Remote C–H Bond Functionalizations: Methods and Strategies in Organic Synthesis

Description

A guide to contemporary advancements in the field of distal C-H functionalizations  An important and dynamic topic within the modern field of organic synthesis, selective functionalization of C-H bonds can be used in a variety of applications across the pharmaceutical and agrochemical industries. Remote C-H Bond Functionalizations presents an inclusive account of the most recent developments and potential applications of performing variegated functionalizations selectively at the distal positions of organic compounds.   Featuring contributions by an international team of experts, this authoritative volume provides deep insight into distal functionalizations, including detailed discussion of mechanisms, the engineering of templates, and the design of strategies. The text covers a diverse range of topics including C-H functionalization of palladium/norbornene catalysis, ruthenium-catalyzed remote functionalization, the non-directed distal C(sp2)-H, functionalization, transition metal catalyzed distal para-selective C-H functionalization, and much more. Reviewing contemporary advancements in the field while laying the foundation for future research, this important resource:  Provides the most recent research and thorough coverage of the subject available in a single volume  Offers practical information on C-H functionalizations in various industries  Includes an up-to-date introduction to distal C-H functionalizations  Remote C-H Bond Functionalizations is a must-read for every synthetic chemist, including chemists working with organometallics, organic chemists and researchers, and industrial chemists.  Cover Title Page Copyright Contents Chapter 1 Introduction Chapter 2 Transition Metal‐Catalyzed Remote meta‐C–H Functionalization of Arenes Assisted by meta‐Directing Templates 2.1 Introduction 2.2 Template‐Assisted meta‐C–H Functionalization 2.2.1 Toluene Derivatives 2.2.2 Acid Derivatives 2.2.2.1 Hydrocinnamic Acid Derivatives 2.2.2.2 Phenylacetic Acid Derivatives 2.2.2.3 Benzoic Acid Derivatives 2.2.3 Amine and N‐Heterocyclic Arene Derivatives 2.2.3.1 Aniline Derivatives 2.2.3.2 Benzylamine Derivatives 2.2.3.3 Phenylethylamine Derivatives 2.2.3.4 N‐Heterocyclic Arene Derivatives 2.2.4 Sulfonic Acid Derivatives 2.2.5 Phenol Derivatives 2.2.6 Alcohol Derivatives 2.2.7 Silane Derivatives 2.2.8 Phosphonate Derivatives 2.3 Mechanistic Considerations 2.4 Conclusion References Chapter 3 C–H Functionalization of Arenes Under Palladium/Norbornene Catalysis 3.1 Introduction 3.2 Pd(0)‐Catalyzed C–H Functionalization of Aryl (Pseudo)Halides 3.2.1 ortho‐Alkylation 3.2.1.1 ortho‐Alkylation with Simple Alkyl Halides 3.2.1.2 ortho‐Alkylation with Bifunctional Alkylating Reagents 3.2.1.3 ortho‐Alkylation with Three‐Membered Heterocycles 3.2.2 ortho‐Arylation 3.2.3 ortho‐Acylation and Alkoxycarbonylation 3.2.4 ortho‐Amination 3.2.5 ortho‐Thiolation 3.3 Pd(II)‐Catalyzed C–H Functionalization of Arenes 3.3.1 C2‐Functionalization of Indoles and Pyrroles 3.3.2 meta‐C–H Functionalization of Arenes Containing an ortho‐Directing Group 3.3.3 ortho‐C–H Functionalization of Arylboron Species 3.4 Conclusions and Outlook Acknowledgments References Chapter 4 Directing Group Assisted meta‐C–H Functionalization of Arenes Aided by Norbornene as Transient Mediator 4.1 Introduction 4.2 meta‐C–H Alkylation of Arenes 4.2.1 Amide as Directing Group 4.2.2 Sulfonamide as Directing Group 4.3 meta‐C–H Arylation of Arenes 4.3.1 Amide as Directing Group 4.3.2 Sulfonamide as Directing Group 4.3.3 Tertiary Amine as Directing Group 4.3.4 Tethered Pyridine‐Type Directing Group 4.3.5 Acetal‐Based Quinoline as Directing Group 4.3.6 Free Carboxylic Acid as Directing Group 4.4 meta‐C–H Chlorination of Arenes 4.5 meta‐C–H Amination of Arenes 4.6 meta‐C–H Alkynylation of Arenes 4.7 Enantioselective meta‐C–H Functionalization 4.8 Conclusion References Chapter 5 Ruthenium‐Catalyzed Remote C–H Functionalizations 5.1 Introduction 5.2 meta‐C–H Functionalizations 5.2.1 C–H Alkylation 5.2.2 C–H Benzylation 5.2.3 C–H Carboxylation 5.2.4 C–H Acylation 5.2.5 C–H Sulfonylation 5.2.6 C–H Halogenation 5.2.7 C–H Nitration 5.3 para‐C–H Functionalizations 5.4 meta‐/ortho‐C–H Difunctionalizations 5.5 Conclusions Acknowledgments References Chapter 6 Harnessing Non‐covalent Interactions for Distal C(sp2)–H Functionalization of Arenes 6.1 Introduction 6.2 Non‐covalent Interactions in Metal Catalyzed CH Bond Functionalization 6.3 Overview of Iridium‐Catalyzed Borylation 6.4 Non‐covalent Interactions in Ir‐Catalyzed Borylation 6.5 meta‐Selective Borylation using Non‐covalent Interactions 6.6 para‐Selective Borylation using Non‐covalent Interactions 6.7 Conclusions References Chapter 7 The Non‐directed Distal C(sp2)–H Functionalization of Arenes 7.1 Introduction 7.1.1 Mechanisms 7.2 C–Het Formation 7.2.1 Borylation 7.2.2 Silylation 7.2.3 Amination 7.2.4 Oxygenation 7.2.5 Other CHet Bond Forming Reactions 7.3 CC Bond Forming Reactions 7.3.1 C–H‐Arylation 7.3.2 Alkenylation/Olefination 7.3.3 Cyanation 7.3.4 Other CC Bond Forming Reactions 7.4 Outlook References Chapter 8 Transition Metal Catalyzed Distal para‐Selective C–H Functionalization 8.1 Introduction 8.2 Template Assisted para‐Selective C–H Functionalization 8.2.1 Palladium Catalyzed Methods 8.2.1.1 Alkenylation 8.2.1.2 Silylation 8.2.1.3 Ketonization 8.2.1.4 Acetoxylation 8.2.1.5 Cyanation 8.2.2 Rhodium Catalyzed Functionalization 8.2.2.1 Alkenylation 8.3 Steric Controlled and Lewis Acid‐Transition Metal Cooperative Catalysis 8.3.1 Nickel Catalyzed Methods 8.3.1.1 Alkylation and Alkenylation 8.3.2 Iridium Catalyzed Methods 8.3.2.1 Borylation 8.4 Non‐covalent Interaction Induced para‐C–H Functionalization 8.4.1 Di‐polar Induced Methods 8.4.2 Ion‐Pair Induced Methods 8.5 Conclusion and the Prospect Acknowledgments References Chapter 9 Regioselective C–H Functionalization of Heteroaromatics at Unusual Positions 9.1 Introduction 9.2 Indole 9.2.1 C–H Functionalization at C4 Position 9.2.2 C–H Functionalization at C7 Position 9.2.3 C–H Functionalization at C5 Position 9.2.4 C–H Functionalization at C6 Position 9.3 (Benzo)Thiophene 9.4 Pyrrole 9.5 Pyridine 9.6 Miscellaneous Heteroarenes 9.6.1 Thiazole 9.6.2 Quinoline 9.7 Conclusion References Chapter 10 Directing Group Assisted Distal C(sp3)–H Functionalization of Aliphatic Substrates 10.1 Introduction 10.2 γ‐C(sp3)–H Functionalization of Aliphatic Acids 10.3 δ‐/ε‐C(sp3)H Bond Functionalization of Aliphatic Amines 10.4 γ‐C(sp3)H Bond Functionalization of Aliphatic Ketones or Aldehydes 10.5 γ‐/δ‐C(sp3)H Bond Functionalization of Aliphatic Alcohols 10.6 Conclusions and Outlook References Chapter 11 Radically Initiated Distal C(sp3)–H Functionalization 11.1 Introduction 11.2 Distal C(sp3)–H Functionalization Promoted by Carbon‐Centered Radicals 11.3 Distal C(sp3)–H Functionalization Promoted by Nitrogen‐Centered Radicals 11.3.1 Generation of Nitrogen Radical from NX (X = F, Cl, Br, I) Bond 11.3.2 Generation of Nitrogen Radical from NN Bond 11.3.3 Generation of Nitrogen Radical from NO Bond 11.3.4 Nitrogen Radical Generated Directly from NH Bond 11.4 Oxygen‐Centered Radicals Initiate Distal C(sp3)–H Functionalization 11.4.1 Oxygen Radical Generated from OX (X = N, O) bond 11.4.2 Oxygen Radical Generated Directly from OH Bond 11.5 Summary and Outlook References Chapter 12 Non‐Directed Functionalization of Distal C(sp3)H Bonds 12.1 Introduction 12.1.1 Bond Dissociation Energy (BDE) of CH Bonds 12.1.2 Scope of the Chapter 12.2 Reactions Occurring Without Formation of Metal–Carbon Bonds 12.2.1 Oxidations with Dioxiranes 12.2.2 Decatungstate‐Photocatalyzed Remote Functionalization 12.2.3 Electrochemical Remote Functionalizations 12.2.4 Carbene Insertion into CH Bonds 12.3 Reactions Occurring via Formation of Metal–Carbon Bonds 12.3.1 Pt‐Based Shilov Chemistry 12.3.2 Rh‐ and Ir‐Catalyzed C–H Borylation of (Functionalized) Alkanes 12.4 Altering Innate Reactivity by Polarity Reversal Strategies 12.4.1 Remote Functionalization of Aliphatic Amines via Quaternary Ammonium Salts 12.4.2 Remote Functionalization of Alcohols and Amides via Hydrogen Bond Interactions Acknowledgments References Chapter 13 Remote Oxidation of Aliphatic CH Bonds with Biologically Inspired Catalysts 13.1 Introduction 13.1.1 Bioinspired Catalysis as a Tool for Site Selective CH Bond Oxidation 13.1.2 Typology of Bioinspired Catalysts 13.1.3 Site Selectivity in Aliphatic C–H Oxidation: Basic Considerations 13.2 Innate Substrate Based Aspects Governing Site Selectivity in C–H Oxidations 13.2.1 CH Bond Strength 13.2.2 Electronic Effects 13.2.3 Steric Effects 13.2.4 Directing Groups 13.2.5 Stereoelectronic Effects 13.2.5.1 Hyperconjugation Effects 13.2.5.2 Strain Release and Torsional Effects 13.2.6 Chirality 13.3 Remote Oxidations by Reversal of Polarity 13.3.1 Remote Oxidation in Amine Containing Substrates by Protonation of the Amine Site 13.3.2 Remote Oxidation of Amide Containing Substrates by Methylation of the Amide Moiety 13.3.3 Remote Oxidation via Polarity Reversal Exerted by Fluorinated Alcohol Solvents 13.4 Remote Oxidations Guided by Supramolecular Recognition 13.4.1 Lipophilic Interactions 13.4.2 Lipophilic Recognition by Cyclodextrins 13.4.3 Ligand to Metal Coordination 13.4.4 Hydrogen Bonding 13.5 Selective Aliphatic C–H Oxidation at Dicopper Complexes 13.6 Conclusions References Index EULA