A method for preparing an allene compound

Abstract

This invention discloses a method for preparing allene compounds. The method involves adding a 1,3-enyne compound, a hydrazone compound, a palladium catalyst, and a base promoter to a solvent, and performing a coupling reaction under a nitrogen atmosphere, stirring, and at 60–100°C. After the reaction is complete, the reaction is quenched, and the reaction products are extracted and the organic phases are combined. The obtained organic phases are then washed, dried, and vacuum concentrated to obtain a crude product. The crude product is then purified to obtain the allene compound. The method of this invention features mild reaction conditions, good functional group tolerance, and advantages such as simple post-processing, green procedures, low pollution, and high economic efficiency.

Description

Technical Field

[0001] This invention belongs to the field of organic compound synthesis technology, and particularly relates to a method for preparing allene compounds. Background Technology

[0002] Allenes possess a unique, mutually perpendicular diene topology and are found in both natural products and pharmaceuticals. Marasin, isolated from Marek's disease culture medium, contains a conjugated diene structure and can serve as a potent antibiotic against Staphylococcus aureus (Org. Biomol. Chem. 2005, 3, 1690-1693). Furthermore, pinoresinic acid, a novel inhibitor of FabF, exhibits target selectivity in gel elongation assays and whole-cell-based two-plate assays, with pinoresinic acid C showing good antibacterial activity (Antimicrob. Agents Chemother. 2006, 50, 519-526). In addition, diene-based bioactive compounds (such as prostaglandins) often act as reactive receptors, inhibiting the catalytic reactions of enzymes and cytotoxic antiviral drugs (Prostaglandins 1987, 33, 169-180). Synthetic methods include the deamination of propargylamine (Org. Chem. Front. 2015, 2, 470-475), the removal of alkynols (Org. Lett. 2010, 12, 1796-1799), and the removal of functionalized alkenes (Angew. Chem. Int. Ed. 2018, 57, 8203-8208). However, these methods are limited by the multi-step synthesis of substrates and harsh reaction conditions. Catalytic carbon-carbon cross-coupling is widely considered an important method for constructing organic molecules in synthetic chemistry (Angew. Chem. Int. Ed. 2012, 51, 5062-5085). Typical examples of such reactions include transition metal-catalyzed intermolecular 1,2-, 3,4-, and 1,4-hydrocarbon functionalization reactions of conjugated alkenes and carbonyl compounds (Chem. Rev. 2002, 102, 813-834). The coupling reaction of enyne compounds with reactants is an effective method for synthesizing allenes (J. Am. Chem. Soc. 2024, 146, 7173-7177; Angew. Chem. Int. Ed. 2021, 60, 217-221; Org. Lett. 2024, 26, 536-541). Furthermore, the 1,4-hydrocarbon functionalization reaction of hydrazones and enyne compounds produces only nitrogen as a byproduct, offering advantages such as mild conditions, good functional group tolerance, simple post-processing, green procedures, low pollution, and high economic benefits. Summary of the Invention

[0003] To overcome the problems mentioned above and / or existing technologies, the present invention provides a method for preparing allene compounds.

[0004] This invention is achieved by providing a method for preparing an allene compound, the method comprising the following steps:

[0005] (1) The 1,3-enyne compound shown in formula (II), the hydrazone compound shown in formula (III), the palladium catalyst, and the base promoter are added to the solvent and coupled under nitrogen atmosphere, stirring, at 60-100℃.

[0006]

[0007] (2) After the reaction in step (1) is completed, the reaction is quenched, the reaction product is extracted and the organic phases are combined, the obtained organic phases are washed, dried and vacuum concentrated to obtain crude product, the crude product is purified to obtain the allene compound shown in formula (I).

[0008]

[0009] Among them, R 1 It is selected from any one of phenyl, methoxy-substituted phenyl, methyl-substituted phenyl, halogen-substituted phenyl, ester-substituted phenyl, cyano-substituted phenyl, nitro-substituted phenyl, naphthyl, and thiophene;

[0010] R 2 It is selected from any one of methyl, isobutyl, n-nonyl, phenethyl, tert-butyl, phenyl, and trifluoromethyl;

[0011] R 3 It is selected from any one of phenyl, methyl-substituted phenyl, isopropyl-substituted phenyl, biphenyl, methoxy-substituted phenyl, halogen-substituted phenyl, naphthyl, phenanthryl, trifluoromethoxyphenyl, trifluoromethylphenyl and thiophene.

[0012] Preferably, in step (1), the molar ratio of the 1,3-enyne compound, hydrazone compound, palladium catalyst, and base promoter is 1:1 to 3:0.05 to 0.1:1.5 to 2.

[0013] Preferably, in step (1), the alkali promoter is selected from any one of cesium carbonate, sodium hydroxide, 1,8-diazobisspirocyclic[5.4.0]undec-7-ene, lithium tert-butoxide, and potassium phosphate.

[0014] Preferably, in step (1), the solvent is selected from any one of acetonitrile, toluene, tetrahydrofuran, dichloroethane, N,N-dimethylformamide, and 1,4-dioxane.

[0015] Preferably, in step (1), the palladium catalyst is PEPPSI-IPr.

[0016] Preferably, in step (1), the molar ratio of the 1,3-enyne compound, hydrazone compound, palladium catalyst, and base promoter is 1:3:0.05:2; the base promoter is lithium tert-butoxide; the solvent is tetrahydrofuran; and the coupling reaction temperature is 60°C.

[0017] Preferably, the 1,3-enyne compound includes (3-methylbut-3-en-1-yn-1-yl)benzene, 1-methoxy-4-(3-methylbut-3-en-1-yn-1-yl)benzene, 1-methyl-4-(3-methylbut-3-en-1-yn-1-yl)benzene, 1-chloro-4-(3-methylbut-3-en-1-yn-1-yl)benzene, 1-fluoro-4-(3-methylbut-3-en-1-yn-1-yl)benzene, 1-fluoro-3-(3-methylbut-3-en-1-yn-1-yl)benzene, 1-fluoro-2-(3-methylbut-3-en-1-yn-1-yl)benzene, ethyl 4-(3-methylbut-3-en-1-yn-1-yl)benzoate, 4-(3- One of the following: methylbut-3-en-1-yn-1-yl)benzonitrile, 1-(3-methylbut-3-en-1-yn-1-yl)-2-nitrobenzene, 2-(3-methylbut-3-en-1-yn-1-yl)naphthalene, 2-(3-methylbut-3-en-1-yn-1-yl)thiophene, (5-methyl-3-methylenehex-1-yn-1-yl)benzene, (3-methylenedodecane-1-yn-1-yl)benzene, (3-methylenepentane-1-yn-1,5-diyl)dibenzene, (4,4-dimethyl-3-methylenepentane-1-yn-1-yl)benzene, but-3-enyl-1-yn-1,3-bis(diphenyl)benzene, and (3-(trifluoromethyl)but-3-enyl-1-yn-1-yl)benzene.

[0018] Preferably, the hydrazone compound includes one of benzylidene hydrazine, (4-methylbenzylidene)hydrazine, (3-methylbenzylidene)hydrazine, (2-methylbenzylidene)hydrazine, (4-isopropylbenzylidene)hydrazine, ([1,1'-biphenyl]-4-ylmethylene)hydrazine, (3-methoxybenzylidene)hydrazine, (2-methoxybenzylidene)hydrazine, (4-fluorobenzylidene)hydrazine, (2-fluorobenzylidene)hydrazine, (naphthyl-1-ylmethylene)hydrazine, (naphthyl-2-ylmethylene)hydrazine, (phenanthrene-9-ylmethylene)hydrazine, (2-(trifluoromethoxy)benzylidene)hydrazine, (3-(trifluoromethyl)benzylidene)hydrazine, and (thiophene-2-ylmethylene)hydrazine.

[0019] Preferably, in step (2), the purification column chromatography separation conditions are: the stationary phase is 300-400 mesh silica gel powder, and the mobile phase is petroleum ether.

[0020] This invention overcomes the shortcomings of the prior art and provides a method for preparing allene compounds. This method is based on a simple 1,4-hydroalkylation reaction of 1,3-yne catalyzed by a universal and efficient palladium / azacarbene ligand. In this method, palladium is used as a catalyst to achieve the coupling reaction of 1,3-enyne compounds with hydrazone compounds under the promotion of a base, thereby preparing allene compounds.

[0021] Specifically, the method of the present invention involves a coupling reaction between a 1,3-enyne compound represented by Formula II and a hydrazone compound represented by Formula III in a solvent, with palladium as a catalyst and a base as a promoter. The preferred equation for this reaction is shown below:

[0022]

[0023] Among them, R 1 Selected from any one of phenyl, methoxy-substituted phenyl, methyl-substituted phenyl, halogen-substituted phenyl, ester-substituted phenyl, cyano-substituted phenyl, nitro-substituted phenyl, naphthyl, and thiophene; R 2 Selected from any one of methyl, isobutyl, n-nonyl, phenethyl, tert-butyl, phenyl, and trifluoromethyl; R 3 It is selected from any one of phenyl, methyl-substituted phenyl, isopropyl-substituted phenyl, biphenyl, methoxy-substituted phenyl, halogen-substituted phenyl, naphthyl, phenanthryl, trifluoromethoxyphenyl, trifluoromethylphenyl and thiophene.

[0024] Compared with the shortcomings and deficiencies of existing technologies, this invention has the following beneficial effects: This invention uses palladium as a catalyst to realize the coupling reaction of 1,3-enyne compounds with hydrazone compounds under the promotion of alkali to generate a series of allene compounds. The reaction conditions are mild, the functional groups are well tolerated, and it has the advantages of simple post-processing, green steps, low pollution, and high economic benefits. This invention provides an efficient synthetic method for various existing and novel allene compounds, shortening the difficulty, cost, and time of compound development. Attached Figure Description

[0025] Figure 1 The proton spectrum of target product a in Example 1 of this invention;

[0026] Figure 2 The carbon spectrum of target product a in Example 1 of this invention;

[0027] Figure 3 The proton spectrum of target product b in Example 2 of this invention;

[0028] Figure 4 The carbon spectrum of target product b in Example 2 of this invention;

[0029] Figure 5The proton spectrum of target product c in Example 3 of this invention;

[0030] Figure 6 This is the carbon spectrum of the target product c in Example 3 of the present invention. Detailed Implementation

[0031] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0032] The 1,3-enyne compounds used in the following examples were prepared according to the methods reported in references (Angew. Chem. Int. Ed. 2021, 60, 217-221); the hydrazone compounds were prepared according to the methods reported in references (Angew. Chem. Int. Ed. 2020, 59, 6466-6472). Other raw materials, unless otherwise specified, were commercially available.

[0033] Example 1

[0034] (1) Add (3-methylbut-3-en-1-yn-1-yl)benzene (42.7 mg, 0.3 mmol, 1 equiv.), benzylhydrazine (108.1 mg, 0.9 mmol, 3 equiv.), PEPPSI-IPr (10.2 mg, 0.015 mmol, 0.05 equiv.), lithium tert-butoxide (48.0 mg, 0.6 mmol, 2 equiv.), and tetrahydrofuran (1 mL) to a 10 mL Schlenk tube in sequence. Stir the reaction mixture at 60 °C for 15 h under a nitrogen atmosphere.

[0035] (2) After the reaction in step (1) is completed, the reaction is quenched with saturated NH4Cl solution and extracted with ethyl acetate (20 mL × 3). The combined organic phases are washed with saturated brine (20 mL), dried with anhydrous sodium sulfate, and concentrated under vacuum to obtain crude product. The crude product is purified by silica gel column chromatography. The column chromatography separation conditions are: 300-400 mesh silica gel powder as the stationary phase and petroleum ether as the mobile phase. Finally, 56.2 mg of the target product a is obtained.

[0036] The target product a was characterized as follows: Figures 1-2 As shown, the characterization data is as follows:

[0037] 1H NMR (400MHz, CDCl3): δ=7.32-7.27(m,4H),7.25-7.17(m,6H),6.12-6.08(m,1H),2.84(t,J=8.3Hz,2H),2.47-2.42(m,2H),1.88(d,J=2.8Hz,3H)ppm.

[0038] 13 C NMR (100MHz, CDCl3): δ=202.9,142.0,135.9,128.60,128.56,128.5,126.7,126.6,126.0,103.2,94.5,35.9,34.0,19.0ppm.

[0039] HRMS(APCI): calcd for C 18 H 19 [M+H] + 235.1481, found: 235.1485.

[0040] Characterization data shows that the obtained reaction product is (3-methyl-1,2-pentadien-1,5-diyl)diphenyl (purity > 98%), and the structural formula of this compound is:

[0041]

[0042] The product yield was calculated to be 80%.

[0043] Example 2

[0044] (1) 1-Methyl-4-(3-methylbut-3-en-1-yn-1-yl)benzene (46.9 mg, 0.3 mmol, 1 equiv.), benzylhydrazine (108.1 mg, 0.9 mmol, 3 equiv.), PEPPSI-IPr (10.2 mg, 0.015 mmol, 0.05 equiv.), lithium tert-butoxide (48.0 mg, 0.6 mmol, 2 equiv.), and tetrahydrofuran (1 mL) were added sequentially to a 10 mL Schlenk tube. The reaction mixture was stirred at 60 °C for 43 h under a nitrogen atmosphere.

[0045] (2) After the reaction in step (1) is completed, the mixture is quenched with saturated NH4Cl solution and extracted with ethyl acetate (20 mL × 3). The combined organic phases are washed with saturated brine (20 mL), dried with anhydrous sodium sulfate, and concentrated under vacuum to obtain crude product. The crude product is purified by silica gel column chromatography. The column chromatography separation conditions are: 300-400 mesh silica gel powder as the stationary phase and petroleum ether as the mobile phase. Finally, 54.3 mg of the target product b is obtained.

[0046] The target product b was characterized as follows: Figures 3-4 As shown, the characterization data is as follows:

[0047] 1 H NMR (400MHz, CDCl3): δ=7.33-7.27(m,2H),7.25-7.18(m,3H),7.10(d,J=2.1Hz,4H),6.09-6.06 (m,1H),2.89-2.76(m,2H),2.46-2.40(m,2H),2.35(d,J=2.0Hz,3H),1.87(t,J=2.5Hz,3H)ppm.

[0048] 13 C NMR (100MHz, CDCl3): δ=202.6,142.1,136.3,132.9,129.3,128.6,128.5,126.6,125.9,103.1,94.2,36.0,34.0,21.3,19.1ppm.

[0049] HRMS(APCI): calcd for C 19 H 21 [M+H] + 249.1638, found: 249.1641.

[0050] Characterization data shows that the obtained reaction product is 1-methyl-4-(3-methyl-5-phenyl-1,2-pentadien-1-yl)benzene (purity > 98%), and the structural formula of this compound is:

[0051]

[0052] The product yield was calculated to be 73%.

[0053] Example 3

[0054] (1) Add (3-methylbut-3-en-1-yn-1-yl)benzene (42.7 mg, 0.3 mmol, 1 equiv.), (4-methylbenzylene)hydrazine (120.8 mg, 0.9 mmol, 3 equiv.), PEPPSI-IPr (10.2 mg, 0.015 mmol, 0.05 equiv.), lithium tert-butoxide (48.0 mg, 0.6 mmol, 2 equiv.), and tetrahydrofuran (1 mL) to a 10 mL Schlenk tube in sequence. Stir the reaction mixture at 60 °C for 40 h under a nitrogen atmosphere.

[0055] (2) After the reaction in step (1) is completed, the reaction is quenched with saturated NH4Cl solution and extracted with ethyl acetate (20 mL × 3). The combined organic phases are washed with saturated brine (20 mL), dried with anhydrous sodium sulfate, and concentrated under vacuum to obtain crude product. The crude product is purified by silica gel column chromatography. The column chromatography separation conditions are: 300-400 mesh silica gel powder as the stationary phase and petroleum ether as the mobile phase. Finally, 44.7 mg of the target product c is obtained.

[0056] The target product c was characterized as follows: Figures 5-6 As shown, the characterization data is as follows:

[0057] 1 H NMR (400MHz, CDCl3): δ=7.33-7.27(m,2H),7.25-7.18(m,3H),7.10(d,J=2.1Hz,4H),6.09-6.06 (m,1H),2.89-2.76(m,2H),2.46-2.40(m,2H),2.35(d,J=2.0Hz,3H),1.87(t,J=2.5Hz,3H)ppm.

[0058] 13 C NMR (100MHz, CDCl3): δ=202.6,142.1,136.3,132.9,129.3,128.6,128.5,126.6,125.9,103.1,94.3,36.0,34.0,21.3,19.1ppm.

[0059] HRMS(APCI): calcd for C 19 H 21 [M+H] + 249.1638, found: 249.1642.

[0060] Characterization data revealed that the obtained reaction product was 1-methyl-4-(3-methyl-5-phenyl-3,4-pentadien-1-yl)benzene (purity > 98%), and the structural formula of this compound is as follows:

[0061]

[0062] The product yield was calculated to be 60%.

[0063] Example 4

[0064] Example 4 is basically the same as Example 1, except that the reaction temperature is different in step (1), as shown in Table 1 below:

[0065] Table 1

[0066] Temperature (°C) Yield (%) 60 80 25 trace 100 44

[0067] As can be seen from Table 1, under the same reaction conditions, within the reaction temperature range of 25 to 100℃, the reaction yield is the highest at 60℃, reaching 80%.

[0068] Example 5

[0069] Example 5 is basically the same as Example 1, except that the alkali used in step (1) at 60°C is different, as shown in Table 2 below:

[0070] Table 2

[0071]

[0072]

[0073] As can be seen from Table 2, under the reaction conditions of 60℃, using different types of bases such as cesium carbonate, sodium hydroxide, 1,8-diazobisspirocyclic[5.4.0]undec-7-ene, lithium tert-butoxide, and potassium phosphate, the reaction yield was the highest at 80% when the base was lithium tert-butoxide.

[0074] Example 6

[0075] Example 6 is basically the same as Example 1, except that in step (1), the molar ratio of the 1,3-enyne compound and the hydrazone compound is different, as shown in Table 3 below:

[0076] Table 3

[0077] Molar ratio of 1,3-enyne compounds to hydrazone compounds Yield (%) 1 / 3 80 1 / 2 56 1 / 1 22

[0078] As can be seen from Table 3, under the same reaction conditions, when the molar ratio of 1,3-enyne compound to hydrazone compound is in the range of 1:1 to 3, reducing the amount of 1,3-enyne compound and hydrazone compound is not conducive to improving the reaction yield. The reaction yield is the highest at 0.3 mmol of 1,3-enyne compound and 0.9 mmol of hydrazone compound, which is 80%.

[0079] Example 7

[0080] Example 7 is basically the same as Example 1, except that in step (1), the molar ratio of the 1,3-enyne compound and the palladium catalyst is different, as shown in Table 4 below:

[0081] Table 4

[0082] The molar ratio of the 1,3-enyne compound to the palladium catalyst Yield (%) 1 / 0.05 80 1 / 0.1 44

[0083] As can be seen from Table 4, under the same reaction conditions, when the molar ratio of 1,3-enyne compound to palladium catalyst is in the range of 1:0.05 to 0.1, increasing the molar ratio of 1,3-enyne compound to palladium catalyst is not conducive to improving the reaction yield. The highest reaction yield, 80%, is achieved when the molar ratio of 1,3-enyne compound is 0.3 mmol and palladium catalyst is 0.015 mmol.

[0084] Example 8

[0085] Example 8 is basically the same as Example 1, except that in step (1), the molar ratio of the 1,3-enyne compound and the base is different, as shown in Table 5 below:

[0086] Table 5

[0087] Molar ratio of 1,3-enyne compound to lithium tert-butoxide Yield (%) 1 / 1.5 63 1 / 2 80

[0088] As can be seen from Table 5, under the same reaction conditions, when the molar ratio of 1,3-enyne compound to lithium tert-butoxide is in the range of 1:1.5 to 2, decreasing the molar ratio of 1,3-enyne compound to lithium tert-butoxide is not conducive to improving the reaction yield. The reaction yield is the highest at 80% when the molar ratio of 1,3-enyne compound is 0.3 mmol and lithium tert-butoxide is 0.6 mmol.

[0089] Example 9

[0090] Example 9 is basically the same as Example 1, except that the solvent used in step (1) is different, as shown in Table 6 below:

[0091] Table 6

[0092] solvent Yield (%) Tetrahydrofuran 80 Acetonitrile 20 Toluene 35 dichloroethane trace N,N-Dimethylformamide trace 1,4-Dioxane 67

[0093] As can be seen from Table 6, under the same reaction conditions, the reaction yield is the highest at 80% when using different solvents such as tetrahydrofuran, acetonitrile, toluene, dichloroethane, N,N-dimethylformamide and 1,4-dioxane, with tetrahydrofuran as the solvent.

[0094] Example 10

[0095] Example 10 is basically the same as Example 1, except that the 1,3-enyne compound is different in step (1). The specific target products obtained are shown in Table 7 below:

[0096] Table 7

[0097] 1,3-Enyne compounds product Yield % 1-Methoxy-4-(3-methylbut-3-en-1-yn-1-yl)benzene 1-Methoxy-4-(3-methyl-5-phenyl-1,2-pentadien-1-yl)benzene 75 1-Chloro-4-(3-methyl-3-buten-1-yn-1-yl)benzene 1-Chloro-4-(3-methyl-5-phenyl-1,2-pentadien-1-yl)benzene 76 1-Fluoro-4-(3-methylbut-3-en-1-yn-1-yl)benzene 1-Fluoro-4-(3-methyl-5-phenyl-1,2-pentadien-1-yl)benzene 69 1-Fluoro-3-(3-methyl-3-buten-1-yn-1-yl)benzene 1-Fluoro-3-(3-methyl-5-phenyl-1,2-pentadien-1-yl)benzene 90 1-Fluoro-2-(3-methylbut-3-en-1-yn-1-yl)benzene 1-Fluoro-2-(3-methyl-5-phenyl-1,2-pentadien-1-yl)benzene 80 Ethyl 4-(3-methylbut-3-en-1-yn-1-yl)benzoate ethyl 4-(3-methyl-5-phenyl-1,2-dien-1-yl)benzoate 5 4-(3-methylbut-3-en-1-yn-1-yl)benzonitrile 4-(3-methyl-5-phenyl-1,2-dien-1-yl)benzonitrile 3 1-(3-methylbut-3-en-1-yn-1-yl)-2-nitrobenzene 1-(3-Methyl-5-phenyl-1,2-dien-1-yl)-2-nitrobenzene 12 2-(3-methyl-3-buten-1-yn-1-yl)naphthalene 2-(3-methyl-5-phenyl-1,2-pentadien-1-yl)naphthalene 68 2-(3-methyl-3-buten-1-yn-1-yl)thiophene 2-(3-methyl-5-phenyl-1,2-pentadien-1-yl)thiophene 64 (5-Methyl-3-methylenehex-1-yn-1-yl)benzene (3-Isobutylpent-1,2-diene-1,5-diyl)diphenyl 71 (3-Methylenedodec-1-yn-1-yl)benzene (3-Nonylpent-1,2-dien-1,5-diyl)diphenyl 45 (3-Methylenepent-1-yne-1,5-diyl)diphenyl (3-Phenylacet-1,2-diene-1,5-diyl)diphenyl 59 (4,4-Dimethyl-3-methylenepent-1-yn-1-yl)benzene (3-(tert-butyl)pent-1,2-dien-1,5-diyl)diphenyl 61 (but-3-enyl-1-yne-1,3-bis(diphenyl)) 5-1,2-diene-1,3,5-triphenyl 51 (3-(trifluoromethyl)but-3-enyl-1-yn-1-yl)benzene (3-(trifluoromethyl)pent-1,2-diene-1,5-diyl)diphenyl 15

[0098] Example 11

[0099] Example 11 is basically the same as Example 1 or 3, except that the hydrazone compound is different in step (1). The specific target products obtained are shown in Table 8 below:

[0100] Table 8

[0101]

[0102]

[0103] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing an allene compound, characterized in that, The method includes the following steps: (1) The 1,3-enyne compound shown in formula (II), the hydrazone compound shown in formula (III), the palladium catalyst, and the base promoter are added to the solvent and coupled under nitrogen atmosphere, stirring, and at 60~100 °C. Formula (II); Formula (Ⅲ); In step (1), the alkali promoter is selected from any one of cesium carbonate, sodium hydroxide, 1,8-diazobisspirocyclic [5.4.0]undec-7-ene, lithium tert-butoxide, and potassium phosphate; In step (1), the solvent is selected from any one of acetonitrile, toluene, tetrahydrofuran, and 1,4-dioxane; In step (1), the palladium catalyst is PEPPSI-Ipr: ; (2) After the reaction in step (1) is completed, the reaction is quenched, the reaction product is extracted and the organic phases are combined, the obtained organic phases are washed, dried and vacuum concentrated to obtain crude product, the crude product is purified to obtain the allene compound shown in formula (I). Formula (I); Among them, R 1 It is selected from any one of phenyl, methoxy-substituted phenyl, methyl-substituted phenyl, halogen-substituted phenyl, nitro-substituted phenyl, naphthyl and thiophene; R 2 It is selected from any one of methyl, isobutyl, n-nonyl, phenethyl, tert-butyl, phenyl, and trifluoromethyl; R 3 It is selected from any one of phenyl, methyl-substituted phenyl, isopropyl-substituted phenyl, biphenyl, methoxy-substituted phenyl, halogen-substituted phenyl, naphthyl, phenanthryl, trifluoromethoxyphenyl, trifluoromethylphenyl and thiophene.

2. The method as described in claim 1, characterized in that, In step (1), the molar ratio of the 1,3-enyne compound, hydrazone compound, palladium catalyst, and base promoter is 1:1~3:0.05~0.1:1.5~2.

3. The method as described in claim 1 or 2, characterized in that, In step (1), the molar ratio of the 1,3-enyne compound, hydrazone compound, palladium catalyst, and base promoter is 1:3:0.05:2; the base promoter is lithium tert-butoxide; the solvent is tetrahydrofuran; and the coupling reaction temperature is 60°C.

4. The method as described in claim 1, characterized in that, In step (2), the purification column chromatography separation conditions are: the stationary phase is 300~400 mesh silica gel powder, and the mobile phase is petroleum ether.

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