An Enolate-Structure-Enabled Anionic Cascade Cyclization Reaction: Easy Access to Complex Scaffolds with Contiguous
Tomas Javorskis1,2, Ieva Karpavičienė1, Arminas Jurys1
1Department of Organic Chemistry, Vilnius University, Naugarduko 24, 03225, Vilnius, Lithuania.
Angewandte Chemie (International Ed. in English)
|July 23, 2020
Summary
Researchers developed a novel anionic cascade reaction for synthesizing complex molecular structures. This catalyst-free method efficiently creates intricate ring systems under mild conditions with high stereoselectivity.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Reaction Mechanisms
Background:
- Direct addition of ketone enolates to unactivated carbon-carbon bonds is challenging due to unreactive partners and harsh conditions.
- Highly aggregated or solvated enolates lack the necessary reactivity for addition to alkenes or alkynes.
Purpose of the Study:
- To report a new anionic cascade reaction for the one-step assembly of complex molecular scaffolds.
- To achieve a formal [2+2] enol-allene cycloaddition under mild conditions.
- To investigate the reaction mechanism and stereochemical outcome.
Main Methods:
- Anionic cascade reaction.
- Cycloaddition.
- Mechanistic studies.
- Computational analysis.
Main Results:
- One-step assembly of molecular scaffolds with contiguous six-, five-, and four-membered rings.
- Successful formal [2+2] enol-allene cycloaddition.
- Excellent diastereoselectivity achieved under very mild conditions.
- Mechanistic studies revealed a slow proton transfer in a cyclic ketone intermediate.
Conclusions:
- The developed anionic cascade reaction provides an efficient route to complex polycyclic structures.
- The reaction proceeds under mild, catalyst-free conditions with high stereocontrol.
- Understanding the slow proton transfer phenomenon is key to explaining the observed stereochemistry.
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