Regenerable Heterogeneous Palladium Single-Atom Catalysts for Direct C–H Arylation

Single-atom catalysts (SACs) offer tunable, recoverable heterogeneous alternatives to homogeneous metal complexes in handle-based cross-coupling reactions. However, their application to direct C–H bond functionalization remains unexplored beyond photochemical methods, as the elevated temperature and demanding reaction conditions place stringent requirements on catalyst stability. Here, we demonstrate a Pd single-atom-catalyzed C–H arylation of indoles, extending heterogeneous SACs to thermal C–H functionalization and achieving cumulative turnover numbers above 200 across five cycles. Among diverse oxygen- and nitrogen-coordinated SACs, nitrogen-coordinated sites in Pd@C3N4 uniquely combined metal retention with high activity after phosphine activation. Recycling studies coupled with in situ X-ray absorption spectroscopy reveal Pd–I bond formation as the dominant catalyst deactivation pathway. Guided by this insight, postreaction treatment in aqueous ammonia overcomes iodide poisoning, enabling catalytic activity over multiple cycles. These findings establish design principles for balancing activity, stability, and regenerability in Pd SACs for demanding C–H functionalizations, advancing their potential for greener, more step-efficient chemical synthesis.