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Synlett
DOI: 10.1055/a-2597-0098
DOI: 10.1055/a-2597-0098
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Radical NHC Organocatalysis: Enabling Ultra-Remote, Site-Selective Functionalization of Arene C–H Bonds
Financial support from NSFC (22271028 and 22301023), the Science & Technology Department of Sichuan Province (2023NSFSC2001 and 2023NSFSC1081), the Research and Development in Key Areas of Guangdong Province (2022B1111050003), and the Longquan Talents Program is gratefully acknowledged.
Abstract
Achieving selective functionalization of distal C–H bonds, particularly remote aromatic C(sp 2)–H bonds, is a formidable challenge in organic synthesis. Recently, we have developed an innovative para-selective acylation strategy that targets ultra-remote aryl C(sp 2)–H bonds located eight bonds away from an activation site, utilizing radical N-heterocyclic carbene (NHC) organocatalysis. This method is based on a novel single-electron pathway, enabling site-selective activation of aryl C–H bonds through generated nitrogen-centered radicals in situ. This approach shows immense potential for the functionalization of pharmaceuticals, amino acids, and peptides, underscoring its importance in medicinal chemistry.
1 Introduction
2 Our Strategy of Ultra-Remote Activation via NHC Organocatalysis
3 Features and Applications of the NHC-Catalytic Ultra-Remote Acylation
4 Conclusion and Perspectives
Key words
ultra-remote activation - para-selective acylation - N-heterocyclic carbene - organocatalysis - late-stage functionalizationPublication History
Received: 07 April 2025
Accepted after revision: 29 April 2025
Accepted Manuscript online:
29 April 2025
Article published online:
17 July 2025
© 2025. Thieme. All rights reserved
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For selected reviews on C–H activation, see:
For selected reviews on proximal C–H activation, see:
For selected reviews on remote C–H activation, see:
For selected examples on transition-metal-mediated remote C–H metalation, see:
For selected reviews on σ-bond activation for remote C–H functionalization, see:
For selected reviews on HAT chemistry, see:
For selected examples on the remote C(sp 3)−H functionalization via HAT processes, see:
For selected reviews and examples on the application of U-shaped templates, see:
For selected reviews on NHC radical catalysis, see:
For our contributions on NHC catalysis, see: