A binuclear chiral ligand containing pyridine and chiral oxazoline units with a chiral diamine as a parent skeleton

Abstract

The present application relates to a kind of chiral six-tooth nitrogen-containing binuclear ligand, the present application is first synthesized chiral diamine as parent skeleton, the binuclear chiral ligand containing pyridine and chiral oxazoline unit, use chiral diamine as chiral skeleton to tie two pyridine oxazoline groups, wherein chiral diamine and chiral oxazoline unit have (S) or (R) configuration chiral center carbon.The synthesis method of ligand is obtained by five steps or six steps reaction with simple available raw materials.The ligand is functional ligand, can be able to with two same or different metal coordination, in reaction binuclear jointly activates substrate or mononuclear activates substrate, another metal as ligand influences catalytic center activity.This kind of binuclear catalyst is expected to realize the reaction that conventional mononuclear catalyst is difficult to realize by unique metal-metal bond, and be applied to many asymmetric catalytic reactions, with good application prospect.

Description

Technical Field

[0001] This invention relates to a class of compounds in the field of chemical technology and their preparation methods, specifically, binuclear chiral ligands with a chiral diamine as the parent skeleton and pyridine and chiral oxazoline units. Background Technology

[0002] Asymmetric catalysis using metal complexes offers advantages such as high efficiency, good atom economy, and minimal environmental impact, making it an important method for preparing pure enantiomers. The development of novel, highly efficient chiral ligands is central to asymmetric catalysis because organic ligands can influence the spatial and electronic properties of metal catalysts, thereby improving the reactivity, regioselectivity, and enantioselectivity of metal-catalyzed organic reactions by lowering reaction temperatures and reducing byproducts. Therefore, designing different chiral coordinating groups or ligand skeletons to meet the requirements of ligands with varying spatial and electronic properties is crucial. Among these, ligands containing oxazoline structures are a particularly important class, attracting extensive research due to their unique properties.

[0003] The development of novel and effective chiral ligands has always been a major direction for solving key and challenging problems in the field of asymmetric catalysis. Among the many developed chiral ligands, nitrogen-containing ligands are a relatively important class, possessing advantages such as easy availability and stability. They can form complexes with transition metals, resulting in highly efficient catalytic reactions. Among nitrogen-containing chiral ligands, oxazoline is a particularly excellent class, as the nitrogen atom in its structure can form stable complexes with metal atoms. Scientists have synthesized many chiral ligands containing oxazoline structures for asymmetric catalytic reactions, achieving significant progress. Currently, the structures of oxazoline-containing ligands developed are mainly bidentate and tridentate, with a very few tetradentate ligands, while chiral ligands with more than four teeth have been almost entirely undeveloped. Based on current research progress, the rational design of chiral ligands with more than four teeth for solving binuclear and polynuclear metal catalytic reactions is a very meaningful area of ​​research. To date, chemists have discovered that many reaction pathways involve processes catalyzed by bimetallic complexes.

[0004] In 2007, Shibasaki's research group synthesized a bimetallic catalyst using a polydentate imine ligand with a cyclohexanediamine framework and copper samarium metal (Handa, S.; Gnanadesikan, V.; Matsunaga, S.; Shibasaki, MJAm. Chem. Soc. 2007, 129, 4900.), and achieved an asymmetric Mannich reaction between nitroalkanes and imines. North et al. reported an asymmetric catalytic cyanidation reaction using Salen bis-titanium catalysts in 1999. In 2010, Academician Ding Kuiling developed a catalyst with two Salen ligands linked together (Zhang, Z.; Wang, Z.; Zhang, R.; Ding, K. Angew. Chem., Int. Ed. 2010, 49, 6746.), reducing the catalyst loading from 0.1% to 5 parts per million. Professor Trost developed a prophenol chiral binuclear ligand (Trost, BM; Bartlett, MJAcc. Chem. Res. 2015, 48, 688.) that reacts with two molecules of diethylzinc to form a binuclear complex. The Zn linked to the ethyl group acts as a Brønsted base, while the other zinc molecule participates in the reaction as a Lewis acid.

[0005] We have discovered that binuclear catalysis can transform intermolecular reactions into intramolecular reactions, thereby improving reaction efficiency, reducing catalyst dosage, and potentially enabling reactions that cannot be catalyzed by mononuclear ligands. However, despite the rapid development and significant progress in this field, many challenges remain to be addressed.

[0006] 1. Properties of hexadentate chiral ligands: Compared with bidentate, tridentate and tetradentate oxazoline-containing ligands, the catalytic properties of other ligands (such as hexadentate) are unknown and need to be further explored;

[0007] 2. Bimetallic catalytic ability of hexadentate chiral ligands: Chiral hexadentate ligands have multiple coordination sites and can form binuclear or polynuclear complexes with metal ions with smaller ionic radii. We propose to investigate the influence of chiral hexadentate ligands on the chiral induction and mass transfer of binuclear / polynuclear catalytic centers.

[0008] Therefore, we believe that the development of binuclear ligands and coordination compounds is necessary and of great significance. Summary of the Invention

[0009] The purpose of this invention is to address the problems existing in the prior art by providing a binuclear chiral ligand with a chiral diamine as the parent skeleton and containing pyridine and chiral oxazoline units.

[0010] The objective of this invention is achieved through the following solution:

[0011] A binuclear chiral ligand compound, with a chiral diamine as the parent skeleton and containing pyridine and chiral oxazoline units, has the structural formula shown in Formula I:

[0012]

[0013] Where: n = 0, 1;

[0014] R1 and R2 include one of alkyl, substituted alkyl, alkoxy, unsaturated group, phenyl, and substituted aryl groups;

[0015] When the nitrogen atom attached to R3 is an imine nitrogen, R3 is not any atom; R9 can be one of hydrogen, alkyl, substituted alkyl, alkoxy, unsaturated group, phenyl, or substituted aryl.

[0016] When the nitrogen atom attached to R3 is an amino group, R3 can be one of hydrogen, methyl, ethyl, or benzyl.

[0017] When R1, R3 or R2, R3 are cyclic structures, -R1---R3-=-R2----R3-=-CH2CH2CH2-;

[0018] R4 includes one of hydrogen, fluorine, chlorine, bromine, iodine, alkyl, substituted alkyl, alkoxy, unsaturated group, phenyl, and substituted aryl;

[0019] R5 includes one of hydrogen, fluorine, chlorine, bromine, iodine, alkyl, substituted alkyl, alkoxy, unsaturated group, phenyl, and substituted aryl;

[0020] R6 includes one of the following: hydrogen, fluorine, chlorine, bromine, iodine, alkyl, substituted alkyl, alkoxy, unsaturated group, phenyl, and substituted aryl.

[0021] R7 includes one of the following: hydrogen, fluorine, chlorine, bromine, iodine, alkyl, substituted alkyl, alkoxy, unsaturated group, phenyl, and substituted aryl.

[0022] R8 includes one of the following: hydrogen, fluorine, chlorine, bromine, iodine, alkyl, substituted alkyl, alkoxy, unsaturated group, phenyl, and substituted aryl.

[0023] In R1-R9, the alkyl group is one of the following: chain alkyl, cyclic alkyl, and dendritic alkyl.

[0024] And / or, the substituted alkyl group is one or more of an alkyl group containing a hydroxyl group, an unsaturated group, a phenyl group, or a substituted aryl group;

[0025] And / or, the alkoxy group comprises one or more of a heteroatom, an unsaturated group, and an aromatic group;

[0026] And / or, the unsaturated group includes one of substituted alkenyl or substituted alkynyl.

[0027] In R1-R9, the alkyl C1-12 is one of chain alkyl, cyclic alkyl, and dendritic alkyl;

[0028] And / or, the substituted alkyl group is a C1-12 substituted alkyl group, and its substituent is one of phenyl, hydroxyl, or halogen atom;

[0029] And / or, the alkoxy group is a C1-12 alkoxy group;

[0030] And / or, one of the substituted alkenyl or substituted alkynyl groups of the unsaturated group C1-12.

[0031] The substituted aryl group has 1 to 5 substituents, including alkyl, methoxy, and substituted alkyl groups. The alkyl group is one of C1-12 chain alkyl, cyclic alkyl, and dendritic alkyl groups, and the substituted alkyl group is a haloalkyl group.

[0032] The structure of the binuclear chiral ligand is one of the following formulas:

[0033]

[0034]

[0035] The binuclear chiral ligand can be synthesized by method one or method two.

[0036] Method 1 includes the following steps:

[0037] The method for synthesizing the binuclear chiral ligand includes the following steps:

[0038] S1, compound II Imine IV was obtained under the reduction of a reducing agent.

[0039] S2, imine ester IV, and the corresponding chiral amino alcohol cyclize to yield the chiral oxazoline phosphine compound V with the benzyl alcohol structure.

[0040]

[0041] S3, chiral oxazoline phosphine compound V is oxidized with an oxidizing agent to yield aldehyde compound VI.

[0042] S4, aldehyde compound VI is condensed with the corresponding chiral diamine compound to obtain the binuclear chiral ligand compound.

[0043] In S1, the reducing agent includes one or more of NaBH4, KBH4, NaBH3CN, and NaBH(OAc)3;

[0044] The molar ratio of compound II to reducing agent is 0.1 to 10:1, the reaction temperature is -10 to 100℃, and the reaction time is 1 to 100 hours;

[0045] And / or, in S2, the molar ratio of compound IV to the corresponding chiral amino alcohol is 0.1 to 10:1; the reaction temperature is -10 to 100 °C, and the reaction time is 1 to 100 hours;

[0046] And / or, in S3, the molar ratio of compound V to oxidant is 0.1 to 10:1, the reaction temperature is -10 to 100°C, and the reaction time is 1 to 100 hours;

[0047] And / or, in S3, the oxidant includes one or more of manganese dioxide, IBX, DMP, and DMSO;

[0048] And / or, in S4, the molar ratio of compound VI to the corresponding chiral diamine compound is 0.1 to 10:1, the temperature of the condensation reaction is -10 to 100°C, and the time of the condensation reaction is 1 to 100 hours.

[0049] Method 2 includes the following steps:

[0050] The method for synthesizing the binuclear chiral ligand compound includes the following steps:

[0051] (1) Compound III Condensation with the corresponding chiral amino alcohol yields chiral amide compound VII.

[0052] (2) Cyclic closure of chiral amide compound VII yields intermediate compound VIII.

[0053] (3) Intermediate compound VIII is reduced by a reducing agent to obtain intermediate compound V.

[0054]

[0055] (4) Intermediate compound V is oxidized by an oxidant to give aldehyde compound VI.

[0056] (5) The aldehyde compound VI is condensed with the corresponding chiral diamine compound to obtain the binuclear chiral ligand compound.

[0057] In step (1), the molar ratio of compound III to the corresponding chiral amino alcohol is 0.1 to 10:1, the reaction temperature is -10 to 100°C, and the reaction time is 1 to 100 hours;

[0058] And / or, in step (2), the molar ratio of compound VII to the reagent used for cyclization is 0.1 to 10:1, the reaction temperature is -10 to 100°C, and the reaction time is 1 to 100 hours; the reagent used for cyclization includes one or more of DAST, MsCl, TsCl, SOCl2 / NaOH;

[0059] And / or, in step (3), the molar ratio of compound VIII to reducing agent is 0.1 to 10:1, the reaction temperature is -10 to 100°C, and the reaction time is 1 to 100 hours; the reducing agent includes one or more of NaBH4, KBH4, NaBH3CN, and NaBH(OAc)3.

[0060] And / or, in step (4), the molar ratio of compound V to oxidant is 0.1 to 10:1, the temperature of the stirring reaction is -10 to 100°C, and the time is 1 to 100 hours; the oxidant includes one or more of manganese dioxide, IBX, DMP, and DMSO.

[0061] And / or, in step (5), the molar ratio of compound VI to the corresponding chiral diamine compound is 0.1 to 10:1, the temperature of the condensation reaction is -10 to 100°C, and the time of the condensation reaction is 1 to 100 hours.

[0062] The chiral diamine described in this invention is a binuclear chiral ligand with a parent skeleton, pyridine, and a chiral oxazoline unit. The diamine structure has one or two chiral central carbons with (S) or (R) configurations, and the oxazoline functional group has one or two chiral central carbons with (S) or (R) configurations. It is a binuclear ligand, which can coordinate with two identical or different metals simultaneously.

[0063] Method 1

[0064] The starting compound II was reduced with NaBH4 to obtain imine ester IV, which was then cyclized with the corresponding chiral amino alcohol to obtain chiral oxazoline phosphine compound V with benzyl alcohol structure. It was then oxidized with an oxidant to obtain aldehyde compound VI, which was finally condensed, reduced and substituted with the corresponding chiral diamine compound to obtain binuclear ligand I. The key intermediate structure is as follows.

[0065]

[0066] Method 2

[0067] Starting compound III condenses with the corresponding chiral amino alcohol to give chiral amide compound VII, which is then cyclized to give intermediate VIII. This intermediate is subsequently reduced to give intermediate V, and then oxidized to give aldehyde compound VI. Finally, it condenses with the corresponding chiral diamine compound, is reduced, and substituted to give binuclear ligand I. The key intermediate structures are as follows:

[0068]

[0069] The reaction formula for Method 1:

[0070]

[0071] The reaction formula for Method 2 is as follows:

[0072]

[0073] In the above structure, R1, R2, R3, and R4 are as described above.

[0074] As one embodiment of the present invention, the specific steps of method one are as follows:

[0075] The molar ratio of compound II to NaBH4 is 0.1–10:1, the reaction temperature is -10–100°C, and the reaction time is 1–100 hours; the molar ratio of compound IV to the corresponding chiral amino alcohol is 0.1–10:1, the reaction temperature is -10–100°C, and the reaction time is 1–100 hours; the molar ratio of compound V to the oxidant is 0.1–10:1, the reaction temperature is -10–100°C, and the reaction time is 1–100 hours; the molar ratio of compound VI to the corresponding chiral diamine compound is 0.1–10:1, the reaction temperature is -10–100°C, and the reaction time is 1–100 hours; the oxidant is one of manganese dioxide, IBX, DMP, DMSO, etc.

[0076] As one embodiment of the present invention, the specific steps of method two are as follows:

[0077] The molar ratio of compound III to the corresponding chiral amino alcohol is 0.1–10:1, the reaction temperature is -10–100 °C, and the reaction time is 1–100 hours; the molar ratio of compound VII to the reagent used for cyclization is 0.1–10:1, the reaction temperature is -10–100 °C, and the reaction time is 1–100 hours; the molar ratio of compound VIII to the reducing agent is 0.1–10:1, the reaction temperature is -10–100 °C, and the reaction time is 1–100 hours; the molar ratio of compound V to the oxidizing agent is 0.1–10:1, the reaction temperature is -10–100 °C, and the reaction time is 1–100 hours; the molar ratio of compound VI to the corresponding chiral diamine is 0.1–10:1, the reaction temperature is -10–100 °C, and the reaction time is 1–100 hours. The cyclization reagents are DAST, MsCl, TsCl, etc. The oxidant is one of manganese dioxide, IBX, DMP, DMSO, etc.

[0078] The present invention also provides an NH-type ligand, which is obtained by reducing the aforementioned binuclear chiral ligand compound.

[0079] The molar ratio of the binuclear chiral ligand I to the reducing agent is 0.1–10:1, the reduction reaction temperature is -10–100°C, and the reduction reaction time is 1–100 hours.

[0080] The reducing agent is selected from one of NaBH4, KBH4, NaBH3CN, and NaBH(OAc)3.

[0081] The structural formula of the NH class ligand is one of the following:

[0082]

[0083]

[0084] The present invention also provides an N-substituted ligand, which is obtained by the substitution reaction of the NH-type ligand with the corresponding aldehyde.

[0085] The molar ratio of the NH ligand to the corresponding aldehyde is 0.1 to 10:1, the temperature of the substitution reaction is -10 to 100°C, and the reaction time is 1 to 100 hours.

[0086] The N-substituted ligand structure is one of the following formulas:

[0087]

[0088]

[0089] The present invention also provides an application of the aforementioned binuclear chiral ligand in the preparation of catalysts. In this application, the metals that can form metal coordination with the binuclear chiral ligand include one or more of copper, gold, palladium, silver, rhodium, ruthenium, and zinc.

[0090] Compared with the prior art, the present invention has the following beneficial effects:

[0091] (1) The ligands in this invention can coordinate with two identical or different metals, enabling the binuclear catalyst to co-activate the substrate or the mononuclear catalyst to activate the substrate in the reaction, while the other metal acts as a ligand to influence the activity of the catalytic center. Such binuclear catalysts are expected to achieve reactions that are difficult to achieve with conventional mononuclear catalysts through unique metal-metal bonds.

[0092] (2) This invention has a wide range of applications. It can coordinate with copper, gold, palladium, silver, rhodium, ruthenium and zinc to form a chiral binuclear catalyst and be applied to many asymmetric catalytic reactions, and has good application prospects. Attached Figure Description

[0093] Other features, objects, and advantages of the present invention will become more apparent from the following detailed description of non-limiting embodiments with reference to the accompanying drawings:

[0094] Figure 1 This is a schematic diagram of the single-crystal structure of the double copper metal complex synthesized using compound I-25 and cuprous tetraacetonitrile tetrafluoroborate in Application Example 1.

[0095] Figure 2 This represents two possible coordination modes between this type of chiral binuclear ligand and metals with smaller atomic radii, such as copper, gold, palladium, silver, rhodium, ruthenium, and zinc. Detailed Implementation

[0096] The following examples will help to further understand the present invention, but do not limit the scope of the invention. The preparation method of the present invention can further represent the compound preparation process, as shown below:

[0097] In asymmetric catalysis, the ligands of chiral catalysts are crucial for achieving high enantioselectivity. This invention provides a class of binuclear chiral ligands with a chiral diamine as the parent skeleton and pyridine and a chiral oxazoline unit, along with their synthetic method. This invention is the first to synthesize a binuclear chiral ligand with a chiral diamine as the parent skeleton and pyridine and a chiral oxazoline unit. The six coordinating N atoms in ligand I are spatially well-suited to the design of binuclear catalysts due to their distance and angle. Therefore, we designed and synthesized this type of binuclear chiral ligand. This type of ligand can coordinate with two identical metals, enabling either co-activation of the substrate by the two nuclei or mononuclear activation of the substrate in the reaction, while the other metal acts as a ligand influencing the activity of the catalytic center. This type of binuclear catalyst holds promise for achieving reactions that are difficult to achieve with conventional mononuclear catalysts through unique metal-metal bonds. (e.g.) Figure 2 The diagram shows two possible coordination modes between this type of chiral binuclear ligand and metals with small atomic radii, such as copper, gold, palladium, silver, rhodium, ruthenium, and zinc. (The question mark indicates two possible coordination modes between two metals with small atomic radii, such as copper, gold, palladium, silver, rhodium, ruthenium, and zinc.)

[0098] Figure 1 This is a schematic diagram of the single-crystal structure of the double copper metal complex synthesized using compound I-25 and cuprous tetraacetonitrile tetrafluoroborate in Application Example 1.

[0099] The compounds involved in the embodiments of this invention are numbered as shown in the figure below (where I-1 to I-19 are binuclear chiral ligands I; I-20 to I-39 are NH-type ligands; and I-40 to I-61 are N-substituted ligands):

[0100]

[0101]

[0102]

[0103] Example 1: Preparation of compound I-1 from monomethyl 2,6-pyridinedicarboxylic acid ester

[0104]

[0105] (1) Dissolve 10 mmol of 2,6-pyridinedicarboxylic acid monomethyl ester in 50 mL of dry dichloromethane (10 mL), add 12 mmol of oxalyl chloride dropwise at 0 °C, add 0.2 mL of DMF (0.2 mL), and after the addition is complete, bring the temperature to room temperature (25 °C) and continue stirring for 1 hour to obtain the acyl chloride compound. The product is used directly in the next step of the reaction without purification.

[0106]

[0107] (2) Dissolve 10 mmol of acyl chloride compound in 50 mL of dry dichloromethane, and then add it dropwise to a dichloromethane solution of amino alcohol (10 mmol) and triethylamine (55 mmol). React at room temperature for 1 h. After the reaction is complete, remove the solvent by rotary evaporation to obtain amide compounds. The product is used directly in the next step of the reaction without purification.

[0108]

[0109] (3) Dissolve 10 mmol of amide compound in 50 mL of dry dichloromethane, add DAST (12.5 mmol) to the reaction system at 0 °C, and after the addition is complete, heat to room temperature and react for 12 h to obtain pyridine methyl ester oxazoline compound. The product is used directly in the next step of the reaction without purification.

[0110]

[0111] (4) 10 mmol of pyridine methyl ester oxazoline compound was dissolved in 50 mL of methanol solution, and sodium borohydride (30 mmol) was added for reduction. After reacting at room temperature for 1 h, pyridine benzyl alcohol compounds were obtained. The reaction was quenched with water, and the solvent was removed by rotary evaporation. The mixture was then extracted with ethyl acetate, and the solvent was removed by rotary evaporation. The residue was dissolved in anhydrous acetonitrile, and 140 mmol of active manganese dioxide was added for oxidation. The reaction was refluxed at 85 °C for 1 h. After the raw material was completely consumed by TLC monitoring, the mixture was filtered through diatomaceous earth. The filtrate was removed by rotary evaporation and purified by column chromatography to obtain pyridine aldehyde compounds.

[0112]

[0113] (5) Dissolve 2 mmol of a pyridine aldehyde in 10 mL of dry methanol solution, add 1 mmol of chiral R,R or S,S cycloethylenediamine for condensation reaction, stir at room temperature for 12 h, remove the solvent by rotary evaporation after the reaction is complete, and dry the compound to obtain ligand I-1 (99%, 0.58 g), the structure of which is shown as I-1 in the above formula, and the structural characterization is as follows: 1 H NMR(500MHz,Chloroform-d)δ8.47(s,2H),8.10(dd,J=7.7,4.8Hz,4H),7.76(t,J=7.8Hz,2H),7.39-7.22(m,10H),5.44(dd,J=10.0 ,8.8Hz,2H),4.89(dd,J=10.2,8.7Hz,2H),4.38(t,J=8.5Hz,2H),3.54(p,J=8.4Hz,2H),1.93-1.70(m,6H),1.50(t,J=17.4Hz,2H).

[0114] Through a similar process described above, a series of compounds I were prepared via route one. The structures and analytical characterization results of each compound are as follows:

[0115]

[0116] 2 mmol of starting material was used to obtain 0.61 g of the target product (Ⅰ-2) in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ8.45(s,2H),8.06(d,J=7.9Hz,2H),7.99(d,J=7.7Hz, 2H),7.74(t,J=7.8Hz,2H),7.33-7.21(m,10H),4.69-4.59(m,2H),4.43(t,J=9.0Hz ,2H),4.22(t,J=8.1Hz,2H),3.56-3.50(m,2H),3.30(dd,J=13.8,5.0Hz,2H),2.73( dd,J=13.7,9.2Hz,2H),1.87(d,J=8.1Hz,2H),1.78(s,4H),1.50(t,J=14.8Hz,2H).

[0117]

[0118] 2 mmol of raw material was added to obtain 0.51 g of the target product (Ⅰ-3) with a yield of 99%. The structure was characterized as follows: ¹H NMR (500MHz, Chloroform-d) δ 8.43 (s, 2H), 8.03 (d, J = 7.9Hz, 2H), 7.99 (d, J = 7.1Hz, 2H), 7.71 (t, J = 7.8Hz, 2H), 4.49 (dd, J = 9.3, 8.5Hz, 2H), 4.19 (t, J = 8.3Hz, 2H), 4.16–4.10 (m, 2H), 3.53–3.48 (m, 2H), 1.87 (dt, J = 9.9, 5.0Hz, 4H), 1.76 (s, 4H), 1.50 (d, J = 11.9Hz, 2H), 1.03 (d, J = 6.7Hz, 6H), 0.91 (d, J = 6.7Hz, 6H).

[0119]

[0120] 2 mmol of starting material was used to obtain 0.54 g of the target product (Ⅰ-4) in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ8.43(s,2H),8.03(d,J=7.8Hz,4H),7.71(t,J=7.8Hz,2H),4.43(dd,J=10.2,8.8Hz,2H),4.29(t,J=8.6Hz, 2H), 4.09 (dd, J = 10.2, 8.4Hz, 2H), 3.50 (dd, J = 10.0, 4.7Hz, 2H), 1.85 (d, J = 8.1Hz, 2H), 1.76 (s, 4H), 1.49 (t, J = 7.9Hz, 2H), 0.94 (s, 18H).

[0121]

[0122] 2 mmol of starting material was used to obtain 0.46 g of the target product (I-5) in 99% yield. The structure was characterized as follows: 1H NMR(500MHz,Chloroform-d)δ8.44(s,2H),8.04(dd,J=7.9,0.9Hz,2H),7.96(dd,J=7.7,0.9Hz,2H),7.73(t,J=7.8Hz,2H),4.60(dd,J=9.4,8.3Hz,2H),4. 43(ddd,J=10.8,9.3,4.6Hz,2H),4.04(t,J=8.1Hz,2H),3.55-3.49(m,2H),1 .89-1.84(m,2H),1.78(s,4H),1.51(d,J=12.0Hz,2H),1.38(d,J=6.7Hz,6H).

[0123]

[0124] 2 mmol of starting material was used to obtain 0.73 g of the target product (I-6) in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ8.50(s,2H),8.13(dd,J=7.8,4.1Hz,4H),7.75(t,J=7.8Hz,2H),7.41-7.35(m,14H),7.33-7.28(m, 6H), 5.52 (d, J = 8.1Hz, 2H), 5.30 (d, J = 8.1Hz, 2H), 3.57-3.49 (m, 2H), 1.84 (dd, J = 27.4, 9.5Hz, 6H), 1.51 (dd, J = 20.3, 11.4Hz, 2H).

[0125]

[0126] 2 mmol of starting material was used to obtain 0.61 g of the target product (I-7) in 99% yield. The structure was characterized as follows: 1H NMR(500MHz,Chloroform-d)δ8.44(s,2H),8.06(dd,J=7.9,0.8Hz,2H),7.99(dd,J=7.7,0.8Hz,2 H),7.74(t,J=7.8Hz,2H),7.30(dd,J=9.5,5.4Hz,4H),7.25-7.21(m,6H),4.63(ddd,J=17.0,9.2, 5.1Hz,2H),4.43(t,J=9.0Hz,2H),4.25-4.18(m,2H),3.53(p,J=8.5Hz,2H),3.30(dd,J=13.8,5.0 Hz,2H),2.73(dd,J=13.8,9.2Hz,2H),1.87(d,J=8.2Hz,2H),1.78(s,4H),1.52(d,J=23.2Hz,2H).

[0127]

[0128] 2 mmol of starting material was used to obtain 0.73 g of the target product (I-8) in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ8.50(s,2H),8.16-8.10(m,4H),7.80(t,J=7.8Hz,2H),7.40-7.34(m,14H),7.32-7.28(m,6H) ,5.51(d,J=8.1Hz,2H),5.29(d,J=8.1Hz,2H),3.54(p,J=8.6Hz,2H),1.87(d,J=8.0Hz,2H),1.79(s,4H),1.55-1.45(m,2H).

[0129] Example 2: Preparation of ligand I-9 from 6-methyl ester-2-pyridinium nitrile

[0130]

[0131] (1) Dissolve 6-methyl ester-2-pyridinium nitrile (10 mmol) in 50 mL of dry methanol solution, add sodium borohydride (30 mmol), and stir at room temperature for 12 h to obtain imine ester.

[0132]

[0133] (2) 10 mmol of imine ester and chiral amino alcohol (11 mmol) were refluxed in 50 mL of dichloroethane at 85 °C for 12 h to obtain benzyl alcohol compounds. After removing the solvent by rotary evaporation, the compounds were extracted with ethyl acetate and the solvent was removed by rotary evaporation to obtain benzyl alcohol compounds.

[0134]

[0135] (3) Dissolve 10 mmol of benzyl alcohol in 50 mL of anhydrous acetonitrile, add 140 mmol of active manganese dioxide, and reflux at 85 °C for 1 h. After the raw material is completely consumed by TLC monitoring, filter through diatomaceous earth, remove the filtrate by rotary evaporation, and then purify by column chromatography to obtain pyridine aldehyde compounds.

[0136]

[0137] 2 mmol of a pyridine aldehyde compound was added to 50 mL of dry methanol solution, and 1 mmol of a chiral R,R or S,S cycloethylenediamine was added to initiate a condensation reaction. The mixture was stirred at room temperature for 12 h. After the reaction was complete, the solvent was removed by rotary evaporation, and the compound was dried to obtain ligand I-9 (99%, 0.73 g), with the structure shown as I-9 in the above formula. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ8.50(s,2H),8.16-8.10(m,4H),7.80(t,J=7.8Hz,2H),7.37(dd,J=14.1,6.5Hz,14H),7.32-7.28(m ,6H),5.52(t,J=6.2Hz,2H),5.29(d,J=8.1Hz,2H),3.54(p,J=8.6Hz,2H),1.87(d,J=8.0Hz,2H),1.79(s,4H),1.55-1.46(m,2H).

[0138] Through a similar process described above, a series of compounds I were prepared via route two. The structures and analytical characterization results of each compound are as follows:

[0139]

[0140] 2 mmol of starting material was used to obtain 0.61 g of the target product (Ⅰ-10) in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ8.40(d,J=4.6Hz,2H),7.97(dd,J=7.3,6.7Hz,2H),7.93(d,J=7.7Hz,2H),7.66(t,J=7.8Hz,2H),7.55(d d,J=5.5,3.5Hz,2H),7.26-7.22(m,6H),5.77(d,J=8.0Hz,2H),5.57-5.52(m,2H),3.53-3.39(m,6H),1.89-1.79(m,6H),1.48(s,2H).

[0141]

[0142] 2 mmol of starting material was used to obtain 0.88 g of the target product (Ⅰ-11) in 99% yield. The structure was characterized as follows: 1 H NMR (500MHz, Chloroform-d) δ8.53 (s, 2H), 8.14 (dd, J=10.6, 7.9Hz, 4H), 7.80 (t, J=

[0143] 7.8Hz,2H),7.71(d,J=7.7Hz,4H),7.39(t,J=7.7Hz,4H),7.32(t,J=7.3Hz,2H),7.01

[0144] (qd,J=6.6,3.9Hz,20H),6.17(s,2H),3.56(dd,J=8.9,4.0Hz,2H),1.90-1.77(m,6H),

[0145] 1.51 (t, J = 8.7 Hz, 2H).

[0146]

[0147] 2 mmol of starting material was used to obtain 0.58 g of the target product (Ⅰ-12) in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ8.49(s,2H),8.13(dd,J=13.0,7.8Hz,4H),7.79(t,J=7.8Hz,2H),7.43-7.29(m,10H),7.21-7.12(m,8H), 5.48(t,J=8.3Hz,2H),5.26(t,J=7.8Hz,2H),3.57-3.49(m,2H),2.35(d,J=9.4Hz,6H),1.87(d,J=8.1Hz,2H),1.79(s,4H),1.50(s,2H).

[0148]

[0149] 2 mmol of starting material was used to obtain 0.64 g of the target product (Ⅰ-13) in 99% yield. The structure was characterized as follows: 1H NMR(500MHz,Chloroform-d)δ8.51(s,2H),8.11-8.06(m,4H),7.76(t,J=7.8Hz,2H),7.33(t,J=7.2Hz,4H),7.30-7.27(m,2H),7.23(d, J=6.9Hz,4H),5.09(s,2H),3.55(p,J=8.6Hz,2H),1.88(s,2H),1.79(s,4H),1.71(d,J=10.1Hz,6H),1.50(s,2H),0.98(d,J=5.5Hz,6H).

[0150] 2 mmol of starting material was used to obtain 0.79 g of the target product (Ⅰ-14) in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ8.50(s,2H),8.13(dd,J=16.4,7.5Hz,4H),7.82-7.76(m,2H),7.40-7.33(m,10H),6.95-6.92(m,2H),6.89(s, 4H),5.52(d,J=7.8Hz,2H),5.22(dd,J=13.3,7.9Hz,2H),3.53(p,J=8.5Hz,2H),2.29(s,12H),1.90-1.85(m,2H),1.78(s,4H),1.49(s,2H).

[0151]

[0152] 2 mmol of starting material was used to obtain 0.86 g of the target product (Ⅰ-15) in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ8.49(s,2H),8.18(d,J=7.7Hz,2H),8.04(d,J=7.9Hz,2H),7.78(t,J=7.8Hz,2H),7.35(dd,J=12.6,7 .1Hz,18H),7.30(t,J=7.9Hz,6H),7.20(dd,J=8.9,5.1Hz,4H),5.50(d,J=7.9Hz,2H),5.29(t,J=7.8Hz,2H),4.30(s,2H),3.70(s,

[0153]

[0154] 2 mmol of starting material was used to obtain 0.83 g of the target product (Ⅰ-16) in 99% yield. The structure was characterized as follows: 1 H NMR (500MHz, Chloroform-d)δ 1 H NMR(500MHz,Chloroform-d)δ8.61(s,2H),8.10(dd,J=6.6,1.3Hz,2H),7.87-7.70(m, 4H),7.46-7.23(m,30H),5.74-5.70(m,2H),5.52(dd,J=7.9,0.9Hz,2H),5.44(s,2H).

[0155]

[0156] 2 mmol of starting material was used to obtain 0.73 g of the target product (Ⅰ-17) in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ8.94(s,2H),8.85(s,2H),8.15-8.08(m,4H),7.83-7.71(m,8H),7.42-7.24(m,40H),5.72(dd,J=8.0,0. 8Hz, 4H), 5.52 (dd, J = 7.9, 0.9Hz, 4H), 4.00 (dd, J = 10.1, 8.1Hz, 2H), 3.92 (dd, J = 10.0, 8.5Hz, 2H), 3.85 (t, J = 8.2Hz, 2H), 0.89 (s, 9H).

[0157]

[0158] 2 mmol of starting material was used to obtain 0.75 g of the target product (Ⅰ-18) in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ8.92(s,1H),8.83(s,1H),8.15-8.02(m,2H),7.84-7.70(m,4H),7.47-7.16(m,20H),5.72(dd,J= 8.0,0.8Hz,2H),5.52(dd,J=7.9,0.9Hz,2H),3.72-3.50(m,3H),1.93(dq,J=11.4,9.2Hz,1H),1.85-1.73(m,1H),0.98(s,9H).

[0159] Example 3: NH-type ligands

[0160]

[0161] 0.5 mmol I-1 was dissolved in 10 mL of dry methanol solution, and 1.5 mmol of sodium borohydride was added for reduction. The mixture was stirred at room temperature for 1 h. After the reaction was completed by TLC monitoring, water was added to quench the reaction, followed by extraction with ethyl acetate and rotary evaporation of the solvent to obtain ligand I-19 (0.29 g, 99% yield). The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ8.00(t,J=7.7Hz,2H),7.76-7.68(m,2H),7.61(dd,J=23.8 ,7.7Hz,2H),7.37-7.32(m,5H),7.31-7.27(m,5H),5.41(t,J=9.4Hz,2H),4.83(dd,J=18. 2,8.8Hz,2H),4.33(t,J=8.5Hz,2H),4.15(d,J=14.9Hz,2H),4.00-3.93(m,2H),2.37-2. 31(m,2H),2.19-2.12(m,4H),1.70(d,J=8.4Hz,2H),1.21(t,J=10.4Hz,2H),1.04(s,2H).

[0162] Through a similar process described above, a series of compounds I were prepared. The structures and analytical characterization results of each compound are as follows:

[0163]

[0164] Starting with 0.5 mmol of raw material, 0.31 g of the target product (I-20) was obtained in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ7.94(dd,J=14.8,7.9Hz,2H),7.73(dt,J=24.1,7.6Hz,2H),7.65-7 .55(m,2H),7.31(t,J=7.4Hz,4H),7.22(dd,J=14.5,8.9Hz,6H),4.66-4.58(m,2H),4.44-4.37(m ,2H),4.21-3.94(m,6H),3.30(dd,J=13.7,4.9Hz,2H),2.74(dd,J=13.7,9.2Hz,2H),2.34-2.28( m,2H),2.15(d,J=12.8Hz,2H),1.70(d,J=8.8Hz,2H),1.36-1.16(m,4H),1.02(d,J=10.0Hz,2H).

[0165]

[0166] Starting with 0.5 mmol of raw material, 0.26 g of the target product (I-21) was obtained in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ7.92(d,J=7.6Hz,2H),7.70(t,J=7.7Hz,2H),7.60(d, J=7.7Hz,2H),4.48-4.43(m,2H),4.18-4.11(m,6H),3.99-3.93(m,2H),2.32-2.29( m,2H),2.14(d,J=13.1Hz,2H),1.88(dd,J=13.2,6.6Hz,2H),1.69(d,J=8.3Hz,2H), 1.28-1.10(m,4H),1.03(d,J=6.8Hz,6H),1.01-0.94(m,2H),0.92(d,J=6.8Hz,6H).

[0167]

[0168] Starting with 0.5 mmol of raw material, 0.27 g of the target product (I-22) was obtained in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ7.97(d,J=7.5Hz,2H),7.72-7.67(m,2H),7.63- 7.58(m,2H),4.42-4.37(m,2H),4.26(t,J=8.5Hz,2H),4.17-4.13(m,2H),4.10 -4.06(m,2H),3.98-3.93(m,2H),2.32(dd,J=5.3,3.7Hz,2H),2.15(d,J=13.4H z,2H),1.72-1.67(m,2H),1.26-1.16(m,4H),1.03-0.98(m,2H),0.95(s,18H).

[0169]

[0170] Starting with 0.5 mmol of raw material, 0.23 g of the target product (I-23) was obtained in 99% yield. The structure was characterized as follows: 1H NMR(500MHz,Chloroform-d)δ8.44(s,2H),8.04(dd,J=7.9,0.9Hz,2H),7.95(dt,J=7.4,3.7Hz,2H),7.75-7.70(m,2H),4.60(dd,J=9.4,8.3Hz,2H),4 .43(qt,J=12.5,6.2Hz,2H),4.04(t,J=8.1Hz,2H),3.55-3.49(m,2H),1.8 9-1.84(m,2H),1.78(s,4H),1.51(d,J=12.0Hz,2H),1.38(d,J=6.7Hz,6H).

[0171]

[0172] Starting with 0.5 mmol of raw material, 0.37 g of the target product (I-24) was obtained in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ8.00(d,J=7.2Hz,2H),7.63(q,J=7.5Hz,4H),7.37 -7.33(m,14H),7.30(t,J=7.0Hz,8H),5.49(d,J=8.0Hz,2H),5.28(d,J=7.9Hz,2H ),4.14(d,J=14.8Hz,2H),3.98(d,J=14.8Hz,2H),2.36-2.33(m,2H),2.17(d,J=1 2.7Hz, 2H), 1.71 (d, J = 8.6Hz, 2H), 1.22 (t, J = 10.0Hz, 2H), 1.05 (d, J = 9.7Hz, 2H).

[0173]

[0174] Starting with 0.5 mmol of raw material, 0.31 g of the target product (I-25) was obtained in 99% yield. The structure was characterized as follows: 1H NMR(500MHz,Chloroform-d)δ7.92(d,J=7.6Hz,2H),7.72(t,J=7.8Hz,2H),7.62(d,J=7.7Hz,2H),7.32-7.28 (m,4H),7.25-7.21(m,6H),4.66-4.58(m,2H),4.40(dd,J=15.5,6.6Hz,2H),4.19(dd,J=14.1,5.9Hz,2H),4. 16-4.11(m,2H),3.96(dd,J=14.2,5.8Hz,2H),3.28(dd,J=13.7,5.0Hz,2H),2.72(dt,J=17.1,8.6Hz,2H),2. 36-2.30(m,4H),2.15(d,J=13.1Hz,2H),1.71(d,J=8.2Hz,2H),1.21(t,J=9.9Hz,2H),1.03(d,J=8.0Hz,2H).

[0175]

[0176] Starting with 0.5 mmol of raw material, 0.37 g of the target product (I-26) was obtained in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ8.01(d,J=6.9Hz,2H),7.71-7.63(m,4H),7.38- 7.33(m,14H),7.31-7.27(m,6H),5.46(d,J=8.0Hz,2H),5.27(t,J=6.5Hz,2H), 4.13(d,J=15.2Hz,2H),3.99-3.94(m,2H),2.38-2.30(m,4H),2.15(d,J=13.0H z,2H),1.70(d,J=8.3Hz,2H),1.20(dd,J=13.4,6.1Hz,2H),1.06-0.97(m,2H).

[0177]

[0178] Starting with 0.5 mmol of raw material, 0.37 g of the target product (I-27) was obtained in 99% yield. The structure was characterized as follows: 1H NMR(500MHz,Chloroform-d)δ8.01(d,J=6.9Hz,2H),7.71-7.63(m,4H),7.38- 7.33(m,14H),7.31-7.27(m,6H),5.46(d,J=8.0Hz,2H),5.27(t,J=6.5Hz,2H), 4.13(d,J=15.2Hz,2H),3.99-3.94(m,2H),2.38-2.30(m,4H),2.15(d,J=13.0H z,2H),1.70(d,J=8.3Hz,2H),1.20(dd,J=13.4,6.1Hz,2H),1.06-0.97(m,2H).

[0179]

[0180] Starting with 0.5 mmol of raw material, 0.31 g of the target product (I-28) was obtained in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ7.85(d,J=7.6Hz,2H),7.61(t,J=7.7Hz,2H),7.58-7.52(m ,4H),7.26-7.20(m,6H),5.76(d,J=8.0Hz,2H),5.56-5.50(m,2H),4.14-4.10(m,2H),3. 94(d,J=14.9Hz,2H),3.44(dt,J=39.2,12.2Hz,4H),2.28(dd,J=11.9,6.6Hz,2H),2.15- 2.07(m,4H),1.68(d,J=8.4Hz,2H),1.16(dd,J=19.2,9.2Hz,2H),1.00(d,J=8.5Hz,2H).

[0181]

[0182] 0.5 mmol of starting material was used to obtain 0.45 g of the target product (I-29) in 99% yield. The structure was characterized as follows: 1H NMR(500MHz,Chloroform-d)δ8.02(d,J=7.4Hz,2H),7.71(d,J=7.8Hz,4H),7.66(t,J=7.7Hz,2H) ,7.61(d,J=7.6Hz,2H),7.39(t,J=7.7Hz,4H),7.31(t,J=7.3Hz,2H),7.04-6.96(m,20H),6.16(s, 2H),4.14(d,J=15.1Hz,2H),3.99(d,J=15.1Hz,2H),2.36(dd,J=5.4,3.6Hz,2H),2.17(d,J=12.9 Hz,2H),1.70(d,J=8.3Hz,2H),1.20(d,J=10.0Hz,2H),1.04(d,J=10.2Hz,2H),0.90-0.82(m,2H).

[0183]

[0184] Starting with 0.5 mmol of raw material, 0.39 g of the target product (I-30) was obtained in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ8.00(d,J=7.4Hz,2H),7.71-7.63(m,4H),7.39-7.31(m,10 H),7.19-7.14(m,8H),5.42(dd,J=13.4,5.1Hz,2H),5.23(d,J=8.0Hz,2H),4.13(d,J=15 .3Hz,2H),3.96(d,J=15.3Hz,2H),2.33(d,J=9.5Hz,8H),2.15(d,J=13.0Hz,2H),1.70(d ,J=8.3Hz,2H),1.34-1.25(m,2H),1.18(dd,J=20.5,10.6Hz,2H),1.00(d,J=9.7Hz,2H).

[0185]

[0186] Starting with 0.5 mmol of raw material, 0.32 g of the target product (I-31) was obtained in 99% yield. The structure was characterized as follows: 1H NMR(500MHz,Chloroform-d)δ7.98(d,J=7.6Hz,2H),7.72(t,J=7.8Hz,2H),7.63(d, J=7.7Hz,2H),7.34-7.28(m,6H),7.25-7.23(m,4H),5.07(d,J=6.2Hz,2H),4.18(d,J =15.1Hz,2H),4.02-3.98(m,2H),2.36(dd,J=5.5,3.6Hz,2H),2.23-2.13(m,4H),2. 08-2.00(m,2H),1.68(s,6H),1.21(t,J=9.8Hz,2H),1.09-1.02(m,2H),0.96(s,6H).

[0187]

[0188] 0.5 mmol of starting material was used to obtain 0.40 g of the target product (I-32) in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ8.04-8.00(m,2H),7.71-7.64(m,4H),7.34(dt,J=7.2,4. 5Hz,10H),6.93(s,2H),6.89(s,4H),5.46(d,J=7.7Hz,2H),5.18(d,J=7.7Hz,2H),4.12 (d,J=15.2Hz,2H),3.97(dd,J=15.2,5.5Hz,2H),2.54(s,2H),2.33(d,J=5.9Hz,2H),2. 30-2.27(m,14H),2.15(d,J=12.3Hz,2H),1.70(d,J=8.1Hz,2H),1.00(d,J=10.1Hz,2H).

[0189]

[0190] 0.5 mmol of starting material was used to obtain 0.40 g of the target product (I-33) in 99% yield. The structure was characterized as follows: 1H NMR(500MHz,Chloroform-d)δ8.50(s,2H),8.13(dd,J=16.4,7.5Hz,4H),7.82-7.76(m,2H),7.40-7.33(m,10H),6.95-6.92(m,2H),6.89(s, 4H),5.52(d,J=7.8Hz,2H),5.22(dd,J=13.3,7.9Hz,2H),3.53(p,J=8.5Hz,2H),2.29(s,12H),1.90-1.85(m,2H),1.78(s,4H),1.49(s,2H).

[0191]

[0192] 0.5 mmol of starting material was used to obtain 0.35 g of the target product (I-34) in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ7.90(d,J=7.6Hz,2H),7.72(t,J=7.7Hz,2H),7.60(d,J=7.8Hz,2H),7. 33-7.26(m,6H),7.21(d,J=6.8Hz,4H),5.15(s,2H),4.20(d,J=15.3Hz,2H),4.03(d,J=15.3Hz,2H),2 .45(s,2H),2.16(d,J=12.6Hz,2H),1.96(dd,J=14.3,7.3Hz,2H),1.91-1.83(m,2H),1.71(d,J=8.5H z,2H),1.36(dt,J=14.8,7.4Hz,2H),1.28-1.08(m,8H),1.05(t,J=7.4Hz,6H),0.75(t,J=7.4Hz,6H).

[0193]

[0194] Starting with 0.5 mmol of raw material, 0.42 g of the target product (I-35) was obtained in 99% yield. The structure was characterized as follows: 1H NMR(500MHz,Chloroform-d)δ8.04(d,J=6.6Hz,2H),7.88(d,J=8.0Hz,2H),7.81(d,J=8.0Hz,2H),7.73-7 .65(m,4H),7.58-7.51(m,4H),7.47(d,J=8.0Hz,4H),7.38(s,10H),7.32(t,J=7.7Hz,2H),6.09(d,J=7.0H z,2H),5.42(d,J=6.9Hz,2H),4.14(d,J=15.2Hz,2H),3.97(d,J=15.3Hz,2H),2.57(d,J=6.1Hz,2H),2.35 (d,J=7.6Hz,2H),2.16(d,J=12.2Hz,2H),1.70(d,J=7.5Hz,2H),1.20(t,J=9.9Hz,2H),1.04-0.96(m,2H).

[0195]

[0196] Starting with 0.5 mmol of raw material, 0.42 g of the target product (I-36) was obtained in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ8.02(dd,J=7.4,1.0Hz,2H),7.86-7.81(m,4H),7.80-7.77(m,2H),7.76(s ,2H),7.71(t,J=7.6Hz,2H),7.67(d,J=6.8Hz,2H),7.48-7.44(m,4H),7.40-7.33(m,12H),5.51(d,J=8.1 Hz,2H),5.43(d,J=8.1Hz,2H),4.14(t,J=13.8Hz,2H),3.99(d,J=15.3Hz,2H),2.57(d,J=7.0Hz,2H),2.3 9-2.34(m,2H),2.16(d,J=12.9Hz,2H),1.71(d,J=8.0Hz,2H),1.26-1.20(m,2H),1.03(d,J=12.4Hz,2H).

[0197]

[0198] Starting with 0.5 mmol of raw material, 0.47 g of the target product (I-37) was obtained in 99% yield. The structure was characterized as follows: 1H NMR(500MHz,Chloroform-d)δ8.76(d,J=8.3Hz,2H),8.67(d,J=8.3Hz,2H),8.04(t,J=4.2Hz,2H),7.84(d,J=7.9 Hz,2H),7.80(s,2H),7.71(t,J=6.2Hz,4H),7.63(t,J=7.5Hz,4H),7.56(t,J=8.0Hz,4H),7.45-7.39(m,12H),6. 13(d,J=6.8Hz,2H),5.42(d,J=6.8Hz,2H),4.17(d,J=15.3Hz,2H),4.00(d,J=15.4Hz,2H),2.59(d,J=6.8Hz,2H) ,2.37(d,J=8.5Hz,2H),2.17(d,J=12.4Hz,2H),1.71(d,J=8.2Hz,2H),1.21(t,J=10.2Hz,2H),1.06-0.99(m,2H).

[0199]

[0200] 0.5 mmol of starting material was used to obtain 0.50 g of the target product (I-38) in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ8.18(t,J=7.0Hz,4H),8.10(d,J=7.5Hz,2H),8.08-8.03(m,8H),7.97(t,J=7.6Hz ,2H),7.90(d,J=9.3Hz,2H),7.77(d,J=9.3Hz,2H),7.75-7.69(m,4H),7.38(ddd,J=9.9,7.6,3.4Hz,10H),6.38 (d,J=7.6Hz,2H),5.45(d,J=7.6Hz,2H),4.17(d,J=15.4Hz,2H),4.00(d,J=15.4Hz,2H),2.55(q,J=7.1Hz,2H), 2.38(d,J=9.0Hz,2H),2.18(d,J=12.9Hz,2H),1.71(d,J=8.3Hz,2H),1.26-1.18(m,2H),1.04(t,J=7.2Hz,4H).

[0201] Example 4: Preparation of ligand I-39 from ligand I-19

[0202]

[0203] 0.1 mmol of I-19 was dissolved in 5 mL of dry dichloromethane solution, and 0.6 mmol of 37% formaldehyde aqueous solution was added. The mixture was stirred at room temperature for half an hour, followed by the addition of 1.2 mmol of NaBH(OAc)3 to initiate the substitution reaction. The reaction was carried out at room temperature for 12 h. After the reaction was completed by TLC monitoring, water was added to quench the reaction, followed by dichloromethane extraction and rotary evaporation of the solvent to obtain ligand I-39 (61.4 mg, 99% yield). The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ8.02(d,J=7.4Hz,2H),7.78-7.72(m,2H),7.71-7.61(m,2H ),7.37-7.29(m,10H),5.44(dd,J=10.1,8.7Hz,2H),4.92-4.86(m,2H),4.38(t,J=8.5Hz ,2H),4.04(t,J=14.6Hz,2H),3.90-3.82(m,2H),2.73-2.64(m,2H),2.30(d,J=8.0Hz,6H ),2.01(d,J=12.3Hz,2H),1.78(s,2H),1.30-1.25(m,2H),1.18(dd,J=13.1,6.0Hz,2H).

[0204] Through a similar process described above, a series of compounds I were prepared. The structures and analytical characterization results of each compound are as follows:

[0205]

[0206] Starting with 0.1 mmol of raw material, 64.2 mg of the target product (I-40) was obtained in 99% yield. The structure was characterized as follows: 1H NMR(500MHz,Chloroform-d)δ7.91(d,J=7.5Hz,2H),7.72(d,J=7.4Hz,2H),7.66(t,J=7.7Hz,2H),7.33-7.28(m, 5H),7.24(dd,J=7.5,4.1Hz,5H),4.68-4.60(m,2H),4.43(t,J=9.0Hz,2H),4.26-4.20(m,2H),4.04(d,J=15.4Hz, 2H),3.85(d,J=15.3Hz,2H),3.31(dd,J=13.8,5.0Hz,2H),2.75(dd,J=13.7,9.3Hz,2H),2.68(d,J=8.9Hz,2H),2 .29(s,6H),2.02-1.98(m,2H),1.78(d,J=7.6Hz,2H),1.28(dd,J=11.5,8.1Hz,2H),1.17(dd,J=10.4,8.6Hz,2H).

[0207]

[0208] Starting with 0.1 mmol of the product, 54.6 mg of the target product (I-41) was obtained in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ7.90(d,J=7.5Hz,2H),7.70-7.66(m,2H),7.61(t,J=7.7Hz,2H),4.49-4.45 (m,2H),4.19(t,J=8.3Hz,2H),4.12(dt,J=14.1,6.9Hz,2H),4.00(d,J=15.4Hz,2H),3.82(d,J=15.4Hz,2H ),2.64(d,J=9.0Hz,2H),2.26(s,6H),1.97(d,J=12.6Hz,2H),1.87(dt,J=12.5,6.3Hz,2H),1.75(d,J=7.8 Hz,2H),1.24(dd,J=10.6,3.3Hz,2H),1.14(t,J=9.5Hz,2H),1.03(d,J=6.7Hz,6H),0.91(d,J=6.8Hz,6H).

[0209]

[0210] Starting with 0.1 mmol of raw material, 57.4 mg of the target product (I-42) was obtained in 99% yield. The structure was characterized as follows: 1H NMR(500MHz,Chloroform-d)δ7.95(d,J=7.1Hz,2H),7.71-7.66(m,2H),7.65-7.59(m,2H), 4.43(dd,J=10.1,8.9Hz,2H),4.30(t,J=8.5Hz,2H),4.09(dd,J=10.2,8.3Hz,2H),4.01(d,J =15.4Hz,2H),3.82(d,J=15.3Hz,2H),2.66(dd,J=5.7,3.2Hz,2H),2.27(s,6H),1.96(s,2H ),1.76(d,J=7.4Hz,2H),1.25(dd,J=15.7,5.0Hz,2H),1.15(t,J=9.6Hz,2H),0.96(s,18H).

[0211]

[0212] 0.1 mmol of starting material was used to obtain 49.0 mg of the target product (I-43) in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ7.88(t,J=9.2Hz,2H),7.69(d,J=7.8Hz,2H),7.64(t,J=7.7 Hz,2H),4.60-4.56(m,2H),4.46-4.39(m,2H),4.03(dd,J=15.4,7.2Hz,4H),3.84(d,J=15 .3Hz,2H),2.67(dd,J=5.7,3.1Hz,2H),2.27(d,J=6.7Hz,6H),1.99(d,J=2.2Hz,2H),1.76 (d,J=7.4Hz,2H),1.38(d,J=6.7Hz,6H),1.27-1.24(m,2H),1.16(dd,J=16.5,6.2Hz,2H).

[0213]

[0214] Starting with 0.1 mmol of raw material, 76.6 mg of the target product (I-44) was obtained in 99% yield. The structure was characterized as follows: 1H NMR(500MHz,Chloroform-d)δ8.04(d,J=7.5Hz,2H),7.78(d,J=7.8Hz,2H),7.71(t,J=7.7H z,2H),7.37(p,J=6.0Hz,16H),7.31(d,J=3.5Hz,4H),5.51(d,J=8.0Hz,2H),5.29(d,J=8.0H z,2H),4.07(d,J=15.3Hz,2H),3.91(d,J=15.4Hz,2H),2.70(d,J=9.0Hz,2H),2.32(s,6H),2 .01(d,J=11.9Hz,2H),1.77(d,J=7.9Hz,2H),1.30(d,J=11.1Hz,2H),1.17(t,J=9.6Hz,2H).

[0215]

[0216] Starting with 0.1 mmol of raw material, 64.2 mg of the target product (I-45) was obtained in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ7.91(d,J=7.3Hz,2H),7.72(d,J=7.7Hz,2H),7.66(t,J=7.6Hz,2H),7.31(t,J=7 .4Hz,4H),7.27-7.23(m,6H),4.68-4.60(m,2H),4.43(t,J=9.0Hz,2H),4.23(t,J=8.1Hz,2H),4.03(d,J=15.4 Hz,2H),3.86(d,J=15.4Hz,2H),3.31(dt,J=12.3,6.2Hz,2H),2.75(dd,J=13.7,9.2Hz,2H),2.68(d,J=9.1Hz, 2H),2.28(d,J=9.7Hz,6H),2.02-1.98(m,2H),1.78(d,J=7.6Hz,2H),1.31-1.26(m,2H),1.17(t,J=9.8Hz,2H).

[0217]

[0218] Starting with 0.1 mmol of raw material, 76.6 mg of the target product (I-46) was obtained in 99% yield. The structure was characterized as follows: 1H NMR(500MHz,Chloroform-d)δ8.04(d,J=7.4Hz,2H),7.80(d,J=7.8Hz,2H),7.71(t,J=7.8Hz ,2H),7.37(ddd,J=7.1,6.1,2.5Hz,14H),7.32-7.30(m,6H),5.51(d,J=8.0Hz,2H),5.29(d,J =8.0Hz,2H),4.09(d,J=15.4Hz,2H),3.90(d,J=15.4Hz,2H),2.71(d,J=9.0Hz,2H),2.33(s, 6H), 2.00 (d, J = 11.2Hz, 2H), 1.77 (d, J = 7.4Hz, 2H), 1.32-1.27 (m, 2H), 1.17 (t, J = 9.6Hz, 2H).

[0219]

[0220] Starting with 0.1 mmol of raw material, 76.6 mg of the target product (I-47) was obtained in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ8.00(s,2H),7.68(d,J=35.9Hz,4H),6.90(d,J=32.7Hz,20H),6.00(s,2H),5.72(s,2H) ,4.00(s,2H),3.83(d,J=13.1Hz,2H),2.63(s,2H),2.26(s,6H),1.93(s,2H),1.68(s,2H),1.18(s,2H),1.09(s,2H).

[0221]

[0222] Starting with 0.1 mmol of raw material, 63.8 mg of the target product (I-48) was obtained in 99% yield. The structure was characterized as follows: 1H NMR(500MHz,Chloroform-d)δ7.76(d,J=7.5Hz,2H),7.54(t,J=9.9Hz,2H),7.52-7.45 (m,4H),7.14(s,6H),5.66(d,J=7.9Hz,2H),5.44(t,J=6.5Hz,2H),3.89(d,J=14.9Hz, 2H),3.73-3.66(m,2H),3.42-3.32(m,4H),2.52(d,J=6.8Hz,2H),2.13(s,6H),1.87(d ,J=11.4Hz,2H),1.65(d,J=6.6Hz,2H),1.18(d,J=12.6Hz,2H),1.05(d,J=9.2Hz,2H).

[0223]

[0224] Starting with 0.1 mmol of raw material, 91.9 mg of the target product (I-49) was obtained in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ8.07(d,J=7.3Hz,2H),7.80(s,2H),7.73(d,J=7.4Hz ,6H),7.40(t,J=7.4Hz,4H),7.32(t,J=7.0Hz,2H),7.06-6.97(m,20H),6.17(s,2H) ,4.11(d,J=14.2Hz,2H),3.92(d,J=14.9Hz,2H),2.71(s,2H),2.34(s,6H),2.02(d, J=8.6Hz,2H),1.77(d,J=6.1Hz,2H),1.28(d,J=17.8Hz,2H),1.18(d,J=8.8Hz,2H).

[0225]

[0226] Starting with 0.1 mmol of raw material, 79.5 mg of the target product (I-50) was obtained in 99% yield. The structure was characterized as follows: 1H NMR(500MHz,Chloroform-d)δ8.04(d,J=7.0Hz,2H),7.80(d,J=7.4Hz,2H),7.70(t,J =7.4Hz,2H),7.37(s,10H),7.19(d,J=7.7Hz,8H),5.50(d,J=7.7Hz,2H),5.25(d,J=7 .7Hz,2H),4.09(d,J=15.4Hz,2H),3.89(d,J=15.3Hz,2H),2.70(d,J=6.5Hz,2H),2.3 4(d,J=10.5Hz,12H),1.99(d,J=11.9Hz,2H),1.77(s,2H),1.29(s,2H),1.17(s,2H).

[0227]

[0228] Starting with 0.1 mmol of raw material, 67.0 mg of the target product (I-51) was obtained in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ7.92(d,J=7.5Hz,2H),7.68(d,J=7.7Hz,2H),7.60(t, J=7.7Hz,2H),7.22(dt,J=17.5,6.9Hz,10H),5.01(s,2H),4.01(d,J=15.4Hz,2H),3 .80(d,J=15.4Hz,2H),2.62(d,J=7.9Hz,2H),2.24(s,6H),1.93(d,J=12.2Hz,2H),1 .70(d,J=6.4Hz,2H),1.62(s,6H),1.22(s,2H),1.09(t,J=9.2Hz,2H),0.91(s,6H).

[0229]

[0230] Starting with 0.1 mmol of raw material, 82.3 mg of the target product (I-52) was obtained in 99% yield. The structure was characterized as follows: 1H NMR(500MHz,Chloroform-d)δ8.05(d,J=7.5Hz,2H),7.81(d,J=7.8Hz,2H),7.71(t,J=7.7Hz,2 H),7.39-7.34(m,10H),6.94(s,2H),6.92(s,4H),5.52(d,J=7.8Hz,2H),5.20(d,J=7.8Hz,2H) ,4.12-4.08(m,2H),3.89(d,J=15.5Hz,2H),2.70(dd,J=6.0,3.0Hz,2H),2.33(s,6H),2.30(s, 12H), 1.99 (d, J = 12.7Hz, 2H), 1.77 (d, J = 7.1Hz, 2H), 1.33-1.29 (m, 2H), 1.16 (d, J = 9.7Hz, 2H).

[0231]

[0232] Starting with 0.1 mmol of raw material, 86.7 mg of the target product (I-53) was obtained in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ8.11(d,J=7.4Hz,2H),7.89(d,J=8.1Hz,2H),7.81(d,J=8.4Hz,4H),7.7 4(t,J=7.3Hz,2H),7.62-7.55(m,4H),7.47(dd,J=13.9,7.1Hz,4H),7.40(s,10H),7.34(t,J=7.6Hz,2H ),6.12(d,J=6.6Hz,2H),5.51(d,J=6.3Hz,2H),4.12(d,J=15.4Hz,2H),3.91(d,J=15.2Hz,2H),2.72( s,2H),2.35(s,6H),2.00(d,J=11.1Hz,2H),1.77(d,J=6.0Hz,2H),1.30(s,2H),1.19(d,J=9.1Hz,2H).

[0233]

[0234] Starting with 0.1 mmol of raw material, 86.7 mg of the target product (I-54) was obtained in 99% yield. The structure was characterized as follows: 1H NMR(500MHz,Chloroform-d)δ8.08(d,J=7.6Hz,2H),7.87-7.78(m,10H),7.73(t,J=7.7 Hz,2H),7.49-7.45(m,4H),7.43-7.36(m,12H),5.58(d,J=8.0Hz,2H),5.46(d,J=8.0Hz, 2H),4.12(d,J=15.4Hz,2H),3.96-3.86(m,2H),2.72(d,J=7.4Hz,2H),2.35(s,6H),2.0 1(d,J=11.9Hz,2H),1.78(d,J=7.6Hz,2H),1.32(d,J=7.9Hz,2H),1.18(t,J=9.8Hz,2H).

[0235]

[0236] Starting with 0.1 mmol of raw material, 96.7 mg of the target product (I-55) was obtained in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ8.77(d,J=8.3Hz,2H),8.68(d,J=8.3Hz,2H),8.15(d,J=7.6Hz,2H),7.91-7.81 (m,6H),7.78(t,J=7.7Hz,2H),7.63(dd,J=17.0,8.2Hz,6H),7.57(t,J=7.4Hz,2H),7.43(dd,J=8.8,3.2Hz,1 2H),6.17(d,J=6.8Hz,2H),5.53(d,J=6.7Hz,2H),4.16(d,J=14.4Hz,2H),4.02-3.86(m,2H),2.75(s,2H),2. 38(s,6H),2.03(d,J=12.2Hz,2H),1.78(d,J=7.7Hz,2H),1.33(d,J=9.3Hz,2H),1.19(dd,J=13.8,8.5Hz,2H).

[0237]

[0238] Starting with 0.1 mmol of raw material, 101.7 mg of the target product (I-56) was obtained in 99% yield. The structure was characterized as follows: 1HNMR(500MHz,Chloroform-d)δ8.22-8.16(m,5H),8.12(dd,J=14.6,8.0Hz,5H),8.06(s,4H),7.99(t, J=7.6Hz,2H),7.93(d,J=9.3Hz,2H),7.84(t,J=10.2Hz,4H),7.78(t,J=7.6Hz,2H),7.42(s,10H),6.44 (d,J=7.6Hz,2H),5.60(d,J=7.2Hz,2H),4.17(d,J=14.7Hz,2H),3.94(d,J=27.6Hz,2H),2.77(s,2H), 2.38(d,J=14.2Hz,6H),2.05-2.00(m,2H),1.78(d,J=7.4Hz,4H),1.33(s,2H),1.19(t,J=10.1Hz,2H).

[0239]

[0240] Starting with 0.1 mmol of raw material, 72.7 mg of the target product (I-57) was obtained in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ7.91(d,J=7.6Hz,2H),7.76(d,J=7.3Hz,2H),7.68(t,J=7.7Hz,2H),7.30(dd,J =16.0,8.5Hz,5H),7.25(dd,J=9.9,5.4Hz,5H),5.19(s,2H),4.09(d,J=14.8Hz,2H),3.94-3.81(m,2H),2.69( s,2H),2.30(d,J=21.1Hz,6H),1.99(dd,J=14.1,7.4Hz,4H),1.93-1.87(m,2H),1.77(d,J=7.3Hz,4H),1.41(d t,J=14.7,7.4Hz,2H),1.28(d,J=7.9Hz,2H),1.23-1.19(m,2H),1.07(t,J=7.4Hz,6H),0.77(t,J=7.4Hz,6H).

[0241]

[0242] Starting with 0.1 mmol of raw material, 83.9 mg of the target product (I-58) was obtained in 99% yield. The structure was characterized as follows: 1H NMR(500MHz,Chloroform-d)δ7.81(d,J=7.5Hz,2H),7.79-7.72(m,2H),7.69(q,J=7.4Hz,2H),7.31(dd,J=15.8 ,7.5Hz,5H),7.25(d,J=7.4Hz,5H),5.28(s,2H),4.12-4.00(m,2H),3.93-3.84(m,2H),2.68(d,J=7.5Hz,2H),2. 34-2.29(m,6H),2.07-1.95(m,6H),1.75(dd,J=14.2,4.9Hz,4H),1.72-1.66(m,2H),1.25(d,J=4.5Hz,4H),1.21 (d,J=7.4Hz,2H),1.18-1.14(m,2H),1.05(dd,J=6.5,2.5Hz,12H),0.79(d,J=6.6Hz,6H),0.70(d,J=6.7Hz,6H).

[0243]

[0244] Starting with 0.1 mmol of raw material, 83.9 mg of the target product (I-59) was obtained in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ7.89(d,J=7.5Hz,2H),7.76(d,J=7.7Hz,2H),7.67(t,J=7.7Hz,2H),7.29(dd,J=13.8,6.4Hz,5 H),7.23(t,J=5.8Hz,5H),5.16(s,2H),4.09(d,J=15.4Hz,2H),3.88(d,J=15.4Hz,2H),2.69(d,J=8.8Hz,2H),2.32(s,6H),2. 00(d,J=11.4Hz,2H),1.89(dd,J=15.0,5.2Hz,4H),1.77(d,J=7.7Hz,2H),1.71(s,2H),1.43(ddd,J=20.6,15.7,7.4Hz,10H) ,1.30(dd,J=17.4,6.9Hz,4H),1.18(dd,J=16.2,8.3Hz,4H),1.08-1.01(m,4H),0.94(d,J=7.1Hz,6H),0.69(t,J=6.9Hz,6H).

[0245]

[0246] Starting with 0.1 mmol of raw material, 89.5 mg of the target product (I-60) was obtained in 99% yield. The structure was characterized as follows: 1 H NMR(500MHz,Chloroform-d)δ8.09(d,J=7.6Hz,2H),7.97(d,J=7.8Hz,2H),7.89(d,J=8.1Hz,2H),7.81(d,J=8.1Hz, 2H),7.68(t,J=7.8Hz,2H),7.62-7.56(m,4H),7.48(dd,J=14.3,7.2Hz,5H),7.42-7.38(m,10H),7.36-7.31(m,3H),6 .13(d,J=7.0Hz,2H),5.51(d,J=7.1Hz,2H),4.09(d,J=16.2Hz,2H),3.86(d,J=16.2Hz,2H),2.81(d,J=7.6Hz,2H),2 .65(td,J=12.6,6.1Hz,4H),2.07(d,J=11.7Hz,2H),1.76(d,J=7.2Hz,2H),1.18-1.12(m,2H),1.03(t,J=7.1Hz,6H).

[0247] Application effect test

[0248] The chiral binuclear ligand of this invention can be applied in the field of asymmetric catalytic synthesis of certain reactions. For example, this ligand can enable the reaction of propargyl esters with phosphine oxides, and can control the axial chirality of the resulting allene phosphine products. Specific tests are as follows:

[0249]

[0250] In a glove box, a 10.0 mL vial equipped with a magnetic stir bar was filled with ligand I59 (8.8 mg, 0.0105 mmol, 5.25 mol%), CuI (3.8 mg, 0.02 mmol, 10 mol%), and dry MeOH (1.0 mL). After stirring at room temperature for 30 min, citric acid (38.4 mg, 0.2 mmol, 1.0 equivalent) and diphenylphosphine oxide (0.24 mmol, 1.2 equivalent) were added. The mixture was stirred at room temperature for another 10 min, and then 0.2 mmol, 1.0 equivalent, of phenylpropynyl ester was added. Finally, the vial was capped, removed from the glove box, and stirred vigorously at room temperature for 12 hours. The mixture was then directly purified by silica gel column chromatography. The product was a colorless oil (52.5 mg, 83% yield). Its structure was characterized as follows: ¹H NMR (400 MHz, CDCl₃) δ 7.84–7.71 (m, 2H), 7.53–7.45 (m, 2H), 7.45–7.38 (m, 4H), 7.29–7.24 (m, 2H), 7.20 (t, J = 6.8 Hz, 1H), 7.14 (d, J = 7.7 Hz, 2H), 6.32–6.24 (m, 2H). ¹³C NMR (101MHz, CDCl3) δ213.1(d,J=1.4Hz), 132.5(d,J=106.8Hz), 132.3(d,J=106.9H z),132.1(d,J=2.2Hz),132.0(d,J=2.6Hz),131.4(d,J=10.0Hz),131.3(2)(d,J=10 .1Hz),131.3(1),128.8(d,J=1.1Hz),128.5(d,J=1.0Hz),128.4(d,J=0.9Hz),127. 8(d,J=1.1Hz),127.1(d,J=2.1Hz),96.3(d,J=13.5Hz),89.8(d,d,J=102.4Hz).31P NMR (202MHz, CDCl3) δ 23.91. The enantiomeric excess of the product was determined by high performance liquid chromatography: 94:6e.r (CHIRALPAK IM, hexane / i-PrOH = 80 / 20, detector: 254nm, T = 40℃, flow rate: 1.0mL / min), t1 (major) = 15.61min, t2 (minor) = 21.80min.

[0251] The specific embodiments of the present invention have been described above. It should be understood that the present invention is not limited to the specific embodiments described above, and those skilled in the art can make various modifications or variations within the scope of the claims, which do not affect the essence of the present invention.

Claims

1. A binuclear chiral ligand compound, characterized in that, With a chiral diamine as the parent skeleton and containing pyridine and chiral oxazoline units, the structural formula of the binuclear chiral ligand is shown in Formula I: Where: n = 0, 1; R1 and R2 include one of alkyl, substituted alkyl, alkoxy, unsaturated group, phenyl, and substituted aryl groups; When the nitrogen atom attached to R3 is an imine nitrogen, R3 is not any atom; R9 can be one of hydrogen, alkyl, substituted alkyl, alkoxy, unsaturated group, phenyl, or substituted aryl. When the nitrogen atom attached to R3 is an amino group, R3 can be one of hydrogen, methyl, ethyl, or benzyl. When R1, R3 or R2, R3 are cyclic structures, -R1---R3-=-R2----R3-=-CH2CH2CH2-; R4 includes one of hydrogen, fluorine, chlorine, bromine, iodine, alkyl, substituted alkyl, alkoxy, unsaturated group, phenyl, and substituted aryl; R5 includes one of hydrogen, fluorine, chlorine, bromine, iodine, alkyl, substituted alkyl, alkoxy, unsaturated group, phenyl, and substituted aryl; R6 includes one of the following: hydrogen, fluorine, chlorine, bromine, iodine, alkyl, substituted alkyl, alkoxy, unsaturated group, phenyl, and substituted aryl. R7 includes one of the following: hydrogen, fluorine, chlorine, bromine, iodine, alkyl, substituted alkyl, alkoxy, unsaturated group, phenyl, and substituted aryl. R8 includes one of the following: hydrogen, fluorine, chlorine, bromine, iodine, alkyl, substituted alkyl, alkoxy, unsaturated group, phenyl, and substituted aryl.

2. The binuclear chiral ligand compound according to claim 1, characterized in that, In R1-R9, the alkyl group is one of the following: chain alkyl, cyclic alkyl, and dendritic alkyl. And / or, the substituted alkyl group is one or more of an alkyl group containing a hydroxyl group, an unsaturated group, a phenyl group, or a substituted aryl group; And / or, the alkoxy group comprises one or more of a heteroatom, an unsaturated group, and an aromatic group; And / or, the unsaturated group includes one of substituted alkenyl or substituted alkynyl.

3. The binuclear chiral ligand compound according to claim 1, characterized in that, In R1-R9, the alkyl group is one of the following: C1-12 chain alkyl, cyclic alkyl, and dendritic alkyl; And / or, the substituted alkyl group is a C1-12 substituted alkyl group, and its substituent is one of phenyl, hydroxyl, or halogen atom; And / or, the alkoxy group is a C1-12 alkoxy group; And / or, the unsaturated group is one of the substituted alkenyl or substituted alkynyl groups of C1-12.

4. The binuclear chiral ligand compound as described in claim 2, characterized in that, The substituted aryl group has 1 to 5 substituents, including alkyl, methoxy, and substituted alkyl groups. The alkyl group is one of C1-12 chain alkyl, cyclic alkyl, and dendritic alkyl groups, and the substituted alkyl group is a haloalkyl group.

5. The binuclear chiral ligand compound as described in claim 1, characterized in that, The structure of the binuclear chiral ligand is one of the following formulas:

6. A method for synthesizing a binuclear chiral ligand compound as described in any one of claims 1-5, characterized in that, The method for synthesizing the binuclear chiral ligand includes the following steps: S1, compound II Imine IV was obtained under the reduction of a reducing agent. S2, imine ester IV, and the corresponding chiral amino alcohol cyclize to yield the chiral oxazoline phosphine compound V with the benzyl alcohol structure. S3, chiral oxazoline phosphine compound V is oxidized with an oxidizing agent to yield aldehyde compound VI. S4, aldehyde compound VI is condensed with the corresponding chiral diamine compound to obtain the binuclear chiral ligand compound.

7. The method for synthesizing the binuclear chiral ligand compound according to claim 6, characterized in that, In S1, the reducing agent includes one or more of NaBH4, KBH4, NaBH3CN, and NaBH(OAc)3; The molar ratio of compound II to reducing agent is 0.1 to 10:1, the reaction temperature is -10 to 100℃, and the reaction time is 1 to 100 hours; And / or, in S2, the molar ratio of compound IV to the corresponding chiral amino alcohol is 0.1 to 10:1; the reaction temperature is -10 to 100 °C, and the reaction time is 1 to 100 hours; And / or, in S3, the molar ratio of compound V to oxidant is 0.1 to 10:1, the reaction temperature is -10 to 100°C, and the reaction time is 1 to 100 hours; And / or, in S3, the oxidant includes one or more of manganese dioxide, IBX, DMP, and DMSO; And / or, in S4, the molar ratio of compound VI to the corresponding chiral diamine compound is 0.1 to 10:1, the temperature of the condensation reaction is -10 to 100°C, and the time of the condensation reaction is 1 to 100 hours.

8. A method for synthesizing a binuclear chiral ligand compound as described in any one of claims 1-5, characterized in that, The method for synthesizing the binuclear chiral ligand compound includes the following steps: (1) Compound III Condensation with the corresponding chiral amino alcohol yields chiral amide compound VII. (2) Cyclic closure of chiral amide compound VII yields intermediate compound VIII. (3) Intermediate compound VIII is reduced by a reducing agent to obtain intermediate compound V. (4) Intermediate compound V is oxidized by an oxidant to give aldehyde compound VI. (5) The aldehyde compound VI is condensed with the corresponding chiral diamine compound to obtain the binuclear chiral ligand compound.

9. The method for synthesizing the binuclear chiral ligand compound according to claim 8, characterized in that, In step (1), the molar ratio of compound III to the corresponding chiral amino alcohol is 0.1 to 10:1, the reaction temperature is -10 to 100°C, and the reaction time is 1 to 100 hours; And / or, in step (2), the molar ratio of compound VII to the reagent used for cyclization is 0.1 to 10:1, the reaction temperature is -10 to 100°C, and the reaction time is 1 to 100 hours; the reagent used for cyclization includes one or more of DAST, MsCl, TsCl, SOCl2 / NaOH; And / or, in step (3), the molar ratio of compound VIII to reducing agent is 0.1 to 10:1, the reaction temperature is -10 to 100°C, and the reaction time is 1 to 100 hours; the reducing agent includes one or more of NaBH4, KBH4, NaBH3CN, and NaBH(OAc)3. And / or, in step (4), the molar ratio of compound V to oxidant is 0.1 to 10:1, the temperature of the stirring reaction is -10 to 100°C, and the time is 1 to 100 hours; the oxidant includes one or more of manganese dioxide, IBX, DMP, and DMSO. And / or, in step (5), the molar ratio of compound VI to the corresponding chiral diamine compound is 0.1 to 10:1, the temperature of the condensation reaction is -10 to 100°C, and the time of the condensation reaction is 1 to 100 hours.

10. An NH-type ligand, characterized in that, The NH-type ligand is obtained by reduction of the dinuclear chiral ligand compound of any one of claims 1-5, or the dinuclear chiral ligand compound prepared by the method of claim 6 or 7, or the dinuclear chiral ligand compound prepared by the method of claim 8 or 9.

11. The NH-type ligand according to claim 10, characterized in that, The structural formula of the NH class ligand is as follows:

12. An N-substituted ligand, characterized in that, It is obtained by substitution reaction of the NH-type ligand as described in claim 10 or 11 with the corresponding aldehyde.

13. The N-substituted ligand according to claim 12, characterized in that, The N-substituted ligand structure is one of the following formulas:

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