Metal-free alkene oxy- and amino-perfluoroalkylations via carbocation formation by using perfluoro acid anhydrides: unique reactivity between styrenes and perfluoro diacyl peroxides

A practical metal-free perfluoroalkylation using acid anhydrides with unique reaction mode via carbocation has been developed.


General Experimental
General: Reactions were conducted in a dry vessel under a positive pressure of nitrogen gas by using a nitrogen-filled balloon. Analytical thin-layer chromatography (TLC) was performed on glass plates coated with 0.25 mm 230-400 mesh silica gel (Merck, Silica gel 60 F 254 ) containing a fluorescent indicator. Visualization was accomplished by means of ultraviolet irradiation at 254 nm and/or by spraying an ethanolic solution of 12molybdo(VI)phosphoric acid as a developing agent. Flash column chromatography was performed using Silica gel N-60 (spherical, neutral, 40-50 µm, Kanto Chemical Co., Inc. (Kanto)) as described by Still et al. 1

Instrumentation:
NMR analysis NMR spectra were recorded at room temperature on a JEOL JNM-ECS-400 NMR spectrometer at 400 MHz for 1 H, 100 MHz for 13 (Hz). The data are presented in the following order: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet and/or multiple resonances, and br = broad), coupling constant and signal area integration in natural numbers.

IR analysis
Infrared spectra were measured on a Thermo Nicolet iS5. Only diagnostic absorptions are listed. Chemical Industry Co., Ltd. and Sigma-Aldrich Inc. Known alkenes 3a 2 and 12 3 were prepared according to the cited literature. Table S1. Optimization of the conditions for the synthesis of 2a a a The reactions were conducted on 0.20 mmol scale. b The yields were estimated by means of 19 F NMR analysis, with a,a,a-trifluorotoluene as an internal standard. c The recovery of 1a was estimated by means of 1 H NMR analysis, with 1,1,2,2-tetrachloroethane as an internal standard. d Yield in parenthesis is the isolated yield.

F NMR monitoring:
Trifluoroacetic anhydride (0.14 mL, 1.0 mmol) was slowly added to a suspension of urea  was stirred for 1 h. The obtained colorless solution containing bis(trifluoroacetyl)peroxide (BTFAP) was transferred to a valve NMR tube containing a,a,a-trifluorotoluene (13 mg, 0.09 mmol) as an internal standard under a N2 atmosphere.
The 19 F NMR spectrum of the sample was measured at room temperature, and 0.21 mmol of the peroxide was found to have been formed. After the measurement, the NMR sample was warmed to 40 °C on an oil bath. After 30 min, 19 F NMR measurement was conducted at room temperature (I) ( Figure S1); and no change of the spectral signals or integration values was observed. Then, styrene 1a (14 mg, 0.10 mmol) was added to the sample solution at room temperature, and the mixture was warmed to 40 °C on an oil bath. After 30 min, the 19 F NMR spectrum of the sample was measured at room temperature (II); the results indicated the presence of 0.09 mmol (86% yield based on 1a) of oxytrifluoromethylation product 2a and 0.10 mmol of BTFAP. This shows that styrene is essential for decomposition of BTFAP and CF3 radical generation.

Preparation of aminoalkene 3b
Substrate 3b was synthesized according to the literature procedure for preparing 3a. 2 A solution of carboxylic acid S-1 (2.0 g, 12 mmol) in dry Et2O (15 mL) was added dropwise to a suspension of lithium aluminum hydride (0.9 g, 24 mmol) in dry Et2O (35 mL) at 0 °C. The mixture was stirred at room temperature for 2 h, and then the reaction was quenched by careful and sequential addition of H2O (7 mL) and 2 M NaOH solution (7 mL) at 0 °C. The resulting suspension was filtered through a Celite pad and the filtrate was dried over Na2SO4, filtered and concentrated in vacuo to provide S-2 (1.5 g, 84% yield) as a yellow oil. Methanesulfonyl chloride (0.97 mL, 13 mmol) was added dropwise to a solution of S-2 (1.5 g, 10 mmol) and triethylamine (

Oxy-and amino-perfluoroalkylation of alkenes: general procedure
To a suspension of urea·H2O2 (47 mg, 0.50 mmol) in DCM (1 mL) perfluoro acid anhydride (2.0 mmol) was slowly added at 0 °C. After stirring for 1 h, styrene (0.20 mmol) was added. Then, the mixture was immediately warmed to 40 °C, further stirred for 1 h, then diluted with Et2O (5 mL), quenched with saturated K2CO3 solution at 0 °C, again stirred for 20 min. The phases were separated and the aqueous layer was extracted with Et2O (2 x 5 mL). 6 The combined organic phase was dried over Na2SO4, filtered and 5 J.-S. Lin, P. Yu, L. Huang, P. Zhang, B. Tan, X.-Y. Liu, Angew. Chem. Int. Ed., 2015, 54, 7847. 6 The combined organic phase was checked with XploSens PS ® to confirm the absence of peroxide, and the water phase was treated with saturated Na2S2O3 to decompose H2O2.
After stirring for 1 h, 4-fluorostyrene (2.0 g, 16 mmol) was added. The mixture was immediately warmed to 40 °C and stirred for further 1 h. After dilution with DCM (50 mL), the reaction was quenched with saturated K2CO3 solution at 0 °C for 20 min. The phases were separated and the aqueous layer was extracted with DCM (2 x 50 mL). 6 The S12 combined organic phase was dried over Na2SO4, filtered and concentrated in vacuo to give pure 2b (4.7 g, 93%) as a yellow oil.

H NMR (400 MHz, CDCl 3 )
The target compound 2b' was obtained as a colorless oil (75 mg, 93% yield) after purification by column chromatography (SiO2; 100% hexane). HRMS-EI (m/z) 10 The carbons of perfluoroalkyl groups could not be assigned because of low intensity of signals, their complex coupling, and overlap due to large J values.

Radical probe test using 12 (Scheme 8):
The reaction of 12 was carried out according to the general procedure (the 19 F NMR spectrum of the crude product is shown in Figure S4).

Computational details:
DFT calculations were conducted with Gaussian 16 series 13 of programs. The structures were optimized at the UB3LYP level of theory, and 6-31+G(d,p) basis set was used. The single-point energy calculation was performed using UMPWB1K/6-311+G(2df,2p), except that LanL2DZ was used for Cu. The CPCM solvation model (dichloromethane) was used to reflect the solvent effect. The free energies described in this work were estimated from the ZPEs from UMPWB1K with thermal corrections by using vibrational analysis at the UB3LYP level of theory. No imaginary frequencies for intermediates and one imaginary frequency for the transition state were observed. The reaction pathway from the transition state was confirmed by IRC calculation and the vibration mode of the imaginary frequency. DFT calculations were conducted according to the literature procedure reported by Houk and Buchwald. 15 The activation energy (DG ‡ ) of SET was estimated according to the Marcus equation with parameters as shown in Scheme S1 (n = 1.424, e = 8.93 for CH 2 Cl 2 ).