Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
The Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.
J Am Chem Soc. 2021 Jun 30;143(25):9478-9488. doi: 10.1021/jacs.1c03007. Epub 2021 Jun 15.
One of the most oft-employed methods for C-C bond formation involving the coupling of vinyl-halides with aldehydes catalyzed by Ni and Cr (Nozaki-Hiyama-Kishi, NHK) has been rendered more practical using an electroreductive manifold. Although early studies pointed to the feasibility of such a process, those precedents were never applied by others due to cumbersome setups and limited scope. Here we show that a carefully optimized electroreductive procedure can enable a more sustainable approach to NHK, even in an asymmetric fashion on highly complex medicinally relevant systems. The e-NHK can even enable non-canonical substrate classes, such as redox-active esters, to participate with low loadings of Cr when conventional chemical techniques fail. A combination of detailed kinetics, cyclic voltammetry, and in situ UV-vis spectroelectrochemistry of these processes illuminates the subtle features of this mechanistically intricate process.
一种最常用于形成 C-C 键的方法是在镍和铬（Nozaki-Hiyama-Kishi，NHK）催化下，使乙烯基卤化物与醛偶联。通过电化学还原途径，该方法变得更加实用。尽管早期的研究表明了这种过程的可行性，但由于繁琐的设置和有限的范围，这些先例从未被其他人应用。在这里，我们展示了一种经过精心优化的电化学还原程序，可以使 NHK 更具可持续性，即使在高度复杂的药用相关体系中也可以采用不对称方式。e-NHK 甚至可以使氧化还原活性酯等非典型底物类参与反应，而在传统化学技术失败时，只需使用低负载量的铬。这些过程的详细动力学、循环伏安法和原位紫外可见光谱电化学的组合阐明了这个机制复杂过程的微妙特征。
