Catalytic Enantioselective Synthesis of Axially Chiral Diaryl Ethers Via Asymmetric Povarov Reaction Enabled Desymmetrization
Abstract Axially chiral diaryl ethers represent a distinct class of atropisomers, characterized by a unique dual C─O axes system, which have been found in a variety of natural products, pharmaceuticals, and ligands. However, the catalytic enantioselective synthesis of these atropoisomers poses signi...
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| Format: | Article |
| Language: | English |
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Wiley
2024-09-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202403125 |
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| author | Zidan Ye Wansen Xie Wei Liu Changyu Zhou Xiaoyu Yang |
| author_facet | Zidan Ye Wansen Xie Wei Liu Changyu Zhou Xiaoyu Yang |
| author_sort | Zidan Ye |
| collection | DOAJ |
| description | Abstract Axially chiral diaryl ethers represent a distinct class of atropisomers, characterized by a unique dual C─O axes system, which have been found in a variety of natural products, pharmaceuticals, and ligands. However, the catalytic enantioselective synthesis of these atropoisomers poses significant challenges, due to the difficulty in controlling both chiral C─O axes, and their more flexible conformations. Herein, an efficient protocol for catalytic enantioselective synthesis of axially chiral diaryl ethers is presented using organocatalyzed asymmetric Povarov reaction‐enabled desymmetrization, followed by aromatizations. This method yields a wide range of novel quinoline‐based diaryl ether atropoisomers in good yields and high enantioselectivities. Notably, various aromatization protocols are developed, resulting in a diverse set of polysubstituted quinoline‐containing diaryl ether atropisomers. Thermal racemization studies suggested excellent configurational stabilities for these novel diaryl ether atropisomers (with racemization barriers up to 38.1 kcal mol−1). Moreover, this research demonstrates for the first time that diaryl ether atropisomers lacking the bulky t‐Bu group can still maintain a stable configuration, challenging the prior knowledge in the field. The fruitful derivatizations of the functional group‐rich chiral products further underscore the value of this method. |
| format | Article |
| id | doaj-art-5743124817e54e65a3e1c0bf84d56771 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-5743124817e54e65a3e1c0bf84d567712025-08-20T01:55:16ZengWileyAdvanced Science2198-38442024-09-011135n/an/a10.1002/advs.202403125Catalytic Enantioselective Synthesis of Axially Chiral Diaryl Ethers Via Asymmetric Povarov Reaction Enabled DesymmetrizationZidan Ye0Wansen Xie1Wei Liu2Changyu Zhou3Xiaoyu Yang4School of Physical Science and Technology Shanghai 201210 ChinaSchool of Physical Science and Technology Shanghai 201210 ChinaSchool of Physical Science and Technology Shanghai 201210 ChinaSchool of Physical Science and Technology Shanghai 201210 ChinaSchool of Physical Science and Technology Shanghai 201210 ChinaAbstract Axially chiral diaryl ethers represent a distinct class of atropisomers, characterized by a unique dual C─O axes system, which have been found in a variety of natural products, pharmaceuticals, and ligands. However, the catalytic enantioselective synthesis of these atropoisomers poses significant challenges, due to the difficulty in controlling both chiral C─O axes, and their more flexible conformations. Herein, an efficient protocol for catalytic enantioselective synthesis of axially chiral diaryl ethers is presented using organocatalyzed asymmetric Povarov reaction‐enabled desymmetrization, followed by aromatizations. This method yields a wide range of novel quinoline‐based diaryl ether atropoisomers in good yields and high enantioselectivities. Notably, various aromatization protocols are developed, resulting in a diverse set of polysubstituted quinoline‐containing diaryl ether atropisomers. Thermal racemization studies suggested excellent configurational stabilities for these novel diaryl ether atropisomers (with racemization barriers up to 38.1 kcal mol−1). Moreover, this research demonstrates for the first time that diaryl ether atropisomers lacking the bulky t‐Bu group can still maintain a stable configuration, challenging the prior knowledge in the field. The fruitful derivatizations of the functional group‐rich chiral products further underscore the value of this method.https://doi.org/10.1002/advs.202403125asymmetric catalysisatropisomerismdesymmetrizationdiaryl ethersPovarov reaction |
| spellingShingle | Zidan Ye Wansen Xie Wei Liu Changyu Zhou Xiaoyu Yang Catalytic Enantioselective Synthesis of Axially Chiral Diaryl Ethers Via Asymmetric Povarov Reaction Enabled Desymmetrization Advanced Science asymmetric catalysis atropisomerism desymmetrization diaryl ethers Povarov reaction |
| title | Catalytic Enantioselective Synthesis of Axially Chiral Diaryl Ethers Via Asymmetric Povarov Reaction Enabled Desymmetrization |
| title_full | Catalytic Enantioselective Synthesis of Axially Chiral Diaryl Ethers Via Asymmetric Povarov Reaction Enabled Desymmetrization |
| title_fullStr | Catalytic Enantioselective Synthesis of Axially Chiral Diaryl Ethers Via Asymmetric Povarov Reaction Enabled Desymmetrization |
| title_full_unstemmed | Catalytic Enantioselective Synthesis of Axially Chiral Diaryl Ethers Via Asymmetric Povarov Reaction Enabled Desymmetrization |
| title_short | Catalytic Enantioselective Synthesis of Axially Chiral Diaryl Ethers Via Asymmetric Povarov Reaction Enabled Desymmetrization |
| title_sort | catalytic enantioselective synthesis of axially chiral diaryl ethers via asymmetric povarov reaction enabled desymmetrization |
| topic | asymmetric catalysis atropisomerism desymmetrization diaryl ethers Povarov reaction |
| url | https://doi.org/10.1002/advs.202403125 |
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