Carbon Trifluoromethylation Reactions of Hydrocarbon Derivatives and Heteroarenes

The incorporation of a trifluoromethyl group into an organic substrate is an important strategy in preparative organic chemistry. Many biologically active compounds contain a trifluoromethyl group as the essential motif, and the trifluoromethyl group has been particularly difficult to install, in part because the reactive intermediates that are generated during trifluoromethylation reactions are unstable under the conditions necessary for the reactions to proceed. The direct trifluoromethylation of unsaturated substrates such as allyl, alkene, and alkyne derivatives in both stoichiometric and catalytic reactions has attracted special interest. Nevertheless, the direct trifluoromethylation of aromatic systems has often the drawback of generating mixtures of regioisomers. The use of new prefunctionalized aromatic compounds bearing directing groups improves the reliability and increases the regioselectivity of these processes in some cases. Excellent challenges for the future imply a better understanding of their mechanism pathways along with the development of new simple trifluoromethylating agents, the design of new cheap catalytic systems and metal-free strategies.