The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives
The LANCA three-component reaction of lithiated alkoxyallenes LA, nitriles N and carboxylic acids CA leads to β-ketoenamides KE in good to excellent yields. The scope of this reaction is very broad and almost all types of nitriles and carboxylic acids have successfully been used. The alkoxy group in...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Beilstein-Institut
2019-03-01
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| Series: | Beilstein Journal of Organic Chemistry |
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| Online Access: | https://doi.org/10.3762/bjoc.15.61 |
| _version_ | 1818612890211450880 |
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| author | Tilman Lechel Roopender Kumar Mrinal K. Bera Reinhold Zimmer Hans-Ulrich Reissig |
| author_facet | Tilman Lechel Roopender Kumar Mrinal K. Bera Reinhold Zimmer Hans-Ulrich Reissig |
| author_sort | Tilman Lechel |
| collection | DOAJ |
| description | The LANCA three-component reaction of lithiated alkoxyallenes LA, nitriles N and carboxylic acids CA leads to β-ketoenamides KE in good to excellent yields. The scope of this reaction is very broad and almost all types of nitriles and carboxylic acids have successfully been used. The alkoxy group introduced via the allene component is also variable and hence the subsequent transformation of this substituent into a hydroxy group can be performed under different conditions. Enantiopure nitriles or carboxylic acids can also be employed leading to chiral KE with high enantiopurity and dinitriles or dicarboxylic acids also lead to the expected bis-β-ketoenamides. β-Ketoenamides incorporate a unique combination of functional groups and hence a manifold of subsequent reactions to highly substituted heterocyclic compounds is possible. An intramolecular aldol-type condensation reaction efficiently furnishes pyridin-4-ols PY that can be further modified by palladium-catalyzed reactions, e.g., to specifically substituted furopyridine derivatives. Condensations of β-ketoenamides with ammonium salts or with hydroxylamine hydrochloride afford pyrimidines PM or pyrimidine N-oxides PO with a highly flexible substitution pattern in good yields. The functional groups of these heterocycles also allow a variety of subsequent reactions to various pyrimidine derivatives. On the other hand, acid-labile alkoxy substituents such as a 2-(trimethylsilyl)ethoxy group are required for the conversion of β-ketoenamides into 5-acetyl-substituted oxazoles OX, again compounds with high potential for subsequent functional group transformations. For acid labile β-ketoenamides bearing bulky substituents the acid treatment leads to acylamido-substituted 1,2-diketones DK that could be converted into quinoxalines QU. All classes of heterocycles accessed through the key β-ketoenamides show a unique substitution pattern – not easily accomplishable by alternative methods – and therefore many subsequent reactions are possible. |
| first_indexed | 2024-12-16T15:53:24Z |
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| institution | Directory Open Access Journal |
| issn | 1860-5397 |
| language | English |
| last_indexed | 2024-12-16T15:53:24Z |
| publishDate | 2019-03-01 |
| publisher | Beilstein-Institut |
| record_format | Article |
| series | Beilstein Journal of Organic Chemistry |
| spelling | doaj.art-48bf8c6bdb5741abb2998d1b860f5ef32022-12-21T22:25:38ZengBeilstein-InstitutBeilstein Journal of Organic Chemistry1860-53972019-03-0115165567810.3762/bjoc.15.611860-5397-15-61The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivativesTilman Lechel0Roopender Kumar1Mrinal K. Bera2Reinhold Zimmer3Hans-Ulrich Reissig4Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, D-14195 Berlin, GermanyInstitut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, D-14195 Berlin, GermanyInstitut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, D-14195 Berlin, GermanyInstitut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, D-14195 Berlin, GermanyInstitut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, D-14195 Berlin, GermanyThe LANCA three-component reaction of lithiated alkoxyallenes LA, nitriles N and carboxylic acids CA leads to β-ketoenamides KE in good to excellent yields. The scope of this reaction is very broad and almost all types of nitriles and carboxylic acids have successfully been used. The alkoxy group introduced via the allene component is also variable and hence the subsequent transformation of this substituent into a hydroxy group can be performed under different conditions. Enantiopure nitriles or carboxylic acids can also be employed leading to chiral KE with high enantiopurity and dinitriles or dicarboxylic acids also lead to the expected bis-β-ketoenamides. β-Ketoenamides incorporate a unique combination of functional groups and hence a manifold of subsequent reactions to highly substituted heterocyclic compounds is possible. An intramolecular aldol-type condensation reaction efficiently furnishes pyridin-4-ols PY that can be further modified by palladium-catalyzed reactions, e.g., to specifically substituted furopyridine derivatives. Condensations of β-ketoenamides with ammonium salts or with hydroxylamine hydrochloride afford pyrimidines PM or pyrimidine N-oxides PO with a highly flexible substitution pattern in good yields. The functional groups of these heterocycles also allow a variety of subsequent reactions to various pyrimidine derivatives. On the other hand, acid-labile alkoxy substituents such as a 2-(trimethylsilyl)ethoxy group are required for the conversion of β-ketoenamides into 5-acetyl-substituted oxazoles OX, again compounds with high potential for subsequent functional group transformations. For acid labile β-ketoenamides bearing bulky substituents the acid treatment leads to acylamido-substituted 1,2-diketones DK that could be converted into quinoxalines QU. All classes of heterocycles accessed through the key β-ketoenamides show a unique substitution pattern – not easily accomplishable by alternative methods – and therefore many subsequent reactions are possible.https://doi.org/10.3762/bjoc.15.61allenescondensationsmulticomponent reactionsoxazolespyrimidinesquinoxalines |
| spellingShingle | Tilman Lechel Roopender Kumar Mrinal K. Bera Reinhold Zimmer Hans-Ulrich Reissig The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives Beilstein Journal of Organic Chemistry allenes condensations multicomponent reactions oxazoles pyrimidines quinoxalines |
| title | The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives |
| title_full | The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives |
| title_fullStr | The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives |
| title_full_unstemmed | The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives |
| title_short | The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives |
| title_sort | lanca three component reaction to highly substituted β ketoenamides versatile intermediates for the synthesis of functionalized pyridine pyrimidine oxazole and quinoxaline derivatives |
| topic | allenes condensations multicomponent reactions oxazoles pyrimidines quinoxalines |
| url | https://doi.org/10.3762/bjoc.15.61 |
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