Difluoroiodomethane (ca. 45%, ca. 3.0mol/L in Acetonitrile)

• Difluoroiodomethane (ca. 45%, ca. 3.0mol/L in Acetonitrile) [D5762]
• 3,5-Dimethoxyphenylboronic Acid (contains varying amounts of Anhydride) [D3513]
• Tetrakis(triphenylphosphine)palladium(0) (= Pd(PPh₃)₄) [T1350]
• Bis[2-(diphenylphosphino)phenyl] Ether (= DPEphos) [B2867]
• Tripotassium Phosphate
• Toluene
• Water

To a solution of 3,5-dimethoxyphenylboronic acid (200 mg, 1.10 mmol), tripotassium phosphate (481 mg, 2.20 mmol, 2.0 eq.), DPEphos (59 mg, 0.11 mmol, 0.1 eq.) and Pd(PPh₃)₄ (127 mg, 0.11 mmol, 0.1 eq.) in toluene (5 mL) and water (0.5 mL) was added difluoroiodomethane (ca. 45%, ca. 3.0mol/L in acetonitrile) (0.55 mL, 1.65 mmol, 1.5 eq.) at r.t. and the mixture was stirred at 65 °C for overnight. The reaction mixture was diluted with ethyl acetate (25 mL) and washed with water (15 mL) and brine (25 mL), then organic layer was dried over sodium sulfate and filtered. The solvent was removed under reduced pressure and the residue was purified by column chromatography (ethyl acetate:hexane = 0:1 - 1:9 on silica gel) to give 1-(difluoromethyl)-3,5-dimethoxybenzene as a colorless liquid (111 mg, 54%).

Toluene was degassed for 10 minutes before use.

1-(Difluoromethyl)-3,5-dimethoxybenzene

¹H NMR (400 MHz, CDCl₃); δ 6.94 (s, 2H), 6.57 (t, J = 57 Hz, 1H), 6.54 (s, 1H), 3.82 (s, 6H).

• Precatalyst Effects on Pd-Catalyzed Cross-Coupling Difluoromethylation of Aryl Boronic Acids
• K. Hori, H. Motohashi, D. Sato, K. Mikami, ACS Catal. 2019, 9, 417.