CHEMISTRY OF N-HETEROCYCLIC CARBENE–BORANE COMPLEXES by Andrey Solovyev B.S., Saint-Petersburg State University, St. Petersburg, Russia, 2007 Submitted to the Graduate Faculty of the Kenneth P. Dietrich School of Arts and Sciences in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Pittsburgh 2012 UNIVERSITY OF PITTSBURGH KENNETH P. DIETRICH SCHOOL OF ARTS AND SCIENCES This dissertation was presented by Andrey Solovyev It was defended on December 13, 2011 and approved by Paul E. Floreancig, Professor, Chemistry Krzysztof Matyjaszewski, Professor, Carnegie Mellon University Peter Wipf, University Professor, Chemistry Committee Chair: Dennis P. Curran, Distinguished Service Professor, Chemistry ii Copyright © by Andrey Solovyev 2012 iii CHEMISTRY OF N-HETEROCYCLIC CARBENE–BORANE COMPLEXES Andrey Solovyev, PhD University of Pittsburgh, 2012 Studies on chemistry of N-heterocyclic carbene-borane complexes (NHC-boranes), a new class of organic reagents, are reported. The radical chain mechanism of xanthate reduction with NHC-boranes has been established by the evaluation of rate constants of hydrogen abstraction, the isolation of boron-derived by-products, and EPR spectroscopic studies. NHC-BH3 complexes have been found to react with many electrophilic compounds. They reduce alkyl halides and sulfonates by an ionic mechanism. The boron products of their reactions with halogenation agents, Brønsted and Lewis acids were isolated and characterized. NHC-boryl iodide and triflate complexes undergo nucleophilic substitutions at the boron atom. In this way, a variety of substituted boranes with unusual and unprecedented structural motifs were prepared, including boryl azides, nitrosooxyborane, and nitroborane. The reaction with phenoxides in tetrahydrofuran (THF) afforded unexpected products of THF ring opening. A compound with a novel dihydroxyborenium cation was obtained from certain disubstituted NHC-boranes under acidic conditions. Reduction of NHC-boryl iodide complex with lithium di-tert-butylbiphenylide (LDDB) gave a reactive NHC-boryl anion. This was trapped with several electrophiles to obtain boron- substituted complexes, including acyl boranes. Deprotonation of imidazol-2-ylidene-boranes with BuLi and subsequent reactions with electrophiles allowed us to prepare ring-functionalized NHC-borane complexes. The resulting complexes of substituted NHC and BH3 can be converted to corresponding substituted imidazolium salts by a simple deboronation protocol. iv TABLE OF CONTENTS PREFACE ................................................................................................................................. XVI 1.0 INTRODUCTION ........................................................................................................ 1 1.1 COMPLEXES OF BORANES WITH LEWIS BASES ................................... 2 1.2 NHC-BORANES .................................................................................................. 6 2.0 MECHANISTIC STUDIES OF RADICAL REDUCTION WITH NHC- BORANES ................................................................................................................................... 11 2.1 BARTON–MCCOMBIE DEOXYGENATION .............................................. 11 2.2 KINETIC STUDIES OF HYDROGEN ABSTRACTION FROM NHC- BORANES ........................................................................................................................... 16 2.3 ISOLATION OF BORON-DERIVED BY-PRODUCT ................................. 24 2.4 EPR STUDIES ................................................................................................... 27 3.0 REACTIONS OF NHC-BH3 COMPLEXES WITH ELECTROPHILES ........... 30 3.1 IONIC REDUCTION OF ALKYL HALIDES AND SULFONATES .......... 30 3.2 ISOLATION OF BORON-DERIVED BY-PRODUCTS OF IONIC REDUCTIONS ................................................................................................................... 37 3.3 REACTIONS WITH HALOGENATING AGENTS AND ACIDS .............. 43 4.0 NUCLEOPHILIC SUBSTITUTION AT BORON ATOM .................................... 52 v 4.1 NUCLEOPHILIC SUBSTITUTION OF NHC-BORYL IODIDE AND TRIFLATE .......................................................................................................................... 52 4.2 RING-OPENING OF TETRAHYDROFURAN AND RELATED REACTIONS ...................................................................................................................... 66 4.3 NHC-STABILIZED DIHYDROXYBORENIUM CATION ......................... 85 5.0 FORMATION OF LITHIATED NHC-BORANES AND THEIR REACTIONS WITH ELECTROPHILES ........................................................................................................ 90 5.1 NHC-BORYL LITHIUM AND ITS REACTIONS WITH ELECTROPHILES ............................................................................................................ 90 5.2 NHC-RING SUBSTITUTION REACTIONS ................................................. 98 6.0 CONCLUSIONS ...................................................................................................... 110 7.0 EXPERIMENTAL ................................................................................................... 111 7.1 GENERAL REMARKS AND METHODS ................................................... 111 7.2 COMPOUND DATA FOR SECTION 2 ........................................................ 113 7.3 COMPOUND DATA FOR SECTION 3 ........................................................ 125 7.4 COMPOUND DATA FOR SECTION 4 ........................................................ 150 7.5 COMPOUND DATA FOR SECTION 5 ........................................................ 188 APPENDIX A ............................................................................................................................ 224 APPENDIX B ............................................................................................................................ 228 BIBLIOGRAPHY ..................................................................................................................... 229 vi LIST OF TABLES Table 1. Results of PTOC experiments for hydrogen donors with the known kH. ....................... 20 Table 2. The isolated yields of dipp-Imd-BH2SC(=O)SMe 84..................................................... 24 Table 3. Ionic reduction of halides with dipp-Imd-BH3 40. ......................................................... 31 Table 4. Ionic reduction of alkyl sulfonates with dipp-Imd-BH3 40. ........................................... 33 Table 5. The formation of dipp-Imd-BH2X by the reduction of alkyl halides and sulfonates. .... 37 Table 6. The reactions of dipp-Imd-BH3 with Brønsted acids...................................................... 45 Table 7. Nucleophilic substitution of dipp-Imd-BH2X at boron. .................................................. 53 Table 8. Double nucleophilic substitution at the boron atom. ...................................................... 62 Table 9. The influence of the amounts of THF on the yield of 163. ............................................ 67 Table 10. The influence of the phenoxide counterion on the yield of 163. .................................. 68 Table 11. The optimization of time and temperature for the synthesis of 163. ............................ 69 Table 12. The influence of the phenoxide counterion on the ratio of products 162 and 163. ...... 71 Table 13. The reaction of 119 with 4-substituted sodium phenoxides 167a-c. ............................ 73 Table 14. Synthesis of dipp-Imd-BH2E by the reaction of 212 with electrophiles. ...................... 93 Table 15. Reactions of deprotonated NHC-BH3 complexes with TMSCl. ................................. 101 Table 16. Reactions of deprotonated NHC-BH3 complexes 40 and 45 with electrophiles. ....... 103 Table 17. Kinetic measurement data for NHC-boranes. ............................................................. 122 vii LIST OF FIGURES Figure 1. The structures of boromycin and bortezomib. ................................................................. 6 Figure 2. The structures of diAd-Imd 29 and the 2nd generation Grubbs catalyst 30. ................... 6 Figure 3. Representative examples of NHC-borane complexes synthesized before 2008. ............ 8 Figure 4. The scale of rates constants of common hydrogen atom donors with primary alkyl radicals. ......................................................................................................................................... 17 –1 –1 Figure 5. Rate constants kH (M s ) measured for 15 NHC-BH3 complexes by the PTOC method........................................................................................................................................... 21 Figure 6. The place of NHC-boranes among other hydrogen donors. .......................................... 23 Figure 7. The X-Ray crystal structure of dipp-Imd-BH2SC(=O)SMe 84. .................................... 26 Figure 8. The EPR spectrum of the radical 88. ............................................................................. 28 Figure 9. The sketches of SOMO orbitals of NHC- and amine-boryl radicals............................. 29 Figure 10. Two independent crystallographic molecules of dipp-Imd-BH2OTs 117. .................. 39 Figure 11. The X-ray crystal structure of dipp-Imd-BH(OTf)Cl 132. .......................................... 48 Figure 12. The X-ray crystal structure of dipp-Imd-BH2SO2PT 156. .........................................