The direct amination of C-H bonds with ammonia is a challenge in synthetic chemistry. Herein, we present a copper-mediated approach that enables a chelation-assisted aromatic C-H bond amination using aqueous ammonia. A key strategy was to use soft low-valent Cu(I) species to avoid the strong coordination of ammonia. Mechanistic investigations suggest that the catalysis is initiated by a facile deprotonation of bound ammonia, and the C-N coupling is achieved by subsequent reductive elimination of the resultant copper-amido intermediate from a Cu(III) intermediate that is readily generated by disproportionation of low-valent copper analogues. This mechanistic postulate was supported by a preliminary kinetic isotope effect study and computations. This new chelation-assisted, copper-mediated C-H bond amination with aqueous ammonia was successfully applied to a broad range of substrates to deliver primary anilines. Moreover, the mild conditions required for this transformation allowed the reaction to operate even under substoichiometric conditions to enable a late-stage application for the preparation of pharmaceutical agents.

中文翻译：

---

通过歧化途径直接使用氨水对芳基 C-H 键进行铜介导胺化

CH 键与氨的直接胺化是合成化学中的一个挑战。在此，我们提出了一种铜介导的方法，该方法能够使用氨水进行螯合辅助的芳族 CH 键胺化。一个关键的策略是使用软的低价 Cu(I) 物种来避免氨的强配位。机理研究表明，催化是由结合氨的轻松去质子化引发的，并且 CN 偶联是通过随后从 Cu(III) 中间体还原消除生成的铜-酰胺中间体来实现的，Cu(III) 中间体很容易通过歧化低价铜类似物。这一机械假设得到了初步动力学同位素效应研究和计算的支持。这种新的螯合辅助，用氨水进行铜介导的 CH 键胺化已成功应用于广泛的基材以提供初级苯胺。此外，这种转化所需的温和条件使反应即使在亚化学计量条件下也能进行，从而能够在后期用于制备药物。