4.14 Vinyl Substitutions with Organopalladium Intermediates

Abstract

This chapter collates the relevant literature on the Heck reaction, the vinylation of aryl/vinyl halides or triflates in the presence of a base and catalyzed by Pd(0) complexes. Descriptions of the currently accepted catalytic cycles of the Heck reaction are discussed in order to understand the concepts underpinning the significant recent developments of this carbon–carbon bond forming process for the construction of functionalized alicyclic and cyclic compounds. The Heck reaction has undergone significant catalyst development and the application of new ligands, the extension of substrate scope, improvements in regioselectivity and its application in domino processes will be described. Much progress has been made in the application of the Heck reaction for the formation of cyclic compounds and examples of the formation of three- to nine-membered rings, many related to the key steps of natural product syntheses, have been given. The asymmetric inter- and intramolecular Heck and related reactions are also comprehensively reviewed, from their original development to recent advances in terms of substrate scope, reactivity, regio-, and enantioselectivity. The design and application of new chiral ligands has been pivotal to reaction enhancements and, for each Heck and related process, we classify ligands by the nature of the denticity, chirality, and donor atoms involved. In this manner, the continued development of ligand architectural design and application can be more easily monitored for each process. Although significant improvements were noted in reaction times, a disadvantage in many Heck reactions, has been addressed through a combined use of microwave (MW)-assisted protocols and ligand design. The Fujiwara–Moritani and oxidative boron Heck-type reactions, recent additions to Heck-type processes, will also be discussed. As with many Pd-catalyzed processes, the Heck reaction has been applied to combinatorial synthesis employing solid-phase supports, in addition to this, the employment of new reaction media and heating techniques and progress in these areas will be described. Finally, the key test of the importance of a synthetic transformation is its utility in natural product synthesis and selected examples of such applications of the Heck reaction are given.