N-Prolinylanthranilic acid derivatives as bifunctional organocatalysts for asymmetric aldol reactions

Several N-prolinylanthranilic acid derivatives were prepared and tested as bifunctional organocatalysts in the direct asymmetric aldol reaction of cyclohexanone with p-nitrobenzaldehyde. It was found that methyl substitution ortho to the carboxylic acid improves enantioselectivity, but substitution ortho to the anilide group does not. The catalyst derived from 2-amino-6-methylbenzoic acid was tested over a range of direct asymmetric aldol reactions and its overall performance is equal to or better than many of the known prolinamide catalysts in terms of yield, diastereoselectivity, and enantioselectivity.

Graphical abstractDownload full-size image