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TCI Practical Example: Trifluoromethylation Reaction Using Umemoto Reagent IV

We are proud to present the trifluoromethylation reaction using Umemoto reagent IV. Umemoto reagent IV is activated by trifluoromethoxy groups, which are strong electron-withdrawing groups, and thus shows higher reactivity compared to the conventional Umemoto reagent series.

Used Chemicals

• Umemoto Reagent IV [T4082]
• α-Acetyl-γ-butyrolactone [A0681]
• Sodium Hydride (60%, dispersion in Paraffin Liquid) [S0481]
• DMF

Procedure

Sodium hydride (60%, 76.1 mg, 3.17 mmol) was added to a solution of α-acetyl-γ-butyrolactone (200 mg, 1.59 mmol) in DMF (4 mL) at room temperature for 15 minutes. The reaction mixture was cooled to -45 °C and Umemoto reagent IV (1.08 g, 1.90 mmol) was added. Then the mixture was allowed to warm to room temperature and was stirred for 1 hour. The reaction was quenched with water and the aqueous layer was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate:hexane = 0:100 - 20:80) to give 3-acetyl-3-(trifluoromethyl)dihydrofuran-2(3H)-one as a yellow oil (218 mg, 71% yield).

Experimenter’s Comments

The reaction mixture was monitored by NMR.

Analytical Data

3-Acetyl-3-(trifluoromethyl)dihydrofuran-2(3H)-one

¹H NMR (270 MHz, CDCl₃); δ 4.45-4.37 (m,1H), 4.31-4.22 (m, 1H), 3.07-2.98 (m, 1H), 2.63-2.52 (m, 1H), 2.51 (s, 3H).

Lead Reference

• Synthesis and applications of S-(trifluoromethyl)-2,8-bis(trifluoromethoxy)dibenzothiophenium triflate (Umemoto reagent IV)
  • S. R. Mudshinge, G. B. Hammond, T. Umemoto, J. Fluor. Chem. 2022, 261, 110015.

Other References

• Introduction of Fluorine and Fluorine-Containing Functional Groups
  • T. Liang, C. N. Neumann, T. Ritter, Angew. Chem. Int. Ed. 2013, 52, 8214.