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

Kim S Mühlfenzl, Vitus J Enemærke, Sahil Gahlawat, Peter I Golbækdal, Nikoline Munksgaard-Ottosen, Karoline T Neumann, Kathrin H Hopmann, Per-Ola Norrby, Charles S Elmore, Troels Skrydstrup*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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 (13CO) and radioactive (14CO) 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.

Original languageEnglish
Article numbere202412247
JournalAngewandte Chemie International Edition
Volume63
Issue51
Number of pages9
ISSN1433-7851
DOIs
Publication statusPublished - 16 Dec 2024

Keywords

  • Carbon isotope labeling
  • Carbonylation
  • Catalysis
  • Ketones
  • Nickel

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