Ultra-Remote Functionalization of Aromatic C–H Bonds via Radical NHC Organocatalysis

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