Planar chiral [2.2] paracyclophane monophosphine ligand pEPCP as well as preparation method and application thereof

Abstract

The invention discloses a planar chiral [2.2] paracyclophane alkane monophosphine ligand pEPCP as well as a preparation method and application thereof, and relates to the technical field of chemical catalysis, the planar chiral [2.2] paracyclophane alkane monophosphine ligand pEPCP is characterized by comprising a racemate or an enantiomer, and the structural formula I of the monophosphine ligand pEPCP is as follows: # imgabs0 #. Different types of ether substituents are introduced into the structure of a unique large-steric-hindrance electron-rich rigid skeleton formed by connecting two benzene rings at para-positions through two ethylidene groups, so that the electron cloud density and steric hindrance of aromatic rings directly connected with phosphine ligands are changed. In addition, the ether substituent can also be used as a weak coordination group and participates in adjusting a dihedral angle of ligand chelation. The metal, the ligand and the substrate form the most appropriate coordination environment in the catalysis process, so that the corresponding catalytic reaction has the advantages of high reaction activity, good enantioselectivity, wide substrate universal application range and the like, is particularly suitable for asymmetric coupling reaction catalyzed by transition metal, and has economic practicability and industrial application prospects.

Description

Technical Field

[0001] The present invention relates to the field of chemical catalysis technology, and more specifically, to a type of planar chiral [2.2]-cyclophane monophosphine ligand pEPCP and a preparation method and application thereof. Background Art

[0002] Chiral phosphine ligands are the most studied and widely used ligands so far. By adjusting their skeleton structure and functional groups (such as dihedral angles, steric hindrance, skeleton rigidity and flexibility, etc.), the reactivity, reaction type, stereoselectivity and substrate universality of the catalytic reaction can be effectively changed. Therefore, the development of new chiral ligands can not only expand asymmetric catalytic systems and new modes of catalytic activation, but also help to discover new catalytic reactions that cannot be achieved by traditional catalytic systems. This can significantly promote the precise synthesis of diversified chiral molecules and serve the creation of chiral drugs and chiral material molecules. The development of new chiral phosphine ligands has always been one of the hot spots and cutting-edge research areas 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 non-C2 symmetric, axial chirality, large steric hindrance, electron-rich oxygen-monodentate phosphine ligand (Sp)-MOP and achieved excellent results in the asymmetric hydrosilylation of olefins (Uozumi, Y.; Hayash, TJ 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 there are fewer types of phosphine ligands developed based on planar chiral aromatic skeletons (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 (PCP) is a minimal cyclophane compound with rich electrons, large steric hindrance, rigid skeleton, and trans-ring π electron system. The rotation of its benzene ring plane around the large ring plane is hindered, and when the substituents cause the symmetry to be broken, planar chirality is generated. It has a wide range of applications in asymmetric catalysis, chiral materials science, and supramolecular chemistry (Hassan, Z.; Spuling, Daniel, E. Angew. Chem. Int. Ed. 2020, 59, 2156).

[0005] Therefore, the present invention aims to provide a type of planar chiral [2.2] paracyclophane monophosphine ligand pEPCP and its preparation method and application, by synthesizing a new type of non-C2 symmetric, planar chiral, sterically hindered, electron-rich oxygen-containing monodentate phosphine ligand pEPCP containing a PCP skeleton, which can be successfully applied to palladium-catalyzed asymmetric allylation reactions, coupling reactions and cyclization reactions. Summary of the invention

[0006] The purpose of the present invention is to provide a type of planar chiral [2.2] p-cyclophane monophosphine ligand pEPCP and a preparation method and application thereof. The present invention designs and synthesizes the corresponding [2.2] p-cyclophane skeleton monophosphine ligand by using the enantiomer and racemate of the bromocyclophane synthesized by using commercial 4-hydroxy [2.2] p-cyclophane as a starting material. The skeleton is stable, easy to modify, has the characteristics of rich electrons and large steric hindrance, and the synthesis route is simple. It will enrich and develop the types of phosphine ligands and has important academic value and application value.

[0007] The above technical objectives of the present invention are achieved through the following technical solutions: a type of planar chiral [2.2] cyclophane monophosphine ligand pEPCP, including racemates or enantiomers, the structural formula-I of the monophosphine ligand pEPCP is as follows:

[0008]

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

[0010] R 1 It 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, one or more hydrogen atoms in the substituted group may 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 as follows: 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-ditrifluoromethylphenyl, 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 as follows: 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 or branched alkyl, cyclopropyl, cyclobutyl, C5-C20 cycloalkyl, benzyl, naphthyl, methoxymethyl, trifluoromethyl, C2-C6 fluoroalkyl, trimethylsilyl, triethylsilyl, triphenylsilyl, C7-C9 silyl.

[0013] The present invention also provides a method for preparing a type of planar chiral [2.2]-cyclophane monophosphine ligand pEPCP, comprising the following steps:

[0014] S1, using a chiral or racemic compound 4-hydroxy[2.2]-p-cyclophane 1 as a starting material, and reacting it with liquid bromine to undergo an electrophilic substitution reaction to generate bromo[2.2]-p-cyclophane 2;

[0015] S2. Under alkaline conditions, R 1 Halogenated R 1 -X undergoes electrophilic substitution reaction with bromo[2.2]-cyclophane 2, and the phenolic hydroxyl group is introduced into the substituent group R 1 Compound 3 is obtained;

[0016] S3, exchanging compound 3 with butyl lithium for lithium bromide to obtain aryl lithium compound intermediate 4;

[0017] S4. Adding a di-R-substituted chlorophosphine R2PCl into the reaction system to cause electrophilic substitution to generate a planar chiral or racemic phosphine ligand compound pEPCP.

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

[0019] The reaction temperature in step S2 is -20 to 40°C, the reaction time is 0.5 to 12 hours, the reaction is carried out in the presence of a base, the reaction environment is an organic solvent environment, and the protective atmosphere of the reaction is nitrogen or argon inert gas;

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

[0021] The reaction temperature in step S4 is -80 to 60°C, the reaction time is 0.5 to 24 hours, the reaction is carried out in the presence of a di-R substituted chlorophosphine R2PCl, the reaction environment is an anhydrous organic solvent environment, and the reaction protective atmosphere is nitrogen or argon inert gas.

[0022] The present invention is further configured as follows: the reaction equation of the monophosphine ligand pEPCP is:

[0023]

[0024] The present invention also provides a type of planar chiral [2.2]-cyclophane monophosphine ligand pEPCP for use in asymmetric catalysis.

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

[0026] 1. The monophosphine ligand pEPCP containing [2.2]-p-cyclophane of the present invention has a unique large steric hindrance, electron-rich rigid skeleton with two benzene rings connected by two ethylene groups at the para position, and introduces different types of ether substituents into the structure, thereby changing the electron cloud density and steric hindrance of the aromatic ring directly connected to the phosphine ligand; in addition, the ether substituent can also serve as a weak coordination group to participate in regulating the dihedral angle of ligand chelation; this allows the metal, ligand and substrate to form the most suitable coordination environment during the catalytic process, so that the corresponding catalytic reaction has the advantages of high reaction activity, good enantioselectivity, wide substrate universality, etc., and is suitable for rhodium-catalyzed asymmetric Hayashi-Miyaura reaction and palladium-catalyzed asymmetric allylic alkylation reaction, and both have excellent reaction catalytic activity and stereoselectivity;

[0027] 2. The monophosphine ligand pEPCP containing [2.2]-p-cyclophane of the present invention has a simple synthesis method and has a unique large steric hindrance and 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 serve as a weak coordinating group to participate in regulating the dihedral angle of ligand chelation; this allows the ligand, metal and substrate to form the most suitable coordination environment during the catalytic process, thereby exhibiting excellent catalytic activity and enantioselectivity control ability. BRIEF DESCRIPTION OF THE DRAWINGS

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

[0029] Figure 2 This is the synthesis route of the (Rp)-pEPCP-L1 compound in Example 1 of the present invention. DETAILED DESCRIPTION

[0030] The following is combined with Figure 1-2 The present invention is described in further detail.

[0031] Example 1: Preparation of a planar chiral phosphine ligand (Rp)-pEPCP-L1 containing a [2.2]-cyclophane skeleton, the structural formula of which is as follows:

[0032]

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

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

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

[0036] 3) Under nitrogen protection, into a dry 250 mL single-mouth eggplant-shaped reaction bottle, (Rp)-3 (10 mmol, 3.16 g) and 50 mL of anhydrous THF were added in sequence, and then the reaction system was transferred to -50 ° C and stirred for 10 min. Then n-BuLi (30 mmol, 3.0 eq., 18.8 mL, 1.6 M n-hexane solution) was added dropwise to the reaction system and stirring was continued for 1 h to obtain the active intermediate lithium reagent 4.

[0037] 4) PPh2Cl (20 mmol, 2.0 eq., 3.6 mL) was then added dropwise to the reaction system, the refrigeration was turned off, and the mixture was stirred overnight; the plate was sampled for detection, and after the reaction was completed, 10 mL of saturated NH4Cl was added to quench the reaction, and the mixture was extracted with EA three times. The organic phases were combined and washed with saturated NaCl, dried over anhydrous Na2SO4, and evaporated under reduced pressure. After the solvent was removed, the crude product was purified by silica gel column chromatography (PE:DCM=2:1) ​​to obtain 3.4 g of a white solid (Rp)-L1 product with a yield of 82%.

[0038] In this example, ligand (Rp)-L1 is characterized as follows: 1 H NMR(400MHz,Chloroform-d)δ7.14–7.01(m,4H),6.90–6.80(m,3H),6.73(dd,J=7.6,1.6Hz,1H),6.47(dd,J=7.6,2.0Hz ,1H),6.07(dd,J=7.6,1.6Hz,1H),5.73(d,J=7.2Hz,1H),5.66(d,J=4.8Hz,1H),3.72(s,3H),2.31(s,6H),2.19(s,6H); 13C NMR(101MHz,Chloroform-d)δ158.4,146.7,146.5,139.9,139.0,138.1,138.0,137.9,137.5,137.5,132.9,132.9,13 2.7,131.6,131.6,131.3,131.0,130.9,130.7,130.1,128.3,118.2,118.1,54.3,34.7,34.5,34.3,33.5,31.4,21.4; 31 P NMR (162MHz, Chloroform-d) δ-7.22; HRMS (ESI) m / z calcd.for423.1878, found: 423.1874.

[0039] Example 2: According to the preparation method of Example 1, a series of planar chiral phosphine ligand compounds pEPCP-L1 to pEPCP-L14 were synthesized by conventional techniques in the art, and the structural formulas are shown below:

[0040]

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

[0042] In this embodiment [2.2], the reaction equation of the monophosphine ligand pEPCP of the cyclophane skeleton in the rhodium-catalyzed asymmetric Hayashi-Miyaura reaction is as follows:

[0043]

[0044] By taking 25mL sealed tube, under argon atmosphere, cyclohexenone (0.1mmol, 1.0eq.), 4-phenylboronic acid (0.15mmol, 1.5eq.), [Rh(C2H4)2Cl]2 (2.5mol%), ligand L* (6mol%), potassium hydroxide (0.5eq.) were added in sequence, and the gas was evacuated three times. 2mL ultra-dry 1,4-dioxane and 0.2mL H2O were added under nitrogen atmosphere, and the reaction was carried out at 40°C for 12h. The yield and ee value of the product were obtained by purification by silica gel column chromatography and HPLC analysis. The catalytic reaction was carried out with ligands different from the present invention and commercially available well-known chiral ligands L1-L8, and their structural formulas are 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 operation as Example 3, different types of substrates were replaced to carry out asymmetric rhodium-catalyzed Hayashi-Miyaura reaction. The reaction equation is as follows:

[0050]

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

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

[0053]

[0054] As can be seen from Tables 1 and 2, the monophosphine ligand pEPCP containing [2.2]-p-cyclophane of the present invention 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 available at present; and the results obtained in ortho-substituted arylboronic acid compounds are also significantly better than those of other related types of chiral phosphine ligands.

[0055] The monophosphine ligand pEPCP containing [2.2]-p-cyclophane of the present invention also has good catalytic activity and enantioselectivity in asymmetric allylic alkylation reaction (AAA).

[0056] Example 5: Experimental application of the monophosphine ligand pEPCP containing [2.2]-p-cyclophane in palladium-catalyzed asymmetric allylic alkylation reaction, the reaction equation is shown below:

[0057]

[0058] Take 25mL sealed tube, under argon atmosphere, add racemic (E)-1,3-diphenylallyl ethyl acetate (0.1mmol, 1.0eq.), dimethyl malonate (0.2mmol, 2.0eq.), [Pd(C3H5)Cl]2 (5mol%), ligand L* (12mol%), lithium acetate (12mol%), N,O-bis(trimethylsilyl)acetamide (0.3mmol, 3.0eq., BSA) in sequence, evacuate three times, add 2mL anhydrous dichloromethane under nitrogen atmosphere, and react at -20℃ for 24h. Purify by silica gel column chromatography and analyze by HPLC to obtain the yield and ee value of the product. Catalytic reactions were carried out with ligands different from the present invention and commercially available well-known chiral ligands L1-L8, and the results are shown in Table 3:

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

[0060]

[0061]

[0062] As can be seen from Table 3, the monophosphine ligand pEPCP containing [2.2]-p-cyclophane of the present invention has good catalytic activity and enantioselectivity in the palladium-catalyzed asymmetric allylic alkylation (AAA) reaction of (E)-1,3-diphenylallyl ethyl acetate and dimethyl malonate, and its results are significantly better than those of other related types and similarly structured biphenylphosphine ligands.

[0063] Example 6: Under the same experimental conditions and operation as Example 5, different types of substrates were replaced to carry out allylic alkylation reaction. The reaction equation is as follows:

[0064]

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

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

[0067]

[0068] As can be seen from Tables 3 and 4, the bridged biphenyl monophosphine ligand pEPCP containing [2.2]cyclophane of the present invention has excellent catalytic activity and enantioselectivity for the asymmetric palladium-catalyzed allylic alkylation reaction of (E)-1,3-diphenylallyl ethyl acetate and dimethyl malonate, and the results are better than those of other related types of chiral phosphine ligands available at present; and the results obtained in alkyl allyl acetate compounds are significantly better than those of other related types of chiral phosphine ligands.

[0069] This specific embodiment is merely an explanation of the present invention and is not a limitation of the present invention. After reading this specification, those skilled in the art may make non-creative modifications to the present embodiment as needed. However, as long as they are within the scope of the claims of the present invention, they are protected by the patent law.

Claims

1. A type of planar chiral [2.2]-cyclophane monophosphine ligand pEPCP, characterized by: Including racemates or enantiomers, the structural formula-Ⅰ of the monophosphine ligand pEPCP is as follows: Wherein, R is a substituted or unsubstituted phenyl or alkyl group, the substituents of the substituted phenyl group are each independently selected from C1-C6 alkyl, C1-C6 alkoxy or halogen, the number of the substituents is 1, 2 or 3, and the alkyl group is C1-C10 alkyl; R 1 It 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, one or more hydrogen atoms in the substituted group may be substituted by C1-C6 alkyl, C1-C6 alkoxy or halogen, and the number of substituents is 1, 2 or 3.

2. A planar chiral [2.2]-cyclophane monophosphine ligand pEPCP according to claim 1, characterized in 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-ditrifluoromethylphenyl, 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.

3. A planar chiral [2.2]-cyclophane monophosphine ligand pEPCP according to claim 1, characterized in 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 or branched alkyl, cyclopropyl, cyclobutyl, C5-C20 cycloalkyl, benzyl, naphthyl, methoxymethyl, trifluoromethyl, C2-C6 fluoroalkyl, trimethylsilyl, triethylsilyl, triphenylsilyl, C7-C9 silyl.

4. A method for preparing a type of planar chiral [2.2]-cyclophane monophosphine ligand pEPCP according to any one of claims 1 to 3, characterized in that: The following steps are involved: S1, using a chiral or racemic compound 4-hydroxy[2.2]-p-cyclophane 1 as a starting material, and reacting it with liquid bromine to undergo an electrophilic substitution reaction to generate bromo[2.2]-p-cyclophane 2; S2. Under alkaline conditions, R 1 Halogenated R 1 -X undergoes electrophilic substitution reaction with bromo[2.2]-cyclophane 2, and the phenolic hydroxyl group is introduced into the substituent group R 1 Compound 3 is obtained; S3, exchanging compound 3 with butyl lithium for lithium bromide to obtain aryl lithium compound intermediate 4; S4. Adding a di-R-substituted chlorophosphine R2PCl into the reaction system to cause electrophilic substitution to generate a planar chiral or racemic phosphine ligand compound pEPCP.

5. The method for preparing a type of planar chiral [2.2]-cyclophane monophosphine ligand pEPCP according to claim 4, characterized in that: The reaction temperature in step S1 is -20 to 40°C, the reaction time is 0.5 to 12 hours, the reaction environment is an organic solvent environment, and the reaction protective atmosphere is nitrogen or argon inert gas; The reaction temperature in step S2 is -20 to 40°C; the reaction time is 0.5 to 12 hours, the reaction is carried out in the presence of a base, the reaction environment is an organic solvent environment, and the protective atmosphere of the reaction is nitrogen or argon inert gas; The reaction temperature in step S3 is -80 to 60°C, and the reaction time is 0.5 to 24 hours; the reaction is carried out in the presence of butyl lithium, the reaction environment is an anhydrous organic solvent environment, and the protective atmosphere of the reaction is nitrogen or argon inert gas; The reaction temperature in step S4 is -80 to 60°C, the reaction time is 0.5 to 24 hours, the reaction is carried out in the presence of a di-R substituted chlorophosphine R2PCl, the reaction environment is an anhydrous organic solvent environment, and the reaction protective atmosphere is nitrogen or argon inert gas.

6. The method for preparing a type of planar chiral [2.2]-cyclophane monophosphine ligand pEPCP according to claim 5, characterized in that: The reaction equation of the monophosphine ligand pEPCP is:

7. Use of a type of planar chiral [2.2]-paracyclophane monophosphine ligand pEPCP according to any one of claims 1 to 3 in asymmetric catalysis.

Images