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Iridium/Silver-Catalyzed H/D Exchange for Perdeuteration of Indoles and Site-Selective Deuteration of Carbazoles: Application in Late-Stage Functionalization
Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.ORCID iD: 0000-0001-7683-2928
Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.ORCID iD: 0000-0003-0774-2528
Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.ORCID iD: 0000-0002-2042-4818
Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Linnaeus University, Sweden.ORCID iD: 0000-0002-0407-6542
2025 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 90, no 33, p. 11791-11801Article in journal (Refereed) Published
Abstract [en]

A novel iridium/silver-based method for catalyzing C-H deuterium labeling of indoles and carbazoles using D2O is presented. The method leverages a carbonyl-based directing group to achieve isotopic incorporation. This method demonstrates broad substrate scope and excellent functional group tolerance, enabling diverse and precise labeling of biologically important heterocycles. Notably, the developed protocol is successfully applied to the late-stage functionalization of carvedilol, showcasing its potential for modifying complex molecules. The operational simplicity, mild conditions, commercially available [Cp*IrCl2]2 as catalyst, D2O as the easily available cheap deuterium source, and high isotopic enrichment make this approach a valuable tool for the synthesis of deuterium-labeled compounds in pharmaceutical and mechanistic studies.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2025. Vol. 90, no 33, p. 11791-11801
Keywords [en]
Aromatic compounds, Catalysts, Hydrogen isotopes, Indoles Reactivity
National Category
Organic Chemistry
Research subject
Chemistry, Organic Chemistry
Identifiers
URN: urn:nbn:se:lnu:diva-140896DOI: 10.1021/acs.joc.5c00702ISI: 001526029800001PubMedID: 40638264Scopus ID: 2-s2.0-105010210236OAI: oai:DiVA.org:lnu-140896DiVA, id: diva2:1985878
Available from: 2025-07-28 Created: 2025-07-28 Last updated: 2025-09-19Bibliographically approved

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Dhillon, PrakritiKathiravan, SuppanWiklander, Jesper G.Nicholls, Ian A.

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