A diamino diphosphine tetradentate ligand, a preparation method thereof and application thereof in suzuki cross-coupling reaction

Abstract

The application relates to the field of organic synthetic chemistry, in particular to a diamino diphosphine tetradentate ligand, a preparation method thereof and application of the diamino diphosphine tetradentate ligand in Suzuki cross-coupling reaction. The diamino diphosphine tetradentate ligand provided by the application has a structure shown in formula I; due to special spatial structure and electronic properties, the diamino diphosphine tetradentate ligand can provide multi-point coordination to metal and form a stable complex with the metal, so that the activity and stability of a palladium catalyst can be improved, the palladium catalyst can efficiently catalyze the Suzuki cross-coupling reaction for constructing a C-C bond at an extremely low dosage, and the diamino diphosphine tetradentate ligand and the metal palladium catalyst have strong universality to Suzuki cross-coupling reaction substrates, and have wide potential application value.

Description

Technical Field

[0001] The present invention relates to the field of organic synthetic chemistry, and in particular to a diaminodiphosphine tetradentate ligand, a preparation method thereof, and application thereof in a Suzuki cross-coupling reaction. Background Art

[0002] The Suzuki cross-coupling reaction is an important organic synthesis method used to construct C-C and C-N bonds. Using palladium catalysts, the reaction couples organohalides with organoboron reagents and has been widely used in pharmaceutical synthesis, materials science, and natural product synthesis.

[0003] In 1998, Buchwald reported an aminophosphine diaminodiphosphine tetradentate ligand for Suzuki coupling. In this system, chloroaryl hydrocarbons can be coupled with phenylboronic acid to form coupling products at room temperature (Journal of the American Chemical Society. 1998, 120(37): 9722-9723). In 2000, Beller's group prepared 1,6-dienepalladium(0) monophosphine complexes (Chemical Communications. 2000, (24): 2475-2476.). In 2010, Buchwald synthesized a class of monodentate diarylphosphine diaminodiphosphine tetradentate ligands and used them in the Suzuki coupling of polyfluorinated and heteroatom-containing arylboronic acids (Journal of the American Chemical Society. 2010, 132(40): 14073-14075). In 2014, Tang's group synthesized Pd-AntPhos diaminodiphosphine tetradentate ligands for the Suzuki coupling of aryl halides with secondary alkylboronic acids (Organic Chemistry Frontiers. 2014, 1(3): 225-229). In 2017, Nakao et al. reported a class of Suzuki coupling reactions with nitro compounds as electrophilic reagents (Journal of the American Chemical Society. 2017, 139 (28): 9423-9426.). Although there are many reported Suzuki reaction catalytic systems, many catalytic systems have low reaction activity and large catalyst dosage. Moreover, compared with halogenated aromatic substrates, halogenated alkane compounds are prone to β-hydrogen elimination during the reaction process, making the reaction difficult to occur. Therefore, the problem to be solved in the current Suzuki coupling reaction is to efficiently catalyze the Suzuki coupling reaction of various types of halogenated compounds with a more active catalytic system under milder conditions. Summary of the Invention

[0004] To address the problems in the prior art, the present invention provides a diaminodiphosphine tetradentate ligand, a preparation method thereof, and its use in a Suzuki cross-coupling reaction. The diaminodiphosphine tetradentate ligand provided by the present invention has a unique spatial structure and electronic effect, which can significantly improve the activity and stability of palladium salts, enabling the palladium salts to efficiently catalyze the Suzuki cross-coupling reaction at extremely low dosages and suppress the occurrence of side reactions, thereby improving the selectivity and yield of the reaction.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0006] The present invention provides a diaminodiphosphine tetradentate ligand having the structure shown in Formula I:

[0007]

[0008] The present invention also provides a method for preparing the above-mentioned diaminodiphosphine tetradentate ligand, comprising the following steps:

[0009] Dicyclic vinyl phosphine oxide, 1,2-cyclobutanediamine and methanol are mixed and subjected to addition reaction to obtain a phosphine oxide compound;

[0010] Under a protective atmosphere, a phosphine oxide compound, lithium aluminum tetrahydride and tetrahydrofuran are mixed and subjected to a reduction reaction to obtain the diaminodiphosphine tetradentate ligand.

[0011] Preferably, the temperature of the addition reaction is 60-100° C. and the holding time is 10-15 hours;

[0012] The temperature of the reduction reaction is 90-100° C., and the insulation time is 4-6 hours.

[0013] The present invention also provides the use of the above-mentioned diaminodiphosphine tetradentate ligand in a Suzuki cross-coupling reaction, wherein the Suzuki cross-coupling reaction is a Suzuki cross-coupling reaction of a halogenated compound and phenylboronic acid under the catalytic conditions of the diaminodiphosphine tetradentate ligand and a palladium salt;

[0014] The molar ratio of the phenylboronic acid to the diaminodiphosphine tetradentate ligand is 1:(0.00001-0.1); and the molar ratio of the palladium salt to the diaminodiphosphine tetradentate ligand is 1:1.

[0015] Preferably, the halogenated compound is 1-bromo-2-toluene, 2-chloro-5-nitropyridine, 4-bromoquinoline, 1-chloro-4-fluorobenzene, 2-chlorobenzonitrile, 1-bromo-cyclohexane, 1-chloro-3-methoxybenzene, 1-bromo-octane, 1-chloro-pentane or 1-bromo-butane;

[0016] The palladium salt is Pd2(dba)3·CHCl3, [Pd(C3H5)Cl]2, Pd(PPh3)4, Pd(OAc2, C 24 H 54 P2Pd, PdCl2, Pd(CH3CN)2Cl2, Pd(acacc)2 or Pd(cinnamyl)Cl2.

[0017] Preferably, the molar ratio of the phenylboric acid to the halogenated compound is 1:(0.5-1).

[0018] The present invention also provides a method for the Suzuki cross-coupling reaction catalyzed by the above-mentioned diaminodiphosphine tetradentate ligand, comprising the following steps:

[0019] Under a protective atmosphere, the palladium salt, the diaminodiphosphine tetradentate ligand and the first solvent are mixed to carry out a coordination reaction to obtain a palladium complex solution;

[0020] The palladium complex solution, the halogenated compound, phenylboronic acid, the basic compound and the second solvent are mixed to carry out a Suzuki cross-coupling reaction to obtain the target product.

[0021] Preferably, the temperature of the coordination reaction is 20-120° C., and the time is 2-12 hours.

[0022] Preferably, the alkaline compound is K2CO3, KHCO3, NaO t Bu, CF3COONa, K3PO4, Na2CO3, Cs2CO3, CsF, LiOH, NaOH, NaHCO3, t BuOK or KOAc; the molar ratio of the phenylboronic acid to the basic compound is 1:(0.01-1).

[0023] Preferably, the temperature of the Suzuki cross-coupling reaction is 20-200° C., and the time is 2-24 h.

[0024] The present invention provides a diaminodiphosphine tetradentate ligand having a structure shown in Formula I. Due to its special spatial structure and electronic properties, the diaminodiphosphine tetradentate ligand provided by the present invention can provide multi-point coordination to a metal and form a stable complex with the metal, thereby improving the activity and stability of a palladium catalyst. This enables the palladium catalyst to efficiently catalyze a Suzuki cross-coupling reaction to construct a C-C bond reaction at an extremely low dosage (up to one hundred thousandth of the substrate dosage). In addition, the diaminodiphosphine tetradentate ligand and the metal palladium catalyst have strong universality for the substrates of the Suzuki cross-coupling reaction and have broad potential application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 is the H NMR spectrum of diaminodiphosphine tetradentate ligand;

[0026] Figure 2 This is the C NMR spectrum of diaminodiphosphine tetradentate ligand. DETAILED DESCRIPTION

[0027] The present invention provides a diaminodiphosphine tetradentate ligand having the structure shown in Formula I:

[0028]

[0029] The present invention also provides a method for preparing the above-mentioned diaminodiphosphine tetradentate ligand, comprising the following steps:

[0030] Dicyclic vinyl phosphine oxide, 1,2-cyclobutanediamine and methanol are mixed and subjected to addition reaction to obtain a phosphine oxide compound;

[0031] Under a protective atmosphere, a phosphine oxide compound, lithium aluminum tetrahydride and tetrahydrofuran are mixed and subjected to a reduction reaction to obtain the diaminodiphosphine tetradentate ligand.

[0032] The present invention mixes dicyclic vinyl phosphine oxide, 1,2-cyclobutanediamine and methanol, and performs addition reaction to obtain a phosphine oxide compound.

[0033] In the present invention, the molar ratio of the dicyclic vinyl phosphine oxide to 1,2-cyclobutanediamine is preferably 2 to 3:1, more preferably 2:1.

[0034] In the present invention, the temperature of the addition reaction is preferably 60-100° C., more preferably 100° C.; the holding time is preferably 10-15 h, more preferably 12 h.

[0035] After obtaining the phosphine oxide compound, the present invention mixes the phosphine oxide compound, lithium aluminum tetrahydride and tetrahydrofuran under a protective atmosphere and performs a reduction reaction to obtain the diaminodiphosphine tetradentate ligand.

[0036] In the present invention, the protective atmosphere is preferably nitrogen.

[0037] In the present invention, the mass ratio of the phosphine oxide compound to lithium aluminum tetrahydride is preferably 3:0.7-1.0, more preferably 3:0.7-0.8.

[0038] In the present invention, the temperature of the reduction reaction is preferably 90-100° C., more preferably 100° C.; the holding time is preferably 4-6 h, more preferably 6 h.

[0039] The present invention also provides the use of a diaminodiphosphine tetradentate ligand in a Suzuki cross-coupling reaction. The Suzuki cross-coupling reaction is a Suzuki cross-coupling reaction of a halogenated compound and phenylboronic acid under the catalytic conditions of a diaminodiphosphine tetradentate ligand and a palladium salt.

[0040] In the present invention, the palladium salt is preferably Pd2(dba)3·CHCl3, [Pd(C3H5)Cl]2, Pd(PPh3)4, Pd(OAc)2, C 24 H 54 P2Pd, PdCl2, Pd(CH3CN)2Cl2, Pd(acacc)2 or Pd(cinnamyl)Cl2. In the present invention, the halogenated compound is preferably 1-bromo-2-toluene, 2-chloro-5-nitropyridine, 4-bromoquinoline, 1-chloro-4-fluorobenzene, 2-chlorobenzonitrile, 1-bromo-cyclohexane, 1-chloro-3-methoxybenzene, 1-bromo-octane, 1-chloro-pentane or 1-bromo-butane.

[0041] In the present invention, the molar ratio of the palladium salt to the diaminodiphosphine tetradentate ligand is preferably 1:1. In the present invention, the molar ratio of the phenylboronic acid to the diaminodiphosphine tetradentate ligand is 1:(0.00001-0.1), more preferably 1:0.00005-0.09. In the present invention, the molar ratio of the phenylboronic acid to the halogenated compound is preferably 1:(0.5-1), more preferably 1:0.6-0.9.

[0042] The present invention also provides a method for catalyzing a Suzuki cross-coupling reaction using the diaminodiphosphine tetradentate ligand, comprising the following steps:

[0043] Under a protective atmosphere, the palladium salt, the diaminodiphosphine tetradentate ligand and the first solvent are mixed to carry out a coordination reaction to obtain a palladium complex solution;

[0044] The palladium complex solution, the halogenated compound, phenylboronic acid, the basic compound and the second solvent are mixed to carry out a Suzuki cross-coupling reaction to obtain the target product.

[0045] The invention mixes palladium salt, diaminodiphosphine tetradentate ligand and a first solvent under a protective atmosphere, performs coordination reaction and obtains a palladium complex solution.

[0046] In the present invention, the first solvent is preferably one or more of DMF, THF and acetone, more preferably DMF. In the present invention, the protective atmosphere is preferably argon.

[0047] In the present invention, the temperature of the complexing reaction is preferably 20-120°C, more preferably 30-110°C; the time is preferably 2-12 hours, more preferably 3-11 hours. In the present invention, the complexing reaction is preferably carried out under stirring conditions.

[0048] After obtaining the palladium complex solution, the present invention mixes the palladium complex solution, a halogenated compound, phenylboronic acid, a basic compound and a second solvent, and performs a Suzuki cross-coupling reaction to obtain a target product.

[0049] In the present invention, the alkaline compound is preferably K2CO3, KHCO3, NaO t Bu, CF3COONa, K3PO4, Na2CO3, Cs2CO3, CsF, LiOH, NaOH, NaHCO3, t BuOK or KOAc. In the present invention, the second solvent is preferably benzene, toluene, tetrahydrofuran, acetone, dimethyl sulfoxide, acetonitrile, N,N-dimethylformamide, 1,4-dioxane, dichloromethane, methanol, ethanol, isopropanol, tert-butyl alcohol, or water. In the present invention, the molar ratio of phenylboronic acid to the basic compound is preferably 1:(0.01-1), more preferably 1:0.02-0.9.

[0050] In the present invention, the temperature of the Suzuki cross-coupling reaction is preferably 20-200°C, more preferably 30-180°C; the time is preferably 2-24 hours, more preferably 3-20 hours. In the present invention, the Suzuki cross-coupling reaction is preferably carried out under stirring conditions.

[0051] In the present invention, after the Suzuki cross-coupling reaction, it is preferred to further include concentration and column chromatography separation in sequence.

[0052] The technical solutions provided by the present invention are described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0053] The preparation of the ligands in Examples 1 to 10 is as follows:

[0054] To a dry reaction bottle equipped with a magnetic bar, dicyclovinylphosphine oxide (10 mmol), 1,2-cyclobutanediamine (5 mmol) and methanol (10 mL) were added in sequence and reacted at 100° C. for 12 h to obtain 3 g of phosphine oxide compound.

[0055] Then, under nitrogen protection, phosphine oxide (3 g), lithium aluminum tetrahydride (20 mmol) and tetrahydrofuran (20 mL) were added to the reaction flask, and the mixture was reacted at 100° C. for 6 h to obtain 2.5 g of diaminodiphosphine tetradentate ligand.

[0056] The yield was determined to be 91% by nuclear magnetic resonance spectroscopy, and the purity of the product was 99% by liquid chromatography analysis.

[0057] The hydrogen spectrum and carbon spectrum of the product of Example 1 are shown in Figure 1 and Figure 2 , the hydrogen spectrum and carbon spectrum information are: 1HNMR (500MHz, CDCl3): δ2.95-2.88(m,2H),2.85-2.78(m,2H),2.62-2.54(m,4H),1.97-1.81(m,4H),1.74-1.60(m,14H),1.58-1.30(m,34H).

[0058] 13 C NMR (125MHz, CDCl3): δ55.19,55.16,47.75,47.65,29.28,29.18,27.23,27.05,26.79,26.64,26.61,26.33,26.26,26.20.

[0059] Example 1

[0060] The reaction equation of Example 1 is:

[0061]

[0062] 0.1 mmol of PdCl2 and 0.1 mmol of a diaminodiphosphine tetradentate ligand of Formula I were dissolved in 0.1 mL of DMF. After three replacements with argon, the reaction flask was placed on a stirrer and stirred at 25°C for 10 hours. Then, 1 mmol of 1-bromo-2-toluene, 1 mmol of phenylboronic acid, 0.5 mmol of K2CO3, and 4 mL of isopropanol were added to a Schlenk tube. The reaction solution of the palladium salt and the diaminodiphosphine tetradentate ligand of Formula I was added. The Schlenk tube was stirred at 60°C for 16 hours. After completion of the reaction, the reaction solution was concentrated in vacuo and separated by column chromatography (eluent: ethyl acetate and petroleum ether in a volume ratio of 1:10) to obtain the desired product. The yield was determined by nuclear magnetic resonance spectroscopy to be 99%, and the purity of the product was 99% by liquid chromatography.

[0063] The hydrogen spectrum and carbon spectrum information of the product of Example 1 are 1 H NMR (500MHz, CDCl3): δ7.68-7.64(m,1H),7.40-7.35(m,3H),7.31-7.23(m,5H),2.37(d,J=0.7Hz,3H). 13 C NMR (125MHz, CDCl3): δ141.09,140.15,135.66,129.64,129.14,128.10,127.73,127.22,126.50,125.95,20.23.

[0064] Example 2

[0065] Reaction equation of Example 2 is as follows:

[0066]

[0067] 0.05 mmol of [Pd(C3H5)Cl]2 and 0.05 mmol of the diamino diphosphine tetradentate ligand shown in the structure of Formula I were weighed into 0.2 mL of DMF, and the reaction bottle was placed on a stirrer after three times of argon replacement, and the reaction was stirred at 50°C for 8 h. Then 2-chloro-5-nitropyridine (0.5 mmol), phenylboronic acid (1 mmol), NaO t Bu (1 mmol) and t-butyl alcohol (4 mL) in a Schlenk tube, and the reaction of the palladium salt and the diamino diphosphine tetradentate ligand shown in the structure of Formula I was added, and the Schlenk tube was stirred at 100°C for 10 h. After the reaction was completed by TLC monitoring, the reaction solution was concentrated under vacuum, and the target product was separated by column chromatography (eluent was dichloromethane and methanol at a volume ratio of 20:1) to obtain the target product with a separation yield of 97%, and the product purity was 99% by liquid chromatograph analysis.

[0068] The hydrogen spectrum and carbon spectrum information of the product of Example 2 are as follows 1 HNMR (500 MHz, CDCl3): δ 9.42 (d, J = 1.8 Hz, 1H), 8.39 (dd, J = 8.4, 1.8 Hz, 1H), 8.03-7.99 (m, 2H), 7.76 (d, J = 8.4 Hz, 1H), 7.43-7.35 (m, 3H). 13 C NMR (125 MHz, CDCl3): δ 160.20, 146.10, 144.51, 137.01, 132.04, 129.61, 128.80, 127.40, 122.36.

[0069] Example 3

[0070] Reaction equation of Example 3 is as follows:

[0071]

[0072] 0.01 mmol of Pd2(dba)3·CHCl3 and 0.01 mmol of a diaminodiphosphine tetradentate ligand of Formula I were dissolved in 0.5 mL of DMF. After three replacements with argon, the reaction flask was placed on a stirrer and stirred at 60°C for 7 hours. 4-Bromoquinoline (0.75 mmol), phenylboronic acid (1 mmol), K3PO4 (0.2 mmol), and 1,4-dioxane (4 mL) were then added to a Schlenk tube. The palladium salt and the diaminodiphosphine tetradentate ligand of Formula I were then added to the Schlenk tube. The reaction was stirred at 60°C for 16 hours. After completion of the reaction, the reaction solution was concentrated in vacuo and separated by column chromatography (eluent: dichloromethane and methanol in a 20:1 volume ratio) to obtain the desired product in a 97% yield. Liquid chromatography analysis confirmed the product to be 99% pure.

[0073] The hydrogen spectrum and carbon spectrum information of the product of Example 3 are 1 H NMR (500MHz, CDCl3): δ8.84(d,J=5.7Hz,1H),8.41-8.35(m,1H),8.11(dd,J=7.9,1.5Hz,1H),7.86(d,J=5.7Hz,1H) ,7.77(td,J=7.5,1.4Hz,1H),7.72(td,J=7.6,1.3Hz,1H),7.67-7.62(m,2H),7.51-7.45(m,2H),7.41-7.35(m,1H). 13 C NMR (125MHz, CDCl3): δ150.24,145.90,143.93,138.16,129.35,129.29,127.73,127.45,126.81,126.63,126.39,124.30,120.30.

[0074] Example 4

[0075] The reaction equation of Example 4 is:

[0076]

[0077] Weigh 0.005 mol of Pd(acacc)2 and 0.005 mol of diaminodiphosphine tetradentate ligand of formula I and dissolve them in 0.1 mL of DMF. After replacing the gas with argon three times, place the reaction bottle on a stirrer and stir at 25°C for 12 hours. Then weigh 1-chloro-4-fluorobenzene (0.5 mmol), phenylboronic acid (1 mmol), tBuOK (0.01 mmol) and tetrahydrofuran (4 mL) were placed in a Schlenk tube, and a reaction solution of a palladium salt and a diaminodiphosphine tetradentate ligand of the structure represented by Formula I was added. The Schlenk tube was stirred at 60°C for 10 hours. After the reaction was complete as monitored by TLC, the reaction solution was concentrated in vacuo and separated by column chromatography (eluent: ethyl acetate and petroleum ether in a volume ratio of 1:10) to obtain the target product in a yield of 94%. Liquid chromatography analysis showed a product purity of 99%.

[0078] The hydrogen spectrum and carbon spectrum information of the product of Example 4 are respectively 1 HNMR (500MHz, CDCl3): δ7.60-7.56(m,2H),7.55-7.50(m,2H),7.45-7.40(m,2H),7.37-7.32(m,1H),7.18-7.12(m,2H). 13 C NMR (125MHz, CDCl3): δ163.43,161.42,140.25,138.50,138.48,129.12,129.05,128.86,127.75,127.18,115.36,115.20.

[0079] Example 5

[0080] The reaction equation of Example 5 is:

[0081]

[0082] Weigh 0.001 mmol of C 24 H 54 P2Pd and 0.001 mmol of a diaminodiphosphine tetradentate ligand of Formula I were dissolved in 0.2 mL of DMF. After three replacements with argon, the reaction flask was placed on a stirrer and stirred at 50°C for 8 hours. 2-Chlorobenzonitrile (1 mmol), phenylboronic acid (1 mmol), KHCO3 (1 mmol), and dimethyl sulfoxide (4 mL) were then weighed into a Schlenk tube. The reaction solution of the palladium salt and the diaminodiphosphine tetradentate ligand of Formula I was added. The Schlenk tube was stirred at 100°C for 6 hours. After completion of the reaction as monitored by TLC, the reaction solution was concentrated in vacuo and separated by column chromatography (eluent: ethyl acetate and petroleum ether in a volume ratio of 1:5) to obtain the desired product in a yield of 92%. Liquid chromatography analysis confirmed the product to be 99% pure.

[0083] The hydrogen spectrum and carbon spectrum information of the product of Example 5 are 1H NMR (500MHz, CDCl3): δ7.76 (m, J=8.4, 3.3, 1.7Hz, 3H), 7.68 (dd, J=7.7, 1.4Hz, 1H ),7.58(td,J=7.6,1.6Hz,1H),7.55-7.49(m,3H),7.36(m,J=8.8,7.1,1.5Hz,1H). 13 C NMR (125MHz, CDCl3): δ145.11,138.01,133.01,132.40,130.24,129.00,128.05,127.92,127.82,118.14,112.14.

[0084] Example 6

[0085] The reaction equation of Example 6 is:

[0086]

[0087] 0.0001 mmol of Pd(OAc)2 and 0.0001 mmol of a diaminodiphosphine tetradentate ligand of Formula I were dissolved in 0.2 mL of DMF. After three replacements with argon, the reaction flask was placed on a stirrer and stirred at 25°C for 8 hours. 1-Bromocyclohexane (0.5 mmol), phenylboronic acid (1 mmol), CF3COONa (0.05 mmol), and toluene (4 mL) were then added to a Schlenk tube. The palladium salt and the diaminodiphosphine tetradentate ligand of Formula I were then added to the Schlenk tube. The reaction mixture was stirred at 150°C for 24 hours. After completion of the reaction, the reaction solution was concentrated in vacuo and separated by column chromatography (eluent: ethyl acetate and petroleum ether in a volume ratio of 1:20) to obtain the desired product in an 85% yield. Liquid chromatography analysis revealed a purity of 99%.

[0088] The hydrogen spectrum and carbon spectrum information of the product of Example 6 are respectively 1 H NMR (500MHz, CDCl3): δ7.34-7.27(m,4H),7.23(m,J=7.6,6.0,2.8Hz,1H),2.63-2.56 (m,1H),1.86-1.75(m,4H),1.70-1.61(m,1H),1.50-1.38(m,4H),1.36-1.28(m,1H). 13 C NMR (125MHz, CDCl3): δ147.81,128.43,127.03,126.57,47.29,34.49,26.98,26.23.

[0089] Example 7

[0090] The reaction equation of Example 7 is:

[0091]

[0092] 0.00001 mmol of Pd(cinnamyl)Cl2 and 0.00001 mmol of a diaminodiphosphine tetradentate ligand of Formula I were dissolved in 0.5 mL of DMF. After three replacements with argon, the reaction flask was placed on a stirrer and stirred at 80°C for 8 hours. 1-Chloro-3-methoxybenzene (1 mmol), phenylboronic acid (1 mmol), Na2CO3 (0.1 mmol), and acetonitrile (4 mL) were then added to a Schlenk tube. The reaction mixture of the palladium salt and the diaminodiphosphine tetradentate ligand of Formula I was then added. The Schlenk tube was stirred at 160°C for 16 hours. After completion of the reaction, the reaction solution was concentrated in vacuo and separated by column chromatography (eluent: ethyl acetate and petroleum ether in a volume ratio of 1:10) to obtain the desired product in a yield of 78%. Liquid chromatography analysis of the product showed a purity of 99%.

[0093] The hydrogen spectrum and carbon spectrum information of the product of Example 7 are 1 H NMR (500MHz, CDCl3): δ7.61(t,J=1.5Hz,1H),7.59(t,J=1.3Hz,1H),7.46-7.40(m,3H),7 .38-7.33(m,2H),7.18(t,J=2.2Hz,1H),6.92(ddd,J=7.7,2.2,1.3Hz,1H),3.84(s,3H). 13 C NMR (125MHz, CDCl3): δ159.53,139.67,138.69,129.98,128.81,127.80,127.17,126.84,113.83,110.38,55.27.

[0094] Example 8

[0095] The reaction equation of Example 8 is:

[0096]

[0097] 0.1 mmol of Pd(PPh3)4 and 0.1 mmol of a diaminodiphosphine tetradentate ligand of Formula I were dissolved in 0.1 mL of DMF. After replacing the atmosphere with argon three times, the reaction flask was placed on a stirrer and stirred at 25°C for 8 hours. 1-Bromooctane (0.5 mmol), phenylboronic acid (1 mmol), Cs2CO3 (0.1 mmol), and N,N-dimethylformamide (4 mL) were then added to a Schlenk tube. The reaction mixture of the palladium salt and the diaminodiphosphine tetradentate ligand of Formula I was then added. The Schlenk tube was stirred at 80°C for 12 hours. After completion of the reaction, the reaction solution was concentrated in vacuo and separated by column chromatography (eluent: ethyl acetate and petroleum ether in a volume ratio of 1:15) to obtain the desired product in a 99% yield. Liquid chromatography analysis confirmed the product to be 99% pure.

[0098] The hydrogen spectrum and carbon spectrum information of the product of Example 8 are respectively 1 H NMR (500MHz, CDCl3): δ7.29-7.24(m,2H),7.23-7.18(m,1H),7.15(ddt,J=7.3,1.9,1.0Hz,2H ),2.57(tt,J=6.4,1.0Hz,2H),1.62(p,J=6.6Hz,2H),1.34-1.25(m,10H),0.91-0.86(m,3H). 13 C NMR (125MHz, CDCl3): δ141.97,128.58,128.51,126.09,35.44,31.89,30.97,29.34,29.32,29.22,22.60,14.08.

[0099] Example 9

[0100] The reaction equation of Example 9 is:

[0101]

[0102] 0.05 mmol of Pd(CH3CN)2Cl2 and 0.05 mmol of a diaminodiphosphine tetradentate ligand of Formula I were dissolved in 0.1 mL of DMF. After three replacements with argon, the reaction flask was placed on a stirrer and stirred at 80°C for 4 hours. 1-Chloropentane (1 mmol), phenylboronic acid (1 mmol), CsF (0.5 mmol), and methanol (4 mL) were then added to a Schlenk tube. The reaction mixture of the palladium salt and the diaminodiphosphine tetradentate ligand of Formula I was then added. The Schlenk tube was stirred at 160°C for 6 hours. After completion of the reaction, the reaction solution was concentrated in vacuo and separated by column chromatography (eluent: ethyl acetate and petroleum ether in a volume ratio of 1:15) to obtain the desired product in a yield of 96%. Liquid chromatography analysis of the product showed a purity of 99%.

[0103] The hydrogen spectrum and carbon spectrum information of the product of Example 9 are respectively 1 H NMR (500MHz, CDCl3): δ7.29-7.24(m,2H),7.23-7.19(m,1H),7.15(ddt,J=7.4,1.7,1.0Hz,2 H),2.62(tt,J=6.4,1.0Hz,2H),1.53(p,J=6.6Hz,2H),1.37-1.30(m,4H),0.92-0.86(m,3H). 13 C NMR (125MHz, CDCl3): δ142.76,128.49,128.29,126.21,35.89,31.55,31.44,22.53,14.07.

[0104] Example 10

[0105] The reaction equation of Example 10 is:

[0106]

[0107] 0.02 mmol of PdCl2 and 0.02 mmol of a diaminodiphosphine tetradentate ligand of Formula I were dissolved in 0.5 mL of DMF. After replacing the gas with argon three times, the reaction flask was placed on a stirrer and stirred at 120°C for 4 hours. 1-Bromobutane (1 mmol), phenylboronic acid (1 mmol), LiOH (0.5 mmol), and acetone (4 mL) were then added to a Schlenk tube. The reaction solution of the palladium salt and the diaminodiphosphine tetradentate ligand of Formula I was added and stirred at 180°C for 6 hours. After TLC monitoring of the reaction completion, the reaction solution was vacuum concentrated and separated by column chromatography (eluent: ethyl acetate and petroleum ether in a volume ratio of 1:15) to obtain the desired product in a 94% yield. Liquid chromatography analysis of the product showed a purity of 99%.

[0108] The hydrogen spectrum and carbon spectrum information of the product of Example 10 are respectively 1 H NMR (500MHz, CDCl3): δ7.28-7.24(m,2H),7.23-7.19(m,1H),7.15(ddt,J=7.5,1.9,1.0Hz,2H),2.60(t t,J=6.4,1.0Hz,2H),1.56(p,J=6.6Hz,2H),1.33(dtd,J=14.4,7.4,6.5Hz,2H),0.94(t,J=7.6Hz,3H). 13 CNMR (125MHz, CDCl3): δ143.27,128.79,128.35,126.29,35.89,32.75,22.84,13.86.

[0109] Although the above embodiment provides a detailed description of the present invention, it is only a part of the embodiments of the present invention, not all of the embodiments. Other embodiments can be obtained based on this embodiment without creativity, and these embodiments all fall within the scope of protection of the present invention.

Claims

1. A diaminodiphosphine tetradentate ligand, characterized in that Having the structure shown in formula I:

2. The method for preparing the diaminodiphosphine tetradentate ligand according to claim 1, comprising the steps of: Dicyclohexylvinylphosphine oxide, 1,2-cyclobutanediamine and methanol are mixed and subjected to addition reaction to obtain a phosphine oxide compound; Under a protective atmosphere, a phosphine oxide compound, lithium aluminum tetrahydride and tetrahydrofuran are mixed and subjected to a reduction reaction to obtain the diaminodiphosphine tetradentate ligand.

3. The preparation method according to claim 2, wherein The temperature of the addition reaction is 60-100° C. and the holding time is 10-15 hours; The temperature of the reduction reaction is 90-100° C., and the insulation time is 4-6 hours.

4. Use of the diaminodiphosphine tetradentate ligand according to claim 1 in a Suzuki cross-coupling reaction, characterized in that: The Suzuki cross-coupling reaction is a Suzuki cross-coupling reaction of a halogenated compound and phenylboronic acid under the catalytic conditions of a diaminodiphosphine tetradentate ligand and a palladium salt; The molar ratio of the phenylboronic acid to the diaminodiphosphine tetradentate ligand is 1:(0.00001-0.1); and the molar ratio of the palladium salt to the diaminodiphosphine tetradentate ligand is 1:

1.

5. The use according to claim 4, characterized in that The halogenated compound is 1-bromo-2-toluene, 2-chloro-5-nitropyridine, 4-bromoquinoline, 1-chloro-4-fluorobenzene, 2-chlorobenzonitrile, 1-bromo-cyclohexane, 1-chloro-3-methoxybenzene, 1-bromo-octane, 1-chloro-pentane or 1-bromo-butane; The palladium salt is Pd2(dba)3·CHCl3, [Pd(C3H5)Cl]2, Pd(PPh3)4, Pd(OAc2, C 24 H 54 P2Pd, PdCl2, Pd(CH3CN)2Cl2, Pd(acacc)2 or Pd(cinnamyl)Cl2.

6. The use according to claim 5, characterized in that The molar ratio of the phenylboric acid to the halogenated compound is 1:(0.5-1).

7. A method for catalyzing a Suzuki cross-coupling reaction using the diaminodiphosphine tetradentate ligand according to claim 1, characterized in that: The following steps are involved: Under a protective atmosphere, the palladium salt, the diaminodiphosphine tetradentate ligand and the first solvent are mixed to carry out a coordination reaction to obtain a palladium complex solution; The palladium complex solution, the halogenated compound, phenylboronic acid, the basic compound and the second solvent are mixed to carry out a Suzuki cross-coupling reaction to obtain the target product.

8. The method according to claim 7, wherein The temperature of the coordination reaction is 20-120° C., and the time is 2-12 hours.

9. The method according to claim 7, wherein The alkaline compound is K2CO3, KHCO3, NaO t Bu, CF3COONa, K3PO4, Na2CO3, Cs2CO3, CsF, LiOH, NaOH, NaHCO3, t BuOK or KOAc; the molar ratio of the phenylboronic acid to the basic compound is 1:(0.01-1).

10. The method according to claim 7, wherein: The temperature of the Suzuki cross-coupling reaction is 20-200° C., and the time is 2-24 hours.

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