A Novel Proline‐Valinol Thioamide Small Organic Molecule for a Highly Enantioselective Direct Aldol Reaction

Abstract

AbstractA new prolinethioamide compound 4, prepared from readily available natural amino acid L‐proline and amino alcohol L‐valinol, has been found to be an active catalyst for the direct aldol reaction of various aldehydes with acetone, cyclohexanone or cyclopentanone at 0 °C. Using only 2 mol% loading of this organocatalyst, the reaction could give high enantioselectivity with up to 96% enantiomeric excess for the reaction of 2‐nitrobenzaldehyde with acetone. And as for the cyclohexanone, the excellent diastereoselectivity (anti/syn: 99/1) and enantioselectivity (99% ee) could be achieved when reacted with 3‐nitrobenzaldehyde in water in the presence of this thioamide 4. This structurally simple catalyst is a highly efficient prolinethioamide derivative, and the terminal hydroxy group in this catalyst is a primary alcohol which is different from the previously reported prerequisite secondary or tertiary alcohol of prolinamides. Our results suggest a new strategy in the design of diversiform organic catalysts for direct asymmetric aldol reactions and related transformations.