Multidentate ligand, multidentate ligand metal catalyst, preparation method therefor and use thereof

Abstract

Disclosed in the present invention are a multidentate ligand, a multidentate ligand metal catalyst, a preparation method therefor and the use thereof. The multidentate ligand of the present invention has a general structural formula shown as formula (1) or formula (2), and the multidentate ligand metal catalyst has a general structural formula shown as formula (3) or formula (4). The preparation method of the multidentate ligand of the present invention is simple and efficient. The multidentate ligand metal catalyst has high catalytic activity, can still maintain catalytic activity under low loads (amounts), and involves a wide range of applicable substrates.

Description

A multidentate ligand, a multidentate ligand metal catalyst, its preparation method and application Technical Field

[0001] This invention relates to the field of metal-catalyzed organic reaction technology, specifically to a multidentate ligand, a multidentate ligand metal catalyst, its preparation method, and its application. Background Technology

[0002] Transition metal catalyst complexes play a crucial role in catalysis, and their properties are primarily influenced by the characteristics of the metal and the properties of the ligands coordinated to the metal center. The structural features of the ligands affect reaction rates, regioselectivity, and stereoselectivity. For example, in coupling reactions, electron-withdrawing ligands may slow down the oxidative insertion of the metal center into the carbon-halogen bond; conversely, electron-rich ligands can accelerate this process.

[0003] Alkyne metathesis, enabling the dynamic exchange of carbon-carbon triple bonds, is an important tool in synthetic chemistry. After a period of development, several metathesis catalysts with well-defined carbaby structures have been reported. With enhanced catalytic activity and stability, as well as better tolerance to polar functional groups, alkyne metathesis catalysts have found increasingly widespread applications, from intramolecular ring closure and intermolecular oligomerization to polymer chemistry; alkyne metathesis has become a crucial method in organic synthesis.

[0004] Initially, effective catalysts for alkyne metathesis reactions consisted of heterogeneous mixtures of tungsten oxide and silica, discovered by Penella et al., which only exhibited catalytic activity at very high temperatures (approximately 200–450 °C) (J. Chem. Soc. Chem. Commun. 1968, 1548–1549.). Blanchar et al. found that a mixture of [Mo(CO)6] and resorcinol exhibited catalytic activity when heated to 160 °C in an inert solvent. Building upon this, further improvements were achieved through screening different molybdenum sources, substituted phenols, and solvents. However, high-temperature reactions were still required in most cases, and the nature of the in-situ generated active substances remained elusive (J. Chem. Soc. Chem. Commun. 1974, 786–787.). Schrock et al. discovered that some molybdenum, tungsten, and rhenium carbapenem structures exhibit significant catalytic activity, and the derived metal cyclobutadienes were shown to be intermediates rather than transition states (Acc. Chem. Res. 1986, 19, 342-348.). Fürstner et al. found that the reaction of the molybdenum complex Mo[N(tBu)(Ar)]3 with dichloromethane in toluene yielded a mixture that could effectively catalyze metathesis reactions of various aliphatic and aromatic alkynes. They demonstrated the presence of a catalytically active substance in the mixture: [(Ar)(tBu)N]3MoCl (as shown in formula (I)) (J. Am. Chem. Soc. 1999, 121, 9453-9454.). Subsequently, Moore et al. discovered that Mo[N(tBu)(Ar)]3 could be converted into alkyl-substituted metal carbapenem structures (as shown in formula (II)) via a disproportionation reaction with alkyl-substituted dichlorides, and the chloride byproduct could be reduced to the starting compound Mo[N(tBu)(Ar)] by magnesium powder. 3，It also participates in disproportionation reactions in a cyclic manner (J. Am. Chem. Soc. 2004, 126, 1, 329-335.). Zhang et al. found that ligand exchange (preferably with p-nitrophenol) of carbaby complexes can yield highly active catalysts. For example, alcoholysis with electron-deficient pyrogallolamine derivatives, linking the tridentate ligand to the metal center (as shown in formula (III)) can increase the catalyst lifetime. The structure of the polydentate ligand provides stronger complexation compared to the monodentate ligand, exhibiting high catalytic activity and a broad substrate range, even tolerating aldehydes and nitro groups. Kinetic studies have shown that the presence of the nitro group reduces the electron density of the metal center, which can enhance catalytic activity; however, this catalyst has low solubility in most solvents and is very sensitive to water and oxygen (Angew. Chem. Int. Ed. 2011, 50, 3435-3438.). Fürstner et al. found that triphenylsilanol ligands, when coordinated with metal centers (as shown in formula (IV)), can provide higher activity and stability. The good match between the characteristics of the high-valence molybdenum center and the electronic and steric properties of the triphenylsilane ester gives the metal center a Lewis acidity balance, which is crucial for high activity, while also providing excellent tolerance to polar and sensitive functional groups (Chem. Eur. J. 2012, 18, 10281-10299.).

[0005] Johnson et al. discovered a highly fluorinated alkoxide ligand (as shown in formula (V)) that can be prepared simply and efficiently from a molybdenum-nitrogen triple bond compound via alkyne metathesis (J. Am. Chem. Soc. 2006, 128, 9614-9615). Fürstner et al. reported a well-defined and easily separable catalyst (as shown in formula (VI)). The design of the tridentate silanol ligand allows for a larger cavity between Mo and the ligand, which may lower the activation energy of the exchange. However, it lacks structural tunability and modifiable reaction sites (J. Am. Chem. Soc. 2020, 142, 11279-11294). Zhang et al. employed a more rigid ligand (as shown in formula (VII)) to improve catalyst activity by minimizing the configurational entropy of the complex formed with the Mo center. This resulted in increased stability and activity, but the excessive rigidity required a higher activation energy in the catalytic reaction (Nat. Commun. 2021, 12, 1136). In 2023, Fürstner et al. significantly improved catalyst stability by using pyridine to complex the Mo center (as shown in formula (VIII)). When dissolved in toluene, the stable pyridine ligand spontaneously dissociates, releasing an active substance with excellent performance and functional group tolerance. Furthermore, this catalyst can be routinely weighed and handled in air and can be stored for extended periods outside a glove box (J. Am. Chem. Soc. 2023, 145, 26993-27009).

[0006] The tridentate ligand catalysts reported by Fürstner, Zhang et al. have shown significant improvements in stability, catalytic activity, and substrate scope. However, the synthesis of these ligands is cumbersome and lacks controllability, indicating considerable room for further improvement in this area. This invention improves the ligand structure of molybdenum carbamate catalysts, enabling the rapid and efficient synthesis of structurally diverse ligands that balance activity and stability while exhibiting good functional group tolerance. This allows for widespread application in alkyne metathesis reactions.

[0007] Summary of the Invention

[0008] In view of the shortcomings of the existing technology, one of the objectives of the present invention is to provide a multidentate ligand and its preparation method.

[0009] The second objective of this invention is to provide a multidentate ligand metal catalyst, its preparation method, and its application.

[0010] Alkyne metathesis catalysts with polydentate ligands typically exhibit good stability and substrate applicability, but their activity is generally significantly reduced compared to monodentate ligand catalysts. This invention improves the ligand structure of molybdenum carbamate catalysts, designing and synthesizing an adaptive tridentate ligand that significantly enhances reaction activity. Its reaction rate is nearly 100 times higher than that of state-of-the-art polydentate ligands, providing a highly active and selective metal catalyst for alkyne metathesis. Its characteristics include: higher stability and significantly enhanced catalytic activity compared to corresponding non-quaternized or non-silyl polydentate ligand catalyst analogs; and good functional group tolerance, fast reaction rate, and long lifetime. This invention of an adaptive polydentate ligand represents a significant advancement not only in the field of alkyne metathesis but also provides an important strategy for the design of polydentate ligands in organometallic chemistry.

[0011] The objective of this invention is achieved through the following technical solution:

[0012] A multidentate ligand has the following general structural formula:

[0013] Where Z is selected from carbon, R 4 Selected from hydrogen, alkoxy; or Z selected from silicon, R 4 Selected from fluoroalkyl, phenyl; or Z selected from phosphorus, R 4 Selected from oxygen subunits;

[0014] R 1 R 2 R 3 Each is independently selected from hydrogen, halogen, trifluoromethyl, cyano, acetyl, methyl, methoxy, methylthio, isopropyl, phenoxy, 1,1,3,3-tetramethylbutyl, 4-tert-butylphenyl, 4-methoxyphenyl, 4-N,N-dimethylaminophenyl, 4-methoxyformylphenyl, 4-(2,4,6-trimethyl)phenyl, 4-carbazolylphenyl;

[0015] Ar can be represented independently by naphthalene, indene dihydrogen hydride, 1-indanone, dimethylfluorene, and estradiol.

[0016] Preferably, the structure of the multidentate ligand is L1-L51.

[0017] The preparation methods for the aforementioned multidentate ligands are as follows: multidentate ligands L1, L2, L3, L4, L5, L6, L7, L8, L11, L14, L15, L16, L17, L18, L19, L20, L22, L23, L24, L25, L26, L27, L35, L36, L37, L38, L42, L43, L44, L45, L46, L47, L48, L49, L50, and L51 are synthesized using Scheme 1; multidentate ligands L9, L10, L12, L13, L21, and L28 are synthesized using Scheme 2; and multidentate ligands L29, L30, L31, L32, L33, L34, L39, L40, and L41 are synthesized using Scheme 3.

[0018] Option 1 is as follows:

[0019] Option 1

[0020] Under a protective atmosphere, with the aid of a palladium catalyst and a base, a bromine-substituted triphenylmethane derivative reacts with arylboronic acid in a mixed solvent of organic solvent and water to yield a multidentate ligand.

[0021] The structural formula of a bromine-substituted triphenylmethane derivative is one of the following:

[0022] Arylboronic acids include 2-hydroxyphenylboronic acid, (3-chloro-2-hydroxyphenyl)boronic acid, (4-chloro-2-hydroxyphenyl)boronic acid, (5-chloro-2-hydroxyphenyl)boronic acid, (3-fluoro-2-methoxyphenyl)boronic acid, (4-fluoro-2-hydroxyphenyl)boronic acid, (5-fluoro-2-hydroxyphenyl)boronic acid, (4-trifluoromethyl-2-hydroxyphenyl)boronic acid, (5-acetyl-2-hydroxyphenyl)boronic acid, (4-isopropyl-2-hydroxyphenyl)boronic acid, (5-isopropyl-2-methoxyphenyl)boronic acid, (5-methoxy-2-hydroxyphenyl)boronic acid, (4-methoxy-2-hydroxyphenyl)boronic acid, and (4-hydroxyphenyl)-2-hydroxyphenyl ... One of the following: (phenyl)boronic acid, (5-methylthio-2-hydroxyphenyl)boronic acid, (5-phenoxy-2-hydroxyphenyl)boronic acid, (5-isopropyl-4-methyl-2-hydroxyphenyl)boronic acid, (5-chloro-4-chloro-2-methoxyphenyl)boronic acid, (5-fluoro-4-fluoro-2-methoxyphenyl)boronic acid, (3-hydroxynaphthyl-2-yl)boronic acid, (6-hydroxy-2,3-dihydro-1H-indene-5-yl)boronic acid, (6-hydroxy-1-oxo-2,3-dihydro-1H-indene-5-yl)boronic acid, and (2-methoxy-9,9-dimethyl-9H-fluorene-3-yl)boronic acid;

[0023] Option 2 is as follows:

[0024] Option 2

[0025] Under a protective atmosphere, with the aid of a palladium catalyst and a base, triphenylmethane substituted with borate pinacol ester reacts with aryl halides in a mixed solvent of organic solvent and water to yield a multidentate ligand.

[0026] The structural formula of triphenylmethane substituted with pinacol borate is:

[0027] The aryl halide is one of 4-bromo-3-hydroxybenzonitrile, 3-bromo-4-hydroxybenzonitrile, 2-bromo-4-methylphenol, 2-bromo-5-methylphenol, 2-bromo-4-(2,4,4-trimethylpentan-2-yl)phenol, and (8R,9S,13S)-3-hydroxy-2-iodo-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthrene-17-one;

[0028] Option 3 is as follows:

[0029] Option 3

[0030] Under a protective atmosphere, with the aid of a palladium catalyst and a base, halogen-substituted tri(biphenyl)methane reacts with arylboronic acid in a mixed solvent of organic solvent and water to yield a multidentate ligand.

[0031] The structural formula of halogen-substituted tri(biphenyl)methane is:

[0032] Arylboronic acid is one of (4-(tert-butyl)phenyl)boronic acid, (4-methoxyphenyl)boronic acid, (4-(dimethylamino)phenyl)boronic acid, (4-(methoxycarbonyl)phenyl)boronic acid, (2',4',6'-trimethyl-[1,1'-biphenyl]-4-yl)boronic acid, and (4-(9H-carbazole-9-yl)phenyl)boronic acid.

[0033] In the preferred option, Scheme 1,

[0034] The molar ratio of bromine-substituted triphenylmethane derivatives to arylboronic acid is 1:5 to 6;

[0035] The palladium catalyst is selected from at least one of tetratriphenylphosphine palladium and methanesulfonyloxy(dadamantyl-n-butylphosphino)-2'-amino-1,1'-biphenyl-2-ylpalladium(II);

[0036] The base is selected from at least one of carbonates and phosphates;

[0037] The organic solvent is selected from at least one of tetrahydrofuran and 1,4-dioxane;

[0038] The reaction temperature is 60-100℃, and the reaction time is 12-24 hours. The solution after the reaction is quenched, extracted, concentrated, and purified by column chromatography to obtain the multidentate ligand.

[0039] In the preferred option, Scheme 2,

[0040] The molar ratio of triphenylmethane substituted with pinacol borate to aryl halide is 1:5-6;

[0041] The palladium catalyst is selected from at least one of bis(triphenylphosphine)palladium dichloride, tetra(triphenylphosphine)palladium, and methanesulfonyloxy(dadamantyl-n-butylphosphino)-2'-amino-1,1'-biphenyl-2-ylpalladium(II);

[0042] The base is selected from at least one of carbonates and phosphates;

[0043] The solvent is selected from at least one of tetrahydrofuran and 1,4-dioxane;

[0044] The reaction temperature is 60-100℃, and the reaction time is 12-24 hours. The solution after the reaction is quenched, extracted, concentrated, and purified by column chromatography to obtain the multidentate ligand.

[0045] In the preferred option, Scheme 3,

[0046] The molar ratio of halogen-substituted tri(biphenyl)methane to arylboronic acid is 1:5 to 6;

[0047] The palladium catalyst is selected from at least one of tetratriphenylphosphine palladium and methanesulfonyloxy(dadamantyl-n-butylphosphino)-2'-amino-1,1'-biphenyl-2-ylpalladium(II);

[0048] The base is selected from at least one of carbonates and phosphates;

[0049] The organic solvent is selected from at least one of tetrahydrofuran and 1,4-dioxane;

[0050] The reaction temperature is 60-100℃, and the reaction time is 12-24 hours. The solution after the reaction is quenched, extracted, concentrated, and purified by column chromatography to obtain the multidentate ligand.

[0051] Preferred,

[0052] The preparation method of compound 1 includes the following steps:

[0053] Under a protective atmosphere, m-dibromobenzene or 1-bromo-3-iodobenzene and n-butyllithium react in tetrahydrofuran at -78 to -85 °C to generate phenyllithium salt. Diethyl carbonate is then added, the reaction solution is brought to room temperature, and stirring is continued for 24 to 48 hours. The reaction is then quenched, extracted, and purified to obtain compound 1.

[0054] The structural formula of compound 1 is as follows:

[0055] The preparation method of compound 2 includes the following steps:

[0056] Compound 1 was reacted with formic acid at 120–140 °C for 24–48 hours, then cooled to room temperature, neutralized, extracted, and purified to obtain compound 2.

[0057] The preparation methods of compounds 3 and 4 include the following steps:

[0058] Under a protective atmosphere, in an ice bath, compound 1 and sodium hydride reacted in N,N-dimethylformamide, and then an N,N-dimethylformamide solution of alkyl bromide (n-butyl bromide or n-decyl bromide) was added. The reaction was continued at 50-60°C, quenched, extracted, and purified to obtain the corresponding compounds 3 and 4.

[0059] The preparation method of compound 5 includes the following steps:

[0060] Under a protective atmosphere, 1-bromo-3-iodobenzene and n-butyllithium reacted in tetrahydrofuran at -78°C to form phenyllithium salt. Then, phenyltrichlorosilane was added, the reaction solution was brought to room temperature, and stirring was continued for 24–48 hours. The reaction was quenched, extracted, and purified to obtain compound 5.

[0061] The preparation method of compound 6 includes the following steps:

[0062] Under a protective atmosphere, 1-bromo-3-iodobenzene and n-butyllithium reacted in tetrahydrofuran at -78°C to form phenyllithium salt. Then, heptadecafluorodecyltrimethoxysilane was added, the reaction solution was brought to room temperature, and stirring was continued for 24–48 hours. The reaction was quenched, extracted, and purified to obtain compound 6.

[0063] The preparation method of compound 7 includes the following steps:

[0064] Under a protective atmosphere, compound 2 and pinacol diboronic acid were heated and stirred at 100 °C for 24 hours in 1,4-dioxane, washed with n-hexane, and recrystallized from methanol to obtain compound 7.

[0065] The preparation method of compound 8 includes the following steps:

[0066] Under a protective atmosphere, compound 2 and 2-hydroxy-4-chlorophenylboronic acid were heated and stirred at 80°C for 24 hours in a mixed solvent of tetrahydrofuran and water, quenched, extracted, and purified to obtain compound 8.

[0067] The preparation method of compound 9 includes the following steps:

[0068] Under a protective atmosphere, compound 3 and 2-hydroxy-4-chlorophenylboronic acid were heated and stirred at 80°C for 24 hours in a mixed solvent of tetrahydrofuran and water, quenched, extracted, and purified to obtain compound 9.

[0069] The protective atmosphere described above is nitrogen or an inert gas (such as argon).

[0070] A multidentate ligand metal catalyst has the following structural formula:

[0071] Where Z is selected from carbon, R 4 Selected from hydrogen, alkoxy; or Z selected from silicon, R 4 Selected from fluoroalkyl, phenyl; or Z selected from phosphorus, R 4 Selected from oxygen subunits;

[0072] R 1 R 2 R 3 Each is independently selected from hydrogen, halogen, trifluoromethyl, cyano, acetyl, methyl, methoxy, methylthio, isopropyl, phenoxy, 1,1,3,3-tetramethylbutyl, 4-tert-butylphenyl, 4-methoxyphenyl, 4-N,N-dimethylaminophenyl, 4-methoxyformylphenyl, 4-(2,4,6-trimethyl)phenyl, 4-carbazolylphenyl;

[0073] Ar can be represented independently by naphthalene, indene dihydrogen hydride, 1-indanone, dimethylfluorene, and estradiol.

[0074] The preparation method of the above-mentioned multidentate ligand metal catalyst includes the following steps:

[0075] The above-mentioned multidentate ligands and metal ion precursors are mixed in an organic solvent and stirred to obtain a multidentate ligand metal catalyst.

[0076] The metal ion precursor is a molybdenum-centered carbabin structure, with the following structural formula:

[0077] Preferably, the molar ratio of the polydentate ligand to the metal ion precursor is 0.5 to 2:1;

[0078] More preferably, the molar ratio of the polydentate ligand to the metal ion precursor is 1:1;

[0079] Preferably, the concentration of the polydentate ligand in the organic solvent is 0.5–5 mM.

[0080] Preferably, the stirring temperature is 20–70°C, and the stirring time is 10–30 minutes;

[0081] Preferably, the organic solvent is CCl4.

[0082] The above-mentioned multidentate ligand metal catalysts are used in the catalytic metathesis of alkynes.

[0083] Preferably, the molar ratio of the multidentate ligand metal catalyst to the alkyne is 0.6 to 3:100.

[0084] Preferably, the temperature for catalytic alkyne metathesis is 25–70°C.

[0085] Compared with the prior art, the present invention has the following beneficial effects:

[0086] (1) The preparation method of the present invention is simple and efficient, and it realizes the preparation of diverse ligands. Up to 51 kinds of tridentate ligands were prepared by the synthesis method of the present invention.

[0087] (2) The catalyst prepared by the ligand of the present invention has high catalytic activity, can maintain catalytic activity under low loading (dosage), and has a wide range of applicable substrates. Attached Figure Description

[0088] Figure 1 shows the structural formulas of the L1, L3, and L29 ligands and the corresponding metal catalysts.

[0089] Figure 2 shows the catalytic activity curves of the metal catalysts corresponding to formulas VI, VII and L1 ligands in Example 3.

[0090] Figure 3 shows the catalytic activity curves of the metal catalysts corresponding to the L1, L3, and L4 ligands in Example 3.

[0091] Figure 4 shows the catalytic activity curve of the metal catalyst corresponding to the L3 ligand (0.6%) in Example 3. Detailed Implementation

[0092] The specific implementation of the present invention will be further described below with reference to the accompanying drawings and embodiments, but the implementation and protection of the present invention are not limited thereto. It should be noted that any processes not specifically described in detail below are those that can be implemented or understood by those skilled in the art by referring to the prior art. Reagents or instruments whose manufacturers are not specified are considered to be conventional products that can be purchased commercially.

[0093] The ligand structure prepared in this embodiment of the invention is as follows:

[0094] (In L33, the Mes group is 4-(2,4,6-trimethyl)phenyl; in L18, the MeS group is methylthio.)

[0095] Example 1

[0096] Synthesis of Compound 1

[0097] Under an argon atmosphere, 1-bromo-3-iodobenzene (14.00 g, 49.49 mmol) and 80 mL of dry tetrahydrofuran were added to a 200 mL dry Schlenk flask. The solution was cooled to -78 °C, and n-butyllithium (31.24 mL, 49.98 mmol, 1.6 M in hexane) was slowly added dropwise. The reaction mixture was stirred at -78 °C for 1 hour. Diethyl carbonate (1.93 g, 16.30 mmol) was slowly added to the reaction mixture, and the mixture was stirred for another 1 hour. The mixture was then brought to room temperature and stirred for another 12 hours. The reaction mixture was quenched with saturated ammonium chloride solution (100 mL) and extracted with ethyl acetate (3 × 75 mL). The combined organic layers were dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. Column chromatography (petroleum ether / dichloromethane = 10:3) was used to purify the mixture to give a colorless solid (6.98 g), in 86% yield.

[0098] 1 H NMR (400MHz, CDCl3) δ7.50-7.42(m,6H),7.21(t,J=7.8Hz,3H),7.16-7.11(m,3H),2.75(s,1H). 13 C NMR(101MHz, CDCl3)δ147.8,131.0,130.6,129.8,126.5,122.7,80.9.HRMS(APCI)calculated for[MH] + :494.8423; found:494.8423.

[0099] Synthesis of Compound 2

[0100] Compound 1 (5.63 g, 11.30 mmol) and formic acid (56 mL) were added to a dry 200 mL round-bottom flask. The mixture was stirred at 120 °C for 24 hours and then allowed to return to room temperature. The reaction mixture was neutralized with aqueous sodium bicarbonate solution, extracted with ethyl acetate (3 × 75 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. Column chromatography (in hexane) was used to purify the mixture to a colorless oily liquid (4.91 g), in 90% yield.

[0101] 1 H NMR (400MHz, CDCl3) δ7.39(d,J=7.9Hz,3H),7.20(dd,J=14.7,6.8Hz,6H),7.00(d,J=7.8Hz,3H),5.42(s,1H). 13C NMR(126MHz, CDCl3)δ144.7,132.3,130.3,130.2,128.0,122.9,55.8.HRMS(ESI)calculated for[M+H] + :478.8474; found:478.8469.

[0102] Synthesis of Compound 3

[0103] Under an argon atmosphere, sodium hydride (211.0 mg, 5.28 mmol, 60% dispersion in mineral oil) and N,N-dimethylformamide (5 mL) were added to a 200 mL dry Schlenk flask, and the solution was cooled to 0 °C. A diluted solution of Compound 1 (N,N-dimethylformamide) was slowly added dropwise to the Schlenk flask, and the mixture was allowed to return to room temperature while stirring for 10 minutes. The reaction mixture was cooled to 0 °C, and a diluted solution of n-butyl bromide (N,N-dimethylformamide) was slowly added dropwise to the Schlenk flask, and the mixture was allowed to return to room temperature while stirring for 3 hours. The reaction mixture was quenched with saturated ammonium chloride solution (100 mL), extracted with ethyl acetate (3 × 75 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. Column chromatography (petroleum ether) was used to purify the mixture to give a colorless oily liquid (700.0 mg), in 72% yield.

[0104] 1 H NMR (500MHz, CDCl3) δ7.65-7.56(m,3H),7.41(d,J=7.8Hz,3H),7.30(t,J=9.3Hz,3H),7.19(t,J=7.9 Hz,3H),3.04(q,J=6.6Hz,2H),1.67-1.58(m,2H),1.43(h,J=7.0Hz,2H),0.91(q,J=6.1,5.5Hz,3H). 13 C NMR(126MHz, CDCl3)δ145.79,131.36,130.70,129.74,127.42,122.51,85.28,63.86,32.09,19.59,14.12.HRMS(ESI)calculated for[M+H] + :623.3887,found:623.3886.

[0105] Synthesis of Compound 4

[0106] Following the preparation procedure for compound 3, compound 1 was reacted with n-decyl bromide and purified to give a colorless oily liquid (0.30 g) with a yield of 67%.

[0107] 1 H NMR (500MHz, CDCl3, ppm) δ7.57(t,3H),7.40(d,J=9.0Hz,3H),7.28(d,J=8.3Hz,3H),7.18(d,J=7.9 Hz,3H),3.01(t,J=6.5Hz,2H),1.60(q,J=6.5,5.0Hz,2H),1.41(h,J=8.1Hz,2H),0.92-0.87(m,3H); 13 C NMR (126MHz, CDCl3, ppm) δ145.8,131.3,130.7,129.7,127.4,122.4,85.2,63.8,32.0,19.5,14.1.

[0108] Synthesis of Compound 5

[0109] Under an argon atmosphere, 1-bromo-3-iodobenzene (1.50 g, 5.30 mmol) and dry tetrahydrofuran (60 mL) were added to a 200 mL dry Schlenk flask. The solution was cooled to -78 °C, and n-butyllithium (3.35 mL, 5.36 mmol, 1.6 M) was slowly added dropwise, with stirring for 1 hour. Trimethoxyphenylsilane was slowly added to the reaction mixture, and stirring was continued at -78 °C for 1 hour, then the mixture was brought to room temperature and stirred overnight. The reaction mixture was quenched with saturated ammonium chloride solution (100 mL), extracted with diethyl ether (3 × 75 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. Column chromatography (petroleum ether) was used to purify the mixture to give a white solid (630.0 mg), in 63% yield.

[0110] 1 H NMR (500MHz, CDCl3) δ7.64-7.59(m,6H),7.53-7.48(m,3H),7.47-7.41(m,5H),7.29(t,J=7.6Hz,3H). 13 C NMR (126MHz, CDCl3) δ138.6,136.3,136.1,134.8,133.4,131.8,130.5,130.0,128.5,123.3.

[0111] Synthesis of Compound 6

[0112] Under an argon atmosphere, 1-bromo-3-iodobenzene (1.50 g, 5.30 mmol) and dry tetrahydrofuran (60 mL) were added to a 200 mL dry Schlenk flask. The solution was cooled to -78 °C, and n-butyllithium (3.35 mL, 5.36 mmol, 1.6 M) was slowly added dropwise, with stirring for 1 hour. Heptadecafluorodecyltrimethoxysilane was slowly added to the reaction mixture, and stirring was continued at -78 °C for 1 hour, then the mixture was brought to room temperature and stirred overnight. The reaction mixture was quenched with saturated ammonium chloride solution (100 mL), extracted with diethyl ether (3 × 75 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. Column chromatography (petroleum ether) was used to purify the mixture to give a white solid (442.0 mg), in 27% yield.

[0113] Synthesis of Compound 7

[0114] In a glove box, compound 2 (0.21 g, 0.45 mmol), pinacol diboronate (0.45 g, 1.78 mmol), palladium dichloride (31.3 mg, 0.04 mmol), potassium acetate (174.9 mg, 1.78 mmol), and 1,4-dioxane (20 mL) were added to a dry Schlenk flask. The flask was then sealed and transferred out of the glove box. The reaction mixture was stirred at 100 °C for 24 hours, quenched with H₂O (20 mL), and extracted with ethyl acetate (3 × 30 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The crude product was washed with n-hexane and recrystallized in methanol to give a white solid (0.16 g), in 58% yield.

[0115] 1 H NMR (500MHz, CDCl3) δ7.65-7.60(m,6H),7.25-7.22(m,3H),7.11(dt,J=7.8,1.7Hz,3H),5.59(s,1H),1.29(s,37H). 13 C NMR(126MHz, CDCl3)δ143.1,136.,132.8,132.3,127.8,83.8,57.0,25.0.HRMS(ESI)calculated for[M+H] + :623.3887; found:623.3886.

[0116] Synthesis of Compound 8

[0117] In a glove box, compound 2 (1.05 g, 2.18 mmol), (4-chloro-2-hydroxyphenyl)boronic acid (1.88 g, 10.91 mmol), tetraphenylphosphine palladium (0.25 g, 0.22 mmol), potassium carbonate (1.81 g, 13.10 mmol), and dry tetrahydrofuran (60 mL) were added to a dry Schlenk flask. The flask was sealed and transferred out of the glove box. Water was bubbled and deoxygenated under argon atmosphere. The reaction mixture was stirred at 80 °C for 24 hours, then cooled to room temperature and extracted with ethyl acetate (3 × 30 mL). The organic layer was washed with water. The mixture was dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. Column chromatography (petroleum ether:ethyl acetate = 3:1) was used to purify the mixture to a white solid (0.98 g), in 72% yield.

[0118] 1 H NMR (400MHz, CDCl3) δ7.44(t,J=7.7Hz,3H),7.31(dt,J=7.7,1.4Hz,3H),7.24(s, 3H),7.20(d,J=7.8Hz,3H),7.12(d,J=8.5Hz,3H),6.95(d,J=7.5Hz,6H),5.68(s,1H),5.23(s,3H). 13 C NMR(101MHz, CDCl3)δ152.9,144.5,136.5,134.3,131.1,130.0,129.7,129.1,127.3,126.5,121.2,116.3,56.8.HRMS(ESI)calculated for[M+Na] + :645.0762; found:645.0755.

[0119] Synthesis of Compound 9

[0120] Following the preparation procedure for compound 8, compound 3 was coupled with (4-chloro-2-hydroxyphenyl)boronic acid via Suzuki coupling to synthesize compound 9, which was purified to give a colorless oily liquid with a yield of 62%.

[0121] 1 H NMR (500MHz, CDCl3) δ7.59-7.53(m),7.44(t,J=7.7Hz),7.32(dt,J=7.5,1.3Hz),7.12(d,J=8.0Hz),6.95 (dd,J=9.9,1.9Hz),5.28,3.14(t,J=6.5Hz),1.65-1.60(m),1.40(dt,J=14.9,7.4Hz),0.86(t,J=7.4Hz). 13C NMR (126MHz, CDCl3) δ153.1,145.4,136.3,135.9,134.4,134.4,131.2,131.1,129.3,129.2,128.5,128.3,127.9 127.5,126.7,126.6,121.4,121.3,116.5,116.4,86.3,63.9,32.1,31.7,22.8,19.6,14.1.HRMS(ESI)calculated for[MH] - :693.1372; found:693.1384.

[0122] Example 2

[0123] Synthesis of ligand L1

[0124] Following the general preparation procedure of Scheme 1: In a glove box, compound 2 (0.30 g, 0.63 mmol), 2-hydroxyphenylboronic acid (0.52 g, 3.75 mmol), tetrakis(triphenylphosphine)palladium (72.1 mg, 0.06 mmol), potassium carbonate (0.52 g, 3.75 mmol), and dry tetrahydrofuran (15 mL) were added to a dry Schlenk flask. The flask was sealed and transferred out of the glove box. Water (5 mL) was added under argon atmosphere and bubbled to remove oxygen. The reaction mixture was stirred at 80 °C for 24 hours, then quenched with water (10 mL) and extracted with ethyl acetate (3 × 30 mL). The organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. Column chromatography (dichloromethane:petroleum ether = 6:1) was used to purify the mixture to give a white solid (0.25 g), in 76% yield.

[0125] 1 H NMR (400MHz, CDCl3) δ7.43 (t, J = 7.6Hz, 3H), 7.38-7.31 (m, 6H), 7.26-7.19 (m, 9H), 7.00-6.92 (m, 6H), 5.70 (s, 1H), 5.16 (s, 3H). 13 C NMR(101MHz, CDCl3)δ152.4,144.5,137.4,130.3,130.2,129.4,129.2,128.8,128.0,127.4,120.9,116.0,56.9.HRMS(ESI)calculated for[M+Na] + :543.1936; found:543.1949.

[0126] Synthesis of ligand L2

[0127] Following the preparation procedure of Scheme 1 (refer to the preparation procedure of L1), compound 2 was Suzuki coupled with (3-chloro-2-hydroxyphenyl)boronic acid to form L2, which was purified to give a white solid with a yield of 61%.

[0128] 1 H NMR (400MHz, CDCl3) δ7.46-7.36(m,9H),7.29(dd,J=8.0,1.6Hz,3H),7.25-7.15(m,6H),6.90(t,J=7.9Hz,3H),5.69(s,1H),5.68(s,2H). 13 C NMR(101MHz, CDCl3)δ148.4,143.9,137.1,130.4,129.7,129.4,128.8,128.6,128.3,127.3,121.0,120.7,57.0.HRMS(ESI)calculated for[MH] - :621.0796; found:621.0796.

[0129] Synthesis of ligand L3

[0130] Following the preparation procedure of Scheme 1 (which is the same as that for Compound 8), Compound 2 was Suzuki coupled with (4-chloro-2-hydroxyphenyl)boronic acid to form L3, which was purified to give a white solid with a yield of 72%.

[0131] 1 H NMR(400MHz, CDCl3) δ7.44(t,J=7.7Hz,3H),7.31(dt,J=7.7,1.4Hz,3H),7.24(s,3H),7.2 0(d,J=7.8Hz,3H),7.12(d,J=8.5Hz,3H),6.95(d,J=7.5Hz,6H),5.68(s,1H),5.23(s,3H). 13 C NMR(101MHz, CDCl3)δ152.9,144.5,136.5,134.3,131.1,130.0,129.7,129.1,127.3,126.5,121.2,116.3,56.8.HRMS(ESI)calculated for[M+Na] + :645.0762; found:645.0755.

[0132] Synthesis of ligand L4

[0133] Following the preparation procedure of Scheme 1 (refer to the preparation procedure of L1), compound 2 was Suzuki coupled with (5-chloro-2-hydroxyphenyl)boronic acid to form L4, which was purified to give a white solid with a yield of 51%.

[0134] 1 H NMR (400MHz, CDCl3) δ7.45(t,J=7.7Hz,3H),7.33(dt,J=7.6,1.2Hz,3H),7.29(d, J=1.6Hz,3H),7.24-7.14(m,9H),6.87(d,J=8.5Hz,3H),5.69(s,1H),5.14(s,3H). 13 C NMR(101MHz, CDCl3)δ151.0,144.4,136.3,130.0,129.8,129.7,129.3,129.2,128.9,127.3,125.6,117.3,56.8.HRMS(ESI)calculated for[MH] - :621.0796; found:621.0798.

[0135] Synthesis of ligand L5

[0136] Following the preparation procedure of Scheme 1 (refer to the preparation procedure of L1), compound 2 was Suzuki coupled with (3-fluoro-2-methoxyphenyl)boronic acid to form the precursor compound of L5 (methoxy protected), which was purified to give a white solid with a yield of 86%.

[0137] Subsequently, under an argon atmosphere, the precursor compound of L5 (methoxy-protected) (42.0 mg, 68.11 μmol) and dichloromethane (10 mL) were added to a dry Schlenk flask, and the solution was cooled to 0 °C. Boron tribromide solution was slowly added dropwise to the Schlenk flask, and the reaction mixture was heated to room temperature and stirred continuously. After monitoring the complete conversion of the starting material by thin-layer chromatography, water (10 mL) was added for quenching, followed by extraction with dichloromethane (3 × 30 mL). The organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. Column chromatography (dichloromethane:petroleum ether = 6:1) purified the product to give a white solid (17.0 mg), in 43% yield.

[0138] 1 H NMR (500MHz, CDCl3) δ7.42-7.35 (m, 9H), 7.19 (dt, J=7.0, 1.7Hz, 3H), 7.03 (dd, J= 8.1,3.9Hz,6H),6.85(td,J=8.0,5.3Hz,3H),5.68(s,1H),5.29(d,J=4.5Hz,3H).13 C NMR (126MHz, CDCl3) δ152.4,150.5,144.1,141.0,140.9,136.7,136.7,130.4,130.4,130.4, 128.9,128.8,127.3,125.8,125.7,120.3,120.3,114.8,114.6,57.0.HRMS(ESI)calculated for[M+Na] + :597.1648; found:597.1641.

[0139] Synthesis of ligand L6

[0140] Following the preparation procedure of Scheme 1 (referencing the preparation procedure for L1), compound 2 was Suzuki coupled with (4-fluoro-2-hydroxyphenyl)boronic acid to form L6, which was purified to give a white solid in 95% yield. HRMS (ESI) calculated for [MH] - :573.1683; found:573.1686.

[0141] Synthesis of ligand L7

[0142] Following the preparation procedure of Scheme 1 (referencing the preparation procedure of L1), compound 2 was Suzuki coupled with (5-fluoro-2-hydroxyphenyl)boronic acid to form L7, which was purified to give a white solid in 42% yield. HRMS (ESI) calculated for [M+Na] + :597.1648; found:597.1646.

[0143] Synthesis of ligand L8

[0144] Following the preparation procedure of Scheme 1 (referencing the preparation procedure of L1), compound 2 was Suzuki coupled with (4-trifluoromethyl-2-hydroxyphenyl)boronic acid to form L8, which was purified to give a white solid in 43% yield. HRMS (ESI) calculated for [M+Na] + :747.1558; found:747.1560.

[0145] Synthesis of ligand L9

[0146] Following the general preparation procedure of Scheme 2: In a glove box, compound 7 (50.0 mg, 0.08 mmol), 4-bromo-3-hydroxybenzonitrile (95.5 mg, 0.48 mmol), methanesulfonate (dadamantyl-n-butylphosphine)-2'-amino-1,1'-biphenyl-2-yl)palladium(II) (5.9 mg, 8.0 μmol), potassium phosphate (102.3 mg, 0.48 mmol), and dry tetrahydrofuran (7 mL) were added to a dry Schlenk flask. The flask was then sealed and transferred out of the glove box. Water (3 mL) was added under argon atmosphere and bubbled to remove oxygen. The reaction mixture was stirred at 80 °C for 24 hours, then quenched with water (10 mL) and extracted with ethyl acetate (3 × 20 mL). The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. Thin-layer chromatography (methanol:dichloromethane = 6:100) was used to purify the mixture to a white solid (30.5 mg), yield 64%. HRMS(ESI) calculated for [M+Na] + :618.1789; found:618.1779.

[0147] Synthesis of L10 ligand precursor

[0148] Following the preparation procedure of Scheme 2 (referencing the preparation procedure for L9), compound 7 was Suzuki coupled with 3-bromo-4-hydroxybenzonitrile to synthesize L10, which was purified to give a white solid in 65% yield. HRMS (ESI) calculated for [M+Na] + :618.1789; found:618.1779.

[0149] Synthesis of ligand L11

[0150] Following the preparation procedure of Scheme 1 (referencing the preparation procedure for L1), compound 2 was Suzuki coupled with (5-acetyl-2-hydroxyphenyl)boronic acid to synthesize L11, which was purified to give a white solid in 51% yield. HRMS (ESI) calculated for [M+Na] + :669.2248; found:669.2261.

[0151] Synthesis of ligand L12

[0152] Following the preparation procedure of Scheme 2 (referencing the preparation procedure for L9), compound 7 was Suzuki-coupled with 2-bromo-4-methylphenol to form L12, which was purified to give a white solid in 62% yield. HRMS (ESI) calculated for [M+Na] +:585.2401; found:585.2390.

[0153] Synthesis of ligand L13

[0154] Following the preparation procedure of Scheme 2 (referencing the preparation procedure for L9), compound 7 was Suzuki-coupled with 2-bromo-5-methylphenol to form L13, which was purified to give a white solid in 61% yield. HRMS (ESI) calculated for [M+H] + :561.2435,found:561.2435.

[0155] Synthesis of ligand L14

[0156] Following the preparation procedure of Scheme 1 (referencing the preparation procedure of L1), compound 2 was Suzuki coupled with (4-isopropyl-2-hydroxyphenyl)boronic acid to form L14, which was purified to give a white solid in 58% yield. HRMS (ESI) calculated for [M+Na] + :669.3345,found:669.3346.

[0157] Synthesis of ligand L15

[0158] Following the preparation procedure of Scheme 1 (referencing the preparation procedure for L1), compound 2 was Suzuki coupled with (5-isopropyl-2-methoxyphenyl)boronic acid to synthesize the precursor compound of L15 (methoxy protected). Subsequently, L15 was deprotected with boron tribromide, and purified to give a white solid in 61% yield. HRMS (ESI) calculated for [M+Na] + :669.3340,found:669.3328.

[0159] Synthesis of ligand L16

[0160] Following the preparation procedure of Scheme 1 (referencing the preparation procedure of L1), compound 2 was Suzuki coupled with (5-methoxy-2-hydroxyphenyl)boronic acid to form L16, which was purified to give a white solid in 41% yield. HRMS (ESI) calculated for [M+Na] + :633.2248; found:633.2256.

[0161] Synthesis of ligand L17

[0162] Following the preparation procedure of Scheme 1 (referencing the preparation procedure of L1), compound 2 was Suzuki coupled with (4-methoxy-2-hydroxyphenyl)boronic acid to form L17, which was purified to give a white solid in 67% yield. HRMS (ESI) calculated for [M+Na] + :633.2248; found:633.2250.

[0163] Synthesis of ligand L18

[0164] Following the preparation procedure of Scheme 1 (referencing the preparation procedure of L1), compound 2 was Suzuki coupled with (5-methylthio-2-hydroxyphenyl)boronic acid to form L18, which was purified to give a white solid in 63% yield. HRMS (ESI) calculated for [M+Na] + :681.1562; found:681.1563.

[0165] Synthesis of ligand L19

[0166] Following the preparation procedure of Scheme 1 (referencing the preparation procedure of L1), compound 2 was Suzuki coupled with (5-phenoxy-2-hydroxyphenyl)boronic acid to form L19, which was purified to give a white solid in 79% yield. HRMS (ESI) calculated for [M+Na] + : 819.2717; found: 819.2719.

[0167] Synthesis of ligand L20

[0168] Following the preparation procedure of Scheme 1 (referencing the preparation procedure of L1), compound 2 was Suzuki coupled with (5-isopropyl-4-methyl-2-hydroxyphenyl)boronic acid to synthesize L20, which was purified to give a white solid in 79% yield. HRMS (ESI) calculated for [M+Na] + :711.3809; found:711.3820.

[0169] Synthesis of ligand L21

[0170] Following the preparation procedure of Scheme 2 (referencing the preparation procedure for L9), compound 7 was Suzuki-coupled with 2-bromo-4-(2,4,4-trimethylpentan-2-yl)phenol to form L21, which was purified to give a white solid in 64% yield. HRMS (ESI) calculated for [M+Na] +:837.5223; found:837.1957.

[0171] Synthesis of ligand L22

[0172] Following the preparation procedure of Scheme 1 (referencing the preparation procedure of L1), compound 2 was Suzuki coupled with (5-chloro-4-chloro-2-methoxyphenyl)boronic acid to synthesize the precursor compound of L22 (methoxy protected). Subsequently, L22 was deprotected with boron tribromide, and purified to give a white solid in 49% yield. HRMS (ESI) calculated for ESI: [MH] - :724.9597; found:724.9606.

[0173] Synthesis of ligand L23

[0174] Following the preparation procedure of Scheme 1 (referencing the preparation procedure of L1), compound 2 was Suzuki coupled with (5-fluoro-4-fluoro-2-methoxyphenyl)boronic acid to synthesize the precursor compound of L23 (methoxy protected). Subsequently, L23 was deprotected with boron tribromide, and purified to give a white solid in 52% yield. HRMS (ESI) calculated for [MH] - :627.1400; found:627.1400.

[0175] Synthesis of ligand L24

[0176] Following the preparation procedure of Scheme 1 (referencing the preparation procedure of L1), compound 2 was Suzuki coupled with (3-hydroxynaphth-2-yl)boronic acid to form L24, which was purified to give a white solid in 64% yield. HRMS (ESI) calculated for [MH] - :693.2406; found:693.2421.

[0177] Synthesis of ligand L25

[0178] Following the preparation procedure of Scheme 1 (referencing the preparation procedure of L1), compound 2 was Suzuki coupled with (6-hydroxy-2,3-dihydro-1H-inden-5-yl)boronic acid to form L25, which was purified to give a white solid in 90% yield. HRMS (ESI) calculated for [M+Na] + :663.2870; found:663.2880.

[0179] Synthesis of ligand L26

[0180] Following the preparation procedure of Scheme 1 (referencing the preparation procedure of L1), compound 2 was Suzuki coupled with (6-hydroxy-1-oxo-2,3-dihydro-1H-inden-5-yl)boronic acid to form L26, which was purified to give a white solid in 90% yield. HRMS (ESI) calculated for [M+Na] + :705.2248; found:705.2264.

[0181] Synthesis of ligand L27

[0182] Following the preparation procedure of Scheme 1 (referencing the preparation procedure of L1), compound 2 was Suzuki coupled with (2-methoxy-9,9-dimethyl-9H-fluorene-3-yl)boronic acid to synthesize the precursor compound of L27 (methoxy protected). Subsequently, L27 was synthesized by deprotection with boron tribromide, and purified to give a white solid in 74% yield. HRMS (ESI) calculated for [M+H] + :891.3814; found:891.3794.

[0183] Synthesis of ligand L28

[0184] Following the preparation procedure of Scheme 2 (referencing the preparation procedure of L9), compound 7 was Suzuki coupled with (8R,9S,13S)-3-hydroxy-2-iodo-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthrene-17-one to synthesize L28, which was purified to give a white solid in 67% yield. HRMS (ESI) calculated for [M+Na] + :1071.5540; found:1071.5543.

[0185] Synthesis of ligand L29

[0186] Following the general preparation procedure of Scheme 3: In a glove box, compound 8 (28.0 mg, 0.04 mmol), (4-(tert-butyl)phenyl)boronic acid (71.9 mg, 0.40 mmol), methanesulfonate (dadamantyl-n-butylphosphine)-2'-amino-1,1'-biphenyl-2-yl)palladium(II) (6.54 mg, 8.98 μmol), potassium phosphate (128.6 mg, 0.61 mmol), and dried 1,4-dioxane (1.8 mL) were added to a dry Schlenk flask. The flask was then sealed and transferred out of the glove box. Water was bubbled and deoxygenated under argon atmosphere. The reaction mixture was stirred at 80 °C for 24 hours, then cooled to room temperature and extracted with ethyl acetate (3 × 30 mL). The organic layer was washed with water. The mixture was dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. Column chromatography (petroleum ether:ethyl acetate = 3:1) was used to purify the mixture to a white solid (25.1 mg), in 60% yield. HRMS(ESI) calculated for [M+Na] + :939.4748; found:939.4741.

[0187] Synthesis of ligand L30

[0188] Following the preparation procedure of Scheme 3 (referencing the preparation procedure for L29), compound 8 was Suzuki-coupled with (4-methoxyphenyl)boronic acid to synthesize L30, which was purified to give a white solid in 65% yield. HRMS (ESI) calculated for [M+Na] + :861.3192; found:861.3194.

[0189] Synthesis of ligand L31

[0190] Following the preparation procedure of Scheme 3 (referencing the preparation procedure of L29), compound 8 was Suzuki coupled with (4-(dimethylamino)phenyl)boronic acid to form L31, which was purified to give a white solid in 52% yield. HRMS (ESI) calculated for [M+H] + :878.4322; found:878.4314.

[0191] Synthesis of ligand L32

[0192] Following the preparation procedure of Scheme 3 (referencing the preparation procedure of L29), compound 8 was Suzuki coupled with (4-(methoxycarbonyl)phenyl)boronic acid to synthesize L32, which was purified to give a white solid in 95% yield. HRMS (ESI) calculated for [M+Na] +:945.3040; found:945.3035.

[0193] Synthesis of ligand L33

[0194] Following the preparation procedure of Scheme 3 (referencing the preparation procedure of L29), compound 8 was Suzuki coupled with (2',4',6'-trimethyl-[1,1'-biphenyl]-4-yl)boronic acid to synthesize L33, which was purified to give a white solid in 57% yield. HRMS (ESI) calculated for [M+Na] + :897.4279; found:897.4273.

[0195] Synthesis of ligand L34

[0196] Following the preparation procedure of Scheme 3 (referencing the preparation procedure of L29), compound 8 was Suzuki coupled with (4-(9H-carbazole-9-yl)phenyl)boronic acid to synthesize L34, which was purified to give a white solid in 35% yield. HRMS (ESI) calculated for [M+Na] + :1266.4611; found:1266.4629.

[0197] Synthesis of ligand L35

[0198] Following the preparation procedure of Scheme 1 (referencing the preparation procedure of L1), compound 3 was Suzuki coupled with 2-hydroxyphenylboronic acid to form L35, which was purified to give a white solid in 77% yield. HRMS (ESI) calculated for [MH] - :591.2540; found:591.2540.

[0199] Synthesis of ligand L36

[0200] Following the preparation procedure of Scheme 1 (the same as that for compound 9), compound 3 was Suzuki coupled with (4-chloro-2-hydroxyphenyl)boronic acid to form L36, which was purified to give a white solid in 62% yield. HRMS (ESI) calculated for [MH] - :693.1372; found:693.1384.

[0201] Synthesis of ligand L37

[0202] Following the preparation procedure of Scheme 1 (referencing the preparation procedure of L1), compound 3 was Suzuki coupled with (5-chloro-2-hydroxyphenyl)boronic acid to form L37, which was purified to give a white solid in 74% yield. HRMS (ESI) calculated for [MH] - :693.1372; found:693.1379.

[0203] Synthesis of ligand L38

[0204] Following the preparation procedure of Scheme 1 (refer to the preparation procedure of L1), compound 3 was Suzuki coupled with (4-trifluoromethyl-2-hydroxyphenyl)boronic acid to form L38, which was purified to give a white solid in 54% yield. HRMS (ESI) calculated for [MH] - :795.2162; found:795.2170.

[0205] Synthesis of ligand L39

[0206] Following the preparation procedure of Scheme 3 (referencing the preparation procedure for L29), compound 9 was Suzuki coupled with (4-(tert-butyl)phenyl)boronic acid to synthesize L39, which was purified to give a white solid in 78% yield. HRMS (ESI) calculated for [M+Na] + :1011.5328; found:1011.5338.

[0207] Synthesis of ligand L40

[0208] Following the preparation procedure of Scheme 3 (referencing the preparation procedure for L29), compound 9 was Suzuki coupled with (4-methoxyphenyl)boronic acid to synthesize L40, which was purified to give a white solid in 79% yield. HRMS (ESI) calculated for [M+Na] + : 933.3767; found: 933.3769.

[0209] Synthesis of ligand L41

[0210] Following the preparation procedure of Scheme 3 (referencing the preparation procedure for L29), compound 9 was Suzuki coupled with (4-(dimethylamino)phenyl)boronic acid to form L41, which was purified to give a white solid in 76% yield. HRMS (ESI) calculated for [M+H] + :950.4897; found:950.4894.

[0211] Synthesis of ligand L42

[0212] Following the preparation procedure of Scheme 1 (referencing the preparation procedure of L1), compound 4 was Suzuki coupled with (4-chloro-2-hydroxyphenyl)boronic acid to form L42, which was purified to give a white solid in 62% yield. HRMS (ESI) calculated for [M+Na] + :801.2276; found:801.2284.

[0213] Synthesis of ligand L43

[0214] Following the preparation procedure of Scheme 1 (referencing the preparation procedure of L1), compound 5 was Suzuki coupled with 2-hydroxyphenylboronic acid to synthesize L43, which was purified to give a white solid in 94% yield. HRMS (ESI) calculated for [MH] - :611.2047; found:611.2048.

[0215] Synthesis of ligand L44

[0216] Following the preparation procedure of Scheme 1 (referencing the preparation procedure of L1), compound 5 was Suzuki coupled with (3-chloro-2-hydroxyphenyl)boronic acid to form L44, which was purified to give a white solid in 79% yield. HRMS (ESI) calculated for [M+Na] + :737.0844; found:737.0839.

[0217] Synthesis of ligand L45

[0218] Following the preparation procedure of Scheme 1 (referencing the preparation procedure of L1), compound 5 was Suzuki coupled with (4-chloro-2-hydroxyphenyl)boronic acid to form L45, which was purified to give a white solid in 90% yield. HRMS (ESI) calculated for [MH] - :713.0878; found:713.0878.

[0219] Synthesis of ligand L46

[0220] Following the preparation procedure of Scheme 1 (refer to the preparation procedure of L1), compound 5 was Suzuki coupled with (5-chloro-2-hydroxyphenyl)boronic acid to form L46, which was purified to give a white solid in 90% yield. HRMS (ESI) calculated for [MH]- :713.0878; found:713.0885.

[0221] Synthesis of ligand L47

[0222] Following the preparation procedure of Scheme 1 (referencing the preparation procedure of L1), compound 5 was deprotected by Suzuki coupling with (3-fluoro-2-methoxyphenyl)boronic acid to synthesize L47. The resulting product was purified to give a white solid in 92% yield. HRMS (ESI) calculated for [M+Na] + :689.1730; found:689.1735.

[0223] Synthesis of ligand L48

[0224] Following the preparation procedure of Scheme 1 (referencing the preparation procedure of L1), compound 6 was Suzuki coupled with (4-chloro-2-hydroxyphenyl)boronic acid to form L48, which was purified to give a white solid in 95% yield. HRMS (ESI) calculated for [M+Na] + :1107.0494; found:1107.0487.

[0225] Synthesis of ligand L49

[0226] Following the preparation procedure of Scheme 1 (referencing the preparation procedure of L1), phosphorus tris(3-bromophenyl)oxide was Suzuki coupled with 2-hydroxyphenylboronic acid to synthesize L49, which was purified to give a white solid in 75% yield. HRMS (ESI) calculated for [M+Na] + :577.1545; found:577.1531.

[0227] Synthesis of ligand L50

[0228] Following the preparation procedure of Scheme 1 (referencing the preparation procedure of L1), phosphorus tris(3-bromophenyl)oxide was Suzuki coupled with (4-chloro-2-hydroxyphenyl)boronic acid to form L50, which was purified to give a white solid in 88% yield. HRMS (ESI) calculated for [MH] - :655.0405; found:655.0424.

[0229] Synthesis of ligand L51

[0230] Following the preparation procedure of Scheme 1 (referencing the preparation procedure of L1), phosphorus tris(3-bromophenyl)oxide was Suzuki coupled with (5-chloro-2-hydroxyphenyl)boronic acid to synthesize L51, which was purified to give a white solid in 89% yield. HRMS (ESI) calculated for [M+Na] + :679.0375; found:655.0358.

[0231] Example 3

[0232] Taking L1 as an example, ligand L1 (3 μmol) and metal ion (molybdenum) precursor (II) (2.1 mg, 3 μmol) were mixed in dry CCl4 (1.0 mL) solvent and stirred at room temperature for 10 minutes to generate catalyst Cat 1 in situ. A CCl4 (1.0 mL) solution of 4-(hexane-1-yn-1-yl)anisole (18.8 mg, 100 μmol) was added to the mixed solution, and the reaction was carried out at room temperature. Sampling and testing were performed at strictly timed intervals (5 minutes, 15 minutes, 30 minutes, and 50 minutes). The reaction was quenched with methanol, and after vacuum drying, the mixture was sent for gas chromatography (GC) to monitor the reaction process. The reaction equation is as follows:

[0233] Replace ligand L1 with L3, L4, and the multidentate ligand reported by Fürstner (VI) and Zhang Wei (VII), and perform the other operations as described above.

[0234] Replace ligand L1 with L3, reduce catalyst loading (addition amount) to as low as 0.6% (molar percentage), and perform the other operations as described above.

[0235] Figure 2 shows the kinetic study of the catalytic activity of the polydentate ligands reported by Fürstner (Ⅵ) and Zhang (Ⅶ) and the polydentate ligand L1 provided by the present invention for the metathesis reaction of alkynes. It can be seen that the catalytic activity of the polydentate ligand L1 provided by the present invention is significantly improved compared with Zhang (Ⅶ) and comparable to that of Fürstner (Ⅵ).

[0236] Figure 3 shows that when polydentate ligands contain halogen substitutions, such as polydentate ligand L3 with chlorine substitution at the meta position of the hydroxyl group and polydentate ligand L4 with chlorine substitution at the para position of the hydroxyl group, their catalytic activity is significantly improved.

[0237] Figure 4 shows that even when the catalyst loading of the in-situ generated polydentate ligand L3 is as low as 0.6% (molar percentage), it can still maintain high catalytic activity, proving that the catalyst provided by the present invention still has high catalytic activity under low loading conditions.

[0238] Example 4

[0239] Alkyne metathesis reaction was carried out using 4-(prop-1-yn-1-yl)benzaldehyde as a substrate: ligand L10 (3 μmol) and metal ion (molybdenum) precursor (II) (2.1 mg, 3 μmol) were mixed in dry CCl4 (2.0 mL) solvent and stirred at 70 °C for 10 min to generate a catalyst in situ. A CCl4 (1.0 mL) solution of 4-(prop-1-yn-1-yl)benzaldehyde (14.4 mg, 100 μmol) was then added to the mixed solution. Molecular sieve (100 mg), reacted at 70 °C for 1.5 h, yielded 90% by NMR.

[0240] Example 5

[0241] Alkyne metathesis reaction was carried out using 4-(prop-1-yn-1-yl)aniline as a substrate: ligand L10 (3 μmol) and metal ion (molybdenum) precursor (II) (2.1 mg, 3 μmol) were mixed in dry CCl4 (2.0 mL) solvent and stirred at 70 °C for 10 min to generate a catalyst in situ. A CCl4 (1.0 mL) solution of 4-(prop-1-yn-1-yl)aniline (13.1 mg, 100 μmol) was then added to the mixed solution. Molecular sieve (100 mg), reacted at 70 °C for 2 h, yielded 60% by NMR.

[0242] Example 6

[0243] Alkyne metathesis reaction was carried out using 4-(prop-1-yn-1-yl)benzonitrile as a substrate: ligand L10 (3 μmol) and metal ion (molybdenum) precursor (II) (2.1 mg, 3 μmol) were mixed in dry CCl4 (2.0 mL) solvent and stirred at 70 °C for 10 min to generate a catalyst in situ. A CCl4 (1.0 mL) solution of 4-(prop-1-yn-1-yl)benzonitrile (14.1 mg, 100 μmol) was then added to the mixed solution. Molecular sieve (100 mg), reacted at 70 °C for 2 h, yielded 72% by NMR.

[0244] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A multidentate ligand, characterized in that, The general structural formula is as follows: (1) or (2): Where Z is selected from carbon, R 4 Selected from hydrogen and alkoxy groups; or Z is selected from silicon, R 4 Selected from fluoroalkyl or phenyl; or Z selected from phosphorus, R 4 Selected from oxygen subunits; R 1 R 2 R 3 Each is independently selected from hydrogen, halogen, trifluoromethyl, cyano, acetyl, methyl, methoxy, methylthio, isopropyl, phenoxy, 1,1,3,3-tetramethylbutyl, 4-tert-butylphenyl, 4-methoxyphenyl, 4-N,N-dimethylaminophenyl, 4-methoxyformylphenyl, 4-(2,4,6-trimethyl)phenyl, 4-carbazolylphenyl; Ar can independently represent naphthalene, indene dihydrogen fluorene, 1-indanone, 9,9-dimethylfluorene, and estradiol.

2. The multidentate ligand according to claim 1, characterized in that, The structural formula is one of the following:

3. The method for preparing the multidentate ligand according to claim 2, characterized in that, Multidentate ligands L1, L2, L3, L4, L5, L6, L7, L8, L11, L14, L15, L16, L17, L18, L19, L20, L22, L23, L24, L25, L26, L27, L35, L36, L37, L38, L42, L43, L44, L45, L46, L47, L48, L49, L50, and L51 were synthesized using Scheme 1. The multidentate ligands L9, L10, L12, L13, L21, and L28 were synthesized via scheme two. The multidentate ligands L29, L30, L31, L32, L33, L34, L39, L40, and L41 were synthesized via scheme three. The first proposed solution is as follows: Under a protective atmosphere, with the aid of a palladium catalyst and a base, a bromine-substituted triphenylmethane derivative reacts with arylboronic acid in a mixed solvent of organic solvent and water to yield a multidentate ligand. The structural formula of a bromine-substituted triphenylmethane derivative is one of the following: Arylboronic acids include 2-hydroxyphenylboronic acid, (3-chloro-2-hydroxyphenyl)boronic acid, (4-chloro-2-hydroxyphenyl)boronic acid, (5-chloro-2-hydroxyphenyl)boronic acid, (3-fluoro-2-methoxyphenyl)boronic acid, (4-fluoro-2-hydroxyphenyl)boronic acid, (5-fluoro-2-hydroxyphenyl)boronic acid, (4-trifluoromethyl-2-hydroxyphenyl)boronic acid, (5-acetyl-2-hydroxyphenyl)boronic acid, (4-isopropyl-2-hydroxyphenyl)boronic acid, (5-isopropyl-2-methoxyphenyl)boronic acid, (5-methoxy-2-hydroxyphenyl)boronic acid, (4-methoxy-2-hydroxyphenyl)boronic acid, and (4-hydroxyphenyl)-2-hydroxyphenyl ... One of the following: (phenyl)boronic acid, (5-methylthio-2-hydroxyphenyl)boronic acid, (5-phenoxy-2-hydroxyphenyl)boronic acid, (5-isopropyl-4-methyl-2-hydroxyphenyl)boronic acid, (5-chloro-4-chloro-2-methoxyphenyl)boronic acid, (5-fluoro-4-fluoro-2-methoxyphenyl)boronic acid, (3-hydroxynaphthyl-2-yl)boronic acid, (6-hydroxy-2,3-dihydro-1H-indene-5-yl)boronic acid, (6-hydroxy-1-oxo-2,3-dihydro-1H-indene-5-yl)boronic acid, and (2-methoxy-9,9-dimethyl-9H-fluorene-3-yl)boronic acid; The second option is as follows: Under a protective atmosphere, with the aid of a palladium catalyst and a base, triphenylmethane substituted with borate pinacol ester reacts with aryl halides in a mixed solvent of organic solvent and water to yield a multidentate ligand. The structural formula of triphenylmethane substituted with pinacol borate is: The aryl halide is one of 4-bromo-3-hydroxybenzonitrile, 3-bromo-4-hydroxybenzonitrile, 2-bromo-4-methylphenol, 2-bromo-5-methylphenol, 2-bromo-4-(2,4,4-trimethylpentan-2-yl)phenol, and (8R,9S,13S)-3-hydroxy-2-iodo-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthrene-17-one; The third option is as follows: Under a protective atmosphere, with the aid of a palladium catalyst and a base, halogen-substituted tri(biphenyl)methane reacts with arylboronic acid in a mixed solvent of organic solvent and water to yield a multidentate ligand. The structural formula of halogen-substituted tri(biphenyl)methane is one of the following: Arylboronic acid is one of (4-(tert-butyl)phenyl)boronic acid, (4-methoxyphenyl)boronic acid, (4-(dimethylamino)phenyl)boronic acid, (4-(methoxycarbonyl)phenyl)boronic acid, (2',4',6'-trimethyl-[1,1'-biphenyl]-4-yl)boronic acid, and (4-(9H-carbazole-9-yl)phenyl)boronic acid.

4. The method for preparing the multidentate ligand according to claim 3, characterized in that, In the first scheme, The molar ratio of bromine-substituted triphenylmethane derivatives to arylboronic acid is 1:5 to 6; The palladium catalyst is selected from at least one of tetratriphenylphosphine palladium and methanesulfonyloxy(dadamantyl-n-butylphosphino)-2'-amino-1,1'-biphenyl-2-ylpalladium(II); The base is selected from at least one of carbonates and phosphates; The organic solvent is selected from at least one of tetrahydrofuran and 1,4-dioxane; The reaction temperature is 60-100℃, and the reaction time is 12-24 hours. The solution after the reaction is quenched, extracted, concentrated, and purified by column chromatography to obtain the multidentate ligand. In the second scheme, The molar ratio of triphenylmethane substituted with pinacol borate to aryl halide is 1:5-6; The palladium catalyst is selected from at least one of bis(triphenylphosphine)palladium dichloride, tetra(triphenylphosphine)palladium, and methanesulfonyloxy(dadamantyl-n-butylphosphino)-2'-amino-1,1'-biphenyl-2-ylpalladium(II); The base is selected from at least one of carbonates and phosphates; The solvent is selected from at least one of tetrahydrofuran and 1,4-dioxane; The reaction temperature is 60-100℃, and the reaction time is 12-24 hours. The solution after the reaction is quenched, extracted, concentrated, and purified by column chromatography to obtain the multidentate ligand. In the third scheme, The molar ratio of halogen-substituted tri(biphenyl)methane to arylboronic acid is 1:5 to 6; The palladium catalyst is selected from at least one of tetratriphenylphosphine palladium and methanesulfonyloxy(dadamantyl-n-butylphosphine)-2'-amino-1,1'-biphenyl-2-ylpalladium(II); The base is selected from at least one of carbonates and phosphates; The organic solvent is selected from at least one of tetrahydrofuran and 1,4-dioxane; The reaction temperature is 60-100℃, and the reaction time is 12-24 hours. The solution after the reaction is quenched, extracted, concentrated, and purified by column chromatography to obtain the multidentate ligand.

5. A multidentate ligand metal catalyst, characterized in that, Structural formulas such as (3) or (4): Where Z is selected from carbon, R 4 Selected from hydrogen and alkoxy groups; or Z is selected from silicon, R 4 Selected from fluoroalkyl or phenyl; or Z selected from phosphorus, R 4 Selected from oxygen subunits; R 1 R 2 R 3 Each element is independently selected from hydrogen, halogen, trifluoromethyl, cyano, acetyl, methyl, methoxy, and methylthio. 4-methyl, isopropyl, phenoxy, 1,1,3,3-tetramethylbutyl, 4-tert-butylphenyl, 4-methoxyphenyl, 4-N,N-dimethylaminophenyl, 4-methoxyformylphenyl, 4-(2,4,6-trimethyl)phenyl, 4-carbazolylphenyl; Ar can be represented independently by naphthalene, indene dihydrogen fluorene, 1-indanone, 9,9-dimethylfluorene, and estradiol.

6. The method for preparing the multidentate ligand metal catalyst according to claim 5, characterized in that, Includes the following steps: The multidentate ligand and metal ion precursor described in claim 1 are mixed in an organic solvent and stirred to obtain a multidentate ligand metal catalyst; The metal ion precursor is a molybdenum-centered carbabin structure, with one of the following structural formulas:

7. The preparation method according to claim 6, characterized in that, The molar ratio of the polydentate ligand to the metal ion precursor is 0.5 to 2:1; The concentration of the polydentate ligand in the organic solvent is 0.5–5 mM.

8. The preparation method according to claim 6, characterized in that, The stirring temperature is 20–70°C, and the stirring time is 10–30 minutes; The organic solvent is CCl4.

9. The application of the polydentate ligand metal catalyst according to claim 5 in the catalytic metathesis of alkynes.

10. The application according to claim 9, characterized in that, The molar ratio of the multidentate ligand metal catalyst to the alkyne is 0.6–3:100.

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