A method for difunctionalization of olefins and delta-trifluoromethyl ketone products prepared thereby

Abstract

The present invention relates to a method for difunctionalizing olefins and delta-trifluoromethyl ketone products prepared thereby. The present invention provides a green mechanochemical approach for difunctionalizing unactivated olefins via a cascade radical trifluoromethylation / distal migration pathway. The present invention enables rapid modification of unactivated olefins via cascade reduction under mechanical redox conditions. Compared with photocatalysis and electrocatalysis, this method offers significant advantages, such as ease of operation, air compatibility, low solvent consumption, and catalyst recyclability, meeting the requirements of green chemistry.

Description

Technical Field

[0001] The present invention relates to a method for difunctionalization of olefins and delta-trifluoromethyl ketone products prepared thereby, which are used for difunctionalization of unactivated olefins via a cascade free radical trifluoromethylation distal migration pathway. Background Art

[0002] Over the past few decades, mechanochemistry has emerged as a practical and sustainable synthetic technique. Due to its advantages such as being solvent-free, having shorter reaction times, being easy to handle, and being air-friendly, it allows for organic transformations to be performed under green and sustainable conditions. Recently proposed mechanochemical concepts can extend the scope of ball-milling-based reactions to radical-type transformations. A typical mechanobody undergoes the following process: the piezoelectric material is transformed into highly polarizable particles under mechanochemical impact, and the polarized piezoelectric material acts as a single electron transfer (SET) donor, reducing the corresponding substrate X to anionic radical X. · ˉ, this reduction leaves behind a "hole", which then returns to the poorly polarized ground state upon single-electron oxidation ( Figure 1 A). Landmark work on mechanooxidation has been reported by a research group, where ball milling and the commercially available piezoelectric material BaTiO3 were used to generate aryl radicals from aryl diazonium salts, subsequently providing direct borylation and arylation. Recently, this strategy has also been extended to the generation of CF3 radicals and thio radicals, leading to the monofunctionalization of (hetero)arenes or the formation of disulfide bonds via radical coupling ( Figure 1 However, mechanically mediated free radical cascade reactions are still rare, with only hydroxyl- and phenyl-mediated intermolecular polymerization of olefins reported, and intramolecular cascade reactions have not been reported ( Figure 1 A (right). Therefore, compared with the widespread application of photoredox catalysis strategies, the field of mechanochemistry is still in its infancy, and the types of mechanical reactions are quite limited, especially in the field of difunctionalization of olefins.

[0003] The difunctionalization of olefins has become increasingly attractive as a powerful and atom-economical method to increase the complexity of molecules. In this field, trifluoromethylation has attracted widespread attention due to its ability to significantly improve the solubility, lipophilicity, permeability and metabolic stability of drug molecules. Trifluoromethyl radical-mediated functional group migration has become a good strategy for the difunctionalization of unactivated olefins. For example, photocatalytic and electrocatalytic strategies have been applied to the trifluoromethylation / alkynylation of unactivated olefins in the following ways. There are reports on 1,4-alkyne migration in solution phase ( Figure 1 B). However, these techniques have drawbacks such as stoichiometric reagents or expensive catalysts, high solvent consumption, inert atmosphere, and long reaction times, thus developing novel environmentally friendly and sustainable methods to activate unactivated olefins is of great importance. Summary of the Invention

[0004] The present invention provides a method for difunctionalization of olefins, which mainly comprises the following steps:

[0005] 1) placing unactivated olefin, Umemoto reagent, and BaTiO3 into a grinding jar and grinding to obtain a first mixture;

[0006] 2) adding acetone to the first mixture, and performing air grinding reaction under sealing to obtain a second compound;

[0007] 3) Passing the second compound through a short diatomaceous earth column to obtain a crude material, which is purified to obtain the corresponding olefin difunctionalized product.

[0008] In step 1), the equivalent ratio of unactivated olefin: Umemoto reagent: BaTiO3 is 1.3:1.0:5.0.

[0009] The unactivated olefin in step 1) is 1,3-diphenylhept-6-ene-1-yn-3-ol.

[0010] During the grinding in step 1), two stainless steel balls with a diameter of 7 mm were placed in the grinding jar; the volume of the stainless steel grinding jar was 5 ml.

[0011] The concentration of acetone in step 2) is 0.2 μL / mg.

[0012] Step 2) The grinding is performed by sealing the grinding jar in air and placing it in a ball mill for grinding for 3 hours.

[0013] In step 3), the short diatomaceous earth column is a short diatomaceous earth column eluted under reduced pressure with ethyl acetate.

[0014] Step 3) The purification is carried out by flash silica gel column chromatography.

[0015] In step 3), the corresponding olefin difunctionalized product is a δ-trifluoromethyl substituted ketone product.

[0016] The present invention also provides a difunctionalized olefin prepared by the above method.

[0017] Furthermore, the difunctionalized olefin is a δ-trifluoromethyl substituted ketone product.

[0018] In the present invention, δ-trifluoromethylated aryl ketones are efficiently synthesized by trifluoromethyl-initiated distal group migration in combination with piezoelectric material BaTiO3 and ball milling in the presence of minimal acetone. 1 The aryl, heteroaryl, alkyl, cycloalkyl and Bn substituents on the α-trifluoromethylated aryl ketones have no effect on the intermolecular tandem process of constructing δ-trifluoromethylated aryl ketones ( Figure 1C). The migration group can be expanded from alkynyl to heteroaryl groups. The present invention discovered that substrates with a methyl group at the α-position of the olefin can provide corresponding products that cannot be synthesized by photocatalysis. Compared with traditional photocatalytic and electrocatalytic methods, the present method uses recyclable and inexpensive BaTiO3 as a catalyst and a trace amount of acetone as a liquid auxiliary grinding agent, completing the conversion in air within 3 hours. ( Figure 1 C).

[0019] This invention utilizes a green mechanochemical approach to difunctionalize unactivated alkenes via a cascade radical trifluoromethylation / distal migration pathway. This method enables rapid modification of unactivated alkenes through cascade reduction under mechanical redox conditions. Compared to photocatalysis and electrocatalysis, this method offers significant advantages such as ease of operation, air compatibility, low solvent consumption, and catalyst recyclability, meeting the requirements of green chemistry.

[0020] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 The free radical cascade reaction is realized for free radical-mediated mechanical redox reaction, difunctionalization of non-activated olefins in solution phase and mechanical redox reaction, where Figure 1 A in the middle shows the reduction of the corresponding substrate X to an anion radical X · ˉ, this reduction leaves behind a "hole", which then returns to the poorly polarized ground state upon single-electron oxidation, Figure 1 The left side of A shows the expansion to the generation of CF3 radicals, nitrogen radicals and thiol radicals, leading to the monofunctionalization of (hetero)arenes or the formation of disulfide bonds through radical coupling. Figure 1 A (right) shows the mechanical redox reaction to achieve olefin polymerization mediated by hydroxyl and aryl radicals; Figure 1 B is the difunctionalization of non-activated olefins in solution phase; Figure 1 C represents the R 1 The aryl, heteroaryl, alkyl, cycloalkyl, and Bn substituents on the α-trifluoromethylated aryl ketones had no effect on the intermolecular tandem process of constructing δ-trifluoromethylated aryl ketones.

[0022] Figure 2A-2B GT 300 and stainless steel tanks used in the present invention.

[0023] Figure 3 This is a diagram of the separation of the crude product and the grinding jar under reduced pressure.

[0024] Figure 4For the detection of CF3 free radical intermediates. DETAILED DESCRIPTION

[0025] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0026] Chemical reagents and equipment used:

[0027] Column chromatography was performed on silica gel (300-400 mesh) eluting with ethyl acetate and petroleum ether;

[0028] TLC was performed on glass-backed silica gel plates;

[0029] All reactions were performed using a grinding vessel in GT 300, which was purchased from Beijing Grinding Instrument Co., Ltd.;

[0030] Grinding jars and steel balls are made of stainless steel ( Figure 2A-2B );

[0031] Umemoto's reagent, piezoelectric material BaTiO3 Buy;

[0032] Unless otherwise stated, all chemicals were commercially available;

[0033] Petroleum ether (60-90°C) needs to be redistilled.

[0034] Unless otherwise stated, all reactions were performed at room temperature in air.

[0035] Example 1: Preparation of unactivated olefin substrates

[0036] ① Place acyl chloride (1.0 equivalent) and cuprous iodide, 5% mol) in a round-bottom flask, purge with nitrogen, then add anhydrous tetrahydrofuran (20 ml), and stir the reaction at -78°C for 30 min. Then, add 3-butenylmagnesium bromide (1.0 equivalent) dropwise, stir for 30 min, and then warm to room temperature. React for 12 h, quench with saturated ammonium chloride solution, extract with ethyl acetate, dry over anhydrous magnesium sulfate, spin dry, and filter through a column to obtain 1s;

[0037] ② Place differently substituted terminal alkynes 2s (1.0 equivalent) and anhydrous oxygen-free tetrahydrofuran (10 ml) in a round-bottom flask, fill with nitrogen, and then place the reaction at -78°C and stir for 30 min. Then, add n-butyl lithium (1.0 equivalent) dropwise and stir for 10 min. Then, add 1s (1.0 equivalent) dropwise and stir for 30 min. After warming to room temperature, react for 12 h, quench with saturated ammonium chloride solution, extract with ethyl acetate, dry over anhydrous magnesium sulfate, spin dry, and pass through a column to obtain 3ss.

[0038]

[0039]

[0040] 3-cyclopropyl-1-phenylhept-6-en-1-yn-3-ol

[0041] 1 H NMR (600 MHz, CDCl3) δ7.41–7.37(m,2H),7.30(dt,J=2.6,1.9Hz,3H),5.92(ddt,J=16.9,10.2,6.6 Hz,1H),5.13–5.06(m,1H),4.99(dd,J=10.2,1.6 Hz,1H),2.41(ddd,J=15.4,7.5,1.2 Hz,2H),2.12(s,1H),1.97(qdd,J=13.4,9.2,6.8 Hz,2H),1.19(ddd,J=10.5,7.7,5.8 Hz,1H),0.72–0.64(m,1H),0.61–0.54(m,2H),0.52–0.45(m,1H). 13 C NMR (150 MHz, CDCl3) δ138.55,131.66,128.31,128.21,122.53,114.56,88.71,85.21,73.49,42.04,29.10,20.96,2.88,1.00.

[0042]

[0043] 3-cyclobutyl-1-phenylhept-6-en-1-yn-3-ol

[0044] 1H NMR(600 MHz,CDCl3)δ7.47–7.42(m,2H),7.31(dd,J=4.1,2.4Hz,3H),5.90(ddt,J=16.9,10.2,6.6 Hz,1H),5.08(ddd,J=17.1,3.3,1.6 Hz,1H),4.98(dd,J=10.2,1.5 Hz,1H),2.63(p,J=8.5 Hz,1H),2.42–2.31(m,2H),2.22–2.14(m,1H),2.07(dt,J=19.2,9.6 Hz,1H),2.03–1.93(m,2H),1.92–1.83(m,1H),1.82–1.76(m,1H),1.71–1.65(m,3H). 13 C NMR(150MHz,CDCl3)δ138.65,131.72,128.23,122.84,114.66,109.99,90.34,85.53,73.57,44.81,38.58,28.86,23.70,22.66,17.04.

[0045]

[0046] 1-(3-methoxyphenyl)-3-phenylhept-6-en-1-yn-3-ol

[0047] 1 H NMR(600 MHz,CDCl3)δ7.69(d,J=8.0 Hz,2H),7.38(t,J=7.5Hz,2H),7.31(dd,J=10.5,4.1 Hz,1H),7.24(d,J=7.1 Hz,1H),7.11–7.07(m,1H),7.01(s,1H),6.90(dd,J=8.3,1.3 Hz,1H),5.84(ddt,J=16.7,10.4,6.5 Hz,1H),5.03(d,J=17.1 Hz,1H),4.95(d,J=10.2 Hz,1H),3.80(s,3H),2.61(d,J=2.5 Hz,1H),2.40–2.31(m,1H),2.21(ddd,J=15.9,12.8,4.8 Hz,1H),2.17–2.09(m,1H),2.05(td,J=12.4,4.5 Hz,1H). 13CNMR(150 MHz,CDCl3)δ159.34,144.55,138.05,129.37,128.22,127.74,125.43,124.26,123.51,116.66,115.06,114.74,91.05,86.24,73.55,55.29,44.48,29.24.

[0048]

[0049] 1-(4,4-dimethylthiochroman-6-yl)-3-phenylhex-5-en-1-yn-3-ol

[0050] 1 H NMR(600 MHz,CDCl3)δ7.68(d,J=6.2 Hz,2H),7.45(d,J=2.5Hz,1H),7.38(t,J=7.5 Hz,2H),7.30(t,J=7.3 Hz,1H),7.14(d,J=8.0 Hz,1H),7.03(d,J=8.1 Hz,1H),5.83(dt,J=10.3,6.8 Hz,1H),5.03(d,J=17.1Hz,1H),4.95(d,J=9.4 Hz,1H),3.05–3.00(m,2H),2.33(s,1H),2.21(d,J=3.6 Hz,1H),2.12(dd,J=14.7,9.6 Hz,1H),2.08–2.00(m,1H),1.97–1.91(m,2H),1.32(s,6H). 13 C NMR(150 MHz,CDCl3)δ144.70,142.03,138.12,133.33,129.65,129.10,128.19,127.67,126.47,125.46,117.78,114.68,90.40,86.61,73.59,44.52,37.24,32.93,29.92,29.25,23.16.

[0051]

[0052] 1-(naphthalen-2-yl)-3-phenylhept-6-en-1-yn-3-ol

[0053] 1H NMR(600 MHz,CDCl3)δ8.02(s,1H),7.85–7.78(m,3H),7.77–7.73(m,2H),7.53(dd,J=8.4,1.4 Hz,1H),7.52–7.48(m,2H),7.41(t,J=7.7 Hz,2H),7.33(dd,J=10.8,3.9 Hz,1H),5.88(ddt,J=16.9,10.2,6.5 Hz,1H),5.07(dd,J=17.1,1.6 Hz,1H),4.98(dd,J=10.2,0.8 Hz,1H),2.59(s,1H),2.40(ddt,J=16.5,11.5,5.8 Hz,1H),2.27(dtd,J=12.6,11.1,5.5 Hz,1H),2.22–2.15(m,1H),2.14–2.07(m,1H). 13 C NMR(150 MHz,CDCl3)δ144.61,138.07,132.90,131.65,128.35,128.26,127.98,127.76,127.73,127.71,126.75,126.57,125.46,119.77,114.78,109.98,86.68,73.65,44.53,29.30.

[0054]

[0055] 3-phenyl-1-(pyren-1-yl)hept-6-en-1-yn-3-ol

[0056] 1H NMR(600 MHz,CDCl3)δ8.55(d,J=9.0 Hz,1H),8.24–8.19(m,2H),8.19–8.14(m,2H),8.10(dd,J=16.0,7.3 Hz,2H),8.04(dd,J=15.1,8.0 Hz,2H),7.84(d,J=7.5Hz,2H),7.45(t,J=7.7 Hz,2H),7.36(t,J=7.4Hz,1H),5.92(ddt,J=16.8,10.2,6.4 Hz,1H),5.10(d,J=17.3 Hz,1H),5.00(d,J=10.0 Hz,1H),4.11(q,J=7.1 Hz,1H),2.56–2.46(m,1H),2.39(dd,J=15.1,10.1 Hz,1H),2.34–2.26(m,1H),2.26–2.19(m,1H),2.03(s,1H). 13 C NMR(150 MHz,CDCl3)δ144.72,138.08,132.10,131.43,131.20,130.98,129.81,128.52,128.35,128.27,127.84,127.16,126.25,125.66,125.64,125.56,125.27,124.43,124.39,124.25,116.92,114.90,96.92,85.41,74.05,44.75,29.49.

[0057]

[0058] 2-phenyl-1-(thiophen-2-yl)hept-6-en-1-yn-3-ol

[0059] 1H NMR (600 MHz, CDCl3) δ7.68–7.64(m,2H),7.39(t,J=7.6 Hz,2H),7.35–7.29(m,1H),7.28(dd,J=5.1,0.9 Hz,1H),7.27–7.24(m,1H),6.99(dd,J=5.1,3.7 Hz,1H),5.84(ddt,J=16.9,10.2,6.4 Hz,1H),5.04(dd,J=17.2,1.6 Hz,1H),4.96(dd,J=10.2,1.4 Hz,1H),2.54(s,1H),2.36–2.28(m,1H),2.20(dddd,J=14.0,12.4,6.0,4.7 Hz,1H),2.16–2.09(m,1H),2.09–2.02(m,1H). 13 C NMR (150 MHz, CDCl3) δ144.28,137.97,132.29,128.26,127.80,127.34,126.95,125.40,122.38,114.81,95.03,79.61,73.73,44.37,29.18.

[0060]

[0061] 6-methyl-1,3-diphenylhept-6-en-1-yn-3-ol

[0062] 1 H NMR (600 MHz, CDCl3) δ7.70 (d, J = 7.4 Hz, 2H), 7.49 (dd, J = 6.5, 2.9 Hz, 2H), 7.39 (t, J = 7.6 Hz,2H),7.35–7.29(m,4H),4.71(s,2H),2.58(s,1H),2.31(dd,J=18.6,7.8 Hz,1H),2.15(ddt,J=29.6,24.2,10.1 Hz,4H),1.73(s,3H). 13 C NMR(150 MHz, CDCl3)δ145.48,144.65,131.72,128.50,128.29,128.22,127.72,125.44,122.55,109.97,91.23,86.34,73.67,43.52,33.05,22.65.

[0063] Example 2: Refunctionalization of unactivated olefins

[0064]

[0065] Unactivated olefin (1) (1.3 equivalents), Umemoto reagent (2c) (1.0 equivalents) and BaTiO3 (5.0 equivalents) were placed in a stainless steel grinding jar (5 ml) with two stainless steel balls (7 mm, diameter) in the jar, and then acetone (0.2 μL / mg) was added to the mixture. The jar was sealed in air and placed in a ball mill (GT 300, 1800 rpm). After grinding for 3 hours, the reaction mixture was passed through a short diatomaceous earth column eluted with ethyl acetate under reduced pressure, as Figure 3 The crude material was purified by flash chromatography (SiO2, hexane / ethyl acetate) to afford the corresponding δ-trifluoromethyl substituted ketone product 3.

[0066] Example 3: Free radical capture experiment

[0067]

[0068] 1a (0.39 mmol), 2c (0.30 mmol), BaTiO3 (1.5 mmol) and TEMPO (0.9 mmol) were placed in a stainless steel grinding jar (5.0 ml) with two stainless steel balls (7 mm, diameter), and acetone (0.2 μL / mg) was added to the mixture. After the jar was sealed in air, it was placed in a ball mill (GT300, 1800 rpm). After grinding for 3 hours, the reaction mixture was passed through a short diatomaceous earth column eluted with ethyl acetate under reduced pressure. The trifluoromethyl radical intermediate was captured by TEMPO and detected by GC-MS, as shown in FIG. Figure 4 shown.

[0069] Example 4: BaTiO3 cycle experiment

[0070]

[0071] 1a (0.39 mmol), 2c (0.30 mmol) and BaTiO3 (1.5 mmol) were placed in a stainless steel grinding jar (5.0 mL) with two stainless steel balls (7 mm in diameter), and the solvent acetone (0.2 μL / mg) was added to the mixture. After the jar was sealed in air, it was placed in a ball mill (GT300, 1800 rpm). After grinding for 3 hours, the reaction mixture was passed through a short diatomaceous earth column equipped with suitable filter paper and eluted under reduced pressure with ethyl acetate. After drying in a 100°C oven for 3 hours, BaTiO3 was reused in the next reaction. After running 5 times, the yield of 3a remained above 60%. It is believed that the loss of BaTiO3 should be the reason for the decrease in yield.

[0072] Example 5: Green Chemistry Index Evaluation

[0073]

[0074] Using 1,3-diphenylhept-6-en-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1 equivalent) and acetone (0.2 μL / mg), the crude reaction mixture was purified by flash silica gel column chromatography (petroleum ether / EtOAc=60 / 1) to give the product 3a as a light yellow solid (87 mg, 88%).

[0075] Example 6: Characterization of δ-trifluoromethyl substituted ketone products

[0076] 1,6-diphenyl-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3a)

[0077]

[0078] 1,3-Diphenylhept-6-en-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=50:1) to give 3a as a yellow solid (87 mg, 88%) with a melting point of 50°C.

[0079] 1 H NMR (600MHz, CDCl3) δ8.03–7.97(m,2H),7.57(t,J=7.4Hz,1H),7.47(t,J=7.7Hz,2H),7.38(dd,J=7.0,2.6Hz,2H),7.31–7.26(m,3H),3.3 4–3.21(m,2H),3.10(tt,J=9.8,4.9Hz,1H),2.57–2.45(m,1H),2.44–2.32(m,1H),2.19(ddd,J=12.8,7.6,4.5Hz,1H),2.02–1.90(m,1H). 13C NMR (150MHz, CDCl3) δ199.14,136.72,133.21,131.59,128.65,128.26,128.14,128.03,126.04 (d,J=277.4Hz),122.93,89.09,83.48,39.38(q,J=27.9Hz),35.90,29.03,26.10(q,J=3.0Hz). 19 F NMR (376MHz, CDCl3) δ-64.06 (t, J=10.5Hz).

[0080] 1-(4-methoxyphenyl)-6-phenyl-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3b)

[0081]

[0082] 3-(4-Methoxyphenyl)-1-phenylhept-6-ene-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=50 / 1-30 / 1) to give the product 3b as a colorless oil (77 mg, 71%).

[0083] 1 H NMR(600MHz, CDCl3)δ7.97(d,J=8.9Hz,2H),7.37(dd,J=6.6,3.0Hz,2H),7.31–7.26(m,3H),6.92(d,J=8.8Hz,2H),3.86(s,3H),3.27– 3.15(m,2H),3.08(tt,J=9.7,4.9Hz,1H),2.54–2.43(m,1H),2.43–2.32(m,1H),2.16(ddd,J=12.9,7.6,4.6Hz,1H),1.97–1.89(m,1H). 13C NMR (150MHz, CDCl3) δ197.62,163.53,131.57,130.27,129.92,128.21,128.06,126.04(d,J=277.5 Hz), 123.02, 113.75, 89.22, 83.41, 55.42, 39.38 (q, J = 27.8Hz), 35.49, 29.27, 26.17 (q, J = 3.0Hz). 19 F NMR (376MHz, CDCl3) δ-64.07 (t, J=10.5Hz).

[0084] phenyl-1-(o-tolyl)-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3c)

[0085]

[0086] 1-Phenyl-3-(o-tolyl)hept-6-en-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=100 / 1) to give the product 3c as a colorless oil (85 mg, 82%).

[0087] 1 H NMR (600MHz, CDCl3) δ7.69(d,J=7.7Hz,1H),7.37(t,J=7.6Hz,3H),7.32–7.22(m,5H),3.19(t,J=7.2Hz,2H),3.08(tt,J=9.8 ,4.9Hz,1H),2.54–2.44(m,4H),2.37(ddd,J=15.1,13.0,7.7Hz,1H),2.21–2.11(m,1H),1.90(ddd,J=17.2,13.6,6.9Hz,1H). 13C NMR (150MHz, CDCl3) δ203.07,138.07,137.70,131.97,131.56,131.32,128.39,128.21,128.08,12 6.31(d,J=276Hz),125.09,122.96,89.05,83.49,39.39(q,J=28.1Hz),38.76,29.14,26.03,21.25. 19 F NMR (376MHz, CDCl3) δ-64.08 (t, J=10.5Hz).

[0088] 6-phenyl-1-(m-tolyl)-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3d)

[0089]

[0090] 1-Phenyl-3-(m-tolyl)hept-6-en-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=100 / 1) to give the product 3d as a colorless oil (99 mg, 96%).

[0091] 1 H NMR(600MHz, CDCl3)δ7.79(d,J=8.1Hz,2H),7.40–7.32(m,4H),7.31–7.26(m,3H),3.30–3.20(m,2H),3 .09(tt,J=9.7,4.9Hz,1H),2.56–2.45(m,1H),2.43–2.32(m,4H),2.22–2.13(m,1H),1.99–1.90(m,1H). 13C NMR (150MHz, CDCl3) δ199.31,138.42,136.87,133.88,131.58,128.53,128.48,128.21,128.08,126.04(d, J=277.4Hz),125.23,123.00,89.16,83.47,39.38(q,J=27.9Hz),35.90,29.16,26.13(d,J=3.0Hz),21.29. 19 F NMR (376MHz, CDCl3) δ-64.07 (t, J=10.5Hz).

[0092] 1-(4-(tert-butyl)phenyl)-6-phenyl-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3e)

[0093]

[0094] 3-(4-(tert-Butyl)phenyl)-1-phenylhept-6-ene-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (35.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=100 / 1) to give the product 3e as a light yellow oil (95.5 mg, 82%).

[0095] 1 H NMR (600MHz, CDCl3) δ7.94(d,J=8.2Hz,2H),7.47(d,J=8.4Hz,2H),7.39–7.34(m,2H),7.28(dd,J=7.4,3.7Hz,3H),3.31–3.19(m,2H),3.0 9(tt,J=9.6,4.9Hz,1H),2.57–2.45(m,1H),2.44–2.32(m,1H),2.18(dt,J=12.7,7.6Hz,1H),1.95(dt,J=18.8,10.9Hz,1H),1.34(s,9H). 13C NMR (150MHz, CDCl3) δ198.73,156.90,134.26,131.58,128.19,128.06,127.99,126.05(d,J=277.4Hz) ,125.54,123.02,89.18,83.46,39.39(q,J=28.0Hz),35.75,35.08,31.04,29.17,26.16(d,J=2.9Hz). 19 F NMR (376MHz, CDCl3) δ-64.05 (t, J=10.5Hz).

[0096] 1-(4-fluorophenyl)-6-phenyl-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3f)

[0097]

[0098] 3-(4-Fluorophenyl)-1-phenylhept-6-en-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=60 / 1) to give the product 3f as a colorless oil (86 mg, 82%).

[0099] 1 H NMR(600MHz, CDCl3)δ8.01(dd,J=8.5,5.5Hz,2H),7.39–7.33(m,2H),7.28(d,J=6.2Hz,3H),7.12(t,J=8.5Hz,2H),3.29–3.16(m,2H), 3.08(tt,J=9.9,5.0Hz,1H),2.57–2.45(m,1H),2.43–2.31(m,1H),2.17(dt,J=12.7,7.6Hz,1H),1.94(ddd,J=18.9,11.9,8.1Hz,1H). 13C NMR (150MHz, CDCl3) δ197.41,165.77(d,J=254.8Hz),133.23(d,J=2.9Hz),131.55,130.62(d,J=9.3Hz),128.23,128.15,1 25.99(d,J=277.5Hz),122.90,115.69(d,J=21.9Hz),89.01,83.56,39.38(q,J=28.0Hz),35.79,29.01,26.11(d,J=3.0Hz). 19 F NMR (376MHz, CDCl3) δ-64.08 (t, J = 10.5Hz), -105.9 (m).

[0100] 1-(4-chlorophenyl)-6-phenyl-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3g)

[0101]

[0102] 3-(4-Chlorophenyl)-1-phenylhept-6-ene-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=70 / 1) to give 3 g of the product as a colorless oil (108 mg, 99%).

[0103] 1 H NMR (600MHz, CDCl3) δ7.92(d,J=8.6Hz,2H),7.42(d,J=8.6Hz,2H),7.38–7.33(m,2H),7.31–7.26(m,3H),3.28–3.18(m,2H) ,3.08(tt,J=10.0,5.0Hz,1H),2.56–2.45(m,1H),2.42–2.31(m,1H),2.17(ddd,J=12.7,7.6,4.5Hz,1H),1.99–1.89(m,1H). 13C NMR (150MHz, CDCl3) δ197.80,139.61,135.09,131.54,129.41,128.93,128.24,128.16,125.98(d ,J=277.6Hz),122.87,88.96,83.60,39.38(q,J=28.1Hz),35.86,28.95,26.09(dd,J=6.0,2.8Hz). 19 F NMR (376MHz, CDCl3) δ-64.08 (t, J=10.5Hz).

[0104] 1-(4-bromophenyl)-6-phenyl-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3h)

[0105]

[0106] 3-(4-Bromophenyl)-1-phenylhept-6-ene-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=100 / 1-80 / 1) to give the product 3h as a colorless oil (89.5 mg, 73%).

[0107] 1 H NMR (600MHz, CDCl3) δ7.84(d,J=8.5Hz,2H),7.59(d,J=8.6Hz,2H),7.38–7.33(m,2H),7.31–7.26(m,3H),3.29–3.15(m,2H) ,3.08(tt,J=9.9,5.0Hz,1H),2.57–2.44(m,1H),2.43–2.30(m,1H),2.17(ddd,J=12.7,7.6,4.5Hz,1H),1.98–1.88(m,1H). 13C NMR (150MHz, CDCl3) δ197.99,135.49,131.93,131.55,129.52,128.31,128.24,128.17,125.98 (d,J=277.4Hz),122.86,88.95,83.62,39.38(q,J=28.0Hz),35.84,28.94,26.09(d,J=3.0Hz). 19 F NMR (376MHz, CDCl3) δ-64.07 (t, J=10.5Hz).

[0108] 6-phenyl-4-(2,2,2-trifluoroethyl)-1-(4-(trifluoromethyl)phenyl)hex-5-yn-1-one(3i)

[0109]

[0110] 1-Phenyl-3-(4-(trifluoromethyl)phenyl)hept-6-en-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=200 / 1) to give the product 3i as a colorless oil (102 mg, 85%).

[0111] 1 H NMR (600MHz, CDCl3) δ8.08(d,J=8.2Hz,2H),7.72(d,J=8.2Hz,2H),7.38–7.32(m,2H),7.31–7.25(m,3H),3.35–3.22(m,2 H),3.10(tt,J=10.0,5.1Hz,1H),2.58–2.46(m,1H),2.44–2.32(m,1H),2.20(dt,J=12.6,7.5Hz,1H),2.01–1.91(m,1H). 13C NMR (150MHz, CDCl3) δ198.03, 139.40, 134.47 (q, J = 32.9Hz), 131.53, 128.32, 128.24, 128.20, 125.97 (d, J = 277.5Hz), 125 .69(q,J=3.6Hz),123.54(d,J=272.6Hz),122.81,88.84,83.72,39.65,39.47,39.28,39.10,36.20,28.81,26.08,26.06. 19 F NMR(376MHz, CDCl3)δ-63.16(s),-64.10(t,J=10.5Hz).

[0112] 1-(naphthalen-2-yl)-6-phenyl-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3j)

[0113]

[0114] 3-(2-Naphthyl)-1-phenylhept-6-en-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=50 / 1) to give the product 3j as a white solid (59 mg, 52%) with a melting point of 70°C.

[0115] 1 H NMR (600MHz, CDCl3) δ8.51 (s, 1H), 8.05 (d, J = 8.6Hz, 1H), 7.95–7.84 (m, 3H), 7. 59(t,J=7.5Hz,1H),7.54(t,J=7.5Hz,1H),7.42–7.36(m,2H),7.27(d,J=6.2Hz ,3H),3.46–3.35(m,2H),3.14(tt,J=9.6,4.9Hz,1H),2.59–2.47(m,1H),2.41( ddd,J=20.2,10.1,5.0Hz,1H),2.24(dt,J=12.6,7.6Hz,1H),2.05–1.97(m,1H). 13C NMR (150MHz, CDCl3) δ199.04,135.62,134.15,132.51,131.59,129.68,129.54,128.48,128.45,128.23,128.11,127.74 ,126.75,126.04(d,J=277.4Hz),123.77,122.98,89.18,83.57,39.70,39.51,39.32,39.14,35.94,29.28,26.20,26.18. 19 F NMR (376MHz, CDCl3) δ-64.05 (t, J=10.5Hz).

[0116] 6-phenyl-1-(thiophen-2-yl)-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3k)

[0117]

[0118] 1-Phenyl-3-(2-thienyl)hept-6-en-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=50 / 1) to give the product 3k as an orange oil (43.5 mg, 43%).

[0119] 1 H NMR (600MHz, CDCl3) δ7.76(d,J=3.7Hz,1H),7.63(d,J=4.9Hz,1H),7.40–7.34(m,2H),7.27(dd,J=10.1,5.1Hz,3H),7.12(t,J=4.3Hz,1H),3 .26–3.14(m,2H),3.08(tt,J=9.7,4.9Hz,1H),2.55–2.43(m,1H),2.36 (dqd,J=15.6,10.5,5.5Hz,1H),2.22–2.13(m,1H),1.98–1.90(m,1H). 13C NMR (150MHz, CDCl3) δ191.94,144.05,133.61,131.86,131.57,128.22,128.12,128.08,126.00 (d,J=277.5Hz),122.94,88.95,83.61,39.32(q,J=28.0Hz),36.60,29.24,26.14(d,J=2.9Hz). 19 F NMR (376MHz, CDCl3) δ-64.06 (t, J=10.5Hz).

[0120] 1-(benzofuran-2-yl)-6-phenyl-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3l)

[0121]

[0122] 3-(2-Benzofuryl)-1-phenylhept-6-en-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=50 / 1) to give the product 31 as a yellow solid (53 mg, 48%) with a melting point of 70°C.

[0123] 1 H NMR (600MHz, CDCl3) δ7.69(d,J=7.8Hz,1H),7.57(d,J=8.4Hz,1H),7.54(s,1H),7.47(t,J=7.8Hz,1H),7.41–7.35(m,2H),7.33–7.23(m,4 H),3.32–3.21(m,2H),3.10(tt,J=9.7,5.0Hz,1H),2.57–2.44(m,1H),2.43–2.30(m,1H),2.21(td,J=12.8,7.6Hz,1H),2.05–1.94(m,1H). 13C NMR (150MHz, CDCl3) δ190.18,155.61,152.43,131.58,128.23,128.20,128.12,126.99,125.99(d,J=277.8Hz), 123.89,123.25,122.92,112.72,112.42,88.90,83.68,39.29(q,J=28.0Hz),36.22,28.80,26.15(d,J=3.0Hz). 19 F NMR (376MHz, CDCl3) δ-64.08 (t, J=10.5Hz).

[0124] 1,7-diphenyl-5-(2,2,2-trifluoroethyl)hept-6-yn-2-one(3m)

[0125]

[0126] 3-Benzyl-1-phenylhept-6-en-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=50 / 1) to give the product 3m as a light yellow solid (75 mg, 73%) with a melting point of 73°C.

[0127] 1 H NMR (600MHz, CDCl3) δ8.51(s,1H),8.08–8.03(m,1H),7.95–7.84(m,3H),7.60(t,J=7.5Hz,1H),7.54(t,J=7.4Hz,1H),7.43–7.36(m,2H),7.28(d,J =5.9Hz,3H),3.47–3.35(m,2H),3.14(tt,J=9.7,4.9Hz,1H),2.61–2.47(m ,1H),2.47–2.34(m,1H),2.24(td,J=12.5,7.6Hz,1H),2.09–1.95(m,1H). 13C NMR (150MHz, CDCl3) δ199.04,135.62,134.14,132.51,131.61,129.69,129.55,128.49,128.46,128.24,128.12,127.75 ,126.76,126.07(d,J=277.3Hz),123.77,122.99,89.20,83.57,39.41(q,J=27.9Hz),35.94,29.28,26.20(d,J=3.0Hz). 19 F NMR (376MHz, CDCl3) δ-64.01 (t, J = 10.5Hz).

[0128] 1-cyclopropyl-6-phenyl-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3n)

[0129]

[0130] 3-Cyclopropyl-1-phenylhept-6-ene-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA = 50 / 1) to give the product 3n as a colorless oil (65.5 mg, 74%).

[0131] 1 H NMR (600MHz, CDCl3) δ7.39 (s, 2H), 7.29 (s, 3H), 2.98 (d, J = 4.0Hz, 1H), 2.91–2.77 (m, 2H), 2.50–2.38 (m, 1H), 2.37–2.2 4(m,1H),2.01(td,J=12.9,7.3Hz,1H),1.97–1.91(m,1H),1.82–1.73(m,1H),1.03(s,2H),0.88(dd,J=4.7,2.8Hz,2H). 13C NMR(150MHz, CDCl3)δ209.59,131.57,128.21,128.07,126.01(d,J=277.5Hz), 123.04, 40.44, 39.28 (q, J = 27.9Hz), 28.67, 25.97 (d, J = 3.0Hz), 20.60, 10.69. 19 F NMR (376MHz, CDCl3) δ-64.13 (t, J=10.5Hz).

[0132] 1-cyclobutyl-6-phenyl-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3o)

[0133]

[0134] 3-Cyclobutyl-1-phenylhept-6-en-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=60 / 1) to give the product 3o as a colorless oil (62.5 mg, 68%).

[0135] 1 H NMR (600MHz, CDCl3) δ7.40–7.33(m,2H),7.28(dd,J=4.4,1.2Hz,3H),3.28(p,J=8.6Hz,1H),2.97(tt,J=9.8,5.0Hz,1H),2.63(t,J=7.2 Hz,2H),2.49–2.37(m,1H),2.36–2.27(m,1H),2.23(dd,J=20.6,11.6Hz,2H),2.20–2.08(m,2H),2.04–1.92(m,2H),1.84–1.70(m,2H). 13C NMR(150MHz, CDCl3)δ210.62,131.53,128.21,128.06,126.00(d,J=277.6Hz),123.01,89.03 ,83.32,45.49,39.31(q,J=27.9Hz),36.97,28.43,25.96(d,J=3.1Hz),24.51,24.18,17.72. 19 F NMR(376MHz, CDCl3)δ-64.13(t,J=10.6Hz).HRMS-EI(m / z):[M+H] + The calculated value is 309.1461; the theoretical value is 309.1457.

[0136] 1-cyclohexyl-6-phenyl-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3p)

[0137]

[0138] 3-Cyclohexyl-1-phenylhept-6-en-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=100 / 1-60 / 1) to give the product 3p as a colorless oil (39.3 mg 39%).

[0139] 1H NMR (600MHz, CDCl3) δ7.37 (dd, J=4.9, 2.1Hz, 2H), 7.31–7.26 (m, 3H), 2.96 (tt, J=9.7, 5.0Hz, 1H), 2.72 (dd,J=10.0,5.4Hz,2H),2.43(ddd,J=19.3,10.3,4.4Hz,1H),2.36(ddd,J=15.0,9.3,3.6Hz,1H),2.30( ddd,J=15.4,10.4,5.2Hz,1H),1.98(dt,J=12.6,7.6Hz,1H),1.89–1.80(m,2H),1.77(d,J=13.1Hz,2H), 1.72(dd,J=11.6,4.9Hz,1H),1.65(d,J=12.3Hz,1H),1.34(dd,J=13.0,10.6Hz,2H),1.28–1.20(m,3H). 13 C NMR (150MHz, CDCl3) δ212.87,131.54,128.21,128.06,126.01(d,J=277.4Hz),123.05,89.12,83.28 ,50.94,39.34(q,J=27.8Hz),37.66,28.57,28.48,28.44,25.93(q,J=3.0Hz),25.80,25.64,25.58. 19 F NMR (376MHz, CDCl3) δ-64.13 (t, J=10.5Hz).

[0140] 6-(2-methoxyphenyl)-1-phenyl-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3q)

[0141]

[0142] 1-(3-Methoxyphenyl)-3-phenylhept-6-en-1-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=60 / 1) to give the product 3q as a colorless oil (68.5 mg, 63%).

[0143] 1 H NMR(600MHz, CDCl3) δ7.99(d,J=7.8Hz,2H),7.56(t,J=7.4Hz,1H),7.46(t,J=7 .6Hz,2H),7.18(t,J=7.9Hz,1H),6.96(d,J=7.6Hz,1H),6.89(s,1H),6.85(d,J= 8.2Hz,1H),3.77(s,3H),3.34–3.20(m,2H),3.09(tt,J=9.7,5.0Hz,1H),2.58–2 .44(m,1H),2.43–2.30(m,1H),2.18(dt,J=12.6,7.5Hz,1H),2.01–1.90(m,1H). 13 C NMR (150MHz, CDCl3) δ199.03,159.30,136.81,133.12,129.28,128.61,128.00,126.02(d,J=277.5Hz),124 .12,123.96,116.55,114.64,88.94,83.41,55.21,39.36(q,J=28.0Hz),35.86,29.03,26.12(d,J=2.9Hz). 19 F NMR(376MHz, CDCl3)δ-64.07(t,J=10.5Hz).HRMS-EI(m / z):[M+H] + The calculated value of j is 361.1410; the theoretical value is 361.1412.

[0144] 1-phenyl-6-(m-tolyl)-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3r)

[0145]

[0146] 3-Phenyl-1-(m-tolyl)hept-6-en-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate on a short diatomaceous earth column under reduced pressure, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=100 / 1) to give the product 3r as a colorless oil (55 mg, 53%).

[0147] 1 H NMR (600MHz, CDCl3) δ8.00(d,J=7.8Hz,2H),7.56(t,J=7.3Hz,1H),7.46(t,J=7.6Hz,2H),7.17(t,J=6.6Hz,3H),7.10(d,J=5.9Hz,1H),3.32– 3.19(m,3H),3.09(tt,J=9.7,5.0Hz,1H),2.56–2.45(m,1H),2.44–2.3 3(m,2H),2.30(s,3H),2.18(dt,J=12.7,7.6Hz,1H),2.00–1.90(m,1H). 13 C NMR (150MHz, CDCl3) δ199.09,137.91,136.82,133.11,132.16,128.98,128.63,128.60,128.11,128.02,12 6.04(d,J=277.4Hz),122.76,88.70,83.65,39.42(q,J=28.0Hz),35.88,29.10,26.13(q,J=2.9Hz),21.11. 19 F NMR (376MHz, CDCl3) δ-64.07 (t, J=10.5Hz).

[0148] 1-phenyl-6-(m-tolyl)-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3s)

[0149]

[0150] 3-Phenyl-1-(p-tolyl)hept-6-en-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=100 / 1) to give the product 3s as a pale yellow oil (61 mg, 59%).

[0151] 1H NMR (600MHz, CDCl3) δ7.99(d,J=7.7Hz,2H),7.59–7.53(m,1H),7.46(t,J=7.6Hz,2H),7.26(dd,J=10.0,4.2Hz,2H),7.09(d,J=7.9H z,2H),3.33–3.19(m,2H),3.08(tt,J=9.8,5.0Hz,1H),2.57–2.44(m,1H),2.42–2.28(m,4H),2.23–2.13(m,1H),2.00–1.89(m,1H). 13 C NMR (150MHz, CDCl3) δ199.11,138.17,136.83,133.09,131.45,128.96,128.60,128.01,126.06(d,J=2 77.5Hz),119.91,88.35,83.57,39.71,39.43(q,J=27.9Hz),35.90,29.12,26.15(q,J=3.0Hz),21.36. 19 F NMR (376MHz, CDCl3) δ-64.06 (t, J=10.6Hz).

[0152] 6-(4-(tert-butyl)phenyl)-1-phenyl-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3t)

[0153]

[0154] 1-(4-(tert-Butyl)phenyl)-3-phenylhept-6-en-1--3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=100 / 1) to give the product 3t as a pale yellow oil (83 mg, 72%).

[0155] 1H NMR (600MHz, CDCl3) δ7.99(d,J=7.7Hz,2H),7.56(t,J=7.4Hz,1H),7.46(t,J=7.7Hz,2H),7.33–7.27(m,4H),3.33–3.20(m,2H), 3.08(tt,J=9.9,5.0Hz,1H),2.55–2.43(m,1H),2.42–2.31(m,1H),2.17(dt,J=12.8,7.7Hz,1H),1.97–1.88(m,1H),1.28(s,9H). 13 C NMR (150MHz, CDCl3) δ199.12,151.38,136.82,133.09,131.29,128.59,128.00,126.03(d,J=277.5Hz) ,125.20,119.94,88.37,83.52,39.45(q,J=28.0Hz),35.91,34.68,31.12,29.12,26.14(q,J=3.0Hz). 19 F NMR (376MHz, CDCl3) δ-64.08 (t, J=10.5Hz).

[0156] 6-(2-fluorophenyl)-1-phenyl-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3u)

[0157]

[0158] 1-(2-Fluorophenyl)-3-phenylhept-6-en-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA = 100 / 1-50 / 1) to give the product 3t as a white solid (82 mg, 79%) with a melting point of 65°C.

[0159] 1H NMR (600MHz, CDCl3) δ8.00(d,J=7.6Hz,2H),7.56(t,J=7.3Hz,1H),7.46(t,J=7.7Hz,2H),7.36(t,J=6.9Hz,1H),7.26(dd,J=13.5,6.4Hz,1H),7.05(dd,J =18.0,8.6Hz,2H),3.36–3.21(m,2H),3.14(tt,J=9.7,4.9Hz,1H),2.58–2.4 6(m,1H),2.44–2.33(m,1H),2.21(dt,J=12.8,7.7Hz,1H),1.99–1.89(m,1H). 13 C NMR (150MHz, CDCl3) δ 199.09, 162.87 (d, J = 251.1Hz), 136.79, 133.43, 133.11, 129.79 (d, J = 7.9Hz), 128.60, 128.02, 125.98 (d, J = 277.5Hz), 123. 84(d,J=3.8Hz),115.37(d,J=20.9Hz),111.50(d,J=15.7Hz),94.52(d,J =3.2Hz),76.93,39.25(q,J=28.1Hz),35.78,28.97,26.30(q,J=2.8Hz). 19 F NMR (376MHz, CDCl3) δ-64.11 (t, J = 10.5Hz), -110.64 (dd, J = 15.0, 6.7Hz).

[0160] 6-(4-fluorophenyl)-1-phenyl-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3v)

[0161]

[0162] 1-(4-Fluorophenyl)-3-phenylhept-6-en-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=100 / 1-50 / 1) to give the product 3v as a light yellow solid (60 mg, 57%) with a melting point of 64°C.

[0163] 1 H NMR (600MHz, CDCl3) δ7.99(d,J=8.0Hz,2H),7.56(t,J=7.4Hz,1H),7.46(t,J=7.7Hz,2H),7.33(dd,J=8.3,5.7Hz,2H),6.96(t,J=8.7Hz,2H),3.32– 3.18(m,2H),3.08(tt,J=9.7,4.9Hz,1H),2.55–2.42(m,1H),2.37(dqd,J =15.6,10.5,5.4Hz,1H),2.17(dt,J=12.7,7.5Hz,1H),2.00–1.89(m,1H). 13 C NMR (150MHz, CDCl3) δ198.95,162.37(d,J=249.3Hz),136.80,133.41(d,J=8.2Hz),133.14,128.61,127.98,126.00(d,J=2 77.5Hz), 119.03 (d, J = 3.6Hz), 115.45 (d, J = 22.0Hz), 88.78, 82.46, 39.34 (q, J = 28.0Hz), 35.81, 29.02, 26.09 (q, J = 2.9Hz). 19 F NMR (376MHz, CDCl3) δ-64.09 (t, J = 10.5Hz), -111.24 (m).

[0164] 6-(2-chlorophenyl)-1-phenyl-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3w)

[0165]

[0166] 1-(2-Chlorophenyl)-3-phenylhept-6-ene-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate on a short diatomaceous earth column under reduced pressure, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=100 / 1-50 / 1) to give the product 3w as a light yellow solid (80.5 mg, 76%) with a melting point of 75°C.

[0167] 1 H NMR (600MHz, CDCl3) δ8.00 (d, J = 7.5Hz, 2H), 7.56 (t, J = 7.4Hz, 1H), 7.46 (t, J = 7. 7Hz,2H),7.41(dd,J=7.5,1.2Hz,1H),7.36(d,J=8.0Hz,1H),7.24–7.15(m,2H), 3.42–3.30(m,2H),3.17(dq,J=14.2,4.9Hz,1H),2.61–2.47(m,1H),2.40(dqd,J =15.6,10.5,5.4Hz,1H),2.22(ddd,J=12.8,7.7,4.7Hz,1H),2.01–1.90(m,1H). 13 C NMR (150MHz, CDCl3) δ199.03,136.80,135.81,133.32,133.11,129.13,128.59,128.01,,126.40,12 5.99(q,J=277.5Hz),122.86,94.66,80.36,39.28(q,J=28.1Hz),35.89,28.95,26.31(q,J=2.9Hz). 19 F NMR (376MHz, CDCl3) δ-64.07 (t, J=10.5Hz).

[0168] 6-(4-chlorophenyl)-1-phenyl-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3x)

[0169]

[0170] 1-(4-Chlorophenyl)-3-phenylhept-6-en-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=100 / 1-50 / 1) to give the product 3x as a pale yellow oil (88.5 mg, 81%).

[0171] 1H NMR (600MHz, CDCl3) δ7.98 (d, J = 7.3Hz, 2H), 7.56 (t, J = 7.4Hz, 1H), 7.46 (t, J = 7.7Hz, 2H), 7.26 (dd, J = 21.4, 8.5Hz, 4H), 3. 33–3.17(m,3H),3.09(tt,J=9.6,4.8Hz,1H),2.57–2.43(m,1H),2.43–2.29(m,1H),2.23–2.11(m,1H),2.01–1.90(m,1H). 13 C NMR (150MHz, CDCl3) δ198.90,136.77,134.13,133.16,132.79,128.62,128.54,127.98,125.98 (d,J=277.4Hz),121.44,90.16,82.45,39.28(q,J=28.0Hz),35.78,28.96,26.13(q,J=2.9Hz). 19 F NMR(376MHz, CDCl3)δ-64.08(m).

[0172] 6-([1,1'-biphenyl]-4-yl)-1-phenyl-4-(2,2,2-trifluoroethyl)hex-5-yn-1-on e(3y)

[0173]

[0174] 1-([1,1'-biphenyl]-4-yl)-3-phenylhept-6-en-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=70 / 1) to give the product 3y as a yellow solid (59 mg, 48%) with a melting point of 80°C.

[0175] 1H NMR (600MHz, CDCl3) δ8.01(d,J=7.9Hz,2H),7.57(d,J=8.0Hz,3H),7.52(d,J=7.7Hz,2H),7.45(dt,J=16.0,7.7Hz,6H),7.35(t,J=7.4Hz,1 H),3.35–3.23(m,2H),3.13(tt,J=9.7,4.9Hz,1H),2.59–2.47(m,1H),2.46–2.33(m,1H),2.21(td,J=12.7,7.5Hz,1H),2.03–1.92(m,1H). 13 C NMR (150MHz, CDCl3) δ199.06,140.92,140.31,136.83,133.14,132.00,128.81,128.63,128.02,127.59,126.96 ,126.91,124.22(d,J=277.4Hz),121.88,89.79,83.39,39.41(q,J=28.0Hz),35.89,29.09,26.22(q,J=2.9Hz). 19 F NMR(376MHz, CDCl3)δ-63.99(t,J=10.0Hz).HRMS-EI(m / z):[M+Na] + calcd for,429.1437; found,429.1513.HRMS-EI(m / z):[M+H] + The calculated value is 381.1461; the theoretical value is 381.1463.

[0176] 6-(4,4-dimethylthiochroman-6-yl)-1-phenyl-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3z)

[0177]

[0178] 1-(4,4-Dimethylthio-6-yl)-3-phenylhept-6-en-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3The mixture was concentrated and purified by column chromatography (PE / EA=50 / 1) to give the product 3z as a pale yellow oil (53 mg, 57%).

[0179] 1 H NMR (600MHz, CDCl3) δ7.99(d,J=8.1Hz,2H),7.55(t,J=7.4Hz,1H),7.45(t,J=7.6Hz,2H ),7.34(s,1H),7.01(d,J=8.2Hz,1H),6.98(d,J=8.1Hz,1H),3.32–3.18(m,2H),3.08(tt ,J=10.0,5.2Hz,1H),3.04–2.98(m,2H),2.56–2.43(m,1H),2.37(ddd,J=20.4,10.2,4.9 Hz, 1H), 2.18 (dt, J=12.5, 7.5Hz, 1H), 1.94 (ddd, J=18.9, 12.8, 7.3Hz, 4H), 1.29 (s, 7H). 13 C NMR (150MHz, CDCl3) δ199.12,141.95,136.83,133.11,132.74,129.52,128.96,128.60,128.00,126.40,126.05(d,J =277.5Hz)118.28,88.22,83.72,39.42(q,J=27.8Hz),37.25,35.93,32.86,29.88,29.08,26.18(d,J=3.0Hz),23.13. 19 FNMR(376MHz, CDCl3)δ-64.04(t,J=10.6Hz).HRMS-EI(m / z):[M+Na] + The calculated value is 431.1651; the theoretical value is 431.1645.

[0180] 6-(naphthalen-2-yl)-1-phenyl-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3aa)

[0181]

[0182] 1-(2-Naphthyl)-3-phenylhept-6-en-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=50 / 1) to give the product 3aa as a pale yellow oil (32.5 mg, 37%).

[0183] 1 H NMR(600MHz, CDCl3)δ8.01(d,J=7.4Hz,2H),7.87(s,1H),7.81–7.76(m,1H),7.7 4(dd,J=8.7,4.1Hz,2H),7.56(t,J=7.4Hz,1H),7.46(t,J=7.1Hz,4H),7.41(d,J =8.5Hz,1H),3.37–3.25(m,3H),3.15(tt,J=9.8,5.0Hz,1H),2.60–2.49(m,1H), 2.46–2.36(m,1H),2.22(dt,J=12.6,7.5Hz,1H),2.00(dt,J=19.0,10.8Hz,1H). 13 C NMR (150MHz, CDCl3) δ199.07,136.83,133.14,132.91,132.70,131.33,128.62,128.40,128.03,127.87,127.68,127.60 ,126.54,126.47,126.05(d,J=277.6Hz),120.24,89.44,83.87,39.43(q,J=27.8Hz),35.90,29.11,26.24(q,J=2.8Hz). 19 FNMR(376MHz, CDCl3)δ-64.03(t,J=10.5Hz).HRMS-EI(m / z):[M+H] + The calculated value is 345.1461; the theoretical value is 345.1460.

[0184] 1-phenyl-6-(pyren-1-yl)-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3ab)

[0185]

[0186] 1-(2-piperyl)-3-phenylhept-6-en-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=50 / 1) to give the product 3ab as a yellow-brown solid (21.5 mg, 16%) with a melting point of 85°C.

[0187] 1 H NMR (600MHz, CDCl3) δ8.46(d,J=9.0Hz,1H),8.18(t,J=7.6Hz,2H),8.11–7.97(m,8H),7.55(dd,J=10.6,4.1Hz,1H),7.45(t,J=7.7Hz,2H),3.43(t,J=7 .1Hz,2H),3.36(ddd,J=14.2,9.5,4.7Hz,1H),2.75–2.63(m,1H),2.58–2.4 7(m,1H),2.33(dt,J=12.6,7.5Hz,1H),2.12(ddd,J=20.3,11.9,7.0Hz,1H). 13 C NMR (150MHz, CDCl3) δ199.05,136.83,133.16,131.92,131.20,131.12,130.98,129.71,128.64,128.31,128.05,128.04,127.15,126.18,126.1 5(d,J=277.6Hz),125.52,125.20,124.41,124.35,124.27,117.49,94. 78,82.65,39.61(q,J=27.6Hz),36.04,29.33,26.65(dd,J=5.8,2.9Hz). 19 F NMR (376 MHz, CDCl3) δ-63.89 (t, J = 10.5 Hz). HRMS-EI (m / z): [M+H]+ calculated value is 455.1617; the theoretical value is 455.1617.

[0188] 1-phenyl-6-(thiophen-2-yl)-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3ac)

[0189]

[0190] 3-Phenyl-1-(2-thienyl)hept-6-en-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=50 / 1) to give the product 3ac as a pale yellow oil (29 mg, 29%).

[0191] 1 H NMR (600MHz, CDCl3) δ7.99(d,J=7.6Hz,2H),7.56(t,J=7.4Hz,1H),7.46(t,J=7.7Hz,2H),7.20(d,J=5.1Hz,1H),7.12(d,J=3.4Hz,1H),6.93(dd,J=4. 8,3.9Hz,1H),3.31–3.18(m,2H),3.11(tt,J=9.9,5.0Hz,1H),2.56–2.43( m,1H),2.43–2.31(m,1H),2.18(td,J=12.8,7.6Hz,1H),2.00–1.89(m,1H). 13 C NMR (150MHz, CDCl3) δ198.98,136.76,133.14,131.70,128.61,128.01,126.81,126.67,125 .93(d,J=277.4Hz),122.90,93.02,39.21(q,J=28.1Hz),35.82,28.92,26.39(d,J=3.0Hz). 19 FNMR(376MHz, CDCl3)δ-64.15(t,J=10.5Hz).HRMS-EI(m / z):[M+H] + Calculated value: 337.0868; theoretical value: 337.0868.

[0192] 1-phenyl-6-(pyridin-3-yl)-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3ad)

[0193]

[0194] 3-Phenyl-1-(3-pyridyl)hept-6-en-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=5 / 1) to give the product 3ad as a pale yellow oil (41 mg, 41%).

[0195] 1 H NMR (600MHz, CDCl3) δ8.55(d,J=53.4Hz,2H),7.97(d,J=8.0Hz,2H),7.62(d, J=7.8Hz,1H),7.56(t,J=7.4Hz,1H),7.45(t,J=7.7Hz,2H),7.23–7.15(m,1H) ,3.32–3.19(m,2H),3.12(dq,J=14.2,4.9Hz,1H),2.57–2.44(m,1H),2.39(dt d,J=15.2,10.4,5.2Hz,1H),2.19(td,J=12.6,7.5Hz,1H),2.02–1.91(m,1H). 13 C NMR (150MHz, CDCl3) δ198.78,152.21,148.47,138.48,136.71,133.22,128.64,127.95,125.91 (d,J=277.4Hz),122.96,92.68,80.31,39.21(q,J=28.1Hz),35.70,28.84,26.16(q,J=2.8Hz). 19 F NMR (376MHz, CDCl3) δ-64.08 (m).

[0196] methyl-1,6-diphenyl-4-(2,2,2-trifluoroethyl)hex-5-yn-1-one(3ae)

[0197]

[0198] 6-Methyl-1,3-diphenylhept-6-en-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=5 / 1) to give the product 3ae as a pale yellow oil (41 mg, 41%).

[0199] 1 H NMR(600MHz, CDCl3)δ8.01(d,J=7.2Hz,2H),7.59–7.55(m,1H),7.49–7.45(m,1H),7.38(dd,J=6.7,3.0Hz,1H),7.29(dd,J=5.0,1.7Hz,2H), 3.32–3.21(m,1H),2.57–2.47(m,1H),2.39(dt,J=10.8,8.6Hz,1H),2.15(dt,J=15.5,8.1Hz,1H),2.05(dd,J=10.0,5.6Hz,1H),1.49(s,2H). 13 C NMR (150MHz, CDCl3) δ199.28,136.78,133.09,131.54,128.61,128.20,128.04,125.96( d, J=278.6Hz), 123.01, 92.17, 83.16, 44.32 (q, J=26.7Hz), 35.94, 34.44, 32.48, 26.48. 19 F NMR (376MHz, CDCl3) δ-60.14 (t, J=11.0Hz).

[0200] 6,6,6-trifluoro-1-phenyl-4-(thiazol-2-yl)hexan-1-one(3af)

[0201]

[0202] 1-Phenyl-1-(thiazol-2-yl)pent-4-en-1-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=20 / 1) to give the product 3af as a light yellow solid (81 mg, 86%) with a melting point of 78°C.

[0203] 1 H NMR (600MHz, CDCl3) δ7.85(d,J=7.8Hz,2H),7.73(d,J=3.1Hz,1H),7.53(t,J=7.3Hz,1H),7.42(t,J=7.6Hz,2H),7.26–7.22(m,1H),3.68–3.57(m,1H ),2.91(dt,J=14.9,7.5Hz,2H),2.86–2.77(m,1H),2.56(dqd,J=15.8,10. 6,5.5Hz,1H),2.33(dt,J=12.8,7.5Hz,1H),2.23(dt,J=14.1,7.3Hz,1H). 13 C NMR (150MHz, CDCl3) δ198.67,171.09,142.70,136.64,133.11,128.54,127.89,126 .10(d,J=277.7Hz),118.46,39.58(q,J=28.1Hz),36.91(d,J=2.5Hz),35.21,30.25. 19 F NMR(376MHz, CDCl3)δ-64.08(m).

[0204] 4-(benzo[d]thiazol-2-yl)-6,6,6-trifluoro-1-phenylhexan-1-one(3ag)

[0205]

[0206] 1-(Benzo[d]-2-thiazolyl)-1-phenylpent-4-en-1-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=30 / 1) to give the product 3ag as a light yellow solid (72 mg, 66%) with a melting point of 99°C.

[0207] 1 H NMR (600MHz, CDCl3) δ7.98(d,J=8.2Hz,1H),7.85(dd,J=7.8,3.1Hz,3H),7.52(t,J=7.4Hz,1H),7.47(t,J=7.7Hz,1H),7.39(dd,J=16 .3,8.1Hz,3H),3.73–3.63(m,1H),3.02–2.88(m,3H),2.68–2.57(m,1H),2.41(dt,J=12.7,7.4Hz,1H),2.32(dt,J=14.3,8.2Hz,1H). 13 C NMR (150MHz, CDCl3) δ198.55,171.98,153.05,136.58,134.64,133.12,128.53,127.91,126.24(d,J =226.8Hz),126.17,125.19,122.97,121.67,39.30(q,J=28.6Hz),37.94(q,J=2.6Hz),35.24,29.97. 19 F NMR (376MHz, CDCl3) δ-64.08 (t, J=10.6Hz).

[0208] 6,6,6-trifluoro-4-(6-methoxybenzo[d]thiazol-2-yl)-1-phenylh exan-1-one(3ah)

[0209]

[0210] 1-(6-Methoxybenzothiazol-2-yl)-1-phenylpent-4-en-1-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate on a short diatomaceous earth column under reduced pressure, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=20 / 1-10 / 1) to give 3ah as a white solid (79 mg, 67%) with a melting point of 75°C.

[0211] 1 H NMR (600MHz, CDCl3) δ7.88–7.82(m,3H),7.51(t,J=7.1Hz,1H),7.39(t,J=7.5Hz,2H),7.29(d,J=1.4Hz,1H),7.06(dd,J=8.9,1.7Hz,1H),3.85( s,3H),3.66–3.59(m,1H),3.02–2.94(m,2H),2.94–2.85(m,1H),2.68–2 .54(m,1H),2.39(dt,J=12.5,7.4Hz,1H),2.29(dt,J=14.3,7.9Hz,1H). 13 C NMR (150MHz, CDCl3) δ198.62,169.25,157.75,147.51,136.61,135.94,133.10,128.52,127.91,126.11 (d,J=277.4Hz),123.38,115.49,104.25,55.78,39.27(q,J=28.4Hz),37.82(d,J=2.3Hz),35.26,29.93. 19 F NMR (376MHz, CDCl3) δ-64.06 (td, J=10.6, 3.2Hz).

[0212] 4-(benzo[d]oxazol-2-yl)-6,6,6-trifluoro-1-phenylhexan-1-one(3ai)

[0213]

[0214] 1-(2-Benzo[d]oxazolyl)-1-phenylpent-4-en-1-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=25 / 1) to give 3ai as a brown solid (56 mg, 54%) with a melting point of 90°C.

[0215] 1 H NMR (600MHz, CDCl3) δ7.85(d,J=7.5Hz,2H),7.67(s,1H),7.56–7.45(m,2H),7.40(t,J=7.4Hz,2H),7.32( d,J=2.8Hz,2H),3.56(s,1H),3.08–2.83(m,3H),2.60(ddd,J=15.0,10.2,4.9Hz,1H),2.46–2.25(m,2H). 13 C NMR (150MHz, CDCl3) δ198.28,166.28,150.69,140.89,136.54,133.16,128.53,127.91,126.07(d,J =240.8Hz),125.03,124.42,119.94,110.58,37.37(q,J=29.0Hz),35.25,33.59(d,J=2.7Hz),27.75. 19 F NMR (376MHz, CDCl3) δ-64.80 (t, J=10.5Hz).

[0216] 6,6,6-trifluoro-4-(1-methyl-1H-imidazol-2-yl)-1-phenylhexan-1-one(3aj)

[0217]

[0218] 1-(1-methyl-1H-imidazol-2-yl)-3-phenylhept-6-en-1-yn-3-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), two stainless steel balls (inner diameter 7 mm) were placed, and then ground in a ball mill (GT 300, 1800 rpm) for 3 hours. The mixture was then eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=25 / 1) to give 3aj as a white solid (26.5 mg, 28%) with a melting point of 78°C.

[0219] 1 H NMR (600MHz, CDCl3) δ7.84(d,J=7.5Hz,1H),7.57–7.52(m,1H),7.43(t,J=7.7Hz,1H),6.99(s,1H),6.73(s,1H),3.52(s,3H) ,3.41(d,J=14.8Hz,1H),2.99–2.91(m,1H),2.76(dd,J=9.1,5.6Hz,1H),2.49(qd,J=10.8,5.4Hz,1H),2.24(d,J=6.9Hz,1H). 13 CNMR (150MHz, CDCl3) δ199.46,169.52,148.14,136.61,133.16,129.83,129.43,129.16,128.57,127. 90,127.64,127.32,125.49,123.65,120.44,68.97,39.05,38.87,38.69,38.50,34.68,29.28,16.59. 19 F NMR (376MHz, CDCl3) δ-65.13 (t, J=10.8Hz).

[0220] 4-(benzofuran-2-yl)-6,6,6-trifluoro-1-phenylhexan-1-one(3ak)

[0221]

[0222] 1-(Benzofuran-2-yl)-1-phenylpent-4-en-1-ol (1.3 equivalents), Umemoto reagent 2c (1.0 equivalents), BaTiO3 (5.0 equivalents), and acetone (0.2 μL / mg) were placed in a stainless steel grinding jar (5 ml), and two stainless steel balls (inner diameter 7 mm) were placed. After grinding in a ball mill (GT 300, 1800 rpm) for 3 hours, the mixture was eluted with ethyl acetate under reduced pressure on a short diatomaceous earth column, as shown in FIG. Figure 3 The mixture was concentrated and purified by column chromatography (PE / EA=100 / 1) to give 3ak as a white solid (58 mg, 55%) with a melting point of 98°C.

[0223] 1 H NMR (600MHz, CDCl3) δ7.84(d,J=7.6Hz,2H),7.56–7.45(m,2H),7.46–7.35(m,3H),7.23(dt,J=27.9,7.3Hz,2H),6.50(s,1H),3.36(tt,J=10. 0,4.9Hz,1H),2.91(t,J=7.1Hz,2H),2.79–2.67(m,1H),2.58–2.47(m,1H),2.30(td,J=12.7,7.5Hz,1H),2.20(ddd,J=20.6,13.6,6.8Hz,1H). 13 C NMR (150MHz, CDCl3) δ198.89,157.35,154.82,136.69,133.07,128.95,128.53,128.22,127.89,126.20(d,J=277 .2Hz),124.31,123.86,122.76,120.70,111.01,103.93,38.12(q,J=28.0Hz),35.56,33.19(q,J=2.5Hz),27.93. 19 F NMR (376MHz, CDCl3) δ-64.31 (t, J=9.6Hz).

[0224] In summary, the present invention has developed a green alternative mechanooxidative pathway for the difunctionalization of unactivated alkenes via a cascade radical trifluoromethylation distal migration pathway. This method enables rapid modification of unactivated alkenes via cascade reduction under mechanooxidation-reduction conditions. Compared to photocatalysis and electrocatalysis, the method provided by the present invention offers significant advantages such as ease of operation, air compatibility, low solvent consumption, and catalyst recyclability. This method meets the requirements of green chemistry and represents a novel, environmentally friendly, and highly compatible method for the carbon trifluoromethylation of unactivated alkenes.

[0225] The above is a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A method for difunctionalizing olefins, characterized in that: The following steps are involved: 1) placing unactivated olefin, Umemoto reagent, and BaTiO3 into a grinding jar and grinding to obtain a first mixture; The unactivated olefin is 1,3-diphenylhept-6-ene-1-yn-3-ol; the structural formula of the Umemoto reagent is as follows 2) adding acetone to the first mixture, and performing air grinding reaction under sealing to obtain a second compound; 3) Passing the second compound through a short diatomaceous earth column to obtain a crude material, which is purified to obtain the corresponding olefin difunctionalized product.

2. The method for difunctionalization of olefins according to claim 1, wherein In step 1), the equivalent ratio of unactivated olefin: Umemoto reagent: BaTiO3 is 1.3:1.0:5.

0.

3. The method for difunctionalization of olefins according to claim 1, wherein During grinding in step 1), two stainless steel balls are placed in the grinding jar.

4. The method for difunctionalization of olefins according to claim 1, wherein The concentration of acetone in step 2) is 0.2 μL / mg.

5. The method for difunctionalization of olefins according to claim 1, wherein Step 2) The grinding is performed by sealing the grinding jar in air and placing it in a ball mill for grinding for 3 hours.

6. The method for difunctionalization of olefins according to claim 1, characterized in that In step 3), the short diatomaceous earth column is a short diatomaceous earth column eluted under reduced pressure with ethyl acetate.

7. The method for difunctionalization of olefins according to claim 1, wherein Step 3) The purification is carried out by flash silica gel column chromatography.

8. The method for difunctionalization of olefins according to claim 1, wherein In step 3), the corresponding olefin difunctionalization product is a δ-trifluoromethyl substituted ketone product.

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