Copper-Catalyzed Direct Amination of Benzoxazoles Using Primary Amines as Nitrogen Sources

Abstract

A facile, efficient, and simple protocol for direct oxidative C–H amination of benzoxazoles with primary amines through copper-catalyzed C–H bond activation using tert-butyl peroxide (TBP) as oxidant under air has been developed. The reaction proceeds smoothly at ambient temperature to furnish the products. A variety of substituted aminobenzoxazoles were synthesized with good to excellent yields.

Key words

C-H activation - amination - copper catalysis - benzoxazole

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• 12a Synthesis of Aminobenzoxazoles from Benzoxazoles and Amines; General Procedure: A mixture of benzoxazole (1.0 mmol), amine (1.0 mmol), CuCl (0.2 mmol), TBP (2.0 mmol), and AcOH (0.8 mmol) in toluene (2.0 mL) was stirred at 80 °C for 16 h. Upon completion, the reaction mixture was diluted with EtOAc (4.0 mL) and filtered through a bed of silica gel. The volatiles were removed under vacuum to afford the crude product, which was analyzed by GC. The crude product was purified by column chromatography on silica gel (EtOAc–hexanes, 10:90) to afford the desired pure product 3. N-(2-Fluorobenzyl)benzo[d]oxazol-2-amine (3b): Colorless solid; ¹H NMR (500 MHz, CDCl₃): δ = 7.36 (t, J = 7.0 Hz, 1 H), 7.23–7.14 (m, 3 H), 7.05 (t, J = 7.3 Hz, 1 H), 6.99 (dd, J = 17.3, 8.8 Hz, 2 H), 6.93 (t, J = 8.6 Hz, 1 H), 6.35 (s, 1 H), 4.63 (s, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 161.0 (s), 159.0 (s), 142.1 (s), 128.7 (d, J = 37.4 Hz), 128.2–127.8 (m), 123.9 (s), 123.2 (d, J = 52.9 Hz), 122.9–122.4 (m), 119.9 (s), 115.4 (s), 114.6 (s), 114.4 (s), 107.9 (s), 40.0 (s). N-Benzyl-5-methylbenzo[d]oxazol-2-amine (3m): Brown solid; ¹H NMR (500 MHz, CDCl₃): δ = 7.42 (t, J = 10.9 Hz, 3 H), 7.37 (d, J = 7.4 Hz, 2 H), 7.36–7.32 (m, 1 H), 7.14 (d, J = 8.0 Hz, 1 H), 6.92 (s, 1 H), 6.85 (d, J = 8.1 Hz, 1 H), 4.68 (s, 2 H), 2.40 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 161.7 (s), 145.9 (s), 141.9 (s), 137.0 (s), 132.6 (s), 127.8 (s), 126.7 (s), 120.4 (s), 115.5 (s), 107.2 (s), 45.9 (s), 20.5 (s)