Spatially Tweaked Amide-Directing Group Enables High-Turnover Pd Catalysts for Site-Selective Remote C–H Arylation

Palladium-catalyzed cross-dehydrogenative coupling (CDC) has prudently advanced the construction of carbon–carbon and C–heteroatom bonds from C–H bonds. In contemporary chemical synthesis, a strong focus on decreased catalyst loading is indispensable, as conventional palladium-catalyzed CDC reactions generally necessitate 10 mol % Pd loading, which is impractical for industrial settings. To tackle this issue, we introduce a new approach utilizing the spatial behavior of phthalazinone-directed highly site-selective arylation through CDC with a minuscule 0.05 mol % of palladium (achieving a TON of >1700) under a light medium. This innovative strategy allows the C–H arylation of various arenes with predictable site-selectivity based on their innate-reactivity pattern. Comprehensive mechanistic studies reveal the roles of ligands, oxidants, visible light, and the distinctive reactivity of the directing group.