DMAP-Promoted Cascade Synthesis of Bispirooxindole-Cyclopentene-Isoxazolones
Wei Zhang1, Rong-Rong Zhu1, Da-Ming Du1
1School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, China.
Molecules (Basel, Switzerland)
|July 28, 2026
Summary
A new DMAP-catalyzed cascade reaction efficiently creates complex bispirooxindole frameworks. This method offers a concise route to novel spiroisoxazolone derivatives with high yield and stereoselectivity.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Medicinal Chemistry
Background:
- Spirooxindoles are privileged scaffolds in medicinal chemistry.
- Efficient synthesis of complex spirocyclic frameworks remains a challenge.
Purpose of the Study:
- To develop a novel cascade reaction for constructing bispirooxindole-cyclopentene-isoxazolone frameworks.
- To explore the scope and efficiency of the developed synthetic methodology.
Main Methods:
- DMAP-catalyzed Michael addition/cyclization cascade reaction.
- Optimization of reaction conditions including catalyst loading, solvent, and temperature.
- Substrate scope exploration with various isoxazolone and oxindole derivatives.
- Structural elucidation using X-ray single-crystal diffraction.
Main Results:
- The reaction efficiently synthesized the target bispirooxindole framework in 92% yield with >20:1 diastereoselectivity.
- Broad substrate scope was observed, yielding products in 72-96% yields.
- A gram-scale experiment confirmed the method's utility with an 82% yield.
- The relative configuration of a product was confirmed by X-ray crystallography.
Conclusions:
- A concise and efficient DMAP-catalyzed cascade reaction was established for synthesizing novel spiroisoxazolone derivatives.
- The method provides access to structurally complex molecules with multiple spiro chiral centers.
- This work offers a valuable synthetic route for potential pharmaceutical applications.
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