Modular access to substituted cyclohexanes with kinetic stereocontrol
Yangyang Li1, Yuqiang Li1, Hongjin Shi1
1The Institute for Advanced Studies, Wuhan University, Wuhan 430072, China.
Science (New York, N.Y.)
|May 13, 2022
Summary
Synthesizing specific stereoisomers of disubstituted cyclohexanes is challenging. This study introduces a novel chain-walking catalysis method for modular synthesis of these compounds with precise stereochemical control.
Area of Science:
- Organic Chemistry
- Catalysis
- Stereoselective Synthesis
Background:
- Six-membered cyclic hydrocarbons are crucial in biologically active molecules.
- Existing methods for synthesizing thermodynamically favored disubstituted cyclohexanes are established, but stereoisomer synthesis remains difficult.
Purpose of the Study:
- To develop a general, modular strategy for synthesizing disubstituted cyclohexanes with excellent kinetic stereocontrol.
- To overcome limitations in current stereoselective synthesis of cyclohexane derivatives.
Main Methods:
- Utilized chain-walking catalysis on substituted methylenecyclohexanes.
- Employed a sterically demanding boron ester group to direct stereochemical outcome.
- Demonstrated late-stage modification of complex bioactive molecules.
Main Results:
- Achieved a general and modular synthesis of disubstituted cyclohexanes.
- Exhibited excellent kinetic stereocontrol in the synthesis.
- Showcased the methodology's utility in complex molecule synthesis and comparison to cross-coupling.
Conclusions:
- The developed chain-walking catalysis offers a reliable and modular approach for stereoselective synthesis of disubstituted cyclohexanes.
- This method provides a valuable tool for accessing challenging stereoisomers, impacting drug discovery and development.
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