Copper-Catalyzed Radical Relay for Asymmetric Radical Transformations.

Area of Science:

• Organic Chemistry
• Catalysis
• Asymmetric Synthesis

Background:

• Direct C-H bond functionalization is atom- and step-economical but asymmetric variants, especially sp3 C-H oxidations, remain underdeveloped.
• Enzyme-inspired non-enzymatic systems for enantioselective sp3 C-H oxidation face challenges due to reactive radical intermediates.

Purpose of the Study:

• To develop enantioselective methods for functionalizing sp3 C-H bonds using a chiral bisoxazoline (Box)/copper catalytic system.
• To explore asymmetric radical transformations, including oxidations, difunctionalizations, and hydrogen atom abstraction (HAA) pathways.

Main Methods:

• Utilized a chiral bisoxazoline (Box)/Cu catalytic system for enantioselective induction of prochiral benzylic radicals.
• Investigated copper-catalyzed intermolecular alkene difunctionalizations (e.g., trifluoromethylation, cyanation, arylation).
• Employed hydrogen atom abstraction (HAA) with bisbenzenesulfonimidyl radical for direct benzylic C-H functionalization.

Main Results:

• Demonstrated enantioselective cyanations and arylations of benzylic radicals using chiral Box/Cu(I) catalysts.
• Achieved successful asymmetric difunctionalizations of styrenes and enantioselective decarboxylative cyanations.
• Developed enantioselective benzylic C-H cyanation via copper-catalyzed radical relay and regioselective arylation.

Conclusions:

• The chiral Box/Cu system effectively controls enantioselectivity in radical-based C-H functionalization.
• Developed methods allow late-stage functionalization of sp3 C-H bonds in complex molecules.
• The study provides valuable tools for asymmetric synthesis and late-stage modification of pharmaceuticals and natural products.