Novel Small Organic Molecules for a Highly Enantioselective Direct Aldol Reaction

Gong and co-workers have examined the use of pyrrolidine carboxamides with a terminal hydroxyl group as catalysts (20 mol %) for the direct aldol reaction between nitrobenzaldehyde and acetone.  The compound shown below was by far the best catalyst with chemical yields of 60-80%, and ee’s of 93% being obtained.  This catalyst was used with a wide variety of other aldehydes and all products were obtained in consistently high ee’s (80-98%), although chemical yields were variable.  In general aromatic aldehydes gave best yields (60-95%), whilst aliphatic aldehydes reacted less well (10-50%).  The exception is cylohexanecarboxaldehyde which gives aldol products in high yields (77-85%) and ee’s (98% ee) even at lower catalyst loadings.  Other related catalysts resulted in good yields, but poorer enantioselectivity (30-80% ee).  (J. Am. Chem. Soc., 2003, 125, 5262-5263).