Advances in Continuous Flow Fluorination Reactions

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.

Deoxyfluorination of Ketones with Sulfur Tetrafluoride (SF4) and Dialkylamines in Continuous Flow Mode

“…An alternative strategy to minimize the hazards associated with DAST is through the development of technological approaches that alleviate many of the challenges. Continuous flow has emerged as an enabling technique for mitigating the risks of handling hazardous chemistry, especially for chemistries that are difficult to perform safely in batch. − Flow reactors provide an improved safety profile, and chemistry can be performed within a much smaller contained system . An additional key benefit of using modular microreactor configurations is that explosive, toxic, and corrosive intermediates and byproducts (e.g., HF) can be quenched in-line immediately after the reaction, which improves the inherent safety.…”