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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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
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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| Summary: | 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. |
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| ISSN: | 2399-3669 |