Light-Driven Enantioselective Carbene-Catalyzed Radical-Radical Coupling

Seunghwan Byun; Meemie U Hwang; Henry R Wise; Anna V Bay; Paul H-Y Cheong; Karl A Scheidt

doi:10.1002/anie.202312829

Light-Driven Enantioselective Carbene-Catalyzed Radical-Radical Coupling

Angew Chem Int Ed Engl. 2023 Dec 4;62(49):e202312829. doi: 10.1002/anie.202312829. Epub 2023 Nov 6.

Authors

Seunghwan Byun¹, Meemie U Hwang¹, Henry R Wise², Anna V Bay¹, Paul H-Y Cheong², Karl A Scheidt¹

Affiliations

¹ Department of Chemistry, Northwestern University, Silverman Hall, Evanston, IL 60208, USA.
² Department of Chemistry, Oregon State University, 153 Gilbert Hall, Corvallis, OR 97331, USA.

Abstract

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.

Keywords: Asymmetric Catalysis; N-Heterocyclic Carbenes; Organocatalysis; Photoredox Catalysis; Radicals.

Abstract

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