Total Synthesis of Apicularen A through Transannular Pyran Formation

Abstract

A macrocyclization–transannulation strategy is the crux of an efficient total synthesis of the benzolactone enamide apicularen A (see scheme; Bn=benzyl). Key steps include a four-component coupling, a Stille cross-coupling to introduce the aromatic moiety, and the formation of the enamide from a hemiaminal. The size-selective macrolactonization of the ethoxyvinyl ester shown was followed by transannular etherification in excellent yield.