Dimethyl sulfonium triflate glycosylation

Scheme 5.1 Mechanism of thioglycoside activation (a) by thiophiles X1 such as /V-bromosuccinimicle (NBS), 11,12 methyl triflate,13 dimethyl(methylthio)sulfonium triflate (DMTST),14 phenylselenyl triflate (PhSeOTf),17,18 iV-iodosuccinimide/triflic acid (MS/TfOH),19 20 and iodonium di-sym-collidine perchlorate (IDCP)21 (b) by tris(4-bromophenyl)ammoniumyl hexachloroantimonate (TBPA,+)25 and (c) via anomeric sulfoxides.26 The stereochemical outcome of these glycosylations follows the same general trends as with many other glycosyl donor/promoter combinations (m-CPBA = mcta-chloroperbenzoic acid).

O. Kanie, M. Kiso, and A. Hasegawa, Glycosylation using methylthioglycosides of W-acetylneuraminic acid and dimethyl(methylthio)sulfonium triflate, J. Carbohydr. Chem. 7 501 (1988). 

A. Hasegawa, M. Ogawa, H. Ishida, and M. Kiso, a-Predominant glycoside synthesis of Af-acetylneuraminic acid with the primary hydroxyl group in carbohydrates using dimethyl-(methylthio)sulfonium triflate as a glycosyl promoter, J. Carbohydr Chem. 9 393 (1990). 

Another popular promoter for glycosylation with thioglycosides is the reagent dimethyl(methylthio)sulfonium triflate (DMTST).60 A comparison between DMTST and NIS/TfOH for the formation of sialoglycoconjugates demonstrated that the iodine system provided superior yields and anomeric selectivity in nearly all cases.61 The yields and stereoselectivity also increased with an increase in solvent polarity, suggesting that enhanced stabilization of the oxacarbenium intermediate, the rate-limiting step in glycosylation, was responsible for the increased... 

Andersson, F, Fugedi, P, Garegg, P J, Nashed, M, Synthesis of 1,2-cA-linked glycosides using dimethyl(methylthio)sulfonium triflate as promoter and thioglycosides as glycosyl donors. Tetrahedron Lett., 27, 3919-3922, 1986. 

Thio-sugars [60,61] are excellent glycosyl donors for oligosaccharide synthesis. Excellent reactivity of activated thioglycosides [62,63] by common promoters such as methyltriflate, dimethyl(methylthio)sulfonium triflate (DMSTS), iodonium dicollidine perchlorate (IDCP), and A-iodosuccininude (NIS) alone or with a combination of triflic acid or silver triflate makes them versatile glycosylation donors. 

Addition of the reagent to double bonds limits the use of unsaturated protecting groups (e.g. allyl, allyloxycarbonyl) in dimethyl(methylthio)sulfonium triflate-promoted glycosylation reactions. 

Ito and coworkers have combined the soluble polymer-supported synthesis with the catch-and-release protocol using the chloroacetyl (ClAc) tag (Scheme 16.20). Glucosamine acceptor bound to a low molecular weight polyethylene glycol (PEG) 70 was glycosylated with a thiogalactoside donor 71 in the presence of dimethyl(methylthio) sulfonium triflate (DMTST) in CH2CI2 to provide the disaccharide 72 in 94% yield. 

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