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Electrochemical Azo-free Mitsunobu-type Reaction
Quanping Guo1, Yangye Jiang1, Rongjin Zhu1
1Key Laboratory of Precise Synthesis of Functional Molecules of Zhejiang Province, Department of Chemistry, School of Science and Research Center for Industries of the Future, Westlake University, 600 Dunyu Road, Hangzhou, 310030, Zhejiang Province, China.
Angewandte Chemie (International Ed. in English)
|March 11, 2024
Summary
An innovative electrochemical Mitsunobu reaction avoids excess reagents and by-products. This user-friendly method enables broad substrate scope for synthesizing complex molecules, including pharmaceuticals.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Electrochemistry
Background:
- The traditional Mitsunobu reaction requires excess reagents and produces substantial by-products.
- Existing catalytic methods for Mitsunobu-type reactions have limited substrate scope.
Purpose of the Study:
- To develop an improved Mitsunobu-type reaction using electrochemistry.
- To broaden the substrate scope and improve the efficiency of the Mitsunobu reaction.
Main Methods:
- An electrochemical approach for Mitsunobu-type alcohol activation was employed.
- The reaction utilized azo-free alcohol activation and a wide range of nucleophiles, including heterocycles.
- Coupling reactions were performed with various chiral cyclic and acyclic alcohols.
Main Results:
- The electrochemical method demonstrated broad substrate scope and high yields with excellent enantioselectivity (ee).
- The reaction is scalable, chemoselective, and operates under mild conditions (air and moisture tolerant).
- It uses a simple Electrasyn setup with inexpensive electrodes.
Conclusions:
- This electrochemical Mitsunobu-type reaction offers a practical, efficient, and versatile alternative to traditional methods.
- The technology is suitable for modifying bioactive natural products and pharmaceutical derivatives.
- It shows potential for application in multi-step synthesis of drug candidates.
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