Direct Carbon Isotope Exchange of Pharmaceuticals via Reversible Decyanation

The incorporation of carbon-14 allows tracking of organic molecules and provides vital knowledge on their fate. This information is critical in pharmaceutical development, crop science and human food safety evaluation. Herein, a transition-metal-catalyzed procedure enabling carbon isotope exchange on aromatic nitriles is described. Utilizing the radiolabeled precursor Zn([¹⁴C]CN)₂, this protocol allows the insertion of the desired carbon tag without need of structural modifications, in a single step. Reducing synthetic costs and limiting the generation of radioactive waste, this procedure will facilitate the labeling of nitrile containing drugs and accelerate ¹⁴C-based ADME studies supporting drug development.