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.