Palladium-Catalyzed Cascade to Benzoxepins by Using Vinyl-Substituted Donor-Acceptor Cyclopropanes

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Palladium-catalyzed reactions are crucial in organic synthesis.
• Benzoxepins are important heterocyclic compounds with various applications.
• Developing efficient and enantioselective synthetic routes remains a key challenge.

Purpose of the Study:

• To report a novel palladium-catalyzed intermolecular cascade (4+3) cyclocondensation reaction.
• To synthesize substituted benzoxepins using salicylaldehydes and vinylcyclopropanes.
• To explore the use of a phosphonate group as an acceptor moiety and achieve enantioselective synthesis.

Main Methods:

• Employing a palladium catalyst for intermolecular cascade cyclocondensation.
• Utilizing salicylaldehydes and vinylcyclopropanes bearing a phosphonate group.
• Implementing a novel chiral ligand to control enantioselectivity.
• Performing subsequent O-allylation for benzoxepin formation.

Main Results:

• Successful synthesis of a range of substituted benzoxepins.
• The phosphonate group facilitated olefination with aldehydes.
• Good yields were generally obtained for the target products.
• Reasonable enantioselectivity was achieved with the chiral ligand.

Conclusions:

• A novel and efficient palladium-catalyzed cascade reaction for benzoxepin synthesis has been established.
• The developed methodology offers a valuable route to substituted benzoxepins.
• The use of a chiral ligand enables enantioselective access to these important heterocyclic compounds.