Organic Chemistry from Retrosynthesis to Asymmetric Synthesis (eBook)

Preface 5
Contents 7
Abbreviations and Acronyms 10
1 Disconnection, Synthons, Introductory Example 13
Abstract 13
1.1 Introduction 13
1.2 General Aspects of Retrosynthetic Analysis 14
1.2.1 Disconnection Versus Interconversion of the Functional Group 15
1.3 Retrosynthesis and Asymmetric Synthesis, Introductory Example 17
1.3.1 Retrosynthetic Analysis of 1-(Pyridine-3-yl)propan-1-ol 17
1.3.2 Asymmetric Synthesis of (S)-1-(Pyridine-3-yl)propan-1-ol 21
1.4 Interconversion of Functional Groups and C–H Acidity 25
1.4.1 Interconversions of Oxygenated Functional Groups 25
1.4.2 Acidity of C–H Bond, Stabilization of Carbanions 26
1.5 Organic Synthesis and the Environment 27
References 31
2 Retrosynthetic Analysis of the Compounds with One Functional Group 33
Abstract 33
2.1 Introduction 33
2.2 Disconnection of Carbinols 33
2.3 Disconnection of Alkenes 40
2.3.1 Examples of the Wittig Reaction on the Industrial Scale 45
2.4 Disconnection of Ketones 49
2.4.1 Disconnection of Dialkyl Ketones 49
2.4.2 Disconnection of Alkyl Aryl Ketones and Diaryl Ketones 54
2.5 Interconversion of the Nitro Group, Nitroalkanes as Building Blocks 57
References 62
3 Stereoisomers and Stereoselective Reactions—“Departure into Third Dimension” 63
Abstract 63
3.1 Introduction 63
3.2 Retrosynthesis and Stereochemical Aspects of Synthetic Reactions 64
3.3 Basics of Stereoselective Reactions 65
3.4 Topological Relation and Stereoselectivity 66
3.5 Stereoselective Processes and Kinetic Control 68
3.6 Reaction Stereochemistry, More About Enantio- and Diastereoselectivity 69
3.7 Examples of Asymmetric Syntheses 71
3.7.1 Hydrogenation of the C=O Bond Catalyzed by Chiral Organometallic Complexes 71
3.7.2 Hydrogenation of the C=N Bond Catalyzed by Chiral Organometallic Complexes 73
3.7.3 Asymmetric Alkylation of Stabilized Carbanion 75
References 78
4 Disconnection with Participation of Two Functional Groups 79
Abstract 79
4.1 Introduction 79
4.2 Match and Mismatch of Charges in Bifunctional Molecules 80
4.3 1,3-Dioxygenated Pattern (1,3-CO) 81
4.3.1 1,3-Hydroxycarbonyl Compounds 81
4.3.1.1 Departure into Third Dimension Enantioselective Aldol Reaction
4.3.1.2 Non-catalytic Enantioselective Aldol Reaction 87
4.3.1.3 Catalytic Enantioselective Aldol Reaction 89
4.3.2 1,3-Dicarbonyl Compounds 91
4.3.3 Concept of Hard and Soft Acids and Bases (HSAB) 93
4.4 1,5-Dicarbonyl Pattern (1,5-CO) 96
4.4.1 From Retrosynthesis to Robinson Annulation 99
4.4.2 Vinyl Ketones via the Mannich Reaction 102
4.4.2.1 Chiral Variants of the Mannich Reaction 108
References 113
5 Illogical Disconnections with Participation of Two Groups 115
Abstract 115
5.1 Introduction 115
5.2 1,2-Dioxygenated Pattern (1,2-CO) 116
5.2.1 Illogical Nucleophiles 116
5.2.2 Three-Membered Heterocyclic Rings, Illogical Electrophiles 126
5.2.3 1,2-Dihidroxy Pattern, Vicinal Diols 133
5.2.3.1 Asymmetric Synthesis of (?)-Frontalin 135
5.3 1,4-Dioxygenated Pattern (1,4-CO) 138
5.3.1 1,4-Dicarbonyl Compounds 138
5.3.2 1,4-Hydroxy Carbonyl Compounds 143
5.4 1,6-Dicarbonyl Pattern (1,6-CO) 145
References 152
6 Specific Synthetic Methods 154
Abstract 154
6.1 Introduction 154
6.2 Multicomponent Reactions 154
6.2.1 General Concept of Multicomponent Reactions 155
6.2.2 Ugi Multicomponent Reactions 156
6.3 Parallel Synthesis and Combinatorial Chemistry 158
6.4 Mechanochemistry in Organic Synthesis 160
6.5 Organic Synthesis Promoted by Microwave Radiation 161
6.6 Syntheses in Ionic Liquids 163
References 165
7 Retrosynthetic Consideration of Heterocyclic Structures 166
Abstract 166
7.1 Introduction 166
7.2 Retrosynthetic Considerations, Examples 167
7.3 Preferred Route to Non-aromatic Cyclic Molecules the Baldwin Rules
References 182
8 Rearrangements—Synthetic Reactions “Not Liable” to Retrosynthetic Analysis 183
Abstract 183
8.1 Introduction 183
8.2 Beckmann Rearrangement 184
8.3 Hofmann Rearrangement 185
8.4 Arndt-Eistert Rearrangement 189
8.5 Favorskii Rearrangement 191
8.6 Pinacol Rearrangement 192
8.7 Baeyer-Villiger Rearrangement 194
References 197
9 Retrosynthetic Considerations and Syntheses of Complex, Biologically Active Molecules 199
Abstract 199
9.1 Introduction 199
9.2 Synthesis of Racemic and (?)-Menthol 200
9.3 Synthesis of Racemic and (1R,2R)-Chloramphenicol 203
9.4 (+)-Sertraline, Interplay of Non-stereoselective and Asymmetric Syntheses 206
9.4.1 Non-stereoselective Synthesis of Sertraline 206
9.4.2 Stereoselective Routes to (+)-Sertraline 207
9.5 Lycoranes, a Goldmine of Pharmaceutical Candidates 211
9.5.1 Polycyclic Framework of Lycoranes 211
9.5.2 Stereoselective Synthesis of Racemic ?- and ?-Lycorane 212
9.5.3 Asymmetric Synthesis of (+)-?-Lycorane 217
References 220