Small Molecule as a Chiral Organocatalyst for Asymmetric Strecker Reaction

A simple and novel chiral amide-based organocatalyst 6 was synthesized from readily available starting materials for the asymmetric Strecker reaction. A variety of N-benzhydryl- and N-tosyl-substituted imines were found to be suitable substrates with i-PrOH as an additive in the presence of chiral organocatalyst 6 at 0 °C with ethylcyanoformate as a source of cyanide for the synthesis of chiral α-amino nitriles. High yield (up to 91%) with excellent enantioselectivity (ee up to 99% of product) were achieved in 24–30 h in the case of both N-benzhydryl- and N-tosyl-substituted imines. To understand the mechanism of the catalytic Strecker reaction, NMR studies and kinetic investigations were carried out with different concentrations of the catalyst 6, ethylcyanoformate, and substrate. It was found that the asymmetric Strecker reaction was first-order with respect to the concentration of the catalyst, EtOCOCN, and saturation kinetics in substrate. An appropriate stereochemical model for the enantioselective Strecker reaction is proposed. We further extend our study, using chiral α-amino nitriles [2-(benzhydrylamino)-2-(pyridin-3-yl)acetonitrile] for the synthesis of chiral amino amide and hydantoin in high yield with high enantioselectivity.