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Electrochemical Nozaki–Hiyama–Kishi Coupling: Scope, Applications, and Mechanism

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journal contribution
posted on 15.06.2021, 13:35 by Yang Gao, David E. Hill, Wei Hao, Brendon J. McNicholas, Julien C. Vantourout, Ryan G. Hadt, Sarah E. Reisman, Donna G. Blackmond, Phil S. Baran
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.