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

• Published in: Journal of fluorine chemistry Vol. 132; no. 3; pp. 175 - 180
• Main Authors: Kobylianskii, Ilia J., Novikov, Mikhail S., Khlebnikov, Alexander F.
• Format: Journal Article
• Language: English
• Published: LAUSANNE Elsevier B.V 01.03.2011; Elsevier
• Subjects: Activation; Carbenes; Chemistry; Chemistry, Inorganic & Nuclear; Chemistry, Organic; Dimethyl; Dipolar cycloaddition; Formations; Indolizines; Lead (metal); Maleates; Mathematical analysis; Physical Sciences; Pyridines; Science & Technology; Ultrasound; Ylides; Pyridines; Indolizines; Carbenes; Ylides; Dipolar cycloaddition; CYCLOADDITION; RESONANCE; AZOMETHINE YLIDES; GENERATION
• ISSN: 0022-1139; 1873-3328
• DOI: 10.1016/j.jfluchem.2010.12.013

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.