Catalytic trifluoromethylation of iodoarenes by use of 2-trifluoromethylated benzimidazoline as trifluoromethylating reagent

The trifluoromethylation of iodoarenes was accomplished by use of a 2-trifluoromethylbenzimidazoline derivative as the trifluoromethylating reagent and a catalytic amount of Cu(I) in the presence of 2,2'-bipyridyl as the ligand. Through a mechanistic study, we found that the oxidative addition of the iodoarene to the Cu(I)–CF3 species is the rate-determining step.

We next screened for the generality of the reaction towards various substrates under the optimized conditions ( Figure 2). Electron-deficient aryl iodides were well tolerated furnishing the corresponding trifluoromethylation products in high yields. Among the tested nitrophenyl derivatives, p-and o-nitrophenyliodide gave the products in highest yields. In contrast, m-iodonitrobenzene afforded the trifluoromethylated product in a decreased yield of 35% due to the higher electron density of the meta-position compared to the ortho-and para-positions. Iodoarenes bearing other electron-withdrawing substituents, such as p-cyano, p-acetyl, and p-methoxycarbonyl, were also suitable and gave products 3d-f in moderate to high yields. Furthermore, the presence of a formyl group was also tolerated in the reaction, and p-formyltrifluoromethylbenzene (3g) was obtained in 40% yield. However, the electron-rich substrate 2-methoxyiodobenzene (1h) gave product 3h in only a modest yield (30%).  Heteroaryl iodides were also suitable substrates ( Figure 3). 2-Iodopyridine (5a) gave the expected trifluoromethylation product 6a in 80% yield. 2-Iodoquinoline (5b) and 1-iodoisoquinoline (5c) were also suitable substrates to furnish desired products 6b and 6c in high yields. Furthermore, iodopyrazine was applicable to furnish 6d in 63% yield.
Finally, a mechanistic study of the reaction was carried out. First, the active species of the reaction was investigated by NMR analysis. The generation of Cu(I)-CF 3 was observed by mixing benzimidazoline 2 and CuI in EtCN at 90 °C ( Figure S1, in Supporting Information File 1). Therefore, CuI and 2 generated CuCF 3 species as the active species for the trifluoromethylation [24].
Then, the dependence of the conversion on the reaction time was estimated ( Figure 4) and no induction period was observed. Although benzimidazoline 2 was completely consumed after 24 h, the yield of the trifluoromethylation product continued to increase up to 48 h. This suggests that product generation proceeded slower than the cleavage of the C-CF 3 bond of benzimidazoline.  We propose a mechanism for the reaction, as shown in Figure 5. The Cu(I)-CF 3 species, generated through the reaction of benzimidazoline 2 with CuI under basic conditions, underwent an oxidative addition reaction with the aryl iodide to generate a Cu(III) complex. A subsequent reductive elimination furnished the trifluoromethylarene and Cu(I). Because an electron-donating ligand was more effective than an electron-deficient one (Table 2), and the reaction with benzimidazoline proceeded rapidly (Figure 4), the oxidative addition was suggested to be the rate-determining step.

Conclusion
In conclusion, we have developed a catalytic trifluoromethylation of aryl iodides by using trifluoromethylated benzimidazoline derivatives. The mechanistic study revealed that the oxidative addition was the rate-determining step of this reaction. 2-Phenyl-2-trifluoromethyl-1-methylbenzimidazoline is a novel type of trifluoromethylating reagents that might be useful for organic synthesis.
Then, the crude products were purified by preparative TLC to give pure products 3.