Jia Ming-Yang, Zhou Yue-Wen, Yang Jun-Lei, Liu Qinlei, Cai Zhen-Feng
Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu, P.R. China.
Nat Commun. 2025 Aug 12;16(1):7453. doi: 10.1038/s41467-025-62706-w.
Ullmann-type coupling reactions are one of the most important transformations in organic synthesis. Achieving catalyst-free Ullmann couplings under mild conditions is crucial to extending the scope of traditional carbon-carbon and carbon-heteroatom couplings. Herein, we show that Ullmann couplings can be effectively achieved at room temperature without the need for metal catalysts in MeOH/HO microdroplets. Mechanistic investigations reveal that the Ullmann reaction in microdroplets is driven by •OH radicals and involves a single-electron transfer pathway via nitrogen-centered radicals. This work not only provides fundamental insights into the •OH radical-mediated coupling reactions in microdroplets but also offers a new strategy for catalyst-free Ullmann couplings.
乌尔曼型偶联反应是有机合成中最重要的转化反应之一。在温和条件下实现无催化剂的乌尔曼偶联对于扩展传统碳-碳和碳-杂原子偶联的范围至关重要。在此，我们表明在甲醇/水微滴中，无需金属催化剂即可在室温下有效地实现乌尔曼偶联。机理研究表明，微滴中的乌尔曼反应由•OH自由基驱动，并且涉及通过氮中心自由基的单电子转移途径。这项工作不仅为微滴中•OH自由基介导的偶联反应提供了基本见解，还为无催化剂的乌尔曼偶联提供了一种新策略。
