Triazole-Enabled Ruthenium(II) Carboxylate-Catalyzed C–H Arylation with Electron-Deficient Aryl Halides

Abstract

A triazole-directed direct C–H arylation of arenes with electron-deficient aryl halides or a synthetically useful pyrimidyl chloride was achieved through ruthenium catalysis. Our novel strategy provides operationally simple and environmentally benign access to highly functionalized hetarenes, avoiding the use of strong organometallic bases. Detailed studies revealed a significant effect of the phosphine ligand, thereby permitting the reaction to occur with excellent levels of chemo- and position selectivity.

Key words

C–H bond activation - arylation - ruthenium catalysis - hetarenes - aryl halides

• References and Notes

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• 12 The mass balance was largely accounted for by the unreacted starting material 1, whereas only minor amounts of the corresponding desilylated triazole were observed.
• 13 4-{5-Chloro-2-[4-(trimethylsilyl)-1H-1,2,3-triazol-1-yl]phenyl}-6-methoxypyrimidine (3a) Under an atmosphere of N₂, a Schlenk tube was charged with triazole 1a (0.30 mmol, 1.00 equiv), 2-chloro-6-methoxypyrimidine (2; 0.45 mmol, 1.5 equiv), [Ru(O₂CMes)₂(p-cymene)] (8.4 mg, 15 μmol, 5.0 mol %), tris[4-(trifluoromethyl)phenyl]phosphine (L12; 7.0 mg, 15 μmol, 5.0 mol %), and K₂CO₃ (82.9 mg, 0.60 mmol, 2.00 equiv). PhMe (1.2 mL) was added and the mixture was stirred at 120 °C for 21 h then cooled to r.t. H₂O (10 mL) was added and the mixture was extracted with EtOAc (3 × 25 mL), washed with brine (25 mL), dried (Na₂SO₄), and concentrated in vacuo. The residue was purified by column chromatography [silica gel, hexane–EtOAc (5:1)] to give a yellow solid; yield: 53.6 mg (50%); mp 87–89 °C. IR (ATR): 1584, 1500, 1468, 1202, 1032, 838, 823, 758, 632, 417 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 8.70 (d, J = 1.0 Hz, 1 H), 7.82 (d, J = 2.2 Hz, 1 H), 7.58 (dd, J = 8.5, 2.2 Hz, 1 H), 7.51 (d, J = 8.1 Hz, 2 H), 6.19 (d, J = 1.1 Hz, 1 H), 3.91 (s, 3 H), 0.29 (s, 9 H). ¹³C NMR (75 MHz, CDCl₃): δ = 170.1 (CH), 161.9 (CH), 158.5 (C_q), 147.2 (CH); 136.2 (CH), 135.8 (CH), 133.9 (CH), 131.2 (C_q), 130.9 (C_q), 130.7 (C_q), 128.2 (C_q), 107.3 (C_q), 54.2 (CH₃), –1.1 (CH₃). MS (ESI): m/z (%) = 741 [2M + Na]⁺ (85), 559 (8), 382 [M + Na]⁺ (49), 360 [M + H]⁺ (100), 332 (16). HRMS (ESI): m/z [M + H]⁺ calcd for C₁₆H₁₉ ³⁵ClN₅OSi: 360.1042; found: 360.1028.
• 14 Ackermann L, Novák P, Vicente R, Pirovano V, Potukuchi HK. Synthesis 2010; 2245