Stereocontrol by the Introduction of a Sulfur Functional Group in the Asymmetric Reduction of β-Keto Esters with Baker's Yeast

Abstract

Stereocontrol in baker's yeast-mediated reduction of β-keto esters was successfully achieved by introducing the sulfenyl functionalities at α-position of the esters to afford optically pure (3 S)-hydroxy esters, such as ethyl (3 S)-hydroxy-2-(methylthio)butanoate [2 a], ethyl (3S)-hydroxy-2-(methylthio)pentanoate [2 f], ethyl 5-benzyloxy-(3 S)-hydroxy-2-(methylthio)pentanoate [2 g]. Reduction of α-alkyl β-keto dithioester derivatives with baker's yeast afforded asymmetric reduction products having S configuration, methyl (2 R, 3 S)-3-hydroxy-2methyldithiobutanoate [7 a] and (1 R, 2 S)-2-[(methylthio)thiocarbonyl]cyclohexanol [7b], with high enantio- and threo diastereoselectivity. The utility of the present method was demonstrated in the stereoselective synthesis of the sex attractant of pine saw-fly, (2 S, 3 S, 7 S)-2-acetoxy-3, 7-dimethylpentadecane [10] from two optically pure hydroxy esters, [2 a] and [7 a].