Preparation of (+)-nemorensic acid and approaches to nemorensine using the partial reduction of electron deficient furans

Abstract

Starting from a commercially available furoic acid, the synthesis of (+)-nemorensic acid is described in nine steps, and in 32% overall yield. Key steps in our sequence are a chiral auxiliary controlled, stereoselective, Birch reduction of 3-methyl-2-furoic acid and the stereoselective reaction of an oxonium ion generated within a tetrahydrofuran ring. Attempts to complete the synthesis of nemorensine did not succeed because of the low nucleophilicity of platynecine, the alkaloid base portion of the natural product.