TMSBr-mediated solvent- and work-up-free synthesis of α-2-deoxyglycosides from glycals

The thio-additions of glycals were efficiently promoted by a stoichiometric amount of trimethylsilyl bromide (TMSBr) to produce S-2-deoxyglycosides under solvent-free conditions in good to excellent yields. In addition, with triphenylphosphine oxide as an additive, the TMSBr-mediated direct glycosylations of glycals with a large range of alcohols were highly α-selective.

mL × 2) and brine (50 mL × 2), dried over anhydrous MgSO 4 , filtered, and then concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel and then the volatiles were removed in vacuo to obtain the product as colorless oil. (1). 1
Then the crude product was dissolved in dried DMF. Benzyl bromide (16.0 mL, 0.135 mol) and NaH (60%, 5.40 g, 0.135 mol) was slowly added at 0 °C. The reaction solution was gradually warmed up to room temperature and stirred for 6 hours under nitrogen atmosphere. H 2 O (30 mL) was added to quench the reaction. The solution was transferred to a separation funnel. The organic layer was separated, and the s3 aqueous layer was extracted with EtOAc (50 mL × 2). The combined organic layers were washed with brine (100 mL × 2), dried over anhydrous MgSO 4 , filtered, and then concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel (EtOAc/Hexane= 0/1 to 1/2) and then the volatiles were removed in vacuo to obtain the product as a white solid.
After stirring for 4 hours, amberlite IR (120 H + ) acid resin was added protionwise until the solution was neutralized. The mixture was filtered, concentrated under reduced pressure, and then volatiles were removed in vacuo to afford tetrol glycoside
To a solution of 4,6-O-benzylidine-D-glucopyranoside S4 in dried DMF (80 mL) was added benzyl bromide (7.0 mL, 0.059 mol) in a flame dried flask under nitrogen atmosphere. Sodium hydride (60% dispersion in mineral oil, 2.560 g, 0.064 mol) was added portionwise and gradually in the reaction solution at 0 °C. After s20 stirring for 16 hours at room temperature, the mixture was diluted with ethyl acetate (100 mL), quenched by water (50 mL×2) and washed with brine (50 mL), dried over anhydrous MgSO 4 , filtered, and then concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel (EtOAc/ Hexane= 0/1 to 1/4) and then volatiles were removed in vacuo to acquire the benzyl glycoside S5 as a white solid.
Compound S5 was dissolved in dried CH 2 Cl 2 (50 mL) in a flame dried flask under nitrogen atmosphere. Borane-tetrahydrofurane complex (1M in THF, 130 mL, 0.13 mol) and trimethyl silyltrifluoromethanesulfonate (2.30 mL, 0.013 mol) was added subsequently in the reaction solution at 0 °C After stirring for 6 hours at 0 o C, the reaction mixture was quenched by NaHCO 3 (50 mL×3), washed with brine (50 mL), dried over anhydrous MgSO 4 , filtered, and then concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel (EtOAc/ Hexane= 0/1 to 1/2) and then volatiles were removed in vacuo to acquire the product (64)