The trifluoromethoxy group (OCF3) is becoming increasingly important in the chemical sciences in reason of its high electronegativity and lipophilicity. However, its installation on pharmaceutically relevant molecules for instance remains a very difficult task as the existing methodologies are either narrow in scope or require the use of a large excess of the valuable substrate and/or harsh reaction conditions.
Here, P. Tang and coworkers from Nankai University describe the selective C-H trifluoromethoxylation of (hetero)arenes as limiting reagent using a trifluoromethyl arylsulfonate (TFMS) which releases OCF3 anion upon reaction with fluorides, and in the presence of silver fluoride and Selectfluor as the oxidant. The scope is vast, with a focus on pyridines which undergo trifluoromethoxylation at the position 2. Importantly, since the (hetero)arene is used as the limiting reagent, the methodology can be used for late-stage trifluoromethoxylation of complex molecules as exemplified in the article. The authors also undertook a mechanistic study and were able to propose a mechanism for this very interesting transformation.

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