Alpha-trifluoromethyl beta-dithiosulfate tertiary alcohol compound as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to an alpha-trifluoromethyl beta-dithiosulfate tertiary alcohol compound as well as a preparation method and application thereof. The alpha-trifluoromethyl beta-dithiosulfate tertiary alcohol compound is efficiently prepared at room temperature in an air atmosphere by using trifluoromethyl olefin, phosphorus pentasulfide and ethanol as raw materials in the absence of a photocatalyst and an additive. Compared with a previously reported preparation method, the method has the advantages of being green, environmentally friendly, safe, efficient and energy-saving, the substrate application range is wide, the compatibility of product functional groups is good, raw materials are easy to obtain, transition metal, a photocatalyst and an external oxidizing agent are not needed, and the medical intermediates and molecules can be simply, conveniently and efficiently synthesized through the method.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and specifically relates to an alpha-trifluoromethyl beta-dithiosulfate tertiary alcohol compound, a preparation method and application thereof. Background Art

[0002] Trifluoromethyl tertiary alcohols are an important class of high-value compounds that are widely present in a series of therapeutic drugs and synthetic intermediates. Traditional methods mostly use the reaction of nucleophiles with trifluoromethyl ketones and the nucleophilic addition of trifluoromethyl nucleophiles with ketones. Although they can prepare relatively simple α-trifluoromethyl β-dithiosulfate tertiary alcohol compounds, they have the disadvantages of using metal catalysts, expensive trifluoromethyl nucleophiles, requiring multiple steps of reaction, and a narrow substrate range.

[0003] In recent years, with the development of visible light catalysis, trifluoromethyl olefin derivatives have shown good reaction compatibility. Although a series of fluorinated compounds have been synthesized in the presence of photocatalysts, the strong electron-withdrawing trifluoromethyl group of trifluoromethyl olefins reduces the LUMO value of the double bond on the olefin, making it easy to undergo β-F elimination, which reduces the synthesis rate.

[0004] Therefore, it would be a more attractive and challenging goal to develop a green and efficient method to convert trifluoromethyl olefin compounds into α-trifluoromethyl β-dithiosulfate tertiary alcohol compounds under mild and neutral reaction conditions without the use of photocatalysts and metal catalysts under visible light conditions. Summary of the invention

[0005] In view of this, in order to solve the problem, the present invention discloses an α-trifluoromethyl β-dithiosulfate tertiary alcohol compound, a preparation method and an application thereof.

[0006] It should be noted that the present invention proposes an efficient, green and environmentally friendly method for easy scale-up preparation, using trifluoromethyl olefin, phosphorus pentasulfide and ethanol as raw materials, and irradiating with visible light to efficiently synthesize a series of α-trifluoromethyl β-dithiosulfate tertiary alcohol compounds at room temperature. The reaction operation is simple, environmentally friendly, carried out at room temperature, and does not require transition metal catalysts, photosensitizers and additives. The method of the present invention can be used to synthesize pharmaceutical intermediates and molecules simply and efficiently.

[0007] In order to achieve the above object, the present invention adopts the following technical solution:

[0008] The first technical purpose of the present invention is to provide an α-trifluoromethyl β-dithiosulfate tertiary alcohol compound, the structure of the α-trifluoromethyl β-dithiosulfate tertiary alcohol compound is as follows:

[0009]

[0010] Wherein, R is phenyl, naphthyl or substituted phenyl, and the substitution is selected from methyl, ethyl, methoxy, tert-butyl, benzyl, thiomethyl, and hydroxyl.

[0011] The second technical purpose of the present invention is to provide a method for synthesizing the α-trifluoromethyl β-dithiosulfate tertiary alcohol compound as described above.

[0012] The synthesis method is as follows:

[0013]

[0014] R is defined as previously described.

[0015] Specifically, trifluoromethyl olefin is used as a raw material, and reacts with phosphorus pentasulfide and ethanol under visible light conditions to generate α-trifluoromethyl β-dithiosulfate tertiary alcohol compounds.

[0016] Synthesis mechanism Figure 1 , the specific instructions are as follows;

[0017] First, P 4 S 10 It reacts with EtOH to generate diethyl dithiophosphate F, which is partially converted into thiol anion A. Intermediate A interacts with 1a to generate EDA complex B, which enters an excited state (EDA complex B*) under visible light irradiation. In the presence of air, EDA complex B* undergoes single electron transfer to obtain sulfur-centered free radical C, 1a and superoxide anion radical (O 2 ·- ); the generated free radical C is added to C=C of 1a to generate a free radical intermediate D; O 2 ·- Under the action of F, peroxide free radicals and intermediate A are transferred to continue to promote the reaction; free radical D cross-couples with peroxide free radicals to generate intermediate E, and finally, with the assistance of F, the peroxide bond of intermediate E is cleaved to generate the product.

[0018] Optionally, the molar ratio of the trifluoromethyl olefin to phosphorus pentasulfide and ethanol is 1:1:10-1:1.5:20.

[0019] Optionally, the visible light irradiation is selected from one or more light sources selected from 5000-5500K white light, 395-400nm purple light, and 455-460nm blue light, and the power of the irradiation light source is 7-10W, specifically one or more of 6W, 8W, 9W, and 10W.

[0020] Optionally, the reaction time is 12-36 hours, the reaction temperature is room temperature, and the reaction atmosphere is air atmosphere.

[0021] Optionally, the reaction solvent is one or more of ethyl acetate, tetrahydrofuran, dichloromethane, and acetonitrile.

[0022] Furthermore, in the method of the present invention, after the reaction is completed, the product is separated and characterized by a conventional separation and purification method to obtain the corresponding product.

[0023] The third technical purpose of the present invention is to provide an application of the above-mentioned α-trifluoromethyl β-dithiosulfate tertiary alcohol compound in a pharmaceutical preparation.

[0024] Furthermore, the α-trifluoromethyl β-dithiosulfate tertiary alcohol compound can be used as a pharmaceutical intermediate or pharmaceutical molecule.

[0025] Specifically, α-trifluoromethyl β-dithiosulfate tertiary alcohol compounds are a class of extremely valuable fluorinated compounds with unique electronegativity, lipophilicity, metabolic stability and bioavailability. 3 Tertiary alcohols are the most representative compounds and can be used as drugs and key synthetic intermediates; dithiophosphorus acids have multiple physical and biological activities such as anti-wear, insecticide, antiviral, and inhibition of butylcholinesterase and acetylcholinesterase, and play a particularly important role in the field of biomolecular chemistry.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] The present invention uses trifluoromethyl olefin, phosphorus pentasulfide and ethanol as raw materials under the condition of no photocatalyst and additives to efficiently prepare α-trifluoromethyl β-dithiosulfate tertiary alcohol compounds at room temperature and in air atmosphere. Compared with the previously reported preparation methods, the present invention has the advantages of being green, environmentally friendly, safe, efficient and energy-saving, its substrate has a wide range of applications, the product functional group compatibility is good, the raw materials are easy to obtain, and no transition metal, photocatalyst and external oxidant are required. The method of the present invention can be used to simply and efficiently synthesize pharmaceutical intermediates and molecules. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the provided drawings without paying creative work.

[0029] Figure 1It is a synthesis mechanism diagram of the α-trifluoromethyl β-dithiosulfate tertiary alcohol compounds of the present invention.

[0030] Figure 2 It is a diagram of the functional groups in the α-trifluoromethyl β-dithiosulfate tertiary alcohol compounds of the present invention.

[0031] Figure 3 These are the hydrogen spectrum (a), carbon spectrum (b), fluorine spectrum (c) and phosphorus spectrum (d) of compound 4 of the present invention.

[0032] Figure 4 These are the hydrogen spectrum (a), carbon spectrum (b), fluorine spectrum (c) and phosphorus spectrum (d) of compound 6 of the present invention.

[0033] Figure 5 These are the hydrogen spectrum (a), carbon spectrum (b), fluorine spectrum (c) and phosphorus spectrum (d) of compound 8 of the present invention.

[0034] Figure 6 These are the hydrogen spectrum (a), carbon spectrum (b), fluorine spectrum (c) and phosphorus spectrum (d) of compound 10 of the present invention.

[0035] Figure 7 These are the hydrogen spectrum (a), carbon spectrum (b), fluorine spectrum (c) and phosphorus spectrum (d) of compound 12 of the present invention. DETAILED DESCRIPTION

[0036] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0037] The word "embodiment" used exclusively herein and any embodiment described as "exemplary" are not necessarily to be construed as preferred or better. In other embodiments, unless otherwise specified, the performance index tests in the embodiments of this application were conducted using conventional test methods in the art. Law It should be understood that the terms used in this application are only used to describe specific implementations and are not used to limit the contents disclosed in this application.

[0038] Unless otherwise specified, the technical and scientific terms used in this document have the same meanings as commonly understood by ordinary technicians in the technical field to which this application belongs; other experimental methods and technical means not specifically specified in this application refer to experimental methods and technical means commonly used by ordinary technicians in this field.

[0039] In order to better illustrate the content of the present application, numerous specific details are provided in the specific examples below. It should be understood by those skilled in the art that the present application can also be implemented without certain specific details. In the embodiments, some methods, means, instruments, equipment, etc. well known to those skilled in the art are not described in detail in order to highlight the main purpose of the present application.

[0040] Under the premise of no conflict, the technical features disclosed in the embodiments of the present application can be combined arbitrarily, and the resulting technical solutions belong to the contents disclosed in the embodiments of the present application.

[0041] The invention discloses a method for synthesizing alpha-trifluoromethyl beta-dithiosulfate tertiary alcohol compounds.

[0042] In order to better understand the present invention, the present invention is further specifically described below through the following examples, but it should not be understood as a limitation of the present invention. Some non-essential improvements and adjustments made by technicians in this field based on the above invention content are also considered to fall within the protection scope of the present invention.

[0043] Example 1

[0044]

[0045] In a 10 mL Shrek reaction tube, naphthalene trifluoromethyl olefin 3 (44.4 mg, 0.20 mmol), phosphorus pentasulfide (88.9 mg, 0.20 mmol), ethanol (92.2 mg, 2.00 mmol) and 1 mL acetonitrile were added in sequence; the reaction tube was stirred for 12 h at room temperature 25°C and irradiated with 10 W blue light (455-460 nm); after the reaction was completed, the volatile components were removed under reduced pressure, and then separated by thin layer chromatography (eluent was petroleum ether (60-90°C) / ethyl acetate, v / v=15:1) to obtain the target product 4 (76.2 mg, yield 90%) as a yellow oil.

[0046] The target product was confirmed by NMR spectroscopy.

[0047] Comparative Example 1

[0048] The reaction steps and operations were the same as those in Example 1, except that the reaction was carried out without light. The reaction was stopped, and the target product 4 was not obtained after the same post-treatment as above, indicating that the reaction could not be carried out without light.

[0049] Comparative Example 2

[0050] The reaction steps and operation were the same as those in Example 1, except that the reaction time was 1 h. The reaction was stopped and the target product 4 (35.6 mg, yield 42%) was obtained after post-treatment. This indicated that reducing the time was not conducive to the reaction.

[0051] Comparative Example 3

[0052] The reaction steps and operation were the same as those in Example 1, except that ethyl acetate was used as the solvent. The reaction was stopped and the target product 4 (28.5 mg, yield 34%) was obtained after post-treatment. This indicated that using ethyl acetate as the solvent was not conducive to the reaction.

[0053] Comparative Example 4

[0054] The reaction steps and operation were the same as those in Example 1, except that dichloromethane was used as the solvent. The reaction was stopped and the target product 4 (31.9 mg, yield 38%) was obtained after post-treatment. This indicated that using dichloromethane as the solvent was not conducive to the reaction.

[0055] Example 2

[0056]

[0057] The reaction steps and operations were the same as those in Example 1, except that the raw material added to the reaction system was α-(trifluoromethyl)styrene 5 (34.4 mg, 0.2 mmol). The reaction was stopped and the target product 6 (57.2 mg, yield 76%) was obtained as a yellow oil after post-treatment.

[0058] The target product was confirmed by NMR spectroscopy.

[0059] Example 3

[0060]

[0061] The reaction steps and operations were the same as those in Example 1, except that 4-methyl-α-(trifluoromethyl)styrene 7 (37.2 mg, 0.2 mmol) was added to the reaction system, and the target product 8 (56.8 mg, yield 73%) was obtained as a yellow oil after post-treatment.

[0062] The target product was confirmed by NMR spectroscopy.

[0063] Example 4

[0064]

[0065] The reaction steps and operations were the same as those in Example 1, except that 3-methyl-α-(trifluoromethyl)styrene 9 (37.2 mg, 0.2 mmol) was added to the reaction system, the reaction was stopped, and the target product 10 (57.9 mg, yield 75%) was obtained as a yellow oil after post-treatment.

[0066] The target product was confirmed by NMR spectroscopy.

[0067] Example 5

[0068]

[0069] The reaction steps and operations were the same as those in Example 1, except that 4-methoxy-α-(trifluoromethyl)styrene 11 (40.4 mg, 0.2 mmol) was added to the reaction system, the reaction was stopped, and the target product 12 (60.9 mg, yield 75%) was obtained as a yellow oil after post-treatment.

[0070] The target product was confirmed by NMR spectroscopy.

[0071] Example 6

[0072]

[0073] The reaction steps and operations were the same as those in Example 1, except that 3-methoxy-α-(trifluoromethyl)styrene 13 (40.4 mg, 0.2 mmol) was added to the reaction system, the reaction was stopped, and the target product 14 (58.0 mg, yield 72%) was obtained as a yellow oil after post-treatment.

[0074] The target product was confirmed by NMR spectroscopy.

[0075] Example 7

[0076]

[0077] The reaction steps and operations were the same as those in Example 1, except that 4-phenoxy-α-(trifluoromethyl)styrene 15 (52.9 mg, 0.2 mmol) was added to the reaction system, the reaction was stopped, and the target product 16 (72.3 mg, yield 78%) was obtained as a yellow oil after post-treatment.

[0078] The target product was confirmed by NMR spectroscopy.

[0079] Example 8

[0080]

[0081] The reaction steps and operations were the same as those in Example 1, except that 4-benzyloxy-α-(trifluoromethyl)styrene 17 (56.7 mg, 0.2 mmol) was added to the reaction system, the reaction was stopped, and the target product 18 (74.1 mg, yield 77%) was obtained as a yellow oil after post-treatment.

[0082] The target product was confirmed by NMR spectroscopy.

[0083] Example 9

[0084]

[0085] The reaction steps and operations were the same as those in Example 1, except that 3-benzyloxy-α-(trifluoromethyl)styrene 19 (56.7 mg, 0.2 mmol) was added to the reaction system, the reaction was stopped, and the target product 20 (80.6 mg, yield 84%) was obtained as a yellow oil after post-treatment.

[0086] The target product was confirmed by NMR spectroscopy.

[0087] Example 10

[0088]

[0089] The reaction steps and operations were the same as those in Example 1, except that 4-propyl-α-(trifluoromethyl)styrene 21 (42.8 mg, 0.2 mmol) was added to the reaction system, the reaction was stopped, and the target product 22 (65.1 mg, yield 78%) was obtained as a yellow oil after post-treatment.

[0090] The target product was confirmed by NMR spectroscopy.

[0091] Embodiment 11

[0092]

[0093] The reaction steps and operations were the same as those in Example 1, except that 4-tert-butyl-α-(trifluoromethyl)styrene 23 (45.7 mg, 0.2 mmol) was added to the reaction system, the reaction was stopped, and the target product 24 (64.4 mg, yield 86%) was obtained as a yellow oil after post-treatment.

[0094] The target product was confirmed by NMR spectroscopy.

[0095] Example 12

[0096]

[0097] The reaction steps and operations were the same as those in Example 1, except that 4-thiomethyl-α-(trifluoromethyl)styrene 25 (43.6 mg, 0.2 mmol) was added to the reaction system, the reaction was stopped, and the target product 26 (56.4 mg, yield 67%) was obtained as a yellow oil after post-treatment.

[0098] The target product was confirmed by NMR spectroscopy.

[0099] Example 13

[0100]

[0101] The reaction steps and operations were the same as those in Example 1, except that 4-hydroxy-α-(trifluoromethyl)styrene 27 (37.6 mg, 0.2 mmol) was added to the reaction system, the reaction was stopped, and the target product 28 (50.4 mg, yield 65%) was obtained as a yellow oil after post-treatment.

[0102] The target product was confirmed by NMR spectroscopy.

[0103] Embodiment 14

[0104]

[0105] The reaction steps and operations were the same as those in Example 1, except that 1,3-dimethyl-5-(3,3,3-trifluoroprop-1-en-2-yl)benzene 29 (40.0 mg, 0.2 mmol) was added to the reaction system, the reaction was stopped, and the target product 30 (60.1 mg, yield 75%) was obtained as a yellow oil after post-treatment.

[0106] The target product was confirmed by NMR spectroscopy.

[0107] Embodiment 15

[0108]

[0109] The reaction steps and operations were the same as those in Example 1, except that 1-(pent-4-ene-1-oxy)-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene 31 (51.3 mg, 0.2 mmol) was added to the reaction system, the reaction was stopped, and the target product 32 (58.2 mg, yield 63%) was obtained as a yellow oil after post-treatment.

[0110] The target product was confirmed by NMR spectroscopy.

[0111] Example 16

[0112]

[0113] The reaction steps and operations were the same as those in Example 1, except that 4-(3,3,3-trifluoroprop-1-en-2-yl)phenyl-4-methylbenzenesulfonate 33 (68.5 mg, 0.2 mmol) was added to the reaction system, the reaction was stopped, and the target product 34 (77.4 mg, yield 71%) was obtained as a yellow oil after post-treatment.

[0114] The target product was confirmed by NMR spectroscopy.

[0115] Embodiment 17

[0116]

[0117] The reaction steps and operations were the same as those in Example 1, except that 2-(3-(3,3,3-trifluoroprop-1-en-2-yl)phenyl)isoindoline-1,3-dione 35 (63.5 mg, 0.2 mmol) was added to the reaction system, the reaction was stopped, and the target product 36 (90.1 mg, yield 87%) was obtained as a yellow oil after post-treatment.

[0118] The target product was confirmed by NMR spectroscopy.

[0119] Embodiment 18

[0120]

[0121] The reaction steps and operations were the same as those in Example 1, except that 4-bromo-N-(3-(3,3,3-trifluoroprop-1-en-2-yl)phenyl)benzamide 37 (74.0 mg, 0.2 mmol) was added to the reaction system, the reaction was stopped, and the target product 38 (87.5 mg, yield 76%) was obtained as a yellow oil after post-treatment.

[0122] The target product was confirmed by NMR spectroscopy.

[0123] Embodiment 19

[0124]

[0125] The reaction steps and operations were the same as those in Example 1, except that 5-(3,3,3-trifluoroprop-1-en-2-yl)benzo[d][1,3]dioxole 39 (43.2 mg, 0.2 mmol) was added to the reaction system, the reaction was stopped, and the target product 40 (57.0 mg, yield 68%) was obtained as a yellow oil after post-treatment.

[0126] The target product was confirmed by NMR spectroscopy.

[0127] Embodiment 20

[0128]

[0129] The reaction steps and operations were the same as those in Example 1, except that 3-(3,3,3-trifluoroprop-1-en-2-yl)phenyl 2-(4-(2,2-dichlorocyclopropyl)phenoxy)-2-methylpropanoate 41 (91.9 mg, 0.2 mmol) was added to the reaction system, the reaction was stopped, and the target product 42 (118.2 mg, yield 89%) was obtained as a yellow oil after post-treatment.

[0130] The target product was confirmed by NMR spectroscopy.

[0131] Embodiment 21

[0132]

[0133] The reaction steps and operations were the same as those in Example 1, except that 3-(3,3,3-trifluoroprop-1-en-2-yl)phenyl 2-((3-(trifluoromethyl)phenyl)amino)nicotinate 43 (90.5 mg, 0.2 mmol) was added to the reaction system, the reaction was stopped, and the target product 44 (99 mg, yield 76%) was obtained as a yellow oil after post-treatment.

[0134] The target product was confirmed by NMR spectroscopy.

[0135] Embodiment 22

[0136]

[0137] The reaction steps and operations were the same as those in Example 1, except that 5-(2,5-dimethylphenoxy)-2,2-dimethyl-N-(3-(3,3,3-trifluoroprop-1-en-2-yl)phenyl)pentanamide 45 (83.9 mg, 0.2 mmol) was added to the reaction system, the reaction was stopped, and post-treatment gave a white solid 46 (97.2 mg, yield 78%).

[0138] The target product was confirmed by NMR spectroscopy.

[0139] Embodiment 23

[0140]

[0141] The reaction steps and operations were the same as those in Example 1, except that n-hexanol 47 (204.4 mg, 2.0 mmol) was added to the reaction system to stop the reaction. The target product 48 (91.0 mg, yield 85%) was obtained as a yellow oil after post-treatment.

[0142] The target product was confirmed by NMR spectroscopy.

[0143] Embodiment 24

[0144]

[0145] The reaction steps and operations were the same as those of Example 1, except that cyclohexanol 49 (200.3 mg, 2.0 mmol) was added to the reaction system, the reaction was stopped, and the target product 50 (87.3 mg, yield 82%) was obtained as a yellow oil after post-treatment.

[0146] The target product was confirmed by NMR spectroscopy.

[0147] Embodiment 25

[0148]

[0149] In a 50 mL round-bottom flask, naphthalene trifluoromethyl olefin 3 (1.11 g, 5.0 mmol), phosphorus pentasulfide (2.22 g, 5.0 mmol), ethanol (2.3 g, 5.0 mmol) and 25 mL acetonitrile were added in sequence; the reaction tube was stirred for 36 h at room temperature (25 ° C) and 20 W blue light irradiation; after the reaction was completed, the volatile components were removed under reduced pressure, and then separated by silica gel column chromatography (eluent was petroleum ether (60-90 ° C) / ethyl acetate, v / v = 120:1) to obtain the target product 4 (1.68 g, yield 79%) as a yellow oil.

[0150] The target product was confirmed by NMR spectroscopy.

[0151] The characterization data of the above compounds are as follows:

[0152] O,O-Diethyl S-[3,3,3-trifluoro-2-hydroxy-2-(naphthalen-2-yl)propyl] dithiophosphate (4): TLC (petroleum ether / ethyl acetate = 15:1, v / v), R f =0.45; yellow oil (76.2 mg, 90%). 1 H NMR (600 MHz, CDCl 3 )δ8.16(s,1H),7.93-7.88(m,3H),7.66(d,J=8.7Hz,1H),7.56-7.53(m,2H),4.26-4.08(m,5H),3.99-3.85(m,2H),1.35(q,J=7.1Hz,6H). 13 C NMR (150 MHz, CDCl 3 )δ133.3,133.2,132.9,128.6,128.4,127.6,127.0,126.9,126.6,125.1(q,J=285.0),123.5, 77.0(qd,J=28.5,J=1.5Hz), 65.0(dd,J=28.5,J=7.5Hz), 40.0(d,J=3.0Hz), 15.8(d,J=9.0Hz). 19 FNMR (565MHz, CDCl 3 )δ-0.57(s). 31 P NMR (243MHz, CDCl 3)δ97.91(s).HRMS(ESI)m / z Calcdfor C 17 H 21 F 3 O 3 PS 2 [M+H] + :425.0616;Found:425.0610.

[0153] O,O-Diethyl S-[3,3,3-trifluoro-2-hydroxy-2-phenylpropyl] dithiophosphate (6): TLC (petroleum ether / ethyl acetate = 15:1, v / v), R f =0.40; yellow oil (57.2 mg, 76%). 1 HNMR (600MHz, CDCl 3 )δ7.55(d,J=7.4Hz,2H),7.43-7.37(m,3H),4.23-4.07(m,4H),3.85(s,1H),3.80-3.70(m,2H),1.34(t,J=7.1Hz,6H). 13 C NMR (150 MHz, CDCl 3 )δ135.9,129.1,128.6,126.7,125.0(q,J=285.0Hz),76.8(qd,J=28.5,J=1.5H z), 65.0 (dd, J = 27.0, J = 6.0Hz), 40.0 (d, J = 1.5Hz), 15.9 (dd, J = 9.0, J = 4.5Hz). 19 F NMR (565MHz, CDCl 3 )δ-0.91(s). 31 P NMR (243MHz, CDCl 3 )δ97.84(s).HRMS(ESI)m / zCalcd for C 13 H 18 F 3 O 3 PS 2 Na[M+Na] + :397.0279;Found:397.0281.

[0154] O,O-Diethyl S-[3,3,3-trifluoro-2-hydroxy-2-(p-tolyl)propyl] dithiophosphate (8): TLC (petroleum ether / ethyl acetate = 15:1, v / v), R f =0.30; yellow oil (56.8 mg, 73%). 1 H NMR (600 MHz, CDCl3 )δ7.43(d,J=8.1Hz,2H),7.22(d,J=8.1Hz,2H),4.24-4.08(m,4H),3.79-3.68(m,3H),2.37(s,3H),1.35(t,J=7.1Hz,6H). 13 C NMR (150 MHz, CDCl 3 )δ139.0,132.9,129.3,126.6,125.0(q,J=285.0Hz),76.8-76.4(m),64.9( dd, J=28.5, J=6.0Hz), 40.0 (d, J=1.5Hz), 21.2, 15.9 (dd, J=7.5, J=4.5Hz). 19 F NMR (565MHz, CDCl 3 )δ-1.08(s). 31 P NMR (243MHz, CDCl 3 )δ97.79(s).HRMS(ESI)m / z Calcd for C 14 H 20 F 3 O 3 PS 2 Na[M+Na] + :411.0436;Found:411.0422.

[0155] O,O-Diethyl S-[3,3,3-trifluoro-2-hydroxy-2-(m-tolyl)propyl] dithiophosphate (10): TLC (petroleum ether / ethyl acetate = 18:1, v / v), R f =0.40; yellow oil (57.9 mg, 75%). 1 H NMR (600 MHz, CDCl 3 )δ7.37(s,1H),7.33-7.28(m,2H),7.20(d,J=7.3Hz,1H),4.24-4.07(m, 4H),3.79(s,1H),3.76-3.68(m,2H),2.39(s,3H),1.35(t,J=7.1Hz,6H). 13 C NMR (150 MHz, CDCl 3)δ138.3,135.8,129.9,128.4,127.3,125.0(q,J=285.0Hz),123.7,76.8-76.4(m,J=28 .5, J=3.0Hz), 65.0 (dd, J=27.0, J=6.0Hz), 40.0 (d, J=3.0Hz), 21.7, 15.9 (q, J=4.5Hz). 19 FNMR (565MHz, CDCl 3 )δ-0.87(s). 31 PNMR (243MHz,CDCl 3 )δ97.74(s).HRMS(ESI)m / z Calcdfor C 14 H 20 F 3 O 3 PS 2 Na[M+Na] + :411.0436;Found:411.0435.

[0156] O,O-Diethyl S-[3,3,3-trifluoro-2-hydroxy-2-(4-methoxyphenyl)propyl] dithiophosphate (12): TLC (petroleum ether / ethyl acetate = 15:1, v / v), R f =0.25; yellow oil (60.9 mg, 75%). 1 H NMR (600 MHz, CDCl 3 )δ7.45(d,J=8.8Hz,2H),6.92(d,J=8.9Hz,2H),4.23-4.07(m,4H),3.81(s,3H),3.79(s,1H),3.76-3.66(m,2H),1.34(t,J=7.1Hz,6H). 13 C NMR (150 MHz, CDCl 3 )δ160.1,128.0,127.8,125.0(q,J=285.0Hz),113.9,76.5(qd,J=27.0,J=1.5 Hz), 64.9 (dd, J = 27.0, J = 6.0Hz), 55.4, 40.0 (d, J = 3.0Hz), 15.9 (q, J = 4.5Hz). 19 F NMR (565MHz, CDCl 3 )δ-1.24(s). 31 P NMR (243 MHz, CDCl 3 )δ97.74(s).HRMS(ESI)m / z Calcd for C 14 H20 F 3 O 4 PS 2 Na[M+Na] + :427.0385;Found:427.0386.

[0157] O,O-Diethyl S-[3,3,3-trifluoro-2-hydroxy-2-(3-methoxyphenyl)propyl] dithiophosphate (14): TLC (petroleum ether / ethyl acetate = 15:1, v / v), R f =0.25; yellow oil (58.0 mg, 72%). 1 H NMR (600 MHz, CDCl 3 )δ7.32(t,J=8.0Hz,1H),7.15(s,1H),7.08(d,J=7.8Hz,1H),6.92(dd,J=8.2,J=2.4Hz,1H ),4.22-4.08(m,4H),3.86(s,1H),3.82(s,3H),3.77-3.67(m,2H),1.34(t,J=7.1Hz,6H). 13 C NMR (150 MHz, CDCl 3 )δ159.8,137.5,129.6,124.9(q,J=285.0Hz),118.7,114.3,113.0,76.8-76.4(m,J=28.5, J=3.0Hz), 65.0 (dd, J=27.0, J=6.0Hz), 55.4, 40.0 (d, J=1.5Hz), 15.9 (dd, J=9.0, J=3.0Hz). 19 F NMR (565MHz, CDCl 3 )δ-0.82(s). 31 P NMR (243 MHz, CDCl 3 )δ97.84(s).HRMS(ESI)m / z Calcd for C 14 H 20 F 3 O 4 PS 2 Na[M+Na] + :427.0385;Found:427.0385.

[0158] O,O-Diethyl S-[2-hydroxy-2-(4-phenoxyphenyl)-3,3,3-trifluoropropyl] dithiophosphate (16): TLC (petroleum ether / ethyl acetate = 15:1, v / v), R f=0.35; yellow oil (72.3 mg, 78%). 1 H NMR (600 MHz, CDCl 3 )δ7.49(d,J=8.6Hz,2H),7.37(t,J=7.7Hz,2H),7.17-7.14(m,1H),7.06(d,J=8.3Hz,2H),7.01(d ,J=8.8Hz,2H),4.25-4.10(m,4H),3.85(s,1H),3.77-3.69(m,2H),1.36(td,J=7.1,J=2.8Hz,6H). 13 C NMR (150 MHz, CDCl 3 )δ158.3,156.4,130.2,130.0,128.3,126.9(q,J=285.0Hz),124.0,119.7,118.1,76.6(qd,J =27.0, J=1.5Hz), 65.0 (dd, J=27.0, J=6.0Hz), 40.0 (d, J=1.5Hz), 15.9 (dd, J=7.5, J=3.0Hz). 19 F NMR (565MHz, CDCl 3 )δ-1.06(s). 31 P NMR (243MHz, CDCl 3 )δ97.83(s).HRMS(ESI)m / z Calcd for C 19 H 22 F 3 O 4 PS 2 Na[M+Na] + :489.0541;Found:489.0524.

[0159] S-[2-(4-(Benzyloxy)phenyl)-3,3,3-trifluoro-2-hydroxypropyl]O,O-diethyl dithiophosphate (18): TLC (petroleum ether / ethyl acetate = 15:1, v / v), R f =0.35; yellow oil (74.1 mg, 77%). 1 H NMR (600 MHz, CDCl 3)δ7.48(d,J=8.8Hz,2H),7.45(d,J=7.4Hz,2H),7.42-7.40(m,2H),7.35(t,J=7.3Hz,1H),7.03-7.02( m,2H),5.08(s,2H),4.25-4.09(m,4H),3.80(s,1H),3.78-3.69(m,2H),1.36(td,J=7.1,J=1.9Hz,6H). 13 C NMR (150 MHz, CDCl 3 )δ159.4,136.8,128.7,128.2,128.1,127.6,125.0(q,J=285.0Hz),114.8,76.5(qd,J=28.5 , J=1.5Hz), 70.1, 64.9 (dd, J=27.0, J=6.0Hz), 40.0 (d, J=1.5Hz), 15.9 (dd, J=9.0, J=4.5Hz). 19 F NMR (565MHz, CDCl 3 )δ-1.15(s). 31 P NMR (243MHz, CDCl 3 )δ97.78(s).HRMS(ESI)m / z Calcd forC 20 H 24 F 3 O 4 PS 2 [M+Na] + :503.0698;Found:503.0680.

[0160] S-[2-(3-benzyloxyphenyl)-3,3,3-trifluoro-2-hydroxypropyl]O,O-diethyl dithiophosphate (20): TLC (petroleum ether / ethyl acetate = 15:1, v / v), R f =0.35; yellow oil (80.6 mg, 84%). 1 H NMR (600 MHz, CDCl 3 )δ7.43(d,J=7.3Hz,2H),7.39-7.38(m,2H),7.33-7.30(m,2H),7.23-7.22(m,1H),7.10(d,J=7.8Hz,1H),6.98( dd,J=8.1,J=2.2Hz,1H),5.06(s,2H),4.22-4.06(m,4H),3.84(s,1H),3.75-3.66(m,2H),1.33(t,J=7.1Hz,6H). 13C NMR (150 MHz, CDCl 3 )δ159.0,137.5,136.8,129.6,128.7,128.2,127.7,124.9(q,J=285.0Hz),119.0,115.2,114.0, 76.8-76.4(m),70.2,65.0(dd,J=27.0,J=6.0Hz),40.0(d,J=1.5Hz),15.9(dd,J=7.5,J=1.5Hz). 19 F NMR (565MHz, CDCl 3 )δ-0.76(s). 31 PNMR (243MHz,CDCl 3 )δ97.87(s).HRMS(ESI)m / z Calcd for C 20 H 24 F 3 O 4 PS 2 Na[M+Na] + :503.0698;Found:503.0680.

[0161] S-[3,3,3-Trifluoro-2-hydroxy-2-(4-propylphenyl)propyl]O,O-diethyl dithiophosphate (22): TLC (petroleum ether / ethyl acetate = 15:1, v / v), R f =0.25; yellow oil (65.1 mg, 78%). 1 H NMR (600 MHz, CDCl 3 )δ7.44(d,J=8.0Hz,2H),7.22(d,J=8.2Hz,2H),4.23-4.07(m,4H),3.77-3.68(m,3H) ,2.62-2.59(m,2H),1.69-1.62(m,2H),1.34(t,J=7.1Hz,6H),0.95(t,J=7.3Hz,3H). 13 C NMR (150 MHz, CDCl 3 )δ143.7,133.0,128.6,126.5,125.0(q,J=285.0Hz),76.8-76.4(m),64.9(dd ,J=27.0,J=6.0Hz),39.94(d,J=1.5Hz),37.7,24.4,15.9(q,J=4.5Hz),14.0. 19 F NMR (565MHz, CDCl 3 )δ-0.99(s). 31P NMR (243MHz, CDCl 3 )δ97.63(s).HRMS(ESI)m / zCalcd for C 16 H 24 F 3 O 3 PS 2 Na[M+Na] + :439.0749;Found:439.0735.

[0162] O,O-Diethyl-S-[2-(4-tert-butylphenyl)-3,3,3-trifluoro-2-hydroxypropyl] dithiophosphate (24): TLC (petroleum ether / ethyl acetate = 15:1, v / v), R f =0.30; yellow oil (64.4 mg, 86%). 1 H NMR (600 MHz, CDCl 3 )δ7.46(d,J=8.5Hz,2H),7.41(d,J=8.6Hz,2H),4.24-4.07(m,4H),3.77-3.68(m,3H),1.36-1.33(m,15H). 13 C NMR (150 MHz, CDCl 3 )δ152.0,132.8,126.3,125.0(q,J=285.0Hz),125.5,76.9-76.3(m,J=27.0,J=1.5Hz), 64.9 (dd, J=27.0, J=6.0Hz), 39.9 (d, J=3.0Hz), 34.7, 31.4, 15.9 (dd, J=7.5, J=1.5Hz). 19 F NMR (565MHz, CDCl 3 )δ-0.89(s). 31 P NMR (243MHz, CDCl 3 )δ97.47(s).HRMS(ESI)m / z Calcd for C 17 H 26 F 3 O 3 PS 2 Na[M+Na] + :453.0905;Found:453.0888.

[0163] O,O-Diethyl-S-[3,3,3-trifluoro-2-hydroxy-2-(4-methylthiophenyl)propyl] dithiophosphate (26): TLC (petroleum ether / ethyl acetate = 15:1, v / v), R f=0.20; yellow oil (56.4 mg, 67%). 1 H NMR (600 MHz, CDCl 3 )δ7.44(d,J=8.4Hz,2H),7.26(d,J=8.5Hz,2H),4.23-4.07(m,4H),3.84(s,1H),3.76-3.67(m,2H),2.49(s,3H),1.34(t,J=7.1Hz,6H). 13 C NMR (150 MHz, CDCl 3 )δ140.1,132.4,127.1,126.0,124.9(q,J=285.0Hz),76.31-76.32(m),65.0 (dd, J=28.5, J=6.0Hz), 39.9 (d, J=3.0Hz), 15.9 (dd, J=7.5, J=4.5Hz), 15.4. 19 F NMR (565MHz, CDCl 3 )δ-1.07(s). 31 P NMR (243 MHz, CDCl 3 )δ97.93(s).HRMS(ESI)m / z Calcd for C 14 H 20 F 3 O 3 PS 3 Na[M+Na] + :443.0156;Found:443.0144.

[0164] O,O-Diethyl S-[3,3,3-trifluoro-2-hydroxy-2-(4-hydroxyphenyl)propyl]phosphoric acid dithioate (28): TLC (petroleum ether / ethyl acetate = 3:1, v / v), R f =0.45; yellow oil (50.4 mg, 65%). 1 H NMR (600 MHz, CDCl 3 )δ7.40(d,J=8.6Hz,2H),6.87-6.85(m,2H),5.41(s,1H),4.23-4.07(m,4H),3.84(s,1H),3.75-3.65(m,2H),1.33(td,J=7.1,J=3.5Hz,6H). 13 C NMR (150 MHz, CDCl 3)δ156.2,128.3,128.0,125.0(q,J=285.0Hz),115.5,76.6(qd,J=27.0,J= 3.0Hz), 65.1 (dd, J=25.5, J=6.0Hz), 39.9 (d, J=1.5Hz), 15.9 (q, J=4.5Hz). 19 F NMR (565MHz, CDCl 3 )δ-1.21(s). 31 P NMR (243MHz, CDCl 3 )δ97.63(s).HRMS(ESI)m / z Calcd for C 13 H 18 F 3 O 4 PS 2 Na[M+Na] + :413.0228;Found:413.0227.

[0165] S-[2-(3,5-dimethylphenyl)-2-hydroxy-3,3,3-trifluoropropyl]O,O-diethyl dithiophosphate (30): TLC (petroleum ether / ethyl acetate = 15:1, v / v), R f =0.45; yellow oil (60.1 mg, 75%). 1 H NMR (600 MHz, CDCl 3 )δ7.15(s,2H),7.02(s,1H),4.24-4.08(m,4H),3.78-3.66(m,3H),2.35(s,6H),1.35(td,J=7.1,J=2.1Hz,6H). 13 C NMR (150 MHz, CDCl 3 )δ138.1,135.7,130.8,125.0(q,J=285.0Hz),124.4,76.8-76.4(m,J=28.5,J=3 .0Hz), 64.9 (dd, J=27.0, J=6.0Hz), 40.0 (d, J=1.5Hz), 21.6, 15.9 (q, J=4.5, Hz). 19 F NMR (565MHz, CDCl 3 )δ-0.83(s). 31 P NMR (243MHz, CDCl 3 )δ97.64(s).HRMS(ESI)m / z Calcd for C 15 H 22 F 3 O3 PS 2 Na[M+Na] + :425.0592;Found:425.0591.

[0166] O,O-Diethyl S-[3,3,3-trifluoro-2-hydroxy-2-(4-pent-4-en-1-yloxyphenyl)propyl]phosphoric acid dithioate (32): TLC (petroleum ether / ethyl acetate = 15:1, v / v), R f =0.30; yellow oil (58.2 mg, 63%). 1 HNMR(600MHz,)δ7.44(d,J=8.7Hz,2H),6.91(d,J=8.9Hz,2H),5.89-5.82(m,1H),5.07(dd,J=17.1,J=1.4Hz,1H),5.01(d,J=10.2 Hz,1H),4.23-4.07(m,4H),3.98(t,J=6.4Hz,2H),3.76-3.66(m,3H),2.26-2.22(m,2H),1.91-1.87(m,2H),1.34(t,J=7.1Hz,6H). 13 CNMR (150MHz, CDCl 3 )δ159.6,137.8,128.0,125.0(q,J=285.0Hz),127.6,115.4,114.4,76.5(qd,J=28.5,J=3.0Hz ), 67.3, 64.9 (dd, J = 28.5, J = 7.5Hz), 40.0 (d, J = 1.5Hz), 30.2, 28.5, 15.9 (dd, J = 9.0, J = 4.5Hz). 19 F NMR (565MHz, CDCl 3 )δ-1.24(s). 31 P NMR (243MHz, CDCl 3 )δ97.75(s).HRMS(ESI)m / zCalcd for C 18 H 26 F 3 O 4 PS 2 Na[M+Na] + :481.0854;Found:481.0841.

[0167] 4-[3-(O,O-diethylthiophosphorylthio)-1,1,1-trifluoro-2-hydroxypropan-2-yl]phenyl 4-methylbenzenesulfonate (34): TLC (petroleum ether / ethyl acetate = 15:1, v / v), Rf =0.30; yellow oil (77.4 mg, 71%). 1 HNMR (600MHz, CDCl 3 )δ7.69(d,J=8.3Hz,2H),7.47(d,J=8.8Hz,2H),7.30(d,J=8.2Hz,2H),7.04-7.02(m,2 H),4.21-4.06(m,4H),3.98(s,1H),3.72-3.63(m,2H),2.44(s,3H),1.34-1.31(m,6H). 13 C NMR (150 MHz, CDCl 3 )δ150.1,145.7,134.8,132.3,129.9,128.6,128.3,124.7(q,J=285.0Hz),122.4,76.8-7 6.2 (m), 65.1 (dd, J = 19.5, J = 6.0Hz), 39.9 (d, J = 3.0Hz), 21.8, 15.9 (dd, J = 7.5, J = 3.0Hz). 19 F NMR (565MHz, CDCl 3 )δ-0.88(s). 31 PNMR (243MHz,CDCl 3 )δ97.73(s).HRMS(ESI)m / z Calcd for C 20 H 24 F 3 O 6 PS 3 Na[M+Na] + :567.0317;Found:567.0301.

[0168] S-[2-(3-(1,3-dioxoisoindolin-2-yl)phenyl)-3,3,3-trifluoro-2-hydroxypropyl]O,O-diethyl dithiophosphate (36): TLC (petroleum ether / ethyl acetate = 15:1, v / v), R f =0.30; yellow oil (90.1 mg, 87%). 1 H NMR (600 MHz, CDCl 3 )δ7.95-7.92(m,2H),7.80-7.77(m,2H),7.69(s,1H),7.58-7.50(m,3H),4.24-4.06(m,5H),3.81-3.73(m,2H),1.35-1.32(m,6H). 13 C NMR (150 MHz, CDCl3 )δ167.1,137.1,134.7,132.1,131.7,129.2,126.9,126.2,125.0,124.8(q,J=285.0Hz),123 .9,76.8-76.4(m),65.1(dd,J=43.5,J=6.0Hz),40.0(d,J=1.5Hz),15.9(dd,J=9.0,J=3.0Hz). 19 F NMR (565MHz, CDCl 3 )δ-0.73(s). 31 P NMR (243 MHz, CDCl 3 )δ98.04(s).HRMS(ESI)m / z Calcd for C 21 H 21 F 3 NO 5 PS 2 Na[M+Na] + :542.0443;Found:542.0428.

[0169] S-[2-(3-(4-bromobenzamido)phenyl)-3,3,3-trifluoro-2-hydroxypropyl]O,O-diethyl dithiophosphate (38): TLC (petroleum ether / ethyl acetate = 15:1, v / v), R f =0.30; yellow oil (87.5 mg, 76%). 1 HNMR (600MHz, CDCl 3 )δ8.16(s,1H),7.81-7.78(m,2H),7.70(d,J=8.5Hz,2H),7.56(d,J=8.5Hz,2H),7.38(t,J=7. 9Hz,1H),7.30(d,J=7.9Hz,1H),4.21-4.04(m,5H),3.78-3.67(m,2H),1.31(t,J=7.0Hz,6H). 13 C NMR (150 MHz, CDCl 3 )δ165.2,138.1,137.0,133.6,132.1,129.4,128.8,126.9,124.9(q,J=285.0Hz),122.9,121 .1,118.8,76.8-76.4(m),65.0(dd,J=25.5,J=6.0Hz),39.7(d,J=1.5Hz),15.9(d,J=9.0Hz). 19 F NMR (565MHz, CDCl 3)δ-0.74. 31 P NMR (243 MHz, CDCl 3 )δ97.57.HRMS(ESI)m / z Calcd forC 20 H 22 F 3 NO 4 PS 2 Na[M+Na] + :593.9756;Found:593.9738.

[0170] S-[2-(Benzo[d][1,3]dioxolan-5-yl)-3,3,3-trifluoro-2-hydroxypropyl]O,O-diethyl dithiophosphate (40): TLC (petroleum ether / ethyl acetate = 15:1, v / v), R f =0.25; yellow oil (57.0 mg, 68%). 1 HNMR (600MHz, CDCl 3 )δ7.05(d,J=1.4Hz,1H),6.99(dd,J=8.2,J=1.4Hz,1H),6.81(d,J=8.2Hz,1H),5.98(dd,J=2 .5,J=1.4Hz,2H),4.23-4.08(m,4H),3.87(s,1H),3.72-3.64(m,2H),1.34(t,J=7.1Hz,6H). 13 C NMR (150 MHz, CDCl 3 )δ148.2,148.0,129.6,124.9(q,J=285.0Hz),120.4,108.1,107.5,101.5,76.6(qd,J=28 .5, J=1.5Hz), 65.0 (dd, J=28.5, J=7.5Hz), 40.0 (d, J=3.0Hz), 15.8 (dd, J=7.5, J=4.5Hz). 19 F NMR (565MHz, CDCl 3 )δ-1.15. 31 P NMR (243 MHz, CDCl 3 )δ97.77.HRMS(ESI)m / z Calcd for C 14 H 18 F 3 O 5 PS 2 Na[M+Na] + :441.0178;Found:441.0169.

[0171] 3-[3-((diethoxythiophosphoryl)thio)-1,1,1-trifluoro-2-hydroxypropan-2-yl]phenyl 2-(4-(2,2-dichlorocyclopropyl)phenoxy)-2-methylpropanoate (42): TLC (petroleum ether / ethyl acetate = 5:1, v / v), R f =0.50; yellow oil (118.2 mg, 89%). 1 H NMR (600 MHz, CDCl 3 )δ7.40-7.38(m,2H),7.22(s,1H),7.17(d,J=8.6Hz,2H),7.02-7.00(m,1H),6.94(d,J=8.5Hz,2H),4.21-4.06(m,4H),4.03(s,1 H),3.75-3.65(m,2H),2.86(dd,J=10.4,J=8.6Hz,1H),1.95(dd,J=10.6,J=7.4Hz,1H),1.81-1.76(m,7H),1.33(q,J=6.9Hz,6H). 13 C NMR (150 MHz, CDCl 3 )δ172.7,155.0,150.8,137.8,129.9,129.6,128.7,124.7(q,J=285.0Hz),124.2,122.1,120.2,118.8,79.4,76.9-76.3(m ), 65.1 (dd, J = 31.5, J = 6.0Hz), 61.0, 39.9 (d, J = 1.5Hz), 34.9, 25.9, 25.6 (dd, J = 6.0, J = 4.5Hz), 15.8 (dd, J = 7.5, J = 4.5Hz). 19 F NMR (565MHz, CDCl 3 )δ-0.77. 31 P NMR (243 MHz, CDCl 3 )δ97.99.HRMS(ESI)m / z Calcd for C 26 H 30 Cl 2 F 3 O 6 PS 2 Na[M+Na] + :683.0443;Found:683.0421.

[0172] 3-[3-((diethoxyphosphorothioyl)thio)-1,1,1-trifluoro-2-hydroxypropan-2-yl]phenyl 2-((3-(trifluoromethyl)phenyl)amino)nicotinate (44): TLC (petroleum ether / ethyl acetate = 5:1, v / v), R f =0.20; yellow oil (99.0 mg, 76%). 1 HNMR (600MHz, CDCl 3 )δ10.23(s,1H),8.52-8.49(m,2H),8.10(s,1H),7.87(d,J=8.1Hz,1H),7.53-7.47(m,3H),7.43(t,J=7.9Hz,1H),7.30- 7.26(m,2H),6.88(dd,J=7.8,J=4.7Hz,1H),4.25-4.10(m,5H),3.79(s,1H),3.76(s,1H),1.36(td,J=7.0,J=2.6Hz,6H). 13 C NMR (150 MHz, CDCl 3 )δ166.2,156.3,154.2,150.6,140.9,140.2,138.1,131.2(q,J=31.5Hz) ,129.8,129.4,124.8(q,J=285.0Hz),124.4,124.2(q,J=270.0Hz),123.7 ,122.5,120.7,119.4(q,J=3.0Hz),117.4(q,J=3.0Hz),114.4,106.5,76 .5(m),65.1(dd,J=27.0,J=6.0Hz),39.9(d,J=1.5Hz),15.9(q,J=4.5Hz). 19 F NMR (565MHz, CDCl 3 )δ15.28(s),-0.73(s). 31 P NMR (243MHz, CDCl 3 )δ98.03(s).HRMS(ESI)m / z Calcd forC 26 H 25 F 6 N 2 O 5 PS 2 Na[M+Na] + :677.0739;Found:677.0720.

[0173] S-[2-(3-(5-(2,5-dimethylphenoxy)-2,2-dimethylpentanamido)phenyl)-3,3,3-trifluoro-2-hydroxypropyl]O,O-diethyl dithiophosphate (46): TLC (petroleum ether / ethyl acetate = 5:1, v / v), R f =0.35; white solid (97.2 mg, 78%); melting point: 134.1-134.2. 1 H NMR (600 MHz, CDCl 3 )δ7.71(dd,J=8.0,J=1.8Hz,1H),7.64(s,1H),7.45(s,1H),7.35(t,J=7.9Hz ,1H),7.25(t,J=4.1Hz,1H),6.99(d,J=7.4Hz,1H),6.65(d,J=7.4Hz,1H),6. 61(s,1H),4.22-4.04(m,4H),4.00(s,1H),3.94(t,J=4.6Hz,2H),3.77-3.67 (m,2H),2.29(s,3H),2.17(s,3H),1.82(d,J=2.2Hz,4H),1.36-1.31(m,12H). 13 C NMR (150 MHz, CDCl 3 )δ176.0,157.0,138.4,136.8,136.7,130.5,129.3,124.9(q,J=285.0Hz),123.6,122.4,121.0,120.8,118.4,112.3, 76.8-76.4(m),68.0,65.0(dd,J=28.5,J=6.0Hz),43.0,39.8,37.8,25.7,25.3,21.5,15.9,15.8(dd,J=3.0,J=7.5Hz). 19 F NMR (565MHz, CDCl 3 )δ-0.78(s). 31 PNMR (243MHz,CDCl 3 )δ97.78(s).HRMS(ESI)m / z Calcd for C 28 H 39 F 3 NO 5 PS 2 Na[M+Na] + :644.1852;Found:644.1830.

[0174] O,O-Dihexyl S-[3,3,3-trifluoro-2-hydroxy-2-(naphthalen-2-yl)propyl] dithiophosphate (48): TLC (petroleum ether / ethyl acetate = 15:1, v / v), R f =0.60; yellow oil (91.0 mg, 85%). 1 H NMR (600 MHz, CDCl 3 )δ8.13(s,1H),7.91-7.86(m,3H),7.63(d,J=8.6Hz,1H),7.56-7.52(m,2H),4.16-3.9 9(m,5H),3.96-3.83(m,2H),1.71-1.65(m,4H),1.38-1.26(m,12H),0.92-0.88(m,6H). 13 C NMR (150 MHz, CDCl 3 )δ133.4,133.2,133.0,128.7,128.4,127.7,127.0,126.6,125.1(q,J=285.0Hz),123.6,76.8,69.0(dd,J=30 .0, J=7.5Hz), 40.1 (d, J=1.5Hz), 31.4, 29.9 (dd, J=7.5, J=1.5Hz), 25.3 (d, J=4.5Hz), 22.6, 14.1 (d, J=3.0Hz). 19 F NMR (565MHz, CDCl 3 )δ-0.59(s). 31 P NMR (243MHz, CDCl 3 )δ98.40(s).HRMS(ESI)m / z Calcd forC 25 H 36 F 3 O 3 PS 2 Na[M+Na] + :559.1688;Found:559.1675.

[0175] O,O-Dicyclohexyl S-[3,3,3-trifluoro-2-hydroxy-2-(naphthalen-2-yl)propyl] dithiophosphate (50): TLC (petroleum ether / ethyl acetate = 15:1, v / v), R f =0.55; yellow oil (87.3 mg, 82%). 1 H NMR (600 MHz, CDCl 3)δ8.14(s,1H),7.91-7.86(m,3H),7.63(d,J=8.6Hz,1H),7.55-7.52(m,2H),4.65-4.49(m,2H),4.25(s,1H),3. 94-3.83(m,2H),1.95-1.91(m,4H),1.74-1.73(m,4H),1.62-1.50(m,6H),1.41-1.32(m,4H),1.29-1.23(m,2H). 13 C NMR (150 MHz, CDCl 3 )δ133.5,133.3,133.0,128.6,128.3,127.7,127.0,126.9,126.5,125.1(q,J=285.0Hz),123.6,79 .5(dd,J=7.5,J=6.0Hz),77.3-76.7(m),40.0(d,J=1.5Hz),33.4-33.0(m),25.1(d,J=7.5Hz),23.7. 19 F NMR (565MHz, CDCl 3 )δ-0.54(s). 31 PNMR (243MHz,CDCl 3 )δ94.25(s).HRMS(ESI)m / zCalcd for C 25 H 32 F 3 O 3 PS 2 Na[M+Na] + :555.1375;Found:555.1378.

[0176] The above description of the disclosed embodiments enables one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. An α-trifluoromethyl β-dithiosulfate tertiary alcohol compound, characterized in that: The structure of the α-trifluoromethyl β-dithiosulfate tertiary alcohol compound is as follows: Wherein, R is phenyl, naphthyl or substituted phenyl, and the substitution is selected from methyl, ethyl, methoxy, tert-butyl, benzyl, thiomethyl, and hydroxyl.

2. A method for synthesizing the α-trifluoromethyl β-dithiosulfate tertiary alcohol compound as claimed in claim 1, characterized in that: R is as defined in claim 1.

3. The method for synthesizing the α-trifluoromethyl β-dithiosulfate tertiary alcohol compound according to claim 2, characterized in that: Using trifluoromethyl olefin as raw material, it reacts with phosphorus pentasulfide and ethanol under visible light conditions to generate α-trifluoromethyl β-dithiosulfate tertiary alcohol compounds.

4. The method for synthesizing the α-trifluoromethyl β-dithiosulfate tertiary alcohol compound according to claim 2 or 3, characterized in that: The molar ratio of the trifluoromethyl olefin to phosphorus pentasulfide and ethanol is 1:1:10-1:1.5:

20.

5. The method for synthesizing the α-trifluoromethyl β-dithiosulfate tertiary alcohol compound according to claim 2 or 3, characterized in that: The visible light irradiation is selected from one or more light sources of 5000-5500K white light, 395-400nm purple light, and 455-460nm blue light, and the power of the irradiation light source is 6-10W.

6. The method for synthesizing the α-trifluoromethyl β-dithiosulfate tertiary alcohol compound according to claim 2 or 3, characterized in that: The reaction time is 12-36 hours, the reaction temperature is room temperature, and the reaction atmosphere is air atmosphere.

7. The method for synthesizing the α-trifluoromethyl β-dithiosulfate tertiary alcohol compound according to claim 2 or 3, characterized in that: The reaction solvent is one or more of tetrahydrofuran and acetonitrile.

8. Use of the α-trifluoromethyl β-dithiosulfate tertiary alcohol compound as claimed in claim 1 or the α-trifluoromethyl β-dithiosulfate tertiary alcohol compound prepared by the method as claimed in claim 2 in a pharmaceutical preparation.

9. The use according to claim 8, characterized in that: The α-trifluoromethyl β-dithiosulfate tertiary alcohol compound can be used as a pharmaceutical intermediate or a pharmaceutical molecule.

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