title: Investigation of the Pyridinium Ylide--Alkyne Cycloaddition as a Fluorogenic Coupling Reaction.
abstract: The cycloaddition of pyridinium ylides with alkynes was investigated under mild conditions. A series of 13 pyridinium salts was prepared by alkylation of 4-substituted pyridines. Their reactivity with propiolic ester or amide in various reaction conditions (different temperatures, solvents, added bases) was studied, and 11 indolizines, with three points of structural variation, were, thus, isolated and characterized. The highest yields were obtained when electron-withdrawing groups were present on both the pyridinium ylide, generated in situ from the corresponding pyridinium salt, and the alkyne (X, Z = ester, amide, CN, carbonyl, etc.). Electron-withdrawing substituents, lowering the acid dissociation constant (pKa) of the pyridinium salts, allow the cycloaddition to proceed at pH 7.5 in aqueous buffers at room temperature.
authors.affiliation: Department of Pharmacochemistry, Université Grenoble Alpes, CNRS, DPM UMR 5063, F-38041 Grenoble, France. simontlse.12@gmail.com.
authors.forename: Simon
authors.initials: S
authors.lastname: Bonte
authors.affiliation: Department of Chemistry, Physics and Environment, Faculty of Science and Environment, "Dunarea de Jos" University of Galati, 111 Domneasca Street, 800201 Galati, Romania. otilia.ghinea@gmail.com.
authors.forename: Ioana Otilia
authors.initials: IO
authors.lastname: Ghinea
authors.affiliation: Department of Chemistry, Physics and Environment, Faculty of Science and Environment, "Dunarea de Jos" University of Galati, 111 Domneasca Street, 800201 Galati, Romania. rodicad@yahoo.com.
authors.forename: Rodica
authors.initials: R
authors.lastname: Dinica
authors.affiliation: Department of Pharmacochemistry, Université Grenoble Alpes, CNRS, DPM UMR 5063, F-38041 Grenoble, France. isabelle.baussanne@ujf-grenoble.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Baussanne
authors.affiliation: Department of Pharmacochemistry, Université Grenoble Alpes, CNRS, DPM UMR 5063, F-38041 Grenoble, France. martine.demeunynck@univ-grenoble-alpes.fr.
authors.forename: Martine
authors.initials: M
authors.lastname: Demeunynck
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D061565:Cycloaddition Reaction; D006863:Hydrogen-Ion Concentration; D007212:Indolizines / Q000737:chemistry; D015394:Molecular Structure; D066244:Proton Magnetic Resonance Spectroscopy; D011726:Pyridinium Compounds / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry
chemical_list: D000480:Alkynes; D007212:Indolizines; D011726:Pyridinium Compounds; D012997:Solvents
keywords: coupling reaction; dipolar cycloaddition; indolizine; ylide