Light-Driven Enantioselective Carbene-Catalyzed Radical-Radical Coupling

An enantioselective carbene-catalyzed radical-radical coupling of acyl imidazoles and racemic Hantzsch esters is disclosed. This method involves the coupling of an N-heterocyclic carbene-derived ketyl radical and a secondary sp3-carbon radical and allows access to chiral alpha-aryl aliphatic ketones in moderate-to-good yields and enantioselectivities without any competitive epimerization. The utility of this protocol is highlighted by the late-stage functionalization of various pharmaceutical compounds and is further demonstrated by the transformation of the enantioenriched products to biologically relevant molecules. Computational investigations reveal the N-heterocyclic carbene controls the double-facial selectivity of the ketyl radical and the alkyl radicals, respectively. An enantioselective radical-radical coupling using combined photoredox/N-heterocyclic carbene (NHC) catalysis was developed. The coupling of a ketyl radical and an sp3-carbon radical allows access to alpha-chiral ketones in moderate-to-good yields and enantioselectivities. Computational investigations reveal the N-heterocyclic carbene controls the double-facial selectivity of the ketyl radical and the alkyl radicals, respectively.image

Automated summary

This study explores the enantioselective carbene-catalyzed radical-radical coupling reaction of acyl imidazoles and racemic Hantzsch esters, leading to the synthesis of chiral alpha-aryl aliphatic ketones. The method shows potential application in pharmaceutical synthesis.