SYNTHESIS OF CHIRAL ALPHA,ALPHA-DIFLUORO-BETA-HYDROXY ESTERS BY ENANTIOSELECTIVE REFORMATSKY REACTION

The addition of the Reformatsky reagent generated from ethyl bromo-alp ha,alpha-difluoroacetate to aldehydes, in the presence of chiral amino alcohols, yields alpha,alpha-difluoro-beta-hydroxy esters with good e nantiomeric excess (ee) for aromatic aldehydes or modest ee for alipha tic ones. (1S,2R)-Ephedrine derivatives are better chiral inductors th an (1S,2R)-dibutylnorephedrine, whereas the enantiodifferentiation is also affected by the molar ratio of the reactants. The best results ar e obtained for a molar ratio aldehyde/Reformatsky reagent/amino alcoho l: 1/4/1.