A method for synthesizing beta-amino acid compounds based on olefin nitrogen carboxylation reaction

Abstract

This invention discloses a method for synthesizing β-amino acid compounds based on the nitrogen carboxylation of olefins, belonging to the field of organic synthesis technology. The method mainly includes the following steps: adding the reaction substrate olefin, the reaction substrate amine, a photocatalyst, a copper catalyst, a base, and additives into a reaction vessel; then adding a solvent under a CO2 atmosphere; stirring the reaction under light irradiation at 0–100°C for 0.1–100 h; separating and purifying the reaction product to obtain β-amino acid compounds. This invention uses readily available olefins, organic amines, and CO2 as reaction raw materials, and through the nitrogen carboxylation reaction of olefins, it prepares a series of β-amino acid compounds with high selectivity and high atom economy. It features readily available and inexpensive raw materials, a wide range of reaction substrates, good functional group compatibility, mild reaction conditions, and good chemical and regioselectivity.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for synthesizing β-amino acid compounds based on olefin nitrogen carboxylation reaction. Background Technology

[0002] Alkenes are important precursors in organic synthesis and are widely used in organic synthesis reactions, especially in the bifunctionalization of alkenes, which can rapidly and efficiently construct complex molecular structures. Carbon dioxide (CO2) is a greenhouse gas, but also a cheap, readily available, non-toxic, and renewable raw material. Using it as a C1 synthon in organic synthesis to convert and synthesize high-value-added chemicals has significant academic importance and broad application prospects. In recent years, CO2-involved bifunctionalization reactions of alkenes have been developed as an important method for obtaining high-value-added carboxylic acids. However, limited by the single reaction mechanism, CO2-involved bifunctionalization reactions of alkenes have focused on α-selective carboxylation, while β-selective carboxylation has been reported very rarely. Furthermore, achieving the construction of carbon-nitrogen bonds simultaneously with the carboxylation of alkenes is extremely challenging and has yet to be reported.

[0003] On the other hand, β-amino acids are a very important class of compounds, and their structural units and derivatives are widely found in natural products and bioactive molecules. Therefore, developing a mild and efficient synthetic method is crucial. Summary of the Invention

[0004] To address the aforementioned problems in existing technologies, this invention provides a method for synthesizing β-amino acid compounds based on olefin nitrogen carboxylation reaction. This method effectively solves the problems of cumbersome preparation steps and the use of toxic CO gas as a carboxyl source in existing preparation methods. At the same time, this method has the advantages of inexpensive and readily available raw materials, a wide range of reaction substrates, good functional group compatibility, mild reaction conditions, and good chemical and regioselectivity.

[0005] To achieve the above objectives, the technical solution adopted by the present invention to solve its technical problem is as follows:

[0006] A method for synthesizing β-amino acid compounds based on olefin nitrogen carboxylation reaction includes the following steps:

[0007] The reaction substrates olefin, amine, photocatalyst, copper catalyst and base are mixed, and then an organic solvent is added to it under CO2 atmosphere. The mixture is stirred for 0.1 to 100 h under light and 0 to 100 °C. The reaction products are separated and purified to obtain β-amino acid compounds.

[0008] The general structural formula of the reaction substrate olefin is shown in formula (I):

[0009]

[0010] Among them, R 1 It can be aryl, heteroaryl, ester, amide, cyano, alkenyl, alkynyl, carboxyl, carbonyl, thioester, or heteroatom; R 2 R 3 R 4 It can be hydrogen, alkyl, aryl, heteroaryl, ester, or heteroatom.

[0011] The general structural formula of the reaction substrate amine is shown in Formula (II):

[0012]

[0013] Among them, R 5 R 6 It can be aryl, heteroaryl, alkyl, hydrogen, or heteroatom.

[0014] Furthermore, the reaction substrate olefins include:

[0015]

[0016] Furthermore, the reaction substrate amines include:

[0017]

[0018] Furthermore, the molar ratio of the reaction substrate olefin, the reaction substrate amine, the photocatalyst, the copper catalyst, and the base is 1:0.5~10:0.001~0.3:0.01~3:0.01~5.

[0019] Furthermore, the photocatalyst is a phenolic photocatalyst, an organic dye photocatalyst, or an organometallic photocatalyst.

[0020] Furthermore, phenolic photocatalysts include:

[0021]

[0022] Among them, R 1 R 2 R 3 It can be aryl, heteroaryl, ester, amide, cyano, alkenyl, alkynyl, carboxyl, carbonyl, hydrogen, alkyl, or heteroatom.

[0023] Furthermore, the organic dye photocatalysts are 4CzIPN, 5CzBN, 4CzPN, 4DPAIPN, 3DPAFIPN, 3DPA2FBN, 4CzBnBN, DPZ, PTH, or PAZ, and the organometallic photocatalysts are fac-Ir(ppy)3, Ir(ppy)2(bpy)PF6, fac-Ir(dF(ppy)3), Ir(ppy)2(dtbbpy)PF6, Ir(dF(CF3)ppy)2(dtbbpy)PF6, or Ir(ppy)2(dtbbpy)PF6.

[0024] Furthermore, the copper catalyst is CuCl, CuBr, CuI, CuOAc, CuCN, CuTc, CuOTf, CuOTs, Cu(CH3CN)4PF6, Cu(CH3CN)4BF4, Cu(CH3CN)4OTf, CuOPiv, or CuO. t Bu, Cu(CH3CN)4OTs, CuCl2, CuBr2, CuI2, Cu(OAc)2, Cu(OTf)2, Cu(BF4)2, Cu(OPiv)2 or Cu(acac)2.

[0025] Furthermore, the base is a carbonate, bicarbonate, fluoride, alkoxy base, phosphate, hydrogen phosphate, carboxylate, or organic base.

[0026] Furthermore, the organic solvent is MeCN, DMF, DMAc, DMSO, NMP, or THF.

[0027] Furthermore, the pressure of the CO2 atmosphere is 0.1 to 30 times the atmospheric pressure; when illuminated, the wavelength is 300-700 nm, and the power of the light is 0.1 to 100 W.

[0028] Furthermore, it also includes the operation of adding molecular sieves to the reaction substrate, wherein the mass ratio of molecular sieves to reaction substrate is 0.1-100:1.

[0029] The reaction formula of this invention is:

[0030]

[0031] The specific process is as follows: After electron transfer occurs between the photocatalyst and the monovalent copper catalyst, the substrate olefin is reduced to an olefin radical anion, and a divalent copper catalyst is generated at the same time. The formed olefin radical anion attacks CO2 to generate a carboxyl-containing radical intermediate, which then undergoes carbon-nitrogen coupling mediated by the divalent copper species. Finally, after acidification, the target β-amino acid compound is obtained.

[0032] The beneficial effects of this invention are as follows:

[0033] 1. This invention provides a method for synthesizing β-amino acid compounds based on the nitrogen carboxylation reaction of olefins. Under visible light catalysis, readily available olefins and amines are used as reaction substrates, CO2 is used as the carboxylic acid source, and a photocatalyst, a copper catalyst, and a base are added simultaneously to obtain β-amino acid compounds. This method has the advantages of convenient operation and inexpensive and readily available raw materials.

[0034] 2. The reaction substrates of this invention have a wide range of applicability, good selectivity, good functional group compatibility, mild reaction conditions, and are easy to scale up and undergo subsequent derivatization and transformation. This invention overcomes the shortcomings of existing synthesis techniques, such as cumbersome steps and the need to use toxic CO gas. The raw materials used are inexpensive and readily available, and it has good prospects for industrial application.

[0035] 3. This invention is the first to achieve the nitrogen carboxylation reaction of olefins involving CO2. This reaction achieves carboxylation under mild conditions while efficiently constructing carbon-nitrogen bonds, and prepares a series of β-amino acid compounds with high selectivity and high atom economy, showing broad application prospects. Attached Figure Description

[0036] Figure 1 This is a schematic diagram of the synthesis mechanism of the present invention. Detailed Implementation

[0037] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are only for explaining the invention and are not intended to limit the invention; that is, the described embodiments are merely some embodiments of the invention, and not all embodiments.

[0038] Therefore, the following detailed description of the embodiments of the present invention is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0039] It should be noted that relational terms such as "first" and "second" are used merely to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus. Unless otherwise specified, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes the element.

[0040] The features and performance of the present invention will be further described in detail below with reference to embodiments.

[0041] The reaction mechanism of this application is as follows: using a phenol catalyst ArO - For example; firstly, the photo-excited phenol catalyst ArO - Generating ArO -* The species reduces the substrate olefin to an olefin radical anion (I) and an ArO· species, which then undergoes electron transfer with a monovalent copper species (III) to yield ArO. - The species completes the catalytic cycle regeneration and generates a divalent copper species (IV). The formed olefin radical anion attacks CO2 to generate a carboxyl-containing radical intermediate (II), which then undergoes carbon-nitrogen coupling mediated by the divalent copper species (IV) to obtain the target β-amino acid compound (V).

[0042] Example 1

[0043] A method for synthesizing β-amino acid compounds based on olefin nitrogen carboxylation reaction, the specific process of which is as follows:

[0044] After drying a 10 mL Schlenk reaction tube equipped with a stirrer under vacuum, 4-phenylstyrene (0.2 mmol, 1.0 equiv), amine (1.0 mmol, 5.0 equiv, if the substrate is solid), and photocatalyst ArOH (0.02 mmol, 10 mol%) were added. The reaction tube was then transferred to a glove box, and KO base was added sequentially. t Bu (0.3mmol, 1.5equiv), CuCl (0.06mmol, 30mol%), Molecular sieve (180 mg); then the reaction tube was sealed, removed from the glove box, and the reaction tube was evacuated to a CO2 atmosphere using a double-row tube, repeated 3 times; subsequently, under a CO2 atmosphere, the reaction substrate amine (1.0 mmol, 5.0 equiv, if the substrate is liquid) and ultra-dry DMAc (3.5 mL) were injected sequentially into the reaction tube using a syringe; the reaction tube was sealed immediately after the addition was completed; the reaction tube was stirred at room temperature for about 15 min, then the reaction tube was moved to a distance of 1 cm from 30 W blue (wavelength 400–480 nm) LEDs, and stirred at 60 °C for 36 h with a fan for cooling; after the reaction was completed, 3 mL of ethyl acetate was added to dilute the reaction mixture, and then 3 mL of 2N hydrochloric acid was added to quench the reaction, and the mixture was stirred for 1 min; then, about 100 mL of water was added to the reaction solution, and the reaction solution was extracted 3 times with 15 mL of ethyl acetate, the organic phases were combined and the residual solvent was completely removed by rotary evaporation; the residue was separated by silica gel column chromatography to obtain the target product. The specific results are as follows:

[0045]

[0046] Note: All yields mentioned above are separation yields. a DMAP (60 mol%) was used as an additive. The product carboxylic acid was esterified by adding 3.0 equivalents of TMSCHN2 and then separated. c DMAP (30 mol%) was used as an additive. 4.5 equivalents of TMSCHN2 were added to esterify the product carboxylic acid, which was then separated.

[0047] The experimental results above demonstrate that substituents on the aromatic ring of aromatic amines are compatible regardless of whether they are electron-rich, electron-depleted, or electron-neutral groups, and all can yield the target β-amino acid product in moderate to high yields. A variety of functional groups are compatible in this reaction system, including fluorine, chlorine, methoxy, ester, and trifluoromethyl groups. Steric hindrance does not significantly inhibit the reaction, and ortho-substituted substrates proceed well. In addition to monosubstituted substrates, disubstituted aromatic amines are also well compatible in this system, and other types of amines, except for primary aromatic amines, can react well.

[0048] Example 2

[0049] A method for synthesizing β-amino acid compounds based on olefin nitrogen carboxylation reaction, the specific process is as follows: A 10 ml Schlenk reaction tube equipped with a stirrer is dried under vacuum, and then the reaction substrate olefin (0.2 mmol, 1.0 equiv, if the olefin is a solid aryl olefin), 4-methylaniline (1.0 mmol, 5.0 equiv), and photocatalyst ArOH (0.02 mmol, 10 mol%) are added; subsequently, the reaction tube is transferred to a glove box, and the base KO is added sequentially. tBu (0.3mmol, 1.5equiv), CuCl (0.06mmol, 30mol%), Molecular sieve (180 mg); then the reaction tube was sealed, removed from the glove box, and the reaction tube was evacuated to a CO2 atmosphere using a double-row tube, repeated 3 times; subsequently, under a CO2 atmosphere, the reaction substrate olefin (0.2 mmol, 1.0 equiv, olefins were acrylates, difluorosubstituted olefins, solid aryl olefins) and ultra-dry DMAc (3.5 mL) were injected sequentially into the reaction tube using a syringe; the reaction tube was sealed immediately after the addition was completed; the reaction tube was stirred at room temperature for about 15 min, then the reaction tube was moved to a distance of 1 cm from 30 W blue (wavelength 400-480 nm) LEDs, and stirred at 60 °C for 36 h with fan cooling; after the reaction was completed, 3 mL of ethyl acetate was added to the reaction mixture for dilution, and then 3 mL of 2N hydrochloric acid was added to quench the reaction, and stirred for 1 min; then 100 mL of water was added to the reaction solution, and the reaction solution was extracted 3 times with 15 mL of ethyl acetate, the organic phases were combined and the residual solvent was completely removed by rotary evaporation; the residue was separated by silica gel column chromatography to obtain the target product. The specific results are as follows:

[0050]

[0051] Note: All yields mentioned above are separation yields. a The product carboxylic acid was esterified by adding 2.0 equivalents of TMSCHN2 to 60 hb and then separated. c dr = 6.0:1. d The product carboxylic acid was esterified by adding 3.0 equivalents of TMSCHN2 and then separated. e dr>20:1. f DMAP (30 mol%) was used as an additive. g The product carboxylic acid was esterified by adding 6.5 equivalents of TMSCHN2 and then separated. h RT; ArOH (15 mol%). i The product carboxylic acid was esterified by adding 5.0 equivalents of TMSCHN2 and then separated. j The product carboxylic acid was esterified by adding 3.0 equivalents of TMSCHN2 and then separated. k dr = 3.0:1.

[0052] The experimental results above indicate that this reaction is compatible with electron-donating, electron-neutral, and weakly electron-withdrawing groups, and can yield the target product in moderate to good yields. Furthermore, it is compatible with various common functional groups, such as alkoxy groups, halogen atoms, and trifluoromethyl groups. In addition, the target product is obtained in good yields for substrates with substituents at various positions. Moreover, internal alkenes and fluoroalkenes can also react well to yield the corresponding target products.

[0053] Example 3

[0054] Using 4-phenylstyrene as a template substrate, the effect of changing reaction conditions on the reaction yield was investigated. The specific process is as follows:

[0055]

[0056] Note: a Yield was determined by liquid chromatography. b Separation yield.

[0057] The experimental results above show that the separation yield of the corresponding carboxylic acid under the reaction conditions of the present invention is as high as 84%. A series of control experiments show that light, photocatalyst, copper catalyst, alkali and carbon dioxide are all essential. Without any one of them, the target product cannot be obtained.

[0058] The product obtained by this invention was analyzed by proton, carbon, and fluorine NMR spectra. The NMR characterization results were consistent with those of the obtained product. Specific characterization data are as follows:

[0059] 3-([1,1'-biphenyl]-4-yl)-3-(phenylamino)propionic acid (3aa)

[0060] 1H),6.34(d,J=8.5Hz,1H),4.92–4.77(m,1H),2.87–2.59(m,2H); 13 C NMR (101MHz, DMSO-d6) δ172.1,147.7,142.8,140.0,138.8,128.9,128.8,127.30,127.26,126.7,126.6,116.0,113.0,53.4,42.9; HRMS (ESI+): calculated m / z[M+H] + for[C 21 H 20 NO2] + :318.1489,found:318.1489.

[0061] 4-([1,1'-biphenyl]-4-yl)-3-(p-Tolylamino)propionic acid (3ab)

[0062]

[0063] DMSO-d6)δ172.1,145.4,142.9,140.0,138.7,129.2,128.9,127.3,126.63,126.60,124.5,113.3,53.6,42.9,20.1; HRMS(ESI+):calculated m / z[M+Na] + for[C 22 H 21 NO2Na] + :354.1465,found:354.1470.

[0064] 3-([1,1'-biphenyl]-4-yl)-3-((4-(tert-butyl)phenyl)amino)propionic acid (3ac)

[0065]

[0066] MHz, DMSO-d6)δ172.2,145.3,143.1,140.0,138.8,138.2,128.9,127.32,127.2 8,126.7,126.6,125.4,112.7,53.5,43.0,33.4,31.5; HRMS(ESI+):calculated m / z[M+H] + for[C 25 H 28 NO2] + :374.2115,found:374.2108.

[0067] 3-([1,1'-biphenyl]-4-yl)-3-((4-chlorophenyl)amino)propionic acid (3ad)

[0068]

[0069] 142.3,139.9,138.9,128.9,128.5,127.3,127.2,126.8,126.6,119.3,114.4,53.4,42.7; HRMS(ESI+):calculated m / z[M+H] + for[C 21 H 19 ClNO2] +:352.1099,found:352.1096.

[0070] 3-([1,1'-biphenyl]-4-yl)-3-((4-fluorophenyl)amino)propionic acid (3ae)

[0071]

[0072] 172.1,154.4(d,J=231.2Hz),144.4(d,J=1.5Hz),142.6,140.0,138.8,128.9,12 7.35,127.29,126.7,126.6,115.2(d,J=22.0Hz),113.8(d,J=7.2Hz),53.8,42.9; 19 FNMR(376MHz, DMSO-d6)δ-129.29(tt,J=8.8,4.6Hz); HRMS(ESI+):calculated m / z[M+H] + for[C 21 H 18 FNO2] + :336.1395,found:336.1399.

[0073] 3-([1,1'-biphenyl]-4-yl)-3-((4-(trifluoromethoxy)phenyl)amino)propionic acid (3af)

[0074]

[0075] 139.0,138.6,128.9,127.3,127.2,126.8,126.6,122.0,120.4(q,J=254.2Hz),113.2,53.5,42.7; 19 F NMR(376MHz,DMSO-d6)δ-57.33; HRMS(ESI+):calculated m / z[M+H] + for[C 22 H 19 F3NO3] + :402.1312,found:402.1314.

[0076] 3-([1,1'-biphenyl]-4-yl)-3-((4-bromophenyl)amino)propionic acid (3ag)

[0077]

[0078] 3-([1,1'-biphenyl]-4-yl)-3-((4-acetaminophenyl)amino)propionic acid (3ah)

[0079]

[0080] DMSO-d6)δ172.5,167.7,144.2,143.3,140.4,139.2,129.5,129.3,127.7,127.09,127.07,121.2,113.5,54.2,43.3,24.1; HRMS(ESI)m / z:[M+H] + calcd forC 21 H 19 BrNO2: 396.0954, found: 396.0591

[0081] 3-([1,1'-biphenyl]-4-yl)-3-((3-(trifluoromethyl)phenyl)amino)propionic acid (3ai)

[0082] Properties: Colorless oily liquid

[0083]

[0084] 127.4,127.2,126.8,126.6,124.5(q,J=272.4Hz),116.0,111.9(q,J=3.8Hz),108.9(q,J=3.8Hz),53.1,42.7; 19 F NMR(376MHz,DMSO-d6)δ-61.44; HRMS(ESI-):calculated m / z[MH] - for[C 22 H 17 F3NO2] - :384.1217,found:384.1216.

[0085] 3-([1,1'-biphenyl]-4-yl)-3-((3-(difluoromethoxy)phenyl)amino)propionic acid (3aj)

[0086]

[0087] 4.89–4.76(m,1H),2.85–2.60(m,2H); 13C NMR(101MHz,DMSO-d6)δ172.0,152.1(t,J=3.0Hz),149.4,142.4,139.9,138.9,130.1,12 8.9,127.4,127.2,126.8,126.6,116.5(t,J=256.2Hz),109.7,105.3,102.9,53.3,42.7; 19 F NMR(376MHz, DMSO-d6)δ-81.00(dd,J=74.5,7.0Hz); HRMS(ESI+):calculated m / z[M+H] + for[C 22 H 20 F2NO3] + :384.1406,found:384.1404.

[0088] 3-([1,1'-biphenyl]-4-yl)-3-((3-chlorophenyl)amino)propionic acid (3ak)

[0089]

[0090] (101MHz, DMSO-d6) δ171.9,149.2,142.2,139.9,138.9,133.5,130.3,128.9,127. 3,127.2,126.8,126.6,115.4,112.1,111.5,53.2,42.7; HRMS(ESI+):calculated m / z[M+H] + for[C 21 H 19 ClNO2] + :352.1099,found:352.1099.

[0091] 3-([1,1'-biphenyl]-4-yl)-3-((3-chlorophenyl)amino)propionic acid (3al)

[0092]

[0093] 7.1Hz, 2H); 13C NMR(101MHz,DMSO-d6)δ172.6,160.6,149.5,143.4,140.4,139.2,129.9,129.3,127.7,12 7.7,127.1,127.1,106.6,101.9,99.3,55.0,53.9,43.4; HRMS(ESI+):calculatedm / z[M+H] + for[C 22 H 22 NO3] + :348.1594,found:348.1590.

[0094] 3-([1,1'-biphenyl]-4-yl)-3-((2-fluorophenyl)amino)propionic acid (3am)

[0095]

[0096] (101MHz, DMSO-d6) δ172.2,151.0(d,J=237.5Hz),142.3,139.9,138.9,135.6(d,J=11.6Hz),128.9,127.3,127 .2,126.7,126.6,124.6(d,J=3.2Hz),116.0(d,J=6.6Hz),114.4(d,J=18.2Hz),113.2(d,J=3.7Hz),53.2,42.2; 19 F NMR(376MHz,DMSO-d6)δ-133.70; HRMS(ESI+):calculated m / z[M+Na] + for[C 21 H 18 FNO2Na] + :358.1214,found:358.1212.

[0097] 3-([1,1'-biphenyl]-4-yl)-3-((3,5-dimethoxyphenyl)amino)propionic acid (3an)

[0098]

[0099] (101MHz, DMSO-d6)δ172.0,161.0,149.5,142.9,140.0,138.8,128.9,127.3,127.2,126.7,126.6,91.9,88.6,54.7,53.4,42.7; HRMS(ESI+):calculated m / z[M+H]+ for[C 23 H 24 NO4] + :378.1700,found:378.1702.

[0100] 3-([1,1'-biphenyl]-4-yl)-3-((3-fluoro-4-methylphenyl)amino)propionic acid (3ao)

[0101]

[0102] (101MHz, DMSO-d6) δ172.0,161.3(d,J=239.2Hz),147.7(d,J=10.9Hz),142.5,140.0,138.9,131.4(d,J=7.1Hz),128.9,1 27.34,127.25,126.7,126.6,110.4(d,J=17.5Hz),109.2(d,J=2.5Hz),99.5(d,J=25.8Hz),53.5,42.8,13.3(d,J=2.9Hz); 19 F NMR(376MHz, DMSO-d6)δ-117.52(t,J=10.8Hz); HRMS(ESI+):calculated m / z[M+H] + for[C 22 H 21 FNO2] + :350.1551,found:350.1553.

[0103] 3-([1,1'-biphenyl]-4-yl)-3-(naphth-1-ylamino)propionic acid (3ap)

[0104]

[0105] 2.88-2.75 (m, 1H); 13 C NMR (101MHz, DMSO-d6) δ172.8,143.3,143.1,140.4,139.3,134.5,129.4,128.5,127.8,127. 7,127.2,127.1,126.1,124.5,123.7,122.3,116.4,105.3,54.1,43.0; HRMS(ESI)m / z:[M+H] + calcd for C 21 H 19 BrNO2:396.0954,found:396.0591.

[0106] 3-([1,1'-biphenyl]-4-yl)-3-((benzofuran-5-yl)amino)propionic acid (3aq)

[0107]

[0108] 143.3,140.4,139.2,129.3,128.2,127.8,127.1,127.0,113.2,111.7,106.9,103.1,54.6,43.8; HRMS(ESI)m / z:[M+H] + calcd for C 21 H 19 BrNO2:396.0954,found:396.0591.

[0109] 3-([1,1'-biphenyl]-4-yl)-3-(bis(4-methoxyphenyl)amino)methyl propionate (3ar)

[0110]

[0111] 2H); 13 C NMR (101MHz, CDCl3) δ172.0,155.0,140.7,140.6,140.3,140.2,128.9,128.1,127.4,127.1,124.5,114.5,59.1,55.6,51.9,38.2; HRMS(ESI+):calculated m / z[M+H] + for[C 30 H 30 NO4] + :468.2170,found:468.2168.

[0112] 3-([1,1'-biphenyl]-4-yl)-3-(2-methyl-2-phenylhydrazyl)propionic acid (3as)

[0113]

[0114] Hz,1H),2.95(s,3H),2.82–2.72(m,1H),2.57–2.51(m,1H); 13C NMR(101MHz,DMSO-d6)δ172.4,152.2,141.2,139.9,139.3,128.9,128.51,128.4 6,127.3,126.6,126.4,117.2,113.1,57.9,40.1,38.6; HRMS(ESI+):calculated m / z[M+H] + for[C 22 H 23 N2O2] + :347.1755,found:347.1753.

[0115] 3-([1,1'-biphenyl]-4-yl)-3-((2-fluorophenyl)amino)propionic acid (3at)

[0116]

[0117] NMR(101MHz, CDCl3)δ171.6,155.8,154.6,140.9,128.9,128.1,127.5,127.3,127.2,81.6,81.2,56.0,52.0,36.2,28.4,28.3; HRMS(ESI+):calculated m / z[M+Na] + for[C 26 H 34 N2O6Na] + :493.2310,found:493.2308.

[0118] 3-Phenylacetic-3-(p-Tolueneamino)propionic acid (3ba)

[0119] Appearance: White solid

[0120]

[0121] 143.6,129.2,128.3,126.8,126.7,124.4,113.3,54.0,43.0,20.1; HRMS(ESI+):calculatedm / z[M+H] + for[C 16 H 18 NO2] + :256.1333,found:256.1329.

[0122] 23-(4-((tert-butoxycarbonyl)oxy)phenyl)-3-(p-tolylamino)propionic acid (3ca)

[0123]

[0124] 149.3,145.3,141.3,129.2,127.7,124.5,121.2,113.2,83.1,53.3,42.9,27.3,20.1; HRMS(ESI+):calculated m / z[M+H] + for[C 21 H 26 NO5] + :372.1806,found:372.1805.

[0125] 3-(4-phenoxyphenyl)-3-(p-tolylamino)propionic acid (3da)

[0126]

[0127] 172.1,156.6,155.5,145.3,138.6,130.1,129.3,128.2,124.5,123.5,118.7,118.3,113.2,53.4,43.0,20.1; HRMS(ESI-):calculated m / z[MH] - for[C 22 H 20 NO3] - :346.1449,found:346.1449.

[0128] 3-(4-(tert-butoxycarbonyl)phenyl)-3-(p-tolylamino)propionic acid (3ea)

[0129]

[0130] 145.2,130.0,129.2,129.1,126.9,124.6,113.3,80.5,53.8,42.6,27.8,20.1; HRMS(ESI+):calculated m / z[M+H] + for[C 21 H 26 NO4] + :356.1857,found:356.1855.

[0131] 3-(4-(hydroxymethyl)phenyl)-3-(p-tolyl)propionic acid (3fa)

[0132]

[0133] 130.0,129.2,129.1,126.9,124.6,113.3,80.5,53.8,42.6,27.8,20.1; HRMS(ESI+):calculatedm / z[M+H] + for[C 21 H 26 NO4] + :356.1857,found:356.1855.

[0134] (p-Tolylamino)-3-(3-(trifluoromethyl)phenyl)propionic acid (3ga)

[0135]

[0136] 131.1, 129.3, 129.3, 129.1 (q, J = 31.3Hz), 124.8, 124.4 ( q, J = 272.2Hz), 123.7 ( q, J = 3.7Hz), 123.2 ( q, J = 3.9Hz), 113.3, 53.5, 42.7, 20.1; 19 F NMR(376MHz,DMSO-d6)δ-60.93; HRMS(ESI+):calculated m / z[M+H] + for[C 17 H 17 F3NO2] + :324.1206,found:324.1202.

[0137] 3-(3-Methoxyphenyl)-3-(p-Tolylamino)propionic acid (3ha)

[0138] Properties: Colorless oily liquid

[0139]

[0140] 20.1; HRMS(ESI+):calculated m / z[M+H] + for[C 17 H 20 NO3] + :286.1438,found:286.1439.

[0141] 3-(3-Chlorophenyl)-3-(p-Tolylamino)propionic acid (3ia)

[0142]

[0143] 126.4,125.6,124.7,113.3,53.4,42.7,20.1; HRMS(ESI+):calculated m / z[M+H] + for[C 16 H 17 ClNO2] + :290.0943,found:290.0939.

[0144] (3-(allyloxy)phenyl)-3-(p-tolyl)propionic acid (3ja)

[0145]

[0146] 4.71(t,J=7.0Hz,1H),4.49(d,J=5.4Hz,2H),2.73–2.54(m,2H),2.08(s,3H); 13 CNMR(101MHz,DMSO-d6)δ172.2,158.3,145.5,145.4,133.8,129.3,129.2,124.5,1 19.1,117.6,113.3,113.2,112.6,68.1,53.9,43.0,20.1; HRMS(ESI+):calculated m / z[M+H] + for[C 19 H 22 NO3] + :312.1595,found:312.1594.

[0147] 3-(2-fluorophenyl)-3-(p-polyamino)propionic acid (3ka)

[0148] 145.1, 130.0 (d, J = 14.2Hz), 129.4, 128.8 (d, J = 8.3Hz), 128.0 (d, J = 4.2Hz), 124. 8,124.5(d,J=3.3Hz),115.2(d,J=22.1Hz),112.9,47.2(d,J=2.9Hz),41.5,20.1; 19 F NMR(376MHz,DMSO-d6)δ-119.74–-120.09(m); HRMS(ESI+):calculated m / z[M+H] + for[C 16 H 17 FNO2] + :274.1238,found:274.1238.

[0149] 3-(2-(but-2-yn-1-yloxy)phenyl)-3-(p-tolyl)propionic acid (3la)

[0150]

[0151] 3H); 13 C NMR(101MHz,DMSO-d6)δ172.2,154.7,145.4,131.6,129.1,127.6,126.7,124.3,12 1.0,113.0,112.6,83.3,75.0,56.3,47.8,41.2,20.0,3.2; HRMS(ESI+):calculated m / z[M+H] + for[C 20 H 22 NO3] + :324.1595,found:324.1591.

[0152] 3-(6-methoxynaphthyl-2-yl)-3-(p-Tolylamino)propionic acid (3ma)

[0153]

[0154] 2.89–2.62(m,2H),2.05(s,3H); 13 C NMR(101MHz,DMSO-d6)δ172.2,157.1,145.4,138.7,133.5,129.2,129.1,128.2,127.0,1 25.4,125.1,124.4,118.6,113.3,105.8,55.2,54.1,42.9,20.1; HRMS(ESI-):calculated m / z[MH] - for[C 21 H 20 NO3] - :334.1449,found:334.1452.

[0155] 3-(9-Ethyl-9H-carbazole-2-yl)-3-(p-Tolylamino)propionic acid (3na)

[0156]

[0157] 6.13(s,1H),4.91(t,J=7.2Hz,1H),4.37(q,J=7.1Hz,2H),2.93–2.65(m,2H),2.04(s,3H),1.27(t,J=7.1Hz,3H); 13 C NMR (101MHz, DMSO-d6) δ172.3,145.5,139.8,138.7,134.0,129.2,125.6,124.5,124.3,122.0,121. 9,120.2,118.6,118.4,113.4,109.1,109.0,54.4,43.6,37.0,20.1,13.8; HRMS(ESI-):calculated m / z[MH] - for[C 24 H 23 N2O2] - :371.1765,found:371.1762.

[0158] 3-(3,5-Dimethoxyphenyl)-3-(p-polyamino)propionic acid (3oa)

[0159]

[0160] Calculated m / z[M+H] + for[C 18 H 22 NO4] + :316.1544,found:316.1542.

[0161] 2-Methyl-3-phenyl-3-(p-toluidine)propionate (3pa)

[0162]

[0163] Chloroform-d)δ175.6,144.7,141.5,129.7,128.7,127.5,127.0,127.0,126.7,113.8,61.0,51.9,46.9,20.5,15.4; HRMS(ESI+):calculated m / z[M+H] + for[C 18 H 22 NO2] + :284.1646,found:284.1644.

[0164] 2,3-Diphenyl-3-(p-polyamino)propionate methyl ester (3qa)

[0165]

[0166] Chloroform-d)δ173.0,144.5,140.8,135.7,129.7,128.9,128.5,128.4,127.7,127.3,127.1,127.0,114.3,61.6,59.0,52.3,20.5.HRMS(ESI+):calculated m / z[M+H] + for[C 23 H 24 NO2] + :346.1802,found:346.1800.

[0167] 3-(2-Methyl-2-phenylhydrazine)-3,3-diphenylpropionic acid (3ra)

[0168]

[0169] 127.3,121.5,118.0,66.8,47.2,42.4; HRMS(ESI+):calculated m / z[M+H] + for[C 22 H 23 N2O2] + :347.1755,found:347.1751.

[0170] Methyl 3-([1,1'-biphenyl]-4-yl)-3-(2-methyl-2-phenylhydrazine)butyrate (3sa)

[0171]

[0172] 144.6,140.8,139.8,128.9,128.8,127.4,127.1,127.0,126.5,119.0,115.1,61.2,51.5,45.3,44.0,25.3; HRMS(ESI+):calculated m / z[M+H] + for[C 24 H 27 N2O2] + :375.2068,found:375.2064.3-([1,1'-biphenyl]-4-yl)-2,2-difluoro-3-(p-tolyl)methyl propionate (3ta)

[0173]

[0174] 31.2Hz),143.0,141.8,140.5,132.9,130.0,128.9,128.8,128.8,127.6,127.5, 127.2,114.8(dd,J=255.9,2.4Hz),114.7,60.3(dd,J=27.3,22.4Hz),53.7,20.5; 19 F NMR(376MHz,Chloroform-d)δ-108.06(d,J=258.3Hz),-119.84(d,J=258.2Hz); HRMS(ESI+):calculated m / z[M+H] + for[C 23 H 22 F2NO2] + :382.1614,found:382.1613.

[0175] Methyl 2,2-difluoro-3-(naphth-2-yl)-3-(p-polyamino)propionate (3ua)

[0176]

[0177] (101MHz,Chloroform-d)δ164.2(dd,J=33.4,30.9Hz),143.0,133.6,133.2,131.4,129.9,128.72,128.66,128. 3,128.2,127.8,126.6,126.5,125.4,114.9(dd,J=255.8,2.1Hz),114.7,60.7(dd,J=27.1,22.4Hz),53.7,20.5; 19 F NMR(376MHz,Chloroform-d)δ-108.2(dd,J=258.2,7.3Hz),-119.4(dd,J=258.2,19.5Hz); HRMS(ESI+):calculated m / z[M+H] + for[C 21 H 20 F2NO2] + :356.1457,found:356.1458.

[0178] 4-Isopropoxy-2-methyl-4-oxo-3-(p-toluamino)butyric acid (3va)

[0179]

[0180] 129.2,129.2,125.4,125.3,113.2,113.1,68.0,67.8,58.6,58.4,41.6,41.4,21.5,21.5,21.4,21.4,20.0,13.1,12.8; HRMS(ESI+):calculated m / z[M+H] + for[C 15 H 22 NO4] + :280.1544,found:280.1545.

[0181] 4-((adamantane-2-yl)oxy)-4-oxo-3-(p-tolylamino)butyric acid (3wa)

[0182]

[0183] 41.1,37.4,36.0,30.8,20.4; HRMS(ESI-):calculated m / z[MH] - for[C 14 H 18 NO4] - :356.1867,found:356.1864.

[0184] 4-Oxo-3-(p-Tolylamino)-4-(((1S,2S,4S)-1,7,7-Trimethylbicyclo[2.2.1]Hept-2-yl)oxy)butyric acid (3xa)

[0185]

[0186] 1.16-1.01(m,2H),0.90(d,J=13.6Hz,3H),0.81(s,3H),0.76(d,J=21.6Hz,3H); 13 C NMR

[0187] (101MHz,Chloroform-d)δ176.2,176.1,171.79,171.77,143.7,143.6,129.8,128.43,128.38,114.35,114.26,82.84,82.80,77.3,77.0,54.0,53. 8,48.67,48.66,46.89,46.85,44.89,44.88,38.7,38.4,37.1,37.0,33.7,33.6,26.9,20.4,20.0,19.8,19.7,11.4,11.3; HRMS(ESI-):calculated m / z[MH] - for[C 21 H 28 NO4] - :358.2024,found:358.2022.

[0188] 4-((2-(4-methylcyclohexyl-3-en-1-yl)propyl-2-yl)oxy)-4-oxo-3-(p-tolylamino)butyric acid (3ya)

[0189]

[0190] =6.0Hz,2H),2.24(s,3H),2.01-1.86(m,4H),1.82-1.66(m,2H),1.62(s,3H),1.44-1.37(m,6H),1.29-1.15(m,1H); 13 C NMR(101MHz,Chloroform-d)δ176.1,171.21,171.19,143.8,133.92,133.91,129.8,128.43,128.40,120.0,114.45,114.42,87.42,87.37,54 .63,54.56,42.8,37.24,37.23,30.72,30.70,26.3,26.2,23.8,23.7,23.3,23.2,23.05,22.97,22.7,20.4; HRMS(ESI-):calculatedm / z[MH] - for[C 21 H 28 NO4] - :358.2024,found:358.2022.

[0191] Although specific embodiments of the present invention have been described in detail with reference to examples, they should not be construed as limiting the scope of protection of this patent. Various modifications and variations that can be made by those skilled in the art without inventive effort within the scope described in the claims are still within the scope of protection of this patent.

Claims

1. A method for synthesizing β-amino acid compounds based on olefin nitrogen carboxylation reaction, characterized in that, Includes the following steps: The reaction substrates olefins, amines, a photocatalyst, a copper catalyst, and a base were mixed. An organic solvent was then added under a CO2 atmosphere, and the mixture was stirred under light irradiation. The reaction products were then separated and purified to obtain β-amino acid compounds. The reaction equation is as follows: ； The reaction substrate olefin is: ； ； The reaction substrate amine is: ； The photocatalyst is a phenolic photocatalyst, an organic dye photocatalyst, or an organometallic photocatalyst; The copper catalyst is CuCl, CuBr, CuI, CuOAc, CuCN, CuTc, CuOTf, CuOTs, Cu(CH3CN)4PF6, Cu(CH3CN)4BF4, Cu(CH3CN)4OTf, CuOPiv, or CuO. t Bu, Cu(CH3CN)4OTs, CuCl2, CuBr2, CuI2, Cu(OAc)2, Cu(OTf)2, Cu(BF4)2, Cu(OPiv)2 or Cu(acac)2.

2. The method for synthesizing β-amino acid compounds based on olefin nitrogen carboxylation reaction as described in claim 1, characterized in that, The molar ratio of the reaction substrate olefin, the reaction substrate amine, the photocatalyst, the copper catalyst, and the base is 1:0.5~10:0.001~0.3:0.01~3:0.01~5.

3. The method for synthesizing β-amino acid compounds based on olefin nitrogen carboxylation reaction as described in claim 1 or 2, characterized in that, The base is a carbonate, bicarbonate, fluoride, alkoxy base, phosphate, hydrogen phosphate, carboxylate, or organic base.

4. The method for synthesizing β-amino acid compounds based on olefin nitrogen carboxylation reaction as described in claim 1, characterized in that, The organic solvent is MeCN, DMF, DMAc, DMSO, NMP, or THF.

5. The method for synthesizing β-amino acid compounds based on olefin nitrogen carboxylation reaction as described in claim 1, characterized in that, When illuminated, the wavelength is 300-700nm.

6. The method for synthesizing β-amino acid compounds based on olefin nitrogen carboxylation reaction as described in claim 1, characterized in that, It also includes the addition of a molecular sieve to the reaction substrate, wherein the mass ratio of the molecular sieve to the reaction substrate is 0.1-100:1.

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