Aza adamantane quaternary ammonium salt phosphine ligand as well as preparation method and application thereof

Abstract

The invention provides an aza-adamantane quaternary ammonium salt phosphine ligand as well as a preparation method and application thereof, and belongs to the technical field of organic synthesis. The preparation method comprises the following steps: under the protection of inert atmosphere, mixing a phosphine-containing compound with a first organic solvent, adding an n-butyllithium solution into the obtained phosphine-containing compound solution, carrying out deprotonation reaction at low temperature, mixing the obtained phosphine-lithium intermediate with dichloromethane, and carrying out chloromethylation reaction to obtain a chloromethyl phosphine compound; mixing the chloromethyl phosphine compound, aza-adamantane and a second organic solvent, and carrying out quaternization reaction to obtain various substituted aza-adamantane quaternary ammonium salt phosphine ligands; the azaadamantane quaternary ammonium salt phosphine ligand can simultaneously exert the space and charge advantages of azaadamantane and the electron adjustability of phosphine, shows better thermal stability and solvent compatibility in a catalytic system, and can be used for constructing a novel bifunctional phase transfer catalyst or a phosphine ligand precursor.

Description

A quaternary ammonium phosphine ligand of azadamane, its preparation method and application Technical Field

[0001] This invention relates to the field of organic synthesis technology, and in particular to an adamantane quaternary ammonium phosphine ligand, its preparation method, and its application. Background Technology

[0002] Phosphine ligands are widely used in transition metal catalytic reactions, and their electronic effects and spatial configurations have a significant impact on catalytic activity and selectivity. However, traditional phosphine ligands are easily oxidized, sensitive to air, and have poor solubility in polar media, making it difficult to meet the requirements of metal catalytic reactions. Therefore, developing a novel quaternary ammonium salt phosphine ligand is of great significance for promoting the high efficiency of transition metal catalytic reactions. Summary of the Invention

[0003] The purpose of this invention is to provide an azaadamantane quaternary ammonium phosphine ligand, its preparation method and application, wherein the azaadamantane quaternary ammonium phosphine ligand exhibits good stability in the presence of air and moisture and has good solvent compatibility.

[0004] To achieve the above-mentioned objectives, the present invention provides the following technical solution: The present invention provides an azaadamantane quaternary ammonium phosphine ligand having the structure shown in Formula I: Formula I; R is aryl or alkyl.

[0005] Preferably, R is phenyl, n-butyl, isopropyl, tert-butyl, cyclohexyl, or adamantyl.

[0006] This invention provides a method for preparing the above-mentioned azaadamandane quaternary ammonium phosphine ligand, comprising the following steps: under an inert atmosphere, mixing a phosphine-containing compound with a first organic solvent to obtain a phosphine-containing compound solution; adding a n-butyllithium solution to the phosphine-containing compound solution and performing a deprotonation reaction at low temperature to obtain a lithium phosphine intermediate; mixing the lithium phosphine intermediate with dichloromethane and performing a chloromethylation reaction to obtain a chloromethylphosphine compound; mixing the chloromethylphosphine compound, azaadamandane, and a second organic solvent and performing a quaternization reaction to obtain the azaadamandane quaternary ammonium phosphine ligand.

[0007] Preferably, the phosphine-containing compound includes diphenylphosphine, di-n-butylphosphine, diisopropylphosphine, di-tert-butylphosphine, dicyclohexylphosphine, or diadamantylphosphine; the concentration of the n-butyllithium solution is 1~1.6 mol / L.

[0008] The first organic solvent includes anhydrous tetrahydrofuran, n-hexane, or diethyl ether.

[0009] Preferably, the molar ratio of the phosphine-containing compound to the n-butyllithium in the n-butyllithium solution is 1:(1~1.2); the deprotonation reaction is carried out at a temperature of -78°C for 0.5~1h.

[0010] Preferably, the molar ratio of the lithium phosphine intermediate to dichloromethane is 1:(2500~3120); the chloromethylation reaction is carried out at a temperature of -78°C for 12~16 hours.

[0011] Preferably, the second organic solvent includes anhydrous acetonitrile, N,N-dimethylformamide, or 1,4-dioxane.

[0012] Preferably, the molar ratio of the chloromethylphosphine compound to azadamane is 1:(1~1.2); the quaternization reaction is carried out at a temperature of 60~80℃ for 8~12h.

[0013] This invention provides the application of the above-mentioned azaadamantane quaternary ammonium phosphine ligand or the azaadamantane quaternary ammonium phosphine ligand prepared by the above preparation method in transition metal catalytic reactions.

[0014] The beneficial effects of the present invention are as follows: The present invention provides an azaadamantane quaternary ammonium phosphine ligand, which combines the rigid cage-like framework of azaadamantane with the positive charge center of the quaternary ammonium salt, which is beneficial to stabilizing the metal coordination environment and improving stereoselectivity. It also enhances substrate binding and improves catalytic efficiency through electrostatic interaction. At the same time, the quaternary ammonium cation has strong chemical inertness, is resistant to acids and alkalis, is resistant to high temperatures, and has good cycle performance.

[0015] In this invention, the substituents (phenyl, butyl, cyclohexyl, isopropyl, tert-butyl, cyclohexyl, or adamantyl) on the phosphine atom in the azaadamantane quaternary ammonium phosphine ligand are tunable, thereby enabling system regulation of electronic effects and spatial volume to adapt to different catalytic systems. The azaadamantane quaternary ammonium phosphine ligand also possesses hydrophobicity and thermal stability, and can be used as a bifunctional phase transfer catalyst or ligand precursor.

[0016] This invention uses azaadamantane as the cationic skeleton and prepares azaadamantane quaternary ammonium salts by quaternization reaction with chloromethyl-substituted organophosphorus compounds. The synthesis method is simple, the raw materials are readily available, the yield is high, and it is easy to expand. By changing the phosphine substituents, structural diversification can be achieved, thus expanding its application in the field of catalysis. Detailed Implementation

[0017] This invention provides a azidane quaternary ammonium phosphine ligand having the structure shown in Formula I: Formula I; R is aryl or alkyl.

[0018] In this invention, unless otherwise specified, all raw materials required for preparation are commercially available products well known to those skilled in the art.

[0019] In this invention, R is preferably phenyl, n-butyl, isopropyl, tert-butyl, cyclohexyl, or adamantyl.

[0020] This invention provides a method for preparing the above-mentioned azaadamandane quaternary ammonium phosphine ligand, comprising the following steps: under an inert atmosphere, mixing a phosphine-containing compound with a first organic solvent to obtain a phosphine-containing compound solution; adding a n-butyllithium solution to the phosphine-containing compound solution and performing a deprotonation reaction at low temperature to obtain a lithium phosphine intermediate; mixing the lithium phosphine intermediate with dichloromethane and performing a chloromethylation reaction to obtain a chloromethylphosphine compound; mixing the chloromethylphosphine compound, azaadamandane, and a second organic solvent and performing a quaternization reaction to obtain the azaadamandane quaternary ammonium phosphine ligand; the reaction formulas involved are as follows: .

[0021] The present invention preferably involves adding a phosphine-containing compound and a first organic solvent to a dry reaction flask equipped with a magnetic stirrer under an inert atmosphere, stirring until completely dissolved, then adding a n-butyllithium solution dropwise to the phosphine-containing compound solution, and conducting a deprotonation reaction under a low-temperature cold bath, causing the solution to gradually turn orange-red. After the addition is complete, the temperature is naturally raised to room temperature, and stirring is continued to obtain a phosphine-lithium intermediate.

[0022] In this invention, the inert atmosphere preferably includes an argon atmosphere or a nitrogen atmosphere.

[0023] In this invention, the phosphine-containing compound preferably includes diphenylphosphine, di-n-butylphosphine, diisopropylphosphine, di-tert-butylphosphine, dicyclohexylphosphine, or diadamantylphosphine, and more preferably diphenylphosphine.

[0024] In this invention, the concentration of the n-butyllithium solution is preferably 1~1.6 mol / L, and more preferably 1.6 mol / L.

[0025] In this invention, the first organic solvent includes anhydrous tetrahydrofuran, n-hexane, or diethyl ether, and is more preferably anhydrous tetrahydrofuran.

[0026] In this invention, the molar ratio of the phosphine-containing compound to the n-butyllithium in the n-butyllithium solution is preferably 1:(1~1.2), and more preferably 1:1.

[0027] In this invention, the temperature of the deprotonation reaction is preferably -78°C, the time is preferably 0.5~1h, and more preferably 0.5h; the stirring speed is preferably 600r / min.

[0028] In this invention, the above-mentioned lithium phosphine intermediate is preferably added dropwise to pre-cooled dichloromethane through a constant pressure dropping funnel to undergo a chloromethylation reaction. The orange color gradually fades. After the addition is complete, stirring is continued until the reaction solution becomes colorless and transparent to obtain the chloromethylphosphine compound.

[0029] In this invention, the molar ratio of the lithium phosphine intermediate to dichloromethane is preferably 1:(2500~3120), and more preferably 1:3120.

[0030] In this invention, the temperature of the chloromethylation reaction is preferably -78°C, and the time is preferably 12~16h, more preferably 12h.

[0031] After the chloromethylation reaction is completed, the present invention preferably removes the cold bath and allows the reaction solution to return to room temperature naturally. The reaction product is then subjected to rotary evaporation to remove most of the solvent, yielding a white paste-like solid. Toluene is then added for extraction, and the resulting mixture is filtered through a sand core funnel containing diatomaceous earth to remove all volatile components, yielding a chloromethylphosphine compound.

[0032] In this invention, the vacuum degree of the first rotary evaporator and the second rotary evaporator are preferably 20 mbar, the temperature is preferably 35°C, and the rotation speed is preferably 150 r / min.

[0033] After the chloromethylation reaction is completed, the present invention preferably removes the cold bath and allows the reaction solution to return to room temperature naturally. The reaction product is then subjected to rotary evaporation until the solvent is evaporated to remove most of the solvent, resulting in a white paste-like solid. Toluene is then added for extraction, and the resulting mixture is filtered through a sand core funnel containing diatomaceous earth. The filtrate is concentrated under reduced pressure to remove all volatile components, yielding a chloromethylphosphine compound.

[0034] In this invention, the vacuum degree of the rotary evaporation is preferably 20 mbar, the temperature is preferably 35°C, and the rotation speed is preferably 150 r / min.

[0035] In this invention, the vacuum degree of the reduced pressure concentration is preferably 20 mbr, and the temperature is preferably 35°C.

[0036] Under dry reaction conditions, the present invention preferably dissolves the above-mentioned chloromethylphosphine compound in a second organic solvent to obtain a chloromethylphosphine solution; dissolves azaadamantane in the second organic solvent to obtain an azaadamantane solution; and adds the obtained chloromethylphosphine solution dropwise to the azaadamantane solution to undergo a quaternization reaction to obtain the azaadamantane quaternary ammonium phosphine ligand.

[0037] In this invention, the second organic solvent includes anhydrous acetonitrile, N,N-dimethylformamide or 1,4-dioxane, and is more preferably anhydrous acetonitrile.

[0038] In this invention, the molar ratio of the chloromethylphosphine compound to adamantane is preferably 1:(1~1.2), and more preferably 1:1.

[0039] In this invention, the temperature of the quaternization reaction is preferably 60~80℃, more preferably 80℃, and the time is preferably 8~12h, more preferably 12h.

[0040] After the quaternization reaction is completed, the system is preferably cooled to room temperature and the solvent is removed by vacuum concentration using a rotary evaporator to obtain a light yellow viscous residue. The light yellow viscous residue is dissolved in 20 mL of dichloromethane and washed three times with 15 mL of water each time. The combined organic phases are dried with anhydrous sodium sulfate at room temperature for 30 min and then filtered. The filtrate is concentrated to obtain a crude product. The crude product is recrystallized from diethyl ether to precipitate a white solid. The white solid is collected by suction filtration and dried to obtain the adamantane quaternary ammonium phosphine ligand.

[0041] In this invention, the vacuum degree of the reduced pressure concentration is preferably 20 mbar, and the temperature is preferably 35°C.

[0042] This invention provides the application of the above-mentioned azaadamantane quaternary ammonium phosphine ligand or the azaadamantane quaternary ammonium phosphine ligand prepared by the above preparation method in transition metal catalytic reactions.

[0043] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0044] Example 1

[0045] Under an argon atmosphere at -78°C, 10.0 mmol of diphenylphosphine and 100 mL of anhydrous tetrahydrofuran were added to a dry reaction flask equipped with a magnetic stirrer. The mixture was stirred at 600 rpm until completely dissolved. A 1.6 mol / L n-butyllithium solution in n-hexane was added dropwise, with a molar amount of 10.0 mmol of n-butyllithium. After the addition was complete, the mixture was allowed to cool naturally to room temperature and stirred at 600 rpm for 0.5 h to obtain a tetrahydrofuran solution of lithium diphenylphosphine. This lithium diphenylphosphine tetrahydrofuran solution was then added to pre-cooled dichloromethane at -78°C using a constant-pressure dropping funnel. The molar ratio of lithium diphenylphosphine to dichloromethane was 1:3120. The mixture was stirred at 600 rpm until the reaction solution became colorless and transparent. The chloromethylation reaction took 12 h. The cold bath was removed, and the reaction solution was allowed to return to room temperature naturally. The mixture was then stirred at 35°C and 20 mbar at a rate of 150 °C. The reaction mixture was rotary evaporated at a rate of r / min to obtain a white paste-like solid. Extraction was performed with 250 mL of toluene, and the resulting mixture was filtered through a diatomaceous earth-filled sand funnel. The filtrate was concentrated under reduced pressure at 35 °C and 20 mbar to remove all volatile components, yielding chloromethyldiphenylphosphine. The crude product was used directly in the next reaction. Under dry conditions, 5 mmol of the above chloromethyldiphenylphosphine was dissolved in 30 mL of anhydrous acetonitrile. The resulting solution was added dropwise to 20 mL of anhydrous acetonitrile solution containing 5 mmol of 1-azadamane at room temperature. After the addition was complete, the mixture was heated to 80 °C under reflux and stirred continuously at 600 r / min for 12 h. After the reaction was complete, the system was cooled to room temperature, and the solvent was removed by concentrated under reduced pressure at 35 °C and 20 mbar using a rotary evaporator, yielding a light yellow viscous residue. This residue was dissolved in 20 mL of dichloromethane and washed three times with 15 mL of water each time. mL, combined organic phases, dried over anhydrous sodium sulfate at room temperature for 30 min, filtered, and the filtrate was concentrated to obtain the crude product; the crude product was recrystallized from diethyl ether, precipitating a white solid, which was collected by suction filtration and dried under vacuum of 35 °C and 20 mbar to obtain 1-[(diphenylphosphino)methyl]-1-azaadamantaneonium chloride, with the structural formula: The yield was 87%, and the NMR data were... 1 H NMR (500 MHz, CDCl3) δ 7.59 – 7.43(m, 4H), 7.43 – 7.24 (m, 6H), 4.45 (s, 2H), 3.71 – 3.40 (m, 5H), 3.44 – 3.14(m, 1H), 2.12 (pt, J = 6.8, 5.6 Hz, 2H), 1.84 – 1.47 (m, 7H). 13C NMR (125MHz, CDCl3) δ 137.35, 133.48, 129.17, 128.59, 66.26, 65.66, 35.32, 30.78. Example 2 differs from Example 1 only in that diphenylphosphine is replaced with di-n-butylphosphine to obtain chloromethyl di-n-butylphosphine, the crude product of which is directly used in the next reaction; other conditions remain unchanged; 1-[(di-n-butylphosphino)methyl]-1-azaadamantaneonium chloride is obtained, with the structural formula […]. The yield was 85%, and the NMR data were... 1 H NMR (500 MHz, CDCl3) δ 3.87 (s, 2H),3.52 – 3.39 (m, 5H), 3.25 – 3.14 (m, 1H), 2.12 (pt, J = 6.8, 5.6 Hz, 2H), 2.05 (t, J = 9.1 Hz, 4H), 1.81 – 1.61 (m, 7H), 1.52 (m, 4H), 1.21 (tq, J =8.2, 6.8 Hz, 4H), 0.77 (t, J = 6.8 Hz, 6H). 13 C NMR (125 MHz, CDCl3) δ 68.97, 65.83, 35.32, 31.05, 28.34, 26.90, 25.37, 14.71.

[0046] Example 3

[0047] The only difference from Example 1 is that diphenylphosphine is replaced with diisopropylphosphine to obtain chloromethyldiisopropylphosphine, and the crude product is used directly in the next reaction; other conditions remain unchanged; 1-[(diisopropylphosphino)methyl]-1-azaadamantaneonium chloride is obtained, with the structural formula as follows: The yield was 81%, and the NMR data were... 1 H NMR (500 MHz, CDCl3) δ 3.80 (s, 2H),3.53 – 3.39 (m, 5H), 3.23 – 3.15 (m, 1H), 2.12 (pt, J = 6.9, 5.6 Hz, 2H),1.84 – 1.55 (m, 9H), 0.97 (d, J = 6.7 Hz, 12H). 13C NMR (125 MHz, CDCl3) δ 66.22, 65.96, 35.32, 31.05, 27.62, 18.85. Example 4 differs from Example 1 only in that diphenylphosphine is replaced with di-tert-butylphosphine to obtain chloromethyldiisopropylphosphine, the crude product of which is directly used in the next reaction; other conditions remain unchanged; 1-[(di-tert-butylphosphino)methyl]-1-azaadamantaneonium chloride is obtained, with the structural formula […]. The yield was 78%, and the NMR data were... 1 H NMR (500 MHz, CDCl3) δ 4.41 (s, 2H), 3.58 – 3.40 (m, 5H), 3.27 – 3.14 (m, 1H), 2.12 (pt, J = 6.8, 5.6 Hz, 2H), 1.79 – 1.62 (m, 7H), 1.11 (s, 18H). 13 C NMR (125 MHz, CDCl3) δ 65.37, 62.10, 35.32, 31.00, 30.64, 28.77. Example 5 differs from Example 1 only in that diphenylphosphine is replaced with dicyclohexylphosphine to obtain chloromethyldicyclohexylphosphine, the crude product of which is directly used in the next reaction; other conditions remain unchanged; 1-[(dicyclohexylphosphino)methyl]-1-azaadamantaneonium chloride is obtained, with the structural formula […]. The yield was 82%, and the NMR data were... 1 H NMR (500 MHz, CDCl3) δ 3.73 (s, 2H), 3.55 – 3.39 (m, 5H), 3.27 – 3.09 (m, 1H), 2.32 – 2.01 (m, 4H), 1.82 – 1.60(m, 11H), 1.53 – 1.42 (m, 8H), 1.42 – 1.29 (m, 8H). 13 C NMR (125 MHz, CDCl3) δ 69.83, 65.97, 35.32, 31.05, 31.01, 30.18, 27.29, 26.49. Example 6 differs from Example 1 only in that diphenylphosphine is replaced with diadamantylphosphine to obtain chloromethyldiadamantylphosphine, the crude product of which is directly used in the next reaction; other conditions remain unchanged; 1-[(diadamantylphosphino)methyl]-1-azaadamantaneonium chloride is obtained, with the structural formula […]. The yield was 81%, and the NMR data were... 1H NMR (500 MHz, CDCl3) δ 4.58 (s, 2H), 3.60 – 3.40 (m, 5H), 3.25 – 3.16 (m, 1H), 2.22 – 2.07 (m, 4H), 2.07 – 1.93(m, 4H), 1.80 – 1.62 (m, 25H), 1.55 – 1.41 (m, 4H). 13 C NMR (125 MHz, CDCl3) δ 65.59, 65.33, 54.46, 49.10, 41.66, 41.25, 40.82, 40.00, 38.43, 36.59, 35.32, 33.30, 31.00, 29.56. Example 7 differs from Example 1 only in that anhydrous acetonitrile is replaced with N,N-dimethylformamide, while all other conditions remain unchanged; 1-[(diphenylphosphino)methyl]-1-azaadamantaneonium chloride is obtained in 86% yield.

[0048] Example 8

[0049] The only difference from Example 1 is that anhydrous acetonitrile was replaced with 1,4-dioxane, while the other conditions remained unchanged; 1-[(di-n-butylphosphino)methyl]-1-azaadamantaneonium chloride was obtained in 83% yield.

[0050] Comparative Example 1

[0051] Using 2'-(diphenylphosphino)-6,6'-dimethoxy-N,N-dimethyl-[1,1'-biphenyl]-2-amine as the organophosphine ligand in Comparative Example 1, the structural formula is as follows: .

[0052] Comparative Example 2

[0053] Using triphenylphosphine as the organophosphine ligand in Comparative Example 2, the structural formula is as follows: .

[0054] Comparative Example 3

[0055] Using tris(1-adamantyl)phosphine ligands as comparative example 3 organophosphine ligands, the structural formula is as follows: .

[0056] Comparative Example 4

[0057] Using 1,2-bis(diphenylphosphino)ethane as the organophosphine ligand in Comparative Example 4, the structural formula is as follows: .

[0058] Application examples

[0059] Using organophosphine ligands from Examples 3 and 6, and Comparative Examples 1-4, after being stored for 90 days respectively, as ligands, sterically hindered coupling reactions of sterically hindered substrates were performed. The yields of 2,6-diisopropyl-1,1':2',1''-terphenyl are shown in Table 1. The specific operating procedures are as follows:

[0060] Under a nitrogen atmosphere, 0.5 mmol of 2-bromo-1,3-diisopropylbenzene, 0.005 mmol of palladium acetate, 0.01 mmol of 1-[(diisopropylphosphino)methyl]-1-azaadamantane ligand, 1.0 mmol of sodium bicarbonate, and 1.2 mmol of 2-biphenylboronic acid were added sequentially to a dry Schlenk reaction tube. Then, a mixed solvent consisting of 0.8 mL of ethylene glycol dimethyl ether and 0.2 mL of water was injected. After sealing the reaction tube, it was placed in an oil bath preheated to 90 °C and stirred for 18 h. After the reaction was complete, the system was cooled to room temperature and the reaction was quenched with water. After extraction with ethyl acetate, drying with anhydrous sodium sulfate, filtration, and concentration under reduced pressure, the crude product was purified by column chromatography to obtain 2,6-diisopropyl-1,1':2',1''-terphenyl.

[0061] Table 1. Yields of 2,6-diisopropyl-1,1':2',1''-terphenyl before and after 90 days of ligand placement in Examples 3, 6 and Comparative Examples 1-4.

[0062] As shown in Table 1, compared with conventional ligands, the azadamane quaternary ammonium phosphine ligands of the present invention not only exhibit excellent catalytic performance in the Suzuki–Miyaura coupling reaction of sterically hindered substrates, but also possess good stability.

[0063] As can be seen from the above embodiments, the present invention provides an azaadamantane quaternary ammonium phosphine ligand. Through the quaternization reaction of chloromethylphosphine with azaadamantane, various substituted azaadamantane quaternary ammonium phosphine ligands can be prepared. The phosphine centers substituted with different alkyl or cycloalkyl groups allow for precise tuning of electronic and stereostructures, providing a diverse source of ligands for further construction of ionic liquid or metal-coordinated catalytic systems.

[0064] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A azidamyne quaternary ammonium phosphine ligand, characterized in that, It has the structure shown in Equation I: Formula I; R is aryl or alkyl.

2. The azadamane quaternary ammonium phosphine ligand according to claim 1, characterized in that, R is phenyl, n-butyl, isopropyl, tert-butyl, cyclohexyl, or adamantyl.

3. The method for preparing the azadamantane quaternary ammonium phosphine ligand according to any one of claims 1 to 2, characterized in that, Includes the following steps: Under an inert atmosphere, a phosphine-containing compound is mixed with a first organic solvent to obtain a phosphine-containing compound solution. A n-butyllithium solution is then added to the phosphine-containing compound solution, and a deprotonation reaction occurs at low temperature to obtain a phosphine-lithium intermediate. The lithium phosphine intermediate is mixed with dichloromethane to undergo a chloromethylation reaction, yielding a chloromethylphosphine compound; the chloromethylphosphine compound, azadamane, and a second organic solvent are mixed to undergo a quaternization reaction, yielding an azadamane quaternary ammonium phosphine ligand.

4. The preparation method according to claim 3, characterized in that, The phosphine-containing compound includes diphenylphosphine, di-n-butylphosphine, diisopropylphosphine, di-tert-butylphosphine, dicyclohexylphosphine, or diadamantylphosphine; the concentration of the n-butyllithium solution is 1~1.6 mol / L.

5. The preparation method according to claim 3 or 4, characterized in that, The first organic solvent includes anhydrous tetrahydrofuran, n-hexane, or diethyl ether.

6. The preparation method according to claim 4, characterized in that, The molar ratio of the phosphine-containing compound to the n-butyllithium in the n-butyllithium solution is 1:(1~1.2); the deprotonation reaction is carried out at a temperature of -78°C for 0.5~1h.

7. The preparation method according to claim 3, characterized in that, The molar ratio of the lithium phosphine intermediate to dichloromethane is 1:(2500~3120); the chloromethylation reaction is carried out at a temperature of -78°C for 12~16 hours.

8. The preparation method according to claim 3, characterized in that, The second organic solvent includes anhydrous acetonitrile, N,N-dimethylformamide, or 1,4-dioxane.

9. The preparation method according to claim 3, characterized in that, The molar ratio of the chloromethylphosphine compound to azadamane is 1:(1~1.2); the quaternization reaction is carried out at a temperature of 60~80℃ for 8~12h.

10. The application of the azaadamantane quaternary ammonium phosphine ligand according to any one of claims 1 to 2 or the azaadamantane quaternary ammonium phosphine ligand prepared by the preparation method according to any one of claims 3 to 9 in transition metal catalytic reactions.

Images