Palladium-catalyzed trifluoromethylthiolation of arenes via C-H activation

Abstract

Fluorinated organic compounds are widely used as pharmaceuticals, agrochemicals and materials. Among them, the trifluoromethylthio(-SCF3) compounds has attracted much attention owning to its strong electron-withdrawing nature and high lipophilicity. Therefore, the development of new trifluoromethylthiolation methods has attracted great interest in synthetic organic chemistry. Traditional approaches for the synthesis of trifluoromethylthiolated arenes include halogen-fluorine exchange and the trifluoromethylation of sulfur-containing compounds such as disulfides, thiols, which suffer from poor functional compatibility and yield. Recent progress on the transition metal-catalyzed directing trifluoromethylthiolation using SCF3 reagents provided an efficient approach to the target. Herein, we reported a Pd(II)-catalyzed highly selective C-H trifluoromethylthiolation of arenes. Different type of pyridines could be used as efficient directing groups for this reaction. In this reaction, benzoyl chloride was found to be crucial to activate the trifluoromethanesulfanamide 2a. It provides an efficient way for the synthesis of ortho-SCF3 substituted arenes in high yields. A representative procedure for this reaction is as following:To a 10 mL glass tube, Pd(OAc)2(4.4 mg, 0.02 mmol), AgOAc(33 mg, 0.2 mmol), PhNHSCF3(50μL, 0.5 mmol), substrate(0.2 mmol) and PhCOCl(58μL, 0.5 mmol) were dissolved in dry DMF(1 mL) under N2 atmosphere. The tube was sealed and the mixture was stirred at 120℃ for 12 h, and then cooled to room temperature. The mixture was concentrated and purified by column chromatography on silica gel with a gradient eluent of petroleum ether and ethyl acetate(range from 15:1 to 4:1) to provide the products in 62%~91% yields.