Electrochemically mediated fluoroalkylation/cyclization of unactivated alkenes: synthesis of polycyclic benzimidazoles containing a CF₃ group

Abstract

Herein, an electrochemical trifluoromethylation/cyclization reaction of unactivated alkenes within benzimidazole molecules by direct cascade with C2-H has been developed. The protocol used the readily available CF3SO2Na as the trifluoromethylation reagent....

Visible Light-Induced Radical Cascade Difluoromethylation/Cyclization of Unactivated Alkenes: Access to CF2H-Substituted Polycyclic Imidazoles

“…Colorless oil (39 mg, 83% yield); purified by silica gel column chromatography (hexanes/ethyl acetate mixtures 10:1–5:1 (v/v)); 1 H NMR (400 MHz, CDCl 3 ) δ 7.73–7.69 (m, 1H), 7.30–7.21 (m, 3H), 6.39 (tdd, J = 56.8, 5.5, 3.8 Hz, 1H), 4.19–4.14 (m, 1H), 3.98–3.91 (m, 1H), 3.32–3.24 (m, 1H), 2.82–2.67 (m, 1H), 2.32–2.00 (m, 4H), 1.78–1.68 (m, 1H); 13 C NMR (101 MHz, CDCl 3 ) δ 153.3, 142.7, 134.7, 122.4, 122.2, 119.2, 116.9 (t, J = 239.0 Hz), 109.1, 42.5, 38.1 (t, J = 21.4 Hz), 31.4 (dd, J = 6.3, 5.2 Hz), 27.6, 21.8; 19 F NMR (376 MHz, CDCl 3 ) δ −(113.05–114.03) (m, 1F), −(117.20–118.21) (m, 1F); HRMS (electrospray ionization (ESI), m / z ) [M + H + ] calcd for C 13 H 15 F 2 N 2 : 237.1198, found 237.1197. The spectral data were in accordance with the literature …”

“…Given the significance of the benzimidazole core and difluoromethyl group, it is beneficial to incorporate CF 2 H into polycyclic benzimidazole skeletons for the synthesis of CF 2 H-substituted N -heterocyclic benzimidazoles. 36 Regretfully, the methodologies for synthesizing difluoromethylated tricyclic imidazoles via direct radical cyclization of imidazoles with olefins have rarely been reported, only a limited number of substrates were reported by Chen’s group 37 in 2023 ( Scheme 1 b). Above all, the development of effective methods to synthesize CF 2 H-substituted tricyclic imidazoles via direct radical cascade addition/cyclization of imidazoles with olefins is still desirable.…”