近日，四川大学刘沁蕾团队研究了电场驱动的双通路吩噻嗪类和胺类在水微滴中的点击偶联。2026年2月23日出版的《美国化学会志》发表了这项最新研究成果。

"点击化学"为分子构建提供了高效策略，然而S−N键的形成通常需要强氧化剂参与，这往往导致副反应发生且与芳香体系兼容性较差。

研究组报道了一种在水相微液滴中常温条件下吩噻嗪与胺类化合物无需氧化剂的点击反应。该反应由界面电场驱动，通过两种不同路径进行，具体路径取决于胺的氧化电位：高氧化电位的胺类通过吩噻嗪双阳离子中间体进行反应，而低氧化电位的胺类则通过氮中心自由基与吩噻嗪自由基阳离子实现偶联。

同位素标记（H₂¹⁸O）与中间体捕获实验证实了吩噻嗪双阳离子和氮中心自由基中间体的参与。循环伏安法测量进一步揭示，不同反应路径从根本上受有机底物固有氧化还原性质的调控。该策略拓展了基于微液滴的点击转化范围，克服了芳香胺反应活性方面的既有局限，展示了微液滴环境在氧化转化中的应用潜力。

附：英文原文

Title: Electric-Field-Driven Dual-Pathway Click Coupling of Phenothiazines and Amines in Aqueous Microdroplets

Author: Yu Zou, Li-Hai Wei, Yu-Jia Qi, Zhen-Feng Cai, Qinlei Liu

Issue&Volume: February 23, 2026

Abstract: “Click chemistry” offers an efficient strategy for molecular construction, yet SN bond formation typically requires strong oxidants, leading to side reactions and poor compatibility with aromatic systems. Here, we report an oxidant-free click reaction between phenothiazines and amines within aqueous microdroplets at room temperature. This reaction is driven by the interfacial electric field and proceeds via two distinct pathways governed by the amine oxidation potential: amines with high oxidation potentials react via the phenothiazine dication intermediate, whereas those with lower oxidation potentials undergo coupling via nitrogen-centered radicals and phenothiazine radical cations. Isotopic labeling (H218O) together with intermediate-trapping experiments supports the involvement of phenothiazine dications and nitrogen-centered radical intermediates. Cyclic voltammetry measurements further reveal that the distinct pathways are fundamentally governed by the intrinsic redox properties of the organic substrates. This strategy expands the scope of microdroplet-based click transformations, overcoming previous limitations in aromatic amine reactivity and showcasing the utility of microdroplet environments for oxidative transformations.

DOI: 10.1021/jacs.5c17939

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.5c17939