Zhou Kehan, Fu Niankai
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function Institute of Chemistry, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.
Nat Commun. 2025 Jul 23;16(1):6767. doi: 10.1038/s41467-025-62137-7.
The heterodifunctionalization of alkenes is an efficient and straightforward method for the preparation of highly functionalized molecules. However, enantioselective introduction of two different carbon-based functional groups in a single step using readily accessible and inexpensive starting materials presents a significant challenge. Herein, we report an electrochemical copper-catalyzed protocol for the asymmetric cyanoesterification of vinylarenes using commercially available alkyl carbazates and trimethylsilyl cyanide (TMSCN) as the sources of ester and cyano groups, respectively. The desired products could be obtained with good yields and enantioselectivities under mild conditions without the need for stoichiometric oxidants, providing sustainable access to versatile synthetic intermediates that could be smoothly converted into a variety of useful chiral building blocks. Mechanistic data are consistent with electrochemical copper-catalyzed generation of alkoxycarbonyl radicals from alkyl carbazates and the copper catalyst is also responsible for the stereoselective C-CN bond formation. The potential synthetic utility of this new electrocatalytic protocol is demonstrated in the concise synthesis of pharmacologically active molecules.
烯烃的异双官能化是制备高度官能化分子的一种有效且直接的方法。然而,使用易于获得且廉价的起始原料在一步中对映选择性地引入两个不同的碳基官能团是一项重大挑战。在此,我们报道了一种电化学铜催化的方法,用于乙烯基芳烃的不对称氰基酯化反应,分别使用市售的氨基甲酸酯和三甲基硅基氰化物(TMSCN)作为酯基和氰基的来源。在温和条件下,无需化学计量的氧化剂,即可获得产率和对映选择性良好的所需产物,为可持续获得通用的合成中间体提供了途径,这些中间体可以顺利转化为各种有用的手性结构单元。机理数据与电化学铜催化从氨基甲酸酯生成烷氧羰基自由基一致,并且铜催化剂也负责立体选择性的C-CN键形成。这种新的电催化方法的潜在合成效用在药理活性分子的简洁合成中得到了证明。