Novel Fluorinated Derivatives of 2-Phenyl-1H-Indole

Abstract

The indole core is a structural component of a huge number of biologically active natural and synthesized compounds and pharmaceuticals, and their efficient synthesis is an important challenge. Fluorinated indoles have attracted considerable attention, since it was established that fluorine introduction can influence the biological activity of organic molecules. The initial PdCl2-catalyzed intramolecular cyclization of 4,5-difluoro-2-(phenylethynyl)aniline led to the formation of the corresponding indole in high yield. The result of its subsequent treatment with Selectfluor was the introduction of one or two fluorine atoms onto position 3. The reaction products were isolated individually by preparative thin-layer chromatography and characterized by spectroscopic methods, including IR, 1H NMR, 19F NMR, 13C NMR and HRMS. The structure of indole, exhaustively fluorinated at position 3—3,3,5,6-tetrafluoro-2-phenyl-3H-indole—was confirmed through single-crystal X-ray diffraction analysis.