A Tandem Metal Carbene Cyclization−Cycloaddition Approach to the Pseudolaric Acids

Abstract

An approach toward the synthesis of the antifungal and cytotoxic pseudolaric acids based on the tandem metal carbene cyclization-cycloaddition reaction is described. Using this strategy, the advanced intermediate 3a bearing three of the four stereocenters of the target molecules has been synthesized. The substrate-controlled diastereoselectivity of the tandem carbene cyclizationcycloaddition was preferential for the undesired diastereomer, but reagent control through the use of Hashimoto's chiral rhodium catalyst Rh 2(S-BPTV) 4 reversed the selectivity in favor of 3a. Ring opening of the oxabicyclic nucleus to give a hydroxycycloheptene has been demonstrated in a model study.link_to_subscribed_fulltex