Metal Free C-H Functionalization of Aromatics: Nucleophilic Displacement of Hydrogen (Topics in Heterocyclic Chemistry Book 37)

The series Topics in Heterocyclic Chemistry presents critical reviews on present and future trends in the research of heterocyclic compounds. Overall the scope is to cover topics dealing with all areas within heterocyclic chemistry, both experimental and theoretical, of interest to the general heterocyclic chemistry community. The series consists of topic related volumes edited by renowned editors with contributions of experts in the field. Preface 6 Reference 8 Contents 10 Metal-Free C-H Functionalization of Aromatic Compounds Through the Action of Nucleophilic Reagents 11 1 Introduction 13 2 Historical Aspects of the SNH Reactions 16 3 The Key Features and Scope of the SNH Reactions 17 3.1 Oxidative Version of the SNH Reactions 21 3.2 Eliminative Version of the SNH Reactions 22 4 Aromatic and Heteroaromatic Substrates 23 4.1 Unactivated Arenes 24 4.2 Arenes and Hetarenes Activated by the Nitro Group 25 4.3 Arene-Metal Complexes 26 4.4 Metallabenzenes 27 4.5 Azines, Quaternary Azinium Salts, and Azine N-Oxides 28 4.6 Azoles 30 4.7 Macroheterocycles 30 5 Nucleophilic Reagents 32 5.1 Nitrogen-Centered Nucleophiles 32 5.1.1 Ammonia, Primary, and Secondary Aliphatic Amines 32 5.1.2 Aromatic Amines as N-Nucleophiles 33 5.2 Oxygen-Centered Nucleophiles 34 5.2.1 Water 34 5.2.2 Alcohols 35 5.3 Carbon-Centered Nucleophiles 35 5.3.1 Carbanions Generated from C-H-Active Compounds 35 5.3.2 Grignard Reagents 36 5.3.3 Carbanions Generated from Ferrocenes and Cymantrenes 37 5.3.4 Carbanions Generated from Carboranes 38 5.3.5 Carbanions Generated from Nitronyl Nitroxide Radicals 38 5.3.6 Aromatic Amines as C-Nucleophiles 39 5.3.7 Phenols as C-Nucleophiles 39 5.4 P-Nucleophiles 41 5.5 S-Nucleophiles 42 6 Intramolecular SNH Reactions 42 7 Tandem SNH-SNH, SNH-SNX, and SNH-Metal-Catalyzed Cross-Coupling Reactions 43 8 Electrochemical Version of the SNH Reactions 46 9 Mechanistic Aspects of the SNH Reactions 47 9.1 Electron Transfer Complexes Between Reactants 47 9.2 Formation of Intermediate sigmaH-Adducts 47 9.2.1 Spectroscopic Evidence for the Formation of sigmaH-Adducts 47 9.2.2 X-Ray Data 50 9.3 Oxidation of Intermediate sigmaH-Adducts 50 10 Concluding Remarks 52 References 54 Nucleophilic Substitution of Hydrogen in Arenes and Heteroarenes 61 1 Introduction 62 2 Vicarious Nucleophilic Substitution of Hydrogen 63 2.1 Mechanism 64 2.2 Scope of the Reaction 67 3 Oxidative Nucleophilic Substitution of Hydrogen 71 4 Conversion of sigmaH Adducts into Nitrosoarenes 74 5 Introduction of Substituents into Electron-Deficient Heterocycles via Nucleophilic Substitution of Hydrogen 76 5.1 Carbon Substituents 76 5.2 Hydroxylation 85 5.3 Amination 86 6 Construction of Heterocyclic Compounds via Nucleophilic Substitution of Hydrogen 89 6.1 Indoles 89 6.2 Quinolines 100 6.3 2,1-Benzisoxazoles 104 6.4 Phenazines and Other Heterocyclic Compounds from 2-Nitrosodiphenylamines 106 6.5 Miscellaneous Syntheses of Heterocycles 108 7 Conclusion 109 References 109 Direct Functionalization of C-H Fragments in Nitroarenes as a Synthetic Pathway to Condensed N-Heterocycles 116 1 Introduction 117 2 Synthesis of Condensed N-heterocycles via Nucleophilic Substitution of Hydrogen (SNH) in Nitroarenes 118 2.1 Vicarious Nucleophilic Substitution of Hydrogen 119 2.2 Oxidative Nucleophilic Substitution of Hydrogen 128 3 Barton-Zard Reaction 135 4 Mannich Cyclization of Anionic Adducts of Nitroarenes 139 5 Pericyclic Reactions of Nitroarenes 143 5.1 [4+2]-Cycloaddition Reactions 144 5.2 [3+2]-Cycloaddition Reactions 148 6 Other Transformations 156 7 Conclusion 159 References 159 C-H Functionalization of Heteroaromatic N-Oxides 164 1 Introduction 165 2 Metal-Free C-H Functionalization with Heteroatom Nucleophiles 170 3 Metal-Free C-H Functionalization with Carbon Nucleophiles 174 4 Functionalization with Arynes 180 5 C-H Functionalization Using Radical Reactions 181 6 Conclusion 184 References 184 The SNH-Amination of Heteroaromatic Compounds 187 1 Introduction 188 2 The Classical Chichibabin Amination 190 3 Oxidative Amination 193 3.1 Introduction of the NH2 group 193 3.2 Alkylamination 197 3.3 Arylamination 214 4 Amination of Azoles 216 5 Amination via the cine- and tele-Substitution 220 5.1 cine-Amination 221 5.2 tele-Amination 228 5.3 Amination via the ANRORC Mechanism 228 6 Amination via the Vicarious Nucleophilic Substitution of Hydrogen 230 7 Representative Procedures for the SNH-Amination 240 7.1 Synthesis of 1-Amino-4-Azafluorene by the Chichibabin Amination [43] 240 7.2 Oxidative Amination of 3-Phenyl-1,2,4,5-Tetrazine [49] 240 7.3 Oxidative Amination of 1,3,7-Triazapyrene [55] 240 7.4 General Procedure for the Oxidative Alkylamination of Quinazoline [87] 241 7.5 General Procedure for the Oxidative Alkylamination of 1,3,5-Triazine [75] 241 7.6 Typical Procedure for Iodine-Catalyzed Amination of Benzoxazoles [102] 242 7.7 Synthesis of 2-Aminopyridine from Pyridine N-oxide [114] 242 7.8 General Procedures for the VNS Amination of 3-Nitropyridines [138] 243 7.8.1 Procedure A with Hydroxylamine 243 7.8.2 Procedure B with 4-Amino-1,2,4-Triazole 243 References 244 Electrochemical C-H Functionalization of Arenes and Heteroarenes 248 1 Introduction 250 2 Mechanisms for Electrochemical Oxidation of sigma-Complexes 251 2.1 Electrochemical Oxidation of sigmaX-Complexes 251 2.2 Electrochemical Oxidation of sigmaH-Complexes 253 2.3 Electrochemical Oxidation of Mixtures of sigmaH- and sigmaX-Complexes 257 2.4 Electrochemical Features of sigmaH- and sigmaX-Complexes 259 3 Synthetic Applications of Electrochemical SNH Reactions 261 3.1 Cyanation Reactions 261 3.2 Amination Reactions 263 3.3 C-Arylation of Ketones 264 3.4 Alkylation Reactions with Organometallic Reagents RM and Tetraalkylborates as Nucleophiles 265 3.5 Phosphonylation Reactions. Phosphorous-Containing Compounds as Nucleophiles 268 4 Electrochemically Induced SNX and SNH Reactions 270 5 Thermodynamic Studies of sigma-Complexes 273 6 Electrochemical C-H Functionalization of Heteroarenes 277 7 Conclusion 279 References 280 Index 283 Front Matter....Pages i-ix Metal-Free C–H Functionalization of Aromatic Compounds Through the Action of Nucleophilic Reagents....Pages 1-50 Nucleophilic Substitution of Hydrogen in Arenes and Heteroarenes....Pages 51-105 Direct Functionalization of C–H Fragments in Nitroarenes as a Synthetic Pathway to Condensed N-Heterocycles....Pages 107-154 C–H Functionalization of Heteroaromatic N -Oxides....Pages 155-177 The S N H -Amination of Heteroaromatic Compounds....Pages 179-239 Electrochemical C–H Functionalization of Arenes and Heteroarenes....Pages 241-275 Back Matter....Pages 277-283