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London Dispersion Favors Cis Selectivity in the Johnson-Corey-Chaykovsky Epoxidation
Marvin H J Domanski1, Lars Rummel1, Saskia N Krug1
1Institute of Organic Chemistry, Justus Liebig University, Heinrich-Buff-Ring 17, 35392 Giessen, Germany.
The Journal of Organic Chemistry
|March 26, 2026
Summary
Dispersion energy donors, like bulky alkyl groups and halides, significantly influence Johnson-Corey-Chaykovsky epoxidation selectivity. London dispersion interactions, not just steric repulsion, stabilize key transition structures, impacting cis/trans outcomes.
Area of Science:
- Organic Chemistry
- Computational Chemistry
- Chemical Physics
Background:
- The Johnson-Corey-Chaykovsky epoxidation is a key reaction in organic synthesis.
- Diastereoselectivity in this reaction is typically explained by steric repulsion.
- The role of noncovalent interactions in transition state stabilization is often underestimated.
Purpose of the Study:
- To investigate the influence of dispersion energy donors on the cis/trans selectivity of the Johnson-Corey-Chaykovsky epoxidation.
- To explore the contribution of London dispersion interactions to transition structure stabilization.
- To challenge the prevailing explanation based solely on steric repulsion.
Main Methods:
- Experimental studies including Nuclear Magnetic Resonance (NMR) measurements, double mutant cycles, and crossover experiments.
- Computational investigations using density functional theory (DFT) and symmetry-adapted perturbation theory (SAPT).
- Quantification of noncovalent interactions within reaction transition states.
Main Results:
- Bulky alkyl groups and halides act as significant dispersion energy donors in the epoxidation.
- London dispersion interactions provide substantial stabilization to preferred transition structures.
- Experimental and computational data confirm the importance of dispersion forces beyond steric effects.
- The study quantifies the role of noncovalent interactions in determining diastereoselectivity.
Conclusions:
- Dispersion energy donors play a crucial role in the cis/trans selectivity of the Johnson-Corey-Chaykovsky epoxidation.
- London dispersion interactions are a key stabilizing factor for transition states, complementing steric explanations.
- A more comprehensive understanding of noncovalent interactions is essential for predicting and controlling reaction outcomes.
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