Nucleophilic Trifluoromethylation Reactions Involving Copper(I) Species: From Organometallic Insights to Scope

Abstract

Over the last decades, trifluoromethyl copper(I) complexes have played a key role as reactive species in C–CF3 bond-forming reactions. This Short Review not only covers selected examples of relevant copper-mediated or catalyzed nucleophilic trifluoromethylation reactions, which is one of the most active fields in organic synthesis, but also provides a comprehensive picture of the real behavior of these copper species, including ubiquitous cuprates, in the reaction media.1 Introduction2 Historical Perspective of the Identification of Relevant Trifluoro- methyl Copper(I) Species3 In Situ Generation of Active Trifluoromethyl Copper(I) Species 4 Well-Defined Active Trifluoromethyl Copper(I) Complexes5 Recent Advances on the Performance of Trifluoromethylation Protocols6 Conclusions

Broad‐scope Syntheses of [11C/18F]Trifluoromethylarenes from Aryl(mesityl)iodonium Salts

“…[6] Consequently, the development of methods for the trifluoromethylation of aryl carbon stands as an essential area of research in bioorganic and medicinal chemistry. Numerous electrophilic, [7] radical, [8] and nucleophilic reagent sources [9] are now available for installing a trifluoromethyl group onto an aryl ring. Many of the methods are however required to be mediated by transition metals.…”

Photoinduced Perfluoroalkylation Mediated by Cobalt Complexes Supported by Naphthyridine Ligands

“…Radical C–H trifluoromethylation catalyzed by base metal complexes attracts significant attention as a convenient synthetic tool to introduce fluorine atoms into organic compounds, which may be used to improve stability and alter the activity of biologically active compounds and pharmaceuticals. − While trifluoromethylation mediated by first-row transition metal complexes, especially Ni − and Cu, − recently became the subject of active research, using this methodology to introduce longer perfluoroalkyl chains is significantly less studied, although the presence of longer perfluoroalkyl groups may have a significant effect on pharmacokinetic properties of organic compounds as compared to trifluoromethyl groups. , In 2021, the Vicic group described perfluoroalkylation by using solvated perfluoroalkyl nickel­(II) complexes that also showed catalytic reactivity in trifluoromethylation. However, only stoichiometric reactivity was observed in perfluoroethylation .…”

Recent advances on non-precious metal-catalysed fluorination, difluoromethylation, trifluoromethylation, and perfluoroalkylation of N-heteroarenes

“…For instance, fluorination technologies selectively based on the application of N -fluorobenzenesulfonimide, applications of organo-fluorine compounds in the agrochemical industries or precious metal-based C–H functionalisation using valuable fluorinated building blocks have been well documented. 4–7,22–27 In addition, several approaches for metal-catalysed trifluoromethylation, 28–41 perfluoroalkylation, 42–45 and difluoromethylation 46–49 have also been reported based on precious or non-precious transition metals as well as under metal-free conditions. However, to the best of our knowledge, to date there has been no such comprehensive review solely focused on the fluorination, difluoromethylation, trifluoromethylation, and perfluoroalkylation of N-heteroarenes using non-precious-metal catalysis.…”