Organocatalytic diastereo- and atroposelective construction of N–N axially chiral pyrroles and indoles
Abstract The construction of N–N axially chiral motifs is an important research topic, owing to their wide occurrence in natural products, pharmaceuticals and chiral ligands. One efficient method is the atroposelective dihydropyrimidin-4-one formation. We present herein a direct catalytic synthesis...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-44743-z |
| _version_ | 1827377283843751936 |
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| author | Shao-Jie Wang Xia Wang Xiaolan Xin Shulei Zhang Hui Yang Ming Wah Wong Shenci Lu |
| author_facet | Shao-Jie Wang Xia Wang Xiaolan Xin Shulei Zhang Hui Yang Ming Wah Wong Shenci Lu |
| author_sort | Shao-Jie Wang |
| collection | DOAJ |
| description | Abstract The construction of N–N axially chiral motifs is an important research topic, owing to their wide occurrence in natural products, pharmaceuticals and chiral ligands. One efficient method is the atroposelective dihydropyrimidin-4-one formation. We present herein a direct catalytic synthesis of N–N atropisomers with simultaneous creation of contiguous axial and central chirality by oxidative NHC (N-heterocyclic carbenes) catalyzed (3 + 3) cycloaddition. Using our method, we are able to synthesize structurally diverse N–N axially chiral pyrroles and indoles with vicinal central chirality or bearing a 2,3-dihydropyrimidin-4-one moiety in moderate to good yields and excellent enantioselectivities. Further synthetic transformations of the obtained axially chiral pyrroles and indoles derivative products are demonstrated. The reaction mechanism and the origin of enantioselectivity are understood through DFT calculations. |
| first_indexed | 2024-03-08T12:36:50Z |
| format | Article |
| id | doaj.art-cc54fadd8d13465093078b596b06c076 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-08T12:36:50Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-cc54fadd8d13465093078b596b06c0762024-01-21T12:26:59ZengNature PortfolioNature Communications2041-17232024-01-0115111310.1038/s41467-024-44743-zOrganocatalytic diastereo- and atroposelective construction of N–N axially chiral pyrroles and indolesShao-Jie Wang0Xia Wang1Xiaolan Xin2Shulei Zhang3Hui Yang4Ming Wah Wong5Shenci Lu6Frontiers Science Center for Flexible Electronics (FSCFE), Shaanxi Institute of Flexible Electronics (SIFE) & Shaanxi Institute of Biomedical Materials and Engineering (SIBME), Northwestern Polytechnical University (NPU)Frontiers Science Center for Flexible Electronics (FSCFE), Shaanxi Institute of Flexible Electronics (SIFE) & Shaanxi Institute of Biomedical Materials and Engineering (SIBME), Northwestern Polytechnical University (NPU)Frontiers Science Center for Flexible Electronics (FSCFE), Shaanxi Institute of Flexible Electronics (SIFE) & Shaanxi Institute of Biomedical Materials and Engineering (SIBME), Northwestern Polytechnical University (NPU)Frontiers Science Center for Flexible Electronics (FSCFE), Shaanxi Institute of Flexible Electronics (SIFE) & Shaanxi Institute of Biomedical Materials and Engineering (SIBME), Northwestern Polytechnical University (NPU)Department of Chemistry, National University of SingaporeDepartment of Chemistry, National University of SingaporeFrontiers Science Center for Flexible Electronics (FSCFE), Shaanxi Institute of Flexible Electronics (SIFE) & Shaanxi Institute of Biomedical Materials and Engineering (SIBME), Northwestern Polytechnical University (NPU)Abstract The construction of N–N axially chiral motifs is an important research topic, owing to their wide occurrence in natural products, pharmaceuticals and chiral ligands. One efficient method is the atroposelective dihydropyrimidin-4-one formation. We present herein a direct catalytic synthesis of N–N atropisomers with simultaneous creation of contiguous axial and central chirality by oxidative NHC (N-heterocyclic carbenes) catalyzed (3 + 3) cycloaddition. Using our method, we are able to synthesize structurally diverse N–N axially chiral pyrroles and indoles with vicinal central chirality or bearing a 2,3-dihydropyrimidin-4-one moiety in moderate to good yields and excellent enantioselectivities. Further synthetic transformations of the obtained axially chiral pyrroles and indoles derivative products are demonstrated. The reaction mechanism and the origin of enantioselectivity are understood through DFT calculations.https://doi.org/10.1038/s41467-024-44743-z |
| spellingShingle | Shao-Jie Wang Xia Wang Xiaolan Xin Shulei Zhang Hui Yang Ming Wah Wong Shenci Lu Organocatalytic diastereo- and atroposelective construction of N–N axially chiral pyrroles and indoles Nature Communications |
| title | Organocatalytic diastereo- and atroposelective construction of N–N axially chiral pyrroles and indoles |
| title_full | Organocatalytic diastereo- and atroposelective construction of N–N axially chiral pyrroles and indoles |
| title_fullStr | Organocatalytic diastereo- and atroposelective construction of N–N axially chiral pyrroles and indoles |
| title_full_unstemmed | Organocatalytic diastereo- and atroposelective construction of N–N axially chiral pyrroles and indoles |
| title_short | Organocatalytic diastereo- and atroposelective construction of N–N axially chiral pyrroles and indoles |
| title_sort | organocatalytic diastereo and atroposelective construction of n n axially chiral pyrroles and indoles |
| url | https://doi.org/10.1038/s41467-024-44743-z |
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