||Carbon-carbon bond-forming reactions are arguably the most important processes in chemistry, as they represent key steps in the building of more complex molecules from simple precursors. In the past 50-100 years, organic chemists have developed a plethora of reactions for carbon-carbon bond formation between molecules with saturated sp3 C-atoms. However, until the discovery mid development of metal-mediated cross-coupling reactions, starting in the 1970s, there were no simple, general direct methodologies known for carbon-carbon bond formation between unsaturated species such as vinyl, aryl, and alkynyl moieties. In other words, carbon-carbon bond formation between sp and sp2 C-atom centers was often difficult and tedious. In the intervening 25 years, a wide variety of cross-coupling methodologies have been developed and cross-coupling reactions have emerged among the most powerful and useful synthetic tools in chemistry.
Metal-catalyzed cross-coupling reactions are extensively employed in a wide range of areas of preparative organic chemistry, from the synthesis of complex natural products to supramolecular chemistry and materials science. For example, the formation of new carbon-rich polymers and networks by acetylenic molecular scaffolding, the development of many abiotic receptors, and the preparation of many dendrimers depends heavily on modern cross-coupling methodologies. In fact, in the 1990s one can hardly open a chemical journal in the broad area of organic chemistry or materials science that does not contain several examples of cross-coupling reactions.
Many of the metal-mediated cross-coupling reactions discussed in this book follow a similar mechanistic scheme. The general features of the catalytic cycles are currently quite well understood and involve an oxidative addition-transmetallation-reductive elimination sequence. The reaction is initiated by the oxidative addition of the electrophile to the zero-valent metal. The most widely used active catalysts are diverse Ni(0) and Pd(0) complexes with organic inflates or halides (mostly iodides or bromides; rarely chlorides) as the electrophilic partners. A wide variety of organometallic reagents (organo-boron-aluminum, -copper, -zirconium, -silicon, -tin, etc.) serve as nucleophiles. However, the details of the individual steps, and in particular the transmetallation process, are less well understood and the reaction pathways are highly dependent upon the specific organometallic nucleophiles as well as reaction conditions.
In this multi-authored monograph, a dozen experts and leaders in the field bring the reader up to date by documenting and critically analyzing current developments and uses of metal-catalyzed cross-coupling reactions. The various methodologies involving organo-silicon, -copper, -tin, -zinc, -zirconium, -aluminum, and -boron reagents, as well as the diverse uses of 1,4-additions to 1,3-dienes, carbometallations, and carbonylations, in natural product synthesis are covered. Emphasis is placed upon key developments and important advances, which are illustrated with attractive and useful examples.