Direct C−H Trifluoromethylation of (Hetero)Arenes in Water Enabled by Organic Photoredox‐Active Amphiphilic Nanoparticles

Photoredox‐catalyzed chemical conversions are predominantly operated in organic media to ensure good compatibility between substrates and catalysts. Yet, when conducted in aqueous media, they are an attractive, mild, and green way to introduce functional groups into organic molecules. We here show that trifluoromethyl groups can be readily installed into a broad range of organic compounds by using water as the reaction medium and light as the energy source. To bypass solubility obstacles, we developed robust water‐soluble polymeric nanoparticles that accommodate reagents and photocatalysts within their hydrophobic interior under high local concentrations. By taking advantage of the high excited state reduction potential of N‐phenylphenothiazine (PTH) through UV light illumination, the direct C−H trifluoromethylation of a wide array of small organic molecules is achieved selectively with high substrate conversion. Key to our approach is slowing down the production of CF(3) radicals during the chemical process by reducing the catalyst loading as well as the light intensity, thereby improving effectiveness and selectivity of this aqueous photocatalytic method. Furthermore, the catalyst system shows excellent recyclability and can be fueled by sunlight. The method we propose here is versatile, widely applicable, energy efficient, and attractive for late‐stage introduction of trifluoromethyl groups into biologically active molecules.