Quinazolinone-to-Isoquinoline Metamorphosis by Ruthenium-Catalyzed [4+2] Annulation with Sulfoxonium Ylides

Area of Science:

• Organic Chemistry
• Catalysis
• Medicinal Chemistry

Background:

• Quinazolinones are versatile scaffolds in medicinal chemistry.
• Efficient synthesis of substituted isoquinolines is crucial for drug development.
• Existing methods for isoquinoline synthesis often lack broad applicability or functional group tolerance.

Purpose of the Study:

• To develop a novel catalytic method for the direct conversion of quinazolinones to aminoisoquinolines.
• To explore the scope and limitations of this new transformation.
• To demonstrate the utility of the developed method in accessing pharmaceutically relevant heterocycles.

Main Methods:

• Ruthenium-catalyzed [4+2] annulation reaction.
• Utilized sulfoxonium ylides as reaction partners.
• Employed various 2-arylquinazolinones and sulfoxonium ylides.
• Investigated directed C-H acetylation, nucleophilic cyclization, and alcoholysis.

Main Results:

• Achieved efficient molecular editing of quinazolinones to multisubstituted aminoisoquinolines.
• Demonstrated broad functional group tolerance with excellent yields.
• Showcased novel programmability of the catalytic system.
• Confirmed compatibility with green chemistry principles using ethanol as a solvent.

Conclusions:

• Developed a novel and efficient ruthenium-catalyzed protocol for synthesizing aminoisoquinolines from quinazolinones.
• The method provides precise and rapid access to complex heterocyclic structures.
• This transformation holds significant potential for applications in organic synthesis and pharmaceutical development.