Markovnikov-Type Hydrotrifluoromethylchalcogenation of Unactivated Terminal Alkenes with [Me4N][XCF3] (X = S, Se) and TfOH

The first Markovnikov-type hydrotrifluoromethylselenolation of unactivated terminal alkenes with the readily accessible [Me4N][SeCF3] reagent and the superacid TfOH is reported. The reaction proceeded at room temperature under catalyst- and additive-free conditions to give the branched trifluoromethylselenolated products in good yields. This protocol is also applicable to the Markovnikov-type hydrotrifluoromethylthiolation of unactivated terminal alkenes using [Me4N][SCF3]/TfOH, but not to the hydrotrifluoromethoxylation with CsOCF3/TfOH under the same conditions. The successful hydrotrifluoromethylselenolation and hydrotrifluoromethylthiolation showed simplicity and high regioselectivity, taming the sensitive −XCF3 (X = Se, S) anions with TfOH, and offered a convenient method for the straightforward synthesis of branched trifluoromethyl selenoethers and thioethers from unactivated alkenes.


General Information
All reactions were carried out under a nitrogen atmosphere unless otherwise specified.
The NMR spectra were recorded in CDCl3 on a 500 MHz (for 1 H), 471 (for 19 F), and 126 (for 13 C) spectrometer. All chemical shifts were reported in ppm relative to TMS (0 ppm) for 1 H NMR and PhOCF3 (58.0 ppm) or PhCF3 (63.0 ppm) for 19 F NMR as an internal or external standard. The coupling constants were reported in Hertz (Hz).
The following abbreviations were used to explain the multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet. The HPLC experiments were carried out on a Wufeng LC-100 II instrument (column: Shodex, C18, 5 μm, 4.6 × 250 mm), and the HPLC yields of the product were determined by using the corresponding pure compound as the external standard. MS experiments were performed on a TOF-Q ESI or EI instrument. Reagents [Me4N][SeCF3] (2a), [Me4N][SCF3] (2b), and CsOCF3 were synthesized according to the literatures. 1 Substrates 1a-f, 2 1g-1h, 3 1i-1l, 2 1m-1n, 4 and 1p-1r 4 were synthesized according to the literatures. Solvents were dried before use according to the literature. 5 Other reagents in the reactions were all purchased from the commercial sources and used without further purification.

2.
Screening the optimal reaction conditions for hydrotrifluoromethylselenolation of alkenes with [Me4N][SeCF3] and TfOH Table S1. Reactions          h. The yields were determined by 19 F NMR using PhCF3 as an internal standard. b
The mixture was maintained at room temperature for 2 minutes and analyzed by 19 F and 1 H NMR using PhOCF 3 (31.9 mg, 0.2 mmol) as an internal standard. Figure S1. 19 F NMR spectrum of the above reaction mixture. S18 Figure S2. 1 H NMR spectrum of the above reaction mixture.

S19
The mixture was maintained at room temperature for 1 hour and analyzed by 19 F and 1 H NMR using PhOCF3 (31.9 mg, 0.2 mmol) as an internal standard. Figure S3. 19 F NMR spectrum of the above reaction mixture. Figure S4. 1 H NMR spectrum of the above reaction mixture.      Figure S14. 1 H NMR spectrum of the above reaction mixture.

Experiment 6:
Under a nitrogen atmosphere, a sealed tube was charged with 1a (10.4 mg, 0.05 mmol) and a solution of TfOH (7.5 mg, 0.05 mmol) in CD2Cl2 (1 mL) with stirring. The S26 mixture was maintained at room temperature for 1 hour and analyzed by 19 F and 1 H NMR using PhOCF3 (28.0 mg, 0.18 mmol) as an internal standard. Figure S15. 19 F NMR spectrum of the above reaction mixture. Under a nitrogen atmosphere, a sealed tube was charged with 1a (20.8 mg, 0.10 mmol) and a solution of TfOH (7.5 mg, 0.05 mmol) in CD2Cl2 (1 mL) with stirring. The mixture was maintained at room temperature for 2 minutes and analyzed by 19 F and 1 H NMR using PhOCF3 (26.5 mg, 0.17 mmol) as an internal standard. Figure S19. 19 F NMR spectrum of the above reaction mixture. Figure S20. 1 H NMR spectrum of the above reaction mixture.

Experiment 8:
Under a nitrogen atmosphere, a sealed tube was charged with 1a (20.8 mg, 0.10 mmol) and a solution of TfOH (7.5 mg, 0.05 mmol) in CD2Cl2 (1 mL) with stirring. The mixture was maintained at room temperature for 1 hour and analyzed by 19 F and 1 H NMR using PhOCF3 (26.5 mg, 0.17 mmol) as an internal standard. Figure S21. 19 F NMR spectrum of the above reaction mixture.
S30 Figure S22. 1 H NMR spectrum of the above reaction mixture.