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.