C–H Alkylation via Multisite-Proton-Coupled Electron Transfer of an Aliphatic C–H Bond

Morton, Carla M. Zhu, Qilei Ripberger, Hunter Troian-Gautier, Ludovic [UCL] Toa, Zi S. D. Knowles, Robert R. Alexanian, Erik J. et al.[show all]

The direct, site-selective alkylation of unactivated C(sp3)–H bonds in organic substrates is a long-standing goal in synthetic chemistry. General approaches to the activation of strong C–H bonds include radical-mediated processes involving highly reactive intermediates, such as heteroatom-centered radicals. Herein, we describe a catalytic, intermolecular C–H alkylation that circumvents such reactive species via a new elementary step for C–H cleavage involving multisite-proton-coupled electron transfer (multisite-PCET). Mechanistic studies indicate that the reaction is catalyzed by a noncovalent complex formed between an iridium(III) photocatalyst and a monobasic phosphate base. The C–H alkylation proceeds efficiently using diverse hydrocarbons and complex molecules as the limiting reagent and represents a new approach to the catalytic functionalization of unactivated C(sp3)–H bonds.