Argon was flushed through the system for approximately 15 minutes. Approximately 120 mL THF from a sodium benzophenone dry still was added such that the thermometer was under the solvent level even when the stirring was vigorous. This solution was sparged for 10 minutes. The sparging was stopped, but positive pressure of argon was in place throughout the reaction. At this point BF 3 2 (1.68 mL, 13.6 mmol) was added. Upon addition the clear solution tur ned cloudy for an instant then went clear again. The temperature also raised approximately 5 . This mixture was allowed to stir for approximately 30 min before being placed in an acetone dry ice bath. As the solution temperature approached - 78 the solution turned cloudy white. After reaching - 78 , n - BuLi (18.25 mL of 1.6 M in hexanes, 29 mmol) was added drop wise taking care that all drops entered the solution and that the temperature never rose above - 73 . This process took about 25 minute s. After the 442 addition of n - BuLi the solution looked opaque or cloudy light yellow. This solution was allowed to stir at - 78 for 1.5 hours. At this point the 2 - ethyl ester dmap (2.17 g, 11.1 mmol) was dissolved in 5mL THF and added rapidly to the reactio n via syringe. The addition took about 5 seconds. A large exotherm was observed the temperature increased by 10 then cooled back to - 78 . The reaction was then allowed to stir for 3.5 hours after which 1 mL ethanol was added to the stirring reaction t o quench it. Upon warming to room temperature, two phases separated, a bright yellow solid phase and liquid phase. The reaction was filtered through a medium frit using dry THF to aid transfer. The collected yellow solid is the BF 3 salt of the ketone. BF 3 removal: The salt was dissolved in a minimum amount of water and transferred to a 250 mL sepratory funnel. Dilute HCl was added to bring the pH to approximately 2. If the NMR of the BF 3 salt showed impurity extract with DCM. If not, bring the pH up to 8 us ing dilute NaOH. It is important not to go above pH 8 because above pH 8 the extraction with DCM forms three layers. After bringing the solution to pH 8, DCM was used to extract the ester from the water layer. Concentration of the combined organic layers g ave the desired ketone as a yellow solid in 75% yield (2.25g). It should be noted that more advanced ways of removing the BF 3 have been developed and are being explored/optimized. One of these methods uses a 10% ethylene glycol solution in KOH. Washing wi th this solution, shaking and extracting with DCM seems to remove the BF 3 every time with decent recovery from the solution. NMR Spectra match previously reported compound6: 1 .56(dd, J = 5.9, 2.7 Hz, 1H), 3.05 (s, 6H). 443 13 Synthesis of dimethylaminodipyridyl hydrazone (dmadphz): A 20 mL pressure tube was charged with ketone (300 mg, 1.1 mmol) and a stir bar. Approximately 10 mL ethanol and acetic acid (0.25 mL, 4.4 mmol) were added. This reaction was heated and stirred for approximately 15 minutes at which time the hydrazine mon ohydrate was added (0.22 mL, 4.4 mmol). Upon addition of the hydrazine the solution went from cloudy to clear. This vessel was sealed and heated at 80 for 24 hours. After 24 hours the reaction was allowed to cool to room temperature while stirring. The vessel was opened and the reaction mixture was transferred to a round bottom. The volatiles were rotovapped away. Before all the solvent was evaporated a white solid began to form. This solid was dried on high vac and NMR was taken showing complete conver sion. The solid was taken into water and extracted with DCM. The combined organic layers gave a 88% yield (277 mg a light brown solid). It should be noted that there may be a better route to this product . The NMR is not known previously in the literature : 1 2H), 7.03 (d, J = 2.6 Hz, 1H), 6.53 (d, J = 2.6 Hz, 1H), 6.46 (dd, J = 6.0, 2.7 Hz, 1H), 6.43 (dd, J = 6.0, 2.7 Hz, 1H), 3.02 (s, 6H), 2.94 (s, 6H). 444 13 C NMR (126 MHz 108.07, 106.10, 105.71, 104.99, 39.22, 39.11. m.p: 195 Synthesis of dimethylaminodipyridyl methylhydrazone: A 100 mL round bottom flask was charged with ketone (400 mg, 1.48 mmol) and a stir bar. Approximately 30 mL ethanol was added followed by the methylhydrazine (0.465 mL, 8.8 mmol, 6 equivalents). The flask was equipped with a condenser and the reaction was refluxed for 24 hours. Crude NMR showed near ly quantitative conversion to the methylhydrazone product with some small peaks present. The reaction mixture was concentrated then passed through a basic alumina plug with DCM then 1:1 EtOAc:MeOH. The resulting yellow solid was further purified by recryst allization from acetone. Finally giving a 52% yield (228 mg). It is likely that the alumina plug is not necessary since the recrystallization seemed to work so well. NMR not known previously in the literature: 1 (dd, J = 5.9, 0.5 Hz, 1H), 7.00 (d, J = 2.6 Hz, 1H), 6.58 (d, J = 2.6 Hz, 1H), 6.42 (ddd, J = 7.0, 6.0, 2.7 Hz, 2H), 3.19 (d, J = 3.6 Hz, 3H), 3.03 (s, 6H), 2.92 (s, 6H ). 13 107.64, 105.72, 105.45, 105.28, 39.22, 39.09, 38.04. Synthesis of dimethylaminodipyridyl dimethylhydrazone: 445 A 50 mL round bottom flask was charged with stir bar and ketone (90 mg, 0.33 mmol) added to this was enough dimethylhydrazine to partially solubilize the ketone approximately 3 mL. The reaction vessel was sealed and stirred at room temperature for 24 hours. The volatiles were remov ed by rotovap followed by high vac. The NMR of the crude showed quantative conversion with extra undesired peaks thus the reaction crude was dissolved in DCM and water 1:1 and extracted into the organic layer. This gave the desired dimethylhydrazone in 83 % yield (86 mg). There is a milder route to this product developed by a lab mate. NMR not known previously in the literature: 1 = 2.6 Hz, 1H), 6.69 (d, J = 2.6 Hz, 1H), 6.43 (dd, J = 6.0, 2.7 Hz, 1H), 6.37 (dd, J = 6.0, 2.7 Hz, 1H), 2.98 (s, 7H), 2.96 (s, 6H), 2.70 (s, 6H). 13 C NMR (126 MHz, cd 107.86, 105.78, 105.65, 104.86, 47.51, 39.18, 39.13. mp: 110 Experimental for table 15 : Entry 1 446 [Ir(OMe)cod] 2 (3.3 mg, 0.005 mmol), HBpin (128 mg, 1 mmol), and dimethylhydrazone ligand (3.1 mg, 0.01 mmol) were added into three separate test tubes. 1,3 - dicyanobenzene (64 mg , 0.5 mmol) was charged into a 20 ml vial equipped with a stir bar. To each test tube 0.25 mL THF was added. The HBpin solution was then t ransferred into the [Ir(OMe)cod] 2 and stirred by shaking the test tube until a golden yellow clear solution was obtained (~30s). Next, the solution containing the [Ir(OMe)cod] 2 and HBpin was transferred into the test tube containing the dmadphz solution, a nd upon stirring by shaking the test tube the resulting solution turned a dark brown - red color. Finally, the contents of the test tube with the pre - generated catalyst were transferred into 20mL vial containing the substrate and magnetic stir bar. To ensure little to no transfer loss, 0.25 mL THF was added to test tube one then transferred to test tube two then to test tube three and finally to the reaction mixture. This procedure was repeated 3 times. This vial was then sealed. The reaction mixture stirred for at room temperature for 24 hours, after which the vial was taken out of the glove box. The solvent of the crude reaction mixture was then removed by rotary evaporation leaving a dark, blackish oil. By the 1 H NMR conversion was determined to be 13% wit h no discernible electronic product. 447 Entry 2: [Ir(OMe)cod] 2 (3.3 mg, 0.005 mmol), HBpin (128 mg, 1 mmol), and dimethylhydrazone ligand (3.1 mg, 0.01 mmol) were added into three separate test tubes. 1,3 - chlorofluorobenzene (65.3mg , 0.5 mmol) was charged into a 20 ml vial equipped with a stir bar. To each test tube 0.25 mL THF was added. The HBpin solution was then transferred into the [Ir(OMe)cod] 2 and stirred by shaking the test tube until a golden yellow clear solution was obtained (~30s). Next, the solution containing the [Ir(OMe)cod] 2 and HBpin was transferred into the test tube containing the dmadphz solution, and upon stirring by shaking the test tube the resulting solution turned a dark brown - r ed color. Finally, the contents of the test tube with the pre - generated catalyst were transferred into 20mL vial containing the substrate and magnetic stir bar. To ensure little to no transfer loss, 0.25 mL THF was added to test tube one then transferred t o test tube two then to test tube three and finally to the reaction mixture. This procedure was repeated 3 times. This vial was then sealed. The reaction mixture stirred for at room temperature for 12 hours, after which the vial was taken out of the glove box. The solvent of the crude 448 reaction mixture was then removed by rotary evaporation leaving a dark, blackish oil. By the 19 F NMR conversion was determined to be 96% with a ratio of 3:1. Entry 3: [Ir(OMe)cod] 2 (3.3 mg, 0 .005 mmol), HBpin (128 mg, 1 mmol), and dimethylhydrazone (3.1 mg, 0.01 mmol) were added into three separate test tubes. 3 - fluorotoluene (55 mg , 0.5 mmol) was charged into a 20 ml vial equipped with a stir bar. To each test tube 0.25 mL THF was added. The HBpin solution was then transferred into the [Ir(OMe)cod] 2 and stirred by shaking the test tube until a golden yellow clear solution was obtained (~30s). Next, the solution containing the [Ir(OMe)cod] 2 and HBpin was transferred into the test tube containi ng the ligand solution, and upon stirring by shaking the test tube the resulting solution turned a dark brown - red color. Finally, the contents of the test tube with the pre - generated catalyst were transferred into 20mL vial containing the substrate and mag netic stir bar. To ensure little to no transfer loss, 0.25 mL THF was added to test tube one then transferred to test tube two then to test tube three and finally to the reaction mixture. This procedure was repeated 3 times. This vial was then sealed. The reaction mixture stirred for at room temperature for 24 hours, after which the vial was taken out of the glove box. The solvent of the crude reaction mixture was then removed by rotary evaporation leaving 449 a dark, blackish oil. By the 19 F NMR conversion wa s determined to be 54% with a ratio of 2:1. E ntry 4: [Ir(OMe)cod] 2 (3.3 mg, 0.005 mmol), HBpin (128 mg, 1 mmol), and methylhydrazone ligand (3.0 mg, 0.01 mmol) were added into three separate test tubes. 1,3 - chlorofluorobe nzene (65.3mg , 0.5 mmol) was charged into a 20 ml vial equipped with a stir bar. To each test tube 0.25 mL THF was added. The HBpin solution was then transferred into the [Ir(OMe)cod] 2 and stirred by shaking the test tube until a golden yellow clear solut ion was obtained (~30s). Next, the solution containing the [Ir(OMe)cod] 2 and HBpin was transferred into the test tube containing the ligand solution, and upon stirring by shaking the test tube the resulting solution turned a dark brown - red color. Finally, the contents of the test tube with the pre - generated catalyst were transferred into 20mL vial containing the substrate and magnetic stir bar. To ensure little to no transfer loss, 0.25 mL THF was added to test tube one then transferred to test tube two the n to test tube three and finally to the reaction mixture. This procedure was repeated 3 times. This vial was then sealed. The reaction mixture stirred for at room temperature for 27 hours, after which the vial was taken out of the glove box. The solvent o f the crude reaction mixture 450 was then removed by rotary evaporation leaving a dark, blackish oil. By the 19 F NMR conversion was determined to be 68% with a ratio of 4:1. Entry 5 [Ir(OMe)cod] 2 (3.3 mg, 0.005 mmol), HBpin (128 mg, 1 mmol), and methylhydrazone ligand (3.0 mg, 0.01 mmol) were added into three separate test tubes. 1,3 - dicyanobenzene (64 mg , 0.5 mmol) was charged into a 20 ml vial equipped with a stir bar. To each test tube 0.25 mL THF was added. The HBpin solution was then transferred into the [Ir(OMe)cod] 2 and stirred by shaking the test tube until a golden yellow clear solution was obtained (~30s). Next, the solution containing the [Ir(OMe)cod] 2 and HBpin was transferred into the test tube containing the ligand solution, and upon stirring by shaking the test tube the resulting solution turned a dark brown - red color. Finally, the contents of the test tube with the pre - generated catalyst were transferred into 20mL vial containing th e substrate and magnetic stir bar. To ensure little to no transfer loss, 0.25 mL THF was added to test tube one then transferred to test tube two then to test tube three and finally to the reaction mixture. This procedure was repeated 3 times. This vial w as then sealed. The reaction mixture stirred for at room temperature for 15 hours, after 451 which the vial was taken out of the glove box. The solvent of the crude reaction mixture was then removed by rotary evaporation leaving a dark, blackish oil. By the 1 H NMR conversion was determined to be 63% with a 4:1 ratio. Example of calculating NMR conversion Table 12 Entry 4: Ratio:2:1 Experimental for Scheme 31 : HBpin and dmadphz without iridium 452 To a J - Young NMR tube was added dmadphz (0.1 mmol, 25 mg), HBpin (0.15 mmol, 19 mg, 22 µL) and THF (0.6 mL). To this tube was added 1 drop of THF - d 8 . The NMR tube was sealed and mixed by inversion. 11 B NMR were collected at the 6h, 21h, 31h, 48h, 144h time points. The data is shown below. HBpin and dmadphz with iridium 453 To a J - Young NMR tube was added dmadphz (0.1 mmol, 25 mg), HBpin (0.11 mmol, 14 mg, 16 µL) and THF (0.6 mL). To this tube was added 1 drop of THF - d8 . The NMR tube was sealed and mixed by inversion. 11 B NMR were collected at the 30 min. The data is shown below. HBpin and dmadphz with iridium: no evidence of N,N - diborylation To a J - Young NMR tube was added dmadphz (0.1 mmol, 25 mg), HBpin (0.11 mmol, 14 mg, 16 µL) and THF (0.6 mL). To this tube was added 1 drop of THF - d8 . The NMR tube was sealed and mixed by inversion. 11 B NMR were collected at 12. The data is shown below. Only a single sharp boron has that was observed previously appeared and by integration the remainder of the boron is accounted for as HBpin. 454 5 .10: Notes The initial isolation and borylation with the active hydrazone ligand was conducted by Suzi Miller. 455 APPENDIX 456 1 H NMR (CDCl 3 , 500 MHz) 457 13 C NMR (CDCl 3 , 126 MHz) 458 1 H NMR (CDCl 3 , 500 MHz) 459 13 C NMR (CDCl 3 , 126 MHz) 460 1 H 13 C NMR (CDCl 3 , 500 MHz) 461 13 C NMR (CDCl 3 , 126 MHz) 462 1 H NMR (CDCl 3 , 500 MHz) 463 13 C NMR (CDCl 3 , 126 MHz) 464 REFEREN C ES 465 REFERENCES (1) Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.; Murphy, J. M.; Hartwig, J. F. Chem. Rev. 2010 , 110 (2), 890. (2) Boller, T. M.; Murphy, J. M.; Hapke, M.; Ishiyama, T.; Miyaura, N.; Hartwig, J. F. J. Am. Chem. Soc. 2005 , 127 (41), 14263. (3) Ros, A.; Fernández, R.; Lassaletta, J. M. Chem. Soc. Rev. 20 14 , 43 (10), 3229. (4) Roosen, P. C.; Kallepalli, V. A.; Chattopadhyay, B.; Singleton, D. A.; Maleczka, R. E., Jr; Smith, M. R., 3rd. J. Am. Chem. Soc. 2012 , 134 (28), 11350. (5) Preshlock, S. M.; Plattner, D. L.; Maligres, P. E.; Krska, S. W.; Maleczka, R. E.; Smith, M. R. Angew. Chem. Int. Ed. 2013 , 52 (49), 12915. (6) Smith, M. R., 3rd; Bisht, R.; Haldar, C.; Pandey, G.; Dannatt, J. E.; Ghaffari, B.; Maleczka, R. E., Jr; Chattopadhyay, B. ACS Catal. 2018 , 8 (7), 6216. (7) Kuninobu, Y.; Ida, H.; Nishi, M.; Kanai, M. Nat. Chem. 2015 , 7 (9), 712. (8) Li, H. L.; Kuninobu, Y.; Kanai, M. Angew. Chem. Int. Ed Engl. 2017 , 56 (6), 1495. (9) Li, H. - L.; Kanai, M.; Kuninobu, Y. Org. Lett. 2017 , 19 (21), 5944. (10) Mihai, M. T.; Davis, H. J.; Genov, G. R.; Phipps, R. J. ACS Catal. 2018 , 8 (5), 3764. (11) Davis, H. J.; Mihai, M. T.; Phipps, R. J. J. Am. Chem. Soc. 2016 , 138 (39), 12759. (12) Chattopadhyay, B.; Dannatt, J. E.; Andujar - De Sanctis, I. L.; Gore, K. A.; Maleczka, R. E., Jr; Singleton, D. A.; Smith, M. R., 3rd. J. Am. Chem. Soc. 2017 , 139 (23), 7864. (13) Xu, L.; Wang, G.; Zhang, S.; Wang, H.; Wang, L.; Liu, L.; Jiao, J.; Li, P. Tetrahedron 2017 , 73 (51), 7123. (14) Wang, J.; Sánchez - Roselló, M.; Aceña, J. L.; del Pozo, C.; Sorochinsky, A. E.; Fustero, S.; Soloshonok, V. A.; Liu, H. Chem . Rev. 2014 , 114 (4), 2432. (15) Gillis, E. P.; Eastman, K. J.; Hill, M. D.; Donnelly, D. J.; Meanwell, N. A. J. Med. Chem. 2015 , 58 (21), 8315. 466 (16) Ilardi, E. A.; Vitaku, E.; Njardarson, J. T. J. Med. Chem. 2014 , 57 (7), 2832. (17) Miller, S . L. Iridium Catalyzed C H Borylation of Arenes: Engineering Selectivity by Ligand Design; Ph.D Dissertation, Michigan State University, East Lansing, MI, 2017. (18) Green, A. G.; Liu, P.; Merlic, C. A.; Houk, K. N. J. Am. Chem. Soc. 2014 , 136 (12), 4575. (19) Britt A. Vanchura, I. I.; Preshlock, S. M.; Roosen, P. C.; Kallepalli, V. A.; Staples, R. J.; Maleczka, R. E., Jr; Singleton, D. A.; Milton R. Smith, I. Chem. Commun. 2010 , 46 (41), 7724. (20) Porter, G. R.; Rydon, H. N.; Schofield, J. A. J. Chem. Soc. 1960 , No. 0, 2686. (21) Menger, F. M.; Singh, T. D.; Bayer, F. L. J. Am. Chem. Soc. 1976 , 98 (16), 5011. (22) Sooväli, L.; Rodima, T.; Kaljurand, I.; Kütt, A.; Koppel, I. A.; Leito, I. Org. Biomol. Chem. 2006 , 4 (11), 2100. (23) Ahn, S.; Sorsche, D.; Berritt, S.; Gau, M. R.; Mindiola, D. J.; Baik, M. - H. ACS Catal. 2018 , 8 (11), 10021. 467 Chapter 6: Synthesis and Study of Double - Decker Shaped Silsesquioxanes 6.1: Background and introduction Functionalized double - decker shaped silsesquioxane (DDSQ - 2(R 1 R 2 )), and corner capped cubic shaped silsesquioxanes (POSS - R 1 ) (Figure 10 ) are cage - like silsesquioxanes with a dimensionally well - defined inorganic core, inert organic groups around the core which provides compatibility with the surround organic matter of interest, and exact specified reactive organic sites. 1,2 Figure 13 . Structure of cis/trans - DDSQ - 2(R 1 R 2 ) and POSS - R 1 where R are inert organic moieties and R 1 and R 2 are active functional groups These structures have become model compounds to investigate effects of nanostructured inorganic additives on polymer properties. 3 - 7 Applications of both DDSQ - 2(R 1 R 2 ) and POSS - R 1 nanostructures have been explored extensively. 1,3 - 5,8 - 30 When used in organic polymers, the hybrid characteristics provide enhanced oxidation tempera ture, improved hydrophobicity, and low dielectric constant. 10 - 14,19,29,31 - 36 Recent research extended the use of DDSQ - 2(R 1 R 2 ) and POSS - R 1 as supports to reduce the amount of packed bed required in heterogenous catalysts. 5,10,37 - 40 Other applications for P OSS - R 1 include improved ionic liquid performance and its thermal stability, 34,41 - 43 microstructure modifier to improve mechanical performance of metallic alloys, 25 superhydrophobicity in coatings, 27,44 - 46 monomer for increased thermal and mechanical 468 perfo rmance of thermosetting polymers, 47 - 50 and use in pharmaceutical applications. 45,51 - 54 Given the impressive use and application of silsesquioxane nanostructrues, it becomes obvious that these compounds offer a wide range of possible property enhancements. However, to achieve this enhancement a user must consider two important factors. First, how will the silsesquioxane additive interact with the system it is integrated into and second what is the best method of dispersing this additive into th e system. The remainder of this chapter will discuss in detail these two factors for one specific silsesquioxane system. 6.2: Selecting a DDSQ target To select a synthetic DDSQ target, first a reasonable application must be located. We started by consideri ng thermoset polymers used in aerospace materials. Thermoset polymers are usually generated from prepolymeric materials or resins. These resins are often viscous liquids or soft solids that can be molded. Once in the mold, the resin is in the shape of the desired product and a curing process can occur. This irreversibly hardens the material by extensively cross linking of the prepolymeric material. The curing process is commonly induced by heating the material hence the name thermoset as the polymer fully s ets itself after heating. 55 Thermoset polymers find applications in a wide range of markets including aerospace applications. Materials specifically used in the aerospace industry must tolerate extreme conditions. For example in low earth orbit (LEO) many organic based materials rapidly breakdown by oxidation due to the high concentration of O 2 at altitudes of 300 to 700 km. 56,57 Furthermore, significant heat and pressure is generated in not only reaching this altitude, but also returning back to earth. 58 A s such 469 materials used in aerospace applications must exhibit high glass transition temperatures, excellent thermal and oxidative stability, and withstand temperatures in excess of 300 o C all while maintaining mechanical stability. 59 dcapped poly(oligoimide) resins exhibit many of these desirable characteristics (Scheme 1A). 60 - 62 This can be attributed to both the ability for the terminal ethynyl group to cross link during curing and to the rigid imide linkers between the ethynyl group s. 63,64 Unfortunately, these materials offer significant draw backs in terms of processability due to their high viscosity. Given the extreme environments these thermoset polymers must operate under, any additive to improve processability must at minimum t olerate these conditions and ideally would improve thermal and oxidative stability. This offers an excellent opportunity to explore silsesquioxane additives. Silsesquioxanes are known for their oxidative and thermal stability; thus, they will not compromis e and may indeed improve the material properties. Furthermore, it has been shown that phenyl POSS can modify viscosity in high temperature polymers. 65,66 Overall, silsesquioxane additives may impart improved properties and processability. With this in min d, we selected compound 1 as a desired DDSQ target (Scheme 32 B). Compound 1 has many structural similarities to phenyl POSS while also containing phenyl ethynyl groups to cross link to the polymer. Ideally, this hybrid compound should provide lower viscosi ty while maintaining material strength via participation in the ethynyl cross linking. 470 Scheme 32 - 1) B) Structure of Phenyl POSS and designed DDSQ additive 1 6.3: Synthesis of compound 1 With a desired target it hand, we set about the synthesis. To accomplish this, we considered the retrosynthetic approach shown in scheme 33 . Compound 1 could be produced from a standard capping rea ction with DDSQ tetrasilanol 3 and the appropriate dichlorosilane 2 . Compound 3 is commercially available or can be produced from phenyltrimethoxysilane. The dichlorosilane, on the other hand, is not commercially available. We envisioned that this intermed iate could be generated from a Grignard reaction between compound 4 and methyltrichlorosilane. Compound 4 can then be accessed by traditional Sonogashira cross coupling. 471 Scheme 33 : Retrosynthetic analysis of compound 1 Ideally, a one - pot two step sequence from isolated compound 4 to the desired capped DDSQ could be achieved. This would avoid isolation of the sensitive dichlorosilane intermediate. To test th e potential for this strategy, optimal conditions for the Sonogashira cross coupling were first found. Based on prior results, nickel catalyzed conditions were initially explored (Table 1 6 ). 67 Unfortunately, reproduction of the prior reactivity was not ob served. Increased reaction time, catalyst loading, and using a separate source of the same nickel catalyst all failed to provide the desired reactivity. In fact, only about three catalytic turnovers were achieved in all conditions explored. 472 Table 16 : Nickel catalyzed Sonogashira cross - coupling a New bottle of nickel catalyst. Given the low reactivity of the nickel catalysts a traditional palladium Sonogashira was considered. Conditions were loc ated that provide full conversion to the desired product which was then isolated in 96% yield at a 100 g scale (scheme 34 ). Scheme 34 : Palladium catalyzed Sonogashira With a reliable procedure to compound 4 , we next considered the one - pot 2 - step synthesis of the compound 1 . Initially, we set out to verify a smooth transition from aryl bromide to dichlorosilane 2 (Scheme 35 ). The Grignard formation proceeded to completio n as judged by analysis of methanol quenched aliquots of the reaction mixture. This Grignard was then cannula transferred into methyltrichlorosilane, and after 10 h solvents and excess chlorosilane were removed by vacuum distillation leaving a yellow stick y solid. Analysis of this solid by 29 Si NMR revealed a single peak at 18.15 ppm. This 473 data along with 1 H NMR spectra with all the expected protons and only one major methyl peak led us to conclude compound 2 was generated in high overall conversion. Scheme 35 : Synthesis of dichlorosilane 2 Next, addition of crude 2 to the appropriate amount of compound 3 under standard chlorosilane capping conditions was carried out. Unfortunately, this led to the generation of a complex mixture of silsesquioxane products. Based on the 29 Si NMR, the silsesquioxane cage was intact; however, multiple cage - like products were formed. All attempts at separation were unsuccessful. We suspect that the magnesium salts from the Grignard reaction cause significant issues in the capping reaction. Based on the crystal structure of 3 , the oxygen - oxygen distance for the diol is 2.78 Å. This distance is close enough that magnesium can likely bind tightly and interfere with the desired reactivity. Scheme 36 : Synthesis of compound 1 474 Given the difficulty in separating compound 1 from the other cage like structures, we set about isolating the dichlorosilane. In general, chlorosilanes are isolated by distillation; however, attempts to distill the crude reaction from scheme 35 provided si gnificant charring. During the distillation attempts, it was noticed that a small amount of white solid moved up the side of the flask before charring. This provided evidence that sublimation may be effective in separating the chlorosilane from the reactio n mixture. Indeed, upon sublimation, a 53% isolated yield of pure dichlorosilane 2 was achieved. With isolated compound 2 , addition to the 3 provided the desired product in 78% yield as a cis/trans mixture. 6.4: Tuning melting points to disperse DDSQ addi tives With a working synthetic route to 1 in hand, we next considered the optimal method to disperse this new additive into the desired matrix. Incorporation into organic polymers without the use of solvents is one such environmentally friendly technique and has been achieved by melting the nanostructures. 28,32,68,69 Thus, we sought to understand the melt characteristics of 1 . It is worth commenting that when capping compound 3 with a dichlorosilane, if the two R groups on the silane are distinct, then the resulting product will be a 50/50 mixture of cis/trans isomers (Scheme 37 ). To gain understanding of the melt characteristics, the isomers must be separated. Scheme 37 : Condensation of 3 with two equivalents of organo - dichlorosilanes 475 Separation of cis and trans DDSQ - 2 (R 1 R 2 ) isomers using fractional crystallization (FC), and/or liquid chromatography (LC) has been achieved. 8,70 In this work we investigate the difference in melting temperatures of cis/trans 1 at select ratios. Results from the differential scanning calorimetry (DSC) were then used to construct the upper portion of the cis - trans binary phase diagram. The resulting binary phase diagram can be used to tailor a specified cis to trans ratio for optimizing the condition needed for melt mixing with organic polymers. 6.5: Separation and identification of DDSQ cis/trans isomers Trans and cis DDSQ - 2((Me)(R)) isomers can be obtained by fractional crystallization; 70 however, the ease of isolating cis or trans isomers varies depending on the R - group. In general, as - synthesized DDSQ - 2 ((Me)(R)) mixtures are dissolved in THF, and addition of hexanes results in crystallization and precipitation of the trans isomers. This in turn enriched the solution with the cis isomer. The isolation process can then be repeated until sufficiently isomerically pure compounds are obtained. Isolation of cis and trans i somers by FC was readily achieved for 1 . 476 Figure 14 : 29 Si NMR peaks representing the isomers after separation; a) cis - 1, b) trans - 1 Isolated isomers were recrystallized by slow evaporation of THF to form high quality single crystals suitable for crystallographic analysis. We obtained crystallographic data for each isomer; however, it should be noted that these structures were previously reported. 71 Data from these crystal structu res are shown in Table 17 . Crystalline packing density for the cis isomer is less than for the trans isomer. Based on the differences in the crystal structures and the ease at which the trans isomer separated from the cis, we hypothesized that these compounds may not be miscible in the solid state. If this was the case, they would exhibit eutectic behavi or at some ratio of these two compounds. This could be determined by evaluating the melting behavior at varied ratios of the isomers, but first analysis ot the separate isomers was conducted. Table 17 : Characteristics of crystal structures of individual isomers Compound Density (g/cm 3 ) Crystal system Space group Unit cell axes dimension ( Å) Unit Cell inclination angles (°) cis - 1 1.321 Triclinic P 1 (2) a 14.44 85.92 b 14.90 74.70 c 18.54 79.89 trans - 1 1.341 Triclinic P 1 (2) a 10.77 91.39 b 13.45 108.68 c 13.61 91.69 477 6.6: Thermal behavior of DDSQ isomers Melting behavior as expressed in DSC trace for pure compounds is usually observed as a single sharp endothermic peak in which the onset temperature (T onset ) is very similar to the peak temperature (T peak ). This was observed for trans - 1 indicating the purit y of these samples was >95% based on the difference between T onset and T peak and the 29 Si NMR spectra shown in Figure 1 1 . However , for cis - 1 a 7 °C difference in T onset and T peak was large enough to indicate this compound may not be as pure as suggested by 29 Si NMR. Melting temperatures (T m ) calculated from the T onset in the endo peak were higher for trans isomers than for cis isomers as seen in Table 18 . The calculated entropy at m ) for trans isomers is higher than cis isomers. This suggests the solid state of the trans isomer is more ordered than that of the cis isomer. Table 18 : Experimental values obtained from cis and trans DDSQ - 2 ((Me)(R)) by m m /T m Compound T peak (°C) T m (°C) m (kJ/mol) m (J/mol K) cis - 1 269.9 263.1 46.7 87 trans - 1 302.7 300.0 63.7 128 6.7: Solid - liquid phase equilibrium of compound 1 The isomers were physically mixed, solubilized in THF and dried using a dynamic vacuum. Three mixtures were prepared with x trans = 0.3, 0.5, and 0.7. DSC traces for cis/trans isomers and their binary mixtures can be observed in Figure 12 a . The trace for x t rans = 0.3 has a single relatively sharp peak. In contrast, traces for x trans = 0.5 and 0.7 have two endo peaks although the second endo peak in the 0.5 mixture is small.. For these traces, T liquidus decreased as the fraction of cis isomer increased in the sample. T onset in the first endotherm transition for x trans = 0.5 and 0.7 is similar to that of x trans = 0.3. 478 This result is distinguishing for eutectic temperature. T onset of cis is higher than T onset of x trans = 0.3 confirming the existence of a eutectic composition close to x trans = 0.3. The calculated phase diagram is close to the collected data indicating proximity to ideal eutectic behavior for compound 3 . In Figure 12 b a re plotted the eutectic temperature and liquidus temperature for each mixture as well as the solid - liquid phase diagram. DSC traces for nearly - pure cis and nearly - pure trans in Figure 12 a are similar to the same traces reported in a prior study. 71 However, the DSC trace for x trans = 0.5 is inconsistent between this and work reported by Moore et al. as they overlooked the existence of the eutectic reaction. 71 Figure 15 : a) DSC curves for compound 3. Every curve was normalized for better identification of peaks. b) Binary phase diagram for structure 3. Green dots ( ) are the onset temperatures of the first endothermic transition in DSC trace. Blue squares ( ) represent t he peak temperature of the highest endothermic transition. The solid line represents the ideal eutectic as calculated using Equation 1; dashed line ( --- ) represents the calculated eutectic temperature T E. . Phase I: L ( cis + trans ) ; Phase II: L ( cis + trans ) + S cis ; Phase III: L ( cis + trans ) + S trans ; Phase IV: S cis + S trans . 6.8: Conclusions Overall, silsesquioxane type additives can offer significant property enhancement and find use in diverse array of applications. While it is possible to screen these additives 479 against many potential polymer and material systems, a more rational design - base d approach is also possible. For a specific case, this chapter demonstrates the logic behind how to select and design one potential silsesquioxane additive. With the designed additive in mind the remainder of the study focuses on 1) the synthetic route to the additive and 2) an exploration of one method to incorporate the additive into a material matrix. In terms of the synthesis, it was discovered that both a nickel catalyzed Sonogashira and one - pot two step synthesis of the final product are not operative . However, with standard palladium catalysts and by isolation of dichlorosilane 2 via sublimation, compound 1 was isolated in our labs for the first time. Finally, after separation of the cis/trans isomers a eutectic temperature was observed. The eutectic composition was located near x trans = 0.3, and the eutectic temperature was approximately 50 °C lower than the melting temperature of the trans isomers. As future work, these compounds will be added into e if viscosity, oxidative and thermal stability, and mechanical strength are improved. 6.9 Experimental Details All commercially available chemicals were used as received unless otherwise indicated. (C 6 H 5 ) 8 Si 8 O 10 (OH) 4 5,11,14,17 - tetra(hydro)octaphenyltetr acyclo[7.3.3. - 3 3,7 ]octasilsesquioxane (DDSQ - (Ph) 8 (OH) 4 ) 3 was purchased from Hybrid Plastics. Methyltrichlorosilane, 4 - [bis(trimethylsilyl)amino]phenyl( bromo )magnesium, 4 - bromoiodobenzene , phenylacetylene, phenylmethyldichlorosilane, Pd(PPh 3 ) 2 Cl 2 , CuI, activated magnesium turnings, CDCl 3 with 1% TMS, dichloromethane (DCM), hexanes, ethyl acetate, and THF were all purchased from commercial sources. THF was refluxed over sodium/benzophenone ketyl and distilled . Column chromatography was performed 480 on Silia P - Flash silica gel. Thin layer chromatography was performed on 0.25 mm thick aluminum - backed silica gel plates and visualized with ultraviolet light (254 nm). Sublimations were conducted with a water - cooled co ld finger. 1 H, 13 C, and 29 Si NMR spectra were recorded on 500 MHz NMR spectrometers. Thermal behavior of isomers with purities superior to 95%, or nearly - pure isomers, and mixtures of cis and trans isomers was studied by DSC Q2000 equipped with a mechanica l cooling accessory. Typically, the temperature range of investigation was from 50 °C to 350 °C with a constant heating rate of 10 °C/min. Synthesis of 1 - bromo - 4 - (phenylethynyl)benzene with a nickel catalyst Table 1 6 Entry 1 To a 250 mL round bottom flask was added 4 - bromoiodobenzene (2.83 g, 10 mmol, 1 equiv), K 2 CO 3 (2.76 g, 20 mmol, 2 equiv), Ni(PPh 3 ) 2 Cl 2 (0.327 g, 0.5 mmol, 5 mol %), CuI (0.1904 g, 1.0 mmol, 10 mol %), and a stir bar. The flask was then fitted with a reflux condenser before 30 mL dioxane and 10 mL H 2 O was added . This mixture was then heated at 115 o C for 5 min before phenylacetylene (1.32 mL, 12 mmol, 1.2 equiv) was added. The reaction was allowed to stir for 17 hours at reflux. At the end of the reaction, the majority of the solvent was removed by vacuum distillation, and the resulting mixture was extracted with DCM/H 2 O. The organic layer was dried with magnesium 481 sulfate and concentrated and the resultant solid was analyzed by GCMS. This showed 16% conversion to the desired product. Table 1 6 Entry 2 and 3 To a 250 mL round bottom flask was added 4 - bromoiodobenzene (2.83 g, 10 mmol, 1 equiv), K 2 CO 3 (2.76 g, 20 mmol, 2 equiv), Ni(PPh 3 ) 2 Cl 2 (0.327 g, 0.5 mmol, 5 mol %), CuI (0.1904 g, 1.0 mmol, 10 mol %), and a stir bar. The flask was then fitted with a reflux condenser before 50 mL dioxane and 10 mL H 2 O was added . This mixture was then heated at 115 o C for 5 min before phenylacetylene (1.32 mL, 12 mmol, 1.2 equiv) was added. The reaction was allowed to stir for 24 hours at reflux. At this point an alloquat was removed and GCMS was collected. This showe d 18% conversion to the product. The reaction mixture was allowed to reflux for another 98 h. At the end of the reaction, the majority of the solvent was removed by vacuum distillation, and the resulting mixture was extracted with DCM/H 2 O. The organic laye r was dried with magnesium sulfate and concentrated and the resultant solid was analyzed by GCMS. This still showed 18% conversion to the desired product. 482 Table 1 6 Entry 4 To a 250 mL round bottom flask was added 4 - bromoiodobenzene (2.83 g, 10 mmol, 1 equiv), K 2 CO 3 (2.76 g, 20 mmol, 2 equiv), Ni(PPh 3 ) 2 Cl 2 (0.654 g, 1 mmol, 10 mol %), CuI (0.3808 g, 2 mmol, 20 mol %), and a stir bar. The flask was then fitted with a reflux condenser before 50 mL dioxane and 10 mL H 2 O was added . This mixture was then heated at 115 o C for 5 min before phenylacetylene (1.32 mL, 12 mmol, 1.2 equiv) was added. The reaction was allowed to stir for 22 hours at reflux. At the end of the reaction, the majority of the solvent was removed by vacu um distillation, and the resulting mixture was extracted with DCM/H 2 O. The organic layer was dried with magnesium sulfate and concentrated and the resultant solid was analyzed by GCMS. This still showed 28% conversion to the desired product. Table 1 6 Entr y 5 To a 250 mL round bottom flask was added 4 - bromoiodobenzene (2.83 g, 10 mmol, 1 equiv), K 2 CO 3 (2.76 g, 20 mmol, 2 equiv), Ni(PPh 3 ) 2 Cl 2 (0.327 g, 0.5 mmol, 5 mol %), CuI (0.1904 g, 1.0 mmol, 10 mol %), and a stir bar. It should be noted that a new 483 bottle of Ni(PPh 3 ) 2 Cl 2 was used for this experiment. The flask was then fitted with a reflux condenser before 50 mL dioxane and 10 mL H 2 O was a dded . This mixture was then heated at 115 o C for 5 min before phenylacetylene (1.32 mL, 12 mmol, 1.2 equiv) was added. The reaction was allowed to stir for 22 hours at reflux. At the end of the reaction, the majority of the solvent was removed by vacuum di stillation, and the resulting mixture was extracted with DCM/H 2 O. The organic layer was dried with magnesium sulfate and concentrated and the resultant solid was analyzed by GCMS. This still showed 15% conversion to the desired product. Synthesis of 1 - bro mo - 4 - (phenylethynyl)benzene (4) with a palladium catalyst This procedure was adapted from prior literature . 72,73 To a 500 mL round bottom flask was added 4 - bromoiodobenzene (100 g, 353 mmol, 1 equiv), Pd(PPh 3 ) 2 Cl 2 (0.2481 g, 0.353 mmol, 0.1 mol %), CuI (0.0673 g, 0.353 mmol, 0.1 mol %), and a stir bar. The flask was sealed with a rubber septum and flushed with nitrogen before 300 mL freshly distilled THF was added . Triethyla mine (54.3 mL, 0.389 mol, 1.1 equiv) was distilled over CaH 2 and added to the reaction mixture. Finally, phenylacetylene (42.7 mL, 0.389 mol, 1.1 equiv) was added dropwise to the reaction mixture. The reaction solution eventually turned a brown color and f ormed a white precipitate. The white precipitate is likely Et 3 NI. The reaction was allowed to stir for 12 hours at room temperature. At the end of the reaction, the solvent was removed , and the resulting solid was extracted with DCM/H 2 O. 484 The organic layer was dried with magnesium sulfate and concentrated and the resultant solid was then purified by silica column chromatography (hexanes) to afford 87.25 g of a white flaky solid (96% yield, mp: 82 - 85 °C) with NMR data matching those previously reported in the literature. 73 1 H NMR (500 MHz, CDCl 3 7.53 (m, 2H), 7.52 7.48 (m, 2H), 7.44 7.39 (m, 2H), 7.39 7.35 (m, 3H). 13 C NMR (126 MHz, CDCl 3 131.62, 128.53, 128.42, 122.92, 122.49, 122.25, 90.53, 88.34. Synthesis of dichloro(methyl)(4 - (phenylethynyl)phenyl)silane (2) To a 250 mL round bottom flask were added Mg 0 turnings (2.08 g, 0.085 mol, 1.1 equiv) and a stir bar. The Mg 0 turnings were stirred under vacuum for 2 hours after which the contents were put under an N 2 atmosphere. 1 - Bromo - 4 - (phenylethynyl)benzene (20 g, 0.077 mol, 1 equiv) was dissolved in 80 mL fre shly distilled THF and injected into the flask containing the Mg 0 turnings. This mixture was allowed to stir for 12 h after which a green solution was observed . An aliquot of the solution was dissolved in methanol, and GC/MS showed only one peak with an m/ z of 178 suggesting full Grignard formation was achieved . In a 500 mL round bottom flask equipped with a stir bar under an N 2 atmosphere, MeSiCl 3 (10 mL, 0.085 mol, 1.1 equiv) was placed in 40 mL THF. The MeSiCl 3 was freshly distilled over CaH 2 . The Grigna rd solution was cannula transferred 485 dropwise into the 500 mL flask containing MeSiCl 3 . The cannula transfer took approximately 45 minutes. The reaction mixture was allowed to stir for 24 h at which time GC - MS showed full conversion. It should be noted that the initial color of the solution was clear colorless, which turned first yellow, then green and finally a yellow - orange color. At the end of the reaction, the excess THF and MeSiCl 3 were removed leaving behind a yellow powder. Fresh hexanes (~300 mL ) were added to the powder creating a slurry. This slurry was filtered through a medium fritted funnel with the use of hexanes (~200 mL) to aid transfer and wash the solid on the frit. The solvent from the filtrate was removed producing a yellow solid whic h was dried under vacuum overnight at room temperature. Once dry, the solid was subjected to sublimation at 70 °C under 0.01 torr . It should be noted after the first batch a crystalline product has collected the temperature of the sublimation was raised to 95 °C. Dichloro(methyl)(4 - (phenylethynyl)phenyl)silane was collected as white crystals (12.1 g, 53% yield) with a sharp melting point at 78 °C. 1 H NMR (500 MHz, CDCl 3 J = 8.2 Hz, 2H), 7.65 7.58 (m, 2H), 7.58 7.53 (m, 2H), 7.37 (dd, J = 4.8 , 1.9 Hz, 3H), 1.05 (s, 3H). 13 C NMR (126 MHz, CDCl 3 122.78, 91.64, 88.69, 5.52. 29 Si NMR (99 MHz, CDCl 3 Synthesis of Compound 1 486 To a 250 mL round bottom flask was added DDSQ(OH)4 (4.28 g, 4.0 mmol, 0.5 equiv), dichloro(methyl)(4 - (phenylethynyl)phenyl)silane (2.33 g, 8.0 mmol, 1 equiv), and a stir bar. The flask was placed under a N2 atmosphere and freshly distilled THF (~120 mL) was added. The mixtu re was stirred at room temperature until all solids had solubilized, approximately 2 minutes. To this solution was added Et3N (2.25 mL, 16 mmol, 2 equiv) dropwise. Upon addition of the triethylamine a white precipitate was observed. The reaction mixture wa s allowed to stir for 4 hours after which solvent was removed and the resulting solid was extracted with DCM/H2O. The organic layer was then dried affording 6.01 g of a product. This product was further purified by silica column chromatography (3:7 DCM:Hex anes to pure DCM) to afford 4.72 g of the desired product (78%). It should be noted that this is a mixture of the cis and trans isomers. 1 7.06 (m, 117H), 0.55 (s, 6H), 0.54 (s, 6H). 13 133.99, 133.94, 133.37, 131.65, 130.94, 130.85 (d, J = 1.9 Hz), 130.61, 130.46, 130.38, 130.32, 130.26, 128.38, 128.37, 127.83, 127.70, 127.61, 127.50, 124.76, 123.23, 90.21, 89.44, - 0.53, - 0.55. 29 - 31.13, - 78.29, - 79.17, - 79.47, - 79.70. 6.10: Notes Parts of this chapter were reprinted with permission from Vogelsang, D. F.; Dannatt, J. cis - trans Mixtures of Double - ACS Appl. Nano Mater. 2019 , 2 , 1223. The work presented in this chapter was not all conducted by Dannatt, J. E. Credit for the thermal analysis belongs to Vogelsang and Lee. 487 APPENDIX 488 1 H NMR (CDCl 3 , 500 MHz) 489 13 C NMR (CDCl 3 , 126 MHz) 490 1 H NMR (CDCl 3 , 500 MHz) 491 13 C NMR (CDCl 3 , 126 MHz) 492 29 Si NMR (CDCl 3 , 99 MHz) 493 1 H NMR (CDCl 3 , 500 MHz) 494 13 C NMR (CDCl 3 , 126 MHz) 495 29 Si NMR (CDCl 3 , 99 MHz) 496 REFERENCES 497 REFERENCES (1) Phillips, S. H.; Haddad, T. S.; Tomczak, S. J. Curr. Opin. Solid State Mater. Sci. 2004 , 8 , 21 29. (2) Li, G.; Wang, L.; Ni, H.; Pittman, C. U. J. Inorg. Organomet. Polym. 2001 , 11 , 123 154. (3) Feher, F. J.; Phillips, S. H.; Ziller, J. W. J. Am. Chem. Soc. 1997 , 119 , 3397 3398. (4) Feher, F. J.; Newman, D. A.; Walzer, J. F. J. Am. Chem. Soc. 1989 , 111 , 1741 1748. (5) Feher, F. J.; Walzer, J. F. Inorg. Chem. 1991 , 30 , 1689 1694. (6) Morimoto, Y.; Watanabe, K.; Ootake, N.; Inagaki, J. - I.; Yoshida, K.; Ohguma, K. Silsesquioxane Derivatives and Process for Production Thereof. U.S. Patent US20040249103A1, December 9, 2004. (7) Lee, D. W.; Kawakami, Y. Polym. J. 2007 , 39 , 230 238. (8) Hoque, M. A.; Kakihana, Y.; Shinke, S.; Kawakami, Y. Macromolecules 2009 , 42 , 33 09 3315. (9) Kawabata, K.; Tajima, A.; Matsuo, T.; Watanabe, Y.; Ayama, K. Compound Including Organopolysiloxane or Silsesquioxane Skeleton Having Isocyanuric Skeleton, Epoxy Group and SiH Group, Thermosetting Resin Composition Containing the Compound as Adhesion - Imparting Agent, Hardened Material and Sealing Agent for Optical Semiconductor. U.S. Patent 20140148536:A1, May 29, 2014. (10) Au - Yeung, H. - L.; Leung, S. Y. - L.; Yam, V. W. - W. Chem. Commun. 2018 , 54 , 4128 4131. (11) Wu, S.; Hayakawa, T.; Kakimoto, M. - A.; Oikawa, H. Macromolecules 2008 , 41 , 3481 3487. (12) Kucuk, A. C.; Matsui, J.; Miyashita, T. J. Colloid Interface Sci. 2011 , 355 , 106 114. (13) Wu, S.; Hayakawa, T.; Kikuchi, R.; Grunzinger, S. J.; Kakimoto, M. - A.; Oikawa, H. Macromolecules 2007 , 40 , 5698 5705. 498 (14) Jiang, Q.; Zhang, W.; Hao, J.; Wei, Y.; Mu, J.; Jiang, Z. J. Mater. Chem. 2015 , 3 , 11729 11734. (15) Liu, N.; Li, L.; Wang, L.; Zheng, S. Polymer 2017 , 109 (Supplement C), 254 265. (16) Hoque, M. A.; Kawakami, Y. Journal of Scientific Research 2016 , 8 , 217 227. (17) RSC Adv. 2016 , 6 , 10054 10063. (18) Haddad, T. S.; Viers, B. D.; Phillips, S. H. J. Inorg. Organomet. Polym. 2001 , 11 , 155 164. (19) Leu, C. - M.; Chang, Y. - T.; Wei, K. - H. Chem. Mater. 2003 , 15 , 3721 3727. (20) Lichtenhan, J. D.; Schwab, J. J.; An, Y.; Liu, Q.; Haddad, T. S. Process for the Functionalization of Polyhedral Oligomeric Silsesquioxanes. U.S. Patent 6927270, August 9, 2005. (21) Li, Y.; Dong, X. - H.; Zou, Y.; Wang, Z.; Yue, K.; Huang, M.; Liu, H.; Feng, X.; Lin, Z.; Zhang, W.; et al. Polymer 2017 , 125 , 303 329. (22) Cao, J.; Fan, H.; Li, B. - G.; Zhu, S. Polymer 2017 , 124 , 157 167. (23) Xu, S.; Zhao, B.; Wei, K.; Zheng, S. J. Polym. Sci. B Polym. Phys. 2018 , 56 , 893 906. (24) Haddad, T. S.; Mabry, J. M.; Ramirez, S. Synthesis of Functional Fluorinated Polyhedral Oligomeric Silsesquioxane (F - POSS). U.S. Patent 9249313, February 2, 2016. (25) Lee, A.; Lu, Y.; Roche, A.; Pan, T. - Y. Int. J. Metalcast 2016 , 10 , 338 341. (26) Blanco, I.; Abate, L.; Bottino, F. A.; Bottino, P. Polym. Degrad. Stab. 2012 , 97 , 849 855. (27) Jin, L.; Ishida, H. Polym. Compos. 2011 , 32 , 1164 1173. (28) Vaha bi, H.; Eterradossi, O.; Ferry, L.; Longuet, C.; Sonnier, R.; Lopez - Cuesta, J. - M. Eur. Polym. J. 2013 , 49 , 319 327. (29) Ke, F.; Zhang, C.; Guang, S.; Xu, H. J. Appl. Polym. Sci. 2013 , 127 , 2628 2634. (30) Ramirez, N. V.; Sanchez - Soto, M. Polym. Compo s. 2012 , 33 , 1707 1718. (31) Wang, Z.; Yonggang, L.; Huijuan, M.; Wenpeng, S.; Tao, L.; Cuifen, L.; Junqi, N.; Guichun, Y.; Zuxing, C. Fire Mater. 2018 , 2 , 16230. 499 (32) Seurer, B.; Vij, V.; Haddad, T.; Mabry, J. M.; Lee, A. Macromolecules 2010 , 43 , 9337 9347. (33) Liu, N.; Wei, K.; Wang, L.; Zheng, S. Polym. Chem. 2016 , 7 , 1158 1167. (34) Cardiano, P.; Lazzara, G.; Manickam, S.; Mineo, P.; Milioto, S.; Lo Schiavo, S . Eur. J. Inorg. Chem. 2012 , 2012 , 5668 5676. (35) Li, H.; Zhao, X.; Chu, G.; Zhang, S.; Yuan, X. RSC Adv. 2014 , 4 , 62694 62697. (36) Xue, Y.; Wang, H.; Yu, D.; Feng, L.; Dai, L.; Wang, X.; Lin, T. Chem. Commun. 2009 , 42 , 6418 6420. (37) Kucuk, A. C.; Matsui, J.; Miyashita, T. RSC Adv. 2018 , 8 , 2148 2156. (38) Espinas, J.; Pelletier, J. D. A.; Abou - Hamad, E.; Emsley, L.; Basset, J. - M. A. Organometallics 2012 , 31 , 7610 7617. (39) Hartmann - Thompson, C. Applications of Polyhedral Oligom eric Silsesquioxanes ; Springer Science & Business Media, 2011. (40) He, F. - A.; Zhang, L. - M. Nanotechnology 2006 , 17 , 5941. (41) Tanaka, K.; Ishiguro, F.; Chujo, Y. J. Am. Chem. Soc. 2010 , 132 , 17649 17651. (42) Tanaka, K.; Ishiguro, F.; Jeon, J. - H.; Hiraoka, T.; Chujo, Y. NPG Asia Materials 2015 , 7 , e174. (43) Tanaka, K.; Ishiguro, F.; Chujo, Y. Polym. J. 2011 , 43 , 708. (44) Zhao, R.; Chen, Y.; Liu, G.; Jiang, Y.; Chen, K. Mater. Lett. 2018 , 229 , 281 285. (45) Rizvi, S. B.; Yildirimer, L.; Ghaderi, S.; Ramesh, B.; Seifalian, A. M.; Keshtgar, M. Int. J. Nanomedicine 2012 , 7 , 3915 3927. (46) Ganesh, V. A.; Nair, A. S.; Rau t, H. K.; Tan, T. T. Y.; He, C.; Ramakrishna, S.; Xu, J. J. Mater. Chem. 2012 , 22 , 18479 18485. (47) Wang, D. K.; Varanasi, S.; Strounina, E.; Hill, D. J. T.; Symons, A. L.; Whittaker, A. K.; Rasoul, F. Biomacromolecules 2014 , 15 , 666 679. (48) Tanaka, K.; Ohashi, W.; Kitamura, N.; Chujo, Y. Bull. Chem. Soc. Jpn. 2011 , 84 , 612 616. 500 (49) Kolel - Veetil, M. K.; Fears, K. P.; Qadri, S. B.; Klug, C. A.; Keller, T. M. J. Polym. Sci. A Polym. Chem. 2012 , 50 , 3158 3170. (50) Bagheri, H.; Soofi, G.; Ja vanmardi, H.; Karimi, M. Microchim. Acta 2018 , 185 , 418. (51) Ghanbari, H.; Cousins, B. G.; Seifalian, A. M. Macromol. Rapid Commun. 2011 , 32 , 1032 1046. (52) Tan, A.; Farhatnia, Y.; Seifalian, A. M. Crit. Rev. Biomed. Eng. 2013 , 41 , 495 513. (53) Olivero, F.; Renò, F.; Carniato, F.; Rizzi, M.; Cannas, M.; Marchese, L. Dalton Trans. 2012 , 41 , 7467 7473. (54) Pu, Y.; Zhang, L.; Zheng, H.; He, B.; Gu, Z. Polym. Chem. 2013 , 5 , 463 470. (55) Biron, M. Thermosets and Composites ; Elsevier, 2003. (56) Champion, K. S. W.; Cole, A. E.; Kantor, A. J. Standard and Reference Atmospheres. In Handbook of Geophysics and the Space Environment ; Jursa, A. (57) Hedin, A. E. J. . 1983 , 88 (A12), 170 (58) Dever, J.; Banks, B.; de Groh, K.; Miller, S. Degradation of Spacecraft Materials. In Handbook of Environmental Degradation of Materials ; Kutz, M., Ed.; William Andrew Publishers: Norwich, NY, 2005. (59) Hamerton, I.; Mooring, L. In Thermosets; Guo, Q., Ed.; Woodhead Publishing, 2012; pp 189 227. (60) Bryant, R. G.; Jensen, B. J.; Hergenrother, P. M. J. Appl. Polym. Sci. 1996 , 59 , 1249 - 1254. (61) Lee, D.; Tippur, H. V.; Jensen, B. J.; Bogert, P. B. J. Eng. Mater. Technol. 2011 , 133 , 021015. (62) Jensen, B. J.; Bryant, R. G.; Smith, J. G.; Hergenrother, P. M. J. Adhes. 1995 , 54, 57 - 66. (63) Li, Y.; Morgan, R. J. J. Appl. Polym. Sci. 2006 , 101 , 4446 - 4453. (64) Fang, X.; Xie, X. - Q.; Simone, C. D.; Stevens, M. P.; Scola, D. A. Macromolecules 2000 , 33 , 1671 - 1681. 501 (65) Knauer, K. M.; Brust, G.; Carr, M.; Cardona, R. J.; Lichtenhan, J. D.; Morgan, S. E. J. Appl. Polym. Sci. 2017 , 134 , 44462 - 44473. (66) Milliman, H. W.; Sánchez - Soto, M.; Arostegui, A.; Schiraldi, D. A. J. Appl. Polym. Sci. 2012 , 125 , 2914 - 2919. (67) Baker, A. J. Organometallic Chemistry Pertaining to Main Group Elements Silicon, Germanium, Tin, and Boron; Ph.D Dissertation, Michigan State Univers ity, East Lansing, MI, 2016. (68) Schoen, B. W. Aminophenyl Double Decker Silsesquioxanes: Spectroscopic Elucidation, Physical and Thermal Characterization, and Their Applications ; Ph.D. Dissertation, Michigan State University, East Lansing, MI, 2013. ( 69) Guo, T.; Wang, B. Polym. Plast. Technol. Eng. 2014 , 53 , 917 926. (70) Schoen, B. W.; Lira, C. T.; Lee, A. J. Chem. Eng. Data 2014 , 59 , 1483 1493. (71) Moore, L. M. J.; Zavala, J. J.; Lamb, J. T.; Reams, J. T.; Yandek, G. R.; Guenthner, A. J.; Haddad, T. S.; Ghiassi, K. B. RSC Adv. 2018 , 8 , 27400 27405. (72) Attanayake, G. K. Study of Different Routes to Develop Asymmetric Double Decker Silsesquioxane (DDSQ) ; Lansing, MI, 2015. (73) Thogiti, S.; Parvathaneni, S. P.; Keesara, S. J. Organomet. Chem. 2016 , 822 , 165 172