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Cercosporin-Photocatalyzed [4+1]- and [4+2]-Annulations of Azoalkenes Under Mild Conditions
Published on: July 17, 2020
Synthesis of optically active 4-substituted 2-cyclohexenones.
Tania I Houjeiry1, Sarah L Poe, D Tyler McQuade
1Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida 32306, USA.
Organic Letters
|August 21, 2012
Summary
Researchers found that a common chemical reaction for synthesizing optically active cyclohexenones loses its effectiveness with unbranched molecules. New organocatalyzed methods were developed to maintain optical purity in these cases.
Area of Science:
- Organic Chemistry
- Asymmetric Synthesis
Background:
- Nicolaou and Baran developed an efficient LiOH-mediated intramolecular aldol condensation for synthesizing optically active 4-substituted 2-cyclohexenones.
- The application of this cyclization method has been restricted to ketoaldehydes with branched R-groups.
Purpose of the Study:
- To investigate the limitations of the LiOH-mediated cyclization for substrates with unbranched R-groups.
- To develop alternative conditions that preserve optical purity during the cyclization of unbranched substrates.
Main Methods:
- Investigated the LiOH-mediated intramolecular aldol condensation using ketoaldehyde substrates with unbranched R-groups.
- Performed mechanistic studies to understand the loss of optical purity.
- Developed and tested neutral, organocatalyzed conditions for the cyclization.
Main Results:
- The LiOH-mediated cyclization of substrates with unbranched R-groups led to significant erosion of optical purity.
- A mechanistic explanation for the observed optical purity loss was established.
- Neutral, organocatalyzed conditions were identified that allow cyclization with minimal loss of optical purity.
Conclusions:
- The LiOH-mediated aldol condensation is not suitable for synthesizing optically active 4-substituted 2-cyclohexenones with unbranched R-groups.
- Neutral organocatalysis offers a viable alternative for achieving high optical purity in these challenging substrates.
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