Catalytic enantioselective difluoroalkylation of aldehydes

Abstract

Copper-catalyzed bond scission of pentafluorobutane-1,3-diones generates difluoroenolates that react with aldehydes to give a wide range of chiral α,α-difluoro-β-hydroxy ketones within a few hours in up to 99 % yield and 92 % ee. The synthetic utility of this reaction is demonstrated with the stereoselective synthesis of a chiral anti-1,3-diol exhibiting a central difluoromethylene unit and efficient conversion to a 2,2-difluoro-3-hydroxy carboxylic acid.

Keywords: aldol reaction; asymmetric catalysis; cleavage reactions; fluoroenolates; reactive intermediates.