Substituent effect on the enantioselectivity in lipase-catalyzed transesterification of trans-2,5-disubstituted pyrrolidines

Kinetic resolutions of N-substituted benzyl-trans-2-acetoxymethyl-5-(hydroxymethyl)pyrrolidines using lipase-catalyzed transesterification have been systematically studied. The enantioselectivity depends significantly on the position of substituent at the aromatic ring and N-3,5-dimethylbenzyl group was found to transform trans-2,5-disubstituted pyrrolidine derivative into an efficiently-resolved substrate. Furthermore, the enantioselectivity could be improved up to E=108 using the immobilized lipase in alkyl silica gel.