The Chemistry of Glucal Halohydrins: The Effect of the Halide on Epoxide Formation

Article abstract of DOI:10.1016/S0040-4020(01)81332-6

Chlorohydrins, bromohydrins, and iodohydrins, formed by hydroxyhalogenation of tri-O-methyl glucal, undergo base induced cyclization to give glucal epoxides.The mechanism of the cyclization reaction was probed using 1H NMR and deuterium incorporation studies.Cyclization and in situ trapping with Cs2CO3 in MeOD gave deuterated methyl 3,4,6-tri-O-methyl-α-D-mannoside and methyl 3,4,6-tri-O-methyl-β-D-glucoside, and an unsaturated aldehyde.These studies led to optimised stereoselectivity for the epoxide formation.Reaction of gluco bromohydrins with NaH or LiHMDS in THF at 5 deg C gave β-epoxide, and reaction of manno iodohydrins with KH and 18-crown-6 in toluene at -70 deg C gave α-epoxide.The epoxides were opened by reaction with sodium phenylthiolate to give phenyl 3,4,6-tri-O-methyl-1-thio-α-D-mannopyranoside (single isomer), and phenyl 3,4,6-tri-O-methyl-1-thio-β-D-glucopyranoside (>18:1), respectively.