Observations on the activation of methyl thioglycosides by iodine and its interhalogen compounds

Treatment of ‘armed’ methyl thiogalactosides with iodine in the absence of an acceptor alcohol results in thioglycoside epimerisation, whereas there is no effect on the corresponding ‘disarmed’ methyl thioglycosides. In contrast, iodine–hexamethyldisilane (which generates iodotrimethylsilane in situ) brings about epimerisation of ‘disarmed’ thioglycosides, ultimately giving rise to the corresponding α-glycosyl iodides on extended exposure. Cross-over experiments show the former iodine-promoted epimerisation process to be intermolecular, whereas the latter iodine–hexamethyldisilane-promoted epimerisation is intramolecular. Treatment of the same methyl thiogalactosides with iodine monobromide gives rise to the thermodynamically favoured α-glycosyl bromides, whereas reaction with iodine monochloride initially gives the kinetic β-glycosyl chlorides, which slowly epimerise to the thermodynamic α-linked products. Differences in the outcome of thioglycoside activation by I–I, I–Br and I–Cl suggest there may be scope for influencing the stereochemical course of thioglycoside-based glycosylation reactions through careful choice of promoter.