title: Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides.
abstract: Reactions of β-azolyl enamines and nitrile oxides were studied by both experimental and theoretical methods. (E)-β-(4-Nitroimidazol-5-yl), (5-nitroimidazol-4-yl) and isoxazol-5-yl enamines smoothly react regioselectively at room temperature in dioxane solution with aryl, pyridyl, and cyclohexylhydroxamoyl chlorides without a catalyst or a base to form 4-azolylisoxazoles as the only products in good yields. The intermediate 4,5-dihydroisoxazolines were isolated astransisomers during the reaction of (E)-β-imidazol-4-yl enamines with aryl and cyclohexylhydroxamoyl chlorides. Stepwise and concerted pathways for the reaction of β-azolyl enamines with hydroxamoyl chlorides were considered and studied at the B3LYP/Def2-TZVP level of theory combined with D3BJ dispersion correction. The reactions of benzonitrile oxide with bothE- andZ-imidazolyl enamines have been shown to proceed stereoselectively to formtrans-andcis-isoxazolines, respectively. The preference ofE-isomers overZ-isomers, driven by the higher stability of the former, apparently controls the stereoselectivity of the investigated cycloaddition reaction with benzonitrilе oxide. Based on the reactivity of azolyl enamines towards hydroxamoyl chlorides, a novel, effective catalyst-free method was elaborated to prepare 4-azolyl-5-substituted isoxazoles that are otherwise difficult to obtain.
authors.affiliation: TOS Department, Ural Federal University named after the first President of Russia B.N. Yeltsin, 19 Mira str., 620002 Yekaterinburg, Russia.
authors.forename: Ilya V
authors.initials: IV
authors.lastname: Efimov
authors.affiliation: TOS Department, Ural Federal University named after the first President of Russia B.N. Yeltsin, 19 Mira str., 620002 Yekaterinburg, Russia; Chemistry Department, University of York, Heslington, York, YO10 5DD, UK.
authors.forename: Marsel Z
authors.initials: MZ
authors.lastname: Shafikov
authors.affiliation: TOS Department, Ural Federal University named after the first President of Russia B.N. Yeltsin, 19 Mira str., 620002 Yekaterinburg, Russia.
authors.forename: Nikolai A
authors.initials: NA
authors.lastname: Beliaev
authors.affiliation: TOS Department, Ural Federal University named after the first President of Russia B.N. Yeltsin, 19 Mira str., 620002 Yekaterinburg, Russia.
authors.forename: Natalia N
authors.initials: NN
authors.lastname: Volkova
authors.affiliation: TOS Department, Ural Federal University named after the first President of Russia B.N. Yeltsin, 19 Mira str., 620002 Yekaterinburg, Russia.
authors.forename: Tetyana V
authors.initials: TV
authors.lastname: Beryozkina
authors.affiliation: Molecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Dehaen
authors.affiliation: State Key Laboratory of Elemento-Organic Chemistry Nankai University, Collaborative Innovation Center of Chemical Science and Engineering 300071 Tianjin, China.
authors.forename: Zhijin
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Laboratory of Biologically Active Compounds, Institute of Technical Chemistry Ural Branch of Russian Academy of Sciences, 3 Academician Korolev str., Perm, Russia.
authors.forename: Viktoria V
authors.initials: VV
authors.lastname: Grishko
authors.affiliation: Medical University of Vienna, Department of Pediatrics, 14 Lazarettgasse, 1090 Vienna, Austria.
authors.forename: Gert
authors.initials: G
authors.lastname: Lubec
authors.affiliation: TOS Department, Ural Federal University named after the first President of Russia B.N. Yeltsin, 19 Mira str., 620002 Yekaterinburg, Russia; I. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of Russian Academy of Sciences, 20 S. Kovalevskaya str., 620990 Yekaterinburg, Russia.
authors.forename: Pavel A
authors.initials: PA
authors.lastname: Slepukhin
authors.affiliation: TOS Department, Ural Federal University named after the first President of Russia B.N. Yeltsin, 19 Mira str., 620002 Yekaterinburg, Russia.
authors.forename: Vasiliy A
authors.initials: VA
authors.lastname: Bakulev
keywords: [3 + 2]-cycloaddition; isoxazole; isoxazoline; nitrile oxide; β-azolyl enamine