intermediate (Scheme 2.21) [41].
Scheme 2.21 Trifluoromethylation with Cu(O2CCF2SO2F)2.
Scheme 2.22 Cu‐catalyzed trifluoromethylation of aryl iodides. using Ag2O as a promoter.
Scheme 2.23 Nucleophilic addition of trifluoromethyl group to carbonyl compounds.
Although various trifluoromethylations with combinations of copper salts and trifluoroacetate salts had been developed, a stoichiometric amount of copper salts was necessary in almost all cases. To overcome this limitation, Li, Duan, and coworkers developed a copper‐catalyzed trifluoromethylation of aryl iodides with sodium trifluoroacetate using Ag2O as a promoter (Scheme 2.22) [42]. The use of copper catalyst alone gave the trifluoromethylation product in low yield, but the addition of Ag2O dramatically improved the yield. Notably, the use of Ag2O alone did not give any product at all.
Beside the cross‐coupling‐type trifluoromethylations, the combination of trifluoroacetate and copper salts could be used as an efficient nucleophilic reagent for addition reaction to carbonyl compounds, as reported by Chang and Cai (Scheme 2.23) [43]. Not only aldehydes but also ketones, acetyl chloride, and phthalic anhydride were available for this reaction.
2.2.3.2 Using Silver Salts
Interestingly, an early example of perfluoroalkylations using silver salts was the synthesis of multi‐trifluoromethylated fullerene [44]. In 2001, Boltalina's group prepared mixtures of multi‐trifluoromethylated fullerenes by solid‐state trifluoromethylation with silver trifluoroacetate at 300 °C [45]. The silver salt could add up to 22 trifluoromethyl groups to C60, although other metal trifluoroacetates such as copper, palladium, and chromium salts could add only less than 8 trifluoromethyl groups. Several multi‐trifluoromethylated fullerenes, including isomers, were independently characterized by means of nuclear magnetic resonance (NMR) and mass spectroscopies by Boltalina and coworkers [46] and Taylor and coworkers [47]. In 2007, Goryunkov and coworkers successfully determined the X‐ray crystal structures of some of them and discussed the observed isomeric distribution in mixtures of C60(CF3)n compounds up to n = 6 [48].
In 2015, Zhang and coworkers reported an electrophilic trifluoromethylation of aromatic compounds with trifluoroacetic acid by using a silver catalyst (Scheme 2.24) [49]. The Ag2CO3 catalyst was considered to facilitate the generation of CF3 radical from trifluoroacetic acid via decarboxylation, and then this radical mediates aromatic trifluoromethylation. The resulting Ag(I) species is reoxidized by K2S2O8, used as an additive.
Zhang's conditions have been applied to several types of fluoroalkylations using fluorine‐containing carboxylic acids. Nielsen and coworkers performed a decarboxylative difluoromethylation of N‐heteroaromatic compounds with difluoroacetic acid (Scheme 2.25a) [50]. Wan, Hao, and coworkers reported an aryldifluoromethylation of isocyanides with potassium difluoroarylacetate, affording phenanthridines bearing an arylated difluoromethene motif (Scheme 2.25b) [51, 52]. Wan, Hao, and coworkers [53] and Deng and coworkers [54] independently reported an oxindole synthesis by the reaction of N‐arylacrylamides with potassium difluoroarylacetate or its acid form in the presence of persulfate salts (Scheme 2.25c). Hashmi and coworker employed ethynyl benziodoxolone, as the coupling partner, in a decarboxylative aryldifluoromethylation with difluoroarylacetic acids (Scheme 2.25d) [55].
Scheme 2.24 Silver‐catalyzed electrophilic trifluoromethylation.
Scheme 2.25 Silver‐catalyzed fluoroalkylations with various fluorinated carboxylic acids. DMSO, dimethylsulfoxide; MS4Å, molecular sieves 4Å.
2.2.4 Photochemical Reactions
In 1993, Mallouk and Lai developed a photochemical approach for trifluoromethylation with silver trifluoroacetate, in which TiO2 was used as a photocatalyst for trifluoromethylation of aromatic compounds (Scheme 2.26a) [56]. The TiO2 catalyst promotes photolysis of trifluoroacetate to generate trifluoromethyl radical. In 2017, Su, Li, and coworkers developed a new catalytic system using Rh‐modified TiO2 nanoparticles for photochemical trifluoromethylation with trifluoroacetic acid in the presence of Na2S2O8 as an additive (Scheme 2.26b) [57].
Scheme 2.26 Photochemical trifluoromethylation using TiO2.
Not only simple arenes but also N‐containing heteroarenes were available, affording the desired products in modest to good yields. Very recently, Hosseini‐Sarvari and Bazyar achieved a photocatalytic trifluoromethylation using sodium trifluoroacetate under blue LED irradiation in the presence of Au‐modified ZnO catalyst (Au@ZnO core–shell nanoparticles) (Scheme 2.27) [58]. Au@ZnO could catalyze not only aromatic trifluoromethylation but also coupling‐type trifluoromethylations of aryl halides as well as boronic acids under appropriate conditions.
Scheme 2.27 Au@ZnO‐catalyzed photochemical trifluoromethylations.
Qing and coworkers developed a homogeneous photocatalytic system for hydro‐aryldifluoromethylation of alkenes with difluoroarylacetic acids by using an iridium photoredox catalyst, Ir[dF(CF3)ppy]2(dtbpy)]BF4 (Scheme 2.28) [59]. Methoxybenziodozole (BIOMe) as an additive plays a crucial role in the catalytic cycle; it accelerates photolysis of the carboxylic acid by forming a hypervalent iodine intermediate possessing carboxylate as a ligand, and promotes turnover of the photoredox catalytic cycle by oxidizing excited‐state IrIII* to IrIV
