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

The selective functionalization of distal C–H bonds, particularly remote aromatic C(sp²)–H bonds, represents a significant challenge in synthetic chemistry. Recently, we have developed an N-heterocyclic carbene (NHC) organocatalytic strategy for the acylation of ultra-remote aryl C(sp2)H bonds located eight bonds away from an activation site. This method proceeds via a novel single-electron pathway, enabling site-selective activation of aryl C–H bonds by in situ generated nitrogen-centered radicals. This approach offers substantial potential for the late-stage functionalization of pharmaceuticals, amino acids, and peptides, underscoring its importance in medicinal chemistry. 1.Introduction 2.Our strategy of ultra-remote C(sp2)H activation via NHC organocatalysis 3.Remote aryl C–H functionalization enabled by photocatalysis 4.Conclusion and perspectives