Total Synthesis of (+)-Pierisketone B

Abstract

We report herein the first total synthesis of (+)-pierisketone B, a bioactive diterpene that possesses a unique tetracyclic 7/5/6/5 carbocyclic framework that is punctuated with numerous stereocenters, two of which are quaternary and five of which are contiguous. The synthesis features an unusual Pauson Khand cyclization to generate the bridged tricyclic core. Creation of the requisite cis-fused hydrindanone moiety was achieved by hydroxyl directed hydrogenation of an allylic alcohol, and the A-ring of the natural product was formed by a Mukaiyama aldol reaction followed by a cyclization involving addition of a vinyl anion to a proximal ketone group. The resulting tetracyclic intermediate was then elaborated in six steps to complete the first total synthesis of (+)-pierisketone B in a longest linear sequence of 20 steps from (−)-linalool.