Alkyl Sulfonylhydrazide-Enabled, Chemoselective Ni-catalyzed Directed C(sp2)–H Alkylation via Low-Temperature, Amine-Assisted Metalation/Deprotonation

Disclosed herein is the invention of a method for facile C–H alkylation of a range of (hetero)arenes under Ni-catalysis. This reaction takes place at 50 °C, is scalable, tolerates heterocyclic substrates, and can be applied to both primary and complex secondary alkyl donors. Success hinges on the use of sulfonylhydrazide-based alkyl donors that mildly generate alkyl radicals thereby obviating the need for alkyl halide precursors that require more harsh conditions to activate. The demonstrated substrate scope is broad (>70 examples), and the reaction was also applied to natural product synthesis. Mechanistic studies (both computational and experimental) suggest that an asynchronous, amine-assisted C–H activation pathway is operative which may have larger implications for the field.