Versatile Palladium-Catalyzed C-H Arylation of Fluoroarenes with 2-Chloropyridine Derivatives.

Abstract

Direct C─H arylation of fluoroarenes with 2-halopyridines remains underexplored, due to the low reactivity of both partners and the reliance on harsh conditions or toxic solvents. Herein, we report a general and sustainable method for the C─H arylation of fluoroarenes with 2-chloropyridines using Pd/SPhos as a simple catalytic system in isopropyl acetate. The protocol employs inexpensive starting materials, shows broad functional group tolerance, and delivers a wide range of 2-(fluorinated aryl)pyridines in up to 90% yield. Substrate scope studies uncovered key substituent effects on both coupling partners, while Density Functional Theory (DFT)-supported mechanistic analysis rationalized the observed reactivity and chemoselectivity. This research advances sustainable and practical methodologies for the synthesis of complex fluorinated aromatic compounds with potential applications in materials science, agrochemistry, and medicinal chemistry.