Preface

In 1929, Dirac famously proclaimed that

This book is a testament to just how difficult it is to adequately account for the properties and reactivities of real chemical systems using quantum mechanics (QM).

Though QM was born in the mid-1920s, it took many years before rigorous solutions for molecular systems appeared. Hylleras2 and others3, 4 developed nearly exact solutions to the single-electron diatomic molecule in the 1930s and 1940s. Reasonable solutions for multielectron multiatom molecules did not appear until 1960, with Kolos'5, 6 computation of H2 and Boys'7 study of CH2. The watershed year was perhaps 1970 with the publication by Bender and Schaefer8 on the bent form of triplet CH2 (a topic of Chapter 5) and the release by Pople's9 group of Gaussian-70, which is the first full-featured quantum chemistry computer package that was to be used by a broad range of theorists and nontheorists alike. So, in this sense, computational quantum chemistry is really only some five decades old.

The application of QM to organic chemistry dates back to Hückel's π-electron model of the 1930s.10–12 Approximate quantum mechanical treatments for organic molecules continued throughout the 1950s and 1960s. Application of ab initio approaches, such as Hartree–Fock theory, began in earnest in the 1970s and really flourished in the mid-1980s, with the development of computer codes that allowed for automated optimization of ground and transition states and incorporation of electron correlation using configuration interaction or perturbation techniques.

In 2006, I began writing the first edition of this book, acting on the notion that the field of computational organic chemistry was sufficiently mature to deserve a critical review of its successes and failures in treating organic chemistry problems. The book was published the next year and met with a fine reception.

As I anticipated, immediately upon publication of the book, it was out of date. Computational chemistry, like all science disciplines, is a constantly changing field. New studies are published, new theories are proposed, and old ideas are replaced with new interpretations. I attempted to address the need for the book to remain current in some manner by creating a complementary blog at http://www.comporgchem.com/blog. The blog posts describe the results of new papers and how these results touch on the themes presented in the monograph. Besides providing an avenue for me to continue to keep my readers posted on current developments, the blog allowed for feedback from the readers. On a few occasions, a blog post and the article described engendered quite a conversation!

Encouraged by the success of the book, Jonathan Rose of Wiley approached me about updating the book with a second edition. Drawing principally on the blog posts, I had written since 2007, I knew that the ground work for writing an updated version of the book had already been done. So I agreed, and what you have in your hands is my perspective of the accomplishments of computational organic chemistry through early 2013.

The structure of the book remains largely intact from the first edition, with a few important modifications. Throughout this book. I aim to demonstrate the major impact that computational methods have had upon the current understanding of organic chemistry. I present a survey of organic problems where computational chemistry has played a significant role in developing new theories or where it provided important supporting evidence of experimentally derived insights. I expand the scope to include computational enzymology to point interested readers toward how the principles of QM applied to organic reactions can be extended to biological system too. I also highlight some areas where computational methods have exhibited serious weaknesses.

Any such survey must involve judicious selecting and editing of materials to be presented and omitted. In order to reign in the scope of the book, I opted to feature only computations performed at the ab initio level. (Note that I consider density functional theory to be a member of this category.) This decision omits some very important work, certainly from a historical perspective if nothing else, performed using semiempirical methods. For example, Michael Dewar's influence on the development of theoretical underpinnings of organic chemistry13 is certainly underplayed in this book since results from MOPAC and its decedents are largely not discussed. However, taking a view with an eye toward the future, the principle advantage of the semiempirical methods over ab initio methods is ever-diminishing. Semiempirical calculations are much faster than ab initio calculations and allow for much larger molecules to be treated. As computer hardware improves, as algorithms become more efficient, ab initio computations become more practical for ever-larger molecules, which is a trend that certainly has played out since the publication of the first edition of this book.

The book is designed for a broad spectrum of users: practitioners of computational chemistry who are interested in gaining a broad survey or an entrée into a new area of organic chemistry, synthetic and physical organic chemists who might be interested in running some computations of their own and would like to learn of success stories to emulate and pitfalls to avoid, and graduate students interested in just what can be accomplished by computational approaches to real chemical problems.

It is important to recognize that the reader does not have to be an expert in quantum chemistry to make use of this book. A familiarity with the general principles of quantum mechanics obtained in a typical undergraduate physical chemistry course will suffice. The first chapter of this book introduces all of the major theoretical concepts and definitions along with the acronyms that so plague our discipline. Sufficient mathematical rigor is presented to expose those who are interested to some of the subtleties of the methodologies. This chapter is not intended to be of sufficient detail for one to become expert in the theories. Rather it will allow the reader to become comfortable with the language and terminology at a level sufficient to understand the results of computations and understand the inherent shortcoming associated with particular methods that may pose potential problems. Upon completing Chapter 1, the reader should be able to follow with relative ease a computational paper in any of the leading journals. Readers with an interest in delving further into the theories and their mathematics are referred to three outstanding texts, Essential of Computational Chemistry by Cramer,14 Introduction to Computational Chemistry by Jensen,15 and Modern Quantum Chemistry: Introduction to Advanced Electronic Structure Theory by Szabo and Ostlund.16 In a way, this book serves as the applied accompaniment to these books.

How is the second edition different from the first edition? Chapter 1 presents an overview of computational methods. In this second edition, I have combined the descriptions of solvent computations and molecular dynamics computations into this chapter. I have added a discussion of QM/molecular mechanics (MM) computations and the topology of potential energy surfaces. The discussion of density functional theory is more extensive, including discussion of double hybrids and dispersion corrections. Chapter 2 of the second edition is mostly entirely new. It includes case studies of computed spectra, especially computed NMR, used for structure determination. This is an area that has truly exploded in the last few years, with computed spectra becoming an important tool in the structural chemists' arsenal. Chapter 3 discusses some fundamental concepts of organic chemistry; for the concepts of bond dissociation energy, acidity, and aromaticity, I have included some new examples, such as π-stacking of aromatic rings. I also added a section on isomerism, which exposes some major problems with families of density functionals, including the most commonly used functional, B3LYP.

Chapter 4 presents pericyclic reactions. I have updated some of the examples from the last edition, but the main change is the addition of bispericyclic reactions, which is a topic that is important for the understanding of many of the examples of dynamic effects presented in Chapter 8. Chapter 5 deals with radicals and carbenes. This chapter contains one of the major additions to the book: a detailed presentation of tunneling in carbenes. The understanding that tunneling is occurring in some carbenes was made possible by quantum computations and this led directly to the brand new concept of tunneling control.

The chemistry of anions is the topic of Chapter 6. This chapter is an update from the material in the first edition, incorporating new examples, primarily in the area of organocatalysis. Chapter 7, presenting solvent effects, is also updated to include some new examples. The recognition of the role of dynamic effects, situations where standard transition state theory fails, is a major triumph of computational organic chemistry. Chapter 8 extends the scope of reactions that are subject to dynamic effects from that presented in the first edition. In addition, some new types of...