Thioglycosides promoter systems

Recently, a number of thiophilic activators that can activate thioglycosides of low reactivity at low temperature have been described. For example, thiophilic promoter systems, such as diphenylsulfoxide [87,99], S-(4-methoxyphenyl)benzenethiosulfinate... 

Several other examples have been reported in which thioglycosides were used as glycosyl acceptors. Thus, thioglycosides containing free hydroxyls can be coupled chemoselectively with glycosyl bromides and chlorides in the presence of silver triflate or tin(II) chloride-silver perchlorate as the promoter system [12,53,56,162,218-221]. 

Given that we find iodine to be a relatively mild promoter for thioglycoside activation, we have investigated its reaction with a panel of thioglycosides of varying reactivity (Fig. 21).53 We also have made a systematic study of the ability of iodine-based promoters to effect activation of a latent nitrothiophenyl galac-toside in an attempt to ascertain the relative reactivity of the various promoter systems we have studied (Fig. 22).53 It is clear that the cheap, readily available promoters we have reported vary in their reactivity by several orders of magnitude. 

Codee JDC, Litjens REJN, den Heeten R, Overkleeft HS, van Boom JH, van der Marel GA. Ph2S0/Tf20 a powerful promoter system in chemoselective glycosylations using thioglycosides. Org. Lett. 2003 5 1519-1522. 

Ldnn, H, Sulfurylchloride trifluoromethanesulfonic acid — a novel promoter system for glycoside synthesis using thioglycosides as glycosyl donors, Glycoconjugate J., 4, 117-118, 1987. 

The results discussed in this chapter clearly indicated that NIS/TfOH is a valuable promoter system for the chemoselective glycosylation of latent acceptor with active thioglycosyl donors. Furthermore, this study revealed that the amount of triflic acid used was crucial for the selective activation of active thioglycosides over relatively latent thioglycosides. 

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... 

Related to the activation of thioglycosides by sulfenylation are selenylation type reactions (E = SeR) (Scheme 4.15). Arylselenylating type promoters used with thioglycosides include benzeneselenenyl triflate [199,200] or the Wphenylselenylphtalimide-trimethylsilyltriflate [201] and Wphenylselenylphtalimide-magnesium perchlorate [202] systems. 

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