A general method for the stereoselective coupling of unprotected oligosaccharides with any substrate containing a N,O-disubstituted hydroxylamine group is described. The cyclic nature of the oligosaccharide reducing unit is preserved and the substrate glycosylated with high diastereoselectivity to sugar through an amino (N[OR2]-) or an aminoxy (N[R-1]-O-) linkage. Due to the uniquely high chemical reactivity and specificity of disubstituted hydroxylamine toward the sugar reducing end, neither protecting groups nor activation methods are required to perform the reaction in aqueous solution. The characteristic features and the scope of this new type of glycosylation reaction are exemplified for the chemoselective synthesis of model glycopeptides. (C) 1998 Elsevier Science Ltd. All rights reserved.