Cyclopropenimine-Enabled Redox Control in Copper-Catalyzed Radical Cyclization to 3,3-Disubstituted Oxindoles

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Radical-mediated synthesis of all-carbon quaternary centers is valuable.
• Tertiary alkyl halides are challenging substrates for mild radical reactions.
• Existing methods often require complex redox orchestration.

Purpose of the Study:

• To develop a mild and efficient method for constructing quaternary carbon centers.
• To utilize cyclopropenimine-enabled copper catalysis for radical cyclization.
• To overcome challenges associated with tertiary alkyl halide reactivity.

Main Methods:

• Copper-catalyzed radical cyclization using a cyclopropenimine ligand.
• Synthesis of 3,3-disubstituted oxindoles.
• Mechanistic studies including radical trapping, EPR, KIE, CV, and DFT.

Main Results:

• Achieved good yields of diverse 3,3-disubstituted oxindoles with quaternary centers.
• Demonstrated efficient reactions with tertiary alkyl halides, including chlorides.
• Identified a balanced redox mechanism involving catalyst activation and regeneration.

Conclusions:

• The cyclopropenimine scaffold effectively modulates copper's redox properties.
• This approach enables efficient radical transformations of challenging alkyl electrophiles.
• Provides a foundation for developing new radical reactions involving difficult substrates.