The vinylogous Catellani reaction: a combined computational and experimental study

Area of Science:

• Organic Chemistry
• Catalysis
• Medicinal Chemistry

Background:

• Palladium-catalyzed reactions are crucial for C-C bond formation.
• Developing efficient synthetic routes for heterocyclic compounds like quinolones is important.
• Benzopyran-fused heterocycles exhibit diverse biological activities.

Purpose of the Study:

• To develop a novel synthetic method for benzopyran-fused 2-quinolones.
• To investigate the reaction mechanism using experimental and computational approaches.

Main Methods:

• Palladium-catalyzed coupling reaction using palladium(II) acetate (Pd(OAc)2) as catalyst.
• Reaction of 4-iodo-2-quinolones with tertiary o-bromobenzylic alcohols in the presence of norbornene and potassium carbonate (K2CO3).
• Mechanistic studies including control experiments and density functional theory (DFT) calculations.

Main Results:

• Successful synthesis of benzopyran-fused 2-quinolones in moderate to high yields.
• Identification of norbornene as a key component in the catalytic cycle.
• Proposed a Catellani-type mechanism involving vinylic C-H cleavage.

Conclusions:

• A novel and efficient palladium-catalyzed cascade reaction for the synthesis of benzopyran-fused 2-quinolones has been established.
• The proposed mechanism provides insights into the reactivity of iodoquinolones and the role of norbornene.
• This methodology offers a valuable tool for accessing complex heterocyclic scaffolds with potential pharmaceutical applications.