Method for preparing polysubstituted allene carboxylic acid methyl ester compound based on CO2 and photocatalysis

Abstract

The invention belongs to the technical field of catalytic methods and catalysts, and particularly relates to a method for preparing a polysubstituted allene carboxylic acid methyl ester compound based on CO2 and photocatalysis, which is based on a photocatalytic reaction system, takes CO2 as a carboxyl source, and is prepared through a 1, 3-enyne 1, 3-polysubstituted allene carboxylic acid methyl ester compound under the mild conditions of no photocatalyst and metal, so that the polysubstituted allene carboxylic acid methyl ester compound is obtained. According to the present invention, the efficient synthesis of the polysubstituted allene carboxylic acid derivative is achieved through the 1, 4-alkane carboxylation reaction, the method has advantages of good yield, wide substrate universality, suitableness for the reaction of a variety of functional groups, non-toxicity of the used reagent, and wide application prospect.

Description

Technical Field

[0001] The present invention belongs to the technical field of catalytic methods and catalysts, and particularly relates to a method for preparing multi-substituted methyl allenoates based on CO2 and photocatalysis. Background Art

[0002] Allenes are a class of unsaturated compounds with cumulated double bonds and special structures, which are widely distributed in natural products and active molecules. By modifying the substituents at the terminal of allenes, allenes can exhibit various reaction activities and chemical, regio- and stereoselectivities. And due to their unique sp 2 structure, allenes are also important synthons in chemical reactions. Developing new methods for synthesizing functionalized allene compounds is of great significance for the fields of organic synthesis, pharmacy, and biochemistry. Allenecarboxylic acid is a class of organic compounds containing an allene structure (two carbon-carbon double bonds directly connected) and a carboxyl group (-COOH). Due to the presence of the carboxyl group, it has acidity and can undergo a neutralization reaction with a base to form the corresponding carboxylate. The double bonds in the allene structure have a relatively high electron cloud density and can undergo an addition reaction with an electrophilic reagent. Allenecarboxylic acid can be oxidized, and its oxidation products depend on the type of oxidant and reaction conditions. For example, it can be oxidized to the corresponding aldehyde or ketone with a mild oxidant, while a strong oxidant may cause the cleavage of the carbon-carbon double bond to form products such as carboxylic acid or carbon dioxide. Under certain conditions, allenecarboxylic acid can undergo a polymerization reaction to form a high molecular polymer. This polymer may have special properties such as optical properties and thermal stability, and has potential application value in the field of materials science. Among various compounds containing allene fragments, allenecarboxylic acid is the core functional group in many natural products and active molecules, and has good reaction activity. As an organic synthesis intermediate, it can be further transformed into a variety of downstream products.

[0003] The existing methods for synthesizing allenecarboxylic acid mainly include: (1) synthesizing allenecarboxylic acid by hydrolyzing 2,3-enoates; (2) oxidizing allene alcohols; (3) synthesizing allenecarboxylic acid through transition metal-catalyzed carbonylation reactions; (4) synthesizing allenecarboxylic acid compounds by capturing carbon dioxide with allene metal reagents. Although there have been quite a number of reports on the methods for synthesizing allenecarboxylic acid, the above methods have problems of low selectivity and conversion rate, and usually require the use of metal catalysts and toxic reagent carbon monoxide. There is room for improvement in terms of cost, safety, or environmental protection.

[0004]

[0005] In the research group where the inventors are located, in the early stage, using 1,3-enynes and iodides as raw materials, potassium formate as the formate source, DABCO as the hydrogen transfer catalyst, Ir(bpy)2(dtbpy)PF6 as the photocatalyst, cesium carbonate as the base, and introducing CO2 under atmospheric pressure, allenic dicarboxylic acid compounds can be obtained in excellent to good yields under visible light irradiation at room temperature for 24 hours (see invention patent CN119191924B). However, in the above reaction, the iodides used generally have certain toxicity and may have adverse effects on the human body.

[0006] On the basis of the above research, with the goal of reducing toxicity, the inventors have developed a method for preparing polysubstituted methyl allenoates based on CO2 and photocatalysis. In this method, through a photocatalytic reaction system, without the need for transition metal catalysis, carbon dioxide is used as the carboxyl source to synthesize polysubstituted allenoic acid derivatives, significantly improving the conversion rate and selectivity of polysubstituted allenoic acids, developing a green and environmentally friendly preparation method, reducing pollution, and improving the efficiency of the catalytic reaction and the preparation efficiency of polysubstituted allenoic acids. Summary of the Invention

[0007] The technical problem to be solved by the present invention is: to provide a synthetic method for synthesizing polysubstituted allenoic acids based on CO2 to solve the technical problems of limited reaction sites, weak chemoselectivity, and strict reaction conditions in the synthesis reaction of allenoic acids.

[0008] To achieve the above object, the technical solution adopted by the present invention is: to provide a method for preparing polysubstituted methyl allenoates based on CO2 and photocatalysis, and the reaction formula of the method is as follows:

[0009] Among them, R 1 is tert-butyl; R 2 is any one of phenyl, 4-methoxyphenyl, 2-methoxyphenyl, 4-chlorophenyl, 4-methylphenyl; R 3 is any one of isopropyl, cyclohexyl, cyclopentyl; The specific reaction steps are as follows: (1) Under an argon atmosphere, add a 1,3-enyne compound, a 1,4-dihydropyridine compound, and a base to a Schlenk reaction tube, add a solvent, and introduce carbon dioxide gas; (2) Place the reaction at room temperature and stir under visible light until the 1,3-enyne compound, 1,4-dihydropyridine compound, and base added in step (1) disappear; (3) After the reaction is completed, acidify the reaction solution, extract the aqueous phase, combine the organic phases, wash, dry, and concentrate under reduced pressure to obtain a concentrated solution; (4) Dissolve the concentrated solution obtained in step (3) in a mixed solution of dichloromethane and methanol, add a methylation reagent, and react at room temperature. After the reaction is completed, concentrate the organic phase under reduced pressure and filter to obtain the target product.

[0010] Preferably, the base described in step (1) is one or more of carbonate, formate, organometallic salt or alkoxy base.

[0011] Preferably, the carbonate is Cs2CO3, the formate is HCO2Li, the organometallic salt is CH3OLi, and the alkoxy base is KO t Bu, NaO t Bu or LiO t One or more of Bu.

[0012] Preferably, the solvent described in step (1) is dimethyl sulfoxide, N , N - dimethylformamide, N-methyl-2-pyrrolidone, acetonitrile, or one or more of them.

[0013] Preferably, the solvent described in step (1) is dimethyl sulfoxide, N , N - dimethylformamide or one or more of N-methyl-2-pyrrolidone.

[0014] Preferably, the visible light described in step (2) is 430-460 nm blue light.

[0015] Preferably, the room temperature described in step (2) is 25-30 °C.

[0016] Preferably, the acidified reaction solution in step (3) uses a dilute hydrochloric acid solution, extraction uses ethyl acetate, and washing uses saturated brine.

[0017] Preferably, the ratio of dichloromethane to methanol in step (4) is 4:1, and the methylation reagent is trimethylsilyldiazomethane.

[0018] The beneficial effects of the present invention are as follows: The present invention provides a method for preparing polysubstituted allenoic acid methyl esters based on CO2 and photocatalysis. This method is based on a photocatalytic reaction system and uses CO2 as the carboxyl source. Under mild conditions without a photocatalyst and metal, the efficient synthesis of polysubstituted allenoic acid derivatives is achieved through the 1,4-alkarboxylation reaction of 1,3-enynes. This method has good yields, broad substrate generality, and various functional groups are applicable to this reaction. Moreover, the reagents used are non-toxic, showing broad application prospects. Specific Embodiments

[0019] The protection scope of the present invention will be further described below through specific embodiments. However, it should not be understood that the scope of the above-mentioned subject matter of the present invention is limited to the following embodiments. All technologies implemented based on the above content of the present invention belong to the scope of the present invention.

[0020] It should be noted that in the following embodiments, unless otherwise specified, the methods are all conventional methods, and the reagents can all be obtained through commercial channels.

[0021] In the following embodiments, the chemical name of 3DPAFIPN is 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile. It is a halogenated dicyanophenyl photosensitizer and also a novel donor-acceptor (D-A) based on halogenated cyanoolefins. As a photocatalyst, it can induce single electron transfer (SET) under visible light irradiation and can be applied to various organic synthesis reactions, such as the photosynthesis of multifunctionalized dihydro-2-oxopyrrole, the cross double deoxygenation carbon-carbon bond coupling reaction between benzyl benzoate and allyl alcohol, etc., providing an efficient, energy-saving and environmentally friendly green method for organic synthesis.

[0022] In the following embodiments, Ir[(ppy)2(dtbbpy)]PF6 is an important cationic iridium(III) complex, which is widely used in organic optoelectronic materials (such as OLED, photocatalysis, bioimaging) and photochemical research (such as photosensitization, photoredox catalysis).

[0023] In the following embodiments, Ir[(dF(CF3)ppy)2(dtbbpy)]PF6 is an iridium(III) complex modified by fluorine atoms and trifluoromethyl groups, belonging to cationic phosphorescent materials. It has more advantages than traditional Ir(ppy)3 derivatives in terms of photophysical properties, stability and application scope, and is particularly outstanding in the fields of deep red light / near-infrared luminescence, photocatalysis and bioimaging.

[0024] In the following embodiments, 4CzIPN is a typical thermally activated delayed fluorescence (TADF) material, which realizes efficient reverse intersystem crossing (RISC) through the strong donor-acceptor (D-A) structure of carbazole (Cz) and cyano (CN).

[0025] In the following embodiments, the Schlenk reaction tube is a laboratory glass instrument designed specifically for anhydrous and anaerobic operations, and is widely used in chemical reactions sensitive to air / moisture (such as organometallic synthesis, transition metal catalysis, free radical reactions, etc.).

[0026] Example 1

[0027] Under an argon atmosphere, (4,4-dimethyl-3-methylidenepent-1-ynyl)benzene 1a (0.3 mmol), ethyl 5-(ethoxycarbonyl)-2,6-dimethyl-4-(propan-2-yl)-1,4-dihydropyridine-3-carboxylate 2a (0.2 mmol), and cesium carbonate (0.6 mmol) were added to a dry 10 mL Schlenk reaction tube. 3 mL of dimethyl sulfoxide was added, and then the carbon dioxide gas was displaced three times. The reaction was stirred at room temperature under a 12 W 460 nm LED blue light until the raw materials disappeared. After the reaction was completed, the reaction solution was acidified with dilute hydrochloric acid, and the aqueous phase was extracted with ethyl acetate 5 times. The organic phases were combined, washed with saturated brine 3 times, and dried over anhydrous Na2SO4. Then the organic phase was concentrated under reduced pressure. Subsequently, the organic phase was dissolved in a 5 mL mixed solution of dichloromethane and methanol (dichloromethane:methanol = 4:1), and trimethylsilyldiazomethane (0.4 mmol) was added. The reaction was carried out at room temperature for 1 hour. After the reaction was completed, the organic phase was concentrated under reduced pressure and filtered through a silica gel column (PE:EA = 100:1 - 60:1) to obtain the target product 3aa.

[0028]

[0029] The product detection data are as follows: Colorless oil, yield 81%.

[0030] 1 H NMR (400 MHz, CDCl3) δ 7.53 – 7.51 (m, 2H), 7.34 – 7.30 (m, 2H),7.25 – 7.21 (m, 1H), 3.77 (s, 3H), 2.09 – 1.94 (m, 2H), 1.77 – 1.70 (m, 1H),1.15 (s, 9H), 0.92 (d, J = 6.4 Hz, 3H), 0.86 (d, J = 6.8 Hz, 3H) 13 C NMR (100 MHz, CDCl3) δ 208.8, 167.6, 133.9, 128.1, 127.9, 127.0,118.1, 104.3, 51.9, 37.1, 35.2, 29.0, 27.1, 23.0, 22.5. Example 2 Under an argon atmosphere, 1-(4,4-dimethyl-3-methylidenepent-1-ynyl)-4-phenylbenzene 1b (0.3 mmol), ethyl 5-(ethoxycarbonyl)-2,6-dimethyl-4-(propan-2-yl)-1,4-dihydropyridine-3-carboxylate 2a (0.2 mmol), and cesium carbonate (0.6 mmol) were added to a dry 10 mL Schlenk reaction tube. 3 mL of dimethyl sulfoxide was added, and then the carbon dioxide gas was displaced three times. The reaction was stirred at room temperature under a 12 W 460 nm LED blue light until the raw materials disappeared. After the reaction was completed, the reaction solution was acidified with dilute hydrochloric acid, and the aqueous phase was extracted with ethyl acetate 5 times. The organic phases were combined, washed with saturated brine 3 times, and dried over anhydrous Na2SO4. Then the organic phase was concentrated under reduced pressure. Subsequently, the organic phase was dissolved in a 5 mL mixed solution of dichloromethane and methanol (dichloromethane:methanol = 4:1), and trimethylsilyldiazomethane (0.4 mmol) was added. The reaction was carried out at room temperature for 1 hour. After the reaction was completed, the organic phase was concentrated under reduced pressure and filtered through a silica gel column (PE:EA = 100:1 - 60:1) to obtain the target product 3ba.

[0031]

[0032] The detection data of the product are as follows: Colorless solid, yield 65%.

[0033] 1 H NMR (400 MHz, CDCl3) δ 7.65 – 7.58 (m, 6H), 7.47 – 7.43 (m, 2H),7.35 (t, J J = 7.6 Hz, 1H), 3.82 (s, 3H), 2.15 – 1.98 (m, 2H), 1.82 – 1.75 (m,1H), 1.20 (s, 9H), 0.97 (d, J J = 6.4 Hz, 3H), 0.91 (d, J J = 6.4 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 208.8, 167.6, 140.8, 139.8, 132.9, 128.7,128.2, 127.2, 127.0, 126.9, 118.3, 104.0, 51.9, 37.1, 35.2, 29.0, 27.2, 23.1,22.5. Example 3 Under an argon atmosphere, 1-(4,4-dimethyl-3-methylidenepent-1-ynyl)-2-methoxybenzene 1c (0.3 mmol), ethyl 5-(ethoxycarbonyl)-2,6-dimethyl-4-(propan-2-yl)-1,4-dihydropyridine-3-carboxylate 2a (0.2 mmol), and cesium carbonate (0.6 mmol) were added to a dry 10 mL Schlenk reaction tube. 3 mL of dimethyl sulfoxide was added, and then the carbon dioxide gas was displaced three times. The reaction was stirred at room temperature under a 12 W 460 nm LED blue light until the raw materials disappeared. After the reaction was completed, the reaction solution was acidified with dilute hydrochloric acid, and the aqueous phase was extracted with ethyl acetate 5 times. The combined organic phases were washed with saturated brine 3 times, and the organic phase was dried over anhydrous Na2SO4. Then the organic phase was concentrated under reduced pressure. Subsequently, the organic phase was dissolved in a 5 mL mixed solution of dichloromethane and methanol (dichloromethane:methanol = 4:1), and trimethylsilyldiazomethane (0.4 mmol) was added. The reaction was carried out at room temperature for 1 hour. After the reaction was completed, the organic phase was concentrated under reduced pressure and filtered through a silica gel column (PE:EA = 100:1 - 60:1) to obtain the target product 3ca.

[0034]

[0035] The detection data of the product are as follows: Colorless oil, yield 67%.

[0036] 1 H NMR (400 MHz, CDCl3) δ 7.28 – 7.24 (m, 1H), 7.21 – 7.19 (m, 1H),6.94 – 6.88 (m, 2H), 3.78 (s, 3H), 3.72 (s, 3H), 1.96 (d, J = 7.2 Hz, 2H), 1.89– 1.79 (m, 1H), 1.12 (s, 9H), 0.94 (d, J = 6.4 Hz, 3H), 0.85 (d, J = 6.4 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 207.8, 167.8, 157.1, 130.5, 128.9, 124.4,120.4, 116.5, 111.0, 101.7, 55.6, 51.9, 37.0, 34.7, 28.9, 26.9, 23.0, 22.5. Example 4 Under an argon atmosphere, (4,4-dimethyl-3-methylidenepent-1-ynyl)benzene 1a (0.3 mmol), ethyl 4-(butan-2-yl)-5-(ethoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine-3-carboxylate 2b (0.2 mmol), and cesium carbonate (0.6 mmol) were added to a dry 10 mL Schlenk reaction tube. 3 mL of dimethyl sulfoxide was added, and then the carbon dioxide gas was displaced three times. The reaction was stirred at room temperature under a 12 W 460 nm LED blue light until the raw materials disappeared. After the reaction was completed, the reaction solution was acidified with dilute hydrochloric acid, and the aqueous phase was extracted with ethyl acetate 5 times. After combining the organic phases, the organic phase was washed with saturated brine 3 times and dried over anhydrous Na2SO4. Subsequently, the organic phase was concentrated under reduced pressure. Then the organic phase was dissolved in a 5 mL mixed solution of dichloromethane and methanol (dichloromethane:methanol = 4:1), and trimethylsilyldiazomethane (0.4 mmol) was added. The reaction was carried out at room temperature for 1 hour. After the reaction was completed, the organic phase was concentrated under reduced pressure and filtered through a silica gel column (PE:EA = 100:1 - 60:1) to obtain the target product 3ab.

[0037]

[0038] The product detection data are as follows: Colorless oil, yield 61%, d.r. = 1:1.1.

[0039] 1 H NMR (400 MHz, CDCl3) δ 7.54 – 7.43 (m, 2H), 7.26 – 7.22 (m, 2H),7.17 – 7.14 (m, 1H), 3.70 (s, 3H), 2.12 – 1.79 (m, 2H), 1.45 – 1.39 (m, 2H),1.08 (s, 9H), 0.83 – 0.68 (m, 7H). 13 C NMR (100 MHz, CDCl3) δ 208.77, 208.72, 167.61, 167.56, 134.00,133.90, 128.09, 128.01, 127.89, 127.89, 127.0, 118.08, 118.05, 51.9, 35.20,35.14, 33.55, 33.53, 29.77, 29.36, 29.33, 29.01, 28.98, 19.55, 19.23, 11.46,11.36. Example 5 Under an argon atmosphere, (4,4-dimethyl-3-methylidenepent-1-ynyl)benzene 1a (0.3 mmol), ethyl 5-(ethoxycarbonyl)-4-(hexan-2-yl)-2,6-dimethyl-1,4-dihydropyridine-3-carboxylate 2c (0.2 mmol), and cesium carbonate (0.6 mmol) were added to a dry 10 mL Schlenk reaction tube. 3 mL of dimethyl sulfoxide was added, and then the carbon dioxide gas was replaced three times. The reaction was stirred at room temperature under a 12 W 460 nm LED blue light until the raw materials disappeared. After the reaction was completed, the reaction solution was acidified with dilute hydrochloric acid, and the aqueous phase was extracted with ethyl acetate 5 times. The combined organic phases were washed with saturated brine 3 times, and the organic phase was dried over anhydrous Na2SO4. Then the organic phase was concentrated under reduced pressure. Subsequently, the organic phase was dissolved in a 5 mL mixed solution of dichloromethane and methanol (dichloromethane:methanol = 4:1), and trimethylsilyldiazomethane (0.4 mmol) was added. The reaction was carried out at room temperature for 1 hour. After the reaction was completed, the organic phase was concentrated under reduced pressure and filtered through a silica gel column (PE:EA = 100:1 - 60:1) to obtain the target product 3ac.

[0040]

[0041] The product detection data is as follows: Colorless oil, yield 50%, d.r. = 1:1.1.

[0042] 1 H NMR (400 MHz, CDCl3) δ 7.45 – 7.43 (m, 2H), 7.26 – 7.22 (m, 2H),7.17 – 7.15 (m, 1H), 3.70 (s, 3H), 2.05 – 1.92 (m, 2H), 1.13 – 1.07 (m, 13H),0.80 – 0.66 (m, 7H). 1313C NMR (100 MHz, CDCl3) δ 208.77, 208.69, 167.60, 167.57, 133.99,133.97, 128.1, 127.9, 126.9, 118.28, 118.20, 104.38, 104.25, 51.8, 38.15,38.08, 35.27, 35.25, 33.13, 32.92, 32.35, 32.29, 29.36, 29.28, 29.08, 29.05,26.23, 26.15, 23.15, 23.01, 14.16, 14.06, 10.90, 10.86. Example VI Under an argon atmosphere, (4,4-dimethyl-3-methylidenepent-1-ynyl)benzene 1a (0.3 mmol), ethyl 4-cyclohexyl-5-(ethoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine-3-carboxylate 2d (0.2 mmol), and cesium carbonate (0.6 mmol) were added to a dry 10 mL Schlenk reaction tube. 3 mL of dimethyl sulfoxide was added, and then the carbon dioxide gas was replaced three times. The reaction was stirred at room temperature under a 12 W 460 nm LED blue light until the raw materials disappeared. After the reaction was completed, the reaction solution was acidified with dilute hydrochloric acid, and the aqueous phase was extracted with ethyl acetate 5 times. The combined organic phases were washed with saturated brine 3 times, and the organic phase was dried over anhydrous Na2SO4. Subsequently, the organic phase was concentrated under reduced pressure. Then the organic phase was dissolved in a 5 mL mixed solution of dichloromethane and methanol (dichloromethane:methanol = 4:1), and trimethylsilyldiazomethane (0.4 mmol) was added. The reaction was carried out at room temperature for 1 hour. After the reaction was completed, the organic phase was concentrated under reduced pressure and filtered through a silica gel column (PE:EA = 100:1 - 60:1) to obtain the target product 3ad.

[0043]

[0044] The product detection data are as follows: Colorless oil, yield 77%.

[0045] 11H NMR (400 MHz, CDCl3) δ 7.44 – 7.42 (m, 2H), 7.27 – 7.22 (m, 2H), 7.18 – 7.14 (m, 1H), 3.69 (s, 3H), 1.99 – 1.86 (m, 2H), 1.81 – 1.76 (m, 2H), 1.58 – 1.49 (m, 4H), 1.35 – 1.27 (m, 1H), 1.11 – 1.02 (m, 12H), 0.83 – 0.76 (m, 2H). 13 13C NMR (100 MHz, CDCl3) δ 208.7, 167.6, 134.0, 128.1, 127.9, 127.0, 117.6, 104.3, 51.8, 36.9, 35.4, 35.1, 33.6, 33.4, 28.9, 26.5, 26.2, 26.1. Application Example 1 According to the reaction formula described in Example 1, by replacing the photocatalyst, base, solvent in the reaction formula, and whether there is light irradiation, the changes in the product yield caused by different condition changes were statistically analyzed. The specific results are shown in Table 1 below.

[0046]

[0047] Table 1 Screening of Reaction Conditions

[0048] Note: PC1 = 4CzIPN, PC2 = Ir[(ppy)2dtbbpy]PF6, PC3 = Ir[(dF(CF3)ppy)2dtbbpy]PF6, PC4 = 3DPAFIPN a Without light irradiation.

[0049] As can be seen from the data results in Table 1, under the optimal reaction conditions of the present invention, the separation yield is as high as 81%; when different bases are replaced, the yield decreases, and strong bases have better effects than weak bases, and light irradiation and base play an indispensable role in the reaction.

[0050] In summary, the present invention provides a method for preparing polysubstituted methyl allenoates based on CO2 and photocatalysis. This method is based on a photocatalytic reaction system, uses CO2 as the carboxyl source, and under mild conditions without a photocatalyst or metal, efficiently synthesizes polysubstituted allenoic acid derivatives through the 1,4-alkoxycarbonylation reaction of 1,3-enynes. This method has good yields, broad substrate generality, is applicable to a variety of functional groups, and the reagents used are non-toxic, thus having broad application prospects.

Claims

1. A method for preparing polysubstituted allene carboxylic acid methyl ester compounds based on CO2 and photocatalysis, characterized in that: The reaction formula of the method is shown below: ； Among them, R 1 is tert-butyl; R 2 is any one of phenyl, 4-methoxyphenyl, 2-methoxyphenyl, 4-chlorophenyl, and 4-methylphenyl; R 3 is any of isopropyl, cyclohexyl or cyclopentyl; The specific reaction steps are as follows: (1) Under argon environment, add 1,3-eneyne compounds, 1,4-dihydropyridine compounds and base into a Schlenk reaction tube, add solvent, and introduce carbon dioxide gas; (2) stirring the reaction mixture at room temperature under visible light until the 1,3-eneyne compound, 1,4-dihydropyridine compound and base added in step (1) disappear; (3) After the reaction is completed, the reaction solution is acidified, the aqueous phase is extracted, the organic phases are combined, washed, dried, and concentrated under reduced pressure to obtain a concentrated solution; (4) The concentrated solution obtained in step (3) is dissolved in a mixed solution of dichloromethane and methanol, and a methyl esterification agent is added to react at room temperature. After the reaction is completed, the organic phase is concentrated under reduced pressure and filtered to obtain the target product.

2. The method for preparing a polysubstituted allene carboxylic acid methyl ester compound according to claim 1, characterized in that: The base in step (1) is one or more of carbonate, formates, organic metal salts or alkoxy bases.

3. The method for preparing a polysubstituted allene carboxylic acid methyl ester compound according to claim 2, characterized in that: The carbonate is Cs2CO3, the formate is HCO2Li, the organic metal salt is CH3OLi, and the alkoxy base is KO t Bu、NaO t Bu or LiO t One or more of the above.

4. The method for preparing a polysubstituted allene carboxylic acid methyl ester compound according to claim 1, characterized in that: The solvent in step (1) is dimethyl sulfoxide, N , N -dimethylformamide, N-methyl-2-pyrrolidone, one or more of acetonitrile.

5. The method for preparing a polysubstituted allene carboxylic acid methyl ester compound according to claim 4, characterized in that: The solvent in step (1) is dimethyl sulfoxide, N , N -dimethylformamide or N-methyl-2-pyrrolidone or more.

6. The method for preparing a polysubstituted allene carboxylic acid methyl ester compound according to claim 1, characterized in that: The visible light described in step (2) is 430-460 nm blue light.

7. The method for preparing a polysubstituted allene carboxylic acid methyl ester compound according to claim 1, characterized in that: The room temperature in step (2) is 25-30°C.

8. The method for preparing polysubstituted allene carboxylic acid methyl ester compounds according to claim 1, characterized in that: The acidification reaction liquid in step (3) uses a dilute hydrochloric acid solution, the extraction uses ethyl acetate, and the washing uses saturated brine.

9. The method for preparing a polysubstituted allene carboxylic acid methyl ester compound according to claim 1, characterized in that: The ratio of dichloromethane to methanol in step (4) is 4:1, and the methyl esterification agent is trimethylsilyldiazomethane.

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