General and efficient synthesis of polyfluorinated 2-aminotolans and 2-arylindoles

•• Synthesis of fluorinated ethenylarenes and 2-aminotolans.•• Effect of fluorination pattern and extent on the heterocyclization of 2-aminotolans.•• Directed synthesis of polyfluorinated 2-phenylindoles.

It was established here that cross-coupling of polyfluorinated 2-iodoanilines with arylacetylenes in MeCN in the presence catalytic amounts of Pd(PPh3)2Cl2, CuI and Et3N produces the corresponding 2-aminotolans although their yields are decreased from 98% to 40% with increasing fluorination of the substrates. It was shown that the 2-aminotolans with six or fewer fluorine atoms in their rings can be heterocyclised by heating in ethanol containing p-TSA to produce the corresponding polyfluorinated indoles. Cyclisation of tolans containing larger numbers of fluorine atoms in their rings proceeds most efficiently in the presence of KOH, resulting in 2-phenylindoles containing the current maximum of eight fluorine atoms.

Graphical abstractEfficient and practical procedures for the synthesis of polyfluorinated 2-aminotolans and 2-arylindoles are described.Figure optionsDownload full-size imageDownload as PowerPoint slide