Heterogeneous Visible-Light Photocatalysis in Continuous-Flow: A Synergistic Strategy for Challenging...

Trifluoromethyl ketones are valuable scaffolds in drug discovery and material science, but their synthesis is often hindered by the need for prefunctionalized substrates, harsh oxidative conditions, and expensive trifluoromethylating reagents. To address these challenges, a continuous-flow heterogeneous photocatalytic trifluoromethylation strategy is developed to synthesize β-trifluoromethyl-α-aryl ketones via visible-light-induced 1,2-aryl migration. Mesoporous graphitic carbon nitride (mpg-C₃N₄) is employed as a recyclable photocatalyst, and trifluoromethanesulfonyl chloride (TfCl) serves as an affordable CF₃ source, enabling a mild and sustainable radical pathway. The reaction is conducted in a continuous oscillatory flow system integrated with a custom photoreactor, ensuring efficient light utilization and stable catalyst handling. For the model substrate, an 83% isolated yield is achieved within 30 min, corresponding to a space-time yield of 6.95 g·L^-1·h^-1, significantly surpassing that obtained under batch conditions (0.36 g·L^-1·h^-1 with 43% isolated yield in 12 h). The method shows broad substrate compatibility, obtaining β-trifluoromethyl-α-aryl ketones in 54%-88% yields from 23 allyl alcohols. The scalability is confirmed with a gram-scale preparation, and the intermediate is converted into a bioactive molecule via an integrated multi-step continuous-flow process. This work provides a sustainable, efficient strategy for synthesizing fluorinated compounds of pharmaceutical relevance.