Asymmetric Synthesis of the epi-Vinigrol Tricyclic Core Enabled by a Wolff Rearrangement Strategy and Formal Total Synthesis of (-)-Vinigrol.

Abstract

A new approach to construct the tricyclic framework of the diterpenoid vinigrol is described. The challenging 1,5-butanodecahydronaphthalene core was established efficiently and diastereoselectively through a combination of type II [5 + 2] cycloaddition and Wolff rearrangement. In addition, a formal total synthesis of (-)-vinigrol was achieved in 12 steps, in which Baran's intermediate was efficiently produced from a known compound by a two-step sequence involving a stereoselective α-hydroxylation and a diastereoselective α-ketol rearrangement.