Metal-Free Photocatalytic Radical Trifluoromethylation Utilizing Methylene Blue and Visible Light Irradiation

The use of organofluorine compounds, especially those with an incorporated trifluoromethyl moiety, has increased dramatically in both the pharmaceutical and agrochemical industry. It has therefore become imperative to develop a mild and efficient synthetic technique for the inclusion of trifluoromethyl groups. Herein, we report the first use of methylene blue as a photosensitizer for the catalytic radical trifluoro- and hydrotrifluoromethylation of electron-rich heterocycles as well as terminal alkenes and alkynes under visible light irradiation. These reactions proceed with moderate to good yields at low catalyst concentrations; short irradiation times; and most importantly, without the need for potentially toxic transition-metal catalysts. In this work, considerable emphasis was also placed on understanding the kinetics of the mechanistically key steps through the use of laser flash photolysis techniques to more efficiently optimize the reaction conditions.