Iron-Catalyzed Thiocyclization for the Synthesis of Trifluoro­methylated Benzothiophenes by C–H Functionalization of Aryl Disulfides

Abstract

An iron-catalyzed thiocyclization of propynols with aryl disulfides has been developed for the synthesis of trifluoromethylated benzothiophenes. The one-pot tandem reaction involves Meyer–Schuster ­rearrangement of propynols and radical cyclization through C–H functionalization of aryl disulfides. A variety of 2-trifluoroacyl benzothiophenes were prepared in moderate to good yields with good functional-group tolerance.

Key words

annulations - C–H functionalization - iron - radical - trifluoromethyl

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• 17 General Procedure for the Synthesis of 2-Trifluoroacylbenzothiophenes To a flame-dried Schlenk tube with a magnetic stirring bar was charged with 1 (0.1 mmol), 2 (0.2 mmol), FeCl₃ (6.4 mg, 0.04 mmol), BPO (0.02 mmol, 4.8 mg), and I₂ (101.6 mg, 0.4 mmol) in MeNO₂ (2 mL) under N₂ atmosphere. The reaction mixture was stirred at 120 °C until complete consumption of starting material as detected by TLC or GC–MS analysis. After the reaction was finished, the mixture was poured into EtOAc, which was washed with sat. Na₂S₂O₃ (2 × 15 mL) and brine (1 × 15 mL). After the aqueous layer was extracted with EtOAc, the combined organic layers were dried over anhydrous Na₂SO₄, and evaporated under vacuum. The residue was purified by flash column chromatography (PE–EtOAc) to afford the desired products 3–20. 2,2,2-Trifluoro-1-(3-phenylbenzo[b]thiophen-2-yl)ethanone (3) Yellow solid (52.0 mg, 85% yield); mp 65–68 °C. ¹H NMR (500 MHz, CDCl₃): δ = 7.84 (d, J = 8.0 Hz, 1 H), 7.51–7.47 (m, 2 H), 7.43–7.40 (m, 3 H), 7.33–7.32 (m, 1 H), 7.29–7.27 (m, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 175.6 (q, J _C–F = 37.1 Hz), 148.6, 141.9, 139.6, 133.8, 129.5, 129.0, 128.7, 128.4, 127.9, 126.4, 125.6, 122.5, 116.0 (q, J _C–F = 289.0 Hz). ¹⁹F NMR (470 MHz, CDCl₃): δ = –73.10 (s, 3 F). LRMS (EI, 70 eV): m/z (%) = 306 (57) [M⁺], 237 (100), 165 (48), 163 (12), 104 (17). ESI-HRMS: m/z calcd for C₁₆H₉F₃NaOS⁺ [M + Na]⁺: 329.0218; found: 329.0223.