Direct Carbon Isotope Exchange through Decarboxylative Carboxylation

J Am Chem Soc. 2019 Jan 16;141(2):774-779. doi: 10.1021/jacs.8b12035. Epub 2019 Jan 3.


A two-step degradation-reconstruction approach to the carbon-14 radiolabeling of alkyl carboxylic acids is presented. Simple activation via redox-active ester formation was followed by nickel-mediated decarboxylative carboxylation to afford a range of complex compounds with ample isotopic incorporations for drug metabolism and pharmacokinetic studies. The practicality and operational simplicity of the protocol were demonstrated by its use in an industrial carbon-14 radiolabeling setting.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Carbon Isotopes / chemistry
  • Carbon Radioisotopes / chemistry
  • Carboxylic Acids / chemical synthesis
  • Carboxylic Acids / chemistry*
  • Catalysis
  • Decarboxylation
  • Isotope Labeling / methods
  • Nickel / chemistry
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / chemistry*


  • Carbon Isotopes
  • Carbon Radioisotopes
  • Carboxylic Acids
  • Radiopharmaceuticals
  • Nickel
  • Carbon-14
  • Carbon-13