Topics in Heterocyclic Chemistry Also Available Electronically 7
Aims and Scope 7
Preface 9
Contents 11
Multicomponent Syntheses of Macrocycles 13
1 Introduction 13
2 Macrocyclization Involving In Situ Generated (Activated) Functional Groups 17
3 Multiple Multicomponent Macrocyclization Using Two Bifunctional Building Blocks 23
4 Sequential Multiple Multicomponent Macrocyclization 31
5 Conclusion 33
References 34
Palladium-Copper Catalyzed Alkyne Activation as an Entry to Multicomponent Syntheses of Heterocycles 37
1 Introduction 40
2 Alkyne Activation by Cross-Coupling 42
2.1 The Coupling-Addition Sequence 43
2.1.1 Sonogashira Coupling of Highly Electron-Deficient Heterocycles to Activated Alkynes and Subsequent Amine Addition 43
2.1.2 Modified Sonogashira Coupling of Acid Chlorides to Alkynones 44
2.1.3 Coupling-Addition Sequence to Enaminones 46
2.2 The Coupling-Isomerization Sequence 46
3 Multicomponent Synthesis of Heterocycles by Coupling-Cycloaddition Sequences 50
3.1 Isoxazoles by a Consecutive 3CR of Acid Chlorides, Alkynes, and Nitrile Oxides 51
3.2 Indolizines by a Consecutive 3CR of Acid Chlorides, Alkynes, and Pyridinium Ylids 53
4 Multicomponent Synthesis of Heterocycles by Coupling-Addition-Cyclocondensation Sequences Concluded by Michael Addition in Basic Media 55
4.1 Pyrazoles by a Consecutive 3CR of Acid Chlorides, Alkynes, and Hydrazines 56
4.2 Pyrimidines by a Consecutive 3CR of Acid Chlorides, Alkynes, and Amidinium Salts 58
4.3 Pyrimidines by a Consecutive 4CR of (Hetero)aryl Iodides, Carbon Monoxide, Alkynes, and Amidinium Salts 59
4.4 Pyrimidines by a Two-Step Sequence of Consecutive 3CR of (Hetero)Arenes, Oxalyl Chloride, Alkynes, and Cyclocondensation with Guanidinium Salts 60
4.5 Benzo[b][1,4]Diazepines by a Consecutive 3CR of Acid Chlorides, Alkynes, and Ortho-Phenylene Diamines 63
4.6 Benzo[b][1,5]Thiazepines by a Consecutive 3CR of Acid Chlorides, Alkynes, and Ortho-Amino Thiophenols 65
5 Multicomponent Synthesis of Heterocycles by Coupling-Addition-Cyclocondensation Sequences Concluded by Michael Addition and Steps in Acidic Media 65
5.1 3-Halo Furans by a Consecutive 3CR of Acid Chlorides, Propargyl Ethers, and Halides 66
5.1.1 Trisubstituted Furans by Coupling-Transacetalization-Addition-Cyclocondensation-Coupling Sequence 68
5.2 Oxazoles by a Consecutive 3CR of Acid Chlorides, Propargyl Amine, and Acid Chlorides 69
5.3 3-Iodo Pyrroles by a Consecutive 3CR of Acid Chlorides, Propargyl Amides, and Iodide 70
5.3.1 3-Alkynylated Pyrroles by Coupling-Addition-Cyclocondensation-Coupling Sequence 71
5.4 Tetrahydro-beta-carbolines by a Consecutive 4CR of Acid Chlorides, Alkynes, Tryptamines, and Acroyl Chlorides 71
6 Multicomponent Synthesis of Annelated Thiopyranones by Coupling-Addition-Nucleophilic Aromatic Substitution Sequence 74
7 Multicomponent Synthesis of Heterocycles by Coupling-Isomerization-Cyclocondensation Sequences 76
7.1 Pyrazoles by a Consecutive 3CR of (Hetero)aryl Halides, Propargyl Alcohols, and Hydrazines 76
7.2 Pyrimidines by a Consecutive 3CR of (Hetero)aryl Halides, Propargyl Alcohols, and Amidinium Salts 77
7.3 Benzoheteroazepine by a Consecutive 3CR of (Hetero)aryl Halides, Propargyl Alcohols, and Ortho-Amino or Ortho-Thio Substituted Anilines 78
7.4 1,4-Diketones by a Consecutive 3CR of (Hetero)aryl Halides, Propargyl Alcohols, and Aldehydes 78
7.4.1 Furans by a Consecutive 3CR of (Hetero)aryl Halides, Propargyl Alcohols, and Aldehydes 80
7.4.2 Pyrroles by a Consecutive 4CR of (Hetero)aryl Halides, Propargyl Alcohols, Aldehydes, and Amines 80
7.5 Annelated and Substituted Pyridines by a Consecutive 4CR of (Hetero)aryl Halides, Propargyl Alcohols, Enamines, and Ammonium Chloride 81
7.6 Annelated and Substituted Pyridines by a Consecutive 4CR of (Hetero)aryl Halides, Propargyl Amides, Ketene Acetals or S,N-Aminals, and Ammonium Chloride 84
8 Domino Syntheses of Heterocycles by Coupling-Isomerization Sequences 87
8.1 Domino Synthesis of 2-Substituted Quinolines 87
8.2 Domino Synthesis of Spiro-Benzofuranones and Spiro-Benzoindolones 88
9 Conclusion and Outlook 91
References 92
Multicomponent Reaction Design Strategies: Towards Scaffold and Stereochemical Diversity 107
1 Introduction 109
1.1 Complexity and Diversity 109
1.2 Multicomponent Reactions 112
2 Molecular Diversity Involving MCRs 114
3 Novel Multicomponent Strategies Towards Scaffold Diversity 119
3.1 Single Reactant Replacement (SRR) 120
3.2 Modular Reaction Sequences 123
3.3 Condition-Based Divergence 127
3.4 Union of MCRs 132
4 Concluding Remarks 135
References 136
Recent Developments in Reissert-Type Multicomponent Reactions 139
1 Introduction 140
2 Range of Activating Agents in Reissert-Type Reactions 144
3 Range of Nucleophiles in Reissert-Type Reactions 146
4 Asymmetric Reissert-Type Processes 154
5 Dipole Formation and Domino Reactions 159
6 MCRs Involving Azines and Isocyanides 164
7 Conclusions 175
References 175
Microwave Irradiation and Multicomponent Reactions 181
1 Introduction 182
2 Recent Literature Reports 183
2.1 Pyridines 183
2.1.1 Dihydropyridines 183
2.1.2 Pyridines 185
2.2 Pyrimidines 195
2.2.1 Dihydropyrimidines 195
2.2.2 Fused Pyrimidines 199
2.3 Quinolines 203
2.3.1 Quinolines 203
2.3.2 Isoquinolines 211
2.3.3 Quinazolines 212
2.3.4 Quinolizines 214
2.3.5 Quinoxalines 215
2.4 Imidazoles 215
2.5 Thiazolines 218
2.6 Pyrazoles 218
2.7 Acridines 219
2.8 Oxazepines, Thiazapines and Benzodiazepines 221
2.9 Chromens 223
2.10 Pyrans and Furans 224
2.11 Propargylamines 225
2.12 Miscellaneous 227
3 Conclusions and Outlook 233
References 234
Applications of MCR-Derived Heterocycles in Drug Discovery 243
1 Introduction 245
2 Isocyanide-Based MCRs 245
2.1 Ugi Reactions 245
2.2 Bienaym茅-Blackburn-Groebke Reactions 247
3 Dicarbonyl, Cyanomalonate and Malononitrile Based MCRs 249
3.1 The Biginelli Condensation 249
3.2 The Hantzsch Reaction 257
3.3 The Gewald Reaction 265
3.4 Knoevenagel/Diels-Alder Sequences 268
3.5 Knoevenagel/Michael-Type Sequences 272
3.6 Knoevenagel/Krohnke Synthesis 275
3.7 Other Knoevenagel-Based MCRs 276
4 Cycloadditions 280
4.1 Hetero-Diels-Alder Reactions 280
4.1.1 The Povarov Reaction 281
4.2 1,3-Dipolar Cycloadditions 283
5 Miscellaneous 284
5.1 The D枚bner Synthesis 284
5.2 The Bucherer-Bergs Reaction 285
5.3 Other Multicomponent Reactions 288
6 Conclusions 294
References 294
Index 300