Strategies and Tactics in Organic Synthesis

Description

Strategies and Tactics in Organic Synthesis, Volume 13, provides a forum for investigators to discuss their approach to the science and art of organic synthesis. Rather than a simple presentation of data or a secondhand analysis, this classic provides stories that vividly demonstrate the power of the human endeavor known as organic synthesis and the creativity and tenacity of its practitioners. Firsthand accounts of each project present the excitement of conception, the frustration of failure and the joy experienced when either rational thought or good fortune gives rise to the successful completion of a project.

Readers will be educated, challenged and inspired by these accounts, which portray the idea that triumphs do not come without challenges. This innovative approach also helps illustrate how challenges to further advance the science and art of organic synthesis can be overcome, driving the field forward to meet the demands of society by discovering new reactions, creating new designs and building molecules with atom and step economies that provide functional solutions to create a better world.

Presents state-of-the-art developments in organic synthesis
Provides insight and offers new perspective to problem-solving
Written by leading experts in the field
Uses firsthand narrative accounts to vividly illustrate the challenges and joys involved in advancing the science of organic synthesis

Front Cover 2
Strategies and Tactics in Organic Synthesis 3
EDITORIAL BOARD 4
Strategies and Tacticsin Organic Synthesis 5
Copyright 6
Dedication 7
Contents 9
Contributors 15
Preface 17
1 - The Chemistry of Lobelia Alkaloids: An Inexhaustible Source for Molecular Diversity 19
- 1. INTRODUCTION 20
- 2. SYNTHESIS PLAN 21
- 3. RING-CLOSING DOUBLE AZA-MICHAEL: SYNTHESIS OF MESO PYRROLIDINES AND PIPERIDINES 23
  - 3.1 Synthesis of Double Michael Acceptors: Two-Directional Olefination 23
    - 3.1.1 Double Wittig Olefination 23

Front Cover 2
Strategies and Tactics in Organic Synthesis 3
EDITORIAL BOARD 4
Strategies and Tacticsin Organic Synthesis 5
Copyright 6
Dedication 7
Contents 9
Contributors 15
Preface 17
1 - The Chemistry of Lobelia Alkaloids: An Inexhaustible Source for Molecular Diversity 19
- 1. INTRODUCTION 20
- 2. SYNTHESIS PLAN 21
- 3. RING-CLOSING DOUBLE AZA-MICHAEL: SYNTHESIS OF MESO PYRROLIDINES AND PIPERIDINES 23
  - 3.1 Synthesis of Double Michael Acceptors: Two-Directional Olefination 23
    - 3.1.1 Double Wittig Olefination 23
    - 3.1.2 Double Cross-Metathesis 26
  - 3.2 Double Aza-Michael Cyclization: Unconventional Activation 28
    - 3.2.1 Ultrahigh Pressure Activation 28
    - 3.2.2 Ultrasound-Mediated Solvent-Free Ring-Closing Double Aza-Michael 30
    - 3.2.3 Microwave-Assisted Telescoped Double Cross-Metathesis/Ring-Closing Double Aza-Michael 35
  - 4. DIVERSITY-ORIENTED SYNTHESIS: INTRAMOLECULAR RAUHUT–CURRIER REACTION 36
    - 4.1 First Example of Bis(Enone) Cycloisomerization With a Primary Amine 36
    - 4.2 Switchable Cyclization Induced by Aza-Michael Addition of Deactivated Amines 37
    - 4.3 Unusual Aza-Michael-Induced Ring Closure With Sulfinamides 39
  - 5. STEP-ECONOMICAL SYNTHESIS OF LOBELIA ALKALOIDS AND RELATED ANALOGS AND HYBRIDS 42
    - 5.1 Synthesis of Pyrrolidine Lobelanine and Lobelane Analogs 42
    - 5.2 Synthesis of Nicotine–Lobeline Hybrids 44
  - 6. CONCLUSION 47
  - ACKNOWLEDGMENTS 49
  - REFERENCES 49
- 2 - Application of Metallacycle-Mediated Annulative Cross-Coupling Chemistry to Neurotrophic seco-Prezizaane Natural Products 53
  - 1. INTRODUCTION 53
  - 2. METALLACYCLE-MEDIATED ANNULATIVE CROSS-COUPLING 54
  - 3. INITIAL RETROSYNTHETIC ANALYSIS AND DISCOVERY OF A NEW ANNULATION METHOD37 60
  - 4. REVISED RETROSYNTHETIC ANALYSIS AND COMPLETION OF A FEW TOTAL SYNTHESES38 61
  - ACKNOWLEDGMENTS 70
  - 5. CONCLUDING REMARKS 70
  - REFERENCES 71
  - FURTHER READING 72
- 3 - Bioinspired Adventures in the Total Synthesis of Mixed Polyketide–Nonribosomal Peptide Natural Products 73
  - 1. INTRODUCTION: NATURAL PRODUCTS FROM THE MIXED POLYKETIDE SYNTHASES–NONRIBOSOMAL PEPTIDE SYNTHETASES PATHWAY 74
    - 1.1 Sources and Biological Significance 74
    - 1.2 Mixed Polyketide Synthases–Nonribosomal Peptide Synthetases Biosynthetic Pathways at the Origin of the Chemical Diversity: 75
    - 1.3 Chemical Diversity in the Polyketide Synthases–Nonribosomal Peptide Synthetases Family of Natural Products 76
  - 2. NATURAL HISTORY AND TOTAL SYNTHESIS OF MYXOMYCETES POLYUNSATURATED PIGMENTS OF THE TETRAMIC ACID TYPE 78
  - 3. BIOSYNTHESIS AND BIOMIMETIC TOTAL SYNTHESIS OF FUNGAL POLYCYCLIC POLYKETIDE SYNTHASES–NONRIBOSOMAL PEPTIDE SYNTHETASES NATUR 81
    - 3.1 Discovery and Biosynthetic Hypotheses 81
    - 3.2 Biosynthesis of Pyrrocidines: A Question of Electronic Activation Answered by Double (13C,18O)-Labeling of the l-Tyrosine P 83
    - 3.3 Biomimetic Formal Synthesis of Hirsutellones 86
      - 3.3.2 Our Biomimetic Formal Synthesis of Hirsutellones 86
      - 3.3.1 The Synthetic Landscape of Hirsutellones and Their Polyketide Synthases–Non ribosomal Peptide Synthetases Congeners 86
    - 4. BIOINSPIRED CHEMICAL DIVERSITY OF CYTOCHALASINS: TOTAL SYNTHESIS, NATURAL HISTORY AND BIOLOGICAL PERSPECTIVES 91
      - 4.1 Introduction on Cytochalasin Diversity and Functions 91
      - 4.2 Total Synthesis and Natural History of Periconiasin G 92
    - 5. CONCLUSION 95
    - ACKNOWLEDGMENTS 96
    - REFERENCES 96
  - 4 - Total Synthesis of Ipomoeassin F and Its Analogs for Biomedical Research 99
    - 1. INTRODUCTION 100
      - 1.1 Resin Glycosides 100
      - 1.2 Ipomoeassins 101
    - 2. TOTAL SYNTHESES 103
      - 2.1 Syntheses of Resin Glycosides 103
      - 2.2 Total Syntheses of Ipomoeassins 104
    - 3. RETROSYNTHETIC ANALYSIS OF IPOMOEASSIN F 105
    - 4. OUR SYNTHESIS OF IPOMOEASSIN F 106
      - 4.1 Fucose Acceptor 106
      - 4.2 Glucosyl Donor 108
      - 4.3 Glycosylation 110
      - 4.4 Optimization of the Disaccharide Synthesis 111
      - 4.5 Completion of the Total Synthesis 113
    - 5. CONCEPTION, SYNTHESIS, AND BIOLOGICAL EVALUATION OF IPOMOEASSIN F ANALOGS 115
      - 5.1 Modifications in the Fatty Acid Aglycone 116
        
        5.1.1 Molecular Design 116
        
        5.1.2 Synthesis 117
        
        5.1.3 Structure–Activity Relationship Studies 117
      - 5.2 Modifications in the Fucosyl Moiety 117
        
        5.2.1 Molecular Design 117
        
        5.2.2 Synthesis 118
        
        5.2.3 Structure–Activity Relationship Studies 121
      - 5.3 Modifications in the Glucosyl Moiety 121
        
        5.3.2 Synthesis 121
        
        5.3.1 Molecular Design 121
        
        5.3.3 Structure–Activity Relationship Studies 123
      - 5.4 Summary of the Structure–Activity Relationship Studies 126
    - 6. CONCLUSIONS AND FUTURE WORK 126
    - REFERENCES 127
    - ACKNOWLEDGMENTS 127
  - 5 - Total Synthesis of Guaianoids: Development of a Strategy Powered by Organocatalytic (4+3)-Cycloaddition Reactions 129
    - 1. INTRODUCTION 129
    - 2. DEVELOPMENT OF A NEW STRATEGY 131
      - 2.1 Englerins A/B and Our Initial Synthetic Plan 131
      - 2.2 The Harmata Organocatalytic (4+3)-Cycloaddition Reaction: The New Strategy 135
      - 2.3 The Regioselective (4+3)-Cycloaddition Reaction 136
      - 2.4 Heck Cyclization and Functional Groups Elaborations 137
      - 2.5 Collective Total Synthesis of Englerins and Orientalols 138
    - 3. RETURNING TO THE HARMATA ORGANOCATALYTIC (4+3)-CYCLOADDITION REACTION 140
    - 4. EXPANDING THE REALM 142
      - 4.1 Guaianolides 142
      - 4.2 Collective Total Synthesis of Hedyosumins and Other Natural Products 144
    - 5. CONCLUSION 149
    - ACKNOWLEDGMENTS 149
    - REFERENCES 149
  - 6 - The Development of Strategies and Tactics Toward the Pseudopterosin Natural Products: Ileabethoxazole As a Platform for Targ 153
    - 1. INTRODUCTION AND BACKGROUND 153
    - 2. STRATEGIES FOR THE SYNTHESIS OF PSEUDOPTEROSIN AGLYCONES 155
      - 2.1 The Corey–Carpino Synthesis From (+)-Menthol 155
      - 2.2 Kocienski’s Synthesis From (1S,2S,5R)-Neoisopulegol 156
      - 2.3 The Corey–Lazerwith Pathway From (S)-(−)-Limonene 157
      - 2.4 RajanBabu’s Asymmetric Hydrovinylation Strategy 157
      - 2.5 Kocienski’s Asymmetric Double Claisen Pathway 160
    - 3. ILEABETHOXAZOLE: A RETROSYNTHETIC ANALYSIS 161
    - 4. THE SYNTHESIS OF 1,1-DISUBSTITUTED ALLENES 162
    - 5. IRON-MEDIATED [2+2+1] CARBOCYCLIZATIONS 165
    - 6. CARBONYL CONDENSATION STRATEGIES FOR ARENE FORMATION 170
    - 7. COMPLETION OF THE SYNTHESIS 172
    - 8. CONCLUSION 175
    - ACKNOWLEDGMENTS 176
    - REFERENCES 176
  - 7 - Total Synthesis of the Lindenane-Associated Terpenoids 179
    - 1. INTRODUCTION 180
    - 2. TOTAL SYNTHESES OF LINDENANE SESQUITERPENOIDS 181
      - 2.1 First-Generation Total Synthesis of Lindenane-Type Sesquiterpenoids 184
        
        2.1.1 Model Synthesis of 3/5/6 Ring System 184
        
        2.1.2 First-Generation Total Syntheses of (±)-Chloranthalactone A and (±)-Shizukanolide E 188
      - 2.2 Second-Generation Total Synthesis of Lindenane-Type Sesquiterpenoids 190
        
        2.2.1 Second-Generation Total Syntheses of (±)-Chloranthalactone A and (±)-Shizukanolide E 192
        
        2.2.2 Total Syntheses of (±)-Chloranthalactone B and F and (±)-9-Hydroxyheterogorgiolide 194
      - 2.3 Novel Deprotection Methodology Mediated by Base 197
        
        2.3.1 Base-Promoted Deprotection of 1,3-Dioxolanes to Ketones 197
        
        2.3.2 Base-Promoted Deprotection of 1,3-Oxathiolanes to Ketones 201
      - 3. ASYMMETRIC TOTAL SYNTHESIS OF BOLIVIANINE 201
        
        3.1 The First-Generation Asymmetric Total Synthesis of Bolivianine: A Chiral Resolution Strategy 206
        
        3.2 Modified Biogenetic Pathways to Bolivianine 208
        
        3.3 The Second-Generation Asymmetric Total Synthesis of Bolivianine: A Biomimetic Strategy 211
        
        3.4 An Alternative Total Synthesis of Bolivianine: Further Improvement 225
        
        3.5 Total Synthesis of Isobolivianine 227
      - ACKNOWLEDGMENTS 228
      - REFERENCES 228
      - 4. CONCLUSION 228
    - 8 - Total Synthesis of Dehaloperophoramidine: Evolution of a Synthesis 235
      - 1. INTRODUCTION 235
      - 2. APPROACHES EXPLOITING THE STEREOSPECIFICITY OF PALLADIUM-CATALYZED DOMINO REACTIONS 237
        
        2.1 Retrosynthetic Analysis of the Core Scaffolds 237
        
        2.2 Competing Pathways in the Palladium-Catalyzed Domino Reaction 239
        
        2.3 Domino Reaction Optimization With Trisubstituted Olefin Substrates 240
        
        2.4 Domino Reaction with Tetrasubstituted Olefins 242
      - 3. APPROACHES TOWARD THE COMMUNESIN MODEL SYSTEM BASED ON THE DIELS–ALDER REACTION 245
        
        3.1 A Revised Retrosynthetic Analysis 245
        
        3.2 Studies Toward the Communesin Core Structure Using a Diels–Alder Reaction 247
      - 4. SYNTHESIS OF DEHALOPEROPHORAMIDINE 251
        
        4.1 Retrosynthetic Analysis and Synthesis Design 251
        
        4.2 Synthesis: First Generation Strategy, First Cascade Sequence 252
        
        4.3 Synthesis: Second Generation Strategy, Second Cascade Sequence 256
      - 5. CONCLUSION 258
      - REFERENCES 259
      - ACKNOWLEDGMENTS 259
    - Index 261
      - B 261
      - C 261
      - A 261
      - D 261
      - G 262
      - E 262
      - F 262
      - K 263
      - H 263
      - L 263
      - I 263
      - P 264
      - N 264
      - O 264
      - M 264
      - R 265
      - S 265
      - T 266
      - Z 266
      - V 266
      - W 266
    - Back Cover 267

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