Regioselective cleavage of the dithiolane S–S bond of (±)-α-lipoic acid by carbon and phosphorus nucleophiles

Abstract

Methyl-lithium and lithium dimethylcuprate react with (±)-α-lipoic acid (1a) to give in low yield a mixture of ring-opened isomers (8:1) resulting from nucleophilic attack at the C-8 and C-6 sulphur atoms respectively of the dithiolane ring. Methylmagnesium iodide, dimethyl sodipmalonate, and 1 -pyrrolidin-1 -ylcyclohexene fail to open the ring of (1a). In contrast, trimethyl phosphite cleaves the S–S bond efficiently and regioselectively at the C-8 sulphur atom; the resultant product is degraded by way of a new conversion of phosphorothioate into thioether.