Photochemical C3-amination of pyridines via Zincke imine intermediates
Abstract Selective skeletal and peripheral editing of the pyridine moiety has broadly expanded the chemical space. While C-H functionalization at C2 and C4 positions are enabled by the inherent reactivity of this heteroarene, selective derivatization at the C3 position has long posed a significant c...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59809-9 |
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| author | Kitti Franciska Szabó Piotr Banachowicz Antoni Powała Danijela Lunic Ignacio Funes Ardoiz Dorota Gryko |
| author_facet | Kitti Franciska Szabó Piotr Banachowicz Antoni Powała Danijela Lunic Ignacio Funes Ardoiz Dorota Gryko |
| author_sort | Kitti Franciska Szabó |
| collection | DOAJ |
| description | Abstract Selective skeletal and peripheral editing of the pyridine moiety has broadly expanded the chemical space. While C-H functionalization at C2 and C4 positions are enabled by the inherent reactivity of this heteroarene, selective derivatization at the C3 position has long posed a significant challenge. Recently, based on a dearomatization-rearomatization sequence, involving Zincke imine intermediates, selective halogenation (-Br, -Cl, and -I) and isotopic labelling were accomplished. Here, we report a mild and regioselective method for C3-amination that relies on the photochemical reaction of Zincke imine with an amidyl radical generated from N-aminopyridinium salts. Mechanistic and theoretical studies indicate that radical intermediates are involved and explain the C3 regioselectivity of the reaction. |
| format | Article |
| id | doaj-art-2859cf054de547e4985f02bb4f36aa28 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-2859cf054de547e4985f02bb4f36aa282025-08-20T03:16:32ZengNature PortfolioNature Communications2041-17232025-05-011611910.1038/s41467-025-59809-9Photochemical C3-amination of pyridines via Zincke imine intermediatesKitti Franciska Szabó0Piotr Banachowicz1Antoni Powała2Danijela Lunic3Ignacio Funes Ardoiz4Dorota Gryko5Institute of Organic Chemistry Polish Academy of SciencesInstitute of Organic Chemistry Polish Academy of SciencesInstitute of Organic Chemistry Polish Academy of SciencesDepartamento de Química, Instituto de Química de la Universidad de La Rioja, Universidad de La RiojaDepartamento de Química, Instituto de Química de la Universidad de La Rioja, Universidad de La RiojaInstitute of Organic Chemistry Polish Academy of SciencesAbstract Selective skeletal and peripheral editing of the pyridine moiety has broadly expanded the chemical space. While C-H functionalization at C2 and C4 positions are enabled by the inherent reactivity of this heteroarene, selective derivatization at the C3 position has long posed a significant challenge. Recently, based on a dearomatization-rearomatization sequence, involving Zincke imine intermediates, selective halogenation (-Br, -Cl, and -I) and isotopic labelling were accomplished. Here, we report a mild and regioselective method for C3-amination that relies on the photochemical reaction of Zincke imine with an amidyl radical generated from N-aminopyridinium salts. Mechanistic and theoretical studies indicate that radical intermediates are involved and explain the C3 regioselectivity of the reaction.https://doi.org/10.1038/s41467-025-59809-9 |
| spellingShingle | Kitti Franciska Szabó Piotr Banachowicz Antoni Powała Danijela Lunic Ignacio Funes Ardoiz Dorota Gryko Photochemical C3-amination of pyridines via Zincke imine intermediates Nature Communications |
| title | Photochemical C3-amination of pyridines via Zincke imine intermediates |
| title_full | Photochemical C3-amination of pyridines via Zincke imine intermediates |
| title_fullStr | Photochemical C3-amination of pyridines via Zincke imine intermediates |
| title_full_unstemmed | Photochemical C3-amination of pyridines via Zincke imine intermediates |
| title_short | Photochemical C3-amination of pyridines via Zincke imine intermediates |
| title_sort | photochemical c3 amination of pyridines via zincke imine intermediates |
| url | https://doi.org/10.1038/s41467-025-59809-9 |
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