Investigations into Transition-Metal-Catalyzed Arene Trifluoromethylation Reactions

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–CF 3 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 ‘CF 3 ’ reagents has emerged as a particularly attractive approach to generating aryl–CF 3 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 CF 3 sources. This Account describes our recent efforts to address some of these challenges by: (1) developing aryltrifluoromethylation reactions involving high oxidation state Pd intermediates, (2) exploiting AgCF 3 for C–H trifluoromethylation, and (3) achieving Cu-catalyzed trifluoromethylation with photogenerated CF 3 • . 1 Introduction 2 Part 1. Aryltrifluoromethylation via High-Valent Palladium 3 Part 2. Aryltrifluoromethylation Using AgCF 3 4 Part 3. Cu-Catalyzed Aryltrifluoromethylation with CF 3 • 5 Outlook