Abstract
We have developed a catalytic protocol for complementary enantioselective reduction of α-ketobenzylamide with pinacolborane and catecholborane catalyzed by chiral oxidovanadium (V) methoxides complexes derived from 3,5-disubstituted-N-salicylidene α-tert-leucinate. The catalysts 1a and its reduce form 1a' (C3 = t-Bu, C5 = Br) with pinacholborane afforded upto 62% yield and 84% (R-form) enantioselectivity, at −20 °C in toluene under Argon. However, asymmetric reduction with catecholborane provides complementary enantioselectivity upto 64% (S-form) and 99% yield. A series of α-ketobenzylamide substrates were examined, the substrates with small and planar α-keto functional groups can get better enantioselectivity. With pinacolborane, α-cinnamyl substituted system shows better enantioselectivity 93% (R-form) and 45% yield. While in the case of catecholborane, 2-thiophenyl case show better enantioselectivity 76% (S-form) and 89% yield. The complementary enantioselectivity can be explained by a plausible mechanism, in which the step is the chelation of carbonyl group of amide with vanadyl(V) center axially anti to vanadyl oxygen . In the next step, the methoxide chelates with bulky pinacholborane lead to a s-trans conformation of the α-ketoamide and directs the hydride transfer from Si-face. This results in the formation of R-isomer. Conversely, the π-π interaction between the catecholborane and substrate coordinates in an s-cis conformation instigate the hydride transfer from Re-face. This results in the formation of S-isomer.