Enantiodivergent Hydroxylation and Recognizable Kinetic of Halocompounds

Chiral recognition constitutes the central element of asymmetric catalysis. The greater diversity of substituent groups introduced, the more precise control over stereoselectivity becomes. The recognition of high similarity between substituents has been a challenge in asymmetric catalysis. Herein, we report an enzymatic approach enabling kinetically enantioselective hydroxylation in excellent stereoselectivity, though the difference of substituent radius between methyl and chloro substituents is 0.07 Å. Mechanistic investigations involving molecular dynamic simulation and DFT calculation reveal that the engineered P450PL2 exhibits remarkable steric discrimination capability, which enables host-guest interaction with a chiral center bearing methyl and chloro substituents. The biocatalytic system provides efficient access to the 2-chloro-benzyl alcohol derivatives with up to 99:1 enantiomeric ratio and > 99:1 diastereomeric ratio.