Iodine → (1R,2S,3S,4R,5R)-4-iodo-6,8-dioxabicyclo[3.2.1]octane-2,3-diol

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Reaction Conditions

Reaction Steps

The de-acetylated syrupy D-glucal IntA1 from step 1 (53.7 g, based on quantitative yield, 367 mmol) is treated with bis(tributyltin)oxide (175 g, 150 mL, 294 mmol, 0.8 eq) and activated powdered 3 A molecular sieves [150 g] in refluxing dry Acetonitrile [3.5 L] for 16 hours. Next morning, the mixture is cooled to 5° C. under N2 and I2 [140 g, 551 mmol] is added in one portion. The dark brown mixture is stirred for 15 nm minutes 5° C., then for 3 hours at room temperature. TLC (either 1/1:toluene/Acetone or 100% EtOAc) showed the complete conversion of D-glucal (Rf 0.14) into iodo derivative (Rf 0.45). The mixture was filtered through Celite and concentrated. To this residue is added saturated aqueous sodium thiosulfate (200 mL) and hexanes (200 mL). The biphasic mixture is vigorously mixed for 16 hours. The aqueous phase is then continuously extracted with DCM (1.5 Lt.) for 24 hours (till no product was detected in the aqueous layer). The organic extract is dried over Na2SO4 and concentrated. To the residue was added 500 mL acetone. The yellow insoluble material was filtered and discarded. The acetone solution was evaporated to dryness. The residue was treated with EtOAc to separate the desired iodo-1,6-anyhdro derivative, hatA2 as a white solid. Yield: 76 g. TLC IntA2 Rf=0.7, SiO2, 100% Ethyl Acetate.

Provenance & Evidence