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Updated: Jan 10, 2026
07:11
Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
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Exploring the formation of medium-sized cyclic amines within self-assembled yoctoliter inner-spaces.
Yahya A Ismaiel1, Douglas Rogers1, Bruce C Gibb1
1Department of Chemistry, Tulane University New Orleans LA 70118 USA bgibb@tulane.edu.
Chemical Science
|November 20, 2025
Summary
This study demonstrates catalytic SN2 cyclizations to form medium-sized cyclic amines in water using a dimeric capsule. The capsule protects substrates from hydrolysis, enabling the synthesis of strained 7- to 11-membered rings.
Area of Science:
- Organic Chemistry
- Supramolecular Chemistry
- Green Chemistry
Background:
- Medium-sized rings (7-11 members) are challenging to synthesize due to enthalpic and entropic barriers.
- SN2 cyclizations in water are hindered by competing substrate hydrolysis.
Purpose of the Study:
- To explore the catalytic potential of a dimeric container's inner space for forming strained cyclic amines.
- To investigate the use of a deep-cavity cavitand capsule to promote SN2 cyclizations in water.
Main Methods:
- Utilized a dimeric capsule of octa-acid 1 assembled via the hydrophobic effect.
- Employed pseudo-halide sulfonate leaving groups to minimize product inhibition.
- Investigated the influence of guest conformation on reaction rates.
Main Results:
- Catalytic formation of strained 7-membered azepane was achieved.
- Hydrolysis rates of bound guests were reduced by up to four orders of magnitude.
- Strained 11-membered azacycloundecane was synthesized within watertight complexes.
Conclusions:
- Demonstrated the first examples of SN2 cyclizations to medium-sized cyclic amines in water.
- Quantified the water tightness of water-based container molecules.
- Highlighted the utility of supramolecular cages for challenging organic transformations.
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