Total Synthesis of the Diterpene Waihoensene

Abstract

A racemic and scalable enantioselective total synthesis of (+)-waihoensene was accomplished. (+)-Waihoensene belongs to the diterpene natural product family, and it features an angular triquinane substructure motif. Its tetracyclic [6.5.5.5]backbone is all-cis-fused, containing six contiguous stereocenters, four of which are quaternary. These structural features were efficiently installed by means of a diastereoselective radical cyclization, followed by an intramolecular Pauson-Khand reaction, a diastereoselective α-alkylation, and a diastereoselective 1,4-addition reaction. Enantioselectivity was introduced at an early stage, by an asymmetric palladium catalyzed decarboxylative allylation reaction on gram scale.

Keywords: Pauson-Khand reaction; natural products; radicals; terpenes; total synthesis.