Key Laboratory of Precise Synthesis of Functional Molecules of Zhejiang Province, School of Science, Westlake University, 18 Shilongshan Road, Hangzhou 310024, Zhejiang Province. China.
Institute of Natural Sciences, Westlake Institute for Advanced Study, 18 Shilongshan Road, Hangzhou 310024, Zhejiang Province, China.
J Am Chem Soc. 2022 Jan 26;144(3):1144-1151. doi: 10.1021/jacs.1c12622. Epub 2022 Jan 11.
Given the wide prevalence and ready availability of both phenols and amines, aniline synthesis through direct coupling between these starting materials would be extremely attractive. Herein, we describe a rhodium-catalyzed amination of phenols, which provides concise access to diverse anilines, with water as the sole byproduct. The arenophilic rhodium catalyst facilitates the inherently difficult keto-enol tautomerization of phenols by means of π-coordination, allowing for the subsequent dehydrative condensation with amines. We demonstrate the generality of this redox-neutral catalysis by carrying out reactions of a large array of phenols with various electronic properties and a wide variety of primary and secondary amines. Several examples of late-stage functionalization of structurally complex bioactive molecules, including pharmaceuticals, further illustrate the potential broad utility of the method.
鉴于酚类和胺类物质的广泛存在和易得性，如果能直接将这些起始原料偶联起来合成苯胺，将极具吸引力。在此，我们描述了一种铑催化的酚胺化反应，该反应以水为唯一副产物，为各种苯胺的合成提供了简洁的途径。芳基化的铑催化剂通过π-配位促进酚类化合物固有地困难的酮-烯醇互变异构，从而实现与胺的后续脱水缩合。我们通过用各种电子性质的大量酚类化合物和各种伯胺和仲胺进行反应，证明了这种氧化还原中性催化的通用性。包括药物在内的结构复杂的生物活性分子的后期功能化的几个实例进一步说明了该方法的潜在广泛应用。
