Investigations into Transition-Metal-Catalyzed Arene Trifluoromethylation Reactions

Abstract

Trifluoromethyl-substituted arenes and heteroarenes are widely prevalent in pharmaceuticals and agrochemicals. As a result, the development of practical methods for the formation of aryl-CF₃ bonds has become an active field of research. Over the past five years, transition metal catalyzed cross-coupling between aryl-X (X = halide, organometallic, or H) and various "CF₃" reagents has emerged as a particularly exciting approach for generating aryl-CF₃ bonds. Despite many recent advances in this area, current methods generally suffer from limitations such as poor generality, harsh reaction conditions, the requirement for stoichiometric quantities of metals, and/or the use of costly CF₃ sources. This Account describes our recent efforts to address some of these challenges by: (1) developing aryl trifluoromethylation reactions involving high oxidation state Pd intermediates, (2) exploiting AgCF₃ for C-H trifluoromethylation, and (3) achieving Cu-catalyzed trifluoromethylation with photogenerated CF₃•.