Azocarboxamide-enabled enantioselective regiodivergent unsymmetrical 1,2-diaminations
Abstract Enantioenriched unsymmetrical vicinal diamines are important basic structural motifs. While catalytic asymmetric intermolecular 1,2-diamination of carbon–carbon double bonds represents the most straightforward approach for preparing enantioenriched vicinal-diamine-containing heterocycles, t...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54598-z |
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| author | Yun-Dong Fu Han Zhang Bei-Bei Li Lihua Huang Xiao Xiao Min-Can Wang Donghui Wei Guang-Jian Mei |
| author_facet | Yun-Dong Fu Han Zhang Bei-Bei Li Lihua Huang Xiao Xiao Min-Can Wang Donghui Wei Guang-Jian Mei |
| author_sort | Yun-Dong Fu |
| collection | DOAJ |
| description | Abstract Enantioenriched unsymmetrical vicinal diamines are important basic structural motifs. While catalytic asymmetric intermolecular 1,2-diamination of carbon–carbon double bonds represents the most straightforward approach for preparing enantioenriched vicinal-diamine-containing heterocycles, these reactions are often limited to the installation of undifferentiated amino functionalities through metal catalysis and/or the use of stoichiometric amounts of oxidants. Here, we report organocatalytic enantioselective unsymmetrical 1,2-diaminations based on the rational design of a bifunctional 1,2-diamination reagent, namely, azocarboxamides (ACAs). Under the catalysis of chiral phosphoric acid, unsymmetrical 1,2-diaminations of ACAs with various electron-rich double bonds readily occur in a regiodivergent manner. Indoles prefer dual hydrogen-bonding mode to give dearomative (4 + 2) products, and 3-vinylindoles and azlactones are inclined to undergo unsymmetrical 1,2-diamination via the (3 + 2) process. DFT calculations are performed to reveal the reaction mechanism and the origin of the regio- and enantioselectivity. Guided by computational design, we are able to reverse the regioselectivity of the dearomative unsymmetrical 1,2-diamination of indoles using Lewis acid catalysis. |
| format | Article |
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| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-6eaef2a6d6864e049d2d553095f2b1e82024-12-01T12:33:56ZengNature PortfolioNature Communications2041-17232024-11-0115111210.1038/s41467-024-54598-zAzocarboxamide-enabled enantioselective regiodivergent unsymmetrical 1,2-diaminationsYun-Dong Fu0Han Zhang1Bei-Bei Li2Lihua Huang3Xiao Xiao4Min-Can Wang5Donghui Wei6Guang-Jian Mei7College of Chemistry, Zhengzhou UniversityCollege of Chemistry, Zhengzhou UniversityCollege of Chemistry, Zhengzhou UniversityCollege of Chemistry, Zhengzhou UniversityCollaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of TechnologyCollege of Chemistry, Zhengzhou UniversityCollege of Chemistry, Zhengzhou UniversityCollege of Chemistry, Zhengzhou UniversityAbstract Enantioenriched unsymmetrical vicinal diamines are important basic structural motifs. While catalytic asymmetric intermolecular 1,2-diamination of carbon–carbon double bonds represents the most straightforward approach for preparing enantioenriched vicinal-diamine-containing heterocycles, these reactions are often limited to the installation of undifferentiated amino functionalities through metal catalysis and/or the use of stoichiometric amounts of oxidants. Here, we report organocatalytic enantioselective unsymmetrical 1,2-diaminations based on the rational design of a bifunctional 1,2-diamination reagent, namely, azocarboxamides (ACAs). Under the catalysis of chiral phosphoric acid, unsymmetrical 1,2-diaminations of ACAs with various electron-rich double bonds readily occur in a regiodivergent manner. Indoles prefer dual hydrogen-bonding mode to give dearomative (4 + 2) products, and 3-vinylindoles and azlactones are inclined to undergo unsymmetrical 1,2-diamination via the (3 + 2) process. DFT calculations are performed to reveal the reaction mechanism and the origin of the regio- and enantioselectivity. Guided by computational design, we are able to reverse the regioselectivity of the dearomative unsymmetrical 1,2-diamination of indoles using Lewis acid catalysis.https://doi.org/10.1038/s41467-024-54598-z |
| spellingShingle | Yun-Dong Fu Han Zhang Bei-Bei Li Lihua Huang Xiao Xiao Min-Can Wang Donghui Wei Guang-Jian Mei Azocarboxamide-enabled enantioselective regiodivergent unsymmetrical 1,2-diaminations Nature Communications |
| title | Azocarboxamide-enabled enantioselective regiodivergent unsymmetrical 1,2-diaminations |
| title_full | Azocarboxamide-enabled enantioselective regiodivergent unsymmetrical 1,2-diaminations |
| title_fullStr | Azocarboxamide-enabled enantioselective regiodivergent unsymmetrical 1,2-diaminations |
| title_full_unstemmed | Azocarboxamide-enabled enantioselective regiodivergent unsymmetrical 1,2-diaminations |
| title_short | Azocarboxamide-enabled enantioselective regiodivergent unsymmetrical 1,2-diaminations |
| title_sort | azocarboxamide enabled enantioselective regiodivergent unsymmetrical 1 2 diaminations |
| url | https://doi.org/10.1038/s41467-024-54598-z |
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