Three-dimensional skeleton large-steric-hindrance nitrogen heterocyclic carbene palladium complex as well as preparation method and application thereof

Abstract

The invention discloses a three-dimensional skeleton large-steric-hindrance nitrogen heterocyclic carbene palladium complex as well as a preparation method and application thereof, and belongs to the technical field of catalysts. The complex provided by the invention has a unique three-dimensional skeleton, not only can regulate and control an electronic effect, but also can increase a steric hindrance effect. By introducing an aromatic naphthalene ring shaped like a butterfly wing into an imidazole ring matrix, turning of arylamine surrounding a carbon-nitrogen bond can be prevented, so that beta-hydrogen elimination and catalyst deactivation are inhibited, and the turnover number and catalytic activity of the catalyst are improved. The heteroatom auxiliary ligand ensures that the complex has good stability in air. The three-dimensional skeleton large-steric-hindrance nitrogen heterocyclic carbene palladium complex provided by the invention provides a new catalysis scheme for efficient and sustainable organic synthesis.

Description

Technical Field

[0001] The invention relates to the technical field of catalysts, and in particular to a stereoscopic three-dimensional framework large steric hindrance nitrogen heterocyclic carbene palladium complex and a preparation method and application thereof. Background Art

[0002] Metal palladium phosphine complexes are widely used to catalyze the formation of carbon-carbon bonds and carbon-hetero bonds and are very effective catalysts. Cross-coupling reactions can construct a variety of functional molecules. Cross-coupling reactions play an important role in many fields such as drug synthesis, natural products, agriculture, optical devices and industrial raw materials. However, the commonly used metal palladium phosphine complexes have low thermal stability, are easily oxidized and decomposed, and are difficult to catalyze coupling reactions under air and water conditions, which has many limitations in application. The design and development of efficient palladium complex catalysts and catalytic systems are of great significance for the efficient and highly selective synthesis of high value-added products and the creation of functional molecules under mild conditions.

[0003] Nitrogen heterocyclic carbene ligands have strong σ-donor and weak π-acceptor properties. The resulting nitrogen heterocyclic carbene metal complex catalysts have excellent stability and easily regulated catalytic centers compared to metal complexes such as phosphine, nitrogen, carbon monoxide, and cyclopentadiene. In addition, the electronic and steric effects of the substituents on the nitrogen atom are easy to regulate, and a relatively rich ligand library can be derived, thereby obtaining nitrogen heterocyclic carbene metal complexes with different catalytic properties, which can be used to construct or cut different types of inert carbon-carbon bonds and carbon-hetero bonds, and have many applications in chemistry, materials science, and industry. However, the catalytic activity and stability of existing nitrogen heterocyclic carbene ligands in air need to be further improved. Summary of the invention

[0004] The purpose of the present invention is to provide a three-dimensional skeleton large steric hindrance nitrogen heterocyclic carbene palladium complex and its preparation method and application. By introducing an aromatic naphthalene ring shaped like a butterfly wing into an imidazole ring matrix, the ultra-large steric hindrance can prevent the aromatic amine from flipping around the carbon-nitrogen bond, thereby inhibiting β-hydrogen elimination and catalyst deactivation, and improving the turnover number and catalytic activity of the catalyst; the heteroatom auxiliary ligand improves the stability of the complex in air.

[0005] To achieve the above object, the present invention provides a three-dimensional framework of a large sterically hindered nitrogen heterocyclic carbene palladium complex, the general structural formula of which is:

[0006]

[0007] Wherein, R is a hydrogen atom, a C1-C8 alkyl group or an aryl group;

[0008] R 1 is a hydrogen atom, a methyl group, an isopropyl group, a C1-C12 alkyl group or an aryl group;

[0009] R 2 is a hydrogen atom, a methyl group, an isopropyl group, a C1-C12 alkyl group or an aryl group;

[0010] X is a hydrogen atom or a halogen atom.

[0011] Preferably, R is a hydrogen atom.

[0012] Preferably, the R 1 It is isopropyl.

[0013] Preferably, the R 2 A hydrogen atom.

[0014] Preferably, X is a chlorine atom.

[0015] The preparation method of the above-mentioned stereoscopic three-dimensional framework large steric hindered nitrogen heterocyclic carbene palladium complex comprises the following steps:

[0016] S1, o-phthalaldehyde and 1,4-cyclohexanedione are added to ethanol, potassium hydroxide is added dropwise, and the mixture is reacted under nitrogen protection to prepare compound A;

[0017] S2, adding the tetrahydrofuran solution of compound A to LiAlH4 under an ice-water bath, reflux, and cool to room temperature; adding hydrochloric acid solution dropwise under an ice-water bath, stirring; extracting, spin-drying, washing, and drying to obtain compound B;

[0018] S3, mixing compound B, vinylene carbonate and o-xylene under nitrogen protection for reaction, and after the reaction, spin-drying and chromatography to obtain compound C;

[0019] S4, compound C, 1,4-dioxane and NaOH solution were mixed, heated under reflux at 100° C. for 2 h, cooled to room temperature, hydrochloric acid solution was added, and compound D was obtained after extraction, drying and spin drying;

[0020] S5, cooling dimethyl sulfoxide and dichloromethane to -70°C, adding trifluoroacetic anhydride dropwise, stirring evenly under nitrogen protection to obtain a mixed solution; adding compound D dropwise to the mixed solution, stirring evenly; then adding triethylamine, stirring evenly; heating the reaction to 2°C-10°C, pouring into a hydrochloric acid solution, extracting, drying, filtering, spin drying, and chromatography to obtain compound E;

[0021] S6. Under nitrogen protection, compound E and 2,6-diisopropylaniline were heated to reflux in the presence of p-toluenesulfonic acid as a catalyst, cooled to room temperature after the reaction, the solvent was evaporated, and recrystallized from anhydrous ethanol to obtain compound F;

[0022] S7. Under nitrogen protection, compound F reacts with chloromethyl ethyl ether. After the reaction is completed, the mixture is spin-dried and chromatographed to obtain compound G;

[0023] S8. Under nitrogen protection, compound G, palladium chloride and 3-chloropyridine are mixed for reaction. After the reaction is completed, the solvent is dried by spin drying and a three-dimensional framework large sterically hindered nitrogen heterocyclic carbene palladium complex is obtained after chromatography.

[0024] Preferably, in S1, the molar ratio of o-phthalaldehyde to 1,4-cyclohexanedione is 1.5-2.5:0.5-1.5, the reaction temperature is 50°C-70°C, and the reaction time is 3h-5h; in S3, the molar ratio of compound B to vinylene carbonate is 0.5-1.5:1.5-2.5, the reaction temperature is 160°C-200°C, and the reaction time is 60h-80h.

[0025] Preferably, in S6, the molar ratio of compound E to 2,6-diisopropylaniline is 0.5-1.5:1.5-2.5, the heating temperature is 100°C-130°C, and the reflux time is 20h-30h; in S7, the molar ratio of compound F to chloromethyl ethyl ether is 1-2:24-28, the reaction temperature is 90°C-110°C, and the reaction time is 20h-30h.

[0026] Preferably, in S8, the molar ratio of compound G to palladium chloride is 3-4:4-5, the reaction temperature is 70°C-100°C, and the reaction time is 20h-30h.

[0027] The three-dimensional framework of the large sterically hindered nitrogen heterocyclic carbene palladium complex is used as a catalyst in the ring-opening reaction of geminal difluorocyclopropane and the coupling reaction of the nucleophilic reagent, wherein the nucleophilic reagent is a malonic ester or an amide.

[0028] The advantages and positive effects of the three-dimensional skeleton large steric hindered nitrogen heterocyclic carbene palladium complex and its preparation method and application described in the present invention are:

[0029] 1. The complex described in the present invention has a unique three-dimensional skeleton, which can not only easily regulate the electronic effect, but also increase the steric hindrance effect.

[0030] 2. The present invention introduces an aromatic naphthalene ring shaped like a butterfly wing into the imidazole ring matrix through the Diels-Alder reaction. Its large steric hindrance can prevent the aromatic amine from flipping around the carbon-nitrogen bond, thereby inhibiting β-hydrogen elimination and catalyst deactivation, thereby greatly improving the turnover number and catalytic activity of the catalyst.

[0031] 3. The heteroatom auxiliary ligand in the present invention can ensure that the complex has good stability in the air.

[0032] 4. The three-dimensional framework of the large steric hindered nitrogen heterocyclic carbene palladium complex described in the present invention provides a new catalytic solution for efficient and sustainable organic synthesis.

[0033] The technical solution of the present invention is further described in detail below through the accompanying drawings and embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 This is the H NMR spectrum of the three-dimensional framework large steric hindered nitrogen heterocyclic carbene palladium complex H according to the embodiment of the present invention;

[0035] Figure 2 This is the NMR carbon spectrum of the three-dimensional framework large steric hindered nitrogen heterocyclic carbene palladium complex H of the embodiment of the present invention;

[0036] Figure 3 is the H NMR spectrum of compound G according to an embodiment of the present invention;

[0037] Figure 4 is the NMR carbon spectrum of compound G in the embodiment of the present invention;

[0038] Figure 5 is the H NMR spectrum of compound 3 of the present invention;

[0039] Figure 6 is the NMR carbon spectrum of compound 3 of the embodiment of the present invention;

[0040] Figure 7 is the NMR fluorine spectrum of compound 3 of the embodiment of the present invention;

[0041] Figure 8 is the H NMR spectrum of compound 5 of the present invention;

[0042] Fig. 9 It is the NMR carbon spectrum of compound 5 of the embodiment of the present invention. DETAILED DESCRIPTION

[0043] The embodiments of the present invention are described in detail below in conjunction with the accompanying drawings.

[0044] A three-dimensional framework of large sterically hindered nitrogen heterocyclic carbene palladium complex, the general structural formula is:

[0045]

[0046] Wherein, R is a hydrogen atom;

[0047] R 1 is isopropyl;

[0048] R 2 is a hydrogen atom;

[0049] X is a chlorine atom.

[0050] The structural formula of the three-dimensional sterically hindered nitrogen heterocyclic carbene palladium complex is:

[0051]

[0052] The preparation method of the stereoscopic three-dimensional framework large steric hindered nitrogen heterocyclic carbene palladium complex comprises the following steps:

[0053] S1. Synthesis of Compound A

[0054]

[0055] Under nitrogen protection, o-phthalaldehyde (2.73 g, 20.0 mmol), 1,4-cyclohexanedione (1.15 g, 10.0 mmol) and ethanol (25.0 mL) were added to a 100 mL reaction bottle in sequence and stirred to dissolve. Potassium hydroxide (15% aqueous solution) (10.0 mL) was then added dropwise, and the solution changed from yellow to red and a yellow solid precipitated. The reaction was continued at 60°C for 4 h. After cooling and filtration, the solid was repeatedly washed with acetone to obtain a yellow solid compound A with a yield of 81%.

[0056] The results of NMR analysis of compound A are:

[0057] 1 H NMR (400MHz, CDCl3) δ8.96 (s, 4H), 8.15-8.12 (m, 4H), 7.73-7.71 (m, 4H).

[0058] S2. Synthesis of compound B

[0059]

[0060] Under nitrogen protection, compound A (1.54 g, 5.0 mmol) and THF (50.0 mL) were added to a 250 ml reaction bottle in sequence. LiAlH4 (0.95 g, 25.0 mmol) was added in batches under an ice-water bath, and then refluxed for 60 h. After the reaction was completed, it was cooled to room temperature and a 6 mol / L hydrochloric acid solution (30.0 mL) was added dropwise under an ice-water bath. After stirring for half an hour, dichloromethane was extracted 2-3 times, and the organic phases were combined. After being spin-dried, the solid was washed with water (30.0 mL), acetone (30.0 mL) and ether (10.0 mL) respectively. Purple solid compound B was obtained by vacuum drying with a yield of 72%.

[0061] S3. Synthesis of Compound C

[0062]

[0063] Under nitrogen protection, compound B (1.0 g, 3.6 mmol), vinylene carbonate (0.5 mL, 7.2 mmol) and o-xylene (20.0 mL) were added in sequence in a 100 mL sealed tube. The reaction was carried out at 180°C for 72 h. After the reaction was completed, the solvent was dried and the mixture was subjected to dichloromethane column chromatography to obtain yellow solid compound C with a yield of 52%.

[0064] The results of NMR analysis of compound C are:

[0065] 1 H NMR (400MHz, CDCl3) δ7.87(s,2H),7.87(s,2H),7.81(m,4H),7.47(m,4H),5.05(m,2H),4.94(m,2H).

[0066] S4. Synthesis of Compound D

[0067]

[0068] Under air, compound C (0.68 g, 1.9 mmol), 1,4-dioxane (25.0 mL) and 4 mol / L NaOH solution (3.0 mL) were added to a 50 mL reaction bottle in sequence, and heated to reflux at 100°C for 2 h. After cooling to room temperature, 2 mol / L hydrochloric acid solution (10.0 mL) was added, and dichloromethane was extracted 2-3 times. The organic layers were combined and dried over anhydrous sodium sulfate, and then spin-dried to obtain white solid compound D with a yield of 89%.

[0069] The results of NMR analysis of compound D are:

[0070] 1 H NMR (400MHz, CDCl3) δ7.85(s,2H),7.80(m,6H),7.43(m,4H),4.66(s,2H)4.22(s,2H).

[0071] S5. Synthesis of Compound E

[0072]

[0073] Under nitrogen protection, dimethyl sulfoxide (2.0mL, 27.2mmol) and dichloromethane (25.0mL) were added to a 200mL reaction bottle. After cooling to -70°C, trifluoroacetic anhydride (TFAA) (3.8mL, 27.2mmol) was added dropwise and stirred for 30 minutes. Compound D (0.58g, 1.7mmol) was then dissolved in a small amount of a mixed solution of dimethyl sulfoxide and dichloromethane and added dropwise. After stirring for 1.5h, triethylamine (6.7mL, 48.0mmol) was added dropwise and stirred for 8h. The reaction was heated to 5°C, poured into a 2mol / L hydrochloric acid solution, extracted with dichloromethane several times, the organic phase was collected and dried with anhydrous sodium sulfate, filtered, and spin-dried and column-dried with dichloromethane to obtain a yellow solid compound E with a yield of 88%.

[0074] The results of NMR analysis of compound E are:

[0075] 1 H NMR (400MHz, CDCl3) δ7.94(s,4H),7.84(m,4H),7.52(m,4H),5.31(s,2H).

[0076] S6. Synthesis of Compound F

[0077]

[0078] Under nitrogen protection, compound E (0.50 g, 1.5 mmol), 2,6-diisopropylaniline (0.65 mL, 3.3 mmol), catalytic amount of p-toluenesulfonic acid (10 mol%) and toluene (5.0 mL) were added to a 100 mL reaction bottle in sequence and heated under reflux for 24 h. After the reaction was completed, the mixture was cooled to room temperature and the solvent was removed by rotary evaporation. Recrystallization with anhydrous ethanol was used to precipitate a yellow solid compound F with a yield of 88%.

[0079] The results of NMR analysis of compound F are:

[0080] 1 H NMR (400MHz, CDCl3) δ7.26–8.05(m,18H),5.26(s,2H),2.52(m,4H),1.15(m,12H),0.99(m,12H).

[0081] S7. Synthesis of Compound G

[0082]

[0083] Under nitrogen protection, compound F (0.87 g, 1.3 mmol) and chloromethyl ethyl ether (3.0 mL, 26.0 mmol) were added to a 10 mL sealed tube in sequence and reacted at 100° C. for 24 h. After the reaction, the mixture was spin-dried and filtered through a column with dichloromethane:methanol = 10:1 to obtain a yellow solid compound G with a yield of 30%.

[0084] The H-NMR spectrum and C-NMR spectrum of compound G are shown as follows: Figure 3 , Figure 4 The results of the nuclear magnetic resonance analysis of compound G are as follows:

[0085] 1 H NMR (600MHz, CDCl3) δ9.99-9.97(m,1H),7.76(s,4H),7.72(dd,J=6.2,3.3Hz,4H),7.64(t,J=7.8Hz,2H) ,7.48(dt,J=6.3,3.1Hz,4H),7.40(d,J=7.7Hz,4H),5.46(s,2H),2.16-2.11(m,4H),1.12-1.10(m,24H).

[0086] 13 C NMR (150MHz, CDCl3) δ145.4,142.7,142.6,138.7,132.2,131.6,128.0,127.7,127.2,124.7,123.2,45.3,29.0,24.1,23.3.

[0087] S8. Synthesis of Compound H

[0088]

[0089] Under nitrogen protection, imidazole salt compound G (0.27 g, 0.39 mmol), palladium chloride (0.07 g, 0.43 mmol) and 3-chloropyridine (4.0 mL) were added to a 100 mL sealed tube in sequence and reacted at 80°C for 24 h. After the reaction, the solvent was dried and yellow solid compound H was obtained by dichloromethane column chromatography with a yield of 56%.

[0090] The H NMR spectrum and C NMR spectrum of compound H are shown as follows: Figure 1 , Figure 2 The NMR analysis results of compound H are as follows:

[0091] 1H NMR (600MHz, CDCl3) δ8.46 (d, J=2.4Hz, 1H), 8.39 (dd, J=5.7, 1.4Hz, 1H), 7.6 6-7.63(m,9H),7.60(t,J=7.8Hz,2H),7.49(ddd,J=8.2,2.4,1.4Hz,1H),7.44 (d,J=7.8Hz,4H),7.40(dd,J=6.3,3.2Hz,4H),6.99(dd,J=8.2,5.6Hz,1H),5. 44(s,2H),2.87-2.83(m,4H),1.36(d,J=6.5Hz,12H),1.07(d,J=6.8Hz,12H).

[0092] 13 C NMR (150MHz, CDCl3) δ152.0,150.4,149.4,148.0,142.5,140.8,137.2,132.6,1 31.7,131.3,130.5,127.5,126.4,124.3,124.1,122.9,46.7,28.3,27.1,23.9.

[0093] Application Examples

[0094] (1) Ring-opening of geminal difluorocyclopropane and coupling with dimethyl malonate catalyzed by H-catalyzed nitrogen heterocyclic carbene palladium complex

[0095]

[0096] In a glove box, sodium hydride (32.0 mg) and tetrahydrofuran (2.0 mL) were first added to a reaction tube equipped with a magnetic stirrer, and then dimethyl malonate 2 (0.8 mmol) was slowly added. After the reaction mixture was stirred at room temperature for 30 minutes, geminal difluorocyclopropane 1 (0.4 mmol) and Pd-PEPPSI-IHept (2.5 mol%) were added to the reaction tube in sequence. The reaction tube was sealed and removed from the glove box. Next, it was heated and stirred in an oil bath at 100 ° C for 3 hours. After the reaction system was cooled to room temperature, the solvent was removed by rotary evaporation. Finally, the crude product was purified by silica gel column chromatography to obtain pure product 3 (115 mg, 91% yield).

[0097] The H-NMR spectrum, C-NMR spectrum and F-NMR spectrum of compound 3 are shown as follows: Figure 5 , Figure 6 and Figure 7 The NMR analysis results of compound 3 are as follows:

[0098] 1H NMR (600MHz, CDCl3) δ7.87(s,1H),7.80-7.76(m,3H),7.62-7.61(m,1H),7.45-7.43(m,2H),5.75(d,J C-F =39.0Hz,1H),3.81(t,J=7.6Hz,1H),3.77(s,6H),3.02(dd,J C-F =19.1 Hz, J =7.6 Hz, 2H).

[0099] 13 C NMR(150MHz,CDCl3)δ168.7,156.7(d,J C-F =266.2Hz),133.4,132.4,130.5(d,J C-F =2.3Hz),128.0,127.9,127.6,127.5,126.4(d,J C-F =7.6Hz),126.1,126.0,108.6(d,J C-F =7.7Hz),52.9,49.1,32.8(d,J C-F =27.8Hz).

[0100] 19 F NMR(565MHz, CDCl3)δ-104.1(1F).

[0101] (2) The ring-opening of geminal difluorocyclopropanes and the cyclization of enamides to polysubstituted pyrroles catalyzed by the H-catalyzed nitrogen heterocyclic carbene palladium complex

[0102]

[0103] In a glove box, sodium hydride (32.0 mg) and tetrahydrofuran (2.0 mL) were first added to a reaction tube equipped with a magnetic stirrer, and then enamide 4 (0.8 mmol) was slowly added. After the reaction mixture was stirred at room temperature for 30 minutes, geminal difluorocyclopropane 1 (0.4 mmol) and Pd-PEPPSI-IHept (5.0 mol%) were added to the reaction tube in sequence. The reaction tube was sealed and removed from the glove box. Next, it was heated and stirred in an oil bath at 100 ° C for 6 hours. After the reaction system was cooled to room temperature, the solvent was removed by rotary evaporation. Finally, the crude product was purified by silica gel column chromatography to obtain pure product 5 (95 mg, 84% yield).

[0104] The H-NMR spectrum and C-NMR spectrum of compound 5 are shown as follows: Figure 8 and Fig. 9 The NMR analysis results of compound 5 are as follows:

[0105] 1 H NMR (600MHz, CDCl3) δ8.22(br,1H),7.86-7.82(m,4H),7.65-7.63(dd,J=8.3,1.74Hz,1H),7.52-7.49(m,2H),7.48 -7.44(m,1H),7.44-7.40(m,1H),7.37(t,J=7.5Hz,2H),7.20(t,J=7.3Hz,1H),6.74(d,J=2.9Hz,1H),2.53(s,3H).

[0106] 13 C NMR (100MHz, CDCl3) δ134.3,133.8,132.6,131.7,130.4,128.9,127.9,127.7 ,127.6,126.8,126.1,126.0,125.8,125.4,125.1,123.5,122.9,106.5,13.0.

[0107] Therefore, the stereoscopic three-dimensional framework large steric hindered nitrogen heterocyclic carbene palladium complex and the preparation method and application thereof described in the present invention have higher catalytic activity and good stability in the air.

[0108] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that they can still modify or replace the technical solution of the present invention with equivalents, and these modifications or equivalent replacements cannot cause the modified technical solution to deviate from the spirit and scope of the technical solution of the present invention.

Claims

1. A three-dimensional framework large steric hindered nitrogen heterocyclic carbene palladium complex, characterized in that: The general structural formula is: Wherein, R is a hydrogen atom, a C1-C8 alkyl group or an aryl group; R 1 is a hydrogen atom, a methyl group, an isopropyl group, a C1-C12 alkyl group or an aryl group; R 2 is a hydrogen atom, a methyl group, an isopropyl group, a C1-C12 alkyl group or an aryl group; X is a hydrogen atom or a halogen atom.

2. A three-dimensional framework large steric hindered nitrogen heterocyclic carbene palladium complex according to claim 1, characterized in that: The R is a hydrogen atom.

3. A three-dimensional framework large steric hindered nitrogen heterocyclic carbene palladium complex according to claim 1, characterized in that: The R 1 It is isopropyl.

4. A three-dimensional framework large steric hindered nitrogen heterocyclic carbene palladium complex according to claim 1, characterized in that: The R 2 A hydrogen atom.

5. A three-dimensional framework large steric hindered nitrogen heterocyclic carbene palladium complex according to claim 1, characterized in that: The X is a chlorine atom.

6. A method for preparing a three-dimensional framework large steric hindered nitrogen heterocyclic carbene palladium complex according to any one of claims 1 to 5, characterized in that: The following steps are involved: S1, o-phthalaldehyde and 1,4-cyclohexanedione are added to ethanol, potassium hydroxide is added dropwise, and the mixture is reacted under nitrogen protection to prepare compound A; S2. Add the tetrahydrofuran solution of compound A to LiAlH4 under ice-water bath, reflux, and cool to room temperature; add hydrochloric acid solution dropwise under ice-water bath and stir; Extraction, spin drying, washing, and drying to obtain compound B; S3, mixing compound B, vinylene carbonate and o-xylene under nitrogen protection for reaction, and after the reaction, spin-drying and chromatography to obtain compound C; S4, compound C, 1,4-dioxane and NaOH solution were mixed, heated under reflux at 100° C. for 2 h, cooled to room temperature, hydrochloric acid solution was added, and compound D was obtained after extraction, drying and spin drying; S5, cooling dimethyl sulfoxide and dichloromethane to -70°C, adding trifluoroacetic anhydride dropwise, stirring evenly under nitrogen protection to obtain a mixed solution; adding compound D dropwise to the mixed solution, stirring evenly; then adding triethylamine, stirring evenly; heating the reaction to 2°C-10°C, pouring into a hydrochloric acid solution, extracting, drying, filtering, spin drying, and chromatography to obtain compound E; S6. Under nitrogen protection, compound E and 2,6-diisopropylaniline were heated to reflux in the presence of p-toluenesulfonic acid as a catalyst, cooled to room temperature after the reaction, the solvent was evaporated, and recrystallized from anhydrous ethanol to obtain compound F; S7. Under nitrogen protection, compound F reacts with chloromethyl ethyl ether. After the reaction is completed, the mixture is spin-dried and chromatographed to obtain compound G; S8. Under nitrogen protection, compound G, palladium chloride and 3-chloropyridine are mixed for reaction. After the reaction is completed, the solvent is dried by spin drying and a three-dimensional framework large sterically hindered nitrogen heterocyclic carbene palladium complex is obtained after chromatography.

7. The method for preparing a three-dimensional framework large steric hindered nitrogen heterocyclic carbene palladium complex according to claim 6, characterized in that: In S1, the molar ratio of o-phthalaldehyde to 1,4-cyclohexanedione is 1.5-2.5:0.5-1.5, the reaction temperature is 50°C-70°C, and the reaction time is 3h-5h; in S3, the molar ratio of compound B to vinylene carbonate is 0.5-1.5:1.5-2.5, the reaction temperature is 160°C-200°C, and the reaction time is 60h-80h.

8. The method for preparing a three-dimensional framework large steric hindered nitrogen heterocyclic carbene palladium complex according to claim 6, characterized in that: In the S6, the molar ratio of compound E to 2,6-diisopropylaniline is 0.5-1.5:1.5-2.5, the heating temperature is 100°C-130°C, and the reflux time is 20h-30h; in the S7, the molar ratio of compound F to chloromethyl ethyl ether is 1-2:24-28, the reaction temperature is 90°C-110°C, and the reaction time is 20h-30h.

9. The method for preparing a three-dimensional framework large steric hindered nitrogen heterocyclic carbene palladium complex according to claim 6, characterized in that: In the S8, the molar ratio of compound G to palladium chloride is 3-4:4-5, the reaction temperature is 70°C-100°C, and the reaction time is 20h-30h.

10. Use of the stereoscopic three-dimensional framework bulky sterically hindered nitrogen heterocyclic carbene palladium complex according to any one of claims 1 to 5 as a catalyst in the ring-opening reaction of geminal difluorocyclopropane and the coupling reaction of a nucleophilic reagent.

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