Non-activated olefin transfer hydrogenation method based on light / cobalt / thiol concerted catalysis

Abstract

The invention discloses a non-activated olefin transfer hydrogenation method driven by a light / cobalt / mercaptan triple catalytic system. Olefin compounds and derivatives thereof are used as raw materials, bio-based gamma-terpinene is used as a hydrogen source, and catalytic circulation is realized through a hydrogen atom transfer (HAT) relay mechanism under the mild condition of visible light irradiation. The method is characterized in that (1) a dual-function activation mode of gamma-terpinene is created for the first time, wherein weak bonding diallyl C-H bonds (BDE = 76kcal / mol) synchronously provide hydrogen atoms and aromatization driving force; and (2) a three-catalyst synergistic system: an organic photosensitizer / cobalt-based catalyst / thiol reagent forms a cascade HAT pathway. (3) normal-temperature normal-pressure operation: high-pressure equipment is not needed, and the reaction time is less than 24 hours; the method breaks through the dependence of traditional hydrogenation on precious metal, high-pressure hydrogen and an oxidizing agent, realizes efficient hydrogenation of non-activated olefin, and provides a new way for synthesis of drug molecule intermediates.

Description

TECHNICAL FIELD

[0001] The application provides a method for realizing transfer hydrogenation of non-activated olefins by a new photocatalytic assembly, and belongs to the field of organic small molecule synthesis and application, and particularly relates to a method for realizing transfer hydrogenation of non-activated olefins based on synergistic catalysis of light / cobalt / thiol. BACKGROUND

[0002] In the past, traditional transition metal complex catalytic systems (such as palladium, platinum, etc.) are the most commonly used method for olefin hydrogenation, but they have many problems such as dependence on high-pressure hydrogen, high cost of noble metals, and safety. In the current industry, there are some technical problems and defects in the hydrogenation of non-activated olefins, mainly manifested as: flammable and explosive hydrogen gas or complex hydride is commonly used as a hydrogen source; noble metal catalysts are involved in the hydrogenation process; some hydrogenation methods need to add excess oxidants to participate in the reaction cycle, or need to use excess additives; the developed method has harsh reaction conditions and produces unnecessary by-products.

[0003] In recent years, in the research method of olefin hydrogenation, complex catalysts based on abundant metals such as iron, cobalt, and manganese have gradually become the core carrier of hydrogen atom transfer reaction due to their unique electronic structure and coordination regulation ability; however, in addition to the need for silane compounds as a hydrogen source, these methods also need stoichiometric amounts of oxidants and proton sources and other hydrogen sources to achieve hydrogenation, and produce stoichiometric amounts of by-products. Recently, a cobalt-based photo-redox synergistic catalytic system has been proposed, which uses ascorbic acid as a single hydrogen source to initiate hydrogen atom transfer by exciting the trivalent cobalt intermediate with visible light, but only exhibits excellent activity in the hydrogenation of tri-substituted olefins. There is also a report (Nature 2023, 619, 506-513.) that water is used as a mild hydrogen source to activate olefins in photocatalysis, but it needs to use a noble metal photosensitizer and a stoichiometric and expensive triarylphosphine to activate water, and the substrate range is limited to terminal olefins.

[0004] Therefore, there is an urgent need for a method for olefin transfer hydrogenation based on a novel catalyst assembly to reduce the dependence on noble metals, high-pressure hydrogen, and oxidants, relax the reaction conditions, and broaden the substrate range. SUMMARY

[0005] The application provides a novel catalyst assembly that can effectively realize the transfer hydrogenation of olefins to solve the problems in the prior art.

[0006] The hydrogenation scheme designed by the present application selects a cheap and widely biologically sourced monoterpene bulk chemical as the only hydrogen source, and through the strategy of transfer hydrogenation, the non-activated olefins and their derivatives are efficiently hydrogenated, and at the same time, the monoterpene hydrogen source is converted into valuable aromatic hydrocarbon chemicals. In addition, the present application selects a cheap and commercially available cobalt-based metal catalyst, without the participation of other additives or oxidants in the reaction, and realizes catalytic circulation under visible light induction to promote efficient hydrogenation of non-activated olefins, the reaction conditions are mild, the hydrogenation efficiency is high, and the application scope is very wide.

[0007] The present application provides a method for transfer hydrogenation of non-activated olefins based on light / cobalt / thiol synergistic catalysis, which uses structurally diverse olefins as raw materials and monoterpene bulk chemicals as single hydrogen source, and through visible light induction to excite organic photosensitizer, with the help of catalytic amount of cobalt catalyst and thiol reagent, hydrogen atom transfer is realized, thereby obtaining the reduction products of olefin compounds and their derivatives, and the catalytic mode is as follows:

[0008]

[0009] R 1 , R 2 , R 3 , R 4 is one or more combinations of the following groups: methyl, ethyl, propyl, butyl, isopropyl, phenyl, benzyl, ester, aldehyde, carbonyl, indole, thiophene, furan, naphthalene, etc.

[0010] Further, PC is selected from one of the following organic photosensitizers:

[0011]

[0012] R 1 is selected from one of the following groups: H, Me, OMe, F, Cl, Br, NMe2;

[0013] R 2 is selected from one of the following groups: H, Me, OMe, F, Cl, Br, NMe2;

[0014] X is selected from one of the following groups: CH2, O, S, NH, NMe, CO.

[0015] Further, Co is selected from one of the following cobalt catalysts:

[0016]

[0017] Further, S reagent is selected from one of the following thiol reagents:

[0018]

[0019] R 1 is selected from one of the following groups: H, Me, OMe, F, Cl, Br, CO2Me;

[0020] R 2 is selected from one of the following groups: H, Me, OMe, F, Cl, Br, CO2Me.

[0021] Further, the above-mentioned method for photo / cobalt / thiol synergistic catalytic non-activated olefin transfer hydrogenation, comprising the following steps:

[0022] (1) adding an olefin compound or its derivative, a hydrogen donor γ-terpinene, an organic photosensitizer, a cobalt catalyst, a thiol reagent into a clean glass reaction bottle with a magnetic stirrer, then adding a solvent, moving the reaction bottle into a photo reactor, and reacting for 12-24 hours at a certain temperature in a nitrogen atmosphere, and monitoring the reaction by GCMS;

[0023] (2) after the reaction is completed, filtering the reaction solution through diatomite, concentrating the filtrate to obtain a crude product, and purifying the crude product by silica gel column chromatography to obtain the hydrogenated product.

[0024] Further, in step (1), the solvent is one or a mixture of two or more of dichloromethane, 1,2-dichloroethane, tetrahydrofuran, ethyl acetate, acetonitrile, methanol, toluene, 1,4-dioxane, and ethanol.

[0025] Further, in step (1), the molar ratio of the olefin compound or its derivative to the γ-terpinene compound is 1:1.5.

[0026] Further, in step (1), based on the number of moles of the olefin compound, the catalytic amount required for the reaction of the PC organic photosensitizer is 5-10 mol%, the catalytic amount required for the reaction of the cobalt-based catalyst is 5-10 mol%, and the catalytic amount required for the reaction of the thiol reagent is 5-10 mol%.

[0027] Further, in step (1), the reaction is carried out under light of a certain wavelength in a photo reactor, the wavelength of the light is between 300-500 nm, and the reaction is carried out at a certain temperature, which is room temperature or heating at 60-70 DEG C.

[0028] Further, in step (2), the eluent used for silica gel column chromatography purification is petroleum ether / ethyl acetate; and the volume ratio of petroleum ether to ethyl acetate is 100-2:1.

[0029] Compared with the prior art, the present application has the following characteristics and advantages:

[0030] (1) The first γ-terpinene bifunctional activation mode: the weakly bonded double allylic C-H bond (BDE = 76 kcal / mol) synchronously provides hydrogen atom and aromatization driving force.

[0031] (2) Three-catalyst synergistic system: organic photosensitizer / cobalt-based catalyst / thiol reagent form cascade HAT pathway.

[0032] (3) Normal temperature and pressure operation: no high-pressure equipment is needed, and the reaction time is less than 24 hours.

[0033] (4) The method provided by the application breaks through the dependence of traditional hydrogenation on noble metals, high-pressure hydrogen and oxidizing agents, realizes efficient hydrogenation of non-activated olefins, and provides a new way for synthesis of drug molecule intermediates. BRIEF DESCRIPTION OF DRAWINGS

[0034] Figure 1 The olefin compound used in the embodiments of the application.

[0035] Figure 2 The catalytic mode diagram of the application. DETAILED DESCRIPTION

[0036] In order to deepen the understanding of the application, the application will be specifically described below in combination with the embodiments, but the application is not limited to the following embodiments.

[0037] The specific steps of the application are as follows:

[0038] (1) A clean glass reaction bottle with a magnetic stirrer is added with an olefin compound or its derivative, a hydrogen donor, an organic photosensitizer, a cobalt catalyst, a thiol reagent, and a solvent, and then the reaction bottle is moved to a photoreactor, the wavelength of the light is between 300-500 nm, and the reaction is carried out at room temperature in a nitrogen atmosphere for 12-24 hours, and GCMS is used to monitor the reaction condition;

[0039] (2) After the reaction is completed, the reaction liquid is filtered through diatomite, and the filtrate is concentrated to obtain a crude product, and the crude product is purified by silica gel column chromatography to obtain the hydrogenated product.

[0040] The application has the advantages of mild reaction conditions, low cost, wide source of raw materials, simple operation, wide application to a wide range of olefin compounds (including terminal olefins, 1,1-disubstituted olefins, 1,2-disubstituted olefins, trisubstituted olefins and tetrasubstituted olefins), high selective hydrogenation effect in derivatives containing multiple olefins, and applicability to gram-scale reactions.

[0041] Example 1

[0042] Preparation of hydrogenated product 2a: under a nitrogen atmosphere, 2a was prepared by the method of the application. Figure 1The olefin shown in Example 1a (35.2 mg, 0.2 mmol), γ-terpinene (0.3 mmol), organic photosensitizer p-dimethylaminobenzo-phenone (0.01 mmol), cobalt catalyst phthalocyanine cobalt (II) (0.01 mmol), thiol reagent 4-(trifluoromethyl)benzenethiol (0.01 mmol) and 1 mL of super dry 1,4-dioxane were placed in a 4 mL glass reaction bottle which was then transferred to a photo reactor, the wavelength of light was between 300-500 nm, and the reaction was carried out at room temperature for 12 hours in a nitrogen atmosphere. After the reaction was completed, the reaction liquid was filtered through diatomite, and the filtrate was concentrated to obtain a crude product, which was then purified by silica gel column chromatography with petroleum ether / ethyl acetate (V PE :V EA = 100:1) as eluent to obtain colorless oily product 2a, as shown below, in a yield of 35.2 mg and a yield of 99%.

[0043]

[0044] The parameters tested were as follows:

[0045] The nuclear magnetic hydrogen spectrum was as follows: 1 H NMR (500 MHz, Chloroform-d) δ 7.28-7.24 (m, 2H), 6.90-6.85 (m, 2H), 4.43 (s, 2H), 3.80 (s, 3H), 3.46 (t, J = 6.8 Hz, 2H), 1.72 (dp, J = 13.4, 6.7 Hz, 1H), 1.49 (q, J = 6.8 Hz, 2H), 0.89 (d, J = 6.6 Hz, 6H);

[0046] The nuclear magnetic carbon spectrum was as follows: 13 C NMR (126 MHz, Chloroform-d) δ 138.9, 128.5, 127.7, 127.6, 73.0, 69.0, 38.7, 25.2, 22.8.

[0047] Example 2

[0048] The other steps of this example were the same as those of Example 1, except that the olefin in Example 1 was replaced with an equal molar amount of Figure 1 1b. Eluent was petroleum ether / ethyl acetate (V PE :V EA = 5:1) to obtain colorless oily product 2b, as shown below, in a yield of 26.9 mg and a yield of 82%.

[0049]

[0050] The parameters tested were as follows:

[0051] The nuclear magnetic hydrogen spectrum is: 1 H NMR (500 MHz, Chloroform-d) δ 7.07 - 7.03 (m, 2H), 6.77 - 6.72 (m, 2H), 4.55 (dd, J = 6.5, 2.5 Hz, 1H), 2.56 - 2.51 (m, 2H), 1.58 (dq, J = 13.2, 6.6 Hz, 1H), 1.48 - 1.43 (m, 2H), 0.92 (d, J = 6.6 Hz, 6H);

[0052] The nuclear magnetic carbon spectrum is: 13 C NMR (126 MHz, Chloroform-d) δ 153.5, 135.5, 129.5, 115.2, 41.2, 33.0, 27.7, 22.7.

[0053] Example 3

[0054] The other steps of this example are the same as those of Example 1, except that the olefin in Example 1 is replaced with an equal molar amount of Figure 1 The eluent used is petroleum ether / ethyl acetate (V PE :V EA = 50:1) to obtain the product 2c as a colorless oil, whose structure is shown below, in an amount of 37.2 mg and a yield of 97%.

[0055]

[0056] The parameters tested are as follows:

[0057] The nuclear magnetic hydrogen spectrum is: 1 H NMR (500 MHz, Chloroform-d) δ 6.72 (d, J = 7.9 Hz, 1H), 6.68 (d, J = 1.7 Hz, 1H), 6.63 (ddd, J = 7.9, 1.7, 0.8 Hz, 1H), 5.91 (s, 2H), 2.55 - 2.50 (m, 2H), 1.61 - 1.52 (m, 1H), 1.48 - 1.43 (m, 2H), 0.92 (d, J = 6.6 Hz, 6H);

[0058] The nuclear magnetic carbon spectrum is: 13 C NMR (126 MHz, Chloroform-d) δ 147.6, 145.5, 137.1, 121.1, 109.0, 108.2, 100.8, 41.3, 33.7, 27.7, 22.7.

[0059] Example 4

[0060] The other steps of this example are the same as example 1, except that the olefin in example 1 is replaced with an equal molar amount of Figure 1 The eluent used was petroleum ether / ethyl acetate (V PE :V EA = 50:1) to give the product 2d as a colorless oil. The structure is shown below. The yield was 30.3 mg, 86%.

[0061]

[0062] The parameters tested are as follows:

[0063] The hydrogen nuclear magnetic resonance spectrum is as follows: 1 H NMR (500 MHz, Chloroform-d) δ 7.30 - 7.26 (m, 2H), 7.21 - 7.15 (m, 3H), 2.61 (m, 2H), 1.67 - 1.59 (m, 1H), 1.51 - 1.39 (m, 2H), 1.38 - 1.28 (m, 3H), 1.18 - 1.11 (m, 1H), 0.93 (d, J = 6.4 Hz, 3H), 0.90 - 0.87 (m, 3H);

[0064] The carbon nuclear magnetic resonance spectrum is as follows: 13 C NMR (126 MHz, Chloroform-d) δ 143.4, 128.5, 128.4, 125.7, 39.4, 39.1, 33.6, 32.4, 20.2, 19.7, 14.5.

[0065] Example 5

[0066] The other steps of this example are the same as example 1, except that the olefin in example 1 is replaced with an equal molar amount of Figure 1 The eluent used was petroleum ether / ethyl acetate (V PE :V EA = 5:1) to give the product 2e as a colorless oil. The structure is shown below. The yield was 30 mg, 96%.

[0067]

[0068] The parameters tested are as follows:

[0069] The hydrogen nuclear magnetic resonance spectrum is as follows: 1H NMR(500MHz,Chloroform-d)δ3.41(tt,J=10.1,4.6Hz,1H),2.17(pd,J=7.0,2.8Hz,1H),1.96(dtd,J=12.1,3.9,2.1Hz,1H),1.69–1.58(m,2H),1 .46–1.37(m,1H),1.33–1.29(m,1H),1.14–1.07(m,1H),1.02–0.93(m,2H ),0.92(dd,J=7.7,6.8Hz,6H),0.88–0.82(m,1H),0.81(d,J=7.0Hz,3H);

[0070] The carbon NMR spectrum is as follows: 13 C NMR (126MHz, Chloroform-d) δ71.7,50.3,45.2,34.7,31.8,26.0,23.2,22.4,21.2,16.2.

[0071] Example 6

[0072] All other steps in this embodiment are the same as in Example 1, except that in Example 1, the olefin is replaced with an equimolar amount. Figure 1 As shown in Figure 1f, 4-(trifluoromethyl)benzylthiophenol was increased to 0.02 mmol, and the reaction was carried out at room temperature for 24 hours. The eluent was petroleum ether / ethyl acetate (V... PE :V EA =50:1), yielding a colorless oily product 2f, the structure of which is shown below, with a yield of 51.7 mg and a yield of 85%.

[0073]

[0074] Its parameters, after testing, are as follows:

[0075] The 1H NMR spectrum is as follows: 1 H NMR(500MHz,Chloroform-d)δ7.55–7.51(m,2H),6.69–6.65(m,2H),3.91(t,J=6.6Hz,2H),1 .76(ddt,J=9.2,7.8,6.5Hz,2H),1.47–1.39(m,2H),1.35–1.30(m,4H),0.90(t,J=5Hz,3H);

[0076] The carbon NMR spectrum is as follows: 13C NMR (126 MHz, Chloroform-d) δ 159.2, 138.3, 117.0, 82.5, 77.4, 68.2, 31.7, 29.2, 25.8, 22.7, 14.2.

[0077] Example 7

[0078] The other steps of this example are the same as example 1, except that the olefin in example 1 is replaced with an equal molar amount of Figure 1 1g, while 4-(trifluoromethyl)benzenethiol is increased to 0.02 mmol, and the reaction is allowed to proceed at room temperature for 24 hours. Eluent is petroleum ether / ethyl acetate (V PE :V EA = 2: 1) to give white solid product 2g, which has the structure shown below, in a yield of 44.7 mg, 95%.

[0079]

[0080] Its parameters are tested as follows:

[0081] The hydrogen nuclear magnetic resonance spectrum is: 1 H NMR (500 MHz, Chloroform-d) δ 7.51 (s, 1H), 4.26 (t, J = 7.2 Hz, 2H), 3.56 (s, 3H), 3.38 (s, 3H), 1.86 - 1.79 (m, 2H), 1.31 (dt, J = 14.8, 7.5 Hz, 2H), 0.93 (t, J = 7.4 Hz, 3H);

[0082] The carbon nuclear magnetic resonance spectrum is: 13 C NMR (126 MHz, Chloroform-d) δ 155.2, 151.8, 149.0, 140.9, 107.1, 47.2, 33.0, 29.9, 28.1, 19.7, 13.6.

[0083] Example 8

[0084] The other steps of this example are the same as example 1, except that the olefin in example 1 is replaced with an equal molar amount of Figure 1 1h, while 4-(trifluoromethyl)benzenethiol is increased to 0.02 mmol, and the reaction is allowed to proceed at room temperature for 24 hours. Eluent is petroleum ether / ethyl acetate (V PE :V EA = 10: 1) to give white solid product 2h, which has the structure shown below, in a yield of 41.4 mg, 99%.

[0085]

[0086] The tested parameters are as follows:

[0087] The nuclear magnetic hydrogen spectrum is: 1 H NMR (500 MHz, Chloroform-d) δ 4.94 (t, J = 6.2 Hz, 1H), 4.46 (t, J = 5.9 Hz, 1H), 2.72 (ddd, J = 16.0, 5.0, 1.8 Hz, 1H), 2.55 (ddd, J = 15.9, 4.8, 2.1 Hz, 1H), 2.47 - 2.29 (m, 4H), 2.19 - 2.11 (m, 1H), 2.09 - 1.99 (m, 1H), 1.79 (ddd, J = 13.0, 9.6, 4.3 Hz, 1H), 1.72 - 1.63 (m, 3H), 1.39 (dp, J = 14.6, 6.9 Hz, 2H), 0.94 (td, J = 7.4, 0.9 Hz, 3H);

[0088] The nuclear magnetic carbon spectrum is: 13 C NMR (126 MHz, Chloroform-d) δ 207.7, 170.1, 53.8, 51.0, 49.9, 49.1, 33.9, 30.1, 28.1, 27.6, 22.8, 14.1.

[0089] Example 9

[0090] The other steps of this example are the same as those of Example 1, except that the olefin in Example 1 is replaced with an equimolar amount of Figure 1 shown 1i, while 4-(trifluoromethyl)benzenethiol is increased to 0.02 mmol, and the reaction is carried out at room temperature for 24 hours. The eluent is petroleum ether / ethyl acetate (V PE :V EA = 100:1), to obtain a colorless oily product 2i, whose structure is shown below, with a yield of 40.7 mg and a yield of 95%.

[0091]

[0092] The tested parameters are as follows:

[0093] The nuclear magnetic hydrogen spectrum is: 1 H NMR (500 MHz, Chloroform-d) δ 4.12 (q, J = 7.1 Hz, 2H), 2.28 (t, J = 7.6 Hz, 2H), 1.65 - 1.56 (m, 2H), 1.32 - 1.23 (m, 17H), 0.87 (t, J = 6.9 Hz, 3H);

[0094] The nuclear magnetic carbon spectrum is: 13C NMR (126 MHz, Chloroform-d) δ 174.1, 60.3, 34.6, 32.0, 29.7, 29.6, 29.5, 29.4, 29.3, 25.1, 22.8, 14.4, 14.3.

[0095] Example 10

[0096] The other steps of this example are the same as example 1, except that the olefin in example 1 is replaced with an equal molar amount of Figure 1 1j, while 4-(trifluoromethyl)benzenethiol is increased to 0.02 mmol, and the reaction is allowed to proceed at room temperature for 24 hours. Eluent is petroleum ether / ethyl acetate (V PE :V EA = 3: 1) to give the product 2j as a colorless oil, which has the structure shown below, in a yield of 29.3 mg, 73%.

[0097]

[0098] The parameters tested are as follows:

[0099] The nuclear magnetic hydrogen spectrum is: 1 H NMR (500 MHz, Chloroform-d) δ 8.73 (dd, J = 5.2, 1.6 Hz, 1H), 8.23 (dt, J = 8.4, 1.6 Hz, 1H), 8.05 - 8.00 (m, 1H), 7.69 (ddd, J = 8.4, 6.9, 1.6 Hz, 1H), 7.50 (ddd, J = 8.2, 6.8, 1.3 Hz, 1H), 6.72 (dd, J = 5.2, 1.6 Hz, 1H), 4.20 (td, J = 6.4, 1.6 Hz, 2H), 1.96 - 1.91 (m, 2H), 1.64 - 1.57 (m, 2H), 1.04 (td, J = 7.4, 1.6 Hz, 3H);

[0100] The nuclear magnetic carbon spectrum is: 13 C NMR (126 MHz, Chloroform-d) δ 162.0, 151.5, 149.2, 129.9, 128.8, 125.7, 122.1, 121.7, 100.8, 68.4, 31.1, 19.5, 14.0.

[0101] Example 11

[0102] The other steps of this example are the same as example 1, except that the olefin in example 1 is replaced with an equal molar amount of Figure 1The cobalt catalyst N,N'-disalicylideneethylenediamine cobalt (II) and methyl thiobenzoate were both increased to 0.02 mmol, and the reaction was carried out at 60-70 °C for 72 hours. The eluent was petroleum ether / ethyl acetate (V PE :V EA = 20:1) to obtain product 2k as a colorless oil, with a yield of 37.4 mg and a yield of 99%.

[0103]

[0104] The parameters tested were as follows:

[0105] The nuclear magnetic hydrogen spectrum was as follows: 1 H NMR (500 MHz, Chloroform-d) δ 7.60 - 7.55 (m, 2H), 6.95 - 6.92 (m, 2H), 4.02 (t, J = 6.7 Hz, 2H), 1.83 (dp, J = 13.3, 6.6 Hz, 1H), 1.69 (q, J = 6.8 Hz, 2H), 0.96 (d, J = 6.6 Hz, 6H);

[0106] The nuclear magnetic carbon spectrum was as follows: 13 C NMR (126 MHz, Chloroform-d) δ 162.6, 134.1, 119.5, 115.3, 103.8, 66.9, 37.8, 25.1, 22.7.

[0107] Example 12

[0108] The other steps of this example were the same as those of Example 1, except that the alkene in Example 1 was replaced with an equimolar amount of Figure 1 The cobalt catalyst N,N'-disalicylideneethylenediamine cobalt (II) and methyl thiobenzoate were both increased to 0.02 mmol, and the reaction was carried out at 60-70 °C for 72 hours. The eluent was petroleum ether / ethyl acetate (V PE :V EA = 50:1) to obtain product 21 as a colorless oil, with a yield of 37.0 mg and a yield of 89%.

[0109]

[0110] The parameters tested were as follows:

[0111] The nuclear magnetic hydrogen spectrum was as follows: 1H NMR (500 MHz, Chloroform-d) δ 6.83 (d, J = 0.7 Hz, 4H), 3.89 (t, J = 6.7 Hz, 2H), 3.77 (s, 3H), 1.80 - 1.72 (m, 2H), 1.60 (dt, J = 13.4, 6.7 Hz, 1H), 1.35 - 1.29 (m, 2H), 0.91 (d, J = 6.7 Hz, 6H);

[0112] The carbon magnetic resonance spectrum is: 13 C NMR (126 MHz, Chloroform-d) δ 153.8, 153.4, 115.5, 114.7, 69.1, 55.9, 35.3, 28.0, 27.4, 22.7.

[0113] Example 13

[0114] The other steps of this example are the same as those of Example 1, except that the olefin in Example 1 is replaced with an equimolar amount of Figure 1 methyl p-thiohydroxybenzoate are both increased to 0.02 mmol, and the reaction is carried out at 60-70 °C for 72 hours. The eluent used is petroleum ether / ethyl acetate (V PE :V EA = 5:1), to obtain colorless oily product 2m, whose structure is shown below, in a yield of 31.8 mg and a yield of 79%.

[0115]

[0116] Its parameters are as follows after testing:

[0117] The hydrogen magnetic resonance spectrum is: 1 H NMR (500 MHz, Chloroform-d) δ 7.66 (dq, J = 7.9, 0.9 Hz, 1H), 7.37 (dt, J = 8.3, 0.9 Hz, 1H), 7.27 - 7.21 (m, 1H), 7.15 - 7.11 (m, 2H), 6.52 (dt, J = 3.1, 0.9 Hz, 1H), 4.12 (t, J = 7.3 Hz, 2H), 1.90 - 1.82 (m, 2H), 1.60 (dq, J = 13.3, 6.7 Hz, 1H), 1.28 - 1.21 (m, 2H), 0.90 (d, J = 10 Hz, 6H);

[0118] The carbon magnetic resonance spectrum is: 13C NMR (126 MHz, Chloroform-d) δ 136.1, 128.7, 127.9, 121.4, 121.1, 119.3, 109.5, 101.0, 46.8, 36.2, 28.3, 27.9, 22.6.

[0119] Example 14

[0120] The other steps of this example are the same as example 1, except that the olefin in example 1 is replaced with an equal molar amount of Figure 1 the organic photosensitizer dimethylaminobenzophenone and the cobalt catalyst N,N'-disalicylideneethylenediamine cobalt (II) and methyl thioglycolate are all increased to 0.02 mmol, and the reaction is carried out at 60-70 °C for 72 hours. The eluent used is petroleum ether / ethyl acetate (V PE :V EA = 3: 1), to obtain colorless oily product 2n, whose structure is shown below, with a yield of 35.7 mg and a yield of 72%.

[0121]

[0122] Its parameters are as follows after testing:

[0123] The nuclear magnetic hydrogen spectrum is: 1 H NMR (500 MHz, Chloroform-d) δ 8.29 (d, J = 4.7 Hz, 2H), 6.46 (t, J = 4.7 Hz, 1H), 3.82 (t, J = 5.0, Hz, 4H), 2.48 (t, J = 5.0 Hz, 4H), 2.35 - 2.30 (m, 2H), 1.58 - 1.48 (m, 3H), 1.21 - 1.15 (m, 2H), 0.88 (d, J = 6.7 Hz, 6H);

[0124] The nuclear magnetic carbon spectrum is: 13 C NMR (126 MHz, Chloroform-d) δ 161.8, 157.8, 109.9, 77.4, 59.4, 53.3, 43.8, 36.9, 28.1, 24.9, 22.7.

[0125] Example 15

[0126] The other steps of this example are the same as example 1, except that the olefin in example 1 is replaced with an equal molar amount of Figure 1 the organic photosensitizer dimethylaminobenzophenone and the cobalt catalyst N,N'-disalicylideneethylenediamine cobalt (II) and methyl thioglycolate are all increased to 0.02 mmol, and the reaction is carried out at 60-70 °C for 72 hours. The eluent used is petroleum ether / ethyl acetate (V PE:V EA = 100:1) to give colorless oil product 2o, whose structure is shown below, yield 58.8 mg, yield 88%.

[0127]

[0128] The parameters tested are as follows:

[0129] The nuclear magnetic hydrogen spectrum is: 1 H NMR (500 MHz, Chloroform-d) δ 4.79 (s, 2H), 7.00-7.05 (m, 4H), 7.09-7.20 (m, 16H);

[0130] The nuclear magnetic carbon spectrum is: 13 C NMR (126 MHz, Chloroform-d) δ 56.4, 125.9, 128.2, 128.6, 143.5.

[0131] Compared with the prior art, the present application has the following characteristics and advantages:

[0132] (1) The γ-terpinene bifunctional activation mode is created: the weakly bonded double allylic C-H bond (BDE = 76 kcal / mol) synchronously provides hydrogen atoms and aromatization driving force.

[0133] (2) Three-catalyst synergistic system: organic photosensitizer / cobalt-based catalyst / thiol reagent form a cascade HAT pathway.

[0134] (3) Normal temperature and pressure operation: no need for high-pressure equipment, reaction time < 24 hours.

[0135] (4) The method provided by the present application breaks through the dependence of traditional hydrogenation on noble metals, high-pressure hydrogen and oxidizing agents, realizes efficient hydrogenation of non-activated olefins, and provides a new way for synthesis of drug molecule intermediates.

[0136] The above description of disclosed embodiments enables a person skilled in the art to implement or use the present application. Various modifications to these embodiments will be apparent to those skilled in the art, and the general principles defined in the present application can be implemented in other embodiments without departing from the spirit or scope of the present application. Therefore, the present application will not be limited to these embodiments shown herein, but will conform to the widest scope consistent with the principles and novel features disclosed in the present application.

Claims

1. A method for the transfer hydrogenation of non-activated olefins based on the synergistic catalysis of light / cobalt / thiol, characterized in that, Visible light induced excitation of organic photosensitizer, hydrogen source from the raw material of γ-terpinene by free radical hydrogen atom transfer process, then relay with catalytic amount of cobalt catalyst and mercaptan reagent to achieve hydrogen atom transfer, thus realizing the hydrogenation of non-activated olefin compounds and their derivatives; the catalytic mode is as follows: In the formula, the bulb represents a light source of a specific wavelength (300-500 nm); In the formula, PC is an organic photosensitizer; In the formula, Co is a cobalt-based catalyst; In the formula, S is a mercaptan reagent; where R 1 , R 2 , R 3 , R 4 is one or more combinations of the following groups into an olefin or its derivatives: methyl, ethyl, propyl, butyl, isopropyl, phenyl, benzyl, ester, aldehyde, carbonyl, indole, thiophene, furan, naphthalene, etc.

2. The method of light / cobalt / thiol synergistic catalysis of non-activated olefin transfer hydrogenation according to claim 1, characterized in that, The PC is selected from one of the following organic photosensitizers: R 1 one selected from the group consisting of H, Me, OMe, F, Cl, Br, NMe2; R 2 one selected from the group consisting of H, Me, OMe, F, Cl, Br, NMe2; X is selected from one of the following groups: CH2, O, S, NH, NMe, CO.

3. The method of photocatalyzed non-activated olefin transfer hydrogenation of Co / SH according to claim 1, characterized in that, The Co is selected from one of the following cobalt catalysts:

4. The method of photocatalyzed non-activated olefin transfer hydrogenation of Co / SH according to claim 1, characterized in that, The S reagent is selected from one of the following mercaptan reagents: R 1 one selected from the group consisting of H, Me, OMe, F, Cl, Br, CO2Me; R 2 one selected from the group consisting of H, Me, OMe, F, Cl, Br, CO2Me.

5. The method of photocatalyzed non-activated olefin transfer hydrogenation of Co / SH according to claim 1, characterized in that, The method comprises the following steps: (1) A clean glass reaction bottle with a magnetic stirrer is added with an olefin compound or its derivative, a hydrogen donor γ-terpinene, an organic photosensitizer, a cobalt catalyst, a mercaptan reagent, and a solvent, and then the reaction bottle is moved to a photoreactor for reaction under a nitrogen atmosphere at a certain temperature for 12-24 hours, and GCMS is used to monitor the reaction; (2) After the reaction is completed, the reaction liquid is filtered through diatomite, and the filtrate is concentrated to obtain a crude product, and the crude product is purified by silica gel column chromatography to obtain the hydrogenated product.

6. A method of photocatalyzed non-activated olefin transfer hydrogenation with cobalt / sulfur containing compound according to claim 5, characterized in that, In step (1), the solvent is one or a mixture of two or more of dichloromethane, 1,2-dichloroethane, tetrahydrofuran, ethyl acetate, acetonitrile, methanol, toluene, 1,4-dioxane, and ethanol.

7. The method of light / cobalt / thiol synergistic catalysis of non-activated olefin transfer hydrogenation according to claim 5, characterized in that, In step (1), the molar ratio of the reaction of the olefin compound or its derivative with the γ-terpinene compound is 1:1.

5.

8. The method of light / cobalt / thiol synergistic catalysis of non-activated olefin transfer hydrogenation according to claim 5, characterized in that, In step (1), based on the number of moles of the olefin compound, the catalytic amount required for the reaction of the PC organic photosensitizer is 5-10 mol%, the catalytic amount required for the reaction of the cobalt-based catalyst is 5-10 mol%, and the catalytic amount required for the reaction of the mercaptan reagent is 5-10 mol%.

9. The method of light / cobalt / thiol synergistic catalysis of non-activated olefin transfer hydrogenation according to claim 5, characterized in that, In step (1), the reaction is carried out under light of a certain wavelength in a photoreactor, and the wavelength of the light is between 300-500 nm; the reaction is carried out at a certain temperature, and the temperature is room temperature or heating at 60-70°C.

10. The method of light / cobalt / thiol synergistic catalysis of non-activated olefin transfer hydrogenation according to claim 5, characterized in that, In step (2), the eluent used for silica gel column chromatography purification is petroleum ether / ethyl acetate; the volume ratio of petroleum ether to ethyl acetate is 100-2:1.

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