Carbon isotopic labelling of carboxylic acids enabled by organic photoredox-catalysed cyanation

The application of molecular imaging has advanced personalized medicine and generated a profound impact on patient care. Positron emission tomography and magnetic resonance imaging are among the most widely used imaging modalities, often requiring the isotopic labelling of bioactive molecules to generate the desired imaging probes. Unfortunately, radiochemistry often limits the development of novel agents due to complicated syntheses and the incompatibility of complex molecules. Here, considering the prevalence of carboxylic acids in drug and bioactive molecules, we have developed a method to perform 11/13C labelling through carboxylic acid groups via organic photoredox reactions to generate radiolabelled nitriles. We applied this strategy to a range of aliphatic carboxylic acids, including complex and functionalized drug molecules, amino acids and short peptides. Notably, when benzylic and alkyl carboxylic acids were used as substrates, a copper co-catalyst was required to obtain the labelled nitriles, whereas when α-amino acids and peptides were used as substrates, a copper co-catalyst was not required to form labelled α-amino nitriles. The radiolabelled nitrile products could be easily converted back to radiolabelled carboxylic acids with high radiochemical yields and molar activities. Positron emission tomography and magnetic resonance imaging are two powerful imaging modalities that require the installation of isotopes in biologically relevant molecules. Now an organic photoredox-catalysed method for the conversion of a range of carboxylic acids to their 11C and 13C isotopomers via decarboxylative cyanation is reported.