Protic acid catalyzed stereoselective glycosylation using glycosyl fluorides

A catalytic and stereoselective glycosylation of various glycosyl acceptors, such as methyl glycosides, thioglycosides, or a disarmed glycosyl fluoride, with benzyl-protected armed glycosyl fluoride was successfully carried out by using various protic acids in the presence of MS 5A. In the cases when trifluoromethanesulfonic acid (TfOH) or perchloric acid (HClO₄) was used in diethyl ether (Et₂O), α-glycosides were obtained as major products, while β-stereoselectivity was observed when tetrakis(pentafluorophenyl)boric acid [HB(C₆F₅)₄] was used in a mixed solvent of trifluoromethylbenzene (BTF)-pivalonitrile (^tBuCN) = 5:1. Stereoselectivity of this glycosylation was controlled by the properties of counter anions of the catalyst as well as by those of solvents. Also, one-pot trisaccharide synthesis was performed by successive addition of NIS and third-sugar to afford Glcα or β1-6Glcβ1-6Glc and Glcα or β1-6GlcNβ1-6Glc in excellent yields.