Nickel Catalyzed Carbonylative Cross Coupling for Direct Access to Isotopically Labeled Alkyl Aryl Ketones

Abstract Here we present an effective nickel‐catalyzed carbonylative cross‐coupling for direct access to alkyl aryl ketones from readily accessible redox‐activated tetrachlorophthalimide esters and aryl boronic acids. The methodology, which is run employing only 2.5 equivalents of CO and simple Ni(II) salts as the metal source, exhibits a broad substrate scope under mild conditions. Furthermore, this carbonylation chemistry provides an easy switch between isotopologues for stable ( 13 CO) and radioactive ( 14 CO) isotope labeling, allowing its adaptation to the late‐stage isotope labeling of pharmaceutically relevant compounds. Based on DFT calculations as well as experimental evidence, a catalytic cycle is proposed involving a carbon‐centered radical formed via nickel(I)‐induced outer‐sphere decarboxylative fragmentation of the redox‐active ester.

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Publication Details

Journal
Angewandte Chemie
Published
2024-08-15
DOI
https://doi.org/10.1002/ange.202412247
Citations
2
Primary Topic
Chemical Reactions and Isotopes
Type
article
Field-Weighted Citation Impact
0.42

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article

Nickel Catalyzed Carbonylative Cross Coupling for Direct Access to Isotopically Labeled Alkyl Aryl Ketones

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Nickel Catalyzed Carbonylative Cross Coupling for Direct Access to Isotopically Labeled Alkyl Aryl Ketones

Per‐Ola Norrby, Charles S. Elmore, Kathrin H. Hopmann, Troels Skrydstrup, Karoline T. Neumann, Sahil Gahlawat, Kim S. Mühlfenzl, Peter I. Golbækdal, Vitus J. Enemærke, Nikoline Munksgaard‐Ottosen
article en
2 citations

Abstract

Abstract Here we present an effective nickel‐catalyzed carbonylative cross‐coupling for direct access to alkyl aryl ketones from readily accessible redox‐activated tetrachlorophthalimide esters and aryl boronic acids. The methodology, which is run employing only 2.5 equivalents of CO and simple Ni(II) salts as the metal source, exhibits a broad substrate scope under mild conditions. Furthermore, this carbonylation chemistry provides an easy switch between isotopologues for stable ( 13 CO) and radioactive ( 14 CO) isotope labeling, allowing its adaptation to the late‐stage isotope labeling of pharmaceutically relevant compounds. Based on DFT calculations as well as experimental evidence, a catalytic cycle is proposed involving a carbon‐centered radical formed via nickel(I)‐induced outer‐sphere decarboxylative fragmentation of the redox‐active ester.

Angewandte ChemieVol. 136(51)
Aarhus University (DK), Chr. Hansen (Denmark) (DK), AstraZeneca (Australia) (AU), AstraZeneca (Sweden) (SE), UiT The Arctic University of Norway (NO)
European Commission, National Research Foundation, Danmarks Grundforskningsfond, Norges Forskningsråd, HORIZON EUROPE Marie Sklodowska-Curie Actions
Clean water and sanitation
Openalex Percentile: Top 43%
Chemical Reactions and Isotopes
0.42
DOIOpen Access PDFOpenAlex
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