Synthesis method of chiral α-allyl amino acid ester

Abstract

The present invention provides a method for synthesizing chiral α-allyl amino acid esters, the method comprising: preparing a chiral α-allyl amino acid ester compound 5 with an α-amino acid ester compound 1 having a free amino group and an allene compound 2: #imgabs0#; in compound 1, R1 is selected from: aryl or alkyl, R2 is selected from: alkyl; in compound 2, R3 is selected from: aryl, aralkyl, heteroaryl, lactam group. The synthetic method has good universality, and can realize a one-step catalytic reaction to efficiently obtain an optically active α-allyl amino acid ester compound. And the yield of most α-allyl amino acid ester compounds can reach more than 80%, and many α-allyl amino acid ester compounds with special structures can also be obtained in one step by the synthetic method.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a method for synthesizing chiral alpha-allyl amino acid esters. Background Art

[0002] Optically active α-amino acids are very important organic molecules in many scientific fields. Therefore, a series of methods for synthesizing this class of compounds have been developed. According to the existing literature reports on the synthesis of chiral α-allyl amino acid esters, it is often necessary to use an equivalent amount of amino protecting groups or amino acid precursors, and generally requires multiple steps of transformation, which greatly reduces the atom economy and step economy. In 2019, our research group reported that chiral aldehydes were used as organic catalysts and transition metals to catalyze the asymmetric α-allylation of amino acid esters to obtain a series of optically active α-allyl amino acid derivatives. The shortcomings of this system are: 1) The substrate enol ester of this reaction requires three steps of synthesis to obtain. 2) The yield of this reaction is low, most of which are between 50% and 60%. Therefore, it is of great research significance to develop a simple, efficient, and catalytic method for the synthesis of chiral α-allyl amino acid ester compounds. Summary of the invention

[0003] In view of this, in order to solve the problems of complicated steps and low yield commonly existing in the synthesis of chiral α-allyl amino acid esters, the present invention provides a method for synthesizing chiral α-allyl amino acid esters. The synthesis method has good universality and can efficiently obtain optically active α-allyl amino acid ester compounds. The yield of most α-allyl amino acid ester compounds can reach more than 80%, and many α-allyl amino acid ester compounds with special structures can also be obtained in one step by the synthesis method. The present application has carried out synthesis verification on nearly 60 α-allyl amino acid ester compounds.

[0004] In order to achieve the above technical objectives, the technical solutions adopted in this application are as follows:

[0005] A method for synthesizing a chiral α-allyl amino acid ester, the method comprising: preparing a chiral α-allyl amino acid ester compound 5 using an α-amino acid ester compound 1 having a free amino group and an allene compound 2:

[0006]

[0007] In compound 1, R1 is selected from: aryl or alkyl, R2 is selected from: alkyl; in compound 2, R3 is selected from: aryl, aralkyl, heteroaryl, lactam group;

[0008] Preferably, the reaction of preparing chiral α-allyl amino acid ester from α-amino acid ester compound 1 having free amino group and allene compound 2 is achieved by combined catalysis of chiral aldehyde catalyst and palladium metal catalyst;

[0009] The chiral aldehyde catalyst has a structure shown in Formula I:

[0010]

[0011] In compound I, R is selected from the group consisting of: H, alkyl, aryl, halogen, and silane.

[0012] Furthermore, the steps of the synthesis method are as follows:

[0013]

[0014] wherein, an α-amino acid ester compound 1 having a free amino group, an allene compound 2, a palladium metal catalyst, a chiral aldehyde catalyst, a ligand, an acid, a Lewis acid and an alkali are reacted in a solvent to obtain a chiral α-allyl amino acid ester; preferably, the palladium metal catalyst, the ligand and the solvent are first mixed, and then the allene compound, the α-amino acid ester compound having a free amino group, the acid, the chiral aldehyde catalyst, the Lewis acid and the alkali are added for mixed reaction; preferably, the molar ratio of the allene compound to the α-amino acid ester compound having a free amino group is 1:2 to 2.5; preferably, the reaction is carried out under a protective atmosphere; preferably, the reaction temperature is 60±5°C, preferably 60°C; and then the reaction mixture is concentrated and purified by chromatography.

[0015] In the above synthesis method, the molar ratio of the allene compound to the chiral aldehyde catalyst is 1:0.05-0.1, preferably 1:0.1.

[0016] In the above synthesis method, the palladium metal catalyst is selected from: [Pd(C3H5)Cl]2 or Pd(PPh3)4, preferably [Pd(C3H5)Cl]2; preferably, the amount of the palladium metal catalyst is 2 to 5% of the molar amount of the allene compound.

[0017] In the above synthesis method, the ligand is at least one of a biphenyl ligand, an arylphosphine ligand, and a ferrocene ligand; preferably, the ligand is selected from: 1,2-bis(diphenylphosphine)ethane, 1,3-bis(diphenylphosphine)propane, 1,4-bis(diphenylphosphine)butane, and at least one of the structures shown in the following 4a to 4h; preferably, the amount of the ligand is 4 to 10% of the molar amount of the allene compound;

[0018]

[0019] In the above synthesis method, the acid agent is selected from at least one of benzoic acid, 1-naphthoic acid, and p-nitrobenzoic acid, preferably benzoic acid; preferably, the amount of the acid agent is 0.5 to 1.0 times the molar amount of the allene compound, preferably 0.7 to 0.8 times;

[0020] and / or, the Lewis acid is selected from at least one of zinc fluoride, zinc bromide, zinc chloride, zinc acetate, zinc trifluoromethanesulfonate, magnesium chloride, and lithium chloride, preferably zinc chloride; preferably, the Lewis acid is used in an amount of 0.4 to 0.5 times the molar amount of the allene compound;

[0021] and / or, the alkaline agent is selected from at least one of tetramethylguanidine, 1,5-diazabicyclo[4.3.0]-5-nonene, potassium tert-butoxide, and quinuclidine, preferably tetramethylguanidine; preferably, the amount of the alkaline agent is 1 to 1.2 times the molar amount of the allene compound;

[0022] and / or, the solvent is selected from: at least one of tetrahydrofuran, toluene, p-xylene, and chlorobenzene, preferably toluene;

[0023] And / or, the protective atmosphere adopts protective gas; preferably, the protective gas is nitrogen or an inert gas, preferably nitrogen.

[0024] In the above synthesis method, in the structure of compound 1, R1 is selected from: phenyl; alkyl, halogen or nitro substituted phenyl; naphthyl; alkyl, halogen or nitro substituted naphthyl; straight chain alkyl or branched alkyl with 1 to 9 carbon atoms; cycloalkyl with no more than 6 carbon atoms; (CH2) n R6, n=1 or 2, R6 is selected from: cycloalkyl, phenyl, substituted phenyl, naphthyl, substituted naphthyl, alkenyl, alkylthio, ester group;

[0025] And / or, R2 is selected from: a linear alkyl group having 1 to 3 carbon atoms or a branched alkyl group having 3 carbon atoms.

[0026] And / or, in the structure of compound 2, R3 is selected from: phenyl; phenyl substituted by alkyl, alkoxy, halogen or aryl; naphthyl; naphthyl substituted by alkyl, alkoxy or halogen; benzyl; benzyl substituted by alkyl, alkoxy or halogen; phenethyl; phenethyl substituted by alkyl, alkoxy, halogen or aryl; four- to seven-membered ring lactam group; four- to seven-membered ring lactam group substituted by alkyl.

[0027] In the above synthesis method, R in the chiral aldehyde catalyst structure is selected from: H, TMS, phenyl, alkyl or halogen-substituted phenyl, CN, a straight-chain alkyl with 1 to 3 carbon atoms or a branched-chain alkyl with 3 carbon atoms, and halogen.

[0028] Furthermore, in the above synthesis method, a chiral α-allyl amino acid ester having a structure shown in Formula II is prepared using 1-phenyl allene and diethyl glutamate:

[0029]

[0030] The present invention also provides a chiral α-allyl amino acid ester, which is obtained by the above-mentioned synthesis method. The chiral α-allyl amino acid ester has a structure as shown in Formula 5 or a structure as shown in Formula II:

[0031]

[0032] The chiral α-allyl amino acid ester synthesis method of the present invention has a wide range of raw materials, is easy to obtain, and is low in price, has a wide range of reaction substrate selection, can realize a one-step catalytic reaction to construct an optically active α-allyl amino acid ester compound, has a short route and good universality, and the yield of most α-allyl amino acid ester compounds can reach more than 80%, and many α-allyl amino acid ester compounds with relatively special structures can also be obtained in one step by the synthesis method, achieving a breakthrough in the chemical synthesis of the system. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 This is the H NMR spectrum of compound 5a obtained in Example 1 of the present invention.

[0034] Figure 2 This is the NMR carbon spectrum of compound 5a obtained in Example 1 of the present invention.

[0035] Figure 3 The high performance liquid chromatogram of the racemic compound 5a obtained in Example 1 of the present invention.

[0036] Figure 4 This is the high performance liquid chromatogram of compound 5a obtained in Example 1 of the present invention. DETAILED DESCRIPTION

[0037] In the description of the present invention, it should be noted that, if the specific conditions are not specified in the examples, the experiments were carried out according to conventional conditions or the conditions recommended by the manufacturer. The reagents or instruments used, if the manufacturer is not specified, are all conventional products that can be purchased commercially.

[0038] It should be further explained that the ee% value of the present invention only retains integer digits.

[0039] The present invention is further described in detail below in conjunction with the accompanying drawings and specific embodiments, which are intended to explain the present invention rather than to limit it.

[0040] Example 1

[0041] In this embodiment, α-benzyl-α-aminoethyl acetate and phenyl allene are used as starting materials, [Pd(C3H5)Cl]2 is used as palladium metal catalyst, and the reaction effects of different chiral aldehyde catalysts, acid agents, solvents, alkaline agents, and ligands are investigated. The specific experimental process includes: under nitrogen (N2) atmosphere, metal palladium catalyst, ligand and solvent (0.5mL) are added to a dry reaction tube, and the reaction system is stirred at room temperature for 30min. Compound 1a (0.4mmol), compound 2a (0.2mmol), acid agent, chiral aldehyde catalyst, Lewis acid and alkaline agent, solvent (0.5mL) are added to the reaction vessel, and the reaction is continued at 60°C. The reaction progress is detected by high-phase liquid chromatography (combined with TLC) until compound 2a completely disappears. After the reaction mixture is concentrated under reduced pressure, α-allyl amino acid ester compound 5a is obtained by column chromatography.

[0042] In the above synthesis process, the amounts of metal palladium catalyst, ligand, acid agent, chiral aldehyde catalyst, Lewis acid and base agent are based on the molar amount of compound 2a, as shown in the molar feed percentage in the reaction equation of the parameter investigation process below.

[0043] (1) Screening of chiral aldehyde catalysts: The results are shown in Table 1.

[0044]

[0045] Table 1

[0046] serial number Chiral aldehyde catalyst Reaction time (h) Yield (%) ee(%) 1 3a 15.5 35 80 2 3b 12 51 85 3 3c 15.5 34 76 4 ent-3d 27 21 65 5 3e 15.5 32 65 6 3f 15.5 38 84 7 3g 12 48 80 8 ent-3h 12 52 82 9 3i 12 39 77

[0047] Note: ent means enantiomer.

[0048] The results in Table 1 show that compound 5a can be obtained by using the above chiral aldehyde catalysts, but the yields of 3b and ent-3h are relatively high. 3b has the best enantioselectivity, so 3b is preferably used as the chiral aldehyde catalyst.

[0049] (2) Screening of acid agents: The results are shown in Table 2.

[0050]

[0051] Table 2

[0052]

[0053]

[0054] The results in Table 2 show that compound 5a can be obtained by using the above acid agents, but the yield and enantioselectivity of benzoic acid are relatively high, followed by p-nitrobenzoic acid and 1-naphthoic acid, and the enantioselectivity of 1-naphthoic acid is the best. Therefore, benzoic acid is preferably used as the acid agent.

[0055] (3) Screening of solvents: The results are shown in Table 3.

[0056]

[0057] Table 3

[0058] serial number Solvents Reaction time (h) Yield (%) ee(%) 1 Tetrahydrofuran 14 46 70 2 1,2-Dichloroethane 15.5 28 44 3 Toluene 12 51 85 4 Ethylbenzene 15.5 33 86 5 o-Xylene 15.5 22 87 6 Meta-Xylene 14 21 85 7 p-Xylene 12 46 86 8 Mesitylene 15.5 20 85 9 chlorobenzene 15.5 48 78

[0059] The results in Table 3 show that compound 5a can be obtained by using the above solvents, but the reaction time using toluene and p-xylene is relatively short, and the yield and enantioselectivity are relatively high, followed by chlorobenzene and tetrahydrofuran, but the enantioselectivity results of these two solvents are not ideal. Comprehensively speaking, toluene is preferred as the solvent.

[0060] (4) Screening of alkali agents: The results are shown in Table 4.

[0061]

[0062] Table 4

[0063] serial number Alkali Reaction time (h) Yield (%) ee(%) 1 TMG 12 51 85 2 DBN 21 42 82 3 Potassium tert-butoxide 21 62 82 4 Quinuclidine 21 49 86

[0064] The results in Table 4 show that the above bases can all be used to obtain compound 5a, among which potassium tert-butoxide has the highest reaction yield, but the reaction time is relatively long, followed by quinuclidine as the base, which has the best enantioselectivity, but the yield is only 49%. When TMG is used as the base, the reaction time is the shortest, the yield can also reach more than 50%, and the enantioselectivity is as high as 85%. It is generally preferred to use TMG as the base.

[0065] (5) Screening of benzoic acid equivalents: The results are shown in Table 5.

[0066] Table 5

[0067] serial number PhCOOH (x mol%) Reaction time (h) Yield (%) ee(%) 1 30 12 16 86 2 50 12 51 85 3 60 12 53 85 4 70 12 58 85 5 80 12 65 83 6 100 12 48 84

[0068] Note: x mol% is based on the molar percentage of PhCOOH in compound 2a.

[0069] The results in Table 5 show that as the amount of benzoic acid gradually increases, the yield increases first and then decreases. The yield is highest when it reaches 80 mol%, and the enantioselectivity is relatively high at this time. Therefore, it is better to control the amount of benzoic acid to 70 mol% to 80 mol% of the molar percentage of compound 2a.

[0070] (6) Screening of Lewis acid types: The results are shown in Table 6.

[0071]

[0072] Table 6

[0073] serial number Lewis acid Reaction time (h) Yield (%) ee(%) 1 <![CDATA[ZnF2]]> 12 51 83 2 <![CDATA[ZnCl2]]> 12 65 83 3 <![CDATA[ZnBr2]]> 12 55 76 4 <![CDATA[Zn(OAc)2]]> 12 58 82 5 <![CDATA[Zn(OTf)2]]> 12 43 82 6 <![CDATA[MgCl2]]> 12 61 39 7 LiCl 12 58 15

[0074] The results in Table 6 show that when the Lewis acid is zinc chloride, the reaction effect is the best.

[0075] (7) Screening of palladium catalyst: The results are shown in Table 7.

[0076]

[0077] Table 7

[0078] serial number Palladium metal catalyst Reaction time (h) Yield (%) ee(%) 1 <![CDATA[[Pd(C3H5)Cl]2]]> 12 65 83 2 <![CDATA[Pd(PPh3)4]]> 12 23 82 3 <h2 style=";text-align:left;direction:ltr"><![CDATA[Pd2(dba) <h2 style=";text-align:left;direction:ltr"> 3. <h2 style=";text-align:left;direction:ltr"> CHCl3<h2 style=";text-align:left;direction:ltr"> 12 trace nd 4 <![CDATA[Pd(OAc)2]]> 12 trace nd 5 <![CDATA[Pd(dppf)Cl2]]> 12 trace nd

[0079] Note: trace means trace, and nd means not detected.

[0080] The results in Table 7 show that among the five palladium catalysts currently used, only [Pd(C3H5)Cl]2 has a good reaction effect.

[0081] (8) Ligand screening: The results are shown in Table 8.

[0082]

[0083] Table 8

[0084]

[0085]

[0086] The results in Table 8 show that PPh3, dppm, and dpppe as ligand combination 3b as chiral aldehyde catalysts cannot obtain compound 5a, while the reaction effects of ent-4a combination 3b, ent-4b combination ent-3b, 4d combination 3b, 4e combination ent-3b, and 4g combination ent-3b are relatively good, among which the reaction effect of 4b combination 3b is the best.

[0087] (9) Temperature screening: The results are shown in Table 9.

[0088]

[0089] Table 9

[0090] serial number temperature Reaction time (h) Yield (%) ee(%) 1 60 12 95 93 2 50 12 62 93

[0091] The results in Table 9 show that when the temperature is 50°C, the yield decreases significantly, so 60°C is selected as the reaction temperature.

[0092] In summary, the optimal parameters for synthesizing 5a obtained in the above experimental exploration process are as follows:

[0093] Under nitrogen (N2) atmosphere, [Pd(C3H5)Cl]2 catalyst (0.01mmol), ligand 4b (0.01mmol) and toluene (0.5mL) were added to a dry reaction tube, and the reaction system was stirred at room temperature for about 30min. Compound 1a (0.4mmol), compound 2a (0.2mmol), benzoic acid (0.16mol), chiral aldehyde catalyst 3b (0.02mmol), zinc chloride (0.08mmol) and alkaline agent TMG (0.2mmol), toluene (0.5mL) were added to the reaction container, and the reaction was continued at 60°C. The reaction progress was detected by high-performance liquid chromatography (combined with TLC) until compound 2a completely disappeared. The reaction mixture was concentrated under reduced pressure and then column chromatography was performed to obtain α-allyl amino acid ester compound 5a.

[0094] The data representation of 5a is as follows:

[0095] Ethyl(S,E)-2-amino-2-benzyl-5-phenylpent-4-enoate:

[0096] 1) Colorless oily liquid (58.6 mg, 95%);

[0097] 2) R f =0.29 (petroleum ether / ethyl acetate=4:1);

[0098] 3) The enantiomeric excess was determined to be 93% by HPLC analysis (n-hexane / isopropanol = 90 / 10, flow rate 1 mL / min, T = 30°C); UV 254 nm, t R (minor)6.852min;t R (major)8.399min;

[0099] 4)[α] D 25 =–12.5 (c = 0.41, CHCl3);

[0100] 5) 1 H NMR (600MHz,CDCl3):δ7.54(d,J=12.0Hz,2H),7.42(d,J=6.0Hz,2H),7.30–7.24(m,4H),7.18–7.16(m,2H),6.54(d,J=18.0Hz,1H),6.26–6.20(m,1H),4.21–4.14(m,2H),3.23(d,J=12.0Hz,1H),2.89–2.83(m,2H),2.52–2.48(m,1H),1.59(s,2H),1.27(t,J=6.0Hz,3H). Figure 1 shown.

[0101] 6) 13 C NMR (151MHz, CDCl3): δ176.01, 137.10, 136.33, 134.52, 130.02, 128.50, 128.33, 127.41, 126.94, 126.23, 124.05, 62.06, 61.05, 45.93, 43.86, 14.28. Figure 2 shown.

[0102] 7) The HPLC chromatogram of compound 5a is as follows Figure 4 As shown, the HPLC chromatogram of the racemic compound 5a was used as a reference ( Figure 3 ).

[0103] Example 2

[0104] In this example, the optimal parameters in Example 1 were used to synthesize a series of chiral α-allyl amino acid esters, and the universality of the synthesis method was verified. The results of the obtained series of chiral α-allyl amino acid esters are shown in Table 10.

[0105] The specific operation is as follows: under nitrogen (N2) atmosphere, metal palladium catalyst (0.01mmol), ligand 4b (0.02mmol) and toluene (0.5mL) were added to a dry reaction tube, and the reaction system was stirred at room temperature for 30min. Compound 1 (0.4mmol), compound 2 (0.2mmol), benzoic acid (0.16mmol), chiral aldehyde catalyst 3b (0.02mmol), zinc chloride (0.08mmol) and tetramethyl guanidine (0.2mmol), toluene (0.5mL), continue to react at 60°C, and detect the reaction progress by high-performance liquid chromatography (TLC). When compound 2 completely disappears, the reaction mixture is concentrated under reduced pressure and then purified by column chromatography to obtain an α-allyl amino acid ester compound.

[0106] Table 10

[0107]

[0108]

[0109]

[0110]

[0111]

[0112]

[0113] The α-allyl amino acid ester compounds in Table 10 were all identified by NMR.

[0114] The above-mentioned embodiments only express several implementation methods of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A method for synthesizing chiral α-allyl amino acid esters, characterized in that: The synthesis method comprises: preparing a chiral α-allyl amino acid ester compound 5 using an α-amino acid ester compound 1 having a free amino group and an allene compound 2: R1 is selected from: phenyl; phenyl substituted with halogen or nitro; naphthyl; naphthyl substituted with halogen or nitro; straight-chain or branched alkyl with 1 to 9 carbon atoms; cycloalkyl with no more than 6 carbon atoms; (CH2) n R6, n = 1 or 2, R6 is selected from: phenyl or naphthyl; R2 is selected from: a straight chain alkyl group having 1 to 3 carbon atoms or a branched chain alkyl group having 3 carbon atoms; R3 is selected from the group consisting of: phenyl; halogen-substituted phenyl; naphthyl; halogen-substituted naphthyl; benzyl; halogen-substituted benzyl; phenethyl; halogen-substituted phenethyl; a four- to seven-membered ring lactam group; Among them, in the reaction of preparing chiral α-allyl amino acid ester from α-amino acid ester compound 1 having free amino group and allene compound 2, the reaction is achieved by combined catalysis of chiral aldehyde catalyst and palladium metal catalyst; The chiral aldehyde catalyst has a structure shown in Formula I: In compound I, R is selected from the group consisting of: H, TMS, phenyl, phenyl substituted with halogen, CN, a linear alkyl group having 1 to 3 carbon atoms or a branched alkyl group having 3 carbon atoms, and halogen; The palladium metal catalyst is selected from: [Pd(C3H5)Cl]2 or Pd(PPh3)4; The steps of the synthetic method are as follows: An α-amino acid ester compound 1 having a free amino group, an allene compound 2, a palladium metal catalyst, a chiral aldehyde catalyst, a ligand, an acid agent, a Lewis acid and a base agent are reacted in a solvent to prepare a chiral α-allyl amino acid ester; The acid agent is selected from at least one of benzoic acid, 1-naphthoic acid, and p-nitrobenzoic acid; The solvent is selected from: at least one of tetrahydrofuran, toluene, p-xylene, and chlorobenzene; The alkaline agent is selected from at least one of tetramethylguanidine, 1,5-diazabicyclo[4.3.0]-5-nonene, potassium tert-butoxide, and quinuclidine; The ligand is selected from: 1,2-bis(diphenylphosphine)ethane, 1,3-bis(diphenylphosphine)propane, 1,4-bis(diphenylphosphine)butane, and at least one of the structures shown in the following 4a to 4h; 2. The method for synthesizing chiral α-allyl amino acid esters according to claim 1, characterized in that: The molar ratio of the allene compound to the α-amino acid ester compound with free amino group is 1:2-2.5; the reaction is carried out under an inert atmosphere; the reaction temperature is 60±5°C; and then the reaction mixture is concentrated and purified by chromatography.

3. The method for synthesizing chiral α-allyl amino acid ester according to claim 2, characterized in that: The molar ratio of the allene compound to the chiral aldehyde catalyst is 1:0.05-0.

1.

4. The method for synthesizing chiral α-allyl amino acid ester according to claim 2, characterized in that: The amount of the palladium metal catalyst used is 2-5% of the molar amount of the allene compound.

5. The method for synthesizing chiral α-allyl amino acid ester according to claim 2, characterized in that: The amount of the ligand used is 4-10% of the molar amount of the allene compound.

6. The method for synthesizing chiral α-allyl amino acid ester according to claim 2, characterized in that: The amount of the acid agent used is 0.5 to 1.0 times the molar amount of the allene compound.

7. The method for synthesizing chiral α-allyl amino acid esters according to claim 2, characterized in that: The Lewis acid is selected from at least one of zinc fluoride, zinc bromide, zinc chloride, zinc acetate, zinc trifluoromethanesulfonate, magnesium chloride and lithium chloride.

8. The method for synthesizing chiral α-allyl amino acid esters according to claim 2, characterized in that: The amount of the Lewis acid used is 0.4 to 0.5 times the molar amount of the allene compound.

9. The method for synthesizing chiral α-allyl amino acid esters according to claim 2, characterized in that: The amount of the alkali agent used is 1 to 1.2 times the molar amount of the allene compound.

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