Formation and reactivity of gem-difluoro-substituted pyridinium ylides: Experimental and DFT investigation

β-Fluoroindolizines have been synthesized by 1,3-dipolar cycloadditions of gem-difluorosubstituted pyridinium ylides reversibly generated from substituted pyridines under difluorocarbene generation conditions. [Display omitted] ▶ Addition of CF2 to pyridines is a reversible process. ▶gem-Difluoro-su...

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Published inJournal of fluorine chemistry Vol. 132; no. 3; pp. 175 - 180
Main Authors Kobylianskii, Ilia J., Novikov, Mikhail S., Khlebnikov, Alexander F.
Format Journal Article
LanguageEnglish
Published LAUSANNE Elsevier B.V 01.03.2011
Elsevier
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Summary:β-Fluoroindolizines have been synthesized by 1,3-dipolar cycloadditions of gem-difluorosubstituted pyridinium ylides reversibly generated from substituted pyridines under difluorocarbene generation conditions. [Display omitted] ▶ Addition of CF2 to pyridines is a reversible process. ▶gem-Difluoro-substituted pyridinium ylides are thermodynamically unstable 1,3-dipoles. ▶gem-Difluoro-substituted pyridinium ylides with π-acceptor substituents can be trapped with active dipolarophiles to give 3-fluoroindolizines. According to DFT B3LYP/6-31G* calculations the reaction of difluorocarbene with pyridines proceeds reversibly with the formation of thermodynamically unstable intermediates, difluoro-substituted pyridinium ylides, which dissociate to carbene and pyridine with low activation barrier. The equilibrium constant of the reaction increases with increasing electron-withdrawing ability of substituents in the pyridine ring. Difluoroylides were generated from 4-cyano, 4-benzoyl- and 4-ethoxycarbonyl-substituted pyridines under difluorocarbene generation conditions (CF2Br2/Pb/Bu4NBr/CH2Cl2/ultrasound) and trapped with dimethyl maleate or fumaronitrile. 3-Fluoroindolizines were isolated as final products of the reaction which involves dehydrofluorination of the primary cycloadducts followed by dehydrogenation by active MnO2.
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ISSN:0022-1139
1873-3328
DOI:10.1016/j.jfluchem.2010.12.013