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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Multicomponent reaction to construct spirocyclic oxindoles with a Michael (triple Michael)/cyclization cascade
Jian Li1, Ning Wang, Chunju Li
1Department of Chemistry, Shanghai University, 99 Shangda Road, Shanghai, 200444, P.R. China. lijian@shu.edu.cn
Chemistry (Weinheim an Der Bergstrasse, Germany)
|July 21, 2012
Summary
This study introduces a catalyst-free multicomponent reaction for synthesizing complex spirocyclic and tricyclic oxindoles. The novel four-component cycloaddition in water offers an efficient strategy for creating highly unusual molecular architectures.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
Background:
- Multicomponent reactions (MCRs) are powerful tools for constructing complex molecules efficiently.
- Oxindole derivatives are prevalent in natural products and pharmaceuticals, making their synthesis a key area of research.
Purpose of the Study:
- To develop a novel, catalyst-free multicomponent cycloaddition strategy for synthesizing spirocyclic and tricyclic oxindoles.
- To explore the scope and limitations of the reaction with various allenoates and substituted starting materials.
Main Methods:
- Utilized readily available isocyanides, allenoates, and isatylidene malononitriles in a multicomponent reaction.
- Investigated a three-component cycloaddition and an extended four-component cycloaddition in the presence of water.
- Explored reactions with diverse α- and γ-substituted allenoates.
Main Results:
- Achieved efficient synthesis of spirocyclic oxindoles with excellent regioselectivity via a catalyst-free three-component reaction.
- Developed an unprecedented four-component cycloaddition yielding highly unusual tricyclic oxindoles.
- Observed unique C=C bond cleavage in reactions involving γ-substituted allenoates.
Conclusions:
- The developed protocol offers a highly efficient, one-step strategy for accessing complex oxindole scaffolds.
- The triple Michael/cyclization mechanism, utilizing allenoate as a three-carbon component, is proposed.
- This work expands the synthetic utility of multicomponent reactions for generating novel heterocyclic structures.
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