Synthesis of 4-[18F]fluorohalobenzenes and Palladium-mediated Cross-coupling Reactions for the Synthesis of 18F-labeled Radiotracers

Organic chemistry with short-lived positron emitters has evolved into a complex chemical science. Special efforts are focused on the development of rapid, selective and functional group-tolerating reactions with the most prominent short-lived positron emitter fluorine-18 (18F, 1/2= 109.8 min). The use of catalysts such as palladium complexes represents a highly promising approach for rapid and efficient syntheses of a wide variety of 18F-labeled PET radiotracers. Palladium-mediated cross-coupling reactions such as STILLE reaction, SUZUKI reaction, SONOGASHIRA reaction and BUCHWALD N-arylation with various 4-[18F]fluoro-halobenzenes as versatile 18F labeling building blocks were shown to be particularly effective reactions. More recently, various palladium-mediated electrophilic and nucleophilic late stage radiofluorination reactions have further expanded the scope of palladium complexes in 18F chemistry. In conclusion, palladium-mediated cross-coupling reactions have significantly advanced and will continue to advance the field of organic PET chemistry with 18F.