In-Flow Generation of Thionyl Fluoride (SOF₂) Enables the Rapid and Efficient Synthesis of Acyl Fluorides from Carboxylic Acids

Herein, we report an approach for generating thionyl fluoride (SOF₂) from the commodity chemicals thionyl chloride (SOCl₂) and potassium fluoride (KF). The methodology relies on a microfluidic device that can efficiently produce and dose this toxic gaseous reagent under extremely mild and safe conditions. Subsequently, the in situ-generated thionyl fluoride is reacted with an array of structurally and electronically differing carboxylic acids, leading to the direct and efficient synthesis of highly sought-after acyl fluorides. Importantly, our investigation also highlights the inherent modularity of this flow-based platform. We demonstrate the adaptability of this approach by not only synthesizing acyl fluorides but also directly converting carboxylic acids into a diverse array of valuable compounds such as esters, thioesters, amides, and ketones. This versatility showcases the potential of this approach for a wide range of synthetic applications, underscoring its significance in the realm of chemical synthesis.