A method for preparing beta-aryl-substituted benzyl alcohol compounds by using visible light driven arylthianthrenium salt

Abstract

The application discloses a visible light driven arylthioxanthium salt preparation method β The application discloses a method for preparing aryl-substituted benzyl alcohol, and belongs to the technical field of organic synthesis. In the presence of a base and a photocatalyst, arylthioxanthium salt is used as an aryl radical precursor to react with an olefin derivative in a solvent under light driving to generate aryl-substituted benzyl alcohol. β The application creatively uses arylthioxanthium salt as an aryl radical precursor for visible light driven olefin hydroxyarylation reaction, which is easy to prepare and has good storage stability, and directly constructs diversified aryl-substituted benzyl alcohol under mild conditions. β The preparation method has a wide substrate application range, good functional group tolerance, is suitable for complex molecule derivative substrates, and the prepared aryl-substituted benzyl alcohol has good storage stability. β The aryl-substituted benzyl alcohol compound can be used as an organic synthesis intermediate to further synthesize drug molecules and organic functional materials, and can also be used as a lead compound for biological activity screening to develop new medicinal active substances.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a visible light-driven preparation of arylthianthaneonium salts. β - Methods for aryl-substituted benzyl alcohol compounds. Background Technology

[0002] Alcohol-containing structural skeletons are widely found in natural products, drug molecules, and functional materials. β -Aryl-substituted benzyl alcohols are an important class of drug-related structural units, with representative compounds including triparanol, ethamoxytriphetol, and eslicarbazepine. Among them, triparanol is a cholesterol-lowering drug, ethamoxytriphetol is a cholesterol-lowering drug, and ethamoxytriphetol is an antiepileptic drug. β The widespread distribution of aryl-substituted benzyl alcohols as core skeletons in bioactive molecules continues to drive the development of efficient and practical methods for constructing aryl-substituted alcohols.

[0003] β-aryl-substituted benzyl alcohols are mainly prepared via stepwise carbonylation routes, such as the reduction of deoxybenzoin derivatives, the addition of benzyl organometallic reagents to aromatic aldehydes, and the reduction- or electron-transfer-mediated benzylation of aromatic aldehydes. These methods typically require the prior preparation of carbonyl bases, and some routes involve organometallic reagents sensitive to water and air, potentially limiting their compatibility with sensitive functional groups. Professor Wang Chao et al. disclosed the preparation of secondary alcohols and aryl bromides... β - Arylation reaction, as shown in (1), uses aryl bromide as the aryl source to directly construct a 1,2-diaryl alcohol skeleton. However, this method still depends on a pre-existing benzyl alcohol substrate. Heinrich et al. disclosed the thermally induced radical carbon hydroxylation of aryl diazonium salts with styrene, as shown in (2). Under thermal initiation conditions, the radical carbon hydroxylation reaction of styrene with aryl diazonium salts was achieved. However, this method depends on thermal initiation conditions, and aryl diazonium salts usually have problems such as limited stability, potential safety risks, and operational limitations, which are particularly unfavorable for the application of complex aromatic hydrocarbons. Visible light-mediated photoredox catalysis has become a powerful and environmentally friendly platform for constructing chemical bonds under mild conditions. However, the current visible light-mediated hydroxyarylation method for olefins still uses aryl diazonium salts as aryl radical precursors, which seriously limits its application.

[0004] Therefore, in olefin hydroxyarylation reactions, replacing aryl diazonium salts with more stable and readily available aryl radical precursors can develop a method applicable to complex aromatic structures. β The preparation method of aryl-substituted benzyl alcohols is of great significance. Summary of the Invention

[0005] To address the problems existing in the prior art, this invention provides a visible light-driven preparation method for arylthianthaneonium salts. β A method for preparing aryl-substituted benzyl alcohols using readily prepared and well-storage-stable arylthianthaneon salts as aryl radical precursors under mild conditions. β -Aryl-substituted benzyl alcohols have a wide range of substrate applications, good functional group tolerance, and are suitable for complex molecular derivatives.

[0006] This invention is achieved through the following technical solution: In a first aspect, the present invention provides a visible light-driven preparation method for arylthianthaneonium salts. β A method for aryl-substituted benzyl alcohols involves a photocatalyst-driven reaction of a substituted thiaanthraium salt as an aryl radical precursor with an olefin derivative in a solvent, under an inert atmosphere and in the presence of a base and a photocatalyst, to generate... β -Aryl-substituted benzyl alcohols.

[0007] Furthermore, the visible light-driven preparation of arylthiathaneonium salts... β The method for aryl-substituted benzyl alcohol compounds specifically includes the following steps: (1) Under an inert atmosphere, the substituted arylthiathaneonium salt of Formula I, the olefin derivative of Formula II, the base, the photocatalyst and the solvent are added to the reaction vessel to form a mixed solution. The reaction solution is irradiated with visible light at room temperature to promote the reaction. (2) After the reaction in step (1) is completed, water is added and mixed evenly. Ethyl acetate is added as an extractant for separation and extraction. The crude product is extracted from the reaction solution. The extracts are combined, the organic solvent is removed, and the residue is purified by silica gel chromatography to obtain the crude product. β- Aryl-substituted benzyl alcohols; R 1 Selected from one or more of aryl, alkyl, and alkenyl substituents; R 2 It is selected from one or more of alkyl, aryl, hydrogen, cyano, and hydrogen groups; R 2 Selected from one or more of alkyl, aryl, and hydrogen groups; R4 is selected from one or more of methyl, propyl, tert-butyl, and hydrogen; X is selected from PF6 or BF4.

[0008] Furthermore, the photocatalyst is one or more of [Ir(dF(CF3)ppy)3(dtbbpy)]PF3, Ir(ppy)3, and 4CzIPN, preferably [Ir(dF(CF3)ppy)3(dtbbpy)]PF3; Furthermore, the alkali is one or more of sodium methoxide, sodium dihydrogen phosphate, sodium carbonate, and sodium acetate, with sodium carbonate being preferred.

[0009] Furthermore, the inert atmosphere is either nitrogen or argon, preferably nitrogen; Furthermore, the wavelength range of the visible light is one of 400 nm to 500 nm, preferably 455 nm; Furthermore, the visible light source is one of LED lamps, mercury lamps, xenon lamps, and sunlight, with LED lamps being preferred.

[0010] Furthermore, the solvent is a mixture of organic solvent and water, with a volume ratio of organic solvent to water of 100-300:1, preferably 200:1; Furthermore, the organic solvent is one or more of acetonitrile, chloroform, tetrahydrofuran, 1,4-dioxane, acetone, dimethyl carbonate, and dimethylacetamide, preferably acetonitrile.

[0011] Furthermore, the molar ratio of the arylthianthaneonium salt to the olefin derivative is 1:1.5-2, preferably 1:2; Furthermore, the amount of catalyst added is 0.02-0.04 times the molar amount of arylthiaanthium salt, preferably 0.025 times; Furthermore, the amount of alkali added is 2-4 times the molar amount of arylthiaanthium salt, preferably 3 times.

[0012] Furthermore, the synthesis reaction is carried out under atmospheric pressure for a reaction time of 10-30 h, preferably 12 h.

[0013] Furthermore, the silica gel column has a mesh size of 200-300, and the eluent is petroleum ether / ethyl acetate with a volume ratio of 10:1.

[0014] Furthermore, the aforementioned β Aryl-substituted benzyl alcohols can serve as intermediates in organic synthesis, enabling the further synthesis of drug molecules and organic functional materials through reactions such as hydroxyl derivatization and aromatic ring modification. They can also act as lead compounds for bioactivity screening and the development of novel pharmaceutical active substances. Furthermore, they can be applied in anticancer, antitumor, and antifungal applications, as well as as herbicides and fungicides in agrochemicals.

[0015] Preparation of this invention β- The reaction mechanism diagram of aryl-substituted benzyl alcohol compounds is shown below. Figure 1 As shown, under photo-driven conditions, the excited-state Ir(III) photocatalyst is first reduced and quenched by thiathracene, generating reduced-state Ir(II) species and thiathracene radical cations. The single-electron reduction of arylthiathracene ononium salts I is thermodynamically feasible because the reduction potential of arylthiathracene ononium salts is generally more readily reached [E] than that of many aryl halides. 0 (ArTT + / ArTT • ) ≈ 1.5 Vvs SCE, CH3CN]. Therefore, the electron transfer from Ir(II) to I promotes the breaking of the CS bond, generating the corresponding aryl radical. The resulting aryl radical then adds to olefin II to form a benzyl radical intermediate. This transient radical is further captured by a long-lived thianthracene radical cation to give a benzyl-thianthracene intermediate. Finally, water undergoes nucleophilic substitution of this intermediate, followed by deprotonation to generate the target alcohol product ( β -Aryl-substituted benzyl alcohols) III.

[0016] Compared with the prior art, the beneficial effects achieved by the present invention are as follows: (1) This invention creatively uses arylthianthaneonium salts, which are easy to prepare and have good storage stability, as aryl radical precursors to drive the hydroxyarylation reaction of olefins under visible light, and directly prepares the olefins under mild conditions. β -Aryl-substituted benzyl alcohol β -Aryl-substituted benzyl alcohol compounds; the thiathracene generated in situ during the reaction can act as a highly efficient reducing quencher for excited-state Ir(III) to generate the corresponding Ir(II) species; subsequently, Ir(II) undergoes single-electron transfer (SET) with aryl thiathracene onium salt, promoting C–S bond cleavage and generating aryl radicals.

[0017] (2) The preparation method of the present invention has a wide range of applicable substrates, good functional group tolerance, and is suitable for complex molecular derivative substrates, and the prepared substrates are... β Aryl-substituted benzyl alcohols can be used as intermediates in organic synthesis, and can be further synthesized into drug molecules and organic functional materials through reactions such as hydroxyl derivatization and aromatic ring modification; at the same time, they can be used as lead compounds for bioactivity screening and development of novel pharmaceutical active substances. Attached Figure Description

[0018] Figure 1 Preparation for the present invention β - Reaction mechanism diagram of aryl-substituted benzyl alcohols; Figure 2 Prepared as in Example 1 β -NMR of aryl-substituted benzyl alcohols 1H NMR spectrum; Figure 3 Prepared as in Example 1 β -NMR of aryl-substituted benzyl alcohols 13 C NMR spectrum; Figure 4 Prepared as in Example 1 β HRMS spectra of aryl-substituted benzyl alcohols. Detailed Implementation

[0019] The present invention is further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods not specifically described in the following examples are generally performed under conventional conditions or as recommended by the manufacturer.

[0020] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of skill in the art. All reagents and materials used in this invention are readily available through conventional means, and unless otherwise specified, they shall be used in accordance with conventional methods in the art or as per the product instructions.

[0021] In this invention, β The general synthetic method for aryl-substituted benzyl alcohols is shown in the following chemical reaction formula: The substituted aryl thiamphazeneium salt I, olefin derivative II, [Ir(dF(CF3)ppy)2(dtbpy)]PF6, Na2CO3, and CH3CN / H2O (200:1, v / v) were sequentially added to an oven-dried 25 mL Schlenk tube. The reaction tube was sealed with a rubber stopper, and three freeze-vacuum-thaw cycles were performed (using liquid nitrogen for freezing and nitrogen purging) to establish an inert atmosphere. Subsequently, the reaction mixture was stirred at room temperature and irradiated with a blue LED (455 nm). After the reaction was completed, saturated brine was added to the reaction residue, and the mixture was extracted with ethyl acetate. The organic phases were combined, dried over anhydrous Na2SO4, concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (200-300 mesh) using petroleum ether and ethyl acetate in a 1:1 v ratio as eluent to obtain the target product. β -Aryl-substituted benzyl alcohols) III.

[0022] Now, in conjunction with specific embodiments, β -The preparation method of aryl-substituted benzyl alcohol is explained: Example 1 The arylthiaanthraium salt (0.2 mmol, 1.0 equiv.), β-substituted styrene (0.4 mmol, 2.0 equiv.), [Ir(dF(CF3)ppy)3(dtbpy)]PF6 (0.005 mol%), Na2CO3 (0.6 mmol, 3.0 equiv.), and CH3CN / H2O (200:1, v / v, total volume 2 mL) from the above reaction formula were sequentially added to 25 mL of oven-dried liquid. In a Schlenk tube, the reaction tube was sealed with a rubber stopper and subjected to three freeze-evacuation-thawing cycles (using liquid nitrogen for freezing and purging with nitrogen) to establish an inert atmosphere. The reaction mixture was then stirred at room temperature and irradiated with a blue LED (455 nm). After the reaction was complete, saturated brine was added to the reaction residue, followed by extraction with ethyl acetate. The combined organic phases were dried over anhydrous Na₂SO₄, concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (200-300 mesh) using petroleum ether / ethyl acetate (1:1) as the eluent. β -Aryl-substituted benzyl alcohol compound (1-([1,1′-biphenyl]-4-yl)-2-phenylprop-2-ol), white solid, in yield of 71%. NMR of the obtained product. 1 1H NMR spectrum (500 MHz, CDCl3), 13 The C NMR spectrum (126 MHz, CDCl3) and HRMS spectrum are shown below. Figure 2 , Figure 3 and Figure 4 Shown, ¹H NMR (500 MHz, CDCl3) δ 7.55 (dd, J =8.23, 1.29 Hz, 2H), 7.45 (s, 1H), 7.44-7.38 (m, 5H), 7.35-7.29 (m, 3H), 7.27-7.23 (m, 1H), 7.06 (d, J = 8.16 Hz, 2H), 3.16 (d, J = 13.33 Hz, 1H), 3.05 (d,J = 13.33 Hz, 1H), 1.59 (s, 3H).¹³C NMR (126 MHz, CDCl3) δ 147.5, 140.8,139.4, 135.8, 131.0, 128.7, 128.1, 127.1, 126.9, 126.7, 126.7, 125.0, 74.5,50.1, 29.4. HRMS (ESI) m / z: [M+H] + Theoretical calculated value: C 17 H 17 F3NO +: 308.1257; Measured value: 308.1260.

[0023] Example 2 In Example 2, the arylthiathaneonium salt shown in the above reaction formula was added to the system, and other conditions were the same as in Example 1, to prepare the following product. β -Aryl-substituted benzyl alcohol compound (2-phenyl-1-[4-(trifluoromethyl)phenyl]prop-2-ol), yellow oily liquid, 33.6 mg, yield 60%. The NMR spectrum data of the obtained product are as follows: ¹H NMR (500 MHz, CDCl3) δ 7.45 (d, J = 8.00 Hz, 2H), 7.38-7.31 (m,4H), 7.27-7.25 (m, 1H), 7.09 (d, J = 7.93 Hz, 2H), 3.16 (d, J = 13.28 Hz,1H), 3.07 (d, J = 13.28 Hz, 1H), 1.58 (s, 3H). ¹³C NMR (126 MHz, CDCl3) δ147.0, 141.1, 130.9, 128.9 (q, J = 32.8 Hz), 128.4, 128.2, 127.0, 125.4,124.9, 124.8, 124.8 (q, J = 3.8 Hz), 124.7, 123.2 (q, J = 273.4 Hz), 74.5,50.3, 29.4. ¹ 9 F NMR (471 MHz, CDCl3) δ -62.4.

[0024] Example 3 In Example 3, the arylthiathaneonium salt shown in the above reaction formula was added to the system, and other conditions were the same as in Example 1, to prepare the following product. β-Aryl-substituted benzyl alcohol (1-[4-(tert-butyl)phenyl]-2-phenylprop-2-ol), yellow oily liquid, 34.9 mg, yield 65%. The NMR spectra of the obtained products are as follows: ¹H NMR (500 MHz, CDCl3) δ 7.43 (d, J = 7.07 Hz, 2H), 7.33 (t, J = 7.78 Hz, 2H), 7.26–7.23 (m, 3H), 6.96 (d, J = 8.30 Hz, 2H), 3.11 (d, J = 13.41 Hz, 1H), 2.99 (d, J = 13.43 Hz, 1H), 1.54 (s, 3H), 1.29 (s, 9H). ¹³C NMR (126 MHz, CDCl3) δ 149.5, 147.8, 133.5, 130.3, 128.0, 126.6, 125.0, 124.9, 74.3, 49.9, 34.4, 31.3, 29.4.

[0025] Example 4 In Example 4, the arylthiathaneonium salt shown in the above reaction formula was added to the system, and other conditions were the same as in Example 1, to prepare the following product. β -Aryl-substituted benzyl alcohol (1-(4-cyclopropylphenyl)-2-phenylprop-2-ol), yellow oily liquid, 35.3 mg, 70% yield. The obtained NMR spectra of the products are as follows: ¹H NMR (500 MHz, CDCl3) δ 7.40 (d, J = 7.04 Hz, 2H), 7.32 (t, J = 7.67 Hz, 2H), 7.26–7.21 (m, 1H), 6.93–6.86 (m, 4H), 3.09 (d, J = 13.42 Hz, 1H), 2.97 (d, J = 13.41 Hz, 1H), 1.86–1.79 (m, 2H), 1.54 (s, 3H), 0.95–0.88 (m, 2H), 0.67–0.61 (m, 2H). ¹³C NMR (126 MHz, CDCl3) δ 147.7, 142.3, 133.5, 130.5, 128.0, 126.6, 125.3, 125.0, 74.4, 50.0, 29.4, 15.0, 9.2.

[0026] Example 5 In Example 5, the arylthiathaneonium salt shown in the above reaction formula was added to the system, and other conditions were the same as in Example 1, to prepare the following product. β -Aryl-substituted benzyl alcohol (1-(4-cyclohexylphenyl)-2-phenylprop-2-ol), yellow oily liquid, 35.3 mg, 70% yield. The obtained NMR spectra of the products are as follows: ¹H NMR (500 MHz, CDCl3) δ 7.40 (d, J = 7.04 Hz, 2H), 7.32 (t, J = 7.67 Hz, 2H), 7.26–7.21 (m, 1H), 6.93–6.86 (m, 4H), 3.09 (d, J = 13.42 Hz, 1H), 2.97 (d, J = 13.41 Hz, 1H), 1.86–1.79 (m, 2H), 1.54 (s, 3H), 0.95–0.88 (m, 2H), 0.67–0.61 (m, 2H). ¹³C NMR (126 MHz, CDCl3) δ 147.7, 142.3, 133.5, 130.5, 128.0, 126.6, 125.3, 125.0, 74.4, 50.0, 29.4, 15.0, 9.2.

[0027] Example 6 In Example 6, the arylthiathaneonium salt shown in the above reaction formula was added to the system, and other conditions were the same as in Example 1, to prepare the following product. β-Aryl-substituted benzyl alcohol (1-(2′-fluoro-[1,1′-biphenyl]-4-yl)-2-phenylprop-2-ol), yellow oily liquid, 31.8 mg, yield 52%. The NMR spectra of the obtained products are as follows: ¹H NMR (500 MHz, CDCl3) δ 7.45–7.38 (m, 5H), 7.34 (t, J = 7.58 Hz, 2H), 7.29–7.24 (m, 2H), 7.18 (t, J = 7.57 Hz, 1H), 7.15–7.10 (m, 1H), 7.08 (d, J = 7.78 Hz, 2H), 3.17 (d, J = 13.33 Hz, 1H), 3.07 (d, J = 13.34 Hz, 1H), 1.60 (s, 3H). ¹³C NMR (126 MHz, CDCl3) ¹³CNMR (126 MHz, CDCl3) δ 159.71 (d, J = 7.58 Hz, 2H), 1.60 (s, 3H). = 248.22 Hz), 146.53, 135.27, 133.09,129.69, 129.63, 129.60, 127.85 (d, J = 8.82 Hz), 127.74, 127.65 (d, J = 3.78Hz), 127.09, 125.71, 123.96, 123.31, 123.28, 115.15(J = 22.68 Hz), 73.49,49.17, 28.68, 28.41. ¹ 9 F NMR (471 MHz, CDCl3) δ -117.97.

[0028] Example 7 In Example 7, the arylthiathaneonium salt shown in the above reaction formula was added to the system, and other conditions were the same as in Example 1, to prepare the following product. β-Aryl-substituted benzyl alcohol (1-(2,3-dihydrobenzo[b][1,4]dioxane-6-yl)-2-phenylprop-2-ol), yellow oily liquid, 33.6 mg, yield 60%. Yellow oily liquid, 35.7 mg, yield 66%. The NMR spectra of the obtained products are as follows: ¹H NMR (500 MHz, CDCl3) δ 7.40 (d, J = 6.93 Hz, 2H), 7.32 (t, J = 7.69 Hz, 2H), 7.26–7.23 (m, 1H), 6.70 (d, J = 8.22 Hz, 1H), 6.54 (d, J = 2.09 Hz, 1H), 6.44 (dd, J = 8.22, 2.09 Hz, 1H), 4.20 (s, 4H), 3.02 (d, J = 13.50 Hz, 1H), 2.90 (d, J = 13.51 Hz, 1H), 1.53 (s, 3H). ¹³C NMR (126 MHz, CDCl3) δ 147.6, 143.0, 142.4, 129.8, 128.0, 126.6, 124.9, 123.5, 119.2, 116.7, 74.3, 64.3, 64.2, 49.7, 29.3.

[0029] Example 8 In Example 8, the arylthiathaneonium salt shown in the above reaction formula was added to the system, and other conditions were the same as in Example 1, to prepare the following product. β-Aryl-substituted benzyl alcohol (1-(dibenzo[b,d]furan-2-yl)-2-phenylprop-2-ol), yellow oily liquid, 31.4 mg, yield 72%. The NMR spectra of the obtained products are as follows: ¹H NMR (500 MHz, CDCl3) δ 7.85 (d, J = 6.43 Hz, 1H), 7.58–7.52 (m, 2H), 7.44–7.37 (m, 4H), 7.36–7.31 (m, 3H), 7.28–7.25 (m, 1H), 7.03 (dd, J = 8.39, 1.83 Hz, 1H), 3.28 (d, J = 13.52 Hz, 1H), 3.17 (d, J = 13.50 Hz, 1H), 1.62 (s, 3H). ¹³C NMR (126 MHz, CDCl3) δ 156.4, 155.2, 147.5, 131.1, 129.7, 128.1, 127.1, 126.7, 125.0, 125.0, 124.1, 124.0, 122.6, 122.4, 120.6, 111.6, 111.0, 74.6, 50.4, 29.4.

[0030] Example 9 In Example 9, the arylthianthaneonium salt shown in the above reaction formula was added to the system, and other conditions were the same as in Example 1, to prepare β-aryl substituted benzyl alcohol (2-phenyl-1-[4-(phenylthio)phenyl]prop-2-ol), a yellow oily liquid, 29.5 mg, with a yield of 46%. The NMR spectra of the obtained products are as follows: ¹H NMR (500 MHz, CDCl3) δ 7.37 (d, J = 7.02 Hz, 2H), 7.34–7.26 (m, 6H), 7.25–7.21 (m, 2H), 7.19 (d, J = 8.18 Hz, 2H), 6.92 (d, J = 8.20 Hz, 2H), 3.09 (d, J = 13.32 Hz, 1H), 3.00 (d, J = 13.30 Hz, 1H), 1.56 (s, 3H). ¹³C NMR (126 MHz, CDCl3) δ 147.3, 136.0, 136.0, 133.6, 131.4, 130.8, 130.7, 129.1, 128.1, 126.9, 126.8, 124.9, 74.5, 50.0, 29.4.

[0031] Example 10 In Example 10, the arylthiathaneonium salt shown in the above reaction formula was added to the system, and other conditions were the same as in Example 1, to prepare the following product. β -Aryl-substituted benzyl alcohol compound (ethyl 5-(2-hydroxy-2-phenylpropyl)-2-methoxybenzoate), yellow oily liquid, 30.8 mg, yield 49%. The NMR spectra of the obtained products are as follows:¹H NMR (500 MHz, CDCl₃) δ 7.39–7.35 (m, 3H), 7.32 (t, J = 7.69 Hz, 2H), 7.26–7.24 (m, 1H), 7.02 (dd, J = 8.50, 2.38 Hz, 1H), 6.79 (d, J = 8.48 Hz, 1H), 4.30 (q, J = 7.14 Hz, 2H), 3.84 (s, 3H), 3.08 (d, J = 13.57 Hz, 1H), 2.98 (d, J = 13.55 Hz, 1H), 1.56 (s, 3H), 1.34 (t, J = 7.19 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 166.1, 157.9, 147.2, 135.3, 133.3, 128.4, 128.1, 126.7.

[0032] Example 11 In Example 11, the arylthiathaneonium salt shown in the above reaction formula was added to the system, and other conditions were the same as in Example 1, to prepare the following product. β -Aryl-substituted benzyl alcohol compound (2-phenyl-1-(3,4,5-trimethoxyphenyl)prop-2-ol), yellow oily liquid, 29.0 mg, yield 48%. The NMR spectrum data of the obtained product are as follows: 1H NMR (500 MHz, CDCl3) δ 7.47(d, J = 7.02 Hz, 2H), 7.31 (t, J = 7.74 Hz, 2H), 7.21 (t, J = 7.32 Hz, 1H), 6.61 (d, J = 8.45 Hz, 1H), 6.53 (d, J = 8.44 Hz, 1H), 3.87 (d, J = 2.15 Hz, 6H), 3.82 (s, 3H), 3.06 (d, J = 13.92 Hz, 1H), 3.01 (d, J=13.88 Hz, 1H), 1.49 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 152.6, 151.9, 148.6, 142.0, 127.9, 126.4,126.3, 124.9, 122.9, 107.2, 74.9, 60.8, 60.8, 55.9, 44.8, 29.2.

[0033] Example 12 In Example 12, the arylthiathaneonium salt shown in the above reaction formula was added to the system, and other conditions were the same as in Example 1, to prepare the following product. β -Aryl-substituted benzyl alcohol compound (methyl 2-[3′-fluoro-4′-(2-hydroxy-2-phenylpropyl)-[1,1′-biphenyl]-4-yl]propionate), yellow oily liquid, 43.1 mg, yield 55%. The NMR spectrum data of the obtained product are as follows: 1 H NMR (500MHz, CDCl3) δ 7.43 (d, J = 6.98 Hz, 2H), 7.39 (d, J = 6.46 Hz, 2H), 7.33 (t,J = 7.74 Hz, 3H), 7.27-7.24 (m, 1H), 7.13-7.06 (m, 4H), 3.74 (q, J = 7.12 Hz, 1H), 3.68 (s, 3H), 3.16 (d, J = 13.31 Hz, 1H), 3.06 (d, J = 13.30 Hz, 1H), 1.59 (s, 3H), 1.52 (d, J = 7.21 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 174.41,160.62 (d, J = 249.48 Hz) 158.64, 147.52, 141.65(d, J = 7.56 Hz), 136.30,133.72, 130.68, 128.51, 128.49, 128.06, 127.51, 127.40, 126.68, 124.94,123.47 (d, J = 3.78 Hz), 115.28 (d, J = 23.94 Hz), 74.47, 52.17, 50.15,44.84, 29.36, 18.37. 19 F NMR (471 MHz, CDCl3) δ -117.48.

[0034] Example 13 In Example 13, the styrene derivative shown in the above reaction formula was added to the system, and other conditions were the same as in Example 1, to prepare the desired product. β -Aryl-substituted benzyl alcohol compound (1-([1,1′-biphenyl]-4-yl)-2-(p-tolyl)but-2-ol), yellow oily liquid, 41.1 mg, yield 65%. The NMR spectrum data of the obtained product are as follows: 1 H NMR (500 MHz, CDCl3) δ7.54 (d, J = 7.25 Hz, 2H), 7.44-7.38 (m, 4H), 7.31 (t, J = 7.33 Hz, 1H), 7.24(d, J = 7.88 Hz, 2H), 7.13 (d, J = 7.91 Hz, 2H), 7.04 (d, J = 8.00 Hz, 2H), 3.17 (d, J = 13.31 Hz, 1H), 3.07 (d, J = 13.32 Hz, 1H), 2.34 (s, 3H), 2.01-1.93 (m, 1H), 1.87 – 1.80 (m, 1H), 0.77 (t, J = 7.40 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 142.5, 140.8, 139.3, 135.9, 135.7, 131.1, 128.7, 128.7, 127.1,126.9, 126.7, 125.5, 77.0, 49.0, 34.5, 21.0, 7.9.

[0035] Example 14 In Example 14, the styrene derivative shown in the above reaction formula was added to the system, and other conditions were the same as in Example 1, to prepare the desired product. β -Aryl-substituted benzyl alcohol compound (2-([1,1′-biphenyl]-4-yl)-1,1-diphenylethyl-1-ol), yellow oily liquid, 42.7 mg, yield 61%. The NMR spectrum data of the obtained product are as follows: 1 H NMR (500 MHz, CDCl3) δ 7.54– 7.51 (m, 2H), 7.47-7.43 (m, 4H), 7.39 (t, J = 7.69 Hz, 4H), 7.33-7.28 (m,5H), 7.24 – 7.21 (m, 2H), 6.96 (d, J = 8.19 Hz, 2H), 3.68 (s, 2H), 2.34 (s,1H). 13 C NMR (126 MHz, CDCl3) δ 146.5, 140.7, 139.5, 134.9, 131.3, 128.7,128.1, 127.2, 126.9, 126.7, 126.2, 78.0, 47.6.

[0036] Example 15 In Example 15, the styrene derivative shown in the above reaction formula was added to the system, and other conditions were the same as in Example 1, to prepare the desired product. β -Aryl-substituted benzyl alcohol compound (1-([1,1′-biphenyl]-4-yl)-4-methyl-2-phenylpentan-2-ol), yellow oily liquid, 27.7 mg, yield 42%. The NMR spectrum data of the obtained product are as follows: 1H NMR (500 MHz, CDCl3) δ7.54 (d, J = 6.98 Hz, 2H), 7.42 – 7.38 (m, 4H), 7.36 – 7.30 (m, 5H), 7.24 (d,J = 8.69 Hz, 1H), 6.97 (d, J = 8.11 Hz, 2H), 3.18 (d, J = 13.28 Hz, 1H), 3.05 (d, J = 13.29 Hz, 1H), 2.00 (dd, J = 14.36, 4.91 Hz, 1H), 1.73 (dd, J =14.36, 7.26 Hz, 1H), 1.60 – 1.54 (m, 1H), 0.90 (d, J = 6.65 Hz, 3H), 0.70 (d,J = 6.69 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 145.9, 140.7, 139.4, 135.3, 131.1,128.7, 127.9, 127.1, 126.9, 126.7, 126.3, 125.6, 50.9, 50.6, 24.6, 24.3, 24.1.

[0037] Example 16 In Example 16, the styrene derivative shown in the above reaction formula was added to the system, and other conditions were the same as in Example 1, to prepare the desired product. β -Aryl-substituted benzyl alcohol compound (1-([1,1′-biphenyl]-4-yl)-2-(thiophen-3-yl)prop-2-ol), yellow oily liquid, 22.4 mg, yield 38%. The NMR spectrum data of the obtained product are as follows: 1 H NMR (500 MHz, CDCl3) δ7.56 (d, J=7.02 Hz, 2H), 7.46 (d, J = 8.21 Hz, 2H), 7.41 (t, J=7.69 Hz, 2H), 7.34-7.29 (m, 2H), 7.10-7.03 (m, 4H), 3.15 (d, J=13.25 Hz, 1H), 3.05 (d, J=13.28 Hz, 1H), 1.58 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 149.5, 140.8, 139.5,135.8, 131.0, 128.7, 127.2, 127.0, 126.7, 125.8, 125.8, 119.9, 73.6, 49.8,29.3.

[0038] Example 17 In Example 17, the styrene derivative shown in the above reaction formula was added to the system, and other conditions were the same as in Example 1, to prepare the desired product. β -Aryl-substituted benzyl alcohol compound (2-(4-isobutylphenyl)propionic acid [4-(1-([1,1′-biphenyl]-4-yl)-2-hydroxypropyl-2-yl)phenyl] ester), yellow oily liquid, 54.1 mg, yield 55%. The NMR spectrum data of the obtained product are as follows: 1 H NMR (500 MHz, CDCl3) δ 7.54 (d, J = 7.02 Hz, 2H), 7.45-7.36 (m, 6H), 7.32-7.29 (m, 3H), 7.14 (d, J = 7.86 Hz, 2H), 7.04 (d, J = 7.98 Hz, 2H), 6.96 (d,J = 8.65 Hz, 2H), 3.93 (q, J = 7.16 Hz, 1H), 3.11 (d, J = 13.32 Hz, 1H), 3.01(d, J = 13.34 Hz, 1H), 2.47 (d, J = 7.17 Hz, 2H), 1.91-1.82 (m, 2H), 1.60 (d,J = 7.21 Hz, 3H), 1.55 (s, 3H), 0.91 (d,J = 6.65 Hz, 6H). 13 C NMR (126 MHz, CDCl3) δ 173.2, 149.6, 145.0, 140.8, 140.7, 139.5, 137.2, 135.6, 131.0,129.5, 128.7, 127.2, 127.1, 126.9, 126.7, 126.1, 120.9, 74.3, 50.1, 45.3, 45.0, 30.2, 29.4, 22.4, 18.5.

[0039] Example 18 In Example 18, the styrene derivative shown in the above reaction formula was added to the system, and other conditions were the same as in Example 1, to prepare the desired product. β -Aryl-substituted benzyl alcohol compound (2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid [4-(1-([1,1′-biphenyl]-4-yl)-2-hydroxypropyl-2-yl)phenyl] ester), yellow oily liquid, 56.6 mg, yield 44%. The NMR spectrum data of the obtained product are as follows: 1 H NMR (500 MHz, CDCl3) δ 7.67 (d, J = 8.53Hz, 2H), 7.54 (d, J = 6.82 Hz, 2H), 7.47-7.43 (m, 4H), 7.42-7.39 (m, 4H), 7.31 (t, J = 7.39 Hz, 1H), 7.07 – 7.01 (m, 5H), 6.90 (d, J = 9.00 Hz, 1H), 6.69 (dd, J = 9.06, 2.53 Hz, 1H), 3.90 (s, 2H), 3.83 (s, 3H), 3.12 (d, J =13.36 Hz, 1H), 3.03 (d, J = 13.36 Hz, 1H), 2.45 (s, 3H), 1.56 (s, 3H). 13 C NMR(126 MHz, CDCl3) δ 169.3, 168.3, 156.1, 149.4, 145.3, 140.7, 139.5, 139.3,136.2, 135.6, 133.8, 131.2, 131.0, 130.8, 130.5, 129.1, 128.7, 127.2, 126.9,126.7, 126.2, 120.8, 115.0, 112.0, 111.8, 101.3, 74.3, 55.7, 50.1, 30.5,29.4, 13.4.

[0040] Example 19 Compared to Example 1, in Example 19, 0.3 mmol of arylthiathaneonium salt and 0.2 mmol of styrene derivative were added to the reaction system, while the remaining conditions were the same as in Example 1, to prepare the following product. β -Aryl-substituted benzyl alcohol (1-([1,1′-biphenyl]-4-yl)-2-phenylprop-2-ol), yield 56%.

[0041] Example 20 In Example 20, the arylthiathaneonium salt was prepared by adding α-substituted styrene to the system, under the same conditions as in Example 1. β -Aryl-substituted benzyl alcohols (Triparanol).

[0042] Example 21 In Example 21, α-substituted styrene was added to the arylthianthane salt and other conditions were the same as in Example 1 to prepare β-aryl substituted benzyl alcohol compounds (MER-25).

[0043] Example 22 In an atmosphere, add to a 25 mL reaction tube equipped with a magnetic stir bar. β -Aryl-substituted benzyl alcohols (1-([1,1′-biphenyl]-4-yl)-2-phenylprop-2-ol) (0.2 mmol, 1.0 equiv.), Pd(OAc)2 (2.3 mg, 0.01 mmol, 0.05 equiv.), Li2CO3 (22.2 mg, 0.3 mmol, 1.5 equiv.), diacetic acid iodobenzene (96.6 mg, 0.3 mmol, 1.5 equiv.), and EA (2.0 mL) were added to a sealed reaction tube and heated to 100 °C. The reaction mixture was stirred at 100 °C for 36 h. The reaction solution was diluted with ether (15 mL), filtered through diatomaceous earth, washed with ether (10 mL × 2), and carefully concentrated under reduced pressure. The residue was purified by silica gel column chromatography using a gradient eluent (dichloromethane / ethyl acetate = 5:1) to give the target product (white solid, 25.8 μL). mg, yield 45%).

[0044] Example 23 In an atmosphere, add to a 25 mL reaction tube equipped with a magnetic stir bar. β- Aryl-substituted benzyl alcohols (1-([1,1′-biphenyl]-4-yl)-2-phenylprop-2-ol) (0.36 mmol, 1.2 equiv.), p-toluene (0.30 mmol, 1.0 equiv.), Cu(OTf)2 (3.3 mg, 0.009 mmol, 3 mol%) and DCM (1.0 mL); the reaction tube was sealed tightly and stirred at 25 °C for 12 h. The reaction mixture was diluted with DCM (10 mL), washed successively with water (5 mL) and saturated brine (5 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluting with a gradient eluent (petroleum ether / ethyl acetate) to give the target product (white solid, 66.2 mg, yield 56%).

[0045] Example 24 The catalyst in Example 1 was changed to [Ir(dF(CF3)ppy)2(dtbbpy)]PF6, while the other conditions remained the same as in Example 1. The different catalysts and the resulting materials... β The yields of aryl-substituted benzyl alcohols (1-([1,1′-biphenyl]-4-yl)-2-phenylprop-2-ol) are shown in Table 1 below: Table 1. Yields of β-aryl-substituted benzyl alcohols under different catalyst conditions Table 1 shows that when the catalyst is [Ir(dF(CF3)ppy)2(dtbbpy)]PF6, the preparation... β -Aryl-substituted benzyl alcohols yielded the best yields.

[0046] Example 25 The alkali (Na2CO3) in Example 1 was changed, while the other conditions remained the same as in Example 1. The different alkalis and the prepared... β The yields of aryl-substituted benzyl alcohols (1-([1,1′-biphenyl]-4-yl)-2-phenylprop-2-ol) are shown in Table 2 below: Table 2. Yields of β-aryl-substituted benzyl alcohols under different alkaline conditions Table 2 shows that when the alkali is sodium carbonate, the preparation... β -Aryl-substituted benzyl alcohols yielded the best yields.

[0047] Example 26 The organic solvent (CH3CN) in Example 1 was changed, while the other conditions remained the same as in Example 1. The different organic solvents and the resulting products... βThe yields of aryl-substituted benzyl alcohols (1-([1,1′-biphenyl]-4-yl)-2-phenylprop-2-ol) are shown in Table 3 below: Table 3. Yields of β-aryl-substituted benzyl alcohols under different organic solvent conditions. Table 3 shows that when the organic solvent is acetonitrile (CH3CN), the preparation... β -Aryl-substituted benzyl alcohols yielded the best yields.

[0048] Example 27 The wavelength of the visible light source in Example 1 was changed, while the other conditions remained the same as in Example 1. The different wavelength conditions and the preparation results... β The yields of aryl-substituted benzyl alcohols (1-([1,1′-biphenyl]-4-yl)-2-phenylprop-2-ol) are shown in Table 4 below: Table 4. Yields of β-aryl-substituted benzyl alcohols under different wavelength driving conditions. Table 4 shows that when the wavelength is 455 nm, the preparation... β -Aryl-substituted benzyl alcohols yielded the best yields.

[0049] Comparative Example 1 Compared to Example 1, Comparative Example 1 did not add water to the solvent, but only the organic solvent acetonitrile. The other conditions were the same as in Example 1, and no reaction occurred under light.

[0050] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention are included within the protection scope of the present invention.

Claims

1. A visible light-driven preparation method for arylthianthaneonium salts β- The method for aryl-substituted benzyl alcohol compounds is characterized by, In an inert atmosphere, in the presence of a base and a photocatalyst, a substituted thiaanthraium salt, as an aryl radical precursor, reacts with an olefin derivative in a solvent under photo-driven conditions to generate... β -Aryl-substituted benzyl alcohols.

2. The visible light-driven preparation of arylthiathianon salt according to claim 1 β A method for aryl-substituted benzyl alcohol compounds, characterized in that... Includes the following steps: (1) Under an inert atmosphere, the substituted arylthiathaneonium salt of Formula I, the olefin derivative of Formula II, the base, the photocatalyst and the solvent are added to the reaction vessel to form a mixed solution. The reaction solution is irradiated with visible light at room temperature to promote the reaction. (2) After the reaction in step (1) is completed, saturated saline solution is added and mixed evenly. Ethyl acetate is added as an extractant for separation and extraction. The crude product is extracted from the reaction solution, the extracts are combined, the organic solvent is removed, and the residue is purified by silica gel chromatography to obtain the product shown in formula III. β- Aryl-substituted benzyl alcohols; R 1 Selected from one or more of aryl, alkyl, and alkenyl substituents; R 2 It is selected from one or more of alkyl, aryl, hydrogen, cyano, and hydrogen groups; R 2 Selected from one or more of alkyl, aryl, and hydrogen groups; R4 is selected from one or more of methyl, propyl, tert-butyl, and hydrogen; X is selected from PF6 or BF4.

3. Preparation of visible light-driven arylthianthaneonium salt according to claim 1 or 2 β A method for aryl-substituted benzyl alcohol compounds, characterized in that... The photocatalyst is one or more of [Ir(dF(CF3)ppy)3(dtbbpy)]PF3, Ir(ppy)3, and 4CzIPN; The alkali is one or more of sodium methoxide, sodium dihydrogen phosphate, sodium carbonate, and sodium acetate. The inert gas is nitrogen or argon; The wavelength range of the visible light is 400 nm to 500 nm.

4. Preparation of visible light-driven arylthianthaneonium salt according to claim 1 or 2 β -A method for aryl-substituted benzyl alcohol compounds, wherein the visible light source is one of LED lamps, mercury lamps, xenon lamps, or sunlight.

5. Preparation of visible light-driven arylthiaanthrannium salt according to claim 1 or 2 β A method for aryl-substituted benzyl alcohol compounds, characterized in that... The solvent is a mixture of organic solvent and water, with a volume ratio of organic solvent to water of 100-300:1; The organic solvent is one or more of acetonitrile, chloroform, tetrahydrofuran, 1,4-dioxane, acetone, dimethyl carbonate, and dimethylacetamide.

6. Preparation of visible light-driven arylthiaanthrannium salt according to claim 1 or 2 β- The method for aryl-substituted benzyl alcohol compounds is characterized by, The molar ratio of the arylthianthracene salt to the olefin derivative is 1:1.5~2; the amount of the photocatalyst added is 0.02-0.04 times the molar amount of the arylthianthracene salt; and the amount of the alkali added is 2-4 times the molar amount of the arylthianthracene salt.

7. Preparation of visible light-driven arylthiathianonium salt according to claim 1 or 2 β The method for aryl-substituted benzyl alcohol is characterized by... The synthesis reaction was carried out at atmospheric pressure for 10-30 h.

8. Preparation of visible light-driven arylthiaanthrannium salt according to claim 1 or 2 β -The method for aryl-substituted benzyl alcohol compounds, wherein the silica gel column in step (2) is 200-300 mesh and the eluent is petroleum ether and ethyl acetate in a volume ratio of 10:1.

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