The C(sp3)–C(sp3) linkages are undoubtedly important in natural products, pharmaceuticals and organic compounds. Electrochemical cross-electrophile coupling with a broad range of available alkyl halides is an attractive and useful strategy for the construction of C(sp3)–C(sp3) bonds, although success could only be seen on activated alkyl halides in previous reports, due to the great challenge of reactivity and selectivity control of unactivated alkyl halides. Here we report a general strategy for electrochemical cross-electrophile coupling of unactivated alkyl halides under nickel catalysis. The highly selective electrochemical cross-electrophile coupling process was carried out in an operationally simple manner with high selectivity, setting the stage for the challenging C(sp3)–C(sp3) bonds construction with versatile unactivated alkyl halides, including the cross-coupling of primary–primary halides, primary–secondary halides, primary–tertiary halides and secondary–secondary halides with high selectivity and excellent functional group compatibility. The diverse products, as well as the various late-stage modifications of bio-relevant compounds, demonstrated its potential use in organic synthesis and pharmaceutical chemistry.
Electrochemical cross-electrophile coupling with alkyl halides for the construction of C(sp3)–C(sp3) bonds is generally limited to activated alkyl halides. Now this approach is extended to coupling of unactivated alkyl halides using a nickel catalyst under mild conditions.