ENZYMATIC-SYNTHESIS OF CHIRAL MONOSUBSTITUTED MALONATES IN ORGANIC-SOLVENTS

Prochiral stereospecificity of enzymes in organic solvents was used to develop a strategy for the formation of heretofore unknown chiral monosubstituted malonate diesters with high enantiomeric excess. The enzymatic reaction involved transesterification of symmetrical monosubstituted dimethyl malonates with benzyl alcohol, exploiting the ability of lipases to discriminate between the enantiotopic ester groups of the symmetrical malonate molecule. This enzymatic approach is not feasible in aqueous solutions because the activated malonic hydrogen invariably undergoes fast exchange accompanied by racemisation. The synthetic utility of this method was further demonstrated by converting the configurationally unstable mixed methyl benzyl diesters into the corresponding half esters, which were in turn selectively reduced into configurationally stable and synthetically useful hydroxyesters.