Science of Synthesis

Shibasaki, M.; Ohshima, T.; Itano, W., Science of Synthesis: Stereoselective Synthesis, (2011) 3, 483.

General Introduction

The palladium-mediated coupling of aryl or alkenyl iodides, bromides, or trifluoromethanesulfonates with alkenes in the presence of base, i.e. the metal-catalyzed arylation or alkenylation of alkenes, is generally referred to as the Mizoroki–Heck reaction.[‌1‌–‌12‌] Since the pioneering work of Mizoroki and co-workers[‌13‌] and Heck and co-workers[‌14‌] in the late 1960s, the reaction has been extensively developed and deployed in the synthesis of various complex natural products, pharmaceuticals, agrochemicals, dyes, functional materials, and other important molecules. The Heck reaction is not limited to activated alkenes: simple alkenes and those with various functional groups, such as ester, ether, carboxy, phenolic, and cyano functionalities are also suitable substrates. Despite many of the benefits usually associated with palladium-mediated reactions,[‌15‌] in particular scalability, tolerance of water and functional groups, interest in the reaction has been sporadic, which is primarily due to problems associated with regiochemical control in unsymmetrical alkene substrates. In fact, both regioselectivity (α and β) and geometrical selectivity (E and Z) have been found to be notoriously difficult to control in intermolecular reactions. In contrast, the tether length and the ligands on the metal center determine the regioselectivity of intramolecular reactions. Additionally, the importance of the asymmetric construction of chiral tertiary and quaternary stereocenters by C—C bond formation has prompted the development of the asymmetric variant of the Mizoroki–Heck reaction. Nevertheless, the reaction was not initially applied to the construction of stereogenic centers,[‌1‌] and chelating diphosphines were generally considered to provide unsuitable catalysts.[‌16‌] Despite the many developments with chiral phosphine ligands dating from the early 1970s,[‌17‌] the asymmetric Heck reaction was not explored until the late 1980s.[‌18‌,‌19‌] In more recent years, interest in this reaction has increased dramatically, with the development of a variety of stereoselective reactions, including asymmetric variants.

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References