Synthetic method of gamma-aminophosphine oxide compound and derivative thereof

Abstract

The invention relates to the field of organic synthesis, in particular to a synthesis method of gamma-aminophosphine oxide compounds and derivatives thereof. According to the synthesis method disclosed by the invention, alpha, beta-unsaturated amide, diaryl phosphine oxide or phosphite ester is taken as raw materials, and under the action of acid, the gamma-aminophosphine oxide compound can be rapidly and efficiently synthesized by a one-pot method. The preparation method comprises the following steps of: generating conjugated nitrile positive ions or imine salt intermediates with strong electrophilicity from alpha, beta-unsaturated amide under the activation of acid, converting diaryl phosphine oxide or phosphite ester into strong nucleophilic three-coordination phosphorus species under the action of alkali, and further performing phosphorus-doped Michael addition reaction on the conjugated intermediates to finally generate the gamma-aminophosphine oxide compounds. According to the method disclosed by the invention, diaryl phosphine oxide or phosphite which is cheap, easy to obtain and stable in structural property is used as a phosphorus source, the substrate applicability is wide, and the economic cost is relatively low; in addition, the method realizes synthesis of a target product without participation of a metal catalyst, and is rapid and efficient.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis, and more particularly to a method for synthesizing γ-aminophosphine oxides and their derivatives. Background Technology

[0002] Aminophosphates are a class of compounds containing both amino and phosphate (or phosphoryl) functional groups. Due to their unique structural features and chemical reactivity, they play a crucial role in pharmaceutical chemistry and materials science. In the pharmaceutical field, aminophosphates are often used as key structural units or prodrug forms for various bioactive molecules. For example, they can mimic natural phosphorylation intermediates, exhibiting excellent enzyme inhibitory activity and playing a vital role in the development of antiviral, antitumor, and antibacterial drugs. Furthermore, some aminophosphates can serve as precursors for nucleotide analogs, improving drug water solubility and bioavailability. Among them, γ-aminophosphates can mimic the structure of natural amino acids or peptide bonds, exhibiting strong enzyme inhibitory activity in vivo and serving as inhibitors of proteases, transaminases, and phosphorylases. Some γ-aminophosphate derivatives have shown inhibitory effects on cancer cell proliferation and can exert antiviral or antibacterial effects by regulating metabolic pathways (e.g., Fosmidomycin). Simultaneously, the structure of γ-aminophosphates can be used to regulate drug polarity, water solubility, and metabolic stability, thereby enhancing bioavailability. Therefore, the simple and efficient synthesis of γ-aminophosphate derivatives has important synthetic application value and is of great significance for the research and design of related drug molecules.

[0003] Existing technologies for introducing phosphate esters or phosphono groups into α,β-unsaturated amide skeletons often rely on metal catalysts to activate the amide substrate or phosphorus reagent. These catalysts may be complex, water- and oxygen-sensitive transition metal or rare earth metal catalysts, or arylphosphine, which has higher nucleophilic activity but is unstable in water and oxygen, may be used as the phosphorus source. However, metal catalysts suffer from drawbacks such as high cost, toxicity, residue, and environmental damage during recycling. Furthermore, the catalytic reaction easily generates byproducts, posing problems for subsequent separation and product purification, thus affecting product quality. On the other hand, the highly reactive and water- and oxygen-sensitive nature of arylphosphine presents challenges for large-scale preparation and subsequent process development.

[0004] Therefore, developing a simple and mild method that does not require metal catalysts to directly realize the phosphorus-Michael reaction of α,β-unsaturated amides and phosphites or arylphosphoxy compounds, and rapidly constructing a series of γ-aminophosphoxy compound skeletons, is of great importance and practical value. Summary of the Invention

[0005] The purpose of this invention is to address the shortcomings of existing technologies by providing a method for synthesizing γ-aminophosphine oxides and their derivatives.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows: The first aspect of the present invention is to provide a method for synthesizing γ-aminophosphine oxide compounds, comprising the steps of:

[0007] Mix the α,β-unsaturated amide shown in formula (1) with the diarylphosphine oxide or phosphite shown in formula (2), add acid, base and organic solvent, and react to synthesize the γ-aminophosphine oxide compound shown in formula (3); R 1 Selected from H, C1-C8 alkyl, C1-C8 haloalkyl, aryl, halogen, cyano, nitro, C1-C8 alkoxy, acyl and amide groups, and heterocycles; R 2 Selected from C1-C8 alkyl, C1-C8 haloalkyl, aryl, C1-C8 alkoxy, acyl and amide groups and heterocycles; R 3 Selected from H, C1-C8 alkyl, C1-C8 haloalkyl, aryl, halogen, cyano, nitro, C1-C8 alkoxy, acyl and amide groups, and heterocycles; R 4 Selected from H, C1-C8 alkyl, C1-C8 haloalkyl, aryl, halogen, cyano, nitro, C1-C8 alkoxy, acyl and amide groups, and heterocycles; R 5 Selected from H, C1-C8 alkyl, C1-C8 haloalkyl, aryl, C1-C8 alkoxy, aryloxy and heterocyclic.

[0008] More preferably, the aryl group includes substituted or unsubstituted benzene rings, naphthalene rings, and heteroaryl rings; the substitution can be one to four; the substituted group is selected from halogens, C1-C8 alkyl groups, C1-C8 alkoxy groups, ester groups, cyano groups, nitro groups, trifluoromethyl groups, methoxy groups, carboxylic acid groups, alkynyl groups, or heterocycles.

[0009] More preferably, the acyl group is -COR a R a It can be H, C1-8 alkyl, or aryl.

[0010] More preferably, the amide group is -NHCOR b R b It can be H, C1-8 alkyl, or phenyl.

[0011] More preferably, the heterocycle is a three- to eight-membered ring containing 1 to 3 heteroatoms; the heteroatoms include N, O, and S.

[0012] More preferably, the ester group is -COOR c R c It is a C1-8 alkyl group.

[0013] Preferably, the acid includes at least one of Lewis acid and Brønsted acid; wherein the Lewis acid includes at least one of trifluoromethanesulfonic anhydride and trifluoroacetic anhydride; and the Brønsted acid includes at least one of trifluoromethanesulfonic acid and trifluoroacetic acid.

[0014] Preferably, the base includes at least one of the following: dimethylpyridine, pyridine, 1,8-diazabicycloundec-7-ene, potassium tert-butoxide, sodium bicarbonate, and potassium fluoride.

[0015] Preferably, the organic solvent includes at least one of acetonitrile, dichloromethane, tetrahydrofuran, 1,2-dichloroethane, chloroform, and toluene.

[0016] Preferably, the molar ratio of α,β-unsaturated amide, diarylphosphine oxide or phosphite, acid to base is 1:(1.5-2.5):(1.0-3.0):(1.0-3.0).

[0017] Preferably, the reaction concentration of the α,β-unsaturated amide is 0.05-5 mmol / mL.

[0018] Preferably, the reaction temperature is 25-70℃ and the reaction time is 4-8h.

[0019] Preferably, the reaction is carried out in an inert gas atmosphere.

[0020] Preferably, the steps further include: quenching with water or an aqueous hydrogen peroxide solution after the reaction is completed, followed by extraction, vacuum distillation, and column chromatography to separate the target product.

[0021] The second aspect of the present invention is to provide a γ-aminophosphine oxide compound, which is prepared by the above-described synthetic method and has the chemical formula shown in formula (3);

[0022] Among them, R 1 Selected from H, C1-C8 alkyl, C1-C8 haloalkyl, aryl, halogen, cyano, nitro, C1-C8 alkoxy, acyl and amide groups, and heterocycles; R 2 Selected from C1-C8 alkyl, C1-C8 haloalkyl, aryl, C1-C8 alkoxy, acyl and amide groups and heterocycles; R 3 Selected from H, C1-C8 alkyl, C1-C8 haloalkyl, aryl, halogen, cyano, nitro, C1-C8 alkoxy, acyl and amide groups, and heterocycles; R 4 Selected from H, C1-C8 alkyl, C1-C8 haloalkyl, aryl, halogen, cyano, nitro, C1-C8 alkoxy, acyl and amide groups, and heterocycles; R 5Selected from H, C1-C8 alkyl, C1-C8 haloalkyl, aryl, C1-C8 alkoxy, aryloxy and heterocyclic.

[0023] A third aspect of the present invention is to provide a method for synthesizing γ-aminophosphine oxide derivatives, comprising the steps of: preparing γ-aminophosphine oxide compounds using the above-described synthesis method, and preparing γ-aminophosphine oxide derivatives using the γ-aminophosphine oxide compounds as intermediates.

[0024] Preferably, the γ-aminophosphine oxide derivative is a γ-aminophosphate compound.

[0025] Preferably, the synthetic route for γ-aminophosphine oxide derivatives includes:

[0026] Among them, R 1 Selected from H, C1-C8 alkyl, C1-C8 haloalkyl, aryl, halogen, cyano, nitro, C1-C8 alkoxy, aryloxy, acyl and amide groups, and heterocycles; R 2 Selected from H, C1-C8 alkyl, C1-C8 haloalkyl, aryl, benzyl, C1-C8 alkoxy, aryloxy, acyl and amide groups, and heterocycles; R 3 Selected from H, C1-C8 alkyl, C1-C8 haloalkyl, aryl, benzyl, C1-C8 alkoxy, aryloxy, acyl and amide groups and heterocycles.

[0027] More preferably, R 1 Specifically, substituted aryl, alkyl, alkoxy, R can be selected. 2 Specifically, the following groups can be selected: hydrogen, phenyl, benzyl, alkyl, acyl, R. 3 Specifically, the following groups can be selected: hydrogen, phenyl, benzyl, alkyl, and acyl.

[0028] The present invention adopts the above technical solution and has the following technical effects compared with the prior art: The synthetic method of this invention uses α,β-unsaturated amides, diarylphosphine oxides, or phosphites as raw materials to achieve a rapid and efficient one-pot synthesis of γ-aminophosphine oxides under acidic conditions. α,β-Unsaturated amides, upon acid activation, generate highly electrophilic conjugated nitrile cations or imine salt intermediates. Under alkaline conditions, diarylphosphine oxides or phosphites tautomerize into highly nucleophilic tricoordinate phosphorus species, which then undergo a phosphatomer Michael addition reaction on the conjugated intermediates, ultimately generating γ-aminophosphine oxides. This method utilizes readily available and structurally stable diarylphosphine oxides or phosphites as phosphorus sources, offering broad substrate applicability and low economic cost. Furthermore, the synthesis of the target product requires no metal catalyst and is rapid and efficient. Detailed Implementation

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

[0030] It should be noted that, unless otherwise specified, the embodiments and features described in the present invention can be combined with each other.

[0031] The present invention will be further described below with reference to specific embodiments, but these are not intended to limit the scope of the invention.

[0032] The N-phenylacrylamide (CAS: 2210-24-4), N-([1,1'-biphenyl]-4-yl)acrylamide, N-hexylacrylamide, 4-(N-methylacrylamido)benzoate, and N-(2-(phenylethynyl)phenyl)-N-toluenesulfonylacrylamide involved in the following examples were synthesized by methods reported in existing literature.

[0033] Diphenylphosphine oxide, ethyl acetate, trifluoromethanesulfonic anhydride (Tf2O), 2,6-dimethylpyridine, and anhydrous MgSO4 were all purchased from Anaiji.

[0034] The chromatographic separation and purification methods involved in the following examples: Column type: G3, stationary phase: silica gel (particle size 300-400 mesh), mobile phase: V 石油醚 :V 乙酸乙酯 =30:70. Example 1

[0035] This embodiment provides a method for synthesizing 3-(diphenylphosphono)-N-phenylpropionamide.

[0036]

[0037] Under nitrogen protection, N-phenylacrylamide (29.4 mg, 0.2 mmol), diphenylphosphine oxide (80.8 mg, 0.4 mmol), 2,6-dimethylpyridine (47 µL, 0.4 mmol), trifluoromethanesulfonic anhydride (47 µL, 0.28 mmol), and 1,2-dichloroethane (2 mL) were added to a 10 mL reaction tube equipped with a stir bar, and reacted at 55 °C and 800 rpm for 4.5 h. After the reaction was completed, the mixture was cooled to room temperature, and 1 mL of saturated sodium bicarbonate solution and 500 µL of 30% hydrogen peroxide were added. After stirring in air for 15 min, the product was extracted, separated by vacuum distillation and column chromatography to obtain 68.4 mg of the target product, with a yield of 98%.

[0038] The obtained product was analyzed and characterized, and the specific data are as follows: 1 H NMR(500MHz ,CDCl3) δ (ppm) 9.93 (br, 1H), 7.73-7.70 (m, 4H), 7.61(d, J = 7.5 Hz, 2H), 7.45 (t, J = 7.0 Hz, 2H), 7.35 (t, J = 6.0 Hz, 4H), 7.23(t, J = 7.8 Hz, 2H), 7.03 (t, J = 7.3 Hz, 1H), 2.91-2.65 (m, 4H). 13 C NMR (125MHz, CDCl3): δ (ppm) 169.9 (d, J = 15.2 Hz), 138.9, 132.3 (d, J = 2.4 Hz), 131.4 (d, J = 101.4 Hz), 130.8 (d, J = 9.5 Hz), 128.9 (d, J = 11.7 Hz), 128.8, 123.7, 119.7, 28.9 (d, J = 2.2 Hz), 24.9 (d, J = 73.6 Hz). 31 P NMR (162MHz, CDCl3): δ (ppm) 35.1.HRMS(APCI)m / z calculated for C 21 H 21 NO2P[M+H] + :350.1304 ,found: 350.1305. Example 2

[0039] This embodiment provides a method for synthesizing N-([1,1'-biphenyl]-4-yl)-3-(diphenylphosphono)propionamide.

[0040]

[0041] Under nitrogen protection, N-([1,1'-biphenyl]-4-yl)acrylamide (44.6 mg, 0.2 mmol), diphenylphosphine oxide (80.8 mg, 0.4 mmol), 2,6-dimethylpyridine (47 µL, 0.4 mmol), trifluoromethanesulfonic anhydride (47 µL, 0.28 mmol), and 1,2-dichloroethane (2 mL) were added to a 10 mL reaction tube equipped with a stir bar and reacted at 55 °C and 800 rpm for 4.5 h. After the reaction was completed, the mixture was cooled to room temperature, and 1 mL of saturated sodium bicarbonate solution and 500 µL of 30% hydrogen peroxide were added. The mixture was stirred in air for 15 min, and then extracted, distilled under reduced pressure, and separated by column chromatography to obtain 74.8 mg of the target product, with a yield of 88%.

[0042] The obtained product was analyzed and characterized, and the specific data are as follows: 1 H NMR(500MHz, CDCl3) δ (ppm) 10.56 (br, 1H), 7.78-7.73 (m, 6H), 7.57-7.46 (m, 10H), 7.41 (t, J = 7.5 Hz, 2H), 7.31 (t, J = 7.0 Hz, 1H), 2.91-2.86(m, 2H), 2.82-2.77 (m, 2H). 13 C NMR(125MHz ,CDCl3) δ (ppm) 170.1 (d, J = 14.5Hz), 140.8, 138.6, 136.4, 132.3, 132.0 (d, J = 100.7 Hz), 130.7 (d, J = 9.6Hz), 129.1 (d, J = 11.5 Hz), 128.8, 127.4, 127.0, 126.9, 120.1, 29.1, 25.1(d,J = 73.0 Hz). 31 P NMR (162 MHz, CDCl3): δ (ppm) 34.6.HRMS(APCI)m / z calcd.for C 27 H 25 NO2P(M+H) + :426.1618; found:426.1621. Example 3

[0043] This embodiment provides a method for synthesizing 3-(diphenylphosphono)-N-hexylpropionamide.

[0044]

[0045] Under nitrogen protection, N-hexylacrylamide (31.0 mg, 0.2 mmol), diphenylphosphine oxide (80.8 mg, 0.4 mmol), 2,6-dimethylpyridine (47 µL, 0.4 mmol), trifluoromethanesulfonic anhydride (47 µL, 0.28 mmol), and 1,2-dichloroethane (2 mL) were added to a 10 mL reaction tube equipped with a stir bar and reacted at 55 °C and 800 rpm for 4.5 h. After the reaction was completed, the mixture was cooled to room temperature, and 1 mL of saturated sodium bicarbonate solution and 500 µL of 30% hydrogen peroxide were added. The mixture was stirred in air for 15 min, and then extracted, distilled under reduced pressure, and separated by column chromatography to obtain 52.8 mg of the target product, with a yield of 74%.

[0046] The obtained product was analyzed and characterized, and the specific data are as follows: 1 H NMR (500MHz , CDCl3) δ (ppm) 7.70-7.67 (m, 4H), 7.48 (t, J = 7.3 Hz, 2H), 7.41 (t, J = 6.7 Hz, 4H), 7.36 (br, 1H), 3.13-2.09 (m, 2H), 2.64-2.59(m, 2H), 2.54-2.49 (m, 2H), 1.42-1.37 (m, 2H), 1.27-1.17 (m, 6H), 0.82 (t, J= 6.7 Hz, 3H). 13 C NMR (125MHz, CDCl3) δ (ppm) 171.4 (d, J = 14.0 Hz), 132.3 (d, J = 99.5 Hz), 132.0 (d, J = 2.7 Hz), 130.7 (d, J = 9.8 Hz), 128.8 (d, J =11.8 Hz), 39.8, 31.5, 29.4, 28.0, 26.7, 25.3 (d, J = 73.6 Hz), 22.5, 14.1. 31 PNMR (162 MHz, CDCl3): δ (ppm) 33.4.HRMS(APCI)m / z calculated for C 21 H 29 NO2P[M+H] + :358.1931,found:358.1930. Example 4

[0047] This embodiment provides a method for synthesizing methyl 4-(3-(diphenylphosphono)-N-methylpropionamido)benzoate.

[0048]

[0049] Under nitrogen protection, 4-(N-methacrylamido)benzoate (43.8 mg, 0.2 mmol), diphenylphosphine oxide (80.8 mg, 0.4 mmol), 2,6-dimethylpyridine (47 µL, 0.4 mmol), trifluoromethanesulfonic anhydride (47 µL, 0.28 mmol), and 1,2-dichloroethane (2 mL) were added to a 10 mL reaction tube equipped with a stir bar and reacted at 55 °C and 800 rpm for 4.5 h. After the reaction was completed, the mixture was cooled to room temperature, and 1 mL of saturated sodium bicarbonate solution and 500 µL of 30% hydrogen peroxide were added. The mixture was stirred in air for 15 min, and then extracted, distilled under reduced pressure, and separated by column chromatography to obtain 49.7 mg of the target product, with a yield of 59%.

[0050] The obtained product was analyzed and characterized, and the specific data are as follows: 1 H NMR(500MHz ,CDCl3) δ (ppm) 8.00 (d, J = 8.5 Hz, 2H), 7.66 (t, J =8.9 Hz, 4H), 7.48 (t, J = 7.2 Hz, 2H), 7.42 (t, J = 6.9 Hz, 4H), 7.10 (d, J =7.3 Hz, 2H), 3.92 (s, 3H), 3.21 (s, 3H), 2.65-2.60 (m, 2H), 2.40-2.33 (m, 2H). 13 C NMR(125MHz, CDCl3) δ (ppm) 171.0 (d, J = 14.0 Hz), 166.2, 147.4,132.9, 131.9 (d, J = 2.2 Hz), 131.7 (d, J = 89.7 Hz), 130.8 (d, J = 9.4 Hz), 129.6, 128.8 (d, J = 11.7 Hz), 127.0, 52.4, 37.6, 26.6, 25.4 (d, J = 73.4Hz). 31 P NMR (162 MHz, CDCl3): δ (ppm) 32.4.HRMS (APCI)m / z calculated forC 24 H 25NO4P[M+H] + :422.1516, found : 422.1514. Example 5

[0051] This embodiment provides a method for synthesizing 3-(diphenylphosphono)-N-(2-(phenylethynyl)phenyl)-N-toluenesulfonylpropionamide.

[0052]

[0053] Under nitrogen protection, N-(2-(phenylethynyl)phenyl)-N-toluenesulfonylacrylamide (80.2 mg, 0.2 mmol), diphenylphosphine oxide (80.8 mg, 0.4 mmol), 2,6-dimethylpyridine (47 µL, 0.4 mmol), trifluoromethanesulfonic anhydride (47 µL, 0.28 mmol), and 1,2-dichloroethane (2 mL) were added to a 10 mL reaction tube equipped with a stir bar and reacted at 55 °C and 800 rpm for 4.5 h. After the reaction was completed, the mixture was cooled to room temperature, and 1 mL of saturated sodium bicarbonate solution and 500 µL of 30% hydrogen peroxide were added. The mixture was stirred in air for 15 min, and then extracted, distilled under reduced pressure, and separated by column chromatography to obtain 108.5 mg of the target product, with a yield of 90%.

[0054] The obtained product was analyzed and characterized, and the specific data are as follows: 1 H NMR(500MHz, CDCl3) δ (ppm) 8.00 (d, J = 8.5 Hz, 2H), 7.60-7.56 (m,2H), 7.54-7.47 (m, 4H), 7.46-7.30 (m, 8H), 7.24-7.20 (m, 3H), 7.11 (d, J =8.2 Hz, 2H), 7.02-7.00 (m, 2H), 2.65-2.41 (m, 4H), 2.18 (s, 3H). 13C NMR(125MHz, CDCl3) δ (ppm) 171.6 (d, J = 17.4 Hz), 145.0, 136.8, 136.1, 133.1, 132.2 (d,J = 100.3 Hz), 131.9 (d, J = 2.8 Hz), 131.8 (d, J = 2.6 Hz), 131.65, 131.59(d, J = 99.6 Hz), 131.5, 130.6 (d, J = 6.4 Hz), 130.5 (d, J = 7.5 Hz), 130.1,129.9, 129.7, 129.0, 128,8 (d, J = 15.1 Hz), 128.6 (d, J = 3.8 Hz), 128.5,128.1, 123.7, 121.8, 95.6, 85.1, 28.9, 24.7 (d, J = 73.6 Hz), 21.5. 31 P NMR(162 MHz, CDCl3): δ (ppm) 32.2.HRMS (APCI)m / z calculated for C 36 H 31 NO4PS[M+H] + :604.1706,found:604.1703. Example 6

[0055] This embodiment provides a method for synthesizing Fosmidomycin, an antibacterial drug molecule, comprising the following steps: In an organic solvent, γ-aminophosphine oxides are synthesized in a one-pot process using α,β-unsaturated amides, diarylphosphine oxides, or phosphites as raw materials and trifluoromethanesulfonic anhydride (Tf₂O). The resulting γ-aminophosphine oxides are then subjected to an amide reduction reaction to yield Fosmidomycin, an antibacterial drug molecule.

[0056] The amide reduction involves dissolving a γ-aminophosphine oxide compound in tetrahydrofuran, then adding lithium aluminum hydride dissolved in tetrahydrofuran dropwise over 30 minutes under ice / water cooling, and reacting at room temperature for a period of time under nitrogen atmosphere. The addition equivalent of lithium aluminum hydride relative to the γ-aminophosphine oxide compound is 1.0-3.0.

[0057] In summary, the synthetic method of this invention uses α,β-unsaturated amides, diarylphosphine oxides, or phosphites as raw materials to achieve a rapid and efficient one-pot synthesis of γ-aminophosphine oxides under acidic conditions. α,β-Unsaturated amides, upon acid activation, generate strongly electrophilic conjugated nitrile cations or imine salt intermediates. Under alkaline conditions, diarylphosphine oxides or phosphites tautomerize into strongly nucleophilic tricoordinate phosphorus species, which then undergo a phosphatomer Michael addition reaction on the conjugated intermediates, ultimately generating γ-aminophosphine oxides. This method utilizes readily available and structurally stable diarylphosphine oxides or phosphites as phosphorus sources, has broad substrate applicability, and low economic cost. Furthermore, the synthesis of the target product does not require a metal catalyst and is rapid and efficient.

[0058] The above description is merely a preferred embodiment of the present invention and does not limit the implementation and protection scope of the present invention. Those skilled in the art should realize that any equivalent substitutions and obvious changes made based on the content of this specification should be included within the protection scope of the present invention.

Claims

1. A method for synthesizing γ-aminophosphine oxide compounds, characterized in that the step... include: Mix the α,β-unsaturated amide shown in formula (1) with the diarylphosphine oxide or phosphite shown in formula (2), add acid, base and organic solvent, and react to synthesize the γ-aminophosphine oxide compound shown in formula (3); R 1 Selected from H, C1-C8 alkyl, C1-C8 haloalkyl, aryl, halogen, cyano, nitro, C1-C8 alkoxy, acyl and amide groups, and heterocycles; R 2 Selected from C1-C8 alkyl, C1-C8 haloalkyl, aryl, C1-C8 alkoxy, acyl and amide groups and heterocycles; R 3 Selected from H, C1-C8 alkyl, C1-C8 haloalkyl, aryl, halogen, cyano, nitro, C1-C8 alkoxy, acyl and amide groups, and heterocycles; R 4 Selected from H, C1-C8 alkyl, C1-C8 haloalkyl, aryl, halogen, cyano, nitro, C1-C8 alkoxy, acyl and amide groups, and heterocycles; R 5 Selected from H, C1-C8 alkyl, C1-C8 haloalkyl, aryl, C1-C8 alkoxy, aryloxy and heterocyclic.

2. The synthesis method according to claim 1, characterized in that, Acids include: At least one of Lewis acid and Brønsted acid; wherein, Lewis acid includes at least one of trifluoromethanesulfonic anhydride and trifluoroacetic anhydride; and Brønsted acid includes at least one of trifluoromethanesulfonic acid and trifluoroacetic acid.

3. The synthesis method according to claim 1, characterized in that, Alkali includes: At least one of dimethylpyridine, pyridine, 1,8-diazabicycloundec-7-ene, potassium tert-butoxide, sodium bicarbonate, and potassium fluoride.

4. The synthesis method according to claim 1, characterized in that, Organic solvents include at least one of acetonitrile, dichloromethane, tetrahydrofuran, 1,2-dichloroethane, chloroform, and toluene.

5. The synthesis method according to claim 1, characterized in that, α,β-unsaturated amides, diarylphosphine oxides or phosphites, and the molar ratio of acid to base is 1:(1.5-2.5):(1.0-3.0):(1.0-3.0).

6. The synthesis method according to claim 1, characterized in that, The reaction temperature is 25-70℃, and the reaction time is 4-8h.

7. A γ-aminophosphine oxide compound, characterized in that, Prepared by the synthetic method according to any one of claims 1-7, with the chemical formula shown in formula (3); Among them, R 1 Selected from H, C1-C8 alkyl, C1-C8 haloalkyl, aryl, halogen, cyano, nitro, C1-C8 alkoxy, acyl and amide groups, and heterocycles; R 2 Selected from C1-C8 alkyl, C1-C8 haloalkyl, aryl, C1-C8 alkoxy, acyl and amide groups and heterocycles; R 3 Selected from H, C1-C8 alkyl, C1-C8 haloalkyl, aryl, halogen, cyano, nitro, C1-C8 alkoxy, acyl and amide groups, and heterocycles; R 4 Selected from H, C1-C8 alkyl, C1-C8 haloalkyl, aryl, halogen, cyano, nitro, C1-C8 alkoxy, acyl and amide groups, and heterocycles; R 5 Selected from H, C1-C8 alkyl, C1-C8 haloalkyl, aryl, C1-C8 alkoxy, aryloxy and heterocyclic.

8. A method for synthesizing a γ-aminophosphine oxide derivative, characterized in that the step... include: γ-aminophosphine oxide compounds are prepared using the synthetic method described in any one of claims 1-6, and γ-aminophosphine oxide derivatives are prepared using the γ-aminophosphine oxide compounds as intermediates.

9. The synthesis method according to claim 8, characterized in that, γ-aminophosphine derivatives are γ-aminophosphate compounds.

10. The synthesis method according to claim 8, characterized in that, Synthetic routes of γ-aminophosphine oxide derivatives include: Among them, R 1 Selected from H, C1-C8 alkyl, C1-C8 haloalkyl, aryl, halogen, cyano, nitro, C1-C8 alkoxy, aryloxy, acyl and amide groups, and heterocycles; R 2 Selected from H, C1-C8 alkyl, C1-C8 haloalkyl, aryl, benzyl, C1-C8 alkoxy, aryloxy, acyl and amide groups, and heterocycles; R 3 Selected from H, C1-C8 alkyl, C1-C8 haloalkyl, aryl, benzyl, C1-C8 alkoxy, aryloxy, acyl and amide groups and heterocycles.

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