A method for preparing polysubstituted allene carboxylic acid methyl ester compounds based on CO2 and photocatalysis

Abstract

The present invention belongs to the technical field of catalytic methods and catalysts, and specifically relates to a method for preparing polysubstituted allene carboxylic acid methyl ester compounds based on CO2 and photocatalysis. The method is based on a photocatalytic reaction system and uses CO2 as a carboxyl source. Under mild conditions without the need for a photocatalyst or metal, the method achieves efficient synthesis of polysubstituted allene carboxylic acid derivatives through a 1,4-alkane carboxylation reaction of 1,3-enynes. The method has good yield and wide substrate universality. Various functional groups are applicable to the reaction, and the reagents used are non-toxic. The method has broad application prospects.

Description

Technical Field

[0001] The present invention belongs to the technical field of catalytic methods and catalysts, and specifically relates to a method for preparing polysubstituted allene carboxylic acid methyl ester compounds based on CO2 and photocatalysis. Background Art

[0002] Allenes are a class of unsaturated compounds with special structures and cumulative double bonds, which are widely distributed in natural products and active molecules. By modifying the substituents at the end of allenes, allenes can exhibit various reactivity and chemical, regio, and stereoselectivity. And due to its unique sp 2 Allenes are important synthons in chemical reactions. The development of new methods for the synthesis of functionalized allene compounds is of great significance in organic synthesis, pharmacy, and biochemistry. Allene carboxylic acids are a class of organic compounds containing an allene structure (two carbon-carbon double bonds directly connected) and a carboxyl group (-COOH). The presence of the carboxyl group imparts acidic properties, allowing neutralization with bases to form the corresponding carboxylates. The double bond in the allene structure has a high electron density, making it susceptible to addition reactions with electrophilic reagents. Allene carboxylic acids can be oxidized, and the resulting products depend on the type of oxidant and reaction conditions. For example, mild oxidants can oxidize them to the corresponding aldehydes or ketones, while strong oxidants may cleave the carbon-carbon double bond, producing products such as carboxylic acids or carbon dioxide. Under certain conditions, allene carboxylic acids can polymerize to form high molecular weight polymers. These polymers may possess unique properties, such as optical properties and thermal stability, and have potential applications in materials science. Among various compounds containing allene fragments, allene carboxylic acid is the core functional group in many natural products and active molecules, and has good reactivity. As an organic synthesis intermediate, it can be further converted into a variety of downstream products.

[0003] Existing methods for synthesizing allene carboxylic acids mainly include: (1) synthesizing allene carboxylic acids by hydrolysis of 2,3-enoic acid esters; (2) oxidizing allene alcohol compounds; (3) synthesizing linked carboxylic acids by carbonyl insertion reactions catalyzed by transition metals; and (4) synthesizing allene carboxylic acid compounds by capturing carbon dioxide with allene metal reagents. Although there have been a considerable number of reports on methods for synthesizing allene carboxylic acids, the above methods have problems with low selectivity and conversion rate, and usually require the use of metal catalysts and the toxic reagent carbon monoxide. Whether from the perspective of cost, safety, or environmental protection, there is room for improvement.

[0004]

[0005] The inventor's research group previously used 1,3-enyne and iodide as raw materials, potassium formate as a formate source, DABCO as a hydrogen transfer catalyst, Ir(bpy)2(dtbpy)PF6 as a photocatalyst, and cesium carbonate as a base. By introducing CO2 at normal pressure and irradiating the reaction under visible light at room temperature for 24 hours, they were able to obtain allenedicarboxylic acid compounds in excellent to good yields (see invention patent CN119191924B). However, the iodide used in the above reaction is generally toxic and may have adverse effects on the human body.

[0006] Based on the above research, the inventors, with the goal of reducing toxicity, have developed a method for preparing polysubstituted allene carboxylic acid methyl ester compounds based on CO2 and photocatalysis. In this method, polysubstituted allene carboxylic acid derivatives are synthesized using carbon dioxide as a carboxyl source through a photocatalytic reaction system without the need for transition metal catalysis, significantly improving the conversion rate and selectivity of polysubstituted allene carboxylic acids. This develops a green and environmentally friendly preparation method, reduces pollution, and improves the efficiency of the catalytic reaction and the preparation efficiency of polysubstituted allene carboxylic acids. Summary of the Invention

[0007] The technical problem to be solved by the present invention is to provide a method for synthesizing polysubstituted allene carboxylic acids based on CO2, so as to solve the technical problems of limited reaction sites, weak chemical selectivity and strict reaction conditions required for allene carboxylic acid synthesis.

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

[0009]

[0010] 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 one of isopropyl, cyclohexyl, and cyclopentyl;

[0011] The specific reaction steps are as follows:

[0012] (1) Under argon atmosphere, add 1,3-eneyne compound, 1,4-dihydropyridine compound and base into Schlenk reaction tube, add solvent, and introduce carbon dioxide gas;

[0013] (2) The reaction is stirred at room temperature under visible light until the 1,3-enyne compound, 1,4-dihydropyridine compound and base added in step (1) disappear;

[0014] (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;

[0015] (4) The concentrated solution obtained in step (3) is dissolved in a mixed solution of dichloromethane and methanol, and a methylation reagent is added. The reaction is carried out at room temperature. After the reaction is completed, the organic phase is concentrated under reduced pressure and filtered to obtain the target product.

[0016] Preferably, the base in step (1) is one or more of carbonate, formates, organic metal salts or alkoxy bases.

[0017] Preferably, 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 following.

[0018] Preferably, the solvent in step (1) is dimethyl sulfoxide. N , N -dimethylformamide, N-methyl-2-pyrrolidone, one or more of acetonitrile.

[0019] Preferably, the solvent in step (1) is dimethyl sulfoxide. N , N -dimethylformamide or N-methyl-2-pyrrolidone or more.

[0020] Preferably, the visible light in step (2) is 430-460 nm blue light.

[0021] Preferably, the room temperature in step (2) is 25-30°C.

[0022] Preferably, the acidified reaction liquid in step (3) uses a dilute hydrochloric acid solution, the extraction uses ethyl acetate, and the washing uses saturated saline.

[0023] Preferably, the ratio of dichloromethane to methanol in step (4) is 4:1, and the methylation reagent is trimethylsilyldiazomethane.

[0024] The beneficial effects of the present invention are as follows: the present invention provides a method for preparing polysubstituted allene carboxylic acid methyl ester compounds based on CO2 and photocatalysis. The method is based on a photocatalytic reaction system and uses CO2 as a carboxyl source. Under mild conditions without the need for a photocatalyst or metal, the method realizes the efficient synthesis of polysubstituted allene carboxylic acid derivatives through the 1,4-alkane carboxylation reaction of 1,3-enyne. The method has good yield and wide substrate universality. A variety of functional groups are suitable for the reaction, and the reagents used are non-toxic, and the method has broad application prospects. DETAILED DESCRIPTION

[0025] The scope of protection of the present invention is further illustrated below through specific embodiments, but this should not be understood as the scope of the above subject matter of the present invention being limited to the following embodiments. All technologies implemented based on the above content of the present invention fall within the scope of the present invention.

[0026] It should be noted that, in the following examples, unless otherwise specified, the methods described are conventional methods and the reagents described can be purchased from commercial sources.

[0027] In the following examples, 3DPAFIPN, chemically known as 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile, is a halogenated dicyanophenyl photosensitizer and a novel donor-acceptor (D-A) based on halogenated cyanoolefins. As a photocatalyst, it can induce single electron transfer (SET) under visible light irradiation. It can be applied to a variety of organic synthesis reactions, such as the photosynthesis of multifunctionalized dihydro-2-oxypyrroles and the cross-dideoxy carbon-carbon coupling reaction between benzyl benzoate and allyl alcohol. This provides a highly efficient, energy-saving, and environmentally friendly green method for organic synthesis.

[0028] In the following examples, 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).

[0029] In the following examples, Ir[(dF(CF3)ppy)2(dtbbpy)]PF6, an iridium(III) complex modified with fluorine atoms and a trifluoromethyl group, is a cationic phosphorescent material. It offers advantages over traditional Ir(ppy)3 derivatives in terms of photophysical properties, stability, and application range, particularly in deep-red / near-infrared luminescence, photocatalysis, and bioimaging.

[0030] In the following examples, the 4CzIPN is a typical thermally activated delayed fluorescence (TADF) material that achieves efficient reverse intersystem crossing (RISC) through a strong donor-acceptor (DA) structure of carbazole (Cz) and cyano (CN).

[0031] In the following examples, the Schlenk tube is a laboratory glass instrument designed for anhydrous and oxygen-free operations and is widely used in chemical reactions that are sensitive to air / moisture (such as organometallic synthesis, transition metal catalysis, free radical reactions, etc.).

[0032] Example 1

[0033] Under argon, (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 the atmosphere was subsequently replaced with carbon dioxide three times. The reaction was stirred at room temperature under 12 W 460 nm LED blue light until the starting material disappeared. After completion of the reaction, the reaction solution was acidified with dilute hydrochloric acid, and the aqueous phase was extracted five times with ethyl acetate. The organic phases were combined, washed three times with saturated brine, dried over anhydrous Na2SO4, and then concentrated under reduced pressure. The organic phase was then dissolved in 5 mL of a mixture of dichloromethane and methanol (dichloromethane:methanol = 4:1), and trimethylsilyldiazomethane (0.4 mmol) was added. The reaction was allowed to react at room temperature for 1 hour. After completion of the reaction, the organic phase was concentrated under reduced pressure and filtered through a silica gel column (PE:EA = 100:1 to 60:1) to yield the desired product 3aa.

[0034]

[0035] Product testing data are as follows:

[0036] Colorless oil, yield 81%.

[0037] 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)

[0038] 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.

[0039] Example 2

[0040] Under argon, 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 the carbon dioxide atmosphere was subsequently replaced three times. The reaction was stirred at room temperature under 12 W 460 nm LED blue light until the starting material disappeared. After completion of the reaction, the reaction solution was acidified with dilute hydrochloric acid, and the aqueous phase was extracted five times with ethyl acetate. The organic phases were combined, washed three times with saturated brine, dried over anhydrous Na2SO4, and then concentrated under reduced pressure. The organic phase was then dissolved in 5 mL of a mixture of dichloromethane and methanol (dichloromethane:methanol = 4:1), and trimethylsilyldiazomethane (0.4 mmol) was added. The reaction was allowed to react at room temperature for 1 hour. After completion of the reaction, the organic phase was concentrated under reduced pressure and filtered through a silica gel column (PE:EA = 100:1 to 60:1) to yield the desired product 3ba.

[0041]

[0042] Product testing data are as follows:

[0043] Colorless solid, yield 65%.

[0044] 1 H NMR (400 MHz, CDCl3) δ 7.65 – 7.58 (m, 6H), 7.47 – 7.43 (m, 2H),7.35 (t, 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 = 6.4 Hz, 3H), 0.91 (d, J = 6.4 Hz, 3H).

[0045] 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.

[0046] Example 3

[0047] Under argon, 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 the carbon dioxide atmosphere was subsequently replaced three times. The reaction was stirred at room temperature under 12 W 460 nm LED blue light until the starting material disappeared. After completion of the reaction, the reaction solution was acidified with dilute hydrochloric acid, and the aqueous phase was extracted five times with ethyl acetate. The organic phases were combined, washed three times with saturated brine, dried over anhydrous Na2SO4, and then concentrated under reduced pressure. The organic phase was then dissolved in 5 mL of a mixture of dichloromethane and methanol (dichloromethane:methanol = 4:1), and trimethylsilyldiazomethane (0.4 mmol) was added. The reaction was allowed to react at room temperature for 1 hour. After completion of the reaction, the organic phase was concentrated under reduced pressure and filtered through a silica gel column (PE:EA = 100:1 to 60:1) to yield the desired product 3ca.

[0048]

[0049] Product testing data are as follows:

[0050] Colorless oil, yield 67%.

[0051] 1H 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).

[0052] 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.

[0053] Example 4

[0054] Under argon, (4,4-dimethyl-3-methylidenepent-1-ynyl)benzene 1a (0.3 mmol), ethyl 4-(but-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 the atmosphere was subsequently replaced with carbon dioxide three times. The reaction was stirred at room temperature under 12 W 460 nm LED blue light until the starting material disappeared. After completion of the reaction, the reaction mixture was acidified with dilute hydrochloric acid, and the aqueous phase was extracted five times with ethyl acetate. The organic phases were combined, washed three times with saturated brine, dried over anhydrous Na2SO4, and then concentrated under reduced pressure. The organic phase was then dissolved in 5 mL of a mixture of dichloromethane and methanol (dichloromethane:methanol = 4:1), and trimethylsilyldiazomethane (0.4 mmol) was added. The reaction was allowed to react at room temperature for 1 hour. After completion of the reaction, the organic phase was concentrated under reduced pressure and filtered through a silica gel column (PE:EA = 100:1 to 60:1) to obtain the desired product 3ab.

[0055]

[0056] Product testing data are as follows:

[0057] Colorless oil, yield 61%, dr = 1:1.1.

[0058] 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).

[0059] 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.

[0060] Example 5

[0061] Under argon, (4,4-dimethyl-3-methylidenepent-1-ynyl)benzene 1a (0.3 mmol), ethyl 5-(ethoxycarbonyl)-4-(hex-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 the atmosphere was subsequently replaced with carbon dioxide three times. The reaction was stirred at room temperature under 12 W 460 nm LED blue light until the starting material disappeared. After completion of the reaction, the reaction mixture was acidified with dilute hydrochloric acid, and the aqueous phase was extracted five times with ethyl acetate. The organic phases were combined, washed three times with saturated brine, dried over anhydrous Na2SO4, and then concentrated under reduced pressure. The organic phase was then dissolved in 5 mL of a mixture of dichloromethane and methanol (dichloromethane:methanol = 4:1), and trimethylsilyldiazomethane (0.4 mmol) was added. The reaction was allowed to react at room temperature for 1 hour. After completion of the reaction, the organic phase was concentrated under reduced pressure and filtered through a silica gel column (PE:EA = 100:1 to 60:1) to yield the desired product 3ac.

[0062]

[0063] Product testing data are as follows:

[0064] Colorless oil, yield 50%, dr = 1:1.1.

[0065] 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).

[0066] 13 C 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.

[0067] Example 6

[0068] Under argon, (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 the atmosphere was subsequently replaced with carbon dioxide three times. The reaction was stirred at room temperature under 12 W 460 nm LED blue light until the starting material disappeared. After completion of the reaction, the reaction mixture was acidified with dilute hydrochloric acid, and the aqueous phase was extracted five times with ethyl acetate. The organic phases were combined, washed three times with saturated brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The organic phase was then dissolved in 5 mL of a mixture of dichloromethane and methanol (dichloromethane:methanol = 4:1), and trimethylsilyldiazomethane (0.4 mmol) was added. The reaction was allowed to react at room temperature for 1 hour. After completion of the reaction, the organic phase was concentrated under reduced pressure and filtered through a silica gel column (PE:EA = 100:1 to 60:1) to yield the desired product 3ad.

[0069]

[0070] Product testing data are as follows:

[0071] Colorless oil, yield 77%.

[0072] 1 H 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).

[0073] 13 C 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.

[0074] Application Example 1

[0075] According to the reaction formula described in Example 1, the photocatalyst, base, solvent and whether or not light was irradiated were replaced in the reaction formula, and the changes in product yield caused by the changes in conditions were statistically analyzed. The specific results are shown in Table 1.

[0076]

[0077] Table 1 Reaction condition screening

[0078]

[0079] Note: PC1 = 4CzIPN, PC2 = Ir[(ppy)2dtbbpy]PF6, PC3 = Ir[(dF(CF3)ppy)2dtbbpy]PF6, PC4 =3DPAFIPN, a No light.

[0080] As can be seen from the data 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, the strong base is better than the weak base, and light and base play an indispensable role in the reaction.

[0081] In summary, the present invention provides a method for preparing polysubstituted allene carboxylic acid methyl ester compounds based on CO2 and photocatalysis. The method is based on a photocatalytic reaction system and uses CO2 as a carboxyl source. Under mild conditions without the need for photocatalysts or metals, the method realizes the efficient synthesis of polysubstituted allene carboxylic acid derivatives through the 1,4-alkane carboxylation reaction of 1,3-enyne. The method has good yield, wide substrate universality, a variety of functional groups are suitable for the reaction, and the reagents used are non-toxic, and has 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 atmosphere, 1,3-enyne compound, 1,4-dihydropyridine compound and base are added to a Schlenk reaction tube, solvent is added, and carbon dioxide gas is introduced; (2) stirring the reaction mixture at room temperature 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, 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 methylation reagent is added, and the reaction is carried out 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, wherein: The base in step (1) is Cs2CO3, HCO2Li, CH3OLi, KO t Bu, NaO t Bu or LiO t One or more of the following.

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

4. The method for preparing a polysubstituted allene carboxylic acid methyl ester compound according to claim 3, wherein: The solvent in step (1) is one or more of dimethyl sulfoxide, N,N-dimethylformamide or N-methyl-2-pyrrolidone.

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

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

7. The method for preparing a polysubstituted allene carboxylic acid methyl ester compound according to claim 1, wherein: The acidified reaction liquid in step (3) uses dilute hydrochloric acid solution, extracted with ethyl acetate, and washed with saturated brine.

8. The method for preparing a polysubstituted allene carboxylic acid methyl ester compound according to claim 1, wherein: The ratio of dichloromethane to methanol in step (4) is 4:1, and the methylation reagent is trimethylsilyldiazomethane.

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