Increased interest in the trifluoromethoxy group in organic synthesis and medicinal chemistry has induced a demand for new, selective, general, and faster methods applicable to natural products and highly functionalized compounds at a later stage of hit-to-lead campaigns. Applying pyrylium tetrafluoroborate, we have developed a mechanochemical protocol to selectively substitute the aromatic amino group with the OCF 3 functionality. The scope of our method includes 31 examples of ring-substituted anilines, including amides and sulfonamides. Expected S N Ar products were obtained in excellent yields. The presented concise method opens a pathway to new chemical spaces for the pharmaceutical industry.

We communicate two mild, solvent-free mechanochemical coupling transformations of CF 3 group with nitro compounds into amides or Schiff bases employing Ytterbia as a catalyst. This process proceeds via CÀ F bond activation, accompanied with utilisation of Si-based reductants/oxygen scavengers -reductants of the nitro group. The scope and limitations of the disclosed methodologies are thoroughly studied. To the best of our knowledge, this work is the first example of mechanical energy promoted transformation of the inert CF 3 group into other functionalities.

We describe a mechanism-guided discovery of a synthetic methodology that enables the preparation of aromatic amides from 2-bromo-2,2-difluoroacetamides utilizing a copper-catalyzed direct arylation. Readily available and structurally simple aryl precursors such as aryl boronic acids, aryl trialkoxysilanes and dimethyl-aryl-sulfonium salts were used as the source for the aryl substituents. The scope of the reactions was tested, and the reactions were insensitive to the electronic nature of the aryl groups, as both electron-rich and electron-deficient aryls were successfully introduced. A wide range of 2-bromo-2,2-difluoroacetamides as either aliphatic or aromatic secondary or tertiary amides were also reactive under the developed conditions. The described synthetic protocols displayed excellent efficiency and were successfully utilized for the expeditious preparation of diverse aromatic amides in good-to-excellent yields. The reactions were scaled up to gram quantities.