Asymmetric Michael addition of aldehydes to nitroolefins catalyzed by l-prolinamide derivatives using phenols as co-catalysts

Abstract

The asymmetric Michael addition of aldehydes to nitroolefins was investigated using l-prolinamide derivatives of 2-(2′-piperidinyl)pyridine as catalyst and a variety of phenols as co-catalyst. Extensive screening toward the effect of prolinamides, phenols, and solvents on this transformation revealed that a combination of (S)-2-(2′-piperidinyl)pyridine-derived trans-4-hydroxy-l-prolinamide 2c, (S)-1,1′-bi-2-naphthol, and dichloromethane was a promising system. This system was shown to be amenable to a rich variety of aldehydes and nitroolefins and afforded the nitroaldehyde products with excellent yield, enantiomeric excess (up to 99%) and diastereoselectivity ratio (up to 99/1), even in the case of 1 mol % catalyst loading and 1.5 equiv of aldehydes. © 2009 Elsevier Ltd. All rights reserved.