Dimethyl sulfonium triflate

Thioglycosides can be activated for gfycosylation reactions with sulfur electrophiles, e.g., with dimethyl(methylthio)sulfonium triflate or with methanesulfenyi bromide and silver(l +) to form reactive sulfonium intermediates (F. Dasgupta, 1988). 

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).

Dimethyl (methylthio)sulfonium Triflate as a Promoter for Creating Glycosidic Linkages in Oligosaccharide Synthesis... 

Scheme 8 Thioglycoside-based glycosidation reactions, (a) thiophile = JV-btvmosuccwimide (NBS) [35], methyl tnflate [38], dimethyl(methyIthto)sulfonium triflate (DMTST) [39], or AModo-succmiraide (NlS)-triflic acid [40]. (b) TBPA+- = tris (4-bromophenyl)ammoniumyl hexachloroanti-monate [42]. (c) mCPHA = m-chloroptrbenmic acid [43],...

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... 

SCHEME 14.14 Synthesis of PS A1 repeating tetrasaccharide unit from Bacteroides fragilis by Seeberger and coworkers. DMTST, dimethyl(methylthio)sulfonium triflate TTBP, 2,4,6-tri-terf-butylpyrimidine. 

Abbreviations Ac acetyl Bn benzyl BSP 1-benzenesulfinyl piperidine BTIB bis(trifluoroacetoxy)iodobenzene DAST (diethylamino)sulfur trifluoride DDQ 2,3-dichloro-5,6-dicyano-/)-benzoquinone DMDO dimethyldioxirane DMTSF dimethyl(methylthio)sulfonium tetrafluoroborate DMTST dimethyl(methylthio)sulfonium triflate DTBMP 2,6-Ai-tert-butyl-4-methylpyridine DTBP 2,6-di-tert-butylpyridine DTBPl 2,6-di-tert-butylpyridinium iodide FDCPT l-fluoro-2,6-dichloropyridinium triflate FTMPT l-fluoro-2,4,6-trimethylpyridinium triflate IDCP iodonium dicollidine perchlorate IDCT idonium dicollidine triflate LPTS 2,6-lutidinium p-toluenesulfonate LTMP lithium tetramethylpiperidide Me methyl MPBT S-(4-methoxyphenyl) benzenethiosulflnate NBS A-bromosuccinimide NIS A-iodosuccinimide NlSac A-iodosaccharin PPTS pyridinium p-toluenesulfonate TBPA tris(4-bromophenyl)ammoniumyl hexachloroantimonate Tf trifluoromethanesulfonyl TMTSB methyl-bis(methylthio)sulfonium hexachloroantimonate TMU tetramethylurea Tr trityl TTBP 2,4,6-tri-tert-butylpyrimidine. 

Another concept for the activation of thioglycosides is their reaction with soft sulfur electrophiles. The first reagents of this type were dimethyl(methylthio)sulfonium triflate (DMTST, 83) and the corresponding tetrafluoroborate (DMTSF, 84) (Figure 4.4) [86,183-185], which are powerful methylsulfenylating agents (E = SMe) (Scheme 4.15), and are still extensively used. 

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. 

DMTST dimethyl(methylthio)sulfonium triflate DTBC 2,6-di-tert-butyl-4-cresol DTBP 2,6 di - te rt-buty Ipyridine... 

Trichloroacetimidate. b Dimethyl(methylthio)sulfonium triflate. c Diphenyl sulfoxide. 

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