NP and NS ligands of the chiral 1,2-ethylenediamine skeleton and their preparation methods

Abstract

This invention discloses a method for designing and preparing N-P and N-S ligands with a chiral 1,2-ethylenediamine skeleton. The structural formula of the N-P ligand is shown in formula (I), and the structural formula of the N-S ligand is shown in formula (II): wherein, R 1 R 2 R 3 R 4 R 5 R 6 R 7 R 8 R 9 Each is selected individually from hydrogen, halogen, substituted or unsubstituted C1-C. 30 alkyl, alkoxy, or aryl; R 10 Each was selected individually from C1-C 30 Alkyl or aryl; Ar 1 and Ar 2 Each is selected individually from substituted or unsubstituted C6-C. 30 The aryl group of the present invention has a simple preparation method and can produce chiral N-P and N-S ligands, which can be used as catalysts for asymmetric reactions, and have economic practicality and industrial application prospects.

Description

Technical Field

[0001] This invention relates to NP and NS ligands of a chiral 1,2-ethylenediamine skeleton and their preparation methods, belonging to the field of organic chemistry technology. Technical Background

[0002] Over the past two decades, asymmetric catalysis has become a research focus in the field of organic synthesis, its importance increasingly prominent, especially in the preparation of chiral compounds (CCS Chem. 2023, 5, 2685-2716). Given the central role of chiral compounds in life sciences and materials science, asymmetric catalysis has become a key technology for obtaining chiral substances. In transition metal-catalyzed asymmetric reactions, the importance of ligands is self-evident, their performance directly affecting the efficiency and selectivity of the catalytic reaction. Therefore, the design and development of novel chiral ligands has become a crucial breakthrough in the field of asymmetric catalysis. The 1,2-ethylenediamine skeleton with a C2 symmetry axis has broad application value in asymmetric catalysis (Angew. Chem., Int. Ed. 1998, 37, 2580-2627). It can serve not only as a chiral cofactor and precursor of chiral catalysts, but also as a building block of chiral ligands, providing rich possibilities for the synthesis of chiral compounds. Meanwhile, phosphorus and nitrogen atoms, due to their unique coordination properties and the variability of substituents, can flexibly adjust the steric and electronic effects of ligands, thereby improving the performance of catalytic reactions (Chem. Soc. Rev. 2014, 43, 819-833; Chem. Rev. 2018, 118, 9344-9411). These ligands not only exhibit excellent catalytic performance but also provide new ideas and methods for the development of asymmetric catalysis. Furthermore, chiral heteroatom ligands have also achieved significant research results in the field of chemistry. Among them, chiral NS ligands, with their unique chiral structure and properties, have shown broad application prospects in asymmetric synthesis, catalytic reactions, and other fields (Chem. Rev. 2017, 117, 4147-4181). Therefore, it is particularly important to design and develop novel chiral ligands by combining the 1,2-ethylenediamine skeleton with a C2 symmetry axis with phosphorus or sulfur atoms. These novel ligands, by adjusting the side chains connected by two nitrogen atoms, can precisely control the electronegativity and steric hindrance of the ligands, thereby achieving precise control over the catalytic performance. In particular, the sulfur atoms have a specific spatial orientation, enabling them to form stable coordinate bonds with metals, thus constructing unique catalytic cavities and providing an ideal reaction environment for asymmetric catalytic reactions. It is worth noting that there are currently no reports on the synthesis and application of these two types of chiral ligands. Therefore, there is an urgent need in this field to develop such novel chiral ligands to fill this gap. Through a simple three-step reaction, we successfully prepared optically active or racemic NP and NS ligands with a C2 symmetry axis and successfully applied them in asymmetric synthesis, injecting new vitality into the development of asymmetric catalysis. Summary of the Invention

[0003] The main objective of this invention is to provide a method for designing and preparing NP ligands and NS ligands with a chiral 1,2-ethylenediamine skeleton, so as to overcome the shortcomings of the prior art.

[0004] To achieve the aforementioned objectives, the technical solution adopted by this invention includes:

[0005] This invention provides an NP ligand and an NS ligand with a chiral 1,2-ethylenediamine skeleton, the structural formulas of which are shown in formula (I) and formula (II):

[0006]

[0007] Among them, R 1 R 2 R 3 R 4 R 5 R 6 R 7 R 8 R 9 Each is selected independently from hydrogen, halogen, substituted or unsubstituted C1-C. 30 Alkyl, alkoxy, or aryl groups;

[0008] R 10 Each of the above is selected individually from C1-C. 30 Alkyl or aryl groups;

[0009] Ar 1 and Ar 2 Each is selected independently from substituted or unsubstituted C6-C. 30 Aryl groups.

[0010] This invention also provides a method for preparing the aforementioned chiral 1,2-ethylenediamine backbone NP ligand and NS ligand, comprising:

[0011] A homogeneous mixture of the compound represented by formula (III), a phosphorus reagent, a sulfoxide reagent, a base, and an organic solvent is reacted to obtain NP ligands and NS ligands with chiral 1,2-ethylenediamine skeletons having structures as shown in formula (I) or formula (II).

[0012]

[0013] In equation (I) or equation (II), R 1 R 2 R 3 R 4 R 5 R 6 R 7 R 8 R 9Each is selected individually from hydrogen, halogen, substituted or unsubstituted C1-C. 30 Alkyl, alkoxy, or aryl groups;

[0014] R 10 Each of the above is selected individually from C1-C. 30 Alkyl or aryl groups;

[0015] Ar 1 and Ar 2 Each is selected individually from substituted or unsubstituted C6-C. 30 Aryl groups.

[0016] The NP and NS ligands of the chiral 1,2-ethylenediamine skeleton are used as catalysts or in the field of synthetic catalysts.

[0017] The catalyst is a catalyst for asymmetric catalytic reactions.

[0018] The catalyst is a complex formed by the NP ligand or NS ligand of the chiral 1,2-ethylenediamine skeleton of claim 1 and a palladium metal catalyst.

[0019] A catalyst for asymmetric catalytic reactions, comprising a complex formed by an NP ligand or NS ligand of the chiral 1,2-ethylenediamine skeleton as described in claim 1 and a palladium metal catalyst.

[0020] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0021] 1) This invention provides a novel NP ligand and NS ligand with an optically active chiral 1,2-ethylenediamine skeleton, which can be used as a catalyst for palladium-catalyzed asymmetric catalytic reactions.

[0022] 2) This invention provides a simple and feasible method for preparing NP and NS ligands with an optically active chiral 1,2-ethylenediamine skeleton. It can be conveniently prepared from optically pure 1,2-ethylenediamine through a simple reaction, and has economic practicality and industrial application prospects. Attached Figure Description

[0023] Figure 1 This is the X-ray crystal diffraction pattern of the 6g compound obtained in Example 4 of this invention;

[0024] Figure 2 This is the X-ray crystal diffraction pattern of compound 7j obtained in Example 5 of the present invention. Detailed Implementation Plan

[0025] As mentioned above, in view of the shortcomings of the prior art, the inventors of this case have conducted extensive and in-depth research and have been able to propose the technical solution of this invention, that is, to obtain the NP ligand and NS ligand of the chiral 1,2-ethylenediamine skeleton by a simple reaction. The ligand can be used as a catalyst for asymmetric catalytic reactions and has economic practicality and industrial application prospects.

[0026] The technical solution of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, 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.

[0027] First, it should be noted that the definitions of the terms used in this invention specification are all known to those skilled in the art. For example, some of the terms are defined as follows:

[0028] The term "alkyl" refers to a saturated hydrocarbon group, which is a hydrocarbon group formed by removing one hydrogen atom from an alkane molecule.

[0029] The term "alkoxy" refers to a type of substituent in an organic compound molecule, consisting of an alkyl group and an oxygen atom.

[0030] The term "aryl" refers to the monovalent group remaining after removing a hydrogen atom from the aromatic carbon atom of an aromatic hydrocarbon molecule.

[0031] Unless otherwise stated, the alkyl, alkoxy, or aryl groups described in this invention include both substituted and unsubstituted portions. Possible substituents on the alkyl, alkoxy, and aryl groups include, but are not limited to, C1-C1 groups. 10 Alkyl, alkenyl, alkoxy, aryl, hydroxyl, halogen, amino, etc.

[0032] One aspect of this invention provides an NP ligand and an NS ligand with a chiral 1,2-ethylenediamine skeleton, the structural formulas of which are shown in formulas (I) and (II):

[0033]

[0034] Among them, R 1 R 2 R 3 R 4 R 5 R 6 R 7 R 8 R 9 Each is selected individually from hydrogen, halogen, substituted or unsubstituted C1-C. 30 Alkyl, alkoxy, or aryl groups;

[0035] R 10 Each is selected independently from C1-C 30 Alkyl or aryl groups;

[0036] Ar 1 and Ar 2 Each is selected individually from substituted or unsubstituted C6-C. 30 Aryl groups.

[0037] The substitution mentioned therein is by the following substituents: C1-C 10 Alkyl, alkenyl, alkoxy, aryl, hydroxyl, halogen, amino, etc.

[0038] In some embodiments, R 10 Each is selected individually from substituted or unsubstituted C1-C. 30 Alkyl or aryl groups, but not limited thereto, wherein the number of substituents used in the substitution is one or more, preferably 1-2, that is, the substitution is mono- or di-substituted by a substituent.

[0039] Furthermore, the substituents are at least independently selected from C1-C1. 10 Alkyl, alkenyl, alkoxy, aryl, hydroxyl, halogen, amino, etc., but not limited to these.

[0040] In some embodiments, R 1 R 2 R 3 R 4 R 5 R 6 R 7 R 8 R 9 Each is selected independently from C1-C 10 The substituted group can be alkyl, alkenyl, alkynyl, alkoxy, aryl, hydroxyl, halogen, amino, etc., but is not limited to these. The number of substituents used in the substitution is one or more, preferably 1-2, that is, the substitution is mono- or di-substituted by a substituent.

[0041] Furthermore, the substituents are at least independently selected from C1-C1. 10 Alkyl, alkenyl, alkoxy, aryl, hydroxyl, halogen, amino, etc., but not limited to these.

[0042] In some embodiments, Ar 1 and Ar 2 Each is selected independently from substituted or unsubstituted C6-C. 30Aryl groups, etc., but not limited to, wherein the number of substituents used in the substitution is one or more, preferably 1-2, that is, the substitution is mono- or di-substituted by the substituent.

[0043] Furthermore, the substituents are at least independently selected from C1-C1. 10 Alkyl, alkenyl, alkoxy, aryl, hydroxyl, halogen, amino, etc., but not limited to these.

[0044] In another preferred embodiment, the aryl group is selected from any one or a combination of two or more of phenyl, naphthyl, pyrene, anthracene, phenanthryl, etc., but is not limited thereto.

[0045] In another preferred example, Ar 1 and Ar 2 These are groups with the same structure.

[0046] In some embodiments, the ligand comprises a structure represented by any of the following formulas (Ia)-(Id) and (IIa)-(IId):

[0047]

[0048] In each formula, R 1 R 2 R 3 R 4 R 5 R 6 R 7 R 8 R 9 R 10 Ar 1 Ar 2 The definition is as described above.

[0049] Specifically, R 1 R 2 R 3 R 4 R 5 R 6 R 7 R 8 R 9 Each is selected individually from hydrogen, halogen, substituted or unsubstituted C1-C. 30 Alkyl, alkoxy, or aryl groups;

[0050] R 10 Each of the above is selected individually from C1-C. 30 Alkyl or aryl groups;

[0051] Ar 1 and Ar 2Each is selected individually from substituted or unsubstituted C6-C. 30 Aryl groups.

[0052] In another preferred embodiment, the ligand is selected from: the structure shown in any of formulas (Ia)-(IId) below, or the enantiomer, racemate, or diastereomer of the structure shown in any of formulas (Ia)-(IId) below. The racemate refers to the racemate formed by any one of the compounds shown in formulas (Ia)-(IId) and its enantiomer.

[0053] In another more specific preferred embodiment, the ligand comprises an enantiomer, racemate or diastereomer of the structure shown in any of formulas (6a)-(7o) below;

[0054]

[0055] Another aspect of the present invention provides a method for preparing the aforementioned chiral 1,2-ethylenediamine backbone NP ligand and NS ligand, comprising:

[0056] A homogeneous mixture of the compound shown in formula (III), a phosphorus reagent, a sulfoxide reagent, a base, and an organic solvent was reacted to obtain NP ligands and NS ligands with chiral 1,2-ethylenediamine skeletons having the structures shown in formulas (I) and (II).

[0057]

[0058] In each formula, R 1 R 2 R 3 R 4 R 5 R 6 R 7 R 8 R 9 R 10 Ar 1 Ar 2 The definition is as described above.

[0059] Specifically, in equations (I), (II), and (III), R 1 R 2 R 3 R 4 R 5 R 6 R 7 R 8 R 9 Each is selected individually from hydrogen, halogen, substituted or unsubstituted C1-C. 10Alkyl, alkenyl, alkoxy, aryl, hydroxyl, halogen, amino, etc.;

[0060] R 10 Each of the above is selected individually from C1-C. 30 Alkyl or aryl groups;

[0061] Ar 1 and Ar 2 Each is selected individually from substituted or unsubstituted C6-C. 30 Aryl groups.

[0062] In some embodiments, Ar 1 and Ar 2 These are groups with the same structure.

[0063] In some embodiments, the phosphorus reagent has the chemical formula R. 10 PCl2, where R 10 Each is selected independently from C1-C 30 Alkyl or aryl groups.

[0064] Furthermore, in an organic solvent, under the action of a base, the compound represented by formula (III) reacts with R. 10 The reaction with PCl2 or SOCl2 directly yields the compound represented by formula (I) or (II). The reaction equation is as follows:

[0065]

[0066] In another preferred embodiment, the molar ratio of the phosphorus reagent or sulfoxide reagent to the compound shown in formula (III) is 1:1 to 2:1, preferably 1.5:1.

[0067] In another preferred embodiment, the molar ratio of the base to the compound represented by formula (III) is 1:1 to 3:1, preferably 3:1.

[0068] Further, the alkali includes any one or a combination of two or more of sodium tert-butoxide, lithium tert-butoxide, potassium tert-butoxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, triethylamine, 1,8-diazobisspirocyclic[5.4.0]undec-7-ene, preferably triethylamine, but not limited thereto.

[0069] Furthermore, the organic solvent includes any one or more combinations of diethyl ether, isopropyl ether, tetrahydrofuran, ethylene glycol dimethyl ether, 1,4-dioxane, N,N-dimethylformamide, N-methylpyrrolidone, acetonitrile, ethyl acetate, methanol, toluene, benzene, cyclohexane, and dichloromethane, preferably toluene, but not limited thereto.

[0070] In another preferred embodiment, the reaction temperature is 0-150°C, preferably 110°C, and the reaction time is 1-48h, preferably 24h.

[0071] Through the above technical solutions, the novel optically active chiral NP and NS ligands with a 1,2-ethylenediamine skeleton provided by this invention can be used as catalysts for asymmetric catalytic reactions catalyzed by transition metals. Furthermore, this invention provides a simple and feasible method for preparing optically active chiral NP and NS ligands with a 1,2-ethylenediamine skeleton, which can be conveniently prepared from optically pure 1,2-ethylenediamine through a simple reaction, avoiding the need to obtain chiral ligands through resolution methods, and has economic practicality and promising industrial application prospects.

[0072] To further understand the present invention, specific embodiments are described below. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Non-essential improvements and adjustments made by those skilled in the art under the core guiding principles of the present invention are still within the scope of protection of the present invention. Experimental methods in the following embodiments that do not specify specific conditions are generally performed under conventional conditions or as recommended by the manufacturer.

[0073] Unless otherwise specified, the experimental materials used in the examples below can be purchased from conventional chemical reagent companies.

[0074] Example 1

[0075] In this embodiment, the preparation method of compound 3a is as follows, and the reaction route is shown below.

[0076]

[0077] In a glove box, add (1S,2S)-1,2-diphenylethylenediamine 1a (1.7 g, 8.0 mmol, 2.0 equivalence), bromobenzene 2a (628.0 mg, 4.0 mmol, 1.0 equivalence), tris(dibenzylideneacetone)dipalladium(0) (183.1 mg, 0.2 mmol, 0.05 equivalence), 1,1'-binaphthyl-2,2'-bis(diphenylphosphine) (249.1 mg, 0.4 mmol, 0.1 equivalence), sodium tert-butoxide (538.2 mg, 5.6 mmol, 1.4 equivalence), and 6 mL of toluene to a 25 mL Shrek tube, and reflux at 110°C for 18 hours. After cooling to room temperature, the solution was diluted with 5 mL of ethyl acetate, washed with 5 mL of water, and the organic phase was separated. The aqueous phase was extracted three times with 5 mL of ethyl acetate. The organic phases were combined, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated and recrystallized to give 806.4 mg of a pale yellow solid of compound 3a, with a yield of 55%.

[0078] The results of testing showed that the compound of formula 3a obtained in this embodiment was 864.0 mg of a pale yellow oil, with a yield of 75%. 1 HNMR(400MHz,Chloroform-d)δ7.38-7.34(m,2H),7.33-7.26(m,6H),7.26-7.20(m,2H),7.09-6. 97(m,2H),6.60-6.54(m,1H),6.48-6.42(m,2H),4.47(d,J=4.6Hz,1H),4.30(d,J=4.6Hz,1H)ppm; 13 C NMR (101MHz, Chloroform-d) δ147.4,142.8,141.5,128.9,128.5,128.3,127.3,127.1,126.9,126.7,116.8,113.4,63.2,61.1ppm; HRMS-ESI(m / z):[M+H] + calcd for C 21 H 23 N2:303.1856; found:303.1854; [α] D 25 = -73.8 (c = 1.0, CHCl3).

[0079] Example 2

[0080] Compounds of formulas 3b-3l were prepared according to the preparation method of Example 1, and their structures are shown in the following formulas:

[0081]

[0082] The data obtained from the compound of formula 3b in this embodiment were as follows: 942.2 mg of a pale yellow oil, with a yield of 78%. 1 HNMR(400MHz,Chloroform-d)δ7.42-7.39(m,2H),7.34-7.27(m,6H),7.25-7.20(m,2H),6.99(d,J=6.8Hz,1H),6.84-6.82(m ,1H),6.55-6.49(m,1H),6.13(d,J=8.8Hz,1H),5.14(brs,1H),4.49(d,J=4.0Hz,1H),4.37(d,J=4.0Hz,1H),2.23(s,3H)ppm; 13C NMR(101MHz,Chloroform-d)δ145.2,143.0,141.7,129.7,128.5,128.3,127.4,127 .2,126.9,126.7,122.1,116.3,110.8,63.3,61.3,17.6ppm; HRMS-ESI(m / z):[M+H] + calcd forC 21 H 23 N2:303.1856; found:303.1854; [α] D 25 = -73.8 (c = 1.0, CHCl3).

[0083] The data obtained from the compound of formula 3c in this embodiment were as follows: 758.4 mg of a pale yellow oil, with a yield of 60%. 1 HNMR(400MHz,Chloroform-d)δ7.38-7.35(m,2H),7.28-7.23(m,6H),7.21-7.16(m,2H),6.99-6.98(m,1H),6.83-6.78(m,1H),6.5 5-6.51(m,1H),6.14-6.12(m,1H),5.26(brs,1H),4.47(s,1H),4.31(d,J=4.0Hz,1H),2.63-2.55(m,2H),1.27(t,J=7.2Hz,3H)ppm; 13 CNMR(101MHz,Chloroform-d)δ144.5,143.0,141.7,128.5,128.3,127.7,127.6,127.3,12 7.1,126.8,126.7,126.6,116.4,111.1,63.1,61.2,24.1,13.0ppm; HRMS-ESI(m / z):[M+H] + calcd for C 22 H 25 N2:317.2012;found:317.2014;[α] D 25 = -13.9 (c = 0.4, CHCl3).

[0084] The data obtained from this embodiment of the 3d compound were as follows: 758.4 mg of a pale yellow oil, with a yield of 52%. 1HNMR(400MHz,Chloroform-d)δ7.38-7.35(m,2H),7.28-7.23(m,6H),7.21-7.16(m,2H),6.99-6.98(m,1H),6.83-6.78(m,1H),6.5 5-6.51(m,1H),6.14-6.12(m,1H),5.26(brs,1H),4.47(s,1H),4.31(d,J=4.0Hz,1H),2.63-2.55(m,2H),1.27(t,J=7.2Hz,3H)ppm; 13 CNMR(101MHz,Chloroform-d)δ144.5,143.0,141.7,128.5,128.3,127.7,127.6,127.3,12 7.1,126.8,126.7,126.6,116.4,111.1,63.1,61.2,24.1,13.0ppm; HRMS-ESI(m / z):[M+H] + calcd for C 22 H 25 N2:317.2012; found:317.2014.

[0085] The data obtained from this example of compound 3e were as follows: 750.0 mg yellow solid, melting point 108.9-110.5 °C, and yield 56%. 1 H NMR(400MHz,Chloroform-d)δ7.40-7.36(m,2H),7.32-7.29(m,3H),7.28-7.25(m,3H),7.23-7.18(m,2H),6.83-6.78(m,1H),6.65-6. 62(m,1H),6.04(d,J=8.1Hz,1H),4.99(s,1H),4.44(d,J=4.3Hz,1H),4.33(d,J=4.3Hz,1H),2.19(s,3H),2.11(s,3H),1.46(s,2H)ppm; 13 C NMR(101MHz,Chloroform-d)δ143.0,142.9,141.7,130.6,128.5,128.3,127.3,127.1,12 7.0,126.8,126.7,125.3,122.2,110.8,63.4,61.2,20.2,17.5ppm; HRMS-ESI(m / z):[M+H] + calcd for C 22 H 25N2:317.2018; found:317.2018; [α] D 25 = -46.0 (c = 1.0, CHCl3).

[0086] The data obtained from the compound of formula 3f in this embodiment were as follows: 1049.1 mg white solid, melting point 99.8-101.3 °C, and yield 83%. 1 H NMR(400MHz,Chloroform-d)δ7.36(d,J=7.2Hz,2H),7.39-7.23(m,8H),6.87(d,J=7.2Hz 1H),6.34(d,J=6.8Hz,1H),6.02(s,1H),4.83(s,3H),4.54(d,J=4.4Hz,1H),4.40(d,J=4.4Hz,1H),2.05(s,6H)ppm; 13 C NMR(101MHz,Chloroform-d)δ145.1,142.2,141.4,136.5,129.8,128.7,128.5,127.7 ,127.3,127.0,119.5,117.3,111.9,63.1,61.1,21.5,17.3ppm; HRMS-ESI(m / z):[M+H] + calcd for C 22 H 25 N2:317.2017;found:317.2018;[α] D 25 = -60.2 (c = 1.0, CHCl3).

[0087] The data obtained from the 3g compound in this embodiment were: 745.8 mg of yellow oily substance, with a yield of 59%. 1 H NMR(400MHz,Chloroform-d)δ7.32-7.30(m,2H),7.21-7.16(m,2H),7.13-7.01(m,6H),6.77(d,J =7.2Hz,2H),6.57(t,J=7.6Hz,1H),4.63(d,J=5.6Hz,1H),4.35(d,J=5.6Hz,1H),2.13(s,6H)ppm; 13C NMR(101MHz,Chloroform-d)δ144.3,142.8,142.2,128.9,128.0,127.9,127.1, 127.0,126.9,126.8,126.5,119.8,66.2,60.9,19.4ppm; HRMS-ESI(m / z):[M+H] + calcd for C 22 H 25 N2:317.2012;found:317.2013;[α] D 25 = +21.7 (c = 1.8, CHCl3).

[0088] The data obtained from the compound of formula 3h in this embodiment were as follows: 792.0 mg of yellow oily substance, with a yield of 60%. 1 H NMR (400MHz, Chloroform-d) δ7.38-7.01(m,10H),6.66(s,2H),5.71(d,J=14.2Hz,1H),4.55(d,J=6.5Hz,1H),4.43(d,J=6.5Hz,1H),2.14(s,9H)ppm; 13 C NMR(101MHz,Chloroform-d)δ143.0,142.2,141.6,129.7,129.4,128.3,128.0 ,127.9,127.3,127.0,126.8,66.8,61.1,20.3,19.4ppm; HRMS-ESI(m / z):[M+H] + calcd for C 22 H 25 N2:317.2012; found:317.2013.

[0089] The data obtained from this example of compound 3i were as follows: 1403.5 mg white solid, melting point 68.7-74.2 °C, and yield 68%. 1 H NMR(400MHz,Chloroform-d)δ7.50-7.46(m,2H),7.43-7.34(m,10H),7.26(d,J=9.6Hz,4H),7.18-7.11(m,4H),6.97(d,J =7.0Hz,3H),6.89-6.84(m,2H),6.44-6.41(m,2H),5.27(d,J=10.9Hz,1H),3.87-3.83(m,1H),3.72(d,J=5.1Hz,1H)ppm;13 C NMR(101MHz,Chloroform-d)δ142.4,141.7,141.2,141.1,140.4,132.0,131.5,129.5,128.8,128.50,128 .45,127.7,127.6,127.1,127.0,126.9,126.8,126.5,126.3,126.2,64.8,60.6ppm; HRMS-ESI(m / z):[M+H] + calcd for C 38 H 33 N2:517.2644; found:517.2640; [α] D 25 = +56.4 (c = 1.0, CHCl3).

[0090] The data obtained from the compound of formula 3j in this embodiment were as follows: 1045.8 mg of yellow oily substance, with a yield of 76%. 1 HNMR(400MHz,Chloroform-d)δ7.33(d,J=7.2Hz,2H),7.21(t,J=7.2Hz,2H),7.16-7.03(m,8H),6.84(d,J=7.6Hz,2H ),6.70(t,J=7.6Hz,1H),4.52(d,J=5.6Hz,1H),4.41(d,J=5.6Hz,1H),2.57-2.46(m,4H),1.11(t,J=7.2Hz,6H)ppm; 13 C NMR(101MHz,Chloroform-d)δ143.0,142.9,141.9,133.2,128.0,127.2,127.1 ,127.0,126.8,126.7,120.5,67.2,61.0,25.0,14.2ppm; HRMS-ESI(m / z):[M+H] + calcd for C 24 H 29 N2:345.2326;found:345.2337;[α] D 25 = +32.0 (c = 0.7, CHCl3).

[0091] The data obtained from this example of compound 3k were: 716.8 mg of yellow oily substance, with a yield of 56%. 1H NMR(400MHz,Chloroform-d)δ7.36(d,J=7.5Hz,2H),7.32-7.25(m,6H),7.24-7.19(m,2H),6.73-6.70(m,1H),6.53-6.48(m, 1H),6.03-5.99(m,1H),5.10-4.92(m,1H),4.39(d,J=4.5Hz,1H),4.30(d,J=4.4Hz,1H),2.20(s,3H),1.51-1.34(m,2H)ppm; 13 C NMR (101MHz, Chloroform-d) δ143.2,141.7,128.8,128.6,127.6,127.5,127.0,116.9,116.7,112.5,111.4,64.0,61.5,17.9ppm; 19 F NMR(376MHz,Chloroform-d)δ-129.3(d,J=8.7Hz)ppm; HRMS-ESI(m / z):[M+H] + calcd for C 21 H 22 N2F:321.1767; found:321.1767; [α] D 25 = +95.2 (c = 1.0, CHCl3).

[0092] The results of testing showed that the compound of formula 3l obtained in this embodiment was 1204.8 mg of a yellow oily substance, with a yield of 91%. 1 HNMR(400MHz,Chloroform-d)δ7.54-7.33(m,11H),6.81(d,J=2.8Hz,1H),6.58-6.56(m,1H), 6.27-6.24(m,1H),4.56(d,J=5.0Hz,1H),4.43(d,J=4.7Hz,1H),3.75(s,3H),2.38(s,3H)ppm; 13 C NMR(101MHz,Chloroform-d)δ151.0,143.0,141.7,139.5,128.3,128.1,127.2,127.0,12 6.8,126.7,123.7,116.7,111.6,111.0,64.0,61.3,55.4,17.7ppm; HRMS-ESI(m / z):[M+H] + calcd for C 22 H 25N2O:332.4470; found:333.1967; [α] D 25 = -65.8 (c = 1.0, CHCl3).

[0093] Example 3

[0094] In this embodiment, the preparation method of compound 5a is as follows, and the reaction route is shown below.

[0095]

[0096] In a glove box, compound 3a (576.0 mg, 2.0 mmol, 1.0 equivalence) prepared in Example 1, 2-bromopyridine 4a (347.6 mg, 2.2 mmol, 1.1 equivalence), tris(dibenzylideneacetone)dipalladium(0) (91.6 mg, 0.1 mmol, 0.05 equivalence), 4,5-bis(diphenylphosphine-9,9-dimethyloxanthracene) (115.7 mg, 0.2 mmol, 0.1 equivalence), sodium tert-butoxide (269.1 mg, 2.8 mmol, 1.4 equivalence), and 3 mL of toluene were added to a 25 mL Shrek tube and refluxed at 110°C for 18 hours. After cooling to room temperature, dilute with 5 mL of ethyl acetate, wash with 5 mL of water, separate the organic phase, extract the aqueous phase three times with 5 mL of ethyl acetate, combine the organic phases, dry with anhydrous magnesium sulfate, and filter; concentrate the filtrate and recrystallize (petroleum ether / ethyl acetate = 20:1) to give 423.4 mg of yellow solid compound 5a with a melting point of 136.5-140.0 °C and a yield of 58%.

[0097] The data obtained from the test of compound 5a in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.08-8.06(m,1H),7.26-7.20(m,1H),7.18-7.17(m,3H),7.15-7.08(m,7H),7.03-6.99(m,2H),6.60(t,J=7.3Hz,1H),6 .54-6.50(m,1H),6.48-6.42(m,2H),6.17(d,J=8.4Hz,1H),5.36(d,J=6.7H z,1H),5.14(d,J=5.1Hz,1H),4.99(t,J=7.2Hz,1H),4.63-4.60(m,1H)ppm; 13C NMR(101MHz,Chloroform-d)δ158.0,147.9,147.1,140.1,139.6,137.4,128.9,128.3,128 .1,127.5,127.5,127.3,127.2,117.5,113.6,107.7,64.0,61.7ppm; HRMS-ESI(m / z):[M+H] + calcd for C 25 H 23 N3:366.1970; found:366.1979; [α] D 25 = -68.9 (c = 1.0, CHCl3).

[0098] Following the preparation method of Example 3, compounds of formulas 5b-5q were prepared, and their structures are shown in the following formulas:

[0099]

[0100] The data obtained from this example of compound 5b were: 629.1 mg of colorless liquid, with a yield of 83%. 1 HNMR(400MHz,Chloroform-d)δ8.11(d,J=4.4Hz,1H),7.31(t,J=6.8Hz.1H),7.26-7.22(m,4H),7.20-7.17(m,6H),6.97(d,J=7.6Hz,1H),6.88(t,J=8. 0Hz,1H),6.60-6.53(m,2H),6.31(d,J=8.0Hz,1H),6.23(d,J=8.4Hz,1H),5 .17-5.15(m,2H),4.96(d,J=4.0Hz,1H),4.73-4.70(m,1H),2.06(s,3H)ppm; 13 C NMR(101MHz,Chloroform-d)δ158.1,147.9,145.1,140.2,139.7,137.9,129.8,128.5,128.2,127.7,127 .4,127.3,127.2,126.7,122.5,116.9,113.6,110.9,107.9,64.2,61.6,17.7ppm; HRMS-ESI(m / z):[M+H] + calcd forC 26 H 26 N3:380.2121; found:380.2136; [α] D25 = -42.4 (c = 3.4, CHCl3).

[0101] The data obtained from the compound of formula 5c in this embodiment were as follows: 628.8 mg of yellow liquid, with a yield of 80%. 1 HNMR(400MHz,Chloroform-d)δ8.11(d,J=4.0Hz,1H),7.32(t,J=7.6Hz,1H),7.26-7.18(m,10H),6.99(d,J=7.2Hz,1H),6.87(t,J=7.6Hz,1H),6.62 -6.59(m,2H),6.30(d,J=8.0Hz,1H),6.24(d,J=8.0Hz,1H),5.19-5.08(m ,3H),4.72(t,J=6.0Hz,1H),2.48-2.33(m,2H),1.15(t,J=7.2Hz,3H)ppm; 13 C NMR(101MHz,Chloroform-d)δ158.2,148.0,144.4,140.3,139.7,137.4,128.6,128.3,127.8,127.7,127.4 ,127.3,127.2,126.6,122.2,117.1,113.7,111.3,108.0,64.1,61.7,24.2,13.0ppm; HRMS-ESI(m / z):[M+H] + calcd forC 27 H 28 N3:394.2278; found:394.2290; [α] D 25 =-91.1 (c=0.65, CHCl3).

[0102] The data obtained from this example of compound 5d were as follows: 661.5 mg of yellow solid, melting point of 72.2-74.3 °C, and yield of 75%. 1H NMR(400MHz,Chloroform-d)δ7.89(d,J=4.0Hz,1H),7.41-7.26(m,5H),7.23-7.06(m,9H),7.04-6.88(m,4H),6.66(t,J=7.2Hz,1H),6.44(d,J=6.4 Hz,1H),6.39(d,J=8.0Hz,1H),6.04(d,J=8.4Hz,1H),5.05(d,J=6.4Hz,1H ),4.95(t,J=6.4Hz,1H),4.89(d,J=4.8Hz,1H),4.71(t,J=5.6Hz,1H)ppm; 13 C NMR(101MHz,Chloroform-d)δ157.5,148.0,143.7,139.4,139.1,138.9,137.2,129.9,129.3,128 .8,128.3,127.4,127.3,127.1,117.2,113.3,111.7,107.2,63.1,61.0ppm; HRMS-ESI(m / z):[M+H] + calcd for C 31 H 28 N3:442.2278; found:442.2282; [α] D 25 = -120.5 (c = 1.58, CHCl3).

[0103] The data obtained from the compound of formula 5e in this embodiment were as follows: 534.5 mg of white solid, melting point of 139.9-140.3 °C, and yield of 68%. 1 H NMR(400MHz,Chloroform-d)δ8.08(d,J=4.2Hz,1H),7.29-7.14(m,11H),6.81(s,1H),6.68(d,J=8.0Hz,1H),6.57-6.51(m ,1H),6.21-6.19(m,2H),5.22(d,J=6.6Hz,1H),5.12(t,J=6.6Hz,1H),4.68(d,J=6.8Hz,2H),2.13(s,3H),2.04(s,3H)ppm; 13C NMR(101MHz,Chloroform-d)δ158.1,148.0,142.8,140.3,139.8,137.4,130.8,128.5,128.3,127.6,127.4, 127.28,127.25,127.0,126.2,122.7,113.6,111.3,107.8,64.2,61.6,20.2,17.6ppm; HRMS-ESI(m / z):[M+H] + calcd for C 27 H 28 N3:394.2283; found:394.2292; [α] D 25 = -108.0 (c = 1.0, CHCl3).

[0104] The data obtained from this example of compound 5f were as follows: 691.7 mg white solid, melting point 161.1-162.8 °C, and yield 88%. 1 H NMR(400MHz,Chloroform-d)δ8.10(d,J=4.8Hz,1H),7.29(t,J=8.0Hz,1H),7.24-7.15(m,10H),6.86(d,J=7.6Hz,1H),6.56(t,J=6.0H z,1H),6.38(d,J=7.2Hz,1H),6.22(d,J=8.4Hz,1H),6.16(s,1H),5.16(s,1H),4.84(s,1H),4.72(s,1H),2.08(s,3H),2.02(s,3H)ppm; 13 C NMR(101MHz,Chloroform-d)δ158.3,148.2,145.2,140.4,139.9,137.6,136.5,129.9,128.7,128.4,127.8 ,127.6,127.5,127.4,119.7,117.8,113.8,112.0,108.1,64.2,61.6,21.6,17.5ppm; HRMS-ESI(m / z):[M+H] + calcd forC 27 H 28 N3:394.2283; found:394.2283; [α] D 25 = -72.2 (c = 1.0, CHCl3).

[0105] The data obtained from this embodiment of the 5g compound were: 589.5 mg of yellow liquid, with a yield of 75%. 1 HNMR(400MHz,Chloroform-d)δ8.10(d,J=4.2Hz,1H),7.25(t,J=7.6Hz,1H),7.17-7.11(m,8H),6.95-6.93(m,2H),6.85-6.83(m,2H),6.68(t, J=7.6Hz,1H),6.22(d,J=8.0Hz,1H),5.88(d,J=4.2Hz,1H),5.07-5.05(m,1H),4.59(t,J=9.6Hz,1H),3.88(d,J=10.4Hz,1H),2.14(s,6H)ppm; 13 C NMR(101MHz,Chloroform-d)δ158.3,148.3,143.9,140.3,137.4,129.1,128.2,128.1,127 .9,127.7,127.4,127.3,121.3,113.5,107.5,65.4,61.5,19.5ppm; HRMS-ESI(m / z):[M+H] + calcd for C 27 H 28 N3:394.2278; found:394.2290; [α] D 25 = -10.4 (c = 1.4, CHCl3).

[0106] The data obtained from this example of compound 5h were as follows: 407.0 mg of yellow solid, melting point of 92.3-93.8 °C, and yield of 50%. 1 H NMR(400MHz,Chloroform-d)δ8.11-8.09(m,1H),7.32-7.28(m,1H),7.17(d,J=2.7Hz,6H),7.14-7.09(m,3H),6.97-6.93(m,2H),6.66(s, 2H),6.58-6.55(m,1H),6.22-6.20(m,1H),6.03(d,J=4.9Hz,1H),5.03-5.00(m,1H),4.47(d,J=8.1Hz,1H),2.13(s,3H),2.09(s,6H)ppm; 13C NMR(101MHz,Chloroform-d)δ158.4,148.3,141.2,140.6,140.5,137.4,130.7,129.7,128 .6,128.1,128.1,128.0,127.6,127.4,127.3,113.5,107.4,66.7,61.4,20.4,19.3ppm;[α] D 25 = -15.6 (c = 1.0, CHCl3).

[0107] The data obtained from this example of compound 5i were as follows: 438.8 mg of white solid, melting point of 92.2-97.6 °C, and yield of 37%. 1 H NMR(400MHz,Chloroform-d)δ8.07-8.02(m,1H),7.54-7.49(m,6H),7.46-7 .42(m,6H),7.36-7.31(m,2H),7.30(s,2H),7.26-7.22(m,2H),7.00-6.85(m ,6H),6.53-6.49(m,3H),6.23-6.16(m,2H),6.10-6.01(m,1H),5.17(d,J=5 .9Hz,1H),4.63(d,J=11.9Hz,1H),4.49-4.45(m,1H),3.98-3.93(m,1H)ppm; 13 C NMR(101MHz,Chloroform-d)δ158.1,148.1,141.3,140.9,140.2,139.8,139.2,137.1,133.,133.04,129.5,128.82,128.7 9,128.6,127.7,127.5,127.4,126.9,126.8,126.6,126.4,112.9,107.1,65.9,65.0,60.6,15.3ppm; HRMS-ESI(m / z):[M+H] + calcd for C 43 H 36 N3:594.2909; found:594.2903; [α] D 25 = -18.6 (c = 1.0, CHCl3).

[0108] The data obtained from the compound of formula 5j in this embodiment were as follows: 715.7 mg of yellow liquid, with a yield of 85%. 1HNMR(400MHz,Chloroform-d)δ8.10(d,J=4.8Hz,1H),7.31(t,J=7.6Hz,1H),7.25-7.11(m,8H),6.96-6.89(m,4H),6.82(t,J=7.6Hz,1H),6.56(t,J=6.0Hz ,1H),6.22(d,J=8.4Hz,1H),5.87(d,J=4.2Hz,1H),5.14-5.10(m,1H),4.47( d,J=7.6Hz,1H),3.83(brs,1H),2.54-2.39(m,4H),1.17(t,J=7.6Hz,6H)ppm; 13 C NMR(101MHz,Chloroform-d)δ158.3,148.3,142.6,140.5,140.1,137.4,135.0,128.2,128.1,127.9 ,127.6,127.4,127.3,126.9,122.1,113.5,107.5,67.6,61.2,24.7,14.5ppm; HRMS-ESI(m / z):[M+H] + calcd forC 29 H 32 N3:422.2591; found:422.2598; [α] D 25 = -16.8 (c = 1.6, CHCl3).

[0109] The data obtained from this example of compound 5k were as follows: 453.6 mg white solid, melting point 58.9-61.3 °C, and yield 60%. 1 H NMR(400MHz,Chloroform-d)δ8.12-8.10(m,1H),7.34-7.30(m,1H),7.24(q,J=4.7,3.9Hz,3H),7.21-7.15(m,7H),6.73-6.70(m,1H),6.6 4-6.51(m,2H),6.25(d,J=8.4Hz,1H),6.19-6.17(m,1H),5.15(d,J=6.6Hz,2H),4.89(d,J=4.6Hz,1H),4.67-4.64(m,1H),2.05(s,3H)ppm; 13C NMR(101MHz,Chloroform-d)δ148.1,141.5,137.6,128.7,128.4,127.9,127.6,127. 52,127.45,116.9,116.7,113.9,112.7,112.5,111.6,108.2,64.9,61.89,18.0ppm; 19 F NMR(376MHz,Chloroform-d)δ-128.6(d,J=6.7Hz)ppm; HRMS-ESI(m / z):[M+H] + calcd for C 26 H 25 N3F:398.2032; found:398.2032; [α] D 25 = -94.2 (c = 1.0, CHCl3).

[0110] The data obtained from the compound of formula 5l in this embodiment were as follows: 457.0 mg white solid, melting point 46.2-50.6 °C, and yield 56%. 1 H NMR(400MHz,Chloroform-d)δ8.09-8.07(m,1H),7.21-7.20(m,12H),6.62(d,J=2.8Hz,1H),6.58-6.52(m,1H),6.46-6.44( m,1H),6.23-6.21(m,2H),5.29(d,J=6.7Hz,1H),5.08(t,J=6.7Hz,1H),4.64(d,J=6.8Hz,1H),3.64(s,3H),2.07(s,3H)ppm; 13 C NMR(101MHz,Chloroform-d)δ158.1,151.6,148.1,140.4,139.8,139.3,137.4,128.5,128.3,127. 7,127.4,127.32,127.29,124.5,116.8,113.6,112.3,111.2,107.7,64.6,61.8,55.6,17.9ppm;[α] D 25 = -106.8 (c = 1.0, CHCl3).

[0111] The data obtained from this example of compound 5m were as follows: 678.9 mg white solid, melting point 141.5-142.8 °C, and yield 84%. 1H NMR(400MHz,Chloroform-d)δ7.94(d,J=5.9Hz,1H),7.28-7.22(m,3H),7.21- 7.15(m,7H),6.98(d,J=7.3Hz,1H),6.91-6.85(m,1H),6.55(t,J=7.3Hz,1H), 6.29(d,J=8.1Hz,1H),6.21-6.19(m,1H),5.69(d,J=2.2Hz,1H),5.24-5.07(m ,2H),5.01(d,J=4.7Hz,1H),4.71-4.68(m,1H),3.65(s,3H),2.07(s,3H)ppm; 13 C NMR(101MHz,Chloroform-d)δ149.2,130.0,128.7,128.4,127.9,127.5,126.9 ,117.1,111.1,102.3,92.0,64.4,62.0,54.9,17.9ppm; HRMS-ESI(m / z):[M+H] + calcd for C 27 H 28 N3O:410.2232; found:410.2232; [α] D 25 = -78.4 (c = 1.0, CHCl3).

[0112] The data obtained from this example of compound 5n were as follows: 804.6 mg white solid, melting point 89.2-90.7 °C, and yield 90%. 1 H NMR(400MHz,Chloroform-d)δ8.21(d,J=5.2Hz,1H),7.25-7.15(m,8H),6.98(d,J=7.2Hz 1H),6.89(t,J=7.6Hz,1H),6.73(d,J=7.2Hz,1H),6.57(t,J=7.2Hz,1H),6.43(s,1H),6.34(t,J= 8.0Hz,1H),5.42(d,J=6.8Hz,1H),5.25(t,J=6.8Hz,1H),4.76(d,J=4.0Hz,2H),2.05(s,3H)ppm; 13C NMR(101MHz,Chloroform-d)δ158.5,149.4,145.0,140.0,139.8,139.5,139.1,130.1,128.8,128.4,12 8.0,127.6,127.5,127.3,126.9,124.3,122.7,121.6,117.4,111.3,108.9,104.1,63.8,61.5,17.8ppm; 19 FNMR(376MHz,Chloroform-d)δ-65.2ppm; HRMS-ESI(m / z):[M+H] + calcd for C 27 H 25 N3F3:448.2000; found:448.2000; [α] D 25 = -55.4 (c = 1.0, CHCl3).

[0113] The data obtained from this example of compound 5o were as follows: 595.8 mg of yellow solid, melting point of 57.9-62.0 °C, and yield of 76%. 1 H NMR (400MHz, Chloroform-d) δ7.91 (s, 1H), 7.25-7.10 (m, 11H), 6.96 (d, J = 7.1Hz, 1H), 6.87 (t, J = 7.7Hz, 1H), 6.54 (t, J = 7.1Hz, 1H), 6. 30(d,J=8.0Hz,1H),6.15(d,J=8.4Hz,1H),5.17-5.04(m,2H),4.97(d,J=4.2Hz,1H),4.71-4.68(m,1H),2.10(s,3H),2.07(s,3H)ppm; 13 C NMR(101MHz,Chloroform-d)δ156.3,147.5,145.2,140.3,139.9,138.4,129.8,128.4,128.2,127.6,127.4 ,127.3,127.2,126.7,122.5,122.4,116.9,111.0,107.6,64.1,61.9,17.7,17.3ppm; HRMS-ESI(m / z):[M+H] + calcd forC 27 H 28 N3:393.5340;found:394.2283;[α] D 25= -104.4 (c = 1.0, CHCl3).

[0114] The data obtained from this example of compound 5p were as follows: 658.6 mg of red solid, melting point of 119.6-123.2 °C, and yield of 84%. 1 H NMR(400MHz,Chloroform-d)δ7.97(d,J=5.2Hz,1H),7.25-7.22(m,3H),7.20-7.13(m,8H),7.01-6.95(m,1H),6.90-6.86(m,1H),6.57-6.53 (m,1H),6.43-6.41(m,1H),6.30-6.28(m,1H),6.07(d,J=1.4Hz,1H),5.16(t,J=7.1Hz,1H),5.07-5.04(m,2H),2.13(s,3H),2.06(s,3H)ppm; 13 C NMR(101MHz,Chloroform-d)δ158.4,147.6,145.2,140.4,139.9,129.8,128.5,128.2,127.6,127.5 ,127.3,126.7,122.5,116.9,115.3,110.9,108.3,64.3,61.6,21.1,17.8ppm; HRMS-ESI(m / z):[M+H] + calcd forC 27 H 27 N3:393.2205; found:393.2283; [α] D 25 = -94.8 (c = 1.0, CHCl3).

[0115] The data obtained from the compound of formula 5q in this embodiment were as follows: 565.9 mg of white solid, melting point of 50.4-51.8 °C, and yield of 72%. 1 H NMR(400MHz,Chloroform-d)δ7.25-7.22(m,3H),7.22-7.16(m,8H),7.02-6.94(m,1H),6.89-6.87(m,1H),6.58-6.54(m,1H),6.45(d,J=7.3Hz,1 H),6.34-6.32(m,1H),6.01(d,J=8.3Hz,1H),5.23-5.04(m,2H),4.89(d, J=4.7Hz,1H),4.72-4.69(m,1H),2.41(s,3H),2.05(d,J=6.4Hz,3H)ppm;13 C NMR(101MHz,Chloroform-d)δ157.0,145.3,137.9,130.0,128.7,128.4,127.8,127.6,127.5,12 7.4,126.9,122.6,117.1,113.1,111.1,104.5,64.3,61.9,24.5,17.9ppm; HRMS-ESI(m / z):[M+H] + calcd forC 27 H 28 N3:394.2283; found:394.2283; [α] D 25 = -123.2 (c = 1.0, CHCl3).

[0116] Example 4-1

[0117] In this embodiment, the preparation steps of compound (S,S)-6a are as follows, and the reaction route is shown below.

[0118]

[0119] In a glove box, the compound of formula 5a (182.5 mg, 0.5 mmol, 1.0 equivalence) prepared in Example 3, phenylphosphine dichloride (134.2 mg, 0.75 mmol, 1.5 equivalence), triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalence), and 3 mL of toluene were added to a 25 mL Shrek tube. After reacting at 110 °C for 12 hours, the mixture was cooled to room temperature, the solvent was removed, and the residue was recrystallized to obtain the ligand of formula 6a.

[0120] The data obtained from this example of compound 6a were as follows: 75.4 mg white solid, melting point 82.3-86.0 °C, and yield 32%. 1 H NMR(400MHz,Chloroform-d)δ8.29-8.27(m,1H),7.61-7.54(m,2H),7.31-7.25(m,4H),7.24-7.16(m,6H),7.13(t,J=7.2Hz,2H),7.06-7 .02(m,2H),6.97(d,J=6.8Hz,2H),6.89(d,J=8.0Hz,2H),6.83-6.80(m,1H),6.31-6.28(m,1H),5.59-5.56(m,1H),5.10-5.08(m,1H)ppm; 13C NMR(101MHz,Chloroform-d)δ153.5,148.2,138.4,138.0,136.8,135.7,129.3,128.9,128.7, 128.5,128.4,127.9,127.5,125.4,124.6,117.0,107.8,72.8,72.1ppm; HRMS-ESI(m / z):[M+H] + calcd for C 31 H 26 N3P:472.1942; found:472.1951; [α] D 25 =-92.0 (c=1.0, CHCl3).

[0121] Example 4-2

[0122] In a glove box, the compound of formula 5b prepared in Example 3 (189.6 mg, 0.5 mmol, 1.0 equivalent), phenylphosphine dichloride (134.2 mg, 0.75 mmol, 1.5 equivalent), triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalent), and 3 mL of toluene were added to a 25 mL Shrek tube. After reacting at 110 °C for 12 hours, the mixture was cooled to room temperature, the solvent was removed, and the residue was recrystallized to obtain the ligand of formula 6b.

[0123] Example 4-3

[0124] In a glove box, the compound of formula 5c prepared in Example 3 (196.6 mg, 0.5 mmol, 1.0 equivalent), phenylphosphine dichloride (134.2 mg, 0.75 mmol, 1.5 equivalent), triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalent), and 3 mL of toluene were added to a 25 mL Shrek tube. After reacting at 110°C for 12 hours, the mixture was cooled to room temperature, the solvent was removed, and the residue was recrystallized to obtain the ligand of formula 6c.

[0125] Example 4-4

[0126] In a glove box, the 5d compound prepared in Example 3 (220.6 mg, 0.5 mmol, 1.0 equivalent), phenylphosphine dichloride (134.2 mg, 0.75 mmol, 1.5 equivalent), triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalent), and 3 mL of toluene were added to a 25 mL Shrek tube. After reacting at 110 °C for 12 hours, the mixture was cooled to room temperature, the solvent was removed, and the residue was recrystallized to obtain the ligand 6d compound.

[0127] Examples 4-5

[0128] In a glove box, the compound of formula 5e prepared in Example 3 (196.6 mg, 0.5 mmol, 1.0 equivalent), phenylphosphine dichloride (134.2 mg, 0.75 mmol, 1.5 equivalent), triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalent), and 3 mL of toluene were added to a 25 mL Shrek tube. After reacting at 110 °C for 12 hours, the mixture was cooled to room temperature, the solvent was removed, and the residue was recrystallized to obtain the ligand of formula 6e.

[0129] Examples 4-6

[0130] In a glove box, the compound of formula 5f (196.6 mg, 0.5 mmol, 1.0 equivalent) prepared in Example 3, phenylphosphine dichloride (134.2 mg, 0.75 mmol, 1.5 equivalent), triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalent), and 3 mL of toluene were added to a 25 mL Shrek tube. After reacting at 110 °C for 12 hours, the mixture was cooled to room temperature, the solvent was removed, and the residue was recrystallized to give the compound of formula 6e.

[0131] Examples 4-7

[0132] In a glove box, 5 g of the compound prepared in Example 3 (196.6 mg, 0.5 mmol, 1.0 equivalence), phenylphosphine dichloride (134.2 mg, 0.75 mmol, 1.5 equivalence), triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalence), and 3 mL of toluene were added to a 25 mL Shrek tube. After reacting at 110 °C for 12 hours, the mixture was cooled to room temperature, the solvent was removed, and the residue was recrystallized to give 6 g of the compound of ligand formula.

[0133] Examples 4-8

[0134] In a glove box, the compound of formula 5h prepared in Example 3 (203.6 mg, 0.5 mmol, 1.0 equivalent), phenylphosphine dichloride (134.2 mg, 0.75 mmol, 1.5 equivalent), triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalent), and 3 mL of toluene were added to a 25 mL Shrek tube. After reacting at 110 °C for 12 hours, the mixture was cooled to room temperature, the solvent was removed, and the residue was recrystallized to obtain the ligand of formula 6h.

[0135] Examples 4-9

[0136] In a glove box, the compound of formula 5i prepared in Example 3 (296.6 mg, 0.5 mmol, 1.0 equivalent), phenylphosphine dichloride (134.2 mg, 0.75 mmol, 1.5 equivalent), triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalent), and 3 mL of toluene were added to a 25 mL Shrek tube. After reacting at 110 °C for 12 hours, the mixture was cooled to room temperature, the solvent was removed, and the residue was recrystallized to obtain the ligand of formula 6i.

[0137] Examples 4-10

[0138] In a glove box, the compound of formula 5j (210.6 mg, 0.5 mmol, 1.0 equivalence) prepared in Example 3, phenylphosphine dichloride (134.2 mg, 0.75 mmol, 1.5 equivalence), triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalence), and 3 mL of toluene were added to a 25 mL Shrek tube. After reacting at 110 °C for 12 hours, the mixture was cooled to room temperature, the solvent was removed, and the residue was recrystallized to obtain the ligand of formula 6j.

[0139] Example 4-11

[0140] In a glove box, the compound of formula 5k prepared in Example 3 (198.6 mg, 0.5 mmol, 1.0 equivalence), phenylphosphine dichloride (134.2 mg, 0.75 mmol, 1.5 equivalence), triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalence), and 3 mL of toluene were added to a 25 mL Shrek tube. After reacting at 110°C for 12 hours, the mixture was cooled to room temperature, the solvent was removed, and the residue was recrystallized to obtain the ligand of formula 6k.

[0141] Example 4-12

[0142] In a glove box, the compound of formula 5o prepared in Example 3 (196.6 mg, 0.5 mmol, 1.0 equivalent), phenylphosphine dichloride (134.2 mg, 0.75 mmol, 1.5 equivalent), triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalent), and 3 mL of toluene were added to a 25 mL Shrek tube. After reacting at 110°C for 12 hours, the mixture was cooled to room temperature, the solvent was removed, and the residue was recrystallized to give the compound of formula 6l.

[0143] Example 4-13

[0144] In a glove box, the compound of formula 5m prepared in Example 3 (204.6 mg, 0.5 mmol, 1.0 equivalent), phenylphosphine dichloride (134.2 mg, 0.75 mmol, 1.5 equivalent), triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalent), and 3 mL of toluene were added to a 25 mL Shrek tube. After reacting at 110°C for 12 hours, the mixture was cooled to room temperature, the solvent was removed, and the residue was recrystallized to obtain the compound of formula 6m.

[0145] Example 4-14

[0146] In a glove box, the compound of formula 5n prepared in Example 3 (223.6 mg, 0.5 mmol, 1.0 equivalent), phenylphosphine dichloride (134.2 mg, 0.75 mmol, 1.5 equivalent), triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalent), and 3 mL of toluene were added to a 25 mL Shrek tube. After reacting at 110 °C for 12 hours, the mixture was cooled to room temperature, the solvent was removed, and the residue was recrystallized to obtain the compound of formula 6n.

[0147] Examples 4-15

[0148] In a glove box, the compound of formula 5l prepared in Example 3 (204.6 mg, 0.5 mmol, 1.0 equivalent), phenylphosphine dichloride (134.2 mg, 0.75 mmol, 1.5 equivalent), triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalent), and 3 mL of toluene were added to a 25 mL Shrek tube. After reacting at 110°C for 12 hours, the mixture was cooled to room temperature, the solvent was removed, and the residue was recrystallized to give the compound of formula 6o.

[0149] Example 4-16

[0150] In a glove box, the 5p compound prepared in Example 3 (196.6 mg, 0.5 mmol, 1.0 equivalence), phenylphosphine dichloride (134.2 mg, 0.75 mmol, 1.5 equivalence), triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalence), and 3 mL of toluene were added to a 25 mL Shrek tube. After reacting at 110 °C for 12 hours, the mixture was cooled to room temperature, the solvent was removed, and the residue was recrystallized to obtain the ligand 6p compound.

[0151]

[0152] The data obtained from the compound of formula 6b in this embodiment were as follows: 172.2 mg white solid, melting point 110.5-111.9 °C, and yield 71%. 1H NMR(400MHz,Chloroform-d)δ8.26(d,J=8.4Hz,1H),7.43-7.09(m,16H),6.95(s,2H) ,6.74(s,1H),6.71-6.68(m,1H),6.35(d,J=8.4Hz,2H),4.85(s,2H),2.72(s,3H)ppm; 13 C NMR(101MHz,Chloroform-d)δ158.4,158.2,148.5,140.4,138.5,137.3,137.1,133.2,131.0,130.8,129.1,128 .6,128.2,128.0,127.9,127.8,125.7,125.5,123.6,114.7,109.2,74.6,71.7,19.9ppm; HRMS-ESI(m / z):[M+H] + calcd forC 32 H 29 N3P:486.2099; found:486.2099; [α] D 25 = -169.6 (c = 1.0, CHCl3).

[0153] The data obtained from the compound of formula 6c in this embodiment were as follows: 92.3 mg white solid, melting point 107.2-109.1 °C, and yield 37%. 1 H NMR(400MHz,Chloroform-d)δ8.22(d,J=4.1Hz,1H),7.39-7.27(m,6H),7.24-7.20(m,4H),7.15(d,J=5.3Hz,2H),7.08(t,J=5.1Hz,3H),6.94-6 .88(m,3H),6.73-6.63(m,2H),6.31(d,J=8.4Hz,1H),6.27(d,J=7.7Hz, 1H), 4.81 (q, J = 9.1Hz, 2H), 3.25-3.09 (m, 2H), 1.38 (t, J = 7.4Hz, 3H) ppm; 13C NMR(101MHz,Chloroform-d)δ158.2,158.0,148.3,141.3,140.8,139.4,138.7,138.2,137.1,136.9,130.9,130.7,128.9,128.5,128.42,12 8.35,128.0,127.74,127.70,127.6,125.4,125.2,123.7,114.5,109.1,74.5,74.4,71.5,71.4,24.1,23.9,14.5ppm; HRMS-ESI(m / z):[M+H] + calcd for C 33 H 31 N3P:500.2256; found:500.2263; [α] D 25 = -177.8 (c = 1.0, CHCl3).

[0154] The data obtained from the 6d compound in this example were as follows: 142.2 mg of white solid, melting point of 105.5-106.9 °C, and yield of 52%. 1 H NMR(400MHz,Chloroform-d)δ8.09(s,1H),7.67(s,1H),7.50-6.79(m,24H),6.6 0(t,J=6.08Hz,1H),6.46-6.34(m,1H),6.23-6.20(m,1H),4.83-4.77(m,1H)ppm; 13 C NMR(101MHz,Chloroform-d)δ171.1,157.9,157.7,147.9,142.7,142.2,141.0,138.4,137.0,136.8,136.5,131.3,130.5 ,130.3,129.4,129.0,128.2,127.6,127.5,126.8,123.2,114.3,108.9,74.3,74.2,71.2,71.1ppm; HRMS-ESI(m / z):[M+H] + calcd forC 37 H 31 N3P:548.2256; found:548.2252; [α] D 25 = -121.6 (c = 1.0, CHCl3).

[0155] The data obtained from the compound of formula 6e in this embodiment were as follows: 132.2 mg of white solid, melting point of 115.3-116.2 °C, and yield of 53%. 1 H NMR (400MHz, Chloroform-d) δ8.23 (d, J=4.9Hz, 1H), 7.41 (s, 2H), 7.34-7.26 (m, 4H), 7.21-7.18 (m, 3H), 7.13-7.05 (m, 5H), 6.92 (t, J= 6.7Hz,3H),6.68-6.65(m,1H),6.61-6.40(m,1H),6.30(d,J=8.4Hz,1H),6.19(s,1H),4.79(s,2H),2.63(s,3H),2.2-2.11(m,3H)ppm; 13 CNMR(101MHz,Chloroform-d)δ158.3,158.1,148.3,138.4,137.3,136.9,132.7,131.5,130.9,130.7,128.8,128.5,128.3,128. 0,127.8,127.63,127.58,126.3,126.2,125.2,114.4,109.0,74.6,74.5,71.6,71.5,20.7,19.6,19.5ppm; HRMS-ESI(m / z):[M+H] + calcd for C 33 H 31 N3P:500.2256; found:500.2252; [α] D 25 = -161.6 (c = 1.0, CHCl3).

[0156] The data obtained from the compound of formula 6f in this embodiment were as follows: 119.8 mg white solid, melting point 88.6-90.3 °C, and yield 48%. 1 H NMR (400MHz, Chloroform-d) δ8.13 (d, J=4.8Hz, 1H), 7.31 (s, 2H), 7.22-6.84 (m, 16H), 6.55 (t, J= 7.2Hz,2H),6.22(d,J=8.4Hz,1H),6.00(s,1H),4.72(s,2H),2.51-2.46(m,3H),1.81(s,3H)ppm; 13C NMR(101MHz,Chloroform-d)δ158.3,158.2,148.4,138.5,136.95,136.93,130.9,130.8,130.6,129.0,128. 6,128.4,128.0,127.9,127.7,127.6,114.6,109.1,71.7,71.6,46.1,20.9,11.4ppm; HRMS-ESI(m / z):[M+H] + calcdfor C 33 H 31 N3P:500.2255; found:500.2256; [α] D 25 = -146.2 (c = 1.0, CHCl3).

[0157] The data obtained from this example of the 6g compound were as follows: 164.7 mg white solid, melting point 92.7-97.8℃, and yield 66%. 1 H NMR(400MHz,Chloroform-d)δ8.19-8.17(m,1H),7.74-7.67(m,2H),7.38(d,J=3.0Hz,3H),7.26-7.12(m,6H),7.08-6.97(m,4H),6.8 7-6.78(m,3H),6.65-6.56(m,2H),6.28(d,J=8.4Hz,1H),4.90(d,J=9.2Hz,1H),4.74(d,J=9.2Hz,1H),2.67(s,3H),1.49(s,3H)ppm; 13 C NMR(101MHz,Chloroform-d)δ158.3,158.2,148.3,143.9,143.4,139.5,139.3,1 38.3,137.2,137.1,136.8,137.7,136.1,135.9,130.3,130.0,129.04,128.96,12 8.8,128.6,128.3,127.94,127.89,127.8,127.6,127.5,125.0,124.9,114.3,10 8.91,108.88,76.1,76.0,72.7,72.6,20.8,20.7,19.9ppm; HRMS-ESI(m / z):[M+H] + calcd for C 33 H 30 N3P:500.2256; found:500.2262; [α]D 25 = -240.0 (c = 1.0, CHCl3).

[0158] The data obtained from this example of compound 6h were as follows: 105.2 mg white solid, melting point 126.2-127.2 °C, and yield 41%. 1 H NMR(400MHz,Chloroform-d)δ8.20-8.19(m,1H),7.74-7.67(m,2H),7.43-7.38(m,3H), 7.30-7.25(m,1H),7.23-7.18(m,3H),7.13-7.11(m,2H),7.10-7.06(m,1H),7.05-7.00 (m,2H),6.86-6.80(m,3H),6.66-6.63(m,1H),6.43-6.39(m,1H),6.29-6.26(m,1H),4. 87(d,J=9.19Hz,1H),4.72(d,J=9.15Hz,1H),2.62(s,3H),2.13(s,3H),1.45(s,3H)ppm; 13 C NMR(101MHz,Chloroform-d)δ158.4,158.3,148.3,144.0,143.6,138.4,13 6.82,136.76,136.7,136.6,136.3,135.5,134.2,130.3,130.1,129.7,129. 4,129.0,128.9,128.3,127.94,127.89,127.7,127.61,127.56,114.2,109. 0,108.9,76.1,76.0,72.8,72.720.7,20.6,19.9ppm; HRMS-ESI(m / z):[M+H] + calcd for C 34 H 33 N3P:514.2412; found:514.2404; [α] D 25 = -216.4 (c = 1.0, CHCl3).

[0159] The data obtained from the compound of formula 6i in this embodiment were as follows: 269.1 mg of yellow solid, melting point of 118.0-122.4 °C, and yield of 77%. 1H NMR(400MHz,Chloroform-d)δ8.04-7.96(m,1H),7.87-7.80(m,2H),7.74-7.68(m,2H),7.6 3-7.60(m,1H),7.57-7.52(m,2H),7.43-7.37(m,3H),7.33-7.27(m,2H),7.24-7.08(m,4H), 7.08-7.03(m,5H),6.93-6.84(m,6H),6.70-6.64(m,2H),6.55-6.49(m,1H),6.43-6.36(m, 2H),6.26-6.20(m,2H),6.06-6.00(m,1H),4.63(d,J=9.6Hz,1H),4.35(d,J=9.6Hz,1H)ppm; 13 CNMR(101MHz,Chloroform-d)δ147.5,135.2,131.5,131.3,129.9,129.6,129.5,129.2,129.2,129.1,128.6,128.1,128.0,127.92,127.87, 127.7,127.22,127.18,127.1,127.0,126.9,126.5,126.4,126.0,114.1,109.1,109.1,74.02,73.96,71.4,71.3ppm; HRMS-ESI(m / z):[M+H] + calcd for C 49 H 39 N3P:700.2881; found:700.2881; [α] D 25 = -131.2 (c = 1.0, CHCl3).

[0160] The compound of formula 6j obtained in this embodiment was tested and found to be: 92.1 mg white solid, melting point 95.6-99.7 °C, and yield 35%. 1H NMR(400MHz,Chloroform-d)δ8.21-8.20(m,1H),7.76-7.69(m,2H),7.45-7.36(m,3H),7.31-7.27(m,1H),7.23- 7.16(m,3H),7.13-7.10(m,3H),7.09-7.04(m,1H),7.02-6.96(m,3H),6.83-6.73(m,3H),6.66-6.64(m,1H),6.3 1-6.29(m,1H),4.91(d,J=9.2Hz,1H),4.80(d,J=9.2Hz,1H),3.15(ddd,J=15.3,7.6,2.3Hz,1H),2.99(dq,J=15. 2,7.5Hz,1H),1.98(dq,J=15.1,7.5Hz,1H),1.87-1.77(m,1H),1.39(t,J=7.5Hz,3H),0.70(t,J=7.5Hz,3H)ppm; 13 C NMR(101MHz,Chloroform-d)δ158.4,158.2,148.3,144.1,143.7,143.0,141.6,138.7,138.5,136.8,135.8,130.4,130.1,129.2,129.0,128.3,127 .91,127.86,127.8,127.51,127.46,125.7,125.5,125.0,114.2,108.9,7 2.6,72.5,25.0,24.8,24.0,14.54,14.49,13.2ppm; HRMS-ESI(m / z):[M+H] + calcd forC 35 H 34 N3P:527.2490; found:527.2568; [α] D 25 = -220.4 (c = 1.0, CHCl3).

[0161] The data obtained from this example of compound 6k were as follows: 65.4 mg white solid, melting point 87.4-89.2 °C, and yield 26%. 1H NMR(400MHz,Chloroform-d)δ8.21(d,J=4.9Hz,1H),7.44-7.28(m,6H),7.22(t, J=6.2Hz,3H),7.14(d,J=6.5Hz,2H),7.09(d,J=7.3Hz,3H),6.91(d,J=7.0Hz,2H ),6.84(d,J=9.3Hz,1H),6.68-6.65(m,1H),6.40(s,1H),6.30(d,J=8.4Hz,1H), 6.24-6.09(m,1H),4.82(d,J=9.1Hz,1H),4.75(d,J=9.5Hz,1H),2.65(s,3H)ppm; 13 C NMR (101MHz, Chloroform-d) δ158.2,158.1,148.4,138.2,137.0,130.9,129.2,128.5,128.1,127.9,127.8,117.4,117.2,114.7,109.1,71.3ppm; 19 F NMR(376MHz,Chloroform-d)δ-119.7ppm; HRMS-ESI(m / z):[M+H] + calcd for C 32 H 28 N3PF:504.2005; found:504.2005; [α] D 25 = -146.4 (c = 1.0, CHCl3).

[0162] The data obtained from the compound of formula 6l in this embodiment were as follows: 94.6 mg white solid, melting point 164.5-167.2 °C, and yield 38%. 1 H NMR(400MHz,Chloroform-d)δ8.04(s,1H),7.41(s,2H),7.27(s,3H),7.20-6.96(m,10H),6.91(d,J=3.5Hz ,2H),6.79(t,J=7.0Hz,1H),6.68(s,1H),6.23(d,J=8.5Hz,2H),4.81(s,2H),2.67(s,3H),2.09(s,3H)ppm; 13C NMR(101MHz,Chloroform-d)δ156.2,156.0,148.1,138.4,137.6,137.6,130.8,130.7,130.5,128.8,128.4 ,128.2,127.9,127.7,127.6,127.5,125.5,123.3,108.5,74.4,71.6,71.5,17.3ppm; HRMS-ESI(m / z):[M+H] + calcd for C 33 H 31 N3P:499.5978; found:500.2256; [α] D 25 = -184.8 (c = 1.0, CHCl3).

[0163] The data obtained from this example of compound 6m were as follows: 72.0 mg white solid, melting point 223.4-226.2 °C, and yield 28%. 1 H NMR(400MHz,Chloroform-d)δ8.04(d,J=5.8Hz,1H),7.42-7.28(m,6H),7.23-7.19(m,4H),7.18-7.11(m,4H),7.10-7.03( m,4H),6.94-6.81(m,4H),6.28-6.26(m,2H),5.81(d,J=2.2Hz,1H),4.85-4.71(m,2H),3.50(s,3H),2.75-2.61(m,3H)ppm; 13 C NMR(101MHz,Chloroform-d)δ166.6,166.5,159.9,159.7,149.1,138.4,137.1,130.9,130.8,130.6,128.9,128.4,128.0,12 7.83,127.76,127.7,127.6,125.5,125.3,123.4,102.5,94.0,74.4,71.8,71,7,54.7,19.8,19.7ppm; HRMS-ESI(m / z):[M+H] + calcd forC 33 H 30 N3PO:515.2126; found:515.2205; [α] D 25 = -202.4 (c = 1.0, CHCl3).

[0164] The data obtained from this example of the compound of formula 6n were as follows: 69.1 mg white solid, melting point 97.8-99.2 °C, and yield 25%. 1 H NMR (400MHz, Chloroform-d) δ8.36 (d, J = 5.2 Hz, 1H), 7.37-7.34 (m, 5H), 7.25-7.21 (m, 4H), 7.16 (s, 3H), 7.11-7.06 (m, 3H), 6.91 (d, J = 7. 6Hz,2H),6.87(d,J=5.6Hz,2H),6.75(s,1H),6.53(s,1H),6.33(s,1H),4.89(d,J=13.2Hz,1H),4.82(d,J=13.2Hz,1H),2.68(s,3H)ppm; 13 C NMR(101MHz,Chloroform-d)δ158.9,158.7,149.5,137.5,131.1,130.8,130.6,129.3,128.8,12 8.5,128.2,128.0,127.9,125.8,124.3,123.8,121.6,110.0,104.9,74.5,71.8,19.7,11.6ppm; 19 F NMR(376MHz,Chloroform-d)δ-65.11ppm; HRMS-ESI(m / z):[M+H] + calcd for C 33 H 28 N3PF3:554.1973; found:554.1973; [α] D 25 = -179.0 (c = 1.0, CHCl3).

[0165] The data obtained from this example of compound 6o were as follows: 56.5 mg white solid, melting point 117.3-120.9 °C, and yield 22%. 1 H NMR(400MHz,Chloroform-d)δ8.04(s,1H),7.41(s,2H),7.27(s,3H),7.21-6.96(m,10H),6.91(d,J=3.5Hz ,2H),6.79(t,J=7.0Hz,1H),6.68(s,1H),6.23(d,J=8.5Hz,2H),4.81(s,2H),2.67(s,3H),2.09(s,3H)ppm; 13C NMR(101MHz,Chloroform-d)δ158.2,158.1,155.5,148.2,138.4,136.8,134.6,133.0,130.9,130.8,128.9,128.5,128.3 ,127.9,127.7,127.6,126.3,123.6,121.0,115.8,114.4,110.8,109.0,74.8,71.4,55.0,34.6ppm; HRMS-ESI(m / z):[M+H] + calcd for C 33 H 31 N3PO:515.5968; found:516.2205; [α] D 25 = -298.6 (c = 1.0, CHCl3).

[0166] The data obtained from this example of the 6p compound were as follows: 64.7 mg white solid, melting point 219.4-221.9 °C, and yield 26%. 1 H NMR(400MHz,Chloroform-d)δ8.09(d,J=5.2Hz,1H),7.46-7.29(m,5H),7.24-7.04(m,10H),6.92-6.8 2(m,3H),6.72(s,1H),6.53(d,J=5.2Hz,1H),6.16(s,1H),4.81(s,2H),2.67(s,3H),2.08(s,3H)ppm; 13 C NMR(101MHz,Chloroform-d)δ158.4,158.3,147.91,147.88,138.5,137.2,130.8,130.6,128.8,128.5,128.3,12 8.0,127.8,127.64,127.59,125.5,123.4,116.0,109.7,74.4,71.5,21.3,19.8,19.7ppm; HRMS-ESI(m / z):[M+H] + calcd for C 33 H 30 N3P:499.2177; found:499.2177; [α] D 25 = -192.6 (c = 1.0, CHCl3).

[0167] Example 5-1

[0168] In this embodiment, the preparation steps of compound (S,S)-7a are as follows, and the reaction route is shown below.

[0169]

[0170] In a glove box, the compound of formula 5a (182.5 mg, 0.5 mmol, 1.0 equivalence) prepared in Example 3 was added to a 25 mL Shrek tube. 5 mL of diethyl ether was added at 0°C, followed by the dropwise addition of triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalence) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 equivalence). After the addition was complete, the mixture was heated to 25°C and reacted for 12 hours. The mixture was then cooled to room temperature, the solvent was removed, and the residue was recrystallized to give the ligand of formula 7a.

[0171] The data obtained from the compound of formula 7a in this example were as follows: 43.2 mg of yellow solid, melting point of 88.2-92.5 °C, and yield of 21%. 1 H NMR (400MHz, Chloroform-d) δ8.29-8.27(m,1H),7.40-7.36(m,1H),7.36-7.34(m,1H),7.34-7.30(m,4H),7.26-7.21(m,3H),7.19(d,J=7. 2Hz,2H),7.17-7.12(m,4H),7.04(t,J=7.3Hz,1H),6.83-6.80(m,1H),6.31-6.28(m,1H),5.58(d,J=8.9Hz,1H),5.09(d,J=8.9Hz,1H)ppm; 13 C NMR(101MHz,Chloroform-d)δ153.5,148.2,138.4,138.0,136.8,135.7,129.6,128.9,128.7, 128.5,128.4,127.9,127.5,125.4,124.6,117.0,107.8,72.8,72.1ppm; HRMS-ESI(m / z):[M+H] + calcd for C 25 H 21 N3OS:412.1483; found:412.1487; [α] D 25 = -49.2 (c = 1.0, CHCl3).

[0172] Example 5-2

[0173] In a glove box, the compound of formula 5b prepared in Example 3 (189.6 mg, 0.5 mmol, 1.0 equivalence) was added to a 25 mL Shrek tube. 5 mL of diethyl ether was added at 0°C, followed by the dropwise addition of triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalence) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 equivalence). After the addition was complete, the mixture was heated to 25°C and reacted for 12 hours. The mixture was then cooled to room temperature, the solvent was removed, and the residue was recrystallized to give the ligand of formula 7b.

[0174] Example 5-3

[0175] In a glove box, the compound of formula 5c prepared in Example 3 (196.6 mg, 0.5 mmol, 1.0 equivalence) was added to a 25 mL Shrek tube. 5 mL of diethyl ether was added at 0°C, followed by the dropwise addition of triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalence) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 equivalence). After the addition was complete, the mixture was heated to 25°C and reacted for 12 hours. The mixture was then cooled to room temperature, the solvent was removed, and the residue was recrystallized to give the ligand of formula 7c.

[0176] Example 5-4

[0177] In a glove box, the 5d compound prepared in Example 3 (220.6 mg, 0.5 mmol, 1.0 equivalence) was added to a 25 mL Shrek tube. 5 mL of diethyl ether was added at 0°C, followed by the dropwise addition of triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalence) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 equivalence). After the addition was complete, the mixture was heated to 25°C and reacted for 12 hours. The mixture was then cooled to room temperature, the solvent was removed, and the residue was recrystallized to give the ligand 7d compound.

[0178] Example 5-5

[0179] In a glove box, the compound of formula 5e prepared in Example 3 (196.6 mg, 0.5 mmol, 1.0 equivalence) was added to a 25 mL Shrek tube. 5 mL of diethyl ether was added at 0°C, followed by the dropwise addition of triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalence) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 equivalence). After the addition was complete, the mixture was heated to 25°C and reacted for 12 hours. The mixture was then cooled to room temperature, the solvent was removed, and the residue was recrystallized to give the ligand of formula 7e.

[0180] Examples 5-6

[0181] In a glove box, the compound of formula 5f (196.6 mg, 0.5 mmol, 1.0 equivalence) prepared in Example 3 was added to a 25 mL Shrek tube. 5 mL of diethyl ether was added at 0°C, followed by the dropwise addition of triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalence) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 equivalence). After the addition was complete, the mixture was heated to 25°C and reacted for 12 hours. The mixture was then cooled to room temperature, the solvent was removed, and the residue was recrystallized to give the ligand of formula 7f.

[0182] Examples 5-7

[0183] In a glove box, 5 g of the compound (196.6 mg, 0.5 mmol, 1.0 equivalence) prepared in Example 3 was added to a 25 mL Shrek tube. 5 mL of diethyl ether was added at 0°C, followed by the dropwise addition of triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalence) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 equivalence). After the addition was complete, the mixture was heated to 25°C and reacted for 12 hours. The mixture was then cooled to room temperature, the solvent was removed, and the residue was recrystallized to give 7 g of the compound of the ligand formula.

[0184] Examples 5-8

[0185] In a glove box, the compound of formula 5h prepared in Example 3 (203.6 mg, 0.5 mmol, 1.0 equivalence) was added to a 25 mL Shrek tube. 5 mL of diethyl ether was added at 0°C, followed by the dropwise addition of triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalence) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 equivalence). After the addition was complete, the mixture was heated to 25°C and reacted for 12 hours. The mixture was then cooled to room temperature, the solvent was removed, and the residue was recrystallized to give the ligand of formula 7h.

[0186] Examples 5-9

[0187] In a glove box, the compound of formula 5i (296.6 mg, 0.5 mmol, 1.0 equivalence) prepared in Example 3 was added to a 25 mL Shrek tube. 5 mL of diethyl ether was added at 0°C, followed by the dropwise addition of triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalence) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 equivalence). After the addition was complete, the mixture was heated to 25°C and reacted for 12 hours. The mixture was then cooled to room temperature, the solvent was removed, and the residue was recrystallized to give the ligand of formula 7i.

[0188] Examples 5-10

[0189] In a glove box, the compound of formula 5j (210.6 mg, 0.5 mmol, 1.0 equivalence) prepared in Example 3 was added to a 25 mL Shrek tube. 5 mL of diethyl ether was added at 0°C, followed by the dropwise addition of triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalence) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 equivalence). After the addition was complete, the mixture was heated to 25°C and reacted for 12 hours. The mixture was then cooled to room temperature, the solvent was removed, and the residue was recrystallized to give the compound of ligand formula 7j.

[0190] Examples 5-11

[0191] In a glove box, the compound of formula 5k (198.6 mg, 0.5 mmol, 1.0 equivalence) prepared in Example 3 was added to a 25 mL Shrek tube. 5 mL of diethyl ether was added at 0°C, followed by the dropwise addition of triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalence) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 equivalence). After the addition was complete, the mixture was heated to 25°C and reacted for 12 hours. The mixture was then cooled to room temperature, the solvent was removed, and the residue was recrystallized to give the ligand of formula 7k.

[0192] Examples 5-12

[0193] In a glove box, the compound of formula 5o prepared in Example 3 (196.6 mg, 0.5 mmol, 1.0 equivalence) was added to a 25 mL Shrek tube. 5 mL of diethyl ether was added at 0°C, followed by the dropwise addition of triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalence) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 equivalence). After the addition was complete, the mixture was heated to 25°C and reacted for 12 hours. The mixture was then cooled to room temperature, the solvent was removed, and the residue was recrystallized to give the compound of ligand formula 7l.

[0194] Examples 5-13

[0195] In a glove box, the compound of formula 5m prepared in Example 3 (204.6 mg, 0.5 mmol, 1.0 equivalence) was added to a 25 mL Shrek tube. 5 mL of diethyl ether was added at 0°C, followed by the dropwise addition of triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalence) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 equivalence). After the addition was complete, the mixture was heated to 25°C and reacted for 12 hours. The mixture was then cooled to room temperature, the solvent was removed, and the residue was recrystallized to give the compound of formula 7m.

[0196] Examples 5-14

[0197] In a glove box, the compound of formula 5n prepared in Example 3 (223.6 mg, 0.5 mmol, 1.0 equivalence) was added to a 25 mL Shrek tube. 5 mL of diethyl ether was added at 0°C, followed by the dropwise addition of triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalence) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 equivalence). After the addition was complete, the mixture was heated to 25°C and reacted for 12 hours. The mixture was then cooled to room temperature, the solvent was removed, and the residue was recrystallized to give the compound of formula 7n.

[0198] Examples 5-15

[0199] In a glove box, the compound of formula 5q (196.6 mg, 0.5 mmol, 1.0 equivalence) prepared in Example 3 was added to a 25 mL Shrek tube. 5 mL of diethyl ether was added at 0°C, followed by the dropwise addition of triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalence) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 equivalence). After the addition was complete, the mixture was heated to 25°C and reacted for 12 hours. The mixture was then cooled to room temperature, the solvent was removed, and the residue was recrystallized to give the compound of formula 7o.

[0200]

[0201] The data obtained from the compound of formula 7b in this embodiment were as follows: 189.1 mg white solid, melting point 103.6-104.3 °C, and yield 89%. 1 H NMR(400MHz,Chloroform-d)δ8.27(d,J=6.0Hz,1H),7.41-7.36(m,5H),7.29(s,5H),7.20-7.19(m,3H),4.15-7.10(m,4H),7 .02-7.00(m,2H),6.83-6.80(m,1H),6.33(d,J=8.4Hz,1H),5.63(d,J=13.2Hz,1H),5.09(d,J=13.6Hz,1H),2.47(s,3H)ppm; 13 C NMR(101MHz,Chloroform-d)δ153.8,148.4,138.1,137.0,136.0,135.3,131.1,129.0,128.7,128 .4,128.3,127.5,126.9,126.7,126.6,117.0,108.2,73.8,71.9,18.8ppm; HRMS-ESI(m / z):[M+H] + calcd for C 26 H 24N3OS:426.1640; found:426.1640; [α] D 25 = -81.6 (c = 1.0, CHCl3).

[0202] The data obtained from the compound of formula 7c in this embodiment were as follows: 90.0 mg white solid, melting point 112.1-113.7 °C, and yield 41%. 1 H NMR(400MHz,Chloroform-d)δ8.28-8.26(m,1H),7.40-7.36(m,1H),7.29(d,J=1.3Hz,5H),7.20-7.16(m,5H),7.14-7.12(m,2H),7.09-7.00 (m,2H),6.82-6.79(m,1H),6.34(d,J=8.4Hz,1H),5.62(d,J=9.3Hz,1H),5.14(d,J=9.3Hz,1H),2.91-2.89(m,2H),1.25(t,J=7.6Hz,3H)ppm; 13 C NMR(101MHz,Chloroform-d)δ153.6,148.3,141.9,137.9,136.8,135.0,128.9,128.8,128.6,128.5,12 8.4,128.2,127.3,127.1,126.6,126.3,116.8,108.0,74.0,71.6,23.5,14.9ppm; HRMS-ESI(m / z):[M+H] + calcd forC 27 H 26 N3OS:440.1797; found:440.1793; [α] D 25 = -95.6 (c = 1.0, CHCl3).

[0203] The data obtained from the 7d compound in this example were as follows: 163.1 mg of yellow solid, melting point of 94.7-96.4 °C, and yield of 67%. 1H NMR(400MHz,Chloroform-d)δ8.22-8.20(m,1H),7.41-7.37(m,3H),7.36-7.27(m,4H),7.26-7.15(m,10H), 7.14-7.10(m,2H),6.87-6.84(m,2H),6.78-6.75(m,1H),6.25(d,J=8.35Hz,1H),4.96(d,J=9.03Hz,1H)ppm; 13 C NMR(101MHz,Chloroform-d)δ153.5,148.1,139.7,137.7,137.0,135.1,131.2,129.8,128.9,128.7,128.6,128.5, 128.3,128.2,128.1,127.9,127.7,127.2,127.0,126.9,126.6,116.8,108.2,74.9,71.7ppm; HRMS-ESI(m / z):[M+H] + calcd for C 31 H 26 N3OS:488.1797; found:488.1805; [α] D 25 = -71.8 (c = 1.0, CHCl3).

[0204] The data obtained from the compound of formula 7e in this embodiment were as follows: 87.8 mg of yellow solid, melting point of 106.4-108.1 °C, and yield of 40%. 1 H NMR(400MHz,Chloroform-d)δ8.27-8.26(m,1H),7.40-7.35(m,1H),7.29(s,5H),7.22-7.18(m,3H),7.14-7.10(m,2H),7.01(d,J=8.1Hz ,1H),6.94(s,1H),6.83-6.78(m,2H),6.33(d,J=8.4Hz,1H),5.60(d,J=9.3Hz,1H),5.09(d,J=9.3Hz,1H),2.43(s,3H),2.16(s,3H)ppm; 13C NMR(101MHz,Chloroform-d)δ153.7,148.2,137.9,136.9,136.4,135.5,135.2,133.0,131.6,128.8, 128.5,128.2,127.33,127.28,126.2,116.8,108.0,73.7,71.8,20.8,18.5ppm; HRMS-ESI(m / z):[M+H] + calcd for C 27 H 26 N3OS:440.1797; found:440.1805; [α] D 25 = -78.4 (c = 1.0, CHCl3).

[0205] The data obtained from the compound of formula 7f in this embodiment were as follows: 116.3 mg white solid, melting point 110.4-112.1 °C, and yield 53%. 1 H NMR(400MHz,Chloroform-d)δ8.27(d,J=6.0Hz,1H),7.41-7.36(m,1H),7.30(s,5H),7.21-7.20(m,3H),7.12-7.10(m,2H),7.02(d,J=8.0H z,1H),6.92(s,1H),6.82-6.80(m,2H),6.34(d,J=8.4Hz,1H),5.62(d,J=13.2Hz,1H),5.09(d,J=13.2Hz,1H),2.42(s,3H),2.13(s,3H)ppm; 13 C NMR(101MHz,Chloroform-d)δ153.8,148.3,137.9,137.1,136.1,135.6,135.4,132.7,130.7,128.8 ,128.6,128.2,127.7,127.4,127.0,116.9,108.1,73.7,71.9,21.0,18.2ppm; HRMS-ESI(m / z):[M+H] + calcd forC 27 H 26 N3OS:440.1796; found:440.1797; [α] D 25 = -65.8 (c = 1.0, CHCl3).

[0206] The data obtained from this example for the 7g compound were as follows: 79.0 mg of yellow solid, melting point of 102.6-105.4℃, and yield of 36%. 1 H NMR(400MHz,Chloroform-d)δ8.26-8.26(m,1H),7.41-7.37(m,1H),7.36-7.24(m,5H),7.26-7.10(m,3H),7.10-7.08(m,2H),7 .02-6.87(m,2H),6.86-6.74(m,2H),6.41-6.39(m,1H),5.78(d,J=8.9Hz,1H),5.17(d,J=8.9Hz,1H),2.41(d,J=3.8Hz,6H)ppm; 13 C NMR(101MHz,Chloroform-d)δ153.9,148.2,138.6,138.0,137.9,137.4,135.0,134.1,129.7,128.8,128 .7,128.41,128.38,128.1,127.6,127.1,116.7,108.1,75.0,72.9,20.6,19.6ppm; HRMS-ESI(m / z):[M+H] + calcd for C 27 H 26 N3OS:440.1797; found:440.1802; [α] D 25 = -105.0 (c = 1.0, CHCl3).

[0207] The data obtained from the 7h compound in this example were as follows: 122.3 mg of yellow solid, melting point 97.5-99.3 °C, and yield 54%. 1 H NMR(400MHz,Chloroform-d)δ8.38-8.36(m,1H),7.45-7.38(m,3H),7.30-7.28(m,3H),7.25-7.22(m,3H),7.21-7.18(m,2H),6.90-6.83 (m,2H),6.71-6.66(m,1H),6.52-6.50(m,1H),5.79(d,J=8.69Hz,1H),4.77(d,J=8.68Hz,1H),2.49(s,3H),2.19(s,3H),1.93(s,3H)ppm; 13C NMR(101MHz,Chloroform-d)δ154.3,148.7,140.6,138.1,138.0,137.9,137.8,137.4,133.7,129.7,129.6,12 9.5,128.9,128.5,128.4,127.9,126.3,117.9,113.6,80.9,69.4,20.9,19.4,19.1ppm; HRMS-ESI(m / z):[M+H] + calcd forC 28 H 28 N3OS:454.1953; found:454.1945; [α] D 25 = +60.0 (c = 1.0, CHCl3).

[0208] The data obtained from the compound of formula 7i in this embodiment were as follows: 233.2 mg white solid, melting point 116.9-121.3 °C, and yield 73%. 1 H NMR(400MHz,Chloroform-d)δ8.04-8.00(m,1H),7.58-7.52(m,3H),7.49-7.45(m,2H),7.40-7.34(m,1H),7.30-7.24(m,3H),7.23-7.0 4(m,14H),7.00-6.93(m,3H),6.63-6.57(m,1H),6.50-6.44(m,2H),6.19-6.14(m,1H),4.96(d,J=9.1Hz,1H),4.80(d,J=9.1Hz,1H)ppm; 13 C NMR(101MHz,Chloroform-d)δ153.4,147.5,141.0,140.4,140.2,139.2,138.5,137.2,136.9,134.1,132.1,130.3,130.1, 129.1,128.5,128.4,128.2,127.9,127.6,127.5,127.3,127.2,126.6,116.3,107.4,73.3,72.6ppm; HRMS-ESI(m / z):[M+H] + calcd for C 43 H 34 N3OS:640.2422; found:640.2415; [α] D 25 = -135.6 (c = 1.0, CHCl3).

[0209] The data obtained from the compound of formula 7j in this embodiment were as follows: 142.1 mg white solid, melting point 157.5-160.1 °C, and yield 61%. 1 H NMR(400MHz,Chloroform-d)δ8.37(d,J=5.0Hz,1H),7.42(t,J=6.9Hz,3H),7.35-7.17(m,10H),7.04-6.83(m,2H),6.55(d,J=8.2Hz,1H),5.83(d ,J=8.4Hz,1H),4.77(d,J=8.4Hz,1H),2.93-2.87(m,2H),2.68-2.63(m, 1H),2.33-2.28(m,1H),1.32(t,J=7.4Hz,3H),0.70(t,J=7.4Hz,3H)ppm; 13 C NMR(101MHz,Chloroform-d)δ154.3,148.7,146.8,144.3,138.1,137.8,137.1,135.0,129.5,128.9,128.7,1 28.5,127.9,127.0,126.8,126.2,117.8,113.6,82.3,69.3,24.3,24.3,15.8,15.3ppm; HRMS-ESI(m / z):[M+H] + calcd for C 29 H 29 N3OS:467.2031; found:467.2110; [α] D 25 = +82.6 (c = 1.0, CHCl3).

[0210] The data obtained from this example of compound 7k were as follows: 53.2 mg white solid, melting point 164.8-166.5 °C, and yield 24%. 1 H NMR(400MHz,Chloroform-d)δ8.36-8.34(m,1H),7.51-7.49(m,2H),7.43-7.39(m,1H),7.36-7.26(m,8H),7.14-7.11(m,1H) ,6.87-6.83(m,2H),6.74-6.71(m,1H),6.45(d,J=8.4Hz,1H),5.59(d,J=6.1Hz,1H),4.85(d,J=6.1Hz,1H),2.25(s,3H)ppm; 13C NMR (101MHz, Chloroform-d) δ148.7,138.8,138.1,132.6,129.3,128.9,128.7,128.4,126.4,117.7,113.5,112.2,81.6,70.0,18.7ppm; 19 F NMR (376MHz, Chloroform-d) δ-113.47 (d, J = 7.3Hz) ppm; HRMS-ESI (m / z): [M+H] + calcd for C 26 H 23 N3OSF:444.1546; found:444.1546; [α] D 25 = -60.4 (c = 1.0, CHCl3).

[0211] The data obtained from the compound of formula 7l in this embodiment were as follows: 210.2 mg of yellow solid, melting point of 108.2-112.6 °C, and yield of 96%. 1 H NMR(400MHz,Chloroform-d)δ8.02(s,1H),7.33-7.31(m,2H),7.26-7.15(m,4H),7.11(s,5H),7.06-7.03(m,2H),6 .93-6.87(m,2H),6.28(d,J=8.4Hz,1H),5.63(d,J=9.3Hz,1H),5.15(d,J=9.3Hz,1H),2.42(s,3H),2.04(s,3H)ppm; 13 C NMR(101MHz,Chloroform-d)δ151.2,147.7,138.2,136.8,135.7,135.4,134.9,130.5,128.4,128.2,128.2 ,127.9,127.8,127.1,126.3,126.1,126.0,125.7,107.5,73.3,71.5,18.2,17.0ppm; HRMS-ESI(m / z):[M+H] + calcd for C 27 H 26 N3OS:439.5770; found:440.1797; [α] D 25 = -75.6 (c = 1.0, CHCl3).

[0212] The data obtained from the compound of formula 7m in this embodiment were as follows: 86.5 mg white solid, melting point 86.6-88.5 °C, and yield 38%. 1 H NMR(400MHz,Chloroform-d)δ8.09(d,J=5.9Hz,1H),7.32-7.28(m,5H),7.20-7.15(m,3H),7.14-7.10(m,4H),7.01-6.99(m ,2H),6.38-6.36(m,1H),5.80(d,J=2.2Hz,1H),5.64(d,J=9.3Hz,1H),5.06(d,J=9.3Hz,1H),3.55(s,3H),2.48(s,3H)ppm; 13 C NMR(101MHz,Chloroform-d)δ149.5,136.0,131.1,129.0,128.7,128.5,128.3,127.5,126.9, 126.7,126.5,104.3,93.7,77.5,77.2,76.8,73.8,72.0,55.1,18.8ppm; HRMS-ESI(m / z):[M+H] + calcd for C 27 H 26 N3O2S:456.1745; found:456.1746; [α] D 25 = -79.0 (c = 1.0, CHCl3).

[0213] The data obtained from the compound of formula 7n in this embodiment were as follows: 76.4 mg white solid, melting point 67.4-72.1 °C, and yield 31%. 1 H NMR(400MHz,Chloroform-d)δ8.45-8.28(m,1H),7.35-7.28(m,5H),7.22-7.11(m,7H),7.0 4-6.97(m,3H),6.55(s,1H),5.69(d,J=9.2Hz,1H),5.15(d,J=9.2Hz,1H),2.47(s,3H)ppm; 13C NMR(101MHz,Chloroform-d)δ154.4,149.4,140.0(q,J=33.8Hz),136.0,135.9,135.4,134.7,131.0,129.0,128.7,1 28.6,128.6,128.1,127.3,127.0,126.6,123.8,121.0,112.3(q,J=3.5Hz),103.9(q,J=4.0Hz),73.8,71.9,18.5ppm; 19 F NMR(376MHz,Chloroform-d)δ-65.1ppm; HRMS-ESI(m / z):[M+H] + calcd forC 27 H 23 N3OSF3:494.1514; found:494.1510; [α] D 25 = -76.6 (c = 1.0, CHCl3).

[0214] The data obtained from this example of compound 7o were as follows: 98.8 mg white solid, melting point 75.4-77.2 °C, and yield 45%. 1 H NMR(400MHz,Chloroform-d)δ7.33-7.23(m,6H),7.19-7.17(m,3H),7.12-7.09(m,4H),7.04-6.96(m,2H),6.64(d ,J=7.4Hz,1H),6.11(d,J=8.2Hz,1H),5.63(d,J=9.3Hz,1H),5.07(d,J=9.3Hz,1H),2.47(s,3H),2.42(s,3H)ppm; 13 C NMR(101MHz,Chloroform-d)δ138.2,137.3,136.1,135.4,131.0,128.9,128.7,128.3,127.6,126. 8,126.7.126.6,116.5,104.8,77.5,77.2,76.9,73.8,71.9,24.3,18.9ppm; HRMS-ESI(m / z):[M+H] + calcd for C 27 H 26 N3OS:440.1796; found:440.1797; [α] D 25 = -62.8 (c = 1.0, CHCl3).

[0215] Example 6

[0216] Experimental Method: In a glove box, the prepared ligand 6c (10 mg, 0.1 mmol) and [Pd(allyl)Cl]₂ (3.7 mg, 0.05 mmol) were added to a 25 mL Shrek tube. The Shrek tube was then removed from the glove box, and 0.5 mL of tetrahydrofuran was added under nitrogen atmosphere, and the mixture was stirred at room temperature for 1 hour. Then, 2-cyclohexenol acetate (28 mg, 0.2 mmol), benzaldehyde (42 mg, 0.4 mmol), hydrazine monohydrate (40%, 0.52 mmol), and lithium tert-butoxide (32 mg, 0.4 mmol) were added to the mixture, and the mixture was reacted at 65°C for 16 hours to obtain a pale yellow oily liquid (13.5 mg, 40% yield).

[0217]

[0218] 1 H NMR(400MHz,Chloroform-d)δ7.35-7.32(m,2H),7.26-7.23(m,3H),5.77-5.73(m,1H),5.65-5.62(m,1H),2.70-2.68(m ,1H),2.62-2.58(m,1H),2.44-2.43(m,1H),2.05-2.04(m,2H),1.74-1.81(m,2H),1.53-1.61(m,1H),1.29-1.36(m,1H); 13 C NMR (101MHz, Chloroform-d) δ140.9,131.4,129.2,128.2,127.4,125.8,42.8,37.2,29.0,25.4,21.3ppm.

[0219]

[0220] In summary, the preparation method of the present invention is simple and can prepare chiral NP ligands and NS ligands. These ligands can be used as catalysts for asymmetric catalytic reactions, and have economic practicality and promising industrial application prospects.

[0221] In addition, the inventors of this case also conducted experiments with other raw materials and conditions listed in this specification, referring to Examples 1-5, and achieved the same results. Chiral NP ligands and NS ligands can be prepared, which can be used as catalysts for asymmetric catalytic reactions and have broad application prospects.

[0222] The above embodiments are merely exemplary and do not constitute any limitation on the scope of the present invention. Those skilled in the art should understand that modifications or substitutions can be made to the details and form of the technical solutions of the present invention without departing from the spirit and scope thereof, but all such modifications and substitutions fall within the protection scope of the present invention.

Claims

1. A chiral nitrogen phosphine ligand of the 1,2-ethanediamine backbone, characterized in that, The structural formula of the nitrogen phosphine ligand is shown as formula (I), ； wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 are each independently selected from the group consisting of hydrogen, halogen, C1-C 30 alkyl, phenyl.

2. A chiral nitrogen phosphine ligand of the 1,2-ethanediamine backbone, characterized in that, The nitrogen phosphine ligand of the chiral 1,2-ethanediamine skeleton is selected from any one of the structures shown in formulas (6a)-(6p): 。 3. A process for the preparation of chiral nitrogen phosphine ligands of the 1,2-ethanediamine backbone according to claim 1, characterized in that, The compound shown in formula (III), a phosphorus reagent, a base and an organic solvent are uniformly mixed to react to obtain the nitrogen phosphine ligand of the chiral 1,2-ethanediamine skeleton having the structure shown in formula (I); ； wherein, in formula (I) and formula (III), wherein, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 are each independently selected from the group consisting of hydrogen, halogen, C1-C 30 alkyl, phenyl, the chemical formula of the phosphorus reagent is PhPCl2; the molar ratio of the phosphorus reagent to the compound shown in formula (III) is 1:1-2:

1.

4. The method of claim 3, wherein: The base is selected from any one or a combination of two or more of sodium tert-butoxide, lithium tert-butoxide, potassium tert-butoxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, triethylamine and 1,8-diazabicyclo[5.4.0]undec-7-ene.

5. The method of claim 3, wherein: The organic solvent is selected from any one or a combination of two or more of diethyl ether, isopropyl ether, tetrahydrofuran, ethylene glycol dimethyl ether, 1,4-dioxane, N,N-dimethylformamide, N-methylpyrrolidone, acetonitrile, ethyl acetate, methanol, toluene, benzene and dichloromethane.

6. The method of claim 3, wherein: The temperature of the reaction is 0-150 ℃, and the time of the reaction is 1-48 h.

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