Ruthenium(II)-Catalyzed Hydrogen Isotope Exchange of Pharmaceutical Drugs by C-H Deuteration and C-H Tritiation

Well-defined ruthenium(II) biscarboxylate complexes enabled selective ortho-deuteration with weakly-coordinating, synthetically useful carboxylic acid with outstanding levels of isotopic labeling. The robust nature of the catalytic system was reflected by a broad functional group tolerance in an operationally-simple manner, allowing the isotope labeling of challenging pharmaceuticals and bioactive heterocyclic motifs. The synthetic power of our method was highlighted by the selective tritium-labeling of repaglinide, an antidiabetic drug, providing access to defined tritium labeled therapeutics.