Macrolactam Synthesis via Ring-Closing Alkene-Alkene Cross-Coupling Reactions
Manikantha Maraswami1, Jeffrey Goh1, Teck-Peng Loh2,3,1
1Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371.
Organic Letters
|December 1, 2020
Summary
A new Rh(III)-catalyzed reaction enables practical macrolactam synthesis. This method utilizes ring closing alkene-alkene cross-coupling and C-H activation for diverse macrocyclic compounds.
Area of Science:
- Organic Chemistry
- Catalysis
- Synthetic Methodology
Background:
- Macrolactams are important structural motifs in natural products and pharmaceuticals.
- Efficient synthetic routes to macrolactams, especially those with specific stereochemistries, remain a challenge.
Purpose of the Study:
- To develop a practical and efficient method for macrolactam synthesis.
- To explore the utility of Rh(III)-catalyzed reactions in constructing macrocyclic frameworks.
Main Methods:
- A Rh(III)-catalyzed ring closing alkene-alkene cross-coupling reaction was employed.
- The reaction proceeds via an alkenyl sp2 C-H activation pathway.
- This approach allows for the synthesis of macrolactams with varying ring sizes.
Main Results:
- The developed method provides access to macrolactams containing a conjugated diene framework.
- The synthesis achieved high chemoselectivities.
- Excellent Z,E stereoselectivities were observed in the formation of the macrolactams.
Conclusions:
- The Rh(III)-catalyzed reaction offers a practical and versatile route for macrolactam synthesis.
- This methodology facilitates the construction of complex macrocyclic molecules with defined stereochemistry.
- The approach is valuable for accessing conjugated diene-containing macrolactams.
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