Total Synthesis of (±)-Cafestol: A Late-Stage Construction of the Furan Ring Inspired by a Biosynthesis Strategy

Abstract

An efficient bioinspired approach to the total synthesis of (±)-cafestol features a late-stage installation of the furan ring with a mild Au-catalyzed cycloisomerization. The Et₂AlCl-promoted aldehyde–ene cyclization and subsequent Friedel–Crafts reaction deliver a requisite tricyclic system in gram scale with high stereo- and regioselectivity. Moreover, a highly stereoselective SmI₂-mediated aldehyde–alkene radical cyclization furnishes the key bicyclo[3.2.1]­octane skeleton to offer an advanced intermediate for the synthesis of other oxygenated <i>ent</i>-kaurene diterpenoids