Homochiral Amine Synthesis by Baker’s Yeast Resolution of a p-Keto Amide: 1-Phenylethylamine

Abstract: Preliminary investigation of the resolution potential of baker’s yeast reduction of P-keto amides has been carried out with 1-phenylethylamine. Enantlomerlc excess was determined by direct comparison of resolved enantiomers with derivatives prepared from commercially available (R)-(+)-l-phenylethylamine and was found to be 56-S&6 % for the S enantiomer and 76-84.64 for the R enantiomer. The enzymatic reduction of 19dicarbonyl compounds by Baker’s yeast and other strains is well established as a reliable procedure for the generation of oxygenated homochiral centers.2d Recently, this type of reduction was applied for the first time to kketo esters of several prochiral alcohols as means of their resolution, providing both enantiomers of the parent alcohols with enantiomeric excesses of O-77%.7 The slower reacting enantiomers 2a remained unreduced and were easily separated from the P-hydroxy esters 3a, Figure l.The rationale for this application was based on the assumption that the secondary resolution site, the alkoxy carbon of the ester moiety, maintained identical distance from the primary reaction site at the ketone carbonyl. The results of these prcchiral resolutions confirmed this assumption and provided practical means for resolution of prochiral alcohols. la x=0 2a 3