Continuous-/Micro-Flow Reactions Using Highly Electrophilic PCl₃ and POCl₃

PCl₃ and POCl₃ are the most important sources of phosphorus-containing compounds. They are also used for large-scale industrial productions. However, chemical reactions using the highly reactive PCl₃ and POCl₃ tend to result in overreactions. In addition, the reactions are usually exothermic and therefore their utilization sometimes involves significant risk. That is why some phosphorylating reagents with mild electrophilicity such as phosphoramidites have been developed. Although these mild electrophiles are very useful for the highly selective synthesis of organophosphorus compounds, problems persist: the high cost of the reagents, the generation of large amounts of waste, and the requirement of long reaction times and high temperatures. Continuous-flow technology is one of the most promising solutions for these problems. In particular, precise control of reaction times and temperatures enabled by micro-flow technology suppresses undesired reactions and allows the safe operation of exothermic reactions using highly reactive PCl₃ and POCl₃ . This Review describes recently reported reactions of PCl₃ and POCl₃ using continuous- and micro-flow technologies.