Organocatalytic asymmetric synthesis of Tröger’s bases
Abstract The stereochemical course of nitrogen in tertiary amines has long been overlooked because of the low energy barriers for pyramidal inversion between nitrogen-based conformers. Tröger’s base (TB) is a textbook three-dimensional (3D) molecule with N-centered chirality. Despite the major devel...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61772-4 |
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| author | Yu-Wei Li Nan-Nan Mo Han Zhang Jian-Xiao Wu Tian-Jiao Han Xiao Xiao Donghui Wei Guang-Jian Mei |
| author_facet | Yu-Wei Li Nan-Nan Mo Han Zhang Jian-Xiao Wu Tian-Jiao Han Xiao Xiao Donghui Wei Guang-Jian Mei |
| author_sort | Yu-Wei Li |
| collection | DOAJ |
| description | Abstract The stereochemical course of nitrogen in tertiary amines has long been overlooked because of the low energy barriers for pyramidal inversion between nitrogen-based conformers. Tröger’s base (TB) is a textbook three-dimensional (3D) molecule with N-centered chirality. Despite the major development of TB chemistry, surprisingly few general strategies are available to access enantioenriched TBs. Here, we report the organocatalytic asymmetric synthesis of TBs via the aminalization of tetrahydrodibenzodiazocines with aromatic aldehydes. This chiral phosphoric acid (CPA)-catalyzed protocol features a broad substrate scope (55 examples), high efficiency (up to 96% yield), and excellent enantioselectivity (up to >99% ee). Density functional theory (DFT) calculations are performed to reveal the reaction mechanism and the origin of the enantioselectivity. The success in preparing TB-polymers and aggregation-induced emission luminogen (AIEgen) demonstrates the potential for widespread applications, especially in the fields of materials science. |
| format | Article |
| id | doaj-art-e4eb64c0f44e4737846297f576076601 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-e4eb64c0f44e4737846297f5760766012025-08-20T03:46:09ZengNature PortfolioNature Communications2041-17232025-07-0116111310.1038/s41467-025-61772-4Organocatalytic asymmetric synthesis of Tröger’s basesYu-Wei Li0Nan-Nan Mo1Han Zhang2Jian-Xiao Wu3Tian-Jiao Han4Xiao Xiao5Donghui Wei6Guang-Jian Mei7College of Chemistry (Pingyuan Laboratory), Zhengzhou UniversityCollege of Chemistry (Pingyuan Laboratory), Zhengzhou UniversityCollege of Chemistry (Pingyuan Laboratory), Zhengzhou UniversityCollege of Chemistry (Pingyuan Laboratory), Zhengzhou UniversityCollege of Chemistry (Pingyuan Laboratory), Zhengzhou UniversityCollaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of TechnologyCollege of Chemistry (Pingyuan Laboratory), Zhengzhou UniversityCollege of Chemistry (Pingyuan Laboratory), Zhengzhou UniversityAbstract The stereochemical course of nitrogen in tertiary amines has long been overlooked because of the low energy barriers for pyramidal inversion between nitrogen-based conformers. Tröger’s base (TB) is a textbook three-dimensional (3D) molecule with N-centered chirality. Despite the major development of TB chemistry, surprisingly few general strategies are available to access enantioenriched TBs. Here, we report the organocatalytic asymmetric synthesis of TBs via the aminalization of tetrahydrodibenzodiazocines with aromatic aldehydes. This chiral phosphoric acid (CPA)-catalyzed protocol features a broad substrate scope (55 examples), high efficiency (up to 96% yield), and excellent enantioselectivity (up to >99% ee). Density functional theory (DFT) calculations are performed to reveal the reaction mechanism and the origin of the enantioselectivity. The success in preparing TB-polymers and aggregation-induced emission luminogen (AIEgen) demonstrates the potential for widespread applications, especially in the fields of materials science.https://doi.org/10.1038/s41467-025-61772-4 |
| spellingShingle | Yu-Wei Li Nan-Nan Mo Han Zhang Jian-Xiao Wu Tian-Jiao Han Xiao Xiao Donghui Wei Guang-Jian Mei Organocatalytic asymmetric synthesis of Tröger’s bases Nature Communications |
| title | Organocatalytic asymmetric synthesis of Tröger’s bases |
| title_full | Organocatalytic asymmetric synthesis of Tröger’s bases |
| title_fullStr | Organocatalytic asymmetric synthesis of Tröger’s bases |
| title_full_unstemmed | Organocatalytic asymmetric synthesis of Tröger’s bases |
| title_short | Organocatalytic asymmetric synthesis of Tröger’s bases |
| title_sort | organocatalytic asymmetric synthesis of troger s bases |
| url | https://doi.org/10.1038/s41467-025-61772-4 |
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