Metal-free quinoline synthesis via Brønsted acid-promoted cyclization of ene-ynamides

Abstract

We report a metal-free strategy for the efficient synthesis of polysubstituted quinolines via Brønsted acid-promoted cyclization of readily accessible ene-ynamides. Promoted by stoichiometric TfOH under mild conditions (30 °C), this method transforms simple, modular substrates into a wide range of quinoline derivatives in a single step, eliminating the need for precious-metal catalysts or prefunctionalized reagents. Its broad functional group tolerance and successful gram-scale operation underscore the method's practical utility and potential for broader application.