IRIDIUM CATALYZED C–H 1,2-DIBORYLATION AND 1,2,3-TRIBORYLATION OF ARENES THROUGH THE USE OF ANTI-AROMATIC PYRAZINE BASED LIGANDS AND OTHER BORON RELATED STUDIES By Thomas Jonathan Oleskey A DISSERTATION Submitted to Michigan State University in partial fulfillment of the requirements for the degree of Chemistry – Doctor of Philosophy 2025 ABSTRACT During the last few decades iridium catalyzed C–H borylations have become an important method to access aryl boronic esters. As aryl C–H borylations are governed predominately by sterics, this reaction offers a complementary regiochemical approach to traditional synthetic routes accessing aromatic boronic esters such as metal halogen exchange and Miyaura borylation. As these reactions can be reliably directed away from positions ortho to any functionality other than hydrogen, fluorine, and nitriles, iridium catalyzed borylations find ample use in industry and total synthesis. Since this reaction is directed sterically and not electronically, regiochemical selectivity can become challenging in cases where multiple activation sites are available, especially in the case of 1,2-disubstituted arenes. To overcome this challenge, we developed a method for para selective borylation of phenols and anilines utilizing alkyl ammonium cations as steric shields to direct borylation. We further show how this methodology can be expanded to utilize in situ heteroatom borylation in place of the alkyl ammonium cations to access the same para selectivity. We further utilized existing 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (Bpin) functionalities to guide the regiochemistry of iridium catalyzed C–H borylation ortho to itself to access 1,2-diborylated arenes as well as new 1,2,3-triborylated arenes. As borylated compounds are important synthetic intermediates, being able to study C–H borylations mechanistically offers important insights into reactions utilizing these compounds. We therefore investigated developing a method to measure boron heavy atom isotope effects using fluorine reporters and NMR to observe boron isotopic distributions. TABLE OF CONTENTS Chapter 1: Introduction to Iridium Catalyzed C–H Borylations ..............................................................1 REFERENCES ............................................................................................................................................ 10 Chapter 2: 1,2 and 1,2,3 Di and TriBorylation Through the Use of Novel Antiaromatic Pyrazine Based Ligands ............................................................................................................................................ 12 Experimental Procedures ........................................................................................................................ 23 REFERENCES ............................................................................................................................................ 43 Chapter 3: Para Selective C–H Borylation of Sulfonated Phenols, Anilines, and Benzyl Alcohols Equipped with a Tetraalkylammonium Steric Sheild .......................................................................... 45 Experimental Procedures ........................................................................................................................ 54 REFERENCES ............................................................................................................................................ 73 Chapter 4: Steric Shielding Effects induced by Intramolecular C–H•••O Hydrogen Bonding: Remote Borylation Directed by Bpin Groups .................................................................................................. 76 Experimental Procedures ........................................................................................................................ 92 REFERENCES ............................................................................................................................................ 98 Chapter 5: Measurement of Isotopic Distribution of Boron .............................................................. 102 Experimental Procedures ...................................................................................................................... 110 REFERENCES .......................................................................................................................................... 114 APPENDIX A: NMR SPECTRA ........................................................................................................... 115 APPENDIX B: CRYSTALLOGRAPHIC DATA .......................................................................................... 355 iii Chapter 1: Introduction to Iridium Catalyzed C–H Borylations It is hard to find a type of substrate as useful as an aryl boronic acid or ester. When it comes to aryl couplings there is hardly a reaction as ubiquitous as the Suzuki coupling.1 In 2011 a review was published characterizing all the palladium catalyzed C-C coupling reactions wherein it was found by no small margin, the Suzuki coupling was the most used reaction reported.2 This speaks volumes to the importance of aryl boronic acids and esters as starting materials. Additionally, these functionalities can undergo a multitude of reactions to generate a myriad of functionalities as shown in Figure 1-1.1,3-11 Because of this utility, I like to affectionately refer to boronic esters as the stem cells of chemistry. Figure 1-1 Derivatization Paths for Aryl Boronic Pinacolate Esters Between boronic acids and esters, both exhibit extraordinarily similar reactivities, to the point that they are often used interchangeably throughout the literature. The more useful of these is generally regarded to be boronic esters, notably as the pinacolate ester, as they tend to be more stable than their corresponding boronic acid counterparts while also often exhibiting superior solubility in organic solvents. Traditionally, aryl boronic esters have been synthesized directly from aryl halides via metal halogen exchange followed by quenching with an isopropyl borate.12 This, however, is a non-ideal way to synthesize these reagents as the metalated intermediate is a highly reactive species that is not tolerant of many functional groups. Therefore, this approach is greatly limited in the products that it can access. 1 Additionally metal halogen exchange is dependent on the availability of halogenated starting materials, further limiting the compounds that can be practically synthesized. Because of this, many alternative routes to aryl boronic esters have been developed. The most notable of these is the Miyaura borylation (Figure 1-2), which can safely be said to be the predominant route to these materials in synthetic literature. Figure 1-2 A Representative Example of a Typical Miyaura Borylation In the Miyaura borylation, an aryl halide is coupled with a borane or diboron reagent most often 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (B2pin2) to generate a boronic ester via palladium catalyzed cross coupling.13 Like metal halogen exchange, Miyaura borylations also suffer from the same problem in the fact that they are reliant on access to an initial halogenated starting material. This often limits the accessible boronic esters to positions that are accessible to electrophilic aromatic substitution type halogenation reactions. While extraordinarily useful, it is inherently limited. Ideally aryl boronic esters would be able to be installed directly from C–H bonds, avoiding reliance on halogenated starting materials, and allowing access to positions not accessible by electrophilic aromatic substitution regioselectivity. This brings us to the rise of Iridium catalyzed borylations. While iridium catalyzed C–H borylations were predated by photochemical tungsten C–H borylations,14 the birth of a thermal catalytic method for C–H borylation allowed for the proliferation of C–H borylations in synthesis. The first thermal catalytic C–H borylation was discovered by the Smith group in 1999 of which Smith affectionately referred to it as “The worst catalyst ever published in JACS” (Figure 1- 3).15 Despite having a turnover of approximately 3, this reaction was a landmark in boron chemistry. Figure 1-3 First Published Thermal Catalytic C–H Borylation This iridium catalyst was quickly improved first by the institution of phosphine ligands followed by transition to dipyridine ligands instituted by Hartwig, which brought the catalytic turnover from 3 all the way to 14000.16,17 This reactivity makes this catalyst industrially relevant. This coupled with how tolerant 2 iridium catalyzed borylations are of functional groups, makes this reaction particularly useful for late- stage functionalization. This was demonstrated by the Baran research group who used this chemistry to install a boronic ester on an indole scaffold late in the synthesis of teleocidins and even on a gram scale.18 This systems robust utility is further demonstrated by Merck which utilized an iridium catalyzed borylation on a 85 Kg scale to in the presence of chlorine and iodine functionalities who are typically activated in most metal catalysis (Figure1-4).19 C–H Boryation Utilized by Baran in the Synthesis of Teleocidins C–H Boryation Utilized by Merk in the Synthesis of c-Met/ALK Inhibitor HS-10168 Figure 1-4 Synthesis towards Teleocidins using Iridium Catalyzed Borylations by Phil Baran and the Kg Scale C–H Borylation of 1-Chloro-3-Iodobenzene by Merck Having developed the current method for iridium catalyzed CH borylation, studies were undertaken by Hartwig to understand the general mechanism of the catalytic cycle. It was debated whether the catalytic cycle was III-V or I-III before it was definitively shown to be III-V by Hartwig in 2009 as shown in Figure 1-5.17 Even more is that the Hartwig group was able to isolate and characterize the resting catalyst which provided an unusual insight into this methodology. 3 Figure 1-5 C–H Borylation Catalytic Cycle as Established by Hartwig In the catalytic cycle, an iridium(I) catalyst is used which when treated with boron source (either HBpin or the preferred B2pin2) and a ligand, undergoes oxidative addition with the boron source and assembles into the active resting catalyst (structure I in Figure 1-5). This active resting catalyst, often referred to as the tris-boryl, is then able to undergo oxidative addition with an aryl C–H bond (Structure II in Figure 1- 5), which subsequently undergoes reductive elimination to generate a borylated arene. The resulting iridium(III) catalyst (Structure III Figure 1-5) once again can undergo oxidative addition with a boron source to generate the iridium(V) intermediate (Structure IV Figure 1-5), which can undergo reductive elimination to release either HBpin or H2 gas thus completing the catalytic cycle. It is important to note that the side product of this catalytic cycle when using B2pin2 is HBpin, which can itself act as a boron source for this reaction. Because of this it is possible to run these reactions at half stoichiometric loadings of B2pin2 or stoichiometric loadings of HBpin. Ligands were also investigated for activity in this system wherein it became evident that iridium metal centers ligated with bipyridine ligands containing electron withdrawing groups were less active than those with donating groups. It is important to note that the pyridine rings of ligands can be borylated. As boronic esters are electron withdrawing this can also lead to lower activity of the catalyst over the course of a reaction.20 Because of this, most ligands have a substituent in the 4 and 4’ position of the pyridine rings such as in 4,4’-di-tert-butyl-2,2’-dipyridine (dtbpy) which has become one of the most commonly used ligands for iridium catalyzed CH borylations along with 3,4,7,8-tetramethyl-1,10- phenanthroline (tmphen). 4 With an active catalyst able to initiate C–H activation followed by borylation, the question becomes which C–H position will be activated? For example, observe anisole shown in Figure 1-6, which hydrogen will be activated? The answer is surprisingly simple. As a rule, unless directed iridium catalyzed C–H borylations are sterically guided. They can only borylate sterically accessible positions or positions that have no groups other than hydrogen, fluorine, or nitriles adjacent to them. In the case of anisole, the hydrogens denoted in red in Figure 1-6 are not active to iridium catalyzed borylations as they are adjacent to the methoxy group. Figure 1-6 Borylation of Anisole Fluorine and nitriles due to their small steric presence, and in the case of nitriles, linear shape can undergo C–H borylation adjacent to themselves, therefore, it is possible and sometimes favorable to borylate positions next to these groups. Two groups worth mentioning as well are chlorine and methoxy. While it is “possible” to borylate adjacent to these groups as well, it is rather unfavorable and rarely observed. This regioselectivity does however have a severe shortcoming, and that is in the case of substrates with more than one sterically accessible hydrogen present. In these cases, both positions will be borylated equally leading to a statistical distribution of regioisomers as also illustrated in Figure 1-6. While steric environment is typically the determining factor in iridium catalyzed borylations, many groups have devoted research to further improving regioselectivity, especially in systems where multiple accessible borylation positions are available. These guided borylations are typically placed into three categories: ortho borylation, meta borylation, and para borylation. 5 Ortho borylation typically refers to borylation ortho to a directing group. These directing groups may be inherent to the target of interest or installed prior to borylation. The first published example of ortho borylation was by the Hartwig group who utilized silyl groups to direct borylation ortho to themselves.21 Hartwig was able to utilize a silane iridium binding interaction to direct borylations. This strategy was then mirrored by Ishiyama who developed a monodentate phosphine ligand that was able to easily dissociate providing a spot for imines to coordinate to direct borylations ortho to themselves. This approach has since been applied to other groups such as esters and phosphates. For a substrate to coordinate to a metal center, the catalyst first must have an open coordination position available. Common bipyridine borylation ligands do not allow for this as they are very ridged and strongly donating and therefore do not allow for two open coordination positions. Unfortunately, the iridium catalyst cannot be easily stabilized with monodentate ligands. This led to the idea of utilizing hemilabile ligands or bidentate ligands with a labile half.30 These hemilabile ligands can dissociate part of themselves from the metal center in solution thus freeing a second coordination spot on the iridium metal center. This allows for chelation to the iridium thus directing borylation ortho to the chelating group. This strategy has since been applied to substrates containing many other functional groups such as thioethers, hydrazones, aldehydes, and benzylamines. If borylations can be directed by attaching a substrate to the metal center, it should be possible to direct borylations by attaching starting materials to the ligand of the active catalyst. This was the approach that a few groups also took to achieve ortho borylations. By utilizing interactions such as electrostatics, Lewis’s acid-base interactions, and hydrogen bonding, borylations were able to be directed ortho to. 6 [A] Hartwig 200821 [B] Ishiyama 201416 [C] Lassaletta 201130 Figure 1-7 Select Examples of ortho-Borylations Meta directed borylations are the easiest position to borylate in the case of 1,3- disubstituted arenes, however, when there is no 3 substituent, to achieve selectively is a bit trickier. In these systems para borylation is possible as well. The trick is differentiating between the meta and para positions. Many of the meta direction strategies mimic that of ortho borylation strategies such as using ligand substrate interactions to guide reactivity. In the meta directed substrates, the same strategies are used albeit with longer tethering groups to push borylation to the meta position as opposed to ortho.22,23 In addition to what was used in ortho borylations a new strategy appeared here; wherein ionic attraction was utilized by the Phipps group to be used to attract quaternary ammonium salts to a sulfate ligand guiding meta selectivity.24-26 7 [A] Kuninobu and Kanai 201529 [B] Phipps 201826 [C] Chattopadhyay 202122 Figure 1-8 Select Examples of meta-Borylations Para borylation is easily the hardest to target selectively. This is because it falls squarely in the domain of remote functionalization, meaning there is no directing group close to the position of interest. That coupled by the competition with the meta position mentioned above makes these positions difficult to target selectively. So far only a handful of strategies have been developed to target these positions. One method is a strategy by Chattopadhyay, where he implemented an unusually long ligand with a potassium alkoxide group to guide borylation para to aryl esters.23 Other methods targeting para borylation take advantage of the high steric selectivity seen in iridium catalyzed borylations. In 2017, two methods were published utilizing modified steric environments to guide selectivity. Nakao utilized bulky aluminum Lewis acids to coordinate to amides to greatly exaggerate their steric presence pushing borylation to the para position.27 This was further expanded to pyridines. The other method of doing this was demonstrated by Itami who developed a particularly bulky diphosphine ligand that when coordinated with an iridium metal center formed a pseudo active pocket only allowing unencumbered arenes access to the metal center and therefore borylate at the para position.28 8 [A] Segawa and Itami 201528 [B] Nakao 201727 [C] Chattopadhyay 201723 Figure 1-9 Select Examples of para-Borylations Iridium catalyzed borylations are one of the most important catalytic reactions developed in the twenty first century. It gives predictable selectivity while being a robust reaction capable of tolerating many functional groups even at low catalytic loadings. This is exemplified by its use in industry and total synthesis by groups other than its developers. As it is one of the most well understood catalytic cycles, much work has been done to push the capabilities of this reaction to their highest potential through guidance of selectivity as well as optimization of catalytic conditions. Despite the work that has already been done, there are ample opportunities to further expand this field of chemistry as well as the selectivity possible with this reaction. 9 REFERENCES (1) Miyaura, N.; Yamada, K.; Suzuki, A. A New Stereospecific Cross-Coupling by the Palladium- Catalyzed Reaction of 1-Alkenylboranes with 1-Alkenyl or 1-Alkynyl Halides. Tetrahedron Lett. 1979, 20, 3437–3440. (2) (3) (4) (5) (6) (7) (8) Colacot, T. J. The 2010 Nobel Prize in Chemistry: Palladium-Catalysed Cross-Coupling. Platin. Met. Rev. 2011, 55, 84–90. Thiebes, C.; Petasis, N. A.; Olah, G. A. Mild Preparation of Haloarenes by Ipso-Substitution of Arylboronic Acids with N-Halosuccinimides Synlett 1998, 2, 141-142. Chan, D. M. T.; Monaco, K. L. Wang, R. P.; Winters, M. P. New N- and O-arylations with Phenylboronic Acids and Cupric Acetate Tetrahedron Letters, 1998, 39, 2933-2936. Evans, D. A.; Katz, J. L.; West, T. R. Synthesis of diaryl ethers through the copper-promoted arylation of phenols with arylboronic acids. An expedient synthesis of thyroxine Tetrahedron Letters, 1998, 39, 2937-2940. Lam, P. Y. S.; Clark, C. G.; Saubern, S.; Adams, J.; Winters, M. P.; Chan, D. M. T.; Combs, A. New Aryl/Heteroaryl C-N Bond Cross-coupling Reactions via Arylboronic Acid/Cupric Acetate Arylation Tetrahedron Letters, 1998, 39, 2941-2944. Yuen, A. K. L.; Hutton, C. A. Deprotection of Pinacolyl Boronate Esters via Hydrolysis of Intermediate Potassium Trifluoroborates Tetrahedron Letters, 2005, 49, 7899-7903. Tang, Y. L.; Xia, X. S.; Gao, J. C.; Li, M. X.; Mao, Z. W. Direct bromodeboronation of arylboronic acids with CuBr2 in water Tetrahedron Letters, 2021, 64, 152738. (9) Molander, G. A.; Fumagalli, T. Palladium(0)-catalyzed Suzuki-Miyaura cross-coupling reactions of potassium aryl- and heteroaryltrifluoroborates with alkenyl bromides J. Org. Chem. 2006, 71, 5743-5747. (10) Liskey, C. W.; Liao, X.; Hartwig, J. F. Cyanation of Arenes via Iridium-Catalyzed Borylation. J. Am. Chem. Soc. 2010, 132, 11389–11391. (11) Molloy, J. J.; Thomas, A.; Irving, C. Anderson, N. A.; Lloyd-Jones, G. C. Chemoselective Oxidation of Aryl Organoboron Systems Enabled by Boronic Acid-Selective Phase Transfer Chemical Science, 2017, 8, 1551-1559. (12) Brown, H.; Cole, T. E. Organoboranes. 31. A Simple Preparation of Boronic Esters From Organolithium Reagents and Selected Trialkoxyboranes Organometallics, 1983, 2, 1316-1319. (13) Ishiyama, T.; Murata, M.; Miyaura, N. Palladium(0)-Catalyzed Cross-Coupling Reaction of Alkoxydiboron with Haloarenes: A Direct Procedure for Arylboronic Esters J. Org. Chem. 1995, 60, 7508-7510. (14) Chen, H.; Hartwig, J. F. Catalytic, Regiospecific End-Functionalization of Alkanes : Rhenium- Catalyzed Borylation under Photochemical Conditions Angew. Chem. Int. Ed. 1999, 38, 3391- 3393. (15) Iverson, C. N.; Smith III, M. R. Stoichiometric and Catalytic B−C Bond Forma(cid:415)on from Unactivated Hydrocarbons and Boranes J. Am. Chem. Soc. 1999, 121, 7696-7697 (16) A.) Ishiyama, T.; Isou, H.; Kikuchi, T.; Miyaura, N. Ortho-C–H Borylation of Benzoate Esters with Bis(Pinacolato)Diboron Catalyzed by Iridium–Phosphine Complexes. Chem. Commun. 2010, 46, 159–161. B.) Sasaki, I.; Amou, T.; Ito, H.; Ishiyama, T. Iridium-catalyzed ortho-C– H 10 Borylation of Aromatic Aldimines Derived from Pentafluoroaniline with bis(pinacolate)diboron org. Biomol. Chem. 2014, 12, 2041-2044. (17) Boller, T. M.; Murphy, J. M.; Hapke, M.; Ishiyama, T.; Miyaura, N.; Hartwig, J. F. Mechanism of the Mild Functionalization of Arenes by Diboron Reagents Catalyzed by Iridium Complexes. Intermediacy and Chemistry of Bipyridine-Ligated Iridium Trisboryl Complexes J. Am. Chem. Soc. 2005, 127, 14263 – 14278 (18) Nakamura, H.; Yasui, K.; Kanda, Y.; Baran, P. S. 11-Step Total Synthesis of Teleocidins B1-B-4. J. Am. Chem. Soc. 2019, 141, 1494–1497. (19) Campeau, L. C.; Chen, Q.; Gauvreau, D.; Girardin, M.; Belyk, K.; Maligres, P.; Zhou, G.; Gu, C.; Zhang, W. Tan, L.; O'Shea, P. D. A Robust Kilo-Scale Synthesis of Doravirine Org. Process Res. Dev. 2016, 20, 1476−1481. (20) Larsen, M. A.; Oeschger, R. J.; Hartwig, J. F. Effect of Ligand Structure on the Electron Density and Activity of Iridium Catalysts for the Borylation of Alkanes ACS Catal. 2020, 10, 3415-3424. (21) Boebel, T. A.; Hartwig, J. F. Silyl-Directed, Iridium-Catalyzed Ortho-Borylation of Arenes. A One-Pot Ortho-Borylation of Phenols, Arylamines, and Alkylarenes J. Am. Chem. Soc. 2008, 130, 7534–7535 (22) Chaturvedi, J.; Haldar, C.; Bisht, R.; Pandey, G. Chattopadhyay, B. Meta Selective C–H Borylation of Sterically Biased and Unbiased Substrates Directed by Electrostatic Interaction J. Am. Chem. Soc. 2021, 143, 7604−7611. (23) Hoque, D.; Bisht, R.; Haldar, C.; Chattopadhyay, B. Noncovalent Interactions in Ir-Catalyzed C–H Activation: L-Shaped Ligand for Para-Selective Borylation of Aromatic Esters J. Am. Chem. Soc. 2017, 139, 7745–7748. (24) Davis, H. J.; Genov, G. R.; Phipps, R. meta-Selective C−H Boryla(cid:415)on of Benzylamine-, Phenethylamine-, and Phenylpropylamine-Derived Amides Enabled by a Single Anionic Ligand J. Angew. Chem. Int. Ed. 2017, 56, 13351–13355. (25) Davis, H. J.; Mihai, M. T.; Phipps, R. J. Ion Pair-Directed Regiocontrol in Transition-Metal Catalysis: A Meta-Selective C–H Borylation of Aromatic Quaternary Ammonium Salts J. Am. Chem. Soc. 2016, 138, 12759−12762. (26) Mihai, M. T.; Davis, H. J.; Genov, G. R.; Phipps, R. Ion Pair-Directed C–H Activation on Flexible Ammonium Salts: meta-Selective Borylation of Quaternized Phenethylamines and Phenylpropylamines J. ACS Catalysis. 2018, 8, 3764–3769. Yang, L.; Semba, K.; Nakao, Y. para-Selective C−H Boryla(cid:415)on of (Hetero)Arenes by Cooperative Iridium/Aluminum Catalysis Angew. Chem. 2017, 129, 4931 –4935. Saito, Y.; Segawa, Y.; Itami, K. para-C–H Borylation of Benzene Derivatives by a Bulky Iridium Catalyst J. Am. Chem. Soc. 2015, 137, 5193–5198. Kuninobu, Y.; Ida, H.; Nishi, M.; Kanai, M. A meta-Selective C–H borylation Directed by a Secondary Interaction Between Ligand and Substrate Nature Chemistry 2015, 7, 712-717. (27) (28) (29) (30) Ros, A.; Estepa, B.; Lopez-Rodriguez, R.; Alvarez, E.; Fernandez, R.; Lassaletta, J. M. Use of Hemilabile N,N Ligands in Nitrogen-Directed Iridium- Catalyzed Borylations of Arenes Angew. Chem. Int. Ed. 2011, 50, 11724-11728. 11 Chapter 2: 1,2 and 1,2,3 Di and TriBorylation Through the Use of Novel Antiaromatic Pyrazine Based Ligands 1,2-Diborylated arenes are interesting starting materials. They can be derivatized like traditional aryl borates and they are amenable for the rapid assembly of polycyclic aromatics through Suzuki couplings.1 With polycyclic aromatics being used in the synthesis of organic semiconductors and ligands such as those shown in Figure 2-1, access to a variety of 1,2 borylated arenes would be useful for the assembly of poly cyclic aromatics containing a variety of functional groups.2-4 Figure 2-1 Organic Semiconductors and Ligands Derived from 1,2-Benzenediboronic Acid bis(Pinacol) Ester Traditionally, formation of 1,2-Diborylated arenes were synthesized via halogen metal exchange of 1,2- dihalogenated arenes with magnesium or lithium followed by addition of an isopropyl borate to form the 1,2-diborylated species.5 As this method relies on the presence of preexisting halogens it can be limited by the availability of starting materials halogenated in the correct positions. Additionally metal halogen exchange is a non-ideal route to 1,2-diborylated aryl structures as the reactive intermediates are highly reactive functionalities and do not tolerate a wide variety of functional groups and risk initiating side reactions such as the halogen dance reaction. This greatly limits the practical utility of these methodologies, especially for late-stage functionalization. Because of this, other routes to 1,2-diborylated arenes have since been developed including benzyne chemistry6,7, earth abundant metal catalysis7,8, electrochemistry10, and photochemistry11. The most notable route to these compounds by far however is Miyaura borylation12. Akin to metal halogen exchange, Miyaura borylation also relies on halogenated 12 starting materials which often means that one is limited to electrophilic aromatic substitution (EAS) halogenation patterns due to availability of halogenated starting materials. Additionally with these methods synthesis of some compounds such as 1,2-diborylated arenes containing iodine functionalities is impossible. Ideally, 1,2-diborylated arenes could be directly synthesized utilizing iridium catalyzed C–H borylation. As previously established in Chapter 1, general selectivity of iridium aryl C–H borylations is well understood. Therefore, it is no surprise that aryl borylation ortho to existing boronic pinacol esters do not happen, due to the steric presence of the existing Bpin. Because of this, synthesis of 1,2 di-borylated arenes are almost impossible to synthesize via C–H borylation. To date, iridium catalyzed C–H aryl borylations ortho to existing boronic pinacolate esters are practically unheard of, with no methods of undirected 1,2 diborylations having been developed. Only one method of accessing this selectivity with iridium C–H borylation has been developed in which the Suginome group mirrored the approach for silylation ortho to aryl boronic acids.13,14 In both cases the starting boronic acids were converted into azaborolidines with pyrazol-5-ylaniline to form the Bpza group that acts as a directing group (Figure 2-2). It is theorized that the Bpza binds to the catalyst metal center to guide C–H activation otho to itself. While this is impressive, it adds an additional 2 steps to the borylation process: adding and removing the Bpza directing / protecting group. This methodology is limited to accessing 1,2-diborylated compounds and no 1,2,3-triborylation was observed. Figure 2-2 C–H Borylation Ortho to a Boronic Pinacolate Ester as Reported by Suginome Previously, while screening ligands for ones that favors electronically activated positions, my prior group member Jayasundara found that iridium C–H borylations using 2,2’-bipyrazine as a ligand generated 1,2 diborylation and 1,2,3-triborylated products (Figure 2-3).15 13 61 % yield 6 % yield N N N N Bipyrazine Figure 2-3 1,2-Diborylatied and 1,2,3-Triborylated Product Observed by Jayasundara As this selectivity was exceedingly unusual, we elected to further investigate this reaction. We did this by utilizing the bipyrazine ligand to borylate a variety of substrates as shown in Figure 2-4. 14 Figure 2-4 C–H Borylation of Arenes Using 2,2'-Bipyrazine as a Ligand (Bolded Percentiles Represent Yields by 1H NMR and Percentiles in Parentheses Represent Isolated Yields.) 15 A few interesting notes emerged from examining this substrate scope. First and most interesting is the regioselectivity seen. While this methodology is notable for being able to borylate ortho to existing boronic pinacolate ester it was not expected to see a preference for borylation ortho to these groups even in cases where traditionally accessible borylation positions are available such as in entries 1 and 5 in Figure 2-4. More notable though, was the difficulty in achieving high conversion of starting material to product. In previous studies it was found that achieving high conversion of starting material to product was not as simple as just raising the catalyst loadings. Even running a reaction with 15 mol% [Ir(OMe)cod]2 did not give complete conversion. This initially led us to believe the catalyst was poisoning itself and that multiple catalyst loadings were needed to achieve high conversion. This theory, however, was not pursued as the 2,2’-bipyrazine system ultimately proved to be too irreproducible. Although the 2,2’- bipyrazine ligand was consistently was able to produce the same products, it often gave low conversion or no conversion at all. A few hypotheses were formed to explain the observed inconsistencies seen in this reaction: Impurities in the starting material mainly looking at palladium, poor glove box atmosphere, and polymerization of the ligand. Reagent purity was looked at as the original 2,2’-bipyrazine used had a tan color despite being reported to have been originally observed to be neon yellow. As 2,2’-bipyrazine is white solid, this was immediately seen to be a potential issue for the reproducibility of this system. After rigorously purifying the 2,2’-bipyrazine and all other starting materials, the following three test reactions shown in Figure 2-5 were completed. 16 Figure 2-5 Test Reactions and Measured Conversions, Run to Evaluate the Role of 2,2'-Bipyrazine Impurities for C–H Borylations As a control the first reaction was run with the original 2,2’-bipyrazine obtained through TCI. A second reaction was run with 2,2’-bipyrazine that had been purified by sublimation to remove any palladium impurities followed by multiple recrystallizations resulting in a spectroscopically pure white flake like crystalline powder. The third and final reaction was run with 2,2’-bipyrazine synthesized via palladium homo-coupling, which after initial work up was yellow in color (thought to be due to palladium impurities from the coupling conditions) and reminiscent of the reported color of the TCI bipyrazine. Unsurprisingly, the rigorously purified starting materials performed the best in this set of test reactions. Unfortunately, despite showing a higher reactivity than the initial 2,2’bipyrazine provided by TCI, rigorous purification of the starting reagents did not alleviate the reproducibility problem. Inspired by work done by Suginome, we elected to look at the pyrazine substructure as Suginome showed that pyrazines dearomatize in the presence of B2pin2 while in solution.16,17 Looking at the 2,2’- bipyrazine scaffold by NMR (shown in Figure 2-6), we found that treating 2,2’-bipyrazine with B2pin2, resulted in the de-aromatization of the pyrazine substructure. 17 2,2’-Bipyrazine De-Aromatized 2,2’-Bipyrazine Figure 2-6 The Result of De-Aromatization of 2,2'-Bipyrazine with B2pin2 (NMR 1) and the NMR of Pure 2,2'-Bipyrazine (NMR 2) The bipyrazine took on a deep green color when it was converted to the 1,1’,4,4’-tetrahydro-2,2’- bipyrazine that quickly turned red in the presence of air indicating auto air oxidation. Noticeably in the case of bipyrazine, the dearomatization failed to give a clean spectrum. It was postulated that this was due to polymerization induced by trace oxygen. When opened to air the solution formed a red precipitate that was unable to be characterized, and all peaks save for bipyrazine disappeared. From this we concluded that bipyrazine is merely a pre-ligand to the active catalytic ligand responsible for the selectivity seen in this system. Since the theorized active dearomatized ligand is formally anti-aromatic we postulated that the inconsistency in the reactions could be due to trace oxygen in the reaction atmosphere poisoning the active catalyst through oxidation and polymerization. We attempted to remedy these problems by designing our own pyrazine-based ligand which we designated as Ligand-213. Figure 2-7 Our Designed Ligand (Ligand-213) We based our ligand around the pyrazine scaffold as it was obvious to us that this substructure is clearly responsible for the unusual regioselectivity seen. We desymmetrized the ligand by replacing one of the pyrazines handles with that of a pyridine. This was done for two reasons. By adding a pyridine half, we in 18 turn stabilize the dearomatized pyrazine. This is accompanied by dative bonding to the N-borylated dihydro pyrazine through the pyridine lone pair. Additionally, it aids in discouraging metal ligand oligomerization by eliminating one of the nitrogens capable of binding to a second metal center.18 Furthermore, by introducing a t-butyl group in the 4 position of the pyridine we can further discourage coordination of the active iridium catalyst with a second metal center. Incidentally, by including a t-butyl group in the 4 position of the pyridine we additionally prevent borylation of the pyridine half of the ligand which has been known to deactivate other common bipyridine ligands.19 With ligand-213 (Figure 2-7) in hand we initially tested its ability to dearomatize. We found that ligand- 213 dearomatizes far slower than 2,2’-bipyrazine (Figure 2-8). Once dearomatized however, it is stable for extended periods of time when kept under nitrogen. 2,2’-Bipyrazine, once dearomatized, quickly degrades into unidentifiable products over the course of a few days, even when stored under nitrogen, as opposed to ligand-213 which once dearomatized is stable in solution for weeks under nitrogen. N N N Ligand-213 De-Aromatized Ligand-213 Figure 2-8 The Result of De-Aromatization of Ligand-213 with B2pin2 (NMR 1) and the NMR of pure Ligand-213 (NMR 2) Having established that Ligand-213 can undergo dearomatization like bipyrazine, we started investigating its reactivity (Figure 2-9). Utilizing this ligand, we found that it was active and gave moderate to good reactivity and yield in a single catalyst loading achieving 1,2-diborylation and 1,2,3-triborylation. 19 Figure 2-9 C–H Borylation of Arenes Using Ligand-213 as a Ligand (Bolded Percentiles Represent Yields by 1H NMR and Percentiles in Parentheses Represent Isolated Yields.) Even though ligand-213 was able to generate the same regiochemical products as bipyrazine, the selectivity seen differed significantly in entry 1. Ligand-213 did not favor 1,2-diborylation as heavily as bipyrazine. The reason for the difference in selectivity may be explained by the higher activity of the ligand. The more reactive a borylation system is the higher the likelihood that kinetics can override direction. This observation could provide helpful insight into the mechanism responsible for the regiochemical outcome pyrazine-based ligands. The improved reactivity of ligand-213 over bipyrazine may possibly be due to increased resistance to oxidation. However, the reproducibility problem that has 20 become characteristic for antiaromatic pyrazine-based ligands remained. Despite the increased stability, we once again propose that trace oxygen in the reaction conditions is responsible for the variance in reactivity, especially due to the anti-aromatic nature of the active ligand. This was evidenced by the qualitative observation that when the glovebox used for these reactions saw low usage, reactions using 2,2’-bipyrazine and Ligand-213 tended to give noticeably more favorable results. With the unusual products that this system is able to produce, it became of great interest to investigate the chemical mechanism behind this selectivity. Initially the mechanism was proposed to be a hemilabile ligand15, however with the insights gained through the two substrate scopes studies we now propose that this system utilizes a Lewis acid-base interaction to guide regioselectivity as shown in Figure 2-10. Figure 2-10 The Proposed Lewis Acid - Base Interaction Thought to be Responsible for Guiding Regioselectivity As the active ligand (the dearomatized pyrazine scaffold) contains an enamine functionality in the form of the 1,4-dihydropyrazine, it can be viewed rather as an amine where in it is possible for it to form a Lewis adduct with a boronic pinacolate ester. The resultant geometry of the adduct allows the arene to adopt the proper orientation to undergo C–H activation ortho to an existing boronic pinacolate ester. The ability of the arene to adopt this geometry, however, will be heavily dependent on the rotational barrier of the preexisting boronic pinacolate ester, which in turn will be dependent on the aryl C–B bond order. Therefore, we would expect to see an increase in selectivity and reactivity as the C–B bond weakens. This should be heavily dependent on the electron density of the arene due to resonance donation into the boronic ester. More electron donation into the boronic pinacolate ester would rigidify the bond as the C–B bond takes on more and more bonding character. This results in higher reactivity in electron deficient substrates and a decrease in reactivity of electron rich substrates which is exactly what we observe. Substrates containing electron donating substituents lack reactivity such as with 4- isopropylphenylboronic acid pinacol ester and 4-methoxyphenylboronic acid pinacol ester showing no reactivity. 21 The only exception to this observation is substrate 1d shown in entry 4 of Figure 2-4 and Figure 2-9. This substrate shows an unusually high reactivity despite containing an electron donating methoxy functionality. It is important to note however, that in this case the boronic pinacolate ester is ortho to a fluorine functionality. This is expected to cause an electronic repulsion between the boronic pinacolate’s oxygen lone pairs and that of fluorine which should largely decrease the boronic pinacolate’s rotational barrier as illustrated in Figure 2-11. OMe Cl F B O O OMe Cl F B O O Figure 2-11 Electronic Repulsion Between the Fluorine and Boronic Pinacolate of Substrate 1d Because of this, it is important to note that electronics of the arene is not the only factor governing this reaction and that any interaction influencing the C–B rotational barrier will play an important role in the reactivity of this methodology. While characterizing some of the new compounds made, we made a second interesting discovery. In isolating a triborylated species we noticed we had inadvertently crystalized an orange/red compound. Intrigued by these crystals, we found that they corresponded to a boryl iridium trimer with a molecular formula of [Ir(Bpin)3]3 (Figure 2-12). While we do not know how this this compound formed, it may be interesting to the community at large. This compound may show activity as a C–H borylation catalyst or may be the product of the death of the active iridium borylation catalysts. Future work will further explore the formation of [Ir(Bpin)3]3 and its role in iridium catalyzed C–H borylations. Figure 2-12 [Ir(Bpin)3]3 Crystalized from a Reaction Mixture In conclusion it is herein reported the ability of pyrazine containing ligands to influence borylation ortho to existing aryl pinacol boronic esters to synthesize 1,2-di and 1,2,3-tri borylated compounds directly through iridium catalyzed C–H activation. This methodology is the first ligand guided C–H borylation ortho 22 to aryl boronic pinacolate esters through iridium catalysis. By taking advantage of what we believe is a Lewis acid base interaction between the substrate and active dearomatized pyrazine ligand, we are able to direct borylation to traditionally unavailable positions. Utilizing this approach 1,2-di and 1,2,3- triborylation can be achieved to synthesize compounds that are impossible to directly synthesize efficiently through known methods. General Information Experimental Procedures All available reagents were purchased through Combi-blocks and used as received unless otherwise indicated. Bis(pinacolato)diborn (B2pin2) was generously supplied by BoroPharm. Hexane was refluxed over CaH2 and distilled. Column chromatography was done using 240-400 mesh silica P-Flash silica gel. TLC was done on 0.25 mm thick aluminum backed silica gel plates and visualized with UV light (λ = 254 nm) with alizarin stain.58 1H, 13C, 11B and 19F NMR spectra were recorded on a Varian 500 MHz DD2 Spectrometer equipped with a 1H-19F/15N-31P 5 mm Pulsed Field Gradient (PFG) Probe. Spectra taken in CDCl3 were referenced to 7.26 ppm in 1H NMR and 77.2 ppm in 13C NMR. Spectra taken in C6D6 were referenced to 7.16 ppm in 1H NMR and 128.1 ppm in 13C. 11B NMR spectra were referenced to neat BF3·Et2O as the external standard. NMR spectra were processed for display using the MNova software program with only phasing and baseline corrections applied. High-resolution mass spectra (HRMS) were obtained at the Molecular Metabolism and Disease Mass Spectrometry Core facility and at the Mass Spectrometry Service Center at Michigan State University using electrospray ionization (ESI+ or ESI-) on quadrupole time-of-flight (Q-TOF) instruments. Synthesis of [Ir(OMe)cod]2 Figure 2-13 Synthesis of [Ir(OMe)cod]2 A 100 mL Schlenk flask was charged with a stir bar and [Ir(OMe)cod]2 (0.8418 g, 1.25 mmol) then sealed with a ribbed rubber septa. The flask was then purged with nitrogen. A second 100 mL round bottom flask was charged with methanol (80 mL, 63.3600 g, 1.98 mol) and K2CO3 (0.3810 g, 2.76 mmol) then sealed with a rubber septum. The methanol solution was stirred for 12 hours over which the K2CO3 dissolved. The K2CO3 solution was sparged with nitrogen for 3 hours before being canula transferred into the Schlenk flask containing the [Ir(cod)Cl]2 with the strongest magnetic stirring possible. The Schlenk 23 flask was covered with aluminum foil and stirred for 12 hours under a positive pressure of nitrogen. Over the 12 hours the reaction turned from an orange suspension to a yellow suspension. The Schlenk flask was then opened, and the contained suspension was filtered using a water aspirator. The resulting yellow solid was then washed with ice cold methanol (3x, 3 mL). The solid was then dried under vacuum to yield [Ir(OMe)cod]2 (0.6713 g, 1.01 mmol) as a fine yellow solid resulting in a yield of 81% yield. Data for [Ir(OMe)cod]2 1H NMR (500 MHz, C6D6) δ 3.56 (d, J = 2.7 Hz, 4H), 3.17 (s, 3H), 2.15 (m, 4H), 1.31 (q, J = 7.7 Hz, 4H). 13C NMR (126 MHz, C6D6) δ 56.0, 54.1, 31.8. Synthesis of Bipyrazine Figure 2-14 Synthesis of Bipyrazine A 100 mL round bottom flask was charged with K2CO3 (4.0200 g, 29.09 mmol), Pd(OAc)2 (221.1 mg, 0.99 mmol), and a stir bar. The flask was sealed with a rubber septum and purged with nitrogen. DMF (55 mL) was added along with isopropanol (3 mL, 39.20 mmol) and 2-iodopyrazine (2 mL, 4.1720 g, 20.30 mmol). The reaction was stirred at 100 °C in an oil bath for 7.5 h. The reaction was then allowed to cool to room temperature, and 40 mL of brine was added. The reaction was extracted with EtOAc (3x, 75 mL). The EtOAc layer was washed 3x with aqueous sodium thiosulfate (50 g in 100 mL of H2O). The EtOAc layer was then dried over Na2SO4, filtered, and dried to yield a brown solid. The solid was then sublimated under vacuum at 78 °C to yield 0.7059 g of a yellow solid consisting of bipyrazine giving a yield of 44%. The product was further purified before use by recrystallization by dissolution of the yellow solid in 50 mL of boiling hexane on an oil bath. EtOAc was then slowly added until all the solid had dissolved. Stirring was stopped and the oil bath was turned off allowing the solution in the oil bath to come to room temperature together over 3 hours allowing crystals to form. The crystals were collected by filtration and washed with 10 mL of cold hexane. Bipyrazine (249.3 mg, 1.60 mmol) was collected as perfectly white flake like crystals giving a yield of 19%. The bipyrazine was dried under Dean-Stark conditions prior to use. Data for Bipyrazine 1H NMR (500 MHz, CDCl3) δ 9.59 (d, J = 1.1 Hz, 1H), 8.66 (m, 2H). 1H NMR (500 MHz, C6D6) δ 9.75 (S, 1H), 8.05 (S, 1H), 7.92 (S, 1H). 24 13C NMR (126 MHz, CDCl3) δ 149.4, 145.4, 143.9, 143.6. Melting Point: 187.3-187.9 °C. Synthesis of 4-(tert-butyl)-2-(tributylstannyl)pyridine (S1) n-BuLi (3 equiv) N OH (1.7 equiv) hexane (50 mL), 0 °C 1 h N 15 mmol Bu3SnCl (2.3 equiv) -78 °C, 10 min then rt, 4 h N SnBu3 Figure 2-15 Synthesis of 4-(tert-butyl)-2-(tributylstannyl)pyridine (S1) A stir bar was added to a 100 mL three neck round bottom flask which was then sealed with a septa. The flask was purged with nitrogen then charged with 50 mL of hexane and dimethylethanolamine (2.25 mL, 2.2150 g, 24.80 mmol) via a syringe and needle. The solution was cooled with stirring to 0 °C in an ice water bath. n-BuLi (2.5M in hexane, 19 mL, 2.2150 g, 47.50 mmol) was then added causing the solution to take on a yellow color. The reaction was allowed to stir at 0 °C for 15 minutes. 4-tButylpyridine (2.2 mL, 2.0306 g, 15.00 mmol) was then added via syringe dropwise over the course of 5 minutes causing the reaction to turn orange after which it eventually took on a red / orange hue. The reaction was stirred at 0 °C for 1 hour. The reaction was then cooled to -78 °C with a dry ice acetone bath. Bu3SnCl (9.25 mL, 11.1000 g, 34.00 mmol) was then added dropwise with a syringe over 5 minutes with strong stirring, causing a white precipitate to form. The reaction was stirred for an additional 30 minutes at -78 °C before being allowed to warm to room temperature and stirred for an additional 7 hours. The reaction was then filtered, and the precipitate washed with 20 mL of diethyl ether. The filtrate was concentrated under vacuum to yield S1 as a yellow oil. The product was used without further purification. 25 Synthesis of Ligand-213 (2-(4-(tert-butyl)pyridin-2-yl)pyrazine) Figure 2-16 Synthesis of Ligand-213 (2-(4-(tert-butyl)pyridine-2-yl)pyrazine) A 500 mL Schlenk flask was charged with Pd(PPh3)4 (0.4330 g, 0.38 mmol, 2.5 mol %) and a stir bar. It is worth noting that the Pd(PPh3)4 was in poor condition and had a black appearance. An Alan reflux condenser was fitted to the flask and the apparatus sealed with a septum. The flask was purged with nitrogen through the sidearm and out through a needle in the septum. Xylene (120 mL) was then added via a syringe to the flask along with 2-chloropyrazine (1.34 mL, 1.7200 g, 15.00 mmol). The reaction was then stirred for 12 hours at reflux. After refluxing the reaction was allowed to cool and gravity filtered. The filtrate was then concentrated under vacuum to yield an oil. The oil was then dissolved in 250 mL of hexane during which bipyrazine precipitated out. This was collected and purified as described in the synthesis of bipyrazine. The hexane layer was then washed with 200 mL of water with 5 g of NaF dissolved in it to remove any residual tin. After being allowed to sit a fine precipitate settled and the reaction was filtered, and the solvent evaporated. The remaining oil was redissolved in 75 mL of hexane. The hexane solution was then extracted with acetonitrile (3x, 75 mL). The acetonitrile was evaporated to give an oil. 2/3 of the oil by weight was purified via silica column chromatography (31cm x 2 cm) using 8:2 hexane:EtOAc as the eluent to yield Ligand-213 as a brown oil (fractions were chosen by GCMS). The brown oil was dissolved in 20 mL of hexane and placed in the freezer overnight over which Ligand-213 crystalized out. This was recrystallized by dissolving in hexane and placing in the freezer to crystalize. Ligand-213 (291.2 mg, 1.40 mmol) was collected as the product giving a yield of 9%. The adjusted yield for the product collected after chromatography was 14%. Data for Ligand-213 (2-(4-(tert-butyl)pyridine-2-yl)pyrazine) 1H NMR (500 MHz, CDCl3) δ 9.63 (d, J = 1.3 Hz, 1H), 8.65-8.61 (m, 2H), 8.59 (d, J = 2.5 Hz, 1H), 8.38 (d, J = 1.9 Hz, 1H), 7.37 (dd, J = 5.2, 1.9 Hz, 1H), 1.40 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 161.5, 154.2, 151.7, 149.6, 144.4, 143.7, 143.6, 121.8, 118.6, 35.2, 30.7. Melting Point: 74.6-75.4 °C. 26 Synthesis of 4,4,5,5-tetramethyl-2-(4-(trifluoromethyl)phenyl)-1,3,2-dioxaborolane (1b) Figure 2-17 Synthesis of 4,4,5,5-tetramethyl-2-(4-(trifluoromethyl)phenyl-1,3,2-dioxaborolane (1b) A 20 mL scintillation vial was charged with (4-(trifluoromethyl)phenyl)boronic acid (3.0009 g, 15.80 mmol) and pinacol (2.8007 g, 23.70 mmol). 10 mL of THF was then added, and the vial closed. The vial was stirred at room temperature for 1 hour. The vial was then opened and the THF evaporated. The remaining oil was redissolved in 10 mL of DCM and the solution washed with water (7x, 10 mL). The organic layer was then dried over MgSO4 before being evaporated. 1b (3.7286 g, 13.70 mmol) was collected as a white waxy solid giving a yield of 86.7%. Data for 4,4,5,5-tetramethyl-2-(4-(trifluoromethyl)phenyl)-1,3,2-dioxaborolane (1b) 1H NMR (500 MHz, CDCl3) δ 7.91 (d, J = 7.7 Hz, 2H), 7.61 (d, J = 7.7 Hz, 2H), 1.36 (s, 12H). 13C NMR (126 MHz, CDCl3) δ 135.1, 133.0 (q, J = 32.1 Hz), 124.5 (q, J = 3.8 Hz), 124.3 (q, J = 272.4 Hz), 84.4, 25.0. 11B NMR (160 MHz, CDCl3) δ 30.5. 19F NMR (470 MHz, CDCl3) δ -64.97 (s). Melting Point: 72.1 – 73.3 °C. Synthesis of 4,4,5,5-tetramethyl-2-(4-(trifluoromethoxy)phenyl)-1,3,2-dioxaborolane (1c) Figure 2-18 Synthesis of 4,4,5,5-tetramethyl-2-(4-(trifluoromethoxy)phenyl)-1,3,2-dioxaborolane (1c) A 20 mL scintillation vial was charged with (4-(trifluoromethoxy)phenyl)boronic acid (1.9996 g, 9.71 mmol) and pinacol (1.3770 g, 11.65 mmol). 10 mL of dichloromethane was then added, and the vial closed. The vial was placed in a pocket and carried for 1 hour of general laboratory work. The vial was then opened, and the solution washed with water (5x, 10 mL). The organic layer was then dried over MgSO4 before being evaporated. 1c (2.5028 g, 8.69 mmol) was collected as a white waxy solid giving a yield of 89%. 27 Data for 4,4,5,5-tetramethyl-2-(4-(trifluoromethoxy)phenyl)-1,3,2-dioxaborolane (1c) 1H NMR (500 MHz, CDCl3) δ 7.84 (d, J = 8.1 Hz, 2H, 7.20 (d, J = 8.3 Hz, 2H), 1.35 (s, 12H). 13C NMR (126 MHz, CDCl3) δ 151.8 (q, J = 1.7 Hz), 136.7, 120.4 (q, J = 257.6 Hz), 84.2, 25.0. 19F NMR (470 MHz, CDCl3) δ -57.50 (s). 11B NMR (160 MHz, CDCl3) δ 30.4. Melting Point: 61.5 – 62.3 °C. Synthesis of 2-(4-chloro-2-fluoro-3-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1d) Figure 2-19 Synthesis of 2-(4-chloro-2-fluoro-3-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1d) A 20 mL scintillation vial was charged with (4-(trifluoromethoxy)phenyl)boronic acid (3.0045 g, 14.70 mmol) and pinacol (2.0814 g, 17.61 mmol). 10 mL of dichloromethane was then added, and the vial closed. The vial was placed in a pocket and carried for 1 hour of general laboratory work. The vial was then opened, and the solution washed with water (5x, 10 mL). The organic layer was then dried over Na2SO4 before being evaporated. 1d (3.6270 g, 12.66 mmol) was collected as a white waxy solid giving a yield of 86.11%. Data for 2-(4-chloro-2-fluoro-3-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1d) 1H NMR (500 MHz, CDCl3) δ 7.35 (dd, J = 8.1, 5.7 Hz, 1H), 7.14 (dd, J = 8.1, 1.3 Hz, 1H), 3.96 (d, J = 1.4 Hz, 3H), 1.36 (s, 12H). 13C NMR (126 MHz, CDCl3) δ 160.5 (d, J = 254.3 Hz), 144.3 (d, J = 15.3Hz), 131.9 (d, J = 4.2), 130.6 (d, J = 9.1Hz), 125.3 (d, J = 3.5 Hz), 84.3, 61.6 (d, J = 4.9 Hz), 25.0. 19F NMR (470 MHz, CDCl3) δ -118.07 (m, 1F). 11B NMR (160 MHz, CDCl3) δ 29.7. Melting Point: 63.1-63.8°C 28 Independent Synthesis of 2,2',2''-(2-fluorobenzene-1,3,5-triyl)tris(4,4,5,5-tetramethyl-1,3,2- dioxaborolane) (3a’’) Figure 2-20 Synthesis of 2,2’,2’’-(2-fluorobenzene-1,3,5-triyl)tris4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3a’’) In a glove box under nitrogen a 5 mL Wheaton conical vial with a triangular stir bar was charged with [Ir(OMe)cod]2 (33.0 mg, 0.05 mmol) and B2pin2 (0.5590 g, 2.20 mmol). THF (1 mL, 0.8890 g, 12.33 mmol) was added and the reaction was stirred at room temperature for 5 minutes over which the solution turned a golden-brown color. Then dtbpy (27.0 mg, 0.10 mmol) was then added along with THF (1 mL, 0.8890 g, 12.33 mmol) causing the reaction to a dark color. The reaction was stirred for an additional 5 minutes at room temperature. 2-(4-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.2220 g, 1.00 mmol) was added and the reaction vial capped and removed from the glove box. The reaction was heated in an aluminum heating block at 80 °C with stirring for 48 hours. After heating the vial was allowed to cool. The solvent was then removed under a vacuum to yield a reddish black oil. The oil was then purified via flash column chromatography (2 cm x 18 cm) using hexane : ethyl acetate (8:2) as an eluent. A significant amount of solid, however, did remain on the sand on top of the column. A brown oil was then collected as the product. The oil was dissolved in 10 mL of DCM and washed with 10 mL of H2O. The oil was then subjected to column chromatography a second time (2 cm x 25 cm) using hexane : ethyl acetate (8:2) as an eluent. After evaporation, 3a’’ (0.1183 g, 0.25 mmol) was collected as a white solid resulting in a yield of 25%. Data for 2,2',2''-(2-fluorobenzene-1,3,5-triyl)tris(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) (3a’’) 1H NMR (500 MHz, CDCl3) δ 8.28 (d, J = 6.4 Hz, 2H), 1.33 (s, 24H), 1.33 (s, 12H). Referenced with CDCl3 = 7.26 ppm. 13C NMR (126 MHz, CDCl3) δ 173.9 (d, J = 260.0 Hz), 147.3 (d, J = 9.2 Hz), 84.0, 83.9, 25.0, 25.0. 19F NMR (470 MHz, CDCl3) δ -87.27(t, J = 6.2 Hz, 1F), -87.28 (t, J = 6.4 Hz, 1F). Two overlapping triplets were seen. This was believed to be an isotopic effect between 10B and 11B. 11B NMR (160 MHz, CDCl3) δ 30.2. Melting Point: 282.9 – 286.6 °C 29 Experimental for Figure 2-4 Entry 1 Figure 2-21 Experimental for Figure 2-4 Entry 1 In a glove box under nitrogen a 5 mL Wheaton conical vial with a triangular stir bar was charged with [Ir(OMe)cod]2 (3.0 mg, 0.05 mmol) and B2pin2 (0.0950 g, 0.37mmol). Hexane (0.5 mL, 0.3325 g, 3.86 mmol) was added and the reaction was stirred at room temperature for 5 minutes over which the solution turned a golden-brown color. Bipyrazine (1.5 mg, 0.01 mmol) was then added along with hexane (0.25 mL, 0.1663 g, 1.93 mmol) causing the reaction to turn green. The reaction was stirred for an additional 5 minutes at room temperature. 2-(4-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.1110 g, 0.50 mmol) was added and the reaction vial capped and removed from the glove box. The reaction was heated in an aluminum heating block at 60 °C with stirring for 48 hours. The vial was then returned to the glove box and opened. [Ir(OMe)cod]2 (3.0 mg, 0.05 mmol) and B2pin2 (0.0711 g, 0.28 mmol) was then added with hexane (0.5 mL, 0.3325 g, 3.86 mmol). The reaction was stirred at room temperature for 5 minutes. Bipyrazine (1.5 mg, 0.01 mmol) was then added along with hexane (0.25 mL, 0.1663 g, 1.93 mmol). The reaction was capped and stirred for an additional 5 minutes at room temperature before being removed from the glove box and stirred at 60 °C in an aluminum heating block for an additional 48 hours. The vial was then returned to the glove box and opened. [Ir(OMe)cod]2 (3.0 mg, 0.05 mmol) and B2pin2 (0.0711 g, 0.28 mmol) was then added with hexane (0.5 mL, 0.3325 g, 3.86 mmol). The reaction was stirred at room temperature for 5 minutes. Bipyrazine (1.5 mg, 0.01 mmol) was then added along with hexane (0.25 mL, 0.1663 g, 1.93 mmol). The reaction was capped and stirred for an additional 5 minutes at room temperature before being removed from the glove box and stirred at 60 °C in an aluminum heating block for an additional 48 hours. After heating for the third time, the vial was allowed to cool. The solvent was then removed under a vacuum to yield a reddish black oil. The oil was then purified via flash column chromatography (2 cm x 18 cm) using hexane : ethyl acetate (8:2) as an eluent to yield 2a, 2a’,3a, 3a’ as a mixture of regio-isomers (116.5mg). This results in a yield of 2a (64.4 mg, 0.19 mmol, ), 2a’ (21.7 mg, 0.06 mmol), 3a (9.9 mg, 0.03 mmol), 3a’ (7.3 mg, 0.15 mmol). In a subsequent reaction run the same as described above a small amount of brown precipitate formed. This 30 was found to be compound 3a. This was further purified by flash column chromatography (2 cm x 18 cm) using hexane : ethyl acetate (8:2) as an eluent to yield pure 3a as a white solid (3.6 mg, 0.01 mmol). Data for Figure 2-4 Entry 1 Compound 2a 1H NMR (500 MHz, CDCl3) δ 7.67 (dd, J = 8.3, 6.0 Hz, 1H), 7.29 (dd, J = 9.5, 2.6 Hz, 1H), 7.04 (m, 1H), 1.370 (s, 12H), 1.351 (s, 12H). 13C NMR (126 MHz, CDCl3) δ 163.9 (d, J = 250.3 Hz), 136.4 (d, J = 7.4 Hz), 120.1 (d, J = 18.8 Hz), 116.1 (d, J = 19.9 Hz), 84.1, 84.0, 25.0, 25.0. 19F NMR (470 MHz, CDCl3) δ -111.35 (dt, J = 9.3, 6.1). 11B NMR (160 MHz, CDCl3) δ 30.9. Data for Figure 2-4 Entry 1 Compound 2a’ 1H NMR (500 MHz, CDCl3) δ 8.20 (dd, J = 6.5, 1.7 Hz, 1H), 7.88 (ddd, J = 8.1, 6.0, 1.8 Hz, 1H), 7.02 (dd, J = 9.5, 8.4 Hz, 1H), 1.35 (s, 12H), 1.33 (s, 12H). 13C NMR (126 MHz, CDCl3) δ 169.6 (d, J = 255.3 Hz), 144.1 (d, J = 8.4 Hz), 140.3 (d, J = 9.2 Hz), 115.0 (d, J = 23.5 Hz), 84.0, 25.0, 25.0. 19F NMR (470 MHz, CDCl3) δ – 98.10 (m). 11B NMR (160 MHz, CDCl3) δ 30.9. Data for Figure 2-4 Entry 1 Compound 3a 1H NMR (500 MHz, CDCl3) δ 7.60 (d, J = 9.5 Hz, 2H), 1.47 (s, 12H), 1.33 (s, 24H). 13C NMR (126 MHz, CDCl3) δ 162.5 (d, J = 248.5 Hz), 124.2 (d, J = 18.1 Hz), 84.3, 25.939, 24.9. 19F NMR (470 MHz, CDCl3) δ -115.39 (t, J = 9.5 Hz, 1F). Referenced with C6F6 = -161.64 ppm. 11B NMR (160 MHz, CDCl3) δ 30.8. Data for Figure 2-4 Entry 1 Compound 3a’ 1H NMR (500 MHz, CDCl3) δ 8.02 (d, J = 6.3 Hz, 1H), 7.25 (d, J = 10.3 Hz, 1H), 19F NMR (470 MHz, CDCl3) δ 101.29 (dd, J = 9.9, 6.4 Hz, 1F). 11B NMR (160 MHz, CDCl3) δ 30.9 31 Experimental for Figure 2-4 Entry 2 Figure 2-22 Experimental for Figure 2-4 Entry 2 In a glove box under nitrogen a 5 mL Wheaton conical vial with a triangular stir bar was charged with [Ir(OMe)cod]2 (3 mg, 0.05 mmol) and B2pin2 (0.0950 g, 0.37 mmol). Hexane (0.5 mL, 0.3325 g, 3.86 mmol) was added and the reaction was stirred at room temperature for 5 minutes over which the solution turned a golden-brown color. Bipyrazine (1.5 mg, 0.01 mmol) was then added along with hexane (0.25 mL, 0.1663 g, 1.93 mmol) causing the reaction to turn green. The reaction was stirred for an additional 5 minutes at room temperature. 4,4,5,5-tetramethyl-2-(4-(trifluoromethyl)phenyl)-1,3,2- dioxaborolane (0.1366 g, 0.50 mmol) was added and the reaction vial capped and removed from the glove box. The reaction was heated in an aluminum heating block at 60 °C with stirring for 48 hours. The vial was then returned to the glove box and opened. [Ir(OMe)cod]2 (3.0 mg, 0.05 mmol) and B2pin2 (0.0711 g, 0.28 mmol) was then added with hexane (0.5 mL, 0.3325 g, 3.86 mmol). The reaction was stirred at room temperature for 5 minutes. Bipyrazine (1.5 mg, 0.01 mmol) was then added along with hexane (0.25 mL, 0.1663 g, 1.93 mmol). The reaction was capped and stirred for an additional 5 minutes at room temperature before being removed from the glove box and stirred at 60 °C in an aluminum heating block for an additional 48 hours. The vial was then returned to the glove box and opened. [Ir(OMe)cod]2 (3.0 mg, 0.05 mmol) and B2pin2 (0.0711 g, 0.28 mmol) was then added with hexane (0.5 mL, 0.3325 g, 3.86 mmol). The reaction was stirred at room temperature for 5 minutes. Bipyrazine (1.5 mg, 0.01 mmol) was then added along with hexane (0.25 mL, 0.1663 g, 1.93 mmol). The reaction was capped and stirred for an additional 5 minutes at room temperature before being removed from the glove box and stirred at 60 °C in an aluminum heating block for an additional 48 hours. After heating for the third time, the vial was allowed to cool. The solvent was then removed under a vacuum to yield a reddish black oil. The oil was then purified via flash column chromatography (2 cm x 18 cm) using hexane : ethyl acetate (8:2) as an eluent. The products were collected in 3 fractions as clear oil and consisted of a mixture of regio-isomers. This results in a yield of 1b’ (1.4 mg, 0.01 mmol), 2b (111.9 mg, 0.28 mmol), 2b’ (2.7 mg, 0.01 mmol), and 3b (22.2 mg, 0.04 mmol). 32 Data for Figure 2-4 Entry 2 Compound 1b’ 1H NMR (500 MHz, CDCl3) δ 8.06 (S, 1H), 7.97 (d, J = 7.3 Hz, 1H), 7.48 (t, J = 7.6 Hz, 1H), 1.35 (s, 12H). 13C NMR (126 MHz, CDCl3) δ 138.1, 131.5 (q, J = 3.8 Hz), 130.1 (q, J = 3.6 Hz), 128.2, 127.9 (q, J = 3.8 Hz), 84.4, 25.0. 19F NMR (470 MHz, CDCl3) δ -62.61 (s) 11B NMR (160 MHz, CDCl3) δ 31.1. Data for Figure 2-4 Entry 2 Compound 2b 1H NMR (500 MHz, CDCl3) δ 7.90 (s, 1H), 7.73 (d, J = 7.8 Hz, 1H), 7.61 (d, J = 7.8 Hz, 1H), 1.37 (s, 12H), 1.37 (s, 12H). 13C NMR (126 MHz, CDCl3) δ 133.6, 130.9, 130.1 (q, J = 3.8 Hz), 125.8 (q, J = 3.7 Hz), 124.4 (q, J = 3.8 Hz), 124.4 (d, J = 272.4 Hz), 84.4, 25.0. 19F NMR (470 MHz, CDCl3) δ -62.93 (s, 3F). 11B NMR (160 MHz, CDCl3) δ 31.1. Data for Figure 2-4 Entry 2 Compound 2b’ 1H NMR (500 MHz, CDCl3) δ 8.42 (s, 1H), 8.13 (S, 2H), 1.35 (s, 24H). 19F NMR (470 MHz, CDCl3) δ -62.51. 11B NMR (160 MHz, CDCl3) δ 31.1. Data for Figure 2-4 Entry 2 Compound 3b 1H NMR (500 MHz, CDCl3) δ 134.02 (q, J = 3.62 Hz), 84.59, 84.46, 25.97, 25.91. 13C NMR (126 MHz, CDCl3) δ 134.0 (q, J = 3.62 Hz), 84.6, 84.5, 26.0, 25.9. 19F NMR (470 MHz, CDCl3) δ -62.79 (s, 1F). 11B NMR (160 MHz, CDCl3) δ 31.0. Experimental for Figure 2-4 Entry 3 Figure 2-23 Experimental for Figure 2-4 Entry 3 In a glove box under nitrogen a 5 mL Wheaton conical vial with a triangular stir bar was charged with [Ir(OMe)cod]2 (3.0 mg, 0.05 mmol) and B2pin2 (0.0950 g, 0.37 mmol). Hexane (0.5 mL, 0.3325 g, 3.86 33 mmol) was added and the reaction was stirred at room temperature for 5 minutes over which the solution turned a golden-brown color. Bipyrazine (1.5 mg, 0.01 mmol) was then added along with hexane (0.25 mL, 0.1663 g, 1.93 mmol) causing the reaction to turn green. The reaction was stirred for an additional 5 minutes at room temperature. 4,4,5,5-tetramethyl-2-(4-(trifluoromethoxy)phenyl)-1,3,2- dioxaborolane (0.1440 g, 0.50 mmol) was added and the reaction vial capped and removed from the glove box. The reaction was heated in an aluminum heating block at 60 °C with stirring for 48 hours. The vial was then returned to the glove box and opened. [Ir(OMe)cod]2 (3.0 mg, 0.05 mmol) and B2pin2 (0.0711 g, 0.28 mmol) was then added with hexane (0.5 mL, 0.3325 g, 3.86 mmol). The reaction was stirred at room temperature for 5 minutes. Bipyrazine (1.5 mg, 0.01 mmol) was then added along with hexane (0.25 mL, 0.1663 g, 1.93 mmol). The reaction was capped and stirred for an additional 5 minutes at room temperature before being removed from the glove box and stirred at 60 °C in an aluminum heating block for an additional 48 hours. The vial was then returned to the glove box and opened. [Ir(OMe)cod]2 (3.0 mg, 0.05 mmol) and B2pin2 (0.0711 g, 0.28 mmol) was then added with hexane (0.5 mL, 0.3325 g, 3.86 mmol). The reaction was stirred at room temperature for 5 minutes. Bipyrazine (1.5 mg, 0.01 mmol) was then added along with hexane (0.25 mL, 0.1663 g, 1.93 mmol). The reaction was capped and stirred for an additional 5 minutes at room temperature before being removed from the glove box and stirred at 60 °C in an aluminum heating block for an additional 48 hours. After heating for the third time, the vial was allowed to cool. The solvent was then removed under a vacuum to yield a reddish black oil. The oil was then purified via flash column chromatography (2 cm x 18 cm) using hexane : ethyl acetate (8:2) as an eluent. Data for Figure 2-4 Entry 3 Compound 2c 1H NMR (500 MHz, CDCl3) δ 7.70 (d, J = 8.2 Hz, 1H), 7.461 (s, 1H), 7.21 (m, 1H), 1.37 (s, 1H), 1.36 (s, 12H). 13C NMR (126 MHz, CDCl3) δ 150.4, 135.6, 125.6, 121.4, 120.0, 84.3, 84.2, 25.0. 19F NMR (470 MHz, CDCl3) δ -57.48 (s, 3F). 11B NMR (160 MHz, CDCl3) δ 31.0. Data for Figure 2-4 Entry 3 Compound 3c 1H NMR (500 MHz, CDCl3) δ 7.75 (s, 2H), 1.48 (s, 12H), 1.33 (s, 12H). 19F NMR (470 MHz, CDCl3) δ -57.36. 11B NMR (160 MHz, CDCl3) δ 31.0. 34 Experimental for Figure 2-4 Entry 4 Figure 2-24 Experimental for Figure 2-4 Entry 4 In a glove box under nitrogen a 5 mL Wheaton conical vial with a triangular stir bar was charged with [Ir(OMe)cod]2 (3 mg, 0.0045 mmol) and B2pin2 (0.0950 g, 0.37 mmol). Hexane (0.5 mL, 0.3325 g, 3.86 mmol) was added and the reaction was stirred at room temperature for 5 minutes over which the solution turned a golden-brown color. Bipyrazine (1.5 mg, 0.01 mmol) was then added along with hexane (0.25 mL, 0.1663 g, 1.93 mmol) causing the reaction to turn green. The reaction was stirred for an additional 5 minutes at room temperature. 2-(4-chloro-2-fluoro-3-methoxyphenyl)-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (0.1430 g, 0.50 mmol) was added and the reaction vial capped and removed from the glove box. The reaction was heated in an aluminum heating block at 60 °C with stirring for 48 hours. The vial was then returned to the glove box and opened. [Ir(OMe)cod]2 (3.0 mg, 0.05 mmol) and B2pin2 (0.0711 g, 0.28 mmol) was then added with hexane (0.5 mL, 0.3325 g, 3.86 mmol). The reaction was stirred at room temperature for 5 minutes. Bipyrazine (1.5 mg, 0.01 mmol) was then added along with hexane (0.25 mL, 0.1663 g, 1.93 mmol). The reaction was capped and stirred for an additional 5 minutes at room temperature before being removed from the glove box and stirred at 60 °C in an aluminum heating block for an additional 48 hours. The vial was then returned to the glove box and opened. [Ir(OMe)cod]2 (3.0 mg, 0.05 mmol) and B2pin2 (0.0711 g, 0.28 mmol) was then added with hexane (0.5 mL, 0.3325 g, 3.86 mmol). The reaction was stirred at room temperature for 5 minutes. Bipyrazine (1.5 mg, 0.01 mmol) was then added along with hexane (0.25 mL, 0.1663 g, 1.93 mmol). The reaction was capped and stirred for an additional 5 minutes at room temperature before being removed from the glove box and stirred at 60 °C in an aluminum heating block for an additional 48 hours. After heating for the third time, the vial was allowed to cool. The solvent was then removed under a vacuum to yield a reddish black oil. The oil was then purified via flash column chromatography (2 cm x 18 cm) using hexane : ethyl acetate (8:2) as an eluent. 2,2'-(5-chloro-3-fluoro-4-methoxy-1,2-phenylene)bis(4,4,5,5- tetramethyl-1,3,2-dioxaborolane) was collected as a white waxy solid (0.1732g, 0.42 mmol) resulting in a yield of 84%. 35 Data for Figure 2-4 Entry 4 Compound 2d 1H NMR (500 MHz, CDCl3) δ 7.59 (d, J = 0.9 Hz, 1H), 3.96 (d, J = 1.8 Hz, 3H), 1.41 (s, 12H), 1.31 (s, 12H). 13C NMR (126 MHz, CDCl3) δ 158.2 (d, J = 244.8 Hz), 145.8 (d, J= 15.4 Hz), 132.6 (d, J = 2.8 Hz), 128.6 (d, J = 3.9 Hz), 84.7, 84.600, 61.5 (d, J = 5.4 Hz), 25.1, 25.9. 19F NMR (470 MHz, CDCl3) δ -121.69 (s, 1F). 11B NMR (160 MHz, CDCl3) δ 30.4. Experimental for Figure 2-4 Entry 5 Figure 2-25 Experimental for Figure 2-4 Entry 5 In a glove box under nitrogen a 5 mL Wheaton conical vial with a triangular stir bar was charged with [Ir(OMe)cod]2 (3.0 mg, 0.05 mmol) and B2pin2 (0.0950 g, 0.37 mmol). Hexane (0.5 mL, 0.3325 g, 3.86 mmol) was added and the reaction was stirred at room temperature for 5 minutes over which the solution turned a golden-brown color. Bipyrazine (1.5 mg, 0.01 mmol) was then added along with hexane (0.25 mL, 0.1663 g, 1.93 mmol) causing the reaction to turn green. The reaction was stirred for an additional 5 minutes at room temperature. 2-(4-chlorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.1190 g, 0.50 mmol) was added and the reaction vial capped and removed from the glove box. The reaction was heated in an aluminum heating block at 60 °C with stirring for 48 hours. The vial was then returned to the glove box and opened. [Ir(OMe)cod]2 (3.0 mg, 0.05 mmol) and B2pin2 (0.0711 g, 0.28 mmol) was then added with hexane (0.5 mL, 0.3325 g, 3.86 mmol). The reaction was stirred at room temperature for 5 minutes. Bipyrazine (1.5 mg, 0.01 mmol) was then added along with hexane (0.25 mL, 0.1663 g, 1.93 mmol). The reaction was capped and stirred for an additional 5 minutes at room temperature before being removed from the glove box and stirred at 60 °C in an aluminum heating block for an additional 48 hours. The vial was then returned to the glove box and opened. [Ir(OMe)cod]2 (3.0 mg, 0.05 mmol) and B2pin2 (0.0711 g, 0.28 mmol) was then added with hexane (0.5 mL, 0.3325 g, 3.86 mmol). The reaction was stirred at room temperature for 5 minutes. Bipyrazine (1.5 mg, 0.01 mmol) was then added along with hexane (0.25 mL, 0.1663 g, 1.93 mmol). The reaction was capped and stirred for an additional 5 minutes at room temperature before being removed from the glove box and stirred at 60 36 °C in an aluminum heating block for an additional 48 hours. After heating for the third time, the vial was allowed to cool. The solvent was then removed under a vacuum to yield a reddish black oil. The oil was then purified via flash column chromatography (2 cm x 18 cm) using hexane : ethyl acetate (8:2) as an eluent to give 61.1 mg of a clear oil consisting of a mixture of mixture of isomers. Data for Figure 2-4 Entry 4 Compound 2e 1H NMR (500 MHz, CDCl3) δ 7.59 (S, 1H), 7.58 (d, J = 5.0 Hz, 1H), 7.33 (d, J = 8.2 Hz, 1H), 1.36 (s, 12H), 1.35 (s, 12H). 13C NMR (126 MHz, CDCl3) 136.1, 135.3, 133.3, 129.3, 84.3, 84.2, 25.0. 11B NMR (160 MHz, CDCl3) δ 30.1. Data for Figure 2-4 Entry 4 Compound 2e’ 1H NMR (500 MHz, CDCl3) δ 8.10 (d, J = 1.6 Hz, 1H), 7.73 (1H), 7.34 (1H), 1.37 (s, 12H), 1.33 (S, 12H). 13C NMR (126 MHz, CDCl3) δ 142.9, 142.8, 138.3, 128.9, 84.2, 84.1, 24.7. 11B NMR (160 MHz, CDCl3) δ 30.1. Experimental for Figure 2-9 Entry 1 Figure 2-26 Experimental for Figure 2-9 Entry 1 In a glove box under nitrogen a 5 mL Wheaton conical vial with a triangular stir bar was charged with [Ir(OMe)cod]2 (3.0 mg, 0.05 mmol) and B2pin2 (0.1270 g, 0.50 mmol). Hexane (0.5 mL, 0.3325 g, 3.86 mmol) was added and the reaction was stirred at room temperature for 5 minutes over which the solution turned a golden-brown color. Ligand-213 (1.5 mg, 0.01 mmol) was then added along with hexane (0.25 mL, 0.1663 g, 1.93 mmol) causing the reaction to turn green. The reaction was stirred for an additional 5 minutes at room temperature. 4,4,5,5-tetramethyl-2-(4-(trifluoromethyl)phenyl)-1,3,2- dioxaborolane (0.1366 g, 0.50 mmol) was added and the reaction vial capped and removed from the glove box. The reaction was heated in an aluminum heating block at 60 °C with stirring for 48 hours after which the reaction vial was cooled to room temperature and opened. The solvent was removed under vacuum to yield a red, black oil. The oil was purified via flash column chromatography (2 cm x 18) using hexane : ethyl acetate (8:2) as the eluent. 37 Data for Figure 2-9 Entry 1 Compound 2a 1H NMR (500 MHz, CDCl3) δ 7.67 (dd, J = 8.2, 6.0 Hz, 1H), 7.29 (dd, J = 9.6, 2.6 Hz, 1H), 7.05 (dt, J = 8.7, 2.6 Hz, 1H), 1.37 (s, 12H), 1.35 (s, 12H). 13C NMR (126 MHz, CDCl3) δ 136.4 (d, J = 7.3 Hz), 120.1 (d, J = 18.7 Hz), 116.2 (d, J = 19.9 Hz), 84.3, 84.2, 24.9, 24.8. 19F NMR (470 MHz, CDCl3) δ -111.35 (dt, J = 9.3, 6.1, 1F). 11B NMR (160 MHz, CDCl3) δ 30.6. Data for Figure 2-9 Entry 1 Compound 2a’ 1H NMR (500 MHz, CDCl3) δ 8.20 (dd, J = 6.5, 1.7 Hz, 1H), 7.88 (ddd, J = 8.1, 6.0, 1.8 Hz, 1H), 7.02 (dd, J = 9.5, 8.4 Hz, 1H), 1.37 (s, 12H), 1.35 (s, 12H). 13C NMR (126 MHz, CDCl3) δ 169.6 (d, J = 255.3 Hz), 144.1 (d, J = 8.4 Hz), 140.4 (d, J = 9.2 Hz), 114.9 (d, J = 23.2 Hz), 84.0, 25.0, 25.0. 19F NMR (470 MHz, CDCl3) δ – 98.11 (m). This peak was characterized as a multiplet although it seemed to be two peaks overlapped with one peak representing compound 2a’ with 10B and the other representing compound 2a’ with 11B. 11B NMR (160 MHz, CDCl3) δ 30.6. Data for Figure 2-9 Entry 1 Compound 3a 1H NMR (500 MHz, CDCl3) δ 7.60 (d, J = 9.5 Hz, 2H), 1.47 (s, 12H), 1.33 (s, 24H). 13C NMR (126 MHz, CDCl3) δ 162.5 (d, J = 248.5 Hz), 124.2 (d, J = 18.1 Hz), 84.3, 25.9, 24.9. 19F NMR (470 MHz, CDCl3) δ -115.39 (t, J = 9.5 Hz, 1F). Referenced with C6F6 = -161.64 ppm. 11B NMR (160 MHz, CDCl3) δ 30.8. Data for Figure 2-9 Entry 1 Compound 3a’ 1H NMR (500 MHz, CDCl3) δ 8.02 (d, J = 6.3 Hz, 1H), 7.25 (d, J = 10.3 Hz, 1H), 19F NMR (470 MHz, CDCl3) δ 101.29 (dd, J = 9.9, 6.4 Hz, 1F). 11B NMR (160 MHz, CDCl3) δ 30.6 Experimental for Figure 2-9 Entry 2 Figure 2-27 Experimental for Figure 2-9 Entry 2 38 In a glove box under nitrogen a 5 mL Wheaton conical vial with a triangular stir bar was charged with [Ir(OMe)cod]2 (3.0 mg, 0.05 mmol) and B2pin2 (0.1270 g, 0.50 mmol). Hexane (0.5 mL, 0.3325 g, 3.8595 mmol) was added and the reaction was stirred at room temperature for 5 minutes over which the solution turned a golden-brown color. Ligand-213 (1.5 mg, 0.01 mmol) was then added along with hexane (0.25 mL, 0.1663 g, 1.93 mmol) causing the reaction to turn green. The reaction was stirred for an additional 5 minutes at room temperature. 4,4,5,5-tetramethyl-2-(4-(trifluoromethyl)phenyl)-1,3,2- dioxaborolane (0.1366 g, 0.50 mmol) was added and the reaction vial capped and removed from the glove box. The reaction was heated in an aluminum heating block at 60 °C with stirring for 48 hours after which the reaction vial was cooled to room temperature and opened. The solvent was removed under vacuum to yield a red, black oil. The oil was purified via flash column chromatography (2 cm x 18) using hexane : ethyl acetate (8:2) as the eluent. Data for Figure 2-9 Entry 2 Compound 1b’ 1H NMR (500 MHz, CDCl3) δ 8.06 (S, 1H), 7.97 (d, J = 7.3 Hz, 1H), 7.48 (t, J = 7.6 Hz, 1H), 1.35 (s, 12H). 13C NMR (126 MHz, CDCl3) δ 138.1, 131.5 (q, J = 3.8 Hz), 130.1 (q, J = 3.6 Hz), 128.2, 127.9 (q, J = 3.8 Hz), 84.4, 25.0. 19F NMR (470 MHz, CDCl3) δ -62.61 (s, 13F) 11B NMR (160 MHz, CDCl3) δ 31.1. Data for Figure 2-9 Entry 2 Compound 2b 1H NMR (500 MHz, CDCl3) δ 7.90 (s, 1H), 7.73 (d, J = 7.8 Hz, 1H), 7.61 (d, J = 7.8 Hz, 1H), 1.374 (s, 12H), 1.37 (s, 12H). 13C NMR (126 MHz, CDCl3) δ 133.6, 130.9, 130.1 (q, J = 3.8 Hz), 125.8 (q, J = 3.7 Hz), 124.4 (q, J = 3.8 Hz), 124.4 (d, J = 272.4 Hz), 84.4, 25.0. 19F NMR (470 MHz, CDCl3) δ -62.93 (s, 3F). 11B NMR (160 MHz, CDCl3) δ 31.1. Data for Figure 2-9 Entry 2 Compound 2b’ 1H NMR (500 MHz, CDCl3) δ 8.42 (s, 1H), 8.13 (S, 2H), 1.35 (s, 24H). 19F NMR (470 MHz, CDCl3) δ -62.51. 11B NMR (160 MHz, CDCl3) δ 31.1. Data for Figure 2-9 Entry 2 Compound 3b 1H NMR (500 MHz, CDCl3) δ 134.02 (q, J = 3.62 Hz), 84.59, 84.46, 25.97, 25.91. 13C NMR (126 MHz, CDCl3) δ 134.0 (q, J = 3.62 Hz), 84.6, 84.5, 25.0, 25.9. 39 19F NMR (470 MHz, CDCl3) δ -62.79 (s, 1F). 11B NMR (160 MHz, CDCl3) δ 31.0. Experimental for Figure 2-9 Entry 3 Figure 2-28 Experimental for Figure 2-9 Entry 3 In a glove box under nitrogen a 5 mL Wheaton conical vial with a triangular stir bar was charged with [Ir(OMe)cod]2 (3.0 mg, 0.05 mmol) and B2pin2 (0.1270 g, 0.50 mmol). Hexane (0.5 mL, 0.3325 g, 3.86 mmol) was added and the reaction was stirred at room temperature for 5 minutes over which the solution turned a golden-brown color. Ligand-213 (1.5 mg, 0.01 mmol) was then added along with hexane (0.25 mL, 0.1663 g, 1.93 mmol) causing the reaction to turn green. The reaction was stirred for an additional 5 minutes at room temperature. 4,4,5,5-tetramethyl-2-(4-(trifluoromethoxy)phenyl)-1,3,2- dioxaborolane (0.1440 g, 0.50 mmol) was added and the reaction vial capped and removed from the glove box. The reaction was heated in an aluminum heating block at 60 °C with stirring for 48 hours after which the reaction vial was cooled to room temperature and opened. The solvent was removed under vacuum to yield a red, black oil. The oil was purified via flash column chromatography (2 cm x 18) using hexane : ethyl acetate (8:2) as the eluent. Data for Figure 2-9 Entry 3 Compound 2c 1H NMR (500 MHz, CDCl3) δ 7.70 (d, J = 8.2 Hz, 1H), 7.46 (s, 1H), 7.21 (m, 1H), 1.37 (s, 1H), 1.36 (s, 12H). 13C NMR (126 MHz, CDCl3) δ 150.4, 135.6, 125.6, 121.4, 120.0, 84.3, 84.2, 25.0. 19F NMR (470 MHz, CDCl3) δ -57.45 (s, 3F). 11B NMR (160 MHz, CDCl3) δ 31.0. Data for Figure 2-9 Entry 3 Compound 3c 1H NMR (500 MHz, CDCl3) δ 7.75 (s, 2H), 1.48 (s, 12H), 1.33 (s, 12H). 19F NMR (470 MHz, CDCl3) δ -57.36. 11B NMR (160 MHz, CDCl3) δ 31.0. 40 Experimental for Figure 2-9 Entry 4 Figure 2-29 Experimental for Figure 2-9 Entry 4 In a glove box under nitrogen a 5 mL Wheaton conical vial with a triangular stir bar was charged with [Ir(OMe)cod]2 (3.0 mg, 0.05 mmol) and B2pin2 (0.1270 g, 0.50 mmol). Hexane (0.5 mL, 0.3325 g, 3.86 mmol) was added and the reaction was stirred at room temperature for 5 minutes over which the solution turned a golden-brown color. Ligand-213 (1.5 mg, 0.01 mmol) was then added along with hexane (0.25 mL, 0.1663 g, 1.93 mmol) causing the reaction to turn green. The reaction was stirred for an additional 5 minutes at room temperature. 2-(4-chloro-2-fluoro-3-methoxyphenyl)-4,4,5,5- tetramethyl-1,3,2-dioxaborolane (0.1430 g, 0.50 mmol) was added and the reaction vial capped and removed from the glove box. The reaction was heated in an aluminum heating block at 60 °C with stirring for 48 hours after which the reaction vial was cooled to room temperature and opened. The solvent was removed under vacuum to yield a red, black oil. The oil was purified via flash column chromatography (2 cm x 18) using hexane : ethyl acetate (8:2) as the eluent. Data for Figure 2-9 Entry 4 Compound 2d 1H NMR (500 MHz, CDCl3) δ 7.59 (d, J = 0.9 Hz, 1H), 3.96 (d, J = 1.8 Hz, 3H), 1.41 (s, 12H), 1.31 (s, 12H). 13C NMR (126 MHz, CDCl3) δ 158.2 (d, J = 244.8 Hz), 145.8 (d, J= 15.4 Hz), 132.6 (d, J = 2.8 Hz), 128.6 (d, J = 3.9 Hz), 84.7, 84.6, 61.5 (d, J = 5.4 Hz), 25.1, 25.9. 19F NMR (470 MHz, CDCl3) δ -121.69 (s, 1F). 11B NMR (160 MHz, CDCl3) δ 30.4. Data for Figure 2-9 Entry 4 Compound 1d’ 1H NMR (500 MHz, CDCl3) δ 7.58 (s, 1H), 7.41 (d, J = 11.1 Hz, 1H), 1.32 (s, 12H). 19F NMR (470 MHz, CDCl3) δ -129.13 (dt, J = 11.0, 1.5 Hz, 1F). 11B NMR (160 MHz, CDCl3) δ 30.0. Data for Figure 2-9 Entry 4 Compound 1d’’ 19F NMR (470 MHz, CDCl3) δ – 114.53 (d, J = 6.1 Hz, 1F). 41 Synthesis and Isolation of 3a and [IrBpin3]3 Figure 2-30 Synthesis and Isolation of 3a and [IrBpin]3 In a glove box under nitrogen a 5 mL Wheaton conical vial with a triangular stir bar was charged with [Ir(OMe)cod]2 (233.0 mg, 0.35 mmol) and B2pin2 (1.0158 g, 4.00 mmol). Hexane (2 mL, 1.3300 g, 15.44 mmol) was added and the reaction was stirred at room temperature for 5 minutes over which the solution turned black. Bipyrazine (90 mg, 0.57 mmol) was then added along with hexane (1 mL, 0.6650 g, 7.72 mmol). The reaction was stirred for an additional 5 minutes at room temperature. 4,4,5,5- tetramethyl-2-(4-(trifluoromethyl)phenyl)-1,3,2-dioxaborolane (0.5440 g, 2.00 mmol) was added and the reaction vial capped and removed from the glove box. The reaction was heated in an aluminum heating block at 60 °C with stirring for 72 hours after which the reaction vial was cooled to room temperature and opened. The solvent was removed under vacuum to yield a red, black oil. The oil was purified via flash column chromatography (2 cm x 12 cm) using hexane : ethyl acetate (8:2) as the eluent yielding a tan oil. The oil was further purified by passing through a silica plug (2 cm x 3 cm) using hexane : ethyl acetate (8:2) which yielded a less tan oil. The oil was re-dissolved in hexane and placed in a freezer at -30 °C for 1 week over which red / orange crystals formed. The crystals were filtered out and washed with hexane to yield [IrBpin3]3 (0.8 mg). 42 REFERENCES (1) (2) (3) (4) (5) (6) (7) Teo, W. J.; Ge, S. Cobalt-Catalyzed Diborylation of 1,1-disubstituted Vinylarenes: A Practical Route to Branched gem-Bis(boryl)alkanes Angew. Chem. Int. Ed. 2018, 57, 1654-1658. Choi, J.; Kwak, S.; Kwak Y.; Kwon, O.; Kim, J.; Lee, K.; Lee, S. Organic Light-Emitting Device Including The Same U.S. Patent 2018/0097189 A1, April 5, 2018. CN 111978355A, June 6, 2015 Liao, G.; Zhang, T.; Jin, L.; Wang, B. J.; X., C. K.; Lan, Y.; Zhao, Y.; Shi, B. F. Experimental and Computational Studies on the Directing Ability of Chalcogenoethers in Palladium-Catalyzed Atroposelective C-H Olefination and Allylation Angew . Chem. 2022, 134, e2021152. Seven, O.; Bolte, M.; Lerner, H. W.; Wagner, M. High-Yield Syntheses and Reactivity Studies of 1,2-Diborylated and 1,2,4,5-Tetraborylated Benzenes Organometallics, 2014, 33, 1291- 1299. Yoshida, H.; Okada, K.; Kawashima, S.; Tanino, K.; Oshita, J. Platinum-Catalysed Diborylation of Arynes: Synthesis and Reaction of 1,2-Diborylarenes Chem. Commun. 2010, 46, 1763-1765. Yoshida, H.; Kawahima, S.; Takemoto, Y.; Okada, K.; Ohshita, J.; Takaki, K. Copper-Catalyzed Borylation Reactions of Alkynes and Arynes Angew. Chem. 2012, 124, 239-242. (8) Moldoveanu, C.; Wilson, D. A.; Wilson C. J.; Leowanawat, P.; Resmerita, A. M.; Liu, C.; Rosen, B. M.; Percec, V. Neopentylglycolborylation of ortho-Substituted Aryl Halides Catalyzed by NiCl2-Based Mixed-Ligand Systems J.Org.Chem. 2010, 75, 5438–5452. (9) (10) Niwa, T; Ochiai, H.; Hosoya, T. Copper-Catalyzed ipso-Borylation of Fluoroarenes ACS Catal. 2017, 7, 4535-4541. Laza, C.; Pintaric, C.; Dunach, E. Electrochemical Reduction of Polyhalogenated Aryl Derivatives in the Presence of Pinacolborane: Electrosynthesis of Functionalised Arylboronic Esters Electrochimica Acta. 2005, 50, 4897–4901. (11) Mfuh, A. M.; Nguyen V. T.; Chhetri, B.; Burch, J. E. Doyle, J. D.; Nesterov, V. N.; Arman, H. D.; Larionov, O. V. Additive- and Metal-Free, Predictably 1,2- and 1,3-Regioselective, Photoinduced Dual C−H/C−X Boryla(cid:415)on of Haloarenes J. Am. Chem. Soc. 2016, 138, 8408−8411. (12) (13) (14) (15) Shimizu, M.; Tomioka, Y.; Nagao, I.; Hiyama, T. Palladium-Catalyzed Double Cross-Coupling Reaction of vic-Diborylalkenes and -arenes with vic-Bromo(bromomethyl)arenes Synlett. 2009, 19, 3147-3150. Yamamato, T.; Suginome, M.; Regioselective Synthesis of o-Benzenediboronic Acids via Ir- Catalyzed o-C−H Boryla(cid:415)on Directed by a Pyrazolylaniline Modified Boronyl Group Org. Lett. 2017, 19, 886-889. Ihara, H.; Suginome, M.; Easily Attachable and Detachable ortho-Directing Agent for Arylboronic Acids in Ruthenium-Catalyzed Aromatic C- H Silylation J. Am. Chem. Soc. 2009, 131, 7502-7503. Jayasundara, C. R. K. IRIDIUM CATALYZED C-H ACTIVATION BORYLATIONS OF FLUORINE BEARING ARENES AND RELATED STUDIES Ph.D. Dissertation, Michigan State University, East Lansing, Mi, 2018. 43 (16) Oshima, K.; Ohmura, T.; Suginome, M. Dearomatizing Conversion of Pyrazines to 1,4- Dihydropyrazine Derivatives via Transition-Metal-Free Diboration, Silaboration, and Hydroboration. Chem. Commun. 2012, 48 (68), 8571–8573. (17) Ohmura, T.; Morimasa, Y.; Suginome, M. Organocatalytic Diboration Involving “Reductive Addition” of a Boron–Boron σ-Bond to 4,4′-Bipyridine. J. Am. Chem. Soc. 2015, 137 (8), 2852– 2855. (18) Galstyan, A.; Shen, W.; Freisinger, E.; Alkam, H.; Hiller, W.; Sanz Miguel, P. J.; Schürmann, M.; Lippert, B. Supramolecular Isomerism of 2,2′-Bipyrazine Complexes with Cis -(NH 3 ) 2 Pt II : Ligand Rotational State and Sequential Orientation Determine the 3D Shape of Metallacycles. Chem. Eur. J. 2011, 17 (38), 10771–10780. (19) Larsen, M. A.; Oeschger, R. J.; Hartwig, J. F. Effect of Ligand Structure on the Electron Density and Activity of Iridium Catalysts for the Borylation of Alkanes ACS Catal. 2020, 10, 3415-3424. 44 Chapter 3: Para Selective C–H Borylation of Sulfonated Phenols, Anilines, and Benzyl Alcohols Equipped with a Tetraalkylammonium Steric Sheild Parts of this chapter were taken from “Para-Selective, Iridium-Catalyzed C–H Borylations of Sulfated Phenols, Benzl Alcohols, and Anilines Directed by Ion-Pair Electrostatic Interactions” J. Am. Chem. Soc. 2019, 141, 15483-15487. For two competing pathways, a difference in barrier heights of 2.5 kcal·mol−1 is sufficient for 99% of the reactants to follow the favored pathway in a chemical reaction. This is lower than the barrier for converting the anti-conformer of butane to the gauche form.1 In transition-metal mediated reactions, a classic mode for selectively functionalizing bonds in a substrate relies on the coordination of an atom in a reactant functional group to the metal center of a compound or catalytic intermediate. The magnitudes of the ligand−metal interactions are at least an order of magnitude greater than the difference in barrier heights necessary for 99:1 selectivity. Consequently, design of catalysts where selectivity is conferred by weakly coordinating groups,2 as well as catalysts that leverage even weaker interactions (e.g., hydrogen-bonding, ion-pairing, dipole−dipole, etc.) for selective transformations,3,4 is attracting significant attention. C−H functionalization offer both atom and step economical means of converting ubiquitous C−H bonds to a range of functional groups.5,6 C−H borylations (CHB) convert C−H bonds to C−B bonds and are mediated by both metal and metal-free catalysts.7-9 CHB reactions are valuable due to (i) facile substitution of the boron moiety by numerous functional groups and (ii) functional group tolerance of C–H borylation catalysts, particularly those containing iridium. The first iridium C–H borylation catalysts enabled C(sp2 )−H functionalization with high selectivity for the most sterically accessible C−H bonds.10-12 In substrates where multiple C−H bonds are sterically accessible, early generation catalysts often give isomer mixtures, as well as multiple borylated products. To overcome these limitations, more selective iridium catalysts have been designed. The first examples were ortho- selective,13 relying on strongly coordinating functional groups in the substrate,14,15 while later reports exploited weaker interactions for ortho selectivity.16-17 By comparison, meta and para C–H borylations pose different challenges because their C−H bonds are farther from the functional group. One meta-selective C–H borylation has been ascribed to a classical chelate-directed mechanism,18 while others rely on iridium ligands bearing groups that engage in noncovalent interactions with substrate functional groups to effect meta C–H borylations.19-24 Figure 3-1 depicts approaches for para selective C–H borylations. The first C–H borylation with high para selectivity involved electrophilic additions of borenium cations to arenes bearing ortho, para-directors.25 45 Sterically directed C–H borylations rely on hindered phosphine ligands and substrates with large substituents.26,27 More recently, para borylations of esters and amides have been achieved through noncovalent interactions with potassium ions or coordination of the amide oxygen to hindered Lewis acids.28,29 Electronically Directed Sterically Directed Directed by Non-Covalent Interactions Ingleson Itami Chattopadhyay Nakao Figure 3-1 Examples of para Selective C–H Borylations Our inspiration was based on the Phipps’ group ion-pair directed C–H borylations with one key difference.20,22 Instead of using oppositely charged groups on the ligand and substrate, combinations where groups on the ligand and substrate had the same charge were surveyed with the expectation that para borylation would be favored because electrostatic repulsions between the ligand and substrate would be minimized. However, a control experiment where tetrabutylammonium 2-chlorophenyl sulfate (4a) was subjected to standard borylation conditions with a neutral 4,4’-di-tert-butyl-2,2’-bipyridine (dtbpy) (3 mol%) with B2pin2, and [Ir(cod)OMe]2 (1.5 mol%), in THF at 80 °C showed promising results with 6:1 para to meta regioselectivity (Figure 3-2). Figure 3-2 Initial para Selectivity Observed in Substrates Containing Tetraalkylammonium Cations We hypothesized that substrate ion-pairing interactions, where the n-butyl groups of the cation shield the meta C−H bonds of the counter-anions, accounted for the para selectivity (Figure 3-3). 46 Figure 3-3 Hypothesized Ion-Pairing Interaction Sheilding meta Borylation Thus Promoting para Borylation In Nakao’s study, ligand geometry played a key role in enhancement of the para selectivity.29 Similarly, we have observed that ligand choice can impact CHB regiochemistry where there is little steric differentiation between different arene C−H bonds.30 Therefore, we tested commercially available substituted bipyridine and phenanthroline ligands (Figure 3- 4) in C–H borylation reactions run at 80 °C. The reactivity of the ligands is in accordance with previously noted electronic effects,31 with electron-rich ligands affording a more active system relative to electron poor ligands. The borylation in THF with 4,4’-dimethoxy-2,2’-bipyridine (L3) as the ligand went to >95% conversion and afforded the best para selectivity (13:1). This observation is notable in that 4,4’-dimethoxy- 2,2’-bipyridine (L3) is a nontraditional C–H borylation ligand. Switching the solvent to 1,4-dioxane slightly increased the para selectivity (14:1), whereas other apolar solvents worsened regioselectivity. 47 Figure 3-4 para meta Ratio of C–H Borylations of 4a Utilizing Different Ligands Running the reactions at lower temperature (60 °C and 40 °C) further improved the para selectivity while still allowing for full conversion (Figure 3-5). The reaction at room temperature afforded 21:1 para selectivity, but starting material remained even after 50 h. Figure 3-5 C–H Borylation of 4a at Different Temperatures Using L3 With the experiments in Figure 3-4 and Figure 3-5 establishing 4,4’-dimethoxy-2,2’-bipyridine (L3) and 1,4- dioxane as our ligand and solvent of choice, we next investigated the effect of the tetraalkylammonium salt on para selectivity. DFT geometry optimization of 4a, using the B3LYP functional and 6-31G* basis set for all the atoms suggested to us that a slightly shorter alkyl chain would still block the meta position but leave the para position more exposed leading to improved para selectivity. Because of this we decided to 48 try shorter chained alkyl ammonium cations in an attempt to obtain better para selectivity. Additionally, it was noticed that there was a particularly short distance between the alpha hydrogens of the alkyl ammonium counterion with the oxygens of the sulfate suggesting the presence of hydrogen bonding. This is a known phenomenon with tetraalkylammonium cations as they are known hydrogen bond donors.32 This potential hydrogen bonding may help maintain the optimal conformation needed for the steric shielding effect seen in borylation. As shown in Figure 3-6, the C–H borylation of tetra propylammonium 2-chlorophenyl sulfate validated this hypothesis, as running the reaction with ligand 4,4’-dimethoxy-2,2’-bipyridine (L3) in 1,4-dioxane at 40 °C pushed the para selectivity to 22:1. We also examined tetraethylammonium 2-chlorophenyl sulfate as a substrate. In terms of chain shortening, clearly diminishing returns had set in as the para selectivity decreased to 17:1. Figure 3-6 Effect of the Tetraalkylammonium Chain Length of para Selectivity in the Borylation of 4a Based on our results, we chose to test a series of phenol derived sulfates with n-Pr4N as the counterion to determine substrate scope (Figure 3-7). As illustrated in Figure 3-7, borylations of a series of 2-substituted phenol derived sulfates produced the para regioisomer as the major isomer, often with >20:1 selectivity. Most isolated yields were in the 70−80% range. Notably upon isolation the para to meta isomer was enhanced, in some cases to >50:1. 49 Figure 3-7 C–H Borylation Substrate Scope of n-Pr4N+ Aryl Sulfates It is clear that the ortho substituents of the phenolic arenes play a role in the selectivity. Those with lone pairs favor the para selectivity (substrates 7a-c) resembling prior work showing that these groups favoring meta C–H borylations33 which in our case is para with respect to the sulfated group. This selectivity decreases significantly without lone pairs in the ortho substituent as seen in 7f and 7g. Additionally, larger 50 ortho substituents improve selectivity irrespective of their electronic withdrawing character. This is illustrated in Figure 3-8 with 7f, 7g, 7h where in 7f and 7g are approximately the same size show the same selectivity while being drastically different electronically. This indicates that the ortho substituent impacts the selectivity by helping to lock the arene sulfate conformation so as it is pointed away from the ortho substituent and towards the meta position to be shielded by the ammonium ion. Figure 3-8 Steric Effects of the ortho Substituent on Regioselectivity Indeed, analysis of the crude reaction mixture indicated that 6i gave a mixture of the para to 5-Bpin to 3,5- diBpin products in a ratio of approximately 7.5:1:0.4. For substrates 6d and 6l, the observed minor isomer was that with the Bpin ortho to the fluoro group and no diborylation was observed. Given this preference, it was perhaps somewhat surprising that 3-fluorophenol sulfate (6e) produced a relatively large amount of the meta regioisomer. Not surprising was that the C–H borylation of 3-substituted phenol sulfates (6n−p) gave the meta isomer as the major product, showing that such ion-pair interactions are limited in their ability to overcome steric crowding of the para C–H position. Last, we borylated the sulfate of phenol (6p) and observed the para, meta, and 3,5-dimeta Borylated products in a ratio of 4.4:1:1.8, or a para:meta ratio of 1.6:1. This result is consistent with the assumption that the ion pairing can only block one meta site and thus the reactions need a 2-substituent to sterically block the second meta C–H bond. Looking at anilines (Figure 3-9), we subjected tetrapropylammonium 2-chlorophenylsulfamate (8a’) to our standard conditions. The para selectivity (40:1) was even better than that observed for 6a. Questioning if the chain length of the tetraalkylammonium salt would also impact the para selectivity for aniline derivatives, we prepared and reacted the tetrabutylammonium salt (8a). In contrast to the phenol sulfates, employing this counterion met with 43:1 para selectivity and a higher isolated yield. Owing to this result and that the tetrabutylammonium salts are somewhat easier to prepare and isolate, we chose n-Bu4N+ as the counterion for C–H borylations of a series of aniline sulfamates. The para selectivities for 8b and 8d were excellent, while again selectivity for a 3-fluoro substrate (38c) suffered, giving only a 2.4:1 94 para:meta ratio. 51 Figure 3-9 C–H Borylation Substrate Scope of n-Bu4N+ Aryl Sulfamates a Substrate was Run as the n-Pr4N+ Salt b The Product was Isolated as the Acetamide Finally, we surveyed benzyl alcohol derived sulfates and found selectivity for the para position. Surprisingly we found that despite the increased distance from the additional methylene, n-Pr4N+ was still the optimal shielding group as opposed to n-Bu4N+. Figure 3-10 C–H Borylation Substrate Scope of n-Pr4N+ Benzyl Sulfates a Substrate was Run as the n-Bu4N+ Salt 52 Generally, benzyl sulfates reacted with somewhat diminished para selectivity relative to their phenol and aniline counterparts (Figure 3-10). Products 11b and 11d were generated in lower yields owing in part to lower conversions and, for 11d, loss of the meta isomer upon isolation. Again, borylation of a substrate with fluorine in the 2-position (10g) afforded a significant amount of product with the Bpin ortho to the fluorine. By applying the C–H borylation conditions to the n-Bu4N+ counterion, 10a−10c revealed that the counterion has a similar influence on the regioselectivity as observed for the phenols. During the course of our work we became aware that the Phipps group had developed the same strategy, using tetraalkylammonium cations as steric shields to direct borylations para to phenols, anilines, benzyl alcohols, benzyl amines, and benzyl sulfones.34 Despite using the same method, the Phipps group focused on substrate exploration whereas we delved deeper into reaction optimization with regards to ligand, solvent, temperature and most importantly ammonium alkyl chain length. Because of this optimization we were able to achieve far more impressive selectivity. As the Phipps group expanded the methodology to additional substrate scaffolds, our work and the work done by Phipps provides a complimentary report and together a better understanding of the method. We are thankful to Phipps for allowing us to publish in a back-to-back manner and for that we are eternally grateful.35 Since the conclusion of our work on this project, Phipps has since expanded use of ionic interactions to direct borylations to the use of chiral cationic shielding groups to de-symmetrize symmetric di-aryl systems by selective borylation of aryl rings based on chirality.36 In summary, ion-pair electrostatic interactions can be used to direct iridium catalyzed borylation to the para position of sulfates and sulfamates derived from phenols, anilines, and benzyl alcohols. We show that the source of the para selectivity is through the steric presence created by the carbon chain of the tetraalkylammonium counterion and is augmented by the ortho substituent. We found that n-Pr4N+ salts gave better selectivity than their n-Bu4N+ counterparts. The chain length of tetraalkylammonium salt however was not as influential on the borylation of the sulfamates derived from anilines. Notably, optimal results were observed with the nontraditional C–H borylation ligand 4,4′-dimethoxy-2,2′-bipyridine (L3) serving to remind the community to look beyond 4,4’-di-tert-butyl-2,2’-bipyridine (dtbpy) (L1) or 3,4,7,8- tetramethyl-1,10-phenanthroline (tmphen) (L7) when optimizing C–H borylation reactions. 53 General Information Experimental Procedures All available reagents were used as received unless otherwise indicated. Bis(pinacolato)diborn (B2pin2) was generously supplied by BoroPharm. THF was refluxed over Na/benzophenone ketyl and distilled. Anhydrous 1,4-dioxane was obtained through Sigma-Aldrich and used as received. 3,4,7,8-tetramethyl- 1,10-phenanthroline (tmphen) and neocuproine were purchased from Combi-blocks and recrystallized from ethanol. 2-chloroaniline, 2-methoxyaniline, 2-methylaniline, 2-ethylaniline, 2-tertbutylaniline and tetrahydroquinoline were distilled over molecular sieves prior to use. Column chromatography was done using 240-400 mesh silica P-Flash silica gel. TLC was done on 0.25 mm thick aluminum backed silica gel plates and visualized with UV light (λ = 254 nm) with alizarin stain.58 1H, 13C, 11B and 19F NMR spectra were recorded on a Varian 500 MHz DD2 Spectrometer equipped with a 1H-19F/15N-31P 5 mm Pulsed Field Gradient (PFG) Probe. Spectra taken in CDCl3 were referenced to 7.26 ppm in 1H NMR and 77.2 ppm in 13C NMR. Spectra taken in C6D6 were referenced to 7.16 ppm in 1H NMR and 128.1 ppm in 13C. 11B NMR spectra were referenced to neat BF3·Et2O as the external standard. NMR spectra were processed for display using the MNova software program with only phasing and baseline corrections applied. High-resolution mass spectra (HRMS) were obtained at the Molecular Metabolism and Disease Mass Spectrometry Core facility and at the Mass Spectrometry Service Center at Michigan State University using electrospray ionization (ESI+ or ESI-) on quadrupole time-of-flight (Q-TOF) instruments. Parts of this chapter were reprinted with permission from Montero Bastidas, J. R.; Oleskey, T. J.; Miller, S. L.; Smith, M. R., III; Maleczka, R. E., Jr. Para-Selective, Iridium-Catalyzed C−H Borylations of Sulfated Phenols, Benzyl Alcohols, and Anilines Directed by Ion-Pair Electrostatic Interactions. J. Am. Chem. Soc. 2019, 141, 15483-15487. Copyright 2021 American Chemical Society The work presented in this chapter was not all conducted by Thomas Oleskey. Substrate exploration was a team effort with Montero Bastidas, J. R. and Miller, S. L. Synthesis of tetrapropylammonium 2-iodophenylsulfate (6c) Figure 3-11 Synthesis of tetrapropylammonium 2-iodophenylsulfate (6c) 54 2-Iodophenol (1.3200 g, 6.00 mmol) and SO3•pyridine complex (1.0500 g, 6.60 mmol) were placed in a 100 mL round bottom flask. Pyridine (8 mL) and dry dichloromethane (5 mL) were added and the mixture was stirred at rt for 18 h. After this time, the reaction was heated to 40 ºC for 1 h. Water (70 mL) was added and the mixture was washed once with dichloromethane (1 x 70 mL). The aqueous phase was treated with tetrapropyl ammonium bromide (1.6000 g, 6.00 mmol) and stirred for 1 h. The solution was extracted with dichloromethane (3 x 70 mL). The organic layer was dried over MgSO4, filtered, and concentrated. Diethyl ether and hexanes were added to evaporate the solvent to dryness and the product was obtained as a white solid (1.5100 g, 52% yield). Data for tetrapropylammonium 2-iodophenylsulfate (6c) 1H NMR (500 MHz, CDCl3) 7.65 (m, 2H), 7.17 (ddd, J = 8.6, 7.3, 1.6 Hz, 1H), 6.70 (td, J = 7.6, 1.5 Hz, 1H), 3.15–2.81 (m, 8H), 1.68–1.22 (m, 8H), 0.84 (t, J = 7.3 Hz, 12H). 13C NMR (126 MHz, CDCl3) δ 153.4, 138.9, 129.05, 124.8, 120.7, 89.5, 60.2, 15.5, 10.8. HRMS (ESI) m/z calcd. for C6H4IO4S [M–Nn-Pr4]– 298.8875, found 298.8890. Synthesis of tetrapropylammonium 3-fluorophenyl sulfate (6e) Figure 3-12 Synthesis of tetrapropylammonium 3-fluorophenyl sulfate (6e) 3-Fluorophenol (0.6730 g, 6.00 mmol) and SO3•pyridine complex (1.0500 g, 6.60 mmol) was placed in a 100 mL round bottom flask. Pyridine (8 mL) and dry dichloromethane (5 mL) were added, and the mixture was stirred at rt for 18 h. After this time, the reaction was heated to 40 ºC for 1 h. Water (70 mL) was added, and the mixture was washed once with dichloromethane (1 x 70 mL). The aqueous phase was treated with tetrapropyl ammonium bromide (1.6000 g, 6.00 mmol) and stirred for 1 h. The solution was extracted with dichloromethane (3 x 70 mL). The organic layer was dried over MgSO4, filtered, and concentrated, resulting in a clear oil. To the concentrated oil, hexanes were added, and the suspension was concentrated by rotary evaporation. This process was repeated until the product was obtained as a white solid. After overnight drying under high vacuum (6e) was obtained as a white solid (1.4600 g, 64% yield). 55 Data for tetrapropylammonium 3-fluorophenyl sulfate (6e) 1H NMR (500 MHz, CDCl3) δ 7.19 (td, J = 8.2, 6.8 Hz, 1H), 7.14 (dt, J = 10.6, 2.4 Hz, 1H), 7.07 (ddd, J = 8.2, 2.4, 0.9 Hz, 1H), 6.74 (tdd, J = 8.2, 2.4, 0.9 Hz, 1H), 3.15–2.90 (m, 8H), 1.68–1.51 (m, 8H), 0.94 (t, J = 7.3 Hz, 12H). 13C NMR (126 MHz, CDCl3) δ 162.8 (d, J = 244.6 Hz), 154.8 (d, J = 11.2 Hz), 129.6 (d, J = 9.6 Hz), 116.5 (d, J = 2.9 Hz), 110.1 (d, J = 21.1 Hz), 108.3 (d, J = 24.3 Hz), 60.3, 15.5, 10.7. 19F NMR (470 MHz, CDCl3) δ –115.73 (m). HRMS (ESI) m/z calcd. for C6H4FO4S [M–Nn-Pr4]– 190.9814, found 190.9821 Synthesis of tetrapropylammonium 2-cyanophenyl sulfate (6i) Figure 3-13 Synthesis of tetrapropylammonium 2-cyanophenyl sulfate (6i) 2-Cyanophenol (0.7140 g, 6.00 mmol) and SO3•pyridine complex (1.0500 g, 6.60 mmol) were placed in a 100 mL round bottom flask. Pyridine (8 mL) and dry dichloromethane (5 mL) were added and the mixture was stirred at rt for 18 h. After this time, the reaction was heated to 40 ºC for 1 h. Water (70 mL) was added and the mixture was washed once with dichloromethane (1 x 70 mL). The aqueous phase was treated with tetrapropyl ammonium bromide (1.6000 g, 6.00 mmol) and stirred for 1 h. The solution was extracted with dichloromethane (3 x 70 mL). The organic layer was dried over MgSO4, filtered, and concentrated, resulting in a clear oil. To the concentrated oil, hexanes and ether were added and the suspension was again concentrated by rotary evaporation. This process was repeated until the product was obtained as a white solid. After overnight drying under high vacuum (6i) was obtained as a white solid (1.0300 g, 45% yield). Data for tetrapropylammonium 2-cyanophenyl sulfate (6i) 1H NMR (500 MHz, CDCl3) δ 7.79 (dd, J = 7.6, 1.1 Hz, 1H), 7,46 (dd, J = 7.6, 1.8 Hz, 1H), 7.45 (td, J = 7.6, 1.8 Hz, 1H), 7.05 (td, J = 7.6, 1.1 Hz, 1H), 3.26 – 2.73 (m, 8H), 1.61 (m, 8H), 0.90 (t, J = 7.3 Hz, 12H). 13C NMR (126 MHz, CDCl3) δ 155.7, 133.9, 132.9, 123.2, 121.0, 116.9, 104.6, 60.2, 15.5, 10.7. HRMS (ESI) m/z calcd. for C7H4NO4S [M–Nn-Pr4]– 197.9861, found 197.8931. 56 Synthesis of tetrapropylammonium 2-(trifluoromethoxy)phenyl sulfate (6k) Figure 3-14 Synthesis of tetrapropylammonium 2-(trifluoromethoxy)phenyl sulfate (6k) 2-(trifluoromethoxy)phenol (1.0700 g, 6mmol) and SO3•pyridine complex (1.0500 g, 6.6 mmol) were placed in a 100 mL round bottom flask. Pyridine (8 mL) and dry dichloromethane (5 mL) were added, and the flask sealed with a glass stopper. The mixture was stirred at rt for 18 h. After this time, the reaction was heated to 40°C for 1h. Water (70 mL) was added, and the mixture was washed once with dichloromethane (70 mL) and the aqueous phase transferred to a 250 mL round bottom flask. Nn-Pr4B r (1.6000 g, 6 mmol) was added to the aqueous phase and the flask sealed with a glass stopper. The mixture was stirred for 1h. The solution was extracted with dichloromethane (3x, 70 mL). The organic layer was dried over MgSO4, filtered, and concentrated. Hexanes (7 mL) were added to the product and the suspension evaporated. This was repeated until no pyridine was seen via NMR. Diethyl ether (7 mL) was added to the product, and the suspension evaporated until no dichloromethane was seen via NMR. After the pyridine and dichloromethane were removed a white solid was collected, which was crushed then dried overnight under high vacuum. 6k was obtained as a white solid (1.0900 g, 41% yield). The NMR values were consistent with previously reported values.6 Data for tetrapropylammonium 2-(trifluoromethoxy)phenyl sulfate (6k) 1H NMR (500 MHz, CDCl3) δ 7.80 (dd, J=8.7, 1.4 Hz, 1H), 7.20-7.12 (m, 2H), 6.99 (td, J=7.9, 1.7 Hz, 1H), 3.11 (p, J=4.2 Hz, 8H), 1.59 (hept, J=7.6 Hz, 8H), 0.89 (t, J=7.3 Hz, 12H). 13CNMR (126 MHz, CDCl3) δ 151.9 (q, J=1.8 Hz), 132.8 (s), 126.2 (q, J=5.0 Hz), 123.5 (q, J=272.4 Hz), 122.2 (s), 120.7 (s), 120.4 (q, J=30.6 Hz), 60.1, 15.4, 10.5. 19F NMR (470 MHz, CDCl3) δ –57.4 (s, 3F). HRMS (ESI) m/z calcd. For C7H4F3O4S [M–Nn-Pr4]–240.9782, found 240.9784. 57 Synthesis of tetrapropylammonium 2-bromo-6-fluorophenyl sulfate (6l) Figure 3-15 Synthesis of tetrapropylammonium 2-bromo-6-fluorophenyl sulfate (6l) 2-bromo-6-fluorophenol (1.1500 g, 6.00 mmol) and SO3•pyridine complex (1.0500 g, 6.60 mmol) were placed in a 100 mL round bottom flask. Pyridine (8 mL) and dry dichloromethane (5 mL) were added, and the flask sealed with a glass stopper. The mixture was stirred at rt for 18 h. After this time, the reaction was heated to 40°C for 1h. Water (70 mL) was added, and the mixture was washed once with dichloromethane (70 mL) and the aqueous phase transferred to a 250 mL round bottom flask. Nn-Pr4Br (1.6000 g, 6.00 mmol) was added to the aqueous phase and the flask sealed with a glass stopper. The mixture was stirred for 1h. The solution was extracted with dichloromethane (3x, 70 mL). The organic layer was dried over MgSO4, filtered, and concentrated. Hexanes (7 mL) were added to the product and the suspension evaporated. This was repeated until no pyridine was seen via NMR. Diethyl ether (7 mL) was added to the product, and the suspension evaporated until no dichloromethane was seen via NMR. After the pyridine and dichloromethane were removed a white solid was collected, which was crushed then dried overnight under high vacuum. 6l was obtained as a white solid (0.7800 g, 28% yield). The NMR values were consistent with previously reported values. Data for tetrapropylammonium 2-bromo-6-fluorophenyl sulfate (6l) 1H NMR (500 MHz, CDCl3) δ 7.24 (d, J=8.0 Hz, 1H), 6.97 (t, J=8.7 Hz, 1H), 6.89 (td, J=8.1, 5.3 Hz, 1H), 3.10 (p, J=4.31 Hz, 8H), 1.58 (hept, J=8.12 Hz, 8H), 0.89 (t, J=7.3 Hz, 12H). 13C NMR (126 MHz, CDCl3) δ 156.8 (d, J=253.8 Hz), 139.7 (d, J=14.4 Hz), 128.3 (d, J=3.5 Hz), 125.5 (d, J =8.1 Hz), 119.8 (d, J=1.9 Hz), 115.7 (d, J=19.9 Hz), 60.2, 15.5, 10.7. 19F NMR (470 MHz, CDCl3) δ –124.4 (dd, J=9.5, 5.1 Hz). HRMS (ESI) m/z calcd. For C6H3BrFO4S [M–Nn-Pr4]– 268.8919, found 268.8919. 58 Synthesis of tetrapropylammonium phenyl sulfate (6p) Figure 3-16 Synthesis of tetrapropylammonium phenyl sulfate (6p) Phenol (1.0700 g, 6.00 mmol) and SO3•pyridine complex (1.0500 g, 6.60 mmol) were placed in a 100 mL round bottom flask. Pyridine (8 mL) and dry dichloromethane (5 mL) were added, and the flask sealed with a glass stopper. The mixture was stirred at 40 °C for 8 h. Water (70 mL) was added, and the mixture was washed once with dichloromethane (70 mL) and the aqueous phase transferred to a 250 mL round bottom flask. Nn-Pr4B r (1.6000 g, 6.00 mmol) was added to the aqueous phase and the flask sealed with a glass stopper. The mixture was stirred for 1 h. The solution was extracted with dichloromethane (3x, 70 mL). The organic layer was dried over MgSO4, filtered, and concentrated. Hexanes (7 mL) were added to the product and the suspension evaporated. This was repeated until no pyridine was seen via NMR. Diethyl ether (7 mL) was added to the product, and the suspension evaporated until no dichloromethane was seen via NMR. After the pyridine and dichloromethane were removed a white solid was collected, which was crushed then dried overnight under high vacuum. 6p was obtained as a white solid (1.5000 g, 69% yield). The NMR values were consistent with previously reported values.6 Data for tetrapropylammonium phenyl sulfate (6p) 1H NMR (500 MHz, CDCl3) δ 7.32 (d, J=8.1 Hz, 2H), 7.23 (t, J=8.1 Hz, 2H), 7.02 (t, J=7.3 Hz, 1H), 3.08 (p, J= 3.8 Hz, 8H), 1.57 (hept, 7.8 Hz, 8H), 0.92 (t, J=7.3Hz, 12H). 13C NMR (126 MHz, CDCl3) δ 153.6, 128.8, 123.4, 121.0, 60.1, 15.4, 10.7. HRMS (ESI) m/z calcd. For C6H5O4S [M–Nn-Pr4]– 172.9909, found 173.0117. Synthesis of tetrabutylammonium 2-chlorophenyl sulfamate (9a) Figure 3-17 Synthesis of tetrabutylammonium 2-chlorophenyl sulfamate (9a) In an open 100 mL round bottom flask in air, 2-chloroaniline (1.6300 g, 12.74 mmol) was added along with 17 mL pyridine, 10 mL dichloromethane, and SO3•Pyridine (2.1900 g, 13.75 mmol). A stir bar was 59 added, and the flask capped with a rubber septum. The solution was stirred at room temperature for 18 hours. The temperature was then raised to 40 °C in an oil bath and the reaction stirred for an additional hour. 150 mL of water was then added. The resulting solution was washed with 150 mL of DCM. The aqueous phase was transferred to a 250 mL round bottom flask and NBu4HSO4 (4.2400 g, 12.50 mmol) added. The flask was capped with a glass stopper. This solution was stirred for 1 hour over which the solution cleared, and a brown oil formed. The aqueous layer was extracted 3x with 150 mL dichloromethane. The organic phase was dried over anhydrous MgSO4. The organic phase was evaporated forming a tan oil. To the oil, approximately 7 mL of hexanes were added, and the oil suspension evaporated. This was repeated until no pyridine was seen via NMR. Diethyl ether was also added, and the oil and the suspension evaporated until no dichloromethane was seen via NMR. After the pyridine and dichloromethane were removed the oil solidified into a light tan solid that was then dried overnight under high vacuum. 9a was collected as a tan solid (3.8200 g, 60 % yield). The NMR values were consistent with previously reported values.6 Data for tetrabutylammonium 2-chlorophenyl sulfamate (9a) 1H NMR (500M Hz, CDCl3) δ 7.80 (d, J=8.3 Hz, 1H), 7.19 (d, J=7.9 Hz, 1H), 7.11 (t, J=7.8 Hz, 1H), 6.71 (t, J=7.6 Hz, 1H), 6.65 (bs, 1H), 3.16 (t, J=8.3 Hz, 8H), 1.54 (p, J=7.2 Hz, 8H), 1.35 (h, J=7.0 Hz, 8H), 0.94 (t, J=7.4Hz, 12H). 13C NMR (126 MHz, CDCl3) δ 139.2, 128.7, 127.6, 120.0, 120.0, 117.7, 58.7, 24.0, 19.8, 13.8. HRMS (ESI) m/z calcd. for C6H5ClNO3S [M–Nn-Bu4]– 205.9679, found 205.9897. Synthesis of tetrabutylammonium 2-bromophenyl sulfamate (9b) Figure 3-18 Synthesis of tetrabutylammonium 2-bromophenyl sulfamate (9b) In a 100 mL round bottom flask in air, 2-bromoaniline (2.1400 g, 12.50 mmol) was added along with pyridine (17 mL), dichloromethane (10 mL), and SO3•Pyridine (2.1900 g, 13.75 mmol). A stir bar was added, and the flask sealed with a glass stopper. The solution was stirred at room temperature for 18 hours. The temperature was then raised to 40 °C in an oil bath and the reaction stirred for an additional hour. Water (150 mL) was then added. The resulting solution was washed with dichloromethane (150 mL). The aqueous phase was transferred to a 250 mL round bottom flask and NBu4HSO4 (4.2400 g, 12.50 60 mmol) added turning the solution an opaque white. The flask was sealed with a glass stopper. This solution was stirred for an hour over which the solution cleared, and a brown oil formed. The reaction was extracted with dichloromethane (3x, 150 mL). The organic phase was dried over anhydrous MgSO4. The organic phase was evaporated forming a tan oil. To the oil, hexanes (7 mL) were added, and the oil suspension evaporated. This was repeated until no pyridine was seen via NMR. Diethyl ether (7 mL) was added to the oil, and the oil suspension evaporated until no dichloromethane was seen via NMR. After the pyridine and dichloromethane were removed the oil solidified into a white solid that was crushed then dried overnight under high vacuum. 9b was collected as an off-white solid (3.8400 g, 62 % yield). The NMR values were consistent with previously reported values. Data for tetrabutylammonium 2-bromophenyl sulfamate (9b) 1H NMR (500 MHz, CDCl3) δ 7.81 (dd, J=8.5, 1.4 Hz,1H), 7.37 (dd, J=8.0, 1.3 Hz,1H), 7.16 (td, J=7.3, 1.2 Hz, 1H), 6.66 (m, 2H), 3.18 (t, J=8.2 Hz, 8H), 1.57 (p, J=7.8 Hz, 8H), 1.37 (h, J=7.3, 8H), 0.96 (t, J=7.3Hz, 12H). 13C NMR (126 MHz, CDCl3 ) δ 140.3, 131.9, 128.3, 120.5, 117.7, 110.5, 58.6, 24.0, 19.8, 13.8. HRMS (ESI) m/z calcd for C6H5BrNO3S [M–Nn-Bu4]– 249.9173, found 249.8044. Synthesis of tetrabutylammonium 3-fluorophenyl sulfamate (9c) Figure 3-19 Synthesis of tetrabutylammonium 3-fluorophenyl sulfamate (9c) In an open 100 mL round bottom flask in air, 2-bromoaniline (1.3900 g, 12.50 mmol) was added along with 17 mL pyridine, 10 mL dichloromethane, and SO3•Pyridine (2.1900 g, 13.75 mmol). A stir bar was added, and the flask capped with a rubber septum. The solution was stirred at room temperature for 18 hours. The temperature was then raised to 40 °C in an oil bath and the reaction stirred for an additional hour. 150 mL of water was then added. The resulting solution was washed with 150 mL of DCM. The aqueous phase was transferred to a 250 mL round bottom flask and NBu4HSO4 (4.2400 g, 12.50 mmol) added turning the solution an opaque white. The flask was capped with a glass stopper. This solution was stirred for 1 hour over which the solution cleared, and a brown oil formed. The aqueous layer was extracted 3x with 150 mL dichloromethane. The organic phase was dried over anhydrous MgSO4. The organic phase was evaporated forming a tan oil. To the oil, approximately 7 mL of hexanes were added, and the oil suspension evaporated. This was repeated until no pyridine was seen via NMR. Diethyl ether 61 was also added, and the oil and the suspension evaporated until no dichloromethane was seen via NMR. After the pyridine and dichloromethane were removed the oil solidified into a pink solid that was then dried overnight under high vacuum. 9c was collected as a pink solid (4.1200 g, 71 % yield). The NMR values were consistent with previously reported values. Data for 3-fluorophenyl sulfamate (9c) 1H NMR (500MHz,CDCl3) δ 7.07 (bs, 1H), 7.12–6.96 (m, 2H), 6.78 (dt, J=8.2, 0.83 Hz, 1H), 6.44 (td, J=8.5,2.2 Hz, 1H), 3.16 (t, J=8.4 Hz, 8H), 1.51 (p, J=7.9 Hz, 8H), 1.33 (h, J=7.3, 8H), 0.91 (t, J=7.3 Hz, 12H). 13C NMR (126 MHz, CDCl3) δ 163.2 (d, J=241.6 Hz), 144.5 (d, J=11.1 Hz), 129.3 (d, J=9.8 Hz), 112.1 (d, J=1.7 Hz), 105.5 (dd, J=21.4, 1.7 Hz), 103.4 (d, J=25.4 Hz), 58.0, 23.5, 19.3, 13.4. 19F NMR (470 MHz, CDCl3) δ –113.56 (dt, J=11.8, 8.3 Hz). HRMS (ESI) m/z calcd. for C6H5FNO3S [M–Nn-Bu4]– 189.9974, found 189.9108. Synthesis of tetrabutylammonium (2-chlorophenyl)methane sulfamate (10a’) Figure 3-20 Synthesis of tetrabutylammonium (2-chlorophenyl)methane sulfamate (10a’) 2-Chlorobenzyl alcohol (0.8600 g, 6.00 mmol) and SO3•pyridine complex (1.0500 g, 6.60 mmol) were placed in a 100 mL round bottom flask. Pyridine (8 mL) and dry dichloromethane (5 mL) were added, and the flask sealed with a glass stopper. The mixture was stirred at rt for 18 h. After this time, the reaction was heated to 40°C for 1h. Water (70 mL) was added, and the mixture was washed once with dichloromethane (70 mL) and the aqueous phase transferred to a 250 mL round bottom flask. Tetrabutylammonium hydrogen sulfate (2.1300 g, 6.00 mmol) was added to the aqueous phase and the flask sealed with a glass stopper. The mixture was stirred for 1 hour. The solution was extracted with dichloromethane (3x, 70 mL). The organic layer was dried over MgSO4, filtered, and concentrated. Hexanes (7 mL) were added to the product and the suspension evaporated. This was repeated until no pyridine was seen via NMR. Diethyl ether (7 mL) was added to the product, and the suspension evaporated until no dichloromethane was seen via NMR. After the pyridine and dichloromethane were removed a white solid was collected, which was crushed then dried overnight under high vacuum. 10a’ was obtained as a white solid (2.2800 g, 83% yield). The NMR values were consistent with previously reported values. 62 Data for tetrabutylammonium (2-chlorophenyl)methane sulfamate (11a’) 1H NMR (500 MHz, CDCl3) δ 7.63 (d, J=7.4 Hz, 1H), 7.18 (d, J=7.5 Hz, 1H), 7.10 (m, 2H), 5.02 (s, 2H), 3.10 (t, J=7.1 Hz, 8H), 1.46 (p, J=7.3 Hz, 8H), 1.25 (h, J=6.5 Hz, 8H), 0.82 (t, J=6.7 Hz, 12H). 13C NMR (126 MHz, CDCl3) δ 135.5, 132.0, 129.1, 128.8, 128.6, 128.2, 126.4, 65.4, 58.1, 23.6, 19.4, 13.4. HRMS (ESI) m/z calcd for C7H6ClO4S [M–Nn-Bu4]– 220.9675, found 220.9689. Synthesis of tetrapropylammonium 2-(trifluoromethyl)benzyl sulfate (11c) Figure 3-21 Synthesis of tetrabutylammonium 2-(trichloromethyl)benzyl sulfate (11c) (2-(trifluoromethyl)phenyl)methanol (0.8600 g, 6.00 mmol) and SO3•pyridine complex (1.0500 g, 6.60 mmol) were placed in a 100 mL round bottom flask. Pyridine (8 mL) and dry dichloromethane (5 mL) were added, and the flask sealed with a glass stopper. The mixture was stirred at rt for 18 h. After this time, the reaction was heated to 40°C for 1h. Water (70 mL) was added, and the mixture was washed once with dichloromethane (70 mL) and the aqueous phase transferred to a 250 mL round bottom flask. Nn-Pr4Br (1.6000 g, 6.00 mmol) was added to the aqueous phase and the flask sealed with a glass stopper. The mixture was stirred for 1h. The solution was extracted with dichloromethane (3x, 70 mL). The organic layer was dried over MgSO4, filtered, and concentrated. Hexanes (7 mL) were added to the product and the suspension evaporated. This was repeated until no pyridine was seen via NMR. Diethyl ether (7 mL) was added to the product, and the suspension evaporated until no dichloromethane was seen via NMR. After the pyridine and dichloromethane were removed a white solid was collected, which was crushed then dried overnight under high vacuum. 11c was obtained as a white solid (1.2000 g, 40% yield). The NMR values were consistent with previously reported values. Data for tetrapropylammonium 2-(trifluoromethyl)benzyl sulfate (11c) 1H NMR (500 MHz, CDCl3) δ 7.86 (d, J=7.7Hz, 1H), 7.55 (dd, J=7.7, 1.2 Hz, 1H), 7.47 (td, J=7.7, 1.2 Hz, 1H), 7.30 (t, J=7.7 Hz, 1H), 5.22 (s, 2H), 3.36–3.09 (m, 8H), 1.61–1.50 (m, 8H), 1.39–1.29 (m, 8H), 0.91 (t, J=7.4 Hz, 12H). 13C NMR (126 MHz, CDCl3) δ 136.7 (q, J=1.9Hz), 131.7, 129.1, 126.9, 126.7 (q, J=30.6Hz), 125.1(q, J=5.8 Hz), 124.3 (q, J=273.7 Hz), 64.5 (q, J=3.1 Hz), 58.5, 23.8, 19.6, 13.6. 19F NMR (470 MHz, CDCl3) δ-63.3. 63 HRMS (ESI) m/z calcd. for C8H6F3O4S [M–Nn-Bu4]– 254.9939, found 255.0028. Synthesis of tetrapropylammonium o-tolymethane sulfonate (11d) Figure 3-22 Synthesis of tetrabutylammonium o-tolymethane sulfonate (11d) o-tolymethanol (0.7300 g, 6.00 mmol) and SO3•pyridine complex (1.0500 g, 6.60 mmol) were placed in a 100 mL round bottom flask. Pyridine (8 mL) and dry dichloromethane (5 mL) were added, and the flask sealed with a glass stopper. The mixture was stirred at rt for 18 h. After this time, the reaction was heated to 40°C for 1h. Water (70 mL) was added, and the mixture was washed once with dichloromethane (70 mL) and the aqueous phase transferred to a 250 mL round bottom flask. Nn-Pr4Br (1.6000 g, 6.00 mmol) was added to the aqueous phase and the flask sealed with a glass stopper. The mixture was stirred for 1h. The solution was extracted with dichloromethane (3x, 70 mL). The organic layer was dried over MgSO4, filtered, and concentrated. Hexanes (7 mL) were added to the product and the suspension evaporated. This was repeated until no pyridine was seen via NMR. Diethyl ether (7 mL) was added to the product, and the suspension evaporated until no dichloromethane was seen via NMR. After the pyridine and dichloromethane were removed a white solid was collected, which was crushed then dried overnight under high vacuum. 11d was obtained as a white solid (1.4100 g, 71% yield). The NMR values were consistent with previously reported values. Data for tetrapropylammonium o-tolymethane sulfonate (11d) 1H NMR (500 MHz, CDCl3) δ 7.33–7.28 (m, 1H), 7.13–7.01 (m, 3H), 4.96 (s, 2H), 3.06 (p, J=3.6 Hz, 8H), 2.29 (s, 3H), 1.53 (hept, J=7.3 Hz, 8H), 0.88 (t, J=7.3 Hz, 12H). 13C NMR (126 MHz, CDCl3) δ 136.9, 135.5, 129.9, 128.8, 127.7, 125.5, 67.0, 60.1, 18.8, 15.4, 10.7. HRMS (ESI) m/z calcd for C8H9O4S [M–Nn-Pr4]– 201.0222, found 201.0271. Synthesis of tetrapropylammonium (2-fluorophenyl)methane sulfonate (11g) Figure 3-23 Synthesis of tetrabutylammonium (2-fluorophenyl)methane sulfonate (11g) 64 (2-fluorophenyl)methanol (0.7600 g, 6.00 mmol) and SO3•pyridine complex (1.0500 g, 6.60 mmol) were placed in a 100 mL round bottom flask. Pyridine (8 mL) and dry dichloromethane (5 mL) were added, and the flask sealed with a glass stopper. The mixture was stirred at 40 °C for 8 h. After this time, the reaction was heated to 40°C for 1 hour. Water (70 mL) was added, and the mixture was washed once with dichloromethane (70 mL) and the aqueous phase transferred to a 250 mL round bottom flask. Nn-Pr4Br (1.6000 g, 6.00 mmol) was added to the aqueous phase and the flask sealed with a glass stopper. The mixture was stirred for 1 hour. The solution was extracted with dichloromethane (3 x 70 mL). The organic layer was dried over MgSO4, filtered, and concentrated. Hexanes (7 mL) were added to the product and the suspension evaporated. This was repeated until no pyridine was seen via NMR. Diethyl ether (7 mL) was added to the product, and the suspension evaporated until no dichloromethane was seen via NMR. After the pyridine and dichloromethane were removed a white solid was collected, which was crushed then dried overnight under high vacuum. 11g was obtained as a white solid (0.9400 g, 40% yield). The NMR values were consistent with previously reported values. Data for tetrapropylammonium (2-fluorophenyl)methane sulfonate (11g) 1H NMR (500 MHz, CDCl3) δ 7.48 (td, J=7.5, 1.7 Hz, 1H), 7.18 (dtd, J=7.6, 5.2, 1.8Hz, 1H), 7.03 (td, J=7.5, 1.1 Hz, 1H), 6.92 (ddd, J=9.5, 8.3, 1.0 Hz, 1H), 5.03 (s, 1H), 3.11 (p, J=4.82 Hz, 8H), 1.58 (hept, J=7.36 Hz, 8H), 0.89 (t, J=7.3 Hz, 8H). 13C NMR (126 MHz, CDCl3) δ 160.4 (d, J=246.9 Hz), 130.5 (d, J=4.1 Hz), 129.2 (d, J=8.0 Hz), 124.8 (d, J=14.4 Hz), 123.9 (d, J=3.6 Hz), 114.8 (d, J=21.3 Hz), 62.3 (d, J=4.5 Hz), 60.2, 15.4, 10.7. 19F NMR (470 MHz, CDCl3) δ –118.9-12.96 (m). HRMS (ESI) m/zcalcd for C7H6FO4S [M–Nn-Pr4]– 204.9971, found 205.0033. Synthesis of tetrapropylammonium (3-fluorophenyl)methane sulfonate (11h) Figure 3-24 Synthesis of tetrabutylammonium (3-fluorophenyl)methane sulfonate (11h) (2-fluorophenyl)methanol (0.7600 g, 6.00 mmol) and SO3•pyridine complex (1.0500 g, 6.60 mmol) were placed in a 100 mL round bottom flask. Pyridine (8 mL) and dry dichloromethane (5 mL) were added, and the flask sealed with a glass stopper. The mixture was stirred at 40 °C for 8 h. After this time, the reaction was heated to 40°C for 1h. Water (70 mL) was added, and the mixture was washed once with 65 dichloromethane (70 mL) and the aqueous phase transferred to a 250 mL round bottom flask. Nn-Pr4Br (1.6000 g, 6.00 mmol) was added to the aqueous phase and the flask sealed with a glass stopper. The mixture was stirred for 1 hour. The solution was extracted with dichloromethane (3 x 70 mL). The organic layer was dried over MgSO4, filtered, and concentrated. Hexanes (7 mL) were added to the product and the suspension evaporated. This was repeated until no pyridine was seen via NMR. Diethyl ether (7 mL) was added to the product, and the suspension evaporated until no dichloromethane was seen via NMR. After the pyridine and dichloromethane were removed a white solid was collected, which was crushed then dried overnight under high vacuum. 11h was obtained as a white solid (1.7500 g, 75% yield). The NMR values were consistent with previously reported values. Data for tetrapropylammonium (3-fluorophenyl)methane sulfonate (11h) 1H NMR (500 MHz, CDCl3) δ 7.2-7.13 (m, 1H), 7.09–7.00 (m, 2H), 6.83 (td, J=8.4, 1.9 Hz, 1H), 4.92 (s, 2H), 3.08 (p, J=4.3 Hz, 8H), 1.56 (hept, J=4.6 Hz, 8H), 0.87 (t, J=7.3Hz, 12H). 13C NMR (126 MHz, CDCl3) δ 162.6 (d, J=245.0 Hz), 140.4 (d, J=7.5 Hz), 129.6 (d, J=8.2 Hz), 123.1 (d, J=2.8 Hz), 114.4 (d, J=19.5 Hz), 114.1 (d, J=21.1 Hz), 67.8, 60.1, 15.4, 10.6. 19F NMR (470 MHz, CDCl3) δ –117.07 (dt, J=9.16, 6.4 Hz). HRMS (ESI) m/z calcd for C7H6FO4S [M–Nn-Pr4]– 204.9971, found 205.0026. Para borylation of tetrapropyl ammonium 2-fluorophenyl sulfate (6e) Figure 3-25 Para borylation of tetrapropyl ammonium 2-fluorophenyl sulfate (6e) In a glovebox, a 5.0 mL Wheaton micro reactor was charged with tetrapropylammonium 3-fluorophenyl sulfate (189.0 mg, 0.50 mmol), [Ir(OMe)COD]2 (5.0 mg, 1.5 mol%), B2pin2 (159.0 mg, 0.63 mmol), and dioxane (1 mL) and stirred at rt. for 5 minutes. Then 4,4′-dimethoxy-2,2′-bipyridine (3.3 mg, 3.0 mol%) and dioxane (0.5 mL) were added. The micro reactor was capped with a Teflon pressure cap and placed into an aluminum block pre-heated to 40°C. After 20 h, an aliquot of the reaction mixture was taken and analyzed directly by 1H NMR to find the conversion and para:meta ratio which was determined to be 2.45:1 para:meta. HCl (12M) was added drop wise until pH=1–2 and the resultant mixture was stirred for 66 1 h. Copious bubbling was observed with the addition of HCl. The solution was concentrated and washed with hexanes (0.5 mL). The remaining solution subjected to chromatographic separation with silica gel (12% EtOAc in CHCl3 as eluent) to give 87.0 mg of a mixture para borylated 3-fluorophenol (7e) with the meta isomer (7e’) (para:meta=3:1) as a white solid (73% yield, mp 89.4-91.2 °C). The NMR values were consistent with previously reported values. Data for 3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (7e) Para: 1H NMR (500 MHz, CDCl3) δ 7.58 (t, J=7.7 Hz, 1H), 6.76 (bs, 1H), 6.61 (dd, J=8.2, 2.2 Hz, 1H), 6.50 (dd, J=10.9, 2.1Hz, 1H), 1.34 (s, 12H). 13C NMR (126 MHz, CDCl3) δ 168.6 (d, J=250.4 Hz), 160.8 (d, J=12.4 Hz), 138.0 (d, J=10.3 Hz), 111.6 (d, J=2.6 Hz), 103.1 (d,J=27.2 Hz), 84.2, 24.8. 11B NMR (160 MHz, CDCl3) δ 31.4. 19F NMR (470 MHz, CDCl3) δ-104.14 – -104.26 (m). HRMS (ESI) m/z calcd. for C12H15BFO3 [M–H]–237.1098, found 237.1320. Data for 3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (7e’) Meta: 1H NMR (500 MHz, CDCl3) δ 7.04 (s, 1H), 7.03 (d, J=2.0 Hz, 1H), 6.67 (dt, J=10.2, 2.3 Hz, 1H), 1.33 (s, 12H). 13C NMR (126 MHz, CDCl3) δ 163.4 (d, J=246.6Hz), 156.8 (d, J=10.6 Hz), 117.2 (d, J=2.5 Hz), 113.1 (d, J=19.8 Hz), 106.3 (d, J=24.4 Hz), 84.5, 24.9. 11B NMR (160 MHz, CDCl3) δ 31.4. 19F NMR (470MHz, CDCl3) δ -116.3 – -116.4 (m). HRMS (ESI) m/z calcd. for C12H15BFO3 [M–H]– 237.1098, found 237.1320. Para borylation of tetrapropyl ammonium 2-methylphenyl sulfate (6g) Figure 3-26 Para borylation of tetrapropyl ammonium 2-methylphenyl sulfate (6g) 67 In a glovebox, a 5.0 mL Wheaton micro reactor was charged with2-Methylphenylsulfate (187.0 mg, 0.50 mmol), [Ir(OMe)COD]2 (5.0 mg, 1.5 mol%), B2pin2 (159.0 mg, 0.63 mmol), and dioxane (1 mL) and stirred at rt. for 5 minutes. Then 4,4′-dimethoxy-2,2′-bipyridine (3.3 mg, 3.0 mol%) and dioxane (0.5 mL) were added. The micro reactor was capped with a Teflon pressure cap and placed into an aluminum block pre- heated to 40°C. After 20 h, an aliquot of the reaction mixture was taken and analyzed directly by 1H NMR to find the conversion and para:meta ratio which was determined to be 10:1 para:meta. HCl (12M) was added drop wise until pH=1–2 and the resultant mixture was stirred for 1 h. Copious bubbling was observed with the addition of HCl. The solution was concentrated and washed with hexanes (0.5 mL). The remaining solution subjected to chromatographic separation with silica gel (CHCl3 as eluent) to give 67.0 mg of a mixture para borylated 2-methylphenol (7g) with the meta isomer (7g’) (para:meta=39:1) as a white solid (57% yield, mp 100.0–102.4 °C). NMR values were consistent with previously reported NMR values. Data for 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (7g) Para: 1H NMR (500 MHz, CDCl3) δ 7.61 (s, 1H), 7.54 (dd, J=8.0, 1.2 Hz, 1H), 6.76 (d, J=8.0 Hz, 1H), 5.81 (bs, 1H), 2.24 (s, 3H), 1.35 (s, 12H). 13C NMR (126 MHz, CDCl3) δ 157.0, 138.0, 134.4, 123.5, 114.6, 83.8, 24.9, 15.6. 11B NMR (160 MHz, CDCl3) δ 31.4. HRMS(ESI) m/z calcd. for C13H18BO3 [M–H]– 233.1349, found 233.1367. Data for 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (7g’) Meta: 1H NMR (500 MHz, CDCl3) δ 7.30 (d, J=7.3 Hz, 1H), 7.20 (s, 1H), 7.14 (d, J=7.3 Hz, 1H), 5.31 (bs, 1H), 2.08 (s, 3H), 1.34 (s, 12H). Para borylation of tetrapropyl ammonium 2-isopropylphenyl sulfate (6h) Figure 3-27 Para borylation of tetrapropyl ammonium 2-isopropylphenyl sulfate (6h) 68 In a glovebox, a 5.0 mL Wheaton micro reactor was charged with 2-isopropylphenylsulfate (201.0 mg, 0.50 mmol), [Ir(OMe)COD]2 (5.0 mg, 1.5 mol%), B2pin2 (159.0 mg, 0.63 mmol), and dioxane (1 mL) and stirred at rt. for 5 minutes. Then 4,4′-dimethoxy-2,2′-bipyridine (3.3 mg, 3.0 mol%) and dioxane (0.5 mL) were added. The micro reactor was capped with a teflon pressure cap and placed into an aluminum block pre-heated to 40°C. After 20h, an aliquot of the reaction mixture was taken and analyzed directly by 1H NMR to find the conversion and para:meta ratio which was determined to be 25:1 para:meta. HCl (12M) was added drop wise until pH=1–2 and the resultant mixture was stirred for 1 h. Copious bubbling was observed with the addition of HCl. The solution was concentrated and washed with hexanes (0.5 mL). The remaining solution subjected to chromatographic separation with silica gel (2 % EtOAc in CHCl3 as eluent) to give 81.0 mg of a mixture para borylated 2-methylphenol (7h) with the meta isomer (7h’) ( para:meta=23:1) as a white solid (62 % yield, mp 138.3–145.9 °C). NMR values were consistent with previously reported NMR values. Data for 2-isopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (7h) Para: 1H NMR (500 MHz, CDCl3) δ 7.68 (s, 1H), 7.54 (d, J=7.9 Hz, 1H), 6.74 (d, J=7.9 Hz, 1H), 5.82 (s, 1H), 3.23 (hept, J=6.8 Hz, 1H), 1.36 (s, 12H), 1.26 (d, J=6.9 Hz, 6H). 13C NMR (126 MHz, CDCl3) δ 156.2, 134.1, 134.1, 133.5, 115.0, 83.8, 27.2, 24.9, 22.6. 11B NMR (160 MHz, CDCl3) δ 31.48. HRMS (ESI) m/z calcd. for C15H22BO3 [M–H]– 261.1662, found 261.1696. Para borylation of tetrapropyl ammonium 2-trifluoromethylphenyl sulfate (6k) Figure 3-28 Para borylation of tetrapropyl ammonium 2-trifluoromethylphenyl sulfate (6k) In a glovebox, a 5.0 mL Wheaton micro reactor was charged with tetrapropylammonium 2- trifluoromethylsulfate (189mg, 0.50 mmol), [Ir(OMe)COD]2 (5.0 mg, 1.5 mol%), B2pin2 (159.0 mg, 0.63 mmol), and dioxane (1 mL) and stirred at rt. for 5 minutes. Then 4,4′-dimethoxy-2,2′-bipyridine (3.3 mg, 3.0 mol%) and dioxane (0.5 mL) were added. The micro reactor was capped with a Teflon pressure cap 69 and placed into an aluminum block pre-heated to 40°C. After 20 h, an aliquot of the reaction mixture was taken and analyzed directly by 1H NMR to find the conversion and para:meta ratio which was determined to be 2.45:1 para:meta. HCl (12M) was added drop wise until pH=1–2 and the resultant mixture was stirred for 1 h. Copious bubbling was observed with the addition of HCl. The solution was concentrated and washed with hexanes (0.5 mL). The remaining solution subjected to chromatographic separation with silica gel (4% EtOAc in CHCl3 as eluent) to give 117.0 mg of a mixture para borylated 3- fluorophenol (7k) with the meta isomer (7k’) (>2%) as a white solid (77% yield, mp 129.6-131.9 °C). The NMR values were consistent with previously reported values. Data for 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethoxy)phenol (7k) 1H NMR (500 MHz, CDCl3) δ 7.65 (s, 1H), 7.63 (d, J=8.2 Hz, 1H), 7.01 (d, J=8.1 Hz, 1H), 5.97 (bs, 1H), 1.33 (s, 12H). 13C NMR (126 MHz, CDCl3) δ 150.6, 136.4, 135.1, 127.8, 120.9 (q, J=259.0 Hz), 117., 84.2, 24.9. 19F NMR (470 MHz, CDCl3) δ -60.98 (s, 3F). 11B NMR (160 MHz, CDCl3) δ 30.5. HRMS (ESI) m/z calcd. for C13H15BF3O4 [M–H]–303.1015, found 303.1244. Para borylation of tetrapropyl ammonium 2-bromobenzyl sulfate (10b) Figure 3-29 Para borylation of tetrapropyl ammonium 2-bromobenzyl sulfate (10b) In a glovebox, a 5.0 mL Wheaton micro reactor was charged with tetrapropylammonium 2-bromobenzyl sulfate (226.0 mg, 0.50 mmol), [Ir(OMe)COD]2 (5.0 mg, 1.5 mol %), B2pin2 (159.0 mg, 0.63 mmol), and dioxane (1 mL) and stirred at rt. for 5 minutes. Then 4,4′-dimethoxy-2,2′-bipyridine (3.3 mg, 3.0 mol%) and dioxane (0.5 mL) were added. The micro reactor was capped with a Teflon pressure cap and placed into an aluminum block pre-heated to 40°C. After 20 h, an aliquot of the reaction mixture was taken and analyzed directly by 1H NMR to find the conversion and para:meta ratio which was determined to be 30:1 para:meta. HCl (12M) was added drop wise until pH=1–2 and the resultant mixture was stirred for 1 h. Copious bubbling was observed with the addition of HCl. The solution was concentrated and washed 70 with hexanes (0.5 mL). The remaining solution subjected to chromatographic separation with silica gel (10 % EtOAc in CHCl3 as eluent) to give 64.0 mg of a mixture para borylated 3-fluorophenol (10b) with the meta isomer (10b) (para:meta=35:1) as a white solid (82 % yield, mp 89.4-91.2 °C). The NMR values were consistent with previously reported values. Data for (2-bromo-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanol (11b) Para: 1H NMR (500 MHz, CDCl3) δ 7.95 (s, 1H), 7.73 (d, J=7.5 Hz, 1H), 7.48 (s, 1H), 4.74 (s, 2H), 2.31 (bs, 1H) 1.34 (s, 12H). 13C NMR (126 MHz, CDCl3) δ 142.8, 138.7, 134.0, 128.1, 122.3, 84.3, 65.1, 25.0. 11B NMR (160 MHz, CDCl3) 30.6. HRMS (APCI+) m/z calcd. for C13H17BBrO2 [M–OH–] 295.0505, found 295.0595. Para borylation of tetrapropyl ammonium 2-fluorobenzyl sulfate (10g) Figure 3-30 Para borylation of tetrapropyl ammonium 2-fluorobenzyl sulfate (10g) In a glovebox, a 5.0 mL Wheaton micro reactor was charged with tetrapropylammonium 2-fluorobenzyl sulfate (196.0 mg, 0.50 mmol), [Ir(OMe)COD]2 (5.0 mg, 1.5 mol %), B2pin2 (159.0 mg, 0.63 mmol), and dioxane (1 mL) and stirred at rt. for 5 minutes. Then 4,4′-dimethoxy-2,2′-bipyridine (3.3 mg, 3.0 mol%) and dioxane (0.5 mL) were added. The micro reactor was capped with a teflon pressure cap and placed into an aluminum block pre-heated to 40°C. After 36 h, an aliquot of the reaction mixture was taken and analyzed directly by 1H NMR to find the conversion and para:meta ratio which was determined to be 7:1:4 para:meta:dimeta. HCl (12M) was added drop wise until pH=1–2 and the resultant mixture was stirred for 1 h. Copious bubbling was observed with the addition of HCl. The solution was concentrated and washed with hexanes (0.5 mL). The remaining solution subjected to chromatographic separation with silica gel (5 % EtOAc in CHCl3 as eluent) to give 91.0 mg of a mixture para borylated (2- fluorophenyl)methanol (11g) with the meta isomer (11g) and dimeta isomer (11g) 71 (para:meta:dimeta=10.6:1:1.2) as an oil (69 % yield). NMR values were consistent with previously reported values. Data for (2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanol (11g) 1H NMR (500 MHz, CDCl3 )δ 7.61–7.52 (m, 1H), 7.48–7.37 (m, 2H), 4.75 (d, J=12.7 Hz, 3H), 2.17 (bs, 1H), 1.34 (s, 12H). 13C NMR (126 MHz, CDCl3) δ 160.1 (d, J=246.6 Hz), 130.9 (d, J=14.7 Hz), 130.6 (d, J=3.4 Hz), 128.5 (d, J=3.9 Hz), 120.8 (d, J=19.5 Hz), 84.1, 59.2 (d, J=4.6 Hz), 24.8. 11B NMR (160 MHz, CDCl3) δ 30.47. 19F NMR (470 MHz, CDCl3) δ –108.48, –112.94 (d, J=6.6 Hz), –124.36, –164.90 (t, J=0.9 Hz). HRMS (APCI+) m/z calcd. for C13H17BFO2 [M–OH–] 235.1306, found 235.1337. 72 REFERENCES (1) (2) (3) (4) (5) (6) Anslyn, E. V.; Dougherty, D. A. 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F.; Miyaura, N. A Stoichiometric Aromatic CH Borylation Catalyzed by Iridium(I)/2,2′-Bipyridine Complexes at Room Temperature Angew. Chem. Int. Ed. 2002, 41, 3056–3058. Shirakawa, S.; Liu, S.; Kaneko, S.; Kumatabara, Y. Fukuda, A.; Omagari, R. Maruoka, K. Tetraalkylammonium Salts as Hydrogen-Bonding Catalysts Angew. Chem. Int. Ed. 2015, 54, 15767–15770. Tajuddin, H.; Harrisson, P.; Bitterlich, B.; Collings, J. C.; Sim, N.; Batsanov, A. S.; Cheung M. S.; Kawamorita, A.; Maxwell, A. C.; Shukla, L.; Morris, J.; Lin, Z. Marder, T. B.; Steel, P. G. Iridium- 74 catalyzed C–H borylation of quinolines and unsymmetrical 1,2-disubstituted benzenes: insights into steric and electronic effects on selectivity Chem. Sci. 2012, 3, 3505-3515. (34) Mihai, M. T.; Williams, b. D.; Phipps, R. J. Para-Selective C–H Borylation of Common Arene Building Blocks Enabled by Ion-Pairing with a Bulky Countercation J. Am. Chem. Soc. 2019, 141, 15477−15482. (35) https://www.chemistryworld.com/news/steric-shield-leads-boron-to-aromatic-rings-most- remote-region/4010603.article Accessed 12-5-2023. (36) Genov, G. R.; Douthwaite, J. L.; Lahdenpera, A. S. K.; Gibson, D. C.; Phipps, R. J. Enantioselective remote C-H activation directed by a chiral cation Science, 2020, 367, 1246– 1251. 75 Chapter 4: Steric Shielding Effects induced by Intramolecular C–H•••O Hydrogen Bonding: Remote Borylation Directed by Bpin Groups Parts of this chapter were taken from “Steric Shielding Effects Induced by Intramolecular C–H···O Hydrogen Bonding: Remote Borylation Directed by Bpin Groups” ACS Catalysis. 2022, 12, 2694–2705. C−H bonds can be diversified via different C− H functionalization methods. Yet, targeting one C−H reactive site in the presence of similar C−H bonds remains challenging.1,2 Although considered weak, noncovalent interactions can differentiate the energetics and therefore relative reactivity of otherwise similar reactive sites. For example, an interaction where Δ G0 ≤−3.5 kcal/mol will be in force for ≥ 99% of the molecules at 100 °C. In the area of sp2 C−H activation, preinstalled directing groups can interact with the catalyst via hydrogen bonding, Lewis acid−base, or electrostatic inter- actions to selectively functionalize ortho, meta, or para positions of arenes.3-9 However, selective reactions at distal C−H sites often require the construction of complex directing groups/ligands.7-11 A different strategy uses steric shields to block nearby C−H bonds, thus leaving the distal position as the only accessible reactive site. For example, Nakao’s group used Lewis acidic additives that interact with aryl amides and shield the meta positions, enabling selective para functionalizations.12-15 In contrast, a complementary approach where intramolecular noncovalent interactions create steric shields leading to remote functionalization is far less common. Iridium catalyzed C−H borylation is currently a standard protocol to make aryl boronic esters.16-18 In the last decade, ortho regioselective sp2 C-H borylation has been achieved by means of chelating and relay directing groups as well as outer- sphere interactions.4,7,19 In 2013, our group reported that meta and para- substituted anilines yield the corresponding ortho borylated product courtesy of a N−H hydrogen bonding with the catalyst.20 Unexpectedly, 2-methoxyaniline was selectively borylated para to nitrogen. A similar result was reported by the Phipps group during their C–H borylation of 2-chloroaniline (Figure 4-1).21 It was proposed that electronic effects might play a role in the change of selectivity for 2-chloro and 2- methoxyaniline, but there was no experimental corroboration of this hypothesis. Based on some of our prior work, it seems likely that this could be due to a steric shielding effect of the N borylated aniline pushing borylation para to itself by blocking the meta position. 76 Figure 4-1 Unexpected para Selectivity Seen in the C–H Borylation of 2-Methoxyanaline and 2- Chloroaniline Previously in conjunction with the Phipps group, we independently discovered a method for achieving para C–H borylation of phenols, anilines, and benzylic alcohols utilizing ion-pairing interactions of sulfates and sulfamates with alkylammonium cations. (Figure 4-2)21,22 By sterically shielding the C−H bonds ortho and meta to the sulfonated alcohol or aniline, we were able to use the alkyl chains of the tetraalkylammonium cation as a shield. Coupled with our previous reported borylations of anilines and amino pyridines20, we envisioned using in situ borylation of hetero atoms to act as a steric shield and thus allow us to access para selectivity. Figure 4-2 Previous Ion-Pair Directed para Borylation of Tetrabutylammonium Sulfamates It is well documented that N–borylation of N–unsubstituted anilines occurs rapidly under C–H borylation conditions.20 We expected that in the presence of an electron rich or bulky ortho substituent such as methoxy, chloro, or tert-butyl, the N−Bpin group could be forced in a conformation in which the Bpin is oriented toward the meta C−H where it would act as a steric shield, leading to para selective C–H borylation (Figure 4-2). Bpin would be an attractive steric shield for primary or secondary anilines since in situ N–borylation with B2pin2 or HBpin is rapid, and the aniline N−H is easily restored during workup by exposing the reaction to water or adding methanol, which rapidly breaks the B−N bond. This contrasts with our previous approach to accessing para-borylated anilines, which required a step to install the sulfamate group and a step where highly acidic conditions were required to remove it from the product. Para C−H Borylation of Anilines, N-Alkylated Anilines, and Indoles. We set out to examine whether para selectivity after N-borylation of anilines and allied substrates was a general phenomenon. To do so, we first looked to optimize the reaction on 2-chloroaniline. Starting with our previously reported conditions, 77 we compared the regioselectivity when B2pin2 was used in place of HBpin and found that the former yielded an improved para to meta ratio: 5.6 to 1 vs 4.5 to 1. With B2pin2 as the new boron partner, we then explored temperature and solvent effects on selectivity (Figure 4-3). Cyclohexane and THF gave higher para selectivity at lower temperatures, but conversion dropped especially with cyclohexane. The best balance between reactivity and selectivity was found with THF at 40 °C. After 4 h, the conversion was 61 and >90% after 24 h. Figure 4-3 Solvent and Temperature Effects on para Selectivity of C–H Borylation of 2-Chloroanaline With these conditions in hand, we evaluated the effect of the ligand (Figure 4-4). Bipyridine ligands (L1−L3) gave modest para:meta ratios (∼5:1). Notably, 4,4′-dimethoxy-2,2′-bipyridine (L3), which was optimal in our previous para-directed C–H borylation of sulfamate salts,22 did not prove superior in this scenario. Selectivity with ligand L9 was similar but yield suffered. In contrast, the para:meta ratio doubled with phenanthrolines L8 and L7, while yields remained high. We chose 3,4,7,8-tetramethyl-1,10- phenanthroline (tmphen) (L7) to continue our studies due to it being slightly better than L8 in terms of regioselectivity and yield. 78 Figure 4-4 Ligand Effects on para Selectivity of C–H Borylation of 2-Chloroanaline Next, we evaluated the para borylation of different anilines, all of which are substituted at the 2-position (Figure 4-5). The highest para selectivity (C4:C5 > 7:1) was observed in C–H borylations for substrates, where ortho substituents have electron lone pairs (13a, 13b, 13c, 13j). Given that C–H borylations are enhanced at the meta positions in monosubstituted benzenes C6H5X when X = Br,23 I,17 or OMe,24 the 2- substiuents are enhancing selectivity para to N. In contrast, 13i with a trifluoromethyl ortho substituent saw selectivity drop to 4:1. Benzoate 13k with an electron- withdrawing group by resonance gave an even lower ratio of 2 to 1 para to meta. This result bears some relationship to previous reports of ester groups favoring para C–H borylation. In our case, that position is meta with respect to aniline nitrogen.25,26 79 Figure 4-5 C–H Borylation Substrate Scope of Anilines The size of alkyl ortho substituents (13e-13h) showed little effect, as para to meta ratios only ranged from 4:1 to 6:1. It should be noted that the 6:1 observed for 2-methylaniline (13e) was achieved by forming the N−Bpin bond prior to the C–H borylation. In contrast, a selectivity of 4:1 is achieved with in situ N−Bpin bond formation of 13e, which suggests a slow formation of the N-borylated intermediate in this case. C– H borylation at C4 was preferred for anilines when C3 was fluorine-substituted (substrate 13l). This is consistent with an electronic preference or C–H borylation ortho to F and attenuated steric interference from F since H, and its isotopes are the only substituents that are less sterically demanding.27,28 Para selectivity for substrate 13h, albeit modest, is more significant since the only literature report where C–H 80 borylation at C4/C7 of an indane structure is preferred has a tert-butyl group at C5, obstructing C4/C6 positions.29 Our hypothesis implies that the Bpin steric shield can only block one meta position of arene. This can explain the necessity of an ortho substituent to block the other meta position. C–H borylation of unsubstituted aniline supports this statement as no para to meta selectivity was observed.30 This feature can allow a meta selective C–H borylation if the para position bears a small substituent. As stated above, fluorine atoms are relatively small and C–H borylation next to them is observed. C-H borylation of 2,4-difluoroaniline (13d) presented a more interesting scenario. In this case, where the N−Bpin orientated away from the ortho fluorine, the resultant steric shield would block C5 leaving 3- borylation as the only option. This was the result as C3 borylation occurred with a 15:1 preference over C5 borylation. It can be argued that 13d’s is electronically biased to favor 3-selective C–H borylation. C–H borylation of 2,4-difluorotoluene shows a modest 3 to 1 preference for the 3-borylated product. The C3- selectivity of 13d′ is 5 times more than that of 2,4-difluorotoluene, which shows that both electronics and the Bpin steric shield play a role in the C3-selectivity of 13d′. To probe other substrates with substituents at the ortho and meta C−H positions, we examined the C–H borylation of N-borylated 5- substitued 1- naphthylamines 13m and 13n. In these substrates, C2, C4, C6, and C8 would be blocked from C–H borylation by substituents, leaving only C3 and C7 sterically unencumbered. However, were our hypothesis correct, the N−Bpin would sterically shield C3, thus favoring C7 in a CHB. Indeed, borylation of 13m and 13n yield their 7-borylated product selectively (C7/C3 7:1 and 24:1, respectively). In the case of 13n, a small amount of diborylation was observed. We next turned our attention to other in situ borylated scaffolds, namely, N-alkylated anilines (Figure 4- 6). Unfortunately, C–H borylation of 2-chloro-N-methylaniline 14a was not para selective under the optimized conditions. A slow rate of N−Bpin formation could explain the lack of selectivity. However, even after formation of the N−Bpin bond, no selectivity was observed. Thus, we considered other explanations. This led us to propose that a reluctance of N-borylated 14a to orientate in the same plane as the aromatic ring, which per our hypothesis creates the N−Bpin steric shield, is responsible for the observed regiochemical result. Such a hypothesized planar conformation is supported by modeling the lowest energy conformation of N-borylated intermediates of N-unsubstituted anilines. In contrast, N-borylated 2- chloro-N-methylaniline does not adopt a planar conformation owing to an A (1,3) interaction between the N-methyl with the ortho chlorine. As N-borylated N-alkyl-2-amino- pyridines should lack this steric clash, 14b and 14c should be para selective. This proved to be the case with 15b and 15c both being the major (4:1) C–H borylation products. 81 Figure 4-6 C–H Borylation Substrate Scope of N-Alkylated Anilines 1,2,3,4-Tetrahydroquinolines also drew our attention as in these N-alkylated anilines, the covalent chain that links the aromatic ring with nitrogen should allow the N-borylated intermediate to achieve a pseudo planar conformation. Para products 15d−15j were obtained as the major regioisomer from their corresponding 1,2,3,4-tetrahydroquinolines. The size of the saturated ring does influence the level of selectivity, as illustrated in 15g where the selectivity was only 3:1. Adding a methyl group about the saturated ring did not significantly change the selectivity, as shown by products 15d−15f. With 3h, borylation next to oxygen was also observed, but the para product still predominated (para:others = 7:1). The fluorinated version of 14h, namely, 14i, was equally selective. Diborylation of phenoxazine 14j mainly yielded the bis para compound along with multiple minor products. N-Borylation of indoles is known to block C2 C–H borylation normally seen in the parent compounds, instead yielding the corresponding 3-borylated product.20 We asked if in a N–borylated 3-subsitued indole, the N−Bpin would shield the closer C6-position, leading to the corresponding 5-borylated indoles. C5 and 82 C6 indole functionalization remains rare. Baran’s group reported that C–H borylation of 3-substituted N- TIPS- indoles yield the 6-borylated product using phenanthroline as ligand.31 C5 borylation of indoles has been elusive besides some specific examples employing electrophilic borylation with borenium cations. The examples are limited to N-methyl carbazole or are triggered by the use of an amine pivaloate directing group at the 4 position.32,33 A protocol to access 3,5- diborylated indoles has been reported, but suffers from low conversions (<30%).34 Under our optimized conditions (Figure 4-7) and after the formation of the N−Bpin intermediate, 3-methyl- indole 16a yielded the 5-borylated product with a modest 3:1 selectivity over the minor 6-borylated isomer. Replacement of the methyl group by a methyl ester as in 16c resulted in the loss of selectivity. However, the presence of substituents at both C2 and C3 impacted selectivity little, as shown in 17b and 17d.It should be stated that for 16b and 16d, formation of the N−Bpin intermediate was slow and additional HBpin and triethylamine as well as a 3 h reaction time was needed to afford full N-borylation. Figure 4-7 C–H Borylation Substrate Scope of Indoles In our efforts to expand the Bpin steric effect to phenols, we found that the C–H borylation of 2- chlorophenol did not show selectivity. Neither QTAIM nor Δδ data (vide infra) show any evidence of intra molecular hydrogen bonding, which explains this experimental result. We speculated that Bpin groups could create a steric shield even when not part of a N−Bpin moiety. We thus focused on 1-borylated naphthalenes, which could bear geometries similar to those of N-borylated 2-substitued anilines and N-borylated tetrahydroquinolines (Figure 4-8). If so, the Bpin derived steric shield would block the C7-position leaving the C6-position available for C–H borylation. The borylation of 1-borylated naphthalene 7a supported our proposition and yielded the 1,6-diborylated product selectively. A ligand screening showed that 4,4 ′- dimethoxy-2,2′-bypiridine (L3) was the best choice for the C6 borylation of 1-borylated naphthalenes. This result is potentially valuable as C6 functionalization 83 of naphthalenes remains rare.35 A notable exception comes from Nakao’s group where a 1-naphtyl amide was made to undergo C6-alkylation using an aluminum Lewis acid as a steric shield.13,14 Figure 4-8 C–H Borylation Substrate Scope of Naphthalenes As shown in Scheme 3, a substituent on the C2- or C4- position is needed to avoid borylation at C3 (18a− 18f). 5-Bpin dihydroacenaphthene 18g was borylated at both the expected C8 position and at C3. Under conditions that promote diborylation, 3,5,8-triborylated product 18g was obtained as the major product along with the 3,5,7-triborylated product as a minor isomer. The Bpin shield in 9-borylated anthracene 18h enabled remote borylation of both sides of the molecule leading to a 2:1 mixture of 3,6,9-triborylated and 2,6,9- triborylated products (19h). We began this study by suggesting that the unusual para selective C–H borylation of 2-methoxy and 2- chloroaniline came about by virtue of a N−Bpin steric shielding in contrast to the previously evoked electronic drivers. This steric shielding hypothesis could be understandably challenged as free rotation around the C−N and N−B bonds can avoid any steric perturbation caused by the N−Bpin group. Moreover, even in the orientation that maximizes the putative steric shield, one could question if the N−Bpin group 84 is close enough to the meta C− H so as to block its borylation. To address these questions and better understand the observed selectivities, we performed the experiments described below. Steel and Marder have shown that 1H NMR chemical shifts can be qualitative predictors of C–H borylation selectivity when there is not a steric difference between two reactive sites.25 More de-shielded hydrogens are expected to be more acidic and more reactive toward C–H borylation. Based on 1D-NOE and 2D NMR experiments, we assigned the 1H NMR chemical shifts of N-borylated 2-chloro (12a*) and 2- tertbutylaniline (12g*)(Figure 4-9). We acquired the spectra in THF-d8 so as to best simulate solution structures present during the C–H borylation. Spectra for both compounds had the meta proton appearing more downfield than the para proton. Per Steel and Marder, this would suggest the meta position should be electronically favored in a C–H borylation. However, a preference for para borylation is the experimentally observed result. This points to factors besides electronic effects being responsible for the para preference. Figure 4-9 Intramolecular Hydrogen Bonding as Seen by 1H NMR A closer comparison of the 1H NMR of the N-borylated intermediate vs the nonborylated version of 2- chloro and 2-tertbutylaniline revealed a surprising de-shielding effect on the chemical shift of the ortho proton after N-borylation (Figure 4-9). This displacement was also observed in other NMR solvents (C6D6, acetone-d6, CDCl3, pyridine-d5). We attribute the downfield chemical shift movement to an intramolecular C−H···O hydrogen bond (IMHB) between the oxygen of the N−Bpin group and the ortho hydrogen in the 85 aniline. De-shielding effects on chemical shifts caused by hydrogen bonds are well documented,36-38 and one of the closest examples to our system is the intramolecular hydrogen bond present in N1,N′-diBoc- protected pyridine-2-yl guanidine (Figure 4-9).39 In this scenario, a C−H···N IMHB is said to change the conformation, vs analogous compound lacking a Boc group, to one where the pertinent protons are de- shielded. While NMR studies argued against electronic effects being responsible for the para borylation of anilines, those studies did not shed light on the question of whether the N−Bpin group is actually close enough to the meta position to act as a steric shield. To begin addressing this question, we ran C–H borylation reactions with larger diboron partners such as B2hg2 and B2pp2 (Figure 4-9 entry [A]). B2hg2 proved less reactive than B2pin2 in accordance with a previous report;40 however, the selectivity for the para position improved. We tested a novel diboron partner for C–H borylation, B2pp2, and interestingly the conversion to the borylated product was greater than with B2hg2. The largest para to meta ratio was also found with B2pp2, which is consistent with our steric shield hypothesis. While this improved selectivity could be due to the size of the installed N−Bpp group, a B2pp2-derived trisboryl active catalyst could also influence regiochemistry. Thus, we generated N−Bpin and N−Bpp compounds from 2-chloro and 2-methylaniline. These intermediates were then independently reacted under the same C–H borylation conditions with B2pin2 as the diboron partner (Figure 4-9 Entry [B] and [C]). For 2-chloroaniline, the N− Bpp borylated derivative yielded a higher para:meta ratio as compared to the N−Bpin substrate. For 2-methylaniline, there was no observable change in selectivity; this may be a reflection of 2-methylaniline being inherently less para selective than 2-chloroaniline. We wondered if a smaller steric shield would reduce para selectivity. However, C–H borylation of N-Beg borylated 2-chloroaniline with B2pin2 as the diboron partner yielded mainly the ortho product in accordance with the previously reported ortho C–H borylation of anilines along with only trace amounts of the para and meta isomers.30 Switching the steric shield and diboron partner, i.e., C–H borylation of N−Bpin borylated 2-chloroaniline with B2eg2 lead to similar results. 86 Figure 4-10 Effect of Diboron Partners on Regioselectivity To probe the significance of the intramolecular hydrogen bond acceptor ability of N−Bpin toward selectivity, we decided to generate N−BBN, a boron group without oxygen, on aniline. With a N−BBN in place, the para selectivity dramatically drops for both 2-chloro and 2-methylaniline. This further supports 87 intramolecular hydrogen bonds playing a direct role in selectivity. With N−BBN generated from 3- methylindole, the C–H borylation regiochemical preference flips and the C6-borylated isomer is major (2:1) as opposed to the C5 selectivity (3:1) seen with N−Bpin. We further evaluated computationally the proximity of the Bpin steric shield to the meta position. We used a B3LYP functional and 6-311++G(d,p) basis set to optimize the geometry of N-borylated 2-chloro (12a*) and 2-methylaniline (12e* )(Figure 4-11 Entry [A]). This basis set has been previously reported to work well when intramolecular hydrogen bonding is present.41 Solid angles around the meta and para positions of 12a* and 12e*show that the meta position is more shielded than the para position supporting our hypothesis.42 Figure 4-11 Energies of Intramolecular Hydrogen Bonding Seeking further evidence of intramolecular hydrogen bonding involvement, we examined N-borylated anilines with the Quantum Theory of Atoms in Molecules (QTAIM) developed by Bader using the multiwfn program.43-45 QTAIM is used to identify intramolecular hydrogen bonding based on a topological analysis of the electronic distribution. Bond critical points (BCP) are defined as the position between two atoms where the electron density reaches a minimum. QTAIM identifies bond critical points when two atoms are connected by any type of bond including intramolecular hydrogen bonding interactions. The QTAIM analysis of both N-borylated anilines shows a bond critical points between the oxygen of the N−Bpin group and the nearest ortho hydrogen of the aromatic ring supporting the existence of a C−H···O intramolecular hydrogen bond. An additional bond critical point is found in N-borylated 2-chloroaniline between the 88 chloride and the N−H. This additional N− H···Cl intramolecular hydrogen bond may be one contributor to the greater para C–H borylation selectivity of 2-chloroaniline vs 2-methylaniline. The energy of hydrogen bonds can be estimated by multiplying the potential energy density (V(r)) at the bond critical point found with QTAIM by a scaling factor determined from plotting V(r) vs experimentally determined hydrogen bonding energies. The linear relationship initially found by Espinosa et al. has been adapted by Afonin et al. for the case of intramolecular hydrogen bonding including cases with C− H···O interactions.41-46 Afonin’s corrected equation to calculate the C−H···O intramolecular hydrogen bond energy of N-borylated 2-chloro and 2-methylaniline gave comparable energies corresponding to 1.10 and 1.07 kcal/mol, respectively (Figure 4-11 Entry [A]). Intramolecular hydrogen Bond energies can also be estimated using NMR spectroscopy. Typically, there is a linear relationship between the intramolecular hydrogen bond stabilization energy and the 1H chemical shift difference, Δδ, of the hydrogen involved in the intramolecular hydrogen bond in the target molecule vs a reference in which no intramolecular hydrogen bond occurs (Figure 4-11 entry [B]).41,47 We used CDCl3 for these experiments since the relationship was established from 1H NMR spectra of CDCl3 solutions. We chose non-borylated anilines as references and found energies of 1.29 and 1.23 kcal/mol for the intramolecular hydrogen bond of 2-chloro and 2-methylaniline, respectively, in excellent agreement to the energy predictions from QTAIM. One potential pitfall in attributing para selectivity to IMHB Bpin shielding is the assumption that there is only one energy minimum on the conformational energy surface. For example, the presence of a second local minimum where the plane of the N−Bpin is orthogonal to the plane containing the aryl ring could erode selectivity if (i) the second local minimum has a comparable or lower Gibbs’ energy than the IMHB local minimum and (ii) the barrier connecting the local minima is small. Indeed, theory predicts that there are local minima similar to the aforementioned scenario for N-borylated 2- chloroaniline and 2- methylaniline at 5.4 and 3.1 kcal/mol relative to their respective IMHB local minima (Figure 4-11 [C]), and the corresponding transition states that connect these local minima are 6.6 and 4.6 kcal/mol above the IMHB local minima. Based on the energies of the higher-energy local minima, theory predicts that more than 99% of N-borylated anilines adopt IMHB structures. These findings support the hypothesis that IMHB between the Bpin O and the C6 proton creates a steric shield that accounts for the para selectivity. We next asked if similar relationships could be found in other scaffolds with and without intramolecular hydrogen bonding (Figure 4-12). Accordingly, good C–H borylation selectivities are seen for substrates when protons proximal to Bpin substituents have the largest 1H NMR chemical shift displacement, as well as a bond critical points between that proton and the Bpin O from QTAIM analysis. Specific examples are described below. 89 Figure 4-12 Naphthalenes with and Without IMHB The H2 of N-borylated 5-bromo-1-aminonaphthalene 13m* shows a 0.85 ppm difference from the reference 5-bromo-1- aminonaphthalene. By comparison, all of the other protons deviate by <0.2 ppm. QTAIM shows a BCP that supports an IMHB with an energy of 1.11 kcal/mol, which is close to 1.25 kcal/mol calculated based on the spectroscopically observed 1H NMR chemical shift displacement. As expected, 5- bromo-1-aminonaphthalene (13m) undergoes a C7-selective borylation by blocking the C3 position (Figure 4-5). In contrast, N-borylated 2-methylnaphthalene 13o*show no evidence of C−H···O IMHB with naphthalene as the hydrogen bond donor. H8 might be available for IMHB, but its Δδ is only 0.30 ppm, which is close to the Δδ of H4 (0.28 ppm), suggesting that chemical shift displacement results from electronic effects after N-borylation. No BCP is detected with arene as the hydrogen bond donor, but a BCP corresponding to a C−H···O IMHB between the N−Bpin and the methyl group is found. The lack of IMHB with the naphthalene ring might be due to steric effects that disrupt any seven-membered ring IMHB from happening. Accordingly, no selectivity was found under CHB reaction conditions. Similar 1H NMR and QTAIM studies were done in N- borylated N-methyl-2-aminopyridine (15b*), 1,2,3,4- tetrahydro- quinoline (15d*), 3-methylindole (17a*), and in 1-borylated naphthalenes 18c and 18f, which show the presence of an IMHB and CHB remote selectivity accordingly. N-Borylated 2-chloro-N- methylaniline (15a*) did not show C–H borylation as shown in Figure 4-6, and there is no presence of an IMHB based on NMR and QTAIM. Seven-Membered Ring IMHB and Pyrimidines as Directing Groups. Inspired by literature precedent,37,38,41 we sought to see if a seven-membered ring can be created with IMHB to N−Bpin groups. As explained in the previous section, steric effects can disrupt IMHB. Hence, seven- membered ring IMHB with arenes as hydrogen bond donors are uncommon. However, exceptions appear when a hydrogen bond donor 90 contains a bicyclic moiety with five- and six- membered fused rings.37,38,41 We expected that 3-amino- indazoles would form a seven-membered IMHB after N-borylation. Figure 4-13 7 Member IMHB Rings Guiding Regioselectivity We were pleased to find that N-methyl-3-aminoindazole 20 undergoes a C6-selective CHB (Figure 4-13). 1H NMR comparison of the N-borylated indazol vs the unborylated version shows a significant movement of the chemical shift of the C4 proton, as expected with an IMHB. QTAIM provides more support to this conclusion by recognizing a C−H···O BCP between the C4 proton and the oxygen in the Bpin group. The calculated energies by QTAIM and Δδ are comparable: 1.19 and 0.85 kcal/mol, respectively. Certainly, Bpin is not the first IMHB acceptor found in molecules. Nitrogen heterocycles have appeared as part of IMHB networks including C−H···N interactions within heteroarenes.48-50 Pyridines, pyrimidines, and triazines are key motifs of biologically active pharmaceuticals, and therefore, their potential use as steric shields via IMHB drew our attention.51-58 In particular, we became interested in osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor, which presents a pyrimidine group attached to produced, although with moderate selectivity. We were fortunate to crystallize 22 and the crystal structure showed the C− H···N that we had proposed with the pyrimidine groups as the hydrogen bond acceptor and the C4 hydrogen of the indole being the hydrogen bond donor. We used X- ray coordinates to evaluate the QTAIM topology of 22 and found a BCP that supports the IMHB C− H···N. Next, changes in 1H NMR of 22 taking N-methylindole as the reference were calculated. Surprisingly, we 91 found that both C2 and C4 hydrogens showed a significant chemical shift displacement. We propose that in solution the pyrimidine ring may equilibrate between two conformations involving IMHB with H2 and H4. The IMHB energy for H4 calculated from Δ δ is 1.13 kcal/mol, which is higher than that calculated by QTAIM. This difference might be due to the different conformations found in the solution in contrast to the solid state. A diverse array of regioselective remote C–H borylations can be driven by intramolecular steric shields created via IMHB. The previously inexplicable para CHB found with 2-chloro and 2-methoxyani- line now is explained by a Bpin steric shield generated after in situ N-borylation. Furthermore, N−Bpin steric shields can lead to para CHB of other ortho-substituted anilines, 7-borylation of 1-naphthylamines, para CHB of certain N-alkylated anilines, and to the elusive 5-borylation of indoles. Bpin steric shielding can be extended to motifs without nitrogen, such as 1- borylated naphthalenes, which undergo C6-selective CHB. The wide variety of scaffolds that can be selectively borylated at remote positions due to a Bpin group highlights the versatility of intramolecular steric shields. We traced back the remote CHB selectivity to the presence of a C−H···O IMHB in N-borylated intermediates with the Bpin as the hydrogen bond acceptor. A BCP found by QTAIM and a characteristic 1H NMR chemical shift displacement of the hydrogen bond donor, the ortho aniline hydrogen after N- borylation here, is support for an IMHB. The energetic cost to disrupt the planarity of N-borylated anilines and the necessity of oxygen in the boryl group to achieve a para CHB also support the observed selectivity to involve IMHB. A seven- membered ring IMHB can also produce the steric as shown in the C6-selective borylation of N-methyl-3-aminoindazole. Furthermore, a C5 borylation of the indole ring in an osimertinib analogue where a pyrimidine forms the steric shield via a C−H···N IMHB further expands this means of remote regiocontrol. The most significant outcome of our study is that the IMHB Bpin steric shielding explains regioselectivities in catalytic C−H borylations, where standard steric models and correlations with NMR chemical shifts fail. We anticipate that our efforts presented here will be used to design other methods for remote functionalization driven by intramolecular interactions. General Information Experimental Procedures All available reagents were used as received unless otherwise indicated. Bis(pinacolato)diborn (B2pin2) was generously supplied by BoroPharm. THF was refluxed over Na/benzophenone ketyl and distilled. Anhydrous 1,4-dioxane was obtained through Sigma-Aldrich and used as received. 3,4,7,8-tetramethyl- 1,10-phenanthroline (tmphen) and neocuproine were purchased from Combi-blocks and recrystallized from ethanol. 2-chloroaniline, 2-methoxyaniline, 2-methylaniline, 2-ethylaniline, 2-tertbutylaniline and 92 tetrahydroquinoline were distilled over molecular sieves prior to use. Column chromatography was done using 240-400 mesh silica P-Flash silica gel. TLC was done on 0.25 mm thick aluminum backed silica gel plates and visualized with UV light (λ = 254 nm) with alizarin stain.58 1H, 13C, 11B and 19F NMR spectra were recorded on a Varian 500 MHz DD2 Spectrometer equipped with a 1H-19F/15N-31P 5 mm Pulsed Field Gradient (PFG) Probe. Spectra taken in CDCl3 were referenced to 7.26 ppm in 1H NMR and 77.2 ppm in 13C NMR. Spectra taken in C6D6 were referenced to 7.16 ppm in 1H NMR and 128.1 ppm in 13C. 11B NMR spectra were referenced to neat BF3·Et2O as the external standard. NMR spectra were processed for display using the MNova software program with only phasing and baseline corrections applied. High-resolution mass spectra (HRMS) were obtained at the Molecular Metabolism and Disease Mass Spectrometry Core facility and at the Mass Spectrometry Service Center at Michigan State University using electrospray ionization (ESI+ or ESI-) on quadrupole time-of-flight (Q-TOF) instruments. Parts of this chapter were reprinted with permission from Montero Bastidas, J. R.; Chhabra, A.; Feng, Y.; Oleskey, T. J.; Smith, M. R.; Maleczka, R. E. Steric Shielding Effects Induced by Intramolecular C−H···O Hydrogen Bonding: Remote Borylation Directed by Bpin Groups ACS. Catal. 2022, 12, 2694-2705. Copyright 2022 American Chemical Society. The work presented in this chapter was not all conducted by Thomas Oleskey. Substrate exploration was a team effort with Montero Bastidas, J. R.; Chhabra, A.; Feng, Y. Unselective Borylation of 2-chloro-N-methylaniline (14a) Figure 4-14 Unselective Borylation of 2-chloro-N-methylaniline (14a) In a glove box, a 5.0 mL Wheaton microreactor was charged with 2-chloro-N-methyl aniline (71 mg, 0.5 mmol, 1 equiv), [Ir(cod)(OMe)]2 (1.7mg, 0.5 mol %), HBpin (77 mg, 0.6 mmol, 1.2 equiv), NEt3 (0.08 mL, 0.5 mmol), and THF (0.5 mL). The microreactor was capped with a teflon pressure cap and placed into an aluminum block pre-heated to 80 ºC. After 1 h, the microreactor was brought back to the glove box. The microreactor was charged [Ir(cod)(OMe)]2 (10 mg, 3 mol %), B2pin2 (190 mg, 0.75 mmol), and THF (0.5 mL). The reaction was then stirred for 5 minutes over which the reaction turned a dark golden color. tmphen (3.6 mg, 6.0 mol %) and THF (0.5 mL) was then added causing the reaction to turn 93 a dark green color. The microreactor was capped with a teflon pressure cap and placed into an aluminum block pre-heated to 40 ºC. After 48 h, an aliquot of the reaction mixture was taken and analyzed directly by 1H NMR showing complete conversion and a 1:1 para : meta borylation ratio. MeOH (2.25 mL) was added resulting in vigorous bubbling, and the mixture was stirred for 1 h at room temperature. The mixture was concentrated and passed through a plug of silica gel (2 cm x 5 cm) (chloroform as eluent). The fractions containing product were collected and concentrated to give a first fraction containing 1.4 mg of para borylated 2- chloro-N-methylaniline 15a (1% yield). The fraction was too small to take an accurate 13C{ 1H} NMR but the peaks could be obtained by subtracting the meta carbon peaks from the para:meta mixture isolated previously. The NMR data of the para isomer were consistent with previously reported NMR values. Three more fractions were collected corresponding to 17.3 mg of meta borylated 2-chloro-N- methylaniline 15a (13% yield), 19.8 mg, and 7.9 mg. Data for 2-chloro-N-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (15a) Para: 1H NMR (500 MHz, CDCl3) δ 7.69 (d, J = 1.4 Hz, 1H), 7.60 (dd, J = 8.1, 1.4 Hz, 1H), 6.61 (d, J = 8.1 Hz, 1H), 4.60 (bs, 1H), 2.92 (d, J = 5.2 Hz, 3H), 1.32 (s, 12H). 13C NMR (126 MHz, CDCl3) δ 147.4, 135.4, 134.9, 118.7, 109.8, 83.6, 30.3, 25.0. 11B NMR (160 MHz, CDCl3) δ 30.9. HRMS (ESI) m/z calcd for C13H20BClNO2 [M+H]+ 268.1276, found 268.1273 Data for 2-chloro-N-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (15a) Meta: 1H NMR (500 MHz, CDCl3) δ 7.25 (d, J = 7.7 Hz, 1H), 7.08 (dd, J = 7.7, 1.4 Hz, 1H), 7.07 (d, J = 1.4 Hz, 1H), 4.32 (bs, 1H), 2.95 (s, 3H), 1.34 (s, 12H). 13C NMR (126 MHz, CDCl3) δ 144.5, 128.6, 123.8, 122.5, 116.5, 84.0, 30.7, 25.0.11B{1H} NMR (160 MHz, CDCl3) δ 30.8. HRMS (ESI) m/z calcd for C13H20BClNO2 [M+H]+ 268.1276, found 268.1271 94 Para Borylation of 1,2,3,4-tetrahydroquinoline (14d) Figure 4-15 Para Borylation of 1,2,3,4-tetrahydroquinoline (14d) In a glove box, a 5.0 mL Wheaton microreactor was charged with 1,2,3,4-tetrahydroquinoline (60 mg, 0.5 mmol, 1 equiv), [Ir(cod)(OMe)]2 (1.7mg, 0.5 mol %), HBpin (77 mg, 0.6 mmol, 1.2 equiv), NEt3 (0.08 mL, 0.5 mmol), and THF (0.5 mL). The microreactor was capped with a teflon pressure cap and placed into an aluminum block pre-heated to 80 ºC. After 1 h, the microreactor was brought back to the glove box. The microreactor was charged [Ir(cod)(OMe)]2 (10 mg, 3 mol %), B2pin2 (190 mg, 0.75 mmol), and THF (0.5 mL). The reaction was then stirred for 5 minutes over which the reaction turned a dark golden color. tmphen (3.6 mg, 6.0 mol %) and THF (0.5 mL) was then added causing the reaction to turn a dark green color. The microreactor was capped with a teflon pressure cap and placed into an aluminum block pre-heated to 60 ºC. After 48 h, an aliquot of the reaction mixture was taken and analyzed directly by 1H NMR showing complete conversion and a 9:1 para : meta borylation ratio. MeOH (2.25 mL) was added resulting in vigorous bubbling, and the mixture was stirred for 1 h at room temperature. The mixture was concentrated and passed through a plug of silica gel (chloroform/hexane/ethyl acetate 7:2:1 as eluent). The fractions containing product were collected as two groups and concentrated to give 46.7 mg of a para borylated 1,2,3,4-tetrahydroquinoline 15d as a colorless oil (36% yield) with the meta isomer as a minor byproduct being collected as a white solid at 4.3 mg (3% yield). Data for 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroquinoline (15d) Para: 1H NMR (500 MHz, CDCl3) δ 7.45-7.39 (m, 2H), 6.45-6.40 (m, 1H), 4.09 (bs, 1H), 3.31 (t, J=5.5, 2H), 2.76 (t, J = 6.3, 2H), 1.95-1.87 (m, 2H), 1.32 (s, 12H). 13C NMR (126 MHz, CDCl3) δ 147.6, 136.4, 133.9, 120.3, 113.2, 83.2, 41.9, 26.9, 24.9, 22.0. 11B NMR (160 MHz, CDCl3) δ 30.6. HRMS (ESI) m/z calcd for C15H23BNO2 [M+H]+ 260.1822, found 260.1814. 95 Data for 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroquinoline (15d) Meta: 1H NMR (500 MHz, CDCl3) δ 7.05 (d, J = 7.4 Hz, 1H), 6.96 (d, J = 7.4 Hz, 1H), 6.91 (s, 1H), 3.81 (bs, 1H), 3.34 – 3.21 (m, 2H), 2.77 (t, J = 6.3 Hz, 2H), 1.93 (p, J = 6.5 Hz, 2H), 1.32 (s, 12H). 13C NMR (126 MHz, CDCl3) δ 144.5, 129.2, 125.1, 123.5, 120.5, 83.6, 42.2, 27.3, 25.0, 22.2. 11B NMR (160 MHz, CDCl3) δ 30.6. HRMS (ESI) m/z calcd for C15H23BNO2 [M+H]+ 260.1822, found 260.1814 Para Borylation of 8-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine (14i) Figure 4-16 Para Borylation of 8-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine (14i) In a glove box, a 5.0 mL Wheaton microreactor was charged with 8-fluoro-3,4-dihydro-2H- benzo[b][1,4]oxazine (77 mg, 0.5 mmol), [Ir(cod)(OMe)]2 (1.7mg, 0.5 mol %), HBpin (77 mg, 0.6 mmol, 1.2 equiv), NEt3 (0.08 mL, 0.5 mmol), and THF (0.5 mL). The microreactor was capped with a teflon pressure cap and placed into an aluminum block pre-heated to 80 ºC. After 1 h, the microreactor was brought back to the glove box. The microreactor was charged [Ir(cod)(OMe)] 2 (10 mg, 3 mol %), B2pin2 (190 mg, 0.75 mmol), and THF (0.5 mL). The reaction was then stirred for 5 minutes over which the reaction turned a dark golden color. tmphen (3.6 mg, 6.0 mol %) and THF (0.5 mL) was then added causing the reaction to turn a dark green color. The microreactor was capped with a teflon pressure cap and placed into an aluminum block pre-heated to 60 ºC. After 24 h, an aliquot of the reaction mixture was taken and analyzed directly by 1H NMR showing complete conversion and a 8:1 para : meta borylation ratio. The mixture was concentrated and passed through a plug of silica gel (2 cm x 5 cm) (hexane/ethyl acetate 7:3 as eluent). The fractions containing product were collected, concentrated and washed with water (2 mL). The water layer was decanted, and the residue was dried to yield 68 mg of a para borylated 4i with the meta isomer as a minor byproduct (para:meta = 10:1) as a tan solid that darkened over time (89% yield). 96 Data for 8-fluoro-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine (15i) Para: 1H NMR (500 MHz, CDCl3) δ 7.07 (dd, J = 8.1, 5.9 Hz, 1H), 6.33 (dd, J = 8.1, 0.9), 4.28-4.22 (m, 2H), 4.14- 4.05 (m, 1H), 3.54-3.39 (m, 2H), 1.32 (s, 12H). 19F NMR (470 MHz, CDCl3) δ -127.4 (d, J = 6.7 Hz). 13C NMR (126 MHz, CDCl3) δ 156.5 (d, J = 248.1 Hz), 138.8 (dd, J = 5.3, 3.3 Hz), 131.4 (d, J = 15.3 Hz), 128.0 (d, J = 9.6 Hz), 110.0 (d, J = 2.4 Hz), 83.4, 64.9, 40.7, 24.9. 11B NMR (160 MHz, CDCl3) δ 30.3. HRMS (ESI) m/z calcd for C14H20BFNO3 [M+H]+ 280.1520, found 280.1508 Data for 8-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine (15i) Meta: 1H NMR (500 MHz, CDCl3) δ 6.92 (dd, J = 10.78, 1.16 Hz, 1H), 6.82 (s, 1H), 4.33-4.30 (m, 1H), 4.14-4.05 (m, 1H), 3.54-3.39 (m, H), 1.31 (s, 12H). 19F NMR (470 MHz, CDCl3) δ -138.73 (d, J = 10.8 Hz). HRMS (ESI) m/z calcd for C14H20BFNO3 [M+H]+ 280.1520, found 280.1 97 REFERENCES (1) (2) Boerner, L. K. C −H Bond Breakers Seek Smarter Tools. Chemical & Engineering News, 2021. Rej, S.; Das, A.; Chatani, N. Strategic Evolution in Transition Metal-Catalyzed Directed C−H Bond Activation and Future Directions. Coord. Chem. Rev. 2021, 431, 213683 (3) Mahmudov, K. T.; Gurbanov, A. V.; da Silva, M. F. C. G.; Pombeiro, A.J.L. Noncovalent Interactions in C− H Bond Functionalization. In Noncovalent Interactions in Catalysis; Royal Society of Chemistry, 2019; Chapter 1, pp 1−25. 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M.; Schonbrunn, E.; Lawrence, N. J. Development of O-Chlorophenyl Substituted Pyrimidines as Exceptionally Potent Aurora Kinase Inhibitors. J. Med. Chem. 2012, 55, 7392− 7416. Patel, H.; Pawara, R.; Ansari, A.; Surana, S. Recent Updates on Third Generation EGFR Inhibitors and Emergence of Fourth Generation EGFR Inhibitors to Combat C797S Resistance. Eur. J. Med. Chem. 2017, 142, 32−47. 101 Chapter 5: Measurement of Isotopic Distribution of Boron Not all atoms of an element are created equal. While isotopes are predominately seen as the interest of physicists, in the world of chemistry they do find ample use. Contrary to simplified teaching, isotopes do react differently, although this difference in reactivity lies in reaction rate. This difference in reaction rate is in turn dependent on the mass of the two atoms sharing the chemical bond. This is called the kinetic isotope effect. The kinetic isotope effect is often seen used in mechanistic studies of chemical reactions and is often encountered as protium and deuterium isotope effects. This is for three reasons. First because deuterium is widely available and easy to incorporate into molecules. Second, because it is extremely easy to observe via NMR. And third is due to the relative difference masses between hydrogen isotopes. This difference in mass is important as the relative mass difference is proportional to the size of the KIE able to be observed. Hydrogen isotopes have the largest relative difference in mass of all the atoms as they are the lightest element known. This intrinsically causes measured KIE effects for hydrogen to be the largest of all atoms. Although hydrogen is undisputedly the main atom of interest for KIE studies, other atomic nuclei can be used to measure kinetic isotope effects. These are most often referred to as heavy atom isotope effects. The main difference between hydrogen kinetic isotope effects and heavy atom isotope effects is simply the size of the values. Typically, hydrogen isotope effects (KH/KD) are between 1 and 8, whereas heavy atom isotope effects typically have a value of 0.975 to 1.075.1,2 The smaller value of heavy atom kinetic isotope effects makes the practicality of measuring these much harder. Additionally, non-hydrogen isotopically labeled compounds are much harder to obtain, and sometimes prohibitively expensive. Ideally heavy atom kinetic isotope effects could be carried out simply with natural abundance of a compound of interest. This was demonstrated to be possible by Singleton who was able to utilize naturally abundant 2H and 13C to measure isotopic perturbation under reaction conditions.3,4 A good candidate for measuring kinetic isotope effects at natural abundance is boron with a natural abundance of about 20 % 10B and 80 % 11B. The problem with boron however is the difficulty in measuring the concentration of each isotope. A few methods have been utilized to do this. The simplest method is the use of mass spectroscopy; however, other methods have also been used such as emission spectroscopy, IR, and neutron absorption.5,6 NMR has also been used; however, boron was paired with a reporter that is able to differentiate between boron isotopes. In a published report measuring a boron kinetic isotope effect, the authors utilized fluorine to report the isotopic distribution of the boron by NMR shift as shown in Figure 5-1. They however, utilized incorporated deuterium labeling to differentiate between the boron isotopic 102 labels through shifting of the fluorine signal.7,8 This presents the same problem associated with having to incorporate labeled boron as well as potential for secondary kinetic isotopic effects.9 F OH H 10B OH D F OH 11B OH F + H F D KOH 1,4-dioxane : H2O (1:1) H F H D + F F D F 10B(OH)3 11B(OH)3 Figure 5-1 Measurement of the Boron KIE for Proto-deborylation as Described by Llyod-Jones Through our previous studies we realized that we could differentiate between 10B and 11B in compounds containing fluorine by 19F NMR. This effect is most pronounced in molecules where the boron is directly fluorinated such as in tetrafluoroborate salts as shown in Figure 5-2. This was reported in 2017 by the university of Ottawa NMR facility in a blog post.10 The two Isotopes of boron can be differentiated from each other by their shift as well as by their splitting pattern. 10B will show up as a septet due to 10B having a spin of 3 and 11B will show up as a quartet due to its spin of 3/2. Na11BF4 Na10BF4 Figure 5-2 19F NMR of NaBF4 in D2O Showing Both the 10B and 11B Isotopic Peaks We immediately saw potential of this observation in the fact it could be used to directly measure boron isotopic distribution and therefore boron heavy atom isotope effects. Essentially, we desired to utilize 19F NMR to measure the concentration of each born isotope in a sample to directly measure boron heavy isotope effects in a reaction as outlined in Figure 5-3. By taking the reaction to high, but not complete conversion, the heavy isotope should be enriched in the leftover starting material while the product should be depleted in the heavy isotope. To study this effect, we elected to investigate the oxidation of 2-fluoro-phenyl boronic acid pinacol ester. 103 Seperation Seperation Figure 5-3 Outline of Our Plan to Measure the Boron KIE for Hydrogen Peroxide Oxidation of 2-Fluoro- Phenylboronic Acid The project first started by looking at conditions for running oxidations of aryl boronic acids. We elected to utilize 23 as a test substrate as our group had prior work with this compound. Initially we started by oxidation of 23 acid following typical oxidation conditions as shown in Figure 5-4. Figure 5-4 Our Initial Attempt at oxidation of a Boronic Acid with Recovery of the Produced Boric Acid We quickly found that using ethanol as a solvent for hydrogen peroxide oxidations of 23 was not optimal as it led to the loss of a significant amount of the resulting boric acid byproduct thus invalidation results. This was due to the formation and evaporation of triethyl borate, which while advantageous for synthetic applications resulted in the loss of the product of interest. We alleviated this problem by utilizing ethereal solvents, particularly 1,4-dioxane as reaction solvents. While changing solvents did work well in eliminating loss of boron, use of 1,4-dioxane was not pursued due to safety concerns, especially since the first step in the work up is evaporation to dryness. Oxidation of boronic acids in 1,4-dioxane was a serious safety hazard as it is a known peroxide former, and treatment with hydrogen peroxide led to charring of some reaction mixtures upon evaporation. This led us to believe that we were forming organic peroxides to some extent and thus we abandoned ethereal solvents. Despite this, it was evident that by using non- alcoholic solvents boron evaporation could be eliminated. Acetonitrile was then used as a replacement solvent as it has ideal properties as a solvent for oxidation of aryl boronic acids (Figure 5-5). It easily 104 solvates aryl boronic acids, is non-reactive with hydrogen peroxide solutions while also being volatile enough to be easily removed. Figure 5-5 Reaction Conditions for Oxidation of 2-Fluoro-Phenylboronic Acid in Acetonitrile After treatment of 23 with hydrogen peroxide, the product was removed from the unreacted starting material by aqueous extraction with chloroform. This was successful in separating the synthesized boric acid from the unreacted 23. From here we converted the isolated boric acid to the boron tetrafluoride anion. We found that the best way of accomplishing this was with hydrofluoric acid. Initially we found that 28% aq. HF added to the boric acid was able to produce the desired fluoroboric acid. This was a serendipitous discovery as the original HF concentration that we planned to use was concentrated HF or 48% in accordance with preparation described for tetrafluoro borate by Brauer (Figure: 5-5).11 While fluoroboric acid can be directly analyzed by 19F NMR for isotope ratios, this is undesirable for a few reasons. Like HF, fluoroboric acid etches glass and therefore can be vulnerable to reactive changes in the concentration of labeled boron. This of course will also damage equipment used for characterization. It cannot simply be fixed by adding a commercial NMR tube protective insert as they are usually made from perfluorinated plastics which becomes evident in the 19F NMR spectra. What is most undesirable though, is the toxicity of fluoroboric acid. As an acidic fluoride source, it shares the same hazards as HF. Nearly all these issues can simply be avoided by quenching the fluoroboric acid with a base to give a far less hazardous tetrafluoroborate salt. We chose to pursue sodium tetrafluoroborate as initial studies showed us that sodium tetrafluoroborate gave superior solubility and resolution of the isotopic peaks. To convert fluoroboric acid to sodium tetrafluoro borate, the fluorination solution merely needs to be brought to a neutral pH with a sodium base. In early trials nearly every attempt failed due to imprecise pH control. While sodium tetrafluoroborate is a stable salt, it is prone to hydrolysis. In the case of hydrolysis, sodium tetrafluoroborate will hydrolyze slowly back to boric acid and HF. This process is accelerated greatly by basic conditions. In our case due to the imprecise quenching of the fluoroboric acid with base, we often had excess base in solution which caused reversion of the sodium tetrafluoro borate back to boric acid. We were able to easily identify this by boron NMR in which we were able to observe the characteristic peak for boric acid as opposed to the 105 tetrafluoroborate anion. This was an issue for quenching with sodium hydroxide and sodium carbonate. We initially thought by measuring the concentration of our solutions of hydrofluoric acid and sodium carbonate by titration with KHP and phenolphthalein we could dial in our quenching, however, we found we could more exactly neutralize the fluoroboric acid by simply adding a small quantity of phenolphthalein to the fluoroboric acid and simply titrating with sodium carbonate. This was successful in precisely forming sodium tetrafluoroborate without addition of excess base. This alleviated our problem with hydrolysis of the tetrafluoroborate anion. The problem with adding phenolphthalein became evident when this mixture was observed by 19F NMR. As shown below, an additional peak was observed forming in the fluorine spectra. It was evident that this was due to an interaction between the sodium tetrafluoroborate and phenolphthalein as addition of additional phenolphthalein caused this peak to grow. We theorized that the fluorine of the sodium tetrafluoroborate was able to bind to the arenes of the phenolphthalein via fluorine – pi orbital interactions, the theorized adduct. This was further supported by the fact that when sodium chloride was added this additional peak disappeared however, additional fluoroborate peaks appeared due to fluorine chlorine scrambling as shown in Figure 5-6.12 It was theorized that by replacement of one or more fluorides of the tetrafluoroborate anion with chlorine was able to disrupt the fluorine-arene interaction and thus separate the adduct that was formed. Na11BF4 Na11BF4 Na10BF4 Phenolphthalein Na10BF4 Phenolphthalein Adduct Na11BClxF4-x Na10BClxF4-x Figure 5-6 Formation of the NaBF4 Phenolphthalein Adduct and Treatment with Sodium Chloride It was hypothesized that the three-dimensional shape of the phenolphthalein was responsible for this interaction as the shape of phenolphthalein would be expected to change with protonation state as demonstrated below in Figure 5-7. By deprotonating phenolphthalein, the lactone will open resulting in flattening of the molecule.12 Once opened, it was theorized that this molecule can undergo fluorine arene electronic interactions to form an unidentified adduct. If this theory is correct by retaining the 106 balled up three-dimensional structure of the phenolphthalein, we can eliminate the proposed fluorine- arene interaction. The problem with this is of course, is that the geometry is entirely dependent on the pH of the solution and therefore to reform the desired geometry, the phenolphthalein would have to be reprotonated. Figure 5-7 Approximate Three-Dimensional Geometries of Phenolphthalein We tried reprotonating the phenolphthalein by adding a small amount of acetic acid. Acetic acid was chosen due to its pKa. As fluoroboric acid is a strong acid with a pKa of approximately -0.4, and acetic acid is a weak acid with a pKa of approximately 5, we postulated that the acetic acid would reprotonate the phenolphthalein without reprotonating the sodium tetrafluoroborate. To our pleasure this worked and eliminated the fluorine peak caused by the addition of the phenolphthalein as shown in Figure 5-8. This concluded our initial method development work on designing a process to oxidize 23, separate the produced 25 from residual starting material, and install a reporter allowing us to directly measure the boron isotopic distribution by 19F NMR. . Na11BF4 Na11BF4 Na11BF4 Na10BF4 Na10BF4 Phenolphthalein Acetic Acid Na10BF4 Phenolphthalein Adduct Figure 5-8 Formation of the NaBF4 Phenolphthalein Adduct and Treatment with Acetic Acid 107 With this method in hand, we started working on how to spectroscopically measure the boronic isotopic distribution. The crux of this project is to be able to accurately measure the boron isotopic distribution in a sample. To do this we need to measure two values, total weight of the sample and boron isotopic distribution. Weighing the sample is simple enough, however measuring the concentration of each boron isotope is not as simple due to the presence of impurities. The fluorinated sample is inherently not pure due to the presence of additives namely phenolphthalein, however this impurity pales in comparison to the amount of NaF that was produced due to the quenching of excess HF leftover from the fluorination of boric acid. This leaves us with only one option and that is to use an internal standard. Due to the inherent solubility of sodium tetrafluoro borate or rather its insolubility in everything save water or for NMR deuterium oxide, the internal standard must be soluble in water. The obvious standard would simply be a fluoride salt, however due to the sodium fluoride impurity no fluoride salts can be utilized. Additionally, if a salt is to be used as a standard it must have the same counter ions as the tetrafluoroborate, which in this case is balanced by sodium. A different counter ion would interchange with the sodium tetrafluoroborate. Because of this we elected to use dried sodium trifluoroacetate as a standard as this seemed to be the simplest and cleanest. The final complication we observed was simply the difficulty in accurately measuring masses and integration values. As most modern reactions are often done on sub-gram scales, the masses that are measured are often quite small. As scales have a standard deviation, usually a tenth of a milligram for most common analytical balances, the error in any given measurement is usually around a percent or two at most although, this rises significantly with smaller and smaller masses being measured. Despite this being a reported accuracy, true accuracy is often far worse, which can be illustrated by measuring the same object multiple times on the same scale. As the anticipated perturbation of boron isotopic rations is expected to be small, accurate measurements are a necessity placing practical limits on the scale of the reactions. To minimize error, we envision doing reactions on the largest reasonable scale and maximizing the mass of products being measured while also averaging multiple mass measurements. Additionally accurate integration of the resulting peaks is imperative. While the Na10BF4 and the Na11BF4 are resolved peaks, they must be carefully integrated. We accomplished this by utilizing two different NMR spectra. First a 19F NMR spectra was run with a wide spectral window in which we integrated the entirety of the NaBF4 as a singular peak. This allowed us to compare it to our internal standard to measure the moles of NaBF4 in solution. Second, we collected a spectrum of the NaBF4 utilizing a small spectral window of only about 5 ppm. This allows us to have a spectrum of the NaBF4 that contains far more critical points in the region of interest resulting in a more resolute peak allowing for more accurate 108 integration. From here careful integration of the Na10BF4 and the Na11BF4 peaks is possible. As the peaks are very close to each other, integration can be done by integrating from the center of each peak to the mathematical center of between the two isotopic peaks and an equal distance in the opposite direction. Additionally, we collected each of these spectra five times using the same NMR sample so that each integration could be averaged. NaF NaBF4 NaOOCCF3 NaBF4 1 2 Figure 5-9 NMR 1 Shows a Full Fluorine Spectral Window with NaOOCCF3 Internal Standard, NaF Biproduct, and NaBF4. NMR 2 Shows the NaBF4 Spectrum Taken with a Small Spectral Window We are confident that utilizing the method outlined within this chapter the heavy atom kinetic isotope effect can be directly measured for boron related reactions. As of now the method has been developed but not validated and thus future work should start with validation. This method however gives the ability to directly measure boron KIEs though NMR which is accessible to practically all synthetic organic chemists. The biggest benefit is this can be utilized at natural abundance which will avoid costly labeled reagents and the necessity to label starting materials. While we emphasized its use in calculating boron KIE’s this method is feasible to any application requiring the measurement or boron isotopic ratios. 109 General Information Experimental Procedures All available reagents were used as received unless otherwise indicated. THF was refluxed over Na/benzophenone ketyl and distilled. Anhydrous 1,4-dioxane was obtained through Sigma-Aldrich and used as received. 1H, 13C, 11B and 19F NMR spectra were recorded on a Varian 500 MHz DD2 Spectrometer equipped with a 1H-19F/15N-31P 5 mm Pulsed Field Gradient (PFG) Probe. Spectra taken in CDCl3 were referenced to 7.26 ppm in 1H NMR and 77.2 ppm in 13C NMR. Spectra taken in C6D6 were referenced to 7.16 ppm in 1H NMR and 128.1 ppm in 13C. 11B NMR spectra were referenced to neat BF3·Et2O as the external standard. NMR spectra were processed for display using the MNova software program with only phasing and baseline corrections applied. High-resolution mass spectra (HRMS) were obtained at the Molecular Metabolism and Disease Mass Spectrometry Core facility and at the Mass Spectrometry Service Center at Michigan State University using electrospray ionization (ESI+ or ESI-) on quadrupole time-of-flight (Q-TOF) instruments. Oxidation of 1 with H2O2 in Ethanol Figure 5-10 Oxidation of 1 with H2O2 in Ethanol In a 125 mL Erlenmeyer flask, (2-fluorophenyl)boronic acid (1 g, 7.15 mmol) was dissolved in ethanol (21 mL, 16.57 g, 0.36 mol) with the help of magnetic stirring utilizing a Teflon coated stir bar. To this solution 30% aq. H2O2 (0.66 mL, 6.46 mmol) was then added. The reaction was stirred for 30 mins at room temperature. The reaction mixture was then evaporated under reduced pressure on a rotavap yielding a white solid. This mass (0.1008 g) was collected and presumed to be boric acid. With this assumption, the total yield of B(OH)3 is 14%. Due to the low yield this product was not spectroscopically investigated. Addition of Phenolphthalein and Sodium Chloride to Sodium Tetrafluoroborate (Reaction 1) Figure 5-11 Addition of Phenolphthalein and Sodium Chloride to Sodium Tetrafluoroborate (Reaction 1) A solution of phenolphthalein was made in 1 mL of water by addition of approximately 0.05 g of phenolphthalein and enough sodium hydroxide to allow the phenolphthalein to dissolve. In a quartz 110 NMR tube, approximately 10 mg of NaBF4. Enough of the phenolphthalein solution was then added to cause the phenolphthalein NaBF4 adduct peak to appear. The addition of the phenolphthalein caused the red color of the phenolphthalein solution to immediately turn colorless. When the adduct peak was clearly observable by 19F NMR a drop of brine was then added to the solution and the sample was observed via 19F NMR. Oxidation of (2-fluorophenyl)boronic acid in 1,4-Dioxane (Reaction 2) Figure 5-12 Oxidation of (2-fluorophenyl)boronic acid in 1,4-Dioxane (Reaction 2) In a new 100 mL round bottom flask, (2-fluorophenyl)boronic acid (1 g, 7.15 mmol) was added with a net Teflon coated stir bar and dissolved in 1,4-dioane (20 mL, 20.6 g, 0.234 mol). 30% aq. H2O2 (2.2 mL, 0.733 g, 0.022 mmol) was added and the reaction stirred at room temperature for 1 h. The 1,4-dioxane was then evaporated under a stream of nitrogen. The resulting white solid was then transferred into a 50 mL plastic conical bottom centrifuge tube with a small stir bar using 5 mL of water. 28% aq. HF (1.5 mL, 0.48 g, 0.024 mmol) was then added and the reaction stirred at room temperature for 24 h. The solution was then neutralized with 3M aq. NaOH while following the neutralization process with pH paper. The water was then evaporated by leaving the container uncovered resulting in 1.3698 g of a white solid consisting predominately of NaBF4 and NaF. This solid was transferred to a plastic bag and homogenized by grinding to a fine powder by rolling a vial over the bag and mixing the resulting powder. 4.7 mg of this powder was mixed with 0.295 mg of sodium trifluoro acetate and dissolved into 0.6 mL of D2O in a quartz NMR tube. Synthesis of sodium tetrafluoroborate from boric acid (Reaction 3) Figure 5-13 Synthesis of sodium tetrafluoroborate from boric acid (Reaction 3) In a 50 mL plastic conical bottom centrifuge tube with a small stir bar boric acid (1g, 0.016 mmol) using 5 mL of water. 28% aq. HF (2.5 mL, 1.38 g, 0.069 mmol) was then added and the reaction stirred at room temperature for 24 h. The solution was then neutralized with 3M aq. NaOH while following the neutralization with pH paper. The water was then evaporated from the reaction mixture to yield 3.0952 g of a white solid. This solid was transferred to a plastic bag and homogenized by grinding to a fine powder 111 by rolling a vial over the bag and mixing the resulting powder. 51.8 mg of this powder was mixed with 0.38 mg of sodium trifluoro acetate and dissolved into 0.6 mL of D2O in a quartz NMR tube. Oxidation of 1 using acetonitrile as a solvent (Reaction 5) Figure 5-14 Oxidation of 1 using acetonitrile as a solvent (Reaction 5) In a 100 mL round bottom flask, (2-fluorophenyl)boronic acid (1 g, 7.15 mmol) was dissolved in acetonitrile (20 mL, 15.72 g, 383 mmol) using a stir bar. 30% aq. H2O2 (1 mL, 0.33 g, 10 mmol) was then added and the reaction flask sealed with a glass stopper. The reaction was stirred for 24 hours. The reaction flask was then opened, and the acetonitrile evaporated under a stream of nitrogen. The remaining white solid was then dissolved in H2O (20 mL) and extracted into CHCl3 (50 mL, 3x). The two layers were separated. The water layer containing boric acid was designated as the primary oxidation. The CHCl3 layer was collected and evaporated to yield the remaining (2-fluorophenyl)boronic acid. The remaining (2-fluorophenyl)boronic acid was then dissolved in acetonitrile (5mL, g, mmol) and 30% aq. H2O2 (0.25 mL, 0.08325 g, 2.5 mmol) added. This reaction was stirred at room temperature for 12 hours. This reaction was then evaporated to yield boric acid as a white powder designated secondary oxidation. The primary oxidation products were then dissolved in H2O (5 mL) and 48% aq. HF (1.5 mL, 0.828 g, 41.39 mmol) added after which the reaction was stirred at room temperature for 24 hours. To the secondary oxidation, the boric acid was dissolved in H2O (6 mL) and 48% aq. (0.15 mL, 0.0828 g , 4.139 mmol) added after which the reaction was stirred for 24 hours. After reacting with HF, both oxidation reactions were neutralized by first adding a drop of a phenolphthalein indicator solution (0.2g phenolphthalein in 2 mL of H2O with enough NaOH to make it soluble), then adding a 1M Na2C2O3 until a slight pink color appeared after which the reactions were evaporated to dryness. Study of Additive effects on the 19F NMR peak of NaBF4 (Reaction 6) Figure 5-15 Study of Additive effects on the 19F peak of NaBF4 (Reaction 6) 112 A quartz NMR tube was charged with NaBF4 (5.8 mg, 0.0528 mmol) and D2O (0.5 mL). The mixture was then analyzed by NMR. After analysis, 0.1 mL of a sodium trifluoroacetate solution (463 mg per 10 mL D2O) was added and the solution analyzed by NMR. Then a drop of a phenolphthalein solution in D2O with enough Na2CO3 added to keep the phenolphthalein soluble. The solution was analyzed by NMR. 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Sci. 1996, 12, 927–930. 114 APPENDIX A: NMR SPECTRA Chapter 2 NMR Spectra1H NMR Spectra of [Ir(OMe)cod]2 Figure 6-1 Conditions: 25 °C, 500 MHz, CDCl3 115 13C NMR Spectra of [Ir(OMe)cod]2 Figure 6-2 Conditions: 25 °C, 500 MHz, CDCl3 116 1H NMR Spectra of Bipyrazine Figure 6-3 Conditions: 25 °C, 500 MHz, CDCl3 117 1H NMR Spectra of Bipyrazine Figure 6-4 Conditions: 25 °C, 500 MHz, C6D6 118 13C NMR Spectra of Bipyrazine Figure 6-5 Conditions: 25 °C, 126 MHz, CDCl3 119 1H NMR of Ligand-213 Figure 6-6 Conditions: 25 °C, 500 MHz, CDCl3 120 13C NMR Spectra of Ligand-213 Figure 6-7 Conditions: 25 °C, 126 MHz, CDCl3 121 1H NMR of 4,4,5,5-tetramethyl-2-(4-(trifluoromethyl)phenyl)-1,3,2-dioxaborolane (1b) Figure 6-8 Conditions: 25 °C, 500 MHz, CDCl3 122 19F NMR of 4,4,5,5-tetramethyl-2-(4-(trifluoromethyl)phenyl)-1,3,2-dioxaborolane (1b) Figure 6-9 Conditions: 25 °C, 470 MHz, CDCl3, Referenced with C6F6 at -161.64 123 13C NMR of 4,4,5,5-tetramethyl-2-(4-(trifluoromethyl)phenyl)-1,3,2-dioxaborolane (1b) Figure 6-10 Conditions: 25 °C, 126 MHz, CDCl3 124 11B NMR of 4,4,5,5-tetramethyl-2-(4-(trifluoromethyl)phenyl)-1,3,2-dioxaborolane (1b) Figure 6-11 Conditions: 25 °C, 160 MHz, CDCl3, Referenced with BF3•OEt2 at 0.00 125 1H NMR Spectra of 4,4,5,5-tetramethyl-2-(4-(trifluoromethoxy)phenyl)-1,3,2-dioxaborolane (1c) Figure 6-12 Conditions: 25 °C, 500 MHz, CDCl3 126 19F NMR Spectra of 4,4,5,5-tetramethyl-2-(4-(trifluoromethoxy)phenyl)-1,3,2-dioxaborolane (1c) Figure 6-13 Conditions: 25 °C, 470 MHz, CDCl3, Referenced with C6F6 at -161.64 127 13C NMR Spectra of 4,4,5,5-tetramethyl-2-(4-(trifluoromethoxy)phenyl)-1,3,2-dioxaborolane (1c) Figure 6-14 Conditions: 25 °C, 126 MHz, CDCl3 128 11B NMR Spectra of 4,4,5,5-tetramethyl-2-(4-(trifluoromethoxy)phenyl)-1,3,2-dioxaborolane (1c) Figure 6-15 Conditions: 25 °C, 160 MHz, CDCl3, Referenced with BF3•OEt2 at 0.00 129 1H NMR Spectra of 2-(4-chloro-2-fluoro-3-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1d) O Cl F B O O 0 0 . 1 0 0 . 1 0 0 . 3 0 0 . 2 1 Figure 6-16 Conditions: 25 °C, 500 MHz, CDCl3 130 19F NMR Spectra of 2-(4-chloro-2-fluoro-3-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1d) O Cl F B O O Figure 6-17 Conditions: Conditions: 25 °C, 470 MHz, CDCl3, Referenced with C6F6 at -161.64 131 13C NMR Spectra of 2-(4-chloro-2-fluoro-3-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1d) O Cl F B O O Figure 6-18 Conditions: 25 °C, 126 MHz, CDCl3 132 11B NMR Spectra of 2-(4-chloro-2-fluoro-3-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1d) O Cl F B O O Figure 6-19 Conditions: 25 °C, 160 MHz, CDCl3, Referenced with BF3•OEt2 at 0.00 133 1H NMR Spectra of Independently Synthesized 2,2',2''-(2-fluorobenzene-1,3,5-triyl)tris(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) (3a’’) Figure 6-20 Conditions: 25 °C, 500 MHz, CDCl3 134 19F NMR Spectra of Independently Synthesized 2,2',2''-(2-fluorobenzene-1,3,5-triyl)tris(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) (3a’’) Figure 6-21 Conditions: 25 °C, 470 MHz, CDCl3, Referenced with C6F6 at -161.64 135 13C NMR Spectra of Independently Synthesized 2,2',2''-(2-fluorobenzene-1,3,5-triyl)tris(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) (3a’’) Figure 6-22 Conditions: 25 °C, 126 MHz, CDCl3 136 1H NMR Spectra of the crude reaction mixture of Table 1 Entry 1 Trial 1 Figure 6-23 Conditions: 25 °C, 500 MHz, CDCl3 137 19F NMR Spectra of the crude reaction mixture of Table 1 Entry 1 Trial 1 Figure 6-24 Conditions: 25 °C, 470 MHz, CDCl3 138 1H NMR Spectra of the purified reaction mixture of Table 1 Entry 1 Trial 1 Figure 6-25 Conditions: 25 °C, 500 MHz, CDCl3 139 19F NMR Spectra of the purified reaction mixture of Table 1 Entry 1 Trial 1 Figure 6-26 Conditions: 25 °C, 470 MHz, CDCl3 140 13C NMR Spectra of the purified reaction mixture of Table 1 Entry 1 Trial 1 Figure 6-27 Conditions: 25 °C, 126 MHz, CDCl3 141 11B NMR Spectra of the purified reaction mixture of Table 1 Entry 1 Trial 1 Figure 6-28 Conditions: 25 °C, 160 MHz, CDCl3 142 1H NMR Spectra of the Isolated 2,2',2''-(5-fluorobenzene-1,2,3-triyl)tris(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) (3a) Figure 2-29 Conditions: 25 °C, 500 MHz, CDCl3 143 19F NMR Spectra of the Isolated 2,2',2''-(5-fluorobenzene-1,2,3-triyl)tris(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) (3a) Figure 6-30 Conditions: 25 °C, 470 MHz, CDCl3 144 13C NMR Spectra of the Isolated 2,2',2''-(5-fluorobenzene-1,2,3-triyl)tris(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) (3a) Figure 6-31 Conditions: 25 °C, 126 MHz, CDCl3 145 11B NMR Spectra of the Isolated 2,2',2''-(5-fluorobenzene-1,2,3-triyl)tris(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) (3a) Figure 6-32 Conditions: 25 °C, 160 MHz, CDCl3 146 1H NMR Spectra of the crude reaction mixture of Table 1 Entry 1 Trial 2 Figure 6-33 Conditions: 25 °C, 500 MHz, CDCl3 147 19F NMR Spectra of the crude reaction mixture of Table 1 Entry 1 Trial 2 Figure 6-34 Conditions: 25 °C, 470 MHz, CDCl3 148 1H NMR Spectra of the crude reaction mixture of Table 1 Entry 1 Trial 3 Figure 6-35 Conditions: 25 °C, 500 MHz, CDCl3 149 19F NMR Spectra of the crude reaction mixture of Table 1 Entry 1 Trial 3 F F O B O F O B O F B O O B O O O B O B O O O B O O B O B O O 1a 2a'' 3a' 3a Figure 6-36 Conditions: 25 °C, 470 MHz, CDCl3 150 1H NMR Spectra of the Crude reaction mixture of Table 1 Entry 2 Trial 1 Figure 6-37 Conditions: 25 °C, 500 MHz, CDCl3 151 19F NMR Spectra of the Crude reaction mixture of Table 1 Entry 2 Trial 1 Figure 6-38 Conditions: 25 °C, 470 MHz, CDCl3 152 1H NMR Spectra of the first purified fraction of the reaction mixture of Table 1 Entry 2 Trial 1 Figure 6-39 Conditions: 25 °C, 500 MHz, CDCl3 153 19F NMR Spectra of the first purified fraction of the reaction mixture of Table 1 Entry 2 Trial 1 Figure 6-40 Conditions: 25 °C, 470 MHz, CDCl3 154 13C NMR Spectra of the first purified fraction of the reaction mixture of Table 1 Entry 2 Trial 1 Figure 6-41 Conditions: 25 °C, 126 MHz, CDCl3 155 11B NMR Spectra of the first purified fraction of the reaction mixture of Table 1 Entry 2 Trial 1 Figure 6-42 Conditions: 25 °C, 160 MHz, CDCl3 156 1H NMR Spectra of the second purified fraction of the reaction mixture of Table 1 Entry 2 Trial 1 Figure 6-43 Conditions: 25 °C, 500 MHz, CDCl3 157 19F NMR Spectra of the second purified fraction of the reaction mixture of Table 1 Entry 2 Trial 1 Figure 6-44 Conditions: 25 °C, 470 MHz, CDCl3 158 13C NMR Spectra of the second purified fraction of the reaction mixture of Table 1 Entry 2 Trial 1 Figure 6-45 Conditions: 25 °C, 126 MHz, CDCl3 159 11B NMR Spectra of the second purified fraction of the reaction mixture of Table 1 Entry 2 Trial 1 Figure 6-46 Conditions: 25 °C, 160 MHz, CDCl3 160 1H NMR Spectra of the third purified fraction of the reaction mixture of Table 1 Entry 2 Trial 1 Figure 6-47 Conditions: 25 °C, 500 MHz, CDCl3 161 19F NMR Spectra of the third purified fraction of the reaction mixture of Table 1 Entry 2 Trial 1 Figure 6-48 Conditions: 25 °C, 470 MHz, CDCl3 162 13C NMR Spectra of the third purified fraction of the reaction mixture of Table 1 Entry 2 Trial 1 Figure 6-49 Conditions: 25 °C, 126 MHz, CDCl3 163 11B NMR Spectra of the third purified fraction of the reaction mixture of Table 1 Entry 2 Trial 1 Figure 6-50 Conditions: 25 °C, 160 MHz, CDCl3 164 1H NMR Spectra of the crude reaction mixture of Table 1 Entry 2 Trial 2 Figure 6-51 Conditions: 25 °C, 500 MHz, CDCl3 165 19F NMR Spectra of the crude reaction mixture of Table 1 Entry 2 Trial 2 Figure 6-52 Conditions: 25 °C, 470 MHz, CDCl3 166 1H NMR Spectra of the crude reaction mixture of Table 1 Entry 2 Trial 3 Figure 6-53 Conditions: 25 °C, 500 MHz, CDCl3 167 1H NMR Spectra of the crude reaction mixture of Table 1 Entry 3 Trial 1 Figure 6-54 Conditions: 25 °C, 500 MHz, CDCl3 168 19F NMR Spectra of the crude reaction mixture of Table 1 Entry 3 Trial 1 Figure 6-55 Conditions: 25 °C, 470 MHz, CDCl3 169 1H NMR Spectra of the Isolated reaction mixture of Table 1 Entry 3 Trial 1 Figure 6-56 Conditions: 25 °C, 500 MHz, CDCl3 170 19F NMR Spectra of the Isolated reaction mixture of Table 1 Entry 3 Trial 1 OCF3 OCF3 OCF3 O B O B O O O B O B O O O B O B O O 1c 2c 3c Figure 6-57 Conditions: 25 °C, 470 MHz, CDCl3 171 13C NMR Spectra of the Isolated reaction mixture of Table 1 Entry 3 Trial 1 Figure 6-58 Conditions: 25 °C, 126 MHz, CDCl3 172 11B NMR Spectra of the Isolated reaction mixture of Table 1 Entry 3 Trial 1 Figure 6-59 Conditions: 25 °C, 160 MHz, CDCl3 173 1H NMR Spectra of the Isolated reaction mixture of Table 1 Entry 3 Trial 2 Figure 6-60 Conditions: 25 °C, 500 MHz, CDCl3 174 19F NMR Spectra of the Crude Reaction mixture of Table 1 Entry 3 Trial 2 Figure 6-61 Conditions: 25 °C, 470 MHz, CDCl3 175 1H NMR Spectra of the Crude Reaction Mixture of Table 1 Entry 4 Trial 1 F B O O OMe Cl B O O 2d Figure 6-62 Conditions: 25 °C, 500 MHz, CDCl3 176 1H NMR Spectra of the Isolated Reaction Mixture of Table 1 Entry 4 Trial 1 F B O O OMe Cl B O O 2d Figure 6-63 Conditions: 25 °C, 500 MHz, CDCl3 177 19F NMR Spectra of the isolated reaction mixture of Table 1 Entry 4 Trial 1 F B O O OMe Cl B O O 2d Figure 6-64 Conditions: 25 °C, 470 MHz, CDCl3 178 13C NMR Spectra of the isolated reaction mixture of Table 1 Entry 4 Trial 1 F B O O OMe Cl B O O 2d Figure 6-65 Conditions: 25 °C, 126 MHz, CDCl3 179 11B NMR Spectra of the isolated reaction mixture of Table 1 Entry 4 Trial 1 F B O O OMe Cl B O O 2d Figure 6-66 Conditions: 25 °C, 160 MHz, CDCl3 180 1H NMR Spectra of the crude reaction mixture of Table 1 Entry 5 Trial 1 Figure 6-67 Conditions: 25 °C, 500 MHz, CDCl3 181 1H NMR Spectra of the isolated reaction mixture of Table 1 Entry 5 Trial 1 Figure 6-68 Conditions: 25 °C, 500 MHz, CDCl3 182 13C NMR Spectra of the isolated reaction mixture of Table 1 Entry 5 Trial 1 Figure 6-69 Conditions: 25 °C, 126 MHz, CDCl3 183 11B NMR Spectra of the isolated reaction mixture of Table 1 Entry 5 Trial 1 Figure 6-70 Conditions: 25 °C, 160 MHz, CDCl3 184 1H NMR Spectra of the Crude reaction mixture of Table 2 Entry 1 Trial 1 Figure 6-71 Conditions: 25 °C, 500 MHz, CDCl3 185 19F NMR Spectra of the Crude reaction mixture of Table 2 Entry 1 Trial 1 Figure 6-72 Conditions: 25 °C, 470 MHz, CDCl3 186 1H NMR Spectra of Fraction 1 of the Purified Reaction Mixture of Table 2 Entry 1 Trial 1 Figure 6-73 Conditions: 25 °C, 500 MHz, CDCl3 187 19F NMR Spectra of Fraction 1 of the Purified Reaction Mixture of Table 2 Entry 1 Trial 1 F F O B O F O B O F B O O B O O O B O B O O O B O B O O O B O 1a 2a'' 3a' 3a Figure 6-74 Conditions: 25 °C, 470 MHz, CDCl3 188 11B NMR Spectra of Fraction 1 of the Purified Reaction Mixture of Table 2 Entry 1 Trial 1 Figure 6-75 Conditions: 25 °C, 160 MHz, CDCl3 189 1H NMR Spectra of Fraction 2 of the Purified Reaction Mixture of Table 2 Entry 1 Trial 1 F F O B O F O B O F B O O B O O O B O B O O O B O B O O O B O 1a 2a'' 3a' 3a Figure 6-76 Conditions: 25 °C, 160 MHz, CDCl3 190 19F NMR Spectra of Fraction 2 of the Purified Reaction Mixture of Table 2 Entry 1 Trial 1 Figure 6-77 Conditions: 25 °C, 470 MHz, CDCl3 191 13C NMR Spectra of Fraction 2 of the Purified Reaction Mixture of Table 2 Entry 1 Trial 1 Figure 6-78 Conditions: 25 °C, 126 MHz, CDCl3 192 11B NMR Spectra of Fraction 2 of the Purified Reaction Mixture of Table 2 Entry 1 Trial 1 Figure 6-79 Conditions: 25 °C, 160 MHz, CDCl3 193 1H NMR Spectra of Fraction 3 of the Purified Reaction Mixture of Table 2 Entry 1 Trial 1 Figure 6-80 Conditions: 25 °C, 160 MHz, CDCl3 194 19F NMR Spectra of Fraction 3 of the Purified Reaction Mixture of Table 2 Entry 1 Trial 1 Figure 6-81 Conditions: 25 °C, 470 MHz, CDCl3 195 13C NMR Spectra of Fraction 3 of the Purified Reaction Mixture of Table 2 Entry 1 Trial 1 F F O B O F O B O F B O O B O O O B O B O O O B O O B O B O O 1a 2a'' 3a' 3a Figure 6-82 Conditions: 25 °C, 126 MHz, CDCl3 196 11B NMR Spectra of Fraction 3 of the Purified Reaction Mixture of Table 2 Entry 1 Trial 1 Figure 6-83 Conditions: 25 °C, 160 MHz, CDCl3 197 1H NMR Spectra of the Crude reaction mixture of Table 2 Entry 1 Trial 2 F F O B O F O B O F B O O B O O O B O B O O O B O B O O O B O 1a 2a'' 3a' 3a Figure 6-84 Conditions: 25 °C, 500 MHz, CDCl3 198 19F NMR Spectra of the Crude reaction mixture of Table 2 Entry 1 Trial 2 Figure 6-85 Conditions: 25 °C, 470 MHz, CDCl3 199 1H NMR Spectra of the Crude reaction mixture of Table 2 Entry 1 Trial 3 Figure 6-86 Conditions: 25 °C, 500 MHz, CDCl3 200 19F NMR Spectra of the Crude reaction mixture of Table 2 Entry 1 Trial 3 Figure 6-87 Conditions: 25 °C, 470 MHz, CDCl3 201 1H NMR Spectra of the Crude reaction mixture of Table 2 Entry 2 Trial 1 Figure 6-88 Conditions: 25 °C, 500 MHz, CDCl3 202 19F NMR Spectra of the Crude reaction mixture of Table 2 Entry 2 Trial 1 Figure 6-89 Conditions: 25 °C, 470 MHz, CDCl3 203 1H NMR Spectra of Fraction 1 of the purified reaction mixture of Table 2 Entry 2 Trial 1 Figure 6-90 Conditions: 25 °C, 500 MHz, CDCl3 204 19F NMR Spectra of Fraction 1 of the purified reaction mixture of Table 2 Entry 2 Trial 1 Figure 6-91 Conditions: 25 °C, 470 MHz, CDCl3 205 13C NMR Spectra of Fraction 1 of the purified reaction mixture of Table 2 Entry 2 Trial 1 Figure 6-92 Conditions: 25 °C, 126 MHz, CDCl3 206 11B NMR Spectra of Fraction 1 of the purified reaction mixture of Table 2 Entry 2 Trial 1 Figure 6-93 Conditions: 25 °C, 160 MHz, CDCl3 207 1H NMR Spectra of Fraction 2 of the purified reaction mixture of Table 2 Entry 2 Trial 1 Figure 6-94 Conditions: 25 °C, 500 MHz, CDCl3 208 19F NMR Spectra of Fraction 2 of the purified reaction mixture of Table 2 Entry 2 Trial 1 Figure 6-95 Conditions: 25 °C, 470 MHz, CDCl3 209 13C NMR Spectra of Fraction 2 of the purified reaction mixture of Table 2 Entry 2 Trial 1 Figure 6-96 Conditions: 25 °C, 126 MHz, CDCl3 210 11B NMR Spectra of Fraction 2 of the purified reaction mixture of Table 2 Entry 2 Trial 1 Figure 6-97 Conditions: 25 °C, 160 MHz, CDCl3 211 1H NMR Spectra of Fraction 3 of the purified reaction mixture of Table 2 Entry 2 Trial 1 Figure 6-98 Conditions: 25 °C, 500 MHz, CDCl3 212 19F NMR Spectra of Fraction 3 of the purified reaction mixture of Table 2 Entry 2 Trial 1 Figure 6-99 Conditions: 25 °C, 470 MHz, CDCl3 213 13C NMR Spectra of Fraction 3 of the purified reaction mixture of Table 2 Entry 2 Trial 1 Figure 6-100 Conditions: 25 °C, 126 MHz, CDCl3 214 11B NMR Spectra of Fraction 3 of the purified reaction mixture of Table 2 Entry 2 Trial 1 Figure 6-101 Conditions: 25 °C, 160 MHz, CDCl3 215 1H NMR Spectra of the crude reaction mixture of Table 2 Entry 2 Trial 2 Figure 6-102 Conditions: 25 °C, 500 MHz, CDCl3 216 19F NMR Spectra of the crude reaction mixture of Table 2 Entry 2 Trial 2 Figure 6-103 Conditions: 25 °C, 470 MHz, CDCl3 217 1H NMR Spectra of the crude reaction mixture of Table 2 Entry 2 Trial 3 Figure 6-104 Conditions: 25 °C, 500 MHz, CDCl3 218 19F NMR Spectra of the crude reaction mixture of Table 2 Entry 2 Trial 3 Figure 6-105 Conditions: 25 °C, 470 MHz, CDCl3 219 1H NMR Spectra of the crude reaction mixture of Table 2 Entry 3 Trial 1 Figure 6-106 Conditions: 25 °C, 500 MHz, CDCl3 220 19F NMR Spectra of the crude reaction mixture of Table 2 Entry 3 Trial 1 Figure 6-107 Conditions: 25 °C, 470 MHz, CDCl3 221 1H NMR Spectra of the Isolated Reaction Mixture of Table 2 Entry 3 Trial 1 Figure 6-108 Conditions: 25 °C, 500 MHz, CDCl3 222 19F NMR Spectra of the Isolated Reaction Mixture of Table 2 Entry 3 Trial 1 Figure 6-109 Conditions: 25 °C, 470 MHz, CDCl3 223 13C NMR Spectra of the Isolated Reaction Mixture of Table 2 Entry 3 Trial 1 Figure 6-110 Conditions: 25 °C, 126 MHz, CDCl3 224 11B NMR Spectra of the Isolated Reaction Mixture of Table 2 Entry 3 Trial 1 Figure 6-111 Conditions: 25 °C, 160 MHz, CDCl3 225 1H NMR Spectra of the Crude reaction mixture of Table 2 Entry 3 Trial 2 Figure 6-112 Conditions: 25 °C, 500 MHz, CDCl3 226 19F NMR Spectra of the Crude reaction mixture of Table 2 Entry 3 Trial 2 Figure 6-113 Conditions: 25 °C, 470 MHz, CDCl3 227 1H NMR Spectra of the Crude reaction mixture of Table 2 Entry 3 Trial 3 Figure 6-114 Conditions: 25 °C, 500 MHz, CDCl3 228 19F NMR Spectra of the Crude reaction mixture of Table 2 Entry 3 Trial 3 Figure 6-115 Conditions: 25 °C, 470 MHz, CDCl3 229 1H NMR Spectra of the Crude reaction mixture of Table 2 Entry 4 Trial 1 Figure 6-116 Conditions: 25 °C, 500 MHz, CDCl3 230 19F NMR Spectra of the Crude reaction mixture of Table 2 Entry 4 Trial 1 Figure 6-117 Conditions: 25 °C, 470 MHz, CDCl3 231 1H NMR Spectra of Fraction 1 of the Isolated Reaction Mixture of Table 2 Entry 4 Trial 1 Figure 6-118 Conditions: 25 °C, 500 MHz, CDCl3 232 19F NMR Spectra of Fraction 1 of the Isolated Reaction Mixture of Table 2 Entry 4 Trial 1 Figure 6-119 Conditions: 25 °C, 470 MHz, CDCl3 233 13C NMR Spectra of Fraction 1 of the Isolated Reaction Mixture of Table 2 Entry 4 Trial 1 Figure 6-120 Conditions: 25 °C, 126 MHz, CDCl3 234 11B NMR Spectra of Fraction 1 of the Isolated Reaction Mixture of Table 2 Entry 4 Trial 1 Figure 6-121 Conditions: 25 °C, 160 MHz, CDCl3 235 1H NMR Spectra of Fraction 2 of the Isolated Reaction Mixture of Table 2 Entry 4 Trial 1 Figure 6-122 Conditions: 25 °C, 500 MHz, CDCl3 236 19F NMR Spectra of Fraction 2 of the Isolated Reaction Mixture of Table 2 Entry 4 Trial 1 Figure 6-123 Conditions: 25 °C, 470 MHz, CDCl3 237 13C NMR Spectra of Fraction 2 of the Isolated Reaction Mixture of Table 2 Entry 4 Trial 1 Figure 6-124 Conditions: 25 °C, 126 MHz, CDCl3 238 11B NMR Spectra of Fraction 2 of the Isolated Reaction Mixture of Table 2 Entry 4 Trial 1 Figure 6-125 Conditions: 25 °C, 160 MHz, CDCl3 239 1H NMR Spectra of Fraction 3 of the Isolated Reaction Mixture of Table 2 Entry 4 Trial 1 Figure 6-126 Conditions: 25 °C, 500 MHz, CDCl3 240 19F NMR Spectra of Fraction 3 of the Isolated Reaction Mixture of Table 2 Entry 4 Trial 1 Figure 6-127 Conditions: 25 °C, 470 MHz, CDCl3 241 13C NMR Spectra of Fraction 3 of the Isolated Reaction Mixture of Table 2 Entry 4 Trial 1 Figure 6-128 Conditions: 25 °C, 126 MHz, CDCl3 242 11B NMR Spectra of Fraction 3 of the Isolated Reaction Mixture of Table 2 Entry 4 Trial 1 Figure 6-129 Conditions: 25 °C, 160 MHz, CDCl3 243 1H NMR Spectra of Fraction 4 of the Isolated Reaction Mixture of Table 2 Entry 4 Trial 1 Figure 6-130 Conditions: 25 °C, 500 MHz, CDCl3 244 19F NMR Spectra of Fraction 4 of the Isolated Reaction Mixture of Table 2 Entry 4 Trial 1 Figure 6-131 Conditions: 25 °C, 470 MHz, CDCl3 245 13C NMR Spectra of Fraction 4 of the Isolated Reaction Mixture of Table 2 Entry 4 Trial 1 Figure 6-132 Conditions: 25 °C, 126 MHz, CDCl3 246 11B NMR Spectra of Fraction 4 of the Isolated Reaction Mixture of Table 2 Entry 4 Trial 1 Figure 6-133 Conditions: 25 °C, 160 MHz, CDCl3 247 1H NMR Spectra of the Isolated Reaction Mixture of Table 2 Entry 4 Trial 2 Figure 6-134 Conditions: 25 °C, 500 MHz, CDCl3 248 1H NMR Spectra of the Isolated Reaction Mixture of Table 2 Entry 4 Trial 3 Figure 6-135 Conditions: 25 °C, 500 MHz, CDCl3 249 Chapter 3 NMR Spectra 250 1H NMR spectrum of tetrapropylammonium 2-iodophenylsulfate (6c) OO S O O I N Figure 7-1 Conditions: 25 °C, 500 MHz, CDCl3 251 13C NMR spectrum of tetrapropylammonium 2-iodophenylsulfate (6c) OO S O O I N 7-2 Conditions: 25 °C, 126 MHz, CDCl3 Figure 252 1H NMR spectrum of tetrapropylammonium 3-fluorophenylsulfate (6e) OO S O O F N Figure 7-3 Conditions: 25 °C, 500 MHz, CDCl3 253 13C NMR spectrum of tetrapropylammonium 3-fluorophenylsulfate (6e) OO S O O F N Figure 7-4 Conditions: 25 °C, 126 MHz, CDCl3 254 19F NMR spectrum of tetrapropylammonium 3-fluorophenylsulfate (6e) OO S O O F N Figure 7-5 Conditions: 25 °C, 470 MHz, CDCl3 255 1H NMR spectrum of tetrapropylammonium 2-cyanophenylsulfate (6i) OO S O O NC N Figure 7-6 Conditions: 25 °C, 500 MHz, CDCl3 256 13C NMR spectrum of tetrapropylammonium 2-cyanophenylsulfate (6i) OO S O O NC N Figure 7-7 Conditions: 25 °C, 126 MHz, CDCl3 257 1H NMR spectrum of tetrapropylammonium 2-(trifluoromethoxy)phenylsulfate (6k) Figure 7-8 Conditions: 25 °C, 500 MHz, CDCl3 OO S O O F3CO N 258 13C NMR spectrum of tetrapropylammonium 2-(trifluoromethoxy)phenylsulfate (6k) OO S O O F3CO N Figure 7-9 Conditions: 25 °C, 126 MHz, CDCl3 259 19F NMR spectrum of tetrapropylammonium 2-(trifluoromethoxy)phenylsulfate (6k) OO S O O F3CO N Figure 7-10 Conditions: 25 °C, 470 MHz, CDCl3 260 1H NMR spectrum of tetrapropylammonium 2-bromo-6-fluorophenylsulfate (6l) OO S O O Br F N Figure 7-11 Conditions: 25 °C, 500 MHz, CDCl3 261 OO S O O Br F N 13C NMR spectrum of tetrapropylammonium 2-bromo-6-fluorophenylsulfate (6l) Figure 7-12 Conditions: 25 °C, 126 MHz, CDCl3 262 19F NMR spectrum of tetrapropylammonium 2-bromo-6-fluorophenylsulfate (6l) OO S O O Br F N Figure 7-13 Conditions: 25 °C, 470 MHz, CDCl3 263 1H NMR spectrum of tetrapropylammonium 2-phenylsulfate (6p) OO S O O N Figure 7-14 Conditions: 25 °C, 500 MHz, CDCl3 264 13C NMR spectrum of tetrapropylammonium 2-phenylsulfate (6p) OO S O O N Figure 7-15 Conditions: 25 °C, 126 MHz, CDCl3 265 1H NMR spectrum of tetrabutylammonium 2-chlorophenylsulfamate (8a) OO S HN O Cl N Figure 7-16 Conditions: 25 °C, 500 MHz, CDCl3 266 13C NMR spectrum of tetrabutylammonium 2-chlorophenylsulfamate (8a) OO S HN O Cl N Figure 7-17 Conditions: 25 °C, 126 MHz, CDCl3 267 1H NMR spectrum of tetrabutylammonium 2-bromophenylsulfamate (8b) OO S HN O Br N Figure 7-18 Conditions: 25 °C, 500 MHz, CDCl3 268 13C NMR spectrum of tetrabutylammonium 2-bromophenylsulfamate (8b) OO S HN O Br N Figure 7-19 Conditions: 25 °C, 126 MHz, CDCl3 269 1H NMR spectrum of tetrabutylammonium 3-fluorophenylsulfamate (8c) Figure 7-20 Conditions: 25 °C, 500 MHz, CDCl3 OO S HN O F N 270 13C NMR spectrum of tetrabutylammonium 3-fluorophenylsulfamate (8c) OO S HN O F N Figure 7-21 Conditions: 25 °C, 126 MHz, CDCl3 271 19F NMR spectrum of tetrabutylammonium 3-fluorophenylsulfamate (8c) OO S HN O F N Figure 7-22 Conditions: 25 °C, 470 MHz, CDCl3 272 1H NMR spectrum of tetrabutylammonium 2-chlorobenzylsulfate (10a′) O O O S O Cl N Figure 7-23 Conditions: 25 °C, 500 MHz, CDCl3 273 13C NMR spectrum of tetrabutylammonium 2-chlorobenzylsulfate (10a′) O O O S O Cl N Figure 7-24 Conditions: 25 °C, 126 MHz, CDCl3 274 1H NMR spectrum of tetrapropylammonium 2-trifluoromethylbenzylsulfate (10c) O O O S O F3C N Figure 7-25 Conditions: 25 °C, 500 MHz, CDCl3 275 13C NMR spectrum of tetrapropylammonium 2-trifluoromethylbenzylsulfate (10c) O O O S O F3C N Figure 7-26 Conditions: 25 °C, 126 MHz, CDCl3 276 19F NMR spectrum of tetrapropylammonium 2-trifluoromethylbenzylsulfate (10c) O O O S O F3C N Figure 7-27 Conditions: 25 °C, 470 MHz, CDCl3 277 1H NMR spectrum of tetrapropylammonium 2-methylbenzylsulfate (11d) O O O S O N Figure 7-28 Conditions: 25 °C, 500 MHz, CDCl3 278 13C NMR spectrum of tetrapropylammonium 2-methylbenzylsulfate (11d) O O O S O N Figure 7-29 Conditions: 25 °C, 126 MHz, CDCl3 279 1H NMR spectrum of tetrapropylammonium 2-fluorobenzylsulfate (10g) O O O S O F N Figure 7-30 Conditions: 25 °C, 500 MHz, CDCl3 280 13C NMR spectrum of tetrapropylammonium 2-fluorobenzylsulfate (10g) O O O S O F N Figure 7-31 Conditions: 25 °C, 126 MHz, CDCl3 281 19F NMR spectrum of tetrapropylammonium 2-fluorobenzylsulfate (10g) O O O S O F N Figure 7-32 Conditions: 25 °C, 470 MHz, CDCl3 282 1H NMR spectrum of tetrapropylammonium 3-fluorobenzylsulfate (10h) O O O S O F N Figure 7-33 Conditions: 25 °C, 500 MHz, CDCl3 283 13C NMR spectrum of tetrapropylammonium 3-fluorobenzylsulfate (10h) O O O S O F N 7-34 Conditions: 25 °C, 126 MHz, CDCl3 284 19F NMR spectrum of tetrapropylammonium 3-fluorobenzylsulfate (10h) O O O S O F N Figure 7-35 Conditions: 25 °C, 470 MHz, CDCl3 285 1H NMR spectrum of para borylated 3-fluorophenol (7e) OH OH F F B O O O B O Figure 7-36 Conditions: 25 °C, 500 MHz, CDCl3 286 13C NMR spectrum of para borylated 3-fluorophenol (7e) OH OH F F B O O O B O Figure 7-37 Conditions: 25 °C, 126 MHz, CDCl3 287 11B NMR spectrum of para borylated 3-fluorophenol (7e) OH OH F F B O O O B O Figure 7-38 Conditions: 25 °C, 160 MHz, CDCl3 288 19F NMR spectrum of para borylated 3-fluorophenol (7e) OH OH F F B O O O B O Figure 7-39 Conditions: 25 °C, 470 MHz, CDCl3 289 1H NMR spectrum of para borylated 2-methylphenol (7g) OH OH B O O O B O v Figure 7-40 Conditions: 25 °C, 500 MHz, CDCl3 290 13C NMR spectrum of para borylated 2-methylphenol (7g) OH OH B O O O B O v Figure 7-41 Conditions: 25 °C, 126 MHz, CDCl3 291 11B NMR spectrum of para borylated 2-methylphenol (7g) OH OH B O O O B O v Figure 7-42 Conditions: 25 °C, 160 MHz, CDCl3 292 1H NMR spectrum of para borylated 2-isopropylphenol (7h) v Figure 7-43 Conditions: 25 °C, 500 MHz, CDCl3 293 13C NMR spectrum of para borylated 2-isopropylphenol (7h) v Figure 7-44 Conditions: 25 °C, 126 MHz, CDCl3 294 11B NMR spectrum of para borylated 2-isopropylphenol (7h) v Figure 7-45 Conditions: 25 °C, 160 MHz, CDCl3 295 1H NMR spectrum of para borylated 2(trifluoromethoxy)phenol (7k) v Figure 7-46 Conditions: 25 °C, 500 MHz, CDCl3 296 13C NMR spectrum of para borylated 2-(trifluoromethoxy)phenol (7k) v Figure 7-47 Conditions: 25 °C, 126 MHz, CDCl3 297 11B NMR spectrum of para borylated 2-(trifluoromethoxy)phenol (7k) v Figure 7-48 Conditions: 25 °C, 160 MHz, CDCl3 298 19F NMR spectrum of para borylated 2-(trifluoromethoxy)phenol (7k) OH F3CO B O O v Figure7-49 Conditions: 25 °C, 470 MHz, CDCl3 299 1H NMR spectrum of reaction mixture of para borylation of tetrapropylammonium 2-bromobenzylsulfate (crude 10b) v Figure 7-50 Conditions: 25 °C, 500 MHz, CDCl3 300 1H NMR spectrum of para borylated of 2-bromobenzylalcohol (11b) v Figure7-51 Conditions: 25 °C, 500 MHz, CDCl3 301 13C NMR spectrum of para borylated 2-bromobenzylalcohol (11b) v v Figure 7-52 Conditions: 25 °C, 126 MHz, CDCl3 302 11B NMR spectrum of para borylated 2-bromobenzylalcohol (11b) v Figure 7-53 Conditions: 25 °C, 160 MHz, CDCl3 303 1H NMR spectrum of the reaction mixture of para borylation of 2-fluorobenzylsulfate (10g) v Figure 7-54 Conditions: 25 °C, 500 MHz, CDCl3 304 1H NMR spectrum of para borylated (2-fluorophenyl)methanol (11g) v Figure 7-55 Conditions: 25 °C, 500 MHz, CDCl3 305 13C NMR spectrum of para borylated (2-fluorophenyl)methanol (11g) v Figure 7-56 Conditions: 25 °C, 126 MHz, CDCl3 306 11B NMR spectrum of para borylated (2-fluorophenyl)methanol (11g) v Figure 7-57 Conditions: 25 °C, 160 MHz, CDCl3 307 19F NMR spectrum of para borylated (2-fluorophenyl)methanol (11g) v Figure 7-58 Conditions: 25 °C, 470 MHz, CDCl3 308 Chapter 4 NMR Spectra 309 1H NMR Spectra of the Crude Reaction Mixture of the Borylation of 2-chloro-N-methylaniline (14a) Bpin N Bpin N Cl Cl B O O O B O Figure 8-1 Conditions: 25 °C, 500 MHz, CDCl3 310 1H NMR Spectra of the Unselective Borylation of 2-chloro-N-methylaniline (14a) Fraction 1 NH NH Cl Cl B O O O B O Figure 8-2 Conditions: 25 °C, 500 MHz, CDCl3 311 1H NMR Spectra of the Unselective Borylation of 2-chloro-N-methylaniline (14a) Fraction 2 NH NH Cl Cl B O O O B O Figure 8-3 Conditions: 25 °C, 500 MHz, CDCl3 312 13C NMR Spectra of the Unselective Borylation of 2-chloro-N-methylaniline (14a) Fraction 2 NH NH Cl Cl B O O O B O Figure 8-4 Conditions: 25 °C, 126 MHz, CDCl3 313 11B NMR Spectra of the Unselective Borylation of 2-chloro-N-methylaniline (14a) Fraction 2 NH NH Cl Cl B O O O B O Figure 8-5 Conditions: 25 °C, 160 MHz, CDCl3 314 1H NMR Spectra of the Unselective Borylation of 2-chloro-N-methylaniline (14a) Fraction 3 NH NH Cl Cl B O O O B O Figure 8-6 Conditions: 25 °C, 500 MHz, CDCl3 315 13C NMR Spectra of the Unselective Borylation of 2-chloro-N-methylaniline (14a) Fraction 3 NH NH Cl Cl B O O O B O Figure 8-7 Conditions: 25 °C, 126 MHz, CDCl3 316 11B NMR Spectra of the Unselective Borylation of 2-chloro-N-methylaniline (14a) Fraction 3 NH NH Cl Cl B O O O B O Figure 8-8 Conditions: 25 °C, 160 MHz, CDCl3 317 1H NMR Spectra of the Unselective Borylation of 2-chloro-N-methylaniline (14a) Fraction 4 NH NH Cl Cl B O O O B O Figure 8-9 Conditions: 25 °C, 500 MHz, CDCl3 318 13C NMR Spectra of the Unselective Borylation of 2-chloro-N-methylaniline (14a) Fraction 4 NH NH Cl Cl B O O O B O Figure 8-10 Conditions: 25 °C, 126 MHz, CDCl3 319 11B NMR Spectra of the Unselective Borylation of 2-chloro-N-methylaniline (14a) Fraction 4 NH NH Cl Cl B O O O B O 8-11 Conditions: 25 °C, 160 MHz, CDCl3 320 1H NMR of the Crude para borylated 1,2,3,4-tetrahydroquinoline (14d) Figure 8-12 Conditions: 25 °C, 500 MHz, CDCl3 321 1H NMR of para borylated 1,2,3,4-tetrahydroquinoline Fraction 1 (14d) Figure 8-13 Conditions: 25 °C, 500 MHz, CDCl3 322 13C NMR of para borylated 1,2,3,4-tetrahydroquinoline (14d) Fraction 1 Figure 8-14 Conditions: 25 °C, 126 MHz, CDCl3 323 11B NMR of para borylated 1,2,3,4-tetrahydroquinoline (14d) Fraction 1 Figure 8-15 Conditions: 25 °C, 160 MHz, CDCl3 324 1H NMR of para borylated 1,2,3,4-tetrahydroquinoline (14d) Fraction 2 Figure 8-16 Conditions: 25 °C, 500 MHz, CDCl3 325 13C NMR of para borylated 1,2,3,4-tetrahydroquinoline (14d) Fraction 2 Figure 8-17 Conditions: 25 °C, 126 MHz, CDCl 326 11B NMR of para borylated 1,2,3,4-tetrahydroquinoline (14d) Fraction 2 Figure 8-18 Conditions: 25 °C, 160 MHz, CDCl3 327 1H NMR of para borylated 1,2,3,4-tetrahydroquinoline (14d) Fraction 3 Figure 8-19 Conditions: 25 °C, 500 MHz, CDC 328 13C NMR of para borylated 1,2,3,4-tetrahydroquinoline (14d) Fraction 3 Figure 8-20 Conditions: 25 °C, 126 MHz, CDCl3 329 11B NMR of para borylated 1,2,3,4-tetrahydroquinoline (14d) Fraction 3 Figure 8-21 Conditions: 25 °C, 160 MHz, CDCl3 330 1H NMR of the Para CHB of 8-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine (14i) O F NH B O O Figure 8-22 Conditions: 25 °C, 500 MHz, CDCl3 331 19F NMR of the Para CHB of 8-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine (14i) O F NH B O O Figure 8-23 Conditions: 25 °C, 470 MHz, CDCl3 332 13C NMR of the Para CHB of 8-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine (14i) O F NH B O O Figure 8-24 Conditions: 25 °C, 126 MHz, CDCl3 333 11B NMR of the Para CHB of 8-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine (14i) O F NH B O O Figure 8-25 Conditions: 25 °C, 160 MHz, CDCl3 334 Chapter 5 NMR Spectra 335 19F NMR Spectra of the addition of Phenolphthalein to Sodium Tetrafluoroborate (Reaction 2) Figure 9-1 Conditions: 25 °C, 470 MHz, D2O 336 19F NMR Spectra of the addition of Phenolphthalein then Sodium Chloride to Sodium Tetrafluoroborate (Reaction 2) Figure 9-2 Conditions: 25 °C, 470 MHz, D2O 337 19F NMR Spectra of the crude reaction mixture of the oxidation of (2-fluorophenyl)boronic acid in 1,4-dioxane (Reaction 3) Figure 9-3 Conditions: 25 °C, 470 MHz, D2O 338 19F NMR Spectra of the homogenized product of fluorination of boric acid to synthesize sodium tetrafluoroborate (Reaction 3) Figure 9-4 Conditions: 25 °C, 470 MHz, D2O 339 19F NMR Spectra of the homogenized product of fluorination of boric acid to synthesize sodium tetrafluoroborate (Reaction 3) Figure 9-5 Conditions: 25 °C, 470 MHz, D2O 340 19F NMR Spectra of synthesis of sodium tetrafluoroborate from boric acid (Reaction 4) Figure 9-6 Conditions: 25 °C, 470 MHz, D2O 341 19F NMR Spectra of synthesis of sodium tetrafluoroborate from boric acid (Reaction 4) Figure 9-7 Conditions: 25 °C, 160 MHz, CDCl3 342 19F NMR Spectra of the Primary Oxidation of 1 (Reaction 5) Figure 9-8 Conditions: 25 °C, 470 MHz, D2O 343 19F NMR Spectra of the Primary Fluorination (Reaction 5) Figure 9-9 Conditions: 25 °C, 470 MHz, D2O 344 19F NMR Spectra of the Secondary Fluorination (Reaction 5) Figure 9-10 Conditions: 25 °C, 470 MHz, D2O 345 19F NMR Small Window Spectra of the Primary Fluorination (Reaction 5) Figure 9-11 Conditions: 25 °C, 470 MHz, D2O 346 19F NMR Small Window Spectra of the Secondary Fluorination (Reaction 5) Figure 9-12 Conditions: 25 °C, 470 MHz, D2O 347 19F NMR Spectra of NaBF4 (Reaction 6) Figure 9-13 Conditions: 25 °C, 470 MHz, D2O 348 Small Spectral Window 19F NMR Spectra of NaBF4 (Reaction 6) Figure 9-14 Conditions: 25 °C, 470 MHz, D2O 349 19F NMR Spectra of NaBF4 with Sodium Trifluoro Acetate (Reaction 6) Figure 9-15 Conditions: 25 °C, 470 MHz, D2O 350 Small Spectral Window 19F NMR Spectra of NaBF4 and Sodium Trifluoroacetate Focusing on the NaBF4 Peak (Reaction 6) Figure 9-16 Conditions: 25 °C, 470 MHz, D2O 351 19F NMR Spectra of NaBF4, Sodium Trifluoro Acetate, and Phenolphthalein (Reaction 6) Figure 9-17 Conditions: 25 °C, 470 MHz, D2O 352 19F NMR Spectra of NaBF4, Sodium Trifluoro Acetate, Phenolphthalein, and Acetic Acid (Reaction 6) Figure 9-18 Conditions: 25 °C, 470 MHz, D2O 353 Small Spectral Window 19F NMR Spectra of NaBF4, Sodium Trifluoroacetate, Phenolphthalein, and Acetic Acid Focusing on the NaBF4 Peak (Reaction 6) Figure 9-19 Conditions: 25 °C, 470 MHz, D2O 354 APPENDIX B: CRYSTALLOGRAPHIC DATA Figure 10-1 Structure of Ligand-213 Formula CCDC Dcalc./ g cm-3 m/mm-1 Formula Weight Color Shape Size/mm3 T/K Crystal System Space Group a/Å b/Å c/Å a/° b/° g/° V/Å3 Z Z' Wavelength/Å Radiation type Qmin/° Qmax/° Measured Refl's. Indep't Refl's Refl's I≥2 s(I) Rint Parameters Restraints Largest Peak Deepest Hole wR2 (all data) wR2 R1 (all data) R1 C52H60N12 2169118 1.212 0.581 853.12 colourless block-shaped 0.24×0.20×0.09 100.00(10) monoclinic P21/c 23.0373(2) 9.76616(9) 20.8418(2) 90 94.2447(9) 90 4676.23(8) 4 1 1.54184 Cu Ka 3.848 77.218 32059 9402 7893 0.0288 589 0 0.441 -0.223 0.1236 0.1152 0.0507 0.0426 Table 10-1 General Crystal Structure Data for Ligand-213. 355 Atom N1A N2A N3A C1 C1A C2 C2A C3A C4A C5A C6A C7A C8A C9A C12A C13A N1B N2B N3B C1B C2B C3B C4B C5B C6B C7B C8B C9B C10B C11B C12B C13B N1C N2C N3C C1C C2C C3C C4C C5C x -808.5(5) 537.2(4) -253.3(5) -29.9(5) -227.2(5) -419.2(6) 170.2(5) -21.8(6) -623.3(6) -989.7(6) 411.6(6) 114.2(8) 705.7(8) 869.5(8) 310.5(6) 701.6(6) 2937.5(4) 1715.7(5) 2066.5(5) 2464.4(5) 2251.7(5) 2528.1(5) 3017.6(5) 3202.8(5) 2297.4(5) 2641.7(7) 1661.7(6) 2353.9(8) 2166.4(5) 2341.4(6) 1617.4(6) 1447.8(5) 2097.4(4) 3304.7(4) 2920.9(5) 2552.9(5) 2754.2(5) 2486.3(5) 2015.3(5) 1838.3(5) y 4166.9(12) 5729.4(11) 7806.3(12) 5610.0(12) 4323.8(12) 6657.7(13) 3352.6(12) 2133.0(13) 1969.1(14) 2997.4(15) 1080.4(13) -270.0(16) 1676.7(17) 765.1(16) 7903.8(13) 6879.3(13) 7125.6(10) 9426.8(10) 9884.9(11) 7711.8(11) 7376.6(11) 6364.7(12) 5761.9(12) 6170.8(12) 5963.2(12) 4757.3(14) 5510.6(17) 7175.5(14) 8749.8(11) 8997.8(12) 10546.8(12) 10333.8(12) 2988.4(10) 632.8(10) 167.9(11) 2323.1(11) 2545.8(11) 3517.9(11) 4216.0(12) 3915.1(12) z 3771.8(6) 4385.9(5) 4631.0(6) 4201.2(6) 3874.4(6) 4322.5(7) 3696.8(6) 3401.3(6) 3306.8(7) 3493.2(7) 3184.7(6) 2973.5(8) 2610.2(8) 3733.8(9) 4818.2(7) 4693.6(6) 5228.4(5) 5018.2(5) 6317.4(5) 4928.2(6) 4304.9(5) 3964.0(6) 4276.5(6) 4898.5(6) 3280.1(6) 3023.4(7) 3278.7(7) 2832.0(6) 5310.5(6) 5956.7(6) 6019.1(6) 5375.4(6) 4571.5(5) 4746.8(5) 3459.2(5) 4864.4(5) 5504.6(5) 5869.4(5) 5562.1(6) 4927.8(6) Ueq 29.8(2) 24.9(2) 32.5(3) 21.9(2) 22.4(2) 28.7(3) 21.8(2) 23.7(3) 30.1(3) 34.2(3) 27.8(3) 42.7(4) 46.5(4) 47.8(4) 28.1(3) 27.2(3) 21.1(2) 23.5(2) 28.3(2) 18.5(2) 19.3(2) 19.7(2) 21.5(2) 22.8(2) 22.0(2) 33.3(3) 38.2(3) 36.9(3) 19.0(2) 24.2(3) 26.4(3) 25.3(3) 19.9(2) 22.3(2) 27.2(2) 17.5(2) 18.3(2) 18.4(2) 20.6(2) 21.4(2) Table 10-2 Fractional Atomic Coordinates (×104) and Equivalent Isotropic Displacement Parameters (Å2×103) for Ligand-213. Ueq is defined as 1/3 of the trace of the orthogonalized Uij. 356 Table 10-2 (cont’d) y 3825.5(12) 2876.1(14) 3655.2(14) 5306.2(13) 1301.9(11) 1056.6(12) -496.0(12) -277.4(12) 4105.1(11) 5710.8(10) 7791.4(11) 4288.2(12) 3326.9(12) 2089.8(12) 1900.1(13) 2920.5(14) 1044.2(13) 743.0(16) 1651.2(17) -313.4(14) 5588.1(12) 6640.1(13) 7885.8(13) 6861.5(13) z 6571.8(6) 6829.4(6) 6986.8(6) 6624.9(6) 4468.1(5) 3827.2(6) 3745.8(6) 4383.4(6) 3730.5(5) 4414.4(5) 4586.0(6) 3854.8(6) 3704.9(6) 3412.3(6) 3290.0(6) 3453.0(6) 3232.7(7) 3823.2(9) 2688.4(9) 3004.0(8) 4185.2(6) 4267.4(6) 4823.3(6) 4733.0(6) Ueq 21.0(2) 30.1(3) 29.3(3) 33.5(3) 18.4(2) 22.9(2) 25.5(3) 24.7(3) 25.5(2) 23.4(2) 29.3(2) 20.8(2) 21.2(2) 22.4(2) 26.1(3) 28.5(3) 29.0(3) 45.3(4) 49.3(4) 36.5(3) 20.1(2) 25.7(3) 26.7(3) 25.0(3) x 2685.0(5) 3174.4(6) 2166.5(6) 2902.4(7) 2845.2(5) 2655.5(6) 3376.3(6) 3563.7(5) 4265.6(5) 5576.9(4) 4766.8(5) 4843.0(5) 5256.3(5) 5082.0(5) 4484.4(6) 4102.9(6) 5534.7(6) 5953.8(7) 5868.3(8) 5255.0(7) 5020.0(5) 4622.1(5) 5318.7(6) 5720.2(5) Atom C6C C7C C8C C9C C10C C11C C12C C13C N1D N2D N3D C1D C2D C3D C4D C5D C6D C7D C8D C9D C10D C11D C12D C13D 357 Atom N1A N2A N3A C1 C1A C2 C2A C3A C4A C5A C6A C7A C8A C9A C12A C13A N1B N2B N3B C1B C2B C3B C4B C5B C6B C7B C8B C9B C10B C11B C12B C13B N1C N2C N3C C1C C2C C3C C4C C5C U11 19.6(5) 20.1(5) 25.3(6) 19.6(6) 19.4(6) 21.0(6) 20.4(6) 27.2(6) 28.4(7) 21.0(6) 32.3(7) 48.6(9) 52.9(10) 52.2(10) 28.2(7) 21.6(6) 21.9(5) 23.1(5) 37.8(6) 19.1(5) 19.9(5) 20.8(5) 21.6(6) 21.0(6) 25.6(6) 40.4(8) 31.1(7) 60.9(10) 20.4(5) 29.9(6) 28.6(6) 22.0(6) 20.7(5) 22.2(5) 37.4(6) 18.1(5) 18.2(5) 20.1(5) 21.7(6) 19.4(5) U22 34.7(6) 25.6(5) 27.5(6) 23.9(6) 26.5(6) 28.0(6) 24.3(6) 25.8(6) 32.0(7) 41.3(8) 22.4(6) 33.6(8) 39.6(8) 33.2(8) 24.1(6) 26.9(6) 18.6(5) 19.4(5) 22.6(5) 15.5(5) 18.1(5) 18.5(5) 18.7(5) 20.7(6) 22.0(6) 30.4(7) 57.0(9) 27.2(7) 14.6(5) 20.1(6) 19.7(6) 19.7(6) 17.5(5) 18.4(5) 21.5(5) 14.3(5) 16.5(5) 16.2(5) 18.2(5) 19.6(5) U33 35.0(6) 29.3(6) 45.2(7) 22.6(6) 21.3(6) 37.1(7) 20.6(6) 17.9(6) 29.9(7) 39.9(8) 28.3(7) 45.7(9) 50.0(10) 55.0(10) 32.5(7) 32.8(7) 22.4(5) 27.7(5) 24.7(5) 20.8(5) 19.6(5) 20.1(6) 24.6(6) 26.1(6) 18.3(6) 28.8(7) 26.2(7) 21.8(6) 22.0(6) 22.6(6) 31.6(7) 34.2(7) 21.0(5) 26.2(5) 23.0(5) 19.9(5) 20.0(5) 19.0(6) 22.3(6) 24.7(6) U23 -3.9(5) -2.8(4) -3.5(5) 2.8(4) 2.0(5) -0.7(5) 1.8(4) 1.7(4) -4.8(5) -7.2(6) -3.6(5) -13.2(7) -2.5(7) -9.0(7) -3.3(5) -3.7(5) 0.7(4) -3.2(4) -3.1(4) 1.5(4) 2.5(4) 1.2(4) -0.9(4) 1.6(5) -1.1(4) -6.8(5) -7.3(6) 1.0(5) 0.8(4) 0.2(4) -5.0(5) -4.1(5) 0.2(4) -3.0(4) -3.2(4) 1.4(4) 1.8(4) 1.2(4) 0.0(4) 2.3(4) U13 1.5(4) 3.0(4) 5.7(5) 4.0(4) 1.3(4) 3.0(5) 1.0(4) 0.3(5) 1.2(5) 0.0(5) 0.0(5) 3.2(7) 23.8(8) -16.0(8) 5.4(5) 1.7(5) -0.8(4) 0.0(4) 4.0(5) 0.8(4) -0.1(4) 2.5(4) 3.7(5) -1.9(5) 1.2(4) 0.2(6) -1.0(6) -2.2(6) 1.1(4) 1.6(5) 7.2(5) 1.2(5) -0.6(4) 0.3(4) 3.5(4) 1.3(4) 1.0(4) 2.3(4) 4.5(4) -0.4(4) U12 -1.6(4) 0.3(4) 3.0(4) 0.5(4) -0.9(5) 1.8(5) -1.7(5) -2.6(5) -7.7(5) -7.2(5) -0.2(5) -4.7(7) 4.8(7) 10.8(7) -1.2(5) -2.3(5) 1.5(4) 2.1(4) 1.5(4) -1.5(4) 0.7(4) -2.8(4) 1.2(4) 3.1(4) -0.9(5) 4.3(6) -7.0(6) -2.7(6) -2.4(4) 1.3(5) -1.3(5) 2.2(5) 1.3(4) 2.8(4) 2.4(4) -1.1(4) 0.8(4) -1.5(4) 2.1(4) 3.5(4) Table 10-3 Anisotropic Displacement Parameters (×104) for Ligand-213. The anisotropic displacement factor exponent takes the form: -2p2[h2a*2 × U11+ ... +2hka* × b* × U12]. 358 Atom C6C C7C C8C C9C C10C C11C C12C C13C N1D N2D N3D C1D C2D C3D C4D C5D C6D C7D C8D C9D C10D C11D C12D C13D U11 25.5(6) 33.0(7) 31.3(7) 50.9(9) 20.0(5) 28.1(6) 29.3(6) 21.6(6) 19.8(5) 19.2(5) 25.2(5) 19.8(6) 19.1(5) 26.3(6) 27.3(6) 20.9(6) 29.2(7) 41.9(9) 53.5(10) 41.9(8) 19.4(5) 20.6(6) 27.8(6) 20.1(6) Table 10-3 (cont’d) U33 17.3(5) 20.4(6) 19.7(6) 23.0(6) 20.3(6) 21.3(6) 29.1(6) 32.7(7) 27.9(5) 26.3(5) 37.5(6) 19.3(6) 20.7(6) 18.1(5) 24.3(6) 31.5(7) 33.5(7) 60.7(10) 59.9(11) 40.5(8) 18.8(5) 31.6(7) 29.5(7) 28.2(6) U23 -0.4(4) -2.0(5) -0.7(5) -1.7(5) 0.6(4) -0.3(4) -5.8(5) -3.9(5) -1.7(4) -2.2(4) -3.2(4) 2.3(4) 1.3(4) 1.2(4) -2.3(5) -2.6(5) -6.1(5) -13.8(7) -11.7(8) -11.6(6) 2.7(4) 0.5(5) -3.2(5) -2.2(5) U22 20.2(6) 36.1(7) 37.2(7) 26.0(6) 14.9(5) 19.0(6) 19.1(6) 20.0(6) 28.5(5) 24.5(5) 25.0(5) 23.2(6) 23.6(6) 22.6(6) 26.3(6) 32.7(7) 24.3(6) 29.8(7) 38.5(8) 26.5(7) 22.3(6) 24.6(6) 22.9(6) 26.6(6) U13 1.3(4) -3.6(5) 4.3(5) -1.9(6) 2.0(4) 0.5(5) 8.3(5) 2.8(5) 0.1(4) 0.9(4) 1.5(5) 0.7(4) -0.1(4) 1.1(5) 0.1(5) -1.1(5) 2.0(5) -18.8(8) 31.6(8) -0.9(6) 2.4(4) 0.2(5) 2.9(5) 0.3(5) U12 -0.3(4) 7.2(6) -0.4(5) -9.5(6) -2.3(4) 1.9(5) 0.1(5) 1.9(5) -0.7(4) 0.9(4) 3.0(4) -0.4(4) -0.9(4) -0.5(5) -4.5(5) -4.5(5) 1.0(5) 12.7(6) -1.1(7) 1.1(6) 0.3(4) 2.4(5) -1.0(5) -1.7(5) 359 Atom N1A N1A N2A N2A N3A N3A C1 C1 C1A C2A C3A C3A C4A C6A C6A C6A C12A N1B N1B N2B N2B N3B N3B C1B C1B C2B C3B C3B C4B C6B C6B C6B C10B C12B N1C N1C N2C N2C N3C N3C C1C C1C C2C Atom C1A C5A C1 C13A C2 C12A C1A C2 C2A C3A C4A C6A C5A C7A C8A C9A C13A C1B C5B C10B C13B C11B C12B C2B C10B C3B C4B C6B C5B C7B C8B C9B C11B C13B C1C C5C C10C C13C C11C C12C C2C C10C C3C Length/Å 1.3491(16) 1.3341(18) 1.3396(16) 1.3342(17) 1.3347(18) 1.3317(18) 1.4841(17) 1.3960(17) 1.3875(17) 1.3976(17) 1.3944(18) 1.5244(18) 1.386(2) 1.5355(19) 1.534(2) 1.529(2) 1.3838(18) 1.3439(15) 1.3335(16) 1.3388(15) 1.3371(16) 1.3369(16) 1.3339(17) 1.3931(16) 1.4883(16) 1.3977(16) 1.3906(17) 1.5349(16) 1.3929(17) 1.5379(17) 1.5295(18) 1.5195(18) 1.3982(17) 1.3851(18) 1.3419(15) 1.3388(15) 1.3394(15) 1.3367(16) 1.3360(16) 1.3359(17) 1.3969(16) 1.4874(15) 1.3892(16) Table 10-4 Bond Lengths in Å for Ligand-213. 360 Table 10-4 (cont’d) Atom C4C C6C C5C C7C C8C C9C C13D C11D C12D C2D C10D C3D C4D C6D C5D C7D C8D C9D C11D C13D Length/Å 1.3963(16) 1.5309(16) 1.3858(17) 1.5263(17) 1.5348(17) 1.5316(17) 1.3343(16) 1.3354(17) 1.3331(17) 1.3891(17) 1.4867(16) 1.3987(17) 1.3937(18) 1.5260(17) 1.3875(19) 1.536(2) 1.536(2) 1.5345(18) 1.3959(17) 1.3847(18) Atom C3C C3C C4C C6C C6C C6C N2D N3D N3D C1D C1D C2D C3D C3D C4D C6D C6D C6D C10D C12D 361 Atom Atom Atom C5A N1A C13A N2A C12A N3A N2A N2A C2 N1A N1A C2A N3A C1A C2A C4A C4A C5A N1A C3A C3A C3A C8A C9A C9A N3A N2A C5B C13B C12B N1B N2B N2B C11B N3B N3B N2B C5C C13C C11C N1C N1C C2C C3C C2C C2C C4C C1A C1 C2 C1A C2 C1A C1 C2A C1 C1 C3A C6A C2A C6A C3A C4A C7A C8A C9A C7A C7A C8A C13A C12A C1B C10B C11B C2B C1B C11B C1B C10B C13B C12B C1C C10C C12C C2C C10C C10C C1C C4C C6C C6C C1 C1 C1 C1A C1A C1A C2 C2A C3A C3A C3A C4A C5A C6A C6A C6A C6A C6A C6A C12A C13A N1B N2B N3B C1B C10B C10B C10B C11B C12B C13B N1C N2C N3C C1C C1C C1C C2C C3C C3C C3C Angle/° 116.17(11) 116.58(11) 116.08(11) 117.68(11) 120.68(11) 121.63(11) 115.82(11) 123.16(11) 121.02(11) 122.57(12) 120.44(11) 120.83(11) 116.03(12) 123.13(11) 119.78(12) 124.41(12) 112.08(12) 108.18(11) 110.17(11) 108.41(12) 108.06(12) 109.91(14) 121.86(12) 122.22(12) 116.40(10) 116.62(11) 115.81(11) 123.46(11) 117.76(10) 120.76(11) 121.47(10) 122.62(12) 122.15(11) 122.01(12) 116.15(10) 116.77(10) 115.87(11) 123.52(10) 116.29(10) 120.18(10) 119.98(10) 116.37(10) 122.96(10) 120.67(10) Table 10-5 Bond Angles in ° for Ligand-213. 362 Table 10-5 (cont’d) Atom Atom Atom C3C C4C C5C C4C C5C N1C C8C C6C C3C C9C C6C C3C C3C C6C C7C C8C C6C C7C C9C C6C C7C C8C C6C C9C C1C C10C N2C C11C C10C N2C C1C C10C C11C C10C C11C N3C C13C C12C N3C C12C C13C N2C C1D N1D C5D C10D N2D C13D C11D N3D C12D C2D C1D N1D C10D C1D N1D C10D C1D C2D C3D C2D C1D C6D C3D C2D C2D C3D C4D C6D C3D C4D C3D C4D C5D C4D C5D N1D C7D C6D C3D C8D C6D C3D C9D C6D C3D C8D C6D C7D C7D C6D C9D C8D C6D C9D C1D C10D N2D C11D C10D N2D C1D C10D C11D C10D C11D N3D C13D C12D N3D C12D C13D N2D Angle/° 119.86(11) 124.10(11) 109.12(10) 109.11(10) 112.21(10) 108.75(10) 108.61(11) 109.00(11) 117.53(10) 120.86(11) 121.61(10) 122.47(11) 122.25(11) 121.76(11) 116.08(11) 116.59(10) 116.02(11) 123.37(11) 115.80(10) 120.81(10) 120.17(11) 120.38(11) 116.25(11) 123.36(11) 119.65(12) 124.48(12) 109.40(11) 108.15(11) 112.05(11) 110.28(14) 107.94(12) 109.01(12) 117.63(10) 120.68(11) 121.68(11) 122.60(11) 121.87(12) 122.21(12) 363 Atom N1A N2A N2A N2A N3A C1 C1 C1A C1A C1A C1A C2 C2 C2 C2A C2A C2A C2A C3A C4A C4A C4A C5A C5A C6A C12A C13A C13A N1B N1B N1B N2B N3B C1B C1B C1B C1B C2B C2B C2B C2B C2B C2B C3B C4B Atom C1A C1 C1 C1 C12A N2A C1A N1A C1 C2A C2A N3A C1 C1 C3A C3A C3A C3A C4A C3A C3A C3A N1A N1A C3A N3A N2A N2A C1B C1B C1B C10B C12B N1B C2B C2B C10B C1B C1B C3B C3B C3B C3B C4B C3B Atom C2A C1A C1A C2 C13A C13A C2A C5A C2 C3A C3A C12A C1A C1A C4A C6A C6A C6A C5A C6A C6A C6A C1A C1A C4A C2 C1 C1 C2B C10B C10B C11B C13B C5B C3B C3B C11B C10B C10B C4B C6B C6B C6B C5B C6B Atom C3A N1A C2A N3A N2A C12A C3A C4A N3A C4A C6A C13A N1A C2A C5A C7A C8A C9A N1A C7A C8A C9A C1 C2A C5A C1 C1A C2 C3B N2B C11B N3B N2B C4B C4B C6B N3B N2B C11B C5B C7B C8B C9B N1B C7B Angle/° -0.58(19) 171.66(11) -7.65(17) -0.9(2) -0.8(2) -0.04(19) 178.67(11) -0.3(2) 178.15(12) -0.49(17) 177.99(11) 0.7(2) -7.46(18) 173.23(12) 1.12(19) 170.83(12) -69.70(15) 50.46(16) -0.8(2) -10.80(18) 108.67(15) -131.17(14) -178.33(12) 0.96(19) -177.32(13) 0.2(2) -178.29(11) 0.84(18) 1.18(17) 175.74(10) -5.43(16) 1.51(19) 1.6(2) -0.17(18) -1.15(16) 179.18(10) -177.28(11) -5.19(16) 173.63(11) 0.55(17) -175.61(11) -56.79(15) 64.70(15) 0.13(19) 4.75(16) Table 10-6 Torsion Angles in ° for Ligand-213. 364 Table 10-6 (cont’d) Angle/° Atom C5B C5B C6B C10B C10B C11B C12B C13B C13B N1C N1C N1C N2C N3C C1C C1C C1C C1C C2C C2C C2C C2C C2C C2C C3C C4C C4C C4C C5C C5C C6C C10C C10C C11C C12C C13C C13C N1D N1D N1D N2D N3D C1D Atom N1B N1B C3B N2B C1B N3B N3B N2B N2B C1C C1C C1C C10C C12C N1C C2C C2C C10C C1C C1C C3C C3C C3C C3C C4C C3C C3C C3C N1C N1C C3C N2C C1C N3C N3C N2C N2C C1D C1D C1D C10D C12D N1D Atom C1B C1B C4B C13B C2B C12B C11B C10B C10B C2C C10C C10C C11C C13C C5C C3C C3C C11C C10C C10C C4C C6C C6C C6C C5C C6C C6C C6C C1C C1C C4C C13C C2C C12C C11C C10C C10C C2D C10D C10D C11D C13D C5D Atom C2B C10B C5B C12B C3B C13B C10B C1B C11B C3C N2C C11C N3C N2C C4C C4C C6C N3C N2C C11C C5C C7C C8C C9C N1C C7C C8C C9C C2C C10C C5C C12C C3C C13C C10C C1C C11C C3D N2D C11D N3D N2D C4D 365 -0.48(17) 178.56(10) -179.80(11) -1.34(18) -177.81(10) -0.28(19) -1.23(18) 178.68(10) -0.15(17) -1.24(17) 179.35(10) 0.18(16) -0.80(18) -1.2(2) 0.47(17) 0.69(16) -179.56(10) 178.35(11) -0.74(16) -179.91(11) 0.33(16) -4.18(16) -124.77(12) 116.24(13) -0.97(18) 175.57(11) 54.98(14) -64.02(15) 0.64(16) -179.46(10) -179.43(10) 1.54(18) 178.86(10) -0.16(18) 1.13(18) -179.75(10) -0.57(17) -0.31(18) 168.98(10) -9.82(17) -1.63(19) -1.3(2) -0.09(19) Table 10-6 (cont’d) Atom C1D C1D C1D C2D C2D C2D C2D C3D C4D C4D C4D C5D C5D C6D C10D C10D C11D C12D C13D C13D Atom C2D C2D C10D C3D C3D C3D C3D C4D C3D C3D C3D N1D N1D C3D N2D C1D N3D N3D N2D N2D Atom C3D C3D C11D C4D C6D C6D C6D C5D C6D C6D C6D C1D C1D C4D C13D C2D C12D C11D C10D C10D Atom C4D C6D N3D C5D C7D C8D C9D N1D C7D C8D C9D C2D C10D C5D C12D C3D C13D C10D C1D C11D Angle/° -0.26(17) 178.60(11) 177.14(11) 0.62(18) 52.53(16) -67.62(16) 172.20(11) -0.5(2) -128.70(14) 111.16(15) -9.02(18) 0.49(18) -177.89(11) -178.20(12) -0.24(18) 177.98(10) 1.25(19) 0.14(19) -177.22(11) 1.60(17) . 366 Atom H2 H2A H4A H5A H7AA H7AB H7AC H8AA H8AB H8AC H9AA H9AB H9AC H12A H13A H2B H4B H5B H7BA H7BB H7BC H8BA H8BB H8BC H9BA H9BB H9BC H11B H12B H13B H2C H4C H5C H7CA H7CB H7CC H8CA H8CB H8CC H9CA H9CB H9CC x -817.83 575.48 -781.44 -1397.25 -90.82 408.52 -164.97 409.85 984.24 911.1 1088.93 1136.28 676.69 448.12 1100.67 1919.4 3224.94 3538.98 2603.47 3053.15 2487.72 1426 1632.62 1519.1 2763.49 2122.9 2211.93 2668.71 1407.04 1131.4 3074.2 1816.53 1512.75 3515.71 3044.64 3277.09 2038.47 1845.91 2284.07 2588.81 3234.76 3022.68 y 6548.98 3517.69 1155.08 2860.42 -644.74 -926.27 -100.72 1878.62 1011.14 2521.49 1599.25 61.14 432.84 8699.12 6998.77 7834.89 5073.56 5743.17 3957.81 5009.93 4535.77 6269.19 4728.11 5244.65 7448.97 7943.13 6916.15 8516.63 11185.09 10847.75 2032.56 4895.75 4396.57 3012.34 1922.54 3083.75 2698.06 4244.75 3914.19 5929.15 5421.93 5514.89 z 4179.86 3776.68 3115.24 3417.49 3329.81 2851.79 2604.07 2260.82 2461.03 2741.78 3850.76 3595.01 4107.51 5043.67 4831.92 4111.86 4066.54 5100.09 3301.25 3020.51 2584.7 3424.59 3568.96 2841.8 2836.05 2976.9 2393.95 6147.1 6255.96 5181.71 5690.48 5787.32 4733.57 6582.61 6787.33 7283.7 6974.06 6819.51 7431.83 6471.17 6362.4 7075.15 Ueq 34 26 36 41 64 64 64 70 70 70 72 72 72 34 33 23 26 27 50 50 50 57 57 57 55 55 55 29 32 30 22 25 26 45 45 45 44 44 44 50 50 50 Table 10-7 Hydrogen Fractional Atomic Coordinates (×104) and Equivalent Isotropic Displacement Parameters (Å2×103) for Ligand-213. Ueq is defined as 1/3 of the trace of the orthogonalized Uij. 367 Atom H11C H12C H13C H5D H7DA H7DB H7DC H8DA H8DB H8DC H9DA H9DB H9DC H11D H12D H13D x 2325.1 3578.29 3885.09 3698.25 5733.46 6156.1 6239.48 6056.2 5596.57 6165.19 5004.21 5021.67 5560.55 4233.03 5440.13 6110.74 Table 10-7 (cont’d) y 1539.69 -1140.2 -787.85 2765.32 393.75 1586.72 56.12 2507.65 1834.27 998.91 -156.95 -679.09 -971.16 6532.71 8678.43 6981.92 z 3645.54 3503.32 4568.01 3360.87 4173.04 3962.54 3711.02 2834.7 2314.07 2569.13 2610.27 3339.27 2916.44 4089.74 5061.1 4903.7 Ueq 27 31 30 34 68 68 68 74 74 74 55 55 55 31 32 30 368 Figure 10-2 Structure of Compound 3a Formula CCDC Dcalc m/mm-1 Formula Weight Colour Shape Size/mm3 T/K Crystal System Flack Parameter Hooft Parameter Space Group a/Å b/Å c/Å a/° b/° g/° V/Å3 Z Z' Wavelength/Å Radiation type Qmin/° Qmax/° Measured Refl's. Indep't Refl's Refl's I≥2 s(I) Rint Parameters Restraints Largest Peak Deepest Hole GooF wR2 (all data) wR2 R1 (all data) R1 C48H76B6F2O12 2112718 1.198 0.705 947.94 colourless irregular-shaped 0.17×0.11×0.05 100(1) orthorhombic -0.03(9) -0.03(9) Pca21 13.32991(18) 13.67698(18) 28.8179(4) 90 90 90 5253.88(12) 4 1 1.54184 Cu Ka 3.067 84.312 18248 18248 16984 . 715 203 0.377 -0.408 1.048 0.1902 0.1780 0.0683 0.0629 Table 10-8 General Crystal Structure Data for Compound 3a. 369 Atom F1 O1 O2 O3 O4 O5 O6 C1 C2 C3 C4 C5 C6 C7 C8 C9 C10 C11 C12 C13 C14 C15 C16 C17 C18 C19 C20 C21 C22 C23 C24 B1 B2 B3 F1A O1A O2A O3A O4A O5A O5B x 2520(3) 4229(3) 4207(2) 2158(2) 3155(2) 1163(2) 907(3) 3165(3) 2629(3) 2042(3) 2018(3) 2549(4) 3124(3) 4787(4) 5013(4) 5646(6) 4035(5) 6006(5) 5038(6) 2239(3) 3113(4) 2453(4) 1221(4) 4139(4) 2916(4) 639(4) 189(4) 1428(4) -134(5) 125(4) -815(4) 3871(4) 2642(3) 1369(4) 2787(3) 850(3) 788(2) 2270(3) 2948(2) 4259(12) 4511(12) y 2471(2) 255(2) 1074(2) 1838(2) 3197(2) 4029(2) 4744(2) 1819(3) 2533(3) 3224(3) 3201(3) 2495(3) 1797(3) -346(4) 363(4) -818(6) -1152(4) 915(6) -68(5) 2095(3) 2872(3) 1173(4) 2520(4) 2441(4) 3747(4) 4950(4) 5204(3) 5678(4) 4785(4) 6282(4) 4724(5) 1037(3) 2529(3) 4012(3) 7566(2) 9613(3) 8660(2) 6762(2) 8281(2) 6126(10) 6375(11) z 7765.7(10) 6594.7(12) 5906.8(12) 5530.0(10) 5519.1(10) 5873.8(11) 6578.2(12) 6583.4(14) 6332.1(15) 6578.0(15) 7060.0(16) 7295.8(15) 7065.6(15) 6270.4(18) 5873(2) 6516(2) 6118(2) 5961(3) 5395(2) 5042.0(15) 5036.5(14) 4766.5(17) 4901.8(16) 4931.7(17) 4725.2(17) 5781.8(16) 6263.6(16) 5622(2) 5406.7(18) 6371(2) 6350(2) 6350.9(17) 5782.1(16) 6335.4(17) 5270.8(10) 4085.1(13) 3441.2(11) 3022.6(10) 3041.3(10) 3372(6) 3429(6) Ueq 47.0(8) 37.9(8) 34.8(7) 28.0(6) 29.7(6) 32.4(7) 35.0(7) 25.9(8) 24.1(8) 26.1(8) 30.9(9) 31.9(10) 29.6(9) 40.2(11) 43.4(11) 66.0(19) 52.2(14) 70(2) 58.1(16) 29.5(9) 31.0(9) 37.5(10) 36.1(10) 38.1(10) 40.0(11) 34.4(10) 34.3(10) 49.8(14) 48.2(14) 44.0(12) 50.0(13) 27.0(9) 25.3(9) 27.3(9) 45.3(7) 46.0(10) 34.8(7) 33.2(7) 32.4(7) 33(2) 31(2) Table 10-9 Fractional Atomic Coordinates (×104) and Equivalent Isotropic Displacement Parameters (Å2×103) for 3a. Ueq is defined as 1/3 of the trace of the orthogonalised Uij. 370 Atom O6A O6B C1A C2A C3A C4A C13A C14A C15A C16A C17A C18A C19A C19B C20A C20B C21A C21B C22A C22B C23A C23B C24A C24B B1A B2A B3A Table 10-9 (cont’d) y 5446(10) 5272(11) 8129(3) 7489(3) 6868(3) 6890(3) 7081(3) 8030(3) 6259(4) 7275(4) 7856(4) 8897(4) 5234(8) 5642(8) 4977(8) 4779(8) 4490(10) 6034(10) 5477(16) 5384(16) 3869(9) 4203(10) 5421(10) 4119(11) 8816(3) 7505(3) 6158(3) z 4083(4) 4004(5) 4091.2(14) 3836.7(14) 4077.5(14) 4563.6(15) 2541.9(14) 2552.4(14) 2244.8(18) 2417.9(18) 2410.7(19) 2288(2) 3270(4) 3370(3) 3764(4) 3650(4) 3113(5) 3608(5) 2904(6) 2857(5) 3839(5) 3347(5) 3848(5) 3909(5) 3861.0(17) 3287.9(16) 3830.5(16) Ueq 36(2) 40(2) 24.5(8) 21.8(7) 24.9(8) 29.8(9) 27.8(9) 26.4(8) 37.7(10) 36.5(10) 39.0(11) 42.2(12) 41.4(13) 39.5(13) 39.8(13) 44.3(13) 51(2) 50.9(19) 41(2) 40(2) 45(2) 54(2) 54.9(19) 53(2) 25.5(9) 22.7(9) 24.8(9) x 4607(8) 4254(8) 2007(3) 2633(3) 3297(3) 3333(3) 2251(3) 2920(3) 2671(4) 1170(4) 4017(4) 2506(4) 4819(8) 5303(8) 5268(8) 4890(9) 4032(9) 6234(8) 5634(11) 5397(12) 5295(10) 4096(10) 6284(9) 5608(11) 1211(3) 2609(3) 4042(4) 371 Atom F1 O1 O2 O3 O4 O5 O6 C1 C2 C3 C4 C5 C6 C7 C8 C9 C10 C11 C12 C13 C14 C15 C16 C17 C18 C19 C20 C21 C22 C23 C24 B1 B2 B3 F1A O1A O2A O3A O4A O5A O5B O6A U11 64(2) 45(2) 36.4(18) 31.4(16) 35.3(16) 39.2(17) 39.2(18) 22.7(19) 20.9(19) 22(2) 32(2) 38(2) 29(2) 47(3) 34(2) 69(4) 60(4) 42(3) 76(4) 36(2) 37(2) 42(3) 36(3) 35(2) 52(3) 35(2) 34(2) 42(3) 61(4) 46(3) 31(3) 24(2) 25(2) 29(2) 60.4(19) 55(2) 34.2(18) 46(2) 38.5(18) 42(7) 38(7) 36(6) U22 53.0(19) 38.4(18) 35.0(16) 28.7(15) 29.8(15) 30.4(15) 36.0(17) 26.3(19) 24.6(19) 26.0(19) 30(2) 34(2) 29(2) 38(3) 48(3) 75(5) 40(3) 67(4) 57(3) 30(2) 35(2) 36(2) 43(3) 48(3) 40(3) 32(2) 36(2) 45(3) 47(3) 39(3) 54(3) 28(2) 25(2) 28(2) 53.0(18) 41(2) 41.0(17) 30.8(15) 35.5(16) 31(7) 29(6) 43(5) U33 23.5(14) 30.2(16) 33.0(16) 23.8(14) 24.1(14) 27.6(15) 30.0(15) 29(2) 26.6(19) 30(2) 30(2) 24(2) 31(2) 36(2) 48(3) 55(4) 56(3) 102(6) 41(3) 21.8(19) 20.6(19) 35(2) 29(2) 31(2) 27(2) 37(2) 33(2) 62(4) 37(3) 47(3) 65(4) 29(2) 27(2) 25(2) 22.4(13) 42(2) 29.1(16) 22.8(14) 23.2(14) 26(4) 26(4) 30(4) U23 1.5(12) 3.7(13) 5.6(13) -0.4(11) -0.2(11) -0.4(12) -5.2(13) 1.3(15) -0.3(14) -0.3(15) -1.8(16) -0.4(16) 1.2(16) -1.5(18) 3(2) -3(3) -4(2) -11(4) 4(3) -0.6(15) 0.1(16) -10.3(18) 2.9(18) -3.9(19) 5.3(18) 0.9(17) -3.7(17) 18(2) -8(2) -10(2) 5(3) 5.4(17) 2.5(15) -2.5(17) 1.6(11) -13.9(15) -6.0(13) 0.9(12) -1.6(12) 0(4) 3(4) 7(3) U13 3.6(11) 1.3(14) 8.4(14) -1.5(12) 0.6(12) -4.8(13) -6.1(13) 0.0(15) -2.2(14) -0.2(15) 1.5(17) 1.4(16) -2.8(17) 3(2) 11(2) -9(3) 17(3) 26(4) 19(3) 0.6(17) 2.6(17) 6(2) -6.2(18) 8.1(19) -6(2) -5.1(18) -5.3(17) 7(2) -18(2) -19(2) 6(2) 1.0(18) 1.0(16) -0.4(18) 1.3(13) -16.6(17) -5.6(13) -1.0(13) 2.8(12) 3(4) 5(4) 1(4) U12 18.8(16) 17.0(15) 9.8(13) -5.0(11) -8.3(12) 9.2(13) 14.0(13) -2.4(14) -2.4(14) 0.2(15) 3.7(17) 2.5(18) 2.5(16) 17(2) 8(2) 36(4) -3(2) -10(3) 26(3) -6.1(16) -8.2(17) -12(2) -7.6(19) -9(2) -13(2) 12.8(18) 8.3(18) 9(2) 20(3) 14(2) 4(2) 1.1(17) 2.5(16) -0.1(17) 19.1(14) 24.6(16) 13.9(13) -11.2(13) -11.9(13) 17(4) 7(4) 18(4) Table 10-10 Anisotropic Displacement Parameters (×104) for 3a. The anisotropic displacement factor exponent takes the form: -2p2[h2a*2 × U11+ ... +2hka* × b* × U12]. 372 Table 10-10 (cont’d) U23 11(4) 0.4(14) 0.9(13) -1.3(15) -0.2(15) -8(2) -0.8(18) 28(4) -18(3) 4(2) 19(3) -0.3(15) -0.2(14) -9.9(19) 3.4(19) -5(2) 11(2) -5(2) -5(2) -6(2) -3(2) -14(4) -20(3) 0(3) -3(3) -6(3) -10(4) -11(3) 0(3) -2.8(17) 0.2(15) 1.1(16) U13 15(4) 2.5(15) 1.2(13) 1.5(16) 2.0(16) -18(2) -1.7(18) -51(5) -12(3) -4(2) -8(3) -0.2(16) 0.0(15) 4.2(19) -2.9(19) 14(2) -11(2) 5(2) 5(2) 2(2) 7(2) -2(4) 3(3) 7(4) 5(4) -1(4) 13(4) -3(3) 3(4) 2.9(17) 1.2(16) -1.4(17) U12 22(5) -0.4(14) -3.6(14) 2.5(17) 5.7(15) 19(2) 13.1(18) -15(3) 47(4) 22(2) 1(2) -2.9(16) -1.5(15) -6.4(18) -6.8(18) -4.4(19) -4(2) 15(2) 16(2) 15(2) 16(2) 11(4) 5(3) 12(4) 15(4) 14(4) 4(4) 10(3) 21(4) 2.2(16) 2.4(16) -0.4(16) Atom O6B C1A C2A C5A C6A C7A C8A C9A C10A C11A C12A C13A C14A C15A C16A C17A C18A C19A C19B C20A C20B C21A C21B C22A C22B C23A C23B C24A C24B B1A B2A B3A U11 42(7) 21.2(19) 19.5(18) 36(2) 32(2) 49(3) 29(2) 77(5) 71(4) 49(3) 35(3) 34(2) 28(2) 35(2) 30(2) 33(2) 42(3) 40(3) 37(3) 37(3) 43(3) 50(4) 39(4) 42(5) 40(5) 43(4) 54(4) 46(4) 50(4) 22(2) 19(2) 25(2) U22 43(5) 25.2(19) 21.3(18) 33(2) 25.7(19) 37(3) 41(2) 46(4) 78(5) 56(3) 61(4) 29(2) 30(2) 37(2) 40(2) 39(2) 36(2) 43(3) 44(3) 43(3) 46(3) 51(4) 63(4) 45(4) 46(4) 45(4) 51(4) 63(4) 56(4) 25(2) 24(2) 24(2) U33 35(5) 27.0(19) 24.6(18) 22(2) 28(2) 53(3) 35(2) 134(8) 59(4) 33(2) 69(4) 20.4(18) 21.0(18) 41(3) 39(2) 45(3) 48(3) 41(3) 38(3) 39(3) 44(3) 53(4) 51(4) 38(4) 34(4) 47(4) 58(4) 56(4) 54(4) 30(2) 25(2) 25(2) 373 Atom F1 O1 O1 O2 O2 O3 O3 O4 O4 O5 O5 O6 O6 C1 C1 C1 C2 C2 C3 C3 C4 C5 C7 C7 C7 C8 C8 C13 C13 C13 C14 C14 C19 C19 C19 C20 C20 F1A O1A O1A O2A O2A Atom C5 C7 B1 C8 B1 C13 B2 C14 B2 C19 B3 C20 B3 C2 C6 B1 C3 B2 C4 B3 C5 C6 C8 C9 C10 C11 C12 C14 C15 C16 C17 C18 C20 C21 C22 C23 C24 C5A C7A B1A C8A B1A Length/Å 1.355(5) 1.450(6) 1.366(6) 1.452(6) 1.357(6) 1.454(5) 1.356(5) 1.461(5) 1.370(5) 1.465(5) 1.358(6) 1.461(5) 1.367(6) 1.410(6) 1.391(6) 1.574(6) 1.417(6) 1.585(6) 1.390(6) 1.567(6) 1.377(6) 1.392(6) 1.532(8) 1.493(8) 1.553(8) 1.545(9) 1.497(8) 1.577(6) 1.517(6) 1.531(7) 1.519(7) 1.519(7) 1.552(7) 1.519(8) 1.511(7) 1.509(7) 1.512(7) 1.361(5) 1.468(6) 1.355(6) 1.461(5) 1.352(6) Table 10-11 Bond Lengths in Å for 3a. 374 Table 10-11 (cont’d) Atom O3A O3A O4A O4A O5A O5A O5B O5B O6A O6A O6B O6B C1A C1A C1A C2A C2A C3A C3A C4A C5A C7A C7A C7A C8A C8A C13A C13A C13A C14A C14A C19A C19A C19A C19B C19B C19B C20A C20A C20B C20B Atom C13A B2A C14A B2A C19A B3A C19B B3A C20A B3A C20B B3A C2A C6A B1A C3A B2A C4A B3A C5A C6A C8A C9A C10A C11A C12A C14A C15A C16A C17A C18A C20A C21A C22A C20B C21B C22B C23A C24A C23B C24B Length/Å 1.453(5) 1.350(5) 1.451(5) 1.354(5) 1.460(19) 1.353(17) 1.46(2) 1.349(17) 1.426(18) 1.430(13) 1.489(18) 1.341(15) 1.414(5) 1.400(6) 1.565(6) 1.409(6) 1.582(6) 1.402(6) 1.561(6) 1.381(6) 1.375(6) 1.534(7) 1.514(11) 1.520(9) 1.515(7) 1.526(8) 1.575(6) 1.521(6) 1.508(7) 1.536(6) 1.514(6) 1.583(16) 1.530(15) 1.551(17) 1.532(17) 1.515(14) 1.527(16) 1.531(15) 1.504(15) 1.583(16) 1.512(15) 375 Atom Atom Atom B1 B1 B2 B2 B3 B3 C2 C6 C6 C1 C1 C3 C2 C4 C4 C5 F1 F1 C4 C1 O1 O1 O1 C8 C9 C9 O2 O2 O2 C7 C12 C12 O3 O3 O3 C15 C15 C16 O4 O4 O4 C17 O6 O1 O2 O3 O4 O5 O6 C1 C1 C1 C2 C2 C2 C3 C3 C3 C4 C5 C5 C5 C6 C7 C7 C7 C7 C7 C7 C8 C8 C8 C8 C8 C8 C13 C13 C13 C13 C13 C13 C14 C14 C14 C14 C20 C7 C8 C13 C14 C19 C20 B1 C2 B1 C3 B2 B2 B3 C2 B3 C3 C4 C6 C6 C5 C8 C9 C10 C10 C8 C10 C7 C11 C12 C11 C7 C11 C14 C15 C16 C14 C16 C14 C13 C17 C18 C13 C24 Angle/° 107.0(4) 106.5(4) 108.3(3) 107.7(3) 106.7(3) 107.0(3) 123.7(4) 120.5(4) 115.7(4) 119.0(4) 120.4(4) 120.5(4) 123.5(4) 119.8(4) 116.6(4) 119.8(4) 119.7(4) 118.4(4) 121.9(4) 118.9(4) 102.9(4) 109.4(4) 104.7(4) 111.4(5) 118.5(5) 108.8(5) 103.2(4) 107.2(5) 110.0(5) 110.8(6) 116.2(5) 109.0(6) 103.2(3) 108.6(4) 106.3(3) 114.6(4) 110.1(4) 113.3(4) 102.9(3) 105.8(4) 109.2(4) 113.9(4) 106.9(4) Table 10-12 Bond Angles in Å for 3a. 376 Table 10-12 (cont’d) Atom Atom Atom C20 C23 C20 C23 C20 C24 B1 O1 B1 O2 B1 O2 B2 O3 B2 O3 B2 O4 B3 O5 B3 O5 B3 O6 O1A B1A O2A B1A O3A B2A O4A B2A O5A B3A B3A O5B C20A O6A O6B B3A C1A C2A C1A C6A C1A C6A C2A C1A C2A C3A C2A C3A C3A C2A C3A C4A C3A C4A C4A C5A C5A F1A C5A F1A C5A C6A C6A C5A C7A O1A C7A O1A C7A O1A C7A C9A C7A C9A C7A C10A C8A O2A C8A O2A C8A O2A C19 C24 C19 C1 O1 C1 O4 C2 C2 O6 C3 C3 C7A C8A C13A C14A C19A C19B B3A C20B B1A C2A B1A B2A C1A B2A B3A C2A B3A C3A C4A C6A C4A C1A C8A C9A C10A C8A C10A C8A C7A C11A C12A Angle/° 115.1(4) 109.9(4) 113.1(4) 121.5(4) 113.5(4) 125.0(4) 114.0(4) 122.2(4) 123.8(4) 113.5(4) 124.3(4) 122.2(4) 106.5(4) 106.5(3) 108.6(3) 108.4(3) 109.4(12) 106.4(12) 107.6(10) 105.8(10) 123.5(4) 119.9(4) 116.6(4) 119.9(3) 119.2(4) 120.9(3) 123.4(4) 120.0(4) 116.6(4) 119.1(4) 118.3(4) 119.3(4) 122.4(4) 119.3(4) 102.1(4) 106.4(5) 107.6(5) 113.2(6) 112.1(6) 114.5(5) 102.3(4) 109.9(4) 106.0(4) 377 Atom F1 O1 O1 O1 O3 O3 O3 O5 O5 O5 C1 C1 C1 C1 C2 C2 C2 C2 C2 C2 C3 C3 C3 C3 C4 C4 C4 C6 C6 C6 C6 C7 C7 C8 C8 C9 C9 C9 C10 C10 C10 C13 C13 Atom C5 C7 C7 C7 C13 C13 C13 C19 C19 C19 C2 C2 C2 C2 C1 C1 C1 C3 C3 C3 C2 C2 C4 C4 C3 C3 C5 C1 C1 C1 C1 O1 O1 O2 O2 C7 C7 C7 C7 C7 C7 O3 O3 Atom C6 C8 C8 C8 C14 C14 C14 C20 C20 C20 C3 C3 B2 B2 C6 B1 B1 C4 B3 B3 B2 B2 C5 C5 B3 B3 C6 C2 C2 B1 B1 B1 B1 B1 B1 C8 C8 C8 C8 C8 C8 B2 B2 Atom C1 O2 C11 C12 O4 C17 C18 O6 C23 C24 C4 B3 O3 O4 C5 O1 O2 C5 O5 O6 O3 O4 F1 C6 O5 O6 C1 C3 B2 O1 O2 O2 C1 O1 C1 O2 C11 C12 O2 C11 C12 O4 C2 Angle/° -179.5(4) -25.9(5) 88.5(5) -146.4(5) -19.3(4) 94.7(4) -137.6(4) 28.5(4) 146.7(4) -85.8(5) 1.2(6) -176.5(4) 71.2(5) -107.1(5) -0.4(6) -167.9(4) 14.2(7) -1.3(7) 9.9(7) -171.8(4) -105.9(5) 75.8(5) -179.7(4) 0.5(7) -167.9(4) 10.4(6) 0.3(7) -0.3(6) -177.5(4) 14.5(6) -163.4(4) -5.9(6) 176.0(4) -11.8(5) 166.2(4) -146.8(5) -32.4(7) 92.8(7) 85.8(5) -159.8(5) -34.6(6) -6.8(5) 174.8(4) Table 10-13 Torsion Angles in ° for 3a. 378 Table 10-13 (cont’d) Atom B2 B2 C14 C14 C14 B3 B3 C20 C20 C20 C20 C20 C20 C7 C7 C7 C8 C8 C8 C2 C2 C6 C13 C13 C13 C14 C14 C14 C3 C3 C19 C19 C19 C20 C20 C20 C4 C6A C8A C8A C8A Atom O3 C2 O4 C17 C18 O5 C3 O6 C23 C24 O6 C23 C24 C8 C9 C10 C7 C11 C12 C3 B2 C5 C14 C15 C16 C13 C17 C18 C4 B3 C20 C21 C22 C19 C23 C24 C5 C1A O2A C11A C12A Angle/° -6.8(5) 171.6(4) -137.2(4) -23.2(5) 104.5(5) 10.1(5) -168.4(4) -86.0(4) 32.2(6) 159.7(4) 146.3(4) -95.6(5) 31.9(6) 19.7(5) 146.6(5) -96.9(5) 23.2(5) -93.9(6) 147.8(5) -177.8(4) 5.0(6) 177.3(4) 16.2(4) 138.2(4) -103.4(4) 16.1(4) -103.8(4) 137.7(4) 178.3(4) 0.6(6) -23.7(5) 95.3(5) -145.0(4) -23.9(5) -146.1(4) 95.0(5) 176.6(4) 179.9(4) -28.9(5) -148.4(4) 84.7(5) Atom O4 O4 C13 C13 C13 O6 O6 C19 C19 C19 C19 C19 C19 O1 O1 O1 O2 O2 O2 C1 C1 C1 O3 O3 O3 O4 O4 O4 C2 C2 O5 O5 O5 O6 O6 O6 C3 C5A C7A C7A C7A Atom C14 C14 C15 C15 C15 C20 C20 C21 C21 C21 C22 C22 C22 B1 B1 B1 B1 B1 B1 B1 B1 B1 B2 B2 B2 B2 B2 B2 B2 B2 B3 B3 B3 B3 B3 B3 B3 F1A O1A O1A O1A 379 Atom O3A O3A O3A O5A O5A O5A O5B O5B O5B C2A C2A C2A C3A C3A C3A C3A C4A C4A C4A C4A C4A C6A C6A C6A C6A C7A C7A C8A C8A C9A C9A C9A C10A C10A C10A C13A C13A C14A C14A C15A C15A C15A Table 10-13 (cont’d) Atom C14A C14A C14A C20A C20A C20A C20B C20B C20B B3A B3A B3A B2A B2A C5A C5A B3A B3A B3A B3A C6A C2A C2A B1A B1A B1A B1A B1A B1A C8A C8A C8A C8A C8A C8A B2A B2A B2A B2A C14A C14A C14A Atom O4A C17A C18A O6A C23A C24A O6B C23B C24B O5B O6A O6B O3A O4A F1A C6A O5A O5B O6A O6B C1A C3A B2A O1A O2A O2A C1A O1A C1A O2A C11A C12A O2A C11A C12A O4A C2A O3A C2A O4A C17A C18A Angle/° -17.6(4) 96.5(4) -135.4(4) 23.7(12) 143.9(11) -90.8(11) -27.9(11) 80.8(11) -145.9(12) 35.8(8) -171.4(6) -143.5(7) 69.1(5) -110.0(5) -178.0(4) -0.1(7) -168.4(7) -142.4(7) 10.5(8) 38.3(8) 2.0(7) 1.9(6) -175.8(4) 21.2(6) -155.5(4) -9.0(6) 173.9(4) -10.8(5) 166.2(4) 85.0(5) -34.4(7) -161.4(5) -144.8(5) 95.7(6) -31.2(7) -7.5(5) 173.3(4) -5.0(5) 174.2(4) -134.2(4) -20.1(5) 107.9(5) Atom C13A C13A C13A C19A C19A C19A C19B C19B C19B C3A C3A C3A C2A C2A C4A C4A C3A C3A C3A C3A C5A C1A C1A C1A C1A O1A O1A O2A O2A C7A C7A C7A C7A C7A C7A O3A O3A O4A O4A C13A C13A C13A 380 Table 10-13 (cont’d) Atom C14A C14A C14A B3A B3A B3A B3A C7A C7A C7A C8A C8A C8A C2A C2A C6A C13A C13A C13A C14A C14A C14A C3A C3A C19A C19A C19A C19B C19B C19B C20A C20A C20A C20B C20B C20B C4A Atom O4A C17A C18A O6A C3A O6B C3A C8A C9A C10A C7A C11A C12A C3A B2A C5A C14A C15A C16A C13A C17A C18A C4A B3A C20A C21A C22A C20B C21B C22B C19A C23A C24A C19B C23B C24B C5A Angle/° 97.8(4) -148.1(4) -20.0(5) 13.0(11) -168.0(7) -13.6(11) 167.1(6) 23.6(6) -95.3(6) 144.5(5) 24.7(5) 148.0(5) -94.2(5) -177.3(4) 4.9(6) 176.4(4) 15.4(4) 136.5(4) -104.6(4) 14.1(4) -105.8(4) 136.9(4) 177.7(4) -0.4(6) -22.3(11) 94.8(11) -141.7(10) 25.6(10) -89.1(10) 143.3(11) -17.2(11) -136.9(10) 102.6(10) 21.1(11) -92.5(10) 147.6(10) 177.3(4) Atom C13A C13A C13A O5A O5A O5B O5B O1A O1A O1A O2A O2A O2A C1A C1A C1A O3A O3A O3A O4A O4A O4A C2A C2A O5A O5A O5A O5B O5B O5B O6A O6A O6A O6B O6B O6B C3A Atom C16A C16A C16A C19A C19A C19B C19B B1A B1A B1A B1A B1A B1A B1A B1A B1A B2A B2A B2A B2A B2A B2A B2A B2A B3A B3A B3A B3A B3A B3A B3A B3A B3A B3A B3A B3A B3A 381 Atom H4 H6 H9A H9B H9C H10D H10E H10F H11D H11E H11F H12D H12E H12F H15D H15E H15F H16D H16E H16F H17D H17E H17F H18D H18E H18F H21G H21H H21I H22G H22H H22I H23G H23H H23I H24G H24H H24I H4A H6A H9AA H9AB H9AC x 1636.18 3481.28 6065.16 6047.73 5389.73 3787.92 4374 3469.74 6053.17 6572.94 6021.55 4368.48 5517.27 5244.02 3066.6 2541.08 1889.64 693.03 1227.35 1091.15 4656.6 4163.77 4258.04 2311.78 2817.59 3490.24 1909.31 1102.53 1780.5 202.76 -595.34 -512.12 -202.24 -266.35 802.27 -775.43 -1328.92 -992.12 3772.42 1678.57 1209.85 452.59 1371.33 y 3671.44 1313.68 -312.76 -1191.37 -1258.39 -1499.99 -1615.01 -850.84 1473.97 473.31 1148.63 -308.99 -610.88 434.04 864.76 1339.89 717.63 2039.32 2677.01 3115.63 2936.2 2232.64 1876.5 4088.42 3523.37 4192.98 5791.8 6296.72 5416.4 4717.86 5342.5 4186.83 6375.16 6611.34 6560.42 4029.88 5042.8 4788.3 6466.79 8608.86 11286.11 11358.66 10606.22 z 7226.4 7234.96 6659.82 6293.15 6756.55 6392.51 5910.93 5954.55 5749.41 5907.65 6282.63 5313.56 5387.66 5172.09 4883.87 4438.39 4799.46 4964.58 4569.98 5080.94 4987.23 4606.54 5133.71 4831.53 4405.23 4737.77 5873.69 5539.49 5351.11 5106.19 5396.4 5474.32 6672.11 6129.02 6380.96 6267.82 6159.48 6678.64 4728.11 4747.87 3778.2 3348.65 3332.45 Ueq 37 36 99 99 99 78 78 78 106 106 106 87 87 87 56 56 56 54 54 54 57 57 57 60 60 60 75 75 75 72 72 72 66 66 66 75 75 75 36 34 129 129 129 Table 10-14 Hydrogen Fractional Atomic Coordinates (×104) and Equivalent Isotropic Displacement Parameters (Å2×103) for 3a. Ueq is defined as 1/3 of the trace of the orthogonalised Uij. 382 Atom H10A H10B H10C H12A H12B H12C H15A H15B H15C H16A H16B H16C H17A H17B H17C H18A H18B H18C H21A H21B H21C H21D H21E H21F H22A H22B H22C H22D H22E H22F H23A H23B H23C H23D H23E H23F H24A H24B H24C H24D H24E H24F x -938.63 -1181.72 -429.26 -1066.02 -1581.39 -870.35 3337.38 2724.62 2223.15 775.99 1126.26 905.93 4406.75 4046.39 4296.57 1842.96 2448.58 2959.58 3580.92 4366.68 3642.96 6382.96 6801.59 6118.64 5327.01 6151.39 5939.8 4751.7 5910.32 5589.68 5500.25 5775.56 4626.2 3757.42 4439.53 3599.96 6755.12 6524.74 6234.55 6122.45 5929.09 5238.32 Table 10-14 (cont’d) z 4228.16 3798.36 4196.84 3365.24 3558.59 3888.95 2359.53 1922.15 2261.24 2465.01 2092.01 2616.07 2465.07 2080.86 2595.83 2410.2 1958.26 2323.67 3371.94 3010.76 2854.94 3490.02 3543.96 3943.47 2595.33 2907.55 2977.59 2742.08 2817.19 2681.15 4158.9 3623.44 3783.54 3540.27 3089.65 3222.97 3611.42 4156.05 3830.75 4062.09 3689.94 4142.75 y 10078.53 10780.56 11136.03 8158.32 9133.44 8497.56 6075.09 6479.04 5691.79 6678.15 7474.95 7796.98 8452.3 7683.93 7320.19 9066.6 8729.03 9455.86 4340.84 3889.73 4763.68 6689.84 5599.1 6065.43 5507.01 4967.79 6110.07 5140.27 4877.74 5968.28 3729.34 3573.63 3595.49 3714.97 3875.08 4662.9 5187.27 5229.81 6134.97 4517.09 3669.3 3743.96 383 Ueq 104 104 104 83 83 83 57 57 57 55 55 55 58 58 58 63 63 63 77 77 77 76 76 76 62 62 62 60 60 60 67 67 67 81 81 81 82 82 82 80 80 80 Atom Occupancy 0.5 O5A 0.5 O5B 0.5 O6A 0.5 O6B 0.5 C19A 0.5 C19B 0.5 C20A 0.5 C20B 0.5 C21A 0.5 H21A 0.5 H21B 0.5 H21C 0.5 C21B 0.5 H21D 0.5 H21E 0.5 H21F 0.5 C22A 0.5 H22A 0.5 H22B 0.5 H22C 0.5 C22B 0.5 H22D 0.5 H22E 0.5 H22F 0.5 C23A 0.5 H23A 0.5 H23B 0.5 H23C 0.5 C23B 0.5 H23D 0.5 H23E 0.5 H23F 0.5 C24A 0.5 H24A 0.5 H24B 0.5 H24C 0.5 C24B 0.5 H24D 0.5 H24E 0.5 H24F Table 10-15 Atomic Occupancies for all atoms that are not fully occupied in 3a. 384 Figure 10-3 Structure of 3a’’ Formula CCDC Dcalc./ g cm-3 m/mm-1 Formula Weight Color Shape Size/mm3 T/K Crystal System Space Group a/Å b/Å c/Å a/° b/° g/° V/Å3 Z Z' Wavelength/Å Radiation type Qmin/° Qmax/° Measured Refl's. Indep't Refl's Refl's I≥2 s(I) Rint Parameters Restraints Largest Peak Deepest Hole GooF wR2 (all data) wR2 R1 (all data) R1 C24H38B3FO6 2126641 1.185 0.697 473.97 colourless block-shaped 0.21×0.12×0.03 100.00(10) trigonal R-3c 12.7356(3) 12.7356(3) 28.3761(7) 90 90 120 3985.8(2) 6 0.166667 1.54184 Cu Ka 5.079 79.643 11224 971 930 0.0585 59 0 0.546 -0.319 1.045 0.1672 0.1654 0.0691 0.0673 Table 10-16 General Crystal Structure Data for Compound 3a’’. 385 Atom F1 O1 C1 C2 C3 C4 C5 B1 x 0 3423.9(13) 0 1118(2) 4369.3(19) 4816(3) 5401(2) 2342(3) y 2258(3) 2445.9(13) 1080(2) 1118(2) 3666.7(18) 3561(2) 4138(2) 2342(3) z 7500 7629.4(5) 7500 7500 7496.1(7) 7015.2(9) 7851.7(10) 7500 Ueq 29.4(9) 37.1(5) 33.1(7) 34.6(7) 33.5(5) 54.7(7) 51.0(7) 31.7(7) Table 10-17 Fractional Atomic Coordinates (×104) and Equivalent Isotropic Displacement Parameters (Å2×103) for 3a’’. Ueq is defined as 1/3 of the trace of the orthogonalised Uij. Atom F1 O1 C1 C2 C3 C4 C5 B1 U11 28(2) 39.3(8) 44.9(16) 42.6(12) 36.8(11) 62.0(17) 35.6(12) 39.2(13) U22 23.4(15) 35.1(8) 37.6(11) 42.6(12) 34.3(10) 52.4(15) 52.7(14) 39.2(13) U33 38(2) 43.5(8) 19.1(11) 18.8(11) 38.5(10) 54.9(15) 68.3(16) 22.3(12) U23 0.7(9) 11.8(6) 0.0(5) 0.2(5) 9.3(8) 3.4(11) 19.0(12) -1.2(5) U13 1.4(18) 6.2(6) 0.0(10) -0.2(5) 8.3(8) 25.4(12) -4.0(11) 1.2(5) U12 13.8(11) 23.7(7) 22.4(8) 21.3(14) 24.7(9) 32.5(13) 24.8(11) 23.8(14) Table 10-18 Anisotropic Displacement Parameters (×104) for 3a’’. The anisotropic displacement factor exponent takes the form: -2p2[h2a*2 × U11+ ... +2hka* × b* × U12]. 386 Atom F1 O1 O1 C1 C1 C2 C3 C3 C3 Atom C1 C3 B1 C21 C2 B1 C32 C4 C5 Length/Å 1.501(5) 1.462(3) 1.367(2) 1.400(2) 1.400(2) 1.559(5) 1.550(4) 1.510(3) 1.522(3) Table 10-19 Bond Lengths in Å for 3a’’. Atom Atom Atom B1 C21 C2 C2 C1 C1 C12 O1 O1 O1 C4 C4 C5 O1 O1 O13 C3 F1 F1 C21 C12 B1 B1 C33 C4 C5 C33 C5 C33 O13 C2 C2 O1 C1 C1 C1 C2 C2 C2 C3 C3 C3 C3 C3 C3 B1 B1 B1 Angle/° 106.73(16) 118.27(15) 118.27(15) 123.5(3) 116.5(3) 121.73(15) 121.73(15) 101.77(10) 106.59(18) 109.71(16) 114.6(2) 110.2(2) 113.35(18) 112.9(3) 123.55(13) 123.55(13) Table 10-20 Bond Angles in ° for 3a’’. 387 Atom F1 F1 C11 C1 C11 C1 C23 C23 C3 C3 B1 B1 B1 Atom C1 C1 C2 C2 C2 C2 C1 C1 O1 O1 O1 O1 O1 Atom C2 C2 B1 B1 B1 B1 C2 C2 B1 B1 C3 C3 C3 Atom C11 B1 O12 O1 O1 O12 C11 B1 O12 C2 C32 C4 C5 Angle/° 180.0 0.000(0) 161.20(8) 161.20(8) -18.80(8) -18.80(8) 0.000(0) 180.000(0) -10.72(9) 169.28(9) 25.8(2) -94.54(18) 146.16(16) Table 10-21 Torsion Angles in ° for 3a’’. Atom H1 H4A H4B H4C H5A H5B H5C x 0 4175.49 5029.25 5532.11 6017.77 5763.26 5085.47 y 1825.47 3359.21 2920.8 4333.91 4967.88 3616.65 4132.71 z Ueq 7500 6781.72 7020.73 6931.14 7768.14 7848.82 8167.29 40 82 82 82 76 76 76 Table 10-22 Hydrogen Fractional Atomic Coordinates (×104) and Equivalent Isotropic Displacement Parameters (Å2×103) for 3a’’. Ueq is defined as 1/3 of the trace of the orthogonalised Uij. Atom Occupancy 0.3333 0.6667 F1 H1 Table 10-23 Atomic Occupancies for all atoms that are not fully occupied in 3a’’. 388 Figure 10-4 Structure of [Ir(Bpin)3]3 Formula CCDC Dcalc./ g cm-3 m/mm-1 Formula Weight Color Shape Size/mm3 T/K Crystal System Space Group a/Å b/Å c/Å a/° b/° g/° V/Å3 Z Z' Wavelength/Å Radiation type Qmin/° Qmax/° Measured Refl's. Indep't Refl's Refl's I≥2 s(I) Rint Parameters Restraints Largest Peak Deepest Hole GooF wR2 (all data) wR2 R1 (all data) R1 C54H108B9Ir3O18 2250220 1.562 10.834 1719.29 red octahedral-shaped 0.24×0.19×0.15 100(2) hexagonal P63/m 14.9030(3) 14.9030(3) 19.0012(4) 90 90 120 3654.75(15) 2 0.166667 1.54184 Cu Ka 3.424 79.784 18124 2718 2590 0.0538 147 1 1.705 -1.597 1.222 0.1647 0.1629 0.0588 0.0565 Table 10-24 General Crystal Structure Data for [Ir(Bpin)3]3. 389 Atom Ir1 O1 O2 O3 O4 C1 C2 C3 C4 C5 C6 C7 C8 C9 C10 C11 C12 B1 B2 x 4192.5(4) 6569(7) 5688(7) 3264(5) 1903(7) 7325(14) 6766(13) 7446(19) 8380(12) 6951(18) 6955(19) 3226(8) 2479(12) 4290(10) 2736(17) 3110(20) 1755(15) 5610(11) 2420(8) y 6284.6(4) 7259(8) 5533(8) 4906(5) 4663(8) 6941(16) 5780(14) 6900(20) 7718(16) 5060(20) 5780(20) 4240(8) 4326(13) 4540(11) 3152(12) 5209(19) 3444(19) 6423(13) 5060(7) z 7500 7500 7500 6770(3) 6122(4) 7256(11) 7500 6470(16) 7500 7224(15) 8345(17) 6192(5) 5677(7) 5932(7) 6506(9) 5145(8) 5266(9) 7500 6744(5) Ueq 29.7(2) 51(2) 48(2) 43.1(14) 69(3) 55(5) 59(4) 76(4) 76(4) 76(4) 76(4) 46(2) 79(4) 70(3) 103(6) 136(10) 130(9) 39(3) 35.0(19) Table 10-25 Fractional Atomic Coordinates (×104) and Equivalent Isotropic Displacement Parameters (Å2×103) for [Ir(Bpin)3]3. Ueq is defined as 1/3 of the trace of the orthogonalised Uij. 390 Atom Ir1 O1 O2 O3 O4 C1 C2 C3 C4 C5 C6 C7 C8 C9 C10 C11 C12 B1 B2 U11 33.5(3) 30(4) 44(5) 46(3) 88(6) 61(12) 54(8) 49(6) 49(6) 49(6) 49(6) 58(6) 100(10) 65(7) 176(19) 240(30) 129(15) 40(7) 46(5) U22 34.5(3) 55(6) 50(5) 55(4) 125(7) 73(13) 76(11) 98(9) 98(9) 98(9) 98(9) 50(5) 121(12) 80(8) 76(10) 220(30) 220(20) 61(9) 35(4) U33 22.3(3) 70(7) 55(6) 33(3) 31(4) 45(10) 44(8) 89(9) 89(9) 89(9) 89(9) 35(5) 51(7) 66(8) 78(10) 49(8) 94(12) 24(6) 27(4) U23 0 0 0 -18(3) -38(4) -6(9) 0 33(9) 33(9) 33(9) 33(9) -16(4) -36(7) -20(7) 16(8) 58(12) -120(15) 0 -2(4) U13 0 0 0 -8(3) -28(4) -11(8) 0 4(7) 4(7) 4(7) 4(7) -5(4) -28(7) 6(6) 37(11) 50(12) -65(11) 0 4(4) U12 18.0(2) 23(4) 28(4) 29(3) 82(6) 45(11) 30(8) 42(6) 42(6) 42(6) 42(6) 30(4) 82(10) 38(7) 78(12) 190(20) 127(17) 31(7) 22(4) Table 10-26 Anisotropic Displacement Parameters (×104) for [Ir(Bpin)3]3. The anisotropic displacement factor exponent takes the form: -2p2[h2a*2 × U11+ ... +2hka* × b* × U12]. 391 Atom Ir1 Ir1 Ir1 Ir1 Ir1 Ir1 Ir1 O1 O1 O2 O2 O3 O3 O4 O4 C1 C1 C1 C2 C2 C7 C7 C7 C8 C8 Atom Ir11 Ir12 O33 O3 B1 B24 B21 C1 B1 C2 B1 C7 B2 C8 B2 C2 C3 C4 C5 C6 C8 C9 C10 C11 C12 Length/Å 2.8423(8) 2.8423(8) 2.284(6) 2.284(6) 2.018(14) 2.022(9) 2.022(9) 1.50(2) 1.346(18) 1.459(19) 1.388(18) 1.463(10) 1.388(12) 1.462(14) 1.371(11) 1.57(3) 1.51(4) 1.486(17) 1.34(3) 1.63(3) 1.536(16) 1.499(16) 1.528(18) 1.55(3) 1.44(2) Table 10-27 Bond Lengths in Å for [Ir(Bpin)3]3. 392 Atom Atom Atom Ir11 O33 O3 O3 O33 O33 B1 B1 B1 B1 B1 B1 B24 B22 B22 B24 B24 B22 B24 B22 B24 B24 B1 B1 C7 B2 B2 B2 O1 O1 C3 C4 C4 C4 O2 O2 C1 C5 C5 C5 O3 O3 O3 C9 C9 C10 Ir12 Ir12 Ir12 Ir11 Ir11 O3 Ir11 Ir12 O3 O33 B22 B24 Ir11 Ir11 Ir12 Ir12 Ir12 O33 O3 O3 O33 B22 C1 C2 Ir1 Ir1 C7 C8 C2 C3 C2 O1 C2 C3 C1 C6 C6 O2 C1 C6 C8 C9 C10 C8 C10 C8 Ir1 Ir1 Ir1 Ir1 Ir1 Ir1 Ir1 Ir1 Ir1 Ir1 Ir1 Ir1 Ir1 Ir1 Ir1 Ir1 Ir1 Ir1 Ir1 Ir1 Ir1 Ir1 O1 O2 O3 O3 O3 O4 C1 C1 C1 C1 C1 C1 C2 C2 C2 C2 C2 C2 C7 C7 C7 C7 C7 C7 Angle/° 60.0 117.95(16) 117.95(16) 71.25(16) 71.25(16) 74.8(4) 172.6(5) 127.4(5) 103.0(4) 103.0(4) 77.6(4) 77.6(4) 107.4(3) 107.4(3) 66.3(3) 66.3(3) 66.3(3) 172.0(3) 172.0(3) 97.3(3) 97.3(3) 90.6(6) 109.0(12) 111.5(12) 150.1(6) 93.7(5) 110.8(7) 110.3(8) 100.9(14) 116.4(16) 104.8(17) 109.1(15) 122.6(16) 103.8(17) 100.8(13) 99.6(11) 107.0(16) 116.0(16) 124.1(16) 106.4(19) 101.8(8) 111.6(8) 105.2(9) 117.8(11) 108.6(11) 110.9(13) Table 10-28 Bond Angles in ° for [Ir(Bpin)3]3. 393 Table 10-28 (cont’d) Atom Atom Atom O4 O4 C7 C12 C12 C12 O1 O1 O2 O3 O4 O4 C7 C11 C11 O4 C7 C11 Ir1 O2 Ir1 Ir11 Ir11 O3 C8 C8 C8 C8 C8 C8 B1 B1 B1 B2 B2 B2 Angle/° 103.5(9) 107.3(12) 109.3(14) 109.0(13) 120.8(14) 106.3(16) 131.8(11) 109.1(11) 119.0(10) 123.6(6) 127.7(7) 108.7(7) 394 Atom Ir1 Ir1 Ir1 Ir1 Ir1 O1 O1 O1 O3 O3 O3 C1 C1 C2 C2 C3 C3 C3 C4 C4 C4 C7 C7 C8 C8 C9 C9 C9 C10 C10 C10 B1 B1 B1 B1 B1 B1 B2 B2 B2 B2 B2 B2 Atom O3 O3 O3 O3 O3 C1 C1 C1 C7 C7 C7 O1 O1 O2 O2 C1 C1 C1 C1 C1 C1 O3 O3 O4 O4 C7 C7 C7 C7 C7 C7 O1 O1 O1 O2 O2 O2 O3 O3 O3 O4 O4 O4 Atom C7 C7 C7 B2 B2 C2 C2 C2 C8 C8 C8 B1 B1 B1 B1 C2 C2 C2 C2 C2 C2 B2 B2 B2 B2 C8 C8 C8 C8 C8 C8 C1 C1 C1 C2 C2 C2 C7 C7 C7 C8 C8 C8 Atom C8 C9 C10 Ir11 O4 O2 C5 C6 O4 C11 C12 Ir1 O2 Ir1 O1 O2 C5 C6 O2 C5 C6 Ir11 O4 Ir11 O3 O4 C11 C12 O4 C11 C12 C2 C3 C4 C1 C5 C6 C8 C9 C10 C7 C11 C12 Angle/° -123.9(12) 2.7(17) 120.3(13) -24.1(7) 153.6(7) 26.3(10) 158.3(17) -77.4(16) -21.3(13) 92.8(12) -143.6(15) -160.9(8) 19.1(8) 180.000(0) 0.000(0) -94.9(14) 37(2) 161.3(16) 147.6(15) -80(2) 44(2) 173.4(7) -8.9(11) 171.3(10) -6.3(13) -143.8(11) -29.7(15) 93.9(18) 90.2(13) -155.7(12) -32.0(19) -28.7(11) 84(2) -159.1(10) -17.5(8) -154.2(14) 92.1(14) 19.1(12) 145.7(10) -96.7(12) 17.8(15) -97.7(14) 147.6(14) Table 10-29 Torsion Angles in ° for [Ir(Bpin)3]3. 395 Atom H3A H3B H3C H4A H4B H4C H5A H5B H5C H6A H6B H6C H9A H9B H9C H10A H10B H10C H11A H11B H11C H12A H12B H12C x 6791.25 7991.82 7635.58 8608.61 8860.97 8365.11 6537.85 7688.21 6760.33 6487.15 7674.46 6815.89 4534.01 4266.24 4763.88 3018.9 2891.45 1983.95 2647.6 3652.86 3427.39 1204.6 2118.17 1451.92 y 6364.77 6732.07 7573.34 8374.55 7466.37 7826.04 4401.5 5283.56 4963.53 5956.58 6296.51 5093.85 5134.87 3955.82 4727.21 3188.66 2712.56 2855.61 5200.08 5107.76 5876.74 2941.46 3120.03 3672.73 z 6266.44 6371.11 6263.56 7252.74 7400.4 8007.69 7474.25 7272.08 6724.91 8595 8455.86 8492.35 5613.84 5679.31 6332.85 6977.67 6204.85 6536.94 4774.96 4934.26 5389.96 5572.49 5046.49 4898.68 Ueq 115 115 115 115 115 115 115 115 115 115 115 115 104 104 104 155 155 155 204 204 204 196 196 196 Table 10-30 Hydrogen Fractional Atomic Coordinates (×104) and Equivalent Isotropic Displacement Parameters (Å2×103) for [Ir(Bpin)3]3. Ueq is defined as 1/3 of the trace of the orthogonalised Uij. 396 Atom Occupancy 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 C1 C3 H3A H3B H3C H4A H4B H4C C5 H5A H5B H5C C6 H6A H6B H6C Table 10-31 Atomic Occupancies for all atoms that are not fully occupied in [Ir(Bpin)3]3. 397