Mn(OAc)₃-Mediated Hydrotrifluoromethylation of Unactivated Alkenes Using CF₃SO₂Na as the Trifluoromethyl Source

Abstract

A simple and efficient method for hydrotrifluoromethylation of unactivated alkenes was reported. The reaction relied on the single electron oxidation of a commercially available sodium trifluoromethanesulfinate (CFSONa, Langlois' reagent) using Mn(OAc)·2HO as the oxidant and the subsequent addition of trifluoromethyl radical to C═C double bonds. The reaction proceeded readily under mild conditions with good tolerance of a variety of functional groups in the substrates. The preliminary reaction mechanism was studied with deuteration, radical clock, and TEMPO inhibition experiments.

CF3SO2Na-Mediated, UV-Light-Induced Friedel–Crafts Alkylation of Indoles with Ketones/Aldehydes and Bioactivities of Products

“…On the basis of the results of the control experiments and those of the literature, we proposed a possible mechanism, as illustrated in Scheme . At the beginning, upon UV irradiation, CF 3 SO 2 Na is oxidized to generate ·CF 3 radical under an O 2 -containing atmosphere, and ·CF 3 attacks the amino hydrogen of indole to form nitrogen radical A and CF 3 H . By a 1,3-H shift (detected by 19 F NMR; see the SI), radical A readily isomerizes to carbon radical B .…”

Mn(OAc)3-Mediated Addition Reactions of NaSO2CF3 and Perhalogenated Carboxylic Acids with Unactivated Alkenes Conjectured by a Single Electron Transfer and Halogen Abstraction Mechanism

“…Recently, we have shown that Mn­(OAc) 3 -mediated hydrotrifluoromethylation of alkenes using CF 3 SO 2 Na as the trifluoromethylating agent and the α-H proton of CH 3 COO – as the H source according to hydrogen abstraction to achieve the last step of hydrogenation process (Scheme ). We anticipated that the hydrogen abstraction process in the final product was driven by the oxidation of CH 3 COOH using Mn­(OAc) 3 ·2H 2 O, and the halotrifluoromethylation reaction may be realized by halogen abstraction if CH 3 COOH was used instead of CF 3 COOH, CCl 3 COOH, or CBr 3 COOH. Due to the stable properties and easy availability of perhalogenated carboxylic acid, it has certain advantages in the synthesis of compounds containing trifluoromethyl (Scheme ).…”

“…Previous work on the hydrotrifluoromethylation reaction indicated that the last step of hydrogenation process requires the participation of Mn(OAc) 3 . 22 Calculation results indicated that the energies of C−X bond breaking in CCl 3 COOH and CBr 3 COOH were 61.4 and 45.8 kcal/mol, respectively, which were both lower than that in CH 3 COOH. Therefore, we speculated that CCl 3 COOH and CBr 3 COOH could be used as halogen reagents to achieve the last step of halogenation process on Mn(OAc) 3 -mediated halotrifluoromethylation reactions.…”

“…As shown in Figure S2, there is significant formation of TEMPO−CF 3 (−53.2 ppm) adduct. 22 Procedure for Radical Clock Experiments. The operation was the same as the general procedure for halotrifluoromethylation, except that the substrate was changed to 7.…”

“…As illustrated in Scheme 4, α-C−H bond abstraction of CH 3 COOH with 1d • via the transition state TS-H required to overcome barriers of 22.4 kcal/mol to afford the desired product, which could be achieved with Mn(OAc) 3 • 2H 2 O under mild conditions (previous work, Scheme 4a). 22 Chlorotrifluoromethylation and bromotrifluoromethylation via TS-Cl (ΔG+ + = 18.3 kcal/mol, 1d • → TS-Cl) and TS-Br (ΔG+ + = 15.0 kcal/mol, 1d • → TS-Br) were more favorable than hydrotrifluoromethylation via TS-H (ΔG+ + = 22.4 kcal/ mol, 1d • → TS-H), leading to chlorotrifluoromethylated products and bromotrifluoromethylated products being much easier to achieve than hydrotrifluoromethylated products (Scheme 4b,c). Subsequently, a path through α-C−F bond abstraction of CF 3 COOH with 1d • via TS-F required to surpass a barrier of 50.1 kcal/mol (1d • → TS-F), which was 27.7 kcal/mol higher than 1d • through TS-H (Scheme 4d).…”