Direct trifluoromethylation of heteroarenes using a commercial CdSe semiconductor photocatalyst

Abstract

Incorporation of the trifluoromethyl group in biologically active compounds have always been regarded of high importance in medicinal and pharmaceuticals chemistry. The selective installation of the trifluoromethyl group onto small molecules can enhance many of its physicochemical and pharmacokinetic properties. The electron-withdrawing CF3 moiety on pharmaceuticals provide metabolic and thermal stability, increases electrostatic interaction with a target molecule in the body, improves cellular membrane permeability and lipophilicity and have many other usage and advantages in biology and agrochemicals. As the field of photoredox catalysis develops, the need to find new methodologies to help in modern drug discovery becomes crucial as well. Herewith we have reported a detailed novel study for the incorporation of trifluoromethyl group in heteroarenes using cadmium selenide (CdSe), a commercially available semiconductor photocatalyst. The new catalyst is air and moisture stable, can tolerate high reactive radical intermediates and can be readily recovered by simple centrifugation after use and can be reused several times. Along with a wide variety of substrate scope, we have shown the applicability of our developed methodology to medicinal chemistry and drug development through examples of trifluoromethylation of some biologically active compounds such as RNA-base Uracil, plant hormone Heteroauxin and flavorant Vanillin.