MODERN TOOLS FOR THESYNTHESIS OF COMPLEXBIOACTIVE MOLECULES

MODERNTOOLSFORTHESYNTHESIS OF COMPLEXBIOACTIVE MOLECULES

Edited by

JANINE COSSY

STELLIOS ARSENIYADIS

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Library of Congress Cataloging-in-Publication Data:

Cossy, Janine.

Modern tools for the synthesis of complex bioactive molecules / edited by Janine Cossy and

Stellios Arseniyadis.

ISBN 978-0-470-61618-5 (hardback)

Printed in the United States of America

10 9 8 7 6 5 4 3 2 1

CONTENTS

FOREWORD vii

PREFACE ix

CONTRIBUTORS xi

CHAPTER 1 C–H FUNCTIONALIZATION: A NEW STRATEGY FOR

THE SYNTHESIS OF BIOLOGICALLY ACTIVE NATURAL PRODUCTS 1

Sophie Rousseaux, Benoıt Liegault, and Keith Fagnou

CHAPTER 2 THE NEGISHI CROSS-COUPLING IN THE SYNTHESIS

OF NATURAL PRODUCTS AND BIOACTIVE MOLECULES 33

Evelina Colacino, Jean Martinez, and Frederic Lamaty

CHAPTER 3 METAL-CATALYZED C–HETEROATOM

CROSS-COUPLING REACTIONS 77

Renata Marcia de Figueiredo, Jean Marc Campagne, and Damien Prim

CHAPTER 4 GOLDEN OPPORTUNITIES IN THE SYNTHESIS OF NATURAL

PRODUCTS AND BIOLOGICALLY ACTIVE COMPOUNDS 111

Fabien Gagosz

CHAPTER 5 METATHESIS-BASED SYNTHESIS OF COMPLEX BIOACTIVES 155

Jean-Alexandre Richard, Sin Yee Ng, and David Y.-K. Chen

CHAPTER 6 ENANTIOSELECTIVE ORGANOCATALYSIS: A POWERFUL

TOOL FOR THE SYNTHESIS OF BIOACTIVE MOLECULES 189

Mitsuru Shoji and Yujiro Hayashi

CHAPTER 7 ASYMMETRIC PHASE-TRANSFER CATALYSIS 213

Seiji Shirakawa, Shin A. Moteki, and Keiji Maruoka

CHAPTER 8 REARRANGEMENTS IN NATURAL PRODUCT SYNTHESIS 243

Jose Marco-Contelles and Elena Soriano

v

CHAPTER 9 DOMINO REACTIONS IN THE ENANTIOSELECTIVE SYNTHESIS

OF BIOACTIVE NATURAL PRODUCTS 271

Lutz F. Tietze, Scott G. Stewart, and Alexander Dufert

CHAPTER 10 FLUOROUS LINKER-FACILITATED SYNTHESIS OF BIOLOGICALLY

INTERESTING MOLECULES 335

Wei Zhang

CHAPTER 11 THE EVOLUTION OF IMMOBILIZED REAGENTS AND THEIR

APPLICATION IN FLOW CHEMISTRY FOR THE SYNTHESIS

OF NATURAL PRODUCTS AND PHARMACEUTICAL COMPOUNDS 359

Rebecca M. Myers, Kimberley A. Roper, Ian R. Baxendale,

and Steven V. Ley

CHAPTER 12 SYNTHETIC APPROACHES TO BIOACTIVE CARBOHYDRATES 395

Xavier Guinchard, Sebastien Picard, and David Crich

CHAPTER 13 AMMONIUM YLIDES AS BUILDING BLOCKS FOR

ALKALOID SYNTHESIS 433

Scott Bur and Albert Padwa

CHAPTER 14 PRECURSOR-DIRECTED BIOSYNTHESIS OF POLYKETIDE

AND NONRIBOSOMAL PEPTIDE NATURAL PRODUCTS 485

Colin J. B. Harvey and Chaitan Khosla

CHAPTER 15 TARGET-ORIENTED AND DIVERSITY-ORIENTED

ORGANIC SYNTHESIS 513

Raphael Rodriguez

CHAPTER 16 DNA AS A TOOL FOR MOLECULAR DISCOVERY 539

Michael Smietana, Jean-Jacques Vasseur, Janine Cossy,

and Stellios Arseniyadis

INDEX 557

vi CONTENTS

FOREWORD

Thanks to a rich evolution over the past century, organic synthesis has allowed the

preparation of complex molecules and new materials with incredible properties. One

of the main challenges is to find new and better ways to access complex molecules in

an atom- and step-economical process (ASEP). To this end, novel and highly selective

reagents and chemical reactions have been developed.

This book, Modern Tools for the Synthesis of Complex Bioactive Molecules,

contains 16 chapters, with particular emphasis given to organic, organometallic, and

bio-oriented processes. The first part is directed toward the development of catalytic

systems for C–H functionalizations, cross-couplings, and reactions involving organo-

metallic catalysts, organocatalysts, and bioorganic catalysts. The second part covers

some of the most recent ASEP methods developed so far, such as domino reactions

and rearrangements. The last two parts of the book are dedicated to the use of efficient

tools for the synthesis of complex bioactives, in particular, carbohydrates and

alkaloids, as well as to new techniques, such as the use of fluorous tags, flow

chemistry, engineered biosynthesis, target- and diversity-oriented synthesis, and

DNA-based asymmetric catalysis.

This book is an excellent source of inspiration for those planning the synthesis

of complexmolecules in themost efficientmanner, for getting a hint on how to solve a

specific synthetic problem, or simply for having fun discovering new chemistries and

elaborating future chemical tools.

E. Negishi

vii

PREFACE

In aworldwhere atom-, step-, redox-, and pot-economyhave become someof themost

important challenges in synthetic organic chemistry, the development of innovative

and synthetically useful tools has more than not transfigured the way chemists devise

their syntheses of complex biologically active molecules. Thus, the idea behind this

book was to emphasize the impact of modern synthetic tools on the synthesis of

complex biologically active compounds, and show how they have provided new and

elegant solutions tomany synthetic puzzles. In this context, we decided to dedicate the

first part of this book to modern catalysis with a special emphasis given to various key

transformations such as C–H functionalizations (Chapter 1, S. Rousseaux, B. Liegault,

and K. Fagnou), cross-couplings (Chapter 2, E. Colacino, J. Martinez, and F. Lamaty

and Chapter 3, R. Marcia de Figueiredo, J.-M. Campagne, and D. Prim), gold-

catalyzed reactions (Chapter 4, F. Gagosz), metathesis-based syntheses (Chapter 5,

J.-A. Richard, S. Y. Ng, and D. Y.-K. Chen), and asymmetric organocatalysis

(Chapter 6,M. Shoji and Y. Hayashi and Chapter 7, S. Shirakawa, S. A. Moteki, and

K. Maruoka). The second part of the book provides a broad coverage of some of the

most elegant and eco-compatible transformations developed so far, such as rearrange-

ments (Chapter 8, J. Marco-Contelles and E. Soriano) and domino reactions

(Chapter 9, L. F. Tietze, S. G. Stewart, and A. D€ufert). The third part of the book

is dedicated to the development of specific tools for the synthesis of carbohydrates

(Chapter 12, X. Guinchard, S. Picard, and D. Crich) and alkaloids (Chapter 13, S. Bur

and A. Padwa), while the fourth part unveils some of the most recent techniques, such

as the use of fluorous tags (Chapter 10, W. Zhang), flow chemistry (Chapter 11,

R. M. Myers, K. A. Roper, I. R. Baxendale, and S. V. Ley) and engineered biosynthesis

(Chapter 14,C. J. B. Harvey and C. Khosla). Finally, the last two chapters of this book

are dedicated to two prospective methods, namely, target- and diversity-oriented

organic synthesis (Chapter 15, R. Rodriguez) and the use of DNA-based asymmetric

catalysis (Chapter 16,M.Smietana, J.-J. Vasseur, J.Cossy, andS. Arseniyadis) that are

particularly promising tools for the synthesis of complex bioactive molecules.

We would like to warmly thank all the authors for their enthusiasm, patience,

professionalism, andmost of all, their particularly didactic and detailed contributions.

We also would like to thank the team at John Wiley & Sons, especially Anita

Lekhwani, Sanchari Sil, and Angioline Loredo, for their helpful assistance during the

entire preparation of this book.

Finally, we hope you will enjoy reading this book as much as we have enjoyed

preparing it. We believe it will be a valuable source of information for both academic

and industrial researchers, as well as to undergraduate and graduate students all over

the world.

Janine Cossy and Stellios Arseniyadis

ix

CONTRIBUTORS

Stellios Arseniyadis, Laboratoire de Chimie Organique, UMR 7084 CNRS ESPCI

ParisTech, Paris, France

Ian R. Baxendale, Department of Chemistry, University of Cambridge, Cambridge,

United Kingdom

Scott Bur, Department of Chemistry, Emory University, Atlanta, Georgia, USA

Jean Marc Campagne, Institut Charles Gerhardt Montpellier, UMR 5253 CNRS-

UM2-UM1-ENSCM, Ecole Nationale Superieure de Chimie, Montpellier, France

David Y.-K. Chen, Department of Chemistry, Seoul National University, Seoul,

South Korea

Evelina Colacino, Institut des Biomolecules Max Mousseron, Universite Montpel-

lier 2, Montpellier, France

Janine Cossy, Laboratoire de Chimie Organique, UMR 7084 CNRS ESPCI

ParisTech, Paris, France

David Crich, Institut de Chimie des Substances Naturelles, Gif-sur-Yvette, France

Renata Marcia de Figueiredo, Institut Charles Gerhardt Montpellier, UMR 5253

CNRS-UM2-UM1-ENSCM, Ecole Nationale Superieure de Chimie, Montpellier,

France

Alexander D€ufert, Institut f€ur Organische und Biomolekulare Chemie, Universit€atG€ottingen, G€ottingen, Germany

Keith Fagnou, Department of Chemistry, University of Ottawa, Ottawa, Ontario,

Canada

Fabien Gagosz, Laboratoire de Synthese Organique, UMR 7652 CNRS Ecole

Polytechnique, Palaiseau, France

Xavier Guinchard, Institut de Chimie des Substances Naturelles, Gif-sur-Yvette,

France

Colin J. B. Harvey, Department of Chemistry, Chemical Engineering, and Bio-

chemistry, Stanford University, Stanford, California, USA

Yujiro Hayashi, Department of Industrial Chemistry, Tokyo University of Science,

Tokyo, Japan

Chaitan Khosla, Department of Chemistry, Chemical Engineering, and Biochem-

istry, Stanford University, Stanford, California, USA

xi

Frederic Lamaty, Institut des Biomolecules Max Mousseron, Universite Montpel-

lier 2, Montpellier, France

Steven V. Ley, Department of Chemistry, University of Cambridge, Cambridge,

United Kingdom

Benoıt Liegault, Department of Chemistry, University of Ottawa, Ottawa, Ontario,

Canada

Jose Marco-Contelles, Laboratorio de Qu�ımica Medica y Computacional, Instituto

de Qu�ımica Org�anica General, Madrid, Spain

Jean Martinez, Institut des Biomolecules Max Mousseron, Universite Montpellier

2, Montpellier, France

Keiji Maruoka, Department of Chemistry, Kyoto University, Sakyo, Kyoto, Japan

Shin A. Moteki, Department of Chemistry, Kyoto University, Sakyo, Kyoto, Japan

Rebecca M. Myers, Department of Chemistry, University of Cambridge,

Cambridge, United Kingdom

Sin Yee Ng, Department of Chemistry, Seoul National University, Seoul, South

Korea

Albert Padwa, Department of Chemistry, EmoryUniversity, Atlanta, Georgia, USA

Sebastien Picard, Institut de Chimie des Substances Naturelles, Gif-sur-Yvette,

France

Damien Prim, Universite Versailles-St-Quentin-en-Yvelines, Institut Lavoisier de

Versailles UMR CNRS 8180, Versailles, France

Jean-Alexandre Richard, Department of Chemistry, Seoul National University,

Seoul, South Korea

Rapha€el Rodriguez, Department of Chemistry, Cambridge University, Cambridge,

United Kingdom

Kimberley A. Roper, Department of Chemistry, University of Cambridge,

Cambridge, United Kingdom

Sophie Rousseaux, Department of Chemistry, University of Ottawa, Ottawa,

Ontario, Canada

Seiji Shirakawa, Department of Chemistry, Kyoto University, Sakyo, Kyoto, Japan

Mitsuru Shoji, Department of Industrial Chemistry, Tokyo University of Science,

Tokyo, Japan

Michael Smietana, Institut des Biomolecules Max Mousseron, UMR 5247 CNRS,

Universite de Montpellier 1 et 2, Montpellier, France

Elena Soriano, Laboratorio de Qu�ımica Medica y Computacional, Instituto de

Qu�ımica Org�anica General, Madrid, Spain

xii CONTRIBUTORS

Scott G. Stewart, Institut f€ur Organische und Biomolekulare Chemie, Universit€atG€ottingen, G€ottingen, Germany

Lutz F. Tietze, Institut f€ur Organische und Biomolekulare Chemie, Universit€atG€ottingen, G€ottingen, Germany

Jean-Jacques Vasseur, Institut des Biomolecules Max Mousseron, UMR 5247

CNRS, Universite de Montpellier 1 et 2, Montpellier, France

Wei Zhang, Department of Chemistry, University of Massachusetts, Boston,

Massachusetts, USA

CONTRIBUTORS xiii