ENZYME-CATALYZED REACTIONS .26. STEREOSELECTIVE SYNTHESIS OF (1R)-1-ARYL-2-ALKYLAMINO AND (1R,2S)-1-ARYL-2-ALKYLAMINO ALCOHOLS FROM (R)-CYANOHYDRINS

Hydrogenation of (R)-cyanohydrins (R)-1 with LiAlH4 occurs without rac emization to give the (R)-2-amino alcohols (R)-3. (1R,2S)-2-Amino alco hols (1R,2S)4 are obtained with high diastereoselectivity by addition of methyl Grignard to O-silyl protected cyanohydrins (R)-2 and subsequ ent hydrogenation with NaBH4. The N-alkylated 2-amino alcohols (R)-8 a nd (1R,2S)-9 can be prepared either by reductive alkylation of the cor responding 2-amino alcohols (R)-3 and (1R,2S)-4, respectively, or by a transimination reaction of the Grignard addition products with primar y amines and subsequent hydrogenation with NaBH4. The lower diastereos electivity of hydrogenation in case of the N-alkylimino compounds in c omparison to the N-unsubstituted imines is explained by a weaker chela ting effect. (C) 1997 Elsevier Science Ltd. All rights reserved.