Synthesis Of Novel Prolinamide-based Ligands And Its Application In Direct Asymmetric Aldol Reaction In Brine

Asymmetric aldol reaction is one sort of the most important carbon-carbon formation reactions, which can generate many valuable biologically optically active 8-hydroxy carbonyl compounds and it has tremendous utility in organic synthesis. The asymmetric organocatalytic aldol reaction is currently the most important and interesting research topic in organic chemistry. Meanwhile, Employment of water as reaction media is the demand of green chemistry on account of its environmental friend and thus is the current interests to chemists. Another challenging topic is using low loading of chiral catalysts to promote the asymmetric reactions.Herein we discuss on this topic that systhesis of novel prolinamide-based secondary-tertiary diamines 5a-e from L-proline and (1R,2R)-diphenylethyldiamide and its applied to the direct asymmetric aldol reactions. It was found that 5a-e were high-efficiency catalysts for direct asymmetric aldol reactions in brine, only 1 mol% of catalysts could afford high enantioselectivity and yield in addition of 2,4-dinitrophenol (DNP) as an acidic additive. The reaction of acetone with arylaldehyde afforded up to 94% ee and 97% yield , whereas up to 97% ee , 99% yield and 98:2 dr were obtained when cyclohexanone was used. Notebly, catalyst 5b could be recycled once without reducing its catalytic activity.