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An Organocatalytic Oxy-Cope/Michael Cascade Reaction.
Ryan R G Barrett1, Donald A Campbell1, James L Gleason1
1Department of Chemistry, McGill University, 801 Sherbrooke West, Montreal, QC H3A 0B8, Canada.
Organic Letters
|January 26, 2023
Summary
Ethyl diazepane carboxylate enables a novel cascade reaction, transforming hexadienes into cyclopentane structures through oxy-Cope rearrangement and Michael addition. This organocatalytic method offers a new pathway for complex molecule synthesis.
Area of Science:
- Organic Chemistry
- Catalysis
- Synthetic Methodology
Background:
- The oxy-Cope rearrangement is a powerful tool for carbon skeleton construction.
- Organocatalysis offers sustainable and efficient alternatives to traditional metal catalysis.
- Developing cascade reactions that build molecular complexity in a single step is a key goal in synthetic chemistry.
Purpose of the Study:
- To develop a novel organocatalytic oxy-Cope rearrangement.
- To investigate the use of ethyl diazepane carboxylate in a cascade reaction.
- To synthesize cyclopentane-containing compounds from hexadiene precursors.
Main Methods:
- Catalysis of the oxy-Cope rearrangement using ethyl diazepane carboxylate.
- Activation of substrates via iminium ion formation.
- Intramolecular Michael reaction to form cyclopentane rings.
- Application to a range of cyclic and acyclic substrates.
Main Results:
- Successful catalysis of the oxy-Cope rearrangement and subsequent Michael reaction.
- Formation of cyclopentane-containing products from diverse hexadiene precursors.
- High stereocontrol observed in ring expansion/cyclopentannulation of fused substrates.
- Demonstration of tolerance to vinyl substituent variations.
Conclusions:
- Ethyl diazepane carboxylate effectively catalyzes a cascade oxy-Cope rearrangement/Michael addition.
- This methodology provides a novel route to complex cyclopentane structures.
- The reaction expands the scope of iminium organocatalysis to cascade transformations.
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