Microwave-Assisted Copper-Catalyzed Coupling of Bromoalkynes and Sulfonamides: Rapid Synthesis of N-Sulfonyl Ynamides

Abstract

The synergistic effect of an alcohol solvent and microwave irradiation dramatically increased the C–N coupling rate, enabling the rapid synthesis of N-sulfonyl ynamides in ten minutes. The optimal catalyst, ligand, and solvent combination was investigated, and various bromoalkynes and sulfonamides were shown to be tolerated under these conditions.

Key words

C–N coupling - ynamides - sulfonamides - microwave irradiation - solvent effect

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• 23 N,4-Dimethyl-N-(phenylethynyl)benzenesulfonamide (3aa); Typical Procedure Ethynylbenzene (1a; 0.28 mmol), sulfonamide 2a (0.42 mmol, 1.5 equiv), CuSO₄·5 H₂O (0.028 mmol, 10 mol%), DMEDA (0.056 mmol, 20 mol%), and K₂CO₃ (0.70 mmol, 2.5 equiv) was suspended in anhyd MeOH (2.8 mL) in a microwave reactor vial. The vial was sealed with a cap, and the mixture was subjected to microwave irradiation at 90 °C for 10 min, then cooled. The precipitate was collected by filtration and washed with CH₂Cl₂. The filtrate was concentrated and purified by column chromatography (silica gel) to give a white solid; yield: 89%; mp 85.0 °C; R_f = 0.2 (EtOAc–hexane, 1:10). IR (neat): 2229, 1359, 1160, 952, 755, 674 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 7.84 (d, J = 8.1 Hz, 2 H), 7.39–7.34 (m, 4 H), 7.31–7.27 (m, 3 H), 3.15 (s, 3 H), 2.46 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 144.8, 133.2, 131.4, 129.8, 128.3, 127.9, 122.7, 84.0, 69.0, 39.3, 21.7. HRMS (EI+): m/z [M⁺] calcd for C₁₆H₁₅NO₂S: 285.0818; found: 285.0820.