Selective Fluorination of Hydroxy Group using DFMBA

N,N-Diethyl-α,α-difluoro-3-methylbenzylamine (DFMBA, 1) has two fluorine atoms which can be easily eliminated, and fluorinate hydroxy groups selectively. Hara et al. have reported the fluorination of hydroxy groups in carbohydrates and nucleosides using 1, by which the corresponding fluorinated products are obtained in good yields.¹⁾

In addition, Hara et al. have also reported the facile synthesis of heterocyclic and bicyclo compounds by the intramolecular cyclization accompanying the elimination of fluorine groups.^2,3)

Typical Procedure: Fluorination of 1,2;3,4-di-O-isopropylidene-α-D-galactopyranose¹⁾
Into a reactor consisting of a PFA tube with a diameter of 10 mm sealed at one end, are introduced heptane (1 mL), 1 (213 mg, 1 mmol), and 1,2;3,4-di-O-isopropylidene-α-D-galactopyranose (130 mg, 0.5 mmol). The open end of the reactor is connected to a port in a domestic microwave oven and the port is connected to a reflux condenser located outside the oven. Then, the reaction mixture is submitted to microwave irradiation for 20 min. During the irradiation, the reaction mixture is refluxed vigorously. After the reaction, the reaction mixture is poured into aq. NaHCO₃ and extracted with ether three times. The combined ethereal layers are dried over MgSO₄, concentrated under reduced pressure. Purification by column chromatography on silica gel (hexane-ether) gives 6-deoxy-6-fluoro-1,2;3,4-di-O-isopropylidene-α-D-galactopyranose (Y. 70%).