中科院理化所吴骊珠团队报道了可见光下有机催化吲哚与杂环芳基腈的位置选择性N-1和C-3杂芳基化反应。相关研究成果于2022年1月5日发表在《德国应用化学》。

由于芳基吲哚的广泛应用以及N-非取代吲哚的多个位点导致的复杂反应性，吲哚的位置选择性N-1和C-3芳基化一直是人们追求的目标。

该文描述了通过可见光辐射的自由基交叉偶联实现的吲哚的第一个区域选择性杂芳基化。稳态和时间分辨光谱和计算研究表明，有机碱及其共轭酸与吲哚和杂芳基腈的氢键相互作用决定了反应途径，它通过质子耦合电子转移或能量转移进行随后的自由基交叉耦合，分别导致吲哚的C-3和N-1杂芳基化的区域选择性形成。

具有良好官能团相容性的区域异构N-1和C-3杂芳基吲哚的平行方法，可用于极温和反应条件下生物活性化合物的克级合成和后期衍生。

附：英文原文

Title: Site-Selective N-1 and C-3 Heteroarylation of Indole with Het-eroarylnitriles by Organocatalysis under Visible Light

Author: Li-Zhu Wu, Chao Zhou, Qi-Chao Gan, Tai-Ping Zhou, Tao Lei, Chen Ye, Xiao-Jun He, Bin Chen, Rong-Zhen Liao, Chen-Ho Tung, Heng Lu, Qian Wan

Issue&Volume: 2022-01-05

Abstract: Site-selective  N  -1 and C-3 arylation of indole has been sought after to achieve because of the prevalent application of arylindoles and the intricate reactivities led by multiple sites of  N  -unsubstituted indole. Represented herein is the first regioselective heteroarylation of indole via radical-radical cross-coupling by visible light irradiation. Steady and time-resolved spectroscopic and computational studies revealed that the hydrogen bonding interaction of organic base and its conjugated acid, respective with indole and heteroarylnitrile, determined the reaction pathway, which underwent either proton-coupled electron-transfer or energy-transfer for the subsequent radical-radical cross-coupling, leading to the regioselective formation of C-3 and  N  -1 heteroarylation of indoles, respectively. The parallel methodologies for regioisomeric  N  -1 and C-3 heteroaryl indoles with good functional group compatibility could be applied to gram-scale synthesis and late-stage derivatization of bioactive compounds under extremely mild reaction conditions.

DOI: 10.1002/anie.202116421

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202116421