Preface xi

1 Photoelectrochemical Pathways for C—X Bond Functionalization 1
Kajal Tiwari, Anukriti Singhal, Gaurav Kumar, Ankit Ghosh, and Sudipta Raha Roy

1.1 Introduction 1
1.2 C—X Bond Functionalization 4
1.3 Summary and Conclusions 29

2 Visible Light-Induced Palladium Catalysis for Bond Functionalizations: Recent Innovations and Future Directions 35
Mahesh Anil Sonawane and Subhash Chandra Ghosh

2.1 Introduction 35
2.2 Significance of Merging Visible Light with Palladium Catalysis 35
2.3 Fundamentals of Palladium Catalysis 36
2.4 Traditional Ground-State Palladium Catalysis 36
2.5 Hydrogen-Atom Transfer (HAT) and Proton-Coupled Electron Transfer (PCET) Pathways 38
2.6 C—C Bond-Forming Reactions 39
2.7 C—X Bond-Forming Reactions 44
2.8 C—N Bond-Forming Reactions 49
2.9 C—O Bond-Forming Reactions 532.10 Future Directions 55
2.11 Conclusions 56

3 Electrochemical C—C and C—X Bond Formation Reactions 59
Sebastian B. Beil, Finn Moeller, Barbara Pavlovic, Marcel N. Perner, Carla M. Stork, Annemijn M. van Koten, and Siegfried R. Waldvogel

3.1 Introduction 59
3.2 Fundamentals 59
3.3 Concepts—Umpolung and Regeneration of Reagents 62
3.4 C—C Bond Formation 64
3.5 C—O Bond Formation 76
3.6 C—N Bond Formation 81
3.7 C—S Bond Formation 86
3.8 C—X Bond Formation (Halogenation Reactions) 89
3.9 Electrochemical Hydrogen Isotope Exchange Reactions 98
3.10 Electro-Conversion of Renewables 102
3.11 Electrochemical Dehydrative Reaction 105
3.12 Conclusions and Perspective 107

4 Electrochemical C—C and C—N Bond Functionalization 127
Subban Kathiravan and Ian A. Nicholls

4.1 Introduction 127
4.2 Principles of Electrochemical Bond Functionalization 128
4.3 Electrochemical C—C Bond Formation 129
4.4 Electrochemical Cathodic Arene–Arene Cross-Couplings 136
4.5 Electrochemical Cross-Coupling Involving Aryl and Alkyl Halides for C(sp2)—C(sp3) Bond Formation 138
4.6 Heterocycle Synthesis Through C—C Bond Formation 139
4.7 Electrochemical C—N Bond Formation 140
4.8 Electrochemical Oxidative C—N Bond Formation Through C—H/N—H Cross-Coupling 142
4.9 Electrochemical Benzylic C—N Bond Formation 144
4.10 Electrochemical Imidation 148
4.11 Electrochemical Intramolecular Strategy for C—N Bond Formation 149
4.12 Electrochemical Amination of Indoles 152
4.13 Photoelectrochemical C—N Bond Formation 153
4.14 Conclusions 153

5 C—H Halogenation Reactions in Continuous Flow Systems 163
Faith M. Akwi and Paul Watts

5.1 Introduction 163
5.2 C—H Halogenation in Reaction and Process Development 163
5.3 C—H Halogenation in the Synthesis of Active Pharmaceutical Intermediates 184
5.4 Conclusion 193

6 Mechanochemical C—H Bond Functionalization in Organic Synthesis 197
Mainak Banerjee, Mussarat Shamim, Ritesh Jha, and Amrita Chatterjee

6.1 Introduction 197
6.2 Mechanochemistry: Tools, Methods, and Features 199
6.3 Conclusion 226

7 Recent Developments in C—H and C—X Bond Functionalization Using Ball Milling 233
Tubai Ghosh and Brindaban C. Ranu

7.1 Introduction 233
7.2 C—H Bond Functionalization Using Ball Milling 234
7.3 C—X Bond Functionalization Using Ball Milling 243

8 Industrial Application of Bond Functionalization Chemistry 257
Pooja Kumari Jat and S. Peruncheralathan

8.1 Introduction 257
8.2 Late-Stage Functionalization Using a Mechanochemical Strategy 258Contents ix
8.3 Photons to Products: Process Translation Strategies for Photoredox Transformations 260
8.4 Industrial Photoredox Case Studies 263
8.5 Photochemical Cross-Coupling Under Visible Light 267
8.6 Waveform-Controlled Electrosynthesis 268
8.7 Reactor Design Strategies for Photon Delivery and Mixing Control 270
8.8 Electrochemical Oxidation in Process Development 273
8.9 Solvent-Free Mechanochemical Nitrene Transfer and Rearrangements 275
8.10 Birch-Type Reductions Without Liquid Ammonia 277
8.11 Electrosynthetic Rearrangements and Reductions for Functional Group Interconversion 280
8.12 Solvent-Free Mechanochemical Synthesis of APIs 282
8.13 RAM as a Scale-Enabling Strategy 283
8.14 Solid-State Processing for Crystallization and Solid-Form Control 287
8.15 Strategy Selection Guidelines for Industrial Bond Functionalization 289
8.16 Challenges and Limitations 289
8.17 Conclusion 289
8.18 Future Outlook 290

References 290
Index 295