Chiral phosphoric acid-catalyzed atroposelective iodination of N-arylindoles
Abstract Axially chiral indoles have garnered significant attention due to their synthetic and biological importance. However, atroposelective halogenation of this scaffold has been rarely explored. This study presents a catalytic and enantioselective iodination of N-arylindoles, achieving precise c...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-06-01
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| Series: | Communications Chemistry |
| Online Access: | https://doi.org/10.1038/s42004-025-01584-1 |
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| author | Ahreum Kim Hyun-A Cho Byeongjun Oh Jayoung Song Yongseok Kwon |
| author_facet | Ahreum Kim Hyun-A Cho Byeongjun Oh Jayoung Song Yongseok Kwon |
| author_sort | Ahreum Kim |
| collection | DOAJ |
| description | Abstract Axially chiral indoles have garnered significant attention due to their synthetic and biological importance. However, atroposelective halogenation of this scaffold has been rarely explored. This study presents a catalytic and enantioselective iodination of N-arylindoles, achieving precise control over the C−N stereogenic axis. The reaction is facilitated by a chiral phosphoric acid, which promotes iodination at the C-3 position of N-arylindole, followed by iodine migration and deprotonation. A hydrogen-bonding donor on the aromatic ring plays a key role in achieving high enantioselectivities. Under optimized reaction conditions, a wide range of substrates are well-tolerated, and subsequent reactions with various carbonyl electrophiles maintain enantioselectivity. Computational studies provide insights into the origin of enantioselectivity at the plausible enantiodetermining step. |
| format | Article |
| id | doaj-art-43a9ee45413a4f0b90be221d2c29d3bc |
| institution | OA Journals |
| issn | 2399-3669 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Chemistry |
| spelling | doaj-art-43a9ee45413a4f0b90be221d2c29d3bc2025-08-20T02:10:34ZengNature PortfolioCommunications Chemistry2399-36692025-06-01811910.1038/s42004-025-01584-1Chiral phosphoric acid-catalyzed atroposelective iodination of N-arylindolesAhreum Kim0Hyun-A Cho1Byeongjun Oh2Jayoung Song3Yongseok Kwon4School of Pharmacy, Sungkyunkwan UniversitySchool of Pharmacy, Sungkyunkwan UniversitySchool of Pharmacy, Sungkyunkwan UniversityCollege of Medicine, Dankook UniversitySchool of Pharmacy, Sungkyunkwan UniversityAbstract Axially chiral indoles have garnered significant attention due to their synthetic and biological importance. However, atroposelective halogenation of this scaffold has been rarely explored. This study presents a catalytic and enantioselective iodination of N-arylindoles, achieving precise control over the C−N stereogenic axis. The reaction is facilitated by a chiral phosphoric acid, which promotes iodination at the C-3 position of N-arylindole, followed by iodine migration and deprotonation. A hydrogen-bonding donor on the aromatic ring plays a key role in achieving high enantioselectivities. Under optimized reaction conditions, a wide range of substrates are well-tolerated, and subsequent reactions with various carbonyl electrophiles maintain enantioselectivity. Computational studies provide insights into the origin of enantioselectivity at the plausible enantiodetermining step.https://doi.org/10.1038/s42004-025-01584-1 |
| spellingShingle | Ahreum Kim Hyun-A Cho Byeongjun Oh Jayoung Song Yongseok Kwon Chiral phosphoric acid-catalyzed atroposelective iodination of N-arylindoles Communications Chemistry |
| title | Chiral phosphoric acid-catalyzed atroposelective iodination of N-arylindoles |
| title_full | Chiral phosphoric acid-catalyzed atroposelective iodination of N-arylindoles |
| title_fullStr | Chiral phosphoric acid-catalyzed atroposelective iodination of N-arylindoles |
| title_full_unstemmed | Chiral phosphoric acid-catalyzed atroposelective iodination of N-arylindoles |
| title_short | Chiral phosphoric acid-catalyzed atroposelective iodination of N-arylindoles |
| title_sort | chiral phosphoric acid catalyzed atroposelective iodination of n arylindoles |
| url | https://doi.org/10.1038/s42004-025-01584-1 |
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