Confined Cationic Covalent Organic Cages Enable Oxidant-Free Hofmann-Löffler-Freytag/Cyclization Sequences.

Developing confined supramolecular environments capable of regulating radical cascade processes with high site selectivity remains a longstanding challenge in catalysis. Herein, we report two imidazolium-functionalized cationic covalent organic cages featuring distinct cavity architectures, including a triangular-prismatic cavity (cage 1) and a bowl-shaped cavity (cage 2), as confined platforms for oxidant-free Hofmann-Löffler-Freytag (HLF)/cyclization cascade catalysis. Both cages efficiently mediate a one-pot transformation of N-chloroamides into pyrrolidine derivatives under mild conditions, whereas cage 1 exhibits substantially enhanced activity and selectivity relative to cage 2 and a monomeric analog. Mechanistic investigations suggest that the geometrically confined cationic cavity of cage 1 promotes substrate preorganization through cooperative host-guest interactions, stabilizes nitrogen-centered radical intermediates via electrostatic and C-H···π interactions, and facilitates the key 1,5-hydrogen atom transfer (1,5-HAT) process by lowering the associated activation barrier. Host-guest binding studies and DFT calculations, reveal a structure-recognition-reactivity relationship in which substrate anchoring, spin delocalization, and cavity confinement collectively govern catalytic efficiency. These findings demonstrate how confined cationic microenvironments can reconstruct radical cascade pathways and provide a general strategy for designing supramolecular catalysts for selective multistep transformations.