Regioselective C-H Trifluoromethylation and Its Related Reactions of (Hetero)aromatic Compounds

Fluorinated functional groups, including trifluoromethyl group, play important roles in the development of drugs, agrochemicals, and organic functional materials. Therefore, the development of highly effective and practical reactions to introduce fluorinated functional groups into (hetero)aromatic compounds is highly desirable. We have achieved several regioselective C-H trifluoromethylation and related reactions by electrophilic and nucleophilic activation of six-membered heteroaromatic compounds and steric protection of aromatic compounds. These reactions proceed in good to excellent yields, even on a gram scale, with high functional group tolerance, and are applicable to the regioselective trifluoromethylation of drug molecules. In this personal account, the background of the introduction reactions of fluorinated functional groups, our reaction designs to achieve regioselective C-H trifluoromethylation and the related reactions of (hetero)aromatic compounds are explained.

Automated summary

Fluorinated functional groups, such as trifluoromethyl group, are of great importance in drug development, agrochemicals, and organic functional materials. To introduce these functional groups efficiently and practically into (hetero)aromatic compounds, we have developed several regioselective C-H trifluoromethylation and related reactions. These reactions exhibit high yields, even on a gram scale, and have high functional group tolerance, making them applicable to the regioselective trifluoromethylation of drug molecules. In this personal account, we provide an explanation of the background and our reaction designs for achieving regioselective C-H trifluoromethylation and related reactions in (hetero)aromatic compounds.