On the Use of 3,5-O-Benzylidene and 3,5-O-(Di-tert-butylsilylene)-2-O-benzylarabinothiofuranosides and Their Sulfoxides as Glycosyl Donors for the Synthesis of β-Arabinofuranosides:  Importance of the Activation Method

A 2-O-benzyl-3,5-O-benzylidene-α-d-thioarabinofuranoside was obtained by reaction of the corresponding diol with α,α-dibromotoluene under basic conditions. On activation with 1-benzenesulfinyl piperidine, or diphenyl sulfoxide, and trifluoromethanesulfonic anhydride in dichloromethane at −55 °C, reaction with glycosyl acceptors affords anomeric mixtures with little or no selectivity. The analogous 2-O-benzyl-3,5-O-(di-tert-butylsilylene)-α-d-thioarabinofuranoside also showed no significant selectivity under the 1-benzenesulfinyl piperidine or diphenyl sulfoxide conditions. With N-iodosuccinimide and silver trifluoromethanesulfonate the silylene acetal showed moderate to high β-selectivity, independent of the configuration of the starting thioglycoside. High β-selectivity was also obtained with a 2-O-benzyl-3,5-O-(di-tert-butylsilylene)-α-arabinofuranosyl sulfoxide donor on activation with trifluoromethanesulfonic anhydride. The high β-selectivities obtained by the N-iodosuccinimide/silver trifluoromethanesulfonate and sulfoxide methods are consistent with a common intermediate, most likely to be the oxacarbenium ion. The poor selectivity observed on activation of the thioglycosides with the 1-benzenesulfinyl piperidine, or diphenyl sulfoxide, and trifluoromethanesulfonic anhydride methods appears to be the result of the formation of a complex mixture of glycosyl donors, as determined by low-temperature NMR work.