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

In this study, we present an efficient protocol for synthesizing 2-(fluorinated aryl)pyridines via direct C-H arylation of fluoroarenes with 2-chloropyridine derivatives. The synthesis of these moieties is typically challenging, often requiring multiple transition metals (Pd, Zn, Ni) and unstable or scarce aryl boronic acids, which limits access to a broad variety of these compounds. The developed methodology employs i-PrOAc as a green reaction medium, exhibits excellent functional group tolerance with minimized catalyst loading, and generates only KCl as the main by-product. Substrate scope studies revealed key substituent effects on both the pyridine and fluoroarene partners, enabling the efficient synthesis of a diverse library of 2-(fluorinated aryl)pyridines. Mechanistic investigations supported by DFT computa-tions provided insights into the catalytic cycle, rationalizing observed trends in reactivity and chemoselectivity. This research advances sustainable and practical methodologies for the synthesis of complex fluorinated aromatic com-pounds with potential applications in materials science, agrochemistry and medicinal chemistry.