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

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.