ENANTIOSELECTIVE SYNTHESIS OF OPTICALLY-ACTIVE SECONDARY-AMINES VIA ASYMMETRIC REDUCTION

The enantioselective synthesis of optically active secondary amiDeS via the asymmetric reduction of N-substituted ketimines with various chiral hydride reagents, such as Itsuno's reagent (1), Corey's reagent (2), K glucoride (3), Sharpless' reagent (4), and Mosher's reagent (5) has been investigated. Among the hydride reagents examined, 1 gave the best results in terms of asymmetric induction. Thus, the reduction of N-phenylimine derivatives of aromatic ketones with 1 provided the corresponding amines in 96 - 98 % yields with high optical induction, such as 73 % ee for acetophenone N-phenylimine (6 a), 87 % ee for propiophenone N-phenylimine (6 b), 88 % ee for butyrophenone N-phenylimine (6 c), and 71 % ee for isobutyrophenone N-phenylimine (6 d). In the case of N-alkyl ketimine derivatives, the reduction afforded somewhat lower optical inductions as compared to those of N-phenyl derivatives, giving 46 % ee for acetophenone N-benzylimine (6 f), 52 % ee for acetophnone N-n-heptylimine (6 g) and 43 % ee for acetophenone N-cyclohexylimine (6 h). However, the substitution of a bulky alkyl group on nitrogen of the ketimines increases remarkably the optical induction of product amine, such as 80 % ee for acetophenone N-tert-butylimine (6 e). The reduction of N-substituted aliphatic ketimines gave very low optical inductions (7.4 - 24 % ee). The catalytic effects of oxazaborolidines (1 a and 2 a) in the reduction of ketimines with 1 and 2 were also examined.