Versatile Palladium-catalysed C-H Arylation of Fluoroarenes with 2-Chloropyridine Derivatives: An Experimental and Mechanistic Study

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 a challenging trans-formation, often requiring multiple transition metals (Pd, Zn, Ni) and, at times, unstable or expensive aryl boronic acids. As a result, access to a wide variety of these com-pounds is limited. This method offers a stream-lined, cost-effective alternative to traditional cross-coupling reactions by eliminating the need for pre-functionalization. Its broad functional group tolerance across various substituted pyri-dines and fluoroarenes facilitates the efficient synthesis of a diverse library of 2-(fluorinated aryl)pyridines and enabled late-stage functionalization. The conditions were tested and optimized across various substrates, offering valuable insights into the influence of substituents on coupling efficiency. Using DFT computations, we explored the mechanistic basis of the experimental observations, providing a clear overview of the catalytic cycle, unveiling interest-ing aspects for future optimization. This research advances sustainable and practical methodologies for synthesizing com-plex fluorinated aromatic compounds with potential applications in materials science, agrochemistry and medicinal chemistry.