Abstract
A series of chiral oxidovanadium (V) methoxides were derived from 3,5-disubstituted-N-salicylidene α-amino carboxylic acids and tetrazoles. These complexes serve as enantioselective catalysts for asymmetric reduction and aldol reaction. We are the first group that used chiral vanadyl (V) complexes to study the asymmetric reduction. In this study, α-keto amides served as the best substrate class and methanol-modified pinacolborane served as the best reducing agent among five different reducing agents examined. With catalysts 1a (C3 = tBu, C5 = Br) and 1a’ (C3 = tBu, C5 = Br), up to 62% yield and 85% ee (R form) of the α-hydroxyamides were afforded at -20 oC in toluene. In the past five years, we have already found that chiral vanadyl (V) complexes derived from N-salicylidene α-amino carboxylic acids 1a and tetrazoles 11a (C3 = 2,5-dimethoxyphenyl, C5 = NO2) could achieve complementary asymmetric catalytic aldol processes in addition of silyl ketene acetals (SKA) to isatins at -40 oC in dichloromethane. Herein we further optimized these reactions in the case of 5-nitro-isatin by adding trichloroethanol to facilitate turnover, leading to the corresponding aldol product in moderate yield (61%) and good enantioselectivity (88% ee, S form) with catalyst 1a. Without any additives, using catalyst 11a could furnish a series of R form isatin adducts with up to 97% yield and 90% ee in a complementary manner. Molecular simulations of the adducts between these two catalysts and N-benzylisatin indicated that the preferred coordination mode involve in a facile π-π interaction between the N-benzyl moiety and N-salicylidene template of catalyst 1a to avoid concomitantly the steric hindrance of the C3 tert-butyl. On the other hand, another π-π interaction between the C3 2,5-dimethoxylphenyl group of catalyst 11a and the N-benzyl group of the isatin to avoid concomitantly the el-el repulsion with the tetrazole moiety is involved, leading to a complementary, enantiofacial exposure of the carbonyl moiety in the N-benzylisatin.