Palladium-Catalyzed Regioselective C-5 Arylation of 1,2,3-Triazoles with Diaryliodonium Salts

^§ These authors contributed equally to this work.

Abstract

An effective method for C-5 arylation of 1,4-disubstituted 1,2,3-triazoles and C-5 regioselective arylation of 1-substituted 1,2,3-triazoles via sp² C–H activation with palladium as a catalyst and diaryliodonium salts as arylating reagents is described. Various electron-rich and electron-deficient substituents attached to triazoles and diaryliodonium salts were tolerable to give the desired products with good isolated yields in 24 hours under air atmosphere.

Key words

arylation - diaryliodonium salts - regioselectivity - 1,2,3-triazoles - C–H activation

• References and Notes

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• 15 General Procedure for Regioselective C-5 Arylation of 1,2,3-Triazoles: To a dried flask were added 1,2,3-triazoles (0.2 mmol), diaryliodonium salt (0.2 mmol), K₂CO₃ (2.0 equiv), Pd(OAc)₂ (5 mol %), tris(o-tolyl)phosphine (10 mol%), and DMF (2 mL). Then the reaction mixture was stirred in an oil bath and heated slowly to 100 °C for 24 h. The reaction was monitored by TLC until no change was observed. The solution was cooled to r.t., and then diluted with EtOAc (10 mL). The organic phase was washed with brine (3 × 10 mL), dried over anhyd Na₂SO₄ and concentrated under vacuum to get the crude product. The crude product was further purified by column chromatography with hexane–EtOAc as eluent and the pure product was obtained. Diaryliodonium salts were prepared in accordance with the method previously reported by Olofsson’s group.^14a 1,4-Disubstituted 1,2,3-triazoles were prepared according to our previous work.^16a 1-Substituted 1,2,3-triazoles were prepared according to the previous literature.¹⁷ The analytical data of new compounds are as follows. 1-(4-Fluorobenzyl)-4-(4-fluorophenyl)-5-phenyl-1H-1,2,3-triazole (3e): white solid; yield: 46.5 mg (67%); mp 112–115 °C. ¹H NMR (600 MHz, CDCl₃): δ = 7.44 (dd, J = 13.8, 6.5 Hz, 3 H), 7.37 (t, J = 7.4 Hz, 2 H), 7.19 (s, 1 H), 7.06 (d, J = 7.2 Hz, 2 H), 6.90–6.97 (m, 2 H), 6.87 (q, J = 8.0 Hz, 3 H), 5.30 (s, 2 H). ¹³C NMR (151 MHz, CDCl₃): δ = 162.4 (d, J _C–F = 227.8 Hz), 143.8, 133.5, 130.9 (d, J _C–F = 3.6 Hz), 129.9, 129.5, 129.4, 129.3, 128.4 (d, J _C–F = 8.1 Hz), 127.6, 115.7 (d, J _C–F = 21.6 Hz), 51.4. HRMS (ESI, MeOH): m/z [M + H]⁺ calcd for C₂₁H₁₆F₂N₃: 348.1307; found: 348.1315. IR (KBr): 3032, 2921, 2853, 1512, 1224, 843, 766, 705 cm^–1. 1-(4-Fluorobenzyl)-5-phenyl-4-(4-tolyl)-1H-1,2,3-triazole (3f): white solid; yield: 52.1 mg (76%); mp 147–150 °C. ¹H NMR (600 MHz, CDCl₃): δ = 7.48–7.53 (m, 3 H), 7.43 (t, J = 7.5 Hz, 2 H), 7.15 (d, J = 7.3 Hz, 2 H), 7.06 (d, J = 7.8 Hz, 2 H), 6.92–6.99 (m, 4 H), 5.36 (s, 2 H), 2.30 (s, 3 H). ¹³C NMR (151 MHz, CDCl₃): δ = 161.5 (d, J _C–F = 247.1 Hz), 143.7, 137.9, 133.6, 132.3, 130.1, 129.7, 129.3, 129.2, 128.4 (d, J _C–F = 8.1 Hz), 127.7, 127.5, 127.1 (d, J _C–F = 3.1 Hz), 115.3 (d, J _C–F = 21.5 Hz), 51.9, 21.1. HRMS (ESI, MeOH): m/z [M + H]⁺ calcd for C₂₂H₁₉FN₃: 344.1558; found: 344.1564. IR (KBr): 3034, 2924, 2854, 1514, 1354, 1216, 839, 746, 696 cm^–1. 1-Benzyl-5-(2-bromophenyl)-4-phenyl-1H-1,2,3-triazole (3k): pale yellow solid; yield: 59.3 mg (76%); mp 99–101 °C. ¹H NMR (600 MHz, CDCl₃): δ = 7.54 (d, J = 7.0 Hz, 2 H), 7.47 (d, J = 7.1 Hz, 1 H), 7.42 (t, J = 7.4 Hz, 2 H), 7.30 (d, J = 8.7 Hz, 1 H), 7.24 (s, 3 H), 7.15 (d, J = 7.2 Hz, 2 H), 7.03 (d, J = 4.6 Hz, 2 H), 6.79 (d, J = 8.7 Hz, 1 H), 5.41 (s, 2 H). ¹³C NMR (151 MHz, CDCl₃): δ = 155.5, 144.5, 135.2, 133.9, 132.3, 130.7, 130.5, 130.1, 129.7, 129.2, 128.5, 128.2, 127.8, 127.5, 126.8, 117.4, 52.1. HRMS (ESI, MeOH): m/z [M + H]⁺ calcd for C₂₁H₁₇BrN₃: 390.0601; found: 390.0609. IR (KBr): 3061, 2925, 2855, 1344, 763, 734, 695, 601 cm^–1.
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