Study On The Copper-Catalyzed Decarboxylative Trifluo Romethylation

The introduction of trifluoromethyl (CF3) groups into organic molecules substantially improves their chemical and metabolic stability, lipophilicity, and binding selectivity since the strong electron-withdrawing nature and large hydrophobic domain of the trifluoromethyl groups. Fluorine-containing compounds have been widely used in medicine, pesticides, materials, etc.On this basis, there has been a recent surge in the number of reports describing the formation of carbon-trifluoromethyl (C-CF3) bonds. A variety of processes for the construction of Csp3-CF3bonds have been reported using electrophilic, nucleophilic, and radical-based reagents. However, the construction of Csp2-CF3and Csp,-CF3, is rarely reported. In this paper, cinnamic acid and phenylpropiolic acid are used as substrate, respectively, and two new methods of decarboxylative trifluoromethylation have been studied.After optimizing the reaction conditions, we found the effective reaction conditions for the trifluoromethylation of cinnamic aicd:20mol%CuCl and60mol%Ag2CO3as the catalyst,3equiv CF3SO2Na as the trifluoromethyl reagent,5equiv TBHP as the radical initiator, DCE as the solvent,0.2mmol cinnamic acid at70℃for24h under air. Thirteen α,β-unsaturated carboxylic acids have been tested with this system, and the E/Z ratio of the product is very high.The effective reaction conditions for the trifluoromethylation ofphenylpropiolic acid are presented as follows:1equiv Cul as the catalyst, lequiv1,10-phenanthroline as the ligand,3equiv KF as the base,2equiv Ag2CO3as the oxidant,5equiv CF3TMS as the trifluoromethyl reagent, DMF as the solvent,0.2mmol phenylpropiolic acid at room temperature for6h under N2, it is important that phenylpropiolic acid should be added to the reaction system gradually.