Synthesis of Perfluoro-tert-butyl Triazoles via Decarboxylative CuAAC of (Perfluoro-tert-butyl)propiolic Acid with Azides

A copper-catalyzed decarboxylative cycloaddition of (perfluoro-tert-butyl)propiolic acid (PFtPA) with azides under mild conditions was developed, enabling the facile synthesis of perfluoro-tert-butyl (PFtB) triazoles. The strong electron-withdrawing nature of the PFtB group facilitates efficient decarboxylative cycloaddition at 30 °C using catalytic copper acetate, avoiding the requirement of traditional harsh conditions. This method provides high yields of products and is compatible with a wide range of azides (including bioactive molecules). This protocol serves as a robust synthetic tool for late-stage fluorination of bioactive compounds, as well as for the development of highly sensitive ¹⁹F NMR probes.