Trifluoromethylated-Imidazolines as Efficient Organocatalyst for Asymmetric Aldol Reaction of Hydroxyacetone with Aldehydes

Aldol reaction of hydroxyacetone is an all-purpose route to construct the 1,2-diol building blocks for the synthesis of multifarious natural products and biological active molecules. In this work, a new series of trifluoromethylated-imidazoline organocatalysts have been designed and synthesized. It is found that the trifluoromethylated chiral organocatalyst (2R,4S)-4-benzyl-H2-dimethyl-2-(trifluoromethyl) imidazolidine (1a) has proved to be very efficient for the direct asymmetric aldol reaction of alpha-hydroxyketones with aldehydes to build the syn-1,2-diol building blocks. Among the synthesized syn-aldol products, a good yield (up to 96%) and high stereo selectivity (up to dr= 15 : 1, 99% ee) could be obtained. The F-H bonding derived from trifluoromethyl group was proposed to play an important role in the stabilization of the transition state.