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TCI Practical Example: One-Pot Palladium-Catalyzed Fluorosulfonylation of an Aryl Bromide Using DABSO and NFSI

We are proud to present the synthetic protocol of arylsulfonyl fluoride from aryl bromide using DABSO, NFSI as reactants, and PdCl₂(Amphos)₂ as a palladium catalyst.

Used Chemicals

• 4-Bromobiphenyl
• Bis(sulfur Dioxide)-1,4-diazabicyclo[2.2.2]octane Adduct (= DABSO) [B3960]
• Bis[di-tert-butyl(4-dimethylaminophenyl)phosphine]dichloropalladium(II) (= PdCl₂(Amphos)₂) [B6255]
• Triethylamine (=Et₃N) [T0424]
• N-Fluorobenzenesulfonimide (=NFSI) [F0335]
• Isopropyl Alcohol (= IPA)

Procedure

To a solution of 4-bromobiphenyl (1.17 g, 5.00 mmol), DABSO (721 mg, 3.00 mmol), and PdCl₂(Amphos)₂ (177 mg, 0.25 mmol) in anhydrous isopropyl alcohol (20 mL) was added triethylamine (2.1 mL, 15 mmol) at room temperature and the mixture was stirred at 75 °C for 23 hours. The suspension was cooled at room temperature and NFSI (2.36 g, 7.5 mmol) was added and the reaction mixture stirred for 3 hours until completion. The solvent was removed under reduced pressure. The residue was diluted with ethyl acetate (20 mL) and filtrated through celite pad. The filtrate was washed with saturated aqueous sodium thiosulfate solution (20 mL) and brine (20 mL), dried over sodium sulfate and filtered. The solvent was removed under reduced pressure and the residue was purified by medium pressure preparative chromatography (ethyl acetate:hexane = 2:98 - 5:95 on silica gel) to give compound 1 as a white solid (928 mg, 79%).

Experimenter’s Comments

The reaction mixture was monitored by TLC (ethyl acetate:hexane = 1:9, Rf = 0.57) and UPLC-MS.

Analytical Data

Compound 1

¹H NMR (400 MHz, CDCl₃); δ 8.12–8.04 (m, 2H), 7.86–7.80 (m, 2H), 7.67–7.58 (m, 2H), 7.44-7.55 (m, 3H).

Lead Reference

• One-pot palladium-catalyzed synthesis of sulfonyl fluorides from aryl bromides
• A. T. Davies, J. M. Curto, S. W. Bagley, M. C. Willis, Chem. Sci. 2017, 8, 1233.