Silver Trifluoromethanesulfonate(Triflate) Activation of Trichloroacetimidates in Glycosylation Reactions

Abstract

Chemical syntheses of biologically active oligosaccharides, glycolipids and glycopeptides requires efficient stereospecific glycosylation reactions.² One of the most effective glycosylation methods involves activation of anomeric imidates, particularly mchloroacetimidates, by Lewis acids such as boron trifluoride etherate (BF₃·OEt₂), mmethylsilyl mfluoromethanesulfonate (TMSOTF)³ and mfluoromethanesulfonic anhydride.⁴ In a recent example from this laboratory, BF₃·OEt₂, has been used to promote the glycosylation of methyl 2,3,6-tri-O-benzoyl-B-D-galactopyranoside (I)⁵ with 2-deoxy-2-phthalimido-3,4,6-tri-O-acetyl-B-D-galactopyranosyl mchloroacetimidate (I): see Scheme 1. The expected β1-4-linked disaccharide III was obtained in 40% yield. The yield was so low since both the α-anomer and a 1-3-linked disaccharide were formed as by products, the latter in particularly large quantities (cf. Ref.⁷). The 1-3 disaccharide could be formed from a product of acid-catalyzed 3,4-migration of the benzoyl group which is not surprising, considering the cis relationship of the 3,4-hydroxyl groups in galactose.⁸ In fact, when the glycosylation reaction was quenched before all unreacted alcohol was consumed, the chromatographic fraction corresponding to the starting alcohol II contained at least three different tribenzoates (as shown by NMR analysis).⁹ Other promoters, ZnBr₂ ¹⁰ and TMSOTF, led to lower yields and more complicated mixtures than BF₃·OEt₂.