An Enantioselective Total Synthesis of (+)- and (−)-Saudin. Determination of the Absolute Configuration

Abstract

A short efficient enantioselective synthesis of both (+)- and (-)-saudin, a naturally occurring hypoglycemic diterpene, is described. This synthesis establishes the absolute configuration of natural (-)-saudin for the first time. The key steps include the enantioselective construction of a dimethyl Hagemann's ester by an asymmetric Michael reaction and establishment of the key 1,3 disposed quaternary centers by means of a novel Ti(IV) promoted Claisen rearrangement. The assembly of the polycyclic ketal skeleton was likely under kinetic control proceeding via formation of the C1oxygen-C7 bond through an oxonium ion intermediate in the final stage.