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 ent-kaurene diterpenoids. © 2014 American Chemical Society.