Preface

From the first isolation of a boronic acid by Frankland in 1860 to the report of their palladium-catalyzed cross-coupling with carbon halides by Suzuki and Miyaura in 1979, advances in the chemistry and biology of boronic acids have been few and far between. The early 1980's announced a drastic turn. In the past decade alone, numerous breakthroughs have been reported. From the discovery of rhodium-catalysed couplings with alkenes and aldehydes to the commercialisation of Velcade^®, the first boronic acid drug used in human health therapy, new applications of boronic acids have been reported at a spectacular rate. As seen on the histogram below, the number of publications focused on boronic acid derivatives has increased exponentially, elevating boronic acids to a new status, that of a prized class of organic compounds.

This sudden rise in the usefulness and popularity of boronic acids necessitated a comprehensive book on their chemistry and biology. In just a few years working in the field of boronic acid chemistry, I had quickly come to regret the absence of a specialised book on this topic. Thus, I could not turn down an opportunity to help fulfill this need and lead such a project. I was most fortunate to assemble a select group of experts that literally includes legends in the field. The result is a book containing 13 chapters that cover all modern aspects of boronic acid derivatives. All efforts were made to achieve comprehensive coverage of the literature up to 2004, with particular emphasis on topics of great interest to a large audience of synthetic organic, organometallic, and medicinal chemists.

Our current understanding of the structure and properties of boronic acids, their important ester derivatives and other parent compounds like trifluoroborate salts, is described in Chapter 1. The limited number of methods for the preparation of boronic acid derivatives had long impeded their use as synthetic reagents. The outlook is changing rapidly, however, and Chapter 1 describes modern methods for the preparation of all types of boronic acid derivatives, with several useful tables of examples. It also provides an overview of their synthetic, biological, and medicinal applications. One of the latest advances in the preparation of boronic acids, the use of C-H activation/borylation methods, is discussed in Chapter 2. Much has happened in the development of new conditions and catalysts to expand the scope of transition metal catalysed C-C bond formation processes using boronic acids. Chapter 3 describes the most recent advances in the Suzuki cross-coupling between aromatic boronic acids and aromatic halides. A few years ago, rhodium(I) complexes were found to catalyse the addition of boronic acids to enones and aldehydes. These discoveries have now flourished into highly efficient catalytic enantioselective processes that can afford functionalyzed products in over 99% optical purity. All the details of such impressive advances are reviewed in Chapter 4. The copper-catalysed coupling of boronic acids with heteroatom functionalities like phenols, amines, and amides is yet another recent synthetic application that has contributed to the recent emergence of boronic acids as a popular class of reagents. This new and useful process, described in Chapter 5, has become firmly established in natural product synthesis and medicinal chemistry research. Already a workhorse in the synthesis of polypropionate compounds, the addition of allylboronates to carbonyl compounds is still getting increasing attention as a result of recent improvements in the preparation of functionalised allylboronates. These new preparative methods and other advances such as the Lewis acid-catalysed allylboration and tandem processes are described in Chapter 6. The important discovery that boronic acids add to imine derivatives and iminium ions, even in a three-component fashion, has been exploited in a number of synthetic applications and progress in this area is reviewed for the first time in Chapter 7. Described in Chapter 8 is the chemistry of alpha-haloalkyl boronic esters, including the seminal Matteson homologation, which has led to a rich field of asymmetric synthesis with applications to the construction of complex natural products and to the preparation of alpha-aminoalkyl boronic acids employed as enzyme inhibitors. Another important area of investigation focuses on the use of unsaturated boronic esters in a wide variety of electrophilic additions and cycloadditions. As described in Chapter 9, the new boronic acid products of these reactions can be exploited further by making use of the numerous possibilities of transformations offered by the residual boronate group. Boronic acids and several of their ester derivatives can serve as stable and mild Lewis acids, and this unique property has inspired the development of catalysts for several reaction processes, including asymmetric transformations; this topic is reviewed in Chapter 10. Likewise, the use of chiral oxazaborolidines in the asymmetric reduction of ketones and imine derivatives is described in Chapter 11. The ability of boronic acids to form reversible covalent adducts with the diol units of carbohydrates has been exploited in the development of receptors for saccharides. Of particular interest is the development of sensors to measure the blood glucose level of diabetes patients, and a comprehensive review of this intensive area of research is presented in Chapter 12. Boronic acids have long been known to bind and inhibit the action of certain classes of proteolytic enzymes. This important topic, as well as the potential of boronic acids as boron neutron capture agents, is discussed inCha

The success of a book project relies heavily on the involvement of several dedicated individuals. I would like to thank all authors and co-authors who have generously agreed to contribute a chapter. Their expert participation and professionalism was an invaluable asset to this ambitious project. Grateful acknowledgements are also offered to the Wiley-VCH editorial staff, in particular to Elke Maase and Renate Doetzer. For their valued support in various stages of editing this book I am also indebted to Hugo Lachance, Barry Touré, Duane Stones, Siu HongYu,VivekRauniyar, Lisa Carosi, Meena Dowlut, Agnieszka Ulaczyk-Lesanko, Diane Burke, Tim Elford, Xuri Gao, Feng Peng, and Annie Tykwinski (Book cover).