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Light-Driven Enantioselective Carbene-Catalyzed Radical-Radical Coupling.

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.

SUBMITTER: Byun S

PROVIDER: S-EPMC10841513 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Light-Driven Enantioselective Carbene-Catalyzed Radical-Radical Coupling.

Byun Seunghwan S Hwang Meemie U MU Wise Henry R HR Bay Anna V AV Cheong Paul H-Y PH Scheidt Karl A KA

Angewandte Chemie (International ed. in English) 20231106 49

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 sp<sup>3</sup> -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 pharmaceu ...[more]

PMID: 37845183

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