Enantioselective aza-electrophilic dearomatization of naphthalene derivatives
Abstract The catalytic asymmetric dearomatization of naphthalenes is a pivotal strategy for generating enantioenriched three-dimensional aliphatic polycycles from flat aromatic precursors. However, achieving such transformations involving electronically unbiased naphthalenes remains a long-standing...
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| Main Authors: | , , , , , |
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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/s41467-025-60660-1 |
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| author | Jun Liu Haina Liu Meijuan Zhou Xiaolong Yu Gang Zhao Hongyu Wang |
| author_facet | Jun Liu Haina Liu Meijuan Zhou Xiaolong Yu Gang Zhao Hongyu Wang |
| author_sort | Jun Liu |
| collection | DOAJ |
| description | Abstract The catalytic asymmetric dearomatization of naphthalenes is a pivotal strategy for generating enantioenriched three-dimensional aliphatic polycycles from flat aromatic precursors. However, achieving such transformations involving electronically unbiased naphthalenes remains a long-standing challenge. Here, we describe a silver-mediated enantioselective aza-electrophilic dearomatization approach that couples readily accessible vinylnaphthalenes in conjunction with azodicarboxylates to afford chiral polyheterocycles via formal [4 + 2] cycloaddition reactions, yielding up to 99% yield and 99 : 1 e.r. Central to the method is the formation of an aziridinium intermediate that facilitates the subsequent dearomatization of naphthalenes. A 100 mmol-scale reaction and the divergent transformation of the products into enantioenriched aliphatic polycycles highlight their synthetic utility. Mechanistic experiments and DFT calculations offer insights into the reaction mechanism and the origin of the observed enantiocontrol outcome. |
| format | Article |
| id | doaj-art-06ae178f55f7454e9b151af4fba11b71 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-06ae178f55f7454e9b151af4fba11b712025-08-20T04:03:06ZengNature PortfolioNature Communications2041-17232025-07-0116111010.1038/s41467-025-60660-1Enantioselective aza-electrophilic dearomatization of naphthalene derivativesJun Liu0Haina Liu1Meijuan Zhou2Xiaolong Yu3Gang Zhao4Hongyu Wang5Key Laboratory of Marine Drugs, Ministry of Education, Molecular Synthesis Center, and School of Medicine and Pharmacy, Ocean University of ChinaKey Laboratory of Marine Drugs, Ministry of Education, Molecular Synthesis Center, and School of Medicine and Pharmacy, Ocean University of ChinaSDU-ANU Joint Science College, Shandong UniversitySDU-ANU Joint Science College, Shandong UniversityKey Laboratory of Fluorine and Nitrogen Chemistry and Advanced Materials, Shanghai Institute of Organic Chemistry, Chinese Academy of SciencesKey Laboratory of Marine Drugs, Ministry of Education, Molecular Synthesis Center, and School of Medicine and Pharmacy, Ocean University of ChinaAbstract The catalytic asymmetric dearomatization of naphthalenes is a pivotal strategy for generating enantioenriched three-dimensional aliphatic polycycles from flat aromatic precursors. However, achieving such transformations involving electronically unbiased naphthalenes remains a long-standing challenge. Here, we describe a silver-mediated enantioselective aza-electrophilic dearomatization approach that couples readily accessible vinylnaphthalenes in conjunction with azodicarboxylates to afford chiral polyheterocycles via formal [4 + 2] cycloaddition reactions, yielding up to 99% yield and 99 : 1 e.r. Central to the method is the formation of an aziridinium intermediate that facilitates the subsequent dearomatization of naphthalenes. A 100 mmol-scale reaction and the divergent transformation of the products into enantioenriched aliphatic polycycles highlight their synthetic utility. Mechanistic experiments and DFT calculations offer insights into the reaction mechanism and the origin of the observed enantiocontrol outcome.https://doi.org/10.1038/s41467-025-60660-1 |
| spellingShingle | Jun Liu Haina Liu Meijuan Zhou Xiaolong Yu Gang Zhao Hongyu Wang Enantioselective aza-electrophilic dearomatization of naphthalene derivatives Nature Communications |
| title | Enantioselective aza-electrophilic dearomatization of naphthalene derivatives |
| title_full | Enantioselective aza-electrophilic dearomatization of naphthalene derivatives |
| title_fullStr | Enantioselective aza-electrophilic dearomatization of naphthalene derivatives |
| title_full_unstemmed | Enantioselective aza-electrophilic dearomatization of naphthalene derivatives |
| title_short | Enantioselective aza-electrophilic dearomatization of naphthalene derivatives |
| title_sort | enantioselective aza electrophilic dearomatization of naphthalene derivatives |
| url | https://doi.org/10.1038/s41467-025-60660-1 |
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