The significance of fluorine atoms: The cover artwork symbolizes the importance of fluorine atoms on drug molecules, just as the red flower blossoms bring beauty and brilliance to an old tree. Although fluorine atoms greatly enhance the biological properties of pharmaceuticals and agrochemicals, fluorination reactions present persistent challenges due to their hazardous nature and limited selectivity and scalability. This review explores recently developed continuous flow techniques that addressed the challenges of fluorination reactions. The design and application of continuous flow systems specifically for fluorination reactions are discussed. More information can be found in the Review by Tsz Chun Lee, Yi Tong, and Wai Chung Fu.

Fluorination reactions are important in constructing organofluorine motifs in pharmaceuticals and agrochemicals, but they pose challenges due to their hazardous nature, high exothermicity, and limited selectivity and scalability. This review explores recent continuous flow techniques that addressed challenges of fluorination reactions, including gas-liquid reactions, packed-bed reactors, in-line purifications, reaction telescoping, large-scale reactions as well as flow photoredox- and electrocatalysis.

Abstract

Fluorination reactions are important in constructing organofluorine motifs, which contribute to favorable biological properties in pharmaceuticals and agrochemicals. However, fluorination reagents and reactions are associated with various problems, such as their hazardous nature, high exothermicity, and poor selectivity and scalability. Continuous flow has emerged as a transformative technology to provide many advantages relative to batch syntheses. This review article summarizes recent continuous flow techniques that address the limitations and challenges of fluorination reactions. Approaches based on different flow techniques are discussed, including gas-liquid reactions, packed-bed reactors, in-line purifications, streamlined multistep synthesis, large-scale reactions well as flow photoredox- and electrocatalysis.