Bowl-shaped phosphine ligand as well as preparation method and application thereof

Abstract

The invention discloses a bowl-shaped phosphine ligand as well as a preparation method and application thereof, and relates to the technical field of organic compounds and synthesis, non-planar phosphorus atoms are introduced into a planar conjugated system, a phosphine ligand with a concave structure is innovatively constructed, and spiral chirality is given to the phosphine ligand, so that a novel chiral phosphine ligand is obtained. Bromine atoms introduced in the design provide key sites for subsequent functionalization, coupling with various functional group reagents can be carried out through a classical Suzuki reaction, the modification potential of the ligand is remarkably enhanced, rapid construction of a diversified phosphine ligand library is facilitated, and the phosphine ligand library is used for various catalytic reactions. In addition, rich benzene ring units in the structure of the ligand endow the ligand with strong stacking capacity, so that the ligand shows good application prospects in the application fields of supramolecular self-assembly materials, molecular cages, catalyst loading and the like.

Description

Technical Field

[0001] The present invention relates to the field of organic compounds and synthesis technology, and in particular to a bowl-shaped phosphine ligand, a preparation method and application thereof. Background Art

[0002] Phosphine ligands, an important class of organic ligands, hold broad application prospects in organometallic chemistry, materials science, and catalysis. However, novel bowl-shaped phosphine ligands, with their unique bowl-shaped structure, significant steric hindrance, and helical chirality, offer broad exploration potential. The high steric hindrance of these ligands offers the potential to enhance selectivity in certain catalytic reactions, such as olefin hydroformylation. Furthermore, bowl-shaped phosphine ligands possess helical chirality, making them suitable for novel chiral phosphine ligands. Their excellent modification potential facilitates the rapid expansion of the phosphine ligand library. Furthermore, the design of multiple coordination sites within bowl-shaped phosphine oxide ligands allows for self-assembly with metals to form metal cages, creating chiral cavities with rich host-guest interactions. However, the preparation of these ligands presents numerous challenges. The reported synthetic route requires eight steps to obtain the phosphine oxide ligand backbone, which is tedious and complex. This not only consumes significant time and labor, but also requires a greater variety and quantity of reagents and solvents, increasing synthesis costs and complicating environmental concerns. Therefore, there is an urgent need to develop a more efficient and simple method for preparing bowl-shaped phosphine ligands to meet the growing needs of scientific research and industrial applications. Summary of the Invention

[0003] In view of the above-mentioned deficiencies in the prior art, the present invention provides a bowl-shaped phosphine ligand and a preparation method and application thereof.

[0004] In order to achieve the above-mentioned object of the invention, the technical solution adopted by the present invention is: Provided is a bowl-shaped phosphine ligand, the structural formula of which is shown in Formula I below;

[0005] I Among them, R 1 Phenyl, 3,5-di-tert-butylphenyl, 4-methoxyphenyl, 4-fluorophenyl, 7-indolyl, 3-pyrrolyl, 7-( N -methyl)indolyl, 3-( N -methyl)pyrrolyl, 3-pyridyl, 4-methylphenyl, C1-C6 alkyl; The structural formulas are shown in the following formulas F1 to F11; .

[0006] The present invention also provides a method for preparing the bowl-shaped phosphine ligand, comprising the following steps: A1: Place a bowl-shaped phosphine oxide ligand framework, phenylboronic acid or one of its derivatives, a base, and a palladium catalyst in a container, then add a mixed solvent; heat to 100°C under nitrogen protection, and reflux for 24 hours; the amount ratio of the bowl-shaped phosphine oxide ligand framework, one of its derivatives, the base, the palladium catalyst, and the mixed solvent is 1.4 mmol: 5.6 mmol: 7 mmol: 0.42 mmol: 40 mL; The structure of the bowl-shaped phosphine oxide ligand skeleton is shown in Formula D5 below;

[0007] D5 The mixed solvent is obtained by mixing any two solvents selected from tetrahydrofuran, toluene, ethanol, acetonitrile and 1,4-dioxane with water; Boric acid derivatives are 3,5-di-tert-butylphenylboronic acid, 4-methoxyphenylboronic acid, 4-fluorophenylboronic acid, 7-indoleboric acid, 3-pyrroleboric acid, N -Methylindole-7-boronic acid, N -methyl-3-pyrroleboric acid, 3-pyridineboronic acid, 4-methylphenylboronic acid, C1-C6 alkylboronic acid; A2: After the reaction is completed, cool to room temperature, wash with deionized water and saturated brine, and then dry; A3: Purify the bowl-shaped phosphine oxide ligand by elution using a silica gel column, with the eluent being petroleum ether: ethyl acetate = 3:1; The structure of the bowl-shaped phosphine oxide ligand is shown in Formula II below;

[0008] II A4: Place a bowl-shaped phosphine oxide ligand, tetraisopropyl titanate, 1,1,3,3-tetramethyldisiloxane, and toluene in a container, heat to 100°C under nitrogen protection, and react for 5 hours. After the reaction is completed, cool to room temperature, concentrate by rotary evaporation under reduced pressure to remove the solvent, and then elute and purify using a silica gel column with an eluent of petroleum ether: ethyl acetate = 5:1.

[0009] Furthermore, the volume ratio of water to any two solvents in the mixed solvent is 1-2:28-22:1-2; The base is K2CO3, Cs2CO3, K3PO4, NaOMe, NaOEt, KO t One of Bu or KOH; The palladium catalyst is one of Pd(PPh3)4, Pd(dppf)Cl2, Pd(PPh3)2Cl2, Pd(OAc)2, PdCl2, Pd(CF3COO)2 or Pd(CH3CN)2Cl2.

[0010] The present invention also provides a method for preparing the bowl-shaped phosphine oxide ligand skeleton, comprising the following specific steps: S1: Under a nitrogen atmosphere, 3-fluoroanisole and tetrahydrofuran were mixed, cooled to -78°C, and n-butyl lithium was slowly added dropwise and reacted for 3 hours. After the reaction was complete, phosphorus trichloride was slowly added dropwise at -78°C and reacted for 5 hours. After the reaction was complete, the temperature was returned to room temperature, and the reaction was quenched with methanol, and then purified to obtain product D1; S2: Product D1 was reacted with 30% hydrogen peroxide and tetrahydrofuran at room temperature with stirring for 30 min. After the reaction, the product was extracted with ethyl acetate, washed with saturated brine, and dried to obtain product D2; S3: Product D2 was reacted with iron powder, bromine, and dichloromethane at room temperature with stirring for 22 hours. After the reaction was completed, a saturated sodium sulfite solution was added dropwise until no bubbles were generated. After the addition was completed, the product was extracted with dichloromethane, washed with saturated brine, and dried to obtain product D3; S4: Under a nitrogen atmosphere, product D3 and dichloromethane were placed in a container, cooled to -78°C, and boron tribromide was added dropwise. The temperature was returned to room temperature and stirred for 20 hours. After the reaction was complete, ice water and hydrochloric acid were added dropwise until no obvious changes occurred. After the addition was complete, the product was extracted with dichloromethane, washed with saturated brine, and dried to obtain product D4; S5: Under a nitrogen environment, the product D4 was stirred with potassium tert-butoxide and N,N-dimethylformamide at 140°C for 23 hours. After the reaction was completed, the N,N-dimethylformamide was removed under reduced pressure, and distilled water was added and extracted with chloroform. The mixture was washed with saturated brine and dried to obtain a bowl-shaped phosphine oxide ligand skeleton.

[0011] Furthermore, in step S1, the usage ratio of 3-fluoroanisole, tetrahydrofuran, n-butyl lithium and phosphorus trichloride is 40 mmol: 200 mL: 45 mmol: 10 mmol.

[0012] Furthermore, the purification method of step S1 is specifically as follows: after the methanol quenching reaction is completed, the solvent is removed by rotary evaporation under reduced pressure, and then elution and purification are performed using a silica gel column, and the eluent is petroleum ether: ethyl acetate = 3:1.

[0013] Furthermore, in step S2, the usage ratio of product D1, hydrogen peroxide and tetrahydrofuran is 5 mmol:15 mmol:10 mL.

[0014] Furthermore, in step S3, the usage ratio of product D2, iron powder, bromine and dichloromethane is 5 mmol: 8 mmol: 50 mmol: 50 mL.

[0015] Furthermore, in step S4, hydrochloric acid is a 1M aqueous solution, and the usage ratio of product D3, dichloromethane, boron tribromide, ice water and hydrochloric acid solution is 4 mmol: 50 mL: 40 mmol: 40 mL: 20 mL.

[0016] Furthermore, in step S5, the usage ratio of product D4, potassium tert-butoxide and N,N-dimethylformamide is 2.4 mmol:7.2 mmol:60 mL.

[0017] The present invention also provides an application of the above-mentioned bowl-shaped phosphine ligand, wherein the bowl-shaped phosphine ligand is used as a ligand in any one of an allylic coupling reaction, a hydrogenation reaction, a transfer hydrogenation reaction, a hydrosilylation reaction, a hydroboration reaction, a hydroformylation reaction, a hydrocarboxylation reaction, a Suzuki coupling, a cyclopropanation reaction, an olefin metathesis reaction, a Diels-Alder reaction, a Heck reaction, an Aldol reaction, a Michael addition reaction, an epoxidation reaction, a kinetic resolution, and an [m+n] cycloaddition reaction.

[0018] The present invention also provides a bowl-shaped phosphine oxide ligand, which is prepared by the above steps A1 to A3.

[0019] The present invention also provides an application of the bowl-shaped phosphine oxide ligand, which can self-assemble with metals Pd and Pt to form an enantiomeric octahedral metal cage, and can form a chiral cavity with rich host-guest interactions.

[0020] The beneficial effects of the present invention are: By introducing a non-planar phosphorus atom into a planar  conjugated system, the present invention innovatively constructs a phosphine ligand with a concave structure and imparts helical chirality, thereby obtaining a new class of chiral phosphine ligands. The bromine atom introduced in this design provides a key site for subsequent functionalization, which can be coupled with a variety of functional groups through the classic Suzuki reaction, significantly enhancing the modification potential of the ligand and facilitating the rapid construction of a diverse library of phosphine ligands. In addition, the abundant benzene ring units in the ligand structure give it a strong - stacking ability, making it show important prospects in applications such as supramolecular self-assembly materials and catalyst loading. By designing a bowl-shaped phosphine ligand with a non-planar phosphorus center, helical chirality, and strong - interaction characteristics, the present invention effectively overcomes the limitations of existing phosphine ligands in terms of structural diversity, functional flexibility, - interaction strength, and chirality control, providing new tools and possibilities for fields such as organic synthesis, supramolecular self-assembly, and asymmetric catalysis. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 Schematic diagram of the synthesis route of the bowl-shaped phosphine oxide ligand skeleton in the prior art; Figure 2 Schematic diagram of the synthesis route of the bowl-shaped phosphine oxide ligand skeleton of the present invention; Figure 3 Schematic diagram of the self-assembly principle of the bowl-shaped phosphine oxide ligand E9 used in supramolecular metal-organic cages according to Example 14; Figure 4 Schematic diagram of the synthesis route of the bowl-shaped phosphine ligand of the present invention. DETAILED DESCRIPTION

[0022] The specific embodiments of the present invention are described below to facilitate understanding of the present invention by those skilled in the art. However, it should be clear that the present invention is not limited to the scope of the specific embodiments. For those skilled in the art, as long as various changes are within the spirit and scope of the present invention as defined and determined by the appended claims, these changes are obvious, and all inventions and creations utilizing the concepts of the present invention are protected.

[0023] The sources of the raw materials used in the embodiments of the present invention are shown in Table 1 below; Table 1

[0024] Example 1 Preparation of bowl-shaped phosphine oxide ligand skeleton The specific steps include: S1: A 500 mL dry, three-necked round-bottom flask was fitted with a 50 mL constant-pressure dropping funnel at the center of the flask. Under nitrogen, 3-fluoroanisole (4.60 mL, 40.0 mmol) and 200 mL of dehydrated and deoxygenated tetrahydrofuran were added to the round-bottom flask. The flask was cooled to -78°C and n-butyllithium (18.00 mL, 45.0 mmol, 2.5 Min hexanes) was slowly added dropwise through the constant-pressure dropping funnel. The solution showed no significant color change. The addition rate was controlled to ensure complete addition within 1 hour. The reaction was maintained at -78°C for 3 hours. After the reaction was complete, PCl3 (0.87 mL, 10.0 mmol) was added to the constant-pressure dropping funnel, diluted with 20 mL of tetrahydrofuran, and added dropwise to the flask. The flow rate was controlled to maintain the complete addition within 30 minutes. The solution then changed from colorless to a clear, bright yellow. The reaction was maintained at -78°C for 5 hours. After the reaction was complete, the mixture was returned to room temperature and quenched with methanol. The solvent was removed by rotary evaporation under reduced pressure, and the product was separated and purified by column chromatography. PE / EA = 3 / 1 was used as the eluent in the early stage, and DCM was used as the eluent in the later stage due to the poor solubility of the product. 1.66 g of white solid product D1 was obtained, with a yield of 41%.

[0025] The product D1 was subjected to nuclear magnetic resonance detection, and the results were: 1 HNMR (400MHz, CDCl3, 25℃): δ 7.25~7.18(m, 3H), 6.64~6.54(m, 6H), 3.70(s, 9H)ppm.

[0026] 13 CNMR (100MHz, CDCl3, 25℃): δ 166.1(d, J =4.2Hz), 163.6(d, J =4.1Hz), 163.1~162.2(m), 133.7~125.7(m), 108.2(d, J =26.6Hz), 105.9, 56.2ppm.

[0027] 31 PNMR (162MHz, CDCl3, 25℃): δ-73.22(q, J =8.3Hz)ppm.

[0028] Its structure is shown in Formula III below;

[0029] III S2: Add product D1 (2.11 g, 5 mmol), 30% hydrogen peroxide (1.53 mL, 15 mmol), and 10 mL of tetrahydrofuran to a 50 mL round-bottom flask. Stir at room temperature for 30 min. After completion, extract three times with 50 mL of ethyl acetate. Combine the organic phases and wash three times with 20 mL of saturated brine. Dry the resulting organic phase over anhydrous sodium sulfate, filter, and remove the solvent from the filtrate by rotary evaporation under reduced pressure to obtain 1.94 g of product D2 as a white solid in a 92% yield.

[0030] The product D2 was subjected to nuclear magnetic resonance detection, and the results were: 1 H NMR (400MHz, CDCl3, 25℃): δ 7.38~7.31(m, 3H), 6.67~6.60(m, 6H), 3.62(s, 9H)ppm. 13 C NMR (100MHz, CDCl3, 25°C): δ 165.1, 162.8 (d, J =7.9Hz), 162.6, 133.3(d, J =11.8Hz), 108.4(dd, J =25.6, 6.0Hz), 107.1(dd, J =6.1, 2.6Hz), 56.1ppm.

[0031] 31 P NMR (162MHz, CDCl3, 25°C): δ4.31ppm.

[0032] Its structure is shown in Formula IV below;

[0033] IV S3: Add product D2 (2.11 g, 5 mmol), iron powder (0.45 g, 8 mmol), bromine (2.57 mL, 50 mmol), and 50 mL of dichloromethane to a 250 mL round-bottom flask. Stir at room temperature for 22 h. After completion, add saturated sodium sulfite solution dropwise. Extract three times with 20 mL of dichloromethane. Combine the organic phases and wash three times with 20 mL of saturated brine. Dry the resulting organic phase over anhydrous sodium sulfate, and remove the solvent under reduced pressure to yield 2.97 g of product D3 as a pale yellow solid in a 90% yield.

[0034] The product D3 was subjected to nuclear magnetic resonance detection, and the results were: 1 H NMR (400MHz, CDCl3, 25°C): δ 7.59 (dd, J =8.9, 7.4Hz, 3H), 6.61(dd, J =8.9, 4.9Hz, 3H), 3.67(s, 9H)ppm.

[0035] 13 C NMR (100MHz, CDCl3, 25°C): δ 161.8 (d, J =6.8Hz), 160.4, 157.9, 136.7, 108.6 (dd, J =6.6,3.3Hz),100.6(dd, J =24.8, 8.2Hz), 56.4ppm.

[0036] 31 P NMR (162MHz, CDCl3, 25°C): δ 3.91ppm.

[0037] Its structure is shown in Formula V below;

[0038] V S4: Under nitrogen, a 250-mL round-bottom flask was charged with product D3 (2.64 g, 4 mmol) and 50 mL of dichloromethane. After cooling to -78°C, boron tribromide (3.85 mL, 40 mmol) was added dropwise. The mixture was allowed to warm to room temperature and stirred for 20 h. After completion of the reaction, ice water and 20 mL of 1 M hydrogen chloride were added dropwise. After the addition was complete, the mixture was extracted three times with 50 mL of dichloromethane. The combined organic phases were washed three times with 20 mL of saturated brine. The resulting organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was then evaporated to remove the solvent under reduced pressure to yield 2.25 g of product D4 as an off-white solid in a 91% yield.

[0039] The product D4 was subjected to nuclear magnetic resonance detection, and the results were: 1 H NMR (400MHz, CDCl3, 25°C): δ 9.76 (s, 3H), 7.67 (ddd, J =9.0, 5.1, 2.6Hz, 3H), 6.78(dd, J =9.0, 5.3 Hz, 3H) ppm.

[0040] 31 P NMR (162MHz, CDCl3, 25°C): δ 37.03 (q, J =6.2Hz)ppm.

[0041] Its structure is shown in Formula VI below;

[0042] VI S5: Under nitrogen, a 150-mL round-bottom flask was charged with product D4 (1.48 g, 2.4 mmol), potassium tert-butoxide (0.81 g, 7.2 mmol), and 60 mL of N,N-dimethylformamide. The reaction was stirred at 140°C for 23 h. After completion of the reaction, the N,N-dimethylformamide was removed under reduced pressure. A small amount of distilled water was added, and the mixture was extracted three times with 20 mL of chloroform. The organic phases were combined and washed three times with 20 mL of saturated brine. The resulting organic phases were dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to yield 1.20 g of product D5 as a light brown solid in a 90% yield.

[0043] The product D5 was subjected to nuclear magnetic resonance detection, and the results were: 1 H NMR (400MHz, CDCl3, 25°C): δ 7.76 (d, J =8.8Hz, 3H), 7.26(dd, 3H)ppm.

[0044] 13C NMR (100MHz, CDCl3, 25°C): δ 158.7, 155.7, 137.2, 117.3 (d, J =5.7Hz), 110.9(d, J =106.6Hz), 108.0(d, J =7.1Hz)ppm.

[0045] 31 P NMR (162MHz, CDCl3, 25°C): δ-48.84ppm.

[0046] The results show that the structure of product D5 is shown in the following formula, i.e., a bowl-shaped phosphine oxide ligand skeleton. It can be seen that the synthesis method provided by the present invention can successfully synthesize the bowl-shaped phosphine oxide ligand skeleton D5. The synthesis route is as follows: Figure 1 As shown, Figure 2 Compared with the bowl-shaped phosphine oxide ligand skeleton used in the prior art, the synthesis steps of the present application are reduced from 8 steps to 5 steps, which effectively reduces the synthesis difficulty, reduces the synthesis cost, and reduces the pollution to the environment.

[0047]

[0048] D5 Example 2 Preparation of bowl-shaped phosphine oxide ligand tri(phenyl)phosphine oxide heterohornene The bowl-shaped phosphine oxide ligand skeleton prepared in Example 1 was used with phenylboronic acid to prepare a bowl-shaped phosphine oxide ligand. The specific steps are as follows: A1: In a 100 mL round-bottom flask, add a bowl-shaped phosphine oxide ligand skeleton (0.78 g, 1.4 mmol), phenylboronic acid (0.68 g, 5.6 mmol), potassium phosphate (1.49 g, 7 mmol), and 1,1'-bis(diphenylphosphino)ferrocenedichloridopalladium (Pd(dppf)Cl2) (0.20 g, 0.42 mol). Then, add 28 mL of 1,4-dioxane, 8 mL of ethanol, and 4 mL of water. Heat at 100°C under nitrogen protection and reflux for 24 h. A2: After the reaction is complete, cool to room temperature, dilute with 60 mL of dichloromethane, transfer to a separatory funnel, and wash twice with 100 mL of deionized water and then 100 mL of saturated brine. The resulting organic phases are combined, dried over anhydrous sodium sulfate, filtered, and concentrated by rotary evaporation under reduced pressure to remove the solvent to obtain a crude product.

[0049] A3: The crude product was purified by silica gel chromatography using a mixture of petroleum ether and ethyl acetate in a ratio of 3:1 to obtain 0.58 g of white solid product E1 in a yield of 75%.

[0050] The product was subjected to nuclear magnetic resonance detection, and the results were: 1 H NMR (400MHz, CDCl3, 25℃): δ 7.62~7.56(m, 6H), 7.56~7.47(m, 9H), 7.47~7.41(m, 3H), 7.16(dd, J =8.6, 5.0 Hz, 3H) ppm.

[0051] 13 C NMR (100MHz, CDCl3, 25°C): δ 159.3, 156.1, 135.5, 134.6, 129.5, 128.7, 128.1, 115.6ppm.

[0052] 31 P NMR (162MHz, CDCl3, 25°C): δ-47.18ppm.

[0053] HRMS(ESI) m / z calculated for C 36 H 21 O4P [M+H] + :549.1250, found 549.1254.

[0054] That is, the product structural formula is shown in the following formula VII, that is, the product E1 is tri(phenyl)phosphine oxide heteroangular olefin.

[0055]

[0056] VII Example 3 Preparation of bowl-shaped phosphine oxide ligand tris(3,5-di-tert-butylphenyl)phosphine oxide heterohornene The bowl-shaped phosphine oxide ligand skeleton prepared in Example 1 was used to prepare a bowl-shaped phosphine oxide ligand with 3,5-di-tert-butylphenylboronic acid. The specific steps are as follows: A1: In a 100 mL round-bottom flask, add a bowl-shaped phosphine oxide ligand skeleton (0.78 g, 1.4 mmol), 3,5-di-tert-butylphenylboronic acid (1.31 g, 5.6 mmol), potassium carbonate (1.32 g, 7.0 mmol), and tetrakis(triphenylphosphine)palladium (Pd(PPh3)4) (0.49 g, 0.42 mol). Then, add 22 mL of 1,4-dioxane, 6 mL of tetrahydrofuran, and 2 mL of water. Heat to 105°C under nitrogen and reflux for 24 h. A2: After the reaction is complete, cool to room temperature, dilute with 60 mL of dichloromethane, transfer to a separatory funnel, and wash twice with 100 mL of deionized water and then 100 mL of saturated brine. The resulting organic phases are combined, dried over anhydrous sodium sulfate, filtered, and concentrated by rotary evaporation under reduced pressure to remove the solvent to obtain a crude product.

[0057] A3: The crude product was purified by silica gel chromatography using a mixture of petroleum ether and ethyl acetate in a ratio of 4:1 to obtain 0.84 g of white solid product E2 in a yield of 68%.

[0058] The product E2 was subjected to nuclear magnetic resonance detection, and the results were: 1 H NMR (400 MHz, CDCl3, 25 ℃) δ 7.62 (d, J = 8.6 Hz, 3H), 7.53 (t, J =1.8 Hz, 3H), 7.46 (d, J = 1.8 Hz, 6H), 7.22 (dd, J = 8.6, 4.9 Hz, 3H), 1.44 (s,54H) ppm. 31 P NMR (162 MHz, CDCl3, 25 ℃) δ -47.67 ppm. The structural formula of the product is shown in the following formula VIII, that is, the product E2 is tris(3,5-di-tert-butylphenyl)phosphine oxide heteroangular olefin.

[0059]

[0060] VIII Example 4 Preparation of bowl-shaped phosphine oxide ligand tris(4-methoxyphenyl)phosphine oxide heterohornene The bowl-shaped phosphine oxide ligand skeleton prepared in Example 1 was mixed with 4-methoxyphenylboronic acid to prepare a bowl-shaped phosphine oxide ligand. The specific steps are as follows: A1: Add a bowl-shaped phosphine oxide ligand skeleton (0.78 g, 1.4 mmol), 4-methoxyphenylboronic acid (0.85 g, 5.6 mmol), cesium carbonate (2.28 g, 7 mmol), and 1,1'-bis(diphenylphosphino)ferrocenedichloride (Pd(dppf)Cl2) (0.20 g, 0.42 mol) to a 100 mL round-bottom flask. Then, add 26 mL of toluene, 3 mL of acetonitrile, and 1 mL of water. Heat to 80°C and reflux under nitrogen for 24 h. A2: After the reaction is complete, cool to room temperature, dilute with 60 mL of dichloromethane, transfer to a separatory funnel, and wash twice with 100 mL of deionized water and then 100 mL of saturated brine. The resulting organic phases are combined, dried over anhydrous sodium sulfate, filtered, and concentrated by rotary evaporation under reduced pressure to remove the solvent to obtain a crude product.

[0061] A3: The crude product was purified by silica gel chromatography using a mixture of petroleum ether and ethyl acetate in a ratio of 1:1 to obtain 0.63 g of a white solid product E3 in a yield of 70%.

[0062] The product was subjected to nuclear magnetic resonance detection, and the results were: 1 H NMR (400 MHz, CDCl3, 25 ℃) δ 7.55 – 7.48 (m, 9H), 7.13 (dd, J = 8.6,5.0 Hz, 3H), 7.05 – 7.01 (m, 6H), 3.89 (s, 9H) ppm. 31 P NMR (162 MHz, CDCl3, 25 ℃) δ -46.30 ppm. The structural formula of the product E3 is shown in the following formula IX, that is, the product E3 is tris(4-methoxyphenyl)phosphine oxide heteroangular olefin.

[0063]

[0064] IX Example 5 Preparation of bowl-shaped phosphine oxide ligand tris(4-fluorophenyl)phosphine oxide heterohornene The bowl-shaped phosphine oxide ligand skeleton prepared in Example 1 was mixed with 4-fluorophenylboric acid to prepare a bowl-shaped phosphine oxide ligand. The specific steps are as follows: A1: In a 100 mL round-bottom flask, add a bowl-shaped phosphine oxide ligand skeleton (0.78 g, 1.4 mmol), 4-fluorophenylboronic acid (0.78 g, 5.6 mmol), sodium ethoxide (2.28 g, 7 mmol), and bistriphenylphosphine palladium dichloride (Pd(PPh3)2Cl2) (0.29 g, 0.42 mol). Then, add 28 mL of 1,4-dioxane, 1 mL of tetrahydrofuran, and 1 mL of water. Heat to 90°C under nitrogen and reflux for 24 h. A2: After the reaction is complete, cool to room temperature, dilute with 60 mL of dichloromethane, transfer to a separatory funnel, and wash twice with 100 mL of deionized water and then 100 mL of saturated brine. The resulting organic phases are combined, dried over anhydrous sodium sulfate, filtered, and concentrated by rotary evaporation under reduced pressure to remove the solvent to obtain a crude product.

[0065] A3: The crude product was purified by silica gel chromatography using petroleum ether:ethyl acetate = 5:1 as eluent to obtain 0.59 g of white solid product E4 in a yield of 70%.

[0066] The product E4 was subjected to nuclear magnetic resonance detection, and the results were: 1H NMR (400 MHz,) δ 7.60 – 7.55 (m, 6H), 7.53 (d, J = 8.6 Hz, 3H), 7.24– 7.19 (m, 6H), 7.16 (dd, J = 8.6, 5.0 Hz, 3H) ppm. 31 P NMR (162 MHz, CDCl3, 25 ℃) δ -47.55 ppm. 19 F NMR (376 MHz, CDCl3, 25 ℃) δ -113.7 ppm. The structural formula of the product is shown in the following formula X, that is, the product E4 is tris(4-fluorophenyl)phosphine oxide heteroangular olefin.

[0067]

[0068] X Example 6 Preparation and Functional Verification of Bowl-Shaped Phosphine Ligand F1 Take the bowl-shaped phosphine oxide ligand product E1 prepared in Example 2 and use the following steps: In a dry 25 mL two-necked flask, product E1 (0.55 g, 1.0 mmol), Ti(O i Pr4 (30 μL, 0.1 mmol), 1,1,3,3-tetramethyldisiloxane (TMDS) (220 μL, 1.3 mmol), and 10 mL of toluene were heated to 90°C under nitrogen for 5 h. After cooling to room temperature, the reaction solution was concentrated by rotary evaporation to remove the solvent, yielding a crude product. The crude product was purified by column chromatography (eluent: PE / EA = 5 / 1) to obtain 0.43 g of product F1 as a white solid, with a yield of 80%.

[0069] The product F1 was subjected to nuclear magnetic resonance detection, and the results were: 1 H NMR (400 MHz, CDCl3, 25 ℃) δ 7.59 – 7.55 (m, 6H), 7.48 (t, J = 7.6Hz, 6H), 7.40 (dd, J = 8.3, 6.2 Hz, 3H), 7.32 (dd, J = 8.4, 1.3 Hz, 3H), 7.02(dd, J = 8.4, 1.5 Hz, 3H) ppm. 31P NMR (162 MHz, CDCl3, 25 ℃) δ -130.21 ppm. Its structural formula is shown in the following formula XI:

[0070] XI The product F1 is used as a ligand to modify the rhodium precursor; the mixture of the product F1 and the rhodium precursor is used as a catalyst to catalyze the hydroformylation of olefins. The reaction equation is as follows:

[0071] The specific steps are: 1 mL of 1-hexene, 8.5 mg of bowl-shaped phosphine ligand F1, 2.0 mg of Rh(acac)(CO)2, and 3 mL of toluene were mixed and placed in a high-pressure reactor with magnetic stirring. The air in the reactor was replaced with synthesis gas, which was then introduced at 2 MPa. The synthesis gas was a mixture of CO and H2 in a 1:1 volume ratio. The reaction was stirred at 80°C for 4 hours. After the reaction was completed, the reactor was cooled to room temperature. The solution in the reactor contained toluene and the hydroformylation product. The olefin conversion and aldehyde yield were determined by gas chromatography. The linear aldehyde yield was 58%, and the branched aldehyde yield was 33%.

[0072] The known phosphine ligand L (the known phosphine ligand is derived from the content disclosed in "Synthesis, Structure, and Properties of 4,8,12-Trioxa-12c-phospha-4,8,12,12c-tetrahydrodibenzo-[cd,mn]pyrene, a Molecular Pyroelectric"), the structural formula of the phosphine ligand L is shown below:

[0073] L Comparisons were performed under the same conditions as above (all other reaction conditions remained unchanged, and the ligand dosage was 4.9 mg). The yields of linear aldehydes were 45%, and those of branched aldehydes were 28%. This highlights the advantages of the new bowl-shaped ligand F1 in rhodium-catalyzed olefin hydroformylation.

[0074] Ligand F1 was applied to a palladium-catalyzed allylic coupling reaction to couple (±)-trans-1,3-diphenylallyl acetate with indole in a carbon-carbon coupling reaction with a yield of 83%.

[0075] When ligand F1 was replaced with the known ligand L and the reaction was carried out under the same conditions, the yield was 72%.

[0076] It is proved that the new bowl-shaped ligand F1 has more advantages in palladium-catalyzed reactions.

[0077]

[0078] Ligand F1 was applied to a palladium-catalyzed allylic coupling reaction, and (±)-trans-1,3-diphenylallyl acetate reacted with benzyl alcohol in 85% yield.

[0079]

[0080] Bowl-shaped phosphine ligand F1 was used for the reduction of trifluoromethyl ketones. Under these reaction conditions, various trifluoromethyl ketones substituted with aromatic groups (e.g., p-chlorophenyl, p-bromophenyl, o-tolyl, etc.) were converted to the corresponding alcohols in high yields.

[0081]

[0082] Example 7 Preparation and Functional Verification of Bowl-Shaped Phosphine Ligand F2 Take the bowl-shaped phosphine oxide ligand product E2 prepared in Example 3 and use the following steps: In a dry 25 mL two-necked flask, E2 (0.89 g, 1.0 mmol), Ti(O i Pr4 (30 μL, 0.1 mmol), 1,1,3,3-tetramethyldisiloxane (TMDS) (220 μL, 1.3 mmol), and 10 mL of THF were heated to 70°C under nitrogen for 5 h. After cooling to room temperature, the reaction solution was concentrated by rotary evaporation to remove the solvent, yielding a crude product. The crude product was purified by column chromatography (eluent: PE / EA = 6 / 1) to obtain 0.72 g of product F2 as a white solid, in an 83% yield.

[0083] The product F2 was subjected to nuclear magnetic resonance detection, and the results were: 1 H NMR (400 MHz, CDCl3, 25 ℃) δ 7.59 – 7.55 (m, 6H), 7.48 (t, J = 7.6Hz, 6H), 7.40 (dd, J = 8.3, 6.2 Hz, 3H), 7.32 (dd, J = 8.4, 1.3 Hz, 3H), 7.02(dd, J = 8.4, 1.5 Hz, 3H) ppm. 31 P NMR (162 MHz, CDCl3, 25 ℃) δ -130.21 ppm. Its structural formula is shown in Formula XII below;

[0084] XII Ligand F2 was applied to the palladium-catalyzed Suzuki reaction, and the reaction equation is as follows:

[0085] The activity of the ligand-modified palladium catalyst was tested using chlorobenzene and phenylboronic acid as substrates. After 23 hours of reaction, the yield was 72%.

[0086] Example 8 Preparation and Functional Verification of Bowl-Shaped Phosphine Ligand F3 Take the bowl-shaped phosphine oxide ligand product E3 prepared in Example 4 and use the following steps: In a dry 25 mL two-necked flask, E3 (0.64 g, 1.0 mmol), Ti(O i Pr4 (30 μL, 0.1 mmol), polymethylhydrogensiloxane PHMS (288 μL, 1.3 mmol), and 10 mL of THF were heated to 70°C under nitrogen for 5 h. After cooling to room temperature, the reaction solution was concentrated by rotary evaporation to remove the solvent, yielding a crude product. The crude product was purified by column chromatography (eluent: PE / EA = 4 / 1) to obtain 0.53 g of product F3 as a white solid, with a yield of 85%.

[0087] The product F3 was subjected to nuclear magnetic resonance detection, and the results were: 1 H NMR (400 MHz, CDCl3, 25 ℃) δ 7.45 – 7.40 (m, 9H), 7.11 (dd, J = 7.9,4.8 Hz, 3H), 7.00 – 7.06 (m, 6H), 3.83 (s, 9H) ppm. 31 P NMR (162 MHz, CDCl3, 25 ℃) δ -130.09 ppm. Its structural formula is shown in Formula XII below;

[0088] XII Ligand F3 was applied to a palladium-catalyzed allylic coupling reaction to react (±)-trans-1,3-diphenylallyl acetate with dimethyl malonate in a carbon-carbon coupling reaction with a yield of 80%.

[0089]

[0090] Example 9 Preparation and Functional Verification of Bowl-Shaped Phosphine Ligand F4 Take the bowl-shaped phosphine oxide ligand product E4 prepared in Example 5 and use the following steps: To a dry 25 mL two-necked flask, E4 (0.64 g, 1.0 mmol), Cu(OTf)2 (0.04 g, 0.1 mmol), 1,1,3,3-tetramethyldisiloxane (TMDS) (0.53 mL, 3 mmol), and 10 mL of toluene were added. The mixture was heated to 100°C under nitrogen for 3 h. After cooling to room temperature, the solvent was concentrated by rotary evaporation to obtain a crude product. The crude product was purified by column chromatography (eluent: PE / EA = 7 / 1) to obtain 0.52 g of F4 as a white solid, in an 89% yield.

[0091] The product F4 was subjected to nuclear magnetic resonance detection, and the results were: 1 H NMR (400 MHz,) δ 7.68 – 7.52 (m, 6H), 7.49 (d, J = 8.1 Hz, 3H), 7.29– 7.17 (m, 6H), 7.12 (dd, J = 7.2, 4.8 Hz, 3H) ppm. 31 P NMR (162 MHz, CDCl3, 25 ℃) δ -131.45 ppm. Its structural formula is shown in Formula XIII below;

[0092] XIII Ligand F4 was applied to a palladium-catalyzed allylic coupling reaction to carbon-nitrogen coupling of (±)-trans-1,3-diphenylallyl acetate with morpholine in 81% yield.

[0093]

[0094] Example 10 Functional Verification of Bowl-Shaped Phosphine Ligand F5 Ligand F5 was applied to a palladium-catalyzed allylic coupling reaction to carbon-nitrogen coupling of (±)-trans-1,3-diphenylallyl acetate with morpholine in 85% yield.

[0095]

[0096] Example 11 Functional Verification of Bowl-Shaped Phosphine Ligand F6 Ligand F6 was applied to a palladium-catalyzed allylic coupling reaction to carbon-nitrogen coupling of (±)-trans-1,3-diphenylallyl acetate with morpholine in 89% yield.

[0097]

[0098] Example 12 Preparation and Functional Verification of Bowl-Shaped Phosphine Ligand F7 Ligand F7 was applied to the palladium-catalyzed allylic coupling reaction to convert (±)- Trans-1,3-diphenylallyl acetate was reacted with morpholine in a carbon-nitrogen coupling reaction with a yield of 86%.

[0099]

[0100] Example 13 Functional Verification of Bowl-Shaped Phosphine Ligand F8 Ligand F8 was applied to a palladium-catalyzed allylic coupling reaction to react (±)-trans-1,3-diphenylallyl acetate with dimethyl malonate in a carbon-carbon coupling reaction with a yield of 88%.

[0101]

[0102] Example 14 Synthesis and Application of Pyridine-Substituted Bowl-Shaped Phosphine Oxide Ligands The bowl-shaped phosphine oxide ligand skeleton prepared in Example 1 and 3-pyridylboronic acid pinacol ester were used to prepare a pyridine-substituted bowl-shaped phosphine oxide ligand. The specific steps are as follows: A1: In a 100 mL round-bottom flask, add a bowl-shaped phosphine oxide ligand framework (0.58 g, 1 mmol), 3-pyridineboronic acid pinacol ester (0.55 g, 4.5 mmol), potassium phosphate (1.9 g, 9 mmol), and 1,1'-bis(diphenylphosphino)ferrocenedichloridopalladium (Pd(dppf)Cl2) (0.33 g, 0.45 mol). Then, add 28 mL of 1,4-dioxane, 8 mL of ethanol, and 4 mL of water. Heat to 100°C under nitrogen and reflux for 24 h. A2: After the reaction is complete, cool to room temperature, dilute with 60 mL of dichloromethane, transfer to a separatory funnel, and wash twice with 100 mL of deionized water and then 100 mL of saturated brine. The resulting organic phases are combined, dried over anhydrous sodium sulfate, filtered, and concentrated by rotary evaporation under reduced pressure to remove the solvent to obtain a crude product.

[0103] A3: The crude product was purified by silica gel chromatography using a dichloromethane:methanol ratio of 20:1 as the eluent to obtain 0.28 g of product E9.

[0104] The product E9 was subjected to nuclear magnetic resonance detection, and the results were: 1 H NMR (400MHz, CDCl3, 25℃): δ 8.81 (d, J = 2.0 Hz, 3H), 8.68 (d,J = 4.9,3H), 7.95 (d, J = 7.9, 3H), 7.56 (d, J = 8.6 Hz, 3H), 7.47 (dd, J = 7.9, 4.9 Hz,3H), 7.22 (dd, J = 8.6, 4.8 Hz, 3H)ppm.

[0105] 13 C NMR (100MHz, CDCl3, 25°C): δ 159.5, 156.1, 149.9, 149.3, 136.7, 134.5, 131.0, 126.0, 123.5, 115.9, 110.9, 109.8ppm.

[0106] 31 P NMR (162MHz, CDCl3, 25°C): δ-48.65ppm.

[0107] HRMS(ESI) m / z calculated for C 33 H 18 N3O4P [M+H] + :552.1108, found548.1111.

[0108] According to the NMR results, the structural formula of product E9 is as follows:

[0109] The reaction equation of the bowl-shaped phosphine oxide ligand E9 is as follows:

[0110] The pyridine-substituted bowl-shaped phosphine oxide ligand E9 was applied in the self-assembly of supramolecular metal-organic cages: Ligand E9 (0.18 mmol, 0.10) and tetrakis(acetonitrile)palladium(II)tetrafluoroborate (0.18 mmol, 0.64 g) were added to a 25 mL round-bottom flask, and 5 mL of DMSO was added to the flask, and the mixture was heated at 80° C. for 24 h.

[0111] After the reaction was completed, the mixture was filtered, and 40 mL of ethyl acetate was added. The precipitate was collected by centrifugation and washed with excess ether to obtain 0.11 mg of a gray solid product with a yield of 73%.

[0112] The product was subjected to nuclear magnetic resonance detection, and the results were: 1H NMR (400MHz, CD3CN, 25°C): δ 10.02 (d, J = 2.0 Hz, 3H), 9.52 (d, J = 5.5Hz, 3H), 8.02 (d, J = 7.9, 3H), 7.85 (dd, J = 7.9,5.5 Hz, 3H), 7.61(d, J = 8.5 Hz,3H), 6.54 (dd, J = 8.5, 4.7 Hz, 3H) ppm.

[0113] 13 C NMR (100MHz, CD3CN, 25°C): δ 159.4, 156.0, 152.5, 150.4, 140.2, 136.5, 134.5, 128.0, 124.2, 117.2, 111.4, 110.3 ppm.

[0114] 31 P NMR (162MHz, CD3CN, 25°C): δ-41.63 ppm.

[0115] According to the NMR results, the bowl-shaped phosphine oxide ligand E9 can be assembled into a supramolecular metal organic cage. The assembly principle is as follows: Figure 3 shown.

[0116] In summary, bowl-shaped phosphine ligands The synthetic route is as follows Figure 4 shown.

Claims

1. A bowl-shaped phosphine ligand, characterized in that Its structural formula is shown in Formula I below; I Among them, R 1 Phenyl, 3,5-di-tert-butylphenyl, 4-methoxyphenyl, 4-fluorophenyl, 7-indolyl, 3-pyrrolyl, 7-( N -methyl)indolyl, 3-( N -methyl)pyrrolyl, 3-pyridyl, 4-methylphenyl, C1-C6 alkyl; The structural formulas are shown in the following formulas F1 to F11; 。 2. A method for preparing the bowl-shaped phosphine ligand according to claim 1, characterized in that: The steps include: A1: Place a bowl-shaped phosphine oxide ligand framework, phenylboronic acid or one of its derivatives, a base, and a palladium catalyst in a container, then add a mixed solvent; heat to 100°C under nitrogen protection, and reflux for 24 hours; the amount ratio of the bowl-shaped phosphine oxide ligand framework, one of its derivatives, the base, the palladium catalyst, and the mixed solvent is 1.4 mmol: 5.6 mmol: 7 mmol: 0.42 mmol: 40 mL; The structure of the bowl-shaped phosphine oxide ligand skeleton is shown in Formula D5 below; D5 The mixed solvent is obtained by mixing any two solvents selected from tetrahydrofuran, toluene, ethanol, acetonitrile and 1,4-dioxane with water; Boric acid derivatives are 3,5-di-tert-butylphenylboronic acid, 4-methoxyphenylboronic acid, 4-fluorophenylboronic acid, 7-indoleboric acid, 3-pyrroleboric acid, N -Methylindole-7-boronic acid, N -Methyl-3-pyrroleboric acid, 3-pyridineboronic acid, 4-methylphenylboronic acid, C1-C6 alkylboronic acid; A2: After the reaction is completed, cool to room temperature, wash with deionized water and saturated brine, and then dry; A3: Purify the bowl-shaped phosphine oxide ligand by elution using a silica gel column, with the eluent being petroleum ether: ethyl acetate = 3:1; The structure of the bowl-shaped phosphine oxide ligand is shown in Formula II below; II A4: Place a bowl-shaped phosphine oxide ligand, tetraisopropyl titanate, 1,1,3,3-tetramethyldisiloxane (TMDS), and toluene in a container, heat to 100°C under nitrogen protection, and react for 5 hours. After the reaction is completed, cool to room temperature, concentrate by rotary evaporation under reduced pressure to remove the solvent, and then elute and purify using a silica gel column to obtain a bowl-shaped phosphine ligand. The eluent is petroleum ether: ethyl acetate = 5:

1.

3. The preparation method according to claim 2, characterized in that The volume ratio of water to any two solvents in the mixed solvent is 1-2:28-22:1-2; The base is K2CO3, Cs2CO3, K3PO4, NaOMe, NaOEt, KO t One of Bu or KOH; The palladium catalyst is one of Pd(PPh3)4, Pd(dppf)Cl2, Pd(PPh3)2Cl2, Pd(OAc)2, PdCl2, Pd(CF3COO)2 or Pd(CH3CN)2Cl2.

4. A method for preparing the bowl-shaped phosphine oxide ligand skeleton according to claim 2, characterized in that: The specific steps include: S1: Under a nitrogen environment, 3-fluoroanisole and tetrahydrofuran were mixed, cooled to -78°C, and n-butyl lithium was slowly added dropwise and reacted for 3 hours. After the reaction was completed, phosphorus trichloride was slowly added dropwise at -78°C and reacted for 5 hours. After the reaction was completed and the temperature was returned to room temperature, methanol was used to quench the reaction. After the solvent was removed by rotary evaporation under reduced pressure, the product was eluted and purified by silica gel chromatography with an eluent of petroleum ether:ethyl acetate = 3:1 to obtain product D1; wherein the amount ratio of 3-fluoroanisole, tetrahydrofuran, n-butyl lithium and phosphorus trichloride was 40 mmol:200 mL:45 mmol:10 mmol; S2: Product D1 was reacted with 30% hydrogen peroxide and tetrahydrofuran at room temperature with stirring for 30 min. After the reaction, the product was extracted with ethyl acetate, washed with saturated brine, and dried to obtain product D2. The ratio of product D1, hydrogen peroxide, and tetrahydrofuran was 5 mmol:15 mmol:10 mL. S3: Product D2 was reacted with iron powder, bromine, and dichloromethane under stirring at room temperature for 22 hours. After the reaction was completed, a saturated sodium sulfite solution was added dropwise until no bubbles were generated. After the addition was completed, the solution was extracted with dichloromethane, washed with saturated brine, and dried to obtain product D3. The ratio of product D2, iron powder, bromine, and dichloromethane was 5 mmol: 8 mmol: 50 mmol: 50 mL. S4: Under a nitrogen environment, product D3 and dichloromethane were placed in a container, cooled to -78°C, and boron tribromide was added dropwise. The temperature was returned to room temperature and stirred for 20 hours. After the reaction was completed, ice water and hydrochloric acid were added dropwise until no obvious changes occurred. After the addition was completed, dichloromethane was used for extraction, and the mixture was washed with saturated brine. After drying, the product D4 was obtained. The hydrochloric acid solution was a 1M aqueous solution, and the dosage ratio of product D3, dichloromethane, boron tribromide, ice water and hydrochloric acid solution was 4mmol:50mL:40mmol:40mL:20mL; S5: Under a nitrogen environment, the product D4 was reacted with potassium tert-butoxide and N,N-dimethylformamide at 140°C with stirring for 23 hours. After the reaction was completed, the N,N-dimethylformamide was removed under reduced pressure, and distilled water was added, followed by extraction with chloroform, washing with saturated brine, and drying to obtain a bowl-shaped phosphine oxide ligand skeleton D5; wherein the amount ratio of the product D4, potassium tert-butoxide and N,N-dimethylformamide was 2.4 mmol: 7.2 mmol: 60 mL.

5. The use of the bowl-shaped phosphine ligand according to claim 1, characterized in that: Bowl-shaped phosphine ligands can be used as ligands in any of the following reactions: allylic coupling reaction, hydrogenation reaction, transfer hydrogenation reaction, hydrosilylation reaction, hydroboration reaction, hydroformylation reaction, hydrocarboxylation reaction, Suzuki coupling, cyclopropanation reaction, olefin metathesis reaction, Diels-Alder reaction, Heck reaction, Aldol reaction, Michael addition reaction, epoxidation reaction, kinetic resolution and [m+n] cycloaddition reaction.

6. A bowl-shaped phosphine oxide ligand, characterized in that The product is prepared by steps A1 to A3 according to claim 2.

7. The use of the bowl-shaped phosphine oxide ligand according to claim 6, characterized in that: Bowl-shaped phosphine oxide ligands can self-assemble with metals Pd and Pt to form enantiomeric octahedral metal cages, which can form chiral cavities with rich host-guest interactions.

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