L-Prolinethioamides - Efficient organocatalysts for the direct asymmetric aldol reaction

A series of novel L-proline derived thioamides has been synthesised. They have been evaluated as organocatalysts in the direct asymmetric aldol reaction for the first time. Thioamides exhibit catalytic ability higher than proline itself and the model aldol reaction of 4-cyanobenzaldehyde with acetone proceeds well in the presence of 5 mol % of catalyst (ee up to 100%). Other aromatic aldehydes gave aldol products with high ees and moderate yields. Small changes in the catalyst's structure [e.g., N-Bn versus N-CH(CH3)Ph] as well as the addition of an acid have a profound effect on their activity. The unexpected formation of the catalyst-derived cyclic adducts was observed and their reactivity was established giving valuable insight into the course of the reaction.