Preparation of chiral glycerol derivatives using chemoenzymatic approaches

Following our preparation of dissymmetric chlorohydrin esters from glycerol, we have used several lipases and whole cells to examine the kinetic resolution (KR) and dynamic kinetic resolution (DKR) of 3-chloro-2-hydroxypropyl esters. Regarding the KR, PS-IM, MmL and CALB lipases and whole cells of Aspergillus flavus showed the best selectivity and activity, depending on the compound studied. PS-IM allowed the isolation of (R)-3-chloro-2-hydroxypropyl pivaloate in 34% yield and with >99% enantiomeric excess (ee). DKR was carried out combining the biocatalysts that performed best for KR and suitable reaction conditions for racemization. Whole cells of A. flavus allowed the preparation of enantioenriched (S)-3-chloro-2-acetoxypropyl-2-methyl-2-phenyl propanoate in 43% yield and with 79% ee. Lipozyme from Mucor miehei used in a reaction subsequent to DKR allowed the purification of the corresponding enantioenriched (S)-3-chloro-2-acetoxypropyl pivaloate. This journal is