Stereoselective synthesis of (S)-3,4-methylenedioxyamphetamines from (R)-cyanohydrins

A stereoselective synthesis of (S)-3,4-methylenedioxyamphetamines (S)-7, which are highly interesting as psychoactive compounds, is described. Starting from readily available (R)-cyanohydrins (R)-2 the 2-amino-1-aryl alcohols (1R,2S)-4 were obtained with high diastereoselectivity by addition of Grignard reagents to the O-protected cyanohydrins (R)-3, transimination of the addition products A with primary amines, and hydrogenation of the imino intermediates B with NaBH4. For the hydrogenation of the benzylic hydroxyl group in the 1,2-amino alcohols (1R,2S)-4 a new, very efficient method was developed. The optically pure amphetamines (S)-7 were obtained under very mild conditions by catalytic hydrogenation of the oxazolidinones (4S,5R)-6, which were readily available by phosgenation of the amino alcohols (1R,2S)-4.