Iron-catalysed stereoselective NH transfer enables dynamic kinetic resolution of sulfoxides
Abstract Transition metal-catalysed asymmetric nitrene transfer provides a powerful means to access various bioactive N-containing compounds as single enantiomers. However, enantioselective NH transfer that allows concise assembly of unprotected enantioenriched amines remains an enduring challenge....
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56860-4 |
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| author | Fang-Xu Fan Hui Xu Shi-Xiong Tang Yanfeng Dang Fei Wang |
| author_facet | Fang-Xu Fan Hui Xu Shi-Xiong Tang Yanfeng Dang Fei Wang |
| author_sort | Fang-Xu Fan |
| collection | DOAJ |
| description | Abstract Transition metal-catalysed asymmetric nitrene transfer provides a powerful means to access various bioactive N-containing compounds as single enantiomers. However, enantioselective NH transfer that allows concise assembly of unprotected enantioenriched amines remains an enduring challenge. We report here an iron-catalysed stereoselective NH imidation of sulfoxide, which is integrated with photocatalytic racemisation of sulfoxide, enabling a dynamic kinetic resolution (DKR) strategy for direct and asymmetric synthesis of NH-sulfoximines. This approach is distinct from the existing methods by avoiding protecting group manipulations and/or the use of chiral substrates. Computational studies on the NH imidation reaction suggest the involvement of an iron-aminyl radical intermediate, and its reaction with sulfoxide proceeds through a synchronous nucleophilic addition of sulfoxide to nitrogen center and ligand-to-metal single electron transfer process to form the N–S bond. In addition, the stereoselectivity is primarily dictated by the difference in dispersion interactions of the transition states. |
| format | Article |
| id | doaj-art-a691aaf727274121a65ba7ea2fea0aae |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-a691aaf727274121a65ba7ea2fea0aae2025-02-09T12:45:00ZengNature PortfolioNature Communications2041-17232025-02-011611910.1038/s41467-025-56860-4Iron-catalysed stereoselective NH transfer enables dynamic kinetic resolution of sulfoxidesFang-Xu Fan0Hui Xu1Shi-Xiong Tang2Yanfeng Dang3Fei Wang4State Key Laboratory of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai UniversityTianjin Key Laboratory of Molecular Optoelectronic Sciences, Department of Chemistry, Tianjin UniversityState Key Laboratory of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai UniversityTianjin Key Laboratory of Molecular Optoelectronic Sciences, Department of Chemistry, Tianjin UniversityState Key Laboratory of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai UniversityAbstract Transition metal-catalysed asymmetric nitrene transfer provides a powerful means to access various bioactive N-containing compounds as single enantiomers. However, enantioselective NH transfer that allows concise assembly of unprotected enantioenriched amines remains an enduring challenge. We report here an iron-catalysed stereoselective NH imidation of sulfoxide, which is integrated with photocatalytic racemisation of sulfoxide, enabling a dynamic kinetic resolution (DKR) strategy for direct and asymmetric synthesis of NH-sulfoximines. This approach is distinct from the existing methods by avoiding protecting group manipulations and/or the use of chiral substrates. Computational studies on the NH imidation reaction suggest the involvement of an iron-aminyl radical intermediate, and its reaction with sulfoxide proceeds through a synchronous nucleophilic addition of sulfoxide to nitrogen center and ligand-to-metal single electron transfer process to form the N–S bond. In addition, the stereoselectivity is primarily dictated by the difference in dispersion interactions of the transition states.https://doi.org/10.1038/s41467-025-56860-4 |
| spellingShingle | Fang-Xu Fan Hui Xu Shi-Xiong Tang Yanfeng Dang Fei Wang Iron-catalysed stereoselective NH transfer enables dynamic kinetic resolution of sulfoxides Nature Communications |
| title | Iron-catalysed stereoselective NH transfer enables dynamic kinetic resolution of sulfoxides |
| title_full | Iron-catalysed stereoselective NH transfer enables dynamic kinetic resolution of sulfoxides |
| title_fullStr | Iron-catalysed stereoselective NH transfer enables dynamic kinetic resolution of sulfoxides |
| title_full_unstemmed | Iron-catalysed stereoselective NH transfer enables dynamic kinetic resolution of sulfoxides |
| title_short | Iron-catalysed stereoselective NH transfer enables dynamic kinetic resolution of sulfoxides |
| title_sort | iron catalysed stereoselective nh transfer enables dynamic kinetic resolution of sulfoxides |
| url | https://doi.org/10.1038/s41467-025-56860-4 |
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