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Sustainable Synthesis of Pharmaceuticals

Sustainable Synthesis of Pharmaceuticals

Mariette M Pereira | Mário J F Calvete

(2018)

Abstract

There is a growing interest in the development of sustainable processes for the synthesis of pharmaceuticals and this book bridges the divide between industrial examples and the fundamental chemistry. It explains the basic principles of using transition metal catalysis with several green approaches for the synthesis of pharmaceuticals. The topic is an important one for green chemistry and the chapters in this book on hydroformylation, green oxidation and olefin metathesis will also be of interest to both medicinal and organic chemists.
Written by leading experts in the field, it provides a valuable and easy tool for scientists and industrialists who require information regarding this topic.

Table of Contents

Section Title Page Action Price
Cover Cover
Preface vii
Contents ix
Chapter 1 Introduction 1
1.1 Introduction 1
References 4
Chapter 2 Transition Metals in Greener Pharmaceutical Chemistry 5
2.1 Transition Metals in Greener Pharmaceutical Chemistry 5
References 7
Chapter 3 Sustainable Synthesis of Pharmaceuticals Using Alternative Techniques: Microwave, Sonochemistry and Mechanochemistry 8
3.1 Introduction 8
3.2 Metrics 10
3.3 Microwave 21
3.4 Sonochemistry 29
3.5 Mechanochemistry 32
3.6 Conclusion 37
Acknowledgements 37
References 37
Chapter 4 Carbonylation Reactions in the Synthesis of Pharmaceutically Active Compounds 40
4.1 Introduction 40
4.2 Hydroalkoxycarbonylation of Alkenes 43
4.3 Carbonylation of Aryl/Alkenyl Halides 44
4.3.1 Aminocarbonylation Reactions 45
4.3.2 Alkoxy-and Hydroxycarbonylations 50
4.3.3 Carbonylative Coupling Reactions 52
4.3.4 The Use of CO Equivalents 54
4.3.5 Industrial Applications 55
4.4 Oxidative Carbonylation Reactions 56
4.5 Conclusion and Outlook 61
Acknowledgements 61
References 61
Chapter 5 Applications of Catalytic Hydroformylation in the Synthesis of Biologically Relevant Synthons and Drugs 66
5.1 Introduction 66
5.2 Hydroformylation Catalysts—A Historical Perspective 68
5.3 Hydroformylation with Alternative Catalytic Systems 75
5.4 Catalytic Hydroformylation in the Synthesis of Biologically Active Molecules: Selected Examples 77
5.4.1 Enantioselective and Diastereoselective Hydroformylation in Drug Synthesis 85
5.5 Conclusion and Future Perspective 96
Acknowledgements 99
References 99
Chapter 6 Transfer Hydrogenation with Non-toxic Metals for Drug Synthesis 105
6.1 Introduction 105
6.2 Transfer Hydrogenation 106
6.2.1 Mechanistic Overview of Transfer Hydrogenation of Ketones 109
6.2.2 Transfer Hydrogenation with Cheap Metals 112
6.2.3 Asymmetric Transfer Hydrogenation in the Synthesis of Bioactive Molecules 116
6.3 Borrowing Hydrogen Methodology 122
6.4 Conclusion 135
Acknowledgements 135
References 135
Chapter 7 Green Metal-catalysed Synthesis of Pharmaceutically Useful Asymmetric Epoxides and Sulfoxides 139
7.1 Epoxidation and Sulfoxidation: Introduction 139
7.2 Asymmetric Transition Metal-catalysed Epoxidation of Olefins 141
7.2.1 The Katsuki–Sharpless Asymmetric Epoxidation of Allylic Alcohols 141
7.2.2 The Jacobsen–Katsuki Epoxidation with M(salen) Complexes 155
7.2.3 M(bis-hydroxamic acid)-catalysed Epoxidations 170
7.2.4 M(aminopyridine)-catalysed Epoxidations 172
7.3 Transition Metal-catalysed Asymmetric Sulfoxidation 174
7.3.1 Asymmetric Sulfoxidation with Sharpless-type Catalysts 175
7.3.2 Asymmetric Sulfoxidation with Jacobsen–Katsuki-type Catalysts 182
7.3.3 Asymmetric Sulfoxidation with M(bis-hydroxamic) Catalysts 182
7.3.4 Catalytic ASO Processes Using Environmentally Sustainable O2 as TO 182
7.3.5 Catalytic ASO Processes Using Environmentally Sustainable H2O2 as TO 183
7.3.6 M(salen), M(salan) and M(salalen) Sulfoxidation with H2O2 as TO 185
7.4 Conclusion 187
References 188
Chapter 8 C–C Bond Formation in the Sustainable Synthesis of Pharmaceuticals 193
8.1 Introduction 193
8.2 C–C Coupling Reactions 196
8.2.1 Suzuki–Miyaura Coupling 196
8.2.2 Negishi and Stille Couplings 198
8.2.3 Sonogashira Coupling 200
8.2.4 Heck Coupling 200
8.2.5 Decarboxylative C–C Coupling 202
8.2.6 The Kumada–Corriu Coupling 203
8.2.7 The α-Arylation of Enolates 205
8.2.8 The Hayashi–Miyaura Reaction 207
8.2.9 Tsuji–Trost Allylation 210
8.2.10 Aromatic Cyanation 213
8.2.11 Nozaki–Hiyama–Kishi Coupling Reaction 216
8.2.12 C–H Activation 219
8.3 Conclusion 224
Abbreviations 224
Acknowledgements 225
References 225
Chapter 9 Metal-catalysed Metathesis Reactions for Greener Synthon/Drug Synthesis 230
9.1 Introduction 230
9.2 Mechanistic Aspects 232
9.3 Catalysts for Metathesis 233
9.3.1 Ruthenium Catalysts with Well-defined Structures 234
9.3.2 Tungsten and Molybdenum Catalysts of Well-defined Structures 236
9.3.3 Molecular Catalyst Stability 237
9.3.4 Catalyst Residue Removal 238
9.4 The Choice of Reaction Conditions 238
9.5 Selected Examples of Metathesis in (Industrial) Organic Synthesis 239
9.5.1 Cross Metathesis 240
9.5.2 Ring-closing Metathesis 244
9.6 Conclusion 248
Acknowledgements 251
References 251
Chapter 10 Tetravalent Boron-based Therapeutics 253
10.1 Introduction 253
10.2 Boron Dipyrromethenes 254
10.2.1 Structure and Properties 254
10.2.2 Application in PDT 256
10.2.3 Structure Modifications 257
10.2.4 Application in BNCT 265
10.3 Naturally Occurring Tetravalent Boron Therapeutics 267
10.3.1 Boromycin 267
10.3.2 Aplasmomycin A, B and C 268
10.3.3 Tartrolons 268
10.3.4 Borophycin 268
10.4 Naturally-inspired Boron Therapeutics 271
10.4.1 Borinate Ester Derivatives 271
10.4.2 Boronate Ester Derivatives 271
10.4.3 Boroxazolidones 271
10.4.4 Arylspiroborates 273
10.5 Conclusion 274
References 274
Subject Index 282