Foreword

The notion of cleaving strong and seemingly inert C–H bonds has been a concept that has intrigued and inspired chemists for nearly a century. The fundamental reactivity and rich mechanistic implication of metal insertion into C–H bonds has attracted chemists from different fields into a wonderland of opportunity since the 1970s. Over the past several decades, subsequent functionalization of such carbon–metal species were made catalytic, and various redox catalytic cycles are now established to deliver synthetically relevant, diverse transformations. Most recently, the ability to perform C–H activation reactions on abundant and broadly useful substrates represents another major step forward towards widespread adoption of C–H activation reactions in organic synthesis. However, for C–H activation to impact asymmetric synthesis, general and efficient asymmetric C–H activation reactions must be developed.

Strictly speaking, asymmetric C–H functionalization reactions refer to those transformations in which the newly defined stereochemistry is controlled by the C–H cleavage step. For example: the carbene, nitrene, and metal-oxo chemistry, as well as the organometallic metal insertion chemistry, have been demonstrated to perform asymmetric C–H activation in this manner. Generally, a new chiral center is created by cleaving a prochiral C–H bond (with the exception of atroposelective C–H cleavage or kinetic resolution via C–H activation). In the interests of readers and practitioners, however, the authors have taken a broader view and included other types of asymmetric transformations that involve C–H cleavage as one of the non-enantio determining steps. Notably, functionalization of highly acidic or weak C–H bonds adjacent to heteroatoms are also discussed. Indeed this approach allows for the inclusion of a larger number of important asymmetric processes and showcases how C–H activation can be connected to asymmetric catalysis. Comprehensive discussions on a broad range of approaches adopted in asymmetric catalysis based on C–H activation chemistry greatly enrich this book and will benefit the readers tremendously.

In conclusion, asymmetric C–H functionalization has emerged as a new avenue for developing asymmetric catalysis and will create practical and enabling synthetic disconnections for asymmetric synthesis in the foreseeable future. This fine book comprehensively details the historic development and state-of-the-art of asymmetric C–H functionalization processes. Various different types of approaches or transformations are also meticulously categorized to improve readability. I anticipate that this book will be a popular and insightful tool for those who are interested in this rapidly rising and yet underdeveloped field.

Jin-Quan Yu

La Jolla, California