<i>Hetero</i>-Diels-Alder Reactions of In Situ-Generated Azoalkenes with Thioketones; Experimental and Theoretical Studies
The <i>hetero</i>-Diels-Alder reactions of in situ-generated azoalkenes with thioketones were shown to offer a straightforward method for an efficient and regioselective synthesis of scarcely known N-substituted 1,3,4-thiadiazine derivatives. The scope of the method was fairly broad, all...
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MDPI AG
2021-04-01
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| Online Access: | https://www.mdpi.com/1420-3049/26/9/2544 |
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| author | Grzegorz Mlostoń Katarzyna Urbaniak Malwina Sobiecka Heinz Heimgartner Ernst-Ulrich Würthwein Reinhold Zimmer Dieter Lentz Hans-Ulrich Reissig |
| author_facet | Grzegorz Mlostoń Katarzyna Urbaniak Malwina Sobiecka Heinz Heimgartner Ernst-Ulrich Würthwein Reinhold Zimmer Dieter Lentz Hans-Ulrich Reissig |
| author_sort | Grzegorz Mlostoń |
| collection | DOAJ |
| description | The <i>hetero</i>-Diels-Alder reactions of in situ-generated azoalkenes with thioketones were shown to offer a straightforward method for an efficient and regioselective synthesis of scarcely known N-substituted 1,3,4-thiadiazine derivatives. The scope of the method was fairly broad, allowing the use of a series of aryl-, ferrocenyl-, and alkyl-substituted thioketones. However, in the case of N-tosyl-substituted cycloadducts derived from 1-thioxo-2,2,4,4-tetramethylcyclobutan-3-one and the structurally analogous 1,3-dithione, a more complicated pathway was observed. By elimination of toluene sulfinic acid, the initially formed cycloadducts afforded 2<i>H</i>-1,3,4-thiadiazines as final products. Advanced DFT calculations revealed that the observed high regioselectivity was due to kinetic reaction control and that the (4 + 2)-cycloadditions of sterically less unhindered thiones occurred via highly unsymmetric transition states with shorter C..S-distances (2.27–2.58 Å) and longer N..C-distances (3.02–3.57 Å). In the extreme case of the sterically very hindered 2,2,4,4-tetramethylcyclobutan-1,3-dione-derived thioketones, a zwitterionic intermediate with a fully formed C‒S bond was detected, which underwent ring closure to the 1,3,4-thiadiazine derivative in a second step. For the hypothetical formation of the regioisomeric 1,2,3-thiadiazine derivatives, the DFT calculations proposed more symmetric transition states with considerably higher energies. |
| first_indexed | 2024-03-10T11:55:22Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T11:55:22Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-c28b555783b742ab9eb8f7c36a5ed3452023-11-21T17:22:05ZengMDPI AGMolecules1420-30492021-04-01269254410.3390/molecules26092544<i>Hetero</i>-Diels-Alder Reactions of In Situ-Generated Azoalkenes with Thioketones; Experimental and Theoretical StudiesGrzegorz Mlostoń0Katarzyna Urbaniak1Malwina Sobiecka2Heinz Heimgartner3Ernst-Ulrich Würthwein4Reinhold Zimmer5Dieter Lentz6Hans-Ulrich Reissig7Department of Organic and Applied Chemistry, Faculty of Chemistry, University of Lodz, 12 Tamka Street, 91-403 Lodz, PolandDepartment of Organic and Applied Chemistry, Faculty of Chemistry, University of Lodz, 12 Tamka Street, 91-403 Lodz, PolandDepartment of Organic and Applied Chemistry, Faculty of Chemistry, University of Lodz, 12 Tamka Street, 91-403 Lodz, PolandDepartment of Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, SwitzerlandOrganisch-Chemisches Institut and Center for Multiscale Theory and Computation (CMTC), Westfälische Wilhelms-Universität Münster, Corrensstrasse 40, 48149 Münster, GermanyInstitut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, 14195 Berlin, GermanyInstitut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, 14195 Berlin, GermanyInstitut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, 14195 Berlin, GermanyThe <i>hetero</i>-Diels-Alder reactions of in situ-generated azoalkenes with thioketones were shown to offer a straightforward method for an efficient and regioselective synthesis of scarcely known N-substituted 1,3,4-thiadiazine derivatives. The scope of the method was fairly broad, allowing the use of a series of aryl-, ferrocenyl-, and alkyl-substituted thioketones. However, in the case of N-tosyl-substituted cycloadducts derived from 1-thioxo-2,2,4,4-tetramethylcyclobutan-3-one and the structurally analogous 1,3-dithione, a more complicated pathway was observed. By elimination of toluene sulfinic acid, the initially formed cycloadducts afforded 2<i>H</i>-1,3,4-thiadiazines as final products. Advanced DFT calculations revealed that the observed high regioselectivity was due to kinetic reaction control and that the (4 + 2)-cycloadditions of sterically less unhindered thiones occurred via highly unsymmetric transition states with shorter C..S-distances (2.27–2.58 Å) and longer N..C-distances (3.02–3.57 Å). In the extreme case of the sterically very hindered 2,2,4,4-tetramethylcyclobutan-1,3-dione-derived thioketones, a zwitterionic intermediate with a fully formed C‒S bond was detected, which underwent ring closure to the 1,3,4-thiadiazine derivative in a second step. For the hypothetical formation of the regioisomeric 1,2,3-thiadiazine derivatives, the DFT calculations proposed more symmetric transition states with considerably higher energies.https://www.mdpi.com/1420-3049/26/9/2544(4 + 2)-cycloadditions<i>hetero</i>-Diels-Alder reactionsazoalkenesthioketonessulfur heterocyclesorganic reaction mechanisms |
| spellingShingle | Grzegorz Mlostoń Katarzyna Urbaniak Malwina Sobiecka Heinz Heimgartner Ernst-Ulrich Würthwein Reinhold Zimmer Dieter Lentz Hans-Ulrich Reissig <i>Hetero</i>-Diels-Alder Reactions of In Situ-Generated Azoalkenes with Thioketones; Experimental and Theoretical Studies Molecules (4 + 2)-cycloadditions <i>hetero</i>-Diels-Alder reactions azoalkenes thioketones sulfur heterocycles organic reaction mechanisms |
| title | <i>Hetero</i>-Diels-Alder Reactions of In Situ-Generated Azoalkenes with Thioketones; Experimental and Theoretical Studies |
| title_full | <i>Hetero</i>-Diels-Alder Reactions of In Situ-Generated Azoalkenes with Thioketones; Experimental and Theoretical Studies |
| title_fullStr | <i>Hetero</i>-Diels-Alder Reactions of In Situ-Generated Azoalkenes with Thioketones; Experimental and Theoretical Studies |
| title_full_unstemmed | <i>Hetero</i>-Diels-Alder Reactions of In Situ-Generated Azoalkenes with Thioketones; Experimental and Theoretical Studies |
| title_short | <i>Hetero</i>-Diels-Alder Reactions of In Situ-Generated Azoalkenes with Thioketones; Experimental and Theoretical Studies |
| title_sort | i hetero i diels alder reactions of in situ generated azoalkenes with thioketones experimental and theoretical studies |
| topic | (4 + 2)-cycloadditions <i>hetero</i>-Diels-Alder reactions azoalkenes thioketones sulfur heterocycles organic reaction mechanisms |
| url | https://www.mdpi.com/1420-3049/26/9/2544 |
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