Direct formation of β-glycosides of N-acetyl glycosamines mediated by rare earth metal triflates

Abstract

A direct, mild and efficient protocol for the preparation of β-glycosides of N-acetyl glucosamine (GlcNAc) and N-acetyl galactosamine (GalNAc) has been developed using peracetylated β-GlcNAc and β-GalNAc as donors. All rare Earth metal triflate promoters screened were found to promote glycosylation with Sc(OTf)₃ being superior in terms of reaction rate. Simple alcohol glycosylation was found to proceed smoothly in refluxing dichloromethane, whereas higher temperatures under microwave conditions were needed to attain acceptable yields with less reactive, carbohydrate based glycosyl acceptors. The protocol developed was applied to provide the first example of direct chemical formation of a disaccharide using both GlcNAc as a glycosyl donor and acceptor. The α-acetate donor was found to be significantly less reactive than the corresponding β-anomer necessitating higher reaction temperatures under which glycoside anomerisation was found to occur. It was established, that the anomerisation only took place in the presence of both Sc(OTf)₃ and acetic acid.