Light-Driven Enantioselective Carbene-Catalyzed Radical-Radical Coupling

Area of Science:

• Organic Chemistry
• Catalysis
• Asymmetric Synthesis

Background:

• Radical-radical coupling reactions are crucial for C-C bond formation.
• Developing enantioselective methods for sp3-sp3 coupling remains challenging.

Purpose of the Study:

• To disclose an enantioselective carbene-catalyzed radical-radical coupling of acyl imidazoles and racemic Hantzsch esters.
• To provide access to chiral α-aryl aliphatic ketones.

Main Methods:

• Utilized N-heterocyclic carbene catalysis for radical generation.
• Coupled N-heterocyclic carbene-derived ketyl radicals with secondary sp3-carbon radicals.
• Employed racemic Hantzsch esters as radical precursors.

Main Results:

• Achieved moderate-to-good yields and enantioselectivities for chiral α-aryl aliphatic ketones.
• Demonstrated the absence of competitive epimerization.
• Showcased late-stage functionalization of pharmaceutical compounds.

Conclusions:

• The developed protocol offers an efficient route to enantioenriched α-aryl aliphatic ketones.
• Computational studies elucidated the N-heterocyclic carbene's role in controlling stereoselectivity.
• The method is applicable to synthesizing biologically relevant molecules.