Sustainable Catalysis E-Book

Peter Dunn

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 668

Veröffentlichungsjahr: 2013

Beschreibung

Opens the door to the sustainable production of pharmaceuticals and fine chemicals Driven by both public demand and government regulations, pharmaceutical and fine chemical manufacturers are increasingly seeking to replace stoichiometric reagents used in synthetic transformations with catalytic routes in order to develop greener, safer, and more cost-effective chemical processes. This book supports the discovery, development, and implementation of new catalytic methodologies on a process scale, opening the door to the sustainable production of pharmaceuticals and fine chemicals. Pairing contributions from leading academic and industrial researchers, Sustainable Catalysis focuses on key areas that are particularly important for the fine chemical and pharmaceutical industries, including chemo-, bio-, and organo-catalytic approaches to C-H, C-N, and C-C bond-forming reactions. Chapters include academic overviews of current innovations and industrial case studies at the process scale, providing new insights into green catalytic methodologies from proof-of-concept to their applications in the synthesis of target organic molecules. Sustainable Catalysis provides the foundation needed to develop sustainable green synthetic procedures, with coverage of such emerging topics as: * Catalytic reduction of amides avoiding LiAlH4 or B2H6 * Synthesis of chiral amines using transaminases * Industrial applications of boric acid and boronic acid catalyzed direct amidation reactions * C-H activation of heteroaromatics * Organocatalysis for asymmetric synthesis Offering a balanced perspective on current limitations, challenges, and solutions, Sustainable Catalysis is recommended for synthetic organic chemists seeking to develop new methodologies and for industrial chemists dedicated to large-scale process development.

Leseprobe

Contents

Cover

Title Page

Copyright

Foreword

Preface

Contributors

Abbreviations

Chapter 1: Catalytic Reduction of Amides Avoiding Lialh4 or B2H6

1.1 Introduction

1.2 Amides

1.3 Importance of Amide Reductions in Pharmaceutical Synthesis

1.4 Heterogeneous Amide Hydrogenation

1.5 Homogeneous Amide Hydrogenation

1.6 Hydrosilation

1.7 Conclusions and Future Perspectives

References

Chapter 2: Hydrogenation of Esters

2.1 Introduction

2.2 Hydrogenation of Aliphatic Esters

2.3 Hydrogenation of Lactones

2.4 Hydrogenation of Aromatic Esters

2.5 Hydrogenation of Furanoic Esters

2.6 Hydrogenation of Chiral Esters (Base-Free Conditions)

2.7 Conclusions

References

Chapter 3: Synthesis of Chiral Amines Using Transaminases

3.1 Importance of Chiral Amines

3.2 Transaminases

3.3 Transaminase-Catalyzed Resolution of Racemic Amines

3.4 Transaminase-Catalyzed Asymmetric Synthesis of Amines

3.5 Conclusions

References

Chapter 4: Development of a Sitagliptin Transaminase

4.1 Introduction

4.2 Creating Activity

4.3 Transaminase Evolution

4.4 Process Optimization

4.5 A General Amination Methodology

4.6 Conclusion and Outlook

4.7 Procedures

References

Chapter 5: Direct Amide Formation Avoiding Poor Atom Economy Reagents

5.1 Introduction

5.2 Mechanism for Boronic and Boric Acid Catalysis

5.3 Boric Acid-Based Catalysis

5.4 Boronic Acid-Based Catalysis

5.5 Triazine-Based Reagents

5.6 Titanium(IV)-Based Reagents

5.7 Antimony-Based Reagents

5.8 Heterogeneous Catalysts and Microwave-Assisted Amide Synthesis

5.9 Summary and Future Directions

References

Chapter 6: Industrial Applications of Boric Acid and Boronic Acid-Catalyzed Direct Amidation Reactions

6.1 Introduction

6.2 The Synthesis of Efaproxiral Utilizing a Direct Amidation Reaction

6.3 Direct Amidation Examples from Dr. Reddy's Laboratories

6.4 Direct Amidation Examples from Pfizer

6.5 Potential Toxicity of Boric Acid

6.6 Conclusions

Acknowledgment

References

Chapter 7: OH Activation for Nucleophilic Substitution

7.1 Introduction

7.2 Formation of C–C Bonds from Alcohols

7.3 Formation of C–N Bonds from Alcohols

References

Chapter 8: Application of a Redox-Neutral Alcohol Amination in the Kilogram-Scale Synthesis of a GlyT1 Inhibitor

8.1 Introduction

8.2 Background and Initial Synthetic Work

8.3 First-Generation Synthesis of 10

8.4 First Application of IR Chemistry and Initial Process Development Efforts

8.5 Process Optimization of the Amination Reaction

8.6 Mechanistic Discussion

8.7 Iridium Control

8.8 Final Comments

Acknowledgments

References

Chapter 9: Olefin Metathesis: From Academic Concepts to Commercial Catalysts

9.1 Introduction

9.2 Recovery and Reuse of Ru-Based Metathesis Catalysts: The Academics' View

9.3 Application of Ruthenium Metathesis Catalysts in Water

9.4 Summary and Outlook

Acknowledgments

References

Chapter 10: Challenge and Opportunity in Scaling-up Metathesis Reaction: Synthesis of Ciluprevir (Biln 2061)

10.1 Introduction

10.2 Synthesis of Ciluprevir (Biln 2061) and Critical Challenges

10.3 Preparations of Building Blocks

10.4 The First Generation Ciluprevir (Biln 2061) Process

10.5 Challenges in Scaling Up The RCM Reaction

10.6 Development of a Practical and Scalable RCM Process

10.7 The Second Generation Ciluprevir (Biln 2061) Process

10.8 Conclusion

References

Chapter 11: C–H Activation of Heteroaromatics

11.1 Introduction

11.2 Direct Arylation

11.3 Direct Alkenylation

11.4 Direct Alkynylation

11.5 Direct Alkylation

11.6 Conclusion

References

Chapter 12: The Discovery of a New Pd/Cu Catalytic System for C–H Arylation and Its Applications in a Pharmaceutical Process

12.1 Introduction

12.2 Development of Initial Process for the Agonist of S1P1

12.3 Development of C–H Arylation for the Synthesis of AMG 369

12.4 Conclusion

References

Chapter 13: Diarylprolinol Silyl Ethers: Development and Application as Organocatalysts

13.1 Introduction and Background

13.2 Enamine Intermediate

13.3 Iminium ion Intermediate

13.4 Formal C–H Insertion

13.5 Reactions in the Presence of Water

13.6 Synthesis of Biologically Active Molecules

13.7 Conclusion

References

Chapter 14: Organocatalysis for Asymmetric Synthesis: From Lab to Factory

14.1 Introduction

14.2 Preparation of Telcagepant, an Application of Iminium Organocatalysis

14.3 Preparation of MK-8613, Application of Asymmetric Michael Addition Catalyzed by Desmethyl Quinidine

14.4 Conclusions

Acknowledgments

References

Chapter 15: Catalytic Variants of Phosphine Oxide-Mediated Organic Transformations

15.1 General Introduction

15.2 Wittig Chemistry

15.3 Aza-Wittig Chemistry

15.4 Mitsunobu Chemistry

15.5 Appel Halogenations

15.6 Conclusions

References

Chapter 16: Formation of C–C Bonds Via Catalytic Hydrogenation and Transfer Hydrogenation

16.1 Introduction: Minimizing Preactivation for Synthetic Efficiency

16.2 Carbonyl and Imine Vinylation

16.3 Carbonyl Allylation and Propargylation

16.4 Aldol, Mannich, and Related Processes

16.5 Future Directions

Acknowledgments

References

Index

Copyright © 2013 by John Wiley & Sons, Inc. All rights reserved.

Published by John Wiley & Sons, Inc., Hoboken, New Jersey.

Published simultaneously in Canada.

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Library of Congress Cataloging-in-Publication Data:

Sustainable catalysis : challenges and practices for the pharmaceutical and fine chemical industries / edited by Peter J. Dunn, Pfizer Green Chemistry Lead, Sandwich, Kent, United Kingdom, K.K. (Mimi) Hii, Imperial College London, South Kensington, London, United Kingdom, Michael J. Krische, University of Texas at Austin, Austin, Texas, United States of America, Michael T. Williams, CMC Consultant, Deal, Kent, United Kingdom.

pages cm

Includes index.

ISBN 978-1-118-15542-4 (cloth)

1. Environmental chemistry–Industrial applications. 2. Chemicalengineering. 3. Catalysts. 4. Pharmaceutical industry–Waste minimization. I. Dunn, Peter J. (Peter James) editor of compilation. II. Hii, K. K., 1969-editor of compilation. III. Krische, Michael J., editor of compilation. IV. Williams, Michael T. (Michael Trevelyan) editor of compilation.

TP155.2.E58S86 2013

541'.395–dc23

2012040248

Foreword

It is our pleasure to introduce this book on the application of catalysis to the manufacture of pharmaceuticals and fine chemicals.

Many scientists study catalysis for the thrill of discovering new knowledge, whereas the applied scientist has the additional motivation of seeking to do something useful with that knowledge. The science of catalysis, in particular, is transformed by the discipline of targeted outcomes. There are an infinite number of combinations of reactions and catalyst formulations, but only a small fraction will ever be useful in some way for mankind.

Until recently catalysis has played a modest role in the pharmaceutical and fine chemical sector, which is concerned with the manufacture of small volumes of large, and often complex, organic molecules by multi-step synthetic routes. The affordable cost of reagents, relative to the high value of the products, meant that there was little incentive to develop individual catalytic steps. This situation began to change with the growing social and industrial interest in “greener,” safer manufacturing processes, which generate less waste and avoid hazardous reagents. Economics was a driver due to the increasing cost of environmental protection and waste treatment. The potential for new catalytic methods to create new “chemical space” was a parallel attraction. Catalysis was now part of the solution, with many opportunities for innovation. In 2005, the ACS Green Chemistry Institute together with leading pharmaceutical corporations, set up the Pharmaceutical Roundtable. In a landmark study, this body developed a list of 12 key research areas for green chemistry research, including 10 types of synthetic reaction [1].

If the matching of industrial need with scientific discovery is the beginning of the story, the next stage is the achievement of efficiency and selectivity in the research laboratory. However, even then there is still much to be done. Many issues arise when a process is scaled up for commercial production, and so the successful development of new catalytic processes also needs the complementary skills of industrial application.

This was the vision for a dedicated symposium on the theme of “Challenges in Catalysis for Pharmaceuticals and Fine Chemicals,” which was jointly organized by the Applied Catalysis Group (ACG)1 of the Royal Society of Chemistry and the Fine Chemicals Group (FCG)2 of the Society of Chemical Industry. The intention from the outset was broad participation and ownership. Having canvassed opinions among our members, we set about finding authoritative speakers from industry who could describe the challenges for commercial application, and from academia who could tell us how to meet them, so combining the industrial perspective with academic reports on the scientific “state of the art.” The first meeting in 2007 was a resounding success, and has since been followed by “Challenges II” and “Challenges III” in 2009 and 2011.

In line with the aims of the “Challenges” meetings, the contents of this book have been selected to represent topical areas of catalytic synthetic chemistry, including several on the original “Challenges” list. In order to encourage a greater degree of realism in research, most subjects have been covered initially from an academic angle and then from an industrial angle.

We hope that this book will be both enjoyable and stimulating for those who are interested in this exciting field. Most of all, we hope that it will inspire both more academic discovery and more industrial application of catalysis for pharmaceuticals and fine chemicals.

John Birtill

Highcliffe Catalysis Ltd. and University of Glasgow, RSC Applied Catalysis Group

Alan Pettman

Pfizer Ltd., SCI Fine Chemicals Group and RSC Applied Catalysis Group

Notes

1.www.rsc.org/appliedcatalysis

2.www.soci.org

Reference

1. Constable DJC, Dunn PJ, Hayler JD, Humphrey GR, Leazer, Jr., JL, Linderman RJ, Lorenz K, Manley J, Pearlman BA, Wells A, Zaks A, Zhang TY (2007). Key green chemistry research areas—a perspective from pharmaceutical manufacturers. Green Chem. 9, 411–420.

Preface

“There must be a better way to make things we want, a way that doesn't spoil the sky, or the rain or the land.”

—Sir Paul McCartney

There has been an increasing awareness within the fine chemicals and pharmaceutical industry of the need to improve the environmental and production costs of synthesis, driven largely by both the perceived need to improve society's image of the industry and the tightening regulatory controls over the release of waste products and toxins into the environment. The replacement of stoichiometric reagents for synthetic transformations by catalytic routes is playing a major role in this drive toward “greener,” safer, and more economic chemical processes. The development of scalable catalytic methodologies suitable for relatively complex pharmaceutical intermediates, which often contain multiple H-bond donors and acceptors, is a significant synthetic chemical challenge. However, robust catalytic processes are increasingly emerging and have begun to make a significant impact upon the “greening” of pharmaceutical processes. The scene is thus set for an exciting period of further growth for the discovery and development of “green” catalytic processes, which will remain an important technology for the foreseeable future.

The content of the book is carefully chosen to represent key areas that are particularly important for the fine and pharmaceutical industries, including C–H, C–N, and C–C bond forming reactions, featuring chemo-, bio-, and organocatalytic approaches. It has been our aim to provide examples of the more recently discovered catalytic methodologies, particularly those that are featured on the list of reactions identified by the GCI Pharmaceutical Roundtable as “most important” or “aspirational,” as well as topical areas of catalytic synthetic chemistry that were highlighted in the “Challenges” meetings, such as the catalytic reduction of amides and esters, biocatalysis, amide formation, addressing concerns with the use of genotoxic intermediates for nucleophilic substitution, and C–H activation of aromatics.

We have enlisted an illustrious team of academic and industrial experts and leaders as contributors. In seven of the chosen topics, an academic overview of the current innovations is followed by an industrial case study at the process scale, with the aim of providing valuable insights into a catalytic methodology, from proof of concept (mg scale) to eventual application on the synthesis of organic molecules (kg to multi-tonne scale). The remits of academic/industrial research are thus united by a common theme, providing a balanced perspective on the current limitations and future challenges.

We hope that this approach will highlight the technology gap between “blue-sky” and “applied” research that will translate curiosity-driven research to the industrial manufacture of high-value chemical products that will sustain and improve quality of life, without exerting unnecessary demands on our environment and the needs of future generations.

We hope that this book provides a useful resource for both academic and industrial readers, and helps foster growing awareness of the challenges involved in this exciting and rapidly developing area. Last but not least, we thank all our authors for the high quality of their contributions, and for their patience with all our demands and deadlines.

Peter J. DunnK. K. (Mimi) HiiMichael J. KrischeMichael T. Williams

Contributors

Joanne E. Anderson, GlaxoSmithKline Inc., Research Triangle Park, NC, USA

Martin A. Berliner, Chemical Research and Development, Pfizer Inc., Groton, CT, USA

Johann Chan, Chemical Process R&D, Amgen Inc., Thousand Oaks, CA, USA; and Chemical Development, Gilead Sciences, Foster City, CA, USA

Jannine Cobb, GlaxoSmithKline Inc., Research Triangle Park, NC, USA

David J. Cole-Hamilton, School of Chemistry, University of St. Andrews, North Haugh, Fife, Scotland, UK

Justyna Czaban, Institute of Organic Chemistry, Polish Academy of Sciences, Warsaw, Poland

Roman Davis, GlaxoSmithKline Inc., Research Triangle Park, NC, USA

Deborah L. Dodds, School of Chemistry, University of St. Andrews, North Haugh, Fife, Scotland, UK; and Johnson Matthey plc, Billingham, UK

Peter J. Dunn, Pfizer Global Supply, Pfizer Ltd, Sandwich, Kent, UK

Russ N. Fitzgerald, GlaxoSmithKline Inc., Research Triangle Park, NC, USA

Hiroaki Gotoh, Department of Applied Chemistry, Graduate School of Engineering, Yokohama National University, Hodogaya-ku, Yokohama, Japan

Karol Grela, Institute of Organic Chemistry, Polish Academy of Sciences, Warsaw, Poland; and Department of Chemistry, Warsaw University, Warsaw, Poland

Yujiro Hayashi, Department Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai, Japan

Koji Hirano, Division of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita, Osaka, Japan

Jinkun Huang, Chemical Process R&D, Amgen Inc., Thousand Oaks, CA, USA; and Chengdu Suncadia Pharmaceutical Co., Ltd., A Subsidiary of Hengrui Medicine Co., Ltd., China

Jacob M. Janey, Department of Process Research, Merck Research Laboratories, Merck & Co Inc., Rahway; and Chemical Development, Bristol-Myers Squibb, New Brunswick, NJ, USA

Michael J. Krische, Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, TX, USA

Stephen P. Marsden, School of Chemistry, University of Leeds, Leeds, UK

Masahiro Miura, Division of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita, Osaka, Japan

Benjamin M. Monks, Department of Chemistry, Durham University, Durham, UK

Joseph Moran, Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, TX, USA; and ISIS, University of Strasbourg, Strasbourg, France

Alan J. Pettman, Chemical Research and Development, Pfizer Ltd, Sandwich, Kent, UK

Lionel A. Saudan, Corporate R&D Division, Firmenich SA, Geneva, Switzerland

Chris Senanayake, Chemical Development, Boehringer Ingelheim Pharmaceutical, Inc., Ridgefield, CT, USA

Christian Torborg, Department of Chemistry, Warsaw University, Warsaw, Poland

Matthew D. Truppo, Merck Research Laboratories, Rahway, NJ, USA

Nicholas J. Turner, Manchester Institute for Biotechnology, School of Chemistry, University of Manchester, Manchester, UK

Xiang Wang, Chemical Process R&D, Amgen Inc., Thousand Oaks, CA, USA; and Chemical Development, Gilead Sciences, Foster City, CA, USA

Xudong Wei, Chemical Development, Boehringer Ingelheim Pharmaceutical, Inc., Ridgefield, CT, USA

Andrew Whiting, Department of Chemistry, Durham University, Durham, UK

Jonathan M.J. Williams, Department of Chemistry, University of Bath, Claverton Down, Bath, UK

Feng Xu, Department of Process Research, Merck Research Laboratories, Rahway, NJ, USA

Nathan Yee, Chemical Development, Boehringer Ingelheim Pharmaceutical, Inc., Ridgefield, CT, USA

Abbreviations

AbbreviationsFull Name3,5-t-Bu-4-MeO-MeO-BIPHEP2,2′-Bis[di(3,5-di-tert-butyl-4-methoxyphenyl)phosphino]-6,6′-dimethoxy-1,1′-biphenylAcAcetylacacAcetylacetonateAd1-AdamantylAlkyl groupsMe, Et, n-Pr, i-Pr, sec-Bu, Pent, Hex, Hep, Octaq.Aqueous solutionBARFTetrakis(3,5-bis(trifluoromethyl)phenyl)borateBINAP2,2′-Bis(diphenylphosphino)-1,1′-binaphthylBINOL1,1′-Bi-2-naphtholBIPHEP2,2′-Bis(diphenylphosphino)-1,1′-biphenylBnBenzylBoctert-Butoxycarbonylb.p.Boiling pointbpyBipyridine/bipyridylBzBenzoyl (PhCO)CBzBenzyloxycarbonylCl,MeO-BIPHEP5,5′-Dichloro-6,6′-dimethoxy-2,2′-bis(diphenylphosphino)-1,1′-biphenylCOD1,5-CyclooctadieneCOECycloocteneCpCyclopentadienyl/cyclopentadieneCTH-P-PHOS2,2′,6,6′-Tetramethoxy-4,4′-bis(diphenylphosphino)-3,3′-bipyridineCyCyclohexyldbaDibenzylideneacetoneDBU1,8-Diazabicyclo-[5.4.0]-undec-7-eneDCE1,2-DichloroethanedeDiastereomeric excessDEADDiethyl azodicarboxylateDIADDiisopropyl azodicarboxylateDIPPF1,1′-Bis(diisopropylphosphino)ferroceneDMAcN,N-DimethylacetamideDMAPN,N-DimethylaminopyridineDME1,2-DimethoxyethaneDMFN,N-DimethylformamideDMPUN,N′-Dimethyl propylene ureaDM-SEGPHOS5,5′-Bis[di(3,5-xylyl)phosphino]-4,4′-bi-1,3-benzodioxoleDMSO/dmsoDimethylsulfoxideDPEphosBis(2-diphenylphosphinophenyl)etherDPPB1,4-Bis(diphenylphosphino)butaneDPPE1,2-Bis(diphenylphosphino)ethaneDPPF1,1′-Bis(diphenylphosphino)ferroceneDPPP1,3-Bis(diphenylphosphino)propanedrDiastereomeric ratioEDCI[3-(Dimethylamino)propyl]ethylcarbodiimideeeEnantiomeric excessequiv.Molar equivalent(s)erEnantiomeric ratioETP2-Bis(diphenylphosphinoethyl)phenylphosphineHBTUO-Benzotriazole-N,N,N′,N′-tetramethyl uronium hexafluorophosphateHOBt1-HydroxybenzotriazoleIMes1,3-Bis(2,4,6-trimethylphenyl)imidazol-2-ylideneIPr1,3-Bis(2,6-diisopropylphenyl)imidazol-2-ylideneJohnPhos2-Di(tert-butyl)phosphinobiphenylJosiphos1-[2-(Diphenylphosphino)ferrocenyl]ethyldicyclohexylphosphineMeO-BIPHEP2,2′-Bis(diphenylphosphino)-6,6′-dimethoxy-1,1′-biphenylMIBKMethyl isobutyl ketonemolMolesMsMethanesulfonylMSMolecular sievesMTBEMethyl tert-butyl etherNBDNorbornadieneNMPN-Methyl pyrrolidoneNsp-NitrophenylsulfonylPEGPoly(ethylene glycol)phenPhenanthrolinePhthPhthaloylPivPivaloyl (t-BuCO)PyPyridyl/pyridinerrRegioisomeric ratiortRoom (ambient) temperatureS/CSubstrate-to-catalyst ratioSEGPHOS5,5′-Bis(diphenylphosphino)-4,4′-bi-1,3-benzodioxoleSIMes1,3-Bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylideneTADDOLα,α,α,α-Tetraaryl-1,3-dioxolane-4,5-dimethanolTBABTetra-n-butylammonium bromideTBAFTetra-n-butylammonium fluorideTBAITetra-n-butylammonium iodideTBDPStert-ButyldiphenylsilylTBStert-ButyldimethylsilylTBTUO-(Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborateTetraphos1,2-Bis((2-(diphenylphosphino)ethyl)(phenyl)phosphino)ethaneTfTrifluoromethanesulfonylTFATrifluoroacetate or trifluoroacetic acidTHFTetrahydrofuranTIPSTriisopropylsilylTMBTP2,2′,5,5′-Tetramethyl-3,3′-bis(diphenylphosphine)-4,4′-bithiopheneTMEDAN,N,N′,N′-TetramethylethylenediamineTMSTrimethylsilylTOFTurnover frequencyTolBINAP2,2′-Bis(di-p-tolylphosphino)-1,1′-binaphthylTONTurnover numberTriphos1,1,1-Tris(diphenylphosphinomethyl)ethaneTsp-ToluenesulfonylWALPHOS1-[(R)-2-(2′-Diphenylphosphinophenyl)ferrocenyl]ethyldiphenylphosphineXantphos4,5-Bis(diphenylphosphino)-9,9-dimethylxantheneXPhos2-Dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenylXyl-BINAP2,2′-Bis[di(3,5-xylyl)phosphino]-1,1′-binaphthylXylylWALPHOS1-[-2-(2′-Di-3,5-xylylphosphinophenyl)ferrocenyl]ethyldi-3,5-xylylphosphineμ-waveMicrowave