Prolinamides derived from aminophenols as organocatalysts for asymmetric direct aldol reactions

N-(2-Hydroxyphenyl)-prolinamides were synthesized with the aim to introduce an additional hydrogen bonding site to the prolinamide structure. These compounds were evaluated as organocatalysts for asymmetric aldol reactions between aromatic aldehydes and cyclohexanone. Very good yields, diastereoselectivities, and enantioselectivities were achieved in both organic solvents and water. The importance of the additional hydrogen bonding site was confirmed by comparative experiments with prolinamide derivatives without the hydroxyl group.

A series of prolinamides derived from 2-aminophenols were synthesized and shown to be efficient organocatalysts for asymmetric aldol reactions between aromatic aldehydes and cyclohexanone.