Benzylation Reactions in DMF Lead to an Impurity Which Acts as an Organocatalyst Poison in Thiourea-Catalyzed Glycosylations

Abstract

The benzylation of alcohols with the commonly used combination of benzyl bromide and sodium hydride in DMF can lead to the formation of an amine side product, N,N'-dimethyl-1-phenyl-1-(o-tolyl)methanamine. This amine coeluted with benzylated galactal during column chromatography and was found to be a catalyst poison in thiourea-catalyzed glycosylations of galactals. It may also be problematic for other base-sensitive reactions involving benzylated substrates. Solutions to this problem are described.