Heck macrocyclization in natural product total synthesis

Covering: 1981-2020 Heck macrocyclization is a logical extension of the award-winning Mizoroki-Heck reaction. Through covalent linking of two otherwise discrete coupling partners, the resultant chimeric substrate is transformed into a large ring with enhanced rigidity and unique functional group disposition. Pioneered in the early 1980s, this methodology has evolved into a competent option for creating diverse macrocycles. Despite its growing influence, hitherto no systematic survey has ever appeared in the literature. The present review delineates the state-of-the-art of Heck macrocyclization in the context of natural product synthesis. Sixteen selected cases, each examined from a different perspective, coalesce into the view that the title reaction is a viable tool for synthesis-enabled macrocycle research.