Electrophilic Cyanation with Carbon Isotopes: A Versatile Access to 13C, 14C, and 11C Aryl Nitriles from Labeled NCTS

In this work, we provide mild and direct access to carbon-labeled electrophilic cyanating agents suitable for both radioactive 14C and 11C. Carbon isotopes are at the foundation of applications in life science such as nuclear medicine and are essential for the determination of pharmacokinetic and dynamic profiles of new pharmaceuticals. While cyanations are key synthetic transformations in the arsenal of radiochemists, access to such precious building blocks still poses a severe challenge. Here, we report a two-step procedure that utilized 14CCO2 and 11CCO2 as primary isotope sources and takes place under exceptionally mild conditions compared to those of the state of the art. The utility of this procedure was demonstrated with the labeling of a panel of nitriles using traditional reactions as well as with unprecedented examples of carbon-isotope exchange.