Preface xiii
1 The Palladium/Norbornene-Catalyzed Annulation Chemistry: Rapid Access to Diverse Ring Structures 1
Mark Lautens and Xavier Abel-Snape
1.1 Introduction 1
1.2 Intramolecular Cyclizations 3
1.2.1 Electrophile Tethered to Terminating Reagent 3
1.2.1.1 Ortho Alkylation 3
1.2.1.2 Ortho Arylation 8
1.2.1.3 Ortho Acylation 11
1.2.1.4 Ortho Amination and Ipso Heck Termination 14
1.2.1.5 Ortho Alkenylation and Ipso Amination via Reversal of Regioselectivity 15
1.2.1.6 Pd(II)-Initiated Annulations 16
1.2.2 Aryl Halide Tethered to Terminating Reagent 17
1.2.2.1 Ortho Alkylation, Ortho Arylation and Ortho Amination 17
1.2.3 Aryl Halide Tethered to Electrophile 17
1.2.3.1 Ortho Alkylation 17
1.2.4 Aryl Halide Tethered to Electrophile and Terminating Reagent 19
1.2.4.1 Ortho Alkylation 19
1.3 Intermolecular Cyclizations Following Intermolecular Ortho Functionalization 21
1.3.1 Ortho Arylation 21
1.3.1.1 Ipso Alkyne Insertion and Ipso Formal Benzyne Insertion 21
1.3.2 Ortho Amination 22
1.3.2.1 Ipso Alkyne Insertion 22
1.4 Cyclizations with Three-Membered Heterocycles as Both the Electrophile and Terminating Reagent 22
1.4.1 2H-Azirines 23
1.4.2 Aziridines 24
1.4.3 Epoxides 25
1.5 Norbornene/Norbornadiene-Integrated Cyclizations 25
1.5.1 Norbornene 25
1.5.2 Norbornadiene 27
1.6 One-Pot Postcatalytic Intramolecular Cyclizations 29
1.6.1 Postcatalytic Intramolecular Michael Additions 29
1.6.1.1 Ortho Alkylation 29
1.6.1.2 Ortho Arylation 30
1.6.2 Postcatalytic Intramolecular Addition to Norbornyl Moiety 31
1.7 Summary 32
References 33
2 Diverse Ipso Arene Functionalization by the Palladium/Norbornene Cooperative Catalysis 45
Bo-Sheng Zhang and Yong-Min Liang
2.1 Introduction 45
2.2 Ipso Functionalization Reaction in the Pd/NBE Catalytic Cycle 46
2.2.1 The Role of Ipso Functionalization Reaction in the Catalytic Cycle 46
2.2.2 Competitive or Side Reactions of Ipso Functionalization 46
2.2.2.1 Competitive Pathways Between Ipso Functionalization and NBE Insertion 46
2.2.2.2 Compatibility Between Electrophile Reagents and Ipso Functionalization Reagents 48
2.2.2.3 Process of NBE Extrusion and Ipso Functionalization 49
2.2.2.4 Dehalogenation Reaction and Ipso Functionalization Reaction 51
2.3 Type of Ipso Functionalization Reactions 52
2.3.1 Alkenylation Reaction 52
2.3.1.1 Heck Coupling 52
2.3.1.2 Carbene Coupling 58
2.3.1.3 Allenylation Reaction 59
2.3.2 Alkynylation Reactions (Sonogashira Coupling) 61
2.3.3 Arylation Reactions 61
2.3.3.1 Suzuki Coupling 61
2.3.3.2 Ipso Câ"H Arylation 64
2.3.3.3 Decarboxylation Coupling Reaction 67
2.3.4 Alkylation Reaction 67
2.3.4.1 Coupling Reaction of Boron Reagents 67
2.3.4.2 Coupling Reaction of Germanium Reagents 67
2.3.4.3 Ipso Ketone α-Arylation 69
2.3.4.4 Câ"H Activation of Inert Alkyl Groups 71
2.3.4.5 The Câ"C Bond Cleavage Reaction 71
2.3.4.6 The 1,4-Pd Shift 72
2.3.5 Hydrogenation Reaction 74
2.3.6 Cyanation Reaction 74
2.3.7 Borylation Reaction 76
2.3.8 The Construction of Câ"N Bond 76
2.3.9 The Construction of Câ"O Bond 76
2.3.10 The Construction of Câ"S or Câ"Se Bonds 78
2.3.11 Ipso Iodination 79
2.4 Prospects and Challenges of Ipso Functionalization 80
References 81
3 Diverse Ortho Câ"H Functionalization by the Palladium/Norbornene Cooperative Catalysis 89
Xin Liu and Guangbin Dong
3.1 Introduction 89
3.2 Carbon-Electrophile 91
3.2.1 Ortho Alkylation 91
3.2.1.1 Alkylation Using Alkyl Halides 91
3.2.1.2 Alkylation Using Methyl Sulfonates, Trimethylphosphate, and Phenyltrimethylammonium Salt 92
3.2.1.3 Annulation Using 2H-Azirines 96
3.2.1.4 Alkylation Using Epoxides 97
3.2.1.5 Alkylation Using Aziridines 97
3.2.1.6 Alkylation Using Ethers and TMSI 98
3.2.2 Ortho Arylation 99
3.2.2.1 âOrtho Effectâ in the Pd/NBE Catalysis 99
3.2.2.2 Arylation Using Aryl Halides 101
3.2.2.3 Homo Ortho Arylation 103
3.2.2.4 Cross Ortho Arylation and the Chelating Effect 103
3.2.2.5 Arylation Using Aryl Diazonium Salts 105
3.2.3 Ortho Acylation 107
3.2.3.1 Acylation Using Acid (Mixed) Anhydrides, Acid Chlorides, and Carboxylic Acids 107
3.2.3.2 Carboxylation Using Thioesters and Selenides 109
3.2.3.3 Alkoxycarbonylation and Aminocarbonylation 110
3.3 Nitrogen-Electrophile 112
3.3.1 Ortho Amination 112
3.3.1.1 Amination Using N-Benzoyloxyamines 113
3.3.1.2 Amination Using Dialkylamino Carbonates 114
3.4 Sulfur-Electrophile 116
3.4.1 Ortho Thiolation 116
3.4.1.1 Thiolation Using Aryl or Alkyl Thiosulfonates 116
3.4.1.2 Thiolation Using Aryl or Alkyl Sulfenamides 116
3.5 Oxygen-Electrophile 117
3.5.1 Ortho Alkoxylation 117
3.6 Conclusion and Outlook 119
References 121
4 Asymmetric Palladium/Norbornene Cooperative Catalysis 129
Shuming Zhan and Zhenhua Gu
4.1 Introduction 129
4.2 Stereochemistry Controlled by the Substrate 131
4.2.1 Intramolecular Chirality Transfer 131
4.2.2 Intermolecular Chirality Transfer 132
4.3 Catalytic Asymmetric Transformations Controlled by Chiral Ligands 138
4.3.1 Catalytic Asymmetric Transformations Controlled by Chiral Phosphine Ligands 138
4.3.2 Catalytic Asymmetric Transformation Controlled by Chiral Amino Acids 139
4.4 Catalytic Asymmetric Transformation Controlled by Chiral Norbornenes 142
4.4.1 Desymmetrization 142
4.4.2 Kinetic Resolution 144
4.4.3 Enantioselective Transformations 147
4.5 Summary and Outlook 152
References 154
5 Pd(II)-Initiated Palladium/Norbornene Cooperative Catalysis 157
Hong-Gang Cheng, Kevin Wu, Qianghui Zhou, and Jin-Quan Yu
5.1 Introduction 157
5.2 Pd/NBE-catalyzed Câ"H Functionalization of NH-containing Heteroarenes 159
5.2.1 C2 Alkylation of NH-Indoles and NH-Pyrroles 159
5.2.1.1 C2 Alkylation of NH-Indoles 159
5.2.1.2 C2 Alkylation of NH-Pyrroles and C1 Alkylation of NH-Carbazoles 164
5.2.2 C2 Arylation of NH-Indoles 166
5.3 Directing Group-Enabled meta-Câ"H Functionalization of Arenes 167
5.3.1 Directing Group-Enabled meta-Câ"H Alkylation of Arenes 168
5.3.2 Directing Group-Enabled meta-Câ"H Arylation of Arenes 170
5.3.2.1 Amide as Directing Group 170
5.3.2.2 Tertiary Amine as Directing Group 172
5.3.2.3 Sulfonamide as Directing Group 172
5.3.2.4 Pyridine Derivative as Directing Group 173
5.3.2.5 Acetal-based Quinoline as Directing Group 175
5.3.2.6 Free Carboxylic Acid as Directing Group 175
5.3.3 Directing Group-Enabled meta-Câ"H Chlorination of Arenes 176
5.3.4 Directing Group-Enabled meta-Câ"H Amination of Arenes 176
5.3.5 Directing Group-Enabled meta-Câ"H Alkynylation of Arenes 178
5.3.6 Directing Group-Enabled Distal Câ"H Functionalization of Z-Alkenes 178
5.4 Directing Group-Free Mono- and Difunctionalization of (Hetero)Arenes 179
5.4.1 Directing Group-Free meta-Câ"H Arylation of (Hetero)Arenes 179
5.4.2 Directing Group-Free Difunctionalization of Heterarenes 181
5.5 Template-Enabled Remote Câ"H Functionalization 183
5.6 Enantioselective Remote Câ"H Functionalization 184
5.7 Borono-Catellani Reactions 188
5.8 Conclusion and Outlook 190
References 194
6 Functionalization of Heteroarenes by the Palladium/Norbornene Cooperative Catalysis 199
Jung Min Joo
6.1 Introduction 199
6.2 Pd/NBE Reactions of Five-Membered Haloheteroarenes 200
6.2.1 Reactions of Haloheteroarenes without Incorporation of NBE 200
6.2.2 Reactions of Haloheteroarenes with Incorporation of NBE 202
6.3 Pd/NBE Reactions of Six-Membered Haloheteroarenes 206
6.3.1 Reactions of Six-Membered Haloheteroarenes without Incorporation of Nbe 206
6.3.2 Reactions of Six-Membered Haloheteroarenes with Incorporation of Nbe 211
6.4 Pd/NBE Reactions of Parent Heteroarenes 214
6.5 Conclusion 219
List of Abbreviations 219
Acknowledgments 219
References 219
7 Addressing the Substrate Limitation in the Palladium/Norbornene Cooperative Catalysis 225
Zhao Wu
7.1 Introduction 225
7.2 Ortho Constraint 227
7.2.1 âOrtho Effectâ and âOrtho Constraintâ 227
7.2.2 Addressing the Ortho Constraint with Bridgehead-Substituted NBEs 230
7.2.3 Annulation with the C7-Modified NBE 234
7.2.4 Hybrid Cycloolefin Ligand Strategy 235
7.3 Meta Constraint 237
7.3.1 Addressing the Meta Constraint with the C2-Amide-Substituted NBE 241
7.4 Aryl Iodide Constraint 243
7.4.1 Aryl Sulfonates 244
7.4.2 Aryl Bromides 246
7.5 Beyond Aromatic Substrates 251
7.5.1 Partially Aromatic Substrates 252
7.5.2 α-Alkylation and Arylation of Alkenyl Triflates and Bromides 253
7.5.3 α-Amination of Alkenyl Triflates: Formal Carbonyl 1,2-Transposition 255
7.5.4 α-Carbamoylation of Alkenyl Triflates 257
7.5.5 Distal Alkenyl Câ"H Bond Functionalization 258
7.6 Conclusions and Outlook 260
Acknowledgments 260
References 261
8 Application of the Palladium/Norbornene Cooperative Catalysis to Synthesis of Natural Products and Materials 265
Jianchun Wang
8.1 Applications in Synthesis of Natural Products and Drugs 265
8.1.1 Synthesis Using Ortho Functionalization of Aryl Halides 265
8.1.1.1 Synthesis Using Ortho Alkylation Reactions 267
8.1.1.2 Synthesis Using Ortho Arylation Reactions 273
8.1.1.3 Synthesis Using Ortho Amination Reactions 275
8.1.1.4 Synthesis Using Ortho Acylation Reactions 277
8.1.2 Synthesis Using 2-Alkylation of Indoles 279
8.1.3 Synthesis Using Ortho Functionalization of Vinyl Substrates 283
8.2 Applications in Synthesis of Organic Aromatic Materials 284
8.3 Summary 290
References 291
Index 295
