Effect of Solvent Polarity on Enantioselectivity in Candida Antarctica Lipase B Catalyzed Kinetic Resolution of Primary and Secondary Alcohols

The Candida antarctica lipase B (CAL-B) catalyzed kinetic resolution of primary and secondary alcohols via acetylation is dependent on the permittivity (ε) of the reaction solvent. For example, the enantiomeric ratio (E) vs ε plot for the acetylation of 1-(naphth-2-yl)ethanol (1) exhibits a convex shape, taking the maximum E value at a medium ε value (11.2), whereas the same plot for the acetylation of benzyl 3-hydroxybutylate (3) exhibits a concave shape, taking the minimum E value at a similar ε value (11.6). Kinetic studies reveal that the difference in shape of the E vs ε plots originates from the relative reaction rate between the enantiomers with different Michaelis constants (K_m). Thus, when the enantiomer with a larger K_m value in the middle ε region reacts more slowly than its antipode, the ε dependence of E exhibits a convex shape. On the other hand, when the enantiomer reacts more quickly, it exhibits a concave shape. The E vs ε plot for the acetylation of 2-methoxy-2-phenylethanol (7) exhibits a convex shape with the maximum E value (20) at ε = 14.1. The E value can be further improved to almost reach the efficiency required for industrial applications (E ≈ 30) by the addition of a nitro compound.