4.8 Review

Modern Strategies for Carbon Isotope Exchange

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WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202303535

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Carbon Dioxide; Carbon Isotope Exchange; Carbon Isotopes; Cyanide; Isotope Labeling

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In contrast to stable and natural abundant carbon-12, the synthesis of organic molecules with carbon (radio) isotopes requires careful planning and optimization due to the challenges of radiochemical requirements. Recently, carbon isotope exchange technologies have emerged as effective methods for late-stage labeling, utilizing primary radiolabeled building blocks and various activation processes. This review provides a brief overview of these technologies and their potential impact on radiosynthesis.
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.

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