C2-Alkylation in a three-component reaction of fluorocarbonyl compounds, pyrrole derivatives and malononitrile in competition with C2-oxyalkylation

Abstract

The C2-alkylation of pyrrole derivatives with 2-(2,2,2-trifluoroethylidene) malononitrile 1, formed in situ from ethyl hemiacetal trifluoroacetaldehyde 2 and malononitrile in the presence of a base, has been carried out. As a result of this three-component reaction, nitriles were obtained derivatives of 4,5,6,7-tetrahydroindole and pyrrole 4a, b, c. A competing reaction is C2-oxyalkylation of the pyrrole ring with hemiacetal 2. It has been shown that the side reaction can be completely suppressed by lowering the reaction temperature to -30∞C. When the ethyl ester of trifluoropyruvic acid 3 reacts with pyrrole derivatives in the presence of malononitrile, the main reaction is the C2-oxyalkylation of the pyrrole ring, rather than its C2-alkylation formed in situ by alkene 10. Nitriles 6 9 were obtained in high yields from pyrrole derivatives and alkene 10. The structure of the compounds was confirmed by 1H, 13C, 19F NMR spectroscopy, mass spectrometry and high-resolution mass spectrometry.