Multicomponent Domino Cyclization of Ethyl Trifluoropyruvate with Methyl Ketones and Amino Alcohols as A New Way to γ-Lactam Annulated Oxazacycles
A new route to bicyclic γ-lactams was found, which was proposed as a three-component cyclization of ethyl trifluoropyruvate with methyl ketones and 1,2-, 1,3-amino alcohols. As a result, a series of trifluoromethyl-substituted tetrahydropyrrolo [2,1-<i>b</i>]oxazol-5-ones and tetrahydrop...
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2023-02-01
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| Online Access: | https://www.mdpi.com/1420-3049/28/4/1983 |
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| author | Marina V. Goryaeva Olesya A. Fefelova Yanina V. Burgart Marina A. Ezhikova Mikhail I. Kodess Pavel A. Slepukhin Vasily S. Gaviko Victor I. Saloutin |
| author_facet | Marina V. Goryaeva Olesya A. Fefelova Yanina V. Burgart Marina A. Ezhikova Mikhail I. Kodess Pavel A. Slepukhin Vasily S. Gaviko Victor I. Saloutin |
| author_sort | Marina V. Goryaeva |
| collection | DOAJ |
| description | A new route to bicyclic γ-lactams was found, which was proposed as a three-component cyclization of ethyl trifluoropyruvate with methyl ketones and 1,2-, 1,3-amino alcohols. As a result, a series of trifluoromethyl-substituted tetrahydropyrrolo [2,1-<i>b</i>]oxazol-5-ones and tetrahydropyrrolo[2,1-<i>b</i>][1,3]oxazine-6-ones was synthesized, in which the substituent at the nodal carbon atom was varied. The introduction of a twofold excess of ethyl trifluoropyruvate in reactions with amino alcohols and acetone made it possible to obtain the same bicycles, but functionalized with a hydroxyester fragment, which are formed due to four-component interactions of the reagents. Transformations with 2-butanone and aminoethanol lead predominantly to similar bicycles, while an analogous reaction with aminopropanol gives <i>N</i>-hydroxypropyl-2,3-dihydropyrrol-5-one. Almost all bicycles are formed as two diastereomers, the structure of which was determined using <sup>1</sup>H, <sup>19</sup>F, <sup>13</sup>C NMR spectroscopy, including two-dimensional experiments and XRD analysis. A domino mechanism for the formation of tetrahydropyrrolo[2,1-<i>b</i>]oxazacycles was proposed, which was confirmed by their stepwise synthesis through the preliminary preparation of the aldol and bis-aldol from ethyl trifluoropyruvate and methyl ketones. |
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| last_indexed | 2024-03-11T08:21:11Z |
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| spelling | doaj.art-a0ae63583b9d49d69e41d372c492694f2023-11-16T22:25:56ZengMDPI AGMolecules1420-30492023-02-01284198310.3390/molecules28041983Multicomponent Domino Cyclization of Ethyl Trifluoropyruvate with Methyl Ketones and Amino Alcohols as A New Way to γ-Lactam Annulated OxazacyclesMarina V. Goryaeva0Olesya A. Fefelova1Yanina V. Burgart2Marina A. Ezhikova3Mikhail I. Kodess4Pavel A. Slepukhin5Vasily S. Gaviko6Victor I. Saloutin7Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Science (IOS UB RAS), Ekaterinburg 620108, RussiaPostovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Science (IOS UB RAS), Ekaterinburg 620108, RussiaPostovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Science (IOS UB RAS), Ekaterinburg 620108, RussiaPostovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Science (IOS UB RAS), Ekaterinburg 620108, RussiaPostovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Science (IOS UB RAS), Ekaterinburg 620108, RussiaPostovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Science (IOS UB RAS), Ekaterinburg 620108, RussiaM.N. Mikheev Institute of Metal Physics, Ural Branch of the Russian Academy of Sciences (IMP UB RAS), Ekaterinburg 620108, RussiaPostovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Science (IOS UB RAS), Ekaterinburg 620108, RussiaA new route to bicyclic γ-lactams was found, which was proposed as a three-component cyclization of ethyl trifluoropyruvate with methyl ketones and 1,2-, 1,3-amino alcohols. As a result, a series of trifluoromethyl-substituted tetrahydropyrrolo [2,1-<i>b</i>]oxazol-5-ones and tetrahydropyrrolo[2,1-<i>b</i>][1,3]oxazine-6-ones was synthesized, in which the substituent at the nodal carbon atom was varied. The introduction of a twofold excess of ethyl trifluoropyruvate in reactions with amino alcohols and acetone made it possible to obtain the same bicycles, but functionalized with a hydroxyester fragment, which are formed due to four-component interactions of the reagents. Transformations with 2-butanone and aminoethanol lead predominantly to similar bicycles, while an analogous reaction with aminopropanol gives <i>N</i>-hydroxypropyl-2,3-dihydropyrrol-5-one. Almost all bicycles are formed as two diastereomers, the structure of which was determined using <sup>1</sup>H, <sup>19</sup>F, <sup>13</sup>C NMR spectroscopy, including two-dimensional experiments and XRD analysis. A domino mechanism for the formation of tetrahydropyrrolo[2,1-<i>b</i>]oxazacycles was proposed, which was confirmed by their stepwise synthesis through the preliminary preparation of the aldol and bis-aldol from ethyl trifluoropyruvate and methyl ketones.https://www.mdpi.com/1420-3049/28/4/1983multicomponent domino cyclizationsethyl trifluoropyruvatemethyl ketonesamino alcoholsγ-lactamstetrahydropyrrolo[2,1-<i>b</i>]oxazolones |
| spellingShingle | Marina V. Goryaeva Olesya A. Fefelova Yanina V. Burgart Marina A. Ezhikova Mikhail I. Kodess Pavel A. Slepukhin Vasily S. Gaviko Victor I. Saloutin Multicomponent Domino Cyclization of Ethyl Trifluoropyruvate with Methyl Ketones and Amino Alcohols as A New Way to γ-Lactam Annulated Oxazacycles Molecules multicomponent domino cyclizations ethyl trifluoropyruvate methyl ketones amino alcohols γ-lactams tetrahydropyrrolo[2,1-<i>b</i>]oxazolones |
| title | Multicomponent Domino Cyclization of Ethyl Trifluoropyruvate with Methyl Ketones and Amino Alcohols as A New Way to γ-Lactam Annulated Oxazacycles |
| title_full | Multicomponent Domino Cyclization of Ethyl Trifluoropyruvate with Methyl Ketones and Amino Alcohols as A New Way to γ-Lactam Annulated Oxazacycles |
| title_fullStr | Multicomponent Domino Cyclization of Ethyl Trifluoropyruvate with Methyl Ketones and Amino Alcohols as A New Way to γ-Lactam Annulated Oxazacycles |
| title_full_unstemmed | Multicomponent Domino Cyclization of Ethyl Trifluoropyruvate with Methyl Ketones and Amino Alcohols as A New Way to γ-Lactam Annulated Oxazacycles |
| title_short | Multicomponent Domino Cyclization of Ethyl Trifluoropyruvate with Methyl Ketones and Amino Alcohols as A New Way to γ-Lactam Annulated Oxazacycles |
| title_sort | multicomponent domino cyclization of ethyl trifluoropyruvate with methyl ketones and amino alcohols as a new way to γ lactam annulated oxazacycles |
| topic | multicomponent domino cyclizations ethyl trifluoropyruvate methyl ketones amino alcohols γ-lactams tetrahydropyrrolo[2,1-<i>b</i>]oxazolones |
| url | https://www.mdpi.com/1420-3049/28/4/1983 |
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