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Asymmetric Synthesis of β-Ketoamides by Sulfonium Rearrangement.
Vincent Porte1, Vinicius R Nascimento1, Ana Sirvent1
1Institute of Organic Chemistry, University of Vienna, Währinger Straße 38, 1090, Vienna, Austria.
Angewandte Chemie (International Ed. in English)
|October 23, 2024
Summary
This study introduces a novel method for synthesizing enantioenriched β-ketoamides using a chiral sulfinimine-mediated rearrangement, overcoming challenges in asymmetric synthesis of dicarbonyl compounds.
Area of Science:
- Organic Chemistry
- Asymmetric Synthesis
- Synthetic Methodology
Background:
- Enantioenriched α-substituted 1,3-dicarbonyl compounds are valuable synthetic intermediates.
- Their synthesis is challenging due to facile racemization via keto-enol tautomerization.
Purpose of the Study:
- To develop a robust method for accessing enantioenriched β-ketoamides.
- To address the challenge of racemization in 1,3-dicarbonyl synthesis.
Main Methods:
- Utilized a chiral sulfinimine-mediated [3,3]-sigmatropic sulfonium rearrangement.
- Employed diastereoselective reduction of the ketone moiety for further functionalization.
Main Results:
- Successfully synthesized enantioenriched β-ketoamides with good chirality transfer.
- Demonstrated excellent chemoselectivity and functional group tolerance.
- Achieved diastereoselective synthesis of enantioenriched β-hydroxyamides in one-pot.
Conclusions:
- The developed method provides a reliable route to enantioenriched β-ketoamides and β-hydroxyamides.
- The methodology overcomes the inherent instability of 1,3-dicarbonyl compounds towards racemization.
- Offers a valuable tool for asymmetric synthesis of complex organic molecules.
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