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Published on: May 26, 2019
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Organopromoted Selectivity-Switchable Synthesis of Polyketones
Jie Liu1, Kang-Fei Hu1, Jian-Ping Qu2
1Department of Chemistry, University of Science and Technology of China , Hefei, Anhui 230026, China.
Organic Letters
|October 6, 2017
Summary
A novel metal-free benzylic oxidation method enables selective oxygenation of heterocycles using oxygen. This approach avoids toxic residues and facilitates gram-scale synthesis of pharmaceuticals like Lenperone.
Area of Science:
- Organic Chemistry
- Catalysis
- Medicinal Chemistry
Background:
- Benzylic oxidation is crucial for synthesizing pharmaceutical compounds.
- Traditional methods often rely on transition metals, posing environmental and safety concerns.
- Metal-catalyzed oxidations can be hindered by substrate chelation, limiting their scope.
Purpose of the Study:
- To develop a metal-free organopromoted benzylic oxidation.
- To achieve selectivity-switchable mono-, di-, and trioxygenation.
- To enable efficient synthesis of enantiopure chiral ketones and pharmaceutical intermediates.
Main Methods:
- Utilized an organocatalyst to promote benzylic oxidation.
- Employed molecular oxygen as the sole oxidant under mild reaction conditions.
- Investigated the oxidation of various heterocyclic compounds, focusing on 2,6-benzylic positions.
Main Results:
- Successfully achieved selective mono-, di-, and trioxygenation of benzylic positions.
- Demonstrated the ability to synthesize enantiopure chiral ketones.
- Developed a process that avoids transition metals and hazardous byproducts.
Conclusions:
- The developed organopromoted oxidation offers a sustainable and efficient alternative to metal-catalyzed methods.
- This metal-free approach overcomes limitations associated with metal chelation in heterocyclic oxidation.
- The method is suitable for late-stage gram-scale synthesis, exemplified by the production of Lenperone.
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