Microwave-Assisted Palladium-Catalyzed Crossover-Annulation: Access to Fused Polycyclic Benzofuran Scaffolds

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Complex fused polycyclic frameworks are important structural motifs in medicinal chemistry and materials science.
• Efficient and regioselective synthetic routes to these structures are highly sought after.
• Palladium-catalyzed reactions have emerged as powerful tools for C-C and C-heteroatom bond formation.

Purpose of the Study:

• To develop a novel, efficient, and regioselective method for constructing heteroatom-embodied complex fused polycyclic frameworks.
• To utilize a palladium-catalyzed domino process involving microwave-assisted crossover annulation.
• To explore the synthesis of these frameworks from readily available starting materials.

Main Methods:

• A palladium-catalyzed domino process involving microwave-assisted crossover annulation.
• Reaction between ortho-alkynylarylhalides and dihydrobenzofuran derivatives.
• Careful design of dihydrobenzofuran precursors to ensure high regioselectivity.

Main Results:

• Successful synthesis of complex fused polycyclic frameworks.
• High regioselectivity achieved, yielding a single regioisomeric product.
• Excellent product yields demonstrated through a one-pot procedure.
• Good substrate scope observed for the developed method.

Conclusions:

• The developed palladium-catalyzed domino process provides rapid access to valuable heteroatom-embodied fused polycyclic frameworks.
• The regioselectivity is controlled by the judicious design of dihydrobenzofuran precursors.
• This one-pot, microwave-assisted method is efficient and offers broad applicability.