Visible-Light-Induced Photocatalyst-Free Radical Trifluoromethylation

Abstract

An attractive, versatile, and operationally simple, visible-light-induced, transition-metal-free, photocatalyst-free, and oxidant-free trifluoromethylation has been demonstrated. Triflic anhydride (Tf 2 O), being inexpensive and readily available, was chosen as the radical trifluoromethyl source. Thianthrene was used as a recyclable Tf 2 O-activating reagent, and a high-yielding and scalable trifluoromethylation reaction was achieved. Density functional theory and mechanistic studies showed that a free radical homolytic process excited by visible light is involved in this reaction, generating a key trifluoromethyl radical intermediate.

Recent Applications of Trifluoromethanesulfonic Anhydride in Organic Synthesis

“…Considering that the homolytic cleavage of Umemoto's reagent was easy to generate trifluoromethyl radical under visible light irradiation and the preparation of trifluoromethyl thianthrenium salts was a simple one-step synthesis protocol, Zhang, Wang, Xia and co-workers developed a visible-light-induced photocatalyst-free, and oxidant-free radical trifluoromethylation method for the preparation of trifluoromethylated N-heterocycles, alkenes, hydrazones, and arenes with excellent yields, in which inexpensive and readily available Tf 2 O was utilized as a radical CF 3 source, and thianthrene served as cyclable Tf 2 O activating reagent (Scheme 30). [50] DFT and mechanistic studies showed that the reaction was more inclined to undergo direct excitation of thianthrenium salts 101 by purple light. Subsequently, excited thianthrenium salts underwent homolytic CÀ S bond cleavage to generate the CF 3 radical and the thianthrenium radical cation TT + * .…”

Photoredox Trifluoromethylation/Cyclization of N-Arylacrylamides with 4-(Difluoroamino)-1-[(trifluoromethyl)sulfonyl]pyridinium Triflate (TFSP)

“…Moreover, a catalyst and oxidant-free trifluoromethylation/cyclization of N-arylacrylamides through visible-light-induced homolysis of thianthrenium salts has also been developed. 14 Despite these impressive advances, the generation of CF 3 radicals through SET reduction using cheap and easily available trifluoromethylating reagents, permitting redox-neutral trifluoromethylation/cyclization of N-arylacrylamides, is rarely reported. 4b,7c,8a Recently, Xiao reported that 4-(difluoroamino)-1-[(trifluoromethyl)sulfonyl]pyridinium triflate (TFSP) is an efficient and stable trifluoromethylation reagent that can be readily prepared from cheap and easily available Tf 2 O and DMAP.…”

“…Moreover, a catalyst and oxidant-free trifluoromethylation/cyclization of N -arylacrylamides through visible-light-induced homolysis of thianthrenium salts has also been developed. 14 Despite these impressive advances, the generation of CF 3 radicals through SET reduction using cheap and easily available trifluoromethylating reagents, permitting redox-neutral trifluoromethylation/cyclization of N -arylacrylamides, is rarely reported. 4b 7c 8a…”

“…The incorporation the trifluoromethyl group into the organic compounds have attracted significant attention, (1) as the trifluoromethyl group is prevalent in pharmaceuticals, agrochemicals, and functional materials. (2) Difunctionalization of alkenes with various CF3 precursors represents one of the most effective strategies for the construction of CF3-containing molecules, including CF3-containing heterocyclics.…”

Visible Light Promotes Cascade Trifluoromethylation/Cyclization, Leading to Trifluoromethylated Polycyclic Quinazolinones, Benzimidazoles and Indoles

“…To address this question, cost-effective and readily available trifluoroacetic acid (TFA), trifluoroacetic anhydride (TFAA) and triflic anhydride (Tf 2 O) have recently been investigated as trifluoromethylation reagents under diverse catalysis by Zhang, Stephenson, Qing and Ritter, etc. [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ].…”