Acridine/Lewis Acid Photocatalysis Enables α-Amidyl Radical Cyclizations

Abstract

A Lewis acid-activated acridine photocatalytic platform is reported that enables intramolecular Giese-type cyclizations of αamidyl radicals under mild photochemical conditions. This approach addresses longstanding challenges associated with αamidyl radical reactivity and provides direct access to bicyclic and polycyclic nitrogen frameworks, including izidinones, izidines, and indoloquinolizidines. The method displays broad substrate scope and enables the efficient construction of annulated azacycles that are difficult to access using existing radical or ionic strategies. The synthetic utility of the protocol is demonstrated through formal syntheses of the indoloquinolizidine alkaloids (±)-eburnaminol and (±)-larutensine, underscoring its value for the rapid assembly of structurally complex, medicinally relevant polycyclic ring system.