Palladium-Catalyzed Phosphine-Free Direct C–H Arylation of Benzothiophenes and Benzofurans Involving MIDA Boronates

Abstract

With high regioselectivity, a series of benzoheterocyclic compounds were synthesized via palladiium-catalyzed phosphine-free C–H arylation of benzothiophenes/benzofurans with aryl MIDA boronates at 30–50 °C in moderate to excellent yields. MIDA boronates were used in C–H arylation of heterocycles for the first time. Under the optimal conditions, the benzothiophenes could be transformed into the β-arylbenzothiophenes, and the benzofurans gave only α-aryl-substituted products.

Key words

C–H arylation - benzothiophene - benzofuran - MIDA boronate - bis(alkoxo)palladium(II) complex

• References and Notes


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• 12 Preparation of 3aa; Typical ProcedureTo a 10 mL round-bottom flask were added III (3.2 mg, 0.005 mmol, 2 mol%), Ag₂O (116 mg, 0.5 mmol, 2 equiv), benzoquinone (14 mg, 0.125 mmol, 0.5 equiv), Cs(tfa) (64 mg, 0.25 mmol, 1 equiv.), benzothiophene (1a; 34 mg, 0.25 mmol, 1 equiv), phenyl MIDA boronate (2a; 86 mg, 0.375 mmol, 1.5 equiv), and H₂O–CF₃SO₃H–TFA (15:2:83; 1 mL). The reaction mixture was stirred at 30–50 °C for 20 h. The suspension was cooled to r.t. and extracted with CH₂Cl₂ (3 × 10 mL). The combined organic layers were washed with 20% aq NaHCO₃ solution (40 mL). After evaporation of the solvent the crude product was purified by chromatography on silica gel to give 3-phenylbenzo[b]thiophene (3aa; 46.7 mg, 89% isolated yield) as a yellow oil. This product has been reported previously.^4f 3-Phenylbenzo[b]thiophene (3aa) ¹H NMR (400 MHz, CDCl₃): δ = 7.95–7.88 (m, 2 H), 7.61–7.56 (m, 2 H), 7.51–7.45 (m, 2 H), 7.43–7.35 (m, 4 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 140.65, 138.06, 137.86, 135.98, 128.70, 128.69, 127.52, 124.38, 124.30, 123.39, 122.90 ppm. MS (EI): m/z calcd for C₁₅H₁₂S [M]⁺: 210.1; found: 210.0.
• 13 CCDC-1008524 (3fa) contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
• 14 CCDC-1008525 (3ia) contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
• 15 Preparation of 5; Typical ProcedureTo a 10 mL round-bottom flask were added III (3.2 mg, 0.005 mmol, 2 mol%), Ag₂O (116 mg, 0.5 mmol, 2 equiv), benzoquinone (14 mg, 0.125 mmol, 0.5 equiv), Cs(tfa) (64 mg, 0.25 mmol, 1 equiv), 3aa (52.5 mg, 0.25 mmol, 1 equiv), phenyl MIDA boronate (115 mg, 0.5 mmol, 2.0 equiv), and H₂O–CF₃SO₃H–TFA (15:2:83; 1 mL). The reaction mixture was stirred at 30 °C and 80 °C for 20 h. The suspension was cooled to r.t. and extracted with CH₂Cl₂ (3 × 10 mL). The combined organic layers were washed with 20% aq NaHCO₃ solution (40 mL). After evaporation of the solvent the crude product was purified by chromatography on silica gel to give 2,3-diphenylbenzo[b]thiophene (5; 6.4 mg, 9% at 30 °C/25.0 mg, 35% at 80 °C isolated yield) as a white solid; mp 111–113 °C. This product has been reported previously.¹⁷ 2,3-Diphenylbenzo[b]thiophene (5) ¹H NMR (400 MHz, CDCl₃): δ = 7.88–7.84 (m, 1 H), 7.61–7.56 (m, 1 H), 7.42–7.28 (m, 9 H), 7.25–7.20 (m, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 140.88, 139.54, 138.85, 135.52, 134.24, 133.24, 130.43, 129.61, 128.63, 128.33, 127.68, 127.36, 124.51, 124.42, 123.34, 122.05 ppm. MS (EI): m/z calcd for C₂₀H₁₄S [M]⁺: 286.1; found: 286.0.
• 16 Preparation of 6; Typical ProcedureTo a 10 mL round-bottom flask were added III (3.2 mg, 0.005 mmol, 2 mol%), Ag₂O (116 mg, 0.5 mmol, 2 equiv), benzoquinone (14 mg, 0.125 mmol, 0.5 equiv), Cs(tfa) (64 mg, 0.25 mmol, 1 equiv), 6 (56mg, 0.25 mmol, 1 equiv), phenyl MIDA boronates (115 mg, 0.5 mmol, 2.0 equiv), and H₂O–CF₃SO₃H–TFA (15:2:83; 1 mL). The reaction mixture was stirred at 30 °C and 80 °C for 20 h. The suspension was cooled to r.t. and extracted with CH₂Cl₂ (3 × 10 mL). The combined organic layers were washed with 20% aq NaHCO₃ solution (40 mL). After evaporation of the solvent the crude product was purified by chromatography on silica gel to give 3-phenyl-2-(p-tolyl)benzo[b]thiophene (6.0 mg, 8% at 30 °C/14.3 mg, 19% at 80 °C isolated yield) as a white solid; mp 149–151 °C. This product has been reported previously.¹⁸ 3-Phenyl-2-(p-tolyl)benzo[b]thiophene (7) ¹H NMR (400 MHz, CDCl₃): δ = 7.90–7.85 (m, 1 H), 7.59 (d, J = 8.2 Hz, 1 H), 7.45–7.31 (m, 7 H), 7.27–7.21 (m, 2 H), 7.10–7.04 (m, 2 H), 2.33 (s, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 141.00, 139.73, 138.73, 137.61, 135.72, 132.80, 131.33, 130.46, 129.44, 129.08, 128.62, 127.30, 124.37, 123.22, 122.01, 21.17 ppm. MS (EI): m/z calcd for C₂₁H₁₆S [M]⁺: 300.1; found: 300.0.
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