Carbene transformations have had an enormous impact on catalysis and organometallic chemistry. With the growth of transition metal-catalyzed carbene transformations in recent decades, carbene transformations are today an important compound class in organic synthesis as well as in the pharmaceutical and agrochemical industries. Edited by leading experts in the field,Transition Metal-Catalyzed Carbene Transformations is a thorough summary of the most recent advances in the rapidly expanding research area.

This authoritative volume covers different reaction types such as ring forming reactions and rearrangement reactions, details their conditions and properties, and provides readers with accurate information on a wide range of carbene reactions. Twelve in-depth chapters address topics including carbene C-H bond insertion in alkane functionalization, the application of engineered enzymes in asymmetric carbene transfer, progress in transition-metal-catalyzed cross-coupling using carbene precursors, and more. Throughout the text, the authors highlight novel catalytic systems, transformations, and applications of transition-metal-catalyzed carbene transfer.Highlights the dynamic nature of the field of transition-metal-catalyzed carbene transformationsSummarizes the catalytic radical approach for selective carbene cyclopropanation, high enantioselectivity in X-H insertions, and bio-inspired carbene transformationsIntroduces chiral N,N'-dioxide and chiral guanidine-based catalysts and different transformations with gold catalysisDiscusses approaches in cycloaddition reactions with metal carbenes and polymerization with carbene transformationsOutlines multicomponent reactions through gem-difunctionalization and transition-metal-catalyzed cross-coupling using carbene precursors

Transition Metal-Catalyzed Carbene Transformations is essential reading for all chemists involved in organometallics, including organic and inorganic chemists, catalytic chemists, and chemists working in industry.

Jianbo Wang is Full Professor at Peking University, China. He has published more than 300 articles in peer-reviewed journals and serves as Associate Editor of Journal of Physical Organic Chemistry and Chinese Journal of Organic Chemistry.

Chi-Ming Che is Dr. Hui Wai-Haan Chair of Chemistry at The University of Hong Kong (HKU) and Director of China's State Key Laboratory of Synthetic Chemistry. His honors include the China State Natural Science Award and the Centenary Prize from the Royal Society of Chemistry.

Michael P. Doyle is Rita and John Feik Distinguished University Chair in Medicinal Chemistry at The University of Texas, San Antonio, TX, USA. He has received numerous awards and is the author and co-author of numerous books and more than 400 journal publications.

Preface xiii

1 Alkane Functionalization by Metal-Catalyzed Carbene Insertion from Diazo Reagents 1María Álvarez, Ana Caballero, and Pedro J. Pérez

1.1 Introduction 1

1.2 Chemo- and Regioselectivity 3

1.2.1 Definitions 3

1.2.2 Catalysts 5

1.2.3 Chemoselectivity 6

1.2.4 Regioselectivity 8

1.3 Enantioselectivity 9

1.4 Methane and Gaseous Alkanes as Substrates 14

1.5 Alkane Nucleophilicity Scale 18

1.6 Conclusions and Outlook 22

Acknowledgments 22

References 22

2 Catalytic Radical Approach for Selective Carbene Transfers via Cobalt(II)-Based Metalloradical Catalysis 25Xiaoxu Wang and X. Peter Zhang

2.1 Introduction 25

2.2 Intermolecular Radical Cyclopropanation of Alkenes 26

2.2.1 Cyclopropanation with Acceptor-Substituted Diazo Compounds 27

2.2.2 Cyclopropanation with Acceptor/Acceptor-Substituted Diazo Compounds 32

2.2.3 Cyclopropanation with Donor-Substituted Diazo Compounds 37

2.3 Intramolecular Radical Cyclopropanation of Alkenes 39

2.4 Intermolecular Radical Cyclopropenation of Alkynes 43

2.5 Intramolecular Radical Alkylation of C(sp3)H Bonds 44

2.5.1 Intramolecular CH Alkylation with Acceptor/Acceptor-Substituted Diazo Compounds 45

2.5.2 Intramolecular CH Alkylation with Donor-Substituted Diazo Compounds 46

2.6 Other Catalytic Radical Processes for Carbene Transfers 54

2.7 Summary and Outlook 59

Acknowledgment 60

References 60

3 Catalytic Enantioselective Carbene Insertions into HeteroatomHydrogen Bonds 67Ming-Yao Huang, Shou-Fei Zhu, and Qi-Lin Zhou

3.1 Introduction 67

3.2 NH Bond Insertion Reactions 67

3.2.1 Chiral Metal Catalysts 68

3.2.1.1 Chiral Cu Catalysts 68

3.2.1.2 Chiral Pd Catalysts 70

3.2.1.3 Other Chiral Metal Catalysts 70

3.2.1.4 Enzymes 72

3.2.1.5 Chiral Proton-Transfer Shuttle Catalysts 72

3.2.1.6 Chiral Phosphoric Acids as CPTS Catalysts 72

3.2.1.7 Chiral Amino Thioureas as CPTS Catalysts 73

3.3 OH Bond Insertion Reactions 74

3.3.1 Chiral Metal Catalysts 74

3.3.1.1 Chiral Cu Catalysts 74

3.3.1.2 Chiral Fe Catalysts 76

3.3.1.3 Chiral Pd Catalysts 77

3.3.1.4 Chiral Au Catalysts 78

3.3.1.5 Chiral Bases as CPTS Catalysts 78

3.3.1.6 Chiral Phosphoric Acids as CPTS Catalysts 79

3.4 SH Bond Insertion Reactions 80

3.4.1 Chiral Metal Catalysts 80

3.4.2 CPTS Catalysts 81

3.4.3 Enzymes 81

3.5 FH Bond Insertion Reactions 82

3.6 SiH Bond Insertion Reactions 83

3.6.1 Chiral Rh Catalysts 83

3.6.2 Chiral Cu Catalysts 85

3.6.3 Other Chiral Metal Catalysts 86

3.6.4 Enzymes 87

3.7 BH Bond Insertion Reactions 88

3.7.1 Chiral Cu Catalysts 88

3.7.2 Chiral Rhodium Catalysts 89

3.7.3 Enzymes 89

3.8 Summary and Outlook 90

References 91

4 Engineering Enzymes for New-to-Nature Carbene Chemistry 95Soumitra V. Athavale, Kai Chen, and Frances H. Arnold

4.1 Introduction: Biology Inspires Chemistry Inspires Biology 95

4.2 P411-Catalyzed Cyclopropanation 99

4.3 The Workflow of Directed Evolution 101

4.4 Expanding Cyclopropanation with Diverse Hemeprotein Carbene Transferases 102

4.5 CH Functionalization with Carbene Transferases 109

4.6 Biocatalytic Carbene XH Insertion 113

4.7 Carbene Transfer Reactions with Artificial Metalloproteins 118

4.8 Structural Studies of Carbene Intermediates in Heme Proteins 125

4.9 Summary 128

Acknowledgments 129

References 129

5 Metal Carbene Cycloaddition Reactions 139Kostiantyn O. Marichev, Haifeng Zheng, and Michael P. Doyle

5.1 Introduction 139

5.2 [3+1]-Cycloaddition 142

5.3 [3+2]-Cycloaddition 145

5.3.1 [3+2]-Cycloaddition with Imines and Indoles 145

5.3.2 [3+2]-Cycloaddition with Polarized Alkenes 149

5.3.3 [3+2]-Cycloaddition with Nitrones 150

5.3.4 Divergent Behavior of Catalysts 151

5.4 [3+3]-Cycloaddition of Enoldiazo Compounds 152

5.4.1 [3+3]-Cycloaddition with Nitrones 152

5.4.2 [3+3]-Cycloaddition with Pyridinium Ylides and Hydrazones 155

5.4.3 Diastereoselective [3+3]-Cycloaddition with Achiral Catalysts 157

5.4.4 [3+3]-Cycloaddition with Diaziridines 158

5.4.5 [3+3]-Cycloaddition with DonorAcceptor Cyclopropanes and Oxiranes 159

5.5 [3+4]-Cycloaddition 160

5.6 [3+5]-Cycloaddition 161

5.7 Summary 162

References 163

6 Metal-Catalyzed Decarbenations by Retro-Cyclopropanation 169Mauro Mato and Antonio M. Echavarren

6.1 Introduction 169

6.2 Reactivity and Generation of Metal Carbenes 169

6.2.1 Decomposition of Diazo Compounds 170

6.2.2 Alternative Methods for the Generation of Metal Carbenes 170

6.2.3 Decarbenation Reactions: General Process and Definition 170

6.3 Retro-Cyclopropanation Reactions: A Historical Walkthrough 171

6.3.1 Early Observations 171

6.3.2 Decarbenation Reactions from Gas Phase to Solution 173

6.3.3 The Discovery of the Gold(I)-Catalyzed Retro-Buchner Reaction 173

6.4 Metal-Catalyzed Aromative-Decarbenation Reactions: A Mechanistic Analysis 175

6.4.1 Basic Mechanistic Picture 175

6.4.2 Alternative Generation of the Same Carbenes from Carbenoids 175

6.4.3 Theoretical Studies on the Mechanism of the Retro-Buchner Reaction 177

6.4.4 Second-Generation Cycloheptatrienes: Low Temperature and Other Metals 179

6.4.5 Mechanism of the Rh(II)-Catalyzed Aromative Decarbenation 181

6.5 Synthetic Methodologies and Applications 181

6.5.1 Cyclopropanation Reactions 181

6.5.1.1 Aryl Cyclopropanations 183

6.5.1.2 Alkenyl Cyclopropanations 184

6.5.1.3 Reactions with Furans 185

6.5.2 Higher Formal Cycloadditions 186

6.5.2.1 (4+1) Cycloadditions 187

6.5.2.2 (3+2) Cycloadditions 187

6.5.2.3 (4+3) Cycloadditions 189

6.5.3 Intramolecular FriedelCrafts Reactivity 190

6.5.4 Insertion Reactions 190

6.5.4.1 CH Insertion 190

6.5.4.2 SiH Insertion 192

6.5.5 Oxidation Reactions 192

6.5.6 Alternative Precursors 193

6.5.7 Decarbenations Based on the Release of Alkenes 193

6.6 General Outlook and Concluding Remarks 195

References 196

7 Gold-Catalyzed Oxidation of Alkynes by N-Oxides or Sulfoxides 199Kaylaa Gutman, Tianyou Li, and Liming Zhang

7.1 Introduction: Gold-Activated Alkynes Attacked by Nucleophilic Oxidants 199

7.2 Sulfoxides as Nucleophilic Oxidants 201

7.3 N-Oxides as Nucleophilic Oxidants 202

7.3.1 Reactions of Carbene/Carbenoid Intermediates with Oxygen-Based Nucleophiles 205

7.3.2 Reactions of Carbene/Carbenoid Intermediates with Nitrogen-Based Nucleophiles 212

7.3.3 Reactions of Carbene/Carbenoid Intermediates with Other Heteronucleophiles 214

7.3.4 FriedelCrafts Reactions of Carbene/Carbenoid Intermediates with Arenes 215

7.3.5 Reactions of Carbene/Carbenoid Intermediates with Alkenes 218

7.3.6 Reactions of Carbene/Carbenoid Intermediates with CC Triple Bonds 224

7.3.7 1,2-CC and 1,2-CH Insertions of Carbene/Carbenoid Intermediates 226

7.3.8 Remote C(sp3)H Functionalizations by Carbene/Carbenoid Intermediates 231

7.4 Conclusion 238

References 238

8 Transition-Metal-Catalyzed Carbene Transformations for Polymer Syntheses 243Eiji Ihara and Hiroaki Shimomoto

8.1 Introduction 243

8.2 Transition-Metal-Catalyzed C1 Polymerization of Diazoacetates 243

8.2.1 PdCl2 -Initiated Polymerization 244

8.2.2 (NHC)Pd(nq)/Borate-Initiated Polymerization 245

8.2.3 -AllylPdCl-Based System-Initiated Polymerization 246

8.2.4 (nq)2 Pd/Borate- and (cod)PdCl(Cl-nq)/Borate-Initiated Polymerization 251

8.2.5 Preparation of Polymers with Densely Packed Functional Groups Around Polymer Main Chain 254

8.2.5.1 Hydroxy Group-Containing Polymers 254

8.2.5.2 Oligo(oxyethylene)-Containing Polymers 256

8.2.5.3 Pyrene-Containing Polymers 257

8.2.5.4 Fluoroalkyl and Fluoroaryl Group-Containing Polymers 258

8.3 Polycondensation of Bis(diazocarbonyl) Compounds 259

8.3.1 Three-Component Polycondensation of Bis(diazocarbonyl) Compound, Diol, and THF 259

8.3.2 Three-Component Polycondensation of Bis(diazocarbonyl) Compound, Dicarboxylic Acid, and THF 262

8.3.3 Three-Component Polycondensation of Bis(diazocarbonyl) Compound, Enol-form of 1,3-Diketone, and THF 263

8.3.4 Two-Component Polycondensation of Bis(diazocarbonyl) Compound with Aromatic Diamine 264

8.3.5 Single-Component Polycondensation of Bis(diazocarbonyl) Compound to Afford Unsaturated Polyesters 264

8.3.6 Single-Component Polycondensation of Bis(diazocarbonyl) Compound to Afford Poly(arylene vinylene)s (PAV) 265

8.4 Concluding Remarks 266

References 266

9 Metal-Catalyzed Quinoid Carbene (QC) Transfer Reactions 269Hai-Xu Wang, Vanessa K.-Y. Lo, and Chi-Ming Che

9.1 Introduction 269

9.2 MetalQuinoid Carbene (QC) Complexes and Stoichiometric Reactivity 269

9.3 Metal-Catalyzed QC Transfer Reactions 273

9.3.1 Cyclopropanation Reactions 273

9.3.2 C(sp2)H Insertion Reactions 275

9.3.3 C(sp3)H Insertion Reactions 284

9.3.4 Nucleophilic Addition and Miscellaneous Reactions 286

9.4 Conclusion 293

Acknowledgment 295

References 295

10 Asymmetric Rearrangement and Insertion Reactions with MetalCarbenoids Promoted by Chiral N,N -Dioxide or Guanidine-Based Catalysts 299Xiaobin Lin, Xiaohua Liu, and Xiaoming Feng

10.1 Introduction 299

10.2 The Introduction of Chiral N,N -Dioxide/Metal Complexes and Guanidine Catalysts 299

10.3 Chiral N,N -Dioxide/Metal Complexes-Catalyzed Rearrangement Reactions 302

10.4 Chiral Guanidine-Based Catalyst-Mediated Asymmetric Carbene Insertion Reactions 315

10.5 Conclusion and Outlook 323

References 323

11 Multi-Component Reaction via gem-Difunctionalization of Metal Carbene 325Mengchu Zhang, Xinfang Xu, and Wenhao Hu

11.1 Introduction 325

11.2 Mannich-Type Interception 327

11.2.1 Interception of Ammonium Ylide 327

11.2.2 Interception of Oxonium Ylide 328

11.2.3 Interception of Zwitterionic Intermediate 339

11.3 Aldol-Type Interception 340

11.3.1 Interception of Ammonium Ylide 340

11.3.2 Interception of Oxonium Ylide 342

11.3.3 Interception of Zwitterionic Intermediate 343

11.4 Michael-Type Interception 345

11.4.1 Interception of Ammonium Ylide 345

11.4.2 Interception of Oxonium Ylide 346

11.4.3 Interception of Zwitterionic Intermediate 348

11.5 Miscellaneous Transformations 349

11.5.1 Interception Other Types of Active Intermediates 349

11.5.2 Interception of Active Intermediates with Other Electrophiles 353

11.5.3 Applications in Cascade Reactions 355

11.6 Synthetic Applications 358

11.6.1 Synthesis and Modification of Natural Products 358

11.6.2 Synthesis of Bioactive Molecules 362

11.7 Conclusion 364

References 365

12 Transition-Metal-Catalyzed Cross-Coupling with Carbene Precursors 371Kang Wang and Jianbo Wang

12.1 Introduction 371

12.2 Palladium-Catalyzed Carbene Cross-Coupling Reactions 372

12.2.1 Diazo Compounds as Carbene Precursors 372

12.2.1.1 Reactions with Electrophiles 372

12.2.1.2 Reactions with Nucleophiles 373

12.2.1.3 Palladium-Catalyzed Cascade Cross-Coupling Reactions 374

12.2.2 N-Tosylhydrazones as Carbene Precursors 377

12.2.2.1 Reactions with Electrophiles 377

12.2.2.2 Reactions with Nucleophiles 379

12.2.2.3 Palladium-Catalyzed Cascade Cross-Coupling Reactions 380

12.2.3 Non-Diazo Compounds as Carbene Precursors 382

12.3 Copper-Catalyzed Carbene Cross-Coupling Reactions 385

12.3.1 Reactions with Terminal Alkynes 385

12.3.1.1 Multi-substituted Allenes as the Coupling Products 385

12.3.1.2 Internal Alkynes as the Coupling Products 386

12.3.2 Reactions with Other Coupling Partners 387

12.4 Rhodium-Catalyzed Carbene Cross-Coupling Reactions 388

12.4.1 Generating Organorhodium Species Through Transmetalation 388

12.4.2 Generating Organorhodium Species Through CC Bond Cleavage 389

12.5 Transition-Metal-Catalyzed CH Bond Functionalizations with Carbene Precursors 391

12.5.1 Non-Directing-Group-Assisted CH Functionalizations 391

12.5.2 Directing-Group-Assisted CH Bond Functionalizations 393

12.5.2.1 Generating Acyclic Products Through CH Bond Activation 393

12.5.2.2 Generating Cyclic Products Through CH Bond Activation 394

12.6 Conclusion Remarks 396

Acknowledgment 397

References 397

Index 401