Comprehensive Study and Development of a Metal‐Free and Mild Nucleophilic Trifluoromethoxylation

Among the general interest in fluorinated compounds, trifluoromethoxylated molecules play a specific role. However, despite this interest, the development of efficient reagents to perform trifluoromethoxylation reactions remains a challenge. Here, 2,4‐dinitro‐trifluoromethoxybenzene (DNTFB) is used as a trifluoromethoxylating reagent to perform nucleophilic substitution under mild metal‐free conditions with different leaving groups, including direct dehydroxytrifluoromethoxylation. A mechanistic study rationalized the reaction and subsequently proposed only three reaction conditions, depending on the reactivity of the starting substrates. Metal‐free trifluoromethoxylation by nucleophilic substitution under mild conditions was developed based on the inexpensive DNTFB/DMAP system. An efficient rationalization was developed to propose optimal conditions depending on the characteristics of the starting substrates. A mechanistic study proved the crucial role of potassium salts in the transient formation of the CF3OK species, which has promising properties.