Supported multidentate P, N, N-iridium catalyst as well as preparation method and application thereof

Abstract

The invention discloses a supported polydentate P, N, N-iridium catalyst as well as a preparation method and application thereof. The preparation method comprises the following steps: polymerizing a P, N, N-tridentate organic ligand and a comonomer, and then complexing with a metal iridium precursor [Ir (COD) Cl] 2 to obtain the supported iridium catalyst as shown in a formula I or a formula II. The supported iridium catalyst provided by the invention can be used for preparing the catalyst with high yield (up to 99%) and high enantioselectivity (up to gt; according to the present invention, various carbonyl compounds can be subjected to catalytic hydrogenation reduction with high diastereoselectivity (up to 99: 1) and high diastereoselectivity (up to 99: 1), and the catalyst can be used in the continuous flow synthesis of the bepotastine besilate key intermediate, can maintain the high catalytic activity and no metal leaching within the long time, can reduce the catalyst cost, can reduce the pollution, can optimize the traditional kettle hydrogenation process, and can be used for the industrial production of the bepotastine besilate key intermediate. Therefore, the device is safer and more automatic, and meets the requirements of industrial production.

Description

Technical Field

[0001] The invention belongs to the technical field of catalyst preparation, and specifically relates to a supported multi-dentate P, N, N-iridium catalyst and a preparation method and application thereof. Background Art

[0002] Asymmetric catalytic hydrogenation has the advantages of good atom economy and high stereoselectivity, and is one of the most efficient methods for obtaining chiral compounds. However, in actual industrial production applications, many processes still require the use of precious metals, which makes the catalyst cost high. In order to develop a greener and more economical asymmetric hydrogenation process, supported catalysts and their corresponding continuous flow processes have received a lot of attention in the past decade.

[0003] Meanwhile, the Kobayashi group (J.Am.Chem.Soc.2020,142,16546-16551; Adv.Synth.Catal.2024,366,757-761), the Cui Yong group (J.Am.Chem.Soc.2023,145,6100-6111), and the Yang Qihua group (ACS Catal.2019,10,1783-1791) have developed several highly efficient catalysts for asymmetric hydrogenation. However, the development of heterogeneous asymmetric hydrogenation catalysts still has the following problems: decreased catalytic activity and enantioselectivity after loading, complicated modification steps, metal loss and agglomeration. In addition, the total TON of the currently developed supported catalysts is still low, which is difficult to meet the needs of industrial production; and some catalysts have not been reported in continuous flow systems. These problems limit the industrial application potential of heterogeneous catalysts.

[0004] Research on heterogeneous catalysts in asymmetric hydrogenation mainly focuses on monodentate and bidentate ligands, while the immobilization of tridentate ligands has not yet been developed; compared with the former two, tridentate ligands have deeper chiral pockets and stronger chelation to metals, which provides better guarantees for the reactivity, selectivity and stability of the catalyst. In 2018, Zhong Weihui's research group at Zhejiang University of Technology developed a P,N,N-tridentate ligand f-diaphos, which is easy to modify and has a simple synthetic route. Under the synergistic catalysis of iridium, it can efficiently perform asymmetric hydrogenation reduction on carbonyl compounds, and has broad prospects for industrial application (J.Org.Chem.2018,83,10749-10761). Summary of the invention

[0005] In view of the problems existing in the prior art, the purpose of the present invention is to provide a supported multidentate P, N, N-iridium catalyst and its preparation method and application. The catalyst combines the strong chelating ability of tridentate ligands to metals and deeper chiral pockets, the characteristics of f-diaphos that are easy to modify and have excellent catalytic effects, and the advantages of heterogeneous catalysts that are easy to recycle and apply. The catalyst has a simple synthesis step, and exhibits catalytic activity and selectivity comparable to homogeneous catalysts in the asymmetric hydrogenation reaction of various carbonyl compounds, and has been successfully applied to continuous flow asymmetric hydrogenation reactions.

[0006] The specific technical solutions are as follows:

[0007] A supported multidentate P,N,N-iridium catalyst, the structure of which is shown below:

[0008]

[0009] The supported iridium catalyst of Formula I or Formula II of the present invention is prepared by polymerizing ligand L1 or L2 with divinylbenzene (DVB) in different proportions, and then coordinating with a metal iridium salt. In the general formula, n is selected from an integer of 1 to 100.

[0010] The method for preparing a supported multidentate P, N, N-iridium catalyst comprises the following steps:

[0011] (1) In the presence of potassium carbonate, palladium acetate and XPhos, intermediate C1 or C2 is subjected to a Suzuki coupling reaction with 4-vinylbenzeneboronic acid to obtain intermediate C1' or C2', followed by a Boc protecting group removal reaction under the catalysis of trifluoroacetic acid to obtain ligand precursor D1 or D2;

[0012] (2) condensing the ligand precursor D1 or D2 with AcO-PPFA to prepare a P,N,N-tridentate organic ligand L1 or L2;

[0013] (3) The organic ligand L1 or L2 is copolymerized with divinylbenzene (DVB) in the presence of azobisisobutyronitrile (AIBN) as a free radical initiator to obtain a porous organic polymer-supported ligand POP@L1-n or POP@L2-n (L represents the type of ligand, and n represents the equivalent of DVB);

[0014] (4) Porous organic polymer-supported ligands POP@L1-n or POP@L2-n and [Ir(COD)Cl] 2 A coordination reaction is carried out to obtain a supported iridium catalyst Ir-POP@L1-n as shown in formula I or a supported iridium catalyst Ir-POP@L2-n as shown in formula II, and the reaction formula is as follows:.

[0015]

[0016] The molar ratio of the intermediate C1 or C2 in step (1) to palladium acetate, XPhos, 4-vinylbenzene boronic acid and potassium carbonate is 1:0.005-0.01:0.01-0.02:0.1-2.5:1-2.5, and the reaction is carried out in a mixed solution of toluene, ethanol and water, the reaction temperature is 60-100°C, and the reaction time is 0.5-5h; the molar ratio of trifluoroacetic acid to the intermediate obtained by the reaction is 5:1, and the reaction is carried out in a dichloromethane solution, the reaction temperature is 0-40°C, and the reaction time is 1-24h.

[0017] The molar ratio of the intermediate D1 or D2 to AcO-PPFA in step (2) is 1:0.5-1.5, and the reaction is carried out in a methanol solution at a reaction temperature of 40-70° C. and a reaction time of 0.5-12 h.

[0018] The molar ratio of the organic ligand L1 or L2 to AIBN and DVB in step (3) is 1:0.01-1:1-100, preferably 1:0.2-0.5:20-60. The reaction is carried out in tetrahydrofuran solution at a reaction temperature of 60-120°C and a reaction time of 8-48h.

[0019] [Ir(COD)Cl] in step (4) 2 The molar ratio of the supported organic ligand POP@L1-n or POP@L2-n to the theoretical ligand content is 1:2.0-2.5, and the reaction is carried out in an isopropanol solution at a reaction temperature of 20-70°C for a reaction time of 0.5-5h. The theoretical ligand content in the supported ligand is calculated as follows: ligand mass in step (4) / (ligand mass+DVB mass).

[0020] Furthermore, the present invention also provides the use of the supported iridium catalyst prepared by the above technical solution in the asymmetric hydrogenation reaction of carbonyl compounds. The application method is: the carbonyl compound is dissolved in an organic solvent, the supported iridium catalyst is added, and a base additive is added at a reaction temperature of 0 to 80°C, and a high enantioselective and high diastereoselective alcohol compound is prepared through reaction and purification.

[0021] Furthermore, the hydrogen pressure is 0.1-4 MPa, the alkali additive used is one of sodium acetate, sodium hydroxide, and lithium tert-butoxide; the feeding molar ratio of the carbonyl compound, the alkali additive, and the supported iridium catalyst is 1:0.005-0.1:0.001-0.05, the organic solvent is one of isopropanol, toluene, and ethyl acetate; the mass ratio of the substrate used to the supported iridium catalyst is 1:0.001-0.05.

[0022] Furthermore, the application of the supported multidentate P, N, N-iridium catalyst in the continuous asymmetric hydrogenation reaction of carbonyl compounds is as follows: the catalyst is fully ground in a mortar, then mixed with lithium tert-butoxide and quartz sand, and loaded into a fixed bed reactor. In one channel is a solution A prepared by dissolving the carbonyl compound in an organic solvent, the concentration of the carbonyl compound in solution A is 0.01-1 mol / L, and it is fed through a feed pump, and the flow rate is set to 0.01-1 mL / min; hydrogen is introduced into another channel, the pressure of hydrogen is 0.1-5 MPa, and the flow rate is 1-100 mL / min. The reaction temperature is 0-80°C, the residence time of the reaction system is 2-60 min, and a highly enantioselective alcohol compound is prepared through reaction and purification.

[0023] By adopting the above technology, compared with the prior art, the present invention has the following characteristics:

[0024] The present invention provides a method for preparing a supported iridium catalyst, which exhibits the same yield (up to 99%), enantioselectivity (ee value up to> 99%) and diastereoselectivity (dr value up to 99:1) as homogeneous catalysts in the asymmetric hydrogenation reaction of carbonyl compounds. It can be applied to the continuous flow asymmetric hydrogenation of bepotastine besylate intermediates, maintain high catalytic activity for a long time, and obtain enantiopure drug intermediates with a higher turnover number (TON) under conditions of lower hydrogen pressure than homogeneous phase. The content of metal Ir in the product is lower than the detection limit of ICP-OES, showing the strong chelating ability of the ligand to the metal, inhibiting the loss of the metal, and solving the problem of metal residue in the drug intermediate. The insertion of the benzene ring makes the catalytic center away from the supporting skeleton, thereby reducing the adverse effect of the supporting skeleton on the catalytic center. These factors all show that the catalyst is very suitable for industrial application. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 The results of scanning electron microscopy characterization (100nm / 500nm) of the supported iridium catalyst Ir-POP@L2-20;

[0026] Figure 2 Results of transmission electron microscopy characterization (50nm), X-ray energy spectrum (100nm) and corresponding element characterization (100nm) of supported iridium catalyst Ir-POP@L2-20;

[0027] Figure 3 This is the nitrogen adsorption-desorption curve of the supported iridium catalyst Ir-POP@L2-20;

[0028] Figure 4 This is the pore size diagram of the supported iridium catalyst Ir-POP@L2-20;

[0029] Figure 5 This is the thermogravimetric analysis diagram of the supported iridium catalyst Ir-POP@L2-20. DETAILED DESCRIPTION

[0030] The content of the present invention is further described in detail below through specific embodiments and drawings, but the protection scope of the present invention is not limited thereto.

[0031] Example 1: Preparation of supported iridium catalyst POP@L1-20

[0032]

[0033] (1) C1 (4.61 g, 10 mmol), 4-vinylbenzeneboronic acid (1.78 g, 12 mmol), palladium acetate (22.4 mg, 0.1 mmol), XPhos (95.3 mg, 0.2 mmol), K 2 CO 3 (2.76 g, 20 mmol) and 100 mL of a mixed solvent of toluene: water: ethanol = 3:1:1, and refluxed for 2 h under an argon atmosphere. After the conversion of the raw materials was completed, the solvent was removed under reduced pressure, 30 mL of water was added, and the mixture was extracted three times with dichloromethane (30 mL). TFA (3.8 mL, 50 mmol) was added to the separated organic phase at 25 °C, and the reaction was continued for 12 h. 20 mL of saturated NaHCO was added 3 The organic phase was quenched, separated, dried, and purified by column chromatography (dichloromethane: methanol = 30: 1) to obtain a white solid D1 (2.23 g, yield 58%);

[0034] (2) Add D1 (1.92 g, 5 mmol) and AcO-PPFA (2.56 g, 5.5 mmol) to a 50 mL single-necked flask. Dissolve in 10 mL of methanol and reflux for 5 h under an argon atmosphere. After the reaction is complete, remove the solvent under reduced pressure and purify by column chromatography (n-hexane: ethyl acetate = 5:1) to obtain an orange-yellow solid L1 (2.66 g, yield 67%).

[0035] Structural characterization of L1: Orangesolid; 1 H NMR (600 MHz, CDCl 3)δ7.60(d,J=7.8Hz,2H),7.51(d,J=7.8Hz,2H),7.47(t,J=7.8Hz,2H),7.38-7.33(m,5H),7.11(t,J=7.2Hz,1H),7.00(p,J=7.2Hz,4H),6.78(dd,J=17.4,10.8Hz,1H),6.01(s,1H),5.84(d,J=18.0Hz,1H),5.33(d,J=10.8Hz,1H),4.52(s,1H),4.34(s,1H),4.08(s,5H),4.07-4.05(m,1H),3.68(s,1H),2.75(s,6H),2.25(d,J=6.6Hz,1H),2.12(t,J=10.8Hz,1H),1.92(d,J=13.2Hz,1H),1.81(t,J=11.4Hz,1H),1.50(d,J=13.8Hz,1H),1.43(d,J=6.0Hz,4H),1.13(q,J=12.0Hz,1H),1.02(q,J=13.2Hz,1H),0.82(q,J=7.2Hz,1H),-0.46(q,J=12.6Hz,1H). 13 CNMR(150MHz,CDCl3)δ143.0,140.0(d,J=11.1Hz),139.6,137.9(d,J=140.6Hz),136.3(d,J=9.0Hz),136.1,135.8,135.0(d,J=21.0Hz),132.5(d,J=19.2Hz),129.3,129.1,128.2(d,J=6.3),128.1,128.0,127.2,126.7,114.5,97.8(d,J=23.1Hz),74.0(d,J=6.0Hz),71.2(d,J=4.2Hz),69.7,69.2(d,J=3.8Hz),69.1,57.8,56.8,46.0(d,J=10.0Hz),32.3,29.6,24.8,23.9,23.5,19.7. 31 P NMR(162MHz,CDCl 3 )δ-24.71(s).HRMS(ESI)calcdforC 46 H 50 FeN 2 O 2 PS[M+H] + :781.2675,found:781.2677.

[0036] (3) DVB (780 mg, 6 mmol) and AIBN (26 mg) were added to L1 (237.3 mg, 0.3 mmol), dissolved in 21 mL of tetrahydrofuran, stirred at room temperature for 0.5 h, then heated to 80 °C and refluxed for 24 h. After filtration, the supported organic ligand POP@L1-20 (748.7 mg, yield 73.6%) was obtained;

[0037] (4) Add POP@L1-20 (500 mg) and [Ir(COD)Cl] into a 50 mL single-necked flask. 2 (46.6 mg, 0.069 mmol), dissolved in 10 mL of isopropanol, reacted at 40 ° C for 3 h for coordination, filtered after the reaction was completed, and washed with dichloromethane to obtain an orange powdered supported iridium catalyst Ir-POP@L1-20 (504.5 mg, yield 92.3%).

[0038] Example 2: Preparation of supported iridium catalyst POP@L2-20

[0039]

[0040] (1) C2 (4.61 g, 10 mmol), 4-vinylbenzeneboronic acid (1.78 g, 12 mmol), palladium acetate (22.4 mg, 0.1 mmol), XPhos (95.3 mg, 0.2 mmol), K 2 CO 3 (2.76 g, 20 mmol) and 100 mL of a mixed solvent of toluene: water: ethanol = 3:1:1, and refluxed for 2 h under an argon atmosphere. After the conversion of the raw materials was completed, the solvent was removed, 30 mL of water was added, and the mixture was extracted three times with dichloromethane (30 mL). TFA (3.8 mL, 50 mmol) was added to the obtained organic phase at 25 °C, and the reaction was continued for 12 h. 20 mL of saturated NaHCO was added 3 The organic phase was separated and dried and then purified by column chromatography (dichloromethane:methanol=30:1) to obtain a white solid D2 (2.30 g, yield 60%);

[0041] (2) Add D2 (1.92 g, 5 mmol) and AcO-PPFA (2.56 g, 5.5 mmol) to a 50 mL single-necked flask. Dissolve in 10 mL of methanol and reflux for 5 h under an argon atmosphere. After the reaction is complete, remove the solvent under reduced pressure and purify by column chromatography (n-hexane: ethyl acetate = 5:1) to obtain an orange-yellow solid L2 (2.69 g, yield 68%).

[0042] Structural characterization of L2: Orangesolid; 1H NMR(600MHz,CDCl 3 )δ7.60(J=7.8Hz,2H),7.50(d,J=8.4Hz,2H),7.47(td,J=7.8,1.8Hz,2H),7.37-7.32(m,5H),7.12-7.09(m,1H),7.03-6.98(m,4H),6.78(dd,J=17.4,10.8Hz,1H),6.00(s,1H),5.84(d,J=17.4Hz,1H),5.32(d,J=10.8Hz,1H),4.53(s,1H),4.34(s,1H),4.08(s,1H),4.07-4.05(m,1H),3.69(s,1H),2.75(s,6H),2.26(d,J=12.6Hz,1H),2.12(t,J=10.8Hz,1H),1.92(dd,J=15.0,4.2Hz,1H),1.84-1.80(m,1H),1.52(d,J=13.8Hz,1H),1.44(d,J=6.0Hz,4H),1.17-1.10(m,1H),1.05-0.97(m,1H),0.86-0.78(m,1H),-0.44(q,J=12.6Hz,1H). 13 C NMR(150MHz,CDCl3)δ143.0,140.0(d,J=11.0Hz),139.6,138.4,137.5,136.4(d,J=9.2Hz),136.2,135.8,134.9(d,J=21.0Hz),132.5(d,J=19.2Hz),129.3,129.1,128.2(d,J=6.6Hz),128.1,128.0,127.2,126.7,114.5,97.8(d,J=23.0Hz),74.0(d,J=6.2Hz),71.2(d,J=4.0Hz),69.7,69.2(d,J=3.8Hz),69.1,57.8,56.8,46.0(d,J=9.8Hz),32.3,29.6,24.8,24.0,23.5,19.7. 31 P NMR(162MHz,CDCl 3 )δ-24.73(s).HRMS(ESI)calcd for C 46 H 50 FeN 2 O 2 PS[M+H] + :781.2675,found:781.2678.

[0043] (3) DVB (780 mg, 6 mmol) and AIBN (26 mg) were added to L2 (237.3 mg, 0.3 mmol), dissolved in 21 mL of tetrahydrofuran, stirred at room temperature for 0.5 h, then heated to 80 °C and refluxed for 24 h. After filtration, the supported organic ligand POP@L2-20 (709.9 mg, yield 71%) was obtained;

[0044] (4) Add POP@L2-20 (570 mg) and [Ir(COD)Cl] into a 50 mL single-necked flask. 2 (53.1 mg, 0.079 mmol), dissolved in 10 mL of isopropanol, reacted at 40 ° C for 3 h for coordination, filtered after the reaction was completed, and washed with dichloromethane to obtain an orange powdered supported iridium catalyst Ir-POP@L2-20 (573.2 mg, yield 92%).

[0045] The prepared supported iridium catalyst Ir-POP@L2-20 was characterized. Figure 1 The following are the scanning electron microscopy characterization results of the supported iridium catalyst Ir-POP@L2-20 at 100nm and 500nm. The results show that the surface structure of the supported catalyst is relatively regular. Figure 2 The results of transmission electron microscopy characterization (50nm), high-angle annular dark field scanning transmission electron microscopy (100nm) and corresponding element analysis (100nm) of the supported iridium catalyst Ir-POP@L2-20 can be observed from the results. The element distribution diagram shows that the catalytically active species are independently distributed in the polymeric skeleton without agglomeration. The nitrogen adsorption and desorption experiment was carried out on the supported iridium catalyst Ir-POP@L2-20 of Example 2, and the results are as follows Figure 3 As shown, Figure 4 This is the pore size diagram of the supported iridium catalyst Ir-POP@L2-20. Through these two characterizations, it can be seen that the catalyst has a high specific surface area and abundant pore volume, which further proves that the catalyst has a rich pore structure; Figure 5 This is the thermogravimetric analysis diagram of the supported iridium catalyst Ir-POP@L2-20. The results show that the mass of the catalyst begins to decrease significantly at 390°C, demonstrating the high thermal stability of the catalyst. The metal content of the product was determined by ICP-OES characterization. The measurement results show that the metal Ir content in the product is lower than the ICP-OES detection limit, indicating that the ligand has a strong metal chelating ability, making it difficult for the metal to be decoordinated / lost.

[0046] Example 3: Preparation of Iridium-loaded Catalyst Ir-POP@L1-n with Different Polymer Ratios

[0047] The polymer-coated mesoporous silica-supported iridium catalyst Ir-POP@L1-n was prepared in a manner similar to that of Example 1, except that the amount of ligand was kept at 0.3 mmol (1 equivalent) and the amount of DVB was changed.

[0048] Table 1 Iridium-loaded catalyst Ir-POP@L1-n with different polymer ratios

[0049] Catalyst name DVB Equivalent Ir-POP@L1-10 10 Ir-POP@L1-30 30 Ir-POP@L1-60 60

[0050] Example 4: Application of supported iridium catalyst Ir-POP@L1-20 in asymmetric hydrogenation of carbonyl compounds

[0051]

[0052] 1a (366.4 mg, 2 mmol), lithium tert-butoxide (4 mg, 0.05 mmol), supported iridium catalyst Ir-POP@L1-20 (2.1 mg) and 10 mL of isopropanol were added to the autoclave. 2 (3.0Mpa), and reacted at room temperature for 10 hours. After the reaction was completed and hydrogen was released, the reaction solution was filtered to separate and recover the supported catalyst. The filtrate was desolventized and separated by column chromatography (n-hexane: ethyl acetate = 2: 1) to obtain the product 2a as a white solid (365.6 mg, yield 99%, purity 99%, ee value > 99%). The catalytic effect was consistent with the homogeneous monomer reported by it.

[0053] Example 5: Application of supported iridium catalyst Ir-POP@L2-20 in asymmetric hydrogenation of carbonyl compounds

[0054]

[0055] 1b (433.2 mg, 2 mmol), lithium tert-butoxide (4 mg, 0.05 mmol), supported iridium catalyst Ir-POP@L2-20 (2.0 mg) and 10 mL of isopropanol were added to the autoclave. 2 (3.0Mpa), and reacted at room temperature for 10 hours. After the reaction was completed and hydrogen was released, the reaction solution was filtered to separate and recover the supported catalyst. The filtrate was desolventized and separated by column chromatography (n-hexane: ethyl acetate = 2: 1) to obtain the product 2b as a white solid (430.8 mg, yield 99%, purity 99%, ee value > 99%).

[0056] Example 6: Application of supported iridium catalyst Ir-POP@L1-10 in asymmetric hydrogenation of carbonyl compounds

[0057]

[0058] 1c (396.4 mg, 2 mmol), lithium tert-butoxide (4 mg, 0.05 mmol), supported iridium catalyst Ir-POP@L1-10 (1.1 mg) and 10 mL of isopropanol were added to the autoclave. 2 (3.0Mpa), and reacted at room temperature for 10 hours. After the reaction was completed and hydrogen was released, the reaction solution was filtered to separate and recover the supported catalyst. The filtrate was desolventized and separated by column chromatography (n-hexane: ethyl acetate = 2: 1) to obtain the product 2c as a white solid (394.4 mg, yield 99%, purity 99%, ee value 99%).

[0059] Example 7: Application of supported iridium catalyst Ir-POP@L1-30 in asymmetric hydrogenation of carbonyl compounds

[0060]

[0061] 1d (504.4 mg, 2 mmol), lithium tert-butoxide (4 mg, 0.05 mmol), supported iridium catalyst Ir-POP@L1-30 (2.4 mg) and 10 mL of isopropanol were added to the autoclave. 2 (3.0Mpa), react at room temperature for 10 hours. After the reaction is completed and hydrogen is released, the reaction solution is filtered to separate and recover the supported catalyst. The filtrate is desolventized and separated by column chromatography (n-hexane: ethyl acetate = 1: 1) to obtain the product 2d (499.1 mg, yield 98%, purity 99%, ee value 98%).

[0062] Example 8: Application of supported iridium catalyst Ir-POP@L1-60 in asymmetric hydrogenation of carbonyl compounds

[0063]

[0064] 1e (420.6 mg, 2 mmol), lithium tert-butoxide (4 mg, 0.05 mmol), supported iridium catalyst Ir-POP@L1-60 (4.7 mg) and 10 mL of isopropanol were added to the autoclave. 2 (3.0Mpa), react at room temperature for 10 hours. After the reaction is completed and hydrogen is released, the reaction solution is filtered to separate and recover the supported catalyst. The filtrate is desolventized and separated by column chromatography (n-hexane: ethyl acetate = 2: 1) to obtain the product 2e (416.2 mg, yield 98%, purity 99%, ee value 99%) as a white solid.

[0065] Example 9: Application of supported iridium catalyst Ir-POP@L1-20 in asymmetric hydrogenation of carbonyl compounds

[0066]

[0067] 3a (242.4 mg, 2 mmol), lithium tert-butoxide (4 mg, 0.05 mmol), supported iridium catalyst Ir-POP@L1-20 (2.1 mg) and 10 mL of isopropanol were added to the autoclave. 2 (3.0Mpa), and reacted at room temperature for 10 hours. After the reaction was completed and hydrogen was released, the reaction solution was filtered to separate and recover the supported catalyst. The filtrate was desolventized and separated by column chromatography (n-hexane: ethyl acetate = 10: 1) to obtain the product 4a (242.2 mg, yield 99%, purity 99%, ee value 97%).

[0068] Example 10: Application of supported iridium catalyst Ir-POP@L2-20 in asymmetric hydrogenation of carbonyl compounds

[0069]

[0070] 3b (294.4 mg, 2 mmol), lithium tert-butoxide (4 mg, 0.05 mmol), supported iridium catalyst Ir-POP@L2-20 (2.0 mg) and 10 mL of isopropanol were added to the autoclave. 2 (3.0Mpa), and reacted at room temperature for 10 hours. After the reaction was completed and hydrogen was released, the reaction solution was filtered to separate and recover the supported catalyst. The filtrate was desolventized and separated by column chromatography (n-hexane: ethyl acetate = 10: 1) to obtain the product 4b (293.3 mg, yield 99%, purity 99%, ee value 97%).

[0071] Example 11: Application of supported iridium catalyst Ir-POP@L1-10 in asymmetric hydrogenation of carbonyl compounds

[0072]

[0073] 3c (266.4 mg, 2 mmol), lithium tert-butoxide (4 mg, 0.05 mmol), supported iridium catalyst Ir-POP@L1-10 (1.1 mg) and 10 mL of isopropanol were added to the autoclave. 2 (3.0Mpa), and reacted at room temperature for 10 hours. After the reaction was completed and hydrogen was released, the reaction solution was filtered to separate and recover the supported catalyst. The filtrate was desolventized and separated by column chromatography (n-hexane: ethyl acetate = 10: 1) to obtain the product 4c (263.0 mg, yield 98%, purity 99%, ee value 98%).

[0074] Example 12: Application of supported iridium catalyst Ir-POP@L1-30 in asymmetric hydrogenation of carbonyl compounds

[0075]

[0076] 5a (384.4 mg, 2 mmol), sodium hydroxide (2.0 mg, 0.05 mmol), supported iridium catalyst Ir-POP@L1-30 (2.4 mg) and 10 mL of ethyl acetate were added to the autoclave. 2 (3Mpa), react at 50°C for 14h. After the reaction is completed and hydrogen is released, the reaction solution is filtered to separate and recover the supported catalyst. The filtrate is desolventized and separated by column chromatography (n-hexane: ethyl acetate = 5:1) to obtain the product 6a (378.8mg, yield 99%, ee value 99.0%) as a colorless liquid.

[0077] Example 13: Application of supported iridium catalyst Ir-POP@L2-20 in asymmetric hydrogenation of α-amino-β-ketoester

[0078]

[0079] Substrate 5b (652.8 mg, 2 mmol), sodium acetate (4.1 mg, 0.05 mol), supported iridium catalyst Ir-POP@L2-20 (2.0 mg) and 10 mL toluene were added to the autoclave. H 2 (3.5Mpa), and reacted at 60℃ for 24h. After the reaction was completed and hydrogen was released, the reaction solution was filtered to separate and recover the supported catalyst. The filtrate was desolventized and separated by column chromatography (n-hexane: ethyl acetate = 5:1) to obtain the product white

[0080] Color solid 6b (614.9 mg, yield 94%, purity 99%, ee value 99%, dr value 99:1).

[0081] Example 14: Application of supported iridium catalyst Ir-POP@L2-20 in continuous catalytic hydrogenation reaction

[0082] Take a 500mL two-necked flask, add substrate 1f (7.9g, 36mmol), dissolve it with 180mL isopropanol, and replace the argon several times for standby use. In a nitrogen atmosphere, add Ir-POP@L2-20 (75mg) to a 25mL single-necked flask. tBuOLi (8 mg), 2.5 mL of isopropanol, stirred at room temperature for 0.5 h, then filtered to obtain the pretreated catalyst, and ground it into a fine orange-yellow powder in a mortar, then mixed with lithium tert-butoxide (300 mg), quartz sand (7.5 g), and loaded into a fixed bed column. The above solution and hydrogen were introduced into the fixed bed column at a rate of 1 mL / min and 50 mL / min, respectively, and the system pressure was adjusted to 2 MPa. When the system pressure reached, the infusion pump flow rate was reduced to 0.3 mL / min. The reaction temperature was room temperature, the residence time in the fixed bed was 6 min, and it was continuously operated for 130 h. After the reaction, isopropanol was pumped into the system at a flow rate of 2 mL / min. All the reaction solutions were combined and the solvent was removed under reduced pressure to obtain a total of 102.7 g of a white solid crude product, of which 100 mg was used for ICP-OES detection. The remaining crude product was recrystallized in 130 mL of n-hexane to obtain the product, a white solid 2f (99.52 g, yield 97.1%, >99% ee).

[0083] Examples 15 to 29: Application of supported iridium catalyst Ir-POP@L1-20 in asymmetric hydrogenation of carbonyl compounds

[0084] The operating steps described in Examples 15 to 29 repeat those of Example 4.

[0085] Table 2 Summary of results of compounds of Examples 15 to 29

[0086]

[0087]

[0088] (Examples 15 to 29 are all known substances)

[0089] The contents described in this specification are merely an enumeration of implementation forms of the inventive concept, and the protection scope of the present invention should not be regarded as being limited to the specific forms described in the embodiments.

Claims

1. A supported multidentate P,N,N-iridium catalyst, characterized in that: Having a structure as shown in Formula I or Formula II: In the general formula, n is an integer selected from 1 to 100.

2. A supported multidentate P,N,N-iridium catalyst as claimed in claim 1, characterized in that: The structure of the catalyst is shown below:

3. A method for preparing a supported multidentate P,N,N-iridium catalyst as claimed in claim 1, characterized in that: The following steps are involved: (1) In the presence of potassium carbonate, intermediate C1 or C2 is subjected to a Suzuki coupling reaction with 4-vinylbenzeneboronic acid under the catalysis of palladium acetate and an organic phosphine ligand XPhos to obtain intermediate C1' or C2', followed by a Boc protecting group removal reaction under the action of trifluoroacetic acid to obtain a ligand precursor D1 or D2; (2) condensing the ligand precursor D1 or D2 with AcO-PPFA to prepare a P,N,N-tridentate organic ligand L1 or L2; (3) The organic ligand L1 or L2 is copolymerized with DVB in the presence of AIBN as a free radical initiator to obtain a porous organic polymer-supported organic ligand POP@L1-n or POP@L2-n, where L represents the type of ligand and n represents the equivalent of DVB; (4) The organic ligand POP@L1-n or POP@L2-n supported by the porous organic polymer undergoes a coordination reaction with the metal iridium precursor [Ir(COD)Cl]2 to obtain a supported iridium catalyst Ir-POP@L1-n as shown in Formula I or a supported iridium catalyst Ir-POP@L2-n as shown in Formula II. The reaction formula is as follows:

4. The preparation method according to claim 3, characterized in that: In the step (3), the molar ratio of the organic ligand L1 or L2 to AIBN and DVB is 1:0.01-1:1-100, and the reaction is carried out in a tetrahydrofuran solution at a reaction temperature of 60-120° C. and a reaction time of 8-48 hours.

5. The preparation method according to claim 3, characterized in that: In the step (4), the molar ratio of the metal iridium precursor [Ir(COD)Cl]2 to the supported organic ligand POP@L1-n or POP@L2-n is 1:2.0-2.5, and the reaction is carried out in an isopropanol solution at a reaction temperature of 20-70°C and a reaction time of 0.5-5h.

6. The preparation method according to claim 4, characterized in that: In step (3), the molar ratio of the organic ligand L1 or L2 to AIBN and DVB is 1:0.2-0.5:20-60.

7. Use of the supported multidentate P,N,N-iridium catalyst as claimed in claim 1 in the asymmetric hydrogenation reaction of carbonyl compounds, characterized in that: The application process is as follows: in an alkaline additive and hydrogen atmosphere, an organic solvent is added, and a supported multidentate P, N, N-iridium catalyst promotes the asymmetric hydrogenation of carbonyl compounds to prepare chiral secondary alcohol compounds with high enantioselectivity.

8. The use according to claim 7, characterized in that The base additive used is one of sodium acetate, sodium hydroxide and lithium tert-butoxide; the feeding molar ratio of the carbonyl compound, the base additive and the supported multidentate P, N, N-iridium catalyst is 1:0.005-0.1:0.001-0.05, and the organic solvent is one of isopropanol, toluene and ethyl acetate.

9. Use of the supported multidentate P,N,N-iridium catalyst as claimed in claim 1 in the continuous asymmetric hydrogenation reaction of carbonyl compounds, characterized in that: The application method is as follows: the catalyst is fully ground in a mortar, then mixed with lithium tert-butoxide and quartz sand, and loaded into a fixed bed reactor; a solution A prepared by dissolving a carbonyl compound in an organic solvent is input into one channel through a feed pump; hydrogen is introduced into another channel, and secondary alcohol compounds with high enantioselectivity are prepared through reaction and purification.

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