DOI: 10.1002/adsc.70624 ISSN: 1615-4150

Flow‐Enabled Direct Photochemical Functionalization of Aryl Fluorides

Jesús Sanjosé‐Orduna, Daniele Esposito, Luigi Dolcini, Niccolò Intini, Demi D. Snabilié, Bas de Bruin, Timothy Noël

Direct functionalization of aryl fluorides remains challenging because of the exceptional strength of the CF bond and the reliance of existing methods on tailored catalysts or activated substrates. Here, we report a catalyst‐free photochemical strategy for the direct functionalization of electron‐rich fluoroarenes using UV irradiation in flow. A simple 3D‐printed microfluidic reactor paired with a commercially available UV source enables CF activation under operationally simple conditions, without the need for redox matching or external catalysts. The method accommodates a broad range of electron‐rich arenes and heteroarenes for CC bond formation and can be extended to CP bond formation using triethyl phosphite as a nucleophilic coupling partner. The continuous‐flow platform also enables direct scale‐up without re‐optimization. Mechanistic studies, including isotope‐labeling experiments, radical trapping studies, intramolecular cyclization probes, EPR spectroscopy, and DFT calculations, support a complex reaction manifold involving contributions from both heterolytic and homolytic CF cleavage pathways. This work establishes direct UV activation in flow as a simple and scalable platform for aryl fluoride diversification.

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