武汉大学雷爱文团队使用时间分辨EPR揭示了电化学C(sp3) -H芳基化反应中N-中心自由基的形成、结构和反应活性。相关研究成果发表在2021年12月1日出版的《美国化学会杂志》。

电化学合成在过去几年中得到了迅速发展，而绝大多数反应都是通过自由基途径进行的。了解自由基中间体的性质对于电化学转化的机理研究至关重要，并将有助于开发新的反应。然而，由于活性高，很难确定“活性”自由基中间体。

该研究在电化学条件下，利用时间分辨电子顺磁共振（EPR）技术直接研究了磺酰胺N-中心自由基的形成和结构。在EPR结果的支持下，讨论了N-中心自由基作为氢原子转移（HAT）方法中介质的反应性。机理研究结果已成功地用于发现未活化的C（sp3）–H芳基化反应。动力学实验表明，速率决定步骤是磺胺类药物的阳极氧化。

附：英文原文

Title: Time-Resolved EPR Revealed the Formation, Structure, and Reactivity of N-Centered Radicals in an Electrochemical C(sp3)–H Arylation Reaction

Author: Yichang Liu, Biyin Shi, Zhao Liu, Renfei Gao, Cunlong Huang, Hesham Alhumade, Shengchun Wang, Xiaotian Qi, Aiwen Lei

Issue&Volume: December 1, 2021

Abstract: Electrochemical synthesis has been rapidly developed over the past few years, while a vast majority of the reactions proceed through a radical pathway. Understanding the properties of radical intermediates is crucial in the mechanistic study of electrochemical transformations and will be beneficial for developing new reactions. Nevertheless, it is rather difficult to determine the “live” radical intermediates due to their high reactivity. In this work, the formation and structure of sulfonamide N-centered radicals have been researched directly by using the time-resolved electron paramagnetic resonance (EPR) technique under electrochemical conditions. Supported by the EPR results, the reactivity of N-centered radicals as a mediator in the hydrogen atom transfer (HAT) approach has been discussed. Subsequently, these mechanistic study results have been successfully utilized in the discovery of an unactivated C(sp3)–H arylation reaction. The kinetic experiments have revealed the rate-determined step is the anodic oxidation of sulfonamides.

DOI: 10.1021/jacs.1c09341

Source: https://pubs.acs.org/doi/10.1021/jacs.1c09341