biostudies-literatureGolden DLNational Institute of General Medical SciencesNIH HHSNIGMS NIH HHS9434-9440https://www.ebi.ac.uk/biostudies/studies/S-EPMC10510071biostudies-literatureUnknown145(17)Copper-catalyzed radical-relay reactions provide a versatile strategy for selective C-H functionalization; however, reactions with peroxide-based oxidants often require excess C-H substrate. Here, we report a photochemical strategy to overcome this limitation by using a Cu/2,2'-biquinoline catalyst that supports benzylic C-H esterification with limiting C-H substrate. Mechanistic studies indicate that blue-light irradiation promotes carboxylate-to-copper charge transfer, reducing resting-state Cu^II to Cu^I, which activates the peroxide to generate an alkoxyl radical hydrogen-atom-transfer species. This "photochemical redox buffering" introduces a unique strategy to sustain the activity of Cu catalysts in radical-relay reactions.Journal of the American Chemical SocietyBenzylic C-H Esterification with Limiting C-H Substrate Enabled by Photochemical Redox Buffering of the Cu Catalyst.PMC10510071R35 GM134929S10 OD020022Vasilopoulos AChen SJGuzei IAStahl SSGolden DLZhang CfalseBenzylic C-H Esterification with Limiting C-H Substrate Enabled by Photochemical Redox Buffering of the Cu Catalyst.Copper-catalyzed radical-relay reactions provide a versatile strategy for selective C-H functionalization; however, reactions with peroxide-based oxidants often require excess C-H substrate. Here, we report a photochemical strategy to overcome this limitation by using a Cu/2,2'-biquinoline catalyst that supports benzylic C-H esterification with limiting C-H substrate. Mechanistic studies indicate that blue-light irradiation promotes carboxylate-to-copper charge transfer, reducing resting-state Cu^II to Cu^I, which activates the peroxide to generate an alkoxyl radical hydrogen-atom-transfer species. This "photochemical redox buffering" introduces a unique strategy to sustain the activity of Cu catalysts in radical-relay reactions.2023-01-01T00:00:00Z2023 May2025-04-26T04:49:56.33Z2025-04-06T11:13:52.498ZS-EPMC105100713708426510.1021/jacs.3c01662