Direct Acylation of C(sp³)-H Bonds Enabled by Nickel and Photoredox Catalysis

Using nickel and photoredox catalysis, the direct functionalization of C(sp³)-H bonds of N-aryl amines by acyl electrophiles is described. The method affords a diverse range of α-amino ketones at room temperature and is amenable to late-stage coupling of complex and biologically relevant groups. C(sp³)-H activation occurs by photoredox-mediated oxidation to generate α-amino radicals which are intercepted by nickel in catalytic C(sp³)-C coupling. The merger of these two modes of catalysis leverages nickel's unique properties in alkyl cross-coupling while avoiding limitations commonly associated with transition-metal-mediated C(sp³)-H activation, including requirements for chelating directing groups and high reaction temperatures. Teamwork: The direct functionalization of C(sp³)-H bonds of N-aryl amines by acyl electrophiles is achieved, thus affording a diverse range of α-amino ketones at room temperature. C(sp³)-H activation occurs by photoredox-mediated oxidation to generate α-amino radicals which are intercepted by nickel in catalytic C(sp³)-C coupling.