Transition-Metal-Free Direct Trifluoromethylthiolation and Trifluoromethylsulfoxidation of Electron-Rich Aromatics with CF₃SO₂Na in the Presence of PCl₃

Abstract

A new transition-metal-free route for the direct trifluoromethylthiolation and trifluoromethylsulfoxidation of electron-rich aromatics with CFSONa in the presence of PCl was developed. Notably, PCl was used as a reducing and chlorination reagent. The transition-metal-free protocol utilized cheap and readily available reagents and exhibited good atom economy; therefore, it will serve as an alternative and practical strategy for the trifluoromethylthiolation and trifluoromethylsulfoxidation of electron-rich aromatics.

CF3SO2X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF3SO2Na

“…At the same time, Zhao, Lu and co-workers described similar observations. The trifluoromethylsulfenylation of indoles and electron-rich aromatics was realised with CF 3 SO 2 Na in the presence of PCl 3 (1.2 instead of 3 equivalents) in acetonitrile at 60 °C ( Scheme 75 ) [ 102 ]. The authors proposed a reaction mechanism that involved the 3-trifluoromethylsulfinyl intermediate 88 ( Scheme 75 ).…”

“…With the same objective of partial reduction of CF 3 SO 2 Na with phosphorus reagents for the selective trifluoromethylsulfinylation, Zhao, Lu and co-workers noticed that a decrease of the amount of PCl 3 and a slight lowering of the temperature were beneficial to the desired trifluoromethylsulfinylation ( Scheme 81 ) [ 102 ].…”

Transition‐Metal‐Free Electrophilic Fluoroalkanesulfinylation of Electron‐Rich (Het)Arenes with Fluoroalkyl Heteroaryl Sulfones via C(Het)−S and S=O Bond Cleavage

“…Therefore, a new, easily accessible, scalable and shelf‐stable trifluoromethanesulfinylation reagent is highly desirable. In previous years, a few direct methods have been reported using Langlois reagent CF 3 SO 2 Na in the presence of TfOH, PCl 3 or POCl 3 (Scheme c–e). In 2003, 1‐(trifluoromethanesulfinyl)‐pyrrolidine‐2,5‐dione was also developed as a direct trifluoromethanesulfinylation reagent by Bertrand's group (Scheme f) .…”

“…However, traditional direct methods need the use of trifluoromethanesulfinyl halides CF 3 S(O)X (X = F, Cl), which suffers from high toxicity, volatility and poor stability. In previous years, a few direct methods have been reported using Langlois reagent CF 3 SO 2 Na in the presence of TfOH, [10] PCl 3 [11] or POCl 3 [12] (Scheme 1c-e). In previous years, a few direct methods have been reported using Langlois reagent CF 3 SO 2 Na in the presence of TfOH, [10] PCl 3 [11] or POCl 3 [12] (Scheme 1c-e).…”

Bismuth(III)-Promoted Trifluoromethylthiolation of Pyrazolin-5-ones with Trifluoromethanesulfenamide

“…However, to the best of our knowledge, only two examples on trifluoromethylthiolation of pyrazolin-5-one have been reported (Scheme 1). 12…”