Late-Stage Molecular Editing Enabled by Ketone Chain-Walking Isomerization
Yannick Brägger1, Ori Green1, Benjamin N Bhawal1,2
1ETH Zürich, Vladimir-Prelog-Weg 3, HCI, 8093 Zürich, Switzerland.
Journal of the American Chemical Society
|August 28, 2023
Summary
Researchers developed a novel ketone isomerization method using inexpensive catalysts. This "chain-walking" reaction allows access to unique steroids with unnatural oxidation patterns.
Area of Science:
- Organic Chemistry
- Catalysis
- Stereochemistry
Background:
- Ketone isomerization is a fundamental organic transformation.
- Existing methods often lack efficiency or broad applicability.
- Mimicking alkene chain-walking offers a new synthetic strategy.
Purpose of the Study:
- To describe a novel method for ketone isomerization.
- To utilize inexpensive and readily available catalysts.
- To explore the stereochemical outcomes and applications in steroid synthesis.
Main Methods:
- Development of a catalytic system using pyrrolidine and elemental sulfur.
- Elucidation of a stereochemical model for predicting reaction products.
- Application of the method to the isomerization of various steroids.
Main Results:
- Successful demonstration of reversible ketone isomerization.
- Identification of thermodynamic and kinetic selectivity.
- Rapid synthesis of novel steroids with unnatural oxidation patterns.
Conclusions:
- The developed ketone chain-walking reaction is a versatile and efficient method.
- The stereochemical model aids in predicting and controlling product formation.
- This approach provides access to previously inaccessible steroid structures.
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