A chiral arylphosphine-oxazoline functionalized porous organic polymer and its preparation and application

Abstract

The present invention provides a chiral arylphosphine-oxazoline functionalized porous organic polymer and its preparation and application. First, a styrene-functionalized PHOX monomer (VPHOX) is designed and synthesized, and the VPHOX is mixed with divinylbenzene. Free radical polymerization is carried out under the initiation of azobisisobutyronitrile to obtain a porous organic polymer (POP-PHOX). The POP-PHOX can be used as a chiral solid ligand in the Ir-catalyzed asymmetric hydrogenation of α,β-unsaturated ketones to prepare α-chiral central ketones. The heterogeneous catalyst system of the present invention has higher catalytic activity than homogeneous catalyst systems reported in the literature, and the catalyst is easy to separate and recover. The recovered catalyst can be recycled for more than 7 times while still maintaining excellent catalytic activity and enantioselectivity. The present invention reduces the preparation cost of the α-chiral central ketone, is simple to post-process, and produces less three wastes, thereby having practical application prospects.

Description

Technical Field

[0001] The present invention relates to a chiral ligand for catalyzing the synthesis of α-chiral carbon-centered ketones and a preparation method thereof, and particularly to a chiral arylphosphine-oxazoline functionalized porous organic polymer (POP-PHOX) and a preparation method thereof, as well as application of the chiral ligand as a multiphase chiral ligand in the preparation of α-chiral carbon-centered ketones by Ir-catalyzed asymmetric hydrogenation of α,β-unsaturated ketones. Background Art

[0002] Ketones with an α-chiral carbon center are an important class of chiral compounds with significant practical applications in the preparation of numerous natural products and bioactive molecules. Transition-metal-catalyzed hydrogenation of α,β-unsaturated ketones is currently the simplest route for preparing these compounds, offering advantages such as readily available raw materials and high atom economy. Over the past decade, chemists have developed a variety of chiral transition metal catalytic systems for this reaction. Among them, iridium-chiral arylphosphine-oxazoline (Ir-PHOX), independently developed by the Bolm group at RWTH Aachen University in Germany and the Hou Xuelong group at the Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, is a popular catalyst for this asymmetric reaction. This catalyst exhibits excellent catalytic activity and chiral recognition for a variety of linear and cyclic α,β-unsaturated ketones, with most hydrogenated products exhibiting ee values ​​exceeding 90%. Furthermore, it offers advantages such as good compatibility with functional groups (e.g., Cl, NO2, furyl groups) and mild reaction conditions (room temperature). The two reported catalytic reaction systems differ slightly. Bolm's group used toluene as the reaction medium, a hydrogen pressure of 2-10 bar, a 1 mol% Ir-PHOX catalyst, and a reaction time of 3-24 hours. They achieved nearly complete conversion of 30 α,β-unsaturated ketones, with isolated yields of 84-96% and ee values ​​of 86-99% for the corresponding α-chiral carbon-centered ketones (Angew. Chem. Int. Ed. 2008, 47, 8920-8923). Hou Xuelong's group, on the other hand, used dichloromethane as the reaction medium, a 1-3 mol% Ir-PHOX catalyst, a hydrogen pressure of 50 bar, a 1 mol% Ir-PHOX catalyst, and a reaction time of 24 hours. They also achieved complete conversion of 10 α,β-unsaturated ketones with ee values ​​of 97-99%. If the hydrogen pressure is reduced to atmospheric pressure, the catalyst dosage for some reactions needs to be increased to 3 mol% to achieve the same reaction results. Furthermore, this document does not provide the isolated yield of the corresponding hydrogenation product (Angew. Chem. Int. Ed. 2008, 47, 10133-10136).

[0003]

[0004] Although the aforementioned asymmetric catalytic hydrogenation method provides a simple, rapid, and highly stereoselective method for preparing α-chiral carbon-centered ketones, the catalyst Ir-PHOX is expensive and requires large quantities. Because the reaction is carried out under homogeneous conditions, the catalyst cannot be recovered or reused, resulting in high production costs. Furthermore, post-processing also generates a large amount of waste liquid containing heavy metals.

[0005] To overcome these limitations, the present invention designed and prepared a PHOX-functionalized porous organic polymer (POP-PHOX), which was used as a chiral solid ligand for online coordination with [Ir(COD)Cl]2 and further ion exchange with NaBARF to catalyze the asymmetric hydrogenation of α,β-unsaturated ketones to produce α-chiral carbon-centered ketones. Because the catalyst is insoluble in the reaction medium, the reaction is carried out under heterogeneous conditions. After the reaction is completed, the catalyst can be separated from the product and recovered by simple centrifugation or filtration. The recovered catalyst can be reused multiple times and still maintain catalytic activity. This not only greatly reduces production costs, but also simplifies the post-processing process and reduces the discharge of three wastes. Summary of the Invention

[0006] The present invention aims to provide a novel chiral arylphosphine-oxazoline functionalized porous organic polymer (POP-PHOX) and a preparation method thereof, as well as the application of POP-PHOX in the Ir-catalyzed asymmetric hydrogenation of α,β-unsaturated ketones to prepare α-chiral carbon-centered ketones.

[0007] The present invention first designs and synthesizes a styryl-functionalized PHOX monomer (VPHOX). VPHOX is then mixed with divinylbenzene (DVB) in a specific ratio and subjected to free radical polymerization initiated by azobisisobutyronitrile (AIBN) to produce a series of porous organic polymers (POP-PHOX). Using POP-PHOX as a ligand, the ligand is first coordinated online with [Ir(COD)Cl]2, followed by ion exchange with NaBARF to obtain the corresponding POP-PHOX-Ir(COD)BARF heterogeneous catalyst. This catalyst is then used to catalyze the asymmetric hydrogenation of α,β-unsaturated ketones to prepare α-chiral carbon-centered ketones.

[0008] The heterogeneous catalyst system of the present invention has higher catalytic activity than homogeneous catalyst systems reported in the literature, and the catalyst is easy to separate and recover. The recovered catalyst can be recycled more than seven times while still maintaining excellent catalytic activity and enantioselectivity.

[0009] The technical solutions of the present invention are as follows:

[0010] A (S)-4-(tert-butyl)-2-(4-(diphenylphosphino)-4'-vinyl-[1,1'-biphenyl]-3-yl)-4,5-dihydrooxazoline monomer, referred to as VPHOX, has a structural formula as shown in Formula VI:

[0011]

[0012] A method for preparing VPHOX comprises the following steps:

[0013] (1) Under a nitrogen atmosphere, 2-fluoro-5-bromobenzoic acid, a compound represented by formula I, oxalyl chloride, and N,N-dimethylformamide (catalyst) are dissolved in dichloromethane, stirred at room temperature for 5 hours, and the dichloromethane and excess oxalyl chloride are recovered under reduced pressure to obtain a bright yellow liquid; then, the liquid is added dropwise to a dichloromethane mixture containing triethylamine and (S)-tert-leucinol at 0°C. After the addition is complete, the mixture is heated to room temperature and stirred for 1 hour. The reaction solution is then post-treated to obtain (S)-5-bromo-2-fluoro-N-(1-hydroxy-2-tert-butyl)benzamide, a compound represented by formula II;

[0014] Preferably, the molar ratio of the compound represented by formula I, oxalyl chloride, N,N-dimethylformamide, triethylamine, and (S)-tert-leucinol is 1:1.6:0.1:1.5:1.1;

[0015] The post-treatment method is as follows: after the reaction is completed, the reaction solution is filtered, the filtrate is washed with 5% hydrochloric acid aqueous solution and 5% sodium bicarbonate aqueous solution in sequence, dried over anhydrous sodium sulfate, filtered, and the solvent is recovered by vacuum rotary evaporation to obtain the compound represented by Formula II;

[0016] (2) Under a nitrogen atmosphere, the compound represented by formula II was dissolved in dichloromethane, cooled to -20°C, and diethylaminosulfur trifluoride was added dropwise. The mixture was stirred and reacted for 30 minutes. The reaction solution was then post-treated to obtain the compound represented by formula III (S)-2-(5-bromo-2-fluorophenyl)-4-(tert-butyl)-4,5-dihydrooxazoline;

[0017] Preferably, the molar ratio of the compound represented by formula II to diethylaminosulfur trifluoride is 1:2.0;

[0018] The post-treatment method is as follows: after the reaction is completed, a saturated aqueous sodium bicarbonate solution is added to quench the reaction, the liquids are separated, the aqueous phase is extracted with dichloromethane, the organic phases are combined, dried over anhydrous sodium sulfate, filtered, and the solvent is recovered by rotary evaporation under reduced pressure in vacuo. The residue is purified by column chromatography (petroleum ether:ethyl acetate = 200:1) to obtain the compound represented by Formula III;

[0019] (3) Under N2 atmosphere and -20°C, the compound represented by Formula III, diphenylphosphine, and n-butyllithium were dissolved in tetrahydrofuran, stirred for 1 hour, and the temperature was naturally raised to room temperature. Sulfur powder was added and the mixture was stirred for 3 hours at room temperature. The reaction solution was then post-treated to obtain the compound represented by Formula IV (S)-(4-bromo-2-(4-(tert-butyl)-4,5-dihydrooxazol-2-yl)phenyl)diphenylphosphine sulfide;

[0020] Preferably, the molar ratio of the compound represented by formula III, diphenylphosphine, n-butyllithium, and sulfur powder is 1:1.3:1.4:1.5;

[0021] The post-treatment method is as follows: after the reaction is completed, methanol is added to quench the reaction, methyl tert-butyl ether is extracted, the organic phase is washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered, and the solvent is recovered by vacuum rotary evaporation. The residue is purified by column chromatography (petroleum ether: ethyl acetate = 80:1) to obtain the compound represented by Formula IV;

[0022] (4) Under N2 atmosphere, the compound represented by formula IV, 4-vinylphenylboronic acid, palladium acetate (catalyst), benzyldiadamantylphosphine (Ad2BnP, ligand), and potassium carbonate were mixed in a mixed solvent of toluene and water (volume ratio 3:1), heated to 70°C and stirred for reaction for 8 hours. The reaction solution was then post-treated to obtain the compound represented by formula V (S)-(3-(4-(tert-butyl)-4,5-dihydrooxazol-2-yl)-4'-vinyl-[1,1'-biphenyl]-4-yl)diphenylphosphine sulfide;

[0023] Preferably, the molar ratio of the compound represented by formula IV, 4-vinylphenylboronic acid, palladium acetate, benzyldiadamantylphosphine, and potassium carbonate is 1:1.5:0.08:0.09:2.2;

[0024] The post-treatment method is as follows: after the reaction is completed, the reaction solution is diluted with water, the organic phase is separated, the aqueous phase is extracted with toluene, the organic phases are combined, dried over anhydrous sodium sulfate, filtered, and the solvent is recovered by vacuum rotary evaporation. The residue is purified by column chromatography (petroleum ether:ethyl acetate = 30:1) to obtain the compound represented by formula V;

[0025] (5) Under N2 atmosphere, the compound represented by Formula V and tri(diethylamino)phosphine were dissolved in toluene, heated to 100°C and stirred for reaction for 7 h. The reaction solution was then post-treated to obtain the compound represented by Formula VI, namely: (S)-4-(tert-butyl)-2-(4-(diphenylphosphino)-4'-vinyl-[1,1'-biphenyl]-3-yl)-4,5-dihydrooxazoline (VPHOX);

[0026] Preferably, the molar ratio of the compound represented by formula V to tri(diethylamino)phosphine is 1:3.0;

[0027] The post-treatment method is as follows: after the reaction is completed, the solvent is recovered by rotary evaporation under reduced pressure and the residue is purified by column chromatography (petroleum ether: ethyl acetate = 400: 1) to obtain VPHOX.

[0028] The present invention also relates to a chiral arylphosphine-oxazoline functionalized porous organic polymer, referred to as POP-PHOX. POP-PHOX is obtained by free radical polymerization of monomers VPHOX and divinylbenzene (DVB) initiated by azobisisobutyronitrile (AIBN). The structural formula is shown in Formula VII:

[0029]

[0030] In formula VII, x:y=10 to 60:1.

[0031] Specifically, the preparation method of POP-PHOX is as follows:

[0032] Under N2 atmosphere, VPHOX monomer, divinylbenzene, and azobisisobutyronitrile were dissolved in an organic solvent, stirred at room temperature for 1 hour, then heated to 100°C and allowed to stand for polymerization reaction for 24 hours. After cooling to room temperature, the solid product was washed with dichloromethane and dried in vacuo at room temperature to obtain POP-PHOX.

[0033] The molar ratio of divinylbenzene to VPHOX monomer is 10 to 60:1;

[0034] The mass ratio of azobisisobutyronitrile to VPHOX monomer is 0.06:1;

[0035] The preferred organic solvent is tetrahydrofuran, and the mass ratio of tetrahydrofuran to VPHOX monomer is 180:1.

[0036] The overall synthesis route of the chiral arylphosphine-oxazoline functionalized porous organic polymer (POP-PHOX) of the present invention is as follows:

[0037]

[0038] The POP-PHOX described in the present invention can be used as a chiral solid ligand in the Ir-catalyzed asymmetric hydrogenation of α,β-unsaturated ketones to prepare α-chiral carbon-centered ketones. The specific application method is as follows:

[0039] Under a nitrogen atmosphere, POP-PHOX, [Ir(COD)Cl]2, and anhydrous toluene were mixed and stirred for 1 hour. NaBARF was added and stirred for 0.5 hour. Then, α,β-unsaturated ketone was added. The system was replaced with hydrogen and the pressure was adjusted to 5 bar. The reaction was stirred at room temperature for 24 hours. After that, the mixture was centrifuged, the supernatant was aspirated, and the lower solid was washed with toluene. The organic phases were combined and the solvent was recovered by vacuum rotary evaporation. The residue was purified by column chromatography to obtain the hydrogenation addition product α-chiral carbon-centered ketone.

[0040] Preferably, the molar ratio of α,β-unsaturated ketone, POP-PHOX, [Ir(COD)Cl]2, and NaBARF is 100:0.3:0.2:0.8;

[0041] The general formulas of α,β-unsaturated ketone and α-chiral carbon-centered ketone are shown in Formula A and Formula B respectively:

[0042]

[0043] In Formula A or Formula B,

[0044] R1 is: phenyl, C1-C3 alkyl substituted phenyl, C1-C3 alkoxy substituted phenyl, nitro substituted phenyl, halogen substituted phenyl or (· indicates the substitution position);

[0045] R2 is: H or C1-C3 alkyl;

[0046] R3 is: C1-C3 alkyl, C1-C3 alkoxy substituted phenyl or halogen substituted phenyl.

[0047] Compared with the prior art, the beneficial effects of the present invention are embodied in:

[0048] This invention designs and develops a novel chiral arylphosphine-oxazoline-functionalized porous organic polymer for use as a chiral solid ligand in the Ir-catalyzed asymmetric hydrogenation of α,β-unsaturated ketones to produce α-chiral central ketones. This heterogeneous catalyst system exhibits higher catalytic activity than homogeneous catalysts reported in the literature. The catalyst is also easily separated and recovered, and the recovered catalyst can be recycled more than seven times. This not only significantly reduces the production cost of α-chiral central ketones, but also simplifies the post-processing process and reduces waste, waste, and other wastes, demonstrating promising practical application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0049] Figure 1 :Polymerization monomer VPHOX 1 H NMR spectrum (500 MHz).

[0050] Figure 2 :Polymerization monomer VPHOX 13 C NMR spectrum (125 MHz).

[0051] Figure 3 :Polymerization monomer VPHOX 31 P NMR spectrum (125 MHz).

[0052] Figure 4 : N2 adsorption-desorption isotherms of polymer POP-PHOX.

[0053] Figure 5 : Pore size distribution diagram of polymer POP-PHOX.

[0054] Figure 6 : Actual pictures of polymers POP-PHOX-10, 20, 30, 40, 50, and 60.

[0055] Figure 7 :Solid state of polymer POP-PHOX-40 31 PNMR diagram.

[0056] Figure 8 : IR spectra of polymer POP-PHOX-40 and monomer PHOX.

[0057] Figure 9 : SEM image of polymer POP-PHOX-40.

[0058] Figure 10 : TEM image of polymer POP-PHOX-40.

[0059] Figure 11 : The result diagram of the catalyst system POP-PHOX-40-Ir(COD)BARF being continuously recycled for 7 times. DETAILED DESCRIPTION

[0060] The present invention is further described below by means of specific examples, but the protection scope of the present invention is not limited thereto.

[0061] Example 1: Preparation of Styrene-Functionalized Chiral Aryl Phosphine-Oxazoline Ligand (VPHOX)

[0062] Preparation of Intermediate II: Under a nitrogen atmosphere, 2-fluoro-5-bromobenzoic acid (2.19 g, 10.0 mmol) was dissolved in 40 mL of dichloromethane, and 3 drops of N,N-dimethylformamide were added dropwise. Oxalyl chloride (2.60 g, 16.0 mmol) was then slowly added dropwise (approximately 5 minutes) at room temperature. After completion, the reaction was stirred for 5 hours. The solvent and excess oxalyl chloride were recovered by rotary evaporation to yield a pale yellow liquid. This liquid was then dissolved in 50 mL of dichloromethane and slowly added dropwise (approximately 5 minutes) at 0°C to a mixture of triethylamine (1.75 mL, 15.0 mmol) and (S)-tert-leucinol (1.29 g, 10.5 mmol) dissolved in 20 mL of dichloromethane. After completion, the mixture was allowed to warm to room temperature and stirred for 1 hour. The above solution was washed with 5% aqueous hydrochloric acid solution and 5% aqueous sodium carbonate solution, dried over anhydrous sodium sulfate, and the solvent was recovered by rotary evaporation under reduced pressure to obtain 2.95 g of a white solid. The intermediate was used directly in the next reaction without further purification. 1H NMR (500MHz, CDCl3): δ = 8.16 (dd, J = 4.2, 2.7Hz, 1H), 7.57-7.54 (m, 1H), 7.03 (dd, J = 8.7, 2.7Hz, 1H), 6.90 (t, J=10.6Hz,1H),4.10-4.05(m,1H),3.95(dd,J=7.9,3.6Hz,1H),3.66(dd,J=7.8,3.6Hz,1H),1.02(s,9H)ppm; 13 CNMR (125MHz, CDCl3): δ163.1 (d, J = 2.5Hz), 159.6 (d, J = 245.0Hz), 136.0 (d, J = 10Hz), 134.8 (d ,J=2.5Hz),122.8(d,J=13.8Hz),118.0,117.8,117.7(d,J=2.5Hz),60.4,63.1,33.7,26.9ppm.

[0063] Preparation of Intermediate III: Under N2 atmosphere, intermediate II (3.04 g, 10.0 mmol) and 40 mL of dichloromethane were added to a 100 mL jacketed flask, cooled to -20°C, and (diethylamino)sulfur trifluoride (3.05 g, 20 mmol) was added dropwise. The mixture was stirred at this temperature for 30 min, and then saturated aqueous sodium bicarbonate solution was added dropwise to quench the reaction until no bubbles were generated. The dichloromethane layer was separated, and the aqueous phase was extracted with dichloromethane. The combined dichloromethane phases were dried over anhydrous sodium sulfate, and the solvent was recovered by rotary evaporation. The residue was purified by column chromatography to give 2.60 g of a white solid in a yield of 90.8%. 1 H NMR (500MHz, CDCl3): δ8.04 (dd, J=3.6, 2.6Hz, 1H), 7.55-7.52 (m, 1H), 7.03 (t, J=9.8Hz, 1H), 4.36 (dd, J=8. 5,1.7Hz,1H),4.25(t,J=8.2Hz,1H),4.09(dd,J=7.8,2.5Hz,1H),3.66(dd,J=7.8,3.6Hz),0.97(s,9H)ppm; 13 C NMR (125MHz, CDCl3): δ160.10 (d, J = 256.3Hz), 158.9 (d, J = 5.1Hz), 135.35 (d, J = 8.4Hz), 133.8, 118.5, 118.4, 118.2 (d, J = 1 1.6Hz), 116.3 (d, J=4.1Hz), 76.3, 68.8, 34.0, 25.8ppm.

[0064] Preparation of Intermediate IV: Under N2 atmosphere, diphenylphosphine (1.96 g, 10.5 mmol) and 8 mL of anhydrous tetrahydrofuran were added to a 25 mL pressure bottle. A 2.5 M solution of n-butyllithium in hexane (4.40 mL, 11.0 mmol) was then added and stirred at room temperature for 10 min to yield an orange-red solution. In another 25 mL pressure bottle, Intermediate III (2.29 g, 8.0 mmol) was dissolved in 5 mL of anhydrous tetrahydrofuran and cooled to -20°C. The orange-red solution obtained above was added dropwise. After completion of the addition, the reaction was stirred at this temperature for 1 h. After completion of the reaction, sulfur powder (0.38 g, 12 mmol) was added and stirred at room temperature for 3 h. The reaction was quenched by adding methanol. The reaction solution was diluted with methyl tert-butyl ether, and the organic phase was washed with water and saturated brine, dried over anhydrous sodium sulfate, and the solvent was recovered by rotary evaporation. The residue was purified by column chromatography to yield 3.29 g of a white solid in an 85.1% yield. 1 H NMR (500MHz, CDCl3): δ8.01(dd,J=2.3,0.9Hz,1H),7.83-7.74(m,4H),7.57-7.54(m,1H),7.51-7.48(m,2H),7.46-7.42(m ,4H),7.30(dd,J=8.5,5.9Hz,1H),3.86(t,J=8.6Hz,1H),3.65(dd,J=8.4,1.9Hz,1H),3.51(t,J=9.0,1H),0.82(s,9H)ppm; 13 C NMR (125MHz, CDCl3): δ162.0 (d, J = 3.4Hz), 136.0, 135.9, 134.3, 134.2, 134.1, 134.0, 133.8, 133.6, 133.2, 133.1, 133.0 ,132.3,132.2,132.1,131.6,131.5,131.3,131.1,128.4(d,J=12.6Hz),126.2(d,J=3.4Hz),76.2,69.0,33.6,26.1ppm.

[0065] Preparation of Intermediate V: Under N2 atmosphere, to a 15 mL pressure tube were added Intermediate IV (0.97 g, 2.0 mmol), 4-vinylphenylboronic acid (0.44 g, 3.0 mmol), palladium acetate (36 mg, 7.5 mol%), benzyldiadamantylphosphine (72 mg, 9 mol%), potassium carbonate (0.61 g, 4.4 mmol), and 10 mL of a toluene / water mixture (30:1, v / v). The mixture was reacted at 70°C for 8 h. Water was added to the reaction solution, and the toluene layer was separated. The aqueous phase was extracted with toluene, and the organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was recovered by rotary evaporation. The residue was purified by column chromatography to afford 0.82 g of a white solid in a yield of 81.3%. 1 H NMR (500MHz, CDCl3): δ8.08 (q, J=1.9Hz, 1H), 7.90-7.82 (m, 4H), 7.65-7.63 (m, 1H), 7.61-7.60(m,2H),7.54-7.50(m,4H),7.49-7.48(m,1H),7.47-7.44(m,4H),6.77(d d,J=10.7,6.8Hz,1H),5.83(d,J=17.6Hz,1H),5.32(d,J=10.9Hz,1H),3.89(t,J=8. 4Hz,1H),3.64(dd,J=8.4,1.9Hz,1H),3.52(dd,J=8.7,1.6Hz,1H),0.84(s,9H)ppm; 13 C NMR (125MHz, CDCl3): δ163.3,163.2,138.2,137.8,136.2,135.2,135.1,134.2,134.1,133.5,133.4,132.9,132.8,132.3,13 2.2,131.7,131.6,131.5,131.1,131.0,130.5,129.9,129.8,128.3,128.2,127.4,126.9,114.7,76.2,68.9,33.7,26.1ppm; 31 P NMR (202MHz, CDCl3): δ45.06ppm.

[0066] Preparation of VI (VPHOX monomer): Under N2 atmosphere, intermediate V (0.51 g, 1.0 mmol), tri(diethylamino)phosphine (0.74 g, 3.0 mmol), and 5 mL of toluene were added to a 15 mL pressure tube. The reaction was carried out at 100°C for 7 h. The solvent was recovered by rotary evaporation, and the residue was purified by column chromatography to obtain 0.43 g of a white solid in a yield of 91.2%. 1H NMR (500MHz, CDCl3): δ8.22(dd,J=2.3,0.9Hz,1H),7.63(s,1H),7.61(s,1H),7.55(dd, J=5.8,2.1Hz,1H),7.51(s,1H),7.49(s,1H),7.29-7.37(m,10H),6.96(q,J=3.8Hz,1H) ,6.77(dd,J=10.9,6.6Hz,1H),5.82(d,J=17.6Hz,1H),5.30(d,J=11.0Hz,1H),4.14(dd ,J=8.6,1.8Hz,1H),4.06(t,J=8.4Hz,1H),3.94(dd,J=8.3,1.9Hz,1H),0.76(s,9H)ppm; 13 C NMR (125MHz, CDCl3): δ162.6,162.5,140.3,139.1,138.7,138.6,138.4,138.3,137.8,137.6,137.1,136.3,134.8,134.4,134.3 ,133.7,133.6,132.6,132.4,128.7,128.6,128.5,128.4,128.3,128.2,128.1,128.0,127.1,126.7,76.9,68.3,33.7,25.8ppm; 31 P NMR (202MHz, CDCl3): δ-6.57ppm.

[0067] Example 2: Preparation of Chiral Aryl Phosphine-Oxazoline Functionalized Porous Organic Polymer POP-PHOX

[0068] Preparation of POP-PHOX: To a 25 mL Schlenk tube, VPHOX (49 mg, 0.1 mmol), DVB (130-781 mg, 1.0-6.0 mmol), 30 mg of azobisisobutyronitrile (AIBN), and 10 mL of anhydrous tetrahydrofuran were added sequentially. The mixture was evacuated with liquid nitrogen and replenished with nitrogen three times, then stirred at room temperature for 1 hour to ensure uniform mixing of the monomers. The magnet was then removed, the temperature was raised to 100°C, and the reaction was allowed to stand for 24 hours. After completion of the reaction, the mixture was cooled to room temperature, washed twice with dichloromethane, and vacuum-dried. The resulting polymer was ground to yield POP-PHOX-M as a white powder (M = 10, 20, 30, 40, 50, or 60, where M represents the molar ratio of DVB / VPHOX).

[0069]

[0070] Furthermore, the prepared polymer POP-PHOX-M was analyzed for P element content to determine the PHOX loading. Nitrogen isothermal adsorption-desorption experiments were also performed to measure the specific surface area, pore volume, and pore diameter of POP-PHOX-M. Specific data are shown in Table 1 below.

[0071] Table 1 Pore structure properties of POP-PHOX-M and PHOX loading

[0072]

[0073] Furthermore, the optimal chiral polymer POP-PHOX-40 was studied in more detail. 31 PNMR, IR, SEM and TEM analysis, the specific spectra are shown in the attached figures.

[0074] Example 3: Asymmetric hydrogenation of α,β-unsaturated ketones catalyzed by POP-PHOX-40 / [Ir(COD)Cl]2 / NaBARF

[0075] Under N2 atmosphere, POP-PHOX-40 (4 mg, 0.3 mol%), [Ir(COD)Cl]2 (0.17 mg, 0.2 mol%) and 3 mL of anhydrous toluene were added to a 4 mL glass vial in sequence. After stirring for 1 hour, the color of the solid changed from white to yellow, and the color of the solution changed from light yellow to colorless. After adding NaBARF (7 mg, 0.8 mol%) and stirring for 0.5 hours, the color of the solid changed from yellow to orange-red. α,β-unsaturated ketone (0.5 mmol) was added, and the glass vial was placed in a kettle. After hydrogen replacement 3 times, the pressure was adjusted to 5 bar, and the reaction was stirred at room temperature for 24 hours. The reaction process was detected by GC. After the reaction was completed, centrifugation was performed, the supernatant was aspirated, and the solid was washed with 2 mL of toluene × 3. The organic phases were combined, the solvent was recovered by vacuum rotary evaporation, and the residue was purified by column chromatography to obtain the corresponding hydrogenation addition product α-chiral center ketone, and the yield was calculated. The structure of the product was determined by 1 H NMR and 13 The results were confirmed by C NMR characterization and the ee value was determined by GC using a chiral column Astec CHIRALDEX B-DM (30 m×0.25 mm). The specific experimental results are shown in Table 2 below.

[0076] Table 2 Asymmetric hydrogenation of α,β-unsaturated ketones catalyzed by POP-PHOX-40 / [Ir(COD)Cl]2 / NaBARF

[0077]

[0078]

[0079] Characterization data of the prepared products of Examples 3-15:

[0080] Example 3:

[0081] (S)-(+)-2-Methyl-1-phenyl-3-pentanone, colorless oily liquid; 1 H NMR (400MHz, CDCl3): δ7.31-7.28(m,2H),7.23-7.15(m,3H),3.01(dd,J=7.2,6.1Hz,1H),2.91-2.82(m,1H),2.5 9(dd,J=7.4,6.0Hz,1H),2.51-2.41(m,1H),2.33-2.23(m,1H),1.11(d,J=11.6Hz,3H),0.99(t,J=7.2Hz,3H)ppm; 13 C NMR (100MHz, CDCl3): δ211.1,139.9,128.9,128.4,125.6,46.9,39.3,35.2,16.6,7.6ppm; Optical Rotation:[α]D 23 +27.2(c=0.2,CH2Cl2).

[0082] Example 4:

[0083] (S)-(+)-3-Methyl-4-phenyl-2-butanone, yellow oily liquid; 1 H NMR (500MHz, CDCl3): δ7.31-7.16(m,4H),2.91(dd,J=9.8,6.5Hz,1H),2.82-2.68(m,1H),2.03(s,3H),1.74-1.50(m,2H),0.92(t,J=9.3Hz,3H)ppm; 13 C NMR (125MHz, CDCl3): δ212.4,139.7,128.8,128.4,128.3,126.2,56.2,37.4,30.2,24.5,11.6ppm; Optical Rotation:[α]D 23 +8.9(c=0.2,CH2Cl2).

[0084] Example 5:

[0085] (S)-(+)-3-(phenylmethyl)-2-pentanone, yellow oily liquid; 1H NMR (500MHz, CDCl3): δ7.16(t,J=7.5Hz,1H),7.08-7.02(m,2H),6.97(d,J=7.5Hz,1H) ,3.06-2.93(m,1H),2.32(s,3H),1.27(d,J=7.0Hz,3H),1.17(s,12H),1.14(m,2H)ppm; 13 C NMR (125MHz, CDCl3): δ149.3,137.7,128.2,127.6,126.5,123.7,83.1,35.8,24.9,24.8,21.6ppm; Optical Rotation:[α]D 23 +18.9 (c=0.2, CHCl3).

[0086] Example 6:

[0087] (S)-(+)-4-(2-methylphenyl)-3-methyl-2-butanone, yellow oily liquid; 1 H NMR(400MHz, CDCl3)δ:7.19-7.09(m,4H),3.03(dd,J=7.2,6.6Hz,1H),2.90-2.82(m, 1H),2.59(dd,J=8.0,5.8Hz,1H),2.35(s,3H),2.12(s,3H),1.13(d,J=7.0Hz,3H)ppm; 13 C NMR (100MHz, CDCl3): δ212.3,137.9,136.1,130.4,129.7,126.4,125.9,47.4,36.1,28.9,19.5,16.3ppm; OpticalRotation:[α]D 23 +20.1(c=0.2,CH2Cl2).

[0088] Example 7:

[0089] (S)-(+)-4-(3-methylphenyl)-3-methyl-2-butanone, yellow oily liquid; 1 H NMR (500MHz, CDCl3): δ7.12-7.05(m,4H),2.97(dd,J=6.9,6.8Hz,1H),2.86-2.79(m, 1H),2.55(dd,J=7.8,5.9Hz,1H),2.33(s,3H),2.11(s,3H),1.10(d,J=7.0Hz,3H)ppm; 13C NMR (125MHz, CDCl3): δ217.0,141.3,140.5,133.9,133.6,53.7,43.3,33.6,25.8,21.0ppm; OpticalRotation:[α]D 23 +18.7(c=0.2,CH2Cl2).

[0090] Example 8:

[0091] (S)-(+)-4-(4-Methylphenyl)-3-methyl-2-butanone, yellow oily liquid; 1 H NMR (500MHz, CDCl3) δ7.20-7.17(m,1H),7.04-7.02(m,1H),7.00-6.96(m,2H),2.98(dd,J=6.9,6.8Hz,1 H),2.88-2.80(m,1H),2.53(dd,J=7.8,5.8Hz,1H),2.34(s,3H),2.11(s,3H),1.10(d,J=7.0Hz,3H)ppm; 13 C NMR (125MHz, CDCl3) δ: 212.2, 139.6, 137.9, 129.7, 128.3, 126.9, 125.9, 48.8, 38.8, 28.8, 21.3, 16.2ppm; Optical Rotation: [α]D 23 +11.4(c=0.2,CH2Cl2).

[0092] Example 9:

[0093] (S)-(+)-4-(4-methoxyphenyl)-3-methyl-2-butanone, yellow oily liquid; 1 H NMR (500MHz, CDCl3): δ7.90-7.06(m,2H),6.84-6.81(m,2H),3.79(s,3H),2.94(dd,J=6.9,6.8 Hz,1H),2.84-2.76(m,1H),2.52(dd,J=7.6,6.1Hz,1H),2.09(s,3H),1.09(d,J=6.9Hz,3H)ppm; 13 CNMR (125MHz, CDCl3): δ212.3,158.0,131.6,129.8,113.8,55.2,49.0,38.1,28.8,16.1ppm; Optical Rotation:[α]D 23 +11.3(c=0.2,CH2Cl2).

[0094] Example 10:

[0095] (S)-(+)-3-Methyl-4-(4-nitrophenyl)-2-butanone, yellow oily liquid; 1 H NMR (500MHz, CDCl3): δ8.14-8.12(m,2H),7.34-7.31(m,2H),3.12(q,J=7.3Hz,1H),2 .91-2.84(m,1H),2.67(dd,J=7.2,6.5Hz,1H),2.12(s,3H),1.14(d,J=7.1Hz,3H)ppm; 13 C NMR (125MHz, CDCl3): δ210.7,147.7,146.6,130.2,129.8,123.6,48.3,38.2,28.7,16.5ppm; OpticalRotation:[α]D 23 =+5.6 (c=0.2, CH2Cl2).

[0096] Example 11:

[0097] (S)-(+)-4-(4-chlorophenyl)-3-methyl-2-butanone, yellow oily liquid; 1 H NMR (500MHz, CDCl3): δ7.26-7.23(m,2H),7.10-7.07(m,2H),2.97(dd,J=7.1,6.7Hz,1H) ,2.84-2.77(m,1H),2.54(dd,J=7.5,6.3Hz,1H),2.10(s,3H),1.10(d,J=7.0Hz,3H)ppm; 13 C NMR (125MHz, CDCl3): δ211.6,138.1,132.0,130.2,128.5,48.6,38.0,28.8,16.3ppm; Optical Rotation:[α]D 23 +5.6(c=0.2,CH2Cl2).

[0098] Example 12:

[0099] (S)-(+)-4-(4-bromophenyl)-3-methyl-2-butanone, yellow oily liquid; 1H NMR (400MHz, CDCl3): δ7.42-7.39(m,2H),7.06-7.02(m,2H),2.96(dd,J=7.0,6.6Hz,1H) ,2.85-2.76(m,1H),2.53(dd,J=7.4,6.2Hz,1H),2.11(s,3H),1.1(d,J=10.9Hz,3H)ppm; 13 C NMR (100MHz, CDCl3): δ211.7,138.7,131.5,130.7,120.1,48.6,38.1,28.9,16.3ppm; Optical Rotation:[α]D 23 +7.6(c=0.2,CH2Cl2).

[0100] Example 13:

[0101] (S)-(+)-4-(4-iodophenyl)-3-methyl-2-butanone, yellow oily liquid; 1 H NMR (400MHz, CDCl3): δ7.42-7.39(m,2H),7.06-7.02(m,2H),2.96(dd,J=7.0,6.6Hz,1H) ,2.85-2.76(m,1H),2.53(dd,J=7.4,6.2Hz,1H),2.11(s,3H),1.1(d,J=10.9Hz,3H)ppm; 13 C NMR (100MHz, CDCl3): δ211.7,138.7,131.5,130.7,120.1,48.6,38.1,28.9,16.3ppm; Optical Rotation:[α]D 23 +16.6(c=0.2,CH2Cl2).

[0102] Example 14:

[0103] (S)-(+)-2-(4-methylbenzyl)-3,4-dihydronaphthalen-1-one, colorless oily liquid; 1H NMR (500MHz, CDCl3): δ8.07(d,J=8.0Hz,1H),7.52-7.40(m,1H),7.25-7.28(m,1H),7.22(d,J=7.5Hz,1H),7.17-7.09(m,4H),3.45(dd ,J=13.5,3.5Hz,1H),3.02-2.85(m,2H),2.78-2.67(m,1H),2.65-2.56(m,1H),2.33(s,3H),2.15-2.06(m,1H),1.84-1.71(m,1H)ppm; 13 C NMR (500MHz, CDCl3): δ199.8,144.3,137.1,135.8,133.5,132.6,129.3,129.2,128.9,127.7,126.8,49.7,35.4,28.8,27.8,21.3ppm; Optical Rotation:[α]D 23 +15.5(c=0.2,CH2Cl2).

[0104] Example 15:

[0105] (S)-(+)-2-(4-chlorobenzyl)-3,4-dihydronaphthalen-1-one, colorless oily liquid; 1 H NMR (500MHz, CDCl3): δ8.06(d,J=8.0Hz,1H),7.50-7.42(m,1H),7.36-7.29(m,1H),7.29-7.24(m,2H),7.22(d,J=7.5Hz,1H ),7.16(d,J=8.0Hz,2H),3.49-3.36(m,1H),2.99-2.87(m,2H),2.76-2.62(m,2H),2.14-2.04(m,1H),1.85-1.72(m,1H)ppm; 13 C NMR (500MHz, CDCl3): δ199.2,144.1,138.7,133.6,132.6,132.1,130.8,128.9,128.7,127.8,126.9,49.5,35.3,28.9,28.0ppm; Optical Rotation:[α]D 23 +13.7(c=0.2,CH2Cl2).

[0106] Example 16: Asymmetric hydrogenation of α,β-unsaturated ketones catalyzed by POP-PHOX-40 / [Ir(COD)Cl]2 / NaBARF

[0107] The amount of POP-PHOX-40 in Example 3 was changed to 0.2 mmol, the amount of [Ir(COD)Cl]2 was changed to 0.05 mmol, the amount of NaBARF was changed to 0.2 mmol, and other conditions remained unchanged. GC determination showed that the yield of the product (S)-(+)-2-methyl-1-phenyl-3-pentanone was 45% and the ee value was 99%.

[0108] Example 17: Asymmetric hydrogenation of α,β-unsaturated ketones catalyzed by POP-PHOX-10 / [Ir(COD)Cl]2 / NaBARF

[0109] The POP-PHOX-40 in Example 14 was replaced with POP-PHOX-10, and other conditions remained unchanged. GC determination showed that the yield of the product (S)-(+)-2-methyl-1-phenyl-3-pentanone was 29% and the ee value was 98%.

[0110] Example 18: Asymmetric hydrogenation of α,β-unsaturated ketones catalyzed by POP-PHOX-20 / [Ir(COD)Cl]2 / NaBARF

[0111] The POP-PHOX-40 in Example 14 was replaced with POP-PHOX-20, and other conditions remained unchanged. GC determination showed that the yield of the product (S)-(+)-2-methyl-1-phenyl-3-pentanone was 35% and the ee value was 98%.

[0112] Example 19: Asymmetric hydrogenation of α,β-unsaturated ketones catalyzed by POP-PHOX-30 / [Ir(COD)Cl]2 / NaBARF

[0113] The POP-PHOX-40 in Example 14 was replaced with POP-PHOX-30, and other conditions remained unchanged. GC determination showed that the yield of the product (S)-(+)-2-methyl-1-phenyl-3-pentanone was 33% and the ee value was 98%.

[0114] Example 20: Asymmetric hydrogenation of α,β-unsaturated ketones catalyzed by POP-PHOX-50 / [Ir(COD)Cl]2 / NaBARF

[0115] The POP-PHOX-40 in Example 14 was replaced with POP-PHOX-50, and other conditions remained unchanged. GC determination showed that the yield of the product (S)-(+)-2-methyl-1-phenyl-3-pentanone was 40% and the ee value was 99%.

[0116] Example 21: Asymmetric hydrogenation of α,β-unsaturated ketones catalyzed by POP-PHOX-60 / [Ir(COD)Cl]2 / NaBARF

[0117] The POP-PHOX-40 in Example 14 was replaced with POP-PHOX-60, and other conditions remained unchanged. GC determination showed that the yield of the product (S)-(+)-2-methyl-1-phenyl-3-pentanone was 41% and the ee value was 99%.

[0118] Example 22: Recovery and Recycling of Catalyst POP-PHOX-40-Ir(COD)BARF

[0119] Under nitrogen protection, the catalyst POP-PHOX-40-Ir(COD)BARF, which had been centrifuged and washed with toluene, was transferred to a 4 mL glass vial, and NaBARF (7 mg, 0.8 mol%) was added. After stirring for 0.5 hour, (E)-2-methyl-1-phenyl-1-pentene-3-one (0.5 mmol, 87 mg) was added. After the addition was complete, the glass vial was placed in an autoclave, and after hydrogen exchange three times, the pressure was adjusted to 5 bar and stirred at room temperature for 24 hours. GC detection showed that the conversion of (E)-2-methyl-1-phenyl-1-pentene-3-one was greater than 99%. After the same post-treatment, 85 mg of (S)-(+)-2-methyl-1-phenyl-3-pentanone was obtained with a yield of 96% and an ee value of 98%. The same operation was used to continuously recycle the catalyst POP-PHOX-40-Ir(COD)BARF for 7 times while still maintaining excellent enantioselectivity. The results are shown in the attached figures. Figure 11 shown.

Claims

1. A (S)-4-(tert-butyl)-2-(4-(diphenylphosphino)-4'-vinyl-[1,1'-biphenyl]-3-yl)-4,5-dihydrooxazoline monomer, referred to as VPHOX, having the structural formula shown in Formula VI:

2. A method for preparing VPHOX, characterized in that: The steps include: (1) Under a nitrogen atmosphere, the compound of formula I, oxalyl chloride, and N,N-dimethylformamide were dissolved in dichloromethane, stirred at room temperature for 5 hours, and the dichloromethane and excess oxalyl chloride were recovered under reduced pressure to obtain a bright yellow liquid. The liquid was then added dropwise to a dichloromethane mixture containing triethylamine and (S)-tert-leucinol at 0°C. After the addition was complete, the mixture was heated to room temperature and stirred for 1 hour. The reaction solution was then post-treated to obtain the compound of formula II. (2) Under a nitrogen atmosphere, the compound of formula II was dissolved in dichloromethane, cooled to -20°C, and diethylaminosulfur trifluoride was added dropwise. The mixture was stirred for 30 minutes, and the reaction solution was post-treated to obtain the compound of formula III. (3) Under N2 atmosphere and -20°C, the compound represented by Formula III, diphenylphosphine, and n-butyllithium were dissolved in tetrahydrofuran, stirred for 1 hour, and the mixture was naturally warmed to room temperature. Sulfur powder was added and the mixture was stirred for 3 hours at room temperature. The reaction solution was then post-treated to obtain the compound represented by Formula IV. (4) Under a nitrogen atmosphere, the compound represented by formula IV, 4-vinylphenylboronic acid, palladium acetate, benzyldiadamantylphosphine, and potassium carbonate were mixed in a mixed solvent of toluene and water, heated to 70° C., stirred, and reacted for 8 h. The reaction solution was then post-treated to obtain the compound represented by formula V; (5) Under a nitrogen atmosphere, the compound represented by formula V and tri(diethylamino)phosphine were dissolved in toluene, heated to 100°C and stirred for reaction for 7 hours. The reaction solution was then post-treated to obtain the compound represented by formula VI, namely: VPHOX; 3. The method for preparing VPHOX according to claim 2, wherein: In step (1), the molar ratio of the compound represented by formula I, oxalyl chloride, N,N-dimethylformamide, triethylamine, and (S)-tert-leucinol is 1:1.6:0.1:1.5:1.1; In step (2), the molar ratio of the compound represented by formula II to diethylaminosulfur trifluoride is 1:2.0; In step (3), the molar ratio of the compound represented by formula III, diphenylphosphine, n-butyl lithium, and sulfur powder is 1:1.3:1.4:1.5; In step (4), the molar ratio of the compound represented by formula IV, 4-vinylphenylboronic acid, palladium acetate, benzyldiadamantylphosphine, and potassium carbonate is 1:1.5:0.08:0.09:2.2; In step (5), the molar ratio of the compound represented by formula V to tri(diethylamino)phosphine is 1:3.

0.

4. A chiral arylphosphine-oxazoline functionalized porous organic polymer, referred to as POP-PHOX, with the structural formula shown in Formula VII: In formula VII, x:y=10 to 60:

1.

5. A method for preparing POP-PHOX, characterized in that: The preparation method is: Under N2 atmosphere, VPHOX monomer, divinylbenzene, and azobisisobutyronitrile were dissolved in an organic solvent, stirred at room temperature for 1 hour, then heated to 100°C and allowed to stand for polymerization reaction for 24 hours. After cooling to room temperature, the solid product was washed with dichloromethane and dried in vacuo at room temperature to obtain POP-PHOX. The VPHOX monomer structure is shown in Formula VI: The structural formula of POP-PHOX is shown in Formula VII: In formula VII, x:y=10 to 60:

1.

6. The method for preparing POP-PHOX according to claim 5, wherein: The molar ratio of divinylbenzene to VPHOX monomer is 10-60:1; the mass ratio of azobisisobutyronitrile to VPHOX monomer is 0.06:

1.

7. The method for preparing POP-PHOX according to claim 5, wherein: The organic solvent is tetrahydrofuran.

8. Use of the POP-PHOX as claimed in claim 4 as a chiral solid ligand in the Ir-catalyzed asymmetric hydrogenation of α,β-unsaturated ketones to prepare α-chiral carbon-centered ketones.

9. The use according to claim 8, characterized in that Here’s how: Under a nitrogen atmosphere, POP-PHOX, [Ir(COD)Cl]2, and anhydrous toluene were mixed and stirred for 1 hour. NaBARF was added and stirred for 0.5 hour. Then, α,β-unsaturated ketone was added. The system was replaced with hydrogen and the pressure was adjusted to 5 bar. The reaction was stirred at room temperature for 24 hours. After that, the mixture was centrifuged, the supernatant was aspirated, and the lower solid was washed with toluene. The organic phases were combined and the solvent was recovered by vacuum rotary evaporation. The residue was purified by column chromatography to obtain the hydrogenation addition product α-chiral carbon-centered ketone. The general formulas of α,β-unsaturated ketone and α-chiral carbon-centered ketone are shown in Formula A and Formula B respectively: In Formula A or Formula B, R1 is: phenyl, C1-C3 alkyl substituted phenyl, C1-C3 alkoxy substituted phenyl, nitro substituted phenyl, halogen substituted phenyl or R2 is: H or C1-C3 alkyl; R3 is: C1-C3 alkyl, C1-C3 alkoxy substituted phenyl or halogen substituted phenyl.

10. The use according to claim 9, characterized in that The molar ratio of α,β-unsaturated ketone, POP-PHOX, [Ir(COD)Cl]2, and NaBARF is 100:0.3:0.2:0.8.

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