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Photochemical preparation of (aza−)indolines: diastereoselective synthesis and polarity reversal strategy

Herein, we present the first light-mediated, diastereoselective de novo synthesis for 2,3-substituted indolines, a privileged scaffold in pharmaceuticals. The protocol was tested with various aryl and alkyl groups, maintaining high yields up to 85% across different substituents. The approach was fur...

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Main Authors: Melder, Julian J. (Author) , Heldner, Maxi L. (Author) , Svetličić, Julia (Author) , Adow, Abdinasir (Author) , Rominger, Frank (Author) , Rudolph, Matthias (Author) , Helmchen, Günter (Author) , Hashmi, A. Stephen K. (Author)
Format: Article (Journal)
Language:English
Published: July 23, 2025
In: Advanced synthesis & catalysis
Year: 2025, Volume: 367, Issue: 13, Pages: 1-7
ISSN:1615-4169
DOI:10.1002/adsc.202500220
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1002/adsc.202500220
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/adsc.202500220
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Author Notes:Julian J. Melder, Maxi L. Heldner, Julia Svetličić, Abdinasir Adow, Frank Rominger, Matthias Rudolph, Günter Helmchen, and A. Stephen K. Hashmi
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Summary:Herein, we present the first light-mediated, diastereoselective de novo synthesis for 2,3-substituted indolines, a privileged scaffold in pharmaceuticals. The protocol was tested with various aryl and alkyl groups, maintaining high yields up to 85% across different substituents. The approach was further extended to enantioselective synthesis, yielding trans-2,3-substituted indolines with high enantiomeric excesses (94%-96% ee). Drawbacks resulting from low efficiencies for nucleophilic radicals in previous studies were addressed by a polarity reversal strategy, incorporating electron-withdrawing groups to improve the efficiency of the initial radical addition. Finally, the methodology was utilized for the synthesis of azaindolines, a highly valuable target in pharmaceutical research. Our approach now encompasses modifications to the aromatic backbone, the use of both nucleophilic and electrophilic radicals as coupling partners, the synthesis of indolines, azaindolines, and tetrahydroquinolines, variation of protecting groups, and the diastereoselective synthesis of 2,3-substituted indolines.
Item Description:Zuerst veröffentlicht: 19. März 2025
Gesehen am 11.09.2025
Physical Description:Online Resource
ISSN:1615-4169
DOI:10.1002/adsc.202500220

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