Practical Synthetic Organic Chemistry: Reactions, Principles, and Techniques 2nd Edition

Book Preface

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
PfizerWorldwide R&D
Groton, CT, USA