Rapid and Efficient Trifluoromethylation of Aromatic and Heteroaromatic Compounds Using Potassium Trifluoroacetate Enabled by a Flow System

摘要

The development of synthetic methods to introduce trifluoro-methyl groups into aromatic and heteroaromatic compounds is of considerable interest as CF3-substituted molecules often possess improved physical and chemical properties. As a result, a variety of synthetic methods have been developed to accomplish this task. Nagib and MacMuillan and Baran and co-workers reported elegant examples of (hetero)-aromatic trifluoromethylation reactions by CF3 radical processes. These have the advantage of being simple and high yielding, though a lack of regiocontrol is observed with certain classes of substrates. Although palladium and copper systems have been developed for the trifluoromethylation of (hetero)aromatic precursors, the scope of heterocyclic substrates handled by these methods is limited (Scheme 1).In addition, they usually necessitate the use of an excess of expensive or gaseous CF3 reagents (the latter which are more difficult to handle in normal laboratory settings) and have reaction times ranging from hours to days. Thus, it would be desirable to devise a rapid and efficient method which can be applied to a broad range of substrates and employs a low-cost CF3 source.