Confined Cationic Covalent Organic Cages Enable Oxidant-Free Hofmann-Löffler-Freytag/Cyclization Sequences
Cheng Wang1, Xiaodong Hu1, Mengzhi Zhang1
1International Joint Laboratory on Resource Chemistry of the Ministry of Education, Shanghai Engineering Research Center of Green Energy Chemical Engineering, Shanghai Normal University, Shanghai, People's Republic of China.
Angewandte Chemie (International Ed. in English)
|June 30, 2026
Summary
Covalent organic cages create confined environments for radical cascade reactions. Cage 1, with a specific cavity, shows enhanced activity and selectivity in synthesizing pyrrolidines via Hofmann-Löffler-Freytag (HLF) catalysis.
Area of Science:
- Supramolecular Chemistry
- Organic Catalysis
- Radical Chemistry
Background:
- Confined supramolecular environments are crucial for selective radical cascade reactions.
- Designing catalysts with high site selectivity for radical processes is challenging.
Purpose of the Study:
- To develop confined supramolecular platforms for oxidant-free Hofmann-Löffler-Freytag (HLF)/cyclization cascade catalysis.
- To investigate the role of cage architecture in controlling radical cascade pathways.
Main Methods:
- Synthesis of two imidazolium-functionalized cationic covalent organic cages with distinct cavity architectures.
- One-pot cascade catalysis of N-chloroamides to pyrrolidine derivatives.
- Mechanistic studies including host-guest binding and DFT calculations.
Main Results:
- Both cages mediated the transformation, but cage 1 showed significantly higher activity and selectivity.
- Cage 1's confined cationic cavity enhanced substrate preorganization and stabilized radical intermediates.
- Key 1,5-hydrogen atom transfer (1,5-HAT) was facilitated by cage 1, lowering activation energy.
Conclusions:
- Confined cationic microenvironments within covalent organic cages can effectively control radical cascade pathways.
- A structure-recognition-reactivity relationship was established, highlighting substrate anchoring, spin delocalization, and cavity confinement.
- This work provides a general strategy for designing supramolecular catalysts for selective multistep transformations.
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