English

• 1.   Introduction

  The incorporation of fluorine-containing groups into organic compounds can substantially change the chemical, physical, and biological properties.^[1] Among various fluorine-containing groups, the trifluoromethylthio group (CF₃S) has recently experienced a strong acceleration of interest because of its remarkable properties, in particular the strong electron-withdrawing effect and extremely high lipophilicity.^[2] Consequently, the development of new trifluoromethylthiolating reagents and new trifluoromethylthiolation reactions has provided sought-after strategies for the preparation of SCF₃-containing compounds.^[3]

  Recently, difunctionalization reactions have become one of the most powerful strategies for the preparation of fluo- rinated compounds with simultaneous introduction of a fluorine or fluoroalkyl group with another functional group into organic molecules. This strategy has been widely applied in the synthesis of SCF₃-containing compounds.^[4~9] For example, a series of trifluoromethylthiolated alkenes have been prepared by difunctionalization of alkynes. Cao and co-workers reported the anti-Markovnikov- and Markovnikov-selective hydrotrifluoromethylthiolation of terminal alkynes with AgSCF₃.^[5] Recently, Liu^[6a] and our group^[6b] respectively disclosed the tandem trifluoromethylthiolation/aryl migration of aryl propynyl ethers or aryl alkynoates for the preparation of corresponding trifluoromethylthiolated alkenes. The stereoselective bis-trifluoro- methylthiolation of alkynes was reported by Tlili and Billard^[7a] as well as by our group.^[7b] Very recently, Yi and Zhang et al.^[8] developed a chlorotrifluoromethylthiolation of alkynes using CF₃SO₂Cl as a bifunctionalization reagent.

  Oxytrifluoromethylthiolation of alkynes is a useful bifunctionalization reaction because O-containing groups (OSO₂R, OCOR, OH, etc.) could be readily transformed to other functional groups. The Billard group^[9a] first reported the oxytrifluoromethylthiolation of alkynes with an electrophilic trifluoromethylthiolating reagent under BF₃•Et₂O activation (Scheme 1a). Recently, Zhao et al.^[9b] disclosed a selenide-catalyzed regio- and stereo-selective difunctionalization of alkynes to afford trifluoromethylthiolated alkenyl triflates (Scheme 1b). However, these electrophilic processes are limited to electron-rich alkynes. To the best of our knowledge, the oxytrifluoromethylthiolation of alkynes bearing electron-withdrawing substituents remains underexplored. To extend the substrate scope of oxytrifluoromethylthiolation, and as part of our continued interest in the difunctionalization reactions, ^{[4b, m, 6b, 7b, 10]} herein we disclose a copper-catalyzed oxidative hydroxytrifluoromethylthiolation of arylpropynones with AgSCF₃ (Scheme 1c).

  Scheme 1

  

  Scheme 1.  Oxytrifluoromethylthiolation of alkynes

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  2.   Results and discussion

  Our initial attempt began by employing 4-phenylbut- 3-yn-2-one (1a) as the model substrate with AgSCF₃ and H₂O as the SCF₃ and OH sources, respectively (Table 1). However, the reaction in the presence of (NH₄)₂S₂O₈ in MeCN could not yield the desired trifluoromethylthiolated enol 2a (Entry 1). To our delight, 2a was formed in 32% yield when catalytic Cu(OAc)₂ was added to the reaction mixture (Entry 2). The screening of oxidants demonstrated that original (NH₄)₂S₂O₈ was the best of choice (Entries 3~5). Subsequently, a series of Cu salts including CuCl₂, CuF₂, CuSO₄, CuCl, Cu(OTf)₂, Cu(TFA)₂, and CuCN were investigated (Entries 6~12), but none of them gave better result. The addition of catalytic monodentate or bidentate ligand was found to be beneficial for the yield (Entries 13~19). Among the ligands L1~L7 tested, 4, 4'-dimethyl- 2, 2'-bipyridine (dmbpy, L3) was optimal, affording 2a in 46% yield (Entry 15). Finally, the effect of solvent on the reaction was examined. Switching MeCN to THF, DMF, or MeCN/H₂O resulted in much lower yields (Entries 20~22). The use of HOAc or HCO₂H as a co-solvent could sharply improve the yields (Entries 23 and 24), whereas slightly lower yield was obtained when the reaction was performed in MeCN/TFA (Entry 25).

  Table 1

  

  Table 1.  Optimization of reaction conditions ^a

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  Entry	Oxidant	Additive	Solvent	Yieldb/%
  1	(NH4)2S2O8	—	MeCN	0
  2	(NH4)2S2O8	Cu(OAc)2	MeCN	32
  3	Na2S2O8	Cu(OAc)2	MeCN	29
  4	K2S2O8	Cu(OAc)2	MeCN	22
  5	TBHP	Cu(OAc)2	MeCN	Trace
  6	(NH4)2S2O8	CuCl2	MeCN	24
  7	(NH4)2S2O8	CuF2	MeCN	27
  8	(NH4)2S2O8	CuSO4	MeCN	15
  9	(NH4)2S2O8	Cu(OTf)2	MeCN	19
  10	(NH4)2S2O8	Cu(TFA)2	MeCN	11
  11	(NH4)2S2O8	CuCI	MeCN	24
  12	(NH4)2S2O8	CuCN	MeCN	19
  13	(NH4)2S2O8	Cu(OAc)2/L1	MeCN	38
  14	(NH4)2S2O8	Cu(OAc)2/L2	MeCN	35
  15	(NH4)2S2O8	Cu(OAc)2/L3	MeCN	46
  16	(NH4)2S2O8	Cu(OAc)2/L4	MeCN	41
  17	(NH4)2S2O8	Cu(OAc)2/L5	MeCN	33
  18	(NH4)2S2O8	Cu(OAc)2/L6	MeCN	40
  19	(NH4)2S2O8	Cu(OAc)2/L7	MeCN	34
  20	(NH4)2S2O8	Cu(OAc)2/L3	THF	13
  21	(NH4)2S2O8	Cu(OAc)2/L3	DMF	19
  22c	(NH4)2S2O8	Cu(OAc)2/L3	MeCN/H2O	8
  23c	(NH4)2S2O8	Cu(OAc)2/L3	MeCN/HOAc	68
  24c	(NH4)2S2O8	Cu(OAc)2/L3	MeCN/HCO2H	89
  25c	(NH4)2S2O8	Cu(OAc)2/L3	MeCN/TFA	35
  a Reaction conditions: 1a (0.1 mmol), AgSCF3 (0.2 mmol), H2O (0.3 mmol), oxidant (0.2 mmol), additive (0.02 mmol), solvent (2.0 mL), under N2, 70 ℃, 3 h. b Yields determined by 19F NMR spectroscopy using trifluoromethybenzene as an internal standard. c MeCN/co-solvent (1.0 mL/1.0 mL).

  With the optimized reaction conditions in hand (Table 1, Entry 19), the scope and limitation of hydroxytrifluoromethylthiolation of arylpropynones were studied. As shown in Table 2, a series of 4-arylbut-3-yn-2-ones (1a~1o) were converted to the corresponding trifluoromethylthiolated enols in moderate to high yields. Notably, in all cases, traces amounts of trifluoromethylthiolated 1, 3-diketones could be detected. This reaction exhibited good functional group compatibility, and different functional groups such as methoxy, fluoro, chloro, nitro, cyano, and trifluoromethyl were well tolerated. Furthermore, the electronic and steric effect of substituent groups exerted a clear influence on this transformation. In general, ortho-substituted (1k) and meta-substituted (1c) substrates distinctly affected the yields, and substrates with electron-deficient moieties (1n, 1o) gave much lower yields than those with electron-rich moieties (1b, 1f). Gratifyingly, this transformation proceeded smoothly for the substrates with a naphthyl group (1m) or a heterocyclic group (2-thienyl, 1p). The final concern was that 1-phenylpent-1-yn-3-one (1q) also showed good compatibility in this reaction system. Notably, when diaryl propynones (R²＝aryl) were subjected to the standard conditions, cascade trifluoromethylthiolation and cyclization happened affording trifluoromethylthiolated indenones as the major products.^[11i]

  Table 2

  

  Table 2.  Hydroxytrifluoromethylthiolation of arylpropynones ^a

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  a Reaction conditions: 1 (0.5 mmol), AgSCF3 (1.0 mmol), H2O (1.5 mmol), (NH4)2S2O8 (1.0 mmol), Cu(OAc)2 (0.1 mmol), L3 (0.1 mmol), MeCN/ HCO2H (5.0 mL/5.0 mL), under N2, 70 ℃, 3 h, isolated yields.

  On the basis of previous reports, a plausible reaction mechanism was proposed (Scheme 2). Initially, AgSCF₃ is oxidized by (NH₄)₂S₂O₈ to furnish the SCF₃ radical.^{[5, 11]} Then, the addition of SCF₃ radical to arylpropynones generates radical intermediate A, which is then oxidized to cation intermediate B by Cu^Ⅱ/(NH₄)₂S₂O₈ (path A). Finally, the attack of cation B with H₂O furnishes the desired product 2. However, an alternative pathway involving the formation of Cu^Ⅲ-complex C^[12] can not be excluded (path B).

  Scheme 2

  

  Scheme 2.  Proposed reaction mechanism

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  3.   Conclusions

  In conclusion, we have developed a copper-catalyzed hydroxytrifluoromethylthiolation of arylpropynones with AgSCF₃ and H₂O as the SCF₃ and OH sources, respectively. This work represents the first example of oxytrifluoromethylthiolation of alkynes bearing electron-withdrawing substituents. A series of trifluoromethylthiolated enols were obtained in moderate to high yields. We believe that this protocol will find applications in the preparation of useful building blocks and bio-relevant molecules.

  4.   Experimental section

  4.1   General information

  ¹H NMR and ¹⁹F NMR (CFCl₃ as outside standard and low field is positive) spectra were recorded on a Bruker AM 400 spectrometer. ¹³C NMR spectra were recorded on a Bruker AM 400 spectrometer. High resolution mass spectra (HRMS) were performed using a GC/MS TOF high-resolution mass spectrometer equipped with a liquid chromatography system. IR spectra were recorded on a Thermo Scientific Nicolet 380 FT-IR spectrometer.

  4.2   General procedure for hydroxytrifluoromethylthiolation of arylpropynones

  A mixture of arylpropynone 1 (0.50 mmol), AgSCF₃ (208.9 mg, 1.0 mmol), H₂O (27 μL, 1.5 mmol), (NH₄)₂- S₂O₈ (228.2 mg, 1.0 mmol), Cu(OAc)₂ (18.2 mg, 0.1 mmol), and 4, 4'-dimethyl-2, 2'-bipyridine (18.4 mg, 0.1 mmol) was added tube that was sealed with a septum. The mixture was evacuated and backfilled with nitrogen three times. MeCN (5.0 mL) and HCO₂H (5.0 mL) were added to the tube. Then, the tube was stirred at 70 ℃ for 3 h. After the reaction was complete, saturated NH₄Cl solution was added. The resulting mixture was extracted with EtOAc for three times. The combined organic layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give product 2.

  (E)-4-Hydroxy-4-phenyl-3-(trifluoromethylthio)but-3-en-2-one (2a)^[13]: yellow oil, 102.7 mg, 78% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.56~7.51 (m, 2H), 7.44~7.38 (m, 1H), 7.38~7.32 (m, 2H), 2.48 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 201.7, 195.0, 135.7, 127.9, 131.3, 129.1 (q, _, J＝312.1 Hz), 128.7, 95.4, 25.2; ¹⁹F NMR (376 MHz, CDCl₃) δ: －45.85 (s, 3F).

  (E)-4-Hydroxy-4-p-tolyl-3-(trifluoromethylthio)but-3-en-2-one (2b): yellow oil, 99.2 mg, 72% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.48 (d, J＝8.2 Hz, 2H), 7.16 (d, J＝7.9 Hz, 2H), 2.48 (s, 3H), 2.33 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 200.6, 193.7, 141.0, 131.8, 128.1 (q, J＝312.1 Hz), 127.9, 127.6, 94.0, 24.1, 20.5; ¹⁹F NMR (376 MHz, CDCl₃) δ: －45.89 (s, 3F); IR (film) ν: 3678, 2933, 1609, 1397, 1100, 825, 750, 565 cm^－1; MS (ESI) m/z: 277 [M+H]⁺; HRMS (ESI-TOF) calcd for C₁₂H₁₂F₃O₂S [M+H]⁺: 277.0505, found 277.0506.

  (E)-4-Hydroxy-4-m-tolyl-3-(trifluoromethylthio)but-3-en-2-one (2c): yellow oil, 61.0 mg, 44% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.30 (s, 2H), 7.19~7.18 (m, 2H), 2.44 (s, 3H), 2.27 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 200.6, 194.2, 136.7, 134.6, 131.0, 128.2 (q, J＝312.1 Hz), 128.1, 126.7, 124.8, 94.3, 24.2, 20.3; ¹⁹F NMR (376 MHz, CDCl₃) δ: －45.84 (s, 3F); IR (film) ν: 3661, 2987, 1695, 1409, 1107, 738 cm^－1; MS (ESI) m/z: 277 [M+H]⁺; HRMS (ESI-TOF) calcd for C₁₂H₁₂F₃O₂S [M+H]⁺: 277.0505, found 277.0503.

  (E)-4-(4-Ethylphenyl)-4-hydroxy-3-(trifluoromethylthio)- but-3-en-2-one (2d): yellow oil, 85.9 mg, 59% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.51 (d, J＝8.2 Hz, 2H), 7.18 (d, J＝8.2 Hz, 2H), 2.63 (q, J＝7.6 Hz, 2H), 2.49 (s, 3H), 1.19 (t, J＝7.6 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 201.7, 194.6, 148.2, 133.0, 129.2 (q, J＝312.1 Hz), 129.1, 127.4, 95.1, 28.9, 25.3, 15.1; ¹⁹F NMR (376 MHz, CDCl₃) δ: －45.87 (s, 3F); IR (film) ν: 3676, 2969, 1609, 1397, 1102, 1018, 838, 751 cm^－1; MS (ESI) m/z: 291 [M+H]⁺; HRMS (ESI-TOF) calcd for C₁₃H₁₄F₃O₂S [M+H]⁺: 291.0661, found 291.0662.

  (E)-4-(4-Butylphenyl)-4-hydroxy-3-(trifluoromethylthio)- but-3-en-2-one (2e): yellow oil, 83.2 mg, 52% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.50 (d, J＝8.2 Hz, 2H), 7.16 (d, J＝7.9 Hz, 2H), 2.58 (t, J＝8.0 Hz, 2H), 2.48 (s, 3H), 1.57~1.51 (m, 2H), 1.31~1.28 (m, 2H), 0.85 (t, J＝7.2 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 200.6, 193.6, 145.9, 131.9, 128.2 (q, J＝312.1 Hz), 128.0, 126.9, 94.0, 34.6, 32.2, 24.3, 21.3, 12.9; ¹⁹F NMR (376MHz, CDCl₃) δ: －45.87 (s, 3F); IR (film) ν: 3673, 2960, 1681, 1603, 1403, 1101, 747 cm^－1; MS (ESI) m/z: 319 [M+H]⁺; HRMS (ESI-TOF) calcd for C₁₅H₁₈F₃O₂S [M+H]⁺: 319.0974, found 319.0973.

  (E)-4-Hydroxy-4-(4-methoxyphenyl)-3-(trifluoromethyl-thio)but-3-en-2-one (2f): yellow oil, 96.9 mg, 66% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.65 (d, J＝8.9 Hz, 2H), 6.86 (d, J＝8.9 Hz, 2H), 3.80 (s, 3H), 2.49 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 200.4, 192.5, 161.3, 130.4, 128.2 (q, J＝313.1 Hz), 126.8, 112.2, 93.5, 54.4, 24.3; ¹⁹F NMR (376 MHz, CDCl₃) δ: －45.97 (s, 3F); IR (film) ν: 3668, 2965, 1602, 1253, 1100, 837, 752 cm^－1; MS (ESI) m/z: 293 [M+H]⁺; HRMS (ESI-TOF) calcd for C₁₂H₁₂F₃O₃S [M+H]⁺: 293.0454, found 293.0455.

  (E)-4-(4-Fluorophenyl)-4-hydroxy-3-(trifluoromethyl-thio)but-3-en-2-one (2g): yellow oil, 71.7 mg, 51% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.62~7.58 (m, 2H), 7.05 (t, J＝8.6 Hz, 2H), 2.49 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 200.5, 192.8, 163.4 (d, J＝251.5 Hz), 130.8 (d, J＝4.0 Hz), 130.3 (d, J＝9.1 Hz), 128.0 (q, J＝312.1 Hz), 114.1 (d, J＝22.2 Hz), 94.1, 24.1; ¹⁹F NMR (376 MHz, CDCl₃) δ: －45.91 (s, 3F), －107.30 (s, 1F); IR (film) ν: 3667, 2984, 1603, 1406, 1104, 841, 748 cm^－1; MS (ESI) m/z: 281 [M+H]⁺; HRMS (ESI-TOF) calcd for C₁₁H₉F₄O₂S [M+H]⁺: 281.0254, found 281.0254.

  (E)-4-(3-Fluorophenyl)-4-hydroxy-3-(trifluoromethyl-thio)but-3-en-2-one (2h): yellow oil, 74.5 mg, 53% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.32~7.31 (m, 2H), 7.25~7.22 (m, 1H), 7.13~7.09 (m, 1H), 2.48 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 201.5, 193.9, 162.0 (d, J＝248.5 Hz), 137.7 (d, J＝7.1 Hz), 129.6 (d, J＝8.1 Hz), 129.0 (q, J＝312.1 Hz), 124.4 (d, J＝3.0 Hz), 118.2 (d, J＝21.2 Hz), 115.8 (d, J＝23.2 Hz), 95.5, 25.0; ¹⁹F NMR (376 MHz, CDCl₃) δ: －45.80 (s, 3F), －112.27 (s, 1F); IR (film) ν: 3670, 2983, 1610, 1435, 1098, 877, 749 cm^－1; MS (ESI) m/z: 281 [M+H]⁺; HRMS (ESI-TOF) calcd for C₁₁H₉F₄O₂S [M+H]⁺: 281.0254, found 281.0256.

  (E)-4-(4-Chlorophenyl)-4-hydroxy-3-(trifluoromethyl-thio)but-3-en-2-one (2i): yellow oil, 88.7 mg, 60% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.50 (d, J＝8.6 Hz, 2H), 7.33 (d, J＝8.6 Hz, 2H), 2.48 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 200.5, 192.9, 136.6, 133.0, 129.2, 128.0 (s, J＝312.1 Hz), 127.2, 94.2, 24.1; ¹⁹F NMR (376 MHz, CDCl₃) δ: －45.84 (s, 3F); IR (film) ν: 3663, 2978, 1607, 1397, 1092, 1013, 835, 750 cm^－1; MS (ESI): m/z 297 [M+H]⁺; HRMS (ESI-TOF) calcd for C₁₁H₉ClF₃O₂S [M+H]⁺: 296.9958, found 296.9956.

  (E)-4-(3-Chlorophenyl)-4-hydroxy-3-(trifluoromethyl-thio) but-3-en-2-one (2j): yellow oil, 81.4 mg, 55% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.51 (t, J＝1.9 Hz, 1H), 7.43~7.35 (m, 2H), 7.29 (t, J＝7.9 Hz, 1H), 2.48 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 201.5, 193.9, 137.4, 134.0, 131.2, 129.3, 129.0 (q, J＝312.1 Hz), 128.6, 126.8, 95.5, 25.0; ¹⁹F NMR (376 MHz, CDCl₃) δ: －45.75 (s, 3F); IR (film) ν: 3665, 2980, 1514, 1397, 1104, 888, 738, 552 cm^－1; MS (ESI) m/z: 297 [M+H]⁺; HRMS (ESI-TOF) calcd for C₁₁H₉ClF₃O₂S [M+H]⁺: 296.9958, found 296.9960.

  (E)-4-(2-Chlorophenyl)-4-hydroxy-3-(trifluoromethyl-thio)but-3-en-2-one (2k): yellow oil, 55.2 mg, 37% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.34~7.23 (m, 4H), 2.47 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 199.7, 195.2, 135.9, 131.2, 130.8, 129.4, 129.2 (q, J＝312.1 Hz), 128.8, 126.6, 97.8, 24.5; ¹⁹F NMR (376 MHz, CDCl₃) δ: －45.31 (s, 3F); IR (film) ν: 3673, 2990, 1588, 1400, 1104, 753 cm^－1; MS (ESI) m/z: 297 [M+H]⁺; HRMS (ESI-TOF) calcd for C₁₁H₉ClF₃O₂S [M+H]⁺: 296.9958, found 296.9957.

  (E)-4-Hydroxy-4-(4-(trifluoromethyl)phenyl)-3-(trifluo-romethylthio)but-3-en-2-one (2l): yellow oil, 68.0 mg, 41% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.66~7.61 (m, 4H), 2.52 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 200.6, 193.1, 138.1, 131.7 (q, J＝33.3 Hz), 127.9 (q, J＝312.1 Hz), 127.9, 124.0 (q, J＝3.0 Hz), 122.6 (q, J＝272.7 Hz), 94.7, 24.0; ¹⁹F NMR (376 MHz, CDCl₃) δ: －45.72 (s, 3F), －63.05 (s, 3F); IR (film) ν: 3676, 2990, 2899, 1400, 1321, 1068, 889 cm^－1; MS (ESI) m/z: 331 [M+H]⁺; HRMS (ESI-TOF) calcd for C₁₂H₉F₆O₂S [M+H]⁺: 331.0222, found 331.0221.

  (E)-4-Hydroxy-4-(naphthalen-1-yl)-3-(trifluoromethyl-thio)but-3-en-2-one (2m): yellow oil, 114.3 mg, 73% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.86 (d, J＝8.1 Hz, 1H), 7.81~7.79 (m, 1H), 7.67~7.65 (m, 1H), 7.47~7.40 (m, 3H), 7.38~7.36 (m, 1H), 2.53 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 200.3, 195.7, 132.5, 132.2, 129.6, 128.6, 127.9 (q, J＝312.1 Hz), 127.5, 126.1, 125.3, 125.0, 123.5, 123.4, 97.1, 24.2; ¹⁹F NMR (376 MHz, CDCl₃) δ: －45.48 (s, 3F); IR (film) ν: 3676, 2990, 2905, 1515, 1403, 1116, 1061, 783 cm^－1; MS (ESI) m/z: 313 [M+H]⁺; HRMS (ESI-TOF) calcd for C₁₅H₁₂F₃O₂S [M+H]⁺: 313.0505, found 313.0503.

  (E)-4-(1-Hydroxy-3-oxo-2-(trifluoromethylthio)but-1-enyl)benzonitrile (2n): yellow oil, 52.0 mg, 36% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.67 (d, J＝8.4 Hz, 2H), 7.61 (d, J＝8.4 Hz, 2H), 2.51 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 200.6, 192.8, 138.8, 130.8, 128.1, 127.8 (q, J＝312.1 Hz), 116.9, 113.7, 94.7, 23.9; ¹⁹F NMR (376 MHz, CDCl₃) δ: －45.68 (s, 3F); IR (film) ν: 3672, 2928, 2231, 1530, 1401, 1105, 840, 732 cm^－1; MS (ESI) m/z: 288 [M+H]⁺; HRMS (ESI-TOF) calcd for C₁₂H₉F₃NO₂S [M+H]⁺: 288.0301, found 288.0298.

  (E)-4-Hydroxy-4-(4-nitrophenyl)-3-(trifluoromethylthio)-but-3-en-2-one (2o): yellow oil, 40.3 mg, 26% yield. ¹H NMR (400 MHz, CDCl₃) δ: 8.22 (d, J＝8.2 Hz, 2H), 7.67 (d, J＝7.9 Hz, 2H), 2.51 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 200.6, 192.7, 148.0, 140.6, 128.5, 127.8 (q, J＝313.1 Hz), 122.2, 94.8, 23.9; ¹⁹F NMR (376 MHz, CDCl₃) δ: －45.68 (s, 3F); IR (film) ν: 3673, 2996, 2899, 1527, 1401, 1107, 862, 832, 708 cm^－1; MS (ESI) m/z: 308 [M+H]⁺; HRMS (ESI-TOF) calcd for C₁₁H₉F₃NO₄S [M+H]⁺: 308.0199, found 308.0199.

  (E)-4-Hydroxy-4-(thiophen-2-yl)-3-(trifluoromethylthio)-but-3-en-2-one (2p): yellow oil, 76.9 mg, 57% yield. ¹H NMR (400 MHz, CDCl₃) δ: 8.23 (dd, J＝4.0, 1.3 Hz, 1H), 7.64 (dd, J＝5.0, 1.3 Hz, 1H), 7.07 (dd, J＝5.0, 4.0 Hz, 1H), 2.47 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 201.4, 183.9, 137.5, 136.6, 135.7, 129.1 (q, J＝313.1 Hz), 127.6, 92.8, 25.2; ¹⁹F NMR (376 MHz, CDCl₃) δ: －45.23 (s, 3F); IR (film) ν: 3674, 2993, 1513, 1408, 1096, 858, 718, 562 cm^－1; MS (ESI): m/z 269 [M+H]⁺; HRMS (ESI- TOF) calcd for C₉H₈F₃O₂S₂ [M+H]⁺: 268.9912, found 268.9910.

  (E)-1-Hydroxy-1-phenyl-2-(trifluoromethylthio)pent-1-en-3-one (2q): yellow oil, 84.6 mg, 61% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.57~7.50 (m, 2H), 7.41 (d, J＝7.3 Hz, 1H), 7.37~7.33 (m, 2H), 2.97~2.83 (m, 2H), 1.15 (t, J＝7.4 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 204.5, 192.9, 134.5, 130.1, 128.0 (q, J＝312.1 Hz), 127.7, 126.8, 93.8, 29.9, 8.1; ¹⁹F NMR (376 MHz, CDCl₃) δ: －45.79 (s, 3F); IR (film) ν: 3673, 2984, 1530, 1397, 1100, 692, 543 cm^－1; MS (ESI) m/z: 277 [M+H]⁺; HRMS (ESI-TOF) calcd for C₁₂H₁₂F₃O₂S [M+H]⁺: 277.0505, found 277.0507.

  Supporting Information  Preparation of substrates. ¹H NMR, ¹³C NMR, and ¹⁹F NMR spectra for all new compounds. The Supporting Information is available free of charge via the Internet at http://sioc-journal.cn/.

• 1. [1]

     (a) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320.
     (b) Meanwell, N. A. J. Med. Chem. 2011, 54, 2529.
     (c) Cametti, M.; Crousse, B.; Metrangolo, P.; Milani, R.; Resnati, G. Chem. Soc. Rev. 2012, 41, 31.
     (d) Wang, J.; Sánchez-Roselló, M.; Aceña, J. L.; del Pozo, C.; Sorochinsky, A. E.; Fustero, S.; Soloshonok, V. A.; Liu, H. Chem. Rev. 2014, 114, 2432.
     (e) Gouverneur, V.; Seppelt, K. Chem. Rev. 2015, 115, 563.
     (f) Zhou, Y.; Wang, J.; Gu, Z.; Wang, S.; Zhu, W.; Aceñ a, J. L.; Soloshonok, V. A.; Izawa, K.; Liu, H. Chem. Rev. 2016, 116, 422.
     (g) Rong, J.; Ni, C.; Wang, Y.; Kuang, C.; Gu, Y.; Hu, J. Acta Chim. Sinica 2017, 75, 105(in Chinese).
     (荣健, 倪传法, 王云泽, 匡翠文, 顾玉诚, 胡金波, 化学学报, 2017, 75, 105.)
     (h) Meanwell, N. A. J. Med. Chem. 2018, 61, 5822.

  2. [2]

     (a) Hansch, C.; Leo, A.; Unger, S. H.; Kim, K. H.; Nikaitani, D.; Lien, E. J. J. Med. Chem. 1973, 16, 1207.
     (b) Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165.

  3. [3]

     (a) Chu, L.; Qing, F.-L. Acc. Chem. Res. 2014, 47, 1513.
     (b) Toulgoat, F.; Alazet, S.; Billard, T. Eur. J. Org. Chem. 2014, 2415.
     (c) Shao, X.; Xu, C.; Lu, L.; Shen, Q. Acc. Chem. Res. 2015, 48, 1227.
     (d) Xu, H.-H.; Matsuzaki, K.; Shibata, N. Chem. Rev. 2015, 115, 731.
     (e) Zhang, K.; Xu, X.-H.; Qing, F.-L. Chin. J. Org. Chem. 2015, 35, 556(in Chinese).
     (张珂, 徐修华, 卿凤翎, 有机化学, 2015, 35, 556.)
     (f) Chachignon, H.; Cahard, D. Chin. J. Chem. 2016, 34, 445.
     (g) Barata-Vallejo, S.; Bonesi, S.; Postigo, A. Org. Biomol. Chem. 2016, 14, 7150.
     (h) Zheng, H.; Huang, Y.; Weng, Z. Tetrahedron Lett. 2016, 57, 1397.

  4. [4]

     (a) Sheng, J.; Li, S.; Wu, J. Chem. Commun. 2014, 50, 578.
     (b) Zhang, K.; Liu, J.-B.; Qing, F.-L. Chem. Commun. 2014, 50, 14157.
     (c) Zhu, L.; Wang, G.; Guo, Q.; Xu, Z.; Zhang, D.; Wang, R. Org. Lett. 2014, 16, 5390.
     (d) Yang, T.; Lu, L.; Shen, Q. Chem. Commun. 2015, 51, 5479.
     (e) Chen, D.-Q.; Gao, P.; Zhou, P.-X.; Song, X.-R.; Qiu, Y.-F.; Liu, X.-Y.; Liang, Y. M. Chem. Commun. 2015, 51, 6637.
     (f) Fuentes, N.; Kong, W.; Fernández-Sánchez, L.; Merino, E.; Nevado, C. J. Am. Chem. Soc. 2015, 137, 964.
     (g) Luo, J.; Zhu, Z.; Liu, Y.; Zhao, X. Org. Lett. 2015, 17, 3620.
     (h) Xu, C.; Shen, Q. Org. Lett. 2015, 17, 4561.
     (i) Liu, X.; An, R.; Zhang, X.; Luo, J.; Zhao, X. Angew. Chem., Int. Ed. 2016, 55, 5846.
     (j) Zhang, P.; Li, M.; Xue, X.-S.; Xu, C.; Zhao, Q.; Liu, Y.; Wang, H.; Guo, Y.; Lu, L.; Shen, Q. J. Org. Chem. 2016, 81, 7486.
     (k) Jin, D.-P.; Gao, P.; Chen, D.-Q.; Chen, S.; Wang, J.; Liu, X.-Y.; Liang, Y.-M. Org. Lett. 2016, 18, 3486.
     (l) Luo, J.; Liu, Y.; Zhao, X. Org. Lett. 2017, 19, 3434.
     (m) Pan, S.; Huang, Y.; Xu, X.-H.; Qing, F.-L. Org. Lett. 2017, 19, 4624.
     (n) Liu, X.; Liang, Y.; Ji, J.; Luo, J.; Zhao, X. J. Am. Chem. Soc. 2018, 140, 4782.
     (o) Xiao, Z.; Liu, Y.; Zheng, L.; Liu, C.; Guo, Y.; Chen, Q.-Y. J. Org. Chem. 2018, 83, 5836.
     (p) Xi, C.-C.; Chen, Z.-M.; Zhang, S.-Y.; Tu, Y.-Q. Org. Lett. 2018, 20, 4227.

  5. [5]

     Wu, W.; Dai, W.; Ji, X.; Cao, S. Org. Lett. 2016, 18, 2918. doi: 10.1021/acs.orglett.6b01286

  6. [6]

     (a) Guo, C.-H.; Chen, D.-Q.; Chen, S.; Liu, X.-Y. Adv. Synth. Catal. 2017, 359, 2901.
     (b) Li, H.; Liu, S.; Huang, Y.; Xu, X.-H.; Qing, F.-L. Chem. Commun. 2017, 53, 10136.

  7. [7]

     (a) Tlili, A.; Alazet, S.; Glenadel, Q.; Billard, T. Chem.-Eur. J. 2016, 22, 10230.
     (b) Pan, S.; Li, H.; Huang, Y.; Xu, X.-H.; Qing, F.-L. Org. Lett. 2017, 19, 3247.

  8. [8]

     Jiang, L.; Ding, T.; Yi, W.-B.; Zeng, X.; Zhang, W. Org. Lett. 2018, 20, 2236. doi: 10.1021/acs.orglett.8b00581

  9. [9]

     (a) Ferry, A.; Billard, T.; Langlois, B. R.; Bacqué, E. Angew. Chem., Int. Ed. 2009, 48, 8551.
     (b) Wu, J.-J.; Xu, J.; Zhao, X. Chem.-Eur. J. 2016, 22, 15265.

  10. [10]

      (a) Yang, Y.; Jiang, X.-L.; Qing, F.-L. J. Org. Chem. 2012, 77, 7538.
      (b) Wu, X.; Chu, L.; Qing, F.-L. Angew. Chem. Int. Ed. 2013, 52, 2198.
      (c) Jiang, X.-Y.; Qing, F.-L. Angew. Chem. Int. Ed. 2013, 52, 14177.
      (d) Yu, W.; Xu, X.-H.; Qing, F.-L. Adv. Synth. Catal. 2015, 357, 2039.
      (e) Yang, B.; Xu, X.-H.; Qing, F.-L. Org. Lett. 2015, 17, 1906.
      (f) Lin, Q.-Y.; Xu, X.-H.; Zhang, K.; Qing, F.-L. Angew. Chem., Int. Ed. 2016, 55, 1479.
      (g) Yang, B.; Xu, X.-H.; Qing, F.-L. Chin. J. Chem. 2016, 34, 465.
      (h) Lin, Q.-Y.; Ran, Y.; Xu, X.-H.; Qing, F.-L. Org. Lett. 2016, 18, 2419.
      (i) Yu, W.; Xu, X.-H.; Qing, F.-L. Org. Lett. 2016, 18, 5130.
      (j) Yang, B.; Xu, X.-H.; Qing, F.-L. Org. Lett. 2016, 18, 5956.
      (k) Yang, B.; Yu, D.; Xu, X.-H.; Qing, F.-L. ACS Catal. 2018, 8, 2839.
      (l) Ouyang, Y.; Xu, X.-H.; Qing, F.-L. Angew. Chem., Int. Ed. 2018, 57, 6926.

  11. [11]

      (a) Yin, F.; Wang, X.-S. Org. Lett. 2014, 16, 1128.
      (b) Guo, S.; Zhang, X.; Tang, P. Angew. Chem., Int. Ed. 2015, 54, 4065.
      (c) Wu, H.; Xiao, Z.; Wu, J.; Guo, Y.; Xiao, J.-C.; Liu, C.; Chen, Q.-Y. Angew. Chem., Int. Ed. 2015, 54, 4070.
      (d) Qiu, Y.-F.; Zhu, X.-Y.; Li, Y.-X.; He, Y.-T.; Yang, F.; Wang, J.; Hua, H.-L.; Zheng, L.; Wang, L.-C.; Liu, X.-Y.; Liang, Y.-M. Org. Lett. 2015, 17, 3694.
      (e) Zeng, Y.-F.; Tan, D.-H.; Chen, Y.; Lv, W.-X.; Liu, X.-G.; Li, Q.; Wang, H. Org. Chem. Front. 2015, 2, 1511.
      (f) Li, C.; Zhang, K.; Xu, X.-H.; Qing, F.-L. Tetrahedron Lett. 2015, 56, 6273.
      (g) Pan, S.; Huang, Y.; Qing, F. L. Chem. Asian J. 2016, 11, 2854.
      (h) Huang, F.-Q.; Wang, Y.-W.; Sun, J.-G.; Xie, J.; Qi, L.-W.; Zhang, B. RSC Adv. 2016, 6, 52710.
      (i) Song, Y.-K.; Qian, P.-C.; Chen, F.; Deng, C.-L.; Zhang, X.-G. Tetrahedron 2016, 72, 7589.
      (j) Ji, M. S.; Wu, Z.; Yu, J. J.; Wan, X. B.; Zhu, C. Adv. Synth. Catal. 2017, 359, 1959.
      (k) He, B.; Xiao, Z.; Wu, H.; Guo, Y.; Chen, Q.-Y.; Liu, C. RSC Adv. 2017, 7, 880.
      (l) Liu, K.; Jin, Q.; Chen, S.; Liu, P. N. RSC Adv. 2017, 7, 1546.
      (m) Li, M.; Petersen, J. L.; Hoover, J. M. Org. Lett. 2017, 19, 638.
      (n) Cheng, Z.-F.; Tao, T.-T.; Feng, Y.-S.; Tang, W.-K.; Xu, J.; Dai, J.-J.; Xu, H.-J. J. Org. Chem. 2018, 83, 499.

  12. [12]

      (a) Ye, Y.; Sanford, M. S. J. Am. Chem. Soc. 2012, 134, 9034.
      (b) Huang, L.; Zheng, S.-C.; Tan, B.; Liu, X.-Y. Chem.-Eur. J. 2015, 18, 6718.
      (c) Yu, L.-Z.; Wei, Y.; Shi, M. Chem. Commun. 2016, 52, 13163.
      (d) Cheng, C.; Liu, S.; Lu, D.; Zhu, G. Org. Lett. 2016, 18, 2852.

  13. [13]

      (a) Wu, W.; Zhang, X.; Liang, F.; Cao, S. Org. Biomol. Chem. 2015, 13, 6992.
      (b) Zhang, J.; Yang, J.-D.; Zheng, H.; Xue, X.-S.; Mayr, H.; Cheng, J.-P. Angew. Chem. Int. Ed. 2018, 57, 12690.

• 

  Scheme 1  Oxytrifluoromethylthiolation of alkynes

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  Scheme 2  Proposed reaction mechanism

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  Table 1.  Optimization of reaction conditions ^a

  Entry	Oxidant	Additive	Solvent	Yieldb/%
  1	(NH4)2S2O8	—	MeCN	0
  2	(NH4)2S2O8	Cu(OAc)2	MeCN	32
  3	Na2S2O8	Cu(OAc)2	MeCN	29
  4	K2S2O8	Cu(OAc)2	MeCN	22
  5	TBHP	Cu(OAc)2	MeCN	Trace
  6	(NH4)2S2O8	CuCl2	MeCN	24
  7	(NH4)2S2O8	CuF2	MeCN	27
  8	(NH4)2S2O8	CuSO4	MeCN	15
  9	(NH4)2S2O8	Cu(OTf)2	MeCN	19
  10	(NH4)2S2O8	Cu(TFA)2	MeCN	11
  11	(NH4)2S2O8	CuCI	MeCN	24
  12	(NH4)2S2O8	CuCN	MeCN	19
  13	(NH4)2S2O8	Cu(OAc)2/L1	MeCN	38
  14	(NH4)2S2O8	Cu(OAc)2/L2	MeCN	35
  15	(NH4)2S2O8	Cu(OAc)2/L3	MeCN	46
  16	(NH4)2S2O8	Cu(OAc)2/L4	MeCN	41
  17	(NH4)2S2O8	Cu(OAc)2/L5	MeCN	33
  18	(NH4)2S2O8	Cu(OAc)2/L6	MeCN	40
  19	(NH4)2S2O8	Cu(OAc)2/L7	MeCN	34
  20	(NH4)2S2O8	Cu(OAc)2/L3	THF	13
  21	(NH4)2S2O8	Cu(OAc)2/L3	DMF	19
  22c	(NH4)2S2O8	Cu(OAc)2/L3	MeCN/H2O	8
  23c	(NH4)2S2O8	Cu(OAc)2/L3	MeCN/HOAc	68
  24c	(NH4)2S2O8	Cu(OAc)2/L3	MeCN/HCO2H	89
  25c	(NH4)2S2O8	Cu(OAc)2/L3	MeCN/TFA	35
  a Reaction conditions: 1a (0.1 mmol), AgSCF3 (0.2 mmol), H2O (0.3 mmol), oxidant (0.2 mmol), additive (0.02 mmol), solvent (2.0 mL), under N2, 70 ℃, 3 h. b Yields determined by 19F NMR spectroscopy using trifluoromethybenzene as an internal standard. c MeCN/co-solvent (1.0 mL/1.0 mL).

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  Table 2.  Hydroxytrifluoromethylthiolation of arylpropynones ^a

  a Reaction conditions: 1 (0.5 mmol), AgSCF3 (1.0 mmol), H2O (1.5 mmol), (NH4)2S2O8 (1.0 mmol), Cu(OAc)2 (0.1 mmol), L3 (0.1 mmol), MeCN/ HCO2H (5.0 mL/5.0 mL), under N2, 70 ℃, 3 h, isolated yields.

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•