Direct Introduction of Perfluoroacyl (−CORF) Groups into Organic Substrates

Abstract The direct addition of perfluoroacyl (−COR F ) groups to organic frameworks has seen a resurgence in interest due to the benefits of these groups in late‐stage modification of pro‐drugs and biologically active compounds, helping to identify new active leads. The presence of −COR F groups positively impacts the structure‐activity relationships of these compounds. In that sense, both polar methods and radical protocols have been developed for the direct syntheses of trifluoromethyl and perfluoroalkyl ketones. In particular, methodologies to tame the unstable trifluoroacyl radical, which could be a key intermediate in the late‐stage syntheses of trifluoroacyl‐substituted compounds, has allowed much progress in this area. In the next sections, the direct incorporation of perfluoroacyl groups into (hetero)aromatic compounds, −COR F substitutions at C sp 3 −H, alkyl halides, alkenes, amides, and N‐atoms will be discussed in detail, suggesting the future directions and perspectives in the field. These known reactions are summarized in Table 1.