Copper-catalyzed trifluoromethylation of alkenes with an electrophilic trifluoromethylating reagent

Abstract

SummaryAn efficient method for the copper-catalyzed trifluoromethylation of terminal alkenes with an electrophilic trifluoromethylating reagent has been developed. The reactions proceeded smoothly to give trifluoromethylated alkenes in good to excellent yields. The results provided a versatile approach for the construction of Cvinyl–CF3 bonds without using prefunctionalized substrates.

Synthesis of trifluoromethylated 2H-azirines through Togni reagent-mediated trifluoromethylation followed by PhIO-mediated azirination

“…It is well documented that Togni reagents can realize the direct trifluoromethylation of alkenes [ 58 – 60 ] and electron-rich enamides [ 61 ]. Inspired by this, we envisaged that Togni reagent 1 could also enable the introduction of a CF 3 group to the β-position of enamine substrates, and the so-obtained trifluoromethylated enamines could undergo a hypervalent iodine-mediated intramolecular azirination to give the corresponding trifluoromethylated 2 H -azirines [ 56 – 57 ].…”

Recent Advances in Trifluoromethylation Reactions with Electrophilic Trifluoromethylating Reagents

“…A trifluoromethylation methodology involving nonfunctionalized alkenes was reported by Xiao and co-workers. [36] The copper-catalyzed trifluoromethylation of terminal aromatic alkenes with reagent 1 b utilizing [(MeCN) 4 Cu]PF 6 as catalyst, 1,8-diazabicyclo-[5.4.0]undec-7-ene (DBU) as base in DMF as solvent is achieved in very good yields (Scheme 17). [36] The reaction could tolerate various functional groups.…”

“…[36] The copper-catalyzed trifluoromethylation of terminal aromatic alkenes with reagent 1 b utilizing [(MeCN) 4 Cu]PF 6 as catalyst, 1,8-diazabicyclo-[5.4.0]undec-7-ene (DBU) as base in DMF as solvent is achieved in very good yields (Scheme 17). [36] The reaction could tolerate various functional groups. Notably, all products were obtained with excellent stereoselectivity (E/Z > 97:3).…”

“…Notably, all products were obtained with excellent stereoselectivity (E/Z > 97:3). [36] Regarding the reaction mechanism, [36] the authors postulated a pathway involving radical intermediates as evidenced by trapping experiments with TEMPO, a well-known radical scavenger. In this case, the desired trifluoromethylation reaction was completely suppressed.…”

“…In the postulated mechanism (Scheme 18), [36] [36] Togni's reagent 1 a (1-trifluoromethyl-1,2-benziodoxol-3-(1 H)-one) has recently been reported by Szabó and co-workers to undergo addition reactions with both alkynes and alkenes in the presence of CuI catalyst, [37] affording vinylÀCF 3 and alkylÀCF 3 substituted products, respectively (Scheme 19). These results and others were recently summarized by Liu and co-workers.…”