Dual Ligand-Enabled Nondirected C─H Olefination of (Hetero)Arenes for the Synthesis of Clickable Derivatives

Herein, we present a highly efficient method for the late-stage introduction of "clickable" alkyne moieties into different (hetero)arene scaffolds. A highly efficient dual ligand-based palladium catalyst combining an N-acylsulfonamide (NASA) ligand with an N-heterocycle enables the introduction of acrylate moiety bearing a terminal alkyne via nondirected C─H activation, providing a versatile platform for subsequent bioconjugation or activity-based protein profiling (ABPP) applications. The utility of the method is demonstrated through a broad substrate scope and the subsequent use of the obtained products in representative click reactions.