Modern Strategies for Carbon Isotope Exchange

In contrast to stable and natural abundant carbon‐12, the synthesis of organic molecules with carbon (radio)isotopes must be conceived and optimized in order to navigate through the hurdles of radiochemical requirements, such as high costs of the starting materials, harsh conditions and radioactive waste generation. In addition, it must initiate from the small cohort of available C‐labeled building blocks. For long time, multi‐step approaches have represented the sole available patterns. On the other side, the development of chemical reactions based on the reversible cleavage of C−C bonds might offer new opportunities and reshape retrosynthetic analysis in radiosynthesis. This review aims to provide a short survey on the recently emerged carbon isotope exchange technologies that provide effective opportunity for late‐stage labeling. At present, such strategies have relied on the use of primary and easily accessible radiolabeled C1‐building blocks, such as carbon dioxide, carbon monoxide and cyanides, while the activation principles have been based on thermal, photocatalytic, metal‐catalyzed and biocatalytic processes. The field of carbon isotope labeling has recently explored new alternative avenues for better dealing with the hurdles of radiochemistry. This review focuses on the emerging opportunities provided by carbon isotope exchange (CIE) technologies. By dramatically reducing the number of steps and radioactive waste generated in preparation of tracers, CIE has great potential for accelerating clinical development of pharmaceuticals.