Asymmetric synthesis of syn-aryl-(2S,3R)-2-chloro-3-hydroxy esters via an engineered ketoreductase-catalyzed dynamic reductive kinetic resolution

We report here a generic, green synthesis of 17 valuable syn-aryl-(2S,3R)-2‑chloro-3‑hydroxy esters (syn-(2S,3R)-1) in 73%-99% isolated yields along with 6.1:1–83:1 dr and 31%∼>99% ee, through dynamic reductive kinetic resolution of racemic aryl α‑chloro β-keto esters (2) catalyzed by an engineered ketoreductase which was obtained via epPCR-based directed evolution. The hectogram scale synthesis of syn-(2S,3R)-1b at a substrate concentration of 120 g/L showcased the application potential of the biocatalytic method developed presently. [Display omitted]