Kinetic resolution of 2,2-difluoro-3-hydroxy-3-aryl-propionates catalyzed by organocatalyst (R)-benzotetramisole

Kinetic resolution of a series of ethyl 2,2-difluoro-3-hydroxy-3-aryl-propionates catalyzed by (R)-benzotetramisole has been performed. It was found that when the aryl group was phenyl or phenyl substituted with electron-donating group (such as –Me, –OMe, and –SMe) or naphthyl groups, the enantio-selectivity factor (s) could reach 20 or higher; electron-withdrawing (such as fluorine) substitution on the benzene ring dramatically lowers the s value. Kinetic resolution in preparative scale for some of the substrates demonstrated the applicability of this method.

Thirteen examples. When R=phenyl, 4-MeO-phenyl, 4-MeS-phenyl, 1-naphthyl, and 2-naphthyl, the enantio-selectivity factor reaches 20–47. The aryl substituent effect on the selectivity factor is examined. Two examples of preparative KR are provided.Figure optionsDownload as PowerPoint slide