Novel double-five-membered ring coordination NNN tridentate chiral ligand based on pyridine skeleton and application of novel double-five-membered ring coordination NNN tridentate chiral ligand in asymmetric catalytic reaction

Abstract

The invention discloses a novel double-five-membered ring coordination NNN tridentate chiral ligand based on a pyridine skeleton and application of the novel double-five-membered ring coordination NNN tridentate chiral ligand in asymmetric catalytic reaction, and belongs to the technical field of asymmetric metal catalysis and organic synthesis. The novel double five-membered ring coordination NNN tridentate chiral ligand based on the pyridine skeleton has a unique structure and properties, and can significantly improve the catalytic efficiency and stereoselectivity of reactions such as free radical asymmetric functionalization. The NNN tridentate chiral ligand is suitable for a cheap metal catalyzed free radical asymmetric functionalization reaction, is especially suitable for an asymmetric phosphorylation reaction, and has a wide application prospect in free radical asymmetric functionalization and related reactions.

Description

Technical Field

[0001] This invention relates to the fields of asymmetric metal catalysis and organic synthesis technology, and in particular to novel bi-five-membered ring coordinated NNN tridentate chiral ligands based on a pyridine skeleton and their application in asymmetric catalytic reactions. Background Technology

[0002] Radical asymmetric functionalization reactions, as a crucial method for constructing chiral compounds, play an irreplaceable role in synthetic chemistry, medicinal chemistry, life sciences, and materials research. Traditional asymmetric functionalization reactions have long relied on precious metals and ligands with complex structures, facing challenges such as high cost and poor environmental friendliness, thus limiting further development. In recent years, due to their abundant reserves, environmental friendliness, and unique reactivity, inexpensive metals have become an emerging research hotspot for catalyzed radical asymmetric functionalization reactions. The synthesis of novel chiral ligands is key to further developing and breaking through these reaction types. Chiral tridentate ligands, with their rich coordination modes and easily modifiable structures, are widely used in inexpensive metal-catalyzed radical asymmetric functionalization reactions.

[0003] In existing applications in this field, four representative tridentate chiral ligands and their coordination modes for radical asymmetric functionalization reactions catalyzed by inexpensive metals are listed below:

[0004] One of the significant characteristics of the aforementioned tridentate chiral ligands is the tridentate coordination mode in which the three coordinating atoms form a "six-membered ring fused to a five-membered ring" with the metal center; another significant characteristic is that the chiral control site (chiral R group) is close to the weakly coordinated alkylamine side. However, the series of ligands based on cinchona bark as the basic framework have complex structures, low atom economy, and relatively simple coordination modes, which limits their ability to control the chirality of challenging substrates.

[0005] To address the aforementioned technical problems, the inventors' research team, in Chinese invention patent publication number CN118146274A, innovatively introduced facial chirality into the ligand structure based on the chiral Ugi amine skeleton, and developed a series of PNN tridentate chiral ligands simultaneously possessing carbon atom chirality, phosphine chirality, and facial chirality. Representative chiral tridentate ligands and their coordination modes are shown below:

[0006] The aforementioned PNN tridentate chiral ligands have also been successfully applied to radical asymmetric functionalization reactions catalyzed by inexpensive metals. These ligands also possess a tridentate coordination mode of "six-membered ring fused to five-membered ring," but their chiral control sites are closer to the strongly coordinated phosphorus atom. These ligands exhibit excellent catalytic efficiency and stereoselectivity in radical asymmetric functionalization and related reactions, and are easy to synthesize and derivatize, making them significant for the development of radical asymmetric functionalization reactions. However, Ugiamine, one of their starting materials, is relatively expensive, resulting in a high economic cost for synthesizing this series of ligands.

[0007] Furthermore, most of the tridentate chiral ligands previously reported for use in inexpensive metal-catalyzed radical asymmetric functionalization reactions exhibit a tridentate coordination mode of "six-membered ring fused to five-membered ring". However, the six-membered ring has lower ring strain and the arrangement of groups is more dispersed, resulting in the chiral control site being farther from the metal center, which may affect chiral control to some extent. Summary of the Invention

[0008] In view of the above-mentioned deficiencies of the prior art, in a first aspect of the present invention, a novel bipentacyclic ring-coordinated NNN tridentate chiral ligand based on a pyridine framework is provided, having a structure as described in general formula I:

[0009] In the formula, R is an alkyl or aryl group; R 1 It is one of hydrogen, alkyl, or aryl; R 2 It is one of hydrogen, alkyl, or aryl; R 3 It is alkyl or aryl; X is either carbon or sulfur. When X is carbon, the dashed line between X and oxygen indicates that there is no bond, meaning the bridging group is carbonyl. When X is an element, the dashed line between X and oxygen indicates that there is a bond, meaning the bridging group is sulfonyl.

[0010] Preferably, in the novel pyridine-based pyridine skeleton-coordinated NNN tridentate chiral ligand, R is one of methyl, ethyl, benzyl, isopropyl, tert-butyl, or one of phenyl, 1-naphthyl, 2-naphthyl, 2-methylphenyl, 2,6-dimethylphenyl, 2,6-dimethoxyphenyl, 3,5-di-tert-butylphenyl, 3,5-diphenylphenyl, 3,5-di-tert-butyl-4-methoxy-phenyl, 4-methoxyphenyl, 4-trifluoromethylphenyl, 4-tert-butylphenyl, 4-adamantylphenyl, 4-phenylphenyl, 4-(9-carbazolyl)phenyl, 4-cyclohexylphenyl, 4-tri-n-butylsilylphenyl, 4-triisopropylsilylphenyl, 4-triphenylsilylphenyl; R 1It is hydrogen, or one of methyl, ethyl, tert-butyl, methoxy, trifluoromethyl, or one of phenyl, 3,5-di-tert-butylphenyl, 3,5-di-trifluoromethylphenyl, 3,5-di-tert-butyl-4-methoxy-phenyl; R 2 It is hydrogen, or one of methyl, ethyl, isopropyl, cyclohexyl, tert-butyl, or phenyl or 3,5-di-tert-butylphenyl; R 3 It is one of methyl, ethyl, n-butyl, isopropyl, tert-butyl, or phenyl.

[0011] More preferably, the novel pyridine-based bipentacyclic ring coordinated NNN tridentate chiral ligands include compounds with the following structural formulas L1 to L62:

[0012]

[0013]

[0014]

[0015]

[0016]

[0017]

[0018]

[0019]

[0020]

[0021]

[0022]

[0023]

[0024]

[0025]

[0026] .

[0027] For the purpose of simplifying the compound structure, the partially substituted groups mentioned above are represented by symbols commonly used in the art, such as "Me" for methyl, "Bn" for benzyl, " t"-Bu" indicates tert-butyl, "Ph" indicates phenyl, "CF3" indicates trifluoromethyl, "Ad" indicates adamantyl, and "Cy" indicates cyclohexyl. n "-Bu" indicates n-butyl, i "-Pr" represents isopropyl, "Et" represents ethyl, and "Ar" represents aryl, with their specific types shown in the corresponding compounds.

[0028] Combining the above technical solutions, this invention replaces six-membered ring coordination with five-membered ring coordination, thereby developing a tridentate ligand with a double five-membered ring coordination mode. Due to the greater ring strain of five-membered ring coordination, the closer arrangement between groups allows the chiral source to be closer to the metal center, thus enabling more efficient control of enantioselectivity. Furthermore, this invention designs the ligand chiral control site closer to the strongly coordinating atom (the nitrogen atom of the pyridine unit), offering potential advantages in enantioselectivity regulation. The coordination mode of the tridentate chiral ligand is shown below:

[0029] Based on the above ideas, this invention develops a series of novel bi-five-membered ring coordinated NNN tridentate chiral ligands (hereinafter referred to as NNN tridentate chiral ligands) based on a pyridine skeleton and applies them to asymmetric phosphorylation and other related reactions. This invention uses inexpensive and readily available chiral sulfinamides as the chiral source, avoiding the use of relatively expensive Ugi amines as raw materials, and introduces new carbon chiral centers through the addition of different Grignard reagents to chiral sulfinamides, resulting in highly precise and tunable chiral sites.

[0030] The specific structural design principle of the NNN tridentate chiral ligand developed in this invention is as follows: Figure 1 As shown.

[0031] Figure 1 In this context, M represents the coordinating metal, and Y represents the fourth coordinating group besides the tripentate ligand and the metal, such as the coordinating anion of a metal compound, a solvent, or a reactant phosphite. The nitrogen atom of the pyridine unit in the ligand acts as a strong coordinating site and also contains a deprotonable secondary amine coordinating site, enabling it to form an electron-rich σ-coordination with the metal and enhance reactivity. The third coordinating site in the ligand is a dialkylamine weak coordinating site, capable of forming a metastable coordination with the metal. This metastable coordination stabilizes the high-valence metal reactive intermediate and can dissociate to form an effective reactive site. The reactivity can be further enhanced by adjusting the steric hindrance of the chiral R group and the substituent R of the pyridine unit. 1 Spatial or electronic effects can enable effective chiral control in the radical functionalization process. Furthermore, the chiral group R on the weakly coordinated side... 2 It can also provide additional chiral environments.

[0032] The synthetic routes for NNN tridentate chiral ligands L1~L49 are as follows:

[0033]

[0034] Wherein, "rt" represents room temperature (25 ℃); "4 h", "16 h", "1 h" represent reaction time, and the same applies to subsequent values.

[0035] In the above synthetic routes, in the general structural formulas of compounds 1, int, 2, 3, or products L1~L49, R represents the corresponding alkyl or aryl group. The alkyl group is selected from methyl, ethyl, benzyl, isopropyl, and tert-butyl, and the aryl group is selected from phenyl, 1-naphthyl, 2-naphthyl, 2-methylphenyl, 2,6-dimethylphenyl, 2,6-dimethoxyphenyl, 3,5-di-tert-butylphenyl, 3,5-diphenylphenyl, 3,-di-tert-butyl-4-methoxy-phenyl, 4-methoxyphenyl, 4-trifluoromethylphenyl, 4-tert-butylphenyl, 4-adamantylphenyl, 4-phenylphenyl, 4-(9-carbazolyl)phenyl, 4-cyclohexylphenyl, 4-tri-n-butylsilylphenyl, 4-triisopropylsilylphenyl, and 4-triphenylsilylphenyl. 1 It is hydrogen, alkyl, or aryl; the alkyl group is selected from methyl, ethyl, tert-butyl, methoxy, and trifluoromethyl; the aryl group is selected from phenyl, 3,5-di-tert-butylphenyl, 3,5-di-trifluoromethylphenyl, and 3,5-di-tert-butyl-4-methoxy-phenyl; R 2 It is hydrogen, alkyl, or aryl; the alkyl group is selected from methyl, ethyl, isopropyl, cyclohexyl, and tert-butyl; the aryl group is selected from phenyl and 3,5-di-tert-butylphenyl; R 3 It is an alkyl or aryl group, where the alkyl group is selected from methyl, ethyl, n-butyl, isopropyl, and tert-butyl, and the aryl group is phenyl.

[0036] The synthetic route for the NNN tridentate chiral ligand L50 is as follows:

[0037] The synthetic route for NNN tridentate chiral ligands L51~L60 is as follows:

[0038] In the general structural formulas of products L51~L60 involved in the above synthetic route, R 7 The corresponding alkyl or aryl group is selected from methyl, methoxy, and trifluoromethyl, and the aryl group is selected from phenyl or 3,5-di-tert-butylphenyl.

[0039] The synthetic route for the NNN tridentate chiral ligand L61 is as follows:

[0040] The synthetic route for the NNN tridentate chiral ligand L62 is as follows:

[0041] In a second aspect of the invention, the application of the novel pyridine-based bipentacyclic coordinated NNN tridentate chiral ligand of the first aspect of the invention in radical asymmetric functionalization reactions is provided.

[0042] Preferably, the method of application includes the following steps: using the product generated by the complexation reaction of a novel pyridine-based bis-pentane coordinated NNN tridentate chiral ligand with a metal compound as a catalyst for a radical asymmetric functionalization reaction.

[0043] More preferably, the metal atoms in the metal compound include at least one of Cu, Fe, Zn, Mn, Cr, Co, Au, Ag, Ni, Ti, Pt, Pd, Rh, Ru, and Ir.

[0044] Furthermore, the metal compound includes at least one of CuI, CuBr, CuCl, CuCN, Cu2O, Cu(CH3CN)4PF6, (CuOTf)2·PhH, (CuOTf)2·PhMe, Cu(OTf)2, Cu(NO3)2, Cu(OAc)2, Cu(OAc)2·H2O, Cu(acac)2, CuCl2, CuBr2, Cu(BF4)2, and CuSO4.

[0045] Preferably, the free radical asymmetric functionalization reaction is asymmetric phosphorylation and other related reactions.

[0046] More preferably, the asymmetric phosphorylation reaction process includes the following steps: (1) Under the protection of an inert gas, a metal compound, a novel pyridine skeleton-based double five-membered ring coordinated NNN tridentate chiral ligand, a photocatalyst and a base were added. After adding a solvent, the complexation reaction was carried out by stirring at room temperature to obtain a catalyst solution. (2) Add olefins and phosphites. After the addition is complete, carry out an asymmetric phosphorylation reaction under the light source at the target temperature and target wavelength. After the reaction is completed, the crude product is purified to obtain the target product.

[0047] Furthermore, in step (1), the base is at least one of lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide, sodium ethoxide, sodium carbonate, potassium carbonate, cesium carbonate, potassium phosphate, 1,8-diazabicyclo-bicyclo(5,4,0)-7-undecene (DBU), 2-tert-butyl-1,1,3,3-tetramethylguanidine (BTMG), and (tert-butylimino)tris(pyrrolidine)phosphine (BTPP); the solvent is at least one of methanol, ethanol, isopropanol, n-butanol, isobutanol, tert-butanol, methyl tert-butyl ether, 1,4-dioxane, tetrahydrofuran, dichloromethane, 1,2-dichloroethane, toluene, or 2-methyl-tetrahydrofuran; the reaction time of the complexation reaction is ≤60 min; and the molar ratio of the metal complex, the novel pyridine-based bis-five-membered ring coordinated NNN tridentate chiral ligand, the photocatalyst, and the base is 1:1.2:1:10.

[0048] Furthermore, in step (2), the target temperature is -20 ~ 50 ℃; the time for the asymmetric phosphorylation reaction is 2 ~ 120 h; and the molar ratio of phosphite to olefin is 1:1.5 ~ 3.

[0049] Taking the addition of a copper compound as an example, the reaction process of the asymmetric phosphorylation reaction involved in this invention is as follows:

[0050] Wherein, ligand L* represents the NNN tridentate chiral ligand, R 4 R 5 Represents aryl or alkyl, R 6 PC represents alkyl groups, and PC represents photocatalysts.

[0051] In a third aspect of the invention, a catalyst for radical asymmetric functionalization reaction is provided, said catalyst being generated by a complexation reaction of a novel pyridine-based bis-pentane coordinated NNN tridentate chiral ligand with a metal compound.

[0052] Compared with the prior art, the present invention has the following advantages and beneficial effects: This invention provides a novel bi-five-membered ring coordinated NNN tridentate chiral ligand based on a pyridine skeleton, which has unique structure and properties and can significantly improve the catalytic efficiency and stereoselectivity of reactions such as radical asymmetric functionalization.

[0053] This invention provides an application of a novel bi-five-membered ring coordinated NNN tridentate chiral ligand based on a pyridine skeleton, which is suitable for radical asymmetric functionalization reactions catalyzed by inexpensive metals, and is especially suitable for asymmetric phosphorylation reactions.

[0054] This invention provides a catalyst generated by the complexation reaction of a novel pyridine-based double five-membered ring coordinated NNN tridentate chiral ligand with a metal compound, which has broad application prospects in radical asymmetric functionalization and related reactions. Attached Figure Description Figure 1 A schematic diagram illustrating the structural design principle of the NNN tridentate chiral ligand. Detailed Implementation

[0055] The present invention is further illustrated below by way of embodiments, but the invention is not limited to the scope of the embodiments described herein. Experimental methods in the following embodiments that do not specify specific conditions were performed according to conventional methods and conditions, or as selected according to the product instructions.

[0056] Example 1 The preparation of intermediate int-1 of NNN tridentate chiral ligands L1~L22 is as follows:

[0057] In a 250 mL round-bottom flask purged with nitrogen, S1 (pyridine-2-carboxaldehyde, 5.36 g, 50 mmol, 1.0 equivalent), (R)-tert-butylsulfinamide (9.09 g, 75 mmol, 1.5 equivalent), tetraisopropyl titanate (21.32 g, 75 mmol, 1.5 equivalent), and anhydrous tetrahydrofuran (100 mL, 0.50 M) were added sequentially, and the mixture was heated to 70 °C and reacted for 4.0 h. After the reaction was complete, 50 mL of saturated ammonium chloride aqueous solution was added to the reaction mixture, and the mixture was filtered through diatomaceous earth. The organic phase was separated from the filtrate, and the aqueous phase was extracted three times with ethyl acetate (50 mL each time). The obtained organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain product int-1 (8.67 g, 41.22 mmol), with a yield of 82%.

[0058] Example 2 The preparation of the NNN tridentate chiral ligand L1, the reaction process is as follows:

[0059]

[0060] In a 250 mL round-bottom flask purged with nitrogen, intermediate int-1 (3.00 g, 14.3 mmol, 1.0 equivalent) from Example 1 and anhydrous dichloromethane (40 mL, 0.36 M) were added dropwise. A 1.0 M tetrahydrofuran solution of methyl magnesium bromide (28.5 mL, 28.5 mmol, 2.0 equivalent) was added dropwise to the resulting solution at -48 °C, and the reaction was carried out for 4 h. The resulting reaction solution was then heated to room temperature and reacted for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (50 mL) was added to the reaction solution, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate (50 mL each time). The resulting organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain product S2 (2.04 g, 9.01 mmol), with a yield of 63%.

[0061] Transfer all of the product S2 from the previous step to a 100 mL round-bottom flask, add 3.8 mL of 12.0 M hydrochloric acid aqueous solution (45.1 mmol, 5.0 equivalent) and 7.5 mL of anhydrous methanol (1.20 M), and react at room temperature for 1 h. After the reaction is complete, add 20 mL of saturated sodium bicarbonate aqueous solution and solid sodium bicarbonate. After the reaction stops bubbling, extract the aqueous phase three times with ethyl acetate (40 mL each time). Dry the resulting organic phase with anhydrous sodium sulfate and then evaporate to dryness under reduced pressure. Crude product S3 is obtained without further separation or purification.

[0062] The crude product S3 from the previous step was transferred to a 100 mL round-bottom flask, and N,N-dimethylglycine (976 mg, 9.46 mmol, 1.05 equivalents), 4-dimethylaminopyridine (DMAP, 110 mg, 0.90 mmol, 0.10 equivalents), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 1.90 g, 9.91 mmol, 1.1 equivalents) were added sequentially. After purging with nitrogen, dichloromethane (DCM, 23 mL, 0.40 M) was added at 0 °C. The reaction was then allowed to return to room temperature for 12 h. After the reaction was complete, water (20 mL) was added to quench the reaction, and the aqueous phase was extracted three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product NNN tridentate ligand L1 (colorless oily liquid, 1.31 g, yield 70%).

[0063] 1H NMR (400 MHz, CDCl3) δ 8.61 - 8.55 (m, 1H), 8.08 (br, 1H), 7.70 -7.60 (m, 1H), 7.31 - 7.15 (m, 2H), 5.26 - 5.14 (m, 1H), 3.05 - 2.91 (m, 2H),2.30 (s, 6H), 1.50 (d, J = 6.8 Hz, 3H). Example 3 The preparation of the NNN tridentate chiral ligand L2, the reaction process is as follows:

[0064]

[0065] In a 250 mL round-bottom flask purged with nitrogen, intermediate int-1 (2.10 g, 10.0 mmol, 1.0 equivalent) from Example 1 and anhydrous dichloromethane (25 mL, 0.40 M) were added dropwise. A 1.0 M solution of benzyl magnesium bromide in tetrahydrofuran (20.0 mL, 20.0 mmol, 2.0 equivalent) was added dropwise to the resulting solution at -48 °C, and the reaction was carried out for 4 h. The resulting reaction solution was then heated to room temperature and reacted for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (50 mL) was added to the reaction solution, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate (50 mL each time). The resulting organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain product S4 (1.22 g, 4.03 mmol), with a yield of 40%.

[0066] Transfer all of the product S4 from the previous step to a 100 mL round-bottom flask, add 1.7 mL of 12.0 M hydrochloric acid aqueous solution (20.2 mmol, 5.0 equivalent) and anhydrous methanol (3.4 mL, 1.20 M), and react at room temperature for 1 h. After the reaction is complete, add 20 mL of saturated sodium bicarbonate aqueous solution and solid sodium bicarbonate. After the reaction stops bubbling, extract the aqueous phase three times with ethyl acetate (40 mL each time). Dry the resulting organic phase with anhydrous sodium sulfate and then evaporate to dryness under reduced pressure. Crude product S5 is obtained without further separation or purification.

[0067] Transfer all of the crude product S5 from the previous step to a 100 mL round-bottom flask, and add N,N-dimethylglycine (436 mg, 4.23 mmol, 1.05 equivalents), 4-dimethylaminopyridine (DMAP, 49.2 mg, 0.40 mmol, 0.10 equivalents), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 850 mg, 4.43 mmol, 1.1 equivalents) sequentially. After purging with nitrogen, add dichloromethane (DCM, 10 mL, 0.40 M) at 0 °C. Then, allow the mixture to return to room temperature and react for 12 h. After the reaction is complete, quench with water (20 mL), and extract the aqueous phase three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN tridentate chiral ligand L2 (white solid, 801 mg, yield 70%).

[0068] 1 H NMR (400 MHz, CDCl3) δ 8.63 - 8.57 (m, 1H), 8.05 (d, J = 8.5 Hz, 1H),7.57 - 7.48 (m, 1H), 7.24 - 7.11 (m, 4H),7.09 - 7.00 (m, 2H), 6.99 - 6.92 (m,1H), 5.38 - 5.27 (m, 1H), 3.28 - 3.09 (m, 2H), 3.00 - 2.85 (m, 2H), 2.20 (s,6H). 13 C NMR (101 MHz, CDCl3) δ 170.21, 159.67, 149.51, 137.61, 136.38,129.52, 128.35, 126.56, 122.64, 122.49, 63.37, 55.05, 46.08, 42.2. Example 4 The preparation of the NNN tridentate chiral ligand L3, the reaction process is as follows:

[0069]

[0070] In a 100 mL round-bottom flask purged with nitrogen, intermediate int-1 (1.26 g, 6.0 mmol, 1.0 equivalent) from Example 1 and anhydrous dichloromethane (15 mL, 0.40 M) were added dropwise. A 1.0 M tetrahydrofuran solution of tert-butylmagnesium bromide (12.0 mL, 12.0 mmol, 2.0 equivalent) was added dropwise to the resulting solution at -48 °C, and the reaction was carried out for 4 h. The resulting reaction solution was then heated to room temperature and reacted for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (30 mL) was added to the reaction solution, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate (30 mL each time). The resulting organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain product S6 (280 mg, 1.05 mmol), with a yield of 18%.

[0071] Transfer all of the product S6 from the previous step to a 50 mL round-bottom flask, add 0.4 mL of 12.0 M hydrochloric acid aqueous solution (5.3 mmol, 5.0 equivalent) and 0.9 mL of anhydrous methanol (1.20 M), and react at room temperature for 1 h. After the reaction is complete, add 10 mL of saturated sodium bicarbonate aqueous solution and solid sodium bicarbonate. After the reaction stops bubbling, extract the aqueous phase three times with ethyl acetate (20 mL each time). Dry the resulting organic phase with anhydrous sodium sulfate and then evaporate to dryness under reduced pressure. Crude product S7 is obtained without further separation or purification.

[0072] Transfer all of the crude product S7 from the previous step to a 50 mL round-bottom flask, and add N,N-dimethylglycine (114 mg, 1.10 mmol, 1.05 equivalents), 4-dimethylaminopyridine (DMAP, 12.8 mg, 0.10 mmol, 0.10 equivalents), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 221 mg, 1.16 mmol, 1.1 equivalents) sequentially. After purging with nitrogen, add dichloromethane (DCM, 2.5 mL, 0.40 M) at 0 °C. Then, allow the mixture to return to room temperature and react for 12 h. After the reaction is complete, quench with water (20 mL), and extract the aqueous phase three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN tridentate chiral ligand L3 (colorless oily liquid, 128 mg, yield 49%).

[0073] 1 H NMR (400 MHz, CDCl3) δ 8.59 - 8.53 (m, 1H), 8.33 (d, J= 9.6 Hz, 1H),7.62 - 7.54 (m, 1H), 7.21 - 7.11 (m, 2H), 4.91 (d, J = 9.8 Hz, 1H), 3.07 - 2.86(m, 2H), 2.30 (s, 6H), 0.93 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 170.13, 158.84, 148.87, 135.61, 124.24,122.18, 63.53, 60.77, 46.20, 36.20, 26.90. Example 5 The preparation of the NNN tridentate chiral ligand L4, the reaction process is as follows:

[0074]

[0075] In a 250 mL round-bottom flask purged with nitrogen, intermediate int-1 (2.00 g, 9.5 mmol, 1.0 equivalent) from Example 1 and anhydrous dichloromethane (24 mL, 0.40 M) were added dropwise. A 1.0 M tetrahydrofuran solution of magnesium phenyl bromide (19.0 mL, 19.0 mmol, 2.0 equivalent) was added dropwise to the resulting solution at -48 °C, and the reaction was carried out for 4 h. The resulting reaction solution was then heated to room temperature and reacted for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (50 mL) was added to the reaction solution, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate (50 mL each time). The resulting organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain product S8 (1.74 g, 6.03 mmol), with a yield of 64%.

[0076] Transfer all of the product S8 from the previous step to a 100 mL round-bottom flask, add 2.5 mL of 12.0 M hydrochloric acid aqueous solution (30.2 mmol, 5.0 equivalent) and 5.0 mL of anhydrous methanol (1.20 M), and react at room temperature for 1 h. After the reaction is complete, add 20 mL of saturated sodium bicarbonate aqueous solution and solid sodium bicarbonate. After the reaction stops bubbling, extract the aqueous phase three times with 40 mL of ethyl acetate each time. Dry the resulting organic phase with anhydrous sodium sulfate and then evaporate to dryness under reduced pressure. Crude product S9 is obtained without further separation or purification.

[0077] Transfer all of the crude product S9 from the previous step to a 100 mL round-bottom flask, and add N,N-dimethylglycine (653 mg, 6.33 mmol, 1.05 equivalents), 4-dimethylaminopyridine (DMAP, 73.7 mg, 0.60 mmol, 0.10 equivalents), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 0.27 g, 6.63 mmol, 1.1 equivalents) sequentially. After replacing the atmosphere with nitrogen, add dichloromethane (DCM, 15 mL, 0.40 M) at 0 °C. Then, return to room temperature and react for 12 h. After the reaction is complete, quench with water (20 mL), and extract the aqueous phase three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN tridentate chiral ligand L4 (white solid, 858 mg, yield 53%).

[0078] 1 H NMR (400 MHz, CDCl3) δ 8.73 (d, J = 8.2 Hz, 1H), 8.64 - 8.58 (m, 1H), 7.66 - 7.58 (m, 1H), 7.37 - 7.14 (m, 7H), 6.23 (d, J = 8.2 Hz, 1H), 3.07 - 2.95(m, 2H), 2.31 (s, 6H). 13 C NMR (101 MHz, CDCl3) δ 170.10, 159.46, 149.43, 142.00, 136.86,128.75, 127.55, 127.47, 122.71, 122.47, 63.51, 57.09, 46.22. Example 6 The preparation of the NNN tridentate chiral ligand L5, the reaction process is as follows:

[0079]

[0080] In a 250 mL round-bottom flask purged with nitrogen, intermediate int-1 (4.21 g, 20.0 mmol, 1.0 equivalent) from Example 1 and anhydrous dichloromethane (40 mL, 0.50 M) were added dropwise. A 1.0 M tetrahydrofuran solution of 1-naphthylmagnesium bromide (40.0 mL, 40.0 mmol, 2.0 equivalent) was added dropwise to the resulting solution at -48 °C, and the reaction was carried out for 4 h. The resulting reaction solution was then heated to room temperature and reacted for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (50 mL) was added to the reaction solution, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate (50 mL each time). The resulting organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain product S10 (3.90 g, 11.53 mmol), with a yield of 58%.

[0081] Transfer the product S10 from the previous step (1.80 g, 5.32 mmol) to a 100 mL round-bottom flask, add 2.2 mL of 12.0 M hydrochloric acid aqueous solution (26.6 mmol, 5.0 equivalent) and anhydrous methanol (4.4 mL, 1.20 M), and react at room temperature for 1 h. After the reaction is complete, add 20 mL of saturated sodium bicarbonate aqueous solution and solid sodium bicarbonate. After the reaction stops bubbling, extract the aqueous phase three times with ethyl acetate (40 mL each time). Dry the resulting organic phase with anhydrous sodium sulfate and then evaporate to dryness under reduced pressure. Crude product S11 is obtained without further separation or purification.

[0082] The crude product S11 from the previous step was transferred to a 100 mL round-bottom flask, and N,N-dimethylglycine (576 mg, 5.59 mmol, 1.05 equivalents), 4-dimethylaminopyridine (DMAP, 65.0 mg, 0.53 mmol, 0.10 equivalents), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 1.12 g, 5.85 mmol, 1.1 equivalents) were added sequentially. After purging with nitrogen, dichloromethane (DCM, 13 mL, 0.40 M) was added at 0 °C. The reaction was then allowed to return to room temperature for 12 h. After the reaction was complete, water (20 mL) was added to quench the reaction, and the aqueous phase was extracted three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN tridentate chiral ligand L5 (white solid, 1.20 g, yield 74%).

[0083] 1 H NMR (400 MHz, CDCl3) δ 8.67 - 8.61 (m, 1H), 8.54 (d, J= 8.5 Hz, 1H), 8.29 (d, J = 8.4 Hz, 1H), 7.88 - 7.81 (m, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.63 -7.56 (m, 1H), 7.55 - 7.44 (m, 2H), 7.41 - 7.33 (m, 1H), 7.31 - 7.23 (m, 2H),7.21 - 7.15 (m, 1H), 7.02 (d, J = 8.5 Hz, 1H), 3.08 - 2.97 (m, 2H), 2.27 (s, 6H). 13 C NMR (101 MHz, CDCl3) δ 170.10, 159.87, 149.31, 137.43, 136.79,134.21, 131.37, 128.92, 128.63, 126.67, 126.48, 125.91, 125.39, 123.98,122.67, 122.41, 63.42, 54.29, 46.18. Example 7 The preparation of the NNN tridentate chiral ligand L6, the reaction process is as follows:

[0084]

[0085] In a 250 mL round-bottom flask purged with nitrogen, intermediate int-1 (2.10 g, 10.0 mmol, 1.0 equivalent) from Example 1 and anhydrous dichloromethane (25 mL, 0.40 M) were added dropwise. A 1.0 M tetrahydrofuran solution of 2-naphthylmagnesium bromide (20.0 mL, 20.0 mmol, 2.0 equivalent) was added dropwise to the resulting solution at -48 °C, and the reaction was carried out for 4 h. The resulting reaction solution was then heated to room temperature and reacted for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (50 mL) was added to the reaction solution, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate (50 mL each time). The resulting organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain product S12 (2.18 g, 6.44 mmol), with a yield of 64%.

[0086] Transfer all of the product S12 from the previous step to a 100 mL round-bottom flask, add 2.7 mL of 12.0 M hydrochloric acid aqueous solution (32.2 mmol, 5.0 equivalent) and 5.4 mL of anhydrous methanol (1.20 M), and react at room temperature for 1 h. After the reaction is complete, add 20 mL of saturated sodium bicarbonate aqueous solution and solid sodium bicarbonate. After the reaction stops bubbling, extract the aqueous phase three times with ethyl acetate (40 mL each time). Dry the resulting organic phase with anhydrous sodium sulfate and then evaporate to dryness under reduced pressure. Crude product S13 is obtained without further separation or purification.

[0087] The crude product S13 from the previous step was transferred to a 100 mL round-bottom flask, and N,N-dimethylglycine (697 mg, 6.76 mmol, 1.05 equivalents), 4-dimethylaminopyridine (DMAP, 78.7 mg, 0.64 mmol, 0.10 equivalents), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 1.36 g, 7.08 mmol, 1.1 equivalents) were added sequentially. After purging with nitrogen, dichloromethane (DCM, 16 mL, 0.40 M) was added at 0 °C. The reaction was then allowed to return to room temperature for 12 h. After the reaction was complete, water (20 mL) was added to quench the reaction, and the aqueous phase was extracted three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN tridentate chiral ligand L6 (white solid, 1.09 g, yield 53%).

[0088] 1 H NMR (400 MHz, CDCl3) δ 8.86 (d, J = 8.1 Hz, 1H), 8.67 - 8.61 (m, 1H), 7.84 - 7.73 (m, 4H), 7.66 - 7.58 (m, 1H), 7.49 - 7.39 (m, 3H), 7.33 - 7.28(m, 1H), 7.21 - 7.16 (m, 1H), 6.40 (d, J = 8.1 Hz, 1H), 3.10 - 2.99 (m, 2H), 2.33 (s, 6H). 13C NMR (101 MHz, CDCl3) δ 170.08, 159.28, 149.41, 139.34, 136.91,133.42, 132.85, 128.65, 128.18, 127.70, 126.46, 126.26, 126.10, 125.36,122.85, 122.53, 63.46, 57.25, 46.19. Example 8 The preparation of the NNN tridentate chiral ligand L7, the reaction process is as follows:

[0089]

[0090] In a 250 mL round-bottom flask purged with nitrogen, intermediate int-1 (1.26 g, 6.0 mmol, 1.0 equivalent) from Example 1 and anhydrous dichloromethane (15 mL, 0.40 M) were added dropwise. A 1.0 M solution of o-tolyl magnesium bromide in tetrahydrofuran (12.0 mL, 12.0 mmol, 2.0 equivalent) was added dropwise to the resulting solution at -48 °C, and the reaction was carried out for 4 h. The resulting reaction solution was then heated to room temperature and reacted for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (50 mL) was added to the reaction solution, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate (50 mL each time). The resulting organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain product S14 (280 mg, 0.91 mmol), with a yield of 15%.

[0091] Transfer all of the product S14 from the previous step to a 50 mL round-bottom flask, add 0.4 mL of 12.0 M hydrochloric acid aqueous solution (4.55 mmol, 5.0 equivalent) and 0.8 mL of anhydrous methanol (1.20 M), and react at room temperature for 1 h. After the reaction is complete, add 20 mL of saturated sodium bicarbonate aqueous solution and solid sodium bicarbonate. After the reaction stops bubbling, extract the aqueous phase three times with 40 mL of ethyl acetate each time. Dry the resulting organic phase with anhydrous sodium sulfate and then evaporate to dryness under reduced pressure. Crude product S15 is obtained without further separation or purification.

[0092] The crude product S15 from the previous step was transferred to a 50 mL round-bottom flask, and N,N-dimethylglycine (98.5 mg, 0.96 mmol, 1.05 equivalents), 4-dimethylaminopyridine (DMAP, 11.1 mg, 0.09 mmol, 0.10 equivalents), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 192 mg, 1.00 mmol, 1.1 equivalents) were added sequentially. After purging with nitrogen, dichloromethane (DCM, 2.3 mL, 0.40 M) was added at 0 °C. The reaction was then allowed to return to room temperature for 12 h. After the reaction was complete, water (20 mL) was added to quench the reaction, and the aqueous phase was extracted three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN tridentate chiral ligand L7 (white solid, 103 mg, yield 40%).

[0093] 1 H NMR (400 MHz, CDCl3) δ 8.63 - 8.57 (m, 1H), 8.53 (d, J = 8.0 Hz, 1H),7.64 - 7.55 (m, 1H), 7.22 - 7.08 (m, 6H), 6.44 (d, J = 7.9 Hz, 1H), 3.07 - 2.96(m, 2H), 2.51 (s, 3H), 2.32 (s, 6H). 13 C NMR (101 MHz, CDCl3) δ 169.91, 159.76, 149.29, 140.01, 136.75,136.19, 130.85, 127.82, 127.55, 126.37, 122.35, 122.29, 63.42, 54.03, 46.20,19.87. Example 9 The preparation of the NNN tridentate chiral ligand L8, the reaction process is as follows:

[0094]

[0095] In a 250 mL round-bottom flask purged with nitrogen, intermediate int-1 (1.26 g, 6.0 mmol, 1.0 equivalent) from Example 1 and anhydrous dichloromethane (15 mL, 0.40 M) were added dropwise. A 1.0 M solution of 2,6-dimethylphenyl magnesium bromide in tetrahydrofuran (12.0 mL, 12.0 mmol, 2.0 equivalent) was added dropwise to the resulting solution at -48 °C, and the reaction was carried out for 4 h. The resulting reaction solution was then heated to room temperature and reacted for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (50 mL) was added to the reaction solution, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate (50 mL each time). The obtained organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain product S16 (958 mg, 3.03 mmol), with a yield of 51%.

[0096] Transfer all of the product S16 from the previous step to a 50 mL round-bottom flask, add 1.3 mL of 12.0 M hydrochloric acid aqueous solution (15.2 mmol, 5.0 equivalent) and 2.5 mL of anhydrous methanol (1.20 M), and react at room temperature for 1 h. After the reaction is complete, add 20 mL of saturated sodium bicarbonate aqueous solution and solid sodium bicarbonate. After the reaction stops bubbling, extract the aqueous phase three times with ethyl acetate (40 mL each time). Dry the resulting organic phase with anhydrous sodium sulfate and then evaporate to dryness under reduced pressure. Crude product S17 is obtained without further separation or purification.

[0097] The crude product S17 from the previous step was transferred to a 100 mL round-bottom flask, and N,N-dimethylglycine (328 mg, 3.18 mmol, 1.05 equivalents), 4-dimethylaminopyridine (DMAP, 37.0 mg, 0.30 mmol, 0.10 equivalents), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 639 mg, 3.33 mmol, 1.1 equivalents) were added sequentially. After purging with nitrogen, dichloromethane (DCM, 7.6 mL, 0.40 M) was added at 0 °C. The reaction was then allowed to return to room temperature for 12 h. After the reaction was complete, water (20 mL) was added to quench the reaction, and the aqueous phase was extracted three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN tridentate chiral ligand L8 (white solid, 482 mg, yield 54%).

[0098] 1 H NMR (400 MHz, CDCl3) δ 8.85 (d, J= 6.9 Hz, 1H), 8.61 - 8.53 (m, 1H), 7.59 - 7.50 (m, 1H), 7.18 - 6.91 (m, 5H), 6.64 (d, J = 6.9 Hz, 1H), 3.13 - 2.99(m, 2H), 2.38 (s, 6H), 2.33 (s, 6H). 13 C NMR (101 MHz, CDCl3) δ 170.39, 159.52, 148.49, 138.32, 137.23,136.67, 129.40, 127.72, 121.83, 121.52, 63.56, 53.16, 46.30, 20.81. Example 10 The preparation of the NNN tridentate chiral ligand L9, the reaction process is as follows:

[0099]

[0100] In a 250 mL round-bottom flask purged with nitrogen, intermediate int-1 (2.10 g, 10.0 mmol, 1.0 equivalent) from Example 1 and anhydrous dichloromethane (25 mL, 0.40 M) were added dropwise. A 1.0 M solution of 2,6-dimethoxyphenyl magnesium bromide in tetrahydrofuran (20.0 mL, 20.0 mmol, 2.0 equivalent) was added dropwise to the resulting solution at -48 °C, and the reaction was carried out for 4 h. The resulting reaction solution was then heated to room temperature and reacted for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (50 mL) was added to the reaction solution, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate (50 mL each time). The resulting organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain product S18 (370 mg, 1.06 mmol), with a yield of 11%.

[0101] Transfer all of the product S18 from the previous step to a 50 mL round-bottom flask, add 0.4 mL of 12.0 M hydrochloric acid aqueous solution (5.30 mmol, 5.0 equivalent) and 0.9 mL of anhydrous methanol (1.20 M), and react at room temperature for 1 h. After the reaction is complete, add 20 mL of saturated sodium bicarbonate aqueous solution and solid sodium bicarbonate. After the reaction stops bubbling, extract the aqueous phase three times with 40 mL of ethyl acetate each time. Dry the resulting organic phase with anhydrous sodium sulfate and then evaporate to dryness under reduced pressure. Crude product S19 is obtained without further separation or purification.

[0102] Transfer all of the crude product S19 from the previous step to a 50 mL round-bottom flask, and add N,N-dimethylglycine (115 mg, 1.11 mmol, 1.05 equivalents), 4-dimethylaminopyridine (DMAP, 13.0 mg, 0.11 mmol, 0.10 equivalents), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 224 mg, 1.17 mmol, 1.1 equivalents) sequentially. After replacing the atmosphere with nitrogen, dichloromethane (DCM, 2.7 mL, 0.40 M) is added at 0 °C. The reaction is then allowed to return to room temperature for 12 h. After the reaction is complete, water (20 mL) is added to quench the reaction, and the aqueous phase is extracted three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN tridentate chiral ligand L9 (white solid, 226 mg, yield 65%).

[0103] 1 H NMR (400 MHz, CDCl3) δ 8.76 (d, J = 9.6 Hz, 1H), 8.53 - 8.46 (m, 1H), 7.56 - 7.47 (m, 1H), 7.25 - 7.14 (m, 2H), 7.09 - 7.00 (m, 2H), 6.64 - 6.55(m, 2H), 3.78 (s, 6H), 3.17 - 2.92 (m, 2H), 2.33 (s, 6H). 13 C NMR (101 MHz, CDCl3) δ 169.89, 161.02, 158.41, 148.72, 136.00,129.13, 121.35, 121.01, 118.02, 104.84, 63.54, 56.15, 48.20, 46.16. Example 11 The preparation of the NNN tridentate chiral ligand L10, the reaction process is as follows:

[0104]

[0105] In a 250 mL round-bottom flask purged with nitrogen, intermediate int-1 (2.10 g, 10.0 mmol, 1.0 equivalent) from Example 1 and anhydrous dichloromethane (25 mL, 0.40 M) were added dropwise. A 1.0 M solution of 3,5-di-tert-butylphenyl magnesium bromide in tetrahydrofuran (20.0 mL, 20.0 mmol, 2.0 equivalent) was added dropwise to the resulting solution at -48 °C, and the reaction was carried out for 4 h. The resulting reaction solution was then heated to room temperature and reacted for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (50 mL) was added to the reaction solution, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate (50 mL each time). The resulting organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain product S20 (2.09 g, 5.22 mmol), with a yield of 52%.

[0106] All of the product S20 from the previous step was transferred to a 100 mL round-bottom flask, and 2.2 mL of 12.0 M hydrochloric acid aqueous solution (26.1 mmol, 5.0 equivalent) and 4.4 mL of anhydrous methanol (1.20 M) were added. The reaction was allowed to proceed at room temperature for 1 h. After the reaction was complete, 20 mL of saturated sodium bicarbonate aqueous solution and solid sodium bicarbonate were added. After the reaction stopped bubbling, the aqueous phase was extracted three times with ethyl acetate (40 mL each time). The resulting organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure. The crude product S21 was obtained without further separation or purification.

[0107] Transfer the product S21 (592 mg, 2.00 mmol) from the previous step to a 50 mL round-bottom flask, and add N,N-dimethylglycine (217 mg, 2.10 mmol, 1.05 equivalents), 4-dimethylaminopyridine (DMAP, 24.4 mg, 0.20 mmol, 0.10 equivalents), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 422 mg, 2.20 mmol, 1.1 equivalents) sequentially. After purging with nitrogen, add dichloromethane (DCM, 5.0 mL, 0.40 M) at 0 °C. Then, allow the mixture to return to room temperature and react for 12 h. After the reaction is complete, quench with water (20 mL), and extract the aqueous phase three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN tridentate chiral ligand L10 (white solid, 566 mg, yield 74%).

[0108] 1 H NMR (400 MHz, CDCl3) δ 8.67 (d, J= 8.4 Hz, 1H), 8.63 - 8.57 (m, 1H), 7.66 - 7.57 (m, 1H), 7.31 - 7.24 (m, 2H), 7.20 - 7.13 (m, 3H), 6.24 (d, J = 8.5Hz, 1H), 3.08 - 2.95 (m, 2H), 2.33 (s, 6H), 1.27 (s, 18H). 13 C NMR (101 MHz, CDCl3) δ 169.97, 159.90, 150.97, 149.34, 141.03,136.74, 122.75, 122.30, 121.76, 121.60, 63.57, 57.44, 46.22, 34.98, 31.56. Example 12 The preparation of the NNN tridentate chiral ligand L11, the reaction process is as follows:

[0109]

[0110] In a 250 mL round-bottom flask purged with nitrogen, intermediate int-1 (2.10 g, 10.0 mmol, 1.0 equivalent) from Example 1 and anhydrous dichloromethane (25 mL, 0.40 M) were added dropwise. A 1.0 M solution of 3,5-diphenylphenyl magnesium bromide in tetrahydrofuran (20.0 mL, 20.0 mmol, 2.0 equivalent) was added dropwise to the resulting solution at -48 °C, and the reaction was carried out for 4 h. The resulting reaction solution was then heated to room temperature and reacted for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (50 mL) was added to the reaction solution, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate (50 mL each time). The resulting organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain product S22 (3.28 g, 7.45 mmol), with a yield of 75%.

[0111] Transfer the product S22 (803 mg, 1.83 mmol) from the previous step to a 50 mL round-bottom flask, add 0.8 mL (9.15 mmol, 5.0 equivalent) of 12.0 M hydrochloric acid aqueous solution and 1.5 mL (1.20 M) of anhydrous methanol, and react at room temperature for 1 h. After the reaction is complete, add 20 mL of saturated sodium bicarbonate aqueous solution and sodium bicarbonate solid. After the reaction stops bubbling, extract the aqueous phase three times with ethyl acetate (40 mL each time). Dry the resulting organic phase with anhydrous sodium sulfate and then evaporate to dryness under reduced pressure. Crude product S23 is obtained without separation and purification.

[0112] The crude product S23 from the previous step was transferred to a 50 mL round-bottom flask, and N,N-dimethylglycine (198 mg, 1.92 mmol, 1.05 equivalents), 4-dimethylaminopyridine (DMAP, 22.4 mg, 0.18 mmol, 0.10 equivalents), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 386 mg, 2.01 mmol, 1.1 equivalents) were added sequentially. After purging with nitrogen, dichloromethane (DCM, 4.6 mL, 0.40 M) was added at 0 °C. The reaction was then allowed to return to room temperature for 12 h. After the reaction was complete, water (20 mL) was added to quench the reaction, and the aqueous phase was extracted three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN tridentate chiral ligand L11 (white solid, 546 mg, yield 71%).

[0113] 1 H NMR (400 MHz, CDCl3) δ 8.88 (d, J = 8.1 Hz, 1H), 8.66 - 8.60 (m, 1H), 7.69 - 7.55 (m, 8H), 7.48 - 7.40 (m, 4H), 7.39 - 7.31 (m, 3H), 7.23 - 7.17(m, 1H), 6.37 (d, J = 8.3 Hz, 1H), 3.13 - 3.02 (m, 2H), 2.36 (s, 6H). 13C NMR (101 MHz, CDCl3) δ 170.04, 159.22, 149.49, 143.07, 142.27,141.08, 136.99, 128.89, 127.60, 127.44, 125.54, 125.38, 122.78, 122.61,63.44, 57.24, 46.19. Example 13 The preparation of the NNN tridentate chiral ligand L12, the reaction process is as follows:

[0114]

[0115] In a 250 mL round-bottom flask purged with nitrogen, intermediate int-1 (2.10 g, 10.0 mmol, 1.0 equivalent) from Example 1 and anhydrous dichloromethane (25 mL, 0.40 M) were added dropwise. A 1.0 M solution of 3,5-di-tert-butyl-4-methoxyphenyl magnesium bromide in tetrahydrofuran (20.0 mL, 20.0 mmol, 2.0 equivalent) was added dropwise to the resulting solution at -48 °C, and the reaction was carried out for 4 h. The resulting reaction solution was then heated to room temperature and reacted for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (50 mL) was added to the reaction solution, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate (50 mL each time). The resulting organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain product S24 (2.79 g, 6.48 mmol), with a yield of 65%.

[0116] Transfer all of the product S24 from the previous step to a 100 mL round-bottom flask, add 2.7 mL of 12.0 M hydrochloric acid aqueous solution (32.4 mmol, 5.0 equivalent) and 5.4 mL of anhydrous methanol (1.20 M), and react at room temperature for 1 h. After the reaction is complete, add 20 mL of saturated sodium bicarbonate aqueous solution and solid sodium bicarbonate. After the reaction stops bubbling, extract the aqueous phase three times with ethyl acetate (40 mL each time). Dry the resulting organic phase with anhydrous sodium sulfate and then evaporate to dryness under reduced pressure. Crude product S25 is obtained without further separation or purification.

[0117] Transfer the product S25 (1.30 g, 4.00 mmol) from the previous step to a 100 mL round-bottom flask, and add N,N-dimethylglycine (433 mg, 4.20 mmol, 1.05 equivalents), 4-dimethylaminopyridine (DMAP, 48.9 mg, 0.40 mmol, 0.10 equivalents), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 843 mg, 4.40 mmol, 1.1 equivalents) sequentially. After purging with nitrogen, add dichloromethane (DCM, 10.0 mL, 0.40 M) at 0 °C. Then, allow the mixture to return to room temperature and react for 12 h. After the reaction is complete, quench with water (20 mL), and extract the aqueous phase three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN tridentate ligand L12 (white solid, 1.10 g, yield 67%).

[0118] 1 H NMR (400 MHz, CDCl3) δ 8.65 - 8.55 (m, 2H), 7.67 - 7.59 (m, 1H), 7.29 - 7.24 (m, 1H), 7.20 - 7.12 (m, 3H), 6.18 (d, J = 8.4 Hz, 1H), 3.64 (s,3H), 3.09 - 2.96 (m, 2H), 2.33 (s, 6H), 1.35 (s, 18H). 13 C NMR (101 MHz, CDCl3) δ 169.87, 159.97, 158.76, 149.38, 143.64,136.71, 135.65, 125.76, 122.71, 122.30, 64.21, 63.48, 56.98, 46.16, 35.88,32.14. Example 14 The preparation of the NNN tridentate chiral ligand L13, the reaction process is as follows:

[0119]

[0120] In a 250 mL round-bottom flask purged with nitrogen, intermediate int-1 (2.10 g, 10.0 mmol, 1.0 equivalent) from Example 1 and anhydrous dichloromethane (25 mL, 0.40 M) were added dropwise. A 1.0 M tetrahydrofuran solution of 4-methoxyphenyl magnesium bromide (20.0 mL, 20.0 mmol, 2.0 equivalent) was added dropwise to the resulting solution at -48 °C, and the reaction was carried out for 4 h. The resulting reaction solution was then heated to room temperature and reacted for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (50 mL) was added to the reaction solution, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate (50 mL each time). The resulting organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain product S26 (2.00 g, 6.28 mmol), with a yield of 63%.

[0121] Transfer all of the product S26 from the previous step to a 100 mL round-bottom flask, add 2.6 mL of 12.0 M hydrochloric acid aqueous solution (31.4 mmol, 5.0 equivalent) and 5.2 mL of anhydrous methanol (1.20 M), and react at room temperature for 1 h. After the reaction is complete, add 20 mL of saturated sodium bicarbonate aqueous solution and solid sodium bicarbonate. After the reaction stops bubbling, extract the aqueous phase three times with ethyl acetate (40 mL each time). Dry the resulting organic phase with anhydrous sodium sulfate and then evaporate to dryness under reduced pressure. Crude product S27 is obtained without further separation or purification.

[0122] Transfer the product S27 (660 mg, 3.08 mmol) from the previous step to a 100 mL round-bottom flask, and add N,N-dimethylglycine (333 mg, 3.23 mmol, 1.05 equivalents), 4-dimethylaminopyridine (DMAP, 37.6 mg, 0.31 mmol, 0.10 equivalents), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 649 mg, 3.39 mmol, 1.1 equivalents) sequentially. After purging with nitrogen, add dichloromethane (DCM, 7.7 mL, 0.40 M) at 0 °C. Then, allow the mixture to return to room temperature and react for 12 h. After the reaction is complete, quench with water (20 mL), and extract the aqueous phase three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN tridentate chiral ligand L13 (white solid, 360 mg, yield 38%).

[0123] 1 H NMR (400 MHz, CDCl3) δ 8.68 (d, J= 8.1 Hz, 1H), 8.63 - 8.57 (m, 1H), 7.65 - 7.58 (m, 1H), 7.29 - 7.21 (m, 3H), 7.20 - 7.14 (m, 1H), 6.85 - 6.79(m, 2H), 6.18 (d, J = 8.1 Hz, 1H), 3.75 (s, 3H), 3.01 (s, 2H), 2.31 (s, 6H). 13 C NMR (101 MHz, CDCl3) δ 169.93, 159.70, 158.98, 149.34, 136.83,134.29, 128.70, 122.61, 122.37, 114.12, 63.46, 56.51, 55.35, 46.16. Example 15 The preparation of the NNN tridentate chiral ligand L14, the reaction process is as follows:

[0124]

[0125] In a 250 mL round-bottom flask purged with nitrogen, intermediate int-1 (2.10 g, 10.0 mmol, 1.0 equivalent) from Example 1 and anhydrous dichloromethane (25 mL, 0.40 M) were added dropwise. A 1.0 M solution of 4-trifluoromethylphenyl magnesium bromide in tetrahydrofuran (20.0 mL, 20.0 mmol, 2.0 equivalent) was added dropwise to the resulting solution at -48 °C, and the reaction was carried out for 4 h. The resulting reaction solution was then heated to room temperature and reacted for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (50 mL) was added to the reaction solution, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate (50 mL each time). The obtained organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain product S28 (2.46 g, 6.91 mmol), with a yield of 69%.

[0126] Transfer all of the product S28 from the previous step to a 100 mL round-bottom flask, add 2.9 mL of 12.0 M hydrochloric acid aqueous solution (34.6 mmol, 5.0 equivalent) and 5.8 mL of anhydrous methanol (1.20 M), and react at room temperature for 1 h. After the reaction is complete, add 20 mL of saturated sodium bicarbonate aqueous solution and solid sodium bicarbonate. After the reaction stops bubbling, extract the aqueous phase three times with ethyl acetate (40 mL each time). Dry the resulting organic phase with anhydrous sodium sulfate and then evaporate to dryness under reduced pressure. Crude product S29 is obtained without further separation or purification.

[0127] Transfer the product S29 (504 mg, 2.00 mmol) from the previous step to a 50 mL round-bottom flask, and add N,N-dimethylglycine (217 mg, 2.10 mmol, 1.05 equivalents), 4-dimethylaminopyridine (DMAP, 24.4 mg, 0.20 mmol, 0.10 equivalents), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 422 mg, 2.20 mmol, 1.1 equivalents) sequentially. After purging with nitrogen, add dichloromethane (DCM, 5.0 mL, 0.40 M) at 0 °C. Then, allow the mixture to return to room temperature and react for 12 h. After the reaction is complete, quench with water (20 mL), and extract the aqueous phase three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN tridentate chiral ligand L14 (white solid, 361 mg, yield 53%).

[0128] 1 H NMR (400 MHz, CDCl3) δ 8.85 (d, J = 7.9 Hz, 1H), 8.65 - 8.59 (m, 1H), 7.68 - 7.61 (m, 1H), 7.57 - 7.51 (m, 2H), 7.50 - 7.44 (m, 2H), 7.27 - 7.15(m, 2H), 6.25 (d, J = 7.9 Hz, 1H), 3.02 (s, 2H), 2.32 (s, 6H). 13 C NMR (101 MHz, CDCl3) δ 170.27, 158.42, 149.65, 145.97, 137.13,129.76 (q, J = 32.4 Hz), 127.83, 125.74 (q, J= 3.8 Hz), 124.18 (q, J = 272.7 Hz),122.87, 122.77, 63.39, 56.81, 46.20. 19 F NMR (377 MHz, CDCl3) δ -62.58. Example 16 The preparation of the NNN tridentate chiral ligand L15, the reaction process is as follows:

[0129]

[0130] In a 250 mL round-bottom flask purged with nitrogen, intermediate int-1 (2.10 g, 10.0 mmol, 1.0 equivalent) from Example 1 and anhydrous dichloromethane (25 mL, 0.40 M) were added dropwise. A 1.0 M solution of 4-tert-butylphenyl magnesium bromide in tetrahydrofuran (20.0 mL, 20.0 mmol, 2.0 equivalent) was added dropwise to the resulting solution at -48 °C, and the reaction was carried out for 4 h. The resulting reaction solution was then heated to room temperature and reacted for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (50 mL) was added to the reaction solution, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate (50 mL each time). The resulting organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain product S30 (2.12 g, 6.15 mmol), with a yield of 61%.

[0131] Transfer all of the product S30 from the previous step to a 100 mL round-bottom flask, add 2.6 mL of 12.0 M hydrochloric acid aqueous solution (30.8 mmol, 5.0 equivalent) and 5.1 mL of anhydrous methanol (1.20 M), and react at room temperature for 1 h. After the reaction is complete, add 20 mL of saturated sodium bicarbonate aqueous solution and solid sodium bicarbonate. After the reaction stops bubbling, extract the aqueous phase three times with ethyl acetate (40 mL each time). Dry the resulting organic phase with anhydrous sodium sulfate and then evaporate to dryness under reduced pressure. Crude product S31 is obtained without further separation or purification.

[0132] Transfer the product S31 (960 mg, 4.00 mmol) from the previous step to a 100 mL round-bottom flask, and add N,N-dimethylglycine (433 mg, 4.20 mmol, 1.05 equivalents), 4-dimethylaminopyridine (DMAP, 48.9 mg, 0.40 mmol, 0.10 equivalents), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 843 mg, 4.40 mmol, 1.1 equivalents) sequentially. After purging with nitrogen, add dichloromethane (DCM, 10.0 mL, 0.40 M) at 0 °C. Then, allow the mixture to return to room temperature and react for 12 h. After the reaction is complete, quench with water (20 mL), and extract the aqueous phase three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN tridentate chiral ligand L15 (white solid, 640 mg, yield 49%).

[0133] 1 H NMR (400 MHz, CDCl3) δ 8.69 (d, J = 8.2 Hz, 1H), 8.63 - 8.57 (m, 1H), 7.65 - 7.58 (m, 1H), 7.34 - 7.22 (m, 5H), 7.20 - 7.13 (m, 1H), 6.21 (d, J = 8.2Hz, 1H), 3.08 - 2.96 (m, 2H), 2.32 (s, 6H), 1.27 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 169.96, 159.71, 150.31, 149.41, 138.84,136.80, 127.09, 125.68, 122.70, 122.38, 63.45, 56.80, 46.19, 34.57, 31.42. Example 17 The preparation of the NNN tridentate chiral ligand L16, the reaction process is as follows:

[0134]

[0135] In a 250 mL round-bottom flask purged with nitrogen, intermediate int-1 (1.57 g, 7.47 mmol, 1.0 equivalent) from Example 1 and anhydrous dichloromethane (19 mL, 0.40 M) were added dropwise. A 1.0 M tetrahydrofuran solution of 4-adamantylphenyl magnesium bromide (14.9 mL, 14.9 mmol, 2.0 equivalent) was added dropwise to the resulting solution at -48 °C, and the reaction was carried out for 4 h. The resulting reaction solution was then heated to room temperature and reacted for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (50 mL) was added to the reaction solution, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate (50 mL each time). The obtained organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain product S32 (2.61 g, 6.18 mmol), with a yield of 83%.

[0136] Transfer all of the product S32 from the previous step to a 100 mL round-bottom flask, add 2.6 mL of 12.0 M hydrochloric acid aqueous solution (30.9 mmol, 5.0 equivalent) and 5.2 mL of anhydrous methanol (1.20 M), and react at room temperature for 1 h. After the reaction is complete, add 20 mL of saturated sodium bicarbonate aqueous solution and solid sodium bicarbonate. After the reaction stops bubbling, extract the aqueous phase three times with 40 mL of ethyl acetate each time. Dry the resulting organic phase with anhydrous sodium sulfate and then evaporate to dryness under reduced pressure. Crude product S33 is obtained without further separation or purification.

[0137] Transfer the product S33 (1.27 g, 4.00 mmol) from the previous step to a 100 mL round-bottom flask, and add N,N-dimethylglycine (433 mg, 4.20 mmol, 1.05 equivalents), 4-dimethylaminopyridine (DMAP, 48.9 mg, 0.40 mmol, 0.10 equivalents), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 843 mg, 4.40 mmol, 1.1 equivalents) sequentially. After purging with nitrogen, add dichloromethane (DCM, 10.0 mL, 0.40 M) at 0 °C. Then, allow the mixture to return to room temperature and react for 12 h. After the reaction is complete, quench with water (20 mL), and extract the aqueous phase three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN tridentate chiral ligand L16 (white solid, 892 mg, yield 61%).

[0138] 1 H NMR (400 MHz, CDCl3) δ 8.68 (d, J= 8.1 Hz, 1H), 8.63 - 8.57 (m, 1H), 7.66 - 7.58 (m, 1H), 7.32 - 7.22 (m, 5H), 7.20 - 7.13 (m, 1H), 6.22 (d, J = 8.4Hz, 1H), 3.09 - 2.95 (m, 2H), 2.32 (s, 6H), 2.10 - 2.03 (m, 3H), 1.88 - 1.83(m, 6H), 1.81 - 1.67 (m, 6H). 13 C NMR (101 MHz, CDCl3) δ 169.91, 159.73, 150.57, 149.40, 138.85,136.80, 127.14, 125.27, 122.71, 122.37, 63.42, 56.83, 46.18, 43.24, 36.88,36.10, 29.03. Example 18 The preparation of the NNN tridentate chiral ligand L17, the reaction process is as follows:

[0139]

[0140] In a 250 mL round-bottom flask purged with nitrogen, intermediate int-1 (2.10 g, 10.0 mmol, 1.0 equivalent) from Example 1 and anhydrous dichloromethane (25 mL, 0.40 M) were added dropwise. A 1.0 M tetrahydrofuran solution of 4-phenylphenyl magnesium bromide (20.0 mL, 20.0 mmol, 2.0 equivalent) was added dropwise to the resulting solution at -48 °C, and the reaction was carried out for 4 h. The resulting reaction solution was then heated to room temperature and reacted for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (50 mL) was added to the reaction solution, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate (50 mL each time). The obtained organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain product S34 (2.44 g, 6.69 mmol), with a yield of 67%.

[0141] Transfer all of the product S34 from the previous step to a 100 mL round-bottom flask, add 2.8 mL of 12.0 M hydrochloric acid aqueous solution (33.5 mmol, 5.0 equivalent) and 5.6 mL of anhydrous methanol (1.20 M), and react at room temperature for 1 h. After the reaction is complete, add 20 mL of saturated sodium bicarbonate aqueous solution and solid sodium bicarbonate. After the reaction stops bubbling, extract the aqueous phase three times with ethyl acetate (40 mL each time). Dry the resulting organic phase with anhydrous sodium sulfate and then evaporate to dryness under reduced pressure. Crude product S35 is obtained without further separation or purification.

[0142] The crude product S35 from the previous step was transferred to a 100 mL round-bottom flask, and N,N-dimethylglycine (724 mg, 7.02 mmol, 1.05 equivalents), 4-dimethylaminopyridine (DMAP, 81.7 mg, 0.67 mmol, 0.10 equivalents), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 1.41 g, 7.36 mmol, 1.1 equivalents) were added sequentially. After purging with nitrogen, dichloromethane (DCM, 16.7 mL, 0.40 M) was added at 0 °C. The reaction was then allowed to return to room temperature for 12 h. After the reaction was complete, water (20 mL) was added to quench the reaction, and the aqueous phase was extracted three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN tridentate chiral ligand L17 (white solid, 1.45 g, yield 63%).

[0143] 1 H NMR (400 MHz, CDCl3) δ 8.82 (d, J = 8.1 Hz, 1H), 8.65 - 8.60 (m, 1H), 7.68 - 7.62 (m, 1H), 7.56 - 7.49 (m, 4H), 7.44 - 7.37 (m, 4H), 7.35 - 7.28(m, 2H), 7.22 - 7.17 (m, 1H), 6.27 (d, J = 7.9 Hz, 1H), 3.16 - 3.05 (m, 2H), 2.40 (s, 6H). 13C NMR (101 MHz, CDCl3) δ 170.13, 159.36, 149.49, 141.03, 140.87,140.49, 136.94, 128.84, 127.89, 127.54, 127.38, 127.20, 122.75, 122.55,63.50, 56.86, 46.23. Example 19 The preparation of the NNN tridentate chiral ligand L18, the reaction process is as follows:

[0144]

[0145] In a 250 mL round-bottom flask purged with nitrogen, intermediate int-1 (2.10 g, 10.0 mmol, 1.0 equivalent) from Example 1 and anhydrous dichloromethane (25 mL, 0.40 M) were added dropwise. A 1.0 M solution of 4-(9-carbazolyl)phenyl magnesium bromide in tetrahydrofuran (20.0 mL, 20.0 mmol, 2.0 equivalent) was added dropwise to the resulting solution at -48 °C, and the reaction was carried out for 4 h. The resulting reaction solution was then heated to room temperature and reacted for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (50 mL) was added to the reaction solution, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate (50 mL each time). The resulting organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain product S36 (2.56 g, 5.66 mmol), with a yield of 57%.

[0146] Transfer all of the product S36 from the previous step to a 100 mL round-bottom flask, add 2.4 mL of 12.0 M hydrochloric acid aqueous solution (28.3 mmol, 5.0 equivalent) and 4.7 mL of anhydrous methanol (1.20 M), and react at room temperature for 1 h. After the reaction is complete, add 20 mL of saturated sodium bicarbonate aqueous solution and solid sodium bicarbonate. After the reaction stops bubbling, extract the aqueous phase three times with 40 mL of ethyl acetate each time. Dry the resulting organic phase with anhydrous sodium sulfate and then evaporate to dryness under reduced pressure. Crude product S37 is obtained without further separation or purification.

[0147] The crude product S37 from the previous step was transferred to a 100 mL round-bottom flask, and N,N-dimethylglycine (613 mg, 5.94 mmol, 1.05 equivalents), 4-dimethylaminopyridine (DMAP, 69.1 mg, 0.57 mmol, 0.10 equivalents), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 1.19 g, 6.23 mmol, 1.1 equivalents) were added sequentially. After purging with nitrogen, dichloromethane (DCM, 14.2 mL, 0.40 M) was added at 0 °C. The reaction was then allowed to return to room temperature for 12 h. After the reaction was complete, water (20 mL) was added to quench the reaction, and the aqueous phase was extracted three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN-30 chiral toothed ligand L18 (white solid, 1.39 g, yield 57%).

[0148] 1 H NMR (400 MHz, CDCl3) δ 8.89 (d, J = 8.1 Hz, 1H), 8.70 - 8.64 (m, 1H), 8.14 - 8.09 (m, 2H), 7.74 - 7.66 (m, 1H), 7.60 - 7.54 (m, 2H), 7.52 - 7.46(m, 2H), 7.41 - 7.32 (m, 5H), 7.30 - 7.21 (m, 3H), 6.36 (d, J = 8.0 Hz, 1H), 3.16 - 3.02 (m, 2H), 2.37 (s, 6H). 13 C NMR (101 MHz, CDCl3) δ 170.21, 159.04, 149.67, 141.16, 140.86,137.11, 136.98, 128.92, 127.26, 126.00, 123.46, 122.87, 122.78, 120.37,120.04, 109.95, 63.44, 56.78, 46.23. Example 20 The preparation of the NNN tridentate chiral ligand L19, the reaction process is as follows:

[0149]

[0150] In a 250 mL round-bottom flask purged with nitrogen, intermediate int-1 (1.26 g, 6.0 mmol, 1.0 equivalent) from Example 1 and anhydrous dichloromethane (15 mL, 0.40 M) were added dropwise. A 1.0 M solution of 4-cyclohexylphenyl magnesium bromide in tetrahydrofuran (12.0 mL, 12.0 mmol, 2.0 equivalent) was added dropwise to the resulting solution at -48 °C, and the reaction was carried out for 4 h. The resulting reaction solution was then heated to room temperature and reacted for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (50 mL) was added to the reaction solution, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate (50 mL each time). The resulting organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain product S38 (1.48 g, 4.00 mmol), with a yield of 67%.

[0151] Transfer all of the product S38 from the previous step to a 100 mL round-bottom flask, add 1.7 mL of 12.0 M hydrochloric acid aqueous solution (20.0 mmol, 5.0 equivalent) and anhydrous methanol (3.3 mL, 1.20 M), and react at room temperature for 1 h. After the reaction is complete, add 20 mL of saturated sodium bicarbonate aqueous solution and solid sodium bicarbonate. After the reaction stops bubbling, extract the aqueous phase three times with ethyl acetate (40 mL each time). Dry the resulting organic phase with anhydrous sodium sulfate and then evaporate to dryness under reduced pressure. Crude product S39 is obtained without further separation or purification.

[0152] Transfer all of the crude product S39 from the previous step to a 100 mL round-bottom flask, and add N,N-dimethylglycine (433 mg, 4.20 mmol, 1.05 equivalents), 4-dimethylaminopyridine (DMAP, 48.9 mg, 0.40 mmol, 0.10 equivalents), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 843 mg, 4.40 mmol, 1.1 equivalents) sequentially. After replacing the atmosphere with nitrogen, dichloromethane (DCM, 10.0 mL, 0.40 M) is added at 0 °C. The reaction is then allowed to return to room temperature for 12 h. After the reaction is complete, water (20 mL) is added to quench the reaction, and the aqueous phase is extracted three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN tridentate chiral ligand L19 (white solid, 910 mg, yield 65%).

[0153] 1 H NMR (400 MHz, CDCl3) δ 8.68 (d, J= 8.2 Hz, 1H), 8.62 - 8.57 (m, 1H), 7.65 - 7.57 (m, 1H), 7.29 - 7.21 (m, 3H), 7.19 - 7.09 (m, 3H), 6.21 (d, J = 8.2Hz, 1H), 3.07 - 2.95 (m, 2H), 2.50 - 2.38 (m, 1H), 2.32 (s, 6H), 1.88 - 1.67(m, 5H), 1.43 - 1.17 (m, 5H). 13 C NMR (101 MHz, CDCl3) δ 169.93, 159.72, 149.40, 147.31, 139.24,136.79, 127.35, 127.20, 122.69, 122.36, 63.44, 56.87, 46.18, 44.29, 34.49,26.99, 26.25. Example 21 The preparation of the NNN tridentate chiral ligand L20, the reaction process is as follows:

[0154]

[0155] In a 250 mL round-bottom flask purged with nitrogen, intermediate int-1 (1.26 g, 6.0 mmol, 1.0 equivalent) from Example 1 and anhydrous dichloromethane (15 mL, 0.40 M) were added dropwise. A 1.0 M tetrahydrofuran solution of 4-tributylsilylphenyl magnesium bromide (12.0 mL, 12.0 mmol, 2.0 equivalent) was added dropwise to the resulting solution at -48 °C, and the reaction was carried out for 4 h. The resulting reaction solution was then heated to room temperature and reacted for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (50 mL) was added to the reaction solution, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate (50 mL each time). The obtained organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain product S40 (2.14 g, 4.41 mmol), with a yield of 73%.

[0156] Transfer all of the product S40 from the previous step to a 100 mL round-bottom flask, add 1.8 mL of 12.0 M hydrochloric acid aqueous solution (22.1 mmol, 5.0 equivalent) and anhydrous methanol (3.7 mL, 1.20 M), and react at room temperature for 1 h. After the reaction is complete, add 20 mL of saturated sodium bicarbonate aqueous solution and solid sodium bicarbonate. After the reaction stops bubbling, extract the aqueous phase three times with ethyl acetate (40 mL each time). Dry the resulting organic phase with anhydrous sodium sulfate and then evaporate to dryness under reduced pressure. Crude product S41 is obtained without further separation or purification.

[0157] The crude product S41 from the previous step was transferred to a 100 mL round-bottom flask, and N,N-dimethylglycine (477 mg, 4.63 mmol, 1.05 equivalents), 4-dimethylaminopyridine (DMAP, 53.9 mg, 0.44 mmol, 0.10 equivalents), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 930 mg, 4.85 mmol, 1.1 equivalents) were added sequentially. After purging with nitrogen, dichloromethane (DCM, 11.0 mL, 0.40 M) was added at 0 °C. The reaction was then allowed to return to room temperature for 12 h. After the reaction was complete, water (20 mL) was added to quench the reaction, and the aqueous phase was extracted three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN tridentate chiral ligand L20 (white solid, 1.39 g, yield 68%).

[0158] 1 H NMR (400 MHz, CDCl3) δ 8.70 (d, J = 8.3 Hz, 1H), 8.63 - 8.58 (m, 1H), 7.67 - 7.59 (m, 1H), 7.43 - 7.36 (m, 2H), 7.32 - 7.24 (m, 3H), 7.21 - 7.15(m, 1H), 6.23 (d, J = 8.3 Hz, 1H), 3.11 - 2.99 (m, 2H), 2.33 (s, 6H), 1.36 -1.19 (m, 12H), 0.85 (t, J = 6.8 Hz, 9H), 0.76 - 0.68 (m, 6H). 13C NMR (101 MHz, CDCl3) δ 169.85, 159.51, 149.48, 141.99, 137.41,136.84, 134.57, 126.62, 122.79, 122.47, 63.32, 57.09, 46.10, 26.89, 26.11,13.86, 12.30. Example 22 The preparation of the NNN tridentate chiral ligand L21, the reaction process is as follows:

[0159]

[0160] In a 250 mL round-bottom flask purged with nitrogen, intermediate int-1 (1.05 g, 5.0 mmol, 1.0 equivalent) from Example 1 and anhydrous dichloromethane (12.5 mL, 0.40 M) were added dropwise. A 1.0 M tetrahydrofuran solution of 4-triisopropylsilylphenylmagnesium bromide (10.0 mL, 10.0 mmol, 2.0 equivalent) was added dropwise to the resulting solution at -48 °C, and the reaction was carried out for 4 h. The resulting reaction solution was then heated to room temperature and reacted for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (50 mL) was added to the reaction solution, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate (50 mL each time). The resulting organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain product S42 (1.70 g, 3.83 mmol), with a yield of 77%.

[0161] Transfer all of the product S42 from the previous step to a 100 mL round-bottom flask, add 1.6 mL of 12.0 M hydrochloric acid aqueous solution (19.2 mmol, 5.0 equivalent) and anhydrous methanol (3.2 mL, 1.20 M), and react at room temperature for 1 h. After the reaction is complete, add 20 mL of saturated sodium bicarbonate aqueous solution and solid sodium bicarbonate. After the reaction stops bubbling, extract the aqueous phase three times with ethyl acetate (40 mL each time). Dry the resulting organic phase with anhydrous sodium sulfate and then evaporate to dryness under reduced pressure. Crude product S43 is obtained without further separation or purification.

[0162] The crude product S43 from the previous step was transferred to a 100 mL round-bottom flask, and N,N-dimethylglycine (415 mg, 4.02 mmol, 1.05 equivalents), 4-dimethylaminopyridine (DMAP, 46.8 mg, 0.38 mmol, 0.10 equivalents), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 808 mg, 4.21 mmol, 1.1 equivalents) were added sequentially. After purging with nitrogen, dichloromethane (DCM, 9.6 mL, 0.40 M) was added at 0 °C. The reaction was then allowed to return to room temperature for 12 h. After the reaction was complete, water (20 mL) was added to quench the reaction, and the aqueous phase was extracted three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN tridentate chiral ligand L21 (white solid, 441 mg, yield 27%).

[0163] 1 H NMR (400 MHz, CDCl3) δ 8.67 (d, J = 8.5 Hz, 1H), 8.64 - 8.59 (m, 1H), 7.67 - 7.60 (m, 1H), 7.43 - 7.37 (m, 2H), 7.32 - 7.24 (m, 3H), 7.21 - 7.16(m, 1H), 6.26 (d, J = 8.5 Hz, 1H), 3.10 - 2.98 (m, 2H), 2.32 (s, 6H), 1.40 -1.30 (m, 3H), 1.03 (d, J = 7.6 Hz, 18H). 13 C NMR (101 MHz, CDCl3) δ 170.01, 159.57, 149.52, 141.84, 136.83,135.67, 134.01, 126.42, 122.86, 122.48, 63.43, 56.97, 46.15, 18.66, 10.89. Example 23 The preparation of the NNN tridentate chiral ligand L22, the reaction process is as follows:

[0164]

[0165] In a 100 mL round-bottom flask purged with nitrogen, intermediate int-1 (0.42 g, 2.0 mmol, 1.0 equivalent) from Example 1 and anhydrous dichloromethane (5.0 mL, 0.40 M) were added dropwise. A 1.0 M tetrahydrofuran solution of 4-triphenylsilylphenyl magnesium bromide (4.0 mL, 4.0 mmol, 2.0 equivalent) was added dropwise to the resulting solution at -48 °C, and the reaction was carried out for 4 h. The resulting reaction solution was then heated to room temperature and reacted for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (50 mL) was added to the reaction solution, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate (50 mL each time). The obtained organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain product S44 (528 mg, 0.96 mmol), with a yield of 48%.

[0166] Transfer all of the product S44 from the previous step to a 50 mL round-bottom flask, add 0.4 mL of 12.0 M hydrochloric acid aqueous solution (4.80 mmol, 5.0 equivalent) and 0.8 mL of anhydrous methanol (1.20 M), and react at room temperature for 1 h. After the reaction is complete, add 20 mL of saturated sodium bicarbonate aqueous solution and solid sodium bicarbonate. After the reaction stops bubbling, extract the aqueous phase three times with ethyl acetate (40 mL each time). Dry the resulting organic phase with anhydrous sodium sulfate and then evaporate to dryness under reduced pressure. Crude product S45 is obtained without further separation or purification.

[0167] Transfer all of the crude product S45 from the previous step to a 50 mL round-bottom flask, and add N,N-dimethylglycine (104 mg, 1.01 mmol, 1.05 equivalents), 4-dimethylaminopyridine (DMAP, 11.7 mg, 0.10 mmol, 0.10 equivalents), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 202 mg, 1.06 mmol, 1.1 equivalents) sequentially. After replacing the atmosphere with nitrogen, dichloromethane (DCM, 2.4 mL, 0.40 M) is added at 0 °C. The reaction is then allowed to return to room temperature for 12 h. After the reaction is complete, water (20 mL) is added to quench the reaction, and the aqueous phase is extracted three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN tridentate chiral ligand L22 (white solid, 363 mg, yield 72%).

[0168] 1 H NMR (400 MHz, CDCl3) δ 8.75 (d, J= 8.3 Hz, 1H), 8.63 - 8.57 (m, 1H), 7.67 - 7.60 (m, 1H), 7.57 - 7.47 (m, 8H), 7.45 - 7.39 (m, 3H), 7.38 - 7.32 (m, 8H), 7.31 - 7.27 (m, 1H), 7.21 - 7.16 (m, 1H), 6.26 (d, J = 8.2 Hz, 1H), 3.11 -2.98 (m, 2H), 2.33 (s, 6H). 13 C NMR (101 MHz, CDCl3) δ 170.05, 159.31, 149.54, 143.16, 136.90,136.85, 136.50, 134.21, 133.33, 129.71, 127.96, 126.84, 122.80, 122.56,63.39, 57.07, 46.19. Example 24 The preparation of int-2, an intermediate of the NNN tridentate chiral ligand L23, is as follows:

[0169] In a 100 mL round-bottom flask purged with nitrogen, S46 (6-methyl-2-pyridinecarboxaldehyde, 2.42 g, 20 mmol, 1.0 equivalent), (R)-tert-butylsulfinamide (2.91 g, 24 mmol, 1.2 equivalent), tetraisopropyl titanate (6.82 g, 24 mmol, 1.2 equivalent), and anhydrous tetrahydrofuran (40 mL, 0.50 M) were added sequentially, and the mixture was heated to 70 °C and reacted for 4.0 h. After the reaction was complete, 50 mL of saturated ammonium chloride aqueous solution was added to the reaction mixture, and the mixture was filtered through diatomaceous earth. The organic phase was separated from the filtrate, and the aqueous phase was extracted three times with ethyl acetate (50 mL each time). The obtained organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain product int-2 (4.38 g, 19.55 mmol), with a yield of 98%.

[0170] Example 25 The preparation of the NNN tridentate chiral ligand L23 was carried out via the following reaction process:

[0171]

[0172] In a 100 mL round-bottom flask purged with nitrogen, intermediate int-2 (897 mg, 4.00 mmol, 1.0 equivalent) from Example 24 and anhydrous dichloromethane (10 mL, 0.40 M) were added dropwise. A 1.0 M tetrahydrofuran solution of 4-adamantylphenyl magnesium bromide (8.0 mL, 8.0 mmol, 2.0 equivalent) was added dropwise to the resulting solution at -48 °C, and the reaction was carried out for 4 h. The resulting reaction solution was then heated to room temperature and reacted for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (50 mL) was added to the reaction solution, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate (50 mL each time). The obtained organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain product S47 (967 mg, 2.21 mmol), with a yield of 55%.

[0173] Transfer all of the product S47 from the previous step to a 50 mL round-bottom flask, add 0.9 mL of 12.0 M hydrochloric acid aqueous solution (11.1 mmol, 5.0 equivalent) and anhydrous methanol (1.8 mL, 1.20 M), and react at room temperature for 1 h. After the reaction is complete, add 20 mL of saturated sodium bicarbonate aqueous solution and solid sodium bicarbonate. After the reaction stops bubbling, extract the aqueous phase three times with ethyl acetate (40 mL each time). Dry the resulting organic phase with anhydrous sodium sulfate and then evaporate to dryness under reduced pressure. Crude product S48 is obtained without further separation or purification.

[0174] The crude product S48 from the previous step was transferred to a 50 mL round-bottom flask, and N,N-dimethylglycine (239 mg, 2.32 mmol, 1.05 equivalents), 4-dimethylaminopyridine (DMAP, 27.0 mg, 0.22 mmol, 0.10 equivalents), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 466 mg, 2.43 mmol, 1.1 equivalents) were added sequentially. After purging with nitrogen, dichloromethane (DCM, 5.5 mL, 0.40 M) was added at 0 °C. The reaction was then allowed to return to room temperature for 12 h. After the reaction was complete, water (20 mL) was added to quench the reaction, and the aqueous phase was extracted three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN tridentate chiral ligand L23 (white solid, 589 mg, yield 64%).

[0175] 1 H NMR (400 MHz, CDCl3) δ 8.75 (d, J= 8.3 Hz, 1H), 7.52 - 7.45 (m, 1H), 7.32 - 7.23 (m, 4H), 7.06 - 6.98 (m, 2H), 6.17 (d, J = 8.3 Hz, 1H), 3.11 - 2.92(m, 2H), 2.56 (s, 3H), 2.34 (s, 6H), 2.10 - 2.02 (m, 3H), 1.89 - 1.83 (m,6H), 1.80 - 1.68 (m, 6H). 13 C NMR (101 MHz, CDCl3) δ 169.80, 158.77, 157.99, 150.45, 139.16,136.88, 127.28, 125.16, 121.74, 119.62, 63.41, 56.56, 46.16, 43.25, 36.90,36.09, 29.04, 24.67. Example 26 The preparation of int-3, an intermediate of the NNN tridentate chiral ligand L24, was carried out via the following reaction process:

[0176] In a 100 mL round-bottom flask purged with nitrogen, S49 (5-methoxypyridine-2-aldehyde, 1.00 g, 7.30 mmol, 1.0 equivalent), (R)-tert-butylsulfinamide (1.06 g, 8.75 mmol, 1.2 equivalent), tetraisopropyl titanate (2.49 g, 8.75 mmol, 1.2 equivalent), and anhydrous tetrahydrofuran (14.6 mL, 0.50 M) were added sequentially, and the mixture was heated to 70 °C and reacted for 4.0 h. After the reaction was complete, 50 mL of saturated ammonium chloride aqueous solution was added to the reaction mixture, and the mixture was filtered through diatomaceous earth. The organic phase was separated from the filtrate, and the aqueous phase was extracted three times with ethyl acetate (50 mL each time). The obtained organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain product int-3 (1.59 g, 6.62 mmol), with a yield of 91%.

[0177] Example 27 The preparation of the NNN tridentate chiral ligand L24, the reaction process is as follows:

[0178]

[0179] In a 100 mL round-bottom flask purged with nitrogen, intermediate int-3 (961 mg, 4.00 mmol, 1.0 equivalent) from Example 26 and anhydrous dichloromethane (10 mL, 0.40 M) were added dropwise. A 1.0 M tetrahydrofuran solution of 4-adamantylphenyl magnesium bromide (8.0 mL, 8.0 mmol, 2.0 equivalent) was added dropwise to the resulting solution at -48 °C, and the reaction was carried out for 4 h. The resulting reaction solution was then heated to room temperature and reacted for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (50 mL) was added to the reaction solution, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate (50 mL each time). The obtained organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain product S50 (816 mg, 1.80 mmol), with a yield of 45%.

[0180] Transfer all of the product S50 from the previous step to a 50 mL round-bottom flask, add 0.8 mL of 12.0 M hydrochloric acid aqueous solution (9.00 mmol, 5.0 equivalent) and 1.5 mL of anhydrous methanol (1.20 M), and react at room temperature for 1 h. After the reaction is complete, add 20 mL of saturated sodium bicarbonate aqueous solution and solid sodium bicarbonate. After the reaction stops bubbling, extract the aqueous phase three times with 40 mL of ethyl acetate each time. Dry the resulting organic phase with anhydrous sodium sulfate and then evaporate to dryness under reduced pressure. Crude product S51 is obtained without further separation or purification.

[0181] The crude product S51 from the previous step was transferred to a 50 mL round-bottom flask, and N,N-dimethylglycine (195 mg, 1.89 mmol, 1.05 equivalents), 4-dimethylaminopyridine (DMAP, 22.0 mg, 0.18 mmol, 0.10 equivalents), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 380 mg, 1.98 mmol, 1.1 equivalents) were added sequentially. After purging with nitrogen, dichloromethane (DCM, 4.5 mL, 0.40 M) was added at 0 °C. The reaction was then allowed to return to room temperature for 12 h. After the reaction was complete, water (20 mL) was added to quench the reaction, and the aqueous phase was extracted three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN tridentate ligand L24 (white solid, 527 mg, yield 68%).

[0182] 1 H NMR (400 MHz, CDCl3) δ 8.58 (d, J= 8.4 Hz, 1H), 8.31 - 8.28 (m, 1H), 7.29 - 7.22 (m, 4H), 7.21 - 7.17 (m, 1H), 7.15 - 7.11 (m, 1H), 6.18 (d, J = 8.3Hz, 1H), 3.83 (s, 3H), 3.07 - 2.94 (m, 2H), 2.31 (s, 6H), 2.09 - 2.03 (m,3H), 1.88 - 1.83 (m, 6H), 1.80 - 1.67 (m, 6H). 13 C NMR (101 MHz, CDCl3) δ 169.83, 154.78, 151.96, 150.43, 139.18,136.87, 127.02, 125.22, 122.86, 121.39, 63.42, 56.12, 55.75, 46.17, 43.25,36.89, 36.09, 29.03. Example 28 The preparation of int-4, an intermediate of the NNN tridentate chiral ligand L25, was carried out via the following reaction process:

[0183] In a 100 mL round-bottom flask purged with nitrogen, S52 (4-methoxypyridine-2-aldehyde, 1.00 g, 7.30 mmol, 1.0 equivalent), (R)-tert-butylsulfinamide (1.06 g, 8.75 mmol, 1.2 equivalent), tetraisopropyl titanate (2.49 g, 8.75 mmol, 1.2 equivalent), and anhydrous tetrahydrofuran (14.6 mL, 0.50 M) were added sequentially, and the mixture was heated to 70 °C and reacted for 4.0 h. After the reaction was complete, 50 mL of saturated ammonium chloride aqueous solution was added to the reaction mixture, and the mixture was filtered through diatomaceous earth. The organic phase was separated from the filtrate, and the aqueous phase was extracted three times with ethyl acetate (50 mL each time). The obtained organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain product int-4 (1.58 g, 6.57 mmol), with a yield of 90%.

[0184] Example 29 The preparation of the NNN tridentate chiral ligand L25, the reaction process is as follows:

[0185]

[0186] In a 100 mL round-bottom flask purged with nitrogen, intermediate int-4 (1.58 g, 6.57 mmol, 1.0 equivalent) from Example 28 and anhydrous dichloromethane (16 mL, 0.40 M) were added dropwise. A 1.0 M tetrahydrofuran solution of 4-adamantylphenyl magnesium bromide (13.1 mL, 13.1 mmol, 2.0 equivalent) was added dropwise to the resulting solution at -48 °C, and the reaction was carried out for 4 h. The resulting reaction solution was then heated to room temperature and reacted for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (50 mL) was added to the reaction solution, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate (50 mL each time). The resulting organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain product S53 (2.28 g, 5.03 mmol), with a yield of 77%.

[0187] Transfer all of the product S53 from the previous step to a 100 mL round-bottom flask, add 2.1 mL of 12.0 M hydrochloric acid aqueous solution (25.2 mmol, 5.0 equivalent) and 4.2 mL of anhydrous methanol (1.20 M), and react at room temperature for 1 h. After the reaction is complete, add 20 mL of saturated sodium bicarbonate aqueous solution and solid sodium bicarbonate. After the reaction stops bubbling, extract the aqueous phase three times with ethyl acetate (40 mL each time). Dry the resulting organic phase with anhydrous sodium sulfate and then evaporate to dryness under reduced pressure. Crude product S54 is obtained without further separation or purification.

[0188] The crude product S54 from the previous step was transferred to a 100 mL round-bottom flask, and N,N-dimethylglycine (545 mg, 5.28 mmol, 1.05 equivalents), 4-dimethylaminopyridine (DMAP, 61.5 mg, 0.50 mmol, 0.10 equivalents), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 1.06 g, 5.53 mmol, 1.1 equivalents) were added sequentially. After purging with nitrogen, dichloromethane (DCM, 12.6 mL, 0.40 M) was added at 0 °C. The reaction was then allowed to return to room temperature for 12 h. After the reaction was complete, water (20 mL) was added to quench the reaction, and the aqueous phase was extracted three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN tridentate chiral ligand L25 (white solid, 1.09 g, yield 50%).

[0189] 1 H NMR (400 MHz, CDCl3) δ 8.63 (d, J= 8.3 Hz, 1H), 8.43 - 8.39 (m, 1H), 7.30 - 7.25 (m, 4H), 6.81 - 6.77 (m, 1H), 6.71 - 6.67 (m, 1H), 6.14 (d, J = 8.1Hz, 1H), 3.80 (s, 3H), 3.07 - 2.95 (m, 2H), 2.31 (s, 6H), 2.10 - 2.03 (m,3H), 1.89 - 1.83 (m, 6H), 1.80 - 1.67 (m, 6H). 13 C NMR (101 MHz, CDCl3) δ 169.89, 166.24, 161.45, 150.67, 150.55,138.77, 127.08, 125.25, 108.82, 108.49, 63.43, 56.94, 55.27, 46.17, 43.24,36.89, 36.10, 29.03. Example 30 The preparation of int-5, an intermediate of the NNN tridentate chiral ligand L26, was carried out via the following reaction process:

[0190] In a 100 mL round-bottom flask purged with nitrogen, S55 (4-phenylpyridin-2-aldehyde, 1.67 g, 9.15 mmol, 1.0 equivalent), (R)-tert-butylsulfinamide (1.33 g, 10.98 mmol, 1.2 equivalent), tetraisopropyl titanate (3.12 g, 10.98 mmol, 1.2 equivalent), and anhydrous tetrahydrofuran (18.3 mL, 0.50 M) were added sequentially, and the mixture was heated to 70 °C and reacted for 4.0 h. After the reaction was complete, 50 mL of saturated ammonium chloride aqueous solution was added to the reaction mixture, and the mixture was filtered through diatomaceous earth. The organic phase was separated from the filtrate, and the aqueous phase was extracted three times with ethyl acetate (50 mL each time). The obtained organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain product int-5 (2.27 g, 7.92 mmol), with a yield of 87%.

[0191] Example 31 The preparation of the NNN tridentate chiral ligand L26, the reaction process is as follows:

[0192]

[0193] In a 100 mL round-bottom flask purged with nitrogen, intermediate int-4 (1.15 g, 4.00 mmol, 1.0 equivalent) from Example 28 and anhydrous dichloromethane (10 mL, 0.40 M) were added dropwise. A 1.0 M tetrahydrofuran solution of 4-adamantylphenyl magnesium bromide (8.0 mL, 8.0 mmol, 2.0 equivalent) was added dropwise to the resulting solution at -48 °C, and the reaction was carried out for 4 h. The resulting reaction solution was then heated to room temperature and reacted for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (50 mL) was added to the reaction solution, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate (50 mL each time). The obtained organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain product S56 (1.36 g, 2.72 mmol), with a yield of 68%.

[0194] Transfer all of the product S56 from the previous step to a 50 mL round-bottom flask, add 1.1 mL of 12.0 M hydrochloric acid aqueous solution (13.6 mmol, 5.0 equivalent) and 2.3 mL of anhydrous methanol (1.20 M), and react at room temperature for 1 h. After the reaction is complete, add 20 mL of saturated sodium bicarbonate aqueous solution and solid sodium bicarbonate. After the reaction stops bubbling, extract the aqueous phase three times with ethyl acetate (40 mL each time). Dry the resulting organic phase with anhydrous sodium sulfate and then evaporate to dryness under reduced pressure. Crude product S57 is obtained without further separation or purification.

[0195] The crude product S57 from the previous step was transferred to a 100 mL round-bottom flask, and N,N-dimethylglycine (295 mg, 2.86 mmol, 1.05 equivalents), 4-dimethylaminopyridine (DMAP, 33.2 mg, 0.27 mmol, 0.10 equivalents), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 574 mg, 2.99 mmol, 1.1 equivalents) were added sequentially. After purging with nitrogen, dichloromethane (DCM, 6.8 mL, 0.40 M) was added at 0 °C. The reaction was then allowed to return to room temperature for 12 h. After the reaction was complete, water (20 mL) was added to quench the reaction, and the aqueous phase was extracted three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN tridentate chiral ligand L26 (white solid, 855 mg, yield 66%).

[0196] 1 H NMR (400 MHz, CDCl3) δ 8.72 (d, J= 8.4 Hz, 1H), 8.67 - 8.62 (m, 1H), 7.62 - 7.56 (m, 2H), 7.51 - 7.37 (m, 5H), 7.34 - 7.26 (m, 4H), 6.30 (d, J = 8.3Hz, 1H), 3.10 - 2.98 (m, 2H), 2.34 (s, 6H), 2.10 - 2.02 (m, 3H), 1.90 - 1.82(m, 6H), 1.80 - 1.67 (m, 6H). 13 C NMR (101 MHz, CDCl3) δ 169.92, 160.33, 150.60, 149.88, 149.29,138.83, 138.18, 129.24, 129.22, 127.19, 127.16, 125.32, 120.66, 120.51,63.45, 56.96, 46.20, 43.24, 36.89, 36.12, 29.03. Example 32 The preparation of the NNN tridentate chiral ligand L51, the reaction process is as follows:

[0197] Transfer S3 (403 mg, 3.30 mmol, 1.0 equivalent) to a 100 mL round-bottom flask, and add 2-pyridinecarboxylic acid (427 mg, 3.47 mmol, 1.05 equivalent), 4-dimethylaminopyridine (DMAP, 40.3 mg, 0.33 mmol, 0.10 equivalent), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 696 mg, 3.63 mmol, 1.1 equivalent) sequentially. After purging with nitrogen, add dichloromethane (DCM, 8.3 mL, 0.40 M) at 0 °C. Then, allow the mixture to return to room temperature and react for 12 h. After the reaction is complete, quench with water (20 mL), and extract the aqueous phase three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN tridentate chiral ligand L51 (colorless oily liquid, 540 mg, yield 72%).

[0198] 1 H NMR (400 MHz, CDCl3) δ 9.03 (d, J= 7.6 Hz, 1H), 8.65 - 8.55 (m, 2H), 8.19 (d, J = 7.8 Hz, 1H), 7.86 - 7.78 (m, 1H), 7.68 - 7.60 (m, 1H), 7.44 - 7.36(m, 1H), 7.31 (d, J = 8.2 Hz, 1H), 7.21 - 7.14 (m, 1H), 5.40 - 5.30 (m, 1H),1.61 (d, J = 6.8 Hz, 3H), 13 C NMR (101 MHz, CDCl3) δ 163.79, 161.37, 150.23, 149.51, 148.37,137.34, 136.91, 126.19, 122.41, 122.32, 121.40, 50.18, 22.44. Example 33 The preparation of the NNN tridentate chiral ligand L52, the reaction process is as follows:

[0199] Transfer S9 (1.40 g, 7.60 mmol, 1.0 equivalent) to a 100 mL round-bottom flask, and add 2-pyridinecarboxylic acid (982 mg, 7.98 mmol, 1.05 equivalent), 4-dimethylaminopyridine (DMAP, 92.8 mg, 0.76 mmol, 0.10 equivalent), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 1.60 g, 8.36 mmol, 1.1 equivalent) sequentially. After purging with nitrogen, add dichloromethane (DCM, 19.0 mL, 0.40 M) at 0 °C. Then, allow the mixture to return to room temperature and react for 12 h. After the reaction is complete, quench with water (20 mL), and extract the aqueous phase three times with dichloromethane (30 mL each time). The organic phase was then washed with brine, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain the target product, NNN tridentate chiral ligand L52 (white solid, 1.50 g, yield 68%).

[0200] 1 H NMR (400 MHz, CDCl3) δ 9.76 (d, J= 7.5 Hz, 1H), 8.70 - 8.60 (m, 2H), 8.20 - 8.15 (m, 1H), 7.85 - 7.78 (m, 1H), 7.67 - 7.60 (m, 1H), 7.47 - 7.39(m, 3H), 7.35 - 7.27 (m, 3H), 7.25 - 7.17 (m, 2H), 6.37 (d, J = 7.7 Hz, 1H). 13 C NMR (101 MHz, CDCl3) δ 163.83, 159.30, 150.21, 149.50, 148.48,141.90, 137.32, 136.96, 128.81, 127.66, 127.62, 126.26, 122.65, 122.54,122.47, 57.99. Example 34 This embodiment studies the effect of NNN tridentate chiral ligands on copper-catalyzed asymmetric phosphorylation of olefin radicals. The reaction results are shown in Tables 1 and 2.

[0201] Table 1: Results of the reaction of different chiral NNN tridentate ligands in the asymmetric phosphorylation of olefins

[0202] In the table, "OEt" represents ethoxy, "Ph" represents phenyl, "Ad" represents adamantyl, "Me" represents methyl, and "Bn" represents benzyl. t "-Bu" represents tert-butyl, "1-Naph" represents 1-naphthyl, "2-Naph" represents 2-naphthyl, "CF3" represents trifluoromethyl, "EtOH" represents ethanol, and "equiv." represents equivalent amount.

[0203] Table 2: Reaction results of tridentate ligands with different chiralities in the asymmetric phosphorylation of olefins

[0204] In the table, "OEt" represents ethoxy, "Ph" represents phenyl, "Ad" represents adamantyl, "Me" represents methyl, and "Cy" represents cyclohexyl. n "-Bu" indicates n-butyl, i "-Pr" indicates isopropyl, EtOH is ethanol, MTBE is methyl tert-butyl ether, and "equiv." indicates equivalent amount.

[0205] Table 1 shows the copper source used in the reaction: CuCl (10 mol.%), the molar ratio of the NNN tridentate chiral ligand, photocatalyst, and CuCl was 1.2:1:1, the base was 1,8-diazabicyclo-bicyclo(5,4,0)-7-undecene (1.0 equivalent), the reaction solvent was ethanol (0.050 M), the reaction temperature was 10 °C, and the reaction time was 36 h. Table 2 shows the optimized reaction solvent as a mixture of ethanol and methyl tert-butyl ether (v / v = 7:3, 0.050 M), and the reaction time was 72 h. The NMR spectrum of the target product P1 is as follows: 1 H NMR (400 MHz, CDCl3) δ 7.30 - 7.06 (m, 8H), 7.03 - 6.96 (m, 2H), 4.15 - 3.98 (m, 2H), 3.96 - 3.84 (m, 1H), 3.75 - 3.63 (m, 1H), 3.51 - 3.41(m, 1H), 3.36 - 3.12 (m, 2H), 1.28 (t, J = 7.1 Hz, 3H), 1.08 (t, J = 7.1 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 139.26 (d, J = 16.0 Hz), 135.73 (d, J = 6.3Hz), 129.59 (d, J = 6.9 Hz), 128.94, 128.46 (d, J = 2.4 Hz), 128.24, 127.21 (d, J =3.0 Hz), 126.27, 62.79 (d, J = 7.0 Hz), 61.90 (d, J = 7.3 Hz), 46.76 (d, J = 136.4Hz), 36.46 (d, J = 2.6 Hz), 16.51 (d, J = 6.0 Hz), 16.35 (d, J = 5.7 Hz). 31 P NMR (162 MHz, CDCl3) δ 28.15. The reaction results in Tables 1 and 2 show that the pyridine-based bis-five-membered ring coordinated NNN tridentate chiral ligands exhibit excellent yields and enantioselectivity in the asymmetric phosphorylation of olefin radicals. When the chiral substituent R at the benzylic position of the pyridine coordination unit is alkyl (Table 1, entries 3-5), the enantioselectivity of the products obtained using the corresponding ligands is very low, while the enantioselectivity is significantly increased when the chiral substituent R is aryl. By comparing different aryl substituents, it was found that when there is a substituent at the ortho position of the aryl substituent (Table 1, entries 9-11), the yield and enantioselectivity of the products decrease significantly; when there is a substituent with a large steric hindrance effect at the para position of the aryl substituent (Table 1, entries 1, 17; Table 2, entries 2-5), the enantioselectivity of the products is improved, and the effect is best when the substituent is 4-adamantylphenyl. Finally, by introducing a methoxy group at the para position of the nitrogen atom of the pyridine unit, the enantioselectivity of the products is further improved. Furthermore, the introduction of substituents at the ortho position of the pyridine coordination unit in ligand L23 also leads to a significant decrease in product yield and enantioselectivity, which may be due to the presence of ortho substituents affecting the coordination of pyridine with Cu.

[0206] Example 35 In this embodiment, L25 was used as the ligand to investigate the application of a novel bi-five-membered ring coordinated NNN tridentate chiral ligand based on a pyridine skeleton in copper-catalyzed asymmetric phosphorylation of olefins. The corresponding results are shown in Table 3.

[0207] The specific operational steps of the reaction in Table 3 are as follows: In a nitrogen-filled glove box, CuCl (1.0 mg, 0.010 mmol, 0.10 equivalent), NNN tridentate chiral ligand L25 (5.2 mg, 0.012 mmol, 0.12 equivalent), photocatalyst (0.010 mmol, 0.10 equivalent), and 1,8-diazabicyclo-bicyclo(5,4,0)-7-undecene (abbreviated as DBU, 15.2 mg, 0.10 mmol, 1.0 equivalent) were added to a 4 mL reaction flask containing a magnetic stir bar. An alcohol solvent and methyl tert-butyl ether (v / v = 7:3, 2.0 mL, 0.050 M) were added, and the mixture was stirred to complex for 30 min. Phosphite (0.10 mmol, 1.0 equivalent) and olefin (0.20 mmol, 2.0 equivalent) were then added. The reaction flask was removed from the glove box and reacted at a reaction temperature of 10 °C under LED light irradiation at a wavelength of 390 nm for 72 h. The target product was then purified by column chromatography. After identification by NMR, the ee value of the purified product was determined by HPLC analysis.

[0208] Table 3: Substrate compatibility of NNN tridentate ligand L25 in asymmetric phosphorylation of olefins

[0209] Note: (1) The reaction time for the reactions involved in Table 3 is 120 h for 3i, 3k, 3o and 3p, and the reaction time for the other products is 72 h; (2) For the reactions involved in Table 3, the equivalent ratio of CuCl:L25:photocatalyst:DBU for 3i, 3o, and 3p is 15 mol.%:18 mol.%:15 mol.%:5.0 equivalents, and the equivalent ratio of the remaining products is 10 mol.%:12 mol.%:10 mol.%:1.0 equivalents; (3) "Et" represents ethyl, "Me" represents methyl, "Ph" represents phenyl, "TMS" represents trimethylsilyl, and "Cy" represents cyclohexyl. i "-Pr" represents isopropyl, "n-Bu" represents n-butyl, "i-Bu" represents isobutyl, "MTBE" represents methyl tert-butyl ether, and "equiv." represents equivalent amount.

[0210] The results in Table 3 show that the novel bipentacyclic coordinated NNN tridentate chiral ligands disclosed in this invention have broad substrate applicability in the asymmetric radical phosphorylation of olefins.

[0211] The preferred embodiments of the present invention have been described in detail above. It should be understood that those skilled in the art can make numerous modifications and variations based on the concept of the present invention without creative effort. Therefore, all technical solutions that can be obtained by those skilled in the art based on the concept of the present invention through logical analysis, reasoning, or limited experimentation on the basis of existing technology should be within the scope of protection defined by the claims.

Claims

1. A novel bi-five-membered ring coordinated NNN tridentate chiral ligand based on a pyridine framework, characterized in that, It has the structure described in general formula I: In the formula, R is an alkyl or aryl group; R 1 It is one of hydrogen, alkyl, or aryl; R 2 It is one of hydrogen, alkyl, or aryl; R 3 It is alkyl or aryl; X is either carbon or sulfur. When X is carbon, the dashed line between X and oxygen indicates that there is no bond, meaning the bridging group is carbonyl. When X is an element, the dashed line between X and oxygen indicates that there is a bond, meaning the bridging group is sulfonyl.

2. The novel bi-five-membered ring coordinated NNN tridentate chiral ligand based on a pyridine framework according to claim 1, characterized in that: In the novel pyridine-based bi-five-membered ring coordinated NNN tridentate chiral ligand, R is one of methyl, ethyl, benzyl, isopropyl, tert-butyl, or one of phenyl, 1-naphthyl, 2-naphthyl, 2-methylphenyl, 2,6-dimethylphenyl, 2,6-dimethoxyphenyl, 3,5-di-tert-butylphenyl, 3,5-diphenylphenyl, 3,5-di-tert-butyl-4-methoxy-phenyl, 4-methoxyphenyl, 4-trifluoromethylphenyl, 4-tert-butylphenyl, 4-adamantylphenyl, 4-phenylphenyl, 4-(9-carbazolyl)phenyl, 4-cyclohexylphenyl, 4-tri-n-butylsilylphenyl, 4-triisopropylsilylphenyl, 4-triphenylsilylphenyl; R 1 It is hydrogen, or one of methyl, ethyl, tert-butyl, methoxy, trifluoromethyl, or one of phenyl, 3,5-di-tert-butylphenyl, 3,5-di-trifluoromethylphenyl, 3,5-di-tert-butyl-4-methoxy-phenyl; R 2 It is hydrogen, or one of methyl, ethyl, isopropyl, cyclohexyl, tert-butyl, or phenyl or 3,5-di-tert-butylphenyl; R 3 It is one of methyl, ethyl, n-butyl, isopropyl, tert-butyl, or phenyl.

3. The novel bi-five-membered ring coordinated NNN tridentate chiral ligand based on a pyridine framework according to claim 2, characterized in that, The novel bi-five-membered ring coordinated NNN tridentate chiral ligands based on the pyridine skeleton include compounds with the following structural formulas L1 to L62: 。 4. The application of a novel bi-five-membered ring coordinated NNN tridentate chiral ligand based on a pyridine skeleton as described in any one of claims 1 to 3 in radical asymmetric functionalization reactions, characterized in that, The process includes the following steps: using the product generated by the complexation reaction of a novel pyridine-based bis-pentane coordinated NNN tridentate chiral ligand with a metal compound as a catalyst for a radical asymmetric functionalization reaction.

5. The application according to claim 4, characterized in that: The metal atoms in the metal compound include at least one of Cu, Fe, Zn, Mn, Cr, Co, Au, Ag, Ni, Ti, Pt, Pd, Rh, Ru, and Ir.

6. The application according to claim 5, characterized in that: The metal compound includes at least one of CuI, CuBr, CuCl, CuCN, Cu2O, Cu(CH3CN)4PF6, (CuOTf)2·PhH, (CuOTf)2·PhMe, Cu(OTf)2, Cu(NO3)2, Cu(OAc)2, Cu(OAc)2·H2O, Cu(acac)2, CuCl2, CuBr2, Cu(BF4)2, and CuSO4.

7. The application according to claim 4, characterized in that, The free radical asymmetric functionalization reaction includes asymmetric phosphorylation and other related reactions. The asymmetric phosphorylation reaction process includes the following steps: (1) Under the protection of an inert gas, a metal compound, a novel pyridine skeleton-based double five-membered ring coordinated NNN tridentate chiral ligand, a photocatalyst and a base were added. After adding a solvent, the complexation reaction was carried out by stirring at room temperature to obtain a catalyst solution. (2) Add olefins and phosphites. After the addition is complete, carry out an asymmetric phosphorylation reaction under the light source at the target temperature and target wavelength. After the reaction is completed, the crude product is purified to obtain the target product.

8. The application according to claim 7, characterized in that: In step (1), the base is at least one of lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide, sodium ethoxide, sodium carbonate, potassium carbonate, cesium carbonate, potassium phosphate, 1,8-diazabicyclo-bicyclo(5,4,0)-7-undecene (DBU), 2-tert-butyl-1,1,3,3-tetramethylguanidine (BTMG), and (tert-butylimino)tris(pyrrolidine)phosphine (BTPP); the solvent is at least one of methanol, ethanol, isopropanol, n-butanol, isobutanol, tert-butanol, methyl tert-butyl ether, 1,4-dioxane, tetrahydrofuran, dichloromethane, 1,2-dichloroethane, toluene, or 2-methyl-tetrahydrofuran; the reaction time of the complexation reaction is ≤60 min; the molar ratio of the metal complex, the novel pyridine-based bis-five-membered ring coordinated NNN tridentate chiral ligand, the photocatalyst, and the base is 1:1.2:1:

10.

9. The application according to claim 7, characterized in that: In step (2), the target temperature is -20 ~ 50℃; the time for the asymmetric phosphorylation reaction is 2 ~ 120 h; and the molar ratio of phosphite to olefin is 1:1.5 ~ 3.

10. A catalyst for radical asymmetric functionalization reactions, characterized in that: It is generated by the complexation reaction of a novel pyridine-based bipentacyclic ring coordinated NNN tridentate chiral ligand as described in any one of claims 1 to 3 with a metal compound.

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