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TCI Practical Example: Deoxygenative Fluorination of an Alcohol Using PyFluor

We are proud to present the deoxygenative fluorination of the hydroxy group of 2,3-O-isopropylidene-D-ribonolactone using PyFluor as a fluorinating agent.

Used Chemicals

• 2,3-O-Isopropylidene-D-ribonic γ-Lactone [I1039]
• Pyridine-2-sulfonyl Fluoride (= PyFluor) [P2398]
• DBU [D1270]
• Toluene

Procedure

A solution of PyFluor (513 mg, 3.19 mmol) in dry toluene (3.6 mL) was added to a solution of 2,3-O-isopropylidene-D-ribonic γ-lactone (500 mg, 2.66 mmol) and DBU (0.79 mL, 5.31 mmol) in toluene (3.0 mL) at 0 °C and the solution was stirred at room temperature for one day. The reaction mixture was quenched with water (10 mL) and the aqueous layer was extracted with ethyl acetate (3 x 5 mL). The combined organic layer was washed with sat. NH₄Cl aq. and brine, dried over anhydrous sodium sulfate and filtered. The solvent was removed under reduced pressure and the residue was purified by column chromatography (ethyl acetate:hexane = 0:100 - 15:85 on silica gel) to give the fluorinated compound 1 as a white solid (309 mg, 61% yield).

Experimenter’s Comments

The reaction mixture was monitored by TLC (ethyl acetate:hexane = 1:2, Rf = 0.33).
It was easier to weigh after melting PyFluor by heating with hot water bath because melting point of PyFluor is 26 °C.

Analytical Data

Fluorinated Compound 1

¹H NMR (270 MHz, DMSO-d₆); δ 4.94-4.74 (m, 4H), 4.64 (ddd, J = 3.0, 10.8, 27.8 Hz, 1H), 1.37 (s, 3H), 1.33 (s, 3H).

Lead Reference

• PyFluor: A Low-Cost, Stable, and Selective Deoxyfluorination Reagent
  • M. K. Nielsen, C. R. Ugaz, W. Li, A. G. Doyle, J. Am. Chem. Soc. 2015, 137, 9571.