Chiral polyamide ligand based on Salen skeleton as well as preparation method and application of chiral polyamide ligand

Abstract

The invention relates to a chiral polyamide ligand based on a Salen skeleton as well as a preparation method and application of the chiral polyamide ligand. According to the ligand, two amino groups are introduced into a Salen skeleton ligand monomer, so that the Salen skeleton ligand monomer can be subjected to condensation reaction with diacyl chloride, and a ligand polymer connected by an amido bond is constructed; in the preparation method, chiral catalytic active sites are embedded into a polyamide main chain in a solution polycondensation manner to prepare the novel functional polymer catalyst. The ligand polymer obtained by the invention has a chiral induction effect and the stability and recoverability of a high polymer material; in addition, molecular oxygen (O2) is used as a green oxidizing agent, use of CHP in the prior art is avoided, and environmental pollution is reduced.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis catalysis technology, specifically relating to the design and preparation method of a chiral polyamide ligand based on the Salen skeleton, and its application in the asymmetric α-hydroxylation reaction of β-keto esters. Background Technology

[0002] Chiral α-hydroxyβ-keto esters play an important role in the total synthesis of complex natural products and drug development. Among them, kjellmanianone [Chemistry–A European Journal, 2004, 10(4): 1042-1045.], which exhibits antibacterial activity against Gram-positive microorganisms, and hamigerans A [Journal of Natural Products, 2000, 63(1): 79-85.], isolated from the sponge Hamigera tarangaensis and possessing anti-inflammatory activity, both have the structure of chiral α-hydroxyβ-keto esters; and chiral α-hydroxyβ-keto esters are also key intermediates in the synthesis of many drugs, such as Rishirilide B [Angewandte Chemie, 2017, 129(23): 6709-6712.], which can act on disease targets such as thrombosis and cancer, and the highly effective insecticide indoxacarb [Advanced Synthesis & Catalysis, 2019, 361(7): 1042-1045.]. The synthesis of [1673-1677.] involves intermediates containing this structure.

[0003] In recent years, catalysts used in the asymmetric hydroxylation of β-keto esters have been mainly classified into two categories: chiral organic small molecule catalysts and chiral metal complex catalysts. For example, the highly enantioselective α-hydroxylation method catalyzed by chiral salon-zirconium complexes and using cumene hydrogen peroxide (CHP) as an oxidant, reported by the Meng Qingwei research group [Organic Letters, 2017, 19(3): 448-451.]. Building on this, to promote green synthesis, the research group further developed a visible light-induced salon-copper catalytic system, using air as a green oxidant to achieve the enantioselective α-hydroxylation of β-keto esters, and successfully applied it to the synthesis of key intermediates of indoxacarb [Advanced Synthesis & Catalysis, 2019, 361(7): 1673-1677.]. However, existing catalytic systems generally suffer from the problem of difficult catalyst recovery and reuse, which limits their practical application efficiency and economy. Summary of the Invention

[0004] The purpose of this invention is to address the problem of the inability to effectively recover and reuse homogeneous catalysts after chiral induction reactions, by providing a Salen-based chiral polyamide ligand, its preparation method, and its applications. This ligand introduces two amino groups into the Salen-based ligand monomer, enabling it to undergo a condensation reaction with diacyl chloride, thereby constructing a ligand polymer linked by amide bonds. In the preparation method, a novel functional polymer catalyst is obtained by embedding chiral catalytic active sites into the polyamide backbone through solution polycondensation. When the catalyst acts on the asymmetric hydroxylation reaction of β-keto esters, the polymer catalyst exists in the reaction system as an insoluble suspension, easily separated from the reaction mixture by simple filtration, and exhibits no significant loss in catalytic activity or enantioselectivity after repeated use. The ligand polymer obtained by this invention combines chiral induction with the stability and recyclability of polymer materials; furthermore, it uses molecular oxygen (O2) as a green oxidant, avoiding the use of CHP in current technologies and reducing environmental pollution.

[0005] To achieve the above objectives, the present invention adopts the following technical solution: A chiral polyamide ligand based on the Salen framework has the following structural formula: , Among them, R 2 It is methyl-1,4-methyl-1,5-methyl-1,6-methyl-1; n is 100 ~ 10000.

[0006] The method for preparing chiral polyamide ligands based on the Salen skeleton includes the following steps: The monomer, triethylamine, and solvent were added to the reactor, sealed, and the reaction system was replaced with argon gas. Then, at 0-10 °C, a diacyl chloride solution dissolved in DCM was added dropwise to the system, and the reaction was carried out at 0-30 °C for 5-7 hours to obtain a chiral polyamide ligand based on the Salen skeleton. The molar ratio is monomer:triethylamine:diacyl chloride = 1:1.1:1; Add 0.5-2 mmol of monomer per 5 ml of solvent; the solvent for the diacyl chloride solution is DCM.

[0007] The solvent is dichloromethane, trichloromethane, 1,2-dichloroethane or 1,1-dichloroethane, preferably dichloromethane; The monomer mentioned is: ; The molar ratio was 1 mmol monomer L1, 1.1 mmol triethylamine, 1 mmol diacyl chloride and 5 mL dichloromethane; The diacyl chloride is malonyl chloride, adipicyl chloride, pimecroyl chloride, or octanoyl chloride; The application of the Salen-based chiral polyamide ligand is for the asymmetric hydroxylation reaction of β-keto esters.

[0008] Specifically, the steps include the following: The raw materials, Salen-based chiral polyamide ligands, Lewis acid, photosensitizer and solvent were added to a reactor, sealed and reacted at -45 ~ 0 ℃, oxygen pressure 0.1 ~ 0.3 MPa and white light irradiation for 15 ~ 20 hours to obtain α-hydroxy-β-keto ester; The molar ratio is: raw material: chiral polyamide ligand: Lewis acid: photosensitizer = 1: 0.13 ~ 0.19: 0.05 ~ 0.2: 0.005 ~ 0.05; The raw material is a 1-indanone-2-carboxylic acid ester derivative with chlorine, bromine, or fluorine substitutions on the benzene ring; specifically, it is 1-indanone-2-carboxylic acid ester, 5-chloro-1-indanone-2-carboxylic acid ester, 5-bromo-1-indanone-2-carboxylic acid ester, 5-fluoro-1-indanone-2-carboxylic acid ester, or 1-adamantane ester.

[0009] The Lewis acid is Cu(OTf)2, Cu(acac)2, Ti(O-iPr)4, Zr(acac)2 or Ni(acac)2, preferably Cu(OTf)2; The photosensitizer is tetraphenylpyridine (TPP), 4CzIPN, Thioxanthen-9-one, or DTBQ, preferably TPP; The solvent is toluene, xylene, dichloromethane, acetonitrile, or methyl tert-butyl ether, preferably toluene; Catalytic system construction: (1) Metal complex: Polyamide ligands coordinate with Cu(OTf)2 to form an active catalytic center; (2) Photosensitizer synergy: TPP acts as a photosensitizer, activating singlet oxygen (OTf) under visible light. 1 O2).

[0010] A monomer, the structural formula of which is as follows: .

[0011] The essential features of this invention are: Currently, the catalysts used in the asymmetric α-hydroxylation reaction of β-keto esters are mostly small organic molecule catalysts and chiral metal complex catalysts. Some small molecule catalysts have limited substrate applicability and cannot be recovered, while homogeneous metal complexes suffer from separation difficulties and poor cycle stability. This invention uses molecular oxygen instead of traditional oxidants and connects the salon structural unit to the diacyl chloride monomer through amide bonds in the polyamide skeleton, followed by complexation with a metal salt to obtain a metal complex catalyst with a chiral catalytic center. This catalyst is easily separated from the reaction mixture by simple filtration, and its catalytic activity and enantioselectivity are not significantly lost after repeated use.

[0012] The beneficial effects of this invention are as follows: This invention presents a novel chiral polyamide ligand: the Salen skeleton is embedded into the polyamide backbone, possessing both high molecular stability and chiral induction capability. The Salen ligand is formed by the condensation of two salicylaldehydes with ethylenediamine. By adjusting the substituents on the aromatic ring of salicylaldehyde or the length and configuration of the diamine ligand chain, the coordination strength and steric hindrance of the ligand can be altered, thereby achieving coordination design. By introducing an amino group into the ligand monomer and then condensing it with a diacyl chloride to construct a ligand polymer linked by amide bonds, followed by complexation with a metal salt, a metal complex catalyst with a chiral catalytic center is obtained. This catalyst is applied to the asymmetric α-hydroxylation reaction of β-keto esters; a green catalytic system is employed, using molecular oxygen (O2) instead of traditional oxidants to achieve an environmentally friendly reaction; photocatalysis and metal catalysis work synergistically, reducing energy consumption and byproduct formation; the product yield is as high as 93%, with an enantiomeric excess of 59%; and it has broad applicability, compatible with electron-withdrawing groups (Cl, Br), electron-donating groups (OMe), and sterically hindered adamantane ester substrates. Attached Figure Description

[0013] Figure 1 The Fourier transform infrared spectrum of the polyamide ligand L1-PA4 obtained in Example 8; Detailed Implementation

[0014] The synthetic routes for chiral polyamide ligands (L1-PA1 to L1-PA4) are shown below:

[0015] Example 1: Synthesis of (1S,2S)-1,2-bis(3-nitrophenyl)ethylenediamine (1) 10 mL of concentrated sulfuric acid was added to a 100 mL round-bottom flask. (1S,2S)-1,2-diphenylethylenediamine (2 g, 9.43 mmol) was added in portions with stirring in an ice bath. After complete dissolution, a mixed acid solution consisting of 6 mL of concentrated sulfuric acid and 4 mL of concentrated nitric acid was slowly added dropwise. The reaction mixture was stirred in an ice bath for 2 hours, and then poured into 100 mL of ice water. The pH was adjusted to 10 with a 50% potassium hydroxide aqueous solution, and the mixture was extracted three times with ethyl acetate. The combined organic phases were washed with 100 mL of saturated brine and dried over anhydrous sodium sulfate. The solvent was removed by rotary evaporation, and the crude product was recrystallized from ethyl acetate to give a yellow solid 1.

[0016]

[0017] The hydrogen NMR spectrum data of the obtained product are as follows: ¹H NMR (400 MHz, DMSO-d⁶) δ 8.10 (t, J = 2.0 Hz, 2H), 8.01–8.00 (m, 2H), 7.64 (d, J = 7.6 Hz, 2H), 7.48 (s, 2H), 4.14 (s, 2H), 1.84 (s, 4H). Example 2: Synthesis of 6,6'-((1E,1'E)-(((1S,2S)-1,2-bis(3-nitrophenyl)ethane-1,2-diyl)bis(azobenzyl))bis(2,4-di-tert-butylphenol) (2) 3,5-Di-tert-butylsalicylaldehyde (1.03 g, 4.4 mmol) and compound 1 (600 mg, 2.0 mmol) were dissolved separately in anhydrous ethanol. The ethanol solutions of the two compounds were slowly mixed under stirring using a constant-pressure dropping funnel. The mixture was heated under reflux for 5 hours, cooled to room temperature, and the solvent was removed by rotary evaporation. The product was then purified by silica gel column chromatography (petroleum ether / ethyl acetate = 5:1) to give a white solid product 2.

[0018]

[0019] The hydrogen atomic nuclear magnetic resonance spectrum data of the obtained product are as follows: 1 H NMR (600 MHz, Chloroform-d) δ13.03 (s, 2H), 8.46 (s, 2H), 8.08 (d, J = 8.2 Hz, 2H), 8.05 (s, 2H), 7.53 (d, J = 7.7 Hz, 2H), 7.44 (t, J= 7.9 Hz, 2H), 7.37 (s, 2H), 7.01 (s, 2H), 4.87(s, 2H), 1.42 (s, 18H), 1.23 (s, 18H); 13 C NMR (151 MHz, Chloroform-d) δ168.87, 157.95, 148.25, 141.14, 140.69, 136.89, 133.95, 129.65, 128.14,126.63, 122.94, 117.49, 79.16, 35.05, 34.07, 31.35, 29.42. Example 3: Synthesis of 6,6'-((((1S,2S)-1,2-bis(3-nitrophenyl)ethane-1,2-diyl)bis(azodiyl))bis(methylene))bis(2,4-di-tert-butylphenol) (3) In a dry 50 mL round-bottom flask, compound 2 (500 mg, 1.0 eq) was dissolved in tetrahydrofuran and cooled to 0 °C in an ice-water bath. Sodium borohydride (101 mg, 4.0 eq) was added first, and the mixture was stirred for 30 minutes. Then, a second portion of sodium borohydride (15 mg, 0.6 eq) was added. The ice bath was removed, and the mixture was stirred at room temperature for 1 hour. After the reaction was complete, the reaction mixture was placed in an ice-water bath, and 50 mL of water was slowly poured in to quench the reaction. The aqueous phase was extracted with dichloromethane (50 mL × 3 times). The organic phases were combined, washed with 100 mL of saturated brine, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation under reduced pressure. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 2:1) to give a pale yellow solid product 3.

[0020]

[0021] The hydrogen NMR spectra of the obtained product are as follows: ¹H NMR (600 MHz, Chloroform-d) δ 9.27 (s, 2H), 8.08 (d, J = 4.3 Hz, 2H), 7.83 (s, 2H), 7.42 (t, J = 4.0 Hz, 2H), 7.32 (d, J = 3.8 Hz, 2H), 7.21 (s, 2H), 6.59 (s, 2H), 4.07 (s, 2H), 3.88 (d, J = 6.6 Hz, 2H), 3.65 (d, J = 6.6 Hz, 2H), 2.42 (s, 2H), 1.39 (s, 18H), 1.21 (s, 18H); ¹³C NMR (151 MHz, Chloroform-d) δ 153.53, 148.39, 141.38, 140.35,136.29, 133.74, 129.86, 123.69, 123.58, 123.31, 122.65, 120.85, 66.60, 51.33,34.90, 34.11, 31.55, 29.62. Example 4: Synthesis of ligand monomer L1 In a 50 mL round-bottom flask, compound 3 (300 mg) was dissolved in 5 mL of anhydrous methanol, and 10% Pd / C catalyst (30.0 mg) was added. A hydrogen gas bag was connected, and an oxygen-free atmosphere was established by three hydrogen purgings. The reaction was stirred at room temperature for 24 hours (TLC monitoring, petroleum ether / ethyl acetate = 2 / 1, product color development by ninhydrin). After the reaction was complete, the Pd / C catalyst was removed by diatomaceous earth filtration, and the filtrate was concentrated by rotary evaporation under reduced pressure to obtain solid L1.

[0022]

[0023] The hydrogen nuclear magnetic resonance (NMR) spectra of the obtained product are as follows: ¹H NMR (600 MHz, Chloroform-d) δ 7.14 (d, J = 1.2 Hz, 2H), 6.99 (t, J = 3.9 Hz, 2H), 6.60 (d, J = 1.2 Hz, 2H), 6.50 (dd, J = 3.9, 1.1 Hz, 2H), 6.32 (d, J = 3.8 Hz, 2H), 6.28 (t, J = 1.0 Hz, 2H), 3.90 (s, 2H), 3.72 (d, J = 6.7 Hz, 2H), 3.57 (d, J = 6.7 Hz, 2H), 3.52 (s, 2H), 1.37 (s, 18H), 1.16 (s, 18H); 13C NMR (151 MHz, Chloroform-d) δ 154.43, 146.41, 140.58, 138.89, 135.99, 129.25, 123.44, 123.06, 121.93, 118.44, 115.01, 114.64, 66.31, 51.34, 34.95, 34.11, 31.63, 29.69. The spectral data are consistent with the structure, indicating that the target product L1 was obtained.

[0024] Example 5: Synthesis of polyamide ligand L1-PA1.

[0025] Take a dry 25 mL round-bottom flask, place a magnetic stir bar inside, and replace the air in the flask with argon gas. Then place the flask in an ice-water bath, controlling the temperature at 0-5 °C. Dissolve L1 (678 mg, 1 mmol) in 5 mL of anhydrous DCM, and add triethylamine (111 mg, 1.1 mmol) to it. Stir for 5 minutes to ensure the triethylamine is evenly dispersed. Dissolve malonyl chloride (140 mg, 1 mmol) in 5 mL of anhydrous DCM, and then slowly add it dropwise to L1. During the addition, a white flocculent precipitate (triethylamine hydrochloride) will form, and the system temperature will rise slightly; the temperature should be controlled not to exceed 10 °C. After the addition is complete, remove the ice-water bath and continue stirring at room temperature for 1 hour. To synthesize high molecular weight polyamide, raise the reaction system to 30 °C and continue the reaction for 6 hours. By monitoring with TLC, ninhydrin no longer shows color after polymer formation, indicating that the reaction is basically complete. After the reaction was complete, 50 mL of deionized water was slowly poured into the reaction solution while stirring vigorously. Since the polymer is insoluble in water, while small molecule impurities are soluble, the mixture was then filtered, and the filter cake was collected and dried under vacuum. It was then recrystallized from dichloromethane / n-hexane to remove trace amounts of monomers and short-chain polymers. The filter cake was transferred to a watch glass and dried in a vacuum oven at 60 °C for 5 hours to obtain the chiral polyamide ligand L1-PA1.

[0026]

[0027] Example 6: Synthesis of chiral polyamide ligand L1-PA2 The other steps are the same as in Example 4, except that malonyl chloride is replaced with adipyl chloride to obtain chiral polyamide ligand L1-PA2.

[0028] Example 7: Synthesis of chiral polyamide ligand L1-PA3 The other steps are the same as in Example 4, except that malonyl chloride is replaced with pimecroyl chloride to obtain chiral polyamide ligand L1-PA3.

[0029] Example 8: Synthesis of chiral polyamide ligand L1-PA4 The other steps are the same as in Example 4, except that malonyl chloride is replaced with octanoyl chloride to obtain the chiral polyamide ligand L1-PA4. (See attached image) Figure 1 The Fourier transform infrared spectrum of L1-PA4 shows that L1 condenses with octanoyl chloride to form an amide bond, with the peak wavelength between 1650 and 1680 cm⁻¹. -1 The newly enhanced peak is located at the amide I band (C=O stretching vibration); while the 1550–1580 cm⁻¹ peak is... -1 An absorption peak appears within the range, which is the amide II band (coupled by NH bending vibration and CN stretching vibration).

[0030] Example 9: Catalytic asymmetric α-hydroxylation of 1-indanone-2-carboxylic acid ester

[0031] A magnetic stir bar was added to a 10 mL dry sealed tube, followed by chiral polyamide ligand L1-PA1 (24 mg, i.e., 15 mol % of the β-keto ester substrate), Cu(OTf)2 (7.2 mg, i.e., 10 mol % of the β-keto ester substrate), and 2 mL of toluene. The mixture was stirred at 50 °C for 1 hour under argon atmosphere to prepare the complex in situ. After coordination, the reaction solution was allowed to cool to room temperature. Then, β-keto ester substrate 1-indanone-2-carboxylic acid ester (1a) (38 mg, 0.2 mmol) and photosensitizer TPP (3 mg, i.e., 2.5 mol % of the β-keto ester substrate) were added, and the air was replaced with O2. This replacement operation was repeated 7 times, and the pressure was maintained at 0.1 MPa. The reaction solution was then transferred to a cold trap set to -30 °C and reacted under the illumination of a 300 W white xenon lamp (irradiation distance of 20 cm). After reacting for 15 hours in a closed environment, the starting material was completely reacted, generating the hydroxylated product and its peroxide. 32 mg of sodium bisulfite was added to the reaction flask, and the mixture was stirred at room temperature for 30 minutes to reduce the peroxide until the starch-potassium iodide test paper did not turn blue. After the reaction was complete, the solvent was removed by rotary evaporation. The product was then subjected to column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the target product 2a. The purification yield was calculated, and the enantiomeric excess (ee) was determined by high-performance liquid chromatography.

[0032] Examples 10-12: Catalytic asymmetric α-hydroxylation of 1-indanone-2-carboxylic acid ester The other steps are the same as in Example 9, except that L1-PA1 is replaced by L1-PA2, L1-PA3, and L1-PA4 respectively.

[0033] The results obtained under different ligands are shown in Table 1.

[0034] Table 1. Effects of different ligands on the reaction

[0035] Examples 13-15: Catalytic asymmetric α-hydroxylation of 1-indanone-2-carboxylic acid ester The other steps are the same as in Example 12, except that the ligand L1-PA4 (24 mg, 15 mol %) is replaced with 13 mol%, 17 mol%, and 19 mol, respectively.

[0036] The results obtained from the reaction at the appropriate amounts of ligand L1-PA4 are shown in Table 2.

[0037] Table 2 Effect of L1-PA4 dosage on the reaction

[0038] Examples 16-18: Catalytic asymmetric α-hydroxylation of 1-indanone-2-carboxylic acid esters The other steps are the same as in Example 14, except that the photosensitizer TPP (3 mg, 2.5 mol %) is replaced with 0.5 mol%, 1 mol%, and 5 mol, respectively.

[0039] The results obtained from the reaction at different amounts of photosensitizer TPP are shown in Table 3.

[0040] Table 3 Effect of photosensitizer TPP dosage on the reaction

[0041] Examples 19-21: Catalytic asymmetric α-hydroxylation of 1-indanone-2-carboxylic acid esters The other steps are the same as in Example 17, except that -30 ℃ is replaced with 0 ℃, -15 ℃, and -45 ℃ respectively.

[0042] The results obtained from the reaction at different temperatures are shown in Table 4.

[0043] Table 4 Effect of temperature on the reaction

[0044] Examples 22-23: Catalytic asymmetric α-hydroxylation of 1-indanone-2-carboxylic acid ester The other steps are the same as in Example 21, except that 0.1 MPa is replaced with 0.2 MPa and 0.3 MPa respectively.

[0045] The results obtained under different pressures are shown in Table 5.

[0046] Table 5 Effect of pressure on the reaction

[0047] Examples 24-28: Substrate screening The other steps are the same as in Example 21, except that 1-indanone-2-carboxylate (1a) is replaced with 5-chloro-1-indanone-2-carboxylate (1b), 5-bromo-1-indanone-2-carboxylate (1c), 5-fluoro-1-indanone-2-carboxylate (1d), or 1-adamantane ester (1e).

[0048]

[0049] The nuclear magnetic resonance spectrum, high-resolution mass spectrum and high-performance liquid chromatography data of the obtained product are as follows:

[0050] (S)-2-hydroxy-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (2a) Prepared according to the general procedure with a reaction time of 20 h. After column chromatography (ether / ethyl acetate = 5 / 1) to give 2a as white solid; m.p. 143-145 ℃; 1H NMR (400 MHz, Chloroform-d) δ 7.83 (d, J = 7.7 Hz, 1H), 7.70 (t, J = 7.6 Hz, 1H), 7.52 (d, J = 7.8 Hz, 1H), 7.46 (t, J = 7.5 Hz, 1H), 4.08 (s, 1H), 3.79 – 3.73 (m, 4H), 3.28 (d, J = 17.3 Hz, 1H). HPLC conditions: Chiralcel OD-H column (250×4.6 mm), hexane / i-PrOH = 90 / 10, 1 mL / min, 254 nm, τR (major) = 11.5 min, τR (minor) = 13.7 min.

[0051] ( S )-Methyl 5-chloro-2-hydroxy-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (2b) Prepared according to the general procedure with a reaction time of 20 h. After column chromatography (petroleum ether / ethyl acetate = 5 / 1) to give 2b as white solid; m.p. 131-133 ℃; 1H NMR (600 MHz, Chloroform-d)δ 7.73 (d, J = 8.2 Hz, 1H), 7.49 (s, 1H), 7.42 (d, J = 8.2 Hz, 1H), 4.01 (s,1H), 3.75 (s, 3H), 3.70 (d, J = 17.4 Hz, 1H), 3.23 (d, J = 17.4 Hz, 1H); HPLCconditions: Chiralcel OD-H column (250×4.6 mm), hexane / i -PrOH = 90 / 10, 1 mL / min, 254 nm, t R (major) = 12.3 min, t R (minor) = 15.0 min.

[0052] (S)-Methyl 5-bromo-2-hydroxy-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (2c) Prepared according to the general procedure with a reactiontime of 20 h. After column chromatography (ether / ethyl acetate = 5 / 1) to give2c as white solid; m.p. 124-126 ℃; 1H NMR (600 MHz, Chloroform-d) δ 8.20 (d,J = 4.2 Hz, 1H), 7.77 (s, 1H), 7.76 (s, 1H), 7.41 (s, 1H), 3.97 (s, 3H), 1.56(s, 2H); HPLC conditions: Chiralcel OD-H column (250×4.6 mm), hexane / i-PrOH= 90 / 10, 1 mL / min, 254 nm, τR (major) = 13.3 min, τR (minor) = 15.6 min.

[0053] (S)-Methyl 2-hydroxy-5-fluorine-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (2d) Prepared according to the general procedure with a reactiontime of 20 h. After column chromatography (ether / ethyl acetate = 5 / 1) to give2d as white solid; m.p. 143-145 ℃; 1H NMR (600 MHz, Chloroform-d) δ 7.82(dd, J = 4.3, 2.6 Hz, 1H), 7.16 (d, J = 4.3 Hz, 1H), 7.13 (dd, J = 4.3, 1.1Hz, 1H), 3.99 (s, 1H), 3.75 (s, 3H), 3.72 (d, J = 8.7 Hz, 1H), 3.24 (d, J =8.7 Hz, 1H); HPLC conditions: Chiralcel OD-H column (250×4.6 mm), hexane / i-PrOH = 90 / 10, 1 mL / min, 254 nm, τR (major) = 12.1 min, τR (minor) = 14.9.

[0054] ( S )-1-Adamantyl 2-hydroxy-1-indanone-2-carboxylate (2e) reparedaccording to the general procedure with a reaction time of 20 h. After columnchromatography (ether / ethyl acetate = 15 / 1 ) to give 2e as white solid; m.p.=81-83 ℃; 29.1mg, 89.4% 1 H NMR (600 MHz, Chloroform- d ) δ 7.71 (d, J = 7.6 Hz,1H), 7.57 (t,J = 7.5 Hz, 1H), 7.39 (d, J = 7.6 Hz, 1H), 7.33 (t, J = 7.5 Hz, 1H), 3.58 (d, J = 17.0 Hz, 1H), 3.14 (d, J = 17.0 Hz, 1H), 2.04 (s, 4H), 1.89(s, 4H), 1.52 (s, 7H). HPLC conditions: Chiralcel AD-H column (250 × 4.6mm), hexane / i -PrOH = 80 / 20, 1 mL / min, 254nm, t R (major) = 9.9 min, t R (minor) = 14.9 min Matters not covered in this invention are common knowledge.

Claims

1. A chiral polyamide ligand based on the Salen skeleton, characterized in that, The structural formula of the ligand is as follows: ， Among them, R 2 It is methyl-1,4-methyl-1,5-methyl-1,6-methyl-1; n is 100 ~ 10000.

2. The method for preparing chiral polyamide ligands based on the Salen framework as described in claim 1, characterized in that, The method includes the following steps: The monomer, triethylamine, and solvent were added to the reactor, and the reaction system was replaced with argon gas after sealing. Then, a diacyl chloride solution was added dropwise to the system at 0-10°C, and the reaction was carried out at 0-30°C for 5-7 hours to obtain a chiral polyamide ligand based on the Salen skeleton. Wherein, the molar ratio is monomer:triethylamine:diacyl chloride = 1:1.1:1; the solvent of the diacyl chloride solution is DCM; The solvent is dichloromethane, trichloromethane, 1,2-dichloroethane, or 1,1-dichloroethane; The monomer mentioned is: 。 3. The method for preparing chiral polyamide ligands based on the Salen framework as described in claim 1, characterized in that, The diacyl chloride is malonyl chloride, adipyl chloride, heptayl chloride, or octyl chloride.

4. The method for preparing chiral polyamide ligands based on the Salen framework as described in claim 1, characterized in that, Add 0.5-2 mmol of monomer per 5 ml of solvent.

5. The application of the Salen-based chiral polyamide ligand as described in claim 1, characterized in that, Used for asymmetric hydroxylation of β-keto esters.

6. The application of the Salen-based chiral polyamide ligand as described in claim 1, characterized in that, Includes the following steps: The raw materials, Salen-based chiral polyamide ligands, Lewis acid, photosensitizer and solvent were added to a reactor, sealed and reacted at -45 ~ 0 ℃, oxygen pressure 0.1 ~ 0.3 MPa and white light irradiation for 15 ~ 20 hours to obtain α-hydroxy-β-keto ester; The molar ratio is: raw material: chiral polyamide ligand: Lewis acid: photosensitizer = 1: 0.13 ~ 0.19: 0.05 ~ 0.2: 0.005 ~ 0.05; The raw material is a 1-indanone-2-carboxylic acid ester derivative with chlorine, bromine, or fluorine substitutions on the benzene ring.

7. The application of the Salen-based chiral polyamide ligand as described in claim 1, characterized in that, The raw materials are 1-indanone-2-carboxylic acid ester, 5-chloro-1-indanone-2-carboxylic acid ester, 5-bromo-1-indanone-2-carboxylic acid ester, 5-fluoro-1-indanone-2-carboxylic acid ester, or 1-adamantane ester.

8. The application of the Salen-based chiral polyamide ligand as described in claim 1, characterized in that, The Lewis acid is Cu(OTf)2, Cu(acac)2, Ti(O-iPr)4, Zr(acac)2 or Ni(acac)2; The photosensitizer is tetraphenylpyridine (TPP), 4CzIPN, Thioxanthen-9-one, or DTBQ; The solvent is toluene, xylene, dichloromethane, acetonitrile, or methyl tert-butyl ether.

9. A monomer, characterized in that, The structural formula of the monomer is as follows: 。

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