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

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.