biostudies-literature00520Lee JWDivision of ChemistryDivision of Advanced CyberinfrastructureNational Institute of General Medical SciencesNIGMS NIH HHS21475-21480https://www.ebi.ac.uk/biostudies/studies/S-EPMC7720849biostudies-literatureUnknown59(48)Applications of TEMPO^. catalysis for the development of redox-neutral transformations are rare. Reported here is the first TEMPO^. -catalyzed, redox-neutral C-H di- and trifluoromethoxylation of (hetero)arenes. The reaction exhibits a broad substrate scope, has high functional-group tolerance, and can be employed for the late-stage functionalization of complex druglike molecules. Kinetic measurements, isolation and resubjection of catalytic intermediates, UV/Vis studies, and DFT calculations support the proposed oxidative TEMPO^. /TEMPO⁺ redox catalytic cycle. Mechanistic studies also suggest that Li₂ CO₃ plays an important role in preventing catalyst deactivation. These findings will provide new insights into the design and development of novel reactions through redox-neutral TEMPO^. catalysis.Angewandte Chemie (International ed. in English)Redox-Neutral TEMPO Catalysis: Direct Radical (Hetero)Aryl C-H Di- and Trifluoromethoxylation.PMC7720849CHE-1654122CHE-1827902R35 GM119652ACI-1053575R35GM119652Lim SLiu PMaienshein DNNgai MYLee JW52falseRedox-Neutral TEMPO Catalysis: Direct Radical (Hetero)Aryl C-H Di- and Trifluoromethoxylation.Applications of TEMPO^. catalysis for the development of redox-neutral transformations are rare. Reported here is the first TEMPO^. -catalyzed, redox-neutral C-H di- and trifluoromethoxylation of (hetero)arenes. The reaction exhibits a broad substrate scope, has high functional-group tolerance, and can be employed for the late-stage functionalization of complex druglike molecules. Kinetic measurements, isolation and resubjection of catalytic intermediates, UV/Vis studies, and DFT calculations support the proposed oxidative TEMPO^. /TEMPO⁺ redox catalytic cycle. Mechanistic studies also suggest that Li₂ CO₃ plays an important role in preventing catalyst deactivation. These findings will provide new insights into the design and development of novel reactions through redox-neutral TEMPO^. catalysis.2020-01-01T00:00:00Z2020 Nov2024-11-08T20:45:14.594Z2022-02-11T13:05:58.61ZS-EPMC77208493283043010.1002/anie.202009490