One‐Pot Enzyme Cascade Catalyzed Asymmetrization of Primary Alcohols: Synthesis of Enantiocomplementary Chiral β‐Nitroalcohols

Abstract

AbstractBiocatalytic asymmetrization of inexpensive and stable primary alcohols to prepare enantioenriched β‐nitroalcohols is an important development in green chemistry for the production of chiral pharmaceutical intermediates. Herein, we report a one‐pot, two‐step cascade reaction sequence in which first benzylic alcohols were oxidized to produce corresponding benzaldehydes using horse liver alcohol dehydrogenase (HLADH). The in situ generated aldehydes were then reacted in a biphasic medium with nitromethane by Arabidopsis thaliana hydroxynitrile lyase (AtHNL) or Baliospermum montanum HNL (BmHNL) catalyzed Henry reaction to produce stereoselective β‐nitroalcohols with (R) or (S) configuration, respectively. Using HLADH‐AtHNL, (R)‐β‐nitroalcohols were obtained in up to 64% conversion, and HLADH‐BmHNL, (S)‐β‐nitroalcohols in up to 70% conversion, while in both cases excellent stereoselectivity (up to >99% ee) was achieved. The concept was proven by functionalization of sp3 C−H bond of ten simple achiral benzylic alcohols to enantiocomplementary chiral β‐nitroalcohols.magnified image