Merging Micellar Catalysis and C-H Activation: Silver-Free Direct Arylation of Fluoroarenes in Water

The direct arylation of fluoroarenes is a powerful but sustainability-limited transformation, as most established protocols rely on organic solvents and stoichiometric silver additives. Here, we report the first silver-free palladium-catalyzed C-H arylation of fluoroarenes in water containing self-assembled surfactant structures (micelles) as reaction medium. Using the designer surfactant PS-750-M, this sustainable method enables the coupling of diverse pyridines and fluoroarenes under mild conditions, displaying broad functional-group tolerance while fully eliminating organic co-solvents. Mechanistic studies, including kinetics, FT-IR spectroscopy, dynamic light scattering (DLS), and freeze-fracture combined transmission electron microscopy (FF-TEM), reveal the nature of interactions between the catalyst, substrates and distinct micellar domains, providing insight into microenvironmental effects on reactivity and selectivity. The robustness of the catalytic system further allows tandem one-pot sequences, such as C-H arylation/S_N Ar reactions, without intermediate workup or adding an additional catalyst. This work demonstrates how merging micellar catalysis with C-H activation unlocks a practical, environmentally responsible platform for cross-coupling chemistry, expanding the utility of aqueous media for sustainable synthesis.