Direct asymmetric aldol reactions catalysed by trans-4-hydroxy-(S)-prolinamide in solvent-free conditions

Abstract

Direct asymmetric aldol reactions between 4-nitrobenzaldehyde and cyclohexanone were catalysed by trans-4-hydroxy-(S)-prolinamide (10mol%) in the presence of CH3COOH (10mol%) as the co-catalyst under solvent-free conditions at 15°C. (2S,4R)-4-Hydroxy-N-((S)-1-phenylethyl)pyrrolidine-2-carboxamide 2 efficiently catalysed the asymmetric aldol reaction to afford the product in >99% yield and with 95% ee with an anti/syn ratio of 88:12 after 18h. The additional trans-hydroxyl group on (S)-prolinamide and (S)-1-phenylethylamine both influenced the ee of the predominant anti aldol product. Different benzaldehyde derivatives with cyclohexanone gave the corresponding aldol products in 38–89% yields and with 56–94% ee with anti/syn (100:0–71:29). Catalyst 2 can be used up to 5 continuous cycles for asymmetric aldol reactions between 4-nitrobenzaldehyde and cyclohexanone with overall 91% yield and 86% yield of anti-product with anti/syn (98:2).