Topics in Heterocyclic Chemistry Also Available Electronically 7
Aims and Scope 7
Preface 8
Contents 10
Synthesis of Heterocycles Through Classical Ugi and Passerini Reactions Followed by Secondary Transformations Involving One or 11
Introduction 12
One Additional Functional Group 14
Isocyanide-Derived Amide Acting as Electrophile 14
Isocyanide-Derived Amide Acting as Nucleophile 16
Post-Condensation Transformations Involving the Acid-Derived Carbonyl 19
Cyclization Exploiting the Aldehyde-Derived Carbon as Nucleophile 21
Two Additional Functional Groups 22
Nucleophilic Alkyl Substitutions 22
Nucleophilic Aryl Substitutions 23
Nucleophilic Acyl Substitution 27
Condensations Leading to C=N Bond Formation 29
Base-Promoted Condensations 31
Cycloadditions 33
Ring-Closing Metathesis and Other Transition Metal-Catalysed Processes 36
Others 40
References 42
Aminoazoles as Key Reagents in Multicomponent Heterocyclizations 50
Introduction 51
Aminoazoles as 1,3-Binucleophiles 52
Reactions with Synthetic Precursors of 伪,beta-Unsaturated Carbonyls 53
Noncyclic CH-Acids 53
Cyclic CH-Acids 65
Groebke-Type Heterocyclizations 76
Other Types of Heterocyclizations 81
Aminoazoles as 1,1-Binucleophiles 84
Concluding Remarks 88
References 89
The Piperazine Space in Isocyanide-based MCR Chemistry 94
Piperazines in Chemistry, Medicine, and Biology 95
The MCR Piperazine Space 98
Monocyclic Piperazines 101
Piperazine 101
Ketopiperazine 104
2,5-Diketopiperazine 108
2,6-Diketopiperazine 116
Condensed Bicyclic Piperazines 119
Polycyclic Fused Piperazines 127
Conclusion 132
References 133
伪-Acidic Isocyanides in Multicomponent Chemistry 137
Introduction 139
Synthesis of 伪-Acidic Isocyanides 140
Reactivity of 伪-Acidic Isocyanides 142
MCRs Involving 伪-Acidic Isocyanides 145
van Leusen Imidazole MCR 145
2,6,7-Trisubstituted Quinozaline MCR 146
4,5-Disubstituted Oxazole MCR 147
Nitropyrrole MCR 148
2,4,5-Trisubstituted Oxazoles 149
Oxazole MCR Variations 151
Oxazole MCR + In Situ Tandem Processes 153
2H-2-Imidazoline MCR 156
2H-2-Imidazoline MCR in the Union of MCRs 159
Dihydropyridone MCR 161
Conclusion 162
References 163
Microreactor Technology as an Efficient Tool for Multicomponent Reactions 168
Introduction 170
Multicomponent Reactions Under Microreactor Conditions (Sensu Stricto) 171
The Passerini Reaction 171
The Formation of Tetrasubstituted Imidazoles 172
Production of Isochromenones and Ring Closure to Isochromeno[3,4-d]imidazol-5-ones 174
Tetrahydropyrazolo Quinolinones 175
Carbonylation Reactions 177
Curtius Rearrangement Followed by Nucleophilic Protection 180
Formation of Triazoles Using the Bestmann-Ohira Reagent 181
The Mannich Reaction 183
Multicomponent Multistep Reactions Performed in Microreactors 184
The Strecker Reaction 184
The Ugi Four-Component Condensation 186
Trisubstituted Oxadiazoles 187
Electrophilic Substitution on Benzene Ring 189
Diarylethenes 190
Azo-Dyes 191
N-Methyl-N-Nitroso-p-Toluenesulfonamide 193
Trisubstituted Imidazoles by a Bifurcated Pathway to 5-Aminothiazoles 194
Multistep Synthesis of Oxomaritidine 195
Multicomponent Reactions Using Preformed Intermediates 197
The Mannich Reaction 197
Aza-Baylis-Hillman Reaction 198
伪-Aminophosphonates 200
Conclusion 200
References 201
Cyclic Peptidomimetics and Pseudopeptides from Multicomponent Reactions 206
Cyclic Peptides 207
Cyclic Peptides and Their Mimetics from MCR/Cyclization Strategies 209
Diketopiperazines 209
Further Six-Membered and Seven-Membered Ring Heterocycle Mimics of Peptide-Turn Motifs 215
Medium-Sized Cyclic Peptidomimetics 218
Macrocyclic Peptidomimetics and Pseudopeptides 219
MCR-Precursor + Macrocyclization 220
Linear (Pseudo) Peptides + MCR-Cyclization 226
References 230
beta-Diketo Building Blocks for MCRs-Based Syntheses of Heterocycles 234
General Introduction 236
Hantzsch Heterocyclic Synthesis 237
The Hantzsch Reaction 237
Synthesis of 1,4-Dihydropyridines 237
Synthesis of Pyridines 239
Modified Hantzsch Reaction 240
Biginelli Heterocyclic Synthesis 243
The Biginelli Reaction 243
Synthesis of Hydropyrimidinone Derivatives 243
Synthesis of Cyclic Guanidine Derivatives 244
The Asymmetric Biginelli Reaction 245
MCRs Based on the Mannich Reaction 247
The Mannich Reaction 247
Five-Membered Heterocycles 247
Pyrrolidine Derivatives 247
Pyrazole Derivatives 248
Six-Membered Heterocycles 249
Piperidine Derivatives 249
Quinoline Derivatives 250
Seven-Membered Heterocycles 252
1,4-Diazepane Derivatives 252
MCRs Based on the Knoevenagel Reaction 253
The Knoevenagel Reaction 253
Five-Membered Heterocycles 253
Synthesis of Dihydroindolone Derivatives 253
Synthesis of Imidazolone Derivatives 254
Synthesis of Dihydropyrazole Derivatives 254
Synthesis of Bispiropyrrolidine Derivatives 255
Six-Membered Heterocycles 256
Synthesis of Pyran Derivatives 256
Synthesis of Tetrahydrobenzoxanthenone Derivatives 260
Synthesis of Dihydropyranopyrazole Derivatives 262
MCRs Based on the Michael Reaction 263
The Michael Addition 263
Five-Membered Heterocycles 263
Synthesis of Pyrrole Derivatives 263
Six-Membered Heterocycles 265
Synthesis of Tetrahydropyridines 265
Synthesis of 1,4-Dihydropyridines 267
Synthesis of Pyridine Derivatives 268
Seven-Membered Heterocycles 270
Polycyclic Heterocycles 271
Miscellaneous 272
Conclusion 275
References 276
Index 285