English

• 1.   Introduction

  Tetrahydrofuran and tetrahydropyran are essential motifs of many natural products and bioactive molecules.^[1] Thus, their synthesis has attracted many research efforts over the last several decades.^[2] On the other hand, the trifluoromethyl group has recently emerged as a greatly useful tool in pharmaceutical^[3] and agrochemical^[4] sciences due to its unique beneficial effects for enhancing chemical and metabolic stability, bioavailability, and interaction with biologically relevant targets.^[5] Therefore, it is highly desirable to develop efficient methods for introducing trifluoromethyl groups^[6] into tetrahydrofurans and tetrahydropyrans for potential drug and agrochemical discovery.^[7] In this respect, intramolecular 1, 2-alkoxyl-trifluoromethylation of unactivated alkene^[8] represents a particularly convenient way for accessing various sorts of trifluoromethylated tetrahydrofurans and tetrahydropyrans using different sources of trifluoromethyl radicals, such as Togni's reagents, ^[9] Umemoto reagents, ^[10] and trifluoromethyl halides (Scheme 1).^[11] However, both of the former two types of reagents are relatively expensive and high molecular weights, while the last one is volatile, all of which render these sources uneconomical and impractical for large scale preparations. In contrast, the readily commercially available trifluoromethanesulfonyl chloride (TfCl, CF₃SO₂Cl) is relatively inexpensive, of much lower molecular weight, and is a liquid at ambient temperature, all of which make it an ideal trifluoromethyl radical precursor.^[12] As our continuing interest in fluorine chemistry, ^[13] we herein report an efficient and practical protocol for preparation of a variety of trifluoromethylated tetrahydrofurans and tetrahydropyrans using TfCl-participated 1, 2-alkoxyl-trifluoromethylation of unactivated alkene under mild visible-light promoted conditions (Scheme 1).^[14]

  Scheme 1

  

  Scheme 1.  Preparation of tetrahydrofuran and tetrahydropyran via 1, 2-alkoxyl-trifluoromethylation of alkene

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  2.   Results and discussion

  Our investigation began with 1a as a model substrate under our previously employed conditions^[15] for generation of trifluoromethyl radical: photosensitizer [Ir(dtbbpy)-(ppy)₂]PF₆ (1 mol%), trifluoromethyl radical source CF₃S- O₂Cl (1.5 equiv.), basic additive Na₂HPO₄• 12H₂O (2 equiv.), and solvent EtOAc under blue LED (light-emitting diode) irradiation. To our delight, the desired trifluoromethylated tetrahydrofuran 2a was successfully obtained, albeit in low yield (Table 1, Entry 1, 36%). Next, several common solvents (Table 1, Entries 2~11) were screened and chlorinated solvents generally performed better than others. In addition, dichloromethane (DCM) was slightly superior to 1, 2-dichloroethane (Table 1, Entries 2 and 3, 70% and 68%, respectively). In order to further improve the reaction efficiency, then the effect of different inorganic bases as additives was examined (Table 1, Entries 12~15). Unfortunately, all these bases were inferior to the original Na₂HPO₄. Another common photosensitizer Ru(bpy₃)Cl₂• 6H₂O^[14c] was also examined but only low yield of desired product 2a (Table 1, Entry 16) was observed. This result was not unexpected given its relatively low reduction capability (E_red＝－0.81 V and －0.96 V vs SCE for excited states of Ru(bpy₃)²⁺ and [Ir(dtbbpy)(ppy)₂]⁺, respectively).^[14e] In addition, several organic photoredox catalysts, ^[14j] such as 9, 10-dicyanoanthracene, Ph-Acr-Me⁺ClO₄^-, and Mes-Me₂Acr-Me⁺ClO₄^-, were explored (Table 1, Entries 17~19). Unfortunately, none of them provided comparable efficiency with the Ir-based photocatalyst, possibly due to different reaction mechanisms. Therefore, the optimal reaction conditions were identified as follows: [Ir(dtbbpy)-(ppy)₂]PF₆ (1 mol%), CF₃SO₂Cl (1.5 equiv.), and Na₂H- PO₄•12H₂O (2 equiv.) in dichloromethane (DCM) (2 mL) under blue LED irradiation, in which the desired product was obtained in 55% isolated yield on a 0.2 mmol scale (Table 2).

  Table 1

  

  Table 1.  Optimization of reaction conditions^a

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  Entry	Catalyst	Additive	Solvent	Yield/%
  1	[Ir(dtbbpy)(ppy)2]PF6	Na2HPO4•12H2O	EtOAc	36
  2	[Ir(dtbbpy)(ppy)2]PF6	Na2HPO4•12H2O	DCM	70
  3	[Ir(dtbbpy)(ppy)2]PF6	Na2HPO4•12H2O	DCE	68
  4	[Ir(dtbbpy)(ppy)2]PF6	Na2HPO4•12H2O	CH3CN	44
  5	[Ir(dtbbpy)(ppy)2]PF6	Na2HPO4•12H2O	PhF	36
  6	[Ir(dtbbpy)(ppy)2]PF6	Na2HPO4•12H2O	DMF	21
  7	[Ir(dtbbpy)(ppy)2]PF6	Na2HPO4•12H2O	DMSO	Messy
  8	[Ir(dtbbpy)(ppy)2]PF6	Na2HPO4•12H2O	THF	39
  9	[Ir(dtbbpy)(ppy)2]PF6	Na2HPO4•12H2O	1, 4-Dioxane	26
  10	[Ir(dtbbpy)(ppy)2]PF6	Na2HPO4•12H2O	Cyclohexane	Messy
  11	[Ir(dtbbpy)(ppy)2]PF6	Na2HPO4•12H2O	MeOH	39
  12	[Ir(dtbbpy)(ppy)2]PF6	NaHCO3	DCM	55
  13	[Ir(dtbbpy)(ppy)2]PF6	Na2CO3	DCM	56
  14	[Ir(dtbbpy)(ppy)2]PF6	KHCO3	DCM	49
  15	[Ir(dtbbpy)(ppy)2]PF6	K2CO3	DCM	31
  16	Ru(bpy)3Cl2•6H2O	Na2HPO4•12H2O	DCM	45
  17	9, 10-Dicyanoanthracene	Na2HPO4•12H2O	DCM	20
  18	Ph-Acr-Me+ClO4-	Na2HPO4•12H2O	DCM	13
  19	Mes-Me2Acr-Me+ ClO4-	Na2HPO4•12H2O	DCM	28
  a Conditions: 1a (0.1 mmol), catalyst (1 mol%), CF3SO2Cl (1.5 equiv.), and additive (2 equiv.) in solvent (1 mL) under blue LED irradiation for 3 h. Yields were based on 19F NMR spectroscopy using α, α, α-trifluorotoluene as an internal standard.

  Table 2

  

  Table 2.  Substrate scope^a

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  a Conditions: 1 (0.2 mmol), [Ir(dtbbpy)(ppy)2]PF6 (1 mol%), CF3SO2Cl (1.5 equiv.), and Na2HPO4•12H2O (2 equiv.) in DCM (2 mL) under blue LED irradiation for 3 h, unless otherwise noted. Yields were isolated ones, unless otherwise noted. b Reaction time: 1 h. c Reaction Time: 1.5 h. d Yield was based on 19F NMR spectroscopy using α, α, α-trifluorotoluene as an internal standard. e Diastereomeric ratio was determined based on quantitative 13C NMR spectra of inseparable mixtures of both diastereomers.

  With the optimized conditions in hand, the substrate scope of the current alkoxyl-trifluoromethylation reaction was subsequently explored (Table 2). Substrates bearing electron-donating or electron-withdrawing groups on the meta- or para-positions of the alkenyl phenyl rings were tolerated to afford desired trifluoromethylated tetrahydrofurans 2b~2f in 45%~70% isolated yields. The sterically bulky substrates 1g and 1h possessing a 2-methyl substituted phenyl ring and a 1-naphtharene ring also worked well, leading to products 2g and 2h, respectively. A labile benzothiophene ring in substrate 1i survived the reaction conditions to provide product 2i in 40% yield. Noteworthy is that gem-dialkyl-substituted alkene 1j and mono-alkyl- substituted alkenes 1k and 1l were also applicable in the reaction, giving rise to corresponding products in moderate to high yields. In addition, alkenols 1m and 1n bearing only one aryl substituent on the tether also underwent the reaction smoothly, albeit in apparently no diastereoselectivity. Most importantly, substrates 1o~1q with one-carbon- longer tethers were workable under the same conditions to deliver trifluoromethylated tetrahydropyrans 2o~2q in good to excellent yields and low diastereoselectivity. Furthermore, substrate 1r featuring a phenyl-fused tether was also compatible with the reaction conditions to give tetrahydrobenzopyran 2r in moderate yield. The successful formation of trifluoromethylated tetrahydropyran under our conditions is in agreement with literature reports, which indicates that visible-light photoredox catalyzed conditions are more robust and versatile than other conditions in terms of the scope for cyclic ether products.^{[9~11, 16]}

  On the basis of literature reports, we propose a possible reaction pathway for the alkoxyl-trifluoromethylation reaction (Scheme 2). First, the photosensitizer Ir(Ⅲ) complex is converted to its excited state Ir(Ⅲ)* under blue LED irradiation, which subsequently reduces TfCl to provide trifluoromethyl radical and Ir(Ⅳ).^[17] Next, the trifluoromethyl radical adds to alkene 1 to provide alkyl radical Ⅰ. This radical Ⅰ is subsequently oxidized by Ir(Ⅳ) to form carbocation Ⅱ, thus regenerating the initial Ir(Ⅲ) complex. Finally, the desired product 2 is forged upon intramolecularly trapping the carbocation with the alkoxyl group followed by facile deprotonation.

  Scheme 2

  

  Scheme 2.  Mechanistic proposal

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  3.   Summary

  In sum, we have prepared a range of trifluoromethylated tetrahydrofurans and tetrahydropyrans using relative inexpensive and atom-economical trifluoromethanesulfonyl chloride as the trifluoromethyl radical source for radical 1, 2-alkoxyl-trifluoromethyaltion of unactivated alkene under mild visible-light irradiation conditions. This practical protocol may find wide applications in discovering novel drugs and agrochemicals.

  4.   Experimental section

  4.1   General information

  All reactions were carried out under argon using Schlenk techniques. Unless otherwise noted, reagents were purchased at the commercial quality and used without further purification. Analytical thin layer chromatography (TLC) was performed on precoated silica gel 60 GF254 plates. Flash column chromatography was performed using Tsingdao silica gel (60, particle size 0.040~0.063 mm). Visualization on TLC was achieved by use of UV light (254 nm), KMnO₄, or iodine stain. NMR spectra were recorded on a Bruker DPX 400/500 spectrometers at 400/500 MHz for ¹H NMR, 100/125 MHz for ¹³C NMR, and 376 MHz for ¹⁹F NMR in CDCl₃ with tetramethylsilane (TMS) as internal standard. ¹⁹F NMR spectra were recorded on a Bruker DPX 400 MHz spectrometer (CFCl₃ as an external reference). Mass spectrometric data were obtained using a "Bruker Apex IV RTMS".

  4.2   General procedure for visible light promoted alkoxyl-trifluoromethylation of alkene

  To a 5-mL single-necked tube equipped with a magnetic stir bar were added compound 1 (0.2 mmol), [Ir(dtbbpy)-(ppy)₂]PF₆ (1.8 mg, 0.002 mmol) and Na₂HPO₄•12H₂O (143 mg, 0.4 mmol). Then the reaction tube was evacuated with oil pump and back-filled with argon three times. After addition of anhydrous DCM (2 mL) and CF₃SO₂Cl (32 µL, 0.3 mmol) under argon atmosphere, the reaction tube was sealed. And the mixture was stirred under the irradiation with blue LED for appropriate time (1~3 h). Upon completion, the solvent was removed directly under reduced pressure to afford the crude product, which was purified by flash column chromatography to afford the desired product.

  3-Phenyl-3-(2, 2, 2-trifluoroethyl)-2-oxaspiro[4.4]nonane (2a):[9d] Colourless oil, 55% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.47~7.41 (m, 2H), 7.39~7.33 (m, 2H), 7.31~7.25 (m, 1H), 3.83 (d, J＝8.3 Hz, 1H), 3.69 (d, J＝8.3 Hz, 1H), 2.69 (q, J＝10.7 Hz, 2H), 2.43 (d, J＝12.8 Hz, 1H), 2.32 (d, J＝12.7 Hz, 1H), 1.84~1.73 (m, 1H), 1.71~1.43 (m, 5H), 1.43~1.19 (m, 2H).

  3-(3-Methoxyphenyl)-3-(2, 2, 2-trifluoroethyl)-2-oxa-spiro[4.4]nonane (2b):[9d] Colourless oil, 45% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.27 (t, J＝8.0 Hz, 1H), 7.05 (dd, J＝2.6, 1.7 Hz, 1H), 6.98 (ddd, J＝7.7, 1.8, 1.0 Hz, 1H), 6.81 (ddd, J＝8.2, 2.6, 0.9 Hz, 1H), 3.87~3.80 (m, 4H), 3.70 (d, J＝8.3 Hz, 1H), 2.68 (q, J＝10.7 Hz, 2H), 2.42 (d, J＝12.7 Hz, 1H), 2.31 (d, J＝12.8 Hz, 1H), 1.85~1.72 (m, 1H), 1.72~1.44 (m, 5H), 1.43~1.33 (m, 1H), 1.32~1.21 (m, 1H).

  3-(m-Tolyl)-3-(2, 2, 2-trifluoroethyl)-2-oxaspiro[4.4]-nonane (2c):[9d] Colourless oil, 60% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.25~7.15 (m, 3H), 7.08~7.03 (m, 1H), 3.79 (d, J＝8.3 Hz, 1H), 3.66 (d, J＝8.3 Hz, 1H), 2.65 (q, J＝10.7 Hz, 2H), 2.38 (d, J＝12.8 Hz, 1H), 2.36 (s, 3H), 2.29 (d, J＝12.7 Hz, 1H), 1.84~1.69 (m, 1H), 1.70~1.42 (m, 5H), 1.39~1.29 (m, 1H), 1.29~1.18 (m, 1H).

  3-([1, 1'-Biphenyl]-3-yl)-3-(2, 2, 2-trifluoroethyl)-2-oxaspiro[4.4]nonane (2d):[9d] Colourless oil, 55% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.67~7.65 (m, 1H), 7.60 (d, J＝7.4 Hz, 2H), 7.51~7.30 (m, 6H), 3.82 (d, J＝8.3 Hz, 1H), 3.69 (d, J＝8.4 Hz, 1H), 2.71 (q, J＝10.7 Hz, 2H), 2.45 (d, J＝12.7 Hz, 1H), 2.34 (d, J＝12.8 Hz, 1H), 1.84~1.70 (m, 1H), 1.70~1.40 (m, 5H), 1.41~1.29 (m, 1H), 1.33~1.19 (m, 1H).

  3-(2, 2, 2-Trifluoroethyl)-3-(3-(trifluoromethyl)phenyl)-2-oxaspiro[4.4]nonane (2e):[9d] Colourless oil, 53% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.72 (s, 1H), 7.62 (d, J＝7.8 Hz, 1H), 7.54 (d, J＝7.8 Hz, 1H), 7.48 (t, J＝7.7 Hz, 1H), 3.84 (d, J＝8.4 Hz, 1H), 3.69 (d, J＝8.4 Hz, 1H), 2.79~2.62 (m, 2H), 2.43~2.33 (m, 2H), 1.86~1.73 (m, 1H), 1.73~1.43 (m, 5H), 1.40~1.16 (m, 2H).

  3-(p-Tolyl)-3-(2, 2, 2-trifluoroethyl)-2-oxaspiro[4.4]-nonane (2f):[9d] Colourless oil, 70% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.29 (d, J＝7.9 Hz, 2H), 7.13 (d, J＝7.8 Hz, 2H), 3.78 (d, J＝8.3 Hz, 1H), 3.64 (d, J＝8.3 Hz, 1H), 2.65 (q, J＝10.8 Hz, 2H), 2.38 (d, J＝12.7 Hz, 1H), 2.33 (s, 3H), 2.27 (d, J＝12.8 Hz, 1H), 1.84~1.68 (m, 1H), 1.70~1.39 (m, 5H), 1.40~1.26 (m, 1H), 1.29~1.17 (m, 1H).

  3-(o-Tolyl)-3-(2, 2, 2-trifluoroethyl)-2-oxaspiro[4.4]-nonane (2g):[9d] Colourless oil, 68% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.74~7.63 (m, 1H), 7.23~7.07 (m, 3H), 3.79 (d, J＝8.4 Hz, 1H), 3.60 (d, J＝8.4 Hz, 1H), 2.93~2.63 (m, 2H), 2.40~2.31 (m, 5H), 1.90~1.78 (m, 1H), 1.75~1.44 (m, 5H), 1.47~1.22 (m, 2H).

  3-(Naphthalen-1-yl)-3-(2, 2, 2-trifluoroethyl)-2-oxaspiro-[4.4]nonane (2h): Colourless oil, 43% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.96~7.81 (m, 3H), 7.78 (d, J＝8.2 Hz, 1H), 7.54~7.43 (m, 3H), 3.88 (d, J＝8.4 Hz, 1H), 3.70 (d, J＝8.3 Hz, 1H), 3.16~2.89 (m, 2H), 2.71~2.58 (m, 2H), 1.96~1.83 (m, 1H), 1.77~1.53 (m, 5H), 1.57~1.43 (m, 1H), 1.45~1.33 (m, 1H); ¹³C NMR (100 MHz, CDCl₃) δ: 140.75, 134.87, 129.82, 129.64, 128.53, 125.82, 125.64 (q, J＝278.9 Hz), 125.41, 125.06, 124.75, 123.56, 83.30~83.05 (m), 77.79, 53.30~52.90 (m), 51.59, 45.06 (q, J＝26.0 Hz), 38.33, 36.76, 24.95, 24.77; ¹⁹F NMR (376 MHz, CDCl₃) δ: －60.54; HRMS (ESI) calcd for C₂₀H₂₂F₃O [M+H]⁺ 335.1617, found 335.1613.

  3-(Benzo[b]thiophen-3-yl)-3-(2, 2, 2-trifluoroethyl)-2-oxaspiro[4.4]nonane (2i): Colourless oil, 40% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.93~7.87 (m, 1H), 7.85~7.78 (m, 1H), 7.50 (s, 1H), 7.46~7.33 (m, 2H), 3.86 (d, J＝8.4 Hz, 1H), 3.74 (d, J＝8.3 Hz, 1H), 3.00~2.85 (m, 2H), 2.61 (d, J＝12.8 Hz, 1H), 2.42 (d, J＝12.7 Hz, 1H), 1.93~1.79 (m, 1H), 1.78~1.43 (m, 5H), 1.43~1.25 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 141.79, 139.56, 136.51, 124.13, 124.11, 123.41, 122.93, 122.90, 82.35 (q, J＝2.0 Hz), 78.54, 51.38, 50.78, 44.17 (q, J＝26.1 Hz), 38.28, 37.31, 24.84, 24.76; ¹⁹F NMR (376 MHz, CDCl₃) δ: －61.01; HRMS (ESI) calcd for C₁₈H₂₀F₃OS [M+H]⁺ 341.1181, found 341.1190.

  3-Methyl-3-(2, 2, 2-trifluoroethyl)-2-oxaspiro[4.5]decane (2j): Colourless oil, 50% yield. ¹H NMR (500 MHz, CDCl₃) δ: 3.79 (dd, J＝11.9, 3.9 Hz, 1H), 3.68 (dd, J＝11.9, 5.1 Hz, 1H), 2.87~2.72 (m, 2H), 2.06~1.96 (m, 2H), 1.85~1.81 (m, 3H), 1.58~1.32 (m, 10H); ¹³C NMR (125 MHz, CDCl₃) δ: 125.22 (q, J＝279.0 Hz), 68.76~68.65 (m), 66.02 (br s), 49.91 (br s), 49.44 (q, J＝27.2 Hz), 39.69, 35.06, 34.46, 31.48, 26.20, 21.66, 21.60; ¹⁹F NMR (376 MHz, CDCl₃) δ: －59.79; HRMS (ESI) calcd for C₁₂H₂₀F₃O [M+H]⁺ 237.1461, found 237.1459.

  4, 4-Diphenyl-2-(2, 2, 2-trifluoroethyl)tetrahydrofuran (2k): Colourless oil, 82% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.49~7.41 (m, 4H), 7.40~7.33 (m, 4H), 7.32~7.25 (m, 2H), 4.26~4.07 (m, 1H), 2.74~2.36 (m, 4H), 2.04~1.85 (m, 1H), 1.83~1.68 (m, 1H); ¹³C NMR (100 MHz, CDCl₃) δ: 146.76, 146.29, 128.49, 128.47, 127.33, 127.26, 126.09, 126.02, 125.31 (d, J＝277.5 Hz), 77.89, 54.78 (q, J＝2.9 Hz), 42.68 (q, J＝28.6 Hz), 38.33, 32.87; ¹⁹F NMR (376 MHz, CDCl₃) δ: －63.88; HRMS (ESI) calcd for C₁₈H₁₈F₃O [M+H]⁺ 307.1304, found 307.1294.

  4, 4-Diethyl-2-(2, 2, 2-trifluoroethyl)tetrahydrofuran (2l): Colourless oil, 90% yield (based on ¹⁹F NMR). ¹H NMR (400 MHz, CDCl₃) δ: 4.21~4.07 (m, 1H), 2.74~2.50 (m, 2H), 2.01~1.88 (m, 1H), 1.85~1.68 (m, 2H), 1.59~1.43 (m, 5H), 0.98~0.83 (m, 6H); ¹³C NMR (100 MHz, CDCl₃) δ: 125.39 (q, J＝277.6 Hz), 74.35, 54.96 (q, J＝3.2 Hz), 42.59 (q, J＝28.4 Hz), 34.50, 32.30, 31.31, 30.86, 7.92, 7.76; ¹⁹F NMR (376 MHz, CDCl₃) δ: －63.87; HRMS (ESI) calcd for C₁₂H₂₂F₃O [M+H]⁺ 211.1304, found 211.1326.

  2-Phenyl-5-(2, 2, 2-trifluoroethyl)tetrahydrofuran (2m): Colourless oil, 87% yield, dr 1.0:1.0 (based on quantitative ¹³C NMR). ¹H NMR (400 MHz, CDCl₃) δ: 7.40~7.26 (m, 5H+5H), 4.80~4.64 (m, 1H+1H), 4.22~4.07 (m, 1H+1H), 2.69~2.43 (m, 2H+2H), 2.11~1.95 (m, 2H+2H), 1.95~1.81 (m, 2H+1H), 1.79~1.67 (m, 1H); ¹³C NMR (126 MHz, CDCl₃) δ: 144.24, 144.17, 128.79, 128.76, 128.66~122.01 (m, 1C+1C), 128.04, 127.98, 125.88, 125.82, 74.18, 73.59, 54.37 (q, J＝3.3 Hz), 53.97 (q, J＝3.2 Hz), 42.93~42.19 (m, 1C+1C), 35.46, 35.15, 34.71, 34.26; ¹⁹F NMR (376 MHz, CDCl₃) δ: －63.83; HRMS (ESI) calcd for C₁₂H₁₄F₃O [M+H]⁺ 231.0991, found 231.0993.

  2-(4-Methoxyphenyl)-5-(2, 2, 2-trifluoroethyl)tetrahydro- furan (2n): Colourless oil, 71% yield, dr 1.0:1.0 (based on quantitative ¹³C NMR). ¹H NMR (400 MHz, CDCl₃) δ: 7.30~7.21 (m, 2H+2H), 6.93~6.84 (m, 2H+2H), 4.70~4.59 (m, 1H+1H), 4.23~4.06 (m, 1H+1H), 3.80 (s, 3H+3H), 2.69~2.41 (m, 2H+2H), 2.14~1.77 (m, 3H+3H), 1.76~1.62 (m, 1H+1H); ¹³C NMR (125 MHz, CDCl₃) δ: 159.37, 159.33, 136.37, 136.29, 128.67~122.01 (m, 1C+1C), 127.17, 127.10, 114.11, 114.09, 73.77, 73.23, 54.37 (q, J＝3.3 Hz), 53.99 (q, J＝3.2 Hz), 42.93~42.18 (m, 1C+1C), 35.36, 35.08, 34.79, 34.38; ¹⁹F NMR (376 MHz, CDCl₃) δ: －63.83; HRMS (ESI) calcd for C₁₃H₁₆F₃O₂ [M+H]⁺ 261.1097, found 261.1088.

  2-Phenyl-6-(2, 2, 2-trifluoroethyl)tetrahydro-2H-pyran(2o): Colourless oil, 90% yield, dr 1.0:1.1 (based on quantitative ¹³C NMR). ¹H NMR (400 MHz, CDCl₃) δ: 7.47~7.27 (m, 5H+5H), 4.76~4.65 (m, 1H+1H), 4.19~4.05 (m, 1H+1H), 2.74~2.44 (m, 2H+2H), 1.98~1.53 (m, 5H+6H), 1.54~1.38 (m, 1H); ¹³C NMR (125 MHz, CDCl₃) δ: 144.58 (1.1C), 144.56 (1C), 128.67 (2.2C+2C), 127.85 (1.1C), 127.83 (1C), 125.94 (2.2C), 125.90 (2C), 125.36 (d, J＝277.5 Hz, 1.1C+1C), 74.47 (1.1C), 74.38 (1C), 54.14~54.06 (m, 1.1C+1C), 42.83~42.13 (m, 1.1C+1C), 38.20 (1C), 38.18 (1.1C), 37.99 (1C), 37.95 (1.1C), 22.52 (1C), 22.49 (1.1C); ¹⁹F NMR (376 MHz, CDCl₃) δ: －63.78; HRMS (ESI) calcd for C₁₃H₁₆F₃O [M+H]⁺ 245.1148, found 245.1139.

  2-(4-Methoxyphenyl)-6-(2, 2, 2-trifluoroethyl)tetrahydro-2H-pyran (2p): Colourless oil, 75% yield, dr 1.0:1.0 (based on quantitative ¹³C NMR). ¹H NMR (400 MHz, CDCl₃) δ: 7.28 (d, J＝8.5 Hz, 2H+2H), 6.91 (d, J＝8.7 Hz, 2H+2H), 4.68~4.57 (m, 1H+1H), 4.17~4.04 (m, 1H+1H), 3.83 (s, 3H+3H), 2.72~2.43 (m, 2H+2H), 1.94~1.51 (m, 5H+6H), 1.51~1.36 (m, 1H); ¹³C NMR (125 MHz, CDCl₃) δ: 159.24 (1.1C), 159.23 (1C), 136.73 (1C), 136.70 (1.1C), 127.21 (2.2C), 127.17 (2C), 125.37 (d, J＝277.4 Hz, 1.1C+1C), 114.02 (2.2C+2C), 74.07 (1C), 74.00 (1.1C), 55.39 (1.1C+1C), 54.16~54.07 (m, 1.1C+1C), 42.84~42.13 (m, 1.1C+1C), 38.11 (1C), 38.09 (1.1C), 38.00 (1.1C), 37.97 (1C), 22.58 (1C), 22.55 (1.1C); ¹⁹F NMR (376 MHz, CDCl₃) δ: －63.81; HRMS (ESI) calcd for C₁₄H₁₈F₃O₂ [M+H]⁺ 275.1253, found 245.1244.

  2-(Naphthalen-2-yl)-6-(2, 2, 2-trifluoroethyl)tetrahydro-2H-pyran (2q): Colourless oil, 76% yield, dr 1.0:1.0 (based on quantitative ¹³C NMR). ¹H NMR (400 MHz, CDCl₃) δ: 7.90~7.83 (m, 3H+3H), 7.80 (s, 2H), 7.57~7.50 (m, 2H+3H), 7.48 (t, J＝2.0 Hz, 1H), 4.91~4.82 (m, 1H+1H), 4.18~4.05 (m, 1H+1H), 2.72~2.43 (m, 2H+2H); 2.01~1.58 (m, 5H+6H), 1.56~1.42 (m, 1H); ¹³C NMR (126 MHz, CDCl₃) δ: 141.90, 141.87, 133.35 (1C+1C), 133.14, 133.13, 128.56, 128.54, 128.03 (1C+1C), 127.82 (1C+1C), 126.38 (1C+1C), 126.06 (1C+1C), 125.36 (q, J＝277.5 Hz, 1C+1C), 124.74, 124.68, 123.99 (1C+1C), 74.59, 74.49, 54.14~54.05 (m, 1C+1C), 42.82~42.12 (m, 1C+1C), 38.06 (1C+1C), 37.99, 37.96, 22.54, 22.49; ¹⁹F NMR (376 MHz, CDCl₃) δ: －63.76; HRMS (ESI) calcd for C₁₇H₁₈F₃O [M+H]⁺ 295.1304, found 295.1300.

  3-(2, 2, 2-Trifluoroethyl)isochromane (2r): Colourless oil, 58% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.44~7.39 (m, 1H), 7.38~7.30 (m, 2H), 7.30~7.26 (m, 1H), 4.81~4.69 (m, 2H), 4.53~4.42 (m, 1H), 3.29 (dd, J＝14.5, 6.0 Hz, 1H), 3.21 (dd, J＝14.5, 8.6 Hz, 1H), 2.77~2.61 (m, 2H); ¹³C NMR (125 MHz, CDCl₃) δ: 138.94, 135.54, 130.81, 129.50, 128.52, 127.85, 125.44 (q, J＝277.6 Hz), 63.61, 54.51 (q, J＝3.1 Hz), 42.05 (q, J＝28.6 Hz), 41.10; ¹⁹F NMR (376 MHz, CDCl₃) δ: －63.51; HRMS (ESI) calcd for C₁₁H₁₂F₃O [M+H]⁺ 217.0835, found 217.0834.

  Supporting Information  ¹H NMR and ¹³C NMR spectra of the products. The Supporting Information is available free of charge via the Internet at http://sioc-journal.cn.

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• 

  Scheme 1  Preparation of tetrahydrofuran and tetrahydropyran via 1, 2-alkoxyl-trifluoromethylation of alkene

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  Scheme 2  Mechanistic proposal

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  Table 1.  Optimization of reaction conditions^a

  Entry	Catalyst	Additive	Solvent	Yield/%
  1	[Ir(dtbbpy)(ppy)2]PF6	Na2HPO4•12H2O	EtOAc	36
  2	[Ir(dtbbpy)(ppy)2]PF6	Na2HPO4•12H2O	DCM	70
  3	[Ir(dtbbpy)(ppy)2]PF6	Na2HPO4•12H2O	DCE	68
  4	[Ir(dtbbpy)(ppy)2]PF6	Na2HPO4•12H2O	CH3CN	44
  5	[Ir(dtbbpy)(ppy)2]PF6	Na2HPO4•12H2O	PhF	36
  6	[Ir(dtbbpy)(ppy)2]PF6	Na2HPO4•12H2O	DMF	21
  7	[Ir(dtbbpy)(ppy)2]PF6	Na2HPO4•12H2O	DMSO	Messy
  8	[Ir(dtbbpy)(ppy)2]PF6	Na2HPO4•12H2O	THF	39
  9	[Ir(dtbbpy)(ppy)2]PF6	Na2HPO4•12H2O	1, 4-Dioxane	26
  10	[Ir(dtbbpy)(ppy)2]PF6	Na2HPO4•12H2O	Cyclohexane	Messy
  11	[Ir(dtbbpy)(ppy)2]PF6	Na2HPO4•12H2O	MeOH	39
  12	[Ir(dtbbpy)(ppy)2]PF6	NaHCO3	DCM	55
  13	[Ir(dtbbpy)(ppy)2]PF6	Na2CO3	DCM	56
  14	[Ir(dtbbpy)(ppy)2]PF6	KHCO3	DCM	49
  15	[Ir(dtbbpy)(ppy)2]PF6	K2CO3	DCM	31
  16	Ru(bpy)3Cl2•6H2O	Na2HPO4•12H2O	DCM	45
  17	9, 10-Dicyanoanthracene	Na2HPO4•12H2O	DCM	20
  18	Ph-Acr-Me+ClO4-	Na2HPO4•12H2O	DCM	13
  19	Mes-Me2Acr-Me+ ClO4-	Na2HPO4•12H2O	DCM	28
  a Conditions: 1a (0.1 mmol), catalyst (1 mol%), CF3SO2Cl (1.5 equiv.), and additive (2 equiv.) in solvent (1 mL) under blue LED irradiation for 3 h. Yields were based on 19F NMR spectroscopy using α, α, α-trifluorotoluene as an internal standard.

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  Table 2.  Substrate scope^a

  a Conditions: 1 (0.2 mmol), [Ir(dtbbpy)(ppy)2]PF6 (1 mol%), CF3SO2Cl (1.5 equiv.), and Na2HPO4•12H2O (2 equiv.) in DCM (2 mL) under blue LED irradiation for 3 h, unless otherwise noted. Yields were isolated ones, unless otherwise noted. b Reaction time: 1 h. c Reaction Time: 1.5 h. d Yield was based on 19F NMR spectroscopy using α, α, α-trifluorotoluene as an internal standard. e Diastereomeric ratio was determined based on quantitative 13C NMR spectra of inseparable mixtures of both diastereomers.

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•