Abstract: (R)-2-Chloro-1-(3-chlorophenyl)ethanol is a key pharmaceutical intermediate in the synthesis of β₃-adrenoceptor receptor (β₃-AR) agonists. The asymmetric reduction of 2-chloro-1-(3-chlorophenyl)ethanone to (R)-2-chloro-1-(3-chlorophenyl)ethanol catalyzed by resting cells of Candida ontarioensis was studied. At a substrate concentration of 10 g/L, the microbial cells showed excellent catalytic activity under the optimum reaction conditions, giving the product in 99.9% ee and 99.0% yield. After cetyltrimethylammonium bromide-pretreatment, the activity of permeabilized Candida ontarioensis cells was increased by more than 2-fold and the product could be produced over the significantly shortened reaction period of 24 h in 99.9% ee and 97.5% yield at a substrate concentration of 30 g/L. This work provides a practical approach for the efficient preparation of the important chiral intermediate (R)-2-chloro-1-(3-chlorophenyl)ethanol.

Key words: (R)-2-chloro-1-(3-chlorophenyl)ethanol, asymmetric reduction, cetyltrimethylammonium bromide, permeability, Candida ontarioensis