A class of planar chiral [2.2]paracyclophane monophosphine ligand pEPCP, its preparation method and application

Abstract

The application discloses a kind of plane chiral [2.2] paracyclophanane monophosphine ligand pEPCP and preparation method and application thereof, it is related to chemical catalysis technical field, and its technical scheme main points are as follows: including racemate or enantiomer, the structural formula-I of the monophosphine ligand pEPCP of the application is as follows: [2.2] paracyclophanane skeleton containing monophosphine ligand pEPCP of the application, with two benzene rings in para position by two ethylene connection unique big steric hindrance, electron-rich rigid skeleton, different types ether substituent group is introduced in structure, change the electron cloud density and steric hindrance of aromatic ring directly connected by phosphine ligand.In addition, ether substituent group can also be used as weak coordination group, participate in adjusting ligand chelate dihedral angle.This makes metal, ligand and substrate form the most suitable coordination environment in catalytic process, so that corresponding catalytic reaction has the advantages such as high reactivity, good enantioselectivity, substrate universal range is wide, especially suitable for transition metal catalyzed asymmetric coupling reaction, with economic practicability and industrial application prospect.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of chemical catalysis, more particularly, it relates to a class of planar chiral [2.2]paracyclophane monophosphine ligand pEPCP, its preparation method and application. BACKGROUND

[0002] Chiral phosphine ligands are the most studied and widely used ligands so far. By adjusting its backbone structure and functional groups (such as dihedral angle, steric hindrance, backbone rigidity and flexibility, etc.), the reaction activity, reaction type, stereoselectivity and substrate universality of the catalytic reaction can be effectively changed. Therefore, the development of new types of chiral ligands not only can expand the asymmetric catalytic system and the catalytic activation mode, but also is conducive to the discovery of new catalytic reactions that cannot be realized by traditional catalytic systems. This can significantly promote the precise synthesis of diversified chiral molecules and serve the creation of chiral drug and chiral material molecules. The development of new types of chiral phosphine ligands has always been one of the hot and frontier research fields in the field of asymmetric catalysis (Noyori, R. Angew. Chem. Int. Ed. 2002, 41, 2008; Fu, X.-F.; Zhou, Q.-L. CCS Chem. 2023, 5, 2685). Since 1991, Hayashi's group first reported the synthesis of a non-C2 symmetric, axially chiral, sterically hindered, electron-rich oxaphospholane monodentate phosphine ligand (Sp)-MOP and achieved excellent results in the asymmetric hydrosilylation of olefins (Uozumi, Y.; Hayash, T. J. Am. Chem. Soc. 1991, 113, 9887). Subsequently, this type of ligand has been widely studied in transition metal-catalyzed asymmetric reactions, solving a series of challenging catalytic asymmetric problems (Hayashi, T. Acc. Chem. Res. 2000, 33, 354). However, most of the phosphine ligands reported in the literature are axially chiral, and the types of phosphine ligands developed based on planar chiral aromatic hydrocarbon skeletons are less (Felder, S.; Wu, S.; Brom, J.; Micouin, L.; Benedetti, E. Chirality. 2021, 33, 506; CN101003549B; CN100379747C), as shown in the following structures:

[0003]

[0004] [2.2]Paracyclophane ([2,2]Paracyclophane, PCP) is a minimum cyclophane compound with electron-rich, steric-hindering, rigid skeleton and cross-ring pi-electron system. The rotation of its benzene ring plane around the macrocyclic face is blocked, and when the symmetry is broken by the substituents, the planar chirality is generated. It has a wide application in asymmetric catalysis, chiral material science and supramolecular chemistry (Hassan, Z.; Spuling, Daniel, E. Angew. Chem. Int. Ed. 2020, 59, 2156).

[0005] Therefore, the present application aims to provide a kind of planar chiral [2.2] paracyclophane monophosphine ligand pEPCP and its preparation method and application, by synthesizing a new type of non-C2 symmetry, planar chiral, steric-hindering, electron-rich oxamonophosphine ligand pEPCP containing PCP skeleton, it can be successfully applied in palladium-catalyzed asymmetric allylation reaction, coupling reaction and cyclization reaction. SUMMARY

[0006] The purpose of the present application is to provide a kind of planar chiral [2.2] paracyclophane monophosphine ligand pEPCP and its preparation method and application, the present application is synthesized by using commercial 4-hydroxy [2.2] paracyclophane as starting material enantiomer and racemate of bromocyclophane, design and synthesis corresponding [2.2] paracyclophane skeleton monophosphine ligand, the skeleton is stable, easy to modify, with electron-rich steric-hindering characteristics, synthesis route is simple, will enrich and develop phosphine ligand type, has important academic value and application value.

[0007] The above technical purpose of the present application is realized by the following technical scheme: a kind of planar chiral [2.2] paracyclophane monophosphine ligand pEPCP, including racemate or enantiomer, the structural formula-I of the monophosphine ligand pEPCP is as follows:

[0008]

[0009] Wherein, R is substituted or unsubstituted phenyl, alkyl, the substituents of substituted phenyl are each independently selected from C1-C6 alkyl, C1-C6 alkoxy or halogen, the number of substituents is 1, 2 or 3, and the alkyl is C1-C10 alkyl;

[0010] R 1 is any one of hydrogen, substituted or unsubstituted C1-C20 alkyl, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted C3-C20 alkylsilyl, substituted or unsubstituted C6-C20 arylsilyl, and one or more hydrogen atoms in the substituent group can be substituted by C1-C6 alkyl, C1-C6 alkoxy or halogen, and the number of substituents is 1, 2 or 3.

[0011] The present invention is further configured such that, in the structural formula-Ⅰ of the monophosphine ligand pEPCP, R is phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-trifluoromethylphenyl, 3,5-dimethylphenyl, 3,5-diethylphenyl, 3,5-dipropylphenyl, 3,5-di-tert-butylphenyl, 3,5-di-trifluoromethylphenyl, 3,5-dimethyl-4-methoxyphenyl, 3,4,5-trimethylphenyl, 3,5-di-tert-butyl-4-methoxyphenyl, or 3,5-di-tert-butyl-4-methylphenyl and methyl, ethyl, isopropyl, tert-butyl, cyclohexyl, or 1-adamantyl.

[0012] The present invention is further configured such that, in the structural formula-Ⅰ of the monophosphine ligand pEPCP, R 1 Selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, C5-C12 straight-chain or branched alkyl, cyclopropyl, cyclobutyl, C5-C20 cycloalkyl, benzyl, naphthyl, methoxymethyl, trifluoromethyl, C2-C6 fluoroalkyl, trimethylsilyl, triethylsilyl, triphenylsilyl, and C7-C9 silyl.

[0013] This invention also provides a method for preparing a class of planar chiral [2.2] pEPCP cyclopiperane monophosphine ligands, comprising the following steps:

[0014] S1. Using the chiral or racemic compound 4-hydroxy[2.2]p-cyclopiranane 1 as the starting material, an electrophilic substitution reaction is carried out with liquid bromine to generate brominated[2.2]p-cyclopiranane 2;

[0015] S2, Under alkaline conditions, make R 1 Halogenated R 1 -X undergoes an electrophilic substitution reaction with bromo[2.2] on cyclophane 2, introducing a substituent group R into the phenolic hydroxyl group. 1 Compound 3 was obtained;

[0016] S3. Compound 3 is subjected to bromolithium exchange with butyllithium to obtain aryl lithium intermediate 4.

[0017] S4. Adding a di-R-substituted chlorophosphine R2PCl to the reaction system results in electrophilic substitution, generating a planar chiral or racemic phosphine ligand compound pEPCP.

[0018] The present invention is further configured such that: the reaction temperature in step S1 is -20 to 40°C, the reaction time is 0.5 to 12 h, the reaction environment is an organic solvent environment, and the protective atmosphere for the reaction is nitrogen or argon inert gas;

[0019] The temperature of the reaction in the step S2 is -20-40 DEG C, the reaction time is 0.5-12h, the reaction is carried out in the presence of base, the reaction environment is organic solvent environment, and the protection atmosphere of the reaction is nitrogen or argon inert gas;

[0020] The temperature of the reaction in the step S3 is -80-60 DEG C, the reaction time is 0.5-24h, the reaction is carried out in the presence of butyl lithium, the reaction environment is anhydrous organic solvent environment, and the protection atmosphere of the reaction is nitrogen or argon inert gas;

[0021] The temperature of the reaction in the step S4 is -80-60 DEG C, the reaction time is 0.5-24h, the reaction is carried out in the presence of double R-substituted chlorophosphine R2PCl, the reaction environment is anhydrous organic solvent environment, and the protection atmosphere of the reaction is nitrogen or argon inert gas.

[0022] The application further provides that the reaction equation of the monophosphine ligand pEPCP is as follows:

[0023]

[0024] The application further provides a kind of planar chiral [2.2] paracyclophan monophosphine ligand pEPCP in asymmetric catalysis.

[0025] In summary, the application has the following beneficial effects:

[0026] 1、the monophosphine ligand pEPCP containing [2.2] paracyclophan of the application, with two benzene rings connected by two ethylene groups at the para position, a unique large steric hindrance, electron-rich rigid skeleton, different types of ether substituents are introduced into the structure, which changes the electron cloud density and steric hindrance of the aromatic ring directly connected to the phosphine ligand. In addition, the ether substituent can also act as a weak ligand, participating in the adjustment of the dihedral angle of the ligand chelation. This makes the metal, ligand and substrate form the most suitable coordination environment in the catalytic process, so that the corresponding catalytic reaction has the advantages of high reaction activity, good enantioselectivity and wide substrate universality, and is suitable for rhodium-catalyzed asymmetric Hayashi-Miyaura reaction and palladium-catalyzed asymmetric allyl alkylation reaction, both of which achieve excellent catalytic activity and stereoselectivity.

[0027] 2、the monophosphine ligand pEPCP containing [2.2] paracyclophan of the application has a simple synthesis method and a unique large steric hindrance, electron-rich rigid skeleton. By introducing different types of substituents on the phenolic hydroxyl group, the electron cloud density of the aromatic ring is increased, and the steric hindrance is changed. The ether substituent can also act as a weak ligand, participating in the adjustment of the dihedral angle of the ligand chelation. This makes the ligand, metal and substrate form the most suitable coordination environment in the catalytic process, so that it shows excellent catalytic activity and enantioselectivity control ability. BRIEF DESCRIPTION OF DRAWINGS

[0028] Figure 1 is a single crystal pattern of (Rp)-pEPCP-L1 in Example 1 of the present application;

[0029] Figure 2 is a synthetic route map of (Rp)-pEPCP-L1 compound in Example 1 of the present application. DETAILED DESCRIPTION

[0030] The following description is in conjunction with the accompanying drawings Figures 1-2 The present application is further described in detail.

[0031] Example 1: Preparation of planar chiral phosphine ligand (Rp)-pEPCP-L1 containing [2.2]paracyclophane skeleton, the structure is as follows:

[0032]

[0033] The preparation method of (Rp)-pEPCP-L1 compound in this embodiment, the synthetic route is as shown in Figure 2 , comprising the following steps:

[0034] 1) Under the protection of nitrogen, a dry 500 mL three-necked flask was added with planar chiral 4-hydroxy[2.2]paracyclophane (Rp)-1 (100 mmol, 22.4 g), 200 mL of anhydrous dichloromethane, and a mixed solution of Br2 (1.0 eq, 100 mmol, 5.2 mL) and dichloromethane 50 mL was added dropwise at room temperature under stirring, and the dropwise addition was completed by using a syringe pump for 30 min, and then the stirring was continued at room temperature for 4 h; the sample was detected by spotting, after the reaction was completed, 100 mL of H2O was added for washing once, 100 mL of saturated NaHCO3 was added for washing three times, DCM was extracted three times, the organic phases were combined and washed with saturated NaCl, dried with anhydrous Na2SO4, rotary evaporation under reduced pressure, and the crude product was purified by silica gel column chromatography (PE:DCM=2:3) to obtain planar chiral brominated [2.2]paracyclophane (Rp)-2 compound 26.3 g, with a yield of 78%.

[0035] 2) Under nitrogen protection, into a dry 500 mL three-necked flask, sequentially added planar chiral bromo[2.2]paracyclophane (Rp)-2 compound (30.2 g, 100 mmol), 100 mL anhydrous DMF, then the reaction system was transferred into an ice bath for stirring for 10 min, NaH (250 mmol, 2.5 eq., 10 g, 60% wt) was added in batches, the ice bath was continued to stir for 10 min, then MeI (200 mmol, 2.0 eq., 12.5 mL) was slowly added dropwise into the reaction system, the ice bath was removed, and the stirring was continued for 1 h; after the reaction was completed, 20 mL saturated NH4Cl was added to quench the reaction, EA extraction was performed for 3 times, the organic phases were combined and washed with saturated NaCl, dried over anhydrous Na2SO4, rotary evaporation was performed under reduced pressure, after the solvent was removed, the crude product was purified by silica gel column chromatography, (Rp)-3 compound 30.9 g was obtained with a yield of 98%.

[0036] 3) Under nitrogen protection, into a dry 250 mL single-necked tomato-shaped flask, sequentially added (Rp)-3 (10 mmol, 3.16 g), 50 mL anhydrous THF, then the reaction system was transferred into -50°C for stirring for 10 min, then n-BuLi (30 mmol, 3.0 eq., 18.8 mL, 1.6 M n-hexane solution) was added dropwise into the reaction system, the stirring was continued for 1 h, and the active intermediate lithium reagent 4 was obtained.

[0037] 4) Then PPh2Cl (20 mmol, 2.0 eq., 3.6 mL) was added dropwise into the reaction system, the refrigeration was turned off, and the stirring was continued overnight; after the reaction was completed, 10 mL saturated NH4Cl was added to quench the reaction, EA extraction was performed for 3 times, the organic phases were combined and washed with saturated NaCl, dried over anhydrous Na2SO4, rotary evaporation was performed under reduced pressure, after the solvent was removed, the crude product was purified by silica gel column chromatography (PE:DCM = 2:1), and white solid (Rp)-L1 product 3.4 g was obtained with a yield of 82%.

[0038] The ligand (Rp)-L1 in the embodiment is characterized as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.14-7.01 (m, 4H), 6.90-6.80 (m, 3H), 6.73 (dd, J = 7.6, 1.6 Hz, 1H), 6.47 (dd, J = 7.6, 2.0 Hz, 1H), 6.07 (dd, J = 7.6, 1.6 Hz, 1H), 5.73 (d, J = 7.2 Hz, 1H), 5.66 (d, J = 4.8 Hz, 1H), 3.72 (s, 3H), 2.31 (s, 6H), 2.19 (s, 6H); 13C NMR (101 MHz, Chloroform-d) δ 158.4, 146.7, 146.5, 139.9, 139.0, 138.1, 138.0, 137.9, 137.5, 137.5, 132.9, 132.9, 132.7, 131.6, 131.6, 131.3, 131.0, 130.9, 130.7, 130.1, 128.3, 118.2, 118.1, 54.3, 34.7, 34.5, 34.3, 33.5, 31.4, 21.4; 31 P NMR (162 MHz, Chloroform-d) δ -7.22; HRMS (ESI) m / z calcd. for 423.1878, found: 423.1874.

[0039] Example 2: A series of planar chiral phosphine ligand compounds pEPCP-L1 to pEPCP-L14 were synthesized according to the preparation method of Example 1 by means of conventional technical means in the art, and the structural formulae are as shown below:

[0040]

[0041] Example 3: Application experiment of monophosphine ligand pEPCP containing [2.2]paracyclophane skeleton in rhodium-catalyzed asymmetric Hayashi-Miyaura reaction

[0042] The reaction equation of monophosphine ligand pEPCP containing [2.2]paracyclophane skeleton in rhodium-catalyzed asymmetric Hayashi-Miyaura reaction in this example is as shown below:

[0043]

[0044] By taking 25 mL of a sealed tube, under an argon atmosphere, cyclohexenone (0.1 mmol, 1.0 eq.), 4-phenylphenylboronic acid (0.15 mmol, 1.5 eq.), [Rh(C2H4)2Cl]2(2.5 mol%), ligand L* (6 mol%), potassium hydroxide (0.5 eq.) were sequentially added, and the gas was exchanged three times, 2 mL of ultradry 1,4-dioxane and 0.2 mL of H2O were added under a nitrogen atmosphere, and the reaction was carried out at 40°C for 12 h. Purification by silica gel column chromatography and HPLC analysis gave the yield and ee value of the product. Different ligands from the present application and commercially available well-known chiral ligands L1-L8 were respectively used to carry out catalytic reactions, and the structural formulae are as shown below:

[0045]

[0046] The results are shown in Table 1:

[0047] Table 1. Results of catalytic reactions of chiral ligands L1-L8

[0048] Ligand structure (L*) Yield (%) Ee value (%) (Rp)-pEPCP-L1 90 95 (Sp)-pEPCP-L1 89 -95 (Rp)-pEPCP-L2 88 86 (Rp)-pEPCP-L3 85 80 (Rp)-pEPCP-L4 80 70 (Rp)-pEPCP-L5 79 72 (Rp)-pEPCP-L6 88 77 (Rp)-pEPCP-L7 65 79 (Rp)-pEPCP-L8 69 81 (Rp)-pEPCP-L9 72 69 (Rp)-pEPCP-L10 78 78 (Rp)-pEPCP-L11 79 79 (Rp)-pEPCP-L12 83 56 (Rp)-pEPCP-L13 88 59 (Rp)-pEPCP-L14 59 67 L1 91 92 L2 90 90 L3 88 93 L4 90 88 L5 87 87 L6 85 89 L7 87 92 L8 88 93

[0049] Example 4: Under the same experimental conditions and operations as in Example 3, different types of substrates were used to perform the asymmetric rhodium-catalyzed Hayashi-Miyaura reaction, and the reaction equation is shown as follows:

[0050]

[0051] The reaction results are shown in Table 2:

[0052] Table 2. Results of asymmetric rhodium-catalyzed Hayashi-Miyaura reactions of different types of substrates

[0053]

[0054] As can be seen from Tables 1 and 2, the monophosphine ligand pEPCP containing [2.2]paracyclophane in the present application has excellent catalytic activity and enantioselectivity for the rhodium-catalyzed asymmetric Hayashi-Miyaura reaction of cyclohexenone and arylboronic acid, and the results are better than those of other related types of chiral phosphine ligands; and in ortho-substituted arylboronic acid compounds, the results are also significantly better than those of other related types of chiral phosphine ligands.

[0055] The monophosphine ligand pEPCP containing [2.2]paracyclophane in the present application also has good catalytic activity and enantioselectivity for asymmetric allyl alkylation reaction (AAA).

[0056] Example 5: Application of the monophosphine ligand pEPCP containing [2.2]paracyclophane in palladium-catalyzed asymmetric allyl alkylation reaction, and the reaction equation is shown as follows:

[0057]

[0058] A 25 mL sealed tube was prepared, and under an argon atmosphere, racemic (E)-1,3-diphenylallyl acetate (0.1 mmol, 1.0 eq.), dimethyl malonate (0.2 mmol, 2.0 eq.), [Pd(C3H5)Cl]2(5 mol%), ligand L* (12 mol%), lithium acetate (12 mol%), and N,O-bistrimethylsilylacetamide (0.3 mmol, 3.0 eq., BSA) were sequentially added, and the tube was purged with argon three times. Then 2 mL of anhydrous dichloromethane was added under a nitrogen atmosphere, and the reaction was carried out at -20°C for 24 h. The product was purified by silica gel column chromatography and analyzed by HPLC to obtain the yield and ee value. Different ligands other than those in the present application and commercially available well-known chiral ligands L1-L8 were used to perform the catalytic reaction, and the results are shown in Table 3:

[0059] Table 3. Results of catalytic reactions with chiral ligands L1-L8

[0060]

[0061]

[0062] As shown in Table 3, the monophosphine ligand pEPCP containing [2.2]paracyclophane in the present application has very good catalytic activity and enantioselectivity in the palladium-catalyzed asymmetric allylic alkylation (AAA) reaction involving (E)-1,3-diphenylallyl acetate and dimethyl malonate, and the results are obviously superior to those of other related types of and similar-structure biphenyl phosphine ligands.

[0063] Example 6: Under the same experimental conditions and operations as in Example 5, different types of substrates were used to perform the allylic alkylation reaction, and the reaction equation is shown as follows:

[0064]

[0065] The reaction results are shown in Table 4.

[0066] Table 4. Results of allylic alkylation reactions with different types of substrates

[0067]

[0068] As shown in Tables 3 and 4, the bridged biphenyl monophosphine ligand pEPCP containing [2.2]paracyclophane in the present application has excellent catalytic activity and enantioselectivity in the palladium-catalyzed asymmetric allylic alkylation reaction involving (E)-1,3-diphenylallyl acetate and dimethyl malonate, and the results are superior to those of other related types of chiral phosphine ligands; and in the alkyl allyl acetate compounds, the results are also significantly superior to those of other related types of chiral phosphine ligands.

[0069] The specific embodiments are only an explanation of the present application, and are not a limitation of the present application. Those skilled in the art can make modifications to the embodiments without creative contribution after reading the present specification, and the modifications are protected by the patent law as long as they are within the scope of the claims of the present application.

Claims

1. A class of planar chiral [2.2] pEPCP cyclophane monophosphine ligands, characterized by: The structural formula of the single phosphine ligand pEPCP is shown in formula I below: ； wherein R is a substituted or unsubstituted phenyl group, the substituents of the substituted phenyl group are each independently selected from C1-C6 alkyl, C1-C6 alkoxy or halogen, and the number of the substituents is 1, 2 or 3; R 1 R is any one of a substituted or unsubstituted C1-C20 alkyl group, a substituted or unsubstituted C6-C20 aryl group, a substituted or unsubstituted C3-C20 alkylsilyl group, a substituted or unsubstituted C6-C20 arylsilyl group, one or more hydrogen atoms in the substituent group can be replaced by a C1-C6 alkyl group, a C1-C6 alkoxy group or a halogen, and the number of the substituents is 1, 2 or 3.

2. A class of planar chiral [2.2]paracyclophane monophosphine ligands pEPCP according to claim 1, characterized by: In the structural formula I of the single phosphine ligand pEPCP, R is a phenyl group, a 4-methylphenyl group, a 4-methoxyphenyl group, a 3,5-dimethylphenyl group, a 3,5-diethylphenyl group, a 3,5-dipropylphenyl group, a 3,5-di-t-butylphenyl group, a 3,5-dimethyl-4-methoxyphenyl group, a 3,4,5-trimethylphenyl group, a 3,5-di-t-butyl-4-methoxyphenyl group or a 3,5-di-t-butyl-4-methylphenyl group.

3. A class of planar chiral [2.2]paracyclophane monophosphine ligands pEPCP according to claim 1, characterized by: In the structural formula -I of the monophosphine ligand pEPCP, R 1 is selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, C5-C12 linear or branched alkyl, cyclopropyl, cyclobutyl, C5-C20 cycloalkyl, benzyl, naphthyl, methoxymethyl, trifluoromethyl, C2-C6 fluoroalkyl, trimethylsilyl, triethylsilyl, triphenylsilyl, C7-C9 silyl.

4. Process for the preparation of a class of planar chiral [2.2]paracyclophane monophosphine ligands pEPCP according to any one of claims 1 to 3, characterized in that: The method comprises the following steps: S1. An electrophilic substitution reaction is performed on a chiral compound 4-hydroxy[2.2]paracyclophane 1 as a starting material and liquid bromine to generate a brominated [2.2]paracyclophane 2; S2, under basic conditions, the halide R 1 of compound 1 is subjected to an electrophilic substitution reaction with bromo[2.2]paracyclophane 2, the phenolic hydroxyl group introducing the substituent R 1 1 to give compound 3;​ S3. A bromine-lithium exchange is performed on the compound 3 and butyl lithium to generate an aryllithium intermediate 4; S4. A double-R-substituted chlorophosphine R2PCl is added to the reaction system to generate an electrophilic substitution and generate a planar chiral phosphine ligand compound pEPCP.

5. A process for the preparation of a class of planar chiral [2.2]paracyclophane monophosphine ligands pEPCP according to claim 4, characterized by: The reaction in the step S1 is performed at a temperature of -20-40°C, for a time period of 0.5-12 h, in an organic solvent environment, and under a nitrogen or argon inert gas atmosphere; The reaction in the step S2 is performed at a temperature of -20-40°C, for a time period of 0.5-12 h, in the presence of a base, in an organic solvent environment, and under a nitrogen or argon inert gas atmosphere; The reaction in the step S3 is performed at a temperature of -80-60°C, for a time period of 0.5-24 h, in the presence of butyl lithium, in an anhydrous organic solvent environment, and under a nitrogen or argon inert gas atmosphere; The reaction in the step S4 is performed at a temperature of -80-60°C, for a time period of 0.5-24 h, in the presence of a double-R-substituted chlorophosphine R2PCl, in an anhydrous organic solvent environment, and under a nitrogen or argon inert gas atmosphere.

6. A process for the preparation of a class of planar chiral [2.2]paracyclophane monophosphine ligands pEPCP according to claim 5, characterized by: The reaction equation of the single phosphine ligand pEPCP is shown in formula II below: 。 7. Application of a planar chiral [2.2]paracyclophane single phosphine ligand pEPCP in asymmetric catalysis, according to any one of claims 1-3.

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