posted on 2021-06-15, 13:35authored byYang 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.