Synthesis of Imidazolidinone-Fused 3,1-Benzoxazines via One-Pot Multicomponent Reactions
Zilong Tang1, Hongjuan Chen1, Yuhua Tan1
1Key Laboratory of Theoretical Organic Chemistry and Functional Molecule of the Ministry of Education, School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, Hunan 411201, China.
The Journal of Organic Chemistry
|January 14, 2026
Summary
A new palladium-catalyzed reaction efficiently synthesizes imidazolidinone-fused 3,1-benzoxazine derivatives in one step. This method offers a simple route to diverse compounds with potential antifungal activity.
Area of Science:
- Organic Chemistry
- Medicinal Chemistry
- Catalysis
Background:
- 3,1-benzoxazine derivatives are important scaffolds in medicinal chemistry.
- Efficient synthetic methods for complex heterocyclic compounds are in high demand.
Purpose of the Study:
- To develop a novel, efficient, and one-pot method for synthesizing imidazolidinone-fused 3,1-benzoxazine derivatives.
- To explore the scope and mechanism of the developed reaction.
Main Methods:
- Palladium-catalyzed one-pot multicomponent reaction.
- Utilized 2-aminoarylmethyl alcohols, ethyl glyoxylate, and amines as starting materials.
- Employed Density Functional Theory (DFT) calculations for mechanistic studies.
Main Results:
- Successfully synthesized imidazolidinone-fused 3,1-benzoxazine derivatives under mild conditions.
- Achieved high *trans*-selectivity and broad substrate scope.
- Demonstrated the construction of five new bonds and two ring systems in a single step.
Conclusions:
- The developed method provides a facile and efficient access to structurally diverse polycyclic fused 3,1-benzoxazine derivatives.
- The reaction mechanism and *trans*-selectivity were elucidated.
- Selected derivatives exhibited promising antifungal activity, suggesting potential therapeutic applications.
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