A Readily Available Trifluoromethylation Reagent and Its Difunctionalization of Alkenes

Abstract

Trifluoromethyl substitution is notably popular in pharmaceuticals and agrochemicals; however, trifluoromethylated compounds normally rely on the use of cost-prohibitive or gaseous trifluoromethylating reagents, which diminishes the general applicability of these methods. Herein an efficient trifluoromethylation reagent trifluoromethylsulfonyl−pyridinium salt (TFSP) was reported, which can be readily prepared from cheap and easily available bulk industrial feedstocks. TFSP can generate a trifluoromethyl radical under photocatalysis and realize the effective azidoor cyano-trifluoromethylation reactions of alkenes.

Recent Advances on the Halo- and Cyano-Trifluoromethylation of Alkenes and Alkynes

“…Trifluoromethylsulfonyl−pyridinium salt ( 101 , TFSP) is an air stable reagent, which can be easily prepared from the reaction of Tf 2 O with 4-(dimethylamino)-pyridine. Very recently, Xiao and co-workers employed this TFSP reagent as a trifluoromethyl radical precursor and successfully applied it in the cyanotrifluoromethylation difuctionalization reaction of alkenes ( Scheme 75 ) [ 107 ]. This reaction was conducted in the presence of blue LEDs with Cu 2 O and Ir(ppy) 3 as co-catalyst, affording the corresponding trifluoromethylated nitriles 92 in moderate to good chemical yields.…”

Starting from Styrene: A Unified Protocol for Hydrotrifluoromethylation of Diversified Alkenes

“…However, a couple of pieces of evidence previously mentioned (i.e., the low catalytic loading, fast reaction rate, insensitivity to the wavelength, power of light, and type of photocatalysts, and the compatibility of a variety of N-containing functional groups and the heteroaryl) still convinced us of the existence of a chain mechanism in addition to the closed catalytic cycle. 19 On the basis of the above mechanistic investigation and reported literature, 12,20 a plausible mechanism is proposed (Scheme 5). An oxidative quench of the excited photocatalyst (E 1/2 (Ir IV/III *) = −1.73 V vs SCE) by TFSP (E p = −0.83 V vs SCE) releases a trifluoromethyl radical, which is subsequently trapped by styrene to generate a benzyl radical intermediate (Int 1).…”

“…Our continuing interest in developing ionic-type fluoroalkylation reagents and the recent concern about pyridinium salts have led us to the development of TFSP, a readily available trifluoromethylation reagent prepared from the common base DMAP and the bulk chemical Tf 2 O . On the basis of this newly developed low-cost trifluoromethylation reagent, herein we present the hydrotrifluoromethylation of diversified olefins (Scheme d).…”

“…On the basis of the above mechanistic investigation and reported literature, , a plausible mechanism is proposed (Scheme ). An oxidative quench of the excited photocatalyst ( E 1/2 (Ir IV/III* ) = −1.73 V vs SCE) by TFSP ( E p = −0.83 V vs SCE) releases a trifluoromethyl radical, which is subsequently trapped by styrene to generate a benzyl radical intermediate (Int 1).…”

Visible light mediated C–H trifluoromethylation of (hetero)arenes

“…13 We have also realized an efficient azido or cyano-trifluoromethylation of alkenes employing TFSP as a facile CF 3 source. 14 Herein, we reported the visible light mediated C–H trifluoromethylation of unactivated (hetero)arenes in the presence of Ir(ppy) 3 under blue LED irradiation.…”