Synthesis of a Library of N‐monofluoromethyl Compounds from N‐monofluoromethyl Carbamoyl/Thiocarbamoyl Fluorides

The distinctive chemical properties of fluorine atoms have enabled fluorine‐containing compounds to make significant strides in the pharmaceutical and materials fields. However, due to the very limited synthetic methods, the enormous potential of N‐monofluoromethyl compounds has not yet been unlocked. In this study, we present an operationally simple and practical protocol for various largely underexplored N‐monofluoromethyl compounds, utilizing two powerful and isolable building blocks: N‐CH2F thio carbamoyl fluorides and N‐CH2F carbamoyl fluorides. Additionally, the reactivity of fluorine atoms located at different positions of the two building blocks toward nucleophilic substitution was investigated both experimentally and theoretically.