Second Edition
This edition first published 2020
© 2020 John Wiley & Sons Inc.
Edition History
John Wiley & Sons Inc. (1e, 2011)
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Library of Congress Cataloging-in-Publication Data
Names: Caron, Stéphane, editor.
Title: Practical synthetic organic chemistry : reactions, principles, and techniques / edited by Stéphane Caron.
Description: Second edition. | Hoboken, NJ : Wiley, [2020] | Includes bibliographical references and index.
Identifiers: LCCN 2019024991 (print) | LCCN 2019024992 (ebook) | ISBN 9781119448853 (paperback) | ISBN 9781119448884 (adobe pdf) | ISBN 9781119448907 (epub)
Subjects: LCSH: Organic compounds–Synthesis.
Classification: LCC QD262 .P688 2020 (print) | LCC QD262 (ebook) | DDC 547/.2–dc23
LC record available at https://lccn.loc.gov/2019024991
LC ebook record available at https://lccn.loc.gov/2019024992
Cover Design: Wiley
Cover Image: © Sebastian Kaulitzki/Shutterstock
Dedicated to the memory of
Frank R. Busch and Mark E. Webster
Two outstanding scientists and friends who left us too soon and to Jean-Yves Caron an exceptional father and role model
When I was approached to prepare a second edition of Practical Synthetic Organic Chemistry, my first inclination was to decline the opportunity remembering the years it took to put together the first edition of the manuscript thanks to the excellent contributions made by my industry collaborators. However, as I reflected on the advancements in the field of synthetic organic chemistry since the publication of our book in 2011, I realized the magnitude of the changes in terms of novel synthetic methodologies, manufacturing technologies, analytical techniques, and multidisciplinary contributions from fields such as engineering, molecular biology, computational assistance, robotics, and automation. The science of synthetic organic chemistry is ever expanding and continues to blossom, impacting multiple industries in a fast-paced and technologically driven global economy. After discussions with many of my contributors, we committed to the preparation of this edition.
The Second Edition of the book retains its original intent: to guide scientists toward proven synthetic methods that have the highest probability of success having been demonstrated on a practical scale. The content differs from several other textbooks which might focus on first principles and reaction mechanisms. In a digital world, where it is becoming increasingly easier to identify potential solutions to a given transformation, Practical Synthetic Organic Chemistry provides a more concise, focused list of likely reaction conditions that could rapidly lead to a desired outcome, especially when an experimentalist may be limited by the amount of starting materials available or not be able to screen a vast array of experimental possibilities. While an explanation is not always provided for the selection of the specific examples shown, the general rule in our methodology was that the conditions described were found to work on a variety of substrates from the primary literature, and that a representative example with an experimental procedure on multigram scale be available.
Building from the First Edition, we sought novel examples that may be superior to what was originally available in 2011. We also included several new reactions from synthetic methods that have emerged or increased in predictability and robustness in the last eight years. When possible, we have used primary references from Organic Process Research and Development (OPR&D), the Journal of Organic Chemistry (JOC), and Organic Syntheses (Org. Syn.), as the experimental procedures from these publications are experimentally robust and would guide scientists conducting a specific reaction for the first time.
There are several key changes from the original edition. The first part of the book (Chapters 1–11) remains focused on reactions based on the type of synthetic transformations. The second part (Chapters 12–19) discusses techniques and additional information that may influence scientists on selecting how to conduct a reaction and preferred conditions including solvent selection, how to safely quench a reaction, and when to use continuous chemistry. The original chapters (Aliphatic Nucleophilic Substitution, Addition to Carbon–Heteroatom Multiple Bonds, Addition to Carbon–Carbon Multiple Bonds, Nucleophilic Substitution and Electrophilic Substitution) have kept a similar structure to the First Edition, providing contemporary examples and new content.
Chapter 6 has been changed from Selected Metal-Mediated Cross-Coupling Reactions to Selected Catalytic Reactions. As the field of catalysis, most notably homogenous catalysis, and the level of understanding and predictability of these reactions has grown significantly in the last decade, we felt this chapter needed to be expanded accordingly. It not only covers the previous substrate in much more detail, it also includes a section on catalytic halogenations and preparation of fluorinated compounds, organocatalysis, and metal-mediated C–H functionalization all of which has been area of extensive research in recent years.
Similar updates have been made to Chapters 7–10 covering rearrangements, elimination, reductions, and oxidations. Chapter 11, Selected Free Radical Reactions, has been extensively updated with focus on Photoredox Catalysis and Electrochemistry, as these topics have received much more attention and provided useful synthetic methods in recent years. Chapter 12 on the Synthesis of Organometallic Reagents has kept the similar organizational structure and content. Chapter 13 on The Synthesis of Common Aromatic Heterocycles has been expanded to include additional ring systems and providing clarity on the heterocycles selected and order of presentation in the chapter. Chapter 14 on Access to Chirality continues to exemplify strategies that differ from chiral synthesis that are covered in the previous chapters.
The First Edition chapter on the development of contemporary pharmaceutical drugs was omitted as this area is constantly evolving and many other sources are now publishing this content. Chapter 15 is now a totally new chapter on Biocatalysis. While enzyme-catalyzed reactions were known and used when the First Edition was published, this field of research has exploded in the last decade with many advancements in molecular biology. The scope and practicality for synthetic organic chemistry based on these findings has been truly remarkable. This new chapter covers four key classes of reactions and offers insights on future developments in this discipline.
Chapter 16 on Green Chemistry was expanded as new metrics have been developed, and several new examples are provided. However, the chapters on Naming Carbocycles and Heterocycles and pKa have been eliminated as computational tools are now routinely used to obtain this information (something the majority of us are grateful for). A completely new Chapter 17 discusses Continuous Chemistry describing the principles for evaluating reactions or developing a chemical process using continuous processing. Numerous examples based on reaction type are included. Chapter 18 on General Solvent Properties and Chapter 19 on Practical Chemistry Concepts have been updated to include additional data and new examples.
Like the previous edition, we created two indexes. The first index is based on functional groups manipulation (i.e. how to obtain one functional group by reaction of a starting material containing another functional group). The second is based on reaction, reagent, or structural names.
I am incredibly grateful to all the contributors of this Second Edition. Based on feedback received, several authors for companies outside of Pfizer made significant contributions to this revised manuscript, and their insights provided additional perspectives. While these changes led to some additional logistical challenges, the dedication and professionalism from each of these already very busy scientists is greatly appreciated.
November 2019
Stéphane Caron
Pfizer Worldwide R&D
Groton, CT, USA