Palladium-Catalyzed Multicomponent Carbonylative Cyclization toward Ynone-Functionalized Isoquinolinones.

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Isoquinolinones are crucial scaffolds in medicinal chemistry.
• Traditional synthesis methods often require harsh conditions or toxic reagents.
• Developing efficient and safe synthetic routes is paramount.

Purpose of the Study:

• To develop a novel palladium-catalyzed carbonylative synthesis of alkynone-substituted isoquinolinones.
• To utilize chloroform as a safe and convenient carbon monoxide (CO) surrogate.
• To establish a CO-free protocol for accessing bioactive isoquinoline derivatives.

Main Methods:

• Palladium-catalyzed coupling reaction.
• Base-mediated hydrolysis of chloroform (CHCl₃) for in situ CO generation.
• Reaction of 2-iodobenzamides with terminal alkynes.

Main Results:

• Successful synthesis of alkynone-substituted isoquinolinones.
• Demonstrated broad substrate scope and excellent functional group tolerance.
• Achieved scalability of the protocol.

Conclusions:

• The developed method offers an efficient and safe route to alkynone-substituted isoquinolinones.
• This protocol provides direct access to potentially bioactive isoquinoline scaffolds.
• The use of chloroform as a CO surrogate simplifies the synthetic procedure.