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Chiral Vicinal Diamines Derived from Mefloquine.
Dawid J Kucharski1, Rafał Kowalczyk2, Przemysław J Boratyński1
1Department of Organic and Medicinal Chemistry, Wrocław University of Technology, Wyb. Wyspiańskiego 26, Wrocław 50370 Poland.
The Journal of Organic Chemistry
|July 27, 2021
Summary
Novel diamines derived from mefloquine were synthesized in pure forms. The erythro-11-aminomefloquine catalyst demonstrated high selectivity in asymmetric Michael addition reactions, outperforming existing catalysts.
Area of Science:
- Organic Chemistry
- Asymmetric Catalysis
- Medicinal Chemistry
Background:
- Cinchona alkaloids are vital chiral catalysts in asymmetric synthesis.
- Mefloquine, an antimalarial drug, offers a unique scaffold for developing novel catalysts.
- Developing new chiral catalysts is crucial for efficient enantioselective transformations.
Purpose of the Study:
- To synthesize novel 1,2-diamines based on the mefloquine scaffold in enantiomerically pure forms.
- To evaluate the catalytic efficacy of these novel diamines in asymmetric transformations.
- To compare the performance of the synthesized catalysts with existing ones, such as epi-aminoquinine.
Main Methods:
- Synthesis of novel 1,2-diamines via conversion of alcohol to azide followed by hydrogenation.
- Alkylation of amine functionalities to introduce structural diversity and diastereomers.
- Stereochemical analysis and resolution techniques to obtain enantiomerically pure products.
- Application of synthesized diamines as catalysts in asymmetric Michael addition reactions.
Main Results:
- Successful preparation of enantiomerically pure 1,2-diamines based on the mefloquine scaffold.
- Identification of erythro-11-aminomefloquine as a highly effective catalyst.
- Achieved up to 96.5:3.5 enantiomeric ratio (er) in the asymmetric Michael addition of nitromethane to cyclohexanone.
- Demonstrated superior selectivity of erythro-11-aminomefloquine compared to epi-aminoquinine.
Conclusions:
- Novel chiral 1,2-diamines derived from mefloquine can be synthesized effectively.
- Erythro-11-aminomefloquine is a potent and selective organocatalyst for asymmetric Michael additions.
- This scaffold holds promise for the development of new chiral catalysts in organic synthesis.
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