Effects of Substituent and Temperature on Enantioselectivity for Lipase-Catalyzed Esterification of 2-(4-Substituted Phenoxy) Propionic Acids in Organic Solvents

Substituent effects on the enantioselectivity for the lipase-catalyzed esterifications in organic solvents were studied by use of 2-(4-substituted phenoxy)propionic acids as the substrates with various substituents of H, F, Cl, CF3, CH3, CH3CH2, and CH3O. The distinction in the behavior of their enantioselectivity was primarily responsible for the size effects of the substituents, although the substituents are far away from the stereocenter of the substrates. For the similar substituents in size, CH3 and CF3, however, their electronic effects played an important role in controlling the enantioselectivity. This variation of the enantioselectivity due to the electronic effects is also supported by the discussion based on the value of the Michaelis constant (Km) obtained. In addition, by raising the reaction temperature with enough water added to isopropyl ether as the reaction medium, the enantioselectivity is found to be dramatically enhanced for the substrate bearing CH3O group due to the strong electron-donating effect.