Aromaticity‐Driven Photochemistry With Thioamide Platforms for Dual‐Mode Cross‐Electrophile Coupling

Modulation of aromaticity upon CS bond cleavage provides a powerful thermodynamic driving force for organic photochemistry. Harnessing this principle, we introduce proaromatic thioamides as a single class of metal‐free chromophores for photochemical C( sp ³ )C( sp ³ ) cross‐electrophile coupling that operates in two complementary modes. Whereas most established platforms for this bond rely on metallaphotoredox catalysis using precious metals (Rh, Ru, Ir, Pd) or earth‐abundant but toxic Ni, the proaromatic thioamides ( TAs ) operate either as recyclable photoauxiliaries or as organic photocatalysts for C( sp ³ )C( sp ³ ) cross‐electrophile coupling under visible‐light irradiation. The intrinsic aromaticity of the thioamide moiety enables a facile, aromaticity‐driven S _N 2 reaction with primary and secondary alkyl, benzylic, allylic, propargylic, and heterocyclic electrophiles, delivering a library of bench‐stable photoreactive salts. Photolysis of these salts furnished unsymmetrical bibenzyl and nonbibenzyl photoproducts in yields of up to 51%, with cross‐selectivity tunable through the electronic and steric properties of the radical precursors. In photocatalytic mode, TA‐3 performed CC coupling at catalyst loadings as low as 1–2 mol% with substrate conversions of 44%–87%. Steady‐state and time‐resolved spectroscopy, complemented by Stern–Volmer analysis ( K _SV  = 0.3 mM ^–1 for TA‐3 /NEt ₃ ), support two operative mechanisms: (i) in situ generation of an electron donor–acceptor (EDA) complex followed by photoinduced single‐electron transfer (SET); and (ii) reductive quenching of the photoexcited thioamide by NEt ₃ to generate a radical anion that activates the electrophile. Demethylation of the polymethoxy‐bibenzyl photoproducts yielded bioactive phenolic compounds with antimicrobial activity against several clinically relevant pathogens (MICs 32–512 µg/mL). The present results establish proaromatic thioamides as a sustainable, modular platform for metal‐free C( sp ³ )C( sp ³ ) bond construction.