Poison to promise: The resurgence of organophosphorus fluoride chemistry

Organophosphorus(V) fluorides have a long and tumultuous history, with early applications as toxins and nerve agents reflecting their poisonous past. Behind these very real safety considerations, there is also growing potential in a wide range of fields, from chemical biology to drug development. The recent inclusion of organophosphorus(V) fluorides in click chemistry exemplifies the promise these compounds possess and brings these molecules to the brink of a resurgence. In this perspective, we delve into the history of phosphorus(V) fluoride (P(V)–F) compounds, discuss the precautions needed to work with them safely, and explore recent advancements in their synthesis and application. We conclude by discussing how this field can continue on a path toward innovation.