Study On The Photo-promoted Phosphine-catalyzed Perfluoroalkylation Of Indol

Polyfluoroalkylation is an important organic reaction.As the core skeleton of active molecules,indole is widely used in pesticides,pharmaceuticals,dyes and spices.The selective introduction of fluorine-containing atoms or groups into indoles can often significantly improve their biological activity,enhance their stability and fat solubility,and thus contribute to the absorption,transmission and diffusion of indole drug molecules in vivo.This has important theoretical research significance and practical application value for the development of structurally diverse indole derivatives.The construction of polyfluoroindoles is mostly based on the participation of transition metals.However,transition metals are expensive,difficult to avoid high temperature reaction conditions,difficult to achieve atomic economy,and limited substrate range.Therefore,it is necessary to develop a green and efficient method for the construction of polyfluoroindoles with mild reaction conditions.In this study,a clean energy source was used as the main source of reaction energy,and triphenylphosphine,which was cheap and easy to obtain compared with metal catalysts,was used as the catalyst,the strategy of visible light-induced organic phosphine catalyzed perfluoroalkylation of indole derivatives was realized,and a variety of 2-polyfluorinated indole derivatives were synthesized.In this article,the model reaction design of 3-methylindole and perfluoroiodobuta ne was completed,and the conditions were screened.Under the interaction of tripheny lphosphine and 440-445 nm blue light,methanol was used as solvent,and nitrogen wa s used as protection.The target compound of polyfluoroindole was obtained in modera te to excellent yields for 24 h at room temperature.A wide range of substrate functiona l groups showed strong tolerance,and a number of natural products and important dru gs containing indole structures could be successfully modified by polyfluorine modific ation(5a-5d)under this condition,finally,44 target compounds were synthesized.The target compounds showed good inhibitory activity against citrus canthus,and the best one 3x had up to 80% activity(50 μg/m L).Therefore,this method is of great syntheti c value for the construction of highly active polyfluorinated indole molecules.