Regioselective Cyclic Iminium Formation of Ugi Advanced Intermediates: Rapid Access to 3,4-Dihydropyrazin-2(1<i>H</i>)-ones and Other Diverse Nitrogen-Containing Heterocycles
Herein, advanced intermediates were synthesized through Ugi four-component reactions of isocyanides, aldehydes, masked amino aldehyde, and carboxylic acids, including <i>N</i>-protected amino acids. The presence of a masked aldehyde enabled acid-mediated deprotection and subsequent cycli...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/7/3062 |
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| author | Naděžda Cankařová Viktor Krchňák |
| author_facet | Naděžda Cankařová Viktor Krchňák |
| author_sort | Naděžda Cankařová |
| collection | DOAJ |
| description | Herein, advanced intermediates were synthesized through Ugi four-component reactions of isocyanides, aldehydes, masked amino aldehyde, and carboxylic acids, including <i>N</i>-protected amino acids. The presence of a masked aldehyde enabled acid-mediated deprotection and subsequent cyclization via the carbonyl carbon and the amide nitrogen. Utilizing <i>N</i>-protected amino acid as a carboxylic acid component, Ugi intermediates could be cyclized from two possible directions to target 3,4-dihydropyrazin-2(1<i>H</i>)-ones. Cyclization to the amino terminus (westbound) and to the carboxyl terminus (eastbound) was demonstrated. Deliberate selection of building blocks drove the reaction regioselectively and yielded diverse heterocycles containing a 3,4-dihydropyrazin-2(1<i>H</i>)-one core, pyrazin-2(1<i>H</i>)-one, and piperazin-2-one, as well as a tricyclic framework with a 3D architecture, 2,3-dihydro-2,6-methanobenzo[<i>h</i>][1,3,6]triazonine-4,7(1<i>H</i>,5<i>H</i>)-dione, from Ugi adducts under mild reaction conditions. The latter bridged heterocycle was achieved diastereoselectively. The reported chemistry represents diversity-oriented synthesis. One common Ugi advanced intermediate was, without isolation, rapidly transformed into various nitrogen-containing heterocycles. |
| first_indexed | 2024-03-11T05:29:58Z |
| format | Article |
| id | doaj.art-ae05518d40e148a380592aff03cd2edb |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T05:29:58Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-ae05518d40e148a380592aff03cd2edb2023-11-17T17:12:58ZengMDPI AGMolecules1420-30492023-03-01287306210.3390/molecules28073062Regioselective Cyclic Iminium Formation of Ugi Advanced Intermediates: Rapid Access to 3,4-Dihydropyrazin-2(1<i>H</i>)-ones and Other Diverse Nitrogen-Containing HeterocyclesNaděžda Cankařová0Viktor Krchňák1Department of Organic Chemistry, Faculty of Science, Palacký University, 17 listopadu 12, 771 46 Olomouc, Czech RepublicDepartment of Organic Chemistry, Faculty of Science, Palacký University, 17 listopadu 12, 771 46 Olomouc, Czech RepublicHerein, advanced intermediates were synthesized through Ugi four-component reactions of isocyanides, aldehydes, masked amino aldehyde, and carboxylic acids, including <i>N</i>-protected amino acids. The presence of a masked aldehyde enabled acid-mediated deprotection and subsequent cyclization via the carbonyl carbon and the amide nitrogen. Utilizing <i>N</i>-protected amino acid as a carboxylic acid component, Ugi intermediates could be cyclized from two possible directions to target 3,4-dihydropyrazin-2(1<i>H</i>)-ones. Cyclization to the amino terminus (westbound) and to the carboxyl terminus (eastbound) was demonstrated. Deliberate selection of building blocks drove the reaction regioselectively and yielded diverse heterocycles containing a 3,4-dihydropyrazin-2(1<i>H</i>)-one core, pyrazin-2(1<i>H</i>)-one, and piperazin-2-one, as well as a tricyclic framework with a 3D architecture, 2,3-dihydro-2,6-methanobenzo[<i>h</i>][1,3,6]triazonine-4,7(1<i>H</i>,5<i>H</i>)-dione, from Ugi adducts under mild reaction conditions. The latter bridged heterocycle was achieved diastereoselectively. The reported chemistry represents diversity-oriented synthesis. One common Ugi advanced intermediate was, without isolation, rapidly transformed into various nitrogen-containing heterocycles.https://www.mdpi.com/1420-3049/28/7/3062Ugifour-component reaction3,4-dihydropyrazin-2(1<i>H</i>)-onesdipeptideiminiumpeptidomimetics |
| spellingShingle | Naděžda Cankařová Viktor Krchňák Regioselective Cyclic Iminium Formation of Ugi Advanced Intermediates: Rapid Access to 3,4-Dihydropyrazin-2(1<i>H</i>)-ones and Other Diverse Nitrogen-Containing Heterocycles Molecules Ugi four-component reaction 3,4-dihydropyrazin-2(1<i>H</i>)-ones dipeptide iminium peptidomimetics |
| title | Regioselective Cyclic Iminium Formation of Ugi Advanced Intermediates: Rapid Access to 3,4-Dihydropyrazin-2(1<i>H</i>)-ones and Other Diverse Nitrogen-Containing Heterocycles |
| title_full | Regioselective Cyclic Iminium Formation of Ugi Advanced Intermediates: Rapid Access to 3,4-Dihydropyrazin-2(1<i>H</i>)-ones and Other Diverse Nitrogen-Containing Heterocycles |
| title_fullStr | Regioselective Cyclic Iminium Formation of Ugi Advanced Intermediates: Rapid Access to 3,4-Dihydropyrazin-2(1<i>H</i>)-ones and Other Diverse Nitrogen-Containing Heterocycles |
| title_full_unstemmed | Regioselective Cyclic Iminium Formation of Ugi Advanced Intermediates: Rapid Access to 3,4-Dihydropyrazin-2(1<i>H</i>)-ones and Other Diverse Nitrogen-Containing Heterocycles |
| title_short | Regioselective Cyclic Iminium Formation of Ugi Advanced Intermediates: Rapid Access to 3,4-Dihydropyrazin-2(1<i>H</i>)-ones and Other Diverse Nitrogen-Containing Heterocycles |
| title_sort | regioselective cyclic iminium formation of ugi advanced intermediates rapid access to 3 4 dihydropyrazin 2 1 i h i ones and other diverse nitrogen containing heterocycles |
| topic | Ugi four-component reaction 3,4-dihydropyrazin-2(1<i>H</i>)-ones dipeptide iminium peptidomimetics |
| url | https://www.mdpi.com/1420-3049/28/7/3062 |
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