Synthesis of chiral building blocks for oxygenated terpenoids through a simultaneous and stereocontrolled construction of contiguous quaternary stereocenters by an ireland-claisen rearrangement

Abstract

Methods for highly stereocontrolled syntheses of chiral building blocks with a triad of contiguous stereocenters, including two quaternary ones, have been developed. Ireland-Claisen rearrangement of the (Z)-silyl ketene acetal generated stereoselectively from the (R)-3-methylcyclohex-2- enyl ester derived from an acyclic carboxylic acid proceeded through a chairlike transition state to give the rearranged product with an S configuration at the position a to the carboxyl group. Introduction of a cyclic conformational constraint in the acid component completely switched the transition state of the rearrangement to a boatlike one, leading to the predominant formation of a product with an R configuration, from which pseudodiastereomeric a-hydroxy esters were obtained in a four-step sequence. The enyne obtained through a base-mediated double eliminative ring-opening reaction was successfully converted into advanced intermediates for the synthesis of 9-oxygenated labdane diterpenoids through a Heck reaction and a regioselective transformation of the resultant diene. © 2013 American Chemical Society.