Stereoselective Esterifications of Racemic Alcohols

Lipases have been extensively used for the kinetic resolution of racemic alcohols or carboxylic acids in organic solvents. Chiral alcohols are usually reacted with achiral activated esters (such as vinyl, isopropenyh and trichloroethyl esters) for shifting the equilibrium to the desired products and avoiding problems of reversibility. For the same reasons, chiral acids are often resolved by using acidolysis of esters. In both cases, the overall stereoselectivity is affected by the thermodynamic activity of water of water favors hydrolytic reactions leading to a decrease in the optical purity of the desired ester. Direct esterifications are therefore difficult to apply since water formed during the reaction may increase the o of the system, favors reversibiUty, and diminishes the overall stereoselectivity. 

Maximum molar conversion (42-43%) was reached after 7 days with a corresponding enantiomeric excess (e.e.) of the R-product in the range of 97-98% the optical purity of the ester slightly diminished (95-96%) after 21 days, while the molar conversion remained the same. This stereochemical behavior indicates that the esterification is not reversible under these conditions, despite formation of water during the esterification. 

A very different situation was observed when the resolution of racemic 1,2-0-isopropyhdeneglycerol (IPG or solketal) was studied [19]. In this case, the kinetics of the esterification with butyric acid catalyzed by A. oryzae MIM and R. oryzae CBS 112.07 were investigated by carrying out independent batch tests on the commercially available R- and S-IPG (Table 6.4). 

The esterification of IPG was largely reversible, with the e.e. of the substrate reaching a maximum after 1 h and progressively diminishing as the reachon progressed further, while the best resolution was obtained after 15 min (e.e. of the product = 68-70%). Biotransformations were performed at different inihal water 

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