Confined Cationic Covalent Organic Cages Enable Oxidant‐Free Hofmann−Löffler−Freytag/Cyclization Sequences

ABSTRACT

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.