Synthesis of a Library of <i>N</i> ‐monofluoromethyl Compounds from <i>N</i> ‐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.