Kinetic Resolution of Racemic P-Chiral -Hydroxymethylphosphonates Catalyzed by Lipase from Porcine Pancreas

The development of enzyme-catalyzed methods for the synthesis of P-chiral phosphine derivatives has important implications. Herein this work presents a direct biocatalytic transesterification of racemic alpha-hydroxyphosphonates and vinyl acetate, which provides a rapid access to P-chiral hydroxymethylphosphonates. Catalyzed by lipase from porcine pancreas (PPL), which is commercially available, the reactions proceed efficiently with a wide array of reaction partners to deliver various tertiary phosphine oxides in up to 49% yield and 83% ee under very mild conditions. The enzyme-substrate binding mode was established and the high enantioselectivity of PPL was revealed through docking simulations.