N-P ligand and N-S ligand of chiral 1, 2-ethylenediamine skeleton and preparation method thereof

Abstract

The invention discloses a design and preparation method of an N-P ligand and an N-S ligand of a chiral 1, 2-ethylenediamine skeleton, the structural formula of the N-P ligand is as shown in a formula (I), the structural formula of the N-S ligand is as shown in a formula (II): # imgabs0, and R1, R2, R3, R4, R5, R6, R7, R8 and R9 are at least independently selected from hydrogen, halogen, substituted or unsubstituted C1-C30 alkyl, alkoxy or aryl respectively; r10 is at least independently selected from C1-C30 alkyl or aryl respectively; and Ar1 and Ar2 are respectively at least independently selected from substituted or unsubstituted C6-C30 aryl groups. The preparation method is simple, chiral N-P ligands and N-S ligands can be prepared, and the ligands can be used as catalysts for asymmetric reactions and have economic practicability and industrial application prospects.

Description

Technical Field

[0001] The present invention relates to N-P ligands and N-S ligands with a chiral 1,2-ethylenediamine backbone and a preparation method, belonging to the technical field of organic chemistry. Technical Background

[0002] Over the past two decades, asymmetric catalysis has become increasingly important as a research focus in organic synthesis, particularly 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, and their performance directly affects the efficiency and selectivity of the catalytic reaction. Therefore, the design and development of new chiral ligands has become a key link in the field of asymmetric catalysis that urgently needs breakthroughs. The 1,2-ethylenediamine skeleton with a C2 symmetry axis has a wide range of applications in asymmetric catalysis (Angew. Chem., Int. Ed. 1998, 37, 2580-2627). It can not only serve as a chiral auxiliary group and a precursor of chiral catalysts, but also as a building block for chiral ligands, providing a wealth of possibilities for the synthesis of chiral compounds. Furthermore, phosphorus and nitrogen atoms, due to their unique coordination properties and the variability of their substituents, can flexibly modulate the stereo- and electronic effects of ligands, thereby improving catalytic performance (Chem. Soc. Rev. 2014, 43, 819-833; Chem. Rev. 2018, 118, 9344-9411). These ligands not only demonstrate excellent catalytic performance but also provide new insights and approaches for the development of asymmetric catalysis. Furthermore, chiral heteroatom ligands have also achieved remarkable research results in chemistry. Among them, chiral NS ligands, with their unique chiral structures and properties, have shown broad application prospects in asymmetric synthesis and catalytic reactions (Chem. Rev. 2017, 117, 4147-4181). Therefore, the design and development of novel chiral ligands by combining the 1,2-ethylenediamine backbone with a C2 symmetry axis with phosphorus or sulfur atoms is particularly important. This type of new ligand can precisely regulate the electrical properties and steric hindrance of the ligand by adjusting the side chain connecting the two nitrogen atoms, thereby achieving precise control of the catalytic reaction performance. In particular, the sulfur atom has a specific spatial orientation and can form a stable coordination bond with the metal, thereby constructing a unique catalytic cavity, providing an ideal reaction environment for asymmetric catalytic reactions. It is worth mentioning that there are currently no reports on the synthesis and application of the above two types of chiral ligands. Therefore, this field urgently needs to develop such new chiral ligands to fill the gap in this field. Through a simple three-step reaction, we successfully prepared optically active or racemic NP ligands and NS ligands with a C2 symmetry axis, and successfully applied them in asymmetric synthesis, injecting new vitality into the development of the field of asymmetric catalysis. Summary of the Invention

[0003] The main object of the present invention is to provide a method for designing and preparing N-P ligands and N-S ligands with a chiral 1,2-ethylenediamine backbone, so as to overcome the deficiencies of the prior art.

[0004] To achieve the aforementioned invention object, the technical solutions adopted by the present invention include:

[0005] The present invention provides N-P ligands and N-S ligands with a chiral 1,2-ethylenediamine backbone, and their structural formulas 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 are each independently selected from at least hydrogen, halogen, substituted or unsubstituted C1-C 30 alkyl, alkoxy or aryl;

[0008] R 10 are each independently selected from at least C1-C 30 alkyl or aryl;

[0009] Ar 1 and Ar 2 are each independently selected from at least substituted or unsubstituted C6-C 30 aryl.

[0010] The embodiment of the present invention also provides a preparation method for the aforementioned N-P ligands and N-S ligands with a chiral 1,2-ethylenediamine backbone, which includes:

[0011] Reacting a homogeneous mixed reaction system containing the compound shown in Formula (III), a phosphorus reagent, a sulfoxide reagent, a base and an organic solvent to obtain N-P ligands and N-S ligands with a chiral 1,2-ethylenediamine backbone having the structure shown in Formula (I) or Formula (II);

[0012]

[0013] Among them, in Formula (I) or Formula (II), R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9Each is at least independently selected from hydrogen, halogen, a substituted or unsubstituted C1-C 30 alkyl, alkoxy or aryl;

[0014] R 10 Each is at least independently selected from a C1-C 30 alkyl or aryl;

[0015] Ar 1 and Ar 2 Each is at least independently selected from a substituted or unsubstituted C6-C 30 aryl.

[0016] Use of the N-P ligand and N-S ligand of the chiral 1,2-ethylenediamine skeleton as a catalyst or in the field of synthesis of catalysts.

[0017] The catalyst is a catalyst for an asymmetric catalytic reaction.

[0018] The catalyst is a complex formed by the N-P ligand or N-S ligand of the chiral 1,2-ethylenediamine skeleton described in claim 1 and a palladium metal catalyst.

[0019] A catalyst for an asymmetric catalytic reaction, which is a complex formed by the N-P ligand or N-S ligand of the chiral 1,2-ethylenediamine skeleton 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) The present invention provides a novel N-P ligand and N-S ligand with optical activity of a chiral 1,2-ethylenediamine skeleton, which can be used as a catalyst for palladium-catalyzed asymmetric catalytic reactions;

[0022] 2) The present invention provides a simple and feasible method for preparing N-P ligands and N-S ligands with optical activity of a chiral 1,2-ethylenediamine skeleton, which can be conveniently prepared from optically pure 1,2-ethylenediamine through simple reactions, and has economic practicality and industrial application prospects. Description of the Drawings

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

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

[0025] As described above, in view of the deficiencies of the prior art, the inventors of the present case have, through extensive and in-depth research, been able to propose the technical solution of the present invention, that is, chiral N-P ligands and N-S ligands with a 1,2-ethylenediamine backbone are prepared by a simple reaction. These ligands can be used as catalysts for asymmetric catalytic reactions and have economic practicality and industrial application prospects.

[0026] The technical solution of the present invention will be described clearly and completely below. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of them. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts belong to the scope of protection of the present invention.

[0027] First, it should be noted that the interpretations of the terms described in the specification of the present invention are well-known to those skilled in the art. For example, the definitions of some of these terms are 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, which is composed of an alkyl group and an oxygen atom.

[0030] The term "aryl" refers to the general name of the monovalent groups remaining after removing one hydrogen atom from the aromatic nucleus carbon of an aromatic hydrocarbon molecule.

[0031] Unless otherwise specified, the alkyl, alkoxy, or aryl described in the present invention includes both substituted and unsubstituted parts. The possible substituents on the alkyl, alkoxy, and aryl include, but are not limited to: C1-C 10 alkyl, alkenyl, alkynyl, alkoxy, aryl, hydroxyl, halogen, amino, etc.

[0032] One aspect of the embodiments of the present invention provides a chiral N-P ligand and an N-S ligand with a 1,2-ethylenediamine backbone, and their structural formulas are shown as Formula (I) and Formula (II):

[0033]

[0034] Among them, R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 are each independently selected from at least hydrogen, halogen, substituted or unsubstituted C1-C 30 alkyl, alkoxy, or aryl;

[0035] R 10 are each at least independently selected from C1-C 30 alkyl or aryl;

[0036] Ar 1 and Ar 2 are each at least independently selected from substituted or unsubstituted C6-C 30 aryl.

[0037] Wherein said substitution is by the following substituents: C1-C 10 alkyl, alkenyl, alkynyl, alkoxy, aryl, hydroxy, halogen, amino, etc.

[0038] In some embodiments, R 10 are each at least independently selected from substituted or unsubstituted C1-C 30 alkyl or aryl, etc., but not limited thereto, wherein the number of substituents for said substitution is one or more, preferably 1-2, that is to say, said substitution is mono-substituted or di-substituted by the substituents.

[0039] Furthermore, the substituents are at least independently selected from C1-C 10 alkyl, alkenyl, alkynyl, alkoxy, aryl, hydroxy, halogen, amino, etc., but not limited thereto.

[0040] In some embodiments, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 are each at least independently selected from C1-C 10 alkyl, alkenyl, alkynyl, alkoxy, aryl, hydroxy, halogen, amino, etc., but not limited thereto, wherein the number of substituents for said substitution is more than one, preferably 1-2, that is to say, said substitution is mono-substituted or di-substituted by the substituents.

[0041] Furthermore, the substituents are at least independently selected from C1-C 10 alkyl, alkenyl, alkynyl, alkoxy, aryl, hydroxy, halogen, amino, etc., but not limited thereto.

[0042] In some embodiments, Ar 1 and Ar 2 are each at least independently selected from substituted or unsubstituted C6-C 30aryl, etc., but not limited thereto, wherein the number of substituents for the substitution is one or more, preferably 1-2, that is, the substitution is mono-substituted or di-substituted by the substituent.

[0043] Further, the substituent is at least independently selected from C1-C 10 alkyl, alkenyl, alkynyl, alkoxy, aryl, hydroxy, halogen, amino, etc., but not limited thereto.

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

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

[0046] In some embodiments, the ligand includes a structure represented by any one 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 are as defined above.

[0049] Specifically, among them, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 are each at least independently selected from hydrogen, halogen, substituted or unsubstituted C1-C 30 alkyl, alkoxy or aryl;

[0050] R 10 are each at least independently selected from C1-C 30 alkyl or aryl;

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

[0052] In another preferred example, the ligand is selected from: the structure shown in any one of the following formulas (Ia)-(IId) or the enantiomer, racemate or diastereoisomer of the structure shown in any one of the following formulas (Ia)-(IId). Among them, the racemate refers to the racemate composed of any one of the compounds shown in the formulas (Ia)-(IId) and its enantiomer.

[0053] In another more specific preferred example, the ligand includes the structure shown in any one of the following formulas (6a)-(7o) or the enantiomer, racemate or diastereoisomer of the structure shown in any one of the following formulas (6a)-(7o);

[0054]

[0055] Another aspect of the embodiments of the present invention also provides a preparation method of the N-P ligand and N-S ligand of the aforementioned chiral 1,2-ethylenediamine skeleton, which includes:

[0056] Reacting a homogeneous mixed reaction system containing the compound shown in formula (III), a phosphorus reagent, a sulfoxide reagent, a base and an organic solvent to obtain the N-P ligand and N-S ligand of the chiral 1,2-ethylenediamine skeleton 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 are as defined above.

[0059] Specifically, in formulas (I), (II) and (III), R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 are each independently selected from hydrogen, halogen, substituted or unsubstituted C1-C 10alkyl, alkenyl, alkynyl, alkoxy, aryl, hydroxyl, halogen, amino, etc.;

[0060] R 10 are each independently selected from C1-C 30 alkyl or aryl;

[0061] Ar 1 and Ar 2 are each independently selected from substituted or unsubstituted C6-C 30 aryl.

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

[0063] In some embodiments, the chemical formula of the phosphorus reagent is R 10 PCl2, wherein R 10 are each independently selected from C1-C 30 alkyl or aryl.

[0064] Furthermore, in an organic solvent and under the action of a base, the compound represented by formula (III) reacts with R 10 PCl2 or SOCl2 to directly obtain the compound represented by formula (I) or formula (II). Among them, the reaction formula of the reaction is:

[0065]

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

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

[0068] Furthermore, the base 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-diazabicyclo[5.4.0]undec-7-ene, etc., preferably triethylamine, but not limited thereto.

[0069] Furthermore, the organic solvent includes 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, cyclohexane, dichloromethane, etc., preferably toluene, but not limited thereto.

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

[0071] Through the above technical solution, the novel N-P ligands and N-S ligands with an optically active chiral 1,2-ethylenediamine skeleton provided by the present invention can be used as catalysts for transition metal-catalyzed asymmetric catalytic reactions; moreover, the present invention provides a simple and feasible method for preparing N-P ligands and N-S ligands with an optically active chiral 1,2-ethylenediamine skeleton, which can be conveniently prepared from optically pure 1,2-ethylenediamine through simple reactions, avoiding the method of obtaining chiral ligands by resolution, and has economic practicality and industrial application prospects.

[0072] To further understand the present invention, the present invention will be further elaborated below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and not to limit the scope of the present invention. Non-essential improvements and adjustments made by those skilled in the art under the core guiding ideology of the present invention still fall within the protection scope of the present invention. The experimental methods without specific conditions noted in the following embodiments are usually carried out under conventional conditions or according to the conditions recommended by the manufacturer.

[0073] The experimental materials used in the following embodiments can be obtained from conventional chemical reagent companies without special instructions.

[0074] Example 1

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

[0076]

[0077] In a glove box, (1S,2S)-1,2-diphenylethylenediamine 1a (1.7 g, 8.0 mmol, 2.0 eq), bromobenzene 2a (628.0 mg, 4.0 mmol, 1.0 eq), tris(dibenzylideneacetone)dipalladium(0) (183.1 mg, 0.2 mmol, 0.05 eq), 1,1'-binaphthalene-2,2'-bis(diphenylphosphine) (249.1 mg, 0.4 mmol, 0.1 eq), sodium tert-butoxide (538.2 mg, 5.6 mmol, 1.4 eq), 6 mL of toluene were added to a 25 mL Schlenk tube, and refluxed at 110 °C for 18 h. After cooling to room temperature, it was diluted with 5 mL of ethyl acetate, washed with 5 mL of water, 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 obtain 806.4 mg of a pale yellow solid of the compound of formula 3a, with a yield of 55%.

[0078] Upon detection, the data of the compound of Formula 3a obtained in this example are as follows: 864.0 mg of 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] Referring to the preparation method of Example 1, the compounds of Formula 3b - 3l were respectively prepared, and their structures are shown as follows:

[0081]

[0082] Upon detection, the data of the compound of Formula 3b obtained in this example are as follows: 942.2 mg of 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; 1313C NMR (101 MHz, Chloroform-d) δ 145.2, 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, 17.6 ppm; 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).

[0083] After detection, the data of the compound of Formula 3c obtained in this example are: 758.4 mg of pale yellow oil, and the yield is 60%. 1 1H NMR (400 MHz, Chloroform-d) δ 7.38 - 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), 6.55 - 6.51 (m, 1H), 6.14 - 6.12 (m, 1H), 5.26 (brs, 1H), 4.47 (s, 1H), 4.31 (d, J = 4.0 Hz, 1H), 2.63 - 2.55 (m, 2H), 1.27 (t, J = 7.2 Hz, 3H) ppm; 13 13C NMR (101 MHz, Chloroform-d) δ 144.5, 143.0, 141.7, 128.5, 128.3, 127.7, 127.6, 127.3, 127.1, 126.8, 126.7, 126.6, 116.4, 111.1, 63.1, 61.2, 24.1, 13.0 ppm; 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] After detection, the data of the compound of Formula 3d obtained in this example are: 758.4 mg of pale yellow oil, and the yield is 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),6.55 - 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)δ144.5,143.0,141.7,128.5,128.3,127.7,127.6,127.3,127.1,126.8,126.7,126.6,116.4,111.1,63.1,61.2,24.1,13.0ppm;HRMS-ESI(m / z):[M+H] + calcd for C 22 H 25 N2:317.2012;found:317.2014.

[0085] After detection, the data of the compound of Formula 3e obtained in this example are as follows: 750.0 mg of 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)δ143.0,142.9,141.7,130.6,128.5,128.3,127.3,127.1,127.0,126.8,126.7,125.3,122.2,110.8,63.4,61.2,20.2,17.5ppm;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 of the compound of formula 3f obtained in this example after detection are as follows: 1049.1 mg of white solid, melting point 99.8 - 101.3 °C, yield 83%. 1 H NMR (400 MHz, Chloroform - d) δ 7.36 (d, J = 7.2 Hz, 2H), 7.39 - 7.23 (m, 8H), 6.87 (d, J = 7.2 Hz 1H), 6.34 (d, J = 6.8 Hz, 1H), 6.02 (s, 1H), 4.83 (s, 3H), 4.54 (d, J = 4.4 Hz, 1H), 4.40 (d, J = 4.4 Hz, 1H), 2.05 (s, 6H) ppm; 13 C NMR (101 MHz, Chloroform - d) δ 145.1, 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, 17.3 ppm; 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 of the compound of formula 3g obtained in this example after detection are as follows: 745.8 mg of yellow oil, yield 59%. 1 H NMR (400 MHz, Chloroform - d) δ 7.32 - 7.30 (m, 2H), 7.21 - 7.16 (m, 2H), 7.13 - 7.01 (m, 6H), 6.77 (d, J = 7.2 Hz, 2H), 6.57 (t, J = 7.6 Hz, 1H), 4.63 (d, J = 5.6 Hz, 1H), 4.35 (d, J = 5.6 Hz, 1H), 2.13 (s, 6H) ppm; 1313C NMR (101 MHz, Chloroform-d) δ 144.3, 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, 19.4 ppm; 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 of the compound of formula 3h obtained in this example were detected as: 792.0 mg of yellow oil, yield 60%. 1 1H NMR (400 MHz, Chloroform-d) δ 7.38 - 7.01 (m, 10H), 6.66 (s, 2H), 5.71 (d, J = 14.2 Hz, 1H), 4.55 (d, J = 6.5 Hz, 1H), 4.43 (d, J = 6.5 Hz, 1H), 2.14 (s, 9H) ppm; 13 13C NMR (101 MHz, Chloroform-d) δ 143.0, 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, 19.4 ppm; HRMS-ESI (m / z): [M+H] + calcd for C 22 H 25 N2: 317.2012; found: 317.2013.

[0089] The data of the compound of formula 3i obtained in this example were detected as: 1403.5 mg of white solid, melting point 68.7 - 74.2 °C, yield 68%. 1 1H NMR (400 MHz, Chloroform-d) δ 7.50 - 7.46 (m, 2H), 7.43 - 7.34 (m, 10H), 7.26 (d, J = 9.6 Hz, 4H), 7.18 - 7.11 (m, 4H), 6.97 (d, J = 7.0 Hz, 3H), 6.89 - 6.84 (m, 2H), 6.44 - 6.41 (m, 2H), 5.27 (d, J = 10.9 Hz, 1H), 3.87 - 3.83 (m, 1H), 3.72 (d, J = 5.1 Hz, 1H) ppm;13 13C NMR (101 MHz, Chloroform-d) δ 142.4, 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, 60.6 ppm; 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] Upon detection, the data of the compound of formula 3j obtained in this example are: 1045.8 mg of yellow oil, with a yield of 76%. 1 1H NMR (400 MHz, Chloroform-d) δ 7.33 (d, J = 7.2 Hz, 2H), 7.21 (t, J = 7.2 Hz, 2H), 7.16 - 7.03 (m, 8H), 6.84 (d, J = 7.6 Hz, 2H), 6.70 (t, J = 7.6 Hz, 1H), 4.52 (d, J = 5.6 Hz, 1H), 4.41 (d, J = 5.6 Hz, 1H), 2.57 - 2.46 (m, 4H), 1.11 (t, J = 7.2 Hz, 6H) ppm; 13 13C NMR (101 MHz, Chloroform-d) δ 143.0, 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, 14.2 ppm; 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] Upon detection, the data of the compound of formula 3k obtained in this example are: 716.8 mg of yellow oil, with a yield of 56%. 11H NMR (400 MHz, Chloroform-d) δ 7.36 (d, J = 7.5 Hz, 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 = 4.5 Hz, 1H), 4.30 (d, J = 4.4 Hz, 1H), 2.20 (s, 3H), 1.51 - 1.34 (m, 2H) ppm; 13 13C NMR (101 MHz, Chloroform-d) δ 143.2, 141.7, 128.8, 128.6, 127.6, 127.5, 127.0, 116.9, 116.7, 112.5, 111.4, 64.0, 61.5, 17.9 ppm; 19 19F NMR (376 MHz, Chloroform-d) δ -129.3 (d, J = 8.7 Hz) 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] Upon detection, the data of the compound of formula 3l obtained in this example are: 1204.8 mg of yellow oil, with a yield of 91%. 1 1H NMR (400 MHz, Chloroform-d) δ 7.54 - 7.33 (m, 11H), 6.81 (d, J = 2.8 Hz, 1H), 6.58 - 6.56 (m, 1H), 6.27 - 6.24 (m, 1H), 4.56 (d, J = 5.0 Hz, 1H), 4.43 (d, J = 4.7 Hz, 1H), 3.75 (s, 3H), 2.38 (s, 3H) ppm; 13 13C NMR (101 MHz, Chloroform-d) δ 151.0, 143.0, 141.7, 139.5, 128.3, 128.1, 127.2, 127.0, 126.8, 126.7, 123.7, 116.7, 111.6, 111.0, 64.0, 61.3, 55.4, 17.7 ppm; 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 example, the preparation method of the compound of formula 5a is carried out as follows, and the reaction route is shown below.

[0095]

[0096] In a glove box, to a 25 mL Schlenk tube was added the compound 3a (576.0 mg, 2.0 mmol, 1.0 equiv) prepared in Example 1, 2-bromopyridine 4a (347.6 mg, 2.2 mmol, 1.1 equiv), tris(dibenzylideneacetone)dipalladium(0) (91.6 mg, 0.1 mmol, 0.05 equiv), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (115.7 mg, 0.2 mmol, 0.1 equiv), sodium tert-butoxide (269.1 mg, 2.8 mmol, 1.4 equiv), 3 mL of toluene, and refluxed at 110 °C for 18 h. After cooling to room temperature, it was diluted with 5 mL of ethyl acetate, washed with 5 mL of water, 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 (petroleum ether / ethyl acetate = 20:1) to give 423.4 mg of a yellow solid of the compound of formula 5a, melting point 136.5 - 140.0 °C, and the yield was 58%.

[0097] Upon detection, the data of the compound of formula 5a obtained in this example are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 8.08 - 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 = 7.3 Hz, 1H), 6.54 - 6.50 (m, 1H), 6.48 - 6.42 (m, 2H), 6.17 (d, J = 8.4 Hz, 1H), 5.36 (d, J = 6.7 Hz, 1H), 5.14 (d, J = 5.1 Hz, 1H), 4.99 (t, J = 7.2 Hz, 1H), 4.63 - 4.60 (m, 1H) ppm; 1313C NMR (101 MHz, Chloroform-d) δ 158.0, 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, 61.7 ppm; 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] Referring to the preparation method of Reference Example 3, the compounds of Formula 5b - 5q were prepared respectively, and their structures are shown as follows:

[0099]

[0100] Upon detection, the data of the compound of Formula 5b obtained in this example were: 629.1 mg of colorless liquid, and the yield was 83%. 1 1H NMR (400 MHz, Chloroform-d) δ 8.11 (d, J = 4.4 Hz, 1H), 7.31 (t, J = 6.8 Hz, 1H), 7.26 - 7.22 (m, 4H), 7.20 - 7.17 (m, 6H), 6.97 (d, J = 7.6 Hz, 1H), 6.88 (t, J = 8.0 Hz, 1H), 6.60 - 6.53 (m, 2H), 6.31 (d, J = 8.0 Hz, 1H), 6.23 (d, J = 8.4 Hz, 1H), 5.17 - 5.15 (m, 2H), 4.96 (d, J = 4.0 Hz, 1H), 4.73 - 4.70 (m, 1H), 2.06 (s, 3H) ppm; 13 13C NMR (101 MHz, Chloroform-d) δ 158.1, 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, 17.7 ppm; HRMS-ESI (m / z): [M+H] + calcd for C 26 H 26 N3: 380.2121; found: 380.2136; [α] D25 = -42.4 (c = 3.4, CHCl3).

[0101] Upon detection, the data of the compound of formula 5c obtained in this example are: 628.8 mg of a yellow liquid, with a yield of 80%. 1 1H NMR (400 MHz, Chloroform-d) δ 8.11 (d, J = 4.0 Hz, 1H), 7.32 (t, J = 7.6 Hz, 1H), 7.26 - 7.18 (m, 10H), 6.99 (d, J = 7.2 Hz, 1H), 6.87 (t, J = 7.6 Hz, 1H), 6.62 - 6.59 (m, 2H), 6.30 (d, J = 8.0 Hz, 1H), 6.24 (d, J = 8.0 Hz, 1H), 5.19 - 5.08 (m, 3H), 4.72 (t, J = 6.0 Hz, 1H), 2.48 - 2.33 (m, 2H), 1.15 (t, J = 7.2 Hz, 3H) ppm; 13 13C NMR (101 MHz, Chloroform-d) δ 158.2, 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, 13.0 ppm; HRMS-ESI (m / z): [M+H] + calcd for C 27 H 28 N3: 394.2278; found: 394.2290; [α] D 25 = -91.1 (c = 0.65, CHCl3).

[0102] Upon detection, the data of the compound of formula 5d obtained in this example are: 661.5 mg of a yellow solid, with a melting point of 72.2 - 74.3 °C and a yield of 75%. 11H NMR (400 MHz, Chloroform-d) δ 7.89 (d, J = 4.0 Hz, 1H), 7.41 - 7.26 (m, 5H), 7.23 - 7.06 (m, 9H), 7.04 - 6.88 (m, 4H), 6.66 (t, J = 7.2 Hz, 1H), 6.44 (d, J = 6.4 Hz, 1H), 6.39 (d, J = 8.0 Hz, 1H), 6.04 (d, J = 8.4 Hz, 1H), 5.05 (d, J = 6.4 Hz, 1H), 4.95 (t, J = 6.4 Hz, 1H), 4.89 (d, J = 4.8 Hz, 1H), 4.71 (t, J = 5.6 Hz, 1H) ppm; 13 13C NMR (101 MHz, Chloroform-d) δ 157.5, 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, 61.0 ppm; 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] After detection, the data of the compound of formula 5e obtained in this example are as follows: 534.5 mg of white solid, melting point 139.9 - 140.3 °C, and yield 68%. 1 1H NMR (400 MHz, Chloroform-d) δ 8.08 (d, J = 4.2 Hz, 1H), 7.29 - 7.14 (m, 11H), 6.81 (s, 1H), 6.68 (d, J = 8.0 Hz, 1H), 6.57 - 6.51 (m, 1H), 6.21 - 6.19 (m, 2H), 5.22 (d, J = 6.6 Hz, 1H), 5.12 (t, J = 6.6 Hz, 1H), 4.68 (d, J = 6.8 Hz, 2H), 2.13 (s, 3H), 2.04 (s, 3H) ppm; 1313C NMR (101 MHz, Chloroform-d) δ 158.1, 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, 17.6 ppm; 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 of the compound of formula 5f obtained in this example were as follows: 691.7 mg of white solid, melting point 161.1 - 162.8 °C, yield 88%. 1 1H NMR (400 MHz, Chloroform-d) δ 8.10 (d, J = 4.8 Hz, 1H), 7.29 (t, J = 8.0 Hz, 1H), 7.24 - 7.15 (m, 10H), 6.86 (d, J = 7.6 Hz, 1H), 6.56 (t, J = 6.0 Hz, 1H), 6.38 (d, J = 7.2 Hz, 1H), 6.22 (d, J = 8.4 Hz, 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 13C NMR (101 MHz, Chloroform-d) δ 158.3, 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, 17.5 ppm; HRMS-ESI (m / z): [M+H] + calcd for C 27 H 28 N3: 394.2283; found: 394.2283; [α] D 25 = -72.2 (c = 1.0, CHCl3).

[0105] Upon detection, the data of the compound of Formula 5g obtained in this example are as follows: 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] Upon detection, the data of the compound of Formula 5h obtained in this example are as follows: 407.0 mg of yellow solid, with a melting point of 92.3 - 93.8 °C and a 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; 1313C NMR (101 MHz, Chloroform-d) δ 158.4, 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, 19.3 ppm; [α] D 25 = -15.6 (c = 1.0, CHCl3).

[0107] Upon detection, the data of the compound of formula 5i obtained in this example are as follows: 438.8 mg of white solid, melting point 92.2 - 97.6 °C, yield 37%. 1 1H NMR (400 MHz, Chloroform-d) δ 8.07 - 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 = 5.9 Hz, 1H), 4.63 (d, J = 11.9 Hz, 1H), 4.49 - 4.45 (m, 1H), 3.98 - 3.93 (m, 1H) ppm; 13 13C NMR (101 MHz, Chloroform-d) δ 158.1, 148.1, 141.3, 140.9, 140.2, 139.8, 139.2, 137.1, 133., 133.04, 129.5, 128.82, 128.79, 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, 15.3 ppm; 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] Upon detection, the data of the compound of formula 5j obtained in this example are as follows: 715.7 mg of yellow liquid, yield 85%. 11H NMR (400 MHz, Chloroform-d) δ 8.10 (d, J = 4.8 Hz, 1H), 7.31 (t, J = 7.6 Hz, 1H), 7.25 - 7.11 (m, 8H), 6.96 - 6.89 (m, 4H), 6.82 (t, J = 7.6 Hz, 1H), 6.56 (t, J = 6.0 Hz, 1H), 6.22 (d, J = 8.4 Hz, 1H), 5.87 (d, J = 4.2 Hz, 1H), 5.14 - 5.10 (m, 1H), 4.47 (d, J = 7.6 Hz, 1H), 3.83 (brs, 1H), 2.54 - 2.39 (m, 4H), 1.17 (t, J = 7.6 Hz, 6H) ppm; 13 13C NMR (101 MHz, Chloroform-d) δ 158.3, 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, 14.5 ppm; HRMS-ESI (m / z): [M+H] + calcd for C 29 H 32 N3: 422.2591; found: 422.2598; [α] D 25 = -16.8 (c = 1.6, CHCl3).

[0109] The data of the compound of Formula 5k obtained in this example were as follows: 453.6 mg of white solid, melting point 58.9 - 61.3 °C, and yield 60%. 1 1H NMR (400 MHz, Chloroform-d) δ 8.12 - 8.10 (m, 1H), 7.34 - 7.30 (m, 1H), 7.24 (q, J = 4.7, 3.9 Hz, 3H), 7.21 - 7.15 (m, 7H), 6.73 - 6.70 (m, 1H), 6.64 - 6.51 (m, 2H), 6.25 (d, J = 8.4 Hz, 1H), 6.19 - 6.17 (m, 1H), 5.15 (d, J = 6.6 Hz, 2H), 4.89 (d, J = 4.6 Hz, 1H), 4.67 - 4.64 (m, 1H), 2.05 (s, 3H) ppm; 1313C NMR (101 MHz, Chloroform-d) δ 148.1, 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, 18.0 ppm; 19 19F NMR (376 MHz, Chloroform-d) δ -128.6 (d, J = 6.7 Hz) 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 of the compound of formula 5l obtained in this example were as follows: 457.0 mg of white solid, melting point 46.2 - 50.6 °C, yield 56%. 1 1H NMR (400 MHz, Chloroform-d) δ 8.09 - 8.07 (m, 1H), 7.21 - 7.20 (m, 12H), 6.62 (d, J = 2.8 Hz, 1H), 6.58 - 6.52 (m, 1H), 6.46 - 6.44 (m, 1H), 6.23 - 6.21 (m, 2H), 5.29 (d, J = 6.7 Hz, 1H), 5.08 (t, J = 6.7 Hz, 1H), 4.64 (d, J = 6.8 Hz, 1H), 3.64 (s, 3H), 2.07 (s, 3H) ppm; 13 13C NMR (101 MHz, Chloroform-d) δ 158.1, 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, 17.9 ppm; [α] D 25 = -106.8 (c = 1.0, CHCl3).

[0111] The data of the compound of formula 5m obtained in this example were as follows: 678.9 mg of white solid, melting point 141.5 - 142.8 °C, yield 84%. 11H NMR (400 MHz, Chloroform-d) δ 7.94 (d, J = 5.9 Hz, 1H), 7.28 - 7.22 (m, 3H), 7.21 - 7.15 (m, 7H), 6.98 (d, J = 7.3 Hz, 1H), 6.91 - 6.85 (m, 1H), 6.55 (t, J = 7.3 Hz, 1H), 6.29 (d, J = 8.1 Hz, 1H), 6.21 - 6.19 (m, 1H), 5.69 (d, J = 2.2 Hz, 1H), 5.24 - 5.07 (m, 2H), 5.01 (d, J = 4.7 Hz, 1H), 4.71 - 4.68 (m, 1H), 3.65 (s, 3H), 2.07 (s, 3H) ppm; 13 13C NMR (101 MHz, Chloroform-d) δ 149.2, 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, 17.9 ppm; 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] Upon detection, the data of the compound of Formula 5n obtained in this example are: 804.6 mg of white solid, melting point 89.2 - 90.7 °C, and yield 90%. 1 1H NMR (400 MHz, Chloroform-d) δ 8.21 (d, J = 5.2 Hz, 1H), 7.25 - 7.15 (m, 8H), 6.98 (d, J = 7.2 Hz 1H), 6.89 (t, J = 7.6 Hz, 1H), 6.73 (d, J = 7.2 Hz, 1H), 6.57 (t, J = 7.2 Hz, 1H), 6.43 (s, 1H), 6.34 (t, J = 8.0 Hz, 1H), 5.42 (d, J = 6.8 Hz, 1H), 5.25 (t, J = 6.8 Hz, 1H), 4.76 (d, J = 4.0 Hz, 2H), 2.05 (s, 3H) ppm; 1313C NMR (101 MHz, Chloroform-d) δ 158.5, 149.4, 145.0, 140.0, 139.8, 139.5, 139.1, 130.1, 128.8, 128.4, 128.0, 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, 17.8 ppm; 19 19F NMR (376 MHz, Chloroform-d) δ -65.2 ppm; 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] Upon detection, the data of the compound of Formula 5o obtained in this example are: 595.8 mg of yellow solid, melting point 57.9 - 62.0 °C, and yield 76%. 1 1H NMR (400 MHz, Chloroform-d) δ 7.91 (s, 1H), 7.25 - 7.10 (m, 11H), 6.96 (d, J = 7.1 Hz, 1H), 6.87 (t, J = 7.7 Hz, 1H), 6.54 (t, J = 7.1 Hz, 1H), 6.30 (d, J = 8.0 Hz, 1H), 6.15 (d, J = 8.4 Hz, 1H), 5.17 - 5.04 (m, 2H), 4.97 (d, J = 4.2 Hz, 1H), 4.71 - 4.68 (m, 1H), 2.10 (s, 3H), 2.07 (s, 3H) ppm; 13 13C NMR (101 MHz, Chloroform-d) δ 156.3, 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, 17.3 ppm; HRMS-ESI (m / z): [M+H] + calcd for C 27 H 28 N3: 393.5340; found: 394.2283; [α] D 25= -104.4 (c = 1.0, CHCl3).

[0114] Upon detection, the data of the compound of Formula 5p obtained in this example are as follows: 658.6 mg of red solid, melting point 119.6 - 123.2 °C, yield 84%. 1 H NMR (400 MHz, Chloroform-d) δ 7.97 (d, J = 5.2 Hz, 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 = 1.4 Hz, 1H), 5.16 (t, J = 7.1 Hz, 1H), 5.07 - 5.04 (m, 2H), 2.13 (s, 3H), 2.06 (s, 3H) ppm; 13 C NMR (101 MHz, Chloroform-d) δ 158.4, 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, 17.8 ppm; HRMS-ESI (m / z): [M+H] + calcd for C 27 H 27 N3: 393.2205; found: 393.2283; [α] D 25 = -94.8 (c = 1.0, CHCl3).

[0115] Upon detection, the data of the compound of Formula 5q obtained in this example are as follows: 565.9 mg of white solid, melting point 50.4 - 51.8 °C, yield 72%. 1 H NMR (400 MHz, Chloroform-d) δ 7.25 - 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 = 7.3 Hz, 1H), 6.34 - 6.32 (m, 1H), 6.01 (d, J = 8.3 Hz, 1H), 5.23 - 5.04 (m, 2H), 4.89 (d, J = 4.7 Hz, 1H), 4.72 - 4.69 (m, 1H), 2.41 (s, 3H), 2.05 (d, J = 6.4 Hz, 3H) ppm;13 13C NMR (101 MHz, Chloroform-d) δ 157.0, 145.3, 137.9, 130.0, 128.7, 128.4, 127.8, 127.6, 127.5, 127.4, 126.9, 122.6, 117.1, 113.1, 111.1, 104.5, 64.3, 61.9, 24.5, 17.9 ppm; HRMS-ESI (m / z): [M+H] + calcd for C 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 example, the preparation method of the compound of formula (S,S)-6a is as follows, and the reaction route is shown below.

[0118]

[0119] In the glove box, add the compound of formula 5a (182.5 mg, 0.5 mmol, 1.0 eq) prepared in Example 3, phenylphosphorus dichloride (134.2 mg, 0.75 mmol, 1.5 eq), triethylamine (151.8 mg, 1.5 mmol, 3.0 eq), and 3 mL of toluene to a 25 mL Schlenk tube. After reacting at 110 °C for 12 hours, cool to room temperature, remove the solvent, and recrystallize the residue to obtain the ligand compound of formula 6a.

[0120] After detection, the data of the compound of formula 6a obtained in this example are: 75.4 mg of white solid, melting point 82.3 - 86.0 °C, and yield 32%. 1 1H NMR (400 MHz, Chloroform-d) δ 8.29 - 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 = 7.2 Hz, 2H), 7.06 - 7.02 (m, 2H), 6.97 (d, J = 6.8 Hz, 2H), 6.89 (d, J = 8.0 Hz, 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; 1313C NMR (101 MHz, Chloroform-d) δ 153.5, 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, 72.1 ppm; 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 eq), phenylphosphorus dichloride (134.2 mg, 0.75 mmol, 1.5 eq), triethylamine (151.8 mg, 1.5 mmol, 3.0 eq), and 3 mL of toluene were added to a 25 mL Schlenk tube. After reacting at 110 °C for 12 hours, it was cooled to room temperature, the solvent was removed, and the residue was recrystallized to obtain the ligand compound 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 eq), phenylphosphorus dichloride (134.2 mg, 0.75 mmol, 1.5 eq), triethylamine (151.8 mg, 1.5 mmol, 3.0 eq), and 3 mL of toluene were added to a 25 mL Schlenk tube. After reacting at 110 °C for 12 hours, it was cooled to room temperature, the solvent was removed, and the residue was recrystallized to obtain the ligand compound of formula 6c.

[0125] Example 4-4

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

[0127] Example 4-5

[0128] In the glove box, add the compound of formula 5e prepared in Example 3 (196.6 mg, 0.5 mmol, 1.0 equivalent), phenylphosphorus dichloride (134.2 mg, 0.75 mmol, 1.5 equivalents), triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalents), and 3 mL of toluene into a 25 mL Schlenk tube. After reacting at 110 °C for 12 hours, cool to room temperature, remove the solvent, and recrystallize the residue to obtain the ligand compound of formula 6e.

[0129] Examples 4 - 6

[0130] In the glove box, add the compound of formula 5f prepared in Example 3 (196.6 mg, 0.5 mmol, 1.0 equivalent), phenylphosphorus dichloride (134.2 mg, 0.75 mmol, 1.5 equivalents), triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalents), and 3 mL of toluene into a 25 mL Schlenk tube. After reacting at 110 °C for 12 hours, cool to room temperature, remove the solvent, and recrystallize the residue to obtain the ligand compound of formula 6e.

[0131] Examples 4 - 7

[0132] In the glove box, add the compound of formula 5g prepared in Example 3 (196.6 mg, 0.5 mmol, 1.0 equivalent), phenylphosphorus dichloride (134.2 mg, 0.75 mmol, 1.5 equivalents), triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalents), and 3 mL of toluene into a 25 mL Schlenk tube. After reacting at 110 °C for 12 hours, cool to room temperature, remove the solvent, and recrystallize the residue to obtain the ligand compound of formula 6g.

[0133] Examples 4 - 8

[0134] In the glove box, add the compound of formula 5h prepared in Example 3 (203.6 mg, 0.5 mmol, 1.0 equivalent), phenylphosphorus dichloride (134.2 mg, 0.75 mmol, 1.5 equivalents), triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalents), and 3 mL of toluene into a 25 mL Schlenk tube. After reacting at 110 °C for 12 hours, cool to room temperature, remove the solvent, and recrystallize the residue to obtain the ligand compound of formula 6h.

[0135] Examples 4 - 9

[0136] In a glove box, add the compound of formula 5i prepared in Example 3 (296.6 mg, 0.5 mmol, 1.0 equivalent), phenylphosphorus dichloride (134.2 mg, 0.75 mmol, 1.5 equivalents), triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalents), and 3 mL of toluene to a 25 mL Schlenk tube. After reacting at 110 °C for 12 hours, cool to room temperature, remove the solvent, and recrystallize the residue to obtain the ligand compound of formula 6i.

[0137] Example 4 - 10

[0138] In a glove box, add the compound of formula 5j prepared in Example 3 (210.6 mg, 0.5 mmol, 1.0 equivalent), phenylphosphorus dichloride (134.2 mg, 0.75 mmol, 1.5 equivalents), triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalents), and 3 mL of toluene to a 25 mL Schlenk tube. After reacting at 110 °C for 12 hours, cool to room temperature, remove the solvent, and recrystallize the residue to obtain the ligand compound of formula 6j.

[0139] Example 4 - 11

[0140] In a glove box, add the compound of formula 5k prepared in Example 3 (198.6 mg, 0.5 mmol, 1.0 equivalent), phenylphosphorus dichloride (134.2 mg, 0.75 mmol, 1.5 equivalents), triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalents), and 3 mL of toluene to a 25 mL Schlenk tube. After reacting at 110 °C for 12 hours, cool to room temperature, remove the solvent, and recrystallize the residue to obtain the ligand compound of formula 6k.

[0141] Example 4 - 12

[0142] In a glove box, add the compound of formula 5o prepared in Example 3 (196.6 mg, 0.5 mmol, 1.0 equivalent), phenylphosphorus dichloride (134.2 mg, 0.75 mmol, 1.5 equivalents), triethylamine (151.8 mg, 1.5 mmol, 3.0 equivalents), and 3 mL of toluene to a 25 mL Schlenk tube. After reacting at 110 °C for 12 hours, cool to room temperature, remove the solvent, and recrystallize the residue to obtain the ligand compound of formula 6l.

[0143] Example 4 - 13

[0144] In the glove box, add the prepared compound of formula 5m (204.6 mg, 0.5 mmol, 1.0 eq) from Example 3, phenylphosphorus dichloride (134.2 mg, 0.75 mmol, 1.5 eq), triethylamine (151.8 mg, 1.5 mmol, 3.0 eq), and 3 mL of toluene to a 25 mL Schlenk tube. After reacting at 110 °C for 12 hours, cool to room temperature, remove the solvent, and recrystallize the residue to obtain the ligand compound of formula 6m.

[0145] Examples 4 - 14

[0146] In the glove box, add the prepared compound of formula 5n (223.6 mg, 0.5 mmol, 1.0 eq) from Example 3, phenylphosphorus dichloride (134.2 mg, 0.75 mmol, 1.5 eq), triethylamine (151.8 mg, 1.5 mmol, 3.0 eq), and 3 mL of toluene to a 25 mL Schlenk tube. After reacting at 110 °C for 12 hours, cool to room temperature, remove the solvent, and recrystallize the residue to obtain the ligand compound of formula 6n.

[0147] Examples 4 - 15

[0148] In the glove box, add the prepared compound of formula 5l (204.6 mg, 0.5 mmol, 1.0 eq) from Example 3, phenylphosphorus dichloride (134.2 mg, 0.75 mmol, 1.5 eq), triethylamine (151.8 mg, 1.5 mmol, 3.0 eq), and 3 mL of toluene to a 25 mL Schlenk tube. After reacting at 110 °C for 12 hours, cool to room temperature, remove the solvent, and recrystallize the residue to obtain the ligand compound of formula 6o.

[0149] Examples 4 - 16

[0150] In the glove box, add the prepared compound of formula 5p (196.6 mg, 0.5 mmol, 1.0 eq) from Example 3, phenylphosphorus dichloride (134.2 mg, 0.75 mmol, 1.5 eq), triethylamine (151.8 mg, 1.5 mmol, 3.0 eq), and 3 mL of toluene to a 25 mL Schlenk tube. After reacting at 110 °C for 12 hours, cool to room temperature, remove the solvent, and recrystallize the residue to obtain the ligand compound of formula 6p.

[0151]

[0152] Upon detection, the data of the compound of formula 6b obtained in this example are as follows: 172.2 mg of white solid, melting point 110.5 - 111.9 °C, and yield 71%. 11H NMR (400 MHz, Chloroform-d) δ 8.26 (d, J = 8.4 Hz, 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 = 8.4 Hz, 2H), 4.85 (s, 2H), 2.72 (s, 3H) ppm; 13 13C NMR (101 MHz, Chloroform-d) δ 158.4, 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, 19.9 ppm; HRMS-ESI (m / z): [M+H] + calcd for C 32 H 29 N3P: 486.2099; found: 486.2099; [α] D 25 = -169.6 (c = 1.0, CHCl3).

[0153] Upon detection, the data of the compound of formula 6c obtained in this example are as follows: 92.3 mg of white solid, melting point 107.2 - 109.1 °C, yield 37%. 1 1H NMR (400 MHz, Chloroform-d) δ 8.22 (d, J = 4.1 Hz, 1H), 7.39 - 7.27 (m, 6H), 7.24 - 7.20 (m, 4H), 7.15 (d, J = 5.3 Hz, 2H), 7.08 (t, J = 5.1 Hz, 3H), 6.94 - 6.88 (m, 3H), 6.73 - 6.63 (m, 2H), 6.31 (d, J = 8.4 Hz, 1H), 6.27 (d, J = 7.7 Hz, 1H), 4.81 (q, J = 9.1 Hz, 2H), 3.25 - 3.09 (m, 2H), 1.38 (t, J = 7.4 Hz, 3H) ppm; 1313C NMR (101 MHz, Chloroform-d) δ 158.2, 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, 128.35, 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, 14.5 ppm; 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] Upon detection, the data of the compound of Formula 6d obtained in this example are as follows: 142.2 mg of white solid, melting point 105.5 - 106.9 °C, yield 52%. 1 1H NMR (400 MHz, Chloroform-d) δ 8.09 (s, 1H), 7.67 (s, 1H), 7.50 - 6.79 (m, 24H), 6.60 (t, J = 6.08 Hz, 1H), 6.46 - 6.34 (m, 1H), 6.23 - 6.20 (m, 1H), 4.83 - 4.77 (m, 1H) ppm; 13 13C NMR (101 MHz, Chloroform-d) δ 171.1, 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, 71.1 ppm; HRMS-ESI (m / z): [M+H] + calcd for C 37 H 31 N3P: 548.2256; found: 548.2252; [α] D 25 = -121.6 (c = 1.0, CHCl3).

[0155] Upon detection, the data of the compound of Formula 6e obtained in this example are as follows: 132.2 mg of white solid, melting point 115.3 - 116.2 °C, and yield 53%. 1 H NMR (400 MHz, Chloroform-d) δ 8.23 (d, J = 4.9 Hz, 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 = 6.7 Hz, 3H), 6.68 - 6.65 (m, 1H), 6.61 - 6.40 (m, 1H), 6.30 (d, J = 8.4 Hz, 1H), 6.19 (s, 1H), 4.79 (s, 2H), 2.63 (s, 3H), 2.2 - 2.11 (m, 3H) ppm; 13 C NMR (101 MHz, Chloroform-d) δ 158.3, 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, 19.5 ppm; 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] Upon detection, the data of the compound of Formula 6f obtained in this example are as follows: 119.8 mg of white solid, melting point 88.6 - 90.3 °C, and yield 48%. 1 H NMR (400 MHz, Chloroform-d) δ 8.13 (d, J = 4.8 Hz, 1H), 7.31 (s, 2H), 7.22 - 6.84 (m, 16H), 6.55 (t, J = 7.2 Hz, 2H), 6.22 (d, J = 8.4 Hz, 1H), 6.00 (s, 1H), 4.72 (s, 2H), 2.51 - 2.46 (m, 3H), 1.81 (s, 3H) ppm; 1313C NMR (101 MHz, Chloroform-d) δ 158.3, 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, 11.4 ppm; HRMS-ESI (m / z): [M+H] + calcd for C 33 H 31 N3P: 500.2255; found: 500.2256; [α] D 25 = -146.2 (c = 1.0, CHCl3).

[0157] The data of the compound of Formula 6g obtained in this example was detected as: 164.7 mg of white solid, melting point 92.7 - 97.8 °C, and yield 66%. 1 1H NMR (400 MHz, Chloroform-d) δ 8.19 - 8.17 (m, 1H), 7.74 - 7.67 (m, 2H), 7.38 (d, J = 3.0 Hz, 3H), 7.26 - 7.12 (m, 6H), 7.08 - 6.97 (m, 4H), 6.87 - 6.78 (m, 3H), 6.65 - 6.56 (m, 2H), 6.28 (d, J = 8.4 Hz, 1H), 4.90 (d, J = 9.2 Hz, 1H), 4.74 (d, J = 9.2 Hz, 1H), 2.67 (s, 3H), 1.49 (s, 3H) ppm; 13 13C NMR (101 MHz, Chloroform-d) δ 158.3, 158.2, 148.3, 143.9, 143.4, 139.5, 139.3, 138.3, 137.2, 137.1, 136.8, 137.7, 136.1, 135.9, 130.3, 130.0, 129.04, 128.96, 128.8, 128.6, 128.3, 127.94, 127.89, 127.8, 127.6, 127.5, 125.0, 124.9, 114.3, 108.91, 108.88, 76.1, 76.0, 72.7, 72.6, 20.8, 20.7, 19.9 ppm; 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] Upon detection, the data of the compound of formula 6h obtained in this example are as follows: 105.2 mg of white solid, melting point 126.2 - 127.2 °C, and yield 41%. 1 H NMR (400 MHz, Chloroform-d) δ 8.20 - 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 = 9.19 Hz, 1H), 4.72 (d, J = 9.15 Hz, 1H), 2.62 (s, 3H), 2.13 (s, 3H), 1.45 (s, 3H) ppm; 13 C NMR (101 MHz, Chloroform-d) δ 158.4, 158.3, 148.3, 144.0, 143.6, 138.4, 136.82, 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, 72.7 20.7, 20.6, 19.9 ppm; 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] Upon detection, the data of the compound of formula 6i obtained in this example are as follows: 269.1 mg of yellow solid, melting point 118.0 - 122.4 °C, and yield 77%. 11H NMR (400 MHz, Chloroform-d) δ 8.04 - 7.96 (m, 1H), 7.87 - 7.80 (m, 2H), 7.74 - 7.68 (m, 2H), 7.63 - 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 = 9.6 Hz, 1H), 4.35 (d, J = 9.6 Hz, 1H) ppm; 13 13C NMR (101 MHz, Chloroform-d) δ 147.5, 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, 71.3 ppm; 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 data of the compound of Formula 6j obtained in this example was detected as follows: 92.1 mg of white solid, melting point 95.6 - 99.7 °C, and yield 35%. 11H NMR (400 MHz, Chloroform-d) δ 8.21 - 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), 6.31 - 6.29 (m, 1H), 4.91 (d, J = 9.2 Hz, 1H), 4.80 (d, J = 9.2 Hz, 1H), 3.15 (ddd, J = 15.3, 7.6, 2.3 Hz, 1H), 2.99 (dq, J = 15.2, 7.5 Hz, 1H), 1.98 (dq, J = 15.1, 7.5 Hz, 1H), 1.87 - 1.77 (m, 1H), 1.39 (t, J = 7.5 Hz, 3H), 0.70 (t, J = 7.5 Hz, 3H) ppm; 13 13C NMR (101 MHz, Chloroform-d) δ 158.4, 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, 72.6, 72.5, 25.0, 24.8, 24.0, 14.54, 14.49, 13.2 ppm; HRMS-ESI (m / z): [M+H] + calcd for C 35 H 34 N3P: 527.2490; found: 527.2568; [α] D 25 = -220.4 (c = 1.0, CHCl3).

[0161] Upon detection, the data of the compound of formula 6k obtained in this example are as follows: 65.4 mg of white solid, melting point 87.4 - 89.2 °C, yield 26%. 11H NMR (400 MHz, Chloroform-d) δ 8.21 (d, J = 4.9 Hz, 1H), 7.44 - 7.28 (m, 6H), 7.22 (t, J = 6.2 Hz, 3H), 7.14 (d, J = 6.5 Hz, 2H), 7.09 (d, J = 7.3 Hz, 3H), 6.91 (d, J = 7.0 Hz, 2H), 6.84 (d, J = 9.3 Hz, 1H), 6.68 - 6.65 (m, 1H), 6.40 (s, 1H), 6.30 (d, J = 8.4 Hz, 1H), 6.24 - 6.09 (m, 1H), 4.82 (d, J = 9.1 Hz, 1H), 4.75 (d, J = 9.5 Hz, 1H), 2.65 (s, 3H) ppm; 13 13C NMR (101 MHz, Chloroform-d) δ 158.2, 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, 71.3 ppm; 19 19F NMR (376 MHz, Chloroform-d) δ -119.7 ppm; 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] Upon detection, the data of the compound of formula 6l obtained in this example are as follows: 94.6 mg of white solid, melting point 164.5 - 167.2 °C, and yield 38%. 1 1H NMR (400 MHz, Chloroform-d) δ 8.04 (s, 1H), 7.41 (s, 2H), 7.27 (s, 3H), 7.20 - 6.96 (m, 10H), 6.91 (d, J = 3.5 Hz, 2H), 6.79 (t, J = 7.0 Hz, 1H), 6.68 (s, 1H), 6.23 (d, J = 8.5 Hz, 2H), 4.81 (s, 2H), 2.67 (s, 3H), 2.09 (s, 3H) ppm; 1313C NMR (101 MHz, Chloroform-d) δ 156.2, 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, 17.3 ppm; 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] Upon detection, the data of the compound of formula 6m obtained in this example are as follows: 72.0 mg of white solid, melting point 223.4 - 226.2 °C, and yield 28%. 1 1H NMR (400 MHz, Chloroform-d) δ 8.04 (d, J = 5.8 Hz, 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 = 2.2 Hz, 1H), 4.85 - 4.71 (m, 2H), 3.50 (s, 3H), 2.75 - 2.61 (m, 3H) ppm; 13 13C NMR (101 MHz, Chloroform-d) δ 166.6, 166.5, 159.9, 159.7, 149.1, 138.4, 137.1, 130.9, 130.8, 130.6, 128.9, 128.4, 128.0, 127.83, 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, 19.7 ppm; 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] Upon detection, the data of the compound of formula 6n obtained in this example are as follows: 69.1 mg of white solid, melting point 97.8 - 99.2 °C, yield 25%. 1 H NMR(400MHz,Chloroform-d)δ8.36(d,J=5.2Hz,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)δ158.9,158.7,149.5,137.5,131.1,130.8,130.6,129.3,128.8,128.5,128.2,128.0,127.9,125.8,124.3,123.8,121.6,110.0,104.9,74.5,71.8,19.7,11.6ppm; 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] Upon detection, the data of the compound of formula 6o obtained in this example are as follows: 56.5 mg of white solid, melting point 117.3 - 120.9 °C, 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; 1313C NMR (101 MHz, Chloroform-d) δ 158.2, 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, 34.6 ppm; 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] After detection, the data of the compound of formula 6p obtained in this example are as follows: 64.7 mg of white solid, melting point 219.4 - 221.9 °C, and yield 26%. 1 1H NMR (400 MHz, Chloroform-d) δ 8.09 (d, J = 5.2 Hz, 1H), 7.46 - 7.29 (m, 5H), 7.24 - 7.04 (m, 10H), 6.92 - 6.82 (m, 3H), 6.72 (s, 1H), 6.53 (d, J = 5.2 Hz, 1H), 6.16 (s, 1H), 4.81 (s, 2H), 2.67 (s, 3H), 2.08 (s, 3H) ppm; 13 13C NMR (101 MHz, Chloroform-d) δ 158.4, 158.3, 147.91, 147.88, 138.5, 137.2, 130.8, 130.6, 128.8, 128.5, 128.3, 128.0, 127.8, 127.64, 127.59, 125.5, 123.4, 116.0, 109.7, 74.4, 71.5, 21.3, 19.8, 19.7 ppm; 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 example, the preparation method of the compound of formula (S,S)-7a is carried out as follows, and the reaction route is shown below.

[0169]

[0170] In a glove box, add the compound of formula 5a (182.5 mg, 0.5 mmol, 1.0 eq) prepared in Example 3 to a 25 mL Schlenk tube. Add 5 mL of diethyl ether at 0 °C, and dropwise add triethylamine (I5I.8 mg, 1.5 mmol, 3.0 eq) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 eq). After the dropwise addition is completed, warm the reaction mixture to 25 °C and react for 12 hours, then cool to room temperature, remove the solvent, and recrystallize the residue to obtain the ligand compound of formula 7a.

[0171] After detection, the data of the compound of formula 7a obtained in this example are as follows: 43.2 mg of yellow solid, melting point 88.2 - 92.5 °C, and yield 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 prepared compound of formula 5b (189.6 mg, 0.5 mmol, 1.0 eq) from Example 3 was added to a 25 mL Schlenk tube. 5 mL of diethyl ether was added at 0 °C, and triethylamine (151.8 mg, 1.5 mmol, 3.0 eq) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 eq) were added dropwise. After the dropwise addition was completed, the temperature was raised to 25 °C and the reaction was carried out for 12 hours, then cooled to room temperature, the solvent was removed, and the residue was recrystallized to obtain the ligand compound of formula 7b.

[0174] Example 5-3

[0175] In a glove box, the prepared compound of formula 5c (196.6 mg, 0.5 mmol, 1.0 eq) from Example 3 was added to a 25 mL Schlenk tube. 5 mL of diethyl ether was added at 0 °C, and triethylamine (151.8 mg, 1.5 mmol, 3.0 eq) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 eq) were added dropwise. After the dropwise addition was completed, the temperature was raised to 25 °C and the reaction was carried out for 12 hours, then cooled to room temperature, the solvent was removed, and the residue was recrystallized to obtain the ligand compound of formula 7c.

[0176] Example 5-4

[0177] In a glove box, the prepared compound of formula 5d (220.6 mg, 0.5 mmol, 1.0 eq) from Example 3 was added to a 25 mL Schlenk tube. 5 mL of diethyl ether was added at 0 °C, and triethylamine (151.8 mg, 1.5 mmol, 3.0 eq) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 eq) were added dropwise. After the dropwise addition was completed, the temperature was raised to 25 °C and the reaction was carried out for 12 hours, then cooled to room temperature, the solvent was removed, and the residue was recrystallized to obtain the ligand compound of formula 7d.

[0178] Example 5-5

[0179] In a glove box, the prepared compound of formula 5e (196.6 mg, 0.5 mmol, 1.0 eq) from Example 3 was added to a 25 mL Schlenk tube. 5 mL of diethyl ether was added at 0 °C, and triethylamine (151.8 mg, 1.5 mmol, 3.0 eq) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 eq) were added dropwise. After the dropwise addition was completed, the temperature was raised to 25 °C and the reaction was carried out for 12 hours, then cooled to room temperature, the solvent was removed, and the residue was recrystallized to obtain the ligand compound of formula 7e.

[0180] Example 5-6

[0181] In the glove box, add the compound of formula 5f prepared in Example 3 (196.6 mg, 0.5 mmol, 1.0 eq) to a 25 mL Schlenk tube. Add 5 mL of diethyl ether at 0 °C, and dropwise add triethylamine (151.8 mg, 1.5 mmol, 3.0 eq) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 eq). After the addition is complete, warm the reaction mixture to 25 °C and react for 12 hours, then cool to room temperature, remove the solvent, and recrystallize the residue to obtain the ligand of formula 7f compound.

[0182] Examples 5 - 7

[0183] In the glove box, add the compound of formula 5g prepared in Example 3 (196.6 mg, 0.5 mmol, 1.0 eq) to a 25 mL Schlenk tube. Add 5 mL of diethyl ether at 0 °C, and dropwise add triethylamine (151.8 mg, 1.5 mmol, 3.0 eq) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 eq). After the addition is complete, warm the reaction mixture to 25 °C and react for 12 hours, then cool to room temperature, remove the solvent, and recrystallize the residue to obtain the ligand of formula 7g compound.

[0184] Examples 5 - 8

[0185] In the glove box, add the compound of formula 5h prepared in Example 3 (203.6 mg, 0.5 mmol, 1.0 eq) to a 25 mL Schlenk tube. Add 5 mL of diethyl ether at 0 °C, and dropwise add triethylamine (151.8 mg, 1.5 mmol, 3.0 eq) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 eq). After the addition is complete, warm the reaction mixture to 25 °C and react for 12 hours, then cool to room temperature, remove the solvent, and recrystallize the residue to obtain the ligand of formula 7h compound.

[0186] Examples 5 - 9

[0187] In the glove box, add the compound of formula 5i prepared in Example 3 (296.6 mg, 0.5 mmol, 1.0 eq) to a 25 mL Schlenk tube. Add 5 mL of diethyl ether at 0 °C, and dropwise add triethylamine (151.8 mg, 1.5 mmol, 3.0 eq) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 eq). After the addition is complete, warm the reaction mixture to 25 °C and react for 12 hours, then cool to room temperature, remove the solvent, and recrystallize the residue to obtain the ligand of formula 7i compound.

[0188] Examples 5 - 10

[0189] In a glove box, add the compound of formula 5j prepared in Example 3 (210.6 mg, 0.5 mmol, 1.0 eq) to a 25 mL Schlenk tube. Add 5 mL of diethyl ether at 0 °C, and dropwise add triethylamine (151.8 mg, 1.5 mmol, 3.0 eq) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 eq). After the addition is complete, warm the reaction mixture to 25 °C and react for 12 hours, then cool to room temperature, remove the solvent, and recrystallize the residue to obtain the ligand of formula 7j compound.

[0190] Example 5-11

[0191] In a glove box, add the compound of formula 5k prepared in Example 3 (198.6 mg, 0.5 mmol, 1.0 eq) to a 25 mL Schlenk tube. Add 5 mL of diethyl ether at 0 °C, and dropwise add triethylamine (151.8 mg, 1.5 mmol, 3.0 eq) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 eq). After the addition is complete, warm the reaction mixture to 25 °C and react for 12 hours, then cool to room temperature, remove the solvent, and recrystallize the residue to obtain the ligand of formula 7k compound.

[0192] Example 5-12

[0193] In a glove box, add the compound of formula 5o prepared in Example 3 (196.6 mg, 0.5 mmol, 1.0 eq) to a 25 mL Schlenk tube. Add 5 mL of diethyl ether at 0 °C, and dropwise add triethylamine (151.8 mg, 1.5 mmol, 3.0 eq) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 eq). After the addition is complete, warm the reaction mixture to 25 °C and react for 12 hours, then cool to room temperature, remove the solvent, and recrystallize the residue to obtain the ligand of formula 7l compound.

[0194] Example 5-13

[0195] In a glove box, add the compound of formula 5m prepared in Example 3 (204.6 mg, 0.5 mmol, 1.0 eq) to a 25 mL Schlenk tube. Add 5 mL of diethyl ether at 0 °C, and dropwise add triethylamine (151.8 mg, 1.5 mmol, 3.0 eq) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 eq). After the addition is complete, warm the reaction mixture to 25 °C and react for 12 hours, then cool to room temperature, remove the solvent, and recrystallize the residue to obtain the ligand of formula 7m compound.

[0196] Example 5-14

[0197] In the glove box, add the compound of formula 5n prepared in Example 3 (223.6 mg, 0.5 mmol, 1.0 eq) to a 25 mL Schlenk tube. Add 5 mL of diethyl ether at 0 °C, and dropwise add triethylamine (151.8 mg, 1.5 mmol, 3.0 eq) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 eq). After the addition is complete, warm the reaction mixture to 25 °C and react for 12 hours, then cool to room temperature, remove the solvent, and recrystallize the residue to obtain the ligand of formula 7n compound.

[0198] Example 5 - 15

[0199] In the glove box, add the compound of formula 5q prepared in Example 3 (196.6 mg, 0.5 mmol, 1.0 eq) to a 25 mL Schlenk tube. Add 5 mL of diethyl ether at 0 °C, and dropwise add triethylamine (151.8 mg, 1.5 mmol, 3.0 eq) and thionyl chloride (83.3 mg, 0.7 mmol, 1.4 eq). After the addition is complete, warm the reaction mixture to 25 °C and react for 12 hours, then cool to room temperature, remove the solvent, and recrystallize the residue to obtain the ligand of formula 7o compound.

[0200]

[0201] After testing, the data of the compound of formula 7b obtained in this example are as follows: 189.1 mg of 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 of the compound of formula 7c obtained in this example was detected as follows: 90.0 mg of white solid, melting point 112.1 - 113.7 °C, yield 41%. 1 H NMR (400 MHz, Chloroform - d) δ 8.28 - 8.26 (m, 1H), 7.40 - 7.36 (m, 1H), 7.29 (d, J = 1.3 Hz, 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 = 8.4 Hz, 1H), 5.62 (d, J = 9.3 Hz, 1H), 5.14 (d, J = 9.3 Hz, 1H), 2.91 - 2.89 (m, 2H), 1.25 (t, J = 7.6 Hz, 3H) ppm; 13 C NMR (101 MHz, Chloroform - d) δ 153.6, 148.3, 141.9, 137.9, 136.8, 135.0, 128.9, 128.8, 128.6, 128.5, 128.4, 128.2, 127.3, 127.1, 126.6, 126.3, 116.8, 108.0, 74.0, 71.6, 23.5, 14.9 ppm; HRMS - ESI (m / z): [M + H] + calcd for C 27 H 26 N3OS: 440.1797; found: 440.1793; [α] D 25 = -95.6 (c = 1.0, CHCl3).

[0203] The data of the compound of formula 7d obtained in this example was detected as follows: 163.1 mg of yellow solid, melting point 94.7 - 96.4 °C, yield 67%. 11H NMR (400 MHz, Chloroform-d) δ 8.22 - 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 = 8.35 Hz, 1H), 4.96 (d, J = 9.03 Hz, 1H) ppm; 13 13C NMR (101 MHz, Chloroform-d) δ 153.5, 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, 71.7 ppm; 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] Upon detection, the data of the compound of formula 7e obtained in this example are as follows: 87.8 mg of yellow solid, melting point 106.4 - 108.1 °C, yield 40%. 1 1H NMR (400 MHz, Chloroform-d) δ 8.27 - 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 = 8.1 Hz, 1H), 6.94 (s, 1H), 6.83 - 6.78 (m, 2H), 6.33 (d, J = 8.4 Hz, 1H), 5.60 (d, J = 9.3 Hz, 1H), 5.09 (d, J = 9.3 Hz, 1H), 2.43 (s, 3H), 2.16 (s, 3H) ppm; 1313C NMR (101 MHz, Chloroform-d) δ 153.7, 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, 18.5 ppm; 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] Upon detection, the data of the compound of formula 7f obtained in this example are as follows: 116.3 mg of white solid, melting point 110.4 - 112.1 °C, and yield 53%. 1 1H NMR (400 MHz, Chloroform-d) δ 8.27 (d, J = 6.0 Hz, 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 = 8.0 Hz, 1H), 6.92 (s, 1H), 6.82 - 6.80 (m, 2H), 6.34 (d, J = 8.4 Hz, 1H), 5.62 (d, J = 13.2 Hz, 1H), 5.09 (d, J = 13.2 Hz, 1H), 2.42 (s, 3H), 2.13 (s, 3H) ppm; 13 13C NMR (101 MHz, Chloroform-d) δ 153.8, 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, 18.2 ppm; HRMS-ESI (m / z): [M+H] + calcd for C 27 H 26 N3OS: 440.1796; found: 440.1797; [α] D 25 = -65.8 (c = 1.0, CHCl3).

[0206] Upon detection, the data of the compound of formula 7g obtained in this example are as follows: 79.0 mg of yellow solid, melting point 102.6 - 105.4 °C, and yield 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] Upon detection, the data of the compound of formula 7h obtained in this example are 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; 1313C NMR (101 MHz, Chloroform-d) δ 154.3, 148.7, 140.6, 138.1, 138.0, 137.9, 137.8, 137.4, 133.7, 129.7, 129.6, 129.5, 128.9, 128.5, 128.4, 127.9, 126.3, 117.9, 113.6, 80.9, 69.4, 20.9, 19.4, 19.1 ppm; HRMS-ESI (m / z): [M+H] + calcd for C 28 H 28 N3OS: 454.1953; found: 454.1945; [α] D 25 = +60.0 (c = 1.0, CHCl3).

[0208] Upon detection, the data of the compound of formula 7i obtained in this example are as follows: 233.2 mg of white solid, melting point 116.9 - 121.3 °C, yield 73%. 1 1H NMR (400 MHz, Chloroform-d) δ 8.04 - 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 - 7.04 (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 = 9.1 Hz, 1H), 4.80 (d, J = 9.1 Hz, 1H) ppm; 13 13C NMR (101 MHz, Chloroform-d) δ 153.4, 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, 72.6 ppm; 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] Upon detection, the data of the compound of formula 7j obtained in this example are as follows: 142.1 mg of white solid, melting point 157.5 - 160.1 °C, and yield 61%. 1 H NMR (400 MHz, Chloroform-d) δ 8.37 (d, J = 5.0 Hz, 1H), 7.42 (t, J = 6.9 Hz, 3H), 7.35 - 7.17 (m, 10H), 7.04 - 6.83 (m, 2H), 6.55 (d, J = 8.2 Hz, 1H), 5.83 (d, J = 8.4 Hz, 1H), 4.77 (d, J = 8.4 Hz, 1H), 2.93 - 2.87 (m, 2H), 2.68 - 2.63 (m, 1H), 2.33 - 2.28 (m, 1H), 1.32 (t, J = 7.4 Hz, 3H), 0.70 (t, J = 7.4 Hz, 3H) ppm; 13 C NMR (101 MHz, Chloroform-d) δ 154.3, 148.7, 146.8, 144.3, 138.1, 137.8, 137.1, 135.0, 129.5, 128.9, 128.7, 128.5, 127.9, 127.0, 126.8, 126.2, 117.8, 113.6, 82.3, 69.3, 24.3, 24.3, 15.8, 15.3 ppm; 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] Upon detection, the data of the compound of formula 7k obtained in this example are as follows: 53.2 mg of white solid, melting point 164.8 - 166.5 °C, and yield 24%. 1 H NMR (400 MHz, Chloroform-d) δ 8.36 - 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 = 8.4 Hz, 1H), 5.59 (d, J = 6.1 Hz, 1H), 4.85 (d, J = 6.1 Hz, 1H), 2.25 (s, 3H) ppm; 1313C NMR (101 MHz, Chloroform-d) δ 148.7, 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, 18.7 ppm; 19 19F NMR (376 MHz, Chloroform-d) δ -113.47 (d, J = 7.3 Hz) 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] Upon detection, the data of the compound of formula 7l obtained in this example are: 210.2 mg of yellow solid, melting point 108.2 - 112.6 °C, yield 96%. 1 1H NMR (400 MHz, Chloroform-d) δ 8.02 (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 = 8.4 Hz, 1H), 5.63 (d, J = 9.3 Hz, 1H), 5.15 (d, J = 9.3 Hz, 1H), 2.42 (s, 3H), 2.04 (s, 3H) ppm; 13 13C NMR (101 MHz, Chloroform-d) δ 151.2, 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, 17.0 ppm; 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] Upon detection, the data of the compound of formula 7m obtained in this example are as follows: 86.5 mg of 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] Upon detection, the data of the compound of formula 7n obtained in this example are as follows: 76.4 mg of 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),7.04-6.97(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; 1313C NMR (101 MHz, Chloroform-d) δ 154.4, 149.4, 140.0 (q, J = 33.8 Hz), 136.0, 135.9, 135.4, 134.7, 131.0, 129.0, 128.7, 128.6, 128.6, 128.1, 127.3, 127.0, 126.6, 123.8, 121.0, 112.3 (q, J = 3.5 Hz), 103.9 (q, J = 4.0 Hz), 73.8, 71.9, 18.5 ppm; 19 19F NMR (376 MHz, Chloroform-d) δ -65.1 ppm; HRMS-ESI (m / z): [M+H] + calcd for C 27 H 23 N3OSF3: 494.1514; found: 494.1510; [α] D 25 = -76.6 (c = 1.0, CHCl3).

[0214] The data of the compound of formula 7o obtained in this example were as follows: 98.8 mg of white solid, melting point 75.4 - 77.2 °C, yield 45%. 1 1H NMR (400 MHz, Chloroform-d) δ 7.33 - 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 = 7.4 Hz, 1H), 6.11 (d, J = 8.2 Hz, 1H), 5.63 (d, J = 9.3 Hz, 1H), 5.07 (d, J = 9.3 Hz, 1H), 2.47 (s, 3H), 2.42 (s, 3H) ppm; 13 13C NMR (101 MHz, Chloroform-d) δ 138.2, 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, 18.9 ppm; 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 Schlenk tube. Then the Schlenk tube was removed from the glove box, 0.5 mL of tetrahydrofuran was added under nitrogen, and the mixture was stirred at room temperature for 1 hour. Then, 2-cyclohexenyl 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 respectively added to the mixture, and the reaction was carried out at 65 °C for 16 hours to obtain a pale yellow oily liquid (13.5 mg, yield 40%).

[0217]

[0218] 1 H NMR (400 MHz, Chloroform-d) δ 7.35 - 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 (101 MHz, Chloroform-d) δ 140.9, 131.4, 129.2, 128.2, 127.4, 125.8, 42.8, 37.2, 29.0, 25.4, 21.3 ppm.

[0219]

[0220] In summary, the preparation method of the present invention is simple, and chiral N-P ligands and N-S ligands can be prepared. These ligands can be used as catalysts for asymmetric catalytic reactions, and have economic practicality and industrial application prospects.

[0221] In addition, the inventors of this case also carried out experiments in the manner of Examples 1 - 5 with other raw materials and conditions listed in this specification, and corresponding effects can also be achieved. Chiral N-P ligands and N-S ligands can be prepared, and these ligands can be used as catalysts for asymmetric catalytic reactions, with broad application prospects.

[0222] The above embodiments are merely exemplary and do not constitute any limitation to the scope of the present invention. Those skilled in the art should understand that details and forms of the technical solution of the present invention may be modified or replaced without departing from the spirit and scope of the present invention, but such modifications and replacements all fall within the protection scope of the present invention.

Claims

1. An N-P ligand and an N-S ligand based on a chiral 1,2-ethylenediamine backbone, characterized in that, 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). Among them, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 are each independently selected from at least hydrogen, halogen, substituted or unsubstituted C1-C 30 alkyl, alkoxy or aryl; R 10 are each independently selected from C1-C 30 alkyl or aryl; Ar 1 and Ar 2 are each independently selected from at least substituted or unsubstituted C6-C 30 aryl groups.

2. The N-P ligand and N-S ligand of the chiral 1,2-ethylenediamine backbone according to claim 1, characterized in that, The N-P ligand with a chiral 1,2-ethylenediamine backbone is selected from the structures shown in any one of the following formulas (6a)-(6p):

3. The N-P ligand and N-S ligand of the chiral 1,2-ethylenediamine backbone according to claim 1, characterized in that, The N-S ligand with a chiral 1,2-ethylenediamine backbone is selected from the structures shown in any one of the following formulas (7a)-(7o):

4. The preparation method of the N-P ligand and N-S ligand of the chiral 1,2-ethylenediamine skeleton according to claim 1, characterized in that, A compound represented by formula (III), a phosphorus reagent, a sulfoxide reagent, a base, and an organic solvent are uniformly mixed and reacted to obtain an N-P ligand and an N-S ligand with a chiral 1,2-ethylenediamine backbone having the structures shown in formulas (I) and (II). Among them, in formula (I), formula (II) and formula (III), R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 are each independently selected from at least hydrogen, halogen, substituted or unsubstituted C1-C 30 alkyl, alkoxy or aryl; R 10 are each independently selected from at least C1-C 30 alkyl or aryl; Ar 1 and Ar 2 are each independently selected from at least substituted or unsubstituted C6-C 30 aryl; Ar 1 and Ar 2 have the same structure; the chemical formula of the phosphorus reagent is R 10 PCl2, wherein R 10 are each independently selected from at least C1-C 30 alkyl or aryl; the molar ratio of the phosphorus reagent and the sulfoxide reagent to the compound shown in formula (III) is 1.5:

1.

5. The preparation method according to claim 4, characterized in that: 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.

6. The preparation method according to claim 4, characterized in that: 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, cyclohexane, and dichloromethane.

7. The preparation method according to claim 4, characterized in that: The temperature of the reaction is 0-150 °C, and the time of the reaction is 1-48 h.

8. Use of the N-P ligand and N-S ligand with a chiral 1,2-ethylenediamine backbone according to claim 1 as a catalyst or in the field of synthesis of catalysts.

9. The application according to claim 8, characterized in that: The catalyst is a catalyst for an asymmetric catalytic reaction.

10. The application according to claim 8, characterized in that: The catalyst is a complex formed by the N-P ligand or N-S ligand with a chiral 1,2-ethylenediamine backbone according to claim 1 and a palladium metal catalyst.

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