Green Processes, Volume 7 E-Book

• Herausgeber: Wiley-VCH
• Kategorie: Wissenschaft und neue Technologien
• Serie: Handbook of Green Chemistry
• Sprache: Englisch

Seitenzahl: 654

Veröffentlichungsjahr: 2014

Beschreibung

Edited by Professor CJ Li, one of the leading international experts in the fields of Green Chemistry and Green Synthesis, this volume presents such hot topics as synthesis without protecting groups, multi-component reactions, and synthesis in green solvents.

The Handbook of Green Chemistry comprises of 9 volumes in total, split into 3 subject-specific sets. The three sets are available individually. All 9 volumes are available individually, too.

Set I: Green Catalysis 
  - Volume 1: Homogeneous Catalysis 
  - Volume 2: Heterogeneous Catalysis 
  - Volume 3: Biocatalysis

Set II: Green Solvents
  - Volume 4: Supercritical Solvents
  - Volume 5: Reactions in Water
  - Volume 6: Ionic Liquids

Set III: Green Processes
  - Volume 7: Green Synthesis
  - Volume 8: Green Nanoscience
  - Volume 9: Designing Safer Chemicals

The Handbook of Green Chemistry is also available as Online Edition.

Podcasts
Listen to two podcasts in which Professor Paul Anastas and Journals Editor Paul Trevorrow discuss the origin and expansion of Green Chemistry and give an overview of The Handbook of Green Chemistry.

Leseprobe

CONTENTS

Cover

Related Titles

Title Page

Copyright

About the Editors

List of Contributors

Preface

Chapter 1: Atom Economy: a Challenge for Enhanced Synthetic Efficiency

1.1 Vinylidenes

1.2 Redox Isomerization

1.3 Ruthenacyclopentadiene Intermediates

1.4 Ruthenacyclopentene Intermediates

1.5 Allylic C–H Insertion

1.6 Reactions of Alkenes

1.7 Conclusion

References

Chapter 2: Evaluating the Greenness of Synthesis

2.1 General Considerations About Green Chemistry and Green Engineering Metrics

2.2 Selected Metrics Used in the Past

2.3 Reaction Mass Efficiency

2.4 Mass Intensity and Mass Productivity (Mass Efficiency)

2.5 Cost Implications and Green Chemistry Metrics

2.6 Life-Cycle Assessment Metrics

2.7 Process Metrics

2.8 Conclusions

References

Chapter 3: Alternative Feedstocks for Synthesis

3.1 Introduction

3.2 Carbohydrates

3.3 Lignin

3.4 Fats and Oils

3.5 Terpenes

3.6 Carbon Dioxide

References

Chapter 4: Synthesis in Green Solvents

4.1 The Role of Solvents in Synthesis

4.2 Types of Solvent

4.3 Problems with Solvents

4.4 Application of Green Solvents

4.5 Conclusion

References

Chapter 5: Development and Application of Isocyanide-based Multicomponent Reactions

5.1 Introduction

5.2 Basic Principle of MCRs

5.3 Discovering Novel MCRs

5.4 MCRs Imitated by Addition of Isocyanides to Alkynes

5.5 Metal-Catalyzed IMCRs

5.6 Enantioselective P-3CR

5.7 Application in Medicinal Chemistry and in Natural Product Synthesis

5.8 Conclusion

References

Chapter 6: Flow Syntheses

6.1 Introduction

6.2 Examples of Their Use as Tools for the Research Chemist

6.3 Process Intensification Achieved Through the Use of Flow Reactors

6.4 Conclusions and Outlook

References

Chapter 7: Synthesis Without Protecting Groups

7.1 The Present Use of Protecting Groups

7.2 Protecting Group-Free Synthesis?

7.3 Use of In Situ Protections in Lieu of Short-Term Protecting Groups

7.4 Follow Nature's Biogenetic Routes to Avoid Protecting Groups

7.5 Apply Functional Group-Tolerant Construction Reactions to Avoid Protecting Groups

7.6 Aim for Higher Chemoselectivity to Avoid Protecting Groups

7.7 Change the Order of Synthesis Steps to Avoid Protecting Groups

7.8 Enlist Latent Functionality to Avoid Explicit Protecting Group Steps

7.9 Summary

References

Chapter 8: Biological Synthesis of Pharmaceuticals

8.1 Introduction

8.2 New Enzymes for Chemical Synthesis

8.3 Synthesis of Pharmaceuticals via Isolated Enzymes

8.4 Synthesis of Pharmaceuticals via Whole Cells

8.5 Conclusion

Acknowledgments

References

Chapter 9: Syntheses via C–H Bond Functionalizations

9.1 Introduction

9.2 Direct Arylations of Arenes

9.3 Catalytic Oxidative Arylations of (Hetero)arenes

9.4 Conclusion

References

Chapter 10: Synthesis Without Metals

10.1 Introduction

10.2 Organic Reactions Promoted by Non-Metallic Catalysts

10.3 Asymmetric Organocatalysts

10.4 Conclusion

References

Chapter 11: Chemistry Beyond Functional Group Transformation

11.1 Introduction

11.2 C–H Bond Activation

11.3 C–C Bond Activation

11.4 C–O Bond Activation

11.5 C–F Bond Activation

11.6 C–N Bond Activation

11.7 Small Molecule Activation

11.8 Conclusions and Outlook

List of Abbreviations

References

Chapter 12: Synthesis Assisted by Electricity

12.1 Electroorganic Synthesis in Green Reaction Media (Homogeneous System)

12.2 Electroorganic Synthesis in Liquid–Liquid Biphasic Systems

12.3 Electroorganic Synthesis in Thermomorphic Liquid–Liquid Biphasic Systems

12.4 Electroorganic Synthesis in Solid–Liquid Biphasic Systems

12.5 Electroorganic Synthesis in Microflow Systems

12.6 Future Outlook

References

Chapter 13: Parameterization and Tracking of Optimization of Synthesis Strategy Using Computer Spreadsheet Algorithms

13.1 Introduction

13.2 Synthesis Strategy Parameterization

13.3 Case Study: Lysergic Acid [30–40]

References

References

Index

End User License Agreement

List of Tables

Table 2.1

Table 2.2

Table 2.3

Table 2.4

Table 2.5

Table 6.1

Table 6.2

Table 6.3

Table 6.4

Table 6.5

Table 6.6

Table 6.7

Table 6.8

Table 6.9

Table 6.10

Table 6.11

Table 6.12

Table 6.13

Table 6.14

Table 6.15

Table 6.16

Table 6.17

Table 9.1

Table 9.2

Table 9.3

Table 9.4

Table 11.1

Table 13.1

Table 13.2

List of Illustrations

Scheme 1.1

Scheme 1.2

Scheme 1.3

Scheme 1.4

Scheme 1.5

Scheme 1.6

Scheme 1.7

Figure 1.1

Figure 3.1

Figure 3.2

Figure 3.3

Figure 3.4

Figure 3.5

Scheme 3.1

Figure 3.6

Figure 3.7

Scheme 3.2

Scheme 3.3

Scheme 3.4

Scheme 3.5

Scheme 3.6

Scheme 3.7

Figure 3.8

Scheme 3.8

Scheme 3.9

Figure 4.1

Scheme 4.1

Scheme 4.2

Scheme 4.3

Figure 4.2

Scheme 4.4

Figure 4.3

Scheme 4.5

Scheme 4.6

Figure 4.4

Scheme 4.7

Figure 5.1

Scheme 5.1

Scheme 5.2

Scheme 5.3

Figure 5.2

Figure 5.3

Scheme 5.4

Scheme 5.5

Scheme 5.6

Scheme 5.7

Scheme 5.8

Scheme 5.9

Scheme 5.10

Scheme 5.11

Figure 5.4

Scheme 5.12

Scheme 5.13

Scheme 5.14

Scheme 5.15

Scheme 5.16

Scheme 5.17

Scheme 5.18

Scheme 5.19

Scheme 5.20

Scheme 5.21

Scheme 5.22

Scheme 5.23

Scheme 5.24

Scheme 5.25

Figure 5.5

Scheme 5.26

Scheme 5.27

Scheme 5.28

Scheme 5.29

Scheme 5.30

Scheme 5.31

Scheme 5.32

Scheme 5.33

Scheme 5.34

Scheme 5.35

Scheme 5.36

Scheme 5.37

Scheme 5.38

Scheme 5.39

Scheme 5.40

Scheme 5.41

Scheme 5.42

Scheme 5.43

Scheme 5.44

Scheme 5.45

Scheme 5.46

Scheme 6.1

Scheme 6.2

Scheme 6.3

Scheme 6.4

Scheme 6.5

Scheme 6.6

Scheme 6.7

Scheme 6.8

Scheme 6.9

Scheme 6.10

Figure 6.1

Scheme 6.11

Scheme 6.12

Scheme 6.13

Scheme 6.14

Scheme 6.15

Scheme 6.16

Scheme 6.17

Scheme 6.18

Scheme 6.19

Scheme 6.20

Scheme 6.21

Scheme 6.22

Scheme 6.23

Scheme 6.24

Scheme 6.25

Scheme 6.26

Scheme 6.27

Scheme 6.28

Scheme 6.29

Scheme 6.31

Scheme 6.30

Scheme 6.32

Scheme 6.33

Scheme 6.34

Scheme 6.35

Scheme 6.36

Scheme 6.37

Scheme 6.38

Scheme 6.39

Scheme 6.40

Scheme 6.41

Scheme 6.42

Scheme 6.43

Scheme 6.44

Scheme 6.45

Figure 6.2

Scheme 6.46

Scheme 6.47

Scheme 6.48

Scheme 7.1

Scheme 7.2

Scheme 7.3

Scheme 7.4

Scheme 7.5

Scheme 7.6

Scheme 7.7

Scheme 7.8

Scheme 7.9

Scheme 7.10

Scheme 7.11

Scheme 7.12

Scheme 7.13

Scheme 7.14

Scheme 7.15

Scheme 7.16

Scheme 7.17

Scheme 7.18

Scheme 7.19

Scheme 7.20

Scheme 7.21

Scheme 7.22

Scheme 7.23

Scheme 7.24

Scheme 7.25

Scheme 7.26

Scheme 8.1

Scheme 8.2

Scheme 8.3

Scheme 8.4

Scheme 8.5

Scheme 8.6

Scheme 8.7

Figure 8.1

Scheme 8.8

Scheme 8.9

Scheme 8.10

Scheme 8.11

Scheme 8.12

Scheme 8.13

Scheme 8.14

Scheme 8.15

Scheme 8.16

Scheme 8.17

Scheme 8.18

Scheme 8.19

Scheme 8.20

Figure 8.2

Figure 8.3

Figure 9.1

Figure 9.2

Scheme 9.1

Scheme 9.2

Scheme 9.3

Scheme 9.4

Scheme 9.5

Scheme 9.6

Figure 9.3

Scheme 9.7

Scheme 9.8

Scheme 9.9

Scheme 9.10

Scheme 9.11

Scheme 9.12

Scheme 9.13

Scheme 9.14

Scheme 9.15

Scheme 9.16

Scheme 9.17

Scheme 9.18

Scheme 9.19

Scheme 9.20

Scheme 9.21

Scheme 9.22

Scheme 9.23

Scheme 9.24

Scheme 9.25

Scheme 9.26

Scheme 9.27

Scheme 9.28

Scheme 9.29

Scheme 9.30

Scheme 9.31

Scheme 9.32

Scheme 9.33

Scheme 9.34

Scheme 9.35

Scheme 9.36

Scheme 9.37

Scheme 9.38

Scheme 9.39

Scheme 9.40

Scheme 9.41

Scheme 9.42

Scheme 9.43

Scheme 9.44

Scheme 9.45

Scheme 9.46

Scheme 9.47

Scheme 9.48

Scheme 9.49

Scheme 9.50

Scheme 9.51

Scheme 9.52

Scheme 9.53

Figure 10.1

Figure 10.2

Figure 10.3

Figure 10.4

Figure 10.5

Scheme 10.1

Figure 10.6

Figure 10.7

Figure 10.8

Scheme 10.2

Scheme 10.3

Scheme 10.4

Figure 10.9

Figure 10.10

Figure 10.11

Figure 10.12

Figure 10.13

Figure 10.14

Figure 10.15

Figure 10.16

Figure 10.17

Figure 10.18

Figure 10.19

Figure 10.20

Figure 10.21

Figure 10.22

Figure 10.23

Scheme 11.1

Scheme 11.2

Scheme 11.3

Scheme 11.4

Scheme 11.5

Scheme 11.6

Scheme 11.7

Scheme 11.8

Scheme 11.9

Scheme 11.10

Scheme 12.1

Figure 12.1

Figure 12.2

Figure 12.3

Figure 12.4

Scheme 12.2

Figure 12.5

Figure 12.6

Scheme 12.3

Figure 12.7

Figure 12.8

Figure 12.9

Scheme 12.4

Scheme 12.5

Figure 12.10

Figure 12.11

Figure 12.12

Figure 13.1

Figure 13.2

Figure 13.3

Figure 13.4

Figure 13.5

Figure 13.6

Figure 13.7

Scheme 13.1

Scheme 13.2

Scheme 13.3

Guide

Cover

Table of Contents

Preface

Chapter 1

Pages

ii

iii

iv

xiii

xiv

xv

xvi

xvii

xix

xx

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

40

41

42

43

44

45

46

47

48

49

50

51

52

53

54

55

56

57

58

59

60

61

62

63

64

65

66

67

68

69

70

71

72

73

74

75

76

77

78

79

80

81

82

83

84

85

86

87

88

89

90

91

92

93

94

95

96

97

98

99

100

101

102

103

104

105

106

107

108

109

110

111

112

113

114

115

116

117

118

119

120

121

122

123

124

125

126

127

128

129

130

131

132

133

134

135

136

137

138

139

140

141

142

143

144

145

146

147

148

149

150

151

152

153

154

155

156

157

158

159

160

161

162

163

164

165

166

167

168

169

170

171

172

173

174

175

176

177

178

179

180

181

182

183

184

185

186

187

188

189

190

191

192

193

194

195

196

197

198

199

200

201

202

203

204

205

206

207

208

209

210

211

212

213

214

215

216

217

218

219

220

221

222

223

224

225

226

227

228

229

230

231

232

233

234

235

236

237

238

239

240

241

242

243

244

245

246

247

248

249

250

251

252

253

254

255

256

257

258

259

260

261

262

263

264

265

266

267

268

269

270

271

272

273

274

275

276

277

278

279

280

281

282

283

284

285

286

287

288

289

290

291

292

293

294

295

296

297

298

299

300

301

302

303

304

305

306

307

308

309

310

311

312

313

314

315

316

317

318

319

320

321

322

323

324

325

326

327

328

329

330

331

332

333

334

335

336

337

338

339

340

341

342

343

344

345

346

347

348

349

350

351

352

353

354

355

356

357

358

359

360

361

362

363

364

365

366

367

368

369

370

371

372

373

374

375

376

377

378

379

380

381

382

383

384

385

386

387

388

389

390

391

392

393

394

395

396

397

398

399

400

401

402

403

404

405

406

407

408

409

410

411

412

413

414

415

416

417

418

419

420

421

422

423

424

425

426

427

428

429

430

431

432

Related Titles

Jiménez-González, C., Constable, D. J. C.

Green Chemistry and Engineering

A Practical Design Approach

2010

ISBN: 978-0-470-17087-8

Dunn, P., Wells, A., Williams, M. T. (eds.)

Green Chemistry in the Pharmaceutical Industry

2010

ISBN: 978-3-527-32418-7

Loos, K. (ed.)

Biocatalysis in Polymer Chemistry

2010

ISBN: 978-3-527-32618-1

Reichardt, C., Welton, T.

Solvents and Solvent Effects in Organic Chemistry

Fourth, Updated and Enlarged Edition

2010

ISBN: 978-3-527-32473-6

Pignataro, B. (ed.)

Tomorrow's Chemistry Today

Concepts in Nanoscience, Organic Materials and Environmental Chemistry

Second Edition

2009

ISBN: 978-3-527-32623-5

Roesky, H. W., Kennepohl, D. (eds.)

Experiments in Green and Sustainable Chemistry

2009

ISBN: 978-3-527-32546-7

Handbook of Green Chemistry

Volume 7Green Synthesis

Edited by

Chao-Jun Li

All books published by Wiley-VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.

Library of Congress Card No.: applied for

British Library Cataloguing-in-Publication Data

A catalogue record for this book is available from the British Library.

Bibliographic information published by the Deutsche Nationalbibliothek

The Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at http://dnb.d-nb.de.

© 2012 Wiley-VCH Verlag & Co. KGaA, Boschstr. 12, 69469 Weinheim, Germany

All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law.

ISBN: 978-3-527-32602-0

About the Editors

Series Editor

Paul T. Anastas joined Yale University as Professor and serves as the Director of the Center for Green Chemistry and Green Engineering there. From 2004–2006, Paul was the Director of the Green Chemistry Institute in Washington, D.C. Until June 2004 he served as Assistant Director for Environment at the White House Office of Science and Technology Policy where his responsibilities included a wide range of environmental science issues including furthering international public-private cooperation in areas of Science for Sustainability such as Green Chemistry. In 1991, he established the industry-governmentuniversity partnership Green Chemistry Program, which was expanded to include basic research, and the Presidential Green Chemistry Challenge Awards. He has published and edited several books in the field of Green Chemistry and developed the 12 Principles of Green Chemistry.

Volume Editor

Chao-Jun Li (FRSC, UK) received his PhD at McGill University (1992) and was an NSERC Postdoctoral Fellow at Stanford University (1992–1994). He was an Assistant Professor (1994), Associate Professor (1998) and Full Professor (2000–2003) at Tulane University, where he received a NSF CAREER Award (1998) in organic synthesis and the 2001 US Presidential Green Chemistry Challenge Award (Academic). In 2003, he became a Canada Research Chair (Tier I) in Organic/Green Chemistry and a Professor of Chemistry at McGill University in Canada. He serves as the Co-Chair of the Canadian Green Chemistry and Engineering Network, the Director of CFI Infrastructure for Green Chemistry and Green Chemicals, and Co-Director the FQRNT Center for Green Chemistry and Catalysis (Quebec). He is the current Associate Editor for Americas for the journal of Green Chemistry (published by the Royal Society of Chemistry). He has been widely recognized as the leader in Green Chemistry for Organic Synthesis in developing innovative and fundamentally new organic reactions that defy conventional reactivities and have high synthetic efficiency.

List of Contributors

Lutz Ackermann

Georg-August-Universität Göttingen

Institut für Organische und Biomolekulare Chemie

Tammannstrasse 2

37077 Göttingen

Germany

Geoffrey R. Akien

City University of Hong Kong

Department of Biology and Chemistry

Kowloon

Hong Kong

Takahiko Akiyama

Gakushuin University

Department of Chemistry

Mejiro 1-5-1, Toshima-ku

171-8588 Tokyo

Japan

John Andraos

CareerChem

504-1129 Don Mills Road

Toronto, ON M3B 2W4

Canada

Arno Behr

Technische Universität Dortmund

Fakultät Bio- und

Chemieingenieurwesen

Lehrstuhl Technische Chemie A

Emil-Figgestrasse 66

44227 Dortmund

Germany

Alex Chu

Metabomics, Inc.

SuZhou

Jiangsu 215600

China

David J.C. Constable

Lockheed Martin

Energy, Environment, Safety and Health

Gaithersburg, MD 20878

USA

Reinhard W. Hoffmann

Philipps-Universität

Fachbereich Chemie

Hans-Meerwein-Strasse

35032 Marburg

Germany

István T. Horváth

City University of Hong Kong

Department of Biology and Chemistry

Kowloon

Hong Kong

Concepción “Conchita” Jiménez-González

GlaxoSmithKline

Operational Sustainability, Sustainability and Environment

Research Triangle Park, NC 27709

USA

Leif Johnen

Technische Universität Dortmund

Fakultät Bio- und

Chemieingenieurwesen

Lehrstuhl Technische Chemie A

Emil-Figgestrasse 66

44227 Dortmund

Germany

Anant R. Kapdi

Georg-August-Universität Göttingen

Institut für Organische und

Biomolekulare Chemie

Tammannstrasse 2

37077 Göttingen

Germany

Sergei I. Kozhushkov

Georg-August-Universität Göttingen

Institut für Organische und

Biomolekulare Chemie

Tammannstrasse 2

37077 Göttingen

Germany

Zhiping Li

Renmin University of China

Department of Chemistry

No.59, Zhong Guan Cun Street

Beijing 100872 China

László Orha

Eötvös University

Institute of Chemistry

Pázmány Péter Sétány 1/A

1117 Budapest

Hungary

Harish K. Potukuchi

Georg-August-Universität Göttingen

Institut für Organische und Biomolekulare Chemie

Tammannstrasse 2

37077 Göttingen

Germany

Seiji Suga

Okayama University

Graduate School of Natural Science and Technology

Division of Chemistry and Biochemistry

3-1-1 Tsushima-naka, Kita-ku

700-8530 Okayama

Japan

Junhua Tao

Metabomics, Inc.

SuZhou

Jiangsu 215600

China

Barry M. Trost

Stanford University

Department of Chemistry

Stanford, CA 94305

USA

Mei-Xiang Wang

The Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education)

Department of Chemistry

Tsinghua University

100084 Beijing

China

Qian Wang

École Polytechnique Fédérale de Lausanne

EPFL-SB-ISIC-LSPN

BCH 5304 (Bât BCH)

1015 Lausanne

Switzerland

Paul Watts

The University of Hull

Department of Chemistry

Cottingham Road

Hull HU6 7RX

UK

Charlotte Wiles

The University of Hull

Department of Chemistry

Cottingham Road

Hull HU6 7RX

UK

and

Chemtrix BV

Burgemeester Lemmensstraat 358

6163JT Geleen

The Netherlands

Jun-ichi Yoshida

Kyoto University

Graduate School of Engineering

Department of Synthetic Chemistry and Biological Chemistry

Nishikyo-ku

615-8510 Kyoto

Japan

Rong Yu

Renmin University of China

Department of Chemistry

No.59, Zhong Guan Cun Street

Beijing 100872

China

Jieping Zhu

École Polytechnique Fédérale de Lausanne

EPFL-SB-ISIC-LSPN

BCH 5304 (Bât BCH)

1015 Lausanne

Switzerland

Preface

Ever since the synthesis of urea by Friedrich Wöhler near two centuries ago, organic synthesis has become the foundation of modern medicines for human health, produced new agrochemicals to boost world food supply, created various synthetic fibers for daily usages, and bestowed a colorful enchantment through synthetic dyes. In spite of these great achievements, the general features of organic syntheses have been, by and large, unchanged over a century?: e.g., non-renewable feedstock, batch reactor, and refluxing. In addition, classical organic syntheses often produce stoichiometric amount of waste, use organic solvents and sometimes dangerous reagents, require extensive protection-deprotection of functional groups, need pre-functionalized starting materials, and involve multi-step operations, which resulted in low efficiency in resource utilization and led to various concerns due to waste generations. While, in the past, the primary goal of organic syntheses is “ to get the target product”, the sustainability of chemical synthesis becomes a more and more important issue. This volume of Green Syntheses illustrated some examples to address this issue ranging from starting materials, reaction design, choice of solvent, energy input, to reactor design. The chapter by Trost describes the general principle of greener synthesis; the chapter by Behr shows examples of using renewable feedstocks for making chemical products; the chapter by Horvath describes the use of alternative solvents for organic synthesis; the chapters by Zhu, Hoffman and Watts describe methods of reducing synthetic steps by running multi-component reactions, avoiding protecting groups, and in flow respectively; the chapters by Ackermann and Li show examples of direct conversion of C–H bonds; the chapters by Varma and Yoshida presents alternative energy input in chemical reactions through light and electricity; the chapters by Tao and Akiyama give examples of using enzymes and organo catalysts for synthetic purposes; and finally the chapter by Andraos uses computation methods to evaluate the relative efficiency of different synthetic routes. We hope that these examples will provide food-for-thought for further innovations in developing greener syntheses.

Montreal, April 2012

C-J Li

1Atom Economy: a Challenge for Enhanced Synthetic Efficiency

Barry M. Trost

The design of structure for function is the major task for helping to solve problems ranging from material science to human health. The demands and expectations for extremely high levels of performance frequently increases the molecular complexity needed. Thus, a major goal must be to allow the synthesis of such complex molecular arrays in a time-effective manner. The strategic design for the synthesis of complex molecules derives from the available basic tools – the reactions, reagents, and catalysts. Although some might think we have a pretty full toolbox, the reality is that, in most likelihood, only a very small fraction of the true total number of reactions possible is known today. Hence a great unknown awaits us, and chipping away at those unknown processes presents a great opportunity for discovery that will undoubtedly change the practice of the science.

In undertaking a program of discovery for new processes, the characteristics that defines the requirements for these new reactions/reagents/catalysts must be appreciated. In 1983, selectivity was noted as key to evolving reasonable efficiency in the synthesis of complex molecules [1]. The issue of chemoselectivity, defined as discriminating reactivity among various bond types in a molecule without employing activating or blocking groups, was placed at the top of the list! There is no question that problems of chemoselectivity are the single biggest factor in creating synthetic inefficiencies. More than 25 years later, the primacy of this selectivity issue was still noted [2]. It is so pervasive in the science that it undoubtedly will remain the greatest challenge for a long time to come. The second issue is regioselectivity, which is defined as orientational control in the joining of a reagent with an unsymmetrical functional group. Controlling stereochemistry constitutes the third major challenge. There are two fundamentally different issues embodied within this topic – controlling relative stereochemistry or diastereoselectivity and absolute stereochemistry or enantioselectivity.