KINETIC RESOLUTION OF ACYCLIC 1,2-DIOLS USING A SEQUENTIAL LIPASE-CATALYZED TRANSESTERIFICATION IN ORGANIC-SOLVENTS

A method for the kinetic resolution of 3-(aryloxy)-1,2-propanediols ra c-1a-n without additional protection-deprotection steps using a lipase -catalyzed sequential transesterification with lipase amnno PS has bee n developed. In the first step of this one-pot procedure the racemic 1 ,2-diols are acylated regioselectively at the primary hydroxy group wi thout enantioselection. The subsequent acylation at the secondary hydr oxy group of the formed primary monoacetate is responsible for high en antioselection. The enantioselectivity of this transformation depends significantly on the substitution pattern of the aryl ring and the org anic solvent used. 3-(Aryloxy)-1,2-propanediols with substituents in t he para-position show a much higher enantioselectivity than the corres ponding derivatives with ortho-substituents. Among other substrates, t he pharmaceuticals Mephenesin, Guaifenesin, and Chlorphenesin have bee n resolved. The replacement of the aryloxy by alkyl substituent causes a dramatic decrease of enantioselectivity.