N–Heterocyclic Carbenes: Effective Tools for Organometallic Synthesis

This comprehensive reference and handbook covers in depth all major aspects of the use of N–heterocyclic carbene–complexes in organic synthesis: from the theoretical background to characterization, and from cross–coupling reactions to olefin metathesis. Edited by a leader and experienced scientist in the field of homogeneous catalysis and use of NHCs, this is an essential tool for every academic and industrial synthetic chemist.

List of Contributors XVII Preface XXI 1 N–Heterocyclic Carbenes 1 David J. Nelson and Steven P. Nolan 1.1 Introduction 1 1.2 Structure and Properties of NHCs 1 1.3 Abnormal Carbenes 5 1.4 Why Are NHCs Stable? 6 1.5 Bonding of NHCs to Metal Centers 8 1.6 Quantifying the Properties of NHCs 13 1.6.1 Steric Impact 13 1.6.2 Electronic Properties 14 1.7 N–Heterocyclic Carbenes in the Context of Other Stable Carbenes 16 1.8 Synthesis of NHCs 19 1.9 Salts and Adducts of NHCs 20 1.10 Summary 22 References 22 2 Tuning and Quantifying Steric and Electronic Effects of N–Heterocyclic Carbenes 25 Laura Falivene, Albert Poater, and Luigi Cavallo 2.1 Introduction 25 2.2 Steric Effects in NHC ligands 26 2.3 Electronic Effects in NHC Ligands 31 2.4 Conclusions 35 References 35 3 Chiral Monodendate N–Heterocyclic Carbene Ligands in Asymmetric Catalysis 39 Linglin Wu, Alvaro Salvador, and Reto Dorta 3.1 Introduction 39 3.2 NHC–Ru 40 3.2.1 Asymmetric Metathesis 40 3.2.2 Asymmetric Hydrogenation 44 3.2.3 Asymmetric Hydrosilylation 47 3.3 NHC–Rh 48 3.3.1 Asymmetric Catalysis Using Boronic Acids as Nucleophiles 48 3.3.2 Asymmetric Hydrosilylation 50 3.3.3 Asymmetric Hydroformylation 53 3.4 NHC–Ir 53 3.5 NHC–Ni 55 3.6 NHC–Pd 56 3.6.1 Asymmetric Intramolecular α–Arylation of Amides 56 3.6.2 Asymmetric Diamination 62 3.6.3 Other Asymmetric Catalysis Using NHC–Pd 63 3.7 NHC–Cu 65 3.7.1 Asymmetric Conjugate Addition 65 3.7.2 Asymmetric Allylic Substitution 67 3.7.3 Silyl Conjugate Addition 69 3.7.4 Enantioselective β–Boration 70 3.7.5 Asymmetric Hydrosilylation 72 3.7.6 Asymmetric Addition to Imines 73 3.8 NHC–Ag 75 3.9 NHC–Au 75 3.9.1 Enantioselective Cycloisomerizations 76 3.9.2 Enantioselective Hydrogenation 78 3.9.3 Enantioselective Cycloaddition 79 3.10 Conclusion 79 References 80 4 (N–Heterocyclic Carbene)–Palladium Complexes in Catalysis 85 Mario Hoyos, Daniel Guest, and Oscar Navarro 4.1 Introduction 85 4.2 Cross–Coupling Reactions 85 4.2.1 Suzuki–Miyaura Coupling 85 4.2.2 Buchwald–Hartwig Aminations 88 4.2.3 Negishi Reactions 89 4.2.4 Hiyama Coupling 89 4.2.5 Kumada Coupling 90 4.2.6 Sonogashira Coupling 90 4.2.7 Heck Reaction 92 4.3 Chelates and Pincer Ligands 93 4.4 Asymmetric Catalysis 97 4.5 Oxidation Reactions 100 4.6 Telomerization, Oligomerization and Polymerization 102 4.7 Anticancer NHC–Pd Complexes 107 References 107 5 NHC Platinum(0) Complexes: Unique Catalysts for the Hydrosilylation of Alkenes and Alkynes 111 Steve Dierick and István E. Markó 5.1 Introduction 111 5.2 Hydrosilylation of Alkenes: The Beginning 112 5.3 Initial Results with Phosphine Ligands 114 5.4 NHC Platinum(0) Complexes: The Breakthrough 115 5.4.1 Synthesis of NHC Platinum(0) Complexes and Kinetic Assays 115 5.4.2 Functional Group Tolerance and Substrate Scope 120 5.4.3 Mechanistic Studies 122 5.5 Hydrosilylation of Alkynes 133 5.5.1 Catalyst Screening and the Impact of NHCs on Regioselectivity 134 5.5.2 Influence of Silane on Regioselectivity 137 5.5.3 Second–Generation Catalyst for the Hydrosilylation of Alkynes 138 5.5.4 Functional Group Tolerance and Substrate Scope 139 5.5.5 Mechanistic Studies 142 5.6 Conclusions 146 References 146 6 Synthesis and Medicinal Properties of Silver–NHC Complexes and Imidazolium Salts 151 Patrick O. Wagers, Kerri L. Shelton, Matthew J. Panzner, Claire A. Tessier, and Wiley J. Youngs 6.1 Introduction 151 6.2 Silver–NHC Complexes as Antimicrobial Agents 152 6.3 Silver–NHC Complexes as Anticancer Agents 163 6.4 Conclusions 170 References 171 7 Medical Applications of NHC–Gold and –Copper Complexes 173 Faïma Lazreg and Catherine S. J. Cazin 7.1 Introduction 173 7.2 Gold Antimicrobial Agents 173 7.3 Metals as Antitumor Reagents 178 7.4 Copper Complexes as Antitumoral Reagents 195 7.5 Conclusion 196 References 197 8 NHC–Copper Complexes and their Applications 199 Faïma Lazreg and Catherine S. J. Cazin 8.1 Introduction 199 8.2 History of NHC–Copper Systems 199 8.3 Hydrosilylation 200 8.4 Allene Formation 202 8.5 1,4–Reduction 205 8.6 Conjugate Addition 206 8.6.1 Zinc Reagents 206 8.6.2 Grignard Reagents 207 8.6.3 Aluminum Reagents 209 8.6.4 Boron Reagents 209 8.7 Hydrothiolation, Hydroalkoxylation, Hydroamination 210 8.8 Carboxylation and Carbonylation (via Boronic Acids, CH Activation): CO2 Insertion 213 8.9 [3 + 2] Cycloaddition Reaction: Formation of Triazole 215 8.10 Allylic Substitution 217 8.10.1 Zinc Reagents 217 8.10.2 Grignard Reagents 217 8.10.3 Aluminum Reagents 219 8.10.4 Boron Reagents 220 8.11 Carbene and Nitrene Transfer 221 8.12 Boration Reaction 222 8.12.1 Boration of Ketone and Aldehyde 222 8.12.2 Boration of Alkene 223 8.12.3 Boration of Alkyne 224 8.12.4 Carboboration 226 8.13 Olefination of Carbonyl Derivatives 226 8.14 Copper–Mediated Cross–Coupling Reaction 228 8.15 Fluoride Chemistry 230 8.16 Other Reactions 231 8.16.1 A3 Coupling 231 8.16.2 Semihydrogenation of Alkyne 232 8.16.3 Borocarboxylation of Alkyne 233 8.16.4 Hydrocarboxylation of Alkyne 234 8.17 Transmetalation 235 8.18 Conclusion 237 References 237 9 NHC–Au(I) Complexes: Synthesis, Activation, and Application 243 Thomas Wurm, Abdullah Mohamed Asiri, and A. Stephen K. Hashmi 9.1 Introduction 243 9.2 Synthesis of NHC–Gold(I) Chlorides 244 9.3 Activation of NHC–Au(I) Chlorides 248 9.4 Applications of NHC–Au(I) Catalysts 253 9.4.1 Improvement of Catalyst Stability During Gold–Catalyzed Reactions Due to the Use of NHC Ligands 253 9.4.2 Improvement of Gold Catalysis Due to Tuning the Steric Properties of the NHC Ligands Used 256 9.4.3 Improvement of Gold Catalysis by Tuning the Electronic Properties of the NHC Ligands Used 257 9.4.4 Alteration of the Reactivity of Gold Catalysis by Switching from Phosphine to NHC Ligands 258 9.4.5 Enantioselective Gold Catalyzed Transformations Based on Chiral, Enantiopure NHC–Based Catalysts 264 9.5 Conclusion 266 References 267 10 Recent Developments in the Synthesis and Applications of Rhodium and Iridium Complexes Bearing N–Heterocyclic Carbene Ligands 271 Macarena Poyatos, Gregorio Guisado–Barrios, and Eduardo Peris 10.1 Introduction 271 10.2 Rh– and Ir–NHC–Based Complexes: Structural and Electronic Features 271 10.2.1 Mono–NHCs 271 10.2.2 Chelating NHCs 273 10.2.3 Bridging NHCs 282 10.3 Catalytic Applications of Rhodium and Iridium NHC–Based Complexes 288 10.3.1 Reductions 288 10.3.2 Arylation and Borylation Reactions with Organoboron Reagents 293 10.3.3 Oxidations 295 10.3.4 Other Important Catalytic Processes 296 10.4 Abbreviations 298 References 299 11 N–Heterocyclic Carbene–Ruthenium Complexes: A Prominent Breakthrough in Metathesis Reactions 307 Sudheendran Mavila and N. Gabriel Lemcoff 11.1 Introduction 307 11.2 Variations of NHC in Ruthenium Complexes 313 11.3 Modifications in Imidazol– and Imidazolin–2–ylidene Ligands 313 11.4 Influence of Symmetrically 1,3–Substituted N–Heterocyclic Carbene in Metathesis 313 11.4.1 N, N´–Dialkyl Substituted N–Heterocyclic Carbene Complexes 313 11.4.2 N, N´–Diaryl Substituted N–Heterocyclic Carbene Complexes 314 11.5 Unsymmetrically N,N´–Substituted N–Heterocyclic Carbenes 319 11.5.1 N–Alkyl–N´–Aryl Substituted N–Heterocyclic Carbene Complexes 319 11.5.2 N, N´–Diaryl–Substituted N–Heterocyclic Carbene Complexes 323 11.5.3 Influence of 4,5–Substituted N–Heterocyclic Carbenes in Metathesis 325 11.5.4 Four–, Six–, and Seven–Membered N–Heterocyclic Carbenes 327 11.5.5 Heteroatom Containing N–Heterocyclic Carbenes 328 11.5.6 N–Heterocyclic Carbene Bearing Chiral Ru Complexes 330 11.5.7 Chiral Monodentate N–Heterocyclic Carbenes 330 11.5.8 Chiral Bidentate N–Heterocyclic Carbenes 334 11.5.9 NHCs for Metathesis in Water and Protic Solvents 335 References 337 12 Ruthenium N–Heterocyclic Carbene Complexes for the Catalysis of Nonmetathesis Organic Transformations 341 Leonid Schwartsburd and Michael K. Whittlesey 12.1 Introduction 341 12.2 Transfer Hydrogenation 341 12.3 Direct Hydrogenation (and Hydrosilylation) 346 12.4 Borrowing Hydrogen 351 12.5 Alcohol Racemization 356 12.6 Arylation 357 12.7 Reactions of Alkynes 359 12.8 Isomerization of C.C Bonds 360 12.9 Allylic Substitution Reactions 361 12.10 Miscellaneous Reactions 363 12.11 Conclusions 365 References 365 13 Nickel Complexes of N–Heterocyclic Carbenes 371 M. Taylor Haynes II, Evan P. Jackson, and John Montgomery 13.1 Introduction 371 13.2 Nickel–NHC Catalysts 372 13.2.1 In Situ Methods to Generate Ni–NHC Complexes 372 13.2.2 Discrete Ni(0)–NHC Catalysts 373 13.2.3 Discrete Ni(I)–NHC Catalysts 374 13.2.4 Discrete Ni(II)–NHC Catalysts 374 13.3 Cross–Coupling Reactions 376 13.3.1 Carbon–Carbon Bond Forming Reactions 376 13.3.2 Carbon–Heteroatom Bond–Forming Reactions 382 13.4 Oxidation/Reduction Reactions 383 13.4.1 Dehalogenation 383 13.4.2 Imine Reduction 383 13.4.3 Alcohol Oxidation 384 13.4.4 Aryl Ether Reduction 384 13.5 Hydrosilylation 385 13.5.1 Hydrosilylation of Alkynes 385 13.5.2 Hydrosilylation of Carbonyls 385 13.6 Cycloadditions 386 13.6.1 [2+2+2] Cycloaddition 386 13.6.2 [3+2] Cycloaddition 388 13.6.3 [4+2+2] Cycloaddition 389 13.7 Isomerization 390 13.8 Reductive Coupling 390 13.8.1 Aldehydes and Dienes 390 13.8.2 Aldehydes and Alkynes 391 13.8.3 Aldehydes and Allenes 392 13.8.4 Aldehydes and Norbornene 393 13.9 Conclusions and Outlook 393 References 394 14 Coordination Chemistry, Reactivity, and Applications of Early Transition Metal Complexes Bearing N–Heterocyclic Carbene Ligands 397 Stéphane Bellemin–Laponnaz and Samuel Dagorne 14.1 Introduction 397 14.2 Group 3 Metal Complexes 398 14.3 Group 4 Metal Complexes 402 14.4 Group 5 Metal Complexes 411 14.5 Group 6 Metal Complexes 413 14.6 Group 7 Metal Complexes 418 14.7 Conclusion 421 References 422 15 NHC Complexes of Main Group Elements: Novel Structures, Reactivity, and Catalytic Behavior 427 Luke J. Murphy, Katherine N. Robertson, Jason D. Masuda, and Jason A. C. Clyburne 15.1 Introduction 427 15.2 Structures of Common NHCs for Main Group Chemistry 428 15.3 NHC Complexes of Group 1 Elements 429 15.3.1 Lithium 429 15.3.2 Sodium 432 15.3.3 Potassium 433 15.4 NHC Complexes of Group 2 Elements 434 15.4.1 Beryllium 434 15.4.2 Magnesium 436 15.4.3 Calcium, Strontium, and Barium 437 15.5 NHC Complexes of Group 13 Elements 438 15.5.1 Boron 438 15.5.2 Aluminum 452 15.5.3 Gallium 454 15.5.4 Indium and Thallium 456 15.6 NHC Complexes of Group 14 Elements 456 15.6.1 Carbon 456 15.6.2 Silicon 459 15.6.3 Germanium 464 15.6.4 Tin and Lead 466 15.7 NHC Complexes of Group 15 Elements 467 15.7.1 Nitrogen 467 15.7.2 Phosphorus 468 15.7.3 Arsenic and Antimony 473 15.8 NHC Complexes of Group 16 Elements 474 15.8.1 Oxygen and Sulfur 474 15.8.2 Selenium 474 15.8.3 Tellurium 475 15.9 NHC Complexes of Group 17 Elements 476 15.10 NHC Reactivity with Protic Reagents 477 15.11 Cyclic Alkyl Amino Carbenes: Closely Related Cyclic Cousins to NHCs with Similar and Differing Reactivities 478 15.11.1 Boron 479 15.11.2 Carbon 481 15.11.3 Silicon 482 15.11.4 Nitrogen 483 15.11.5 Phosphorus 483 15.12 Summary and Outlook 487 References 488 16 Catalysis with Acyclic Aminocarbene Ligands: Alternatives to NHCs with Distinct Steric and Electronic Properties 499 LeGrande M. Slaughter 16.1 Introduction 499 16.2 Metalation Routes of Acyclic Carbene Ligands 500 16.3 Ligand Properties of Acyclic Carbenes 502 16.3.1 Donor Ability 502 16.3.2 Structural Properties 503 16.3.3 Decomposition Routes 504 16.4 Catalytic Applications 505 16.4.1 Coupling Reactions 505 16.4.2 Allylic Alkylations 509 16.4.3 Olefin Metathesis 510 16.4.4 Gold Catalysis 510 16.4.5 Enantioselective Catalysis with Chiral Acyclic Carbenes 513 16.5 Frontiers in Acyclic Carbene Chemistry 516 16.6 Conclusion 521 References 521 Index 525

Steven P. Nolan was born in Canada. He received his B.Sc. in Chemistry from the University of West Florida and his Ph.D. from the University of Miami where he worked under the supervision of Professor Carl D. Hoff. After a postdoctoral stay with Professor Tobin J. Marks at Northwestern University, he joined the Department of Chemistry of the University of New Orleans in 1990. In 2006 he joined the Institute of Chemical Research of Catalonia (ICIQ) as Group leader and ICREA Research Professor. In early 2009, he joined the School of Chemistry at the University of St Andrews where he is Professor and holds the Chair in Inorganic chemistry.