Reductive N–O cleavage of Weinreb amides by sodium in alumina and silica gels: synthetic and mechanistic studies

Abstract

The use of sodium in alumina and silica gels for the reductive cleavage of the N–O bond of N-methoxy-N-methylamides, commonly referred to as Weinreb amides, has been investigated. This method reduces a diverse set of Weinreb amides with different functional groups to give modest to excellent yields. In the course of the studies to explore mechanisms and functional group tolerance, an apparently novel group transfer emerged, implying base-promoted cleavage of the Weinreb amide to form formaldehyde, followed by aldol condensation.