A C-H Functionalization Strategy Enables an Enantioselective Formal Synthesis of (-)-Aflatoxin B2
Nicholas A Falcone1, Aaron T Bosse2, Hojoon Park3
1Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States.
Organic Letters
|December 6, 2021
Summary
Researchers achieved an enantioselective synthesis of (-)-aflatoxin B2 using novel C-H functionalization methods. This approach efficiently creates key bonds and stereocenters under mild conditions, preserving sensitive configurations.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Natural Product Synthesis
Background:
- Aflatoxins are toxic secondary metabolites with complex structures.
- Efficient and stereoselective synthesis of natural products like aflatoxins remains a significant challenge.
- Developing novel C-H functionalization strategies is crucial for streamlining complex molecule synthesis.
Purpose of the Study:
- To develop an enantioselective formal synthesis of (-)-aflatoxin B2.
- To demonstrate the utility of site-selective C-H functionalization in natural product synthesis.
- To establish a novel method for forming arene carbon-oxygen bonds via carbonyl-directed acetoxylation.
Main Methods:
- Utilized three site-selective C-H functionalizations starting from 4-methoxyphenylacetic acid.
- Employed carbonyl-directed acetoxylation for two arene C-H bonds.
- Ensured mild reaction conditions to preserve a sensitive benzylic stereocenter.
Main Results:
- Successfully achieved an enantioselective formal synthesis of (-)-aflatoxin B2.
- Generated a key carbon-carbon bond and a benzylic stereocenter.
- Formed two arene carbon-oxygen bonds through unprecedented site-selective C-H functionalization.
Conclusions:
- The developed approach offers an efficient route to (-)-aflatoxin B2.
- The carbonyl-directed acetoxylation is a novel and valuable transformation for natural product synthesis.
- Mild conditions and site-selectivity highlight the power of modern C-H functionalization strategies.
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