DMTST triflate

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).

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],...

Methyl triflate is volatile and extremely toxic therefore the use of DMTST is recommended. Other promotes such as A-iodosuccinimide (NIS) can be used. 

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. 

Recently, several more effective activators have been introduced, including NBS [35], methyl triflate [38], dimethyl(methylthio)sulfomum triflate (DMTST) [39], N-iodo-succinimide-triflic acid (NiS-TfOH) [40], and trimethylsilyl triflate (TMSOTO (41]- The... 

Pyruvate ketals can be synthesized [161] by direct condensation of a pyruvate ester with a diol in the presence of a Lewis acid, but this is less preferred because of the electron-withdrawing effect of the adjacent carboxylate group [162,163]. Therefore, several indirect methods for the acetalization have been introduced including condensation with pyruvate derivatives [164,165] or generation of the carboxylate group by oxidation of a suitable precursor [166,167,168,169]. A more efficient route to pyruvic acid acetals starts from silylated diols [170] or by the reaction between diols and methyl pyruvate dialkyl dithioacetal [171,172] activated by methyl triflate, dimethyl(methylthio)sulfonium trifluoromethane sulfonate (DMTST), nitroso tetraflu-oroborate (NOBF4), S02Cl2-trifluoromethanesulfonic acid, or Al-Iodosuccinimide (NIS) and trifluoromethanesulfonic acid [173] (O Scheme 24). 

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

Similarly, reaction of a thioglycoside with a hydroxylic compound in the presence of an excess of a tetraalkylammonium bromide and the thiophilic promoter dimethyl(methylthio)sulfonium triflate (DMTST) proceeds with high stereoselectivity.131-133... 

---