Kinetic Resolution of Racemic 2-Substituted 3-Cyclopenten-1-ols by Lipase-Catalyzed Transesterifications: A Rational Strategy To Improve Enantioselectivity

The effect of the acyl group of acylating agents on the enantioselectivity in the Pseudomonas cepacia lipase-catalyzed acylations of racemic alcohols has been studied. 2-[( N, N -Dimethylcarbamoyl)methyl]-3-cyclopenten-1-ol ( 1 ) and 2-[2-( tert -butyldimethylsilyloxy)ethyl]-3-cyclopenten-1-ol ( 4 ) were resolved with a variety of enantioselectivities. In the case of alcohol 1, the enantiomeric ratio (the E value) was increased by changing the acylating agent from vinyl acetate ( E = 30) to vinyl butyrate ( E = 156) and dropped substantially with longer acyl donors. With vinyl chloroacetate, the reaction rate was fast and the enantioselectivity was high ( E = 89), whereas the resolution with vinyl trifluoroacetate resulted in a very poor enantioselectivity ( E = 4). The bulky acylating agent, vinyl pivalate, gave a moderate enantioselectivity ( E = 15). In the case of alcohol 4, the enantioselectivities were excellent ( E > 142) except vinyl pivalate ( E = 12). It is indicated that the acyl group transiently attached at the active site of the lipase acts as a stereochemical controller. The solvent effect is also described briefly. A clear correlation was observed between the E values and the log P values of the organic solvents; the smaller the log P value of the solvent, the higher the E value.