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

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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