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Enantioselective Copper-Catalyzed Quinoline Alkynylation
Mukesh Pappoppula1, Flavio S P Cardoso1, B Owen Garrett1
1Department of Chemistry, Center for Heterocyclic Compounds, University of Florida, Gainesville, FL 32611 (USA).
Angewandte Chemie (International Ed. in English)
|October 31, 2015
Summary
A new copper-catalyzed reaction enables enantioselective alkynylation of quinolinium salts using a novel chiral ligand. This method efficiently synthesizes valuable tetrahydroquinoline alkaloids with high yields and enantioselectivity.
Area of Science:
- Organic Chemistry
- Catalysis
- Medicinal Chemistry
Background:
- Quinolinium salts are important heterocyclic compounds.
- Enantioselective synthesis is crucial for pharmaceutical development.
- Developing efficient catalytic methods for complex molecule synthesis remains a challenge.
Purpose of the Study:
- To develop a highly enantioselective copper-catalyzed alkynylation of quinolinium salts.
- To introduce a novel imidazole-based chiral biaryl phosphine-nitrogen (P,N) ligand, StackPhos.
- To demonstrate the utility of this method in synthesizing valuable alkaloids.
Main Methods:
- A three-component reaction involving a quinoline, a terminal alkyne, and ethyl chloroformate.
- Utilized copper bromide as the catalyst and StackPhos as the chiral ligand.
- Optimized reaction conditions for high yield and enantioselectivity.
Main Results:
- Achieved highly enantioselective copper-catalyzed alkynylation of quinolinium salts.
- Obtained products in high yields with enantiomeric excess (ee) values up to 98%.
- Demonstrated broad functional group tolerance for both alkyne and quinoline starting materials.
- Successfully synthesized enantioselective tetrahydroquinoline alkaloids: (+)-galipinine, (+)-angustureine, and (-)-cuspareine.
Conclusions:
- The reported method provides an efficient and enantioselective route to functionalized quinolinium derivatives.
- The developed catalytic system is versatile and applicable to the synthesis of complex natural products.
- The synthesized products serve as valuable synthons for further chemical transformations.
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