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

Carla M. Morton, Qilei Zhu, Hunter Ripberger, Ludovic Troian-Gautier, Zi S. D. Toa, Robert R. Knowles, Erik J. Alexanian:

https://pubs.acs.org/doi/10.1021/jacs.9b06834

ABSTRACT: 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.