[18F]Fluorine‐Labeled Pharmaceuticals: Direct Aromatic Fluorination Compared to Multi‐Step Strategies

Positron emission tomography (PET) presents an important tool for medicinal and pharmaceutical investigations, with applications ranging from fundamental research to the diagnosis of a broad variety of diseases. Crucial for the use of this technique is, however, a robust labeling strategy for the preparation of the required radiolabeled compound. For 18‐fluorine‐labeling, which represents the most widely applied method in this field, it is interesting to note that a kind of paradigm change occurred over the last years. While multi‐step labeling strategies were the preferred approach for many decades, mainly due to the lack of suitable leaving groups for direct [18F]fluorination reactions, the synthetic tools to achieve the highly attractive direct 18‐fluorine‐labeling rapidly increased recently. This focus review points out a comparison between the multi‐step approaches and the newly developed direct fluorination strategies available for nucleophilic 18‐fluorination of carbocyclic aromatic systems, including a discussion of advantages and limitations. Positron emission tomography (PET) represents an attractive tool for medicinal and pharmaceutical investigations at which 18‐fluorine‐labeling is the most widely applied method to prepare radiopharmaceuticals. Although multi‐step labeling strategies were the preferred approach for many decades, mainly due to the lack of suitable leaving groups for direct [18F]fluorination reactions, the synthetic tools to achieve the highly attractive direct introduction of 18‐fluorine into complex target molecules rapidly increased recently.