Dual-Role Iron Species in Photoelectrocatalytic Radical Trifluoromethylation with Trifluoroacetates

The incorporation of trifluoromethyl groups into organic molecules represents a pivotal transformation in drug discovery, contributing to numerous top-selling pharmaceuticals. Despite substantial progress in the design of trifluoromethylating reagents, the repurposing of readily available trifluoroacetates as radical trifluoromethyl sources, enabled by iron ligand-to-metal charge transfer (LMCT) catalysis, has recently reshaped the landscape of fluoroalkylation chemistry. Recent methods for (hetero)arene trifluoromethylation generally required stoichiometric inorganic oxidants to promote the turnover of the photoactive iron catalysts, thereby limiting their broader applicability. Herein, we present an integrated photocatalytic and electrocatalytic strategy employing in-situ generated multifunctional iron species that facilitate C(sp²)–H trifluoromethylation without stoichiometric oxidants, and generate only traceless byproducts. Mechanistic studies revealed the formation of catalytically active iron species exhibiting a dual function in a synergistic pathway: (1) enabling the photodecarboxylation of trifluoroacetates and (2) mediating redox turnover of the catalytic reaction. This photoelectrocatalytic protocol offers tunable, scalable, and mild reaction conditions, harnessing visible light and electrical current as clean energy inputs. The method exhibits broad substrate scope, encompassing a wide variety of (hetero)cyclic scaffolds and enabling the functionalization of challenging electron-rich and easily oxidizable substrates. This highlights its potential for sustainable late-stage functionalization in pharmaceutical synthesis.