Electrophotocatalytic Undirected C-H Trifluoromethylations of (Het)Arenes

Abstract

Electrophotochemistry has enabled arene C-H trifluoromethylation with the Langlois reagent CF₃ SO₂ Na under mild reaction conditions. The merger of electrosynthesis and photoredox catalysis provided a chemical oxidant-free approach for the generation of the CF₃ radical. The electrophotochemistry was carried out in an operationally simple manner, setting the stage for challenging C-H trifluoromethylations of unactivated arenes and heteroarenes. The robust nature of the electrophotochemical manifold was reflected by a wide scope, including electron-rich and electron-deficient benzenes, as well as naturally occurring heteroarenes. Electrophotochemical C-H trifluoromethylation was further achieved in flow with a modular electro-flow-cell equipped with an in-operando monitoring unit for on-line flow-NMR spectroscopy, providing support for the single electron transfer processes.

Keywords: C−H trifluoromethylation; arenes; catalysis; electrophotochemistry; oxidant-free.

Figure 1

Electrophotochemical undirected C−H trifluoromethylation.

Scheme 1

Preliminary electrophotochemical C−H trifluoromethylation.

Scheme 2

Electrophotochemical C−H trifluoromethylation of arenes 1.

Scheme 3

Electrophotochemical C−H trifluoromethylation of heteroarenes 4.

Scheme 4

Electrophotochemical late‐stage diversification of bioactive and natural products.

Scheme 5

Electrophotochemical C−H trifluoromethylation in a flow setup, flow rate: 1.0 mL min⁻¹, residence time in the electrochemical flow reactor: 6 min.

Scheme 6

Mechanistic studies.

Figure 2

a) Stern–Volmer plot analysis: Fluorescence quenching of [Mes‐Acr⁺]ClO₄ ⁻ with reagent 2. b) On‐line reaction monitoring in flow by ¹⁹F NMR spectroscopy.

Figure 3

Cyclic voltammetry. Conditions: (a) and (b) substrates (5 mmol L⁻¹), LiClO₄ (100 mmol L⁻¹), MeCN, 100 mV s⁻¹. (a) PC (black), 2 (red), PC+2 (blue). (b) PC+2 (black), PC+2 after being irradiated for 10 minutes with blue light (red).

Scheme 7

Plausible mechanism.