Copper Catalysis in Organic Synthesis contains an up-to-date overview of the most important reactions in the presence of copper catalysts. The contributors?noted experts on the topic?provide an introduction to the field of copper catalysis, reviewing its development, scope, and limitations, as well as providing descriptions of various homo- and cross-coupling reactions. In addition, information is presented on copper-catalyzed C?H activation, amination, carbonylation, trifluoromethylation, cyanation, and click reactions.
Comprehensive in scope, the book also describes microwave-assisted and multi-component transformations as well as copper-catalyzed reactions in green solvents and continuous flow reactors. The authors highlight the application of copper catalysis in asymmetric synthesis and total synthesis of natural products and heterocycles as well as nanocatalysis. This important book: - Examines copper and its use in organic synthesis as a more cost-effective and sustainable for researchers in academia and industry - Offers the first up-to-date book to explore copper as a first line catalyst for many organic reactions - Presents the most significant developments in the area, including cross-coupling reactions, C?H activation, asymmetric synthesis, and total synthesis of natural products and heterocycles - Contains over 20 contributions from leaders in the field
Written for catalytic chemists, organic chemists, natural products chemists, pharmaceutical chemists, and chemists in industry, Copper Catalysis in Organic Synthesis offers a book on the growing field of copper catalysis, covering cross-coupling reactions, C?H activation, and applications in the total synthesis of natural products.
Table of Contents
Preface xvii
Abbreviations xix
1 Copper Catalysis: An Introduction 1
Salim Saranya and Gopinathan Anilkumar
References 4
2 Cu-Catalyst in Reactions Involving Pyridinium and Indolizinium Moieties 7
Bianca Furdui, Andrea V. Dediu (Botezatu), and RodicaM. Dinica
2.1 Cu-Catalyst in Reactions Involving Pyridinium Moieties 7
2.1.1 Introduction 7
2.1.2 Synthesis and Functionalization of Pyridinium Compounds Catalyzed by Copper 7
2.1.3 Green Methods for Pyridine Synthesis 13
2.2 Cu-Catalyst in Reactions Involving Indolizinium Moieties 15
2.2.1 Introduction 15
2.2.2 Synthesis of Indolizinium Compounds Using a Copper Catalyst 15
2.2.3 Cu-Catalyzed Green Synthesis of Indolizine Moieties 19
2.3 Conclusions 21
References 21
3 Copper-Catalyzed Cross-Coupling Reactions of Organoboron Compounds 23
Jan Nekvinda and Webster L. Santos
3.1 Introduction 23
3.2 Ring Opening Cross-Coupling Reactions 24
3.3 Coupling Reactions with Atoms Other than Carbon 26
3.3.1 Amines, Amides, and Sulfonamides 27
3.3.2 Nitrones 33
3.3.3 Sulfones 35
3.3.4 Silyls 35
3.3.5 Selanyls 36
3.4 Coupling Reactions Involving Carbon 36
3.4.1 Boronic Acid Esters 36
3.4.2 Boronic Acids 41
3.4.3 Single Electron Mechanism 42
3.5 Conclusion 43
References 43
4 Cu-Catalyzed Homocoupling Reactions 51
Ganesh C. Nandi, Sundaresan Ravindra, Cholakkaparambil Irfana Jesin, Parameswaran Sasikumar, and Kokkuvayil V. Radhakrishnan
4.1 Introduction 51
4.2 Synthesis of 1,3-Diynes via Homocoupling Reactions 51
4.2.1 Synthesis of 1,3-Diynes with Homogeneous Cu Catalysis 52
4.2.1.1 Synthesis of Symmetrical 1,3-Diynes with Substrates Other than Terminal Alkynes 54
4.2.2 Synthesis of Symmetrical 1,3-Diynes with Heterogeneous Cu Catalysis 55
4.2.3 Synthesis of Macrocycles Through Intramolecular Coupling of Terminal Alkynes 56
4.3 Cu-Catalyzed Synthesis of Symmetrical Biaryls Through Homocoupling Reactions 57
4.3.1 Homocoupling of Aryl Boronic Acids 58
4.3.1.1 Homogeneous Cu-Catalyzed Homocoupling Reactions 58
4.3.1.2 Heterogeneous Copper-Catalyzed Homocoupling Reactions 58
4.3.2 Synthesis of Symmetrical Biaryls Through C-H Activation 59
4.3.3 Homocoupling of Arylstannane/Silane Derivatives 62
4.3.4 Cu-Catalyzed Homocoupling of Aryl Halides for the Synthesis of Biaryls 62
4.3.4.1 Symmetrical Biaryl Formation Using Homogeneous Copper Catalyst 62
4.3.4.2 Biaryl Formation Using Heterogeneous Cu Catalyst 65
4.3.5 Cu-Catalyzed Homocoupling of Aryl Halides for the Formation of Biaryls in Natural Products 66
4.4 Homocoupling of Alkenes 68
4.5 Summary and Conclusions 69
References 69
5 Cu-Catalyzed Organic Reactions in Aqueous Media 73
Noel Nebra and Joaquín García-Álvarez
5.1 Introduction 73
5.2 Cu-Catalyzed Azide-Alkyne Cycloaddition Reactions (CuAAC) 74
5.2.1 Ligand-Accelerated Cu(I) Catalysts 74
5.2.2 Supported Cu(I) Catalysts 75
5.2.3 Micellar Cu(I) Catalysis 77
5.2.4 Heterogeneous Catalysis: CuNPs 77
5.2.5 Miscellaneous 80
5.3 Cu-Mediated Cross-Coupling Reactions: C - C and C-Heteroatom Bond Formation 81
5.3.1 The Ullmann Coupling 81
5.3.2 The Chan-Lam-Evans (CEL) Coupling 83
5.3.3 Cu-Catalyzed Cyclization Reactions via Cross-Coupling Events 85
5.3.4 Cu-Catalyzed C - H Bond Functionalization Reactions 86
5.4 Cu-Catalyzed Hydroelementation Reactions of Double and Triple C - C Bonds 89
5.4.1 Michael-Type Additions: Enone Hydrations Enabled by Cu-Based Metallo-Hydratases 89
5.4.2 Cu-Catalyzed Hydroelementation of α,β-Unsaturated Carbonyl Compounds 90
5.4.3 Cu-Catalyzed Hydroelementation of Inactivated C - C Multiple Bonds 92
5.5 Miscellaneous 96
5.6 Summary and Conclusions 98
Acknowledgments 98
References 100
6 Cu-Catalyzed Organic Reactions in Deep Eutectic Solvents (DESs) 103
Noel Nebra and Joaquín García-Álvarez
6.1 Introduction 103
6.2 Cu-Catalyzed Azide-Alkyne Cycloaddition Reactions (CuAAC) in DESs 106
6.3 Cu-Catalyzed C - C and C - N Bond Formations in DESs 108
6.3.1 Cu-Catalyzed Sonogashira C-C Coupling Using the Eutectic Mixture 1CuCl/1Gly 108
6.3.2 Synthesis of Heterocyclic Compounds via Cu-Catalyzed Cross-Coupling Reactions 110
6.3.3 Cu-Catalyzed C - N Bond Formation in DESs 110
6.4 Cu-Catalyzed Atom Transfer Radical Polymerization Processes in DESs (SARA and ARGET) 112
6.5 Summary and Conclusions 113
Acknowledgments 114
References 114
7 Microwave-Assisted Cu-Catalyzed Organic Reactions 119
Bogdan Štefane, Helena Brodnik-ugelj, Uroš Grošelj, Jurij Svete, and Franc Pogan
7.1 Introduction 119
7.2 Ring-Forming Reactions 121
7.2.1 Synthesis of Heterocycles 121
7.2.1.1 Cycloadditions 121
7.2.1.2 Annulation Reactions 123
7.2.1.3 Intramolecular Cyclizations 126
7.2.1.4 Multicomponent Reactions (MCRs) 126
7.2.2 Synthesis of Carbocycles 128
7.3 Cross-Coupling Reactions 130
7.3.1 Carbon-Carbon Couplings 130
7.3.2 Carbon-Heteroatom Couplings 134
7.3.2.1 C-N Couplings 134
7.3.2.2 C-Chalcogen Couplings 138
7.4 Multicomponent Reactions 141
7.5 Miscellaneous Reactions 144
7.6 Summary and Conclusions 146
Acknowledgments 146
References 146
8 Cu-Catalyzed Asymmetric Synthesis 153
Hidetoshi Noda, Naoya Kumagai, and Masakatsu Shibasaki
8.1 Introduction 153
8.1.1 Cu-Catalyzed Asymmetric Synthesis: Scope of This Chapter 153
8.1.2 Structures of Chiral Ligands: Trends of the Last Decade 154
8.2 In Situ Generation of Cu Nucleophiles from Unsaturated Hydrocarbons 155
8.2.1 Reductive Aldol Reactions 155
8.2.2 Intramolecular Oxy- and Amidocupration 156
8.2.3 Hydrocupration of Unsaturated Compounds 158
8.2.4 Borylcupuration of Unsaturated Compounds 163
8.3 Generation of Cu Nucleophiles Under Proton Transfer Conditions 165
8.4 Summary and Conclusions 172
References 172
9 Cu-Catalyzed Click Reactions 177
Rajagopal Ramkumar and Pazhamalai Anbarasan
9.1 Introduction 177
9.2 Background 178
9.2.1 Huisgen’s Cycloaddition Reaction 178
9.2.2 Copper(I)-Catalyzed Azide-Alkyne Cycloaddition (CuAAC) 178
9.2.3 Mechanistic Study of Copper Azide-Alkyne Cycloaddition Reaction 179
9.3 CuAAC for the Synthesis of Substituted 1,2,3-Triazoles 180
9.4 Heterogeneous CuAAC Reactions 188
9.5 Ligand-Stabilized Cu(I)-Catalyzed Click Reaction 191
9.6 Synthesis of Rotaxanes and Catenanes Using CuAAC 196
9.7 Synthesis of N-Sulfonyl-1,2,3-Triazoles and Their Applications 198
9.8 CuAAC and Asymmetric Synthesis 198
9.9 CuAAC for Synthesis of Biologically Active Molecules 202
9.10 Summary 204
References 204
10 Cu-Catalyzed Multicomponent Reactions 209
Thachapully D. Suja and Rajeev S. Menon
10.1 Introduction 209
10.2 Cu-Catalyzed MCRs of Alkynes 209
10.2.1 Cu-Catalyzed Multicomponent Alkyne-Azide Cycloadditions 210
10.2.1.1 CuAAC Reactions Initiated by Azide Generation 210
10.2.1.2 CuAAC Reactions Initiated by Alkyne Generation 214
10.2.1.3 Other Multicomponent CuAAC Reactions 214
10.2.2 Cu-Catalyzed Generation and Interception of Ketenimines from Alkynes and Azides 216
10.2.3 Cu-Catalyzed Aldehyde, Alkyne, and Amine (A3) Coupling 221
10.2.3.1 A3-Coupling ReactionsThat Afford Propargyl Amine Derivatives 222
10.2.3.2 Variation of the Reaction Components in A3-Coupling 224
10.2.3.3 Asymmetric A3 (AA3)-Coupling Reactions 226
10.2.3.4 Synthetic Applications of Cu-Catalyzed A3-Coupling Reactions 227
10.3 Other Cu-Catalyzed Multicomponent Reactions 229
10.4 Summary and Conclusions 233
References 233
11 Copper-Catalyzed Aminations 239
Nissy A. Harry and Rajenahally V. Jagadeesh
11.1 Introduction 239
11.2 Copper-Catalyzed Amination of Aryl and Alkenyl Electrophiles 240
11.2.1 Ammonia as a Nucleophile 240
11.2.2 Sodium Azide as Nucleophile 241
11.2.3 Amines as Nucleophile 242
11.2.4 Mechanism of Cu-Catalyzed Amination of Aryl/Alkyl Halides 244
11.3 Chan-Lam Coupling Reaction 244
11.4 Copper-Catalyzed Hydroaminations 246
11.4.1 Hydroamination of Alkenes 247
11.4.2 Hydroamination of Alkynes 250
11.4.3 Hydroamination of Allenes 251
11.5 Copper-Catalyzed C - H amination Reactions 251
11.6 Conclusion 254
References 254
12 Cu-Catalyzed Carbonylation Reactions 261
Parameswaran Sasikumar, Thoppe S. Priyadarshini, Sanjay Varma, Ganesh C. Nandi, and Kokkuvayil V. Radhakrishnan
12.1 Introduction 261
12.2 Single Carbonylation Reactions 262
12.2.1 Copper-Catalyzed Carbonylative Coupling Reactions 262
12.2.2 Cu-Catalyzed Carboxylation Reaction 268
12.2.3 Cu-Catalyzed Oxidative Carbonylation Reactions 269
12.2.4 Carbonylative Acetylation Reaction 272
12.2.5 Aminocarbonylation Reaction 273
12.2.6 Copper-Catalyzed Oxidative Amidation 275
12.3 Cu-Catalyzed Double Carbonylation Reactions 275
12.4 Summary and Conclusions 278
References 278
13 Ligand-Free, Cu-Catalyzed Reactions 279
Muhammad F. Jamali, Sanoop P. Chandrasekharan, and Kishor Mohanan
13.1 Introduction 279
13.2 Heterocycle Synthesis 279
13.2.1 Five-Membered Heterocycles 280
13.2.2 Six-Membered Heterocycles 280
13.2.3 Benzofused Five-Membered Heterocycles Containing One Heteroatom 281
13.2.4 Benzofused Five-Membered Heterocycles Containing Two Heteroatoms 283
13.2.5 Benzofused Five-Membered Heterocycles Containing Three Heteroatoms 284
13.2.6 Benzofused Six-Membered Heterocycles 284
13.2.7 Polycyclic Compounds 286
13.2.8 Spirocyclic Compounds 286
13.3 Carbon-Heteroatom Bond Formations 289
13.3.1 C - N Bond Formation 289
13.3.2 C - O Bond Formation 291
13.3.3 C - S Bond Formation 291
13.3.4 C - P Bond Formation 295
13.3.5 C - B Bond Formation 295
13.3.6 C - Se Bond Formation 295
13.4 C-H Activation Reactions 297
13.5 Cross-coupling Reactions 299
13.6 Azide-Alkyne Cycloaddition Reactions (CuAAC) 301
13.7 Trifluoromethylation Reactions 302
13.8 Cyanation Reactions 303
13.9 Carbonylation Reactions 304
13.10 Conclusion 305
References 305
14 Copper-Catalyzed Decarboxylative Coupling 309
Firas El-Hage and Jola Pospech
14.1 Introduction 309
14.2 Copper-Catalyzed Decarboxylation of Benzoic Acids 309
14.3 Copper-Catalyzed Decarboxylation of Alkenyl Carboxylic Acids 315
14.4 Copper-Catalyzed Decarboxylation of Alkynyl Carboxylic Acids 316
14.5 Copper-Catalyzed Decarboxylation of Alkyl Carboxylic Acids 320
14.6 Summary and Conclusions 325
References 326
15 Copper-Catalyzed C-H Activation 329
Xun-Xiang Guo
15.1 Introduction 329
15.2 Carbon-Carbon Bond Formation via Cu-Catalyzed C-H Activation 329
15.2.1 Cu-Catalyzed C(sp2)-H Activation 329
15.2.2 Cu-Catalyzed C(sp3)-H Activation 332
15.3 Carbon-Heteroatom Bond Formation via Cu-Catalyzed C-H Activation 334
15.3.1 C - N Bond Formation 334
15.3.2 C - O Bond Formation 339
15.3.3 C - X Bond Formation 341
15.3.4 C - P Bond Formation 345
15.3.5 C - S Bond Formation 346
15.4 Conclusion 347
References 347
16 Aerobic Cu-Catalyzed Organic Reactions 349
Ahmad A. Almasalma and Esteban Mejía
16.1 Introduction 349
16.2 C - C Bond Formation Reactions 351
16.2.1 Cross-dehydrogenative Couplings Under Thermal Conditions 352
16.2.2 Cross-dehydrogenative Couplings Under Photochemical Conditions 354
16.3 Carbonyl Synthesis via Oxidation of Alcohols 357
16.3.1 “Copper-Only” Biomimetic Catalyst Systems 358
16.3.2 Cu/Nitroxyl “Dual” Systems 360
16.4 Summary and Conclusions 362
References 363
17 Copper-Catalyzed Trifluoromethylation Reactions 367
Dzmitry G. Kananovich
17.1 Introduction 367
17.2 Trifluoromethylation of Arenes and Heteroarenes (C(sp2) - CF3 Bond Formation) 370
17.3 Trifluoromethylation of Alkenes and Alkynes 374
17.4 Trifluoromethylation of Aliphatic Precursors (C(sp3) - CF3 Bond Formation) 378
17.4.1 Transformations via Functional Group Interconversions 378
17.4.2 Direct C(sp3)-H Trifluoromethylation 382
17.4.3 Ring-opening Trifluoromethylation 386
17.5 Copper-Mediated Formation of CF3-Heteroatom Bonds 388
17.6 Summary and Conclusions 388
References 389
18 Cu-Catalyzed Reactions for Carbon-Heteroatom Bond Formations 395
Govindasamy Sekar, Subramani Sangeetha, Anuradha Nandy, and Rajib Saha
18.1 Introduction 395
18.2 Cu-Catalyzed Reactions for Carbon-Nitrogen Bond Formations 395
18.2.1 Coupling Reactions with Ammonia and its Surrogates 396
18.2.2 Coupling Reactions with Amines 396
18.2.3 Coupling Reactions with Amides, Lactams, and Carbamates 398
18.2.4 Coupling Reactions with Protected Hydrazines and Hydroxylamines 400
18.2.5 Coupling Reactions with Guanidines 400
18.2.6 Coupling Reactions with N-Heterocycles 401
18.3 Cu-Catalyzed Reactions for Carbon-Oxygen Bond Formations 401
18.3.1 Mechanism and Presence of Cu(I) Intermediate in Ullmann Ether Synthesis 402
18.3.2 Role of Ligands in Copper-Catalyzed Ether Synthesis 403
18.3.3 Copper-Catalyzed C - O Bond Formation for Synthesizing Phenols 404
18.3.4 Copper-Catalyzed C - H Functionalization for C - O Bond Formation 405
18.3.5 Copper-Catalyzed Synthesis of Oxygen Heterocycles 405
18.3.6 Selectivity of Copper-Catalyzed C - O and C - N Bond Formation 406
18.4 Cu-Catalyzed Reactions for Carbon-Sulfur Bond Formations 407
18.5 Cu-Catalyzed Reactions for Carbon-Selenium and Carbon-Tellurium Bond Formations 413
18.6 Cu-Catalyzed Reactions for Carbon-Phosphorous Bond Formations 414
18.7 Cu-Catalyzed Reactions for Carbon-Silicon Bond Formations 415
18.8 Cu-Catalyzed Reactions for Carbon-Halogen Bond Formations 415
18.9 Conclusions 416
References 416
19 Cu-Assisted Cyanation Reactions 423
Sumanta Garai and Ganesh A. Thakur
19.1 Introduction 423
19.2 Cyanation Reaction Using CN-Containing Source 423
19.2.1 Metallic Bound CN-Source 423
19.2.1.1 Metal Cyanide 423
19.2.1.2 Potassium Ferrocyanide [K3Fe(CN)6] 427
19.2.2 Nonmetallic CN-Source 427
19.2.2.1 Acetone Cyanohydrin 427
19.2.2.2 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) 428
19.2.2.3 2,2′-Azobisisobutyronitrile (AIBN) 429
19.2.2.4 Benzyl Cyanide 429
19.2.2.5 Acetonitrile 432
19.2.2.6 Malononitrile 435
19.2.2.7 Cyanogen Iodide 436
19.2.2.8 α-Cyanoacetate 436
19.3 Cyanation Reaction Using Non-CN-Containing Source 437
19.3.1 N,N-Dimethylformamide (DMF) 437
19.3.2 Ammonium Iodide (NH4I) and N,N-Dimethylformamide (DMF) 439
19.3.3 Nitromethane 441
Acknowledgments 441
References 441
20 Application of Cu-Mediated Reactions in the Synthesis of Natural Products 443
Anas Ansari and Ramesh Ramapanicker
20.1 Introduction 443
20.2 Classification 443
20.3 Total Synthesis Employing Cu-Catalyzed C-C Coupling Reactions 445
20.3.1 (+)-Nocardioazine B 445
20.3.2 (-)-Rhazinilam 447
20.3.3 Isohericenone and Erinacerin A 447
20.3.4 (+)-Piperarborenine B 449
20.3.5 Macrocarpines D and E 450
20.4 Total Synthesis Employing Cu-Catalyzed C-N Coupling Reactions 454
20.4.1 (-)-Aspergilazine A 454
20.4.2 (-)-Psychotriasine 454
20.4.3 (-)-Indolactam V 455
20.4.4 (-)-Palmyrolide A 458
20.5 Total Synthesis Employing Cu-Catalyzed C-O Coupling Reactions 458
20.5.1 (±})-Untenone A 458
20.5.2 Coumestrol and Aureol 460
20.6 Total Synthesis Employing Cu-Catalyzed Domino Reactions 463
20.6.1 (±})-Sacidumlignan D 463
20.7 Conclusion 463
References 465
Index 469
