A method for synthesizing α-amino acid compounds

Abstract

The present invention discloses a method for synthesizing α-amino acid compounds. The synthesis method includes: in a protective atmosphere, subjecting a mixed reaction system containing an imine compound, a photocatalyst, oxalate, an additive and a solvent to a light irradiation reaction, and then performing an esterification treatment to obtain the α-amino acid compounds. The synthesis method of the α-amino acid compounds provided by the present invention does not require the participation of CO<subgt;2< / subgt>. Under visible light induction, oxalate itself serves as both a reducing agent and a C1 source, and efficiently synthesizes the α-amino acid compounds. At the same time, the reaction conditions of the synthesis method of the present invention are mild, the reaction substrate has a wide selectivity, and it can be scaled up to the gram scale, and the yield is basically not affected, having good industrial application prospects.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic chemical synthesis, and particularly relates to a method for synthesizing α - amino acid compounds. Background Art

[0002] Amino acids are important components of proteins and play an indispensable role in living organisms. α - Amino acids are widely present in many natural products and bioactive compounds and play important roles in biochemistry, pharmaceutical science, materials science, and synthetic organic chemistry. So far, many reported drug structures contain α - amino acids, such as levodopa for treating Parkinson's disease, azaserine for treating acute leukemia and Hodgkin's disease, etimicin for broad - spectrum antibiotics, arginine for treating hepatic encephalopathy, and glutamine for treating digestive tract diseases. In the field of organic synthesis, α - amino acids can not only be used as starting materials to synthesize various bioactive compounds but also play an important ligand role in catalytic reactions involving transition metals. Therefore, methods for synthesizing α - amino acid derivatives have very important scientific significance and application value, and adopting mild and efficient methods is one of the hotspots in the current field of organic synthesis.

[0003] Imine refers to a class of organic compounds containing a C = N double bond and is widely used in the fields of drugs, organic synthesis, etc. It can usually be prepared by condensing commercially available ammonia with corresponding aldehydes and ketones. Due to its simple and easily available characteristics, imine compounds have become one of the commonly used substrates for synthesizing α - amino acids.

[0004] Previously, methods for synthesizing α - amino acids using imines mainly included the Strecker reaction, electrochemical, and photochemical methods. In the Strecker reaction, highly toxic cyanides are used, and the reaction needs to be carried out under strong acid, high temperature, and high - pressure conditions. Electrochemistry has the defects of using sacrificial anodes and being difficult to operate. In the photochemical method, the substrate generality is difficult to guarantee. At the same time, the aforementioned methods require the introduction of carbon dioxide gas, and the operation is inconvenient. Therefore, providing a method for synthesizing α - amino acid compounds under non - CO2 gas conditions and with mild and efficient reaction conditions is an urgent problem to be solved. Summary of the Invention

[0005] The main object of the present invention is to provide a method for synthesizing α - amino acid compounds to overcome the deficiencies of the prior art.

[0006] To achieve the aforementioned invention object, the technical solutions adopted by the present invention include:

[0007] An embodiment of the present invention provides a method for synthesizing α - amino acid compounds, which includes:

[0008] In a protective atmosphere, a mixed reaction system containing an imine compound, a photocatalyst, oxalate, an additive, and a solvent is subjected to a photoirradiation reaction, followed by an esterification treatment to obtain an α-amino acid compound.

[0009] In some more specific embodiments, the imine compound includes a carbonyl-containing imine and / or an aryl imine.

[0010] Compared with the prior art, the beneficial effects of the present invention are as follows: The synthesis method of the α-amino acid compound provided by the present invention does not require the participation of CO2. Under visible light induction, oxalate itself serves as both a reducing agent and a C1 source, efficiently synthesizing the α-amino acid compound; at the same time, the reaction conditions of the synthesis method of the present invention are mild, the reaction substrate has a wide selectivity, and it can be scaled up to the gram scale, and the yield is basically not affected; in addition, the present invention overcomes the defects of high reagent toxicity and harsh reaction conditions in the prior art, and has good industrial application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for the description of the embodiments or the prior art. Obviously, the drawings in the following description are only some embodiments described in the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0012] Figure 1 It is a schematic diagram of the mechanism for synthesizing an α-amino acid compound in a typical embodiment of the present invention. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0013] In view of the defects of the prior art, the inventors of this case have proposed the technical solution of the present invention through long-term research and a large number of practices. The following will clearly and completely describe the technical solution of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, rather than 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 efforts belong to the scope of protection of the present invention.

[0014] Specifically, as an aspect of the technical solution of the present invention, a method for synthesizing an α-amino acid compound involves: in a protective atmosphere, a mixed reaction system containing an imine compound, a photocatalyst, oxalate, an additive, and a solvent is subjected to a photoirradiation reaction, followed by an esterification treatment to obtain an α-amino acid compound.

[0015] In some preferred embodiments, the imine compound includes a carbonyl-containing imine and / or an aryl imine.

[0016] Further, the carbonyl-containing imine has a structure shown in formula (I):

[0017]

[0018] Wherein, Ar 1 、Ar 2 、Ar 3 are independently selected from aryl groups containing a halogen atom, an ester group, a cyano group, an alkyl group or an alkoxy group.

[0019] In some preferred embodiments, the arylimine has a structure shown in formula (II):

[0020]

[0021] Wherein, Ar 4 、Ar 5 、Ar 6 are independently selected from aryl groups.

[0022] In some preferred embodiments, the photocatalyst includes any one or a combination of two or more of 4DPAIPN, Ir(ppy)3, Ir[df(CF3)ppy]2(dtppy)PF6, [Ir(dtbbpy)(ppy)2]PF6, 3DPAFIPN, Eosin Y, Eosin B, and is not limited thereto.

[0023] Further, the photocatalyst is 3DPAFIPN.

[0024] In some preferred embodiments, the oxalate includes any one or a combination of two or more of Na2C2O4, SrC2O4, H2C2O4, [N(CH3)4]2C2O4, [N(CH2CH3)4]2C2O4, [N(nBu)4]2C2O4, and is not limited thereto.

[0025] Further, the oxalate is [N(nBu)4]2C2O4.

[0026] In some preferred embodiments, the additive includes any one or a combination of two or more of TMG, 2-tert-butyl-1,1,3,3-tetramethylguanidine, and moroxydine hydrochloride, and is not limited thereto.

[0027] Further, the additive is TMG.

[0028] In some preferred embodiments, the solvent includes any one or a combination of two or more of DMF, DMA, DMSO, NMP, MeCN, 1,4-dioxane, MeOH, and is not limited thereto.

[0029] Further, the solvent is DMF.

[0030] In some preferred embodiments, the molar ratio of the imine compound, the photocatalyst, the oxalate and the additive is 1:0.01 - 0.02:0.9 - 2:0.6 - 2.

[0031] Further, the molar ratio of the imine compound, the photocatalyst, the oxalate and the additive is 1:0.02:1.2:1.1.

[0032] In some preferred embodiments, the synthesis method specifically comprises: placing the imine compound, the photocatalyst, the oxalate and the additive in a reaction vessel, then adding a solvent under a protective atmosphere and stirring the reaction at room temperature for 2 h - 12 h under visible light irradiation to obtain the α-amino acid compound.

[0033] Further, the wavelength of the visible light is 400 - 550 nm.

[0034] In the reaction process of the present invention, the reactants are irradiated with visible light of 400 - 550 nm. The light in this wavelength range is blue light. The energy of blue light is relatively low, and it only acts on the photocatalyst. Moreover, the light in this wavelength range is more easily absorbed by the photocatalyst, which can efficiently activate the photocatalyst and improve the reaction efficiency. In addition, blue light will not be absorbed by organic compounds, so it will not cause the decomposition of the compounds, ensuring that the synthesis reaction has a high yield.

[0035] Further, the synthesis method further comprises: after the reaction is completed, adding methyl iodide to the obtained reaction system for esterification treatment, and then performing separation and purification.

[0036] In some preferred embodiments, the synthesis method of the α-amino acid compound comprises:

[0037] Adding the imine compound, the photocatalyst, the oxalate and the additive into a reaction vessel according to 1:0.01 - 0.02:0.9 - 2:0.6 - 2, then adding a solvent under N2 atmosphere, and then stirring the reaction at room temperature for 5 h. The reaction solution is irradiated with visible light having a wavelength of 400 - 550 nm during the reaction process; then it is post-treated with methyl iodide, and then the reaction mixture is separated and purified to obtain the α-amino acid compound.

[0038] In some more specific examples, the synthesis method of the α-amino acid compound comprises:

[0039] (1) Adding 0.2 mmol of the reaction substrate (imine compound) and 0.004 mmol of the photocatalyst (2 mol%) to a dry Schlenk tube (5 mL) containing a magnetic stirrer.

[0040] (2) Transfer the Schlenk tube into the glove box and charge 0.24 mmol of oxalate (1.2 equiv) into the Schlenk tube;

[0041] (3) After sealing the Schlenk tube, take it out of the glove box and connect it to a double manifold connected to an N2 cylinder. Loosen the lid and evacuate and refill with N2 on the double manifold at least 3 times;

[0042] (4) Add 0.22 mmol of additive (such as TMG) (1.1 equiv) and 2 mL of solvent (such as DMF) to the Schlenk tube filled with N2;

[0043] (5) Place the Schlenk tube containing the reaction solution at a distance from a 45 w blue LED lamp (wavelength about 450 nm) and stir the reaction at room temperature (about 25 °C) for 5 hours;

[0044] (6) After the imine is completely converted, add CH3I (8 equiv) to the reaction system and stir at room temperature for 4 h;

[0045] (7) After the reaction is completed, add water (30 mL) and ethyl acetate (3 × 30 mL) to extract, concentrate and dry by rotary evaporation, and purify the residue by flash column chromatography. The purification conditions are: first use petroleum ether / ethyl acetate = 10 / 1 to 5 / 1 to obtain the pure product (α-amino acid compound).

[0046] The technical solutions of the present invention will be further described in detail below in conjunction with several preferred embodiments and accompanying drawings. This embodiment is implemented on the premise of the technical solution of the invention, and the detailed implementation methods and specific operation processes are given, but the protection scope of the present invention is not limited to the following embodiments.

[0047] The experimental materials used in the following examples can be purchased from conventional biochemical reagent companies without special instructions.

[0048] Example 1

[0049] The method for α-amino acid compounds in this example includes the following steps:

[0050] (1) Add 0.2 mmol of reaction substrate (imine compound) and 0.004 mmol of photocatalyst 3DPAFIPN (2 mol%) to a dry Schlenk tube (5 mL) containing a magnetic stir bar;

[0051] (2) Transfer the Schlenk tube into the glove box and charge 0.24 mmol of oxalate [N(nBu)4]2C2O4 (1.2 equiv) into the Schlenk tube;

[0052] (3) After sealing the Schlenk tube, take it out of the glove box and connect it to a double manifold connected to an N2 cylinder. Loosen the lid and evacuate and refill with N2 on the double manifold at least 3 times;

[0053] (4) Add 0.22 mmol of additive TMG (1.1 equiv) and 2 mL of DMF to the Schlenk tube filled with N2;

[0054] (5) Place the Schlenk tube containing the reaction solution at a distance from a 45 W blue LED lamp (wavelength around 450 nm) and stir the reaction at room temperature (around 25 °C) for 5 hours;

[0055] (6) After the imine is completely converted, add CH3I (8 equiv) to the reaction system and stir at room temperature for 4 h;

[0056] (7) After the reaction is completed, add water (30 mL) and ethyl acetate (3 × 30 mL) to the system for extraction, concentrate and dry it in a rotary evaporator, and purify the residue by flash column chromatography. The purification conditions are: first use petroleum ether / ethyl acetate = 10 / 1 - 5 / 1 to obtain the pure product (α-amino acid compound).

[0057] The reaction formula in this example is shown as follows:

[0058]

[0059] The imine compounds, corresponding α-amino acid compound products and yields used in this example are as follows:

[0060]

[0061] Among them, when the product α-amino acid compound is the yield is 99%, and the characterization results are as follows:

[0062] 1 H NMR (400 MHz, CDCl3) δ 7.92 (s, 1H), 7.84 (d, J = 8.0 Hz, 2H), 7.46 (dp, J = 15.2, 7.2 Hz, 7H), 7.32 (q, J = 8.0, 7.2 Hz, 6H), 3.78 (s, 3H).

[0063] 1313C NMR (100 MHz, CDCl3) δ 172.9, 165.5, 138.9, 134.5, 131.9, 128.7 (2), 128.6 (6), 128.1, 128.0, 127.3, 70.2, 53.7.

[0064] ESIHRMS: m / z Calcd. For C 22 H 19 NO3: (M + Na) + 368.1257. Found: 368.1253.

[0065] The product α - amino acid compound is when the yield is 87%, the characterization results are as follows:

[0066] 1 1H NMR (400 MHz, CDCl3) δ 7.82 (s, 1H), 7.60 (dd, J = 3.6, 1.2 Hz, 1H), 7.52 - 7.42 (m, 5H), 7.38 - 7.29 (m, 6H), 7.08 (dd, J = 4.8, 3.6 Hz, 1H), 3.78 (s, 3H).

[0067] 13 13C NMR (100 MHz, CDCl3) δ 172.9, 160.1, 139.2, 138.6, 130.5, 128.7 (0), 128.6 (5), 128.1 (4), 128.1 (0), 127.8, 70.3, 53.8.

[0068] ESIHRMS: m / z Calcd. For C 20 H 17 NO3S: (M - H) + 350.0856. Found: 350.0851.

[0069] The product α - amino acid compound is when the yield is 67%, the characterization results are as follows:

[0070] 1 1H NMR (400 MHz, CDCl3) δ 7.25 (ddt, J = 8.8, 5.2, 2.8 Hz, 12H), 7.17 (dd, J = 5.2, 3.2 Hz, 2H), 7.05 (s, 1H), 3.70 (t, J = 2.0 Hz, 3H), 2.92 (t, J = 7.2 Hz, 2H), 2.57 (tt, J = 7.2, 1.6 Hz, 2H).

[0071] 1313C NMR (100 MHz, CDCl3) δ 172.5, 170.4, 140.8, 138.9, 128.7, 128.6, 128.5, 128.0, 127.9, 126.3, 69.9, 53.5, 38.4, 31.2.

[0072] ESIHRMS: m / z Calcd. For C 24 H 23 NO3: (M + Na) + 396.1570. Found: 396.1570.

[0073] The product α - amino acid compound is When, the yield is 55%, and the characterization results are as follows:

[0074] 1 1H NMR (400 MHz, CDCl3) δ 7.53 (dd, J = 7.6, 1.6 Hz, 4H), 7.39 - 7.32 (m, 6H), 7.12 (s, 1H), 6.80 (s, 2H), 3.77 (s, 3H), 2.26 (s, 3H), 2.17 (s, 6H).

[0075] 13 13C NMR (100 MHz, CDCl3) δ 172.1, 168.8, 139.3, 138.7, 134.9, 134.2, 128.8, 128.5, 128.1, 128.0, 70.0, 53.4, 21.2, 19.2.

[0076] ESIHRMS: m / z Calcd. For C 25 H 25 NO3: (M + Na) + 410.1727. Found: 410.1720.

[0077] The product α - amino acid compound is When, the yield is 94%, and the characterization results are as follows:

[0078] 1 1H NMR (400 MHz, CDCl3) δ 8.01 (s, 1H), 7.94 - 7.89 (m, 2H), 7.67 - 7.62 (m, 2H), 7.59 (dd, J = 7.2, 1.2 Hz, 2H), 7.51 - 7.42 (m, 6H), 7.39 - 7.29 (m, 7H), 3.78 (s, 3H).

[0079] 1313C NMR (100 MHz, CDCl3) δ 172.9, 165.2, 144.7, 140.0, 138.8, 132.9, 129.0, 128.7, 128.1, 128.0, 127.8, 127.3 (4), 127.3 (0), 70.2, 53.7.

[0080] ESIHRMS: m / z Calcd. For C 28 H 23 NO3: (M + Na) + 444.157. Found: 444.1561.

[0081] The product α - amino acid compound is when the yield is 83%, and the characterization results are as follows:

[0082] 1 1H NMR (400 MHz, CDCl3) δ 7.93 (s, 1H), 7.84 (dd, J = 8.0, 5.6 Hz, 2H), 7.46 (d, J = 7.2 Hz, 4H), 7.33 (q, J = 6.8, 6.4 Hz, 6H), 7.09 (t, J = 8.4 Hz, 2H), 3.78 (s, 3H).

[0083] 13 13C NMR (100 MHz, CDCl3) δ 173.0, 164.9 (d, J = 250.8 Hz), 164.4, 138.6, 130.5 (d, J = 2.7 Hz), 129.6 (d, J = 8.9 Hz), 128.6, 128.1 (3), 128.1 (0), 115.7 (d, J = 21.7 Hz), 70.2, 53.8.

[0084] 19 19F NMR (376 MHz, CDCl3) δ - 107.6.

[0085] ESIHRMS: m / z Calcd. For C 22 H 18 FNO3: (M - H) + 362.1198. Found: 362.1192.

[0086] The product α - amino acid compound is when the yield is 93%, and the characterization results are as follows:

[0087] 11H NMR (400 MHz, CDCl3) δ 7.90 (s, 1H), 7.74 (d, J = 8.0 Hz, 2H), 7.50 - 7.43 (m, 4H), 7.36 - 7.27 (m, 6H), 7.22 (d, J = 8.0 Hz, 2H), 3.77 (s, 3H), 2.38 (s, 3H).

[0088] 13 13C NMR (100 MHz, CDCl3) δ 172.9, 165.5, 142.3, 138.9, 131.5, 129.3, 128.6, 128.1, 128.0, 127.2, 70.1, 53.7, 21.6.

[0089] ESI HRMS: m / z Calcd. For C 23 H 21 NO3: (M + Na) + 382.1414. Found: 382.1411.

[0090] The product α - amino acid compound is When, the yield is 95%, and the characterization results are as follows:

[0091] 1 1H NMR (400 MHz, CDCl3) δ 7.84 (s, 1H), 7.82 - 7.78 (m, 2H), 7.48 - 7.44 (m, 4H), 7.35 - 7.27 (m, 6H), 6.94 - 6.88 (m, 2H), 3.82 (s, 3H), 3.77 (s, 3H).

[0092] 13 13C NMR (100 MHz, CDCl3) δ 173.0, 165.1, 162.5, 139.0, 129.1, 128.6, 128.1, 127.9, 126.6, 113.8, 70.1, 55.5, 53.7.

[0093] ESI HRMS: m / z Calcd. For C 23 H 21 NO4: (M + Na) + 398.1363. Found: 398.1365.

[0094] The product α - amino acid compound is When, the yield is 90%, and the characterization results are as follows:

[0095] 11H NMR (400 MHz, CDCl3) δ 7.90 (s, 1H), 7.79 - 7.74 (m, 2H), 7.49 - 7.44 (m, 4H), 7.36 - 7.27 (m, 6H), 7.25 - 7.22 (m, 2H), 3.78 (s, 3H), 2.66 - 2.58 (m, 2H), 1.68 - 1.60 (m, 2H), 0.93 (t, J = 7.2 Hz, 3H).

[0096] 13 13C NMR (100 MHz, CDCl3) δ 172.9, 165.5, 147.0, 138.9, 131.7, 128.8, 128.6, 128.1, 128.0, 127.3, 70.1, 53.7, 37.9, 24.4, 13.8.

[0097] ESIHRMS: m / z Calcd. For C 25 H 25 NO3: (M + Na) + 410.1727. Found: 410.1724.

[0098] The product α - amino acid compound is when the yield is 82%, the characterization results are as follows:

[0099] 1 1H NMR (400 MHz, CDCl3) δ 8.36 (s, 1H), 8.12 (s, 1H), 7.92 - 7.82 (m, 4H), 7.57 - 7.48 (m, 6H), 7.38 - 7.29 (m, 6H), 3.80 (s, 3H).

[0100] 13 13C NMR (100 MHz, CDCl3) δ 173.0, 165.6, 138.8, 134.9, 132.7, 131.5, 129.1, 128.8, 128.7, 128.6, 128.1(4), 128.0(6), 127.9, 127.8, 126.9, 123.7, 70.3, 53.8.

[0101] ESIHRMS: m / z Calcd. For C 26 H 21 NO3: (M + Na) + 418.1414. Found: 418.1404.

[0102] The product α - amino acid compound is when the yield is 91%, the characterization results are as follows:

[0103] 1 1H NMR (400 MHz, CDCl3) δ 7.37 - 7.27 (m, 10H), 3.74 (s, 3H), 1.23 (s, 9H).

[0104] 13 13C NMR (100 MHz, CDCl3) δ 176.6, 172.7, 139.3, 128.3, 128.0, 127.8, 69.4, 53.5, 39.1, 27.5.

[0105] ESI HRMS: m / z Calcd. For C 20 H 23 NO3: (M + Na) + 348.157. Found: 348.1568.

[0106] The product α - amino acid compound is When, the yield is 99%, and the characterization results are as follows:

[0107] 1 1H NMR (400 MHz, CDCl3) δ 7.99 (s, 1H), 7.91 - 7.77 (m, 2H), 7.57 - 7.34 (m, 7H), 7.08 - 6.98 (m, 2H), 6.94 - 6.83 (m, 2H), 3.80 (d, J = 0.8 Hz, 6H).

[0108] 13 13C NMR (100 MHz, CDCl3) δ 173.0, 165.5, 162.2 (d, J FC = 246.2 Hz), 159.3, 134.6 (d, J FC = 3.1 Hz), 134.3, 131.9, 130.7, 130.6, 129.8, 128.7, 127.2, 114.8 (d, J F c = 21.4 Hz), 113.6, 69.2, 55.4, 53.8.

[0109] 19 19F NMR (376 MHz, CDCl3) δ - 114.7.

[0110] ESI HRMS: m / z Calcd. For C 23 H 20 FNO4: (M + Na) + 416.1269. Found: 416.1266.

[0111] The product α - amino acid compound is When

[0112] 1 1H NMR (400 MHz, CDCl3) δ 7.90 (s, 1H), 7.87 - 7.79 (m, 2H), 7.53 - 7.38 (m, 5H), 7.37 - 7.18 (m, 6H), 7.12 (d, J = 6.4 Hz, 1H), 3.78 (s, 3H), 2.32 (s, 3H).

[0113] 13 13C NMR (100 MHz, CDCl3) δ 173.0, 165.5, 138.9, 138.8, 137.8, 134.5, 131.9, 129.1, 128.9, 128.7, 128.1, 128.0, 127.3, 125.7, 70.1, 53.7, 21.8.

[0114] ESIHRMS: m / z Calcd. For C 23 H 21 NO3: (M + Na) + 328.1414. Found: 328.1417.

[0115] The product α - amino acid compound is When

[0116] 1 1H NMR (400 MHz, CDCl3) δ 7.96 (s, 1H), 7.84 (dq, J = 6.4, 1.6 Hz, 2H), 7.51 - 7.30 (m, 7H), 7.19 - 7.08 (m, 4H), 3.76 (s, 3H), 2.33 (s, 6H).

[0117] 13 13C NMR (100 MHz, CDCl3) δ 173.2, 165.4, 137.7, 135.9, 134.5, 131.8, 128.8, 128.6, 128.5, 127.2, 69.8, 53.7, 21.2.

[0118] ESIHRMS: m / z Calcd. For C 24 H 23 NO3: (M + Na) + 396.1570. Found: 396.1561.

[0119] The product α - amino acid compound is When the yield is 85%, the characterization results are as follows:

[0120] 1 H NMR (400MHz, CDCl3) δ8.03 (s, 1H), 7.86-7.80 (m, 2H), 7.56-7.50 (m, 1H), 7.48-7.39 (m, 6H), 7.09-6.98 (m, 4H), 3.80 (s, 3H).

[0121] 13 C NMR (100MHz, CDCl3) δ172.8, 165.4, 162.4 (d, J FC =246.8Hz), 134.2, 134.0, 132.1, 130.5 (d, J FC =8.1Hz), 128.8, 127.2, 115.1 (d, J FC =21.5Hz), 69.2, 54.0.

[0122] 19 F NMR (376MHz, CDCl3) δ-114.4.

[0123] ESIHRMS: m / z Calcd.For C 22 H 17 F2NO3: (M+Na) + 404.1069.Found:404.1057.

[0124] The product α-amino acid compounds are When the yield is 83%, the characterization results are as follows:

[0125] 1 H NMR (400MHz, CDCl3) δ8.18 (s, 1H), 7.85 (dt, J=6.8, 1.6Hz, 2H), 7.61-7.26 (m, 10H), 7.15-6.97 (m, 2H), 3.79 (s, 3H).

[0126] 13 C NMR (100MHz, CDCl3) δ172.7, 165.4, 160.8 (d, J FC =245.6Hz), 135.1, 134.4, 133.1 (d, J FC =2.8Hz), 131.9, 130.1 (d, J FC =8.9Hz), 128.7, 128.4, 128.4, 128.2, 127.6 (d, J FC=10.8Hz), 127.3, 123.0 (d, J FC =3.1Hz), 115.4(d, J FC =22.0Hz), 66.7, 54.0.

[0127] 19 F NMR (376MHz, CDCl3) δ-114.3.

[0128] ESIHRMS: m / z Calcd.For C 22 H 18 FNO3: (M+Na) + 386.1163.Found:386.1155.

[0129] The product α-amino acid compounds are The yield was 88%, and the characterization results were as follows:

[0130] 1 H NMR (400MHz, CDCl3) δ7.92 (s, 1H), 7.70-7.58 (m, 2H), 7.53-7.42 (m, 4H), 7.39-7.24 (m, 8H), 3.78 (s, 3H), 2.38 (s, 3H).

[0131] 13 C NMR (100MHz, CDCl3) δ173.0, 165.7, 138.9, 138.6, 134.3, 132.6, 128.7, 128.6, 128.1, 128.0, 124.2, 70.2, 53.7, 21.5.

[0132] ESIHRMS: m / z Calcd.For C 23 H 21 NO3: (M+Na) + 382.1414.Found:382.1412.

[0133] The product α-amino acid compounds are When the yield is 94%, the characterization results are as follows:

[0134] 1 H NMR (400MHz, CDCl3) δ 8.16-8.00 (m, 3H), 7.96-7.80 (m, 2H), 7.53-7.40 (m, 4H), 7.40-7.26 (m, 6H), 3.93 (s, 3H), 3.80 (s, 3H).

[0135] 13C NMR (100MHz, CDCl3) δ172.9, 166.4, 164.6, 138.4, 138.3, 133.0, 130.0, 128.7, 128.2, 127.3, 70.4, 53.9, 52.5.

[0136] ESIHRMS: m / z Calcd.For C 24 H 21 NO5: (M+Na) + 426.1312.Found:426.1305.

[0137] The product α-amino acid compounds are When the yield is 69%, the characterization results are as follows:

[0138] 1 H NMR (400MHz, CDCl3) δ8.08 (s, 1H), 7.98-7.86 (m, 2H), 7.78-7.65 (m, 2H), 7.51-7.41 (m, 4H), 7.39-7.31 (m, 6H), 3.80 (s, 3H).

[0139] 13 C NMR (100MHz, CDCl3) δ172.9, 163.6, 138.3, 138.0, 132.6, 128.7, 128.3, 128.2, 128.0, 118.1, 115.4, 70.4, 54.0.

[0140] ESIHRMS: m / z Calcd.For C 23 H 18 N2O3: (M+Na) + 393.1210.Found:393.1201.

[0141] The product α-amino acid compounds are The yield was 59%, and the characterization results were as follows:

[0142] 1 H NMR (400MHz, CDCl3) δ7.41-7.19 (m, 11H), 3.75 (s, 3H), 1.53 (dddd, J=11.2, 8.0, 4. 0, 1.6Hz, 1H), 0.88 (tq, J=8.4, 3.6, 2.4Hz, 2H), 0.71 (ddt, J=10.8, 4.4, 2.0Hz, 2H).

[0143] 13C NMR (100MHz, CDCl3) δ172.6, 171.9, 139.4, 128.5, 128.0, 127.8, 69.9, 53.5, 15.2, 7.2.

[0144] ESIHRMS: m / z Calcd.For C 19 H 19 NO3: (M+Na) + 332.1257.Found:332.1262.

[0145] The product α-amino acid compounds are When the yield is 91%, the characterization results are as follows:

[0146] 1 H NMR (400MHz, CDCl3) δ7.97 (s, 1H), 7.89-7.79 (m, 2H), 7.54-7.39 (m, 7H), 7.38-7.29 (m, 3H), 7.05-6.96 (m, 2H), 3.79 (s, 3H).

[0147] 13 C NMR (100MHz, CDCl3) δ172.8, 165.5, 162.3 (d, J FC =246.2Hz), 138.6, 134.4 (d, J FC =3.2Hz), 134.2, 132.0, 130.7 (d, J FC =6.5Hz), 128.8, 128.5, 128.2(9), 128.2(5), 127.2, 114.9(d, J FC =21.4Hz), 69.7, 53.8.

[0148] 19 F NMR (376MHz, CDCl3) δ-114.8.

[0149] ESIHRMS: m / z Calcd.For C 22 H 18 FNO3: (M+Na) + 386.1163.Found:386.1169.

[0150] The product α-amino acid compounds are When the yield is 96%, the characterization results are as follows:

[0151] 1H NMR (400MHz, CDCl3) δ7.95 (s, 1H), 7.89-7.79 (m, 2H), 7.53-7.45 (m, 3H), 7.44 -7.37(m, 2H), 7.37-7.26(m, 5H), 7.19-7.09(m, 2H), 3.77(s, 3H), 2.33(s, 3H).

[0152] 13 C NMR (100MHz, CDCl3) δ173.1, 165.4, 138.8, 137.8, 135.9, 134.4, 131.8, 128.8, 128.7, 128.5, 128.1, 127.9, 127.5, 127.2, 70.0, 53.7, 21.2.

[0153] ESIHRMS: m / z Calcd.For C 23 H 21 NO3: (M+Na) + 382.1414.Found:382.1415.

[0154] The product α-amino acid compounds are The yield was 84%, and the characterization results were as follows:

[0155] 1 H NMR (400MHz, CDCl3) δ7.98 (dt, J=6.8, 3.6Hz, 1H), 7.87 (m, 2H), 7.58-7.29 (m, 9 H), 7.26-7.08 (m, 3H), 3.81 (dt, J=6.8, 3.6Hz, 3H), 2.25 (dq, J=6.8, 3.6Hz, 3H).

[0156] 13 C NMR (100MHz, CDCl3) δ173.6, 165.4, 137.8, 137.1, 136.2, 134.3, 131.9, 131.8, 1 31.4, 128.8, 128.5, 128.4, 128.2(4), 128.2(0), 127.3, 125.1, 70.3, 53.9, 20.6.

[0157] ESIHRMS: m / z Calcd.For C 23 H 21 NO3: (M+Na) + 382.1414.Found:382.1419.

[0158] The product α-amino acid compounds are When the yield was 30%, the characterization results were as follows:

[0159] 1 1H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 10.8 Hz, 4H), 7.34 - 7.25 (m, 6H), 7.00 (d, J = 2.4 Hz, 2H), 6.67 - 6.58 (m, 1H), 6.44 (d, J = 10.4 Hz, 2H), 5.43 (s, 1H), 3.69 (s, 3H).

[0160] 13 13C NMR (100 MHz, CDCl3) δ 173.8, 145.3, 140.2, 128.7, 128.5, 128.3, 127.8, 118.1, 115.6, 71.7, 53.3.

[0161] ESIHRMS: m / z Calcd. For C 21 H 19 NO2: (M + Na) + 340.1308. Found: 340.1301.

[0162] Example 2

[0163] The method was the same as that of Example 1, except that the reactants and their amounts used were as shown in Table 1:

[0164] Table 1 Amounts of each reactant, reaction conditions and product yield

[0165]

[0166]

[0167] a Yeilds were determined by 1 HNMR using 1,2 - dichloroethane as an internal standard.

[0168] In addition, the inventors of this case studied the mechanism of synthesizing α - amino acid compounds in this application. A radical inhibition test was carried out according to the equation in the following formula. When 2 equivalents of a radical scavenger such as 2,2,6,6 - tetramethylpiperidine - 1 - oxyl radical (TEMPO) was added to the reaction system, no product was detected and 40% of the raw materials were recovered, indicating that this reaction may involve a radical process.

[0169]

[0170] When D2O is added to the reactants under standard conditions, deuterated products can be obtained, which indicates that carbon anions may be generated during the synthesis process. The mechanism diagram of the synthesis of α-amino acid compounds in the present invention is as follows: Figure 1 As shown, the organic small molecule photocatalyst (such as 3DPAFIPN) is excited by light to produce 3DPAFIPN * The excited singlet state then undergoes SET with oxalate to provide the strong reducing agent 3DPAFIPN ·- , and carbon dioxide radical anions and CO2 are obtained at the same time. Carbon dioxide radical anions can reduce imine substrates to form carbon radical intermediates, which can be further treated with a strong reducing agent 3DPAFIPN ·- Reduction produces a carbon-negative intermediate, which can then nucleophilically attack the CO2 produced by the oxalate itself to produce α-amino acid compounds.

[0171] In addition, the inventors of this case also referred to the aforementioned embodiments and conducted experiments using other raw materials, process operations, and process conditions described in this specification, and obtained relatively ideal results.

[0172] It should be understood that the technical solution of the present invention is not limited to the above-mentioned specific implementation cases. Any technical variations made according to the technical solution of the present invention without departing from the scope of protection of the purpose of the present invention and the claims shall fall within the scope of protection of the present invention.

Claims

1. A method for synthesizing an α-amino acid compound, characterized in that, Comprising: In a protective atmosphere, subjecting a mixed reaction system containing an imine compound, a photocatalyst, oxalate, an additive, and a solvent to a light irradiation reaction, and then performing an esterification treatment to obtain an α-amino acid compound; Wherein, the imine compound is selected from carbonyl-containing imines and / or aryl imines; The carbonyl-containing imine has a structure shown in formula (I): Formula (I) Among them, Ar 1 ,Ar 2 ,Ar 3 independently selected from aryl groups containing halogen atoms, ester groups, cyano groups, alkyl groups or alkoxy groups; The aryl imine has a structure shown in formula (II): Formula (II) Among them, Ar 4 、Ar 5 、Ar 6 are independently selected from aryl groups; The photocatalyst is selected from any one or a combination of two or more of Ir(ppy)3, Ir[dF(CF3)ppy]2(dtppy)PF6, and 3DPAFIPN; The oxalate is selected from [N(nBu)4]2C2O4; The additive is selected from TMG.

2. The synthesis method according to claim 1, wherein: The photocatalyst is 3DPAFIPN.

3. The synthesis method according to claim 1, characterized in that: The solvent is selected from any one or a combination of two or more of DMF, DMA, DMSO, NMP, MeCN, 1,4-dioxane, and MeOH.

4. The synthesis method according to claim 3, characterized in that: The solvent is DMF.

5. The synthesis method according to claim 1, characterized in that: The molar ratio of the imine compound, photocatalyst, oxalate, and additive is 1:0.01 - 0.02:0.9 - 2:0.6 - 2.

6. The synthesis method according to claim 1, characterized in that, Specifically including: Placing the imine compound, photocatalyst, oxalate, and additive in a reaction vessel, then adding the solvent under a protective atmosphere and stirring the reaction at room temperature for 2 h - 12 h under visible light irradiation.

7. The synthesis method according to claim 6, wherein: The wavelength of the visible light is 400 - 550 nm.

8. The synthesis method according to claim 1, characterized in that, Specifically including: After the light irradiation reaction is completed, adding methyl iodide to the obtained reaction system for esterification treatment and then performing separation and purification.

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