Auxiliary-Directed δ-C(sp ³ )–H Functionalization Enabled by Dual Photoredox and Palladium Catalysis

Functionalizing unactivated C(sp3)–H bonds has been a significant challenge in synthetic organic chemistry. To overcome this challenge, bidentate auxiliaries have been designed to access the distal positions of such aliphatic C–H bonds. However, these transformations usually require harsh reaction conditions and (super)stoichiometric amounts of toxic and expensive oxidants. These requirements limit the viability of the C–H activation strategy with regard to cost, atom economy, toxic waste, and functional group compatibility. To overcome these limitations, herein we develop a dual photoredox/Pd-catalysis strategy that enables the distal δ-functionalization of unactivated C(sp3)–H bonds. The merger of photocatalysis (PC) and visible light serves as a compatible oxidant with only catalytic amounts of the photocatalyst required for this transformation, reducing the generation of toxic waste typically observed under thermal conditions. The synergistic combination of visible-light-induced photoredox and Pd catalysis offers a highly viable strategy for enabling site-selective distal δ-C(sp3)–H functionalization. Diverse classes of functional groups (borylation, thioarylation and olefination) can be installed regioselectively at the δ-position under mild photoredox conditions. Initial mechanistic studies provide insight into the nature of the organometallic intermediates and the plausible mechanistic pathway.