FeCl₃-catalyzed intramolecular cyclization of N-allyl phenyl enamine ketones for the synthesis of 3,4-disubstituted quinolines

In this paper, we investigate the synthesis of the key intermediate 2-vinyl phenyl enamine ketone 3 by refluxing the starting materials N,N-dimethyl enamine ketone 1 and ortho-vinyl aniline 2 in acetic acid solution for 4 hours. Intermediate 3 undergoes Fe(Ⅲ)-catalyzed intramolecular radical cyclization and oxidative aromatization reactions in toluene solvent, successfully developing a synthetic method for 3,4-disubstituted quinolines 4. The synthesized target products were characterized and confirmed using ¹H NMR, ¹³C NMR, and HRMS. The study demonstrates that this method features easily accessible raw materials, a simple operation, and diverse target product structures. We obtain the diverse 3,4-disubstituted quinoline derivatives 4, which provide a solid foundation for the screening of compounds with potential antitumor and other biological activities.