Remote C-H Bond Functionalizations

Debabrata Maiti, PhD, is an Associate Professor in the Department of Chemistry at the Indian Institute of Technology (IIT) Bombay, India, and Visiting Faculty at the University of Pavia, Italy. He is the Associate Editor of the Journal of Organic Chemistry and a member of Editorial Advisory Board of Organometallics and Chemistry - An Asian Journal. Srimanta Guin, PhD, is a National Post-doctoral Fellow at the Indian Institute of Technology (IIT) Bombay, India. His current research is focused on the development of transition metal catalyzed distal C-H functionalization of arenes and aliphatic substrates.

• 1 Introduction 1Uttam Dutta, Srimanta Guin, and Debabrata Maiti2 Transition Metal-Catalyzed Remote meta-C–H Functionalization of Arenes Assisted by meta-Directing Templates 7Yuzhen Gao and Gang Li2.1 Introduction 72.2 Template-Assisted meta-C–H Functionalization 92.2.1 Toluene Derivatives 92.2.2 Acid Derivatives 102.2.2.1 Hydrocinnamic Acid Derivatives 102.2.2.2 Phenylacetic Acid Derivatives 162.2.2.3 Benzoic Acid Derivatives 202.2.3 Amine and N-Heterocyclic Arene Derivatives 232.2.3.1 Aniline Derivatives 232.2.3.2 Benzylamine Derivatives 272.2.3.3 Phenylethylamine Derivatives 272.2.3.4 N-Heterocyclic Arene Derivatives 292.2.4 Sulfonic Acid Derivatives 332.2.5 Phenol Derivatives 402.2.6 Alcohol Derivatives 442.2.7 Silane Derivatives 502.2.8 Phosphonate Derivatives 512.3 Mechanistic Considerations 532.4 Conclusion 55Abbreviations 56References 573 C–H Functionalization of Arenes Under Palladium/Norbornene Catalysis 59Juntao Ye and Mark Lautens3.1 Introduction 593.2 Pd(0)-Catalyzed C–H Functionalization of Aryl (Pseudo)Halides 643.2.1 ortho-Alkylation 643.2.1.1 ortho-Alkylation with Simple Alkyl Halides 643.2.1.2 ortho-Alkylation with Bifunctional Alkylating Reagents 703.2.1.3 ortho-Alkylation with Three-Membered Heterocycles 753.2.2 ortho-Arylation 773.2.3 ortho-Acylation and Alkoxycarbonylation 893.2.4 ortho-Amination 943.2.5 ortho-Thiolation 1013.3 Pd(II)-Catalyzed C–H Functionalization of Arenes 1013.3.1 C2-Functionalization of Indoles and Pyrroles 1013.3.2 meta-C–H Functionalization of Arenes Containing an ortho-Directing Group 1023.3.3 ortho-C–H Functionalization of Arylboron Species 1053.4 Conclusions and Outlook 108Acknowledgments 109References 1104 Directing Group Assisted meta-C–H Functionalization of Arenes Aided by Norbornene as Transient Mediator 115Hong-Gang Cheng and Qianghui Zhou4.1 Introduction 1154.2 meta-C–H Alkylation of Arenes 1164.2.1 Amide as Directing Group 1164.2.2 Sulfonamide as Directing Group 1184.3 meta-C–H Arylation of Arenes 1194.3.1 Amide as Directing Group 1194.3.2 Sulfonamide as Directing Group 1224.3.3 Tertiary Amine as Directing Group 1224.3.4 Tethered Pyridine-Type Directing Group 1234.3.5 Acetal-Based Quinoline as Directing Group 1264.3.6 Free Carboxylic Acid as Directing Group 1264.4 meta-C–H Chlorination of Arenes 1274.5 meta-C–H Amination of Arenes 1294.6 meta-C–H Alkynylation of Arenes 1304.7 Enantioselective meta-C–H Functionalization 1304.8 Conclusion 133Abbreviations 134References 1345 Ruthenium-Catalyzed Remote C–H Functionalizations 137Korkit Korvorapun, Ramesh C. Samanta, Torben Rogge, and Lutz Ackermann5.1 Introduction 1375.2 meta-C–H Functionalizations 1385.2.1 C–H Alkylation 1385.2.2 C–H Benzylation 1465.2.3 C–H Carboxylation 1505.2.4 C–H Acylation 1515.2.5 C–H Sulfonylation 1515.2.6 C–H Halogenation 1525.2.7 C–H Nitration 1555.3 para-C–H Functionalizations 1585.4 meta-/ortho-C–H Difunctionalizations 1615.5 Conclusions 161Acknowledgments 163References 1636 Harnessing Non-covalent Interactions for Distal C(sp2)–H Functionalization of Arenes 169Georgi R. Genov, Madalina T. Mihai, and Robert J. Phipps6.1 Introduction 1696.2 Non-covalent Interactions in Metal Catalyzed C—H Bond Functionalization 1706.3 Overview of Iridium-Catalyzed Borylation 1716.4 Non-covalent Interactions in Ir-Catalyzed Borylation 1746.5 meta-Selective Borylation using Non-covalent Interactions 1766.6 para-Selective Borylation using Non-covalent Interactions 1816.7 Conclusions 186References 1867 The Non-directed Distal C(sp2)–H Functionalization of Arenes 191Arup Mondal, Philipp Wedi, and Manuel van Gemmeren7.1 Introduction 1917.1.1 Mechanisms 1927.2 C–Het Formation 1937.2.1 Borylation 1937.2.2 Silylation 1957.2.3 Amination 1967.2.4 Oxygenation 2007.2.5 Other C—Het Bond Forming Reactions 2027.3 C—C Bond Forming Reactions 2057.3.1 C–H-Arylation 2067.3.2 Alkenylation/Olefination 2077.3.3 Cyanation 2097.3.4 Other C—C Bond Forming Reactions 2127.4 Outlook 212References 2138 Transition Metal Catalyzed Distal para-Selective C–H Functionalization 221Uttam Dutta and Debabrata Maiti8.1 Introduction 2218.2 Template Assisted para-Selective C–H Functionalization 2248.2.1 Palladium Catalyzed Methods 2248.2.1.1 Alkenylation 2248.2.1.2 Silylation 2268.2.1.3 Ketonization 2278.2.1.4 Acetoxylation 2308.2.1.5 Cyanation 2328.2.2 Rhodium Catalyzed Functionalization 2338.2.2.1 Alkenylation 2338.3 Steric Controlled and Lewis Acid-Transition Metal Cooperative Catalysis 2338.3.1 Nickel Catalyzed Methods 2348.3.1.1 Alkylation and Alkenylation 2348.3.2 Iridium Catalyzed Methods 2408.3.2.1 Borylation 2408.4 Non-covalent Interaction Induced para-C–H Functionalization 2428.4.1 Di-polar Induced Methods 2428.4.2 Ion-Pair Induced Methods 2438.5 Conclusion and the Prospect 244Acknowledgments 246References 2469 Regioselective C–H Functionalization of Heteroaromatics at Unusual Positions 253Koji Hirano and Masahiro Miura9.1 Introduction 2539.2 Indole 2539.2.1 C–H Functionalization at C4 Position 2549.2.2 C–H Functionalization at C7 Position 2589.2.3 C–H Functionalization at C5 Position 2619.2.4 C–H Functionalization at C6 Position 2619.3 (Benzo)Thiophene 2629.4 Pyrrole 2649.5 Pyridine 2669.6 Miscellaneous Heteroarenes 2719.6.1 Thiazole 2719.6.2 Quinoline 2719.7 Conclusion 272References 27310 Directing Group Assisted Distal C(sp3)–H Functionalization of Aliphatic Substrates 279Ya Li, Qi Zhang, and Bing-Feng Shi10.1 Introduction 27910.2 γ-C(sp3)–H Functionalization of Aliphatic Acids 28010.3 δ-/ε-C(sp3)—H Bond Functionalization of Aliphatic Amines 28810.4 γ-C(sp3)—H Bond Functionalization of Aliphatic Ketones or Aldehydes 30110.5 γ-/δ-C(sp3)—H Bond Functionalization of Aliphatic Alcohols 30510.6 Conclusions and Outlook 307References 30911 Radically Initiated Distal C(sp3)–H Functionalization 315Weipeng Li and Chengjian Zhu11.1 Introduction 31511.2 Distal C(sp3)–H Functionalization Promoted by Carbon-Centered Radicals 31711.3 Distal C(sp3)–H Functionalization Promoted by Nitrogen-Centered Radicals 32511.3.1 Generation of Nitrogen Radical from N—X (X = F, Cl, Br, I) Bond 32511.3.2 Generation of Nitrogen Radical from N—N Bond 32811.3.3 Generation of Nitrogen Radical from N—O Bond 32911.3.4 Nitrogen Radical Generated Directly from N—H Bond 33111.4 Oxygen-Centered Radicals Initiate Distal C(sp3)–H Functionalization 33311.4.1 Oxygen Radical Generated from O—X (X = N, O) bond 33311.4.2 Oxygen Radical Generated Directly from O—H Bond 33611.5 Summary and Outlook 338References 33912 Non-Directed Functionalization of Distal C(sp3)—H Bonds 343Carlo Sambiagio and Bert U. W. Maes12.1 Introduction 34312.1.1 Bond Dissociation Energy (BDE) of C—H Bonds 34412.1.2 Scope of the Chapter 34612.2 Reactions Occurring Without Formation of Metal–Carbon Bonds 34612.2.1 Oxidations with Dioxiranes 34612.2.2 Decatungstate-Photocatalyzed Remote Functionalization 3481.2.3 Electrochemical Remote Functionalizations 35312.2.4 Carbene Insertion into C—H Bonds 35612.3 Reactions Occurring via Formation of Metal–Carbon Bonds 36012.3.1 Pt-Based Shilov Chemistry 36112.3.2 Rh- and Ir-Catalyzed C–H Borylation of (Functionalized) Alkanes 36312.4 Altering Innate Reactivity by Polarity Reversal Strategies 36712.4.1 Remote Functionalization of Aliphatic Amines via Quaternary Ammonium Salts 36812.4.2 Remote Functionalization of Alcohols and Amides via Hydrogen Bond Interactions 376Acknowledgments 378References 37813 Remote Oxidation of Aliphatic C—H Bonds with Biologically Inspired Catalysts 383Miquel Costas13.1 Introduction 38313.1.1 Bioinspired Catalysis as a Tool for Site Selective C—H Bond Oxidation 38313.1.2 Typology of Bioinspired Catalysts 38513.1.3 Site Selectivity in Aliphatic C–H Oxidation: Basic Considerations 38713.2 Innate Substrate Based Aspects Governing Site Selectivity in C–H Oxidations 38813.2.1 C—H Bond Strength 38813.2.2 Electronic Effects 38813.2.3 Steric Effects 39113.2.4 Directing Groups 39213.2.5 Stereoelectronic Effects 39313.2.5.1 Hyperconjugation Effects 39313.2.5.2 Strain Release and Torsional Effects 39413.2.6 Chirality 39513.3 Remote Oxidations by Reversal of Polarity 39513.3.1 Remote Oxidation in Amine Containing Substrates by Protonation of the Amine Site 39513.3.2 Remote Oxidation of Amide Containing Substrates by Methylation of the Amide Moiety 39713.3.3 Remote Oxidation via Polarity Reversal Exerted by Fluorinated Alcohol Solvents 39713.4 Remote Oxidations Guided by Supramolecular Recognition 40113.4.1 Lipophilic Interactions 40313.4.2 Lipophilic Recognition by Cyclodextrins 40413.4.3 Ligand to Metal Coordination 40613.4.4 Hydrogen Bonding 40813.5 Selective Aliphatic C–H Oxidation at Dicopper Complexes 41613.6 Conclusions 417References 418Index 423