Efficient Biocatalytic Synthesis of Highly Enantiopure α‐Alkylated Arylglycines and Amides

A number of racemic α‐alkylarylglycine amides including 1‐amino‐1‐carbamoyl‐1,2,3,4‐tetrahydronaphthalene underwent efficient biocatalytic hydrolysis under very mild conditions to afford the corresponding (S)‐α‐alkylarylglycines and (R)‐α‐alkylarylglycine amides in excellent yields with enantiomeric excesses higher than 99.5%. Both the reaction rate and enantioselectivity of biocatalytic kinetic resolution were strongly dependent upon the nature of the substituent and the substitution pattern on the benzene ring of the substrate. In contrast, no effective biotransformation of the Strecker nitrile derived from acetophenone was observed under the catalysis of a nitrile hydratase/amidase‐containing microbial Rhodococcus sp. AJ270 whole‐cell catalyst. Coupled with the chemical hydrolysis of amide, this biotransformation process provided efficient syntheses of α‐substituted arylglycines in both enantiomeric forms from readily available racemic amides.