Asymmetric synthesis of a β-ketol moiety via 3,5-disubstituted isoxazoles: application to (+)-(S)-[6]-gingerol

Abstract

A new synthesis of (±)-[6]-gingerol (13), (+)-(S)-[6]-gingerol, and (+)-methyl-[6]-gingerol (12c) using 3,5-disubstituted isoxazoles as masked β-ketols, is described. Reductive fission of the labile N–O bond of the isoxazoles (8a) and (8b) gave the enamino-ketones (9a) and (9b) which were converted into the vinylogous imides (10c) and (10b) using N-tosyl-L-prolyl chloride. Reduction of (10c) and (10b) gave diastereoisomenc mixtures of the alcohols (11c) and (11b), which on controlled hydrolysis in aqueous acetic acid gave β-ketols. Optical yields of 30–40% were obtained.