Science of Synthesis: Knowledge Updates 2018 Vol. 2 (eBook)

Science of Synthesis: Knowledge Updates 2018/2 1
Title Page 7
Copyright 8
Preface 9
Abstracts 11
Overview 13
Table of Contents 15
10.23 Product Class 23: Pyrido[X,Y-b]indoles (Carbolines) 33
10.23.1 Product Subclass 1: 9H-Pyrido[2,3-b]indoles (?-Carbolines) 38
10.23.1.1 Synthesis by Ring-Closure Reactions 38
10.23.1.1.1 By Annulation to an Arene 38
10.23.1.1.1.1 By Formation of Four N–C and Two C–C Bonds 38
10.23.1.1.1.1.1 With Formation of 1–2, 2–3, 4–4a, 1–9a, 8a–9, and 9–9a Bonds 38
10.23.1.1.1.1.1.1 Method 1: From 1-Bromo-2-(2,2-dibromovinyl)benzenes, Ammonia, and Alkyl Aldehydes 38
10.23.1.1.1.2 By Formation of Two N–C and One C–C Bonds 40
10.23.1.1.1.2.1 With Formation of 1–9a, 4–4a, and 9–9a Bonds 40
10.23.1.1.1.2.1.1 Method 1: From (2-Nitroaryl)acetonitriles and 3-Acetoxy-3-aryl-2-methylene Ketones 40
10.23.1.1.1.2.1.2 Method 2: From (2-Nitrophenyl)acetonitrile and 3-Arylenones 42
10.23.1.1.1.2.1.2.1 Variation 1: From (2-Nitrophenyl)acetonitrile and 4H-1-Benzopyran-4-ones 44
10.23.1.1.1.3 By Formation of Two N–C Bonds 45
10.23.1.1.1.3.1 With Formation of 8a–9 and 9–9a Bonds 45
10.23.1.1.1.3.1.1 Method 1: From Primary Amines and 3-(2-Bromophenyl)-2-chloropyridine 45
10.23.1.1.1.4 By Formation of One N–C Bond and One C–C Bond 47
10.23.1.1.1.4.1 With Formation of 4a–4b and 9–9a Bonds 47
10.23.1.1.1.4.1.1 Method 1: From 2,3-Dihalopyridines and Anilines 47
10.23.1.1.1.4.1.2 Method 2: From 2-Iodopyridine and a 2-Bromoaniline 48
10.23.1.1.1.5 By Formation of Two C–C Bonds 49
10.23.1.1.1.5.1 With Formation of 3–4 and 4a–9a Bonds 49
10.23.1.1.1.5.1.1 Method 1: From (2-Alkenylaryl)carbodiimides 49
10.23.1.1.1.5.1.2 Method 2: From N-Acyl-N-(2-alkynylaryl)pyrimidin-2-amines or 3-[(2-Alkynylphenyl)amino]pyrazin-2-ones 51
10.23.1.1.1.6 By Formation of One N–C Bond 53
10.23.1.1.1.6.1 With Formation of the 9–9a Bond 53
10.23.1.1.1.6.1.1 Method 1: From 3-(2-Azidoaryl)pyridines 53
10.23.1.1.1.6.1.1.1 Variation 1: From 3-(2-Azidoaryl)pyridinium Trifluoromethanesulfonates and a Rhodium Catalyst 54
10.23.1.1.1.6.1.2 Method 2: From 3-(2-Nitroaryl)pyridines 55
10.23.1.1.1.6.1.2.1 Variation 1: From 3-(2-Nitrosoaryl)pyridines 56
10.23.1.1.1.6.1.3 Method 3: From 2-(3-Pyridyl)-N-tosylanilines or N-Acetyl-2-(3-pyridyl)-anilines 56
10.23.1.1.1.6.1.4 Method 4: From N-[2-(2-Fluoropyridin-3-yl)phenyl]pivalamide 58
10.23.1.1.1.7 By Formation of One C–C Bond 58
10.23.1.1.1.7.1 With Formation of the 4a–4b Bond 58
10.23.1.1.1.7.1.1 Method 1: From N-Arylpyridin-2-amines 58
10.23.1.1.1.7.1.1.1 Variation 1: From N,N-Diphenylpyridin-2-amine or N-Methyl-N-phenylpyridin-2-amine 59
10.23.1.1.1.7.1.2 Method 2: From N2-Phenylpyridine-2,3-diamines 60
10.23.1.1.1.7.1.3 Method 3: From an N-Arylpyridin-2-amine with at Least One Halogen on at Least One Ring 61
10.23.1.1.1.7.1.3.1 Variation 1: From N-Aryl-3-chloropyridin-2-amines by Palladium Catalysis 61
10.23.1.1.1.7.1.3.2 Variation 2: From N-Aryl-3-bromopyridin-2-amines with Palladium Catalysis 62
10.23.1.1.1.7.1.3.3 Variation 3: From N-[3-Chloro-1-methylpyridin-2(1H)-ylidene]anilines 65
10.23.1.1.1.7.1.3.4 Variation 4: From N-(Chloroaryl)-3-chloro-1-methylpyridin-2(1H)-imines and Secondary Amines 66
10.23.1.1.1.7.1.3.5 Variation 5: From N-Aryl-3-halopyridin-2-amines by Photostimulated SRN1 Reactions 69
10.23.1.1.1.7.1.3.6 Variation 6: From 3-Bromo-N-(2-bromophenyl)pyridin-2-amines by Palladium(0)-Catalyzed Bond Formation via Tributylstannyl Intermediates 71
10.23.1.1.2 By Annulation to a Heterocycle 71
10.23.1.1.2.1 By Annulation to a Pyridine 71
10.23.1.1.2.1.1 By Formation of One N–C and One C–C Bond 71
10.23.1.1.2.1.1.1 With Formation of 4a–4b and 8a–9 Bonds 71
10.23.1.1.2.1.1.1.1 Method 1: From Pyridin-2,4,6-triamine 71
10.23.1.1.2.2 By Annulation to an Indole 72
10.23.1.1.2.2.1 By Formation of Two N–C and One C–C Bonds 72
10.23.1.1.2.2.1.1 With Formation of 1–2, 1–9a, and 4–4a Bonds 72
10.23.1.1.2.2.1.1.1 Method 1: From 2-Bromo-1H-indole 72
10.23.1.1.2.2.2 By Formation of One N–C and Two C–C Bonds 73
10.23.1.1.2.2.2.1 With Formation of 1–2, 2–3, and 4–4a Bonds 73
10.23.1.1.2.2.2.1.1 Method 1: From Ethyl 2-Amino-1H-indole-3-carboxylates, an Arylacetylene, and an Aryl Aldehyde 73
10.23.1.1.2.2.3 By Formation of Two N–C Bonds 75
10.23.1.1.2.2.3.1 With Formation of 1–2 and 1–9a Bonds 75
10.23.1.1.2.2.3.1.1 Method 1: From 1,5-Dicarbonyl Compounds or Equivalents 75
10.23.1.1.2.2.4 By Formation of One N–C and One C–C Bonds 78
10.23.1.1.2.2.4.1 With Formation of 1–2 and 4–4a Bonds 78
10.23.1.1.2.2.4.1.1 Method 1: From 1H-Indol-2-amines and Alkynones 78
10.23.1.1.2.2.4.1.1.1 Variation 1: From 1H-Indol-2-amines and 1,3-Diketones 80
10.23.1.1.2.2.4.1.1.2 Variation 2: From N-(Phosphoranylidene)indol-2-amines 81
10.23.1.1.2.2.4.1.2 Method 2: From N-(Arylsulfonyl)-3-diazo-1,3-dihydroindol-2-imines 82
10.23.1.1.2.2.4.2 With Formation of 1–2 and 2–3 Bonds 84
10.23.1.1.2.2.4.2.1 Method 1: From 3-Alkenyl-N-(triphenylphosphoranylidene)-1H-indol-2-amines 84
10.23.1.1.2.2.4.2.1.1 Variation 1: From 3-(2-Nitrovinyl)-N-(triphenylphosphoranylidene)-1H-indol-2-amines 85
10.23.1.1.2.2.4.3 With Formation of 1–2 and 3–4 Bonds 86
10.23.1.1.2.2.4.3.1 Method 1: From a 2-Amino-1H-indole-3-carbothioaldehyde 86
10.23.1.1.2.2.4.4 With Formation of 1–9a and 3–4 Bonds 87
10.23.1.1.2.2.4.4.1 Method 1: From 3-[Bis(methylsulfanyl)methylene]-1-methyl-1,3-dihydro-2H-indol-2-one 87
10.23.1.1.2.2.5 By Formation of Two C–C Bonds 88
10.23.1.1.2.2.5.1 With Formation of 3–4 and 4–4a Bonds 88
10.23.1.1.2.2.5.1.1 Method 1: From N-(1H-Indol-2-yl)acetamide 88
10.23.1.1.2.2.6 By Formation of One N–C Bond 88
10.23.1.1.2.2.6.1 With Formation of the 1–9b Bond 88
10.23.1.1.2.2.6.1.1 Method 1: From 3-(1H-Indol-3-yl)allyl Azides 88
10.23.1.1.2.2.6.1.2 Method 2: From 3-(1H-Indol-3-yl)propanone O-2,4-Dinitrophenyl Oximes 89
10.23.1.1.2.2.6.1.2.1 Variation 1: From 3-(1H-Indol-3-yl)propanone O-Pentafluorobenzoyl Oximes 90
10.23.1.1.2.2.6.1.2.2 Variation 2: From 3-(1H-Indol-3-yl)propanone O-Acetyl Oximes 91
10.23.1.1.2.2.6.1.2.3 Variation 3: From 3-(1H-Indol-3-yl)prop-2-enone O-Methyl Oximes 92
10.23.1.1.2.2.6.1.3 Method 3: From a 3-(2-Bromo-1H-indol-3-yl)allylamine 93
10.23.1.1.2.2.6.2 With Formation of the 1–2 Bond 94
10.23.1.1.2.2.6.2.1 Method 1: From a 3-Propargyl-1H-indol-2-amine 94
10.23.1.1.2.2.6.2.2 Method 2: From a 3-(2-Amino-1H-indol-3-yl)-2-cyanoacrylate 96
10.23.1.1.2.2.6.2.3 Method 3: From N'-[3-(2-Aroylvinyl)-1H-indol-2-yl]alkanimidamides 97
10.23.1.1.2.2.7 By Formation of One C–C Bond 98
10.23.1.1.2.2.7.1 With Formation of the 2–3 Bond 98
10.23.1.1.2.2.7.1.1 Method 1: From 3-Acetyl-2-(acylamino)-1H-indoles with Phosphoryl Chloride 98
10.23.1.1.2.2.7.1.1.1 Variation 1: From 3-Acetyl-2-(acylamino)-1H-indoles with Potassium tert-Butoxide 100
10.23.1.1.2.2.7.1.1.2 Variation 2: From N'-[3-(2-Aroylvinyl)-1H-indol-2-yl]alkanimidamides 101
10.23.1.1.2.2.7.2 With Formation of the 3–4 Bond 102
10.23.1.1.2.2.7.2.1 Method 1: From N'-(3-Cyano-1H-indol-2-yl)acetimidamides 102
10.23.1.1.2.2.7.2.2 Method 2: From N'-(3-Formyl-1H-indol-2-yl)alkanimidamides 103
10.23.1.1.2.2.7.2.3 Method 3: From a 2-Amino-1H-indole-3-carboxylate and a 1,3-Oxo Ester Equivalent 104
10.23.1.1.2.3 By Annulation to a 1H-Pyrrolo[2,3-b]pyridine (a 7-Azaindole) 105
10.23.1.1.2.3.1 By Formation of Three C–C Bonds 105
10.23.1.1.2.3.1.1 With Formation of 4b–5, 6–7, and 8–8a Bonds 105
10.23.1.1.2.3.1.1.1 Method 1: From a 1H-Pyrrolo[2,3-b]pyridine and Two Equivalents of Methyl Acrylate 105
10.23.1.1.2.3.2 By Formation of Two C–C Bonds 106
10.23.1.1.2.3.2.1 With Formation of 4b–5 and 8–8a Bonds 106
10.23.1.1.2.3.2.1.1 Method 1: From a 1H-Pyrrolo[2,3-b]pyridine-3-boronic Acid 106
10.23.1.1.2.3.2.2 With Formation of 4b–5 and 6–7 Bonds 106
10.23.1.1.2.3.2.2.1 Method 1: From a 2-Vinyl-1H-pyrrolo[2,3-b]pyridine 106
10.23.1.1.2.3.2.3 With Formation of 6–7 and 8–8b Bonds 108
10.23.1.1.2.3.2.3.1 Method 1: From a 3-Vinyl-1H-pyrrolo[2,3-b]pyridine 108
10.23.1.1.2.3.3 By Formation of One C–C Bond 108
10.23.1.1.2.3.3.1 With Formation of the 8–8a Bond 108
10.23.1.1.2.3.3.1.1 Method 1: Intramolecular Acylation 108
10.23.1.2 Synthesis by Ring Transformation 109
10.23.1.2.1 Method 1: From 1-(2-Pyridyl)-1H-benzotriazoles 109
10.23.1.2.2 Method 2: From 3-Aryl-3H-[1,2,3]-triazolo[4,5-b]pyridines 110
10.23.1.3 Aromatization 111
10.23.1.4 Synthesis by Substituent Modification 114
10.23.1.4.1 Substitution of Existing Substituents 114
10.23.1.4.1.1 Substitution of N-Hydrogen 114
10.23.1.4.1.1.1 Giving N-Sulfur 9H-Pyrido[2,3-b]indoles 114
10.23.1.4.1.1.2 Giving N-Carbon 9H-Pyrido[2,3-b]indoles 115
10.23.1.4.1.1.2.1 Method 1: Using an Alkyl or Aryl Halide 115
10.23.1.4.1.1.2.2 Method 2: Via 1-Alkyl-9H-pyrido[2,3-b]indol-1-ium Salts 118
10.23.1.4.1.1.2.3 Method 3: Using Acyl Halides or Anhydrides 119
10.23.1.4.1.2 Substitution of N-Carbon and N-Sulfur 120
10.23.1.4.1.2.1 Giving N-Hydrogen 9H-Pyrido[2,3-b]indoles 120
10.23.1.4.1.2.1.1 Method 1: N-Deprotection 120
10.23.1.4.1.3 Substitution of C-Hydrogen 121
10.23.1.4.1.3.1 Direct Substitution by Electrophiles 121
10.23.1.4.1.3.1.1 Method 1: Giving C-Halogen 9H-Pyrido[2,3-b]indoles 121
10.23.1.4.1.3.1.2 Method 2: Giving C-Sulfur 9H-Pyrido[2,3-b]indoles 122
10.23.1.4.1.3.1.3 Method 3: Giving C-Nitrogen 9H-Pyrido[2,3-b]indoles 123
10.23.1.4.1.3.1.4 Method 4: Giving C-Carbon 9H-Pyrido[2,3-b]indoles 124
10.23.1.4.1.3.2 Substitution via Metalation 124
10.23.1.4.1.3.3 Substitution via 1-Oxides 126
10.23.1.4.1.3.4 Substitution via Displacement of Halogen 130
10.23.1.4.1.3.4.1 Method 1: Direct Nucleophilic Displacement 130
10.23.1.4.1.3.4.2 Method 2: Substitution of Halogen via Cross-Coupling Processes 133
10.23.1.4.1.3.4.2.1 Variation 1: Forming Amines 133
10.23.1.4.1.3.4.2.2 Variation 2: Forming Phenolic Ethers 135
10.23.1.4.1.3.4.2.3 Variation 3: Adding Carbon Substituents 136
10.23.1.4.2 Modification of Substituents 141
10.23.1.4.2.1 Modification of C-Oxygen Functionalities 141
10.23.1.4.2.1.1 Method 1: Giving C-Halogen 141
10.23.1.4.2.1.2 Method 2: Giving Quinones 141
10.23.1.4.2.1.3 Method 3: Giving Phenolic Ethers 142
10.23.1.4.2.2 Modification of C-Nitrogen Functionalities 142
10.23.1.4.2.2.1 Method 1: Giving C-Nitrogen 9H-Pyrido[2,3-b]indoles 142
10.23.1.4.2.2.2 Method 2: Giving C-Halogen 9H-Pyrido[2,3-b]indoles 143
10.23.1.4.2.2.3 Method 3: Giving C-Carbon 9H-Pyrido[2,3-b]indoles 143
10.23.1.4.2.3 Modification of C-Carbon Functionalities 144
10.23.1.4.2.3.1 Method 1: Giving C-Carbon 5H-Pyrido[3,2-b]indoles 144
10.23.2 Product Subclass 2: 9H-Pyrido[3,4-b]indoles (?-Carbolines) 146
10.23.2.1 Synthesis by Ring-Closure Reactions 146
10.23.2.1.1 By Annulation to an Arene 146
10.23.2.1.1.1 By Formation of One N–C and Two C–C Bonds 146
10.23.2.1.1.1.1 With Formation of 1–2, 3–4, and 4a–9b Bonds 146
10.23.2.1.1.1.1.1 Method 1: From 2,N-Dialkynyl-N-tosylanilines and Methyl Cyanoformate 146
10.23.2.1.1.1.1.2 Method 2: By Intramolecular Reaction of a Cyano-Substituted 2,N-Dialkynyl-N-tosylaniline 147
10.23.2.1.1.2 By Formation of One N–C Bond and One C–C Bond 148
10.23.2.1.1.2.1 With Formation of 4a–4b and 9–9a Bonds 148
10.23.2.1.1.2.1.1 Method 1: From (2-Aminophenyl)boronic Acid 148
10.23.2.1.1.3 By Formation of Two C–C Bonds 149
10.23.2.1.1.3.1 With Formation of 3–4 and 4a–9a Bonds 149
10.23.2.1.1.3.1.1 Method 1: From 3-[(2-Alkynylphenyl)amino]pyrazin-2-ones 149
10.23.2.1.1.4 By Formation of One N–C Bond 150
10.23.2.1.1.4.1 With Formation of the 2–3 Bond 150
10.23.2.1.1.4.1.1 Method 1: From 3-Alkynyl-1H-indole-2-carbaldehyde Oximes 150
10.23.2.1.1.4.1.2 Method 2: From 3-Alkenyl-1H-indole-2-carbaldehyde Oximes 150
10.23.2.1.1.4.1.3 Method 3: From 3-Alkynyl-1H-indole-2-carboxamides 151
10.23.2.1.1.4.2 With Formation of the 8a–9 Bond 152
10.23.2.1.1.4.2.1 Method 1: From 4-Aryl-3-nitropyridines 152
10.23.2.1.1.4.2.2 Method 2: From 4-(2-Bromoaryl)pyridin-3-amines 153
10.23.2.1.1.4.2.3 Method 3: From 3-Acetamido-4-(2-bromoaryl)-3,4-dihydropyridin-2-ones 154
10.23.2.1.1.4.3 With Formation of the 9–9a Bond 154
10.23.2.1.1.4.3.1 Method 1: From a 4-(2-Azidophenyl)pyridine by Thermolysis 154
10.23.2.1.1.4.3.2 Method 2: From 4-(2-Azidoaryl)pyridinium Trifluoromethanesulfonates and a Rhodium Catalyst 155
10.23.2.1.1.4.3.3 Method 3: From 4-(2-Nitroaryl)pyridines 157
10.23.2.1.1.4.3.4 Method 4: From 2-(3-Halopyridin-4-yl)anilines 157
10.23.2.1.1.4.3.5 Method 5: From N-[2-(3-Fluoropyridin-4-yl)phenyl]pivalamides 158
10.23.2.1.1.4.3.6 Method 6: From 2-(2-Chloropyridin-4-yl)-N-tosylanilines 159
10.23.2.1.1.5 By Formation of One C–C Bond 160
10.23.2.1.1.5.1 With Formation of the 4a–4b Bond 160
10.23.2.1.1.5.1.1 Method 1: From an N-Arylpyridin-3-amine by Irradiation 160
10.23.2.1.1.5.1.2 Method 2: From N-(2-Haloaryl)pyridin-3-amines by Palladium(0)-Catalyzed Bond Formation 161
10.23.2.1.1.5.1.3 Method 3: From 4-Halo-N-phenylpyridin-3-amines by Intramolecular Palladium(0)-Catalyzed Bond Formation 163
10.23.2.1.1.5.1.4 Method 4: From 4-Bromo-N-phenylpyridin-3-amines by Intramolecular Photostimulated SRN1 Reaction 163
10.23.2.1.1.5.1.5 Method 5: From 4-Bromo-N-(2-bromophenyl)pyridin-3-amines by Palladium(0)-Catalyzed Bond Formation via Tributylstannyl Intermediates 164
10.23.2.1.1.5.1.6 Method 6: From an N-(2-Diazophenyl)-N-methylpyridin-3-amine 165
10.23.2.1.2 By Annulation to a Heterocycle 165
10.23.2.1.2.1 By Annulation to an Indole 165
10.23.2.1.2.1.1 By Formation of Two N–C Bonds 166
10.23.2.1.2.1.1.1 With Formation of 1–2 and 2–3 Bonds 166
10.23.2.1.2.1.1.1.1 Method 1: From 1H-Indolic 1,5-Dicarbonyls and Ammonia 166
10.23.2.1.2.1.1.1.1.1 Variation 1: From 2-Acyl-3-(2-ethoxyvinyl)-1H-indoles and Ammonia 167
10.23.2.1.2.1.1.1.1.2 Variation 2: From Ethyl 3-[1-(Dimethylamino)-3-ethoxy-3-oxoprop-1-en-2-yl]-1-methyl-1H-indole-2-carboxylate 168
10.23.2.1.2.1.1.1.1.3 Variation 3: From 3-Alkynyl-1H-indole-2-carbaldehydes and Ammonia 168
10.23.2.1.2.1.1.1.1.4 Variation 4: From 2-Acyl-3-alkynyl-1H-indoles and Ammonia 169
10.23.2.1.2.1.2 By Formation of One N–C Bond and One C–C Bond 170
10.23.2.1.2.1.2.1 With Formation of 1–2 and 3–4 Bonds 170
10.23.2.1.2.1.2.1.1 Method 1: From Ethyl 3-(2-Ethoxy-2-oxoethyl)-1H-indole-2-carboxylate. 170
10.23.2.1.2.1.2.2 With Formation of 2–3 and 4–4a Bonds 171
10.23.2.1.2.1.2.2.1 Method 1: From tert-Butylimines of 1H-Indole-2-carbaldehydes 171
10.23.2.1.2.1.2.2.1.1 Variation 1: From tert-Butylimines of 3-Iodo-1H-indole-2-carbaldehydes 171
10.23.2.1.2.1.2.2.1.2 Variation 2: From tert-Butylimines of 3-Unsubstituted 1H-Indole-2-carbaldehydes 172
10.23.2.1.2.1.2.2.1.3 Variation 3: From O-Acetyloximes of 2-Acyl-1H-indoles and Internal Alkynes by a Copper/Rhodium Bimetallic Relay Catalyst 173
10.23.2.1.2.1.2.2.1.4 Variation 4: From a 2-(1-Azidovinyl)-1H-indole with an Internal Alkyne and Copper/Rhodium Bimetallic Catalysis 174
10.23.2.1.2.1.2.2.2 Method 2: From 1H-Indole-2-carboxamides 175
10.23.2.1.2.1.2.2.2.1 Variation 1: From 1-Alkyl-1H-indole-2-carboxamides with Internal Alkynes and Palladium(II) Acetate 175
10.23.2.1.2.1.2.2.2.2 Variation 2: From 1-Methyl-1H-indole-2-carboxamide with Diphenylacetylene and a Ruthenium Catalyst 176
10.23.2.1.2.1.2.2.2.3 Variation 3: From 1-Alkyl-1H-indole-2-carboxamides with Ethynyl N-Methyliminodiacetic Acid (MIDA) Boronate and a Rhodium Catalyst 176
10.23.2.1.2.1.2.2.2.4 Variation 4: From 1-Methyl-1H-indole-2-carboxamide with Vinyl Acetate 177
10.23.2.1.2.1.2.2.3 Method 3: From 2-(Azidomethyl)-1H-indoles and Ynamides 177
10.23.2.1.2.1.2.3 With Formation of 1–2 and 1–9a Bonds 179
10.23.2.1.2.1.2.3.1 Method 1: From 2-(1H-Indol-3-yl)ethan-1-amines (Tryptamines) and Aldehydes 179
10.23.2.1.2.1.2.3.1.1 Variation 1: With Hetaryl Aldehydes 179
10.23.2.1.2.1.2.3.1.2 Variation 2: With a-Oxoaldehydes 184
10.23.2.1.2.1.2.3.1.3 Variation 3: From Tryptamine with an Arylglyoxal and Palladium on Carbon 188
10.23.2.1.2.1.2.3.1.4 Variation 4: With Aryl Methyl Ketones or Styrenes 189
10.23.2.1.2.1.2.3.2 Method 2: From Tryptophan Esters or Amides and Trifluoroacetic Acid 190
10.23.2.1.2.1.2.3.3 Method 3: From Iminophosphoranes 191
10.23.2.1.2.1.2.4 With Formation of 2–3 and 1–9a Bonds 194
10.23.2.1.2.1.2.4.1 Method 1: From 3-Alkenyl-1H-indoles and an Oxime 194
10.23.2.1.2.1.3 By Formation of Two C–C Bonds 196
10.23.2.1.2.1.3.1 With Formation of 1–9a and 4–4a Bonds 196
10.23.2.1.2.1.3.1.1 Method 1: From a 1H-Indole and a 2-Aza-1,3-diene 196
10.23.2.1.2.1.3.1.2 Method 2: From 1H-Indoles and 1,2,4-Triazines via Cycloaddition then Elimination of Nitrogen 198
10.23.2.1.2.1.3.1.2.1 Variation 1: Intramolecularly from a 1-Acyl-1H-indole with a 1,2,4-Triazine Substituent 198
10.23.2.1.2.1.3.1.2.2 Variation 2: Intramolecularly from a 1-Alkyl-1H-indole with a 1,2,4-Triazine Substituent 198
10.23.2.1.2.1.3.1.2.3 Variation 3: Intermolecularly from 1H-Indoles and 1,2,4-Triazines 199
10.23.2.1.2.1.3.1.2.4 Variation 4: From 1H-Indoles and 1,2,4-Triazines Generated In Situ 200
10.23.2.1.2.1.4 By Formation of One N–C Bond 201
10.23.2.1.2.1.4.1 With Formation of the 1–2 Bond 201
10.23.2.1.2.1.4.1.1 Method 1: From a 2-[Bis(acetylsulfanyl)methyl]-1H-indole-3-pyruvate Oxime 201
10.23.2.1.2.1.4.1.2 Method 2: From a 2-{2-[Bis(methylsulfanyl)methylene]-2,3-dihydroindol-3-yl}acetonitrile 202
10.23.2.1.2.1.4.2 With Formation of the 2–3 Bond 202
10.23.2.1.2.1.4.2.1 Method 1: From 2-Acyl-3-alkenyl-1H-indole Oximes 202
10.23.2.1.2.1.4.2.2 Method 2: From 2-Acyl-3-alkynyl-1H-indole Imines or Oximes 204
10.23.2.1.2.1.4.2.3 Method 3: From tert-Butylimines of 3-Alkynyl-1H-indole-2-carbaldehydes 206
10.23.2.1.2.1.4.2.4 Method 4: From 3-Alkynyl-2-(azidomethyl)-1H-indoles 207
10.23.2.1.2.1.5 By Formation of One C–C Bond 207
10.23.2.1.2.1.5.1 With Formation of the 1–9a Bond 207
10.23.2.1.2.1.5.1.1 Method 1: From N-Acyltryptamines 207
10.23.2.1.2.1.5.2 With Formation of the 4–4a Bond 210
10.23.2.1.2.1.5.2.1 Method 1: From N-(2,2-Dialkoxyethyl)-1H-indole-2-carboxamides 210
10.23.2.1.2.1.5.2.2 Method 2: From an N-Allyl-3-iodo-1H-indole-2-carboxamide 212
10.23.2.1.2.1.5.2.3 Method 3: From an N-(2-Oxoalkyl)-1H-indole-2-carboxamide 212
10.23.2.1.2.1.5.2.4 Method 4: From an N-Propargyl-1H-indole-2-carboxamide 215
10.23.2.2 Synthesis by Ring Transformation 215
10.23.2.2.1 Method 1: From 1-(3-Pyridyl)-1H-benzotriazoles 215
10.23.2.2.2 Method 2: From 3-Aryl-3H-1,2,3-triazolo[4,5-c]pyridines 216
10.23.2.2.3 Method 3: From 4-[(1H-Indol-3-yl)methyl]oxazol-5(4H)-ones 216
10.23.2.2.4 Method 4: From Pyrano[3,4-b]indol-3(9H)-ones 217
10.23.2.3 Aromatization 218
10.23.2.3.1 Method 1: From 2,3,4,9-Tetrahydro-1H-pyrido[3,4-b]indoles 219
10.23.2.3.2 Method 2: From 4,9-Dihydro-3H-pyrido[3,4-b]indoles 228
10.23.2.3.3 Method 3: From 2-Aryl-4,9-dihydro-3H-pyrido[3,4-b]indol-2-iums 233
10.23.2.3.4 Method 4: From 2,9-Dihydro-1H-pyrido[3,4-b]indoles 233
10.23.2.3.5 Method 5: From 6,7,8,9-Tetrahydro-5H-pyrido[3,4-b]indoles 237
10.23.2.4 Synthesis by Substituent Modification 238
10.23.2.4.1 Substitution of Existing Substituents 238
10.23.2.4.1.1 Substitution of N-Hydrogen 238
10.23.2.4.1.1.1 Giving N-Carbon 9H-Pyrido[3,4-b]indoles 238
10.23.2.4.1.1.1.1 Method 1: 9-Alkylation Using an Alkyl Halide 238
10.23.2.4.1.1.1.2 Method 2: 9-Arylation Using an Aryl Halide 240
10.23.2.4.1.1.1.3 Method 3: 9-Acylation 242
10.23.2.4.1.1.1.4 Method 4: 2-Alkylation Giving 2-Alkyl-9H-pyrido[3,4-b]indol-2-ium Salts and thence 2-Alkyl-2H-pyrido[3,4-b]indoles 243
10.23.2.4.1.2 Substitution of N-Carbon and N-Sulfur 247
10.23.2.4.1.2.1 Giving N-Hydrogen 9H-Pyrido[3,4-b]indoles 247
10.23.2.4.1.2.1.1 Method 1: N-Deprotection 247
10.23.2.4.1.3 Substitution of C-Hydrogen 248
10.23.2.4.1.3.1 Direct Substitution by Electrophiles 248
10.23.2.4.1.3.1.1 Method 1: Giving C-Halogen 9H-Pyrido[3,4-b]indoles 248
10.23.2.4.1.3.1.2 Method 2: Giving C-Sulfur 9H-Pyrido[3,4-b]indoles 250
10.23.2.4.1.3.1.3 Method 3: Giving C-Nitrogen 9H-Pyrido[3,4-b]indoles 251
10.23.2.4.1.3.1.4 Method 4: Giving C-Carbon 9H-Pyrido[3,4-b]indoles 252
10.23.2.4.1.3.2 Direct Substitution by Radicals 253
10.23.2.4.1.3.3 Substitution via Metalation 255
10.23.2.4.1.3.4 Substitution via 2-Oxides (N-Oxides) 256
10.23.2.4.1.3.4.1 Variation 1: With Formation of 9H-Pyrido[3,4-b]indole-1-carbonitriles 257
10.23.2.4.1.3.4.2 Variation 2: With Formation of 9H-Pyrido[3,4-b]indol-1-ols (2,9-Dihydro-1H-pyrido[3,4-b]indol-1-ones) 258
10.23.2.4.1.3.4.3 Variation 3: With Formation of 1-Halo-9H-pyrido[3,4-b]indoles 260
10.23.2.4.1.3.4.4 Variation 4: With Formation of 1-Carbon-9H-pyrido[3,4-b]indoles 260
10.23.2.4.1.3.5 Substitution via Displacement of Halogen 261
10.23.2.4.1.3.5.1 Method 1: Direct Nucleophilic Displacement 261
10.23.2.4.1.3.5.1.1 Variation 1: With Formation of Amines 261
10.23.2.4.1.3.5.1.2 Variation 2: With Formation of Ethers 262
10.23.2.4.1.3.5.1.3 Variation 3: With Formation of Halides 262
10.23.2.4.1.3.5.2 Method 2: Substitution of Halogen (or Trifluoromethanesulfonate) via Cross-Coupling Processes 263
10.23.2.4.1.3.5.2.1 Variation 1: Reaction at C1 263
10.23.2.4.1.3.5.2.2 Variation 2: Reaction at C4 266
10.23.2.4.1.3.5.2.3 Variation 3: Reaction at Benzene Ring Positions 267
10.23.2.4.1.3.6 Substitution via Displacement of Oxygen 268
10.23.2.4.2 Modification of Substituents 268
10.23.2.4.2.1 Modification of C-Oxygen Functionalities 268
10.23.2.4.2.1.1 Method 1: Giving C-Halogen 268
10.23.2.4.2.1.2 Method 2: Giving C-Oxygen 269
10.23.2.4.2.2 Modification of C-Nitrogen Functionalities 272
10.23.2.4.2.2.1 Method 1: Giving C-Nitrogen 272
10.23.2.4.2.2.2 Method 2: Giving C-Halogen 274
10.23.2.4.2.2.3 Method 3: Giving C-Oxygen 274
10.23.2.4.2.3 Modification of C-Carbon Functionalities 276
10.23.2.4.2.3.1 Method 1: Giving C-Carbon 9H-Pyrido[3,4-b]indoles 276
10.23.2.4.2.3.1.1 Variation 1: From Alkyl-Substituted 9H-Pyrido[3,4-b]indoles 276
10.23.2.4.2.3.1.2 Variation 2: From 9H-Pyrido[3,4-b]indolyl Alcohols 277
10.23.2.4.2.3.1.3 Variation 3: From 9H-Pyrido[3,4-b]indolyl Aldehydes and Ketones 278
10.23.2.4.2.3.1.4 Variation 4: From 9H-Pyrido[3,4-b]indole Acids, Esters, and Amides 279
10.23.2.4.2.3.2 Method 2: Giving C-Nitrogen 9H-Pyrido[3,4-b]indoles 281
10.23.2.4.2.3.3 Method 3: Giving C-Hydrogen 9H-Pyrido[3,4-b]indoles 283
10.23.3 Product Subclass 3: 5H-Pyrido[4,3-b]indoles (?-Carbolines) 283
10.23.3.1 Synthesis by Ring-Closure Reactions 283
10.23.3.1.1 By Annulation to an Arene 283
10.23.3.1.1.1 By Formation of One N–C and Two C–C Bonds 283
10.23.3.1.1.1.1 With Formation of 1–2, 3–4, and 4a–9b Bonds 283
10.23.3.1.1.1.1.1 Method 1: From 2,N-Dialkynyl-N-tosylanilines and Methyl Cyanoformate 283
10.23.3.1.1.2 By Formation of One N–C Bond and One C–C Bond 284
10.23.3.1.1.2.1 With Formation of 4a–5 and 9a–9b Bonds 284
10.23.3.1.1.2.1.1 Method 1: From Arylhydrazines 284
10.23.3.1.1.2.1.1.1 Variation 1: Using a 4-Hydroxypyridin-2-one 284
10.23.3.1.1.2.1.1.2 Variation 2: Using 1-Acetyl-3-bromopiperidin-4-one 285
10.23.3.1.1.2.1.2 Method 2: From 4-Fluoro-3-iodopyridine 286
10.23.3.1.1.2.2 With Formation of 1–2 and 1–9b Bonds 287
10.23.3.1.1.2.2.1 Method 1: From Iminophosphoranes 287
10.23.3.1.1.3 By Formation of One N–C Bond 289
10.23.3.1.1.3.1 With Formation of the 4a–5 Bond 289
10.23.3.1.1.3.1.1 Method 1: From 3-(2-Azidoaryl)pyridines 289
10.23.3.1.1.3.1.1.1 Variation 1: From 3-(2-Azidoaryl)pyridinium Salts and a Ruthenium Catalyst 289
10.23.3.1.1.3.1.2 Method 2: From 3-(2-Nitrosoaryl)pyridines 291
10.23.3.1.1.3.1.3 Method 3: From 2-(3-Pyridyl)-N-tosylanilines or N-Acetyl-2-(3-pyridyl)-anilines 291
10.23.3.1.1.3.1.4 Method 4: From 4-Fluoro-3-(2-pivaloylaminophenyl)pyridine 292
10.23.3.1.1.4 By Formation of One C–C Bond 293
10.23.3.1.1.4.1 With Formation of the 9a–9b Bond 293
10.23.3.1.1.4.1.1 Method 1: From N-Arylpyridin-4-amines 293
10.23.3.1.1.4.1.2 Method 2: From an N-Arylpyridin-4-amine with at Least One Halogen on at Least One Ring 294
10.23.3.1.1.4.1.2.1 Variation 1: From an N-(2-Bromophenyl)pyridin-4-amine 294
10.23.3.1.1.4.1.2.2 Variation 2: From an N-Aryl-3-bromopyridin-4-amine 294
10.23.3.1.1.4.1.2.3 Variation 3: From an N-(2-Bromophenyl)-3-bromopyridin-4-amine by Palladium(0)-Catalyzed Bond Formation via Tributylstannyl Intermediates 295
10.23.3.1.1.4.1.3 Method 3: From N-Aryl-3-halopyridin-4-amines by Photostimulated SRN1 Reactions 296
10.23.3.1.2 By Annulation to a Heterocycle 296
10.23.3.1.2.1 By Annulation to a Pyridine 296
10.23.3.1.2.2 By Annulation to an Indole 297
10.23.3.1.2.2.1 By Formation of Two N–C and One C–C Bonds 297
10.23.3.1.2.2.1.1 With Formation of 1–2, 2–3, and 4–4a Bonds 297
10.23.3.1.2.2.1.1.1 Method 1: From 3-Acetyl-1H-indole, an Alkyne and a Primary Amine 297
10.23.3.1.2.2.1.2 With Formation of 1–2, 2–3, and 3–4 Bonds 298
10.23.3.1.2.2.1.2.1 Method 1: From 2-(2-Oxoalkyl)-1H-indole-3-carbaldehydes and Aryl Aldehydes 298
10.23.3.1.2.2.2 By Formation of Two N–C Bonds 299
10.23.3.1.2.2.2.1 With Formation of 1–2 and 2–3 Bonds 299
10.23.3.1.2.2.2.1.1 Method 1: From 2-(3-Acetyl-1H-indol-2-yl)acetonitrile 299
10.23.3.1.2.2.2.1.2 Method 2: From 2-(3-Formyl-1H-indol-2-yl)acrylates 300
10.23.3.1.2.2.2.1.2.1 Variation 1: From a 2-Alkynyl-1H-indole-3-carbaldehyde 301
10.23.3.1.2.2.2.1.2.2 Variation 2: From a 2-Alkenyl-1H-indole-3-carbaldehyde 301
10.23.3.1.2.2.2.1.3 Method 3: From (3-Acyl-1H-indol-2-yl)malonates 302
10.23.3.1.2.2.3 By Formation of One N–C Bond and One C–C Bond 304
10.23.3.1.2.2.3.1 With Formation of 2–3 and 3–4 Bonds 304
10.23.3.1.2.2.3.1.1 Method 1: From Secondary 2-Alkyl-1H-indole-3-carboxamides 304
10.23.3.1.2.2.3.2 With Formation of 2–3 and 4–4a Bonds 306
10.23.3.1.2.2.3.2.1 Method 1: From Oxime O-Methyl Ethers of 1H-Indol-3-yl Aldehydes or Ketones 306
10.23.3.1.2.2.3.2.1.1 Variation 1: Reaction with Alkynes and Alkenes 306
10.23.3.1.2.2.3.2.1.2 Variation 2: Reaction with Diphenylacetylene under Rhodium Catalysis 308
10.23.3.1.2.2.3.2.2 Method 2: From Tosylhydrazones of 1H-Indol-3-yl Aldehydes and Ketones 308
10.23.3.1.2.2.3.2.3 Method 3: From tert-Butylimines of 1H-Indole-3-carbaldehydes 310
10.23.3.1.2.2.3.2.3.1 Variation 1: From tert-Butylimines of 2-Halo-1H-indole-3-carbaldehydes 310
10.23.3.1.2.2.3.2.3.2 Variation 2: From tert-Butylimines of 2-Unsubstituted 1H-Indole-3-carbaldehydes 312
10.23.3.1.2.2.3.2.4 Method 4: From N-Methoxy or N-Alkyl/Aryl 1-Methyl-1H-indole-3-carboxamides 313
10.23.3.1.2.2.4 By Formation of Two C–C Bonds 314
10.23.3.1.2.2.4.1 With Formation of 1–9b and 4–4a Bonds 314
10.23.3.1.2.2.4.1.1 Method 1: From Triethyl 1,2,4-Triazine-3,5,6-tricarboxylate 314
10.23.3.1.2.2.5 By Formation of One N–C Bond 315
10.23.3.1.2.2.5.1 With Formation of the 1–2 Bond 315
10.23.3.1.2.2.5.1.1 Method 1: From a 3-Methyl-1H-indole-2-carbaldehyde 315
10.23.3.1.2.2.5.2 With Formation of the 2–3 Bond 316
10.23.3.1.2.2.5.2.1 Method 1: From a 3-Acyl-2-alkenyl-1H-indole Oxime 316
10.23.3.1.2.2.5.2.2 Method 2: From tert-Butylimines of 2-Alkynyl-1H-indole-3-carbaldehydes 317
10.23.3.1.2.2.6 By Formation of One C–C Bond 319
10.23.3.1.2.2.6.1 With Formation of the 4–4a Bond 319
10.23.3.1.2.2.6.1.1 Method 1: From 3-{[(2,2-Diethoxyethyl)imino]methyl}-1H-indoles 319
10.23.3.1.2.2.6.1.1.1 Variation 1: From 3-{[(2,2-Diethoxyethyl)amino]methyl}-1H-indoles 320
10.23.3.1.2.2.6.1.2 Method 2: From Ethyl [(1H-Indol-3-yl)methyl]glycinates 321
10.23.3.1.2.2.6.1.3 Method 3: From N-Allyl-2-iodo-1H-indole-3-carboxamides 322
10.23.3.2 Synthesis by Ring Transformation 323
10.23.3.2.1 Method 1: From 1-(4-Pyridyl)-1H-benzotriazoles 323
10.23.3.2.2 Method 2: From 1-Aryl-1H-1,2,3-triazolo[4,5-c]pyridines 325
10.23.3.2.3 Method 3: By Ring Expansion of 5-Azidocyclopent-2-en-1-ols To Form Pyridines 325
10.23.3.3 Aromatization 326
10.23.3.3.1 Method 1: From Tetrahydro-5H-pyrido[4,3-b]indoles and Octahydro-5H-pyrido[4,3-b]indoles 326
10.23.3.3.2 Method 2: From Dihydro-5H-pyrido[4,3-b]indoles 330
10.23.3.4 Synthesis by Substituent Modification 333
10.23.3.4.1 Substitution of Existing Substituents 333
10.23.3.4.1.1 Substitution of N-Hydrogen 333
10.23.3.4.1.1.1 Giving N-Sulfur 5H-Pyrido[4,3-b]indoles 333
10.23.3.4.1.1.2 Giving N-Carbon 5H-Pyrido[4,3-b]indoles 334
10.23.3.4.1.1.2.1 Method 1: 5-Alkylation Using an Alkyl Halide 334
10.23.3.4.1.1.2.2 Method 2: 5-Arylation Using an Aryl Halide 336
10.23.3.4.1.1.2.3 Method 3: 2-Alkylation Giving 2-Alkyl-5H-pyrido[4,3-b]indol-2-ium Salts and thence 5-Alkylation 336
10.23.3.4.1.2 Substitution of N-Carbon and N-Sulfur 338
10.23.3.4.1.2.1 Giving N-Hydrogen 5H-Pyrido[4,3-b]indoles 338
10.23.3.4.1.2.1.1 Method 1: N-Deprotection 338
10.23.3.4.1.3 Substitution of C-Hydrogen 339
10.23.3.4.1.3.1 Direct Substitution by Electrophiles 339
10.23.3.4.1.3.1.1 Method 1: Giving C-Halogen 339
10.23.3.4.1.3.1.2 Method 2: Giving C-Sulfur 339
10.23.3.4.1.3.1.3 Method 3: Giving C-Nitrogen 340
10.23.3.4.1.3.1.4 Method 4: Giving C-Carbon 340
10.23.3.4.1.3.2 Substitution via Metalation 341
10.23.3.4.1.3.3 Substitution via 2-Oxides 342
10.23.3.4.1.3.4 Substitution via Displacement of Halogen 344
10.23.3.4.1.3.4.1 Method 1: Direct Nucleophilic Displacement 344
10.23.3.4.1.3.4.2 Method 2: Substitution of Halogen via Cross-Coupling Processes 347
10.23.3.4.2 Modification of Substituents 350
10.23.3.4.2.1 Modification of C-Oxygen Functionalities 350
10.23.3.4.2.1.1 Method 1: Giving C-Halogen 350
10.23.3.4.2.2 Modification of C-Nitrogen Functionalities 351
10.23.3.4.2.2.1 Method 1: Giving C-Nitrogen 351
10.23.3.4.2.3 Modification of C-Carbon Functionalities 351
10.23.3.4.2.3.1 Method 1: Giving C-Carbon 5H-Pyrido[4,3-b]indoles 351
10.23.3.4.2.3.2 Method 2: Giving C-Nitrogen 5H-Pyrido[4,3-b]indoles 352
10.23.3.4.2.3.3 Method 3: Giving C-Hydrogen 5H-Pyrido[4,3-b]indoles 352
10.23.4 Product Subclass 4: 5H-Pyrido[3,2-b]indoles (?-Carbolines) 353
10.23.4.1 Synthesis by Ring-Closure Reactions 353
10.23.4.1.1 By Annulation to an Arene 353
10.23.4.1.1.1 By Formation of One N–C and Two C–C Bonds 353
10.23.4.1.1.1.1 With Formation of 2–3, 4a–5, and 9a–9b Bonds 353
10.23.4.1.1.1.1.1 Method 1: From 2-Iodoanilines and N-Tosyl Enynamines 353
10.23.4.1.1.2 By Formation of Two N–C Bonds 354
10.23.4.1.1.2.1 With Formation of 4a–5 and 5–5a Bonds 354
10.23.4.1.1.2.1.1 Method 1: From Primary Amines and 3-Bromo-2-(2-bromophenyl)pyridine 354
10.23.4.1.1.3 By Formation of Two C–C Bonds 355
10.23.4.1.1.3.1 With Formation of 2–3 and 4a–9b Bonds 355
10.23.4.1.1.3.1.1 Method 1: From 2-(Aminomethyl)aniline Cinnamaldehyde Diimine 355
10.23.4.1.1.4 By Formation of One N–C Bond 356
10.23.4.1.1.4.1 With Formation of the 4a–5 Bond 356
10.23.4.1.1.4.1.1 Method 1: From 1-Methyl-2-(2-Azidoaryl)pyridinium Trifluoromethanesulfonates 356
10.23.4.1.1.4.1.2 Method 2: From 3-Fluoro-2-[2-(pivaloylamino)phenyl]pyridines 357
10.23.4.1.1.4.2 With Formation of the 5–5a Bond 359
10.23.4.1.1.4.2.1 Method 1: From 3-Azido-2-phenylpyridine 359
10.23.4.1.1.4.2.2 Method 2: From 2-Aryl-3-nitropyridines 360
10.23.4.1.1.4.2.3 Method 3: From 2-(2-Chlorophenyl)pyridin-3-amine by Intramolecular Photostimulated SRN1 Reaction 361
10.23.4.1.1.5 By Formation of One C–C Bond 362
10.23.4.1.1.5.1 With Formation of the 9a–9b Bond 362
10.23.4.1.1.5.1.1 Method 1: From N-Arylpyridin-3-amines by Irradiation 362
10.23.4.1.1.5.1.2 Method 2: From N-Arylpyridin-3-amines by Palladium(0)-Catalyzed Bond Formation 363
10.23.4.1.1.5.1.2.1 Variation 1: From Cyclohexanone and Pyridin-3-amine 364
10.23.4.1.1.5.1.3 Method 3: From N-(2-Halophenyl)pyridin-3-amines by Palladium(0)-Catalyzed Bond Formation 364
10.23.4.1.1.5.1.4 Method 4: From N-Aryl-2-halopyridin-3-amines by Intramolecular Palladium(0)-Catalyzed Bond Formation 365
10.23.4.1.1.5.1.5 Method 5: From N-Aryl-2-bromopyridin-3-amines by Intramolecular Photostimulated SRN1 Reaction 367
10.23.4.1.1.5.1.6 Method 6: From 2-Bromo-N-(2-bromophenyl)pyridin-3-amines by Palladium(0)-Catalyzed Bond Formation via Tributylstannyl Intermediates 367
10.23.4.1.1.5.1.7 Method 7: From an N-(2-Diazophenyl)-N-methylpyridin-3-amine 368
10.23.4.1.2 By Annulation to a Heterocycle 368
10.23.4.1.2.1 By Annulation to a Pyridine 368
10.23.4.1.2.1.1 By Formation of One N–C Bond and One C–C Bond 368
10.23.4.1.2.1.1.1 With Formation of 5–5a and 9a–9b Bonds 368
10.23.4.1.2.1.1.1.1 Method 1: From Benzyne and an N-Tosylpyridinium Imide 368
10.23.4.1.2.2 By Annulation to an Indole 370
10.23.4.1.2.2.1 By Formation of One N–C and Two C–C Bonds 370
10.23.4.1.2.2.1.1 With Formation of 1–9b, 2–3, and 4–4a Bonds 370
10.23.4.1.2.2.1.1.1 Method 1: From 3-Acetyl-1H-indole Oxime and Acetylene 370
10.23.4.1.2.2.1.2 With Formation of 1–2, 2–3, and 4–4a Bonds 371
10.23.4.1.2.2.1.2.1 Method 1: From N-(tert-Butoxycarbonyl)indol-3-amines, Aryl Aldehydes, and Terminal Arylalkynes 371
10.23.4.1.2.2.2 By Formation of One N–C Bond and One C–C Bond 373
10.23.4.1.2.2.2.1 With Formation of 1–9b and 3–4 Bonds 373
10.23.4.1.2.2.2.1.1 Method 1: From 2-[Bis(methylsulfanyl)methylene]-1-methyl-1,3-dihydro-2H-indol-3-one and a ß-(Lithioamino)acrylonitrile 373
10.23.4.1.2.2.2.1.1.1 Variation 1: From 2-[Bis(methylsulfanyl)methylene]-1-methyl-1,3-dihydro-2H-indol-3-one and Malononitrile 374
10.23.4.1.2.2.2.2 With Formation of 1–2 and 4–4a Bonds 374
10.23.4.1.2.2.2.2.1 Method 1: From an N-Acetyl-1H-indol-3-amine and a 1,3-Dialdehyde Equivalent 374
10.23.4.1.2.3 By Annulation to a 1H-Pyrrolo[3,2-b]pyridine (a 4-Azaindole) 375
10.23.4.1.2.3.1 By Formation of Two C–C Bonds 375
10.23.4.1.2.3.1.1 With Formation of 7–8 and 9–9a Bonds 375
10.23.4.1.2.3.1.1.1 Method 1: From a 2-Vinyl-1H-Pyrrolo[3,2-b]pyridine and Dimethyl Acetylenedicarboxylate 375
10.23.4.2 Synthesis by Ring Transformation 376
10.23.4.2.1 Method 1: From 1-(3-Pyridyl)-1H-benzotriazoles 376
10.23.4.2.2 Method 2: From 2-Alkoxypyrano[3,2-b]indoles and Hydroxylamine 376
10.23.4.3 Aromatization 377
10.23.4.4 Synthesis by Substituent Modification 379
10.23.4.4.1 Substitution of Existing Substituents 379
10.23.4.4.1.1 Substitution of N-Hydrogen 379
10.23.4.4.1.1.1 Giving N-Carbon 5H-Pyrido[3,2-b]indoles 379
10.23.4.4.1.1.1.1 Method 1: Using an Alkyl Halide and Sodium Hydride 379
10.23.4.4.1.1.1.2 Method 2: Demethylation of a 1-Methyl-5H-pyrido[3,2-b]indol-1-ium Iodide 380
10.23.4.4.1.1.1.3 Method 3: 5-Arylation Using an Aryl Halide 383
10.23.4.4.1.2 Substitution of C-Hydrogen 384
10.23.4.4.1.2.1 Substitution by Electrophiles 384
10.23.4.4.1.2.1.1 Method 1: Giving C-Nitrogen 5H-Pyrido[3,2-b]indoles 384
10.23.4.4.1.2.2 Substitution via Metalation 385
10.23.4.4.2 Modification of Substituents 386
10.23.4.4.2.1 Modification of C-Carbon Functionalities 386
10.23.4.4.2.1.1 Method 1: Giving C-Nitrogen 5H-Pyrido[3,2-b]indoles 386
10.23.4.4.2.1.2 Method 2: Giving C-Carbon 5H-Pyrido[3,2-b]indoles 386
30.3 Product Class 3: S, S-Acetals 401
30.3.2.2 1,3-Dithietanes 415
30.3.2.2.1 Symmetrical Dithietanes 415
30.3.2.2.1.1 Method 1: Dimerization of Thioketones Formed In Situ from Bunte Salts 415
30.3.2.2.1.2 Method 2: Synthesis from Thiophosgene: Dimerization of Thiocarbonates 416
30.3.2.2.1.3 Method 3: Dimerization of Thioacetamides 417
30.3.2.2.2 Unsymmetrical Dithietanes 417
30.3.2.2.2.1 Method 1: Synthesis from Thioketones and Imines 417
30.3.2.2.2.2 Method 2: Synthesis from Aromatic Aldehydes and Carbon Disulfide 418
30.3.2.2.2.3 Method 3: Synthesis of Dithietane Cations 419
30.3.3.2 1,3-Dithiolanes 421
30.3.3.2.1 Method 1: Reaction of Ethane-1,2-dithiol with Aldehydes or Ketones Catalyzed by Protic Acids 421
30.3.3.2.1.1 Variation 1: Catalyzed by Hydrogen Chloride 421
30.3.3.2.1.2 Variation 2: Catalyzed by 4-Toluenesulfonic Acid 422
30.3.3.2.1.3 Variation 3: Catalyzed by Sulfuric Acid on Silica Gel 422
30.3.3.2.1.4 Variation 4: Catalyzed by Alumina Sulfuric Acid, Silica Sulfuric Acid, and Tungstate Sulfuric Acid 423
30.3.3.2.1.5 Variation 5: Catalyzed by Sulfamic Acid on Silica Gel 427
30.3.3.2.1.6 Variation 6: Catalyzed by Sulfonic Acids on Solid Supports and Ionic Liquids 428
30.3.3.2.1.7 Variation 7: Catalyzed by Sodium Hydrogen Sulfate on Silica Gel 431
30.3.3.2.1.8 Variation 8: Catalyzed by Solid-Supported Perchloric Acid 432
30.3.3.2.1.9 Variation 9: Catalyzed by Trichloroacetic Acid in Sodium Dodecyl Sulfate Micelles 432
30.3.3.2.2 Method 2: Reactions of Ethane-1,2-dithiol with Aldehydes or Ketones Catalyzed by Lewis Acids 433
30.3.3.2.2.1 Variation 1: Catalyzed by Boron-Based Reagents 433
30.3.3.2.2.2 Variation 2: Catalyzed by Aluminum Chloride and Related Reagents 435
30.3.3.2.2.3 Variation 3: Catalyzed by Indium(III) Reagents 437
30.3.3.2.2.4 Variation 4: Catalyzed by Silicon-Based Reagents 439
30.3.3.2.2.5 Variation 5: Catalyzed by Tin-Based Reagents 440
30.3.3.2.2.6 Variation 6: Catalyzed by Titanium-Based Reagents 441
30.3.3.2.2.7 Variation 7: Catalyzed by Vanadium-Based Reagents 442
30.3.3.2.2.8 Variation 8: Catalyzed by Iron-Based Reagents 444
30.3.3.2.2.9 Variation 9: Catalyzed by Ruthenium-Based Reagents 446
30.3.3.2.2.10 Variation 10: Catalyzed by Nickel-Based Reagents 448
30.3.3.2.2.11 Variation 11: Promoted by Copper-Based Reagents 449
30.3.3.2.2.12 Variation 12: Catalyzed by Zinc-Based Reagents 450
30.3.3.2.2.13 Variation 13: Catalyzed by Hafnium-Based Reagents 451
30.3.3.2.3 Method 3: Reaction of Ethane-1,2-dithiol with Aldehydes or Ketones Catalyzed by Heterogeneous Catalysts 452
30.3.3.2.3.1 Variation 1: Catalyzed by Phosphorus Pentoxide on Alumina and Silica Gel Reagents 452
30.3.3.2.3.2 Variation 2: Using Dithiolanylium Tetrafluoroborate Salts on Solid Support 455
30.3.3.2.3.3 Variation 3: Catalyzed by Graphene Oxide 456
30.3.3.2.4 Method 4: Reaction of Ethane-1,2-dithiol with Aldehydes or Ketones Catalyzed by Halogens and Derivatives 457
30.3.3.2.4.1 Variation 1: Catalyzed by Iodine 457
30.3.3.2.4.2 Variation 2: Catalyzed by Tribromide Salts 459
30.3.3.2.4.3 Variation 3: Catalyzed by N-Bromosuccinimide 461
30.3.3.2.4.4 Variation 4: Catalyzed by Poly(N-bromoacrylamide) 462
30.3.3.2.4.5 Variation 5: Catalyzed by N,N,N',N'-Tetrabromobenzene-1,3-disulfonamide and Poly(ethylene-N,N'-dibromobenzene-1,3-disulfonamide) 463
30.3.3.2.4.6 Variation 6: Catalyzed by Trichloromelamine 464
30.3.3.2.5 Method 5: Reaction of Ethane-1,2-dithiol with Aldehydes or Ketones Catalyzed by Ionic Liquids 465
30.3.3.2.5.1 Variation 1: Catalyzed by Iminium Salts Structurally Similar to Ionic Liquids 465
30.3.3.2.6 Method 6: Reaction of Ethane-1,2-dithiol with Masked Carbonyl Groups 467
30.3.3.2.6.1 Variation 1: Conversion of (E)-2-Chlorovinyl Sulfones into 1,3-Dithiolane Derivatives 467
30.3.3.2.6.2 Variation 2: One-Pot Conversion of Ethoxyacetylene, an a,ß-Unsaturated Aldehyde, and Ethane-1,2-dithiol into a 2-(Buta-1,3-dienyl)-1,3-dithiolane 467
30.3.3.2.7 Method 7: Reaction of O,O-Acetals or Hemiacetals with Ethane-1,2-dithiol 468
30.3.3.2.7.1 Variation 1: Catalyzed by Protic Acids 468
30.3.3.2.7.2 Variation 2: Catalyzed by Lewis Acids 471
30.3.3.2.7.3 Variation 3: Catalyzed by Heterogeneous Catalysts 473
30.3.3.2.7.4 Variation 4: Catalyzed by Halogens and Derivatives 474
30.3.3.2.8 Method 8: Dithioacetalization from a 1,3-Dithiolane to Another Carbonyl Group 476
30.3.3.2.9 Method 9: Addition of Ethane-1,2-dithiol to Alkynes 477
30.3.3.2.9.1 Variation 1: Gold(I)/Silver(I) Tetrafluoroborate Catalyzed Bishydrothiolation of Alkynes 477
30.3.3.2.9.2 Variation 2: Calcium Nonafluorobutane-1-sulfonate Catalyzed anti-Markovnikov Bishydrothiolation of Alkynes 477
30.3.3.2.9.3 Variation 3: Double Michael Addition of Ethane-1,2-dithiol to Propargylic Carbonyl Systems 478
30.3.3.2.10 Method 10: Metalation 481
30.3.3.2.10.1 Variation 1: 2-(Trimethylsilyl)-1,3-dithiolanes as Masked 1,3-Dithiolane Anions 482
30.3.3.2.11 Method 11: Annulation 483
30.3.3.2.11.1 Variation 1: Tandem Hydride Shift/Cyclization 483
30.3.3.2.11.2 Variation 2: [6 + 3] Cycloaddition 484
30.3.3.2.11.3 Variation 3: [4 + 2] Cycloaddition 485
30.3.3.2.12 Method 12: Metal-Free Cross-Dehydrogenative Coupling of 1H-Benzimidazoles with 1,3-Dithiolane 486
30.3.3.2.13 Method 13: Reduction of Ketene S,S-Acetals 487
30.3.3.2.14 Method 14: [3 + 2] Cycloaddition of Ketene S,S-Acetals 488
30.3.3.2.15 Method 15: Intramolecular Cyclization of Ketene S,S-Acetals 489
30.3.3.2.15.1 Variation 1: Nazarov Cyclization–Halovinylation of a-Alkenoyl Ketene S,S-Acetals 489
30.3.3.2.15.2 Variation 2: Intramolecular Michael Reaction 490
30.3.3.2.16 Method 16: Double-Bond Migration in Ketene S,S-Acetals 491
Author Index 497
Abbreviations 517