Metal-catalyzed Arylsulfinate Salts Trifluoromethylation And Cross-Coupling With Polyfluoroarenes

In the metal organic chemical,trifluoromethylation reaction is a hot topic in recent years. To introduce a trifluoromethyl group to the compound can significantly enhance the polarity, stability and lipophilicity of the compound, and compounds contain one or more trifluoromethyl groups are widely used in pesticides, pharmaceuticals, dyes and other fields.Many anti-inflammatory drugs containing a group of-SO(n)CF3. But there are little methods of preparing aryl trifluoromethyl sulfones, and a common approach is direct to oxidize the corresponding aryl trifluoromethyl sulfide. Yagupolski and coworker also reported recently that a fluoride compound catalyze cross-coupling to prepare aryl trifluoromethyl sulfone, but the method described is still more limited, such as reactants containing alkenyl group, an amino group and a nitrogen-containing heterocyclic usually not reaction, lower yields, or poor selectivity. Therefore, the development of a new kind method of the preparation of aryl trifluoromethyl sulfone to overcome the above problem is of great significance.Due to the superiority of arylsulfinate salts in the nature, such as easy to prepare, non-toxic, high reactivity, and easy to save.The most important thing is that they are less applied in the trifluoromethylation reaction fields.We use them as reaction substrates and Togni reagent as the trifluoromethylating reagent to explore copper catalyzed sodium benzene sulfinate salt trifluoromethyl reaction.First, we should explore the trifluoromethylation reaction conditions by using different CF3+ reagent, copper salts, ligand, solvent, temperature, as well as reaction time affecting on the reaction. The experimental results show that the optimization of experimental conditions are as follow, Cu (TFA)2 (trifluoroacetic acid copper) (0.2 equiv),1,10-phenanthroline(0.4equiv),1-(Trifluoromethyl)-1,2-benziodoxol-3(1 H)-on e(Togni reagent,2.5 equiv) and arylsulfinate salts (1.0 equiv), DMSO as solvent, and react for 8.5 hours in 130℃. Then we extend substrates, and most of the functional groups can be reacted in this method. The corresponding isolated yield of trifluoromethylated product can reach 32-88%.In addition, we studied the cross-coupling reaction of the arylsulfinate salts and pentafluorobenzene. The C-H bond of pentafluorophenyl has good activity in the palladium-catalyzed conditions, and arylsulfinate salts participating in the reaction is commonly departe -SO2Na group, so that the cross-coupling reaction is feasible in theory. After several attempts, a selected optimal experimental conditions are as follows, [PdCl(η-C3Hs)]2(0.2 equiv),tricyclohexylphosphine(0.2 equiv), pentafluoro-phenyl (2.0 equiv), and arylsulfinate salts (1.0 equiv), Ag2O (2.0 equiv), DMF as solvent, and react for 18 hours in 110℃.The cross-coupling product are the only product, and there are no self-coupling vice product detected on the MS. According to this method, we extend substrates and make the most arylsulfinate salts cross-couple with polyfluoroarenes.