Enzymatic kinetic resolution of secondary alcohols by esterification with FA under vacuum

Kinetic resolution of some chiral secondary alcohols [2-octanol, 1-phenylethanol, and 1-(2-naphthyl)ethanol] with high enantioselectivity (E > 300) was achieved by direct esterification with FFA catalyzed by immobilized Candida antarctica B lipase. The reaction equilibrium was shifted toward the synthetic side by the removal of the water formed under vacuum. Esterification of rac-2-octanol at an alcohol/FFA molar ratio of 2:1 was used as a model reaction. The chain length of FFA and their structure influenced the reaction rate but did not have a measurable effect on E. The best acyl donor was decanoic acid: >47% conversion at 4 h with virtually perfect E Temperature did not affect E in the range studied (15-45degreesC), but temperatures at the higher end afforded improved reaction rates. The reaction rates and E were compared for three different acyl donors. The initial reaction rate increased in the following order: ethyl laurate < lauric acid < vinyl acetate. E was high (E > 300) for all acyl donors. Racemic 1-phenylethanol and 1-(2-naphthyl)ethanol were also resolved by direct esterification with decanoic acid in short times (3 and 4 h, respectively) with E > 300 and excellent conversions. Preparative-scale kinetic resolution of 2-octanol was also performed.