Liu Ye, Chen Yu, Zhao Yu-Jie, Zhang Guo-Qing, Zheng Yongxiang, Yu Peiyuan, Chen Peng, Jia Zhi-Jun
Department of Biopharmaceutics, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children, Children's Medicine Key Laboratory of Sichuan Province, Department of Pharmacy/Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
J Am Chem Soc. 2024 Sep 11;146(36):24863-24870. doi: 10.1021/jacs.4c05407. Epub 2024 Aug 27.
Primary amines are privileged molecules in drug development. Yet, there is a noticeable scarcity of methods for directly introducing a primary amine group into the ubiquitous C(sp)-H bonds within organic compounds. Here, we report an iron-based catalytic system that enables direct primary amination of C(sp)-H bonds under aqueous conditions and air. Various types of C(sp)-H bonds, including benzylic, allylic, and aliphatic ones, can be readily functionalized with high selectivity and efficiency. The broad utility of this method has been further verified by late-stage amination of 11 complex bioactive molecules. Mechanistic studies unveil a protonated iron-nitrene complex as the key intermediate for the C-H bond activation. This work extends the toolbox for direct C(sp)-H functionalizations, opening up new opportunities for late-stage modifications of organic molecules.
伯胺是药物开发中具有优势的分子。然而，将伯胺基团直接引入有机化合物中普遍存在的C(sp) - H键的方法明显匮乏。在此，我们报道了一种铁基催化体系，该体系能够在水性条件和空气中实现C(sp) - H键的直接伯胺化反应。各种类型的C(sp) - H键，包括苄基、烯丙基和脂肪族的C(sp) - H键，都能以高选择性和高效率轻松实现官能团化。通过对11种复杂生物活性分子的后期胺化反应，进一步验证了该方法的广泛实用性。机理研究揭示了质子化的铁氮宾络合物是C - H键活化的关键中间体。这项工作扩展了直接C(sp) - H官能团化的工具库，为有机分子的后期修饰开辟了新的机会。
