Synthesis of Polyfluoroalkylquinolines by Pd-Catalyzed Heteroannulation

Significance

A number of 4-chloro-2-polyfluoroalkyl quinolines were synthesized by Pd-catalyzed intramolecular heteroannulation of N-(2-ethynyl­phenyl)-2-polyfluoroalkyl-imidoyl chlorides in good to excellent preparative yields. The screening of conditions was performed, the scope of the reaction was found to be limited by polyfluorinated imidoyl chlorides. The suggested mechanism of the chloroimination includes oxidative addition of C-Cl bond of imidoyl chloride fragment to Pd(0) followed by acetylenic coordination, chloropalladation and reductive elimination. The synthetic value of the method was illustrated by the further DoM chemistry of 3 which led to the synthesis of a known skeleton of quinolone antibiotics 4 (M. Schlosser at al. Eur. J. Org. Chem. 2006, 729).