Oxidative Radical Intermolecular Trifluoromethylthioarylation

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Note Cite This: J. Org. Chem. 2018, 83, 5836−5843

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Oxidative Radical Intermolecular Trifluoromethylthioarylation of Styrenes by Arenediazonium Salts and Copper(I) Trifluoromethylthiolate Zhiwei Xiao,† Yongan Liu,† Liping Zheng,‡ Chao Liu,*,† Yong Guo,† and Qing-Yun Chen*,† †

Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China ‡ School of Chemical Engineering and Food Science, Zhengzhou Institute of Technology, 18 Yingcai Street, Zhengzhou 450044, China S Supporting Information *

ABSTRACT: An efficient oxidative radical intermolecular trifluoromethylthioarylation of styrenes with arenediazonium salts and copper(I) trifluoromethylthiolate under mild conditions is described for the first time. The reactions provide good yields of the corresponding trifluoromethylthioarylation products with broad substrate scope and excellent functional group compatibility.

I

introduction of an aryl group and another valuable functional group, including F,9a Cl,9b Br,9c SCN,9c to the best of our knowledge, there is no report on Meerwein trifluoromethylthioarylation of alkenes. In 2015, we reported the direct oxdative radical trifluoromethylthiolation of unactivated alkanes using AgSCF3 and K2S2O8 (Scheme 1a).5b Later on, oxidative

t is well-known that incorporation of a trifluoromethylthio (CF3S) group into an organic molecule can drastically alter its chemical, physical, and biological properties due to the intrinsic properties of CF3S, including the strong electronwithdrawing power and high lipophilicity, 1 which has stimulated increasing interest in the development of new methods for the direct and efficient introduction of the CF3S group into organic compounds.2 Among numerous approaches to prepare various trifluoromethylthiolated compounds, relatively limited methods for the formation of C(sp3)-SCF3 bonds are available, compared with those for the formation of C(sp2)SCF3 and C(sp)-SCF3 bonds. Recent and representative methods for direct construction of C(sp3)-SCF3 bonds include nucleophilic,3 electrophilic,4 and radical5 trifluoromethylthiolation. On the other hand, radical difunctionalization of simple alkenes has developed into a powerful tool for the generation of highly functionalized organic compounds commonly with the formation of two C(sp3)-X bonds and has been widely applied in the synthesis of many fluorinated compounds with simultaneous introduction of a fluorine or fluoroalkyl group with another functional group into alkenes.6 Despite the successful development of radical difunctionalization of alkenes for incorporating both the CF3S group and another functional group,5d−l radical intermolecular trifluoromethylthioarylation of alkenes is only recently described in related systems.5m Arenediazonium salts, commonly derived from economical arylamines under mild conditions in high yields, are very important organic intermediates that have been extensively utilized in organic synthesis due to their ready availability, rich reactivity, and diverse transformations.7 Besides their classical applications in aromatic substituents, they are important sources of aryl radicals and extensively used in the famous Meerwein arylation.8 Although much progress has been achieved on Meerwein arylation of alkenes with the © 2018 American Chemical Society

Scheme 1. Oxidative Radical Trilfuoromethylthiolation

decarboxylative radical trifluoromethylthiolation of aliphatic carboxylic acids by AgSCF3/selectfluor was developed (Scheme 1b).5c As an extension of our oxidative radical trilfuoromethylthiolation, we wish to present herein the first example of oxidative radical intermolecular trifluoromethylthioarylation of styrenes with arenediazonium salts and copper(I) trifluoromethylthiolate (CuSCF3)10 under mild conditions, efficiently leading to simultaneous formation of both C(sp3)-SCF3 and C(sp3)-aryl bonds (Scheme 1c). Our initial study commenced with the attempted reaction of 4-methoxybenzenediazonium tetrafluoroborate 1a with methyl acrylate using silver(I) trifluoromethylthiolate (AgSCF3) or CuSCF3 as CF3S source under an Ar atmosphere in DMSO at room temperature for 1 h (Scheme 2). It was found that the Received: March 14, 2018 Published: April 16, 2018 5836

DOI: 10.1021/acs.joc.8b00650 J. Org. Chem. 2018, 83, 5836−5843

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The Journal of Organic Chemistry Table 1. Optimization of Reaction Conditionsa

Scheme 2. Reaction of 4-Methoxybenzenediazonium Tetrafluoroborate 1a with Methyl Acrylate and AgSCF3 or CuSCF3 under Various Conditions

entry 1 2 3 4 5 6 7 8 9 10 11 12

reaction proceeded fast and mainly led to a mixture of various trifluoromethylthioarylation polymethyl acrylates with a small amount of Sandmeyer product. Careful examination of the influence of the number of equivalents of 1a and methyl acrylate, solvents, and additive sequence did not provide better results (see the Supporting Information for details). These results suggest that 1a is very prone to undergoing telomerization, although 1a as an electron-deficient olefin is the preferred substrate for Meerwein arylations and comparatively fast addition of aryl radical to the olefin allows effective suppression of the corresponding Sandmeyer product. For the desired trifluoromethylthioarylation product to be achieved, it is very important to maintain the specific reaction order among the aryl radical source, the olefin, and the trapping reagent.8a Considering that arenediazonium salt 1a and CF3S source in the above reaction system are not easily changed, we reasoned that the intermolecular trifluoromethylthioarylation may be improved by switching the activated olefin methyl acrylate to styrene, which has comparatively fast addition with aryl radical and is not prone to telomerization compared with methyl acrylate. We then focused on optimization of reaction conditions of the trifluoromethylthioarylation of styrene 2a with the arenediazonium salt and AgSCF3 or CuSCF3 (Table 1). To our delight, the reaction of 1a with 2a and CuSCF3 or AgSCF3 + CuI in DMSO at room temperature for 1 h successfully resulted in the desired trifluoromethylthioarylation product 3a with almost no formation of various trifluoromethylthioarylation polystyrenes or Sandmeyer product being observed, whereas no desired product was formed with the use of AgSCF3 under similar conditions (Table 1, entries 1−3). These results exhibit the importance of the copper cation for the reaction. Moreover, it was found that the ligand plays a key role in the reaction and that 1,10-phenanthroline (phen) stood out as the best one among the ligands examined (Table 1, entries 4−8). However, a stoichiometric amount of the ligand phen was required for the desired reaction, whereas a lesser amount of phen led to lower yields of the desired product (see the Supporting Information for details). In addition, a careful survey of solvents revealed that DMSO was the best solvent and that water was harmful for the desired reaction (Table 1, entries 8−12). With the optimized reaction conditions in hand (Table 1, entry 8), the substrate scope of various styrenes was examined. As can be seen in Scheme 3, a series of substrates bearing electron-rich (3b−c) and electron-deficient (3i,j) groups were

MSCF3 b

AgSCF3 + CuI CuSCF3 AgSCF3 CuSCF3 CuSCF3 AgSCF3 + CuIb CuSCF3 CuSCF3 CuSCF3 CuSCF3 CuSCF3 CuSCF3

ligand

solvent

yield (%)d

c c c 2,2′-bpyf L1g 1,10-pheni L2h 1,10-pheni 1,10-pheni 1,10-pheni 1,10-pheni 1,10-pheni

DMSO DMSO DMSO DMSO DMSO DMSO DMSO DMSO DMF CH3CN acetone DMSOe

25 32 0 30 22 46 23 80 38 38 16 0

a

Reaction conditions: MSCF3 (0.2 mmol, 1.0 equiv), ligand (0.2 mmol, 1.0 equiv), 1a (0.6 mmol, 3.0 equiv), 2a (1.2 mmol, 6.0 equiv), solvent (2 mL), Ar atmosphere, RT, 1 h. bAgSCF3 (0.2 mmol) and CuI (0.2 mmol) were used. cNo ligand was used. dYields were determined by 19F NMR spectroscopy using trifluoromethylbenzene as an internal standard. eDMSO:H2O = 95:5 vol/vol was used. f2,2′bpy = 2,2′-bipyridine. gL1 = 4,4′-ditert-butyl-2,2′-bipyridine. hL2 = N,N,N′,N′-tetramethylethylenediamine. i1,10-phen = 1,10-phenanthroline.

Scheme 3. Substrate Scope of Styrenes for the Intermolecular Trifluoromethylthioarylation Reactionsa

a Reaction conditions: CuSCF3 (0.5 mmol, 1.0 equiv), 1,10phenanthroline (0.5 mmol, 1.0 equiv), 1a (1.5 mmol, 3.0 equiv), 2 (3.0 mmol, 6.0 equiv), DMSO (5 mL), Ar atmosphere, RT, 1 h. Yields of isolated products were reported.

all applied to the intermolecular trifluoromethylthioarylation reactions. The structure of the product was unambiguously characterized by X-ray diffraction studies of 3k (see the Supporting Information for details). Interestingly, the position of substituents on the benzene ring of styrene had a slight effect on the reaction because o-, m- and p-substituted styrenes gave similar yields of the desired products (3f−h). Next, the scope of the intermolecular trifluoromethylthioarylation reaction was evaluated on various arenediazonium salts, 5837

DOI: 10.1021/acs.joc.8b00650 J. Org. Chem. 2018, 83, 5836−5843

Note

The Journal of Organic Chemistry and the results are summarized in Scheme 4. A wide range of arenediazonium salts underwent the intermolecular trifluor-

Scheme 5. Proposed Mechanism for the Intermolecular Trifluoromethylthioarylation of Styrenes with Arenediazonium Salts and CuSCF3

Scheme 4. Substrate Scope of Arenediazonium Salts for the Intermolecular Trifluoromethylthioarylation Reactionsa

corresponding [(phen)Cu(II)SCF3]2 species and aryl radical, respectively. Fast addition of the aryl radical with styrenes results in the formation of intermediate A. Its following reaction with (phen)Cu(II)SCF3 could proceed in two different ways. The alkyl radical intermediate A could be trapped by (phen)Cu(II)SCF3 to generate intermediate B, followed by reductive elimination to afford the desired trifluoromethylthioarylation product.12 Alternatively, it might be readily oxidized by Cu(II) cation to generate intermediate C, and the subsequent attack by CF3S ion finished the final desired product. In summary, we have developed the oxidative radical intermolecular trifluoromethylthioarylation of styrenes with arenediazonium salts and CuSCF3 under mild conditions to simultaneously construct both C(sp3)-SCF3 and C(sp3)-aryl bonds. The reaction exhibits broad substrate scope and excellent functional group compatibility. Copper cation and 1,10-phenanthroline play a key role in the reaction. Further investigation on other difunctionalization of alkenes to introduce both CF3S and another functional group is on the way.

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EXPERIMENTAL SECTION

General Information. NMR spectra were obtained on a 400 MHz spectrometer using CDCl3 as deuterated solvents with proton, carbon, and fluorine resonances at 400, 100, and 376 MHz, respectively. 1H and 13C NMR chemical shifts were determined relative to internal standard TMS at δ 0.0 ppm, and 19F NMR chemical shifts were determined relatived to CFCl3 as internal standard. Chemical shifts (δ) are reported in ppm, and coupling constants (J) are in hertz (Hz). The following abbreviations were used to explain the multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad. The NMR yield was determined by 19F NMR using benzotrifluoride (19F NMR: δ −63.0 ppm) as an internal standard before working up the reaction. GC-MS (EI) data were determined on an Agilent 5975C. LRMS (EI) and HRMS (EI) data were tested on a Water Micromass GCT Premier. Element analysis data were determined on Elementar VARIO EL apparatus. IR spectra were recorded on a Thermo Scientific Nicolet 380 FT-IR spectrometer. Unless otherwise noted, solvents were freshly dried and degassed according to the purification handbook Purification of Laboratory Chemicals before use. Flash column chromatography was carried out using 300−400 mesh silica gel. General Procedure for Arenediazonium salts.13 To a solution of arylamine (8.0 mmol, 1.0 equiv) in THF (10.0 mL) was added BF3· Et2O (12.0 mmol, 1.5 equiv) slowly under cooling with an ice−water bath. tBuONO (9.6 mmol, 1.2 equiv) was then added dropwise. The reaction mixture was stirred for 20 min, and then diethyl ether (50 mL) was added. The precipitate formed was filtered, washed with diethyl ether, and dried under reduced pressure at room temperature to give the desired arenediazonium salt. General Procedure for Oxidative Radical Intermolecular Trifluoromethylthioarylation of Various Styrenes with Arenediazonium Salts and CuSCF3. To an oven-dried Schlenk tube was

a

Reaction conditions: CuSCF3 (0.5 mmol, 1.0 equiv), 1,10phenanthroline (0.5 mmol, 1.0 equiv), 2 (3.0 mmol, 6.0 equiv), 1a (1.5 mmol, 3.0 equiv), DMSO (5 mL), Ar atmosphere, RT, 1 h. Yields of isolated products were reported. bCuSCF3 (6.0 mmol, 1.0 equiv), 1,10-phen (6 mmol, 1.0 equiv), 2 (18 mmol, 6.0 equiv), 1a (36 mmol, 3.0 equiv), and DMSO (50 mL) were used. cYields were determined by 19F NMR spectroscopy with trifluoromethylbenzene as an internal standard.

omethylthioarylation with styrenes to produce the desired products in good yields. A variety of functional groups in Scheme 3, including halogens (4a−d, 4k, 4l), nitro (4h), acetyl (4o), cyano (4p), and ether (4g, 4s), were all well-tolerated under the standard conditions. Noticeably, pyridinyl (4n), amino (4t), amido (4r), and carboxyl (4v) groups were also compatible with the reaction conditions, resulting in the corresponding products in good yields, but ortho-substituted arenediazonium salt 4i only resulted in a trace amount of the desired product. Finally, gram-scale synthesis of 4h was conducted, and a good yield of the desired product was obtained, demonstrating good scalability of the reaction. On the basis of the experimental results presented above and the literature,8 a plausible reaction mechanism was proposed as shown in Scheme 5. Dimeric complex [(phen)Cu(I)SCF3]211 was in situ oxidized by arenediazonium salts to produce the 5838

DOI: 10.1021/acs.joc.8b00650 J. Org. Chem. 2018, 83, 5836−5843

Note

The Journal of Organic Chemistry

MHz, CDCl3) δ: −39.69 (s, 3F). 13C NMR (100 MHz, CDCl3) δ: 158.6, 139.0, 131.7, 130.3 (q, J = 305.7 Hz), 130.2, 129.4, 128.8, 121.8, 113.9, 55.2, 50.7 (d, J = 1.2 Hz), 42.2. HRMS (EI): calcd for C16H14BrF3OS (M+) 389.9901, found 389.9903. (1-(3-Bromophenyl)-2-(4-methoxyphenyl)ethyl)(trifluoromethyl)sulfane (3g). This compound was obtained as a colorless liquid in 75% yield (147 mg) by silica gel flash column chromatography eluted with PE:EA = 30:1 v/v. And an analytical sample was obtained by HPLC. 1H NMR (400 MHz, CDCl3) δ: 7.40−7.36 (m, 2H), 7.17− 7.09 (m, 2H), 6.90 (d, J = 8.7 Hz, 2H), 6.75 (d, J = 8.7 Hz, 2H), 4.46− 4.39 (m, 1H), 3.75 (s, 3H), 3.23−3.05 (m, 2H). 19F NMR (376 MHz, CDCl3) δ: −39.71 (s, 3F). 13C NMR (100 MHz, CDCl3) δ: 158.6, 142.4, 131.1, 130.7, 130.2 (q, J = 305.7 Hz), 130.2, 130.1, 128.7, 126.5, 122.6, 113.9, 55.2, 50.7 (d, J = 1.3 Hz), 42.2. HRMS (EI): calcd for C16H14BrF3OS (M+) 389.9901, found 389.9897. (1-(2-Bromophenyl)-2-(4-methoxyphenyl)ethyl)(trifluoromethyl)sulfane (3h). This compound was obtained as a colorless liquid in 80% yield (156 mg) by silica gel flash column chromatography eluted with PE:EA = 30:1 v/v. 1H NMR (400 MHz, CDCl3) δ: 7.50 (d, J = 7.4 Hz, 1H), 7.47−7.40 (m, 1H), 7.30 (t, J = 7.4 Hz, 1H), 7.11 (td, J = 8.0, 1.6 Hz, 1H), 6.97 (d, J = 8.5 Hz, 2H), 6.76 (d, J = 8.6 Hz, 2H), 5.15 (brs, 1H), 3.77 (s, 3H), 3.26−3.09 (m, 2H). 19F NMR (376 MHz, CDCl3) δ: −39.86 (s, 3F). 13C NMR (100 MHz, CDCl3) δ: 158.6, 139.2, 133.0, 130.4 (q, J = 306.0 Hz), 130.3, 129.5, 129.2, 128.7, 127.7, 123.6, 113.7, 55.2, 49.6, 41.6. HRMS (EI): calcd for C16H14BrF3OS (M+) 389.9901, found 389.9894. (2-(4-Methoxyphenyl)-1-(4-nitrophenyl)ethyl)(trifluoromethyl)sulfane (3i). This compound was obtained as a colorless liquid in 76% yield (135 mg) by silica gel flash column chromatography eluted with PE:EA = 10:1 v/v. 1H NMR (400 MHz, CDCl3) δ: 8.15 (d, J = 8.8 Hz, 2H), 7.38 (d, J = 8.8 Hz, 2H), 6.87 (d, J = 8.7 Hz, 2H), 6.75 (d, J = 8.7 Hz, 2H), 4.60−4.54 (m, 1H), 3.76 (s, 3H), 3.29−3.05 (m, 2H). 19F NMR (376 MHz, CDCl3) δ: −39.69 (s, 3F). 13C NMR (100 MHz, CDCl3) δ: 158.8, 147.6, 147.4, 130.1, 130.0 (q, J = 305.7 Hz), 128.7, 128.0, 123.8, 114.0, 55.2, 50.4 (d, J = 1.3 Hz), 41.9. HRMS (EI): calcd for C16H14F3NO3S (M+) 357.0647, found 357.0643. (2-(4-Methoxyphenyl)-1-(3-nitrophenyl)ethyl)(trifluoromethyl)sulfane (3j). This compound was obtained as a colorless liquid in 70% yield (125 mg) by silica gel flash column chromatography eluted with PE:EA = 10:1 v/v. 1H NMR (400 MHz, CDCl3) δ: 7.30 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.4 Hz, 2H), 6.92 (d, J = 8.7 Hz, 2H), 6.74 (d, J = 8.7 Hz, 2H), 4.63−4.57 (m, 1H), 3.74 (s, 3H), 3.26−3.12 (m, 2H), 1.29 (s, 9H). 19F NMR (376 MHz, CDCl3) δ: −39.63 (s, 3F). 13C NMR (100 MHz, CDCl3) δ: 158.8, 148.3, 142.5, 133.9, 130.2, 130.1 (q, J = 305.7 Hz), 129.6, 128.0, 123.0, 122.7, 114.0, 55.2, 50.4 (d, J = 1.3 Hz), 41.9. HRMS (EI): calcd for C16H14F3NO3S (M+) 357.0647, found 357.0638. (1-([1,1′-Biphenyl]-4-yl)-2-(4-methoxyphenyl)ethyl)(trifluoromethyl)sulfane (3k). This compound was obtained as a white solid in 84% yield (164 mg) by silica gel flash column chromatography eluted with PE:EA = 10:1 v/v. 1H NMR (400 MHz, CDCl3) δ: 7.60−7.56 (m, 2H), 7.52 (d, J = 8.3 Hz, 2H), 7.43 (t, J = 7.5 Hz, 2H), 7.37−7.31 (m, 1H), 7.28 (d, J = 8.3 Hz, 2H), 6.93 (d, J = 8.6 Hz, 2H), 6.75 (d, J = 8.7 Hz, 2H), 4.68−4.37 (m, 1H), 3.74 (s, 3H), 3.29−3.16 (m, 2H). 19F NMR (376 MHz, CDCl3) δ: −39.63 (s, 3F). 13C NMR (100 MHz, CDCl3) δ: 158.6, 139.0, 131.7, 130.3 (q, J = 305.7 Hz), 130.2, 129.4, 128.8 (d, J = 2.8 Hz), 121.8, 113.9, 55.2, 50.7 (d, J = 1.2 Hz), 42.2. HRMS (EI): calcd for C22H19F3OS (M+) 388.1109, found 388.1103. Mp 91−92 °C. (2-(4-Fluorophenyl)-1-phenylethyl)(trifluoromethyl)sulfane (4a). This compound was obtained as a yellow liquid in 73% yield (110 mg) by silica gel flash column chromatography eluted with PE:EA = 30:1 v/v. 1H NMR (400 MHz, CDCl3) δ: 7.33−7.25 (m, 3H), 7.21− 7.16 (m, 2H), 6.95−6.85 (m, 4H), 4.50−4.43 (m, 1H), 3.32−3.14 (m, 2H). 19F NMR (376 MHz, CDCl3) δ: −39.72 (s, 3F), −115.80 (ddd, J = 14.0, 8.5, 5.6 Hz). 13C NMR (100 MHz, CDCl3) δ: 161.8 (d, J = 245.2 Hz), 139.4, 132.9 (d, J = 3.3 Hz), 130.7 (d, J = 8.0 Hz), 130.4 (q, J = 305.3 Hz), 128.7, 128.1, 127.6, 115.2 (d, J = 21.3 Hz), 51.1, 42.5. HRMS (EI): calcd for C15H12F4S (M+) 300.0596, found 300.0593.

added CuSCF3 (98.5 mg, 0.5 mmol), 1,10-phenanthroline (36.0 mg, 0.5 mmol), and freshly distilled DMSO (5.0 mL) under an Ar atmosphere at room temperature. After stirring for 10 min, styrene (3.0 mmol) and arenediazonium salts (1.5 mmol) were added in turn. The mixture was stirred at room temperature for 1 h and concentrated under reduced pressure after extraction. The crude product was purified by column chromatography on silica gel or HPLC to give the desired product. (2-(4-Methoxyphenyl)-1-phenylethyl)(trifluoromethyl)sulfane (3a). This compound was obtained as a colorless liquid in 81% yield (127 mg) by silica gel flash column chromatography eluted with PE:EA = 30:1 v/v. 1H NMR (400 MHz, CDCl3) δ: 7.31−7.19 (m, 5H), 6.89 (d, J = 8.5, 2H), 6.73 (d, J = 8.5, 2H), 4.53−4.44 (m, 1H), 3.74 (s, 3H), 3.27−3.08 (m, 2H). 19F NMR (376 MHz, CDCl3) δ: −39.72 (s, 3F). 13C NMR (100 MHz, CDCl3) δ: 158.6, 134.0, 130.6 (q, J = 305.7 Hz), 131.0, 129.5, 128.8, 128.4, 127.9, 113.9, 55.3, 51.5(d, J = 1.2 Hz), 42.6. HRMS (EI): calcd for C16H15F3OS (M+) 312.0796, found 312.0789. (2-(4-Methoxyphenyl)-1-(p-tolyl)ethyl)(trifluoromethyl)sulfane (3b). This compound was obtained as a colorless liquid in 76% yield (128 mg) by silica gel flash column chromatography eluted with PE:EA = 30:1 v/v. And an analytical sample was obtained by HPLC. 1H NMR (400 MHz, CDCl3) δ: 7.09 (s, 3H), 6.91 (d, J = 8.6 Hz, 2H), 6.74 (d, J = 8.6 Hz, 1H), 4.49−4.40 (m, 1H), 3.74 (s, 3H), 3.28−3.08 (m, 2H), 2.31 (s, 3H). 19F NMR (376 MHz, CDCl3) δ: −39.72 (s, 3F). 13C NMR (100 MHz, CDCl3) δ: 158.4, 137.6, 136.7, 130.5 (q, J = 305.7 Hz), 130.2, 129.5, 129.3, 127.6, 113.7, 55.2, 51.2 (d, J = 1.3 Hz), 42.4, 21.1. HRMS (EI): calcd for C17H17F3OS (M+) 326.0952, found 326.0944. ( 1 - (4 - ( te rt - B u ty l) p h e n y l )- 2 - ( 4- m e t h o x y ph e n y l) e t h y l ) (trifluoromethyl)sulfane (3c). This compound was obtained as a colorless liquid in 82% yield (145 mg) by silica gel flash column chromatography eluted with PE:EA = 30:1 v/v. And an analytical sample was obtained by HPLC. 1H NMR (400 MHz, CDCl3) δ: 7.30 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.4 Hz, 2H), 6.92 (d, J = 8.7 Hz, 2H), 6.74 (d, J = 8.7 Hz, 2H), 4.49−4.43 (m, 1H), 3.74 (s, 3H), 3.26−3.12 (m, 2H), 1.29 (s, 9H). 19F NMR (376 MHz, CDCl3) δ: −39.72 (s, 3F). 13C NMR (100 MHz, CDCl3) δ: 158.4, 150.9, 136.7, 130.6 (q, J = 305.7 Hz), 130.2, 129.6, 127.3, 125.5, 113.7, 55.2, 51.1 (d, J = 1.2 Hz), 42.4, 34.5, 31.3. HRMS (EI): calcd for C20H23F3OS (M+) 368.1422, found 368.1425. (1-(4-Fluorophenyl)-2-(4-methoxyphenyl)ethyl)(trifluoromethyl)sulfane (3d). This compound was obtained as a colorless liquid in 81% yield (134 mg) by silica gel flash column chromatography eluted with PE:EA = 30:1 v/v. 1H NMR (400 MHz, CDCl3) δ: 7.19−7.14 (m, 2H), 6.96 (t, J = 8.6 Hz, 2H), 6.87 (d, J = 8.6 Hz, 2H), 6.74 (d, J = 8.7 Hz, 2H), 4.51−4.46 (m, 1H), 3.75 (s, 3H), 3.26−3.01 (m, 2H). 19F NMR (376 MHz, CDCl3) δ: −39.73 (s, 3F), −114.04, −114.11 (m, 1F). 13C NMR (100 MHz, CDCl3) δ: 162.2 (d, J = 246.9 Hz), 158.6, 135.6 (d, J = 3.3 Hz), 130.4 (q, J = 305.3 Hz), 130.2, 129.4 (d, J = 8.2 Hz), 129.0, 115.5 (d, J = 21.7 Hz), 113.8, 55.2, 50.6 (d, J = 1.1 Hz), 42.4. HRMS (EI): calcd for C16H14F4OS (M+) 330.0702, found 330.0704. (1-(4-Chlorophenyl)-2-(4-methoxyphenyl)ethyl)(trifluoromethyl)sulfane (3e). This compound was obtained as a colorless liquid in 80% yield (139 mg) by silica gel flash column chromatography eluted with PE:EA = 30:1 v/v. And an analytical sample was obtained by HPLC. 1H NMR (400 MHz, CDCl3) δ: 7.25 (d, J = 8.5 Hz, 2H), 7.13 (d, J = 8.5 Hz, 2H), 6.88 (d, J = 8.6 Hz, 2H), 6.74 (d, J = 8.7 Hz, 2H), 4.49−4.38 (m, 1H), 3.74 (s, 3H), 3.26−3.03 (m, 2H). 19F NMR (376 MHz, CDCl3) δ: −39.68 (s, 3F). 13C NMR (100 MHz, CDCl3) δ: 158.6, 138.5, 133.7, 130.3 (q, J = 305.7 Hz), 130.2, 129.1, 128.8, 125.7, 113.8, 55.2, 50.6 (d, J = 1.4 Hz), 42.2. HRMS (EI): calcd for C16H14ClF3OS (M+) 346.0406, found 346.0402. (1-(4-Bromophenyl)-2-(4-methoxyphenyl)ethyl)(trifluoromethyl)sulfane (3f). This compound was obtained as a colorless liquid in 75% yield (146 mg) by silica gel flash column chromatography eluted with PE:EA = 30:1 v/v. 1H NMR (400 MHz, CDCl3) δ: 7.40 (d, J = 8.4, 2H), 7.08 (d, J = 8.5, 2H), 6.88 (d, J = 8.5, 2H), 6.74 (d, J = 8.6, 2H), 4.49−4.38 (m, 1H), 3.75 (s, 4H), 3.27−3.01 (m, 2H). 19F NMR (376 5839

DOI: 10.1021/acs.joc.8b00650 J. Org. Chem. 2018, 83, 5836−5843

Note

The Journal of Organic Chemistry (2-(4-Bromophenyl)-1-phenylethyl)(trifluoromethyl)sulfane (4b). This compound was obtained as a colorless liquid in 75% yield (135 mg) by silica gel flash column chromatography eluted with PE:EA = 30:1 v/v. And an analytical sample was obtained by HPLC. 1H NMR (400 MHz, CDCl3) δ: 7.34−7.22 (m, 5H), 7.22−7.15 (m, 2H), 6.84 (d, J = 8.2 Hz, 2H), 4.50−4.42 (m, 1H), 3.29−3.13 (m, 2H). 19F NMR (376 MHz, CDCl3) δ: −39.78 (s, 3F). 13C NMR (100 MHz, CDCl3) δ: 139.2, 136.2, 131.5, 130.9, 130.4 (q, J = 305.7 Hz), 128.8, 128.2, 127.6, 120.9, 50.8 (d, J = 1.2 Hz), 42.7. HRMS (EI): calcd for C15H12BrF3S (M+) 359.9795, found 359.9789. (2-(3-Bromophenyl)-1-phenylethyl)(trifluoromethyl)sulfane (4c). This compound was obtained as a yellow liquid in 76% yield (138 mg) by silica gel flash column chromatography eluted with PE:EA = 30:1 v/v. And an analytical sample was obtained by HPLC. 1H NMR (400 MHz, CDCl3) δ: 7.28 (q, J = 8.2 Hz, 4H), 7.20 (d, J = 7.6 Hz, 2H), 7.14 (s, 1H), 7.05 (t, J = 7.8 Hz, 1H), 6.88 (d, J = 7.6 Hz, 1H), 4.54−4.43 (m, 1H), 3.31−3.13 (m, 2H). 19F NMR (376 MHz, CDCl3) δ: −39.76 (s, 3F). 13C NMR (100 MHz, CDCl3) δ: 139.5, 139.2, 132.2, 130.3 (q, J = 305.3 Hz), 130.1, 129.9, 128.8, 128.2, 127.9, 127.6, 122.4, 50.8, 42.9. HRMS (EI): calcd for C15H12BrF3S (M+) 359.9795, found 359.9802. (2-(4-Iodophenyl)-1-phenylethyl)(trifluoromethyl)sulfane (4d). This compound was obtained as a yellow liquid in 77% yield (158 mg) by silica gel flash column chromatography eluted with PE:EA = 30:1 v/v. And an analytical sample was obtained by HPLC. 1H NMR (400 MHz, CDCl3): δ 7.45 (d, J = 8.2 Hz, 2H), 7.26−7.18 (m, 3H), 7.15−7.10 (m, 2H), 6.65 (d, J = 8.1 Hz, 2H), 4.42−4.36 (m, 1H), 3.23−3.04 (m, 2H). 19F NMR (376 MHz, CDCl3): δ −39.82 (s, 3F). 13 C NMR (100 MHz, CDCl3): δ 139.2, 137.4, 136.8, 131.8 (q, J = 305.7 Hz), 131.2, 128.7, 128.1, 127.6, 92.4, 50.7 (d, J = 1.3 Hz), 42.8. HRMS (EI): calcd for C15H12F3IS (M+) 407.9657, found 407.9652. (1-Phenyl-2-(4-(trifluoromethyl)phenyl)ethyl)(trifluoromethyl)sulfane (4e). This compound was obtained as a yellow liquid in 91% yield (160 mg) by silica gel flash column chromatography eluted with PE:EA = 30:1 v/v. And an analytical sample was obtained by HPLC. 1H NMR (400 MHz, CDCl3): δ 7.46 (d, J = 8.2 Hz, 2H), 7.33−7.24 (m, 3H), 7.22−7.17 (m, 2H), 7.09 (d, J = 8.0 Hz, 2H), 4.63−4.39 (m, 1H), 3.42−3.22 (m, 2H). 19F NMR (376 MHz, CDCl3): δ −39.86 (s, 3F), −62.55 (s, 3F). 13C NMR (100 MHz, CDCl3): δ 141.2 (d, J = 1.0 Hz), 139.0, 130.3 (q, J = 305.7 Hz), 129.5, 129.2 (q, J = 32.3 Hz), 128.8, 128.3, 127.6, 125.3 (q, J = 3.7 Hz), 124.1 (q, J = 270.0 Hz), 50.6, 43.0. HRMS (EI): calcd for C16H12F6S (M+) 350.0564, found 350.0563. (2-(4-(tert-Butyl)phenyl)-1-phenylethyl)(trifluoromethyl)sulfane (4f). This compound was obtained as a yellow liquid in 72% yield (122 mg) by silica gel flash column chromatography eluted with PE:EA = 30:1 v/v. And an analytical sample was obtained by HPLC. 1H NMR (400 MHz, CDCl3) δ: 7.31−7.19 (m, 7H), 6.93 (d, J = 7.9 Hz, 2H), 4.56−4.49 (m, 1H), 3.29−3.15 (m, 2H), 1.27 (s, 9H). 19F NMR (376 MHz, CDCl3) δ: −39.72 (s, 3F). 13C NMR (100 MHz, CDCl3) δ: 149.8, 140.1, 134.2, 130.5 (q, J = 305.3 Hz), 128.8, 128.6, 127.9, 127.7, 125.3, 51.1, 42.7, 34.4, 31.3. HRMS (EI): calcd for C19H21F3S (M+) 338.1316, found 338.1311. (2-(2-Methoxyphenyl)-1-phenylethyl)(trifluoromethyl)sulfane (4g). This compound was obtained as a yellow liquid in 70% yield (110 mg) by silica gel flash column chromatography eluted with PE:EA = 30:1 v/v. 1H NMR (400 MHz, CDCl3) δ: 7.29−7.20 (m, 5H), 7.19−7.13 (m, 1H), 6.88−6.72 (m, 3H), 4.72−4.65 (m, 1H) 3.79 (s, 3H), 3.40−3.04 (m, 2H). 19F NMR (376 MHz, CDCl3) δ: −39.86 (s, 3F). 13C NMR (100 MHz, CDCl3) δ: 157.6, 140.7, 131.1, 130.6 (q, J = 305.3 Hz),128.4, 128.3, 127.7, 127.6, 125.8, 120.3, 110.3, 55.2, 49.5 (d, J = 1.3 Hz), 38.3 (d, J = 0.9 Hz). HRMS (EI): calcd for C16H15F3OS (M+) 312.0796, found 312.0793. (2-(3-Nitrophenyl)-1-phenylethyl)(trifluoromethyl)sulfane (4h). This compound was obtained as a yellow liquid in 61% yield (100 mg) by silica gel flash column chromatography eluted with PE:EA = 10:1 v/v. 1H NMR (400 MHz, CDCl3): δ 8.08−8.03 (m, 1H), 7.86 (s, 1H), 7.38 (t, J = 7.9 Hz, 1H), 7.33−7.27 (m, 3H), 7.23−7.18 (m, 2H), 4.55−4.50 (m, 1H), 3.47−3.28 (m, 2H). 19F NMR (376 MHz, CDCl3): δ −39.79 (s, 3F). 13C NMR (100 MHz, CDCl3): δ 148.2,

139.1, 138.6, 135.4, 130.2 (q, J = 305.7 Hz), 129.3, 128.9, 128.5, 127.5, 124.1, 122.1, 50.4 (d, J = 1.5 Hz), 42.8. HRMS (EI): calcd for C15H12F3NO2S (M+) 327.0541, found 327.0538. (1-(4-Nitrophenyl)-2-(p-tolyl)ethyl)(trifluoromethyl)sulfane (4j). This compound was obtained as a yellow liquid in 70% yield (120 mg) by silica gel flash column chromatography eluted with PE:EA = 10:1 v/v. 1H NMR (400 MHz, CDCl3) δ: 8.14 (d, J = 8.7 Hz, 2H), 7.38 (d, J = 8.7 Hz, 2H), 7.02 (d, J = 7.8 Hz, 2H), 6.85 (d, J = 7.9 Hz, 2H), 4.63−4.57 (m, 1H), 3.31−3.07 (m, 2H), 2.28 (s, 3H). 19F NMR (376 MHz, CDCl3) δ: −39.69 (s, 3F). 13C NMR (100 MHz, CDCl3) δ: 147.6, 147.4, 137.0, 132.9, 130.0 (q, J = 306.0 Hz), 129.3, 128.9, 128.7, 123.8, 50.3 (d, J = 1.3 Hz), 42.2, 21.1. HRMS (EI): calcd for C16H14F3NO2S (M+) 341.0697, found 341.0691. (2-(3-Bromophenyl)-1-(4-nitrophenyl)ethyl)(trifluoromethyl)sulfane (4k). This compound was obtained as a yellow liquid in 77% yield (157 mg) by silica gel flash column chromatography eluted with PE:EA = 10:1 v/v. 1H NMR (400 MHz, CDCl3) δ: 8.17 (d, J = 8.3 Hz, 2H), 7.40 (d, J = 8.5 Hz, 2H), 7.35 (d, J = 8.0 Hz, 1H), 7.19 (s, 1H), 7.09 (t, J = 7.8 Hz, 1H), 6.88 (d, J = 7.6 Hz, 1H), 4.63−4.56 (m, 1H), 3.34−3.09 (m, 2H). 19F NMR (376 MHz, CDCl3) δ: −39.67 (s, 3F). 13 C NMR (100 MHz, CDCl3) δ: 147.6, 146.9, 138.3, 132.1, 130.6, 130.2, 129.9 (q, J = 306.0 Hz), 128.6, 127.7, 124.0, 122.7, 49.9 (d, J = 1.4 Hz), 42.1. HRMS (EI): calcd for C15H11BrF3NO2S (M+) 404.9646, found 404.9643. (2-(4-Chlorophenyl)-1-(4-nitrophenyl)ethyl)(trifluoromethyl)sulfane (4l). This compound was obtained as a yellow solid in 74% yield (133 mg) by silica gel flash column chromatography eluted with PE:EA = 10:1 v/v. 1H NMR (400 MHz, CDCl3) δ: 8.16 (d, J = 8.6 Hz, 2H), 7.38 (d, J = 8.7 Hz, 2H), 7.20 (d, J = 8.3 Hz, 2H), 6.91 (d, J = 8.3 Hz, 2H), 4.61−4.54 (m, 1H), 3.34−3.09 (m, 2H). 19F NMR (376 MHz, CDCl3) δ: −39.71 (s, 3F). 13C NMR (100 MHz, CDCl3) δ: 147.6, 147.0, 134.5, 133.4, 130.4, 129.9 (q, J = 306.0 Hz), 128.9, 128.6, 124.0, 45.0 (d, J = 1.4 Hz), 42.0. HRMS (EI): calcd for C15H11ClF3NO2S (M+) 361.0151, found 361.0150. Mp 73−74 °C. (2-(Naphthalen-1-yl)-1-(4-nitrophenyl)ethyl)(trifluoromethyl)sulfan (4m). This compound was obtained as a red liquid in 75% yield (142 mg) by silica gel flash column chromatography eluted with PE:EA = 10:1 v/v. 1H NMR (400 MHz, CDCl3) δ: 8.10 (d, J = 8.8 Hz, 2H), 7.93 (d, J = 8.2 Hz, 1H), 7.88 (d, J = 7.4 Hz, 1H), 7.73 (d, J = 8.2 Hz, 1H), 7.58 (dd, J = 15.2, 1.4 Hz, 1H), 7.54−7.49 (m, 1H), 7.32 (d, J = 8.7 Hz, 2H), 7.22 (d, J = 8.2 Hz, 1H), 6.92 (d, J = 7.0 Hz, 1H), 4.85−4.78 (m, 1H), 3.92−3.43 (m, 2H). 19F NMR (376 MHz, CDCl3) δ: −39.60 (s, 3F). 13C NMR (100 MHz, CDCl3) δ: 147.7, 147.5, 134.0, 131.9, 131.4, 130.0 (q, J = 306.0 Hz), 129.3, 128.5, 128.3, 128.0, 126.7, 125.9, 125.1, 123.8, 122.6, 49.1 (d, J = 1.3 Hz), 40.1. HRMS (EI): calcd for C19H14F3NO2S (M+) 377.0697, found 377.0699. 3-(2-(4-Nitrophenyl)-2-((trifluoromethyl)thio)ethyl)quinoline (4n). This compound was obtained as a yellow liquid in 80% yield (151 mg) by silica gel flash column chromatography eluted with PE:EA = 10:1 v/v. 1H NMR (400 MHz, CDCl3): δ 8.54 (d, J = 2.1 Hz, 1H), 8.16 (d, J = 8.8 Hz, 2H), 8.05 (d, J = 8.5 Hz, 1H), 7.80 (d, 1H), 7.75−7.67 (m, 2H), 7.58−7.52 (m, 1H), 7.44 (d, J = 8.7 Hz, 2H), 4.75−4.69 (m, 1H), 3.56−3.35 (m, 2H). 19F NMR (376 MHz, CDCl3): δ −39.61 (s, 3F). 13C NMR (100 MHz, CDCl3): δ 151.1, 147.7, 147.3, 146.6, 135.9, 129.8 (q, J = 306.0 Hz), 129.7, 129.3, 128.9, 128.6, 127.6, 127.5, 127.2, 124.2, 49.8 (d, J = 1.4 Hz), 39.9. HRMS (EI): calcd for C18H13F3N2O2S (M+) 378.0650, found 378.0647. 1-(3-(2-(4-Nitrophenyl)-2-((trifluoromethyl)thio)ethyl)phenyl)ethanone (4o). This compound was obtained as a yellow liquid in 57% yield (105 mg) by silica gel flash column chromatography eluted with PE:EA = 10:1 v/v. 1H NMR (400 MHz, CDCl3) δ: 8.16 (d, J = 8.8 Hz, 2H), 7.80 (d, J = 7.8 Hz, 1H), 7.66 (s, 1H), 7.41 (d, J = 8.8 Hz, 2H), 7.34 (t, J = 7.7 Hz, 1H), 7.16 (d, J = 7.6 Hz, 1H), 4.67−4.61 (m, 1H), 3.41−3.19 (m, 2H), 2.56 (s, 3H). 19F NMR (376 MHz, CDCl3) δ: −39.64 (s, 3F). 13C NMR (100 MHz, CDCl3) δ: 197.6, 147.6, 147.1, 137.5, 136.7, 133.7, 129.8 (q, J = 306.0 Hz), 128.9, 128.6, 128.6, 127.7, 124.0, 49.9 (d, J = 1.6 Hz), 42.3, 26.6. HRMS (EI): calcd for C17H14F3NO3S(M+) 369.0647, found 369.0640. 5840

DOI: 10.1021/acs.joc.8b00650 J. Org. Chem. 2018, 83, 5836−5843

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The Journal of Organic Chemistry

NMR (376 MHz, CDCl3): δ −39.72 (s, 3F). 13C NMR (100 MHz, CDCl3): δ 171.1, 147.6, 146.8, 142.2, 130.6, 129.3, 128.6, 128.4, 128.3 (q, J = 306.3 Hz), 124.0, 49.7 (d, J = 1.4 Hz), 42.6. HRMS (EI): calcd for C16H12F3NO4S (M+) 371.0439, found 371.0431. Mp 149−150 °C.

4-(2-(4-Nitrophenyl)-2-((trifluoromethyl)thio)ethyl)benzonitrile (4p). This compound was obtained as a yellow solid in 70% yield (124 mg) by silica gel flash column chromatography eluted with PE:EA = 10:1 v/v. 1H NMR (400 MHz, CDCl3): δ 8.18 (d, J = 8.8 Hz, 2H), 7.55 (d, J = 8.3 Hz, 2H), 7.40 (d, J = 8.7 Hz, 2H), 7.12 (d, J = 8.2 Hz, 2H), 4.63−4.57 (m, 1H), 3.44−3.20 (m, 2H). 19F NMR (376 MHz, CDCl3): δ −39.72 (s, 3F). 13C NMR (100 MHz, CDCl3): δ 147.7, 146.5, 141.4, 132.5, 129.9, 129.7 (q, J = 306.0 Hz), 128.5, 124.1, 118.3, 111.6, 49.5 (d, J = 1.6 Hz), 42.5. HRMS (EI): calcd for C16H11F3N2O2S (M+) 352.0493, found 352.0498. Mp 165−166 °C. (2-(4-(Methylsulfonyl)phenyl)-1-(4-nitrophenyl)ethyl)(trifluoromethyl)sulfane (4q). This compound was obtained as a yellow solid in 69% yield (140 mg) by silica gel flash column chromatography eluted with PE:EA = 10:1 v/v. 1H NMR (400 MHz, CDCl3): δ 8.19 (d, J = 8.7 Hz, 2H), 7.83 (d, J = 8.2 Hz, 2H), 7.44 (d, J = 8.7 Hz, 2H), 7.24 (d, J = 8.2 Hz, 2H), 4.68−4.61 (m, 1H), 3.48− 3.24 (m, 2H), 3.04 (s, 3H). 19F NMR (376 MHz, CDCl3): δ −39.68 (s, 3F). 13C NMR (100 MHz, CDCl3): δ 147.7, 146.6, 142.4, 139.7, 130.1, 129.8 (q, J = 306.0 Hz), 128.6, 127.8, 124.2, 49.6 (d, J = 1.6 Hz), 44.4, 42.2. HRMS (EI): calcd for C16H14F3NO4S2 (M+) 405.0316, found 405.0318. Mp 74−75 °C. N-(4-(2-(4-Nitrophenyl)-2-((trifluoromethyl)thio)ethyl)phenyl)acetamide (4r). This compound was obtained as a yellow liquid in 77% yield (148 mg) by silica gel flash column chromatography eluted with PE:EA = 10:1 v/v. 1H NMR (400 MHz, CDCl3) δ: 8.14 (d, J = 8.5 Hz, 2H), 7.38 (d, J = 8.6 Hz, 4H), 7.33−7.28 (m, 1H), 6.95−6.87 (m, 2H), 4.61−4.55 (m, 1H), 3.32−3.07 (m, 2H), 2.15 (s, 3H). 19F NMR (376 MHz, CDCl3) δ: −39.69 (s, 3F). 13C NMR (100 MHz, CDCl3) δ: 168.4, 147.4, 137.2, 131.8, 130.0 (q, J = 306.0 Hz), 129.7, 128.7, 123.9, 119.9, 50.2, 42.0, 24.6. HRMS (ESI/DART): calcd for C17H16F3N2O3S (M + H+) 385.0828, found 385.0825. (2-(4-(Benzyloxy)phenyl)-1-(4-nitrophenyl)ethyl)(trifluoromethyl)sulfane (4s). This compound was obtained as a yellow solid in 70% yield (152 mg) by silica gel flash column chromatography eluted with PE:EA = 10:1 v/v. 1H NMR (400 MHz, CDCl3) δ: 8.14 (d, J = 8.7 Hz, 2H), 7.42−7.31 (m, 6H), 7.26 (s, 1H), 6.89−6.80 (m, 4H), 5.00 (s, 2H), 4.60−4.54 (m, 1H), 3.30−3.03 (m, 2H). 19F NMR (376 MHz, CDCl3) δ: −39.68 (s, 3F). 13C NMR (100 MHz, CDCl3) δ: 158.0, 147.6, 147.4, 136.8, 130.2, 130.0 (q, J = 305.7 Hz), 128.7, 128.6, 128.3, 128.0, 127.5, 123.8, 115.0, 70.0, 50.4 (d, J = 1.2 Hz), 41.9. HRMS (EI): calcd for C22H18F3NO3S (M+) 433.0960, found 433.0955. Mp 63−64 °C. 4-(2-(4-Nitrophenyl)-2-((trifluoromethyl)thio)ethyl)-N-phenylaniline (4t). This compound was obtained as a red liquid in 61% yield (129 mg) by silica gel flash column chromatography eluted with PE:EA = 10:1 v/v. 1H NMR (400 MHz, CDCl3) δ: 8.15 (d, J = 8.7 Hz, 2H), 7.40 (d, J = 8.7 Hz, 2H), 7.28−7.22 (m, 2H), 7.02 (d, J = 7.7 Hz, 2H), 6.93 (dd, J = 14.3, 7.9 Hz, 3H), 6.84 (d, J = 8.4 Hz, 2H), 5.66 (s, 1H), 4.62−4.55 (m, 1H), 3.30−3.03 (m, 2H). 19F NMR (376 MHz, CDCl3) δ: −39.63 (s, 3F). 13C NMR (100 MHz, CDCl3) δ: 147.7, 147.4, 142.6, 142.5, 130.1 (q, J = 306.0 Hz), 130.0, 129.4, 128.8, 128.1, 123.8, 121.4, 118.1, 117.4, 50.4 (d, J = 1.3 Hz), 42.0. HRMS (EI): calcd for C21H17F3N2O2S (M+) 418.0963, found 418.0965. (1-(4-Nitrophenyl)-2-(4-tritylphenyl)ethyl)(trifluoromethyl)sulfane (4u). This compound was obtained as a yellow solid in 80% yield (229 mg) by silica gel flash column chromatography eluted with PE:EA = 10:1 v/v. 1H NMR (400 MHz, CDCl3) δ: 8.10 (d, J = 8.6 Hz, 2H), 7.31 (d, J = 8.7 Hz, 2H), 7.27−7.16 (m, 10H), 7.12 (d, J = 7.1 Hz, 5H), 7.05 (d, J = 8.2 Hz, 2H), 6.82 (d, J = 8.2 Hz, 2H), 4.61−4.55 (m, 1H), 3.36−3.02 (m, 2H). 19F NMR (376 MHz, CDCl3) δ: −39.74 (s, 3F). 13C NMR (100 MHz, CDCl3) δ: 147.4, 147.4, 146.5, 146.1, 133.6, 131.4, 131.02, 129.99 (q, J = 305.3 Hz), 128.7, 128.2, 127.5, 126.0, 123.7, 64.7, 50.1, 42.2. HRMS (EI): calcd for C34H26F3NO2S (M+) 569.1636, found 569.1639. Mp 130−131 °C. 4-(2-(4-Nitrophenyl)-2-((trifluoromethyl)thio)ethyl)benzoic Acid (4v). This compound was obtained as white solid in 73% yield (136 mg) by silica gel flash column chromatography eluted with MeOH:CH2Cl2 = 1:1 v/v. 1H NMR (400 MHz, CDCl3): δ 8.17 (d, J = 8.7 Hz, 2H), 7.98 (d, J = 8.2 Hz, 2H), 7.40 (d, J = 8.7 Hz, 2H), 7.11 (d, J = 8.2 Hz, 2H), 4.68−4.60 (m, 1H), 3.45−3.20 (m, 2H). 19F

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.8b00650. Optimization of reaction conditions and copies of 1H, 19 F, and 13C NMR spectra (PDF) X-ray crystallography data of 3k (CIF) X-ray crystallography data of CuSCF3·0.8H2O (CIF) Accession Codes

CCDC 1829535 and 1814890 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing [email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: + 44 1223 336033.

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Chao Liu: 0000-0003-1968-031X Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The authors gratefully acknowledge the financial support from the National Natural Science Foundation of China (Nos. 21421002, 21672239, 21737004), Science and Technology Commission of Shanghai Municipality (No. 17ZR1437000), and the Foundation of Science and Technology on Sanming Institute of Fluorochemical Industry (FCIT201701BR).

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REFERENCES

(1) (a) Bégué, J.-P.; Bonnet-Delpon, D. Bioorganic and Medicinal Chemistry of Fluorine; John Wiley & Sons: NJ, 2008. (b) Ojima, I. Fluorine in Medicinal Chemistry and Chemical Biology; Wiley-Blackwell: Hong Kong, 2009. (c) Hagmann, W. K. The Many Roles for Fluorine in Medicinal Chemistry. J. Med. Chem. 2008, 51, 4359−4369. (d) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Fluorine in medicinal chemistry. Chem. Soc. Rev. 2008, 37, 320−330. (e) Müller, K.; Faeh, F.; Diederich, F. Fluorine in Pharmaceuticals: Looking Beyond Intuition. Science 2007, 317, 1881−1886. (f) Wang, J.; Sánchez-Roselló, M.; Aceña, J. L.; del Pozo, C.; Sorochinsky, A. E.; Fustero, S.; Soloshonok, V. A.; Liu, H. Fluorine in pharmaceutical industry: fluorine-containing drugs introduced to the market in the last decade (2001−2011). Chem. Rev. 2014, 114, 2432−2506. (g) Gillis, E. P.; Eastman, K. J.; Hill, M. D.; Donnelly, D. J.; Meanwell, N. A. Applications of Fluorine in Medicinal Chemistry. J. Med. Chem. 2015, 58, 8315−8359. (2) For leading reviews on various trifluoromethylthiolation reactions, see: (a) Toulgoat, F.; Alazet, S.; Billard, T. Direct Trifluoromethylthiolation Reactions: The “Renaissance” of an Old Concept. Eur. J. Org. Chem. 2014, 2014, 2415−2428. (b) Chu, L.; Qing, F.-L. Oxidative Trifluoromethylation and Trifluoromethylthiolation Reactions Using (Trifluoromethyl)trimethylsilane as a Nucleophilic CF3 Source. Acc. Chem. Res. 2014, 47, 1513−1522. (c) Xu, X.-H.; Matsuzaki, K.; Shibata, N. Synthetic Methods for Compounds Having CF3-S Units on Carbon by Trifluoromethylation, 5841

DOI: 10.1021/acs.joc.8b00650 J. Org. Chem. 2018, 83, 5836−5843

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DOI: 10.1021/acs.joc.8b00650 J. Org. Chem. 2018, 83, 5836−5843

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The Journal of Organic Chemistry analysis, which is consistent with the literature: Rheingold, A. L.; Munavalli, S.; Rossman, D. I.; Ferguson, C. P. X-ray Crystallographic Structure of the Acetonitrile Solvate of Copper(I) Trifluoromethanethiolate: (CF3SCu)10·8CH3CN. Inorg. Chem. 1994, 33, 1723−1724 For simplicity, we used CuSCF3 instead of CuSCF3·0.8CH3CN in the text. For details, see the Supporting Information. (11) Weng, Z.; He, W.; Chen, C.; Lee, R.; Tan, D.; Lai, Z.; Kong, D.; Yuan, Y.; Huang, K. W. An Air-Stable Copper Reagent for Nucleophilic Trifluoromethylthiolation of Aryl Halides. Angew. Chem., Int. Ed. 2013, 52, 1548−1552. (12) For representative examples of high-valent copper-mediated coupling reactions via radical pathway for the formation of C(sp3)-X bonds, see: (a) Zhu, R.; Buchwald, S. L. Versatile Enantioselective Synthesis of Functionalized Lactones via Copper-Catalyzed Radical Oxyfunctionalization of Alkenes. J. Am. Chem. Soc. 2015, 137, 8069− 8077. (b) Tran, B. L.; Li, B.; Driess, M.; Hartwig, J. F. CopperCatalyzed Intermolecular Amidation and Imidation of Unactivated Alkanes. J. Am. Chem. Soc. 2014, 136, 2555−2563. (c) Zhang, W.; Wang, F.; Mccann, S. D.; Wang, D.; Chen, P.; Stahl, S. S.; Liu, G. Enantioselective cyanation of benzylic C-H bonds via copper-catalyzed radical relay. Science 2016, 353, 1014−1018. For a computational study, see: (d) Lin, J.-S.; Dong, X.-Y.; Li, T.-T.; Jiang, N.-C.; Tan, B.; Liu, X.-Y. A Dual-Catalytic Strategy To Direct Asymmetric Radical Aminotrifluoromethylation of Alkenes. J. Am. Chem. Soc. 2016, 138, 9357−9360. (e) Cheng, Y.-F.; Dong, X.-Y.; Gu, Q.-S.; Yu, Z.-L.; Liu, X.-Y. Achiral Pyridine Ligand-Enabled Enantioselective Radical Oxytrifluoromethylation of Alkenes with Alcohols. Angew. Chem., Int. Ed. 2017, 56, 8883−8886. For reading examples of high-valent copper-mediated coupling reactions via radical pathway for the formation of C(sp2)-X bonds, see: (f) Creutz, S. E.; Lotito, K. J.; Fu, G. C.; Peters, J. C. Photoinduced Ullmann C-N Coupling: Demonstrating the Viability of a Radical Pathway. Science 2012, 338, 647−651. (g) Kainz, Q. M.; Matier, C. D.; Bartoszewicz, A.; Zultanski, S. L.; Peters, J. C.; Fu, G. C. Asymmetric copper-catalyzed C-N crosscouplings induced by visible light. Science 2016, 351, 681−684. (h) Hickman, A. J.; Sanford, M. S. High-valent organometallic copper and palladium in catalysis. Nature 2012, 484, 177−185. (13) Doyle, M. P.; Bryker, W. J. Alkyl nitrite-metal halide deamination reactions. 6. Direct synthesis of arenediazonium tetrafluoroborate salts from aromatic amines, tert-butyl nitrite, and boron trifluoride etherate in anhydrous media. J. Org. Chem. 1979, 44, 1572−1574.

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NOTE ADDED AFTER ASAP PUBLICATION This paper was published ASAP on April 20, 2018. One additional reference was cited. The revised paper was reposted on April 30, 2018.

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DOI: 10.1021/acs.joc.8b00650 J. Org. Chem. 2018, 83, 5836−5843