Stereocontrolled α-galactosylation under cooperative catalysis

In spite of many methods developed for the synthesis of glycans, glycosyl halide donors discovered by Michael continue to find wide application. Under classical Koenigs-Knorr reaction conditions, a glycosyl bromide (or chloride) donor is coupled with a glycosyl acceptor (alcohol, ROH) in the presence of silver oxide (or carbonate). This reaction is slow, and even glycosidations of reactive, per-benzylated donors require many hours (or even days) to produce the respective glycoside products. This reaction is particularly sluggish with less reactive per-benzoylated bromides.

A recent discovery of a cooperative catalysis comprising a silver salt and an acid led a dramatic improvement in the way glycosyl halides are glycosidated. Excellent yields have been achieved, but the stereoselectivity achieved with 2-O-benzylated donors was poor. Reported herein is our effort to refine the stereoselectivity of the cooperatively catalyzed galactosylation reaction. Careful optimization of the reaction conditions along with studying effects of the remote protecting groups led to excellent stereocontrol of α-galactosylation of a variety of glycosyl acceptors with differentially protected glycosyl donors. The developed method has the following advantages in comparison with the known methods: no specialized protecting groups are required therefore synthesis of donors is straightforward. In addition, the reaction is swift and can be conducted at ambient temperature without losing stereoselectivity and the promoter systems are stable and commonly available.