Converting a Birch Reduction Product into a Polyketide: Application to the Synthesis of a C1–C11 Building Block of Rimocidin

Abstract

AbstractA stereoselective synthesis of a C1–C11 building block for the polyol‐polyene antibiotic rimocidin has been developed. Its functional groups originate from a disubstituted indane, which underwent Birch reduction, and oxidative cleavage. This provided a dihydropyranone with a β‐keto ester side‐chain. The latter was subjected to a Noyori hydrogenation (ds > 97:3). An oxy‐Michael addition gave a mixture of two spiroketals. Luche reduction then led to three spiroketals in an 80:10:10 ratio. The major spiroketal became isolable by separating one of the by‐products chromatographically and the other by a diastereomer‐selective thioketalization. The remaining spiroketal was ring‐opened to give a dithiolane. Its CO2Me group was converted into the 1,3‐dithiane unit of the target compound (i.e., 47) using an odor‐reducing work‐up procedure, which should prove to be generally useful.