Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides
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 cyclohexylhydro...
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| Format: | Article |
| Language: | English |
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Beilstein-Institut
2016-11-01
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| Series: | Beilstein Journal of Organic Chemistry |
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| Online Access: | https://doi.org/10.3762/bjoc.12.233 |
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| author | Ilya V. Efimov Marsel Z. Shafikov Nikolai A. Beliaev Natalia N. Volkova Tetyana V. Beryozkina Wim Dehaen Zhijin Fan Viktoria V. Grishko Gert Lubec Pavel A. Slepukhin Vasiliy A. Bakulev |
| author_facet | Ilya V. Efimov Marsel Z. Shafikov Nikolai A. Beliaev Natalia N. Volkova Tetyana V. Beryozkina Wim Dehaen Zhijin Fan Viktoria V. Grishko Gert Lubec Pavel A. Slepukhin Vasiliy A. Bakulev |
| author_sort | Ilya V. Efimov |
| collection | DOAJ |
| description | 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 as trans isomers 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 both E- and Z-imidazolyl enamines have been shown to proceed stereoselectively to form trans- and cis-isoxazolines, respectively. The preference of E-isomers over Z-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. |
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| institution | Directory Open Access Journal |
| issn | 1860-5397 |
| language | English |
| last_indexed | 2024-12-16T06:32:18Z |
| publishDate | 2016-11-01 |
| publisher | Beilstein-Institut |
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| series | Beilstein Journal of Organic Chemistry |
| spelling | doaj.art-a88517865b28444f89e062cf2b56a1ee2022-12-21T22:40:52ZengBeilstein-InstitutBeilstein Journal of Organic Chemistry1860-53972016-11-011212390240110.3762/bjoc.12.2331860-5397-12-233Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxidesIlya V. Efimov0Marsel Z. Shafikov1Nikolai A. Beliaev2Natalia N. Volkova3Tetyana V. Beryozkina4Wim Dehaen5Zhijin Fan6Viktoria V. Grishko7Gert Lubec8Pavel A. Slepukhin9Vasiliy A. Bakulev10TOS Department, Ural Federal University named after the first President of Russia B.N. Yeltsin, 19 Mira str., 620002 Yekaterinburg, RussiaTOS Department, Ural Federal University named after the first President of Russia B.N. Yeltsin, 19 Mira str., 620002 Yekaterinburg, RussiaTOS Department, Ural Federal University named after the first President of Russia B.N. Yeltsin, 19 Mira str., 620002 Yekaterinburg, RussiaTOS Department, Ural Federal University named after the first President of Russia B.N. Yeltsin, 19 Mira str., 620002 Yekaterinburg, RussiaTOS Department, Ural Federal University named after the first President of Russia B.N. Yeltsin, 19 Mira str., 620002 Yekaterinburg, RussiaMolecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, 3001 Leuven, BelgiumState Key Laboratory of Elemento-Organic Chemistry Nankai University, Collaborative Innovation Center of Chemical Science and Engineering 300071 Tianjin, ChinaLaboratory of Biologically Active Compounds, Institute of Technical Chemistry Ural Branch of Russian Academy of Sciences, 3 Academician Korolev str., Perm, RussiaMedical University of Vienna, Department of Pediatrics, 14 Lazarettgasse, 1090 Vienna, AustriaTOS Department, Ural Federal University named after the first President of Russia B.N. Yeltsin, 19 Mira str., 620002 Yekaterinburg, RussiaTOS Department, Ural Federal University named after the first President of Russia B.N. Yeltsin, 19 Mira str., 620002 Yekaterinburg, RussiaReactions 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 as trans isomers 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 both E- and Z-imidazolyl enamines have been shown to proceed stereoselectively to form trans- and cis-isoxazolines, respectively. The preference of E-isomers over Z-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.https://doi.org/10.3762/bjoc.12.233β-azolyl enamine[3 + 2]-cycloadditionisoxazoleisoxazolinenitrile oxide |
| spellingShingle | Ilya V. Efimov Marsel Z. Shafikov Nikolai A. Beliaev Natalia N. Volkova Tetyana V. Beryozkina Wim Dehaen Zhijin Fan Viktoria V. Grishko Gert Lubec Pavel A. Slepukhin Vasiliy A. Bakulev Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides Beilstein Journal of Organic Chemistry β-azolyl enamine [3 + 2]-cycloaddition isoxazole isoxazoline nitrile oxide |
| title | Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides |
| title_full | Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides |
| title_fullStr | Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides |
| title_full_unstemmed | Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides |
| title_short | Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides |
| title_sort | combined experimental and theoretical studies of regio and stereoselectivity in reactions of β isoxazolyl and β imidazolyl enamines with nitrile oxides |
| topic | β-azolyl enamine [3 + 2]-cycloaddition isoxazole isoxazoline nitrile oxide |
| url | https://doi.org/10.3762/bjoc.12.233 |
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