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 α‐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 α‐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.