Asymmetric Strecker Reaction Catalyzed by a Brønsted Acid

Significance

A highly enantioselective Strecker reaction furnishing N-protected α-amino nitriles is presented. Viable substrates are N-benzyl- and N-para-methoxybenzyl-protected imines derived from both aromatic and heteroaromatic aldehydes. Good to excellent results were obtained with electron-rich as well as electron-deficient starting materials. Aliphatic imines can also be employed, albeit the enantioselectivity is severely reduced [for example, 2-(benzylamino)-3-methylbutyronitrile was obtained in 55% ee]. Screening different catalysts revealed that increasing steric bulk benefits the selectivity of the reaction, while HCN emerged as the reactant and toluene as the solvent of choice.