Mechanism of the Arene‐Limited Nondirected C−H Activation of Arenes with Palladium**

Abstract Recently palladium catalysts have been discovered that enable the directing‐group‐free C−H activation of arenes without requiring an excess of the arene substrate, thereby enabling methods for the late‐stage modification of complex organic molecules. The key to success has been the use of two complementary ligands, an N‐acyl amino acid and an N‐heterocycle. Detailed experimental and computational mechanistic studies on the dual‐ligand‐enabled C−H activation of arenes have led us to identify the catalytically active species and a transition state model that explains the exceptional activity and selectivity of these catalysts. These findings are expected to be highly useful for further method development using this powerful class of catalysts.