DIRECTED IRIDIUM C(sp3)–H BORYLATION CATALYSIS WITH HIGH N-ADJACENT SELECTIVITY By Anshu Yadav A THESIS Submitted to Michigan State University in partial fulfillment of the requirements for the degree of Chemistry—Master of Science 2022 ABSTRACT DIRECTED IRIDIUM C(sp3)–H BORYLATION CATALYSIS WITH HIGH N-ADJACENT SELECTIVITY By Anshu Yadav Modern approaches for the conversion of C–H bonds to C–B bonds involve transition metal catalysts that have various advantages over traditional methods by using cheap and abundant hydrocarbon starting materials, reducing toxic by-products and streamlining the synthesis of biologically important molecules. Metal-catalyzed C–H borylation reactions that produce organoboronic esters are mostly focused on the functionalization of sp2 C–H bonds of heteroarenes and aromatic hydrocarbons. However, in this work the functionalization of sp3 C–H bonds is being explored. Borylation involving sp3 C–H bonds have been shown by Sawamura and co-workers with solid silica supported phosphine ligands offering a directing strategy where a metal center can accept donor directing groups. While this ligand generates highly active borylation catalysts, it requires a lot of steps in the synthesis of the ligand. In this work, easily synthesized homogeneous bidentate monoanionic ligands were tested for the borylation of sp3 C–H bonds. Herein is reported borylation of sp3 C–H bonds of N-methyl amide groups using [Ir(OMe)(cod)]2 as a precatalyst and B2pin2 as a commercially available boron source. Following the borylation of amide as a directing group, amidine molecules are being investigated. To my friends and family iii ACKNOWLEDGEMENTS I would like to thank Professor Milton R. Smith III for giving me this opportunity to work in his lab. His guidance, advice and encouragement throughout my studies at Michigan state university are priceless to me. I would also like to thank Dr. Robert Maleczka Jr., Dr. Kin Sing Lee and Dr. James Geiger for serving on my guidance committee. I would also like to thank my parents and my family for their support and encouragement throughout this journey. My studies would not have been possible without their support. I thank all my group members of the Smith lab and Maleczka lab for their friendship and help. I always enjoyed working with them in the lab. iv TABLE OF CONTENTS LIST OF TABLES ...……………………………………………………………………..………vi LIST OF FIGURES ...………………………………………………………………...………….vii LIST OF SCHEMES ...…………………………………………………………………………....x KEY TO ABBREVIATIONS ...………………………………………………………………….xi CHAPTER 1: INTRODUCTION …………………………………………………………………1 CHAPTER 2: AMIDE DIRECTED IRIDIUM (sp3) C-H BORYLATION CATALYSIS WITH HIGH N-METHYL SELECTIVITY ..……………………………………………………………8 CHAPTER 3: AMIDINE DIRECTED IRIDIUM (sp3) C-H BORYLATION CATALYSIS WITH HIGH N-METHYL SELECTIVITY ...…………………………………………………………..15 CHAPTER 4: SUMMARY AND FUTURE WORK ...………………………………………….20 CHAPTER 5: EXPERIMENTAL DETAILS AND CHARACTERIZATION DATA ………….23 APPENDIX ...……………………………………………………………………………………80 REFERENCES …………………………………………………………………………………140 v LIST OF TABLES Table 1: Optimization of reaction conditions ................................................................................. 9 Table 2: Optimization of reaction conditions: Screening of boron partner .................................. 19 vi LIST OF FIGURES Figure 1: 1H NMR spectrum of crude material at different interval of time of reaction of 5 with [Ir(OMe)(cod)]2 (1.5 mol %, 0.0075 mmol), L3 (3 mol %, 0.015 mmol), 1.5 equiv of B2pin2 at 80 ºC in 2 mL THF…………………………………………………………………………………..17 Figure 2: 11B NMR spectrum of crude material at different interval of time of reaction of 5 with [Ir(OMe)(cod)]2 (1.5 mol %, 0.0075 mmol), L3 (3 mol %, 0.015 mmol), 1.5 equiv of B2pin2 at 80 ºC in 2 mL THF………………………………………………………………………..…………18 Figure 3: 1H NMR (500 MHz, CDCl3) L3.................................................................................... 81 Figure 4: 13C NMR (125 MHz, CDCl3) L3................................................................................... 82 Figure 5: 29Si NMR (99 MHz, CDCl3) L3 .................................................................................... 83 Figure 6: 1H NMR (500 MHz, CDCl3) L4.................................................................................... 84 Figure 7: 13C NMR (125 MHz, CDCl3) L4................................................................................... 85 Figure 8: 29Si NMR (99 MHz, CDCl3) L4 .................................................................................... 86 Figure 9: 1H NMR (500 MHz, CDCl3) L5.................................................................................... 87 Figure 10: 13C NMR (125 MHz, CDCl3) L5................................................................................. 88 Figure 11: 1H NMR (CDCl3, 500 MHz) 3a .................................................................................. 89 Figure 12: 13C NMR (125 MHz, CDCl3) 3a ................................................................................. 90 Figure 13: 11B NMR (CDCl3, 160 MHz) 3a ................................................................................. 91 Figure 14: 1H NMR (CDCl3, 500 MHz) 3c .................................................................................. 92 Figure 15: 13C NMR (125 MHz, CDCl3) 3c ................................................................................. 93 Figure 16: 11B NMR (CDCl3, 160 MHz) 3c ................................................................................. 94 Figure 17: 1H NMR (CDCl3, 500 MHz) 3b .................................................................................. 95 Figure 18: 13C NMR (125 MHz, CDCl3) 3b ................................................................................. 96 Figure 19: 11B NMR (CDCl3, 160 MHz) 3b ................................................................................. 97 vii Figure 20: 1H NMR (CDCl3, 500 MHz) 3e .................................................................................. 98 Figure 21: 13C NMR (125 MHz, CDCl3) 3e ................................................................................. 99 Figure 22: 11B NMR (CDCl3, 160 MHz) 3e ............................................................................... 100 Figure 23: 1H NMR (CDCl3, 500 MHz) 3d ................................................................................ 101 Figure 24: 13C NMR (125 MHz, CDCl3) 3d ............................................................................... 102 Figure 25: 11B NMR (CDCl3, 160 MHz) 3d ............................................................................... 103 Figure 26: 1H NMR (CDCl3, 500 MHz) 3f ................................................................................. 104 Figure 27: 13C NMR (125 MHz, CDCl3) 3f................................................................................ 105 Figure 28: 11B NMR (CDCl3, 160 MHz) 3f................................................................................ 106 Figure 29: 1H NMR (CDCl3, 500 MHz) 3g ................................................................................ 107 Figure 30: 13C NMR (125 MHz, CDCl3) 3g ............................................................................... 108 Figure 31: 11B NMR (CDCl3, 160 MHz) 3g ............................................................................... 109 Figure 32: 1H NMR (CDCl3, 500 MHz) 3h ................................................................................ 110 Figure 33: 13C NMR (125 MHz, CDCl3) 3h ............................................................................... 111 Figure 34: 11B NMR (CDCl3, 160 MHz) 3h ............................................................................... 112 Figure 35: 1H NMR (CDCl3, 500 MHz) 3i ................................................................................. 113 Figure 36: 13C NMR (125 MHz, CDCl3) 3i ................................................................................ 114 Figure 37: 11B NMR (CDCl3, 160 MHz) 3i ................................................................................ 115 Figure 38: 1H NMR (CDCl3, 500 MHz) 3k ................................................................................ 116 Figure 39: 13C NMR (125 MHz, CDCl3) 3k ............................................................................... 117 Figure 40: 11B NMR (CDCl3, 160 MHz) 3k ............................................................................... 118 Figure 41: 1H NMR (CDCl3, 500 MHz) 3l ................................................................................. 119 Figure 42: 13C NMR (125 MHz, CDCl3) 3l ................................................................................ 120 viii Figure 43: 11B NMR (CDCl3, 160 MHz) 3l ................................................................................ 121 Figure 44: 1H NMR (CDCl3, 500 MHz) 3o ................................................................................ 122 Figure 45: 13C NMR (125 MHz, CDCl3) 3o ............................................................................... 123 Figure 46: 11B NMR (CDCl3, 160 MHz) 3o ............................................................................... 124 Figure 47: 1H NMR (CDCl3, 500 MHz) 3q ................................................................................ 125 Figure 48: 13C NMR (125 MHz, CDCl3) 3q ............................................................................... 126 Figure 49: 11B NMR (CDCl3, 160 MHz) 3q ............................................................................... 127 Figure 50: 1H NMR (CDCl3, 500 MHz) 3m ............................................................................... 128 Figure 51: 13C NMR (125 MHz, CDCl3) 3m .............................................................................. 129 Figure 52: 11B NMR (CDCl3, 160 MHz) 3m .............................................................................. 130 Figure 53: 1H NMR (CDCl3, 500 MHz) 4a ................................................................................ 131 Figure 54: 11B NMR (CDCl3, 160 MHz) 4a ............................................................................... 132 Figure 55: 1H NMR (CDCl3, 500 MHz) 4b ................................................................................ 133 Figure 56: 11B NMR (CDCl3, 160 MHz) 4b ............................................................................... 134 Figure 57: 1H NMR (CDCl3, 500 MHz) 4c ................................................................................ 135 Figure 58: 11B NMR (CDCl3, 160 MHz) 4c ............................................................................... 136 Figure 59: 1H NMR (C6D6, 500 MHz) 6a ................................................................................... 137 Figure 60: 11B NMR (C6D6, 160 MHz) 6a.................................................................................. 138 Figure 61: GC/MS Data 6a’ ........................................................................................................ 139 Figure 62: GC/MS Data 6a’’....................................................................................................... 139 ix LIST OF SCHEMES Scheme 1: Mechanism of iridium catalyzed C–H borylation ......................................................... 1 Scheme 2: Early examples of using transition metals in sp3 C–H borylation ................................ 2 Scheme 3: Primary benzylic sp3 C–H borylation ........................................................................... 3 Scheme 4: Secondary sp3 C–H borylation ...................................................................................... 4 Scheme 5: Pyridine as directing group ........................................................................................... 5 Scheme 6: Amide as directing group .............................................................................................. 6 Scheme 7: C–H Borylation at N-methyl position using amide as directing group ......................... 6 Scheme 8: Substrate Scope of amide borylation........................................................................... 11 Scheme 9: Competitive KIE study ................................................................................................ 13 Scheme 10: Plausible catalytic cycle ............................................................................................ 13 Scheme 11: Substrate scope of amidine borylation ...................................................................... 15 Scheme 12: Attempted borylation of secondary amidine using bis(pinacolato)diboron .............. 16 Scheme 13: CHB of N,N-diethyl-N’-methylformimidamide ....................................................... 19 Scheme 14: Substrate scope for CHB on primary amidines ......................................................... 20 Scheme 15: Substrate scope for CHB on secondary amidines ..................................................... 21 Scheme 16: Functionalization of borylated amidine .................................................................... 21 Scheme 17: Introducing chirality in amidine CHB....................................................................... 22 x KEY TO ABBREVIATIONS B2pin2 bis(pinacolato)diboron BG butane-1,2-diol C–H carbon–hydrogen CHB C–H Borylation COD 1,5-cyclooctadiene COE 1-cyclooctene DTBPY 4,4’-di-tert-butyl-2,2’-dipyridyl EG ethane-1,2-diol HBpin pinacolborane KIE kinetic isotope study MBG 3-methylbutane-1,3-diol PG propane-1,2-diol TMPHEN 3,4,7,8-tetramethyl-1,10-phenanthroline xi CHAPTER 1: INTRODUCTION C–H borylation (CHB) is the direct functionalization of a C–H bond into a C-B bond eliminating the need of pre-installed halogens for the formation of boronic esters. Since the first thermal iridium catalyzed C–H borylation of arenes,3 use of transition metals for borylation has become a method of choice for the formation of aryl boronic esters.2 The standard procedure for iridium catalyzed C–H borylation involves use of [Ir(OMe)(cod)]2 (cod = 1,5-cyclooctadiene) as the precatalyst, 4,4’-di-tert-butyl-2,2’-dipyridyl (dtbpy) as the ligand and pinacolborane(HBpin) or bis(pinacolato)diboron (B2pin2) as the boron source.2 Borylation of arenes has been predominated by steric factors resulting in formation of meta and para substituted aryl boronic esters. Scheme 1: Mechanism of iridium catalyzed C–H borylation Bpin t-Bu N Bpin Ir Bpin N H O O O H t-Bu Bpin B B H B O O O B2pin2 HBpin II Me O t-Bu Bpin t-Bu Bpin Ir Ir N Bpin N Bpin O Ir Ir N Bpin N H Me t-Bu t-Bu I III [Ir(cod)OMe]2 H Bpin pinB Bpin or or H H t-Bu Bpin H Bpin N Bpin Ir Bpin N N N H t-Bu H/Bpin dtbpy IV Adding the precatalyst, ligand and boron source results in the formation of trisboryl Ir(III) complex I as the active form of the catalyst. After the formation of trisboryl Ir(III) complex I, the oxidative addition of the arene C–H bond to the metal center by C–H activation has been determined to be the rate determining step to form Ir(V) complex II. Reductive elimination of the boronic ester 1 results in formation of intermediate complex III. To regenerated complex I B2pin2/HBpin adds to the metal center to form complex IV followed by reductive elimination of HBpin/H2 respectively to close the catalytic cycle (Scheme 1).4,5 Borylation of sp2 C–H bonds using transition metal catalysts has been researched extensively while sp3 C–H bond has not been, which can be implied due to the large number of publications of C–H borylation of arenes following initial discovery as compared to the small prevalence of sp3 C–H borylation in the literature.2 Early interest in sp3 C–H borylation used an electrophilic, covalently bound ligand with tungsten metal as center. Irradiation of the transition metal complex with a 450- W, medium-pressure hanovia mercury arc lamp resulted in the formation of alkyl boronic esters with regioselectivity for the terminal positions.6 Scheme 2: Early examples of using transition metals in sp3 C–H borylation hν Bcat’ Me O 74% OC B W O OC CO Me hν Bcat’ 85% O O Cp*Ir(C2H4)2 (10 mol %) B B O B O O 200 ºC, 10 days O 58% Yield As Hartwig and co-workers demonstrated a photo induced sp3 CHB of alkanes, the interest of many others to further study this type of reactions sparked. An iridium metal catalyst was used for formation of a single product at the terminal position of linear alkanes from commercially available 2 boron reagents under thermal conditions. It allowed catalytic, regiospecific borylation of alkanes (Scheme 2).7 Scheme 3: Primary benzylic sp3 C–H borylation 1 mol % [Ir(OMe)(cod)]2 2 mol % dtbpy Et3SiBpin (1 equiv) Bpin R R neat, 80 ºC (10 equiv) F3C CF3 SiEt3 1 mol % catalyst H N Ir Et3SiBpin (1 equiv) Bpin R R Cl N MeCy, 100 ºC 2 (1.5 equiv) F3C CF3 catalyst Substrates other than alkane containing terminal methyl groups have been used for sp3 C–H borylation.8 Hartwig and co-workers showed that by installing a silane in a diboron reagent, sp3 C–H borylation could be done on derivatives of toluene, although borylation was observed both at aryl and methyl C–H bonds. Also, in absence of a terminal methyl position in case of ethylbenzene, borylation was observed exclusively on aryl C–H bonds.9 Another example of benzylic C–H borylation involves the use of a preassembled catalyst. The preassembled catalyst was generated by combining a 1:1 mixture of iridium precatalyst [Ir(COE)2(Cl)]2 and an electron deficient phenanthroline ligand in THF with triethyl silane to form a purple/brown solid. The preassembled catalyst along with Et3SiBpin as the boron reagent of choice was used for the benzylic C–H borylation tolerating halogens, methoxy, carboalkoxy, carbamoyl and dialkylamino functional groups (Scheme 3).10 3 Scheme 4: Secondary sp3 C–H borylation (η6-mes)Ir(Bpin)3 (4 mol %) 2,9-Me2phen (4 mol %) X B2pin2 (1 equiv) X R R n n Ir Y H neat, 120 ºC, 14 h Y Bpin Bpin Bpin Bpin n = 0,1,2 X = O, CH2 (η6-mes)Ir(Bpin)3 Y = CH2, O, NPiv (η6-mes)Ir(Bpin)3 (4 mol %) 2,9-Me2phen (4 mol %) B2pin2 (1 equiv) R R N N THF, 90 ºC, 12 h Me Me H Bpin 2,9-Me2phen Hartwig and co-workers later found that in absence of terminal methyl groups, successful borylation of secondary sp3 C–H bond could be done on cyclic ethers. The borylation happen with selectivity for C–H bonds at 3-position over the weaker C–H bonds located at 2-position.11 Moreover, the borylation on cyclopropane derivatives were shown to occur selectively at the methylene C–H bonds of the cyclopropane ring over methine C–H bonds catalyzed by the combination of [(η6-mes)Ir(Bpin)3] pre-catalyst and 2,9-Me4phen ligand to yield predominantly the trans-substituted boronic esters . The high diastereoselectivity was proposed to be due to the greater steric demand of ligand near the metal center (Scheme 4).12 4 Scheme 5: Pyridine as directing group P Internal C(sp3)-H [Ir(OMe)(COD)]2 (2 mol %) Silica-SMAP (2 mol %) Si N H N Bpin B2pin2 (1 equiv) O H t-BuOMe, 60 °C H Si 2 2 O O H H O Terminal C(sp3)-H Benzylic C-H Yield - 95% Silica-SMAP [Ir(OMe)(COD)]2 (3 mol %) (R,R)P-Si (3 mol %) N H N Bpin Si H B2pin2 (1 equiv) O O CH3 CPME, 80 °C CH3 P O O Yield - 83% 99% ee (R,R)P-Si Directing groups have been used to facilitate borylation on secondary sp3 C–H bonds in presence of primary sp3 C–H bonds. Sawamura et. al. showed that they could direct sp3 CHB using an iridium pre-catalyst bound by a silica tethered monodentate heterogeneous ligand. This system was capable of activating gamma(γ) C–H bonds from nitrogen atom in the presence of benzylic and primary C–H bonds.13 Furthermore, asymmetric borylation of secondary C–H bonds was shown to be possible by the same group using pyridine again as the directing group and a chiral homogenous ligand with high enantioselectivity. This reaction was successful with both electron donating and electron withdrawing groups on pyridyl moiety (Scheme 5).14 5 Scheme 6: Amide as directing group Ph Ph [Ir(COD)Cl]2 (2.5 mol %) H O Ligand (5 mol %) OH O Ph H N N B2pin2 (1 equiv) B Me R N R N N n-hexane, 60 ºC Si then NaOH/H2O2 Me Ph R THF/H2O2, rt Ph R = Adamantane Ligand Enantioselective borylation of methylene C–H bonds β to the carbonyl group was later achieved by Xu and co-workers where amides were used as a directing group using commercially available iridium precatalyst and chiral bidentate ligand (Scheme 6).15 Scheme 7: C–H Borylation at N-methyl position using amide as directing group [Rh(OMe)(COD)]2 (0.5 mol %) O Silica-TRIP (0.5 mol %) O Bpin O SiO2 Si O Si P B2pin2 (1 equiv) O R N R N n-hexane, 60 ºC (2 equiv) Silica-TRIP [Ru catalyst] 0.05-1 mol % Bpin O O O B2pin2 (1 equiv) H O R X i-Pr2P Ru Pi-Pr2 R X neat, 120 ºC X = N, O Ru catalyst [Ir(OMe)(COD)]2 (1.25 mol %) Ligand (2.5 mol %) O O Bpin B2pin2 (2 equiv) N R N R N H Si dioxane, 120 ºC R R (2 equiv) Ligand 6 Various transition metals have been used for the borylation at the N-methyl position of amide group. A monodentate heterogeneous ligand with [Rh(OMe)(cod)]2 as precatalyst was employed for the borylation in hexane by Sawamura and co-workers16 while a ruthenium pincer catalyst was used by Hao group in a neat solution of amide and ester derivatives involving high temperature.17 The Clark group has shown borylation of amide by [Ir(OMe)(cod)]2 precatalyst and quinoline silyl ligand at high temperature with a limited substrate scope (Scheme 7).18 Building on previous observations, amides were further studied by our group targeting N-methyl position for borylation using silylated pyridine ligands. 7 CHAPTER 2: AMIDE DIRECTED IRIDIUM (sp3) C–H BORYLATION CATALYSIS WITH HIGH N-METHYL SELECTIVITY This project was in collaboration with Dr. Jonathan Dannat of the Maleczka Lab, who performed the optimization of reaction conditions and competitive kinetic isotope study. The study was initiated with the borylation of N,N-dimethylacetamide (1a) under various conditions (Table 1). As it has been shown that sp3 CHB can occur without addition of a ligand,19 and both dtbpy and tmphen (dtbpy = 4,4’-tert-butyl-2,2’-bipyridine, tmphen = 3,4,7,8-tetramethyl-1,10- phenanthroline) are common CHB ligands, we started by screening these conditions. No reaction occurred without ligand addition and both dtbpy and tmphen provided a complex mixture of products in the 1H NMR spectrum (Table 1, entries 1-3). Ligand (L1), which has been used for ortho-selective borylations of arylimines,20 provided low conversion of (1a). Unfortunately, increased reaction temperature provided no additional conversion (entry 5). Given the low reactivity of (L1) and that Sawamura demonstrated immobilization of the phosphine ligand was necessary for the sp3 C–H activation to occur,21 we expected that a covalent bond between the ligand and the precatalyst would be crucial for generating a catalyst with the proper geometry for directed CHB. In 2014, we published silyl phosphorus and nitrogen based bidentate, monoanionic ligand frameworks for iridium catalyzed ortho selective borylations.22 The anionic silyl ligand replaces a spectating boryl and due to the bidentate nature, the metal to neutral donor ligand ratio is well controlled. Satisfyingly, previously reported silyl-nitrogen ligand (L2) provided 60% conversion of (1a) (entry 6). With this result, we sought to optimize the structure of this ligand framework. The pKa of 2- methylpyridinium is 1.36 units higher than the pKa of quinolinium in acetonitrile.23 Since more electron rich ligands accelerate borylation rates, we prepared pyridine-based ligand (L3), which 8 Table 1: Optimization of reaction conditions O 1.5 mol % [Ir(OMe)(cod)]2 O Bpin 3 mol % ligand N Boron Source N THF, temp 1a 2a N N N MeO N N N N N N NH2 H Si iPr H Si iPr H Si iPr H Si Me iPr iPr iPr Me dtbpy tmphen L1 L2 L3 L4 L5 entry ligand temp ºC boron source 2aa 1 no ligand 60 B2pin2 0% 2 dtbpy 60 B2pin2 complex mixture 3 tmphen 60 B2pin2 complex mixture 4 L1 60 B2pin2 10% 5 L1 80 B2pin2 10% 6 L2 60 B2pin2 60% 7 L3 60 B2pin2 91% 8 L4 60 B2pin2 complex mixture 9 L5 60 B2pin2 11% 10b L3 80 B2pin2 100% 11c L3 80 HBpin complex mixture 12 L3 80 B2eg2 0% 13d L3 80 B2pin2 85% Conditions: 1 (1 equiv, 0.5 mmol), Boron source (1.2 equiv, 0.6 mmol), [Ir(OMe)(cod)]2 (1.5 mol %, 0.0075 mmol), ligand (3 mol %, 0.015 mmol) in 2 mL THF. aBased on 1H NMR. bReaction time: 7.5 h. c2 equiv HBpin. d0.75 mol % [Ir(OMe)(cod)]2, 1.5 mol % L3. pin = pinacolate, eg = ethylene glycolate gave nearly full conversion to the desired product. Additional donation (L4) and decreasing the steric hindrance around the silyl site (L5) both provided inferior results (entries 8 and 9); however, by simply increasing the reaction temperature to 80 °C, full conversion to the product was achieved in 7.5 hours (entry 10). Adjusting the boron source and lowering the catalyst loading all had negative impacts on the reaction. Solvent optimization revealed ethereal solvents provided superior conversion. Non-polar solvents such as hexane, cyclohexane and toluene provided 75%- 9 86% conversion while dioxane provided full conversion (see CH 5 for details). With optimum reaction conditions in hand, we sought to explore substrate scope. We first selected a number of acyclic and cyclic alkyl dimethyl amides (1a-l). Notably, perfect N- methyl regioselectivity was observed for compounds (1b) and (1c) where two primary C(sp3)–H bonds are equidistant from the directing carbonyl and could potentially be activated. The increased sterics of the isopropyl group (1c) had no adverse effect on the reaction. Moreover, increased chain length and acyclic alkyls (1d-i) were tolerated. Cyclic amides (1j-l) proceeded smoothly; however, the reactivity of (1j) was significantly attenuated. We attribute the low reactivity to the increased distance of the N-methyl C–H bond from the directing carbonyl in the 5-membered ring (2.414 Å, calculated at ωB97x-D 6-31G*) compared to the 6- and 7-membered rings (2.243 Å and 2.241 Å respectively). Where both primary and secondary C–H bonds are available, the catalyst displays high regioselectivity for the sterically least hindered C–H bond (1m). While compound (1m) showed high selectivity for primary methyl C–H bonds, in cases with only secondary C–H bonds no reaction occurs (1r). Other amide-like moieties such as a carbamate and urea directed the C(sp3)–H borylation (1n-o). Product (1n) is a promising result as carbamates can be readily generated from the corresponding amines using standard protecting group protocols.24 Since iridium based borylation catalysts are notably active toward C(sp2)–H bonds, we wondered about the regioselectivity of N,N- dimethylbenzamide (1p). Interestingly, the C(sp2)–H borylation was significantly favored and no C(sp3)–H activation was observed. Interestingly, increasing the distance between the directing amide and the C(sp2)–H bonds by two methylene linkers yielded perfect selectivity for the C(sp3)– H bond (2q). This important result demonstrates the tolerance of aromatic C–H bonds. 10 There were also a number of instructive substrates with no observed reactivity. Trifluoromethyl and chloro-substituted compounds (1s-1u) showed little to no evidence of borylation. We hypothesized that this could be due to 1) a weaker interaction between the carbonyl oxygen and Scheme 8: Substrate Scope of amide borylation 1.5 mol % [Ir(OMe)(cod)]2 O 3.0 mol % L3 O Bpin B2pin2 (1.5 equiv) R1 N R1 N THF, 80 ºC R2 R2 1 2 Yield% (Conversion%) O Bpin O Bpin O Bpin O Bpin O Bpin N N N N N 2a, 63% (100%) 2b, 77% (95%) 2c, 55% (75%) 2d, 70% (100%) 2e, 68% (100%) O Bpin O Bpin O Bpin O Bpin O Bpin n-Bu N n-hep N N N N 2f, 80% (100%) 2g, 67% (86%) 2h, 79% (92%) 2i, 80% (100%) 2j, 8%(55%)a O Bpin O Bpin O Bpin O Bpin O Bpin N N N O N N N 2k, 70% (100%) 2l, 70% (100%) 2m, 71% (94%) 2n, (47%)b 2o, 89% (97%) Bpin O O Bpin O Bpin O Bpin O Bpin Cl N Ph N N F3C N N 2p, (100%)c 2q, 63% (83%) 2r, (0%) 2s, (0%) 2t, (0%) O Bpin Cl N 2u, (5%)b Conditions: 1 (1 equiv, 1.0 mmol), Boron Source (1.5 equiv, 1.5 mmol), [Ir(OMe)(cod)]2 (1.5 mol %, 0.015 mmol), L3 (3 mol %, 0.03 mmol) in 4 mL THF. aAt 100 °C. bLow conversion inhibited isolation. cmono:diborylated 1.2:1 all C(sp2)–H activation 11 iridium vacant site prohibiting the directing effect or 2) substrates (1s-1u) poison the catalyst. To test these ideas, we performed two borylations of (1a) in the presence of (1s) and (1t), respectively. For the experiment with (1s), a 60% conversion of (1a) to (2a) was observed. This shows that the fluorinated substrate (1s) is not borylated when an active borylation catalyst is present, but (1s) does impede borylation. Substrate (1a) was not borylated in the presence of (1t), which indicates (1t) completely inhibits CHB. The cause of this inhibition is unclear, but it is noteworthy that B2pin2 is present at the conclusion of both reactions. Yao and co-workers recently reported Ru- catalyzed CHBs with B2pin2 in neat amide (1 equiv) at 120 °C.17 Using these conditions, we attempted CHBs of substrates (1a), (1c), (1f) and (1o), but no borylation occurred (see CH 5 for details). We were curious if increasing the reaction temperature would increase the reaction conversion in substrates with low conversion. For substrates (1j) and (1s), borylation at 100 °C was conducted. No change in conversion was observed for substrate (1s). In the case of (1j), conversion increased from 23% to 55%. Interestingly, this higher conversion also revealed small percentages of diborylation. One noteworthy feature of these borylations is the difference between conversion and isolated yield. We found that the borylated products decomposed significantly when exposed to standard silica flash purification techniques. Initially, we attempted neutral alumina to isolate (2a) however, in our hands, only 39% isolated yield was observed. One method to mitigate the decomposition on silica was to deactivate the silica by adding deionized water to the gel (35% w/w) prior to packing the silica column. Deactivation of the silica with water presumably decreases the adsorption capacity of the silica and has been shown to increase isolated yields of borylated products previously.18,25,26 We would note that silica isolation may not be necessary depending on a user’s 12 desired follow-up chemistry as the only byproducts observed from these reactions are borates from the excess boron source. Scheme 9: Competitive KIE study 1.5 mol % O O [Ir(OMe)(cod)]2 O Bpin O Bpin CD3 3.0 mol % L3 CD2 N N N N B2pin2 (1.0 equiv) CD3 THF, 80 ºC CD3 1, 1.5 equiv 1-d6, 1.5 equiv 1a = 5.0 1a-d5 Scheme 10: Plausible catalytic cycle [Ir(OMe)(cod)]2 L3, B2pin2 Bpin Si O Ir Bpin HBpin N I N B2pin2 1a Bpin Bpin Si Bpin Si Si N Ir Ir H = N O N N H Si II IV N O Bpin Bpin N Si Bpin Ir H 2a N O III N 13 Typically, C–H activation is the turnover-limiting step for Ir-catalyzed aromatic C–H borylations, substantiated by primary kinetic isotope effects (KIEs) where kH/kD values range from 3-5.4 Reported primary KIEs for Ir-catalyzed C(sp3)–H borylations are typically lower, with kH/kD values ranging from 2-3.27,10,12 In our system, a competitive kinetic isotope study between N,N- dimethylacetamide (1) and N,N-dimethylacetamide-d6 (1-d6) with limiting B2pin2 was conducted (Scheme 9). The kH/kD value of 5.0 is the largest primary KIE value reported for a C(sp3)–H borylation. Thus, C–H cleavage is the turnover limiting step. A proposed mechanism for amide borylation is presented in Scheme 10. Upon mixing the iridium precatalyst, ligand (L3) and B2pin2 complex I is generated. This 14-electron complex can readily coordinate amide substrate 1 generating 16-electron complex II. This initial coordination event explains the lack of reactivity observed in electron deficient substrates as they will only weakly coordinate. Complex II then proceeds through the turnover limiting step activating the amide N- methyl C(sp3)–H bond generating complex III. This intermediate must then reductively eliminate the C-B bond and lose the product from the coordination sphere. The loss of product from the coordination sphere is likely assisted by a strong interaction between the carbonyl oxygen and boron in the boronic ester. This interaction is supported by a sharp boron peak in the 11B NMR observed for all C(sp3) borylated products. Finally, regeneration of complex I from complex IV can occur through oxidative addition of B2pin2 followed by reductive elimination of HBpin. 14 CHAPTER 3: AMIDINE DIRECTED IRIDIUM (sp3) C–H BORYLATION CATALYSIS WITH HIGH N-ADJACENT SELECTIVITY Scheme 11: Substrate scope of amidine borylation R 1.5 mol % [Ir(OMe)(cod)]2 R N 3 mol % L3 N Bpin B2pin2 (1.50 equiv) N N THF, 80 ºC, 1 h 3 4 Conversion(%) N Bpin N Bpin N Bpin N N N 4a, 100% 4b, 100% 4c, 100% Conditions: 3 (1 equiv, 0.5 mmol), boron source (1.5 equiv, 0.75 mmol), [Ir(OMe)(cod)]2 (1.5 mol %, 0.0075 mmol), L3 (3 mol %, 0.015 mmol) in 2 mL THF. Successful CHB of amides28 inspired me to try CHB on amidines as the oxygen atom in amides is replaced by a nitrogen atom that is a better donor and could act as a directing group. The study was initiated using the same reaction conditions as used for amide substrates. N’-(sec-Butyl)-N,N- dimethylacetimidamide (3a) was tested for the C–H borylation at the N-methyl position and 100% conversion of N’-(sec-butyl)-N,N-dimethylacetimidamide was observed in 1 hour as compared to 24 hours required for most amides. Two other amidine substrates (3b-3c), not having any chiral centers, gave complete conversion of starting material. Further, 0.5, 0.75, 1.0 and 1.5 equivalents of bis(pinacolato)diboron were tested with (3c) and C–H borylation was observed in all cases with 100% conversion. 15 Scheme 12: Attempted borylation of secondary amidine using bis(pinacolato)diboron 1.5 mol % [Ir(OMe)(cod)]2 N 3 mol % L3 B2pin2 (XX equiv) N COMPLEX MIXTURE THF, temp, 24-48 h 5a Equivalents of B2pin2 (Boron Source) S.No. Temp (ºC) 0.5 0.75 1.0 1.5 1 40 Complex Complex Complex Complex mixture mixture mixture mixture 2 60 Complex Complex Complex Complex mixture mixture mixture mixture 3 80 Complex Complex Complex Complex mixture mixture mixture mixture Conditions: 5 (1 equiv, 0.5 mmol), boron source (XX equiv, xx mmol), [Ir(OMe)(cod)]2 (1.5 mol %, 0.0075 mmol), L3 (3 mol %, 0.015 mmol) in 2 mL THF. Excited with results for C–H borylation at the N-methyl position of amidines, the same reaction conditions were tested for C–H borylation of amidines at secondary C–H bonds. This resulted in 11 formation of complex mixture. Upon looking at B NMR spectrum of reaction, a peak at 8.57 ppm increases in intensity over time indicating formation of a bond between nitrogen and boron, which is an indication of formation of product. However, in the 1H NMR spectrum no product peaks are observed and hence a complex mixture is observed. As C–H borylation was observed for different equivalents (0.5, 0.75, 1.0 and 1.5) of bis(pinacolato)diboron with (3b), we started our screening conditions with using those equivalents. Unfortunately, a complex mixture was 16 observed in all cases. Decreasing the reaction temperature from 80 ºC to 60 ºC and 40 ºC resulted in low reactivity. AY_209a_27h_PROTON_01 6 AY_209a_12h_PROTON_01 5 AY_209a_9h_PROTON_01 4 AY_209a_6h_PROTON_01 3 AY_209a_3h_PROTON_01 2 AY_209a_1h_PROTON_01 1 4.3 4.2 4.1 4.0 3.9 3.8 3.7 3.6 3.5 3.4 3.3 3.2 3.1 3.0 2.9 2.8 2.7 2.6 2.5 2.4 2.3 2.2 2.1 2.0 1.9 1.8 1.7 1.6 1.5 1.4 1.3 1.2 1.1 1.0 0.9 0.8 0.7 0.6 f1 (ppm) Figure 1: 1H NMR spectrum of crude material at different interval of time of reaction of 5 with [Ir(OMe)(cod)]2 (1.5 mol %, 0.0075 mmol), L3 (3 mol %, 0.015 mmol), 1.5 equiv of B2pin2 at 80 ºC in 2 mL THF 17 AY_209a_27h_s2pul_01 6 AY_209a_12h_s2pul_01 5 AY_209a_9h_s2pul_01 4 AY_209a_6h_s2pul_01 3 AY_209a_3h_s2pul_01 2 AY_209a_1h_s2pul_01 1 90 80 70 60 50 40 30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 f1 (ppm) Figure 2: 11B NMR spectrum of crude material at different interval of time of reaction of 5 with [Ir(OMe)(cod)]2 (1.5 mol %, 0.0075 mmol), L3 (3 mol %, 0.015 mmol), 1.5 equiv of B2pin2 at 80 ºC in 2 mL THF Pinacolborane and different diboron partners were also tested. Diboron partners were synthesized from the corresponding glycol and B2(OH)4 via a procedure developed in our lab by Ryan Fornwald.29 B2eg2, B2pg2, B2bg2, B2mbg2 (eg = ethane-1,2-diol, pg = propane-1,2-diol, bg = butane-1,2-diol, mbg = 3-methylbutane-1,3-diol) were used as boron partners. Results are shown in Table 2. Reactions with diboron reagents B2eg2 and B2pg2 gave 100% conversion of starting material in 1 h. A racemic mixture was observed with B2pg2 as the diboron partner. CHB on 18 substrate (5b) was performed successfully with 71% conversion of starting material (based on GC) with prior work showing its amide analog poisoning the catalyst. Table 2: Optimization of reaction conditions: Screening of boron partner 1.5 mol % [Ir(OMe)(cod)]2 N 3 mol % L3 N Bgly B2gly2 (1.0 equiv) N N THF, 80 ºC, 24-26 h 5a 6a O O O O O O O O O B H B B B B B B B B O O O O O O O O O HBpin B2eg2 B2pg2 B2bg2 B2mbg2 S.No. B2gly2 Conversion (%) 1 HBpin 0 a 2 B2eg2 100 b 3 B2pg2 100 b 4 B2bg2 15 5 B2mbg2 0 Conditions: 5 (1 equiv, 0.5 mmol), boron source (1.0 equiv, 0.5 mmol), [Ir(OMe)(cod)]2 (1.5 mol %, 0.0075 mmol), L3 (3 mol %, 0.015 mmol) in 2 mL THF. aNMR Yield = 33% with 1,3,5-trimethoxybenzene as internal standard. b Based on GC/MS. Scheme 13: CHB of N,N-diethyl-N’-methylformimidamide 1.5 mol % [Ir(OMe)(cod)]2 N 3 mol % L3 N Beg B2eg2 (1.0 equiv) H N H N THF, 80 ºC, 1 h 5b 6b 19 CHAPTER 4: SUMMARY AND FUTURE WORK CHB on the N-methyl position of a variety of substrates was made possible with ligand (L3). Following successful CHB on amides, ligand (L3) was used to attempt CHB on the N-methyl position of amidines with 100% conversion of starting material in 1 h as compared to 24 h for amides. CHB from primary C–H bonds to secondary C–H bonds on amidines required change in the diboron partner, with racemic mixture being observed with B2pg2. With optimized conditions in hand, substrates for primary and secondary CHB would be attempted. Scheme 14: Substrate scope for CHB on primary amidines Ph N N N N N N N N N N 3d 3e 3f 3g 3h Scheme 14 shows such informative substrates. Substrate (3d) has two competing primary positions for CHB while substrate (3e) has three primary positions for CHB and substrate (3f) has primary vs secondary positions competing for CHB. It would be interesting to see CHB on primary sp3 C– H bonds in presence of sp2 C–H bonds (3g) and sp C–H bonds (3h). With the CHB on an amidine secondary sp3 C–H bonds demonstrated, extension of the substrate scope is needed. Scheme 15 shows several instructive substrates. Substrates (5d) and (5e) has two secondary position available competing for CHB, whereas (5f) and (5g) have different ring sizes. Morpholine derived amidine (5h) with nitrile group and (5i) would also be interesting, especially if the functionalized morpholine can be extruded from amidine. Reaction in presence of sp2 C–H bonds would be tested with (5j) and (5k). Lastly, borylation of DBU (5c) could be a first step towards making this base chiral. 20 Scheme 15: Substrate scope for CHB on secondary amidines N N N N N N N N N N 5c 5d 5e 5f 5g N N Ph N N N N H N Ph N N O O 5h 5i 5j 5k Scheme 16: Functionalization of borylated amidine Proposed amidine approach N Ph Ph NaOH N HN Proposed aminal formation N Bpg NH Bpg NaBH4 N N Further functionalization of CHB products would be attempted. The borylation of amidine could be followed by cross-couplings to install various aryl groups. Borylated amidines would be an attractive route to synthesize primary borylated amines, as after cross-coupling, simple saponification would free the amine. Likewise, reduction would result in formation of borylated aminals (Scheme 16). 21 Scheme 17: Introducing chirality in amidine CHB [Ir(OMe)(cod)]2 (1.5 mol %) O O Ligand L3 (3 mol %) O O O O N N B N B B B (R,R)-B2pg2 (1.0 equiv) O O N N N (R,R)-B2pg2 THF, 80 ºC With regards to chirality, using (R,R)-B2pg2 in the CHB of (E)-N,N-diethyl-N’- methylacetimidamide would result in formation of two diastereomers, the separation of which would provide the two enantiomers. Chiral variants of ligand (L3) would also be explored. 22 CHAPTER 5: EXPERIMENTAL DETAILS AND CHARACTERIZATION DATA General Methods - All commercially available chemicals were used as received unless otherwise indicated. Bis(pinacolato)diboron (B2pin2) was generously supplied by BoroPharm, Inc. Bis(η4- 1,5-cyclooctadiene)-di-μ-methoxy-diiridium(I) [Ir(OMe)(cod)]2 was made by a literature procedure30 or purchased from Sigma-Aldrich. Tetrahydrofuran (THF) was refluxed over sodium/benzophenone ketyl, distilled and degassed before use. Column chromatography was performed on 240–400 mesh Silica P-Flash silica gel. In cases where deactivated silica gel was used, this was accomplished by adding deionized water (35% w/w) to silica gel and shaking for 60 seconds, afterwards any small chunks were crushed with spatula resulting a uniform powder in a round bottom flask, which was added into column. Thin layer chromatography was performed on 0.25 mm thick aluminum–backed silica gel plates and visualized with ultraviolet light (λ = 254 nm) and alizarin stain to visualize boronic esters according to a literature procedure.31 Sublimations were conducted with a water-cooled cold finger. 1 H, 13C, 11B, 19F and 29Si 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, or an Innova 300 MHz spectrometer equipped with a QUAD (1H/19F and 11B) PFG probe. Spectra were taken in CDCl3 referenced to 7.26 ppm in 1H NMR and 77.0 ppm in 13C NMR. Resonances for the boron-bearing carbon atom were not observed due to quadrupolar relaxation. All coupling constants are apparent J values measured at the indicated field strengths in Hertz (s = singlet, d = doublet, t = triplet, q = quartet, dd = doublet of doublets, ddd = doublet of doublet of doublets, bs = broad singlet). NMR spectra were processed for display using the MNova software program with only phasing and 23 baseline corrections applied. Reaction conversions were calculated by comparing the integration of the starting amide N-methyl peak with the borylated product methylene peak. High-resolution mass spectra (HRMS) were obtained at the Mass spectrometry analysis was performed at the Molecular Metabolism and Disease Mass Spectrometry Core facility at Michigan State University using electrospray ionization (ESI+ or ESI-) on quadrupole time-of-flight (Q- TOF) instruments. Melting points were measured in a capillary melting point apparatus and are uncorrected. Preparation of Ligand L2 sec- butyllithium (1.1 equiv) i-Pr2SiClH (1.0 equiv) THF, -78 ºC, 15 min THF, -78 ºC to rt, 2 h N N H Si Br 1.1 equiv L2 Ligand L2 was prepared in similar yield following the previously reported procedure.22 Preparation of Ligand L3 LDA (1.1 equiv) i-Pr2SiClH (1.0 equiv) THF, -78 ºC THF, -78 ºC to rt, 2 h N N H Si L3 To an oven dried 250 mL round bottom flask equipped with a stir bar, under nitrogen was added THF (40 mL) and diisopropylamine (1.1 equiv, 15.9 mmol, 2.25 mL) which was freshly distilled over calcium hydride. This solution was cooled to –78 °C in an acetone dry ice bath. Then n- butyllithium (2.5 M in hexanes, 1.1 equiv, 15.9 mmol, 6.36 mL) was added dropwise. This solution was allowed to stir for 5 min after which 2-methylpyridine (1.0 equiv, 14.5 mmol, 1.43 mL) which was freshly distilled over calcium hydride was slowly added dropwise. This addition took 24 approximately 5 min after which a reddish-orange solution was observed. In a separate oven dried 250 mL round bottom flask equipped with a stir bar, under nitrogen was added THF (20 mL) and diisopropylchlorosilane (1.0 equiv, 14.5 mmol, 2.47 mL) which was freshly distilled over calcium hydride. This solution was cooled to –78 °C in an acetone dry ice bath. The contents of the flask containing the lithiated 2-methylpyridine were then slowly cannula transferred into the second flask containing the chlorosilane. This cannula transfer took approximately 20 min. Upon completion the resulting solution was allowed to stir at –78 °C for 30 min after which an aliquot was removed, quenched with methanol, and GCMS was collected. The GCMS revealed two products in a 9:1 ratio with masses corresponding to the desired monosilylated product and undesired disilylated product. The entire reaction mixture was then quenched by the addition of methanol (5 mL), solvents were removed under reduced pressure and a DCM/H2O extraction was performed. The resulting material was further purified by distillation (oil bath temperature: 60–80 °C; vacuum: 0.01 torr). This provided L3 as a clear colorless liquid in 58% yield (1.743 g). 1 H NMR (500 MHz, CDCl3): δH 8.42 (d, J = 4.9 Hz, 1H), 7.48 (td, J = 7.7, 1.9 Hz, 1H), 7.05 (d, J = 7.9 Hz, 1H), 6.96 (dd, J = 7.4, 5.0 Hz, 1H), 3.71–3.58 (s, 1H), 2.43 (d, J = 3.7 Hz, 2H), 0.99 (s, 12H). 13C NMR (125 MHz, CDCl3): δC 161.45, 149.10, 135.91, 122.61, 119.39, 22.08, 18.70, 18.56, 10.60. 29Si NMR (99 MHz, CDCl3): δSi 7.32. Preparation of Ligand L4 LDA (1.1 equiv) i-Pr2SiClH (1.0 equiv) THF, -78 ºC THF, -78 ºC to rt, 2 h MeO N MeO N H Si L4 To an oven dried 250 mL round bottom flask equipped with a stir bar, under nitrogen was added THF (50 mL) and diisopropylamine (1.1 equiv, 9.2 mmol, 1.3 mL) which was freshly distilled 25 over calcium hydride. This solution was cooled to –78 °C in an acetone dry ice bath. Then n- butyllithium (2.5 M in hexanes, 1.1 equiv, 9.2 mmol, 3.7 mL) was added dropwise. This solution was allowed to stir for 10 min after which 2-methoxy-6-methylpyridine (1.0 equiv, 8.4 mmol, 1.02 mL) which was placed over 4 Å molecular sieves 24 h before use was slowly added dropwise. This addition took approximately 5 min after which an orange-yellow solution was observed. The solution was allowed to stir for 30 min after which diisopropylchlorosilane (1.0 equiv, 8.4 mmol, 1.4 mL) freshly distilled over calcium hydride was added. This mixture stirred for 1 h then quenched by the addition of methanol (5 mL). Solvents were removed under reduced pressure and a DCM/H2O extraction was performed. The resulting material was further purified by a silica column with a DCM/hexanes (1:9) solvent system. This provided L4 as a clear colorless liquid in 38% yield (0.754 g). 1 H NMR (500 MHz, CDCl3): δH 7.38 (t, J = 7.4 Hz, 1H), 6.63 (d, J = 7.2 Hz, 1H), 6.43 (d, J = 8.1 Hz, 1H), 3.88 (s, 3H), 3.59 (bs, 1H), 2.34 (d, J = 3.2 Hz, 2H), 1.02 (s, 12H). 13C NMR (125 MHz, CDCl3): δC 163.31, 159.32, 138.52, 114.93, 105.64, 53.12, 21.47, 18.75, 18.58, 10.67. 29Si NMR (99 MHz, CDCl3): δSi 7.04. Preparation of Ligand L5 LDA (1.1 equiv) Me2SiClH (1.0 equiv) THF, -78 ºC THF, -78 ºC to rt, 2 h N N H Si L5 To an oven dried 250 mL round bottom flask equipped with a stir bar, under nitrogen was added THF (50 mL) and diisopropylamine (1.1 equiv, 14.5 mmol, 2.05 mL) which was freshly distilled from calcium hydride. This solution was cooled to –78 °C in an acetone dry ice bath. Then n- butyllithium (2.5 M in hexanes, 1.1 equiv, 14.5 mmol, 5.8 mL) was added dropwise. This solution 26 was allowed to stir for 10 min after which 2-methylpyridine (1.0 equiv, 13.1 mmol, 1.3 mL) which was freshly distilled over calcium hydride was slowly added dropwise. This addition took approximately 5 min after which a bright red-orange solution was observed. In a separate oven dried 250 mL round bottom flask equipped with a stir bar, under nitrogen was added THF (20 mL) and dimethylchlorosilane (1.0 equiv, 13.1 mmol, 1.46 mL) which was freshly distilled over calcium hydride. This solution was cooled to –78 °C in an acetone dry ice bath. The contents of the flask containing the lithiated 2-methylpyridine were then slowly cannula transferred into the second flask containing the chlorosilane. This cannula transfer took approximately 20 min. Upon completion the resulting solution was allowed to stir at –78 °C for 30 min after which the reaction was quenched by addition of silica. The silica was then rinsed with THF (250 mL) then volatiles were removed under reduced pressure. The oil was dissolved in DCM, and the solution was washed with H2O. The organic phase was dried over MgSO4, filtered, and the solvent was removed in vacuo. The 1H NMR at this point showed 95% conversion of the starting material. Unusually, at ambient temperature over a week the product slowly converted back into the starting pyridine. To remove the starting materials and silicon byproducts, the compound was distilled twice with a short-path distillation head (oil bath temperature: 60–80 °C; vacuum: 0.01 torr). This provided L5 as a clear colorless liquid in 22% yield (0.436 g), which matched previously reported spectra.32 Unfortunately, this purified compound also slowly decomposed in a nitrogen filled glove box at ambient temperature. 1 H NMR (500 MHz, CDCl3)4: δH 8.44 (d, J = 5.0 Hz, 1H), 7.51 (td, J = 7.7, 1.9 Hz, 1H), 7.04– 6.93 (m, 2H), 4.02 (m, J = 3.6 Hz, 1H), 2.42 (d, J = 3.6 Hz, 2H), 0.10 (d, J = 3.6 Hz, 6H). 13C NMR (125 MHz, CDCl3)4: δC 160.88, 149.17, 136.03, 122.28, 119.42, 27.56, –4.50. 27 1.5 mol % [Ir(OMe)(cod)]2 O No Ligand O Bpin B2pin2 (1.2 equiv) N N THF, 60 ºC, 24 h 1a 2a In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (4.97 mg, 0.0075 mmol, 1.5 mol %) and B2pin2 (152.4 mg, 0.6 mmol, 1.2 equiv) were weighed into separate test tubes and N,N-dimethylacetamide (43.5 mg, 0.5 mmol, 1.0 equiv) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.3 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the test tube containing B2pin2. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the 5 mL conical vial followed by a similar rinsing procedure described above. The conical vial was then sealed and placed in an aluminum block pre-heated to 60 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. Only starting material was observed. 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % dtbpy O Bpin B2pin2 (1.2 equiv) N N THF, 60 ºC, 24 h N N 1a 2a dtbpy In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (4.97 mg, 0.0075 mmol, 1.5 mol %), dtbpy (4.0 mg, 0.015 mmol, 3 mol %), and B2pin2 (152.4 mg, 0.6 mmol, 1.2 equiv) were weighed into separate test tubes and N,N-dimethylacetamide (43.5 mg, 0.5 mmol, 1.0 equiv) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the test tube containing B2pin2. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test 28 tube containing dtbpy and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 60 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. A complex mixture of products was observed. 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % tmphen O Bpin B2pin2 (1.2 equiv) N N THF, 60 ºC, 24 h N N 1a 2a tmphen In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (4.97 mg, 0.0075 mmol, 1.5 mol %), tmphen (3.5 mg, 0.015 mmol, 3 mol %), and B2pin2 (152.4 mg, 0.6 mmol, 1.2 equiv) were weighed into separate test tubes and N,N-dimethylacetamide (43.5 mg, 0.5 mmol, 1.0 equiv) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the test tube containing B2pin2. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing tmphen and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 60 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. A complex mixture of products was observed. 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L1 O Bpin B2pin2 (1.2 equiv) N N N THF, 60 ºC, 24 h NH2 1a 2a L1 29 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (4.97 mg, 0.0075 mmol, 1.5 mol %), L1 (2.2 mg, 0.015 mmol, 3 mol %), and B2pin2 (152.4 mg, 0.6 mmol, 1.2 equiv) were weighed into separate test tubes and N,N-dimethylacetamide (43.5 mg, 0.5 mmol, 1.0 equiv) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the test tube containing B2pin2. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L1 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 60 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. A 10% conversion of starting material was observed. 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L1 O Bpin B2pin2 (1.2 equiv) N N N THF, 80 ºC, 24 h NH2 1a 2a L1 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (4.97 mg, 0.0075 mmol, 1.5 mol %), L1 (2.2 mg, 0.015 mmol, 3 mol %), and B2pin2 (152.4 mg, 0.6 mmol, 1.2 equiv) were weighed into separate test tubes and N,N-dimethylacetamide (43.5 mg, 0.5 mmol, 1.0 equiv) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the test tube containing B2pin2. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L1 and the rinsing procedure was repeated. Finally, the resulting solution was 30 added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. A 10% conversion of starting material was observed. 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L2 O Bpin B2pin2 (1.2 equiv) N N N THF, 60 ºC, 24 h H Si 1a 2a L2 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (4.97 mg, 0.0075 mmol, 1.5 mol %), L2 (3.7 mg, 0.015 mmol, 3 mol %), and B2pin2 (152.4 mg, 0.6 mmol, 1.2 equiv) were weighed into separate test tubes and N,N-dimethylacetamide (43.5 mg, 0.5 mmol, 1.0 equiv) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the test tube containing B2pin2. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L2 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 60 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. A 60% conversion of starting material was observed. 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.2 equiv) N N N THF, 60 ºC, 7.5 h H Si 1a 2a L3 31 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (4.97 mg, 0.0075 mmol, 1.5 mol %), L3 (3.1 mg, 0.015 mmol, 3 mol %), and B2pin2 (152.4 mg, 0.6 mmol, 1.2 equiv) were weighed into separate test tubes and N,N-dimethylacetamide (43.5 mg, 0.5 mmol, 1.0 equiv) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the test tube containing B2pin2. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 60 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. A 91% conversion of starting material was observed. 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L4 O Bpin B2pin2 (1.2 equiv) N N MeO N THF, 60 ºC, 24 h H Si 1a 2a L4 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (4.97 mg, 0.0075 mmol, 1.5 mol %), L4 (3.6 mg, 0.015 mmol, 3 mol %), and B2pin2 (152.4 mg, 0.6 mmol, 1.2 equiv)were weighed into separate test tubes and N,N-dimethylacetamide (43.5 mg, 0.5 mmol, 1.0 equiv) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L4 and the rinsing procedure was repeated. Finally, the resulting solution was 32 added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 60 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. A complex mixture of products was observed. 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L5 O Bpin B2pin2 (1.2 equiv) N N N THF, 60 ºC, 24 h H Si 1a 2a L5 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (4.97 mg, 0.0075 mmol, 1.5 mol %), L5 (2.3 mg, 0.015 mmol, 3 mol %), and B2pin2 (152.4 mg, 0.6 mmol, 1.2 equiv)were weighed into separate test tubes and N,N-dimethylacetamide (43.5 mg, 0.5 mmol, 1.0 equiv) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the test tube containing B2pin2. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L5 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 60 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. An 11% conversion of starting material was observed. 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.5 equiv) N N N THF, 80 ºC, 7.5 h H Si 1a 2a L3 33 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (4.97 mg, 0.0075 mmol, 1.5 mol %), L3 (3.1 mg, 0.015 mmol, 3 mol %), and B2pin2 (152.4 mg, 0.6 mmol, 1.2 equiv) were weighed into separate test tubes and N,N-dimethylacetamide (43.5 mg, 0.5 mmol, 1.0 equiv) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the test tube containing B2pin2. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 7.5 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. A 100% conversion of starting material was observed. 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin HBpin (2.0 equiv) N N N THF, 80 ºC, 24 h H Si 1a 2a L3 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (4.97 mg, 0.0075 mmol, 1.5 mol %), L3 (3.1 mg, 0.015 mmol, 3 mol %), and HBpin (128.0 mg, 1.0 mmol, 2.0 equiv) were weighed into separate test tubes and N,N-dimethylacetamide (43.5 mg, 0.5 mmol, 1.0 equiv) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing HBpin. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the test tube containing HBpin. The solution of [Ir(OMe)(cod)]2 and HBpin was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was 34 added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. A complex mixture of products was observed. 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2eg2 (1.2 equiv) O O N N N B B THF, 80 ºC, 24 h O O H Si 1a 2a B2eg2 L3 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (4.97 mg, 0.0075 mmol, 1.5 mol %), L3 (3.1 mg, 0.015 mmol, 3 mol %), and B2eg2 (85.0 mg, 0.6 mmol, 1.2 equiv) were weighed into separate test tubes and N,N-dimethylacetamide (43.5 mg, 0.5 mmol, 1.0 equiv) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2eg2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the test tube containing B2eg2. The solution of [Ir(OMe)(cod)]2 and B2eg2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. Only starting material was observed. 0.75 mol % [Ir(OMe)(cod)]2 O 1.5 mol % L3 O Bpin B2pin2 (1.2 equiv) N N N THF, 80 ºC, 24 h H Si 1a 2a L3 35 For the procedure see below. A 85% conversion of starting material was observed after 24 h. Effect of Catalyst Loading, stock solutions of [Ir(OMe)cod]2 and ligand L3 were prepared to ensure accuracy in the amount of catalyst added. The procedure for the preparation of each stock solution is provided below. Preparation of [Ir(OMe)cod]2 stock solution: In a test tube, 66.3 mg of [Ir(OMe)cod]2 was weighed. Then THF was used to transfer this compound from the test tube to a 4 mL volumetric flask. The flask was shaken until no solids were observed. Then the flask was filled with THF to exactly 4 mL. Preparation of ligand L3 stock solution: To a 2 mL volumetric flask, 62.2 mg of ligand L3 was added. Then 1.5 mL THF was added and the flask was shaken to ensure the solution was well mixed. The flask was then filled with THF to exactly 2 mL. Catalyst Loading 1.5 mol % [Ir(OMe)cod]2 1.5 mol % [Ir(OMe)(cod)]2 time(h) % 2a O 3 mol % L3 O Bpin 1 70 B2pin2 (1.2 equiv) N N 4 84 THF, 80 ºC N 7.5 100 H Si 1a 2a 10 100 L3 24 100 In a nitrogen filled glove box, B2pin2 (152.3 mg, 0.6 mmol, 1.2 equiv) was weighed into a test tube and N,N-dimethylacetamide (43.5 mg, 0.5 mmol, 1.0 equiv) was weighed into a 5 mL conical reaction vial equipped with a stir bar. [Ir(OMe)cod]2 (0.3 mL from the stock solution, 1.5 mol %) and ligand L3 (0.1 mL from the stock solution, 3 mol %) were added to the test tube with a microsyringe. The resulting solution was then transferred to the 5 mL reaction vial followed by rinsing the test tube with approximately 0.4 mL of THF three times. The reaction vials were then sealed and placed in an aluminum block pre-heated to 80 ˚C and allowed to stir. Aliquots were 36 removed at 1 h, 4 h, 7.5 h, 10 h, and 24 h. Proton NMR of each aliquot was obtained and the conversion of starting material to product was calculated. These data are displayed in the Scheme above. Catalyst Loading 1.0 mol % [Ir(OMe)cod]2 1.0 mol % [Ir(OMe)(cod)]2 time(h) % 2a O 2 mol % L3 O Bpin 1 61 B2pin2 (1.2 equiv) N N 4 70 THF, 80 ºC N 7.5 78 H Si 1a 2a 10 83 L3 24 92 In a nitrogen filled glove box, B2pin2 (152.3 mg, 0.6 mmol, 1.2 equiv) was weighed into a test tube and N,N-dimethylacetamide (43.5 mg, 0.5 mmol, 1.0 equiv) was weighed into a 5 mL conical reaction vial equipped with a stir bar. [Ir(OMe)cod]2 (0.2 mL from the stock solution, 1.0 mol %) and ligand L3 (0.066 mL from the stock solution, 2 mol %) were added to the test tube with a microsyringe. The resulting solution was then transferred to the 5 mL reaction vial followed by rinsing the test tube with approximately 0.4 mL of THF three times. The reaction vials were then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir. Aliquots were removed at 1 h, 4 h, 7.5 h, 10 h, and 24 h. Proton NMR of each aliquot was obtained and the conversion of starting material to product was calculated. These data are displayed in the Scheme above. Catalyst Loading 0.75 mol % [Ir(OMe)cod]2 0.75 mol % [Ir(OMe)(cod)]2 time(h) % 2a O 1.5 mol % L3 O Bpin 1 55 B2pin2 (1.2 equiv) N N 4 68 THF, 80 ºC N 7.5 73 H Si 1a 2a 10 75 L3 24 85 37 In a nitrogen filled glove box, B2pin2 (152.3 mg, 0.6 mmol, 1.2 equiv) was weighed into a test tube and N,N-dimethylacetamide (43.5 mg, 0.5 mmol, 1.0 equiv) was weighed into a 5 mL conical reaction vial equipped with a stir bar. [Ir(OMe)cod]2 (0.15 mL from the stock solution, 0.75 mol %) and ligand L3 (0.05 mL from the stock solution, 1.5 mol %) were added to the test tube with a microsyringe. The resulting solution was then transferred to the 5 mL reaction vial followed by rinsing the test tube with approximately 0.4 mL of THF three times. The reaction vials were then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir. Aliquots were removed at 1 h, 4 h, 7.5 h, 10 h, and 24 h. Proton NMR of each aliquot was obtained and the conversion of starting material to product was calculated. These data are displayed in the Scheme above. Catalyst Loading 0.5 mol % [Ir(OMe)cod]2 0.5 mol % [Ir(OMe)(cod)]2 time(h) % 2a O 1 mol % L3 O Bpin 1 49 B2pin2 (1.2 equiv) N N 4 58 THF, 80 ºC N 7.5 61 H Si 1a 2a 10 63 L3 24 70 In a nitrogen filled glove box, B2pin2 (152.3 mg, 0.6 mmol, 1.2 equiv) was weighed into a test tube and N,N-dimethylacetamide (43.5 mg, 0.5 mmol, 1.0 equiv) was weighed into a 5 mL conical reaction vial equipped with a stir bar. [Ir(OMe)cod]2 (0.10 mL from the stock solution, 0.5 mol %) and ligand L3 (0.033 mL from the stock solution, 1 mol %) were added to the test tube with a microsyringe. The resulting solution was then transferred to the 5 mL reaction vial followed by rinsing the test tube with approximately 0.4 mL of THF three times. The reaction vials were then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir. Aliquots were removed at 1 h, 4 h, 7.5 h, 10 h, and 24 h. Proton NMR of each aliquot was obtained and the 38 conversion of starting material to product was calculated. These data are displayed in the Scheme above. Borylation of N,N-dimethylacetamide (2a) 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.5 equiv) N N N THF, 80 ºC, 7.5 h H Si 1a 2a L3 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B2pin2 (1.5 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and N,N-dimethylacetamide (1 mmol, 1.0 equiv, 87.1 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 100% conversion of starting material. The crude reaction mixture was passed through deactivated silica (35% H2O w/w) with a gradient solvent system of 10% to 15% MeOH in EtOAc. After overnight drying under high vacuum, (2a) was obtained as a white solid (132.7 mg, 62% yield, mp = 116–121 °C, lit mp = 145.2-147.5 °C21, 157.4–162.8 °C18) which matched previously reported spectra.21 39 1 H NMR (500 MHz, CDCl3)21: δH 3.07 (s, 3H), 2.40 (s, 2H), 2.14 (s, 3H), 1.19 (s, 4H). 13C NMR (125 MHz, CDCl3)21: δC 174.21, 79.76, 35.98, 24.99, 15.40. 11B NMR (160 MHz, CDCl3): δB 12.61 (s). HRMS (ESI) m/z calc for C10H20BNO3Na [(M+Na)+] 236.1433, found 236.1463. Borylation of N,N-dimethylpropionamide (2b) 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.5 equiv) N N N THF, 80 ºC, 24 h H Si 1b 2b L3 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B2pin2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and N,N-dimethylpropionamide (1 mmol, 1.0 equiv, 101.2 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 95% conversion of starting material. The crude reaction mixture was passed through deactivated silica (35% H2O w/w) with a gradient solvent system of 10% to 15% MeOH in EtOAc. After overnight drying under high vacuum (2b) was obtained as a white solid (174.9 mg, 77% yield, mp = 118–120 °C, lit mp = 151.1–152.7 °C17) which matched previously reported spectra.17 40 1 H NMR (500 MHz, CDCl3)17: δH 3.05 (s, 3H), 2.43–2.36 (m, 4H), 1.21 (t, J = 7.6 Hz, 3H), 1.19 (s, 12H). 13C NMR (125 MHz, CDCl3)17: δC. 177.48, 79.88, 35.51, 25.13, 22.07, 8.70. 11B NMR (160 MHz, CDCl3)17: δB 12.2 (s) (12.5 ppm lit). HRMS (ESI) m/z calc for C11H22BNO3Na [(M+Na)+] 250.1590, found 250.1953. Borylation of N,N-dimethylisobutyramide (2c) 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.5 equiv) N N N THF, 80 ºC, 24 h H Si 1c 2c L3 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B2pin2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and N,N-dimethylisobutyramide (1 mmol, 1.0 equiv, 115.2 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 75% conversion of starting material. The crude reaction mixture was passed through deactivated silica (35% H2O w/w) with a gradient solvent system of 10% to 15% MeOH in EtOAc. After overnight drying under high vacuum (2c) was obtained as a white solid (132.6 mg, 55% yield, mp = 81–85 °C) which matched previously reported spectra.17 41 1 H NMR (500 MHz, CDCl3)17: δH 3.09 (s, 3H), 2.75 (sept, J = 6.9 Hz, 1H), 2.40 (s, 2H), 1.18 (d, J = 6.0 Hz, 6H), 1.19 (s, 12H). 13C NMR (125 MHz, CDCl3)17: δC 180.15, 79.75, 35.42, 27.36, 25.12, 18.47. 11B NMR (160 MHz, CDCl3)17: δB 12.37 (s) (12.1 ppm lit). HRMS (ESI) m/z calc for C12H24BNO3Na [(M+Na)+] 264.1746, found 264.1778. Borylation of N,N-dimethylpivalamide (2d) 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.5 equiv) N N N THF, 80 ºC, 24 h H Si 1d 2d L3 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B2pin2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and N,N-dimethylpivalamide (1 mmol, 1.0 equiv, 129.2 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 100% conversion of starting material. The crude reaction mixture was passed through deactivated silica (35% H2O w/w) with a gradient solvent system of 10% to 15% MeOH in EtOAc. After overnight drying under high vacuum (2d) was obtained as a white solid (178.6 mg, 70% yield, mp = 61–64 °C, lit mp = 60.8-63.9 °C6) which matched previously reported spectra.18 42 1 H NMR (500 MHz, CDCl3)18: δH 3.20 (s, 3H), 2.45 (s, 2H), 1.31 (s, 9H), 1.17 (s, 12H). 13C NMR (125 MHz, CDCl3)18: δC 181.12, 79.65, 37.57, 35.64, 27.24, 25.09. 11B NMR (160 MHz, CDCl3): δB 11.74 (s). HRMS (ESI) m/z calc for C13H26BNO3 [M]+ 255.2005, found 255.2099. Borylation of N,N,3-trimethylbutanamide (2e) 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.5 equiv) N N N THF, 80 ºC, 24 h H Si 1e 2e L3 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B2pin2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and N,N,3-trimethylbutanamide (1 mmol, 1.0 equiv, 129.20 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 100% conversion of starting material. The crude reaction mixture was passed through deactivated silica (35% H2O w/w) with a gradient solvent system of 10% to 15% MeOH in EtOAc. After overnight drying under high vacuum (2e) was obtained as a white solid (173.5 mg, 68% yield, mp = 62–65 °C). 43 1 H NMR (500 MHz, CDCl3): δH 3.06 (s, 3H), 2.25 (d, J = 7.6 Hz, 2H), 2.10 (s, 2H), 2.17 (m, 1H), 1.18 (s, 12H), 0.99 (d, J = 6.6 Hz, 6H). 13C NMR (125 MHz, CDCl3): δC 176.28, 79.70, 36.86, 35.85, 25.87, 25.08, 22.48. 11B NMR (160 MHz, CDCl3): δB 12.41 (s). HRMS (ESI) m/z calc for C13H26BNO3 [M]+ 255.2005, found 255.2138. Borylation of N,N-dimethylpentanamide (2f) 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.5 equiv) N n-Bu N n-Bu N THF, 80 ºC, 24 h H Si 1f 2f L3 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B2pin2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and N,N-dimethylpentanamide (1 mmol, 1.0 equiv, 129.2 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 100% conversion of starting material. The crude reaction mixture was passed through deactivated silica (35% H2O w/w) with a gradient solvent system of 10% to 15% MeOH in EtOAc. After overnight drying under high vacuum (2f) was obtained as a white solid (202.8 mg, 80% yield, mp = 104–106 °C). 44 1 H NMR (500 MHz, CDCl3): δH 3.05 (s, 3H), 2.38 (s, 2H), 2.36 (t, J = 7.8 Hz, 2H), 1.65 (m, 2H), 1.37 (h, J = 7.4 , 2H), 1.18 (s, 12H), 0.91 (t, J = 7.4 Hz, 3H). 13C NMR (125 MHz, CDCl3): δC 176.93, 79.78, 35.67, 28.15, 26.55, 25.13, 22.28, 13.57. 11B NMR (160 MHz, CDCl3): δB 12.44 (s). HRMS (ESI) m/z calc for C13H26BNO3Na [(M+Na)+] 278.1903, found 278.1937. Borylation of N,N-dimethyloctanamide (2g) 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.5 equiv) N n-hep N n-hep N THF, 80 ºC, 24 h H Si 1g 2g L3 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B2pin2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and N,N-dimethyloctanamide (1 mmol, 1.0 equiv, 171.2 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 86% conversion of starting material. The crude reaction mixture was passed through deactivated silica (35% H2O w/w) with a gradient solvent system of 10% to 15% MeOH in EtOAc. After overnight drying under high vacuum (2g) was obtained as a white solid (199.1 mg, 67% yield, mp = 120–123 °C). 45 1 H NMR (500 MHz, CDCl3): δH 3.05 (s, 3H), 2.38 (s, 2H), 2.35 (t, J = 7.6 Hz, 2H), 1.66 (q, J = 7.7 Hz, 2H), 1.35–1.26 (m, 8H), 1.18 (s, 12H), 0.88 (t, J = 7.1 Hz, 3H). 13C NMR (125 MHz, CDCl3): δC 176.97, 79.81, 35.68, 31.54, 29.11, 28.77, 28.46, 25.16, 24.54, 22.54, 14.04. 11B NMR (160 MHz, CDCl3): δB 12.49 (s). HRMS (ESI) m/z calc for C16H32BNO3 [M]+ 297.2475, found 297.2606. Borylation of N,N-dimethylcyclopentanecarboxamide (2h) 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.5 equiv) N N N THF, 80 ºC, 24 h H Si 1h 2h L3 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B2pin2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and N,N-dimethylcyclopentanecarboxamide (1 mmol, 1.0 equiv, 141.2 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 92% conversion of starting material.. The crude reaction mixture was passed through deactivated silica (35% H2O w/w) with a gradient solvent system of 10% to 15% MeOH 46 in EtOAc. After overnight drying under high vacuum (2h) was obtained as a white solid (210.2 mg, 79% yield, mp = 98–99 °C). 1 H NMR (500 MHz, CDCl3): δH 3.06 (s, 3H), 2.83 (p, J = 8.0 Hz, 1H), 2.37 (s, 2H), 1.91–1.71 (m, 6H), 1.65–1.51 (m, 2H), 1.16 (s, 12H). 13C NMR (125 MHz, CDCl3): δC 179.79, 79.72, 37.39, 35.59, 29.79, 25.87, 25.13. 11B NMR (160 MHz, CDCl3): δB 12.31 (s). HRMS (ESI) m/z calc for C14H26BNO3Na [(M+Na)+] 290.1903, found 290.1940. Borylation of N,N-dimethylcyclohexanecarboxamide (2i) 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.5 equiv) N N N THF, 80 ºC, 24 h H Si 1i 2i L3 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B2pin2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and N,N-dimethylcyclohexanecarboxamide (1 mmol, 1.0 equiv, 155.2 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 100% conversion of starting material. The crude reaction mixture was passed through deactivated silica (35% H2O w/w) with a gradient solvent system of 10% to 15% MeOH 47 in EtOAc. After overnight drying under high vacuum (2i) was obtained as a white solid (225.1 mg, 80% yield, mp = 139–140 °C). 1 H NMR (500 MHz, CDCl3): δH 3.07 (s, 3H), 2.44 (tt, J = 11.6, 3.5 Hz, 1H), 2.37 (s, 2H), 1.87– 1.67 (m, 5H), 1.61–1.51 (m, 2H), 1.32–1.21 (m, 3H), 1.18 (s, 12H). 13C NMR (125 MHz, CDCl3): δC 179.21, 79.68, 37.00, 35.43, 28.21, 25.34, 25.32, 25.14. 11B NMR (160 MHz, CDCl3): δB 12.38 (s). HRMS (ESI) m/z calc for C15H28BNO3Na [(M+Na)+] 304.2059, found 304.2095. Borylation of 1-methylpyrrolidin-2-one (2j) 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.5 equiv) N N N THF, 80 ºC, 24 h H Si 1j 2j L3 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B2pin2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and 1-methylpyrrolidin-2-one (1 mmol, 1.0 equiv, 99.1 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 38% conversion of starting material to the product. No other byproducts were observed in the 1H NMR or the GCMS of crude reaction mixture. 48 Borylation of 1-methylpiperidin-2-one (2k) 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.5 equiv) N N N THF, 80 ºC, 24 h H Si L3 1k 2k In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B2pin2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and 1-methylpiperidin-2-one (1 mmol, 1.0 equiv, 113.2 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 100% conversion of starting material. The crude reaction mixture was passed through deactivated silica (35% H2O w/w) with a gradient solvent system of 10% to 15% MeOH in EtOAc. After overnight drying under high vacuum (2k) was obtained as a white solid (107.1 mg, 70% yield, mp = 127–131 °C). 1 H NMR (500 MHz, CDCl3): δH 3.31 (t, J = 5.7 Hz, 2H), 2.49 (t, J = 6.2 Hz, 2H), 2.34 (s, 2H), 1.90–1.75 (m, 4H), 1.19 (s, 12H). 13C NMR (125 MHz, CDCl3): δC 173.93, 79.91, 47.82, 26.43, 11 25.15, 21.99, 19.45. B NMR (160 MHz, CDCl3): δB 12.68 (s). HRMS (ESI) m/z calc for C12H22BNO3Na [(M+Na)+] 262.1590, found 262.1624. 49 Borylation of 1-methylazepan-2-one (2l) 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.5 equiv) N N N THF, 80 ºC, 24 h H Si L3 1l 2l In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B2pin2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and 1-methylazepan-2-one (1 mmol, 1.0 equiv, 127.2 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 100% conversion of starting material. The crude reaction mixture was passed through deactivated silica (35% H2O w/w) with a gradient solvent system of 10% to 15% MeOH in EtOAc. After overnight drying under high vacuum (2l) was obtained as a white solid (176.6 mg, 70% yield, mp = 110–113 °C, lit mp =118.3–120.2 °C17, 116.8–120.6 °C18, 128.3-129.8 °C21), which matched previously reported spectra. 17 1 H NMR (500 MHz, CDCl3)17: δH 3.45–3.34 (m, 2H), 2.61–2.52 (m, 2H), 2.49 (s, 2H), 1.77–1.68 (m, 2H), 1.67–1.60 (m, 4H), 1.15 (s, 12H). 13C NMR (125 MHz, CDCl3)17: δC 179.46, 79.83, 50.37, 50 31.19, 29.77, 26.32, 25.11, 22.11. 11B NMR (160 MHz, CDCl3): δB 12.52 (s). HRMS (ESI) m/z calc for C13H24BNO3Na [(M+Na)+] 276.1746, found 276.1786. Borylation of N-ethyl-N-methylacetamide (2m) 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.5 equiv) N N N THF, 80 ºC, 24 h H Si L3 1m 2m In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B2pin2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and N-ethyl-N-methylacetamide (1 mmol, 1.0 equiv, 101.2 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 94% conversion of starting material. The crude reaction mixture was passed through deactivated silica (35% H2O w/w) with a gradient solvent system of 10% to 15% MeOH in EtOAc. After overnight drying under high vacuum (2m) was obtained as a white solid (161.2 mg, 71% yield, mp = 149–153 °C) 51 1 H NMR (500 MHz, CDCl3): δH 3.37 (q, J = 7.3 Hz, 2H), 2.36 (s, 2H), 2.13 (s, 3H), 1.20 (t, J = 7.3 Hz, 3H), 1.17 (s, 12H). 13C NMR (125 MHz, CDCl3): δC 173.70, 79.86, 43.65, 25.12, 15.40, 11 12.65. B NMR (160 MHz, CDCl3): δB 12.41 (s). HRMS (ESI) m/z calc for C11H22BNO3Na [(M+Na)+] 250.1590, found 250.1620. Borylation of tert-butyl dimethylcarbamate (2n) 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.5 equiv) N O N O N THF, 80 ºC, 24 h H Si L3 1n 2n In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B2pin2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and tert-butyl dimethylcarbamate (1 mmol, 1.0 equiv, 145.2 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 47% conversion of starting material. 1H NMR of crude material matched previous spectra.33 No other byproducts were observed in the 1H NMR or the GCMS of crude reaction mixture. Borylation of 1,3-dimethyltetrahydropyrimidin-2(1H)-one (2o) 52 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.5 equiv) N N N N N THF, 80 ºC, 24 h H Si L3 1o 2o In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B2pin2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and 1,3-dimethyltetrahydropyrimidin-2(1H)-one (1 mmol, 1.0 equiv, 128.2 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h.The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 97% conversion of starting material. The crude reaction mixture was passed through deactivated silica (35% H2O w/w) with a gradient solvent system of 10% to 15% MeOH in EtOAc. After overnight drying under high vacuum (2o) was obtained as a white solid (227.4 mg, 89% yield, mp = 165–167 °C, lit mp = 165.2–166.6 °C21) which matched previously reported spectra.21 1 H NMR (500 MHz, CDCl3)21: δH 3.34–3.14 (m, 4H), 2.98 (s, 3H), 2.34 (s, 2H), 1.96 (m, 2H), 1.18 (s, 12H). 13C NMR (125 MHz, CDCl3)21: δC 159.52, 79.56, 46.55, 44.64, 36.01, 25.15, 20.93. 11 B NMR (160 MHz, CDCl3): δB 11.53 (s). HRMS (ESI) m/z calc for C12H23BN2O3Na [(M+Na)+] 277.1699, found 277.1705. 53 Borylation of N,N-dimethylbenzamide (2p) 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 Bpin O B2pin2 (1.5 equiv) N N N THF, 80 ºC, 24 h H Si L3 1p 2p In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B2pin2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and N,N-dimethylbenzamide (1 mmol, 1.0 equiv, 149.2 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. The starting material was 100% consumed with the major product being the ortho borylated product. The spectra for 2p was in accordance with a previous report.34 The spectra also showed diborylated material in 1.2:1 ratio of mono:di-borylated. Borylation of N,N-dimethyl-3-phenylpropanamide (2q) 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.5 equiv) N Ph N Ph N THF, 80 ºC, 24 h H Si 1q 2q L3 54 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B2pin2 (1.2 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and N,N-dimethyl-3-phenylpropanamide (1 mmol, 1.0 equiv, 177.3 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 83% conversion of starting material. The crude reaction mixture was passed through deactivated silica (35% H2O w/w) with a gradient solvent system of 10% to 15% MeOH in EtOAc. After overnight drying under high vacuum (2q) was obtained as a white solid (191.0 mg, 63% yield, mp = 98–103 °C). 1 H NMR (500 MHz, CDCl3): δH 7.34–7.27 (m, 2H), 7.24–7.22 (m, 1H), 7.21–7.15 (m, 2H), 3.05– 2.97 (t, J = 8.2, 2H), 2.93 (s, 3H), 2.71–2.60 (t, J = 7.9, 2H), 2.39 (s, 2H), 1.21 (s, 12H). 13C NMR (125 MHz, CDCl3): δC 175.84, 139.69, 128.72, 128.28, 126.64, 79.96, 35.54, 30.75, 30.59, 25.17. 11 B NMR (160 MHz, CDCl3): δB 13.09 (s). HRMS (ESI) m/z calc for C17H26BNO3Na [(M+Na)+] 326.1903, found 326.1956. Borylation of N,N-diethylacetamide (2r) 55 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.5 equiv) N N N THF, 80 ºC, 24 h H Si 1r 2r L3 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.0075 mmol, 1.5 mol %, 4.9 mg), L3 (0.015 mmol, 3 mol %, 3.1 mg), and B2pin2 (0.75 mmol, 1.5 equiv, 190.5 mg) were weighed into separate test tubes and N,N-diethylacetamide (0.5 mmol, 1.0 equiv, 57.6 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 21 h. The vial was then opened and 1H and 11 B NMR of crude material were collected. In the 1H NMR spectrum, starting material, B2pin2 and borates made up most of the material; however, some new peaks with complex multiplicity did appear. The 11B NMR showed only two peaks corresponding to B2pin2 at 30 ppm and borates at 22 ppm. Based on these data, it was concluded that no product-like material was formed under these reaction conditions. Borylation of 2,2,2-trifluoro-N,N-dimethylacetamide (2s) 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.5 equiv) N F3C N F3C N THF, 80 ºC, 24 h H Si 1s 2s L3 56 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.0075 mmol, 1.5 mol %, 4.9 mg), L3 (0.015 mmol, 3 mol %, 3.1 mg), and B2pin2 (0.6 mmol, 1.2 equiv, 152.4 mg) were weighed into separate test tubes and 2,2,2-trifluoro-N,N-dimethylacetamide (0.5 mmol, 1.0 equiv, 70.5 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. Only starting material was observed. Borylation of 2-chloro-N,N-dimethylacetamide (2t) 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.5 equiv) N Cl Cl N N THF, 80 ºC, 24 h H Si 1t 2t L3 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B2pin2 (0.75 mmol, 1.5 equiv, 380.8 mg) were weighed into separate test tubes and 2-chloro-N,N-dimethylacetamide (1.0 mmol, 1.0 equiv, 121.5 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test 57 tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. Only starting material was observed. Borylation of 2-chloro-N,N-dimethylpropanamide (2u) 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.5 equiv) N Cl Cl N N THF, 80 ºC, 24 h H Si 1u 2u L3 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B2pin2 (0.75 mmol, 1.5 equiv, 380.8 mg) were weighed into separate test tubes and 2-chloro-N,N-dimethylpropanamide (1.0 mmol, 1.0 equiv, 135.5 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. 5% conversion of starting material was observed. Competitive Kinetic Isotope Effect 58 1.5 mol % [Ir(OMe)(cod)]2 O O 3 mol % L3 O Bpin O Bpin B2pin2 (1.0 equiv) CD3 CD2 N N N N N THF, 60 ºC H Si CD3 CD3 2a L3 1a, 1.5 equiv 1a-d6, 1.5 equiv = 5.0 2a-d5 time (h) Vial 1 Vial 2 Vial 3 2 5.0 5.3 5.1 3 4.8 5.2 4.9 4 4.6 5.1 4.9 Stock solutions of each of the reagents were used for these reactions, and the reaction was carried out in triplicate to ensure accuracy. The procedure for the preparation of each stock solution is provided below. Preparation of [Ir(OMe)cod]2 stock solution: In a test tube, 59.7 mg of [Ir(OMe)cod]2 was weighed. Then THF was used to transfer this compound from the test tube to a 2 mL volumetric flask. The flask was shaken until no solids were observed then filled with THF to exactly 2 mL. Preparation of ligand L3 stock solution: To a 2 mL volumetric flask, 37.3 mg of ligand L3 was added. Then 1.5 mL THF was added and the flask was shaken to ensure the solution was well mixed. The flask was then filled with THF to exactly 2 mL. Preparation of B2pin2 stock solution: In a test tube, 634.9 mg of B2pin2 was weighed. Then THF was used to transfer this compound from the test tube to a 5 mL volumetric flask. The flask was shaken until no solids were observed then filled with THF to exactly 5 mL. Preparation of N,N- dimethylacetamide 1a stock solution: To a 2 mL volumetric flask, 261.4 mg of N,N- dimethylacetamide 1a was added. Then 1.5 mL THF was added and the flask was shaken to ensure the solution was well mixed. The flask was then filled with THF to exactly 2 mL. 59 Preparation of N,N-dimethylacetamide-d6 1a-d6 stock solution: To a 2 mL volumetric flask, 106.2 mg of N,N-dimethylacetamide-d6 1a-d6 was added. Then 1.5 mL THF was added and the flask was shaken to ensure the solution was well mixed. The flask was then filled with THF to exactly 2 mL. In a nitrogen filled glove box, [Ir(OMe)cod]2 (0.1 mL from the stock solution, 1.5 mol %) and B2pin2 (0.2 mL from the stock solution, 0.1 mmol, 1.0 equiv) were added to three separate 3 mL conical reaction vials equipped with stir bars. To these solutions was then added ligand L3 (0.1 mL from the stock solution, 3 mol %). Then to each of the three reaction vessels was added N,N- dimethylacetamide 1a (0.1 mL from the stock solution, 0.15 mmol, 1.5 equiv) and N,N- dimethylacetamide-d6 1a-d6 (0.263 mL, 0.15 mmol, 1.5 equiv). The reaction vials were then sealed and placed in an aluminum block pre-heated to 60 °C and allowed to stir. Aliquots from each reaction vessel were removed at 2 h, 3 h, and 4 h and the ratio of 2a to 2a-d5 was obtained by GC/MS analysis. The average of these data points is 5.0. Borylation of N,N-dimethylacetamide in hexane 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.5 equiv) N N N n-hexane, 80 ºC, 24 h H Si L3 1a 2a In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.0075 mmol, 1.5 mol %, 4.9 mg), L3 (0.015 mmol, 3 mol %, 3.1 mg), and B2pin2 (0.75 mmol, 1.5 equiv, 190.4 mg) were weighed into separate test tubes and N,N-dimethylacetamide (0.5 mmol, 1.0 equiv, 43.5 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL hexane. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test 60 tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 75% conversion of starting material. Borylation of N,N-dimethylacetamide in cyclohexane 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.5 equiv) N N N cyclohexane, 80 ºC, 24 h H Si L3 1a 2a In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.0075 mmol, 1.5 mol %, 4.9 mg), L3 (0.015 mmol, 3 mol %, 3.1 mg), and B2pin2 (0.75 mmol, 1.5 equiv, 190.4 mg) were weighed into separate test tubes and N,N-dimethylacetamide (0.5 mmol, 1.0 equiv, 43.5 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL cyclohexane. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 86% conversion of starting material. Borylation of N,N-dimethylacetamide in dioxane 61 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.5 equiv) N N N dioxane, 80 ºC, 24 h H Si L3 1a 2a In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.0075 mmol, 1.5 mol %, 4.9 mg), L3 (0.015 mmol, 3 mol %, 3.1 mg), and B2pin2 (0.75 mmol, 1.5 equiv, 190.4 mg) were weighed into separate test tubes and N,N-dimethylacetamide (0.5 mmol, 1.0 equiv, 43.5 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL dioxane. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 100% conversion of starting material. Borylation of N,N-dimethylacetamide in toluene 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.5 equiv) N N N toluene, 80 ºC, 24 h H Si L3 1a 2a In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.0075 mmol, 1.5 mol %, 4.9 mg), L3 (0.015 mmol, 3 mol %, 3.1 mg), and B2pin2 (0.75 mmol, 1.5 equiv, 190.4 mg) were weighed into separate test tubes and N,N-dimethylacetamide (0.5 mmol, 1.0 equiv, 43.5 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 62 mL toluene. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 81% conversion of starting material. Isolation of borylated N,N-dimethylacetamide using neutral alumina 1.5 mol % [Ir(OMe)(cod)]2 O 3 mol % L3 O Bpin B2pin2 (1.5 equiv) N N N THF, 80 ºC, 7.5 h H Si 1a 2a L3 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), and B2pin2 (1.5 mmol, 1.5 equiv, 380.9 mg) were weighed into separate test tubes and N,N-dimethylacetamide (1 mmol, 1.0 equiv, 87.1 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 63 100% conversion of starting material. The crude reaction mixture was passed through neutral alumina with a gradient solvent system of 10% MeOH in EtOAc. After overnight drying under high vacuum, (2a) was obtained as a white solid (83.1 mg, 39% yield) which matched previously reported spectra.5 Repetition of reaction conditions shown by Yao for borylation of N,N-dimethylacetamide 0.05 mol % [Ir(OMe)(cod)]2 O 0.05 mol % L3 O Bpin B2pin2 (1.0 equiv) N N N Neat, 120 ºC, 24 h H Si L3 1a 2a In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.005 mmol, 0.05 mol %, 3.3 mg), L3 (0.005 mmol, 0.05 mol %, 1.0 mg), and N,N-dimethylacetamide (10.0 mmol, 1.0 equiv, 0.87 g) were weighed into separate test tubes and B2pin2 (10.0 mmol, 1.0 equiv, 2.54 g) was weighed into a oven dried 25 mL round bottom flask equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL N,N-dimethylacetamide. The resulting solution was then transferred into the round bottom flask containing B2pin2. The contents of the first test tube were rinsed two times (~0.2 mL/rinse) and added to the round bottom flask containing B2pin2. To the test tube containing L3 was added ~0.2 mL N,N-dimethylacetamide. The contents of the second test tube were rinsed three times (~0.2 mL/rinse) and added to the round bottom flask containing B2pin2. Finally, the rest of N,N-dimethylacetamide was transferred into a round bottom flask which was sealed with a septa and placed in an oil bath pre-heated to 120 °C and allowed to stir for 24 h. The flask was then opened and 1H and 11B NMR of crude material were collected. In the 1H NMR spectrum, starting material, B2pin2 and borates made up all the material. The 11B NMR showed only three peaks corresponding to B2pin2 at 30 ppm and borates at 21 ppm and 22 ppm. Based on 64 these data, it was concluded that no product-like material was formed under these reaction conditions. Repetition of reaction conditions shown by Yao for borylation of N,N-dimethylisobutyramide 0.05 mol % [Ir(OMe)(cod)]2 O 0.05 mol % L3 O Bpin B2pin2 (1.0 equiv) N N N Neat, 120 ºC, 24 h H Si L3 1c 2c In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.005 mmol, 0.05 mol %, 3.3 mg), L3 (0.005 mmol, 0.05 mol %, 1.0 mg), and N,N-dimethylisobutyramide (10.0 mmol, 1.0 equiv, 1.15 g) were weighed into separate test tubes and B2pin2 (10.0 mmol, 1.0 equiv, 2.54 g) was weighed into a oven dried 25 mL round bottom flask equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL N,N-dimethylisobutyramide. The resulting solution was then transferred into the round bottom flask containing B2pin2. The contents of the first test tube were rinsed two times (~0.2 mL/rinse) and added to the round bottom flask containing B2pin2. To the test tube containing L3 was added ~0.2 mL N,N-dimethylisobutyramide. The contents of the second test tube were rinsed three times (~0.2 mL/rinse) and added to the round bottom flask containing B2pin2. Finally, the rest of N,N-dimethylisobutyramide was transferred into a round bottom flask which was sealed with a septa and placed in an oil bath pre-heated to 120 °C and allowed to stir for 24 h. The flask was then opened and 1H and 11B NMR of crude material were collected. In the 1H NMR spectrum, starting material, B2pin2 and borates made up all of the material. The 11B NMR showed only three peaks corresponding to B2pin2 at 30 ppm and borates at 21 ppm and 22 ppm. Based on these data, it was concluded that no product-like material was formed under these reaction conditions. Repetition of reaction conditions shown by Yao for borylation of N,N-dimethylpentanamide 65 0.05 mol % [Ir(OMe)(cod)]2 O 0.05 mol % L3 O Bpin B2pin2 (1.0 equiv) N n-Bu N n-Bu N Neat, 120 ºC, 24 h H Si L3 1f 2f In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.005 mmol, 0.05 mol %, 3.3 mg), L3 (0.005 mmol, 0.05 mol %, 1.0 mg), and N,N-dimethylpentanamide (10.0 mmol, 1.0 equiv, 1.29 g) were weighed into separate test tubes and B2pin2 (10.0 mmol, 1.0 equiv, 2.54 g) was weighed into a oven dried 25 mL round bottom flask equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL N,N-dimethylpentanamide. The resulting solution was then transferred into the round bottom flask containing B2pin2. The contents of the first test tube were rinsed two times (~0.2 mL/rinse) and added to the round bottom flask containing B2pin2. To the test tube containing L3 was added ~0.2 mL N,N-dimethylpentanamide. The contents of the second test tube were rinsed three times (~0.2 mL/rinse) and added to the round bottom flask containing B2pin2. Finally, the rest of N,N-dimethylpentanamide was transferred into a round bottom flask which was sealed with a septa and placed in an oil bath pre-heated to 120 °C and allowed to stir for 24 h. The flask was then opened and 1H and 11B NMR of crude material were collected. In the 1 H NMR spectrum, starting material, B2pin2 and borates made up all of the material. The 11B NMR showed only two peaks corresponding to B2pin2 at 30 ppm and borates at 22 ppm. Based on these data, it was concluded that no product-like material was formed under these reaction conditions. Repetition of reaction conditions shown by Yao for borylation of 1,3- dimethyltetrahydropyrimidin-2(1H)-one 0.05 mol % [Ir(OMe)(cod)]2 O 0.05 mol % L3 O Bpin B2pin2 (1.0 equiv) N N N N N Neat, 120 ºC, 24 h H Si L3 1o 2o 66 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.005 mmol, 0.05 mol %, 3.3 mg), L3 (0.005 mmol, 0.05 mol %, 1.0 mg), and 1,3-dimethyltetrahydropyrimidin-2(1H)-one (10.0 mmol, 1.0 equiv, 1.28 g) were weighed into separate test tubes and B2pin2 (10.0 mmol, 1.0 equiv, 2.54 g) was weighed into a oven dried 25 mL round bottom flask equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL 1,3-dimethyltetrahydropyrimidin-2(1H)-one. The resulting solution was then transferred into the round bottom flask containing B2pin2. The contents of the first test tube were rinsed two times (~0.2 mL/rinse) and added to the round bottom flask containing B2pin2. To the test tube containing L3 was added ~0.2 mL 1,3- dimethyltetrahydropyrimidin-2(1H)-one. The contents of the second test tube were rinsed three times (~0.2 mL/rinse) and added to the round bottom flask containing B2pin2. Finally, the rest of 1,3-dimethyltetrahydropyrimidin-2(1H)-one was transferred into a round bottom flask which was sealed with a septa and placed in an oil bath pre-heated to 120 °C and allowed to stir for 24 h. The flask was then opened and 1H and 11 B NMR of crude material were collected. In the 1H NMR spectrum, starting material, B2pin2 and borates made up all of the material. The 11B NMR showed four peaks corresponding to B2pin2 at 30 ppm and borates at 21 ppm, 22 ppm, and 28 ppm. Based on these data, it was concluded that no product-like material was formed under these reaction conditions. Competition reaction between 2-chloro-N,N-dimethylacetamide and N,N-dimethylacetamide 1.5 mol % [Ir(OMe)(cod)]2 3 mol % L3 Bpin Bpin O O O O N 1.5 equiv B2pin2 Cl Cl H Si N N THF, 80 ºC, 24 h N N L3 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), B2pin2 (0.75 mmol, 1.5 equiv, 380.8 mg), and N,N-dimethylacetamide (0.5 mmol, 0.5 equiv, 43.5 mg) were weighed into separate test tubes and 2-chloro-N,N- 67 dimethylacetamide (0.5 mmol, 0.5 equiv, 60.7 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. The solution of [Ir(OMe)(cod)]2, B2pin2 and L3 was then transferred into the test tube containing N,N-dimethylacetamide and the rinsing procedure was repeated Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. Only starting material was observed. Competition reaction between 2,2,2-trifluoro-N,N-dimethylacetamide and N,N-dimethylacetamide 1.5 mol % [Ir(OMe)(cod)]2 3 mol % L3 Bpin Bpin O O O O 1.5 equiv B2pin2 N F3C N N THF, 80 ºC, 24 h F3C N N H Si L3 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.015 mmol, 1.5 mol %, 9.9 mg), L3 (0.03 mmol, 3 mol %, 6.2 mg), B2pin2 (0.75 mmol, 1.5 equiv, 380.8 mg), and N,N-dimethylacetamide (0.5 mmol, 0.5 equiv, 43.5 mg) were weighed into separate test tubes and 2,2,2-trifluoro-N,N- dimethylacetamide (0.5 mmol, 0.5 equiv, 70.5 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. The solution of [Ir(OMe)(cod)]2, B2pin2 and L3 was then transferred into 68 the test tube containing N,N-dimethylacetamide and the rinsing procedure was repeated Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 24 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. Approximately 60% conversion of starting material was observed. Experimental details Chapter 3 Borylation of N’-(sec-butyl)-N,N-dimethylacetimidamide 1.5 mol % [Ir(OMe)(cod)]2 N 3 mol % L3 N Bpin B2pin2 (1.0 equiv) N N N THF, 80 ºC, 1 h H Si L3 3a 4a In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.0075 mmol, 1.5 mol %, 4.9 mg), L3 (0.015 mmol, 3 mol %, 3.1 mg), and B2pin2 (0.75 mmol, 1.5 equiv, 190.9 mg) were weighed into separate test tubes and N’-(sec-butyl)-N,N-dimethylacetimidamide (0.5 mmol, 1.0 equiv, 71.1 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 1 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR 69 of crude material was collected. There was 100% conversion of starting material. The crude product was sublimed at 80 ºC to obtain 4a as white solid (5mg, 4% yield). 1 H NMR (500 MHz, CDCl3): δH 3.64 (m, 1H), 2.90 (s, 3H), 2.28 (s, 2H), 2.0 (s, 3H), 1.73 (m, 1H), 1.59 (m, 1H) 1.27 (d, J = 7.14 Hz, 3H), 1.15 (s, 6H), 1.08 (d, J = 2.11 Hz, 6H), 0.9 (t, J = 7.4 Hz, 3H). 11B NMR (160 MHz, CDCl3): δB 8.54 (s). Borylation of N’-(tert-butyl)-N,N-dimethylacetimidamide 1.5 mol % [Ir(OMe)(cod)]2 N 3 mol % L3 N Bpin B2pin2 (1.5 equiv) N N N THF, 80 ºC, 1 h H Si L3 3b 4b In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.0075 mmol, 1.5 mol %, 4.9 mg), L3 (0.015 mmol, 3 mol %, 3.1 mg), and B2pin2 (0.75 mmol, 1.5 equiv, 190.9 mg) were weighed into separate test tubes and N’-(tert-butyl)-N,N-dimethylacetimidamide (0.5 mmol, 1.0 equiv, 71.1 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 1 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 100% conversion of starting material. The crude 1H and 11B NMR contains product 4b and B2pin2. 70 1 H NMR (500 MHz, CDCl3): δH 2.93 (s, 3H), 2.29 (s, 2H), 1.93 (s, 3H), 1.24 (s, 12H), 1.16 (s, 6H), 1.09 (s, 6H). 11B NMR (160 MHz, CDCl3): δB 8.41 (s). Borylation of N’-isopropyl-N,N-dimethylacetimidamide 1.5 mol % [Ir(OMe)(cod)]2 N 3 mol % L3 N Bpin B2pin2 (1.5 equiv) N N N THF, 80 ºC, 1 h H Si L3 3c 4c In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.0075 mmol, 1.5 mol %, 4.9 mg), L3 (0.015 mmol, 3 mol %, 3.1 mg), and B2pin2 (0.75 mmol, 1.5 equiv, 190.9 mg) were weighed into separate test tubes and N’-isopropyl-N,N-dimethylacetimidamide (0.5 mmol, 1.0 equiv, 64.1 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 1 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 100% conversion of starting material. The crude 1H and 11B NMR contains product 4c and B2pin2. 1 H NMR (500 MHz, CDCl3): δH 3.99 (m, 1H), 2.92 (s, 3H), 2.29 (s, 2H), 2.05 (s, 3H), 1.32 (d, J = 7.13 Hz, 6H), 1.18 (s, 6H), 1.10 (s, 6H). 11B NMR (160 MHz, CDCl3): δB 8.52 (s). Borylation of N’-isopropyl-N,N-dimethylacetimidamide with 1.0 equiv B2pin2 71 1.5 mol % [Ir(OMe)(cod)]2 N 3 mol % L3 N Bpin B2pin2 (1.0 equiv) N N N THF, 80 ºC, 1 h H Si L3 3c 4c In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.0075 mmol, 1.5 mol %, 4.9 mg), L3 (0.015 mmol, 3 mol %, 3.1 mg), and B2pin2 (0.5 mmol, 1.0 equiv, 126.5 mg) were weighed into separate test tubes and N’-isopropyl-N,N-dimethylacetimidamide (0.5 mmol, 1.0 equiv, 64.1 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 1 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 100% conversion of starting material. Borylation of N’-isopropyl-N,N-dimethylacetimidamide with 0.75 equiv B2pin2 1.5 mol % [Ir(OMe)(cod)]2 N 3 mol % L3 N Bpin B2pin2 (0.75 equiv) N N N THF, 80 ºC, 1 h H Si L3 3c 4c In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.0075 mmol, 1.5 mol %, 4.9 mg), L3 (0.015 mmol, 3 mol %, 3.1 mg), and B2pin2 (0.375 mmol, 0.75 equiv, 94.9 mg) were weighed into separate test tubes and N’-isopropyl-N,N-dimethylacetimidamide (0.5 mmol, 1.0 equiv, 64.1 mg) was 72 weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 1 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 100% conversion of starting material. Borylation of N’-isopropyl-N,N-dimethylacetimidamide with 0.5 equiv B2pin2 1.5 mol % [Ir(OMe)(cod)]2 N 3 mol % L3 N Bpin B2pin2 (0.50 equiv) N N N THF, 80 ºC, 1 h H Si L3 3c 4c In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.0075 mmol, 1.5 mol %, 4.9 mg), L3 (0.015 mmol, 3 mol %, 3.1 mg), and B2pin2 (0.25 mmol, 0.5 equiv, 63.9 mg) were weighed into separate test tubes and N’-isopropyl-N,N-dimethylacetimidamide (0.5 mmol, 1.0 equiv, 64.1 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to 73 stir for 1 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 100% conversion of starting material. Borylation of N’,N’-diethyl-N-methylacetimidamide with HBpin 1.5 mol % [Ir(OMe)(cod)]2 N 3 mol % L3 N Bpin HBpin (2.0 equiv) N N N THF, 80 ºC, 19 h H Si L3 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.0075 mmol, 1.5 mol %, 4.9 mg), L3 (0.015 mmol, 3 mol %, 3.1 mg), and HBpin (0.5 mmol, 1.0 equiv, 127.9 mg) were weighed into separate test tubes and N’,N’-diethyl-N-methylacetimidamide (1.0 mmol, 2.0 equiv, 64.1 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pin2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pin2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 19 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 0% conversion of starting material. Also, 0% conversion of starting material was observed according to GC/MS. Borylation of N’,N’-diethyl-N-methylacetimidamide with B2eg2 74 1.5 mol % [Ir(OMe)(cod)]2 N 3 mol % L3 N Beg O O B2eg2 (1.0 equiv) N B B N N O O THF, 80 ºC, 1 h H Si L3 B2eg2 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.0075 mmol, 1.5 mol %, 4.9 mg), L3 (0.015 mmol, 3 mol %, 3.1 mg), and N’,N’-diethyl-N-methylacetimidamide (0.5 mmol, 1.0 equiv, 64.1 mg) were weighed into separate test tubes and B2eg2 (0.5 mmol, 1.0 equiv, 70.5 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the conical vial containing B2eg2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2eg2 containing conical vial. To the test tube containing ligand L3 was added ~0.2 mL THF. The resulting solution was then transferred into the conical vial containing B2eg2. The contents of the second test tube were rinsed three times (~0.2 mL/rinse) and added to the B2eg2 containing conical vial. Finally, To the test tube containing N’,N’-diethyl-N-methylacetimidamide was added ~0.2 mL THF. The resulting solution was then transferred into the conical vial containing B2eg2. The contents of the third test tube were rinsed three times (~0.2 mL/rinse) and added to the B2eg2 containing conical vial. The conical vial was then sealed and placed in an aluminum block pre- heated to 80 °C and allowed to stir for 1 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 100% conversion of starting material. 1 H NMR (500 MHz, C6D6): δH 4.20 (m, 1H), 4.13 (t, J = 7.12 Hz, 2H), 4.08 (m, 1H) 2.64 (s, 2H), 2.55 (s, 3H), 2.47 (m, 2H), 1.30 (d, J = 7.27 Hz, 3H), 0.98 (t, J = 7.11 Hz, 2H), 0.80 (s, 3H), 0.55 (t, J = 7.19 Hz 3H). 11B NMR (160 MHz, C6D6): δB 10.05 (s). Borylation of N’,N’-diethyl-N-methylacetimidamide with B2pg2 75 1.5 mol % [Ir(OMe)(cod)]2 N 3 mol % L3 N Bpg O O B2pg2 (1.0 equiv) N B B N N O O THF, 80 ºC, 1 h H Si L3 B2pg2 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.0075 mmol, 1.5 mol %, 4.9 mg), L3 (0.015 mmol, 3 mol %, 3.1 mg), and B2pg2 (0.5 mmol, 1.0 equiv, 85.5 mg) were weighed into separate test tubes and N’,N’-diethyl-N-methylacetimidamide (0.5 mmol, 1.0 equiv, 64.1 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2pg2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2pg2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 1 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 100% conversion of starting material according to GC/MS. Borylation of N’,N’-diethyl-N-methylacetimidamide with B2bg2 1.5 mol % [Ir(OMe)(cod)]2 N 3 mol % L3 N Bbg B2bg2 (1.0 equiv) O O N N N B B THF, 80 ºC, 26 h H Si O O L3 B2bg2 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.0075 mmol, 1.5 mol %, 4.9 mg), L3 (0.015 mmol, 3 mol %, 3.1 mg), and B2bg2 (0.5 mmol, 1.0 equiv, 98.9 mg) were weighed into separate test tubes and N’,N’-diethyl-N-methylacetimidamide (0.5 mmol, 1.0 equiv, 64.1 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was 76 added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2bg2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2bg2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 26 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 15% conversion of starting material according to GC/MS. Borylation of N’,N’-diethyl-N-methylacetimidamide with B2mbg2 1.5 mol % [Ir(OMe)(cod)]2 N 3 mol % L3 N Bmbg B2mbg2 (1.0 equiv) O O N N N B B THF, 80 ºC, 26 h H Si O O L3 B2mbg2 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.0075 mmol, 1.5 mol %, 4.9 mg), L3 (0.015 mmol, 3 mol %, 3.1 mg), and B2mbg2 (0.5 mmol, 1.0 equiv, 112.9 mg) were weighed into separate test tubes and N’,N’-diethyl-N-methylacetimidamide (0.5 mmol, 1.0 equiv, 64.1 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the test tube containing B2mbg2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2mbg2 containing test tube. The solution of [Ir(OMe)(cod)]2 and B2pin2 was then transferred into the test tube containing L3 and the rinsing procedure was repeated. Finally, the resulting solution was added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 26 h. 77 The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 0% conversion of starting material. NMR Yield for borylated amidine with B2eg2 with 1,3,5-trimethoxybenzene as internal standard 1.5 mol % [Ir(OMe)(cod)]2 O N 3 mol % L3 N Beg O B2eg2 (1.0 equiv) N N N H Si THF, 80 ºC, 1 h O O O O L3 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.0075 mmol, 1.5 mol %, 4.9 mg), L3 (0.015 mmol, 3 mol %, 3.1 mg), N’,N’-diethyl-N-methylacetimidamide (0.5 mmol, 1.0 equiv, 64.8 mg) and 1,3,5-trimethoxybenzene (0.5 mmol, 1.0 equiv, 84 mg) were weighed into separate test tubes and B2eg2 (0.5 mmol, 1.0 equiv, 126.5 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the conical vial containing B2eg2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2eg2 containing conical vial. To the test tube containing ligand L3 was added ~0.2 mL THF. The resulting solution was then transferred into the conical vial containing B2eg2. The contents of the second test tube were rinsed three times (~0.2 mL/rinse) and added to the B2eg2 containing conical vial. To the test tube containing N’,N’-diethyl-N-methylacetimidamide was added ~0.2 mL THF. The resulting solution was then transferred into the conical vial containing B2eg2. The contents of the third test tube were rinsed three times (~0.2 mL/rinse) and added to the B2eg2 containing conical vial. Finally, to the test tube containing 1,3,5-trimethoxybenzene was added ~0.2 mL THF. The resulting solution was then transferred into the conical vial containing B2eg2. The contents of the fourth test tube were rinsed three times (~0.2 mL/rinse) and added to the B2eg2 containing conical vial. The conical vial was then sealed and placed in an aluminum block pre-heated to 80 °C and allowed to stir for 1 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude 78 material was collected. 33% NMR yield with respect to internal standard 1,3,5-trimethoxybenzene was observed. Borylation of N’,N’-diethyl-N-methylformimidamide with B2eg2 1.5 mol % [Ir(OMe)(cod)]2 N 3 mol % L3 N Beg O O B2eg2 (1.0 equiv) N B B H N H N H Si O O THF, 80 ºC, 1 h L3 B2eg2 In a nitrogen filled glove box, [Ir(OMe)(cod)]2 (0.0075 mmol, 1.5 mol %, 4.9 mg), L3 (0.015 mmol, 3 mol %, 3.1 mg), and N’,N’-diethyl-N-methylformimidamide (0.5 mmol, 1.0 equiv, 57.1 mg) were weighed into separate test tubes and B2eg2 (0.5 mmol, 1.0 equiv, 70.5 mg) was weighed into a 5 mL conical vial equipped with a stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added ~0.2 mL THF. The resulting solution was then transferred into the conical vial containing B2eg2. The contents of the first test tube were rinsed three times (~0.2 mL/rinse) and added to the B2eg2 containing conical vial. To the test tube containing ligand L3 was added ~0.2 mL THF. The resulting solution was then transferred into the conical vial containing B2eg2. The contents of the second test tube were rinsed three times (~0.2 mL/rinse) and added to the B2eg2 containing conical vial. Finally, To the test tube containing N’,N’-diethyl-N-methylacetimidamide was added ~0.2 mL THF. The resulting solution was then transferred into the conical vial containing B2eg2. The contents of the third test tube were rinsed three times (~0.2 mL/rinse) and added to the B2eg2 containing conical vial. The conical vial was then sealed and placed in an aluminum block pre- heated to 80 °C and allowed to stir for 1 h. The vial was then opened, solvent was removed via rotary evaporation, and 1H NMR of crude material was collected. There was 71% conversion of starting material based on GC/MS. 79 APPENDIX 80 APPENDIX Spectra Figure 3: 1H NMR (500 MHz, CDCl3) L3 81 Figure 4: 13C NMR (125 MHz, CDCl3) L3 82 Figure 5: 29Si NMR (99 MHz, CDCl3) L3 83 Figure 6: 1H NMR (500 MHz, CDCl3) L4 84 Figure 7: 13C NMR (125 MHz, CDCl3) L4 85 Figure 8: 29Si NMR (99 MHz, CDCl3) L4 86 Figure 9: 1H NMR (500 MHz, CDCl3) L5 87 Figure 10: 13C NMR (125 MHz, CDCl3) L5 88 Figure 11: 1H NMR (CDCl3, 500 MHz) 3a 89 Figure 12: 13C NMR (125 MHz, CDCl3) 3a 90 Figure 13: 11B NMR (CDCl3, 160 MHz) 3a 91 Figure 14: 1H NMR (CDCl3, 500 MHz) 3c 92 Figure 15: 13C NMR (125 MHz, CDCl3) 3c 93 Figure 16: 11B NMR (CDCl3, 160 MHz) 3c 94 Figure 17: 1H NMR (CDCl3, 500 MHz) 3b 95 Figure 18: 13C NMR (125 MHz, CDCl3) 3b 96 Figure 19: 11B NMR (CDCl3, 160 MHz) 3b 97 Figure 20: 1H NMR (CDCl3, 500 MHz) 3e 98 Figure 21: 13C NMR (125 MHz, CDCl3) 3e 99 Figure 22: 11B NMR (CDCl3, 160 MHz) 3e 100 Figure 23: 1H NMR (CDCl3, 500 MHz) 3d 101 Figure 24: 13C NMR (125 MHz, CDCl3) 3d 102 Figure 25: 11B NMR (CDCl3, 160 MHz) 3d 103 Figure 26: 1H NMR (CDCl3, 500 MHz) 3f 104 Figure 27: 13C NMR (125 MHz, CDCl3) 3f 105 Figure 28: 11B NMR (CDCl3, 160 MHz) 3f 106 Figure 29: 1H NMR (CDCl3, 500 MHz) 3g 107 Figure 30: 13C NMR (125 MHz, CDCl3) 3g 108 Figure 31: 11B NMR (CDCl3, 160 MHz) 3g 109 Figure 32: 1H NMR (CDCl3, 500 MHz) 3h 110 Figure 33: 13C NMR (125 MHz, CDCl3) 3h 111 Figure 34: 11B NMR (CDCl3, 160 MHz) 3h 112 Figure 35: 1H NMR (CDCl3, 500 MHz) 3i 113 Figure 36: 13C NMR (125 MHz, CDCl3) 3i 114 Figure 37: 11B NMR (CDCl3, 160 MHz) 3i 115 Figure 38: 1H NMR (CDCl3, 500 MHz) 3k 116 Figure 39: 13C NMR (125 MHz, CDCl3) 3k 117 Figure 40: 11B NMR (CDCl3, 160 MHz) 3k 118 Figure 41: 1H NMR (CDCl3, 500 MHz) 3l 119 Figure 42: 13C NMR (125 MHz, CDCl3) 3l 120 Figure 43: 11B NMR (CDCl3, 160 MHz) 3l 121 Figure 44: 1H NMR (CDCl3, 500 MHz) 3o 122 Figure 45: 13C NMR (125 MHz, CDCl3) 3o 123 Figure 46: 11B NMR (CDCl3, 160 MHz) 3o 124 Figure 47: 1H NMR (CDCl3, 500 MHz) 3q 125 Figure 48: 13C NMR (125 MHz, CDCl3) 3q 126 Figure 49: 11B NMR (CDCl3, 160 MHz) 3q 127 Figure 50: 1H NMR (CDCl3, 500 MHz) 3m 128 Figure 51: 13C NMR (125 MHz, CDCl3) 3m 129 Figure 52: 11B NMR (CDCl3, 160 MHz) 3m 130 AY_147_sub1_PROTON_01 7.26 cdcl3 3.67 3.66 3.66 3.65 3.64 3.63 3.63 3.62 3.62 3.60 2.90 2.89 2.28 2.11 H2O 2.00 2.00 2.00 1.77 1.76 1.76 1.74 1.74 1.73 1.72 1.71 1.70 1.70 1.69 1.63 1.62 1.61 1.60 1.60 1.60 1.59 1.59 1.58 1.57 1.57 1.57 1.56 1.56 1.54 1.28 1.26 1.24 1.21 1.20 1.20 1.15 1.09 1.08 1.07 0.91 0.90 0.88 H3C CH3 H3C H3C CH3 O O H3C N B J (d) H3C N 1.08 J(2.11) CH3 F (ddq) 1.59 J(13.31, 8.93, 7.27) B (s) 2.90 D (d) H (d) 2.00 1.20 J(1.03) J(1.75) A (dp) C (s) I (s) 3.64 2.28 1.15 J(9.04, 7.05) E (m) K (t) 1.73 3.8 3 .6 3 .4 3 .2 3 .0 2. 8 2.6 2.4 2.2 2.0 1. 8 1.6 1.4 1.2 1.0 0. 8 0.90 f1 (ppm) J(7.41) G (d) 1.27 J(7.14) 1.03 2.84 2.18 3.00 1.08 1.10 3.02 0.80 6.52 6.29 2.89 13 .5 13 .0 12.5 12.0 11.5 11.0 10.5 10.0 9.5 9.0 8 .5 8 .0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3 .5 3 .0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 -1.0 -1.5 f1 (ppm) Figure 53: 1H NMR (CDCl3, 500 MHz) 4a 131 AY_147_sub1_s2pul_01 8.54 H3C CH3 H3C H3C CH3 O O H3C N B H3C N CH3 90 80 70 60 50 40 30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 f1 (ppm) Figure 54: 11B NMR (CDCl3, 160 MHz) 4a 132 AY_152_crude_1h_PROTON_01 2.93 2.29 1.25 1.24 1.93 1.16 1.92 1.09 H3C CH3 CH3 H3C CH3 B2pin2 H3C O O H3C N B H3C N CH3 G (s) 1.24 H (s) F (s) 1.93 1.16 A (s) B (s) E (s) 2.93 2.29 1.09 3 .2 3 .0 2. 8 2.6 2.4 2.2 2.0 1. 8 1.6 1.4 1.2 1.0 0. 8 D (s) f1 (ppm) 1.25 18.59 3.00 2.21 2.39 13.75 6.84 6.15 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1 f1 (ppm) Figure 55: 1H NMR (CDCl3, 500 MHz) 4b 133 AY_152_crude_1h_s2pul_01 30.24 22.26 8.41 H3C CH3 H3C CH3 CH3 H3C O O H3C N B H3C N CH3 B2pin2 90 80 70 60 50 40 30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 f1 (ppm) Figure 56: 11B NMR (CDCl3, 160 MHz) 4b 134 AY_156_crude_PROTON_01 4.03 2.92 4.02 2.29 2.05 4.00 3.99 1.33 1.31 1.26 3.97 3.96 1.26 1.18 3.95 1.10 H3C CH3 H3C CH3 CH3 H3C N O B O B2pin2 H (d) 1.26 J(1.82) H3C N CH3 F (s) 1.10 D (s) 2.05 E (d) A (m) B (s) C (s) 1.32 3.99 2.92 2.29 J(7.13) 4.0 3.8 3 .6 3 .4 3 .2 3 .0 2. 8 2.6 2.4 2.2 2.0 1. 8 1.6 1.4 1.2 1.0 f1 (ppm) G (s) 1.18 6.11 0.95 3.06 2.02 59.05 7.20 3.19 6.79 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1 f1 (ppm) Figure 57: 1H NMR (CDCl3, 500 MHz) 4c 135 AY_156_crude_s2pul_01 30.51 22.37 8.52 H3C CH3 H3C CH3 CH3 O O H3C N B H3C N CH3 B2pin2 90 80 70 60 50 40 30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 f1 (ppm) Figure 58: 11B NMR (CDCl3, 160 MHz) 4c 136 AY_294_crude_benz_PROTON_01 4.22 4.21 4.21 4.20 4.20 4.19 4.14 4.13 4.13 4.12 4.10 4.10 4.09 4.08 4.08 4.07 4.06 2.68 2.67 2.66 2.65 2.64 2.63 2.61 2.60 2.55 2.51 2.50 2.48 2.48 2.47 2.47 2.46 2.45 2.44 2.44 1.30 1.29 0.99 0.98 0.97 0.80 0.80 0.57 0.55 0.54 H3C O O N B H3C N CH3 CH3 J (t) 0.98 J(7.11) B (t) H (t) 4.13 0.55 4.35 4.30 4.25 4.20 4.15 4.10 4.05 4.00 2. 8 2.7 2.6 2.5 2.4 2.3 E (m) f1 (ppm) f1 (ppm) J(7.12) J(7.19) 2.47 G (d) A (m) D (m) 1.30 4.20 2.64 J(7.27) C (m) F (s) 4.08 2.55 I (s) 0.80 1.5 1.4 1.3 1.2 1.1 1.0 0.9 0. 8 0.7 0.6 0.5 0.4 f1 (ppm) 1.00 2.16 3.77 1.69 1.98 2.71 2.80 1.03 2.33 3.05 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1 f1 (ppm) Figure 59: 1H NMR (C6D6, 500 MHz) 6a 137 AY_294_crude_benz_s2pul_01 10.05 H3C O O N B H3C N CH3 CH3 90 80 70 60 50 40 30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 f1 (ppm) Figure 60: 11B NMR (C6D6, 160 MHz) 6a 138 O O N B N Figure 61: GC/MS Data 6a’ SM O O N B N Figure 62: GC/MS Data 6a’’ 139 REFERENCES 140 REFERENCES 1. 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