A process for the asymmetric alkylation of a chain-like racemic allyl ether

Abstract

The application relates to a method for asymmetric alkylation reaction of a chain racemic allyl ether, which comprises the following steps: uniformly mixing a chain racemic allyl ether, a Grignard reagent, a phosphoramidite ligand, a catalyst, boron trifluoride ether and a solvent, and carrying out asymmetric allyl alkylation reaction to prepare an asymmetric allyl alkyl compound; the asymmetric allyl alkyl compound has the following structural formula: wherein, R 1 is a primary alkyl or secondary alkyl, R 2 is a primary alkyl, and the asymmetric allyl alkyl compound is a mixture containing Z configuration and E configuration. The application utilizes the chain racemic allyl methyl ether as a substrate to carry out asymmetric allyl alkylation reaction, and constructs a chain olefin with optical activity. The chain racemic allyl methyl ether as a raw material has excellent reaction activity and enantioselectivity, is high in stability, is not prone to deterioration, and is easy to store.

Description

Technical Field

[0001] This invention relates to the field of chemical synthesis technology, specifically to a method for the asymmetric alkylation reaction of chain-like racemic allyl ethers. Background Technology

[0002] Asymmetric alkylation reactions using racemic compounds as substrates are an important method for constructing chiral carbon-carbon bonds and are widely used in the synthesis of natural products and biologically active compounds. Racemic compounds are those containing two enantiomers in equal proportions, resulting in zero optical rotation. Compared to chiral substrates without chiral components, these substrates present a more complex and challenging reaction process due to the presence of chirality.

[0003] Current research on the asymmetric alkylation of racemic allyl substrates still faces certain limitations. Previous studies often used chain-like allyl halides for asymmetric alkylation reactions; however, these substrates are highly sensitive, unstable, and require stringent storage conditions. They deteriorate rapidly at room temperature and readily react with nucleophiles, leading to the removal of halogen or ester groups, thus limiting their application in multi-step reactions. Therefore, researching the asymmetric alkylation of stable racemic ether substrates is crucial. Furthermore, these substrates perform poorly with nucleophiles containing secondary alkyl groups. Although cyclic racemic allyl ether substrates with fixed skeletons that cannot rotate have been successfully developed (application number CN202211115323.6, authorization announcement number CN 115583863 B), chain-like racemic allyl ether substrates remain undeveloped.

[0004] In the asymmetric allylic alkylation of cyclic racemic allyl ether substrates, carbon-carbon single bond rotation does not occur, resulting only in a single Z-configuration product. However, in the asymmetric alkylation of chain racemic allyl ether substrates, single bond rotation occurs, leading to the formation of two distinct intermediates: pro-Z and pro-E. For linear substrates, this results in a mixture of Z and E configurations, posing a greater challenge to enantioselectivity control. Furthermore, the catalytic system described in patent application CN202211115323.6 is not applicable to linear substrates. For chain substrates, using the catalytic conditions disclosed for cyclic substrates, the best results are: the reaction produces both Z and E configurations, with the Z configuration product having an ee of 85%, but the E configuration product having an ee of only 7%. This also illustrates that, due to the different reaction mechanisms of cyclic substrates (enantiomeric aggregation) and chain substrates (stereoscopic divergent kinetic resolution), the reaction conditions of cyclic substrates and chain substrates are significantly different. Summary of the Invention

[0005] Therefore, it is necessary to provide a method for the asymmetric alkylation reaction of chain racemic allyl ethers, aiming to solve the technical problems of substrate sensitivity and low ee value of reaction products in the asymmetric alkylation reaction of racemic compounds in the prior art.

[0006] To achieve the above objectives, the present invention provides a technical solution:

[0007] A method for the asymmetric alkylation reaction of chain-like racemic allyl ethers, comprising the following steps:

[0008] A chain-like racemic allyl methyl ether, Grignard reagent, phosphoramidite ligand, catalyst, boron trifluoride diethyl ether, and solvent are mixed evenly to undergo an asymmetric allyl alkylation reaction, yielding an asymmetric allyl alkyl compound.

[0009] The structural formula of the asymmetric allyl alkyl compound is as follows:

[0010]

[0011] Wherein, R1 is a primary alkyl or secondary alkyl, R2 is a primary alkyl, and the asymmetric allyl alkyl compound is a mixture containing Z configuration and E configuration.

[0012] Preferably, the phosphoramidite ligand comprises at least one of the following molecular structural formulas:

[0013]

[0014]

[0015] Preferably, the Grignard reagent includes at least one of methyl magnesium bromide, ethyl magnesium bromide, n-butyl magnesium bromide, isobutyl magnesium bromide, n-heptyl magnesium bromide, 4-methyl-3-n-pentenyl magnesium bromide, phenethyl magnesium bromide, isopropyl magnesium bromide, cyclobutyl magnesium bromide, cyclohexyl magnesium bromide, cycloheptyl magnesium bromide, cyclopentyl magnesium bromide, methyl magnesium chloride, ethyl magnesium chloride, n-butyl magnesium chloride, isobutyl magnesium chloride, n-heptyl magnesium chloride, 4-methyl-3-n-pentenyl magnesium chloride, phenethyl magnesium chloride, isopropyl magnesium chloride, cyclobutyl magnesium chloride, cyclohexyl magnesium chloride, cycloheptyl magnesium chloride, methyl magnesium chloride, ethyl magnesium chloride, n-butyl magnesium chloride, isobutyl magnesium chloride, n-heptyl magnesium chloride, 4-methyl-3-n-pentenyl magnesium chloride, phenethyl magnesium chloride, isopropyl magnesium chloride, cyclobutyl magnesium chloride, cyclohexyl magnesium chloride, cycloheptyl magnesium chloride, and cyclopentyl magnesium chloride.

[0016] Preferably, the catalyst comprises at least one of cuprous bromide dimethyl sulfide, cuprous chloride, cuprous iodide, cuprous thiophene-2-carboxylate, and copper trifluoromethanesulfonate.

[0017] Preferably, the solvent includes at least one selected from toluene, dichloromethane, diethyl ether, tetrahydrofuran, and p-xylene.

[0018] Preferably, the molar ratio of the chain-like racemic allyl methyl ether, the phosphoramidite ligand, the catalyst, the boron trifluoride ethyl ether, and the Grignard reagent is 1:(0.05~0.20):(0.05~0.20):(0.50~3.00):(0.50~3.00).

[0019] Preferably, the specific steps of the method for the asymmetric alkylation reaction of the chain-like racemic allyl ether include:

[0020] S1. Under the protection of an inert gas, the phosphoramide ligand, the catalyst, and the solvent are added to a container and mixed evenly to obtain a first mixture;

[0021] S2. Add the chain-like racemic allyl methyl ether to the first mixed liquid to obtain a second mixture;

[0022] S3. Add the boron trifluoride ether and the Grignard reagent to the second mixture. After the addition is complete, keep the mixture warm for 0.5 to 4 hours to obtain the third mixture.

[0023] S4. The reaction of the third mixture is quenched with a quenching agent, then the organic phase is extracted and washed, dried and concentrated to obtain the asymmetric allyl alkyl compound.

[0024] Preferably, the quenching agent includes any one of saturated ammonium chloride solution, saturated hydrochloric acid solution, ethanol, and methanol.

[0025] Preferably, the reaction temperature of the heat preservation reaction is -20 to -78°C.

[0026] Preferably, the Grignard reagent needs to be dissolved in ether before use.

[0027] The beneficial effects of this invention are:

[0028] This invention utilizes chain-like racemic allyl methyl ether as a substrate for asymmetric alkylation reactions. Because the leaving power of the methoxy group is several orders of magnitude weaker than that of halogens and phospholipids, the chain-like racemic allyl methyl ether used as a raw material exhibits high stability, is not easily degraded, and is easy to store, remaining stable at room temperature for at least 30 days. Furthermore, by adding a Lewis acid to activate the substrate during the reaction, the reactivity of the substrate can be effectively improved, allowing the desymmetry reaction to occur effectively, thus solving the technical problem of substrate sensitivity in the asymmetric alkylation reaction of chain-like allyl halides in existing technologies. Simultaneously, the suitability of this type of substrate for nucleophiles of secondary alkyl groups is significantly improved; compared to using allyl halides as substrates, the ee value of the product is significantly increased, solving the technical problem of poor substrate performance for nucleophiles of secondary alkyl groups in the asymmetric alkylation reaction of chain-like allyl halides in existing technologies. Detailed Implementation

[0029] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0030] Unless otherwise specified, the experimental methods used in the following examples are conventional methods. Unless otherwise specified, the experimental materials and reagents used in the following examples are commercially available. All quantitative experiments in the following examples were performed in triplicate, and the data are the average of the three replicates or the average ± standard deviation.

[0031] Furthermore, the term "and / or" in the text includes three solutions. Taking A and / or B as an example, it includes technical solution A, technical solution B, and technical solution that simultaneously satisfies both A and B. In addition, the technical solutions of various embodiments can be combined with each other, but this must be based on the ability of a person skilled in the art to implement them. When the combination of technical solutions is contradictory or cannot be implemented, it should be considered that such combination of technical solutions does not exist and is not within the scope of protection claimed by this invention.

[0032] Embodiments of the present invention provide a method for the asymmetric alkylation reaction of chain-like racemic allyl ethers, comprising the following steps:

[0033] A chain-like racemic allyl methyl ether, Grignard reagent, phosphoramidite ligand, catalyst, boron trifluoride diethyl ether, and solvent are mixed evenly to undergo an asymmetric allyl alkylation reaction, yielding an asymmetric allyl alkyl compound.

[0034] The structural formula of the asymmetric allyl alkyl compound is as follows:

[0035]

[0036] Among them, R 1 It is a primary alkyl or secondary alkyl group, R 2 It is a primary alkyl group, and the asymmetric allyl alkyl compound is a mixture containing Z and E configurations.

[0037] This invention utilizes chain-like racemic allyl methyl ether as a substrate for deasymmetric alkylation reaction. The cyclic chain-like racemic allyl methyl ether used as a raw material not only has excellent reactivity and enantioselectivity, but also has high stability, is not easily deteriorated, and is easy to store.

[0038] Specifically, the asymmetric alkylation of chain-like racemic allyl methyl ethers is a nucleophilic substitution reaction, and the reaction rate is positively correlated with the leaving ability of the substituents in the substrate. Most of the substrates used previously are chain-like racemic allyl halides. However, the leaving ability of the alkoxy group in chain-like racemic allyl methyl ether substrates is several orders of magnitude lower than that of halides and phospholipids. Therefore, chain-like racemic allyl methyl ether substrates are more stable, less prone to deterioration, easier to store, and more challenging than chain-like racemic allyl halides. Furthermore, cyclic racemic allyl ether substrates with fixed skeletons do not undergo carbon-carbon single bond rotation during the reaction, producing only a single Z-configuration product. In contrast, chain-like racemic allyl methyl ether substrates undergo carbon-carbon single bond rotation during the reaction, generating both pro-Z and pro-E intermediates, resulting in two Z / E products. This also presents a significant challenge to the enantioselectivity control of the reaction, making it even more challenging. This also illustrates that, due to the different reaction mechanisms of cyclic substrates (enantiomeric aggregation) and chain substrates (stereoscopic divergent kinetic resolution), the reaction conditions of cyclic substrates and chain substrates are significantly different.

[0039] Preferably, the method for asymmetric allyl alkylation reaction includes the following specific steps:

[0040] S1. Under the protection of an inert gas, the phosphoramide ligand, the catalyst, and the solvent are added to a container and mixed evenly to obtain a first mixture.

[0041] Preferably, the phosphoramide ligand comprises at least one of the following molecular structural formulas:

[0042]

[0043] Preferably, the catalyst includes at least one of cuprous bromide dimethyl sulfide, cuprous chloride, cuprous iodide, cuprous thiophene-2-carboxylate, and copper trifluoromethanesulfonate.

[0044] Preferably, the solvent includes at least one of toluene, dichloromethane, diethyl ether, tetrahydrofuran, and p-xylene.

[0045] Preferably, the container is a dry Schlenk reaction tube equipped with a stir bar.

[0046] Preferably, the Grignard reagent is dissolved in diethyl ether. Specifically, Grignard reagents readily react with water, acid, or air, releasing flammable gases. Therefore, the Grignard reagent is dissolved in diethyl ether and the reaction needs to be carried out under the protection of an inert gas.

[0047] S2. Add the chain-like racemic allyl methyl ether to the first mixed liquid to obtain a second mixture;

[0048] Specifically, in step S2, the temperature is -78°C.

[0049] S3. Add the boron trifluoride ether and the Grignard reagent to the second mixture. After the addition is complete, keep the mixture warm for 0.5 to 4 hours to obtain the third mixture.

[0050] Specifically, the reaction temperature for the heat preservation reaction is -20 to -78℃.

[0051] Preferably, the Grignard reagent includes at least one of methyl magnesium bromide, ethyl magnesium bromide, n-butyl magnesium bromide, isobutyl magnesium bromide, n-heptyl magnesium bromide, 4-methyl-3-n-pentenyl magnesium bromide, phenethyl magnesium bromide, isopropyl magnesium bromide, cyclobutyl magnesium bromide, cyclohexyl magnesium bromide, cycloheptyl magnesium bromide, cyclopentyl magnesium bromide, methyl magnesium chloride, ethyl magnesium chloride, n-butyl magnesium chloride, isobutyl magnesium chloride, n-heptyl magnesium chloride, 4-methyl-3-n-pentenyl magnesium chloride, phenethyl magnesium chloride, isopropyl magnesium chloride, cyclobutyl magnesium chloride, cyclohexyl magnesium chloride, cycloheptyl magnesium chloride, and cyclopentyl magnesium chloride.

[0052] Specifically, the reaction formula for the asymmetric allyl alkylation reaction in one embodiment is as follows:

[0053]

[0054] Where L is the phosphoramidite ligand, and R... 1 It is a primary alkyl or secondary alkyl group, R 2 It is a primary alkyl group; asymmetric allyl alkyl compounds are mixtures containing Z and E configurations.

[0055] More specifically, the asymmetric allyl alkyl compound is any one of the following compounds a to g:

[0056]

[0057] Preferably, the molar ratio of the chain-like racemic allyl methyl ether, the phosphoramide ligand, the catalyst, the boron trifluoride ethyl ether, and the Grignard reagent is 1:(0.05~0.20):(0.05~0.20):(0.50~3.00):(0.50~3.00).

[0058] S4. The reaction of the third mixture is quenched with a quenching agent, then the organic phase is extracted and washed, dried and concentrated to obtain the asymmetric allyl alkyl compound.

[0059] Preferably, the quenching agent includes any one of saturated ammonium chloride solution, saturated hydrochloric acid solution, ethanol, and methanol.

[0060] Preferably, the extractant is ethyl acetate.

[0061] Preferably, the detergent is a mixture of water and salt water.

[0062] Preferably, the desiccant is anhydrous magnesium sulfate.

[0063] The following are specific embodiments. Unless otherwise specified, the raw materials used in the embodiments are all commercially available products.

[0064] Example 1

[0065] Synthesis of asymmetric allyl alkyl compound a

[0066] S1. Add 0.02 mol of phosphorus amide ligand L13 and 0.01 mmol of cuprous chloride to a dry Schlenk reaction tube equipped with a stir bar and mix thoroughly. Replace the argon gas three times with a vacuum pump. Under the protection of argon gas, add 2.0 mL of dichloromethane (DCM) and stir at 25 °C for 15 min to obtain the first mixture.

[0067] S2. Add 0.2 mmol (E)-7-methoxy-5-undecene to the first mixture, cool to -78°C and maintain for 10 min to obtain the second mixture;

[0068] S3. Add 0.4 mmol of boron trifluoride ether and 0.4 mL of 1 mol / L ethyl magnesium bromide solution (solvent is ether) to the second mixture using a syringe pump. After the addition is complete, keep the mixture at -78℃ for 2 h to obtain the third mixture.

[0069] S4. The reaction of the third mixture was quenched with 2.0 mL of saturated NH4Cl aqueous solution. The mixture was then diluted with 10 mL of ethyl acetate for extraction, washed with a mixture of water and brine, and the organic phase was dried with anhydrous magnesium sulfate. The mixture was then filtered and concentrated under reduced pressure to obtain compound a.

[0070] The expected product was obtained by silica gel column chromatography with a separation yield of 90%, Z / E = 53:47, Z configuration ee value of 93%, and E configuration ee value of 96%.

[0071] The NMR data for compound a are as follows:

[0072] 1 H NMR(400MHz,Chloroform-d)δ5.44–5.25(m,1H),5.13–4.94(m,1H),2.19(ddq,J=13.7,9.2,4.7Hz,1H Z ),2.00(ddt,J=10.4,8.5,3.6Hz,2H),1.76(qt,J=8.9,4.8Hz,1H E ),1.44–1.23(m,9H),1.22–1.08(m,3H),0.94–0.79(m,9H).

[0073] Examples 2-7 follow the same preparation steps as Example 1, except for the formulation and ratio of the reaction raw materials (Table 1) and the reaction conditions (Table 2).

[0074] Table 1

[0075]

[0076]

[0077] Table 2

[0078]

[0079] The yields, Z / E values, Z configuration ee values, and E configuration ee values ​​of the products prepared in Examples 1-7 are shown in Table 3.

[0080] Table 3

[0081] product a b c d e f g Yield / % 90 74 86 81 91 92 88 Z / E 53:47 64:36 53:47 63:37 55:45 54:46 52:48 Z-configuration ee value / % 93 98 95 97 83 85 92 E configuration ee value / % 96 82 91 95 62 98 93

[0082] The NMR data of compound b prepared in Example 2 are as follows:

[0083] 1 H NMR(400MHz,Chloroform-d)δ5.38–5.21(m,1H+1H E ),5.10(ddd,J=10.9,9.6,1.6Hz,1H Z ),2.41(dq,J=15.4,6.1Hz,1H),2.07–1.94(m,2H+1H E),1.35–1.28(m,5H),1.27–1.19(m,5H),0.95–0.86(m,9H).

[0084] The NMR data of compound c prepared in Example 3 are as follows:

[0085] 1 H NMR(400MHz,Chloroform-d)δ5.44–5.33(m,1H),5.08(ddt,J=15.2,8.8,1.5Hz,1H E ),5.02–4.94(m,1H Z ),2.18(qt, J=9.1, 4.4Hz, 1H) Z ),2.09–1.96(m,2H),1.76(qt,J=8.8,4.7Hz,1H E ),1.47–1.11(m,8H),0.96(q,J=7.6Hz,3H),0.89–0.80(m,6H).

[0086] The NMR data of compound d prepared in Example 4 are as follows:

[0087] 1 H NMR(400MHz,Chloroform-d)δ5.45–5.32(m,1H),5.08(ddd,J=15.3,8.8,1.5Hz,1H E ), 5.02–4.93 (m, 1H) Z ),2.25–2.12(m,1H Z ),2.08–1.96(m,2H),1.79–1.72(m,1H E ),1.33–1.19(m,14H),1.01–0.92(m,3H),0.88(t,J=6.7Hz,3H),0.85–0.80(m,3H).

[0088] The NMR data of compound e prepared in Example 5 are as follows:

[0089] 1 H NMR (400MHz, Chloroform-d) δ5.41 (dt, J=11.2, 7.2Hz, 1H Z ),5.30(dt,J=14.0,6.7Hz,1H E ),5.16–5.04(m,1H),2.15–2.06(m,1H Z),2.00(dq,J=9.2,6.4,5.1Hz,2H),1.67(tt,J=9.2,4.8Hz,1H E ),1.56–1.47(m,1H),1.44–1.35(m,1H),1.34–1.28(m,4H),1.28–1.21(m,3H),1.20–1.09(m,2H),0.91–0.83(m,9H),0.83–0.78(m,3H).

[0090] The NMR data of compound f prepared in Example 6 are as follows:

[0091] 1 H NMR(400MHz,Chloroform-d)δ5.48–5.21(m,2H),2.37–2.23(m,1H) Z ), 1.97–1.86 (m, 1H) E ),1.80–1.69(m,4H),1.69–1.61(m,4H),1.27–1.07(m,6H),0.95(t,J=7.0Hz,3H).

[0092] The NMR data of compound g prepared in Example 7 are as follows:

[0093] 1 H NMR(400MHz,Chloroform-d)δ5.44–5.26(m,1H),5.12–4.96(m,1H),2.18(ddq,J=13.7,9.1,4.3Hz,1H Z ),2.05–1.94(m,2H),1.76(tt,J=8.8,5.6Hz,1H E ),1.43–1.10(m,20H),0.90–0.85(m,6H),0.82(td,J=7.4,2.8Hz,3H).

[0094] The difference between Comparative Example 1 and Example 6 is that an equal amount of the reaction substrate (E)-4-methoxy-2-pentene was replaced with an equal amount of allyl chloride, and boron trifluoride diethyl ether was not added. The reaction yield was 87%, Z / E = 52:48, the ee value for the Z configuration was 76%, and the ee value for the E configuration was 80%. This comparative example demonstrates that this technique overcomes the technical difficulty of the inapplicability of chain allyl halides to nucleophiles of secondary alkyl groups in previously disclosed methods.

[0095] The difference between Comparative Example 2 and Example 1 is that the ligand used in the reaction is replaced with the optimal ligand of the cyclic allyl ether substrate in the disclosed method (application number CN202211115323.6). The reaction yield was 75%, Z / E = 70:30, Z configuration ee value was 85%, and E configuration ee value was 7%. This comparative example demonstrates that the catalytic system for the asymmetric alkylation of cyclic allyl methyl ethers in previously disclosed methods is not applicable to chain allyl methyl ethers. This technique is not a simple extension of previously disclosed methods, but rather a completely new catalytic system.

[0096] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0097] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention. Therefore, the protection scope of this invention patent should be determined by the appended claims.

Claims

1. A method for the asymmetric alkylation reaction of chain-like racemic allyl ethers, characterized in that, Includes the following steps: A chain-like racemic allyl methyl ether, Grignard reagent, phosphoramide ligand, catalyst, boron trifluoride diethyl ether and solvent are mixed evenly to undergo an asymmetric allyl alkylation reaction to obtain an asymmetric allyl alkyl compound; the reaction temperature is -20~-78℃. The structural formula of the chain-like racemic allyl methyl ether is as follows: ； The structural formula of the asymmetric allyl alkyl compound is as follows: ； Among them, R 1 It is a primary alkyl or secondary alkyl group, R 2 It is a primary alkyl group, and the asymmetric allyl alkyl compound is a mixture containing Z and E configurations; Grignard reagents include at least one of the following: methyl magnesium bromide, ethyl magnesium bromide, n-butyl magnesium bromide, isobutyl magnesium bromide, n-heptyl magnesium bromide, 4-methyl-3-n-pentenyl magnesium bromide, phenethyl magnesium bromide, isopropyl magnesium bromide, cyclobutyl magnesium bromide, cyclohexyl magnesium bromide, cycloheptyl magnesium bromide, cyclopentyl magnesium bromide, methyl magnesium chloride, ethyl magnesium chloride, n-butyl magnesium chloride, isobutyl magnesium chloride, n-heptyl magnesium chloride, 4-methyl-3-n-pentenyl magnesium chloride, phenethyl magnesium chloride, isopropyl magnesium chloride, cyclobutyl magnesium chloride, cyclohexyl magnesium chloride, cycloheptyl magnesium chloride, and cyclopentyl magnesium chloride. The phosphoramide ligand is at least one of the following molecular structural formulas: ; The catalyst is at least one of cuprous bromide dimethyl sulfide and cuprous chloride; The solvent includes at least one of toluene, dichloromethane, diethyl ether, tetrahydrofuran, and p-xylene.

2. The method for asymmetric alkylation of a chain-like racemic allyl ether according to claim 1, characterized in that, The molar ratio of the chain-like racemic allyl methyl ether, the phosphoramide ligand, the catalyst, the boron trifluoride ethyl ether, and the Grignard reagent is 1:(0.05~0.20):(0.05~0.20):(0.50~3.00):(0.50~3.00).

3. The method for asymmetric alkylation of a chain-like racemic allyl ether according to claim 1, characterized in that, The specific steps include: S1. Under the protection of an inert gas, the phosphoramide ligand, the catalyst, and the solvent are added to a container and mixed evenly to obtain a first mixture; S2. Add the chain-like racemic allyl methyl ether to the first mixed liquid to obtain a second mixture; S3. Add the boron trifluoride ether and the Grignard reagent to the second mixture. After the addition is complete, keep the mixture warm for 0.5 to 4 hours to obtain the third mixture. S4. The reaction of the third mixture is quenched with a quenching agent, then the organic phase is extracted and washed, dried and concentrated to obtain the asymmetric allyl alkyl compound.

4. The method for asymmetric alkylation of a chain-like racemic allyl ether according to claim 3, characterized in that, The quenching agent includes any one of saturated ammonium chloride solution, saturated hydrochloric acid solution, ethanol, and methanol.

5. The method for asymmetric alkylation of a chain-like racemic allyl ether according to claim 3, characterized in that, The Grignard reagent must be dissolved in ether before use.

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