Three-component reaction method of electro-catalytic olefin, 1, 3-dicarbonyl compound and alcohol

Abstract

The invention discloses a three-component reaction method of electro-catalytic olefin, a 1, 3-dicarbonyl compound and alcohol. Under the electro-catalysis condition, styrene reacts with malonate and an alcohol compound, and a series of alkylated malonate compounds are prepared through direct C (sp3)-H / C-O bond bifunctionalization. Compared with a traditional preparation method, the method has the advantages that expensive halogenated malonate raw materials do not need to be used, precious metals and additional oxidants do not exist, and the method has wide substrate adaptability, excellent functional group tolerance and fine site selectivity.

Description

Technical Field

[0001] This application belongs to the technical field of organic synthesis, and specifically relates to a method for electrocatalytic three-component reaction of olefins with 1,3-dicarbonyl compounds and alcohols. Background Art

[0002] Olefin compounds are widely present in natural products and are one of the most readily available and abundant chemical raw materials. They are widely used by organic chemists and can be used to construct various complex molecular structures. The olefin difunctionalization reaction strategy can directly introduce two functional groups into small organic compounds to achieve the efficient construction of two or more new bonds, which is crucial for the development of organic synthesis and is widely welcomed by synthetic chemists. Traditional olefin difunctionalization reaction routes mainly use transition metals to catalyze. However, transition metal catalysis relies on precious metals, harsh reaction conditions, and substrate pre-functionalization, which greatly hinders its development. Using radical chemistry to achieve olefin difunctionalization can effectively avoid the limitations of transition metal catalysis. In recent years, great progress has been made in the electrocatalytic radical-mediated olefin difunctionalization reaction.

[0003] Difunctionalization reaction is an effective bonding strategy that rapidly increases molecular complexity by simultaneously attaching two non-hydrogen substituents to readily available starting materials. In the field of organic electrochemistry, the electrocatalytic difunctionalization reaction of olefins is an area constantly explored by many chemists. Compared with other reaction strategies, the electrocatalytic olefin difunctionalization reaction has several significant advantages: (1) By simply adjusting the applied potential, current density, electrolyte, electrode material, and reaction time, the chemistry, regioselectivity, and stereoselectivity of the reaction can be significantly changed, precisely controlling the selectivity of the reaction with minimal competing reactions; (2) Electrocatalytic reactions use electricity as a source of oxidizing and reducing agents, which usually reduces the dependence on traditional chemical oxidants, reducing agents, and expensive transition metal catalysts, thereby reducing the use of external oxidants such as transition metals and peroxides and mitigating environmental impacts; (3) In addition, electrochemical reactions can be designed to have higher atom / step economy, maximizing the utilization of starting materials and minimizing waste generation.

[0004] Malonic ester compounds are an important class of organic synthesis intermediates, which can undergo various transformations through, for example, hydrolysis. In the prior art, three-component reactions of olefins with 1,3-dicarbonyl compounds and alcohols have been reported. These radical reactions often need to be carried out in the presence of expensive photocatalysts, high-valent metal salts such as ammonium cerium nitrate, etc. (Synthetic Communications, 27(17), 3053-3064, 1997; Journal of Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry, (15), 1881-1882, 1995; Journal of Organic Chemistry, 55(22), 5688-5691, 1990). The selectivity of the above methods is not high, and it is often easier to obtain the products of benzylic position oxidative carbonylation. In 2023, the Shi research group developed a photocatalytic HTRA reaction, which realized the difunctionalization of olefins with haloalkyl radicals under mild conditions, had a wide range of substrate scopes and good functional group tolerance, and generated a series of highly functionalized aromatic or heteroaromatic haloalkyl derivatives with medium to high yields (Chemistry–A European Journal, 2024, 30(62): e202402458). However, the above method requires the use of halogenated malonic ester substrates, with low atom economy and expensive substrates.

[0005] Through in-depth research, the inventors accidentally discovered a new C-H activation reaction strategy for styrene with malonic esters and alcohols by directly C(sp3)-H / C-O bond difunctionalization, and thus completed the present invention. Summary of the Invention

[0006] The object of the present invention is to overcome the deficiencies of the prior art and propose a simple, green, efficient and environmentally friendly olefin difunctionalization strategy. Under electrocatalytic conditions, a three-component reaction of styrene with malonic esters and alcohols is carried out, and a series of alkylated malonic ester compounds are prepared through direct C(sp3)-H / C-O bond difunctionalization. Compared with the traditional preparation methods, it does not require the use of expensive halogenated malonic ester raw materials, no precious metals and no external oxidants, has a wide range of substrate adaptability, excellent functional group tolerance and fine site selectivity.

[0007] A three-component reaction method of electrocatalytic olefin with 1,3-dicarbonyl compound and alcohol provided by the present invention comprises the following steps:

[0008] Into an electrolytic reactor equipped with a platinum sheet cathode and a graphite felt anode, successively add the styrene compound shown in Formula 1, the malonic ester compound shown in Formula 2, and the alcohol compound shown in Formula 3. Subsequently, add the catalyst Cp2Fe, an inorganic base, an electrolyte, and an organic solvent. Place the reactor at a certain temperature, pass a constant current, stir, and electrolyze until the reaction is complete. After the reaction is complete, obtain the alkyl malonic ester compound shown in Formula 4 through post-treatment;

[0009] The reaction formula is as follows:

[0010]

[0011] In the above reaction formula, m is an integer of 1, 2, 3, 4, or 5; each R1 is the same or different and is independently selected from halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 6-20 aryloxy, C 6-20 arylthio; and / or two adjacent R1s are connected to each other and together with the benzene ring carbon atom connecting the two R1s form a C3-C6 ring containing one or more O, N, or S heteroatoms; preferably, at least one R1 group is C 1-6 alkoxy, C 1-6 alkylthio, C 6-20 aryloxy, C 6-20 arylthio.

[0012] R2 is C 1-6 alkyl; preferably, the two R2s are the same group.

[0013] R3 is hydrogen, halogen, C 1-6 alkoxycarbonyl; preferably, when R3 is selected from alkoxycarbonyl, the alkyl in the alkoxycarbonyl is the same as R2.

[0014] R4 is selected from C 1-6 alkyl, C 6-20 aryl-C 1-3 alkyl.

[0015] Preferably, in the above reaction formula, m is an integer of 1 or 2; each R1 is the same or different and is independently selected from fluorine, chlorine, bromine, iodine, methyl, ethyl, methoxy, ethoxy, methylthio, phenoxy, phenylthio; and / or two adjacent R1s are connected to each other and together with the benzene ring carbon atom connecting the two R1s form structure; preferably, at least one R1 group is one of methoxy, ethoxy, methylthio, phenoxy, phenylthio.

[0016] R2 is methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl; preferably, the two R2s are the same group.

[0017] R3 is hydrogen, fluorine, chlorine, bromine, iodine, methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, tert-butoxycarbonyl; preferably, when R3 is selected from alkoxycarbonyl, the alkyl group in the alkoxycarbonyl is the same as R2.

[0018] R4 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, benzyl.

[0019] According to the reaction method described above of the present invention, wherein the inorganic base is selected from any one or a mixture of several of Na2HPO4, K2CO3, Na2CO3, and preferably Na2HPO4.

[0020] According to the reaction method described above of the present invention, wherein the electrolyte is selected from one or both of nBu4NBF4 or nBu4NPF6, and preferably nBu4NBF4.

[0021] According to the reaction method described above of the present invention, wherein the organic solvent is selected from one or a mixed solvent of both THF and MeCN, and preferably a mixed solvent of THF / MeCN; most preferably, in the mixed solvent of THF / MeCN, the volume ratio of THF to MeCN is 1:1.

[0022] According to the reaction method described above of the present invention, wherein the feeding ratio of the styrene compound shown in formula 1, the malonic ester compound shown in formula 2, the alcohol compound shown in formula 3, the catalyst Cp2Fe, the inorganic base, the electrolyte is 1 mmol:(2 - 5 mmol):(0.05 - 0.2 mL):(0.01 - 0.1 mmol):(0.2 - 2 mmol):(1 - 3 mmol); preferably 1 mmol:3 mmol:0.1 mL:0.05 mmol):0.5 mmol):2 mmol. The dosage of the organic solvent is not particularly specified, for example, it is 1 mmol / (5 - 20 mL) based on the styrene compound shown in formula 1.

[0023] According to the reaction method described above of the present invention, wherein the constant current is 5 - 10 mA, and preferably 10 mA.

[0024] According to the reaction method described above of the present invention, wherein the certain temperature is from room temperature to 60 °C, and preferably 50 °C.

[0025] According to the reaction method described above of the present invention, wherein the time for the reaction to be complete is 3 - 5 h, and preferably 4 h.

[0026] According to the preparation method described above of the present invention, wherein the post-treatment operation is as follows: the reaction solution is quenched with water, extracted with ethyl acetate, the organic phases are combined, dried and concentrated to obtain a residue, and then separated by silica gel column chromatography to obtain the alkyl malonate compound shown in Formula 4.

[0027] Compared with the prior art, the method of the present invention has the following remarkable advantages:

[0028] (1) Compared with the traditional transition metal-catalyzed difunctionalization reaction strategy, this strategy obtains a series of substrates with medium yields under the conditions of no noble metal and no external oxidant.

[0029] (2) This method has a wide range of substrate adaptability, excellent functional group tolerance and fine site selectivity. Specific Embodiments

[0030] The present invention will be further described in detail below in conjunction with specific embodiments. In the following text, unless otherwise specified, the methods used are conventional methods in the art, and the reagents used are obtained through conventional commercial channels in the art and have not been further purified, dried, etc.

[0031] Raw Material Preparation Example 1 Preparation of Styrene Compounds

[0032]

[0033] Add 20 mL of ultra-dry tetrahydrofuran solution to a 100 mL round-bottom flask, then add 10 mmol of methyltriphenylphosphonium bromide, shake well, seal the reactor, fill it with argon for protection, place the reactor in a 0 °C water bath for cooling, add n-butyllithium dropwise to the reaction solution, activate for 30 minutes, then take 10 mmol of aldehyde diluted with ultra-dry tetrahydrofuran, slowly add it to the reaction solution with a syringe, stir evenly, raise the temperature of the reaction system to room temperature, continue the reaction for 1 h, and detect the progress of the reaction by TLC. After the reaction is completed, add saturated NH4Cl solution to the reaction system to quench the reaction, extract the reaction solution with saturated brine and ethyl acetate 3-4 times, take the upper organic layer and dry it with anhydrous magnesium sulfate, concentrate the reaction solution under reduced pressure, and purify the mixture by column chromatography to obtain the product. The corresponding olefin substrates can all be synthesized and / or commercially obtained from the corresponding aldehydes by this method.

[0034] Example 1

[0035]

[0036] To a 10 mL three-necked flask, p-methoxystyrene 1a (0.2 mmol, 1.0 equiv), diethyl malonate 2a (0.4 mmol, 2.0 equiv), potassium carbonate (0.1 mmol, 0.5 equiv), ferrocene (0.01 mmol, 5 mol%), tetrabutylammonium tetrafluoroborate (nBu4NBF4, 0.4 mmol, 2.0 equiv), 2 mL of tetrahydrofuran, and 2 mL of acetonitrile were added successively. The three-necked flask was used as an electrolytic cell with a platinum electrode (1.0×1.0 cm2) as the cathode and a graphite felt electrode (10×10×3 mm) as the anode under air conditions. The reaction mixture was stirred and electrolyzed at a constant current of 10 mA at 50 °C for 4 h to complete the reaction. After completion, the solution was extracted with ethyl acetate (3×10 mL). The combined organic layers were dried over Na2SO4. After drying, the clear organic liquid was filtered through a short column. The organic solvent was removed by concentration under reduced pressure on a rotary evaporator to obtain the crude product, which was separated and purified by column chromatography (petroleum ether:ethyl acetate = 10:1) to obtain the target product 3aa as a colorless oil. 47.9 mg, 74% yield; colorless liquid; 1 H NMR (500 MHz, CDCl3) δ: 7.22 (d, J = 8.0 Hz, 2H), 6.89 (d, J = 8.0 Hz, 2H), 4.22 - 4.16 (m, 4H), 4.13 - 4.10 (m, 1H), 3.81 (s, 3H), 3.56 (t, J = 7.5 Hz, 1H), 3.16 (s, 3H), 2.33–2.28 (m, 1H), 2.23 - 2.19 (m, 1H), 1.29 - 1.25 (m, 6H). 13 C NMR (126 MHz, CDCl3) δ: 169.55, 169.40, 159.28, 133.08, 127.79, 113.89, 80.92, 61.38, 61.36, 56.53, 55.27, 49.13, 37.08, 14.11, 14.08.

[0037] Example 2 - 24 Reaction Condition Optimization Experiment

[0038] On the basis of Example 1, the reaction variables were replaced, and the remaining operations and parameters were the same as those in Example 1 to explore the effect of different reaction conditions on the yield of the target product 3aa. The results are shown in Table 1:

[0039] Table 1:

[0040]

[0041]

[0042] The implementation results show that the reaction atmosphere has no effect on the reaction. When no current is applied to the reaction system, the reaction cannot proceed, so a constant current is necessary for this reaction. At the same time, when the reaction current is increased or decreased, the reaction yield will decrease to varying degrees. It is worth noting that when the reaction current increases to 15 mA, most of the products are electrolyzed due to the excessive current, so almost no products can be obtained. When the base Na2HPO4 and the catalyst Cp2Fe are removed from the reaction system, the reaction yields both decrease to trace product formation. We found that both the base and the catalyst play a promoting role in the reaction system. The type and amount of the base have more or less an impact on the reaction yield. Organic bases (such as DABCO and triethylamine) have a relatively poor reaction effect on the system, so inorganic bases, including K2CO3, Na2CO3, and Na2HPO3, were selected, and the reaction effects were all good. Among them, Na2HPO4 had the best reaction effect. The adjustment of the amount of the base showed that a 50 mol% dosage had the best reaction effect.

[0043] The electrolyte plays a role in conducting electricity in the reaction. Removing the electrolyte will result in no current in the reaction system, so the electrolyte is crucial for this reaction system. At the same time, the type of the electrolyte has a great impact on the reaction. Using LiCl as the electrolyte has poor conductivity and low yield. When using nBu4NPF6 as the electrolyte, although the reaction effect is better than that of LiCl, it is still not as good as that of nBuNBF4. Through the screening of solvents, using only acetonitrile or only tetrahydrofuran as the solvent, the reaction effects are both not good, and the yields are only about 35%. By changing the solvent ratio, it was found that whether the ratio of acetonitrile to tetrahydrofuran is 1:3 or 3:1, the reaction effect is not as good as that of a 1:1 ratio. The type of electrode will also affect the reaction system. By changing the positive electrode to a graphite rod and the negative electrode to a nickel sheet respectively, the reaction activity will decrease. By changing the reaction time, when the reaction time is extended by 1 hour and shortened by 1 hour, the reaction effect is not as good as that of a 4-hour reaction.

[0044] In summary, the optimal reaction conditions are as follows: 0.2 mmol of p-methoxystyrene (1a), 0.4 mmol of diethyl malonate (2a), 0.1 mL of methanol (3a), 5 mol% of ferrocene, 50 mol% of disodium hydrogen phosphate, 0.5 equivalent of electrolyte nBu4NBF4, the solvent is acetonitrile and tetrahydrofuran with a ratio of 1:1, the reaction temperature is 50 °C, under an air atmosphere, a 10 mA constant current reaction for 4 hours.

[0045] Reaction substrate expansion experiment

[0046] On the basis of obtaining the optimal reaction conditions, the universality of the optimal reaction conditions for different substrates was further explored, and the results are shown in Table 2:

[0047]

[0048] Table 2:

[0049]

[0050]

[0051]

[0052]

[0053] The above results show that under the optimal reaction conditions of the present invention, it has a relatively broad substrate generality, especially for styrene substrates with alkoxy / alkylthio strong electron-donating groups, and medium to good yields of the target products can be obtained.

[0054] Structural characterization of the product:

[0055] Compound 4aaa:

[0056] 47.9 mg, 74% yield; colorless liquid; 1 H NMR (500 MHz, CDCl3) δ: 7.22 (d, J = 8.0 Hz, 2H), 6.89 (d, J = 8.0 Hz, 2H), 4.22 - 4.16 (m, 4H), 4.13 - 4.10 (m, 1H), 3.81 (s, 3H), 3.56 (t, J = 7.5 Hz, 1H), 3.16 (s, 3H), 2.33–2.28 (m, 1H), 2.23 - 2.19 (m, 1H), 1.29 - 1.25 (m, 6H). 13 C NMR (126 MHz, CDCl3) δ: 169.55, 169.40, 159.28, 133.08, 127.79, 113.89, 80.92, 61.38, 61.36, 56.53, 55.27, 49.13, 37.08, 14.11, 14.08.

[0057] Compound 4baa:

[0058] 44.6 mg, 66% yield; colorless liquid; 11H NMR (500 MHz, CDCl3) δ: 6.78 - 6.74 (m, 2H), 6.70 - 6.67 (m, 1H), 4.19 (s, 4H), 4.15 - 4.10 (m, 4H), 3.99 - 3.96 (m, 1H), 3.50 - 3.46 (m, 1H), 3.10 (s, 3H), 2.21 - 2.17 (m, 1H), 2.14 - 2.11 (m, 1H), 1.22 - 1.17 (m, 6H). 13 13C NMR (126 MHz, CDCl3) δ: 169.60, 169.45, 143.63, 143.24, 134.54, 119.71, 117.33, 115.45, 80.91, 64.43, 61.45, 61.43, 56.73, 49.17, 37.13, 14.20, 14.16。

[0059] Compound 4caa:

[0060] 43.0 mg, 60% yield; colorless liquid; 1 1H NMR (500 MHz, CDCl3) δ 7.32 (s, 1H), 7.16 (d, J = 7.5 Hz, 1H), 6.92 (d, J = 8.5 Hz, 1H), 4.22 - 4.18 (m, 4H), 4.11 - 4.08 (m, 1H), 3.90 (s, 3H), 3.56 (t, J = 7.5 Hz, 1H), 3.17 (s, 3H), 2.29 - 2.25 (m, 1H), 2.22 - 2.17 (m, 1H), 1.30 - 1.26 (m, 6H). 13 13C NMR (126 MHz, CDCl3) δ: 169.40, 169.26, 154.60, 134.36, 128.37, 125.96, 122.57, 112.02, 80.43, 61.44, 61.42, 56.74, 56.19, 48.97, 37.04, 14.10, 14.07。

[0061] Compound 4daa:

[0062] 38.2 mg, 59% yield; colorless liquid; 11H NMR (500 MHz, CDCl3) δ: 7.37 (d, J = 7.5 Hz, 1H), 7.27 - 7.23 (m, 1H), 6.98 (t, J = 7.5 Hz, 1H), 6.86 (d, J = 8.0 Hz, 1H), 4.66 - 4.63 (m, 1H), 4.23 - 4.19 (m, 2H), 4.18 - 4.13 (m, 2H), 3.81 (s, 3H), 3.60 (t, J = 7.5 Hz, 1H), 3.22 (s, 3H), 2.29 - 2.26 (m, 1H), 1.29 (t, J = 7.0 Hz, 3H), 1.25 (d, J = 7.0 Hz, 3H). 13 13C NMR (126 MHz, CDCl3) δ: 169.61, 169.57, 156.89, 129.18, 128.44, 126.38, 120.70, 110.22, 75.16, 61.28, 61.22, 56.98, 55.25, 49.19, 35.50, 14.14, 14.08。

[0063] Compound 4eaa:

[0064] 39.4 mg, 51% yield; colorless liquid; 1 1H NMR (500 MHz, CDCl3) δ: 7.36 - 7.32 (m, 2H), 7.27 - 7.25 (m, 2H), 7.11 (t, J = 9.5 Hz, 1H), 7.03 - 6.97 (m, 4H), 4.23 - 4.17, (m, 4H), 3.61 - 3.57 (m, 1H), 3.19 (s, 3H), 2.33 - 2.23 (m, 2H), 1.30 - 1.25 (m, 6H). 13 13C NMR (126 MHz, CDCl3) δ: 169.58, 169.43, 157.15, 157.07, 135.96, 129.85, 128.03, 123.45, 119.08, 118.81, 80.96, 61.49, 61.46, 56.80, 49.16, 37.22, 14.21, 14.16。

[0065] Compound 4faa:

[0066] 46.2 mg, 68% yield; colorless liquid; 11H NMR (500 MHz, CDCl3) δ: 7.16 (t, J = 4.5 Hz, 4H), 4.15 - 4.10 (m, 4H), 4.08 - 4.05 (m, 1H), 3.51 - 3.48 (m, 1H), 3.10 (s, 1H), 2.41 (s, 1H), 2.20 - 2.12 (m, 2H), 2.20 - 2.12 (m, 2H), 1.23 - 1.17 (m, 6H). 13 13C NMR (126 MHz, CDCl3) δ: 169.56, 169.41, 138.10, 138.06, 127.18, 126.74, 81.04, 61.49, 61.47, 56.82, 49.10, 37.11, 15.90, 14.19, 14.15。

[0067] Compound 4gaa:

[0068] 35.2 mg, 50% yield; colorless liquid; 1 1H NMR (500 MHz, CDCl3) δ: 7.53 (d, J = 8.2 Hz, 2H), 7.36 (d, J = 8.1 Hz, 2H), 7.05 (d, J = 8.5 Hz, 2H), 6.79 (d, J = 8.6 Hz, 2H), 3.76 (s, 3H), 3.69 (s, 2H). 13 13C NMR (126 MHz, CDCl3) δ: 157.29, 128.15, 127.52, 124.25, 112.99, 54.17, 31.77, 28.68. 19 19F NMR (470 MHz, CDCl3) δ: -62.69, -88.93。

[0069] Compound 4haa:

[0070] 51.6 mg, 62% yield; colorless liquid; 1 1H NMR (500 MHz, CDCl3) δ: 6.90 (s, 1H), 6.86 (s, 1H), 5.92 - 5.90 (m, 2H), 4.48 - 4.45 (m, 1H), 4.17 - 4.15 (m, 2H), 4.12 - 4.10 (m, 2H), 3.59 - 3.56 (m, 1H), 3.12 (s, 3H), 2.18 - 2.14 (m, 1H), 2.10 - 2.069 (m, 1H), 1.24 - 1.17 (m, 6H). 1313C NMR (126 MHz, CDCl3) δ: 169.47, 169.32, 148.08, 147.92, 133.80, 113.26, 112.62, 107.11, 101.85, 79.82, 61.54, 61.47, 57.04, 49.12, 35.76, 14.23, 14.14。

[0071] Compound 4iaa:

[0072] 47.3 mg, 70% yield; colorless liquid; 1 1H NMR (500 MHz, CDCl3) δ: 7.22 (d, J = 11.0 Hz, 2H), 6.80 (d, J = 11.0 Hz, 2H), 4.11 - 4.05 (m, 2H), 4.04 - 3.95 (m, 2H), 3.73 (s, 1H), 3.36 (t, J = 7.5 Hz, 1H), 2.99 (s, 3H), 2.41 - 2.28 (m, 2H), 1.45 (s, 3H), 1.18 (t, J = 8.0 Hz, 3H), 1.33 (t, J = 9.0 Hz, 3H). 13 13C NMR (126 MHz, CDCl3) δ: 170.06, 169.80, 158.63, 136.03, 127.51, 113.58, 77.76, 61.39, 55.30, 50.33, 48.06, 41.28, 23.50, 14.12, 14.05。

[0073] Compound 4aba:

[0074] 50.8 mg, 74% yield; colorless liquid; 1 1H NMR (500 MHz, CDCl3) δ:

[0075] 7.21 (d, J = 8.5 Hz, 2H), 6.89 (d, J = 8.5 Hz, 2H), 4.12 - 4.09 (m, 1H), 3.81 (s, 3H), 3.74 (d, J = 8.5 Hz, 6H), 3.61 (t, J = 7.5 Hz, 1H), 3.15 (s, 3H), 2.34 - 2.29 (m, 1H), 2.24 - 2.22 (m, 1H). 13 13C NMR (126 MHz, CDCl3) δ: 169.97, 169.79, 159.31, 132.95, 127.79, 113.91, 80.89, 56.58, 55.29, 52.56, 52.54, 48.78, 37.17。

[0076] Compound 4aca:

[0077] 34.6 mg, 54% yield; colorless liquid; 1H NMR (500 MHz, CDCl3) δ: 7.22 (d, J = 8.0 Hz, 2H), 6.89 (d, J = 8.5 Hz, 2H), 5.06 (d, J = 6.5 Hz, 2H), 4.12 - 4.09 (m, 1H), 3.81 (s, 3H), 3.48 (t, J = 7.5 Hz, 1H), 3.16 (s, 3H), 2.32 - 2.26 (m, 1H), 2.20 - 2.14 (m, 1H), 1.24 (d, J = 5.3 Hz, 12H). 13C NMR (126 MHz, CDCl3) δ: 169.04, 168.20, 133.22, 127.78, 113.88, 80.95, 69.17, 68.71, 56.54, 55.27, 49.80, 49.51, 36.96, 21.65, 21.61。

[0078] Compound 4ada:

[0079] 32.1 mg, 47% yield; colorless liquid; 1 1H NMR (500 MHz, CDCl3) δ: 7.23 (d, J = 8.5 Hz, 2H), 6.89 (d, J = 8.0 Hz, 2H), 4.34 - 4.29 (m, 2H), 4.24 - 4.20 (m, 2H), 3.81 (s, 3H), 3.10 (s, 3H), 2.81–2.71 (m, 1H), 2.33–2.28 (m, 1H), 1.35 (d, J = 6.5 Hz, 3H), 1.28 (d, J = 7.5 Hz, 3H). 13 13C NMR (126 MHz, CDCl3) δ: 166.30, 166.16, 159.41, 132.60, 127.82, 113.92, 62.63, 62.23, 56.29, 55.27, 42.85, 42.68, 14.02, 13.88. 19 19F NMR (470 MHz, CDCl3) δ: -166.85。

[0080] Compound 4aea:

[0081] 60.2 mg, 76% yield; colorless liquid; 11H NMR (500 MHz, CDCl3) δ: 7.26 (d, J = 8.5 Hz, 2H), 6.88 (d, J = 8.5 Hz, 2H), 4.62 - 4.59 (m, 1H), 4.27 - 4.22 (m, 6H), 3.81 (s, 3H), 3.08 (s, 3H), 2.60 - 255 (m, 1H), 2.46 - 42 (m, 1H), 1.29 (t, J = 7.0 Hz, 9H). 13 13C NMR (126 MHz, CDCl3) δ: 166.84, 159.16, 133.94, 127.78, 113.79, 79.07, 63.65, 61.94, 56.42, 55.27, 41.83, 13.94。

[0082] Compound 4aab:

[0083] 43.9 mg, 65% yield; colorless liquid; 1 1H NMR (500 MHz, CDCl3) δ: 7.22 (d, J = 8.0 Hz, 2H), 6.88 (d, J = 8.0 Hz, 2H), 4.23 - 4.18 (m, 5H), 3.80 (s, 3H), 3.59 (t, J = 7.0 Hz, 1H), 3.38 - 3.32 (m, 1H), 3.27 - 3.21 (m, 1H), 2.32 - 2.27 (m, 1H), 2.23 - 2.17 (m, 1H), 1.29 - 1.25 (m, 6H), 1.13 (t, J = 7.0 Hz, 3H). 13 13C NMR (126 MHz, CDCl3) δ: 169.51, 169.40, 159.11, 133.85, 127.60, 113.79, 78.87, 64.04, 61.28, 55.22, 49.16, 37.19, 15.11, 14.08, 14.04。

[0084] Compound 4aac:

[0085] 35.9 mg, 51% yield; colorless liquid; 11H NMR (400 MHz, CDCl3) δ: 7.24 (d, J = 7.2 Hz, 2H), 6.87 (d, J = 7.2 Hz, 2H), 4.36 - 4.33 (m, 1H), 4.23 - 4.20 (m, 2H), 4.19 - 4.16 (m, 2H) 3.80 (s, 3H), 3.65 - 3.62 (m, 1H), 3.45–3.40 (m, 1H), 2.23 - 2.17 (m, 2H), 1.29 (t, J = 5.6 Hz, 3H), 1.26 (t, J = 5.6 Hz, 3H) 1.09 (d, J = 4.8 Hz, 3H), 1.04 (d, J = 5.2 Hz, 3H). 13 13C NMR (126 MHz, CDCl3) δ: 169.50, 169.40, 159.00, 134.66, 127.53, 113.69, 75.77, 68.60, 61.23, 61.20, 55.17, 49.06, 37.60, 23.33, 20.84, 14.05, 14.01。

[0086] Compound 4aad:

[0087] 40.3 mg, 55% yield; colorless liquid; 1 1H NMR (400 MHz, CDCl3) δ: 7.22 (d, J = 6.8 Hz, 2H), 6.88 (d, J = 6.8 Hz, 2H), 4.22 (d, J = 2.0 Hz, 1H), 4.22 - 4.20 (m, 2H), 4.19 - 4.16 (m, 2H), 3.80 (s, 3H), 3.63 - 3.60 (m, 1H), 3.31 - 3.26 (m, 1H), 3.19 - 3.14 (m, 1H), 2.32 - 2.26 (m, 1H), 2.23 - 2.17 (m, 1H), 1.52 - 1.46 (m, 2H), 1.36 - 1.31 (m, 2H), 1.28 (t, J = 3.2 Hz, 3H), 1.26 (t, J = 5.6 Hz, 3H), 0.87 (t, J = 7.5 Hz, 3H). 13 13C NMR (126 MHz, CDCl3) δ: 169.46, 169.36, 159.07, 133.89, 127.56, 113.73, 78.96, 68.46, 61.22, 61.20, 55.15, 49.05, 37.28, 31.79, 19.28, 14.04, 13.98, 13.81。

[0088] Compound 4aae:

[0089] 30.7 mg, 42% yield; colorless liquid;1 1H NMR (400 MHz, CDCl3) δ: 7.25 (d, J = 6.8 Hz, 2H), 6.84 (d, J = 6.8 Hz, 2H), 4.52 - 4.49 (m, 1H), 4.23–4.19 (m, 2H), 4.17–4.15 (m, 2H) 3.79 (s, 3H), 3.55 - 3.52 (m, 1H), 2.17 - 2.12 (m, 2H), 1.28 (t, J = 5.6 Hz, 3H), 1.25 (t, J = 5.6 Hz, 3H), 1.07 (s, 9H). 13 13C NMR (126 MHz, CDCl3) δ: 169.64, 169.51, 158.56, 137.63, 127.09, 113.54, 74.29, 71.30, 61.29, 61.23, 55.19, 49.02, 38.82, 28.57, 14.08, 14.05。

[0090] Compound 4aaf:

[0091] 37.6 mg, 47% yield; colorless liquid; 1 1H NMR (400 MHz, CDCl3) δ: 7.32 (t, J = 6.0 Hz, 2H), 7.28 - 7.25 (m, 5H), 6.91 (d, J = 6.8 Hz, 2H), 4.40 (d, J = 9.2 Hz, 1H), 4.35 - 4.32 (m, 1H), 4.18 (d, J = 9.2 Hz, 1H), 4.16 - 4.13 (m, 2H), 4.13 - 4.09 (m, 2H), 3.82 (s, 3H), 3.65 - 3.62 (m, 1H), 2.40 - 2.34 (m, 1H), 2.27 - 2.22 (m, 1H), 1.24 (t, J = 2.0 Hz, 3H), 1.22 (t, J = 5.6 Hz, 3H). 13 13C NMR (126 MHz, CDCl3) δ: 169.50, 169.33, 159.36, 138.26, 133.25, 128.30, 127.95, 127.89, 127.54, 113.99, 78.35, 70.36, 61.36, 61.32, 55.30, 49.12, 37.24, 14.09, 14.04。

[0092] The above - described embodiments are only the preferred embodiments of the present invention and not an exhaustive list of all feasible embodiments of the present invention. For those skilled in the art, any obvious modifications made without departing from the principle and spirit of the present invention should be considered to be included within the scope of the claims of the present invention.

Claims

1. A method for the three-component reaction of an electrocatalytic olefin with a 1,3-dicarbonyl compound and an alcohol, comprising the following steps: Into an electrolytic reactor equipped with a platinum cathode and a graphite felt anode, a styrene compound represented by Formula 1, a malonate compound represented by Formula 2, and an alcohol compound represented by Formula 3 are added in sequence, and then a catalyst Cp2Fe, an inorganic base, an electrolyte, and an organic solvent are added, the reactor is placed at a certain temperature, a constant current is passed through to stir and electrolyze until the reaction is complete, and after the reaction is complete, an alkyl malonate compound represented by Formula 4 is obtained by post-treatment; The reaction formula is as follows: In the above reaction formula, m=an integer of 1, 2, 3, 4, or 5; each R1 is the same or different and is independently selected from halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 6-20 Aryloxy, C 6-20 and / or two adjacent R1 groups are connected to each other and together with the carbon atoms of the benzene ring connecting the two R1 groups form a C3-C6 ring containing one or more heteroatoms of O, N, and S; preferably, at least one R1 group is C 1-6 Alkoxy, C 1-6 Alkylthio, C 6-20 Aryloxy, C 6-20 One of the arylthio groups; R2 is C 1-6 Alkyl; preferably, two R2 are the same group; R3 is hydrogen, halogen, C 1-6 Alkoxycarbonyl; preferably, when R3 is selected from alkoxycarbonyl, the alkyl group in the alkoxycarbonyl is the same as R2; R4 is selected from C 1-6 Alkyl, C 6-20 Aryl-C 1-3 alkyl; in, The inorganic base is selected from any one of Na2HPO4, K2CO3, and Na2CO3, or a mixture of several thereof; the electrolyte is selected from one or both of nBu4NBF4 and nBu4NPF6; and the organic solvent is selected from one of THF and MeCN, or a mixed solvent of the two.

2. The method according to claim 1, characterized in that m=an integer of 1 or 2; each R1 is the same or different and is independently selected from fluorine, chlorine, bromine, iodine, methyl, ethyl, methoxy, ethoxy, methylthio, phenoxy, and phenylthio; and / or two adjacent R1s are connected to each other and together with the carbon atom of the benzene ring connecting the two R1s form a Structure; preferably, at least one R1 group is one of methoxy, ethoxy, methylthio, phenoxy, and phenylthio; R2 is methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl; preferably, two R2 are the same group; R3 is hydrogen, fluorine, chlorine, bromine, iodine, methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, tert-butoxycarbonyl; preferably, when R3 is selected from alkoxycarbonyl, the alkyl group in the alkoxycarbonyl is the same as R2. R4 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, benzyl.

3. The method according to claim 1 or 2, characterized in that: The inorganic base is selected from Na2HPO4.

4. The method according to claim 1 or 2, characterized in that: The electrolyte is selected from nBu4NBF4.

5. The method according to claim 1 or 2, characterized in that: The organic solvent is selected from a mixed solvent of THF / MeCN; preferably, in the mixed solvent of THF / MeCN, the volume ratio of THF to MeCN is 1:

1.

6. The method according to claim 1 or 2, characterized in that: The feed ratio of the styrene compound shown in Formula 1, the malonic ester compound shown in Formula 2, the alcohol compound shown in Formula 3, the catalyst Cp2Fe, the inorganic base, and the electrolyte is 1mmol: (2~5mmol): (0.05~0.2mL): (0.01~0.1mmol): (0.2~2mmol): (1~3mmol); preferably 1mmol: 3mmol: 0.1mL: 0.05mmol): 0.5mmol): 2mmol.

7. The method according to claim 1 or 2, characterized in that: The constant current is 5-10 mA, preferably 10 mA.

8. The method according to claim 1 or 2, characterized in that: The certain temperature is room temperature to 60°C, preferably 50°C.

9. The method according to claim 1 or 2, characterized in that: The time required for the reaction to be complete is 3 to 5 hours, preferably 4 hours.

10. The method according to claim 1 or 2, characterized in that: The post-treatment operation is as follows: the reaction solution is quenched with water, extracted with ethyl acetate, the organic phases are combined, dried and concentrated to obtain a residue, and then separated by silica gel column chromatography to obtain the alkyl malonate compound shown in formula 4.

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