Anilines and their derivatives play pivotal roles in the advancement of medicinal chemistry, life sciences, and advanced materials. Beyond conventional synthetic approaches to anilines, including nitration/reduction, C—N cross-coupling, and arene C—H amination, dehydrogenative amination has emerged as a highly efficient strategy for constructing aniline-based compounds. However, current dehydrogenative amination approaches for aniline synthesis inevitably require elevated temperatures, precious metal catalysts, stoichiometric oxidants, or additional energy input. Therefore, the development of green, sustainable, and mild-condition protocols for aniline synthesis remains a formidable challenge. In this study, we have developed a green and sustainable dehydrogenative amination of cyclohexenones for aniline synthesis using O₂ as the oxidant and inexpensive CoCl₂•6H₂O as the catalyst under ambient temperature. This method eliminates the need for precious metal catalysts, features mild reaction conditions, simple operation, and environmental friendliness, while exhibiting excellent substrate generality to afford target products in high yields. Furthermore, the plausible mechanistic pathway of this dehydrogenative amination was elucidated through X-ray photoelectron spectroscopy (XPS) and high-resolution mass spectrometry (HRMS) analysis. The practical synthetic potential of this methodology was subsequently demonstrated through late-stage functionalization of drug molecules, laying a solid foundation for its broader application in organic synthesis. The experimental procedure is as follows: To a 15 mL reaction tube equipped with a magnetic stir bar was added CoCl₂•6H₂O (4.8 mg, 4 mol%), 1,4-diaza[2.2.2]bicyclooctane (168.0 mg, 3.0 equiv.), cyclohexenone 1 (0.5 mmol, 1.0 equiv.), amine 2 (1.2 mmol, 2.4 equiv.), CH₃CN (1.5 mL), and CF₃SO₃H (18 µL, 40 mol%). The tube was evacuated and backfilled with O₂ three times. The reaction mixture was stirred at room temperature for 24 h. Subsequently, the mixture was diluted with saturated aqueous NaHCO₃ (25 mL) and extracted with ethyl acetate (30 mL×3). The combined organic layers were washed with brine (15 mL), dried over anhydrous Na₂SO₄, and concentrated to give the crude product, which was purified by silica gel column chromatography to afford the desired product.

Key words: C—N bond construction, dehydrogenative amination, cobalt catalysis, aniline synthesis, green oxidant