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Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
Cascade condensation, cyclization, intermolecular dipolar cycloaddition by multi-component coupling and application
Iain Coldham1, Samaresh Jana, Luke Watson
1Department of Chemistry, University of Sheffield, Brook Hill, Sheffield, U KS3 7HF. i.coldham@sheffield.ac.uk
Organic & Biomolecular Chemistry
|April 4, 2009
Summary
This study introduces a versatile method for synthesizing nitrogen-containing heterocycles via cycloaddition reactions. The approach efficiently creates complex polycyclic amines, including a synthesis of the alkaloid (+/-)-crispine A.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Heterocyclic Chemistry
Background:
- Nitrogen-containing heterocyclic compounds are crucial in pharmaceuticals and natural products.
- Efficient synthetic routes to complex heterocycles are highly sought after.
- Azomethine ylides and nitrones are versatile 1,3-dipoles for cycloaddition reactions.
Purpose of the Study:
- To develop a general and efficient synthetic strategy for nitrogen-containing heterocyclic compounds.
- To explore the utility of intermolecular dipolar cycloaddition reactions involving azomethine ylides and nitrones.
- To demonstrate the application of this methodology in the synthesis of a natural product.
Main Methods:
- Generation of azomethine ylide dipoles or nitrones from halo-aldehydes and amino-acid/ester or hydroxylamine derivatives.
- Condensation to form imines, followed by cyclization and decarboxylation or deprotonation.
- Intermolecular 1,3-dipolar cycloaddition with activated dipolarophiles.
Main Results:
- Successful synthesis of various bicyclic and polycyclic amines.
- Demonstrated the formation of complex amine structures through a tandem/domino 3-component coupling.
- Achieved a concise synthesis of the alkaloid (+/-)-crispine A.
Conclusions:
- The described intermolecular dipolar cycloaddition provides a general and powerful approach for synthesizing diverse nitrogen-containing heterocycles.
- This method offers an efficient route to complex polycyclic amine scaffolds.
- The strategy is applicable to the total synthesis of natural products.
![Solid-phase Synthesis of [4.4] Spirocyclic Oximes](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F58508.jpg&w=3840&q=50)
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