A method of synthesizing 5-hydroxymethyl oxazolidinone

Abstract

The application develops a halogen-free pyridine anion organic ion pair catalyst, which catalyzes intramolecular cycloaddition reaction of epoxy amine and CO2 to realize efficient preparation of 5-hydroxymethyl oxazolidinone. The application first proposes that the halogen-free organic ion pair catalyst composed of a hydroxypyridine and a common organic base catalyzes epoxy amine and CO2 to generate 5-hydroxymethyl oxazolidinone.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, and specifically relates to a method for the synthesis of 5-hydroxymethyloxazolidinone catalyzed by a halogen-free ion-pair catalyst. Background Technology

[0002] Nitrogen- and oxygen-containing five-membered heterocyclic compounds, such as 2-oxazolidinone, are structural units commonly found in pharmaceutical chemistry and organic synthesis. Active drugs with this core structure, such as toloxacin, rivaroxaban, linezolid, and depazolid, have been developed for clinical use (Med. Chem., 2008, 51:6558; Med. Chem., 2007, 7:389; Drugs., 2000, 59:7). Since the first synthesis of oxazolidinone in 1958, many novel synthetic strategies have been developed, such as: multi-component coupling of amine derivatives with carbonylating agents (J. Org. Chem., 2014, 79:9347; CN112851597B), cycloaddition reactions using epoxides or pyridines as starting materials and CO2 (ChemSusChem., 2019, 12:3296), intramolecular cyclization reactions of carbamates (Org. Lett., 2014, 16:1434), and addition reactions of glycidyl and isocyanates (CN113200932B). In previous synthetic methods, the target product was mostly a 4-substituted oxazolidinone that could not be modified later; however, currently, drug molecules containing an oxazolidinone core mostly have 5-substituted functional groups.

[0003] Currently, all work on the synthesis of 5-hydroxymethyloxazolidinone is limited to metal catalysis and organocatalysis. The Lewis acid (LA) monofunctional catalysis of the cycloaddition reaction of epoxides and CO2 was first proposed by Kleij, where an aluminum complex activates the epoxide, which then reacts with carbon dioxide under pressure to convert it into the target oxazolidinone (Angew. Chem. Int. Ed., 2016, 55:3972). Metal catalysts have the advantages of high efficiency and high activity, but the problem of metal residue often limits the high-end application of the product in pharmaceutical research. Cases using organocatalysis are rarely reported; known examples include the use of triethylamine catalysis (CN113461629A) and the use of an organic hydrogen-bonded supported catalyst, polystyrene-supported 1,5,7-triazabicyclodec-5-ene, to achieve a continuous flow reaction of epoxides and CO2 (Green Chem., 2022, 24:4628). Summary of the Invention

[0004] To address the shortcomings of existing technologies, our research has revealed that the Payne-type rearrangement reaction of epoxides and CO2 can efficiently synthesize 5-hydroxymethyloxazolidinones, representing an atom-economical method. The Payne-type rearrangement phenomenon was first discovered in 1962, referring to the rearrangement of 2,3-epoxides to 1,2-epoxides under basic conditions (Org. Chem., 1962, 27:3819). Therefore, the method for synthesizing 5-hydroxymethyloxazolidinones proposed in this invention efficiently and in one step yields the target compound containing modifiable side chains through a cycloaddition reaction of simply prepared epoxides and CO2 under mild conditions, adaptable to various post-modification reactions.

[0005] Unlike the aforementioned metal catalysts and the triethylamine catalytic mechanism, the bifunctional ion pair in this method uses the oxygen anion of the catalyst as a hydrogen bond acceptor (HBA) to coordinate with the amino group via hydrogen bonds, thereby enhancing the nucleophilicity of the nitrogen atom. Simultaneously, the cation moiety acts as a hydrogen bond donor (HBD) to form hydrogen bonds with the oxygen atom of the epoxide, activating the epoxide and making it more susceptible to nucleophilic ring-opening. Through dual activation of the substrate's nucleophilic site (NH) and potentiophilic site (COC), the target product is obtained with high selectivity and efficiency. Our proposed method is entirely free of metals and halogens in the catalytic system, which opens up possibilities for future industrial applications and applications in more stringent medical research fields.

[0006] Through research, we have proposed a method for synthesizing 5-hydroxymethyloxazolidinone from epoxides and CO2 using a metal-free, halogen-free ion-pair catalyst. The technical solution to achieve the above objective is as follows:

[0007] A method for synthesizing 5-hydroxymethyloxazolidinone, using an epoxide of formula (II) and carbon dioxide in the presence of a catalyst of formula (I) to generate 5-hydroxymethyloxazolidinone;

[0008]

[0009] In formula (I), the cation is a hydrogen bond donor selected from cations containing amidine organic bases, cations of bicyclic guanidine organic bases, or cations of aminopyridine compounds; the anion is a hydrogen bond acceptor selected from anions of hydroxypyridine.

[0010] When R 1 ~R 5 When one of the substituents is selected from fluorine, chlorine, bromine, methyl, trifluoromethyl, methoxy, or ester, the other substituents are selected from hydrogen; the ester group is selected from methyl acetate or ethyl acetate;

[0011] Or when R 1 R 3 R 5When methyl is selected, the other substituents are selected from hydrogen;

[0012] Or when R 2 R 4 When the substituents are simultaneously selected from fluorine, chlorine, or bromine, the other substituents are selected from hydrogen.

[0013] Or when R 1 R 5 When isopropyl is selected, the other substituents are selected from hydrogen;

[0014] Or when R 2 R 4 When isopropyl is selected, the other substituents are selected from hydrogen;

[0015] Or when R 3 When selected from morpholino, R 4 The molecule is selected from fluorine, and other substituents are selected from hydrogen.

[0016] The cation of the amidine organic base is selected from the cation of 1,8-diazobisspirocyclic [5.4.0]undec-7-ene; the cation of the bicyclic guanidine organic base is selected from the cation of 1,5,7-triazidobiscyclic (4.4.0)dec-5-ene or the cation of 7-methyl-1,5,7-triazabicyclic (4.4.0)dec-5-ene; the cation of the aminopyridine organic base is selected from the cation of 4-dimethylaminopyridine.

[0017] The anion of the hydroxypyridine is selected from the anion of 2-hydroxypyridine, the anion of 3-hydroxypyridine, or the anion of 4-hydroxypyridine.

[0018] Preferably, the catalyst represented by formula (I) is selected from the following structures:

[0019]

[0020] More preferably, the catalyst shown in formula (I) is selected from the following structures:

[0021]

[0022] Preferably, the epoxide shown in formula (II) is selected from the following structures:

[0023]

[0024] More preferably, the epoxide shown in formula (II) is selected from the following structures:

[0025]

[0026] The method for synthesizing 5-hydroxymethyloxazolidinone is as follows: the epoxide shown in formula (II) and the catalyst shown in formula (I) are mixed and reacted in a reaction vessel at a molar ratio of 100:0.5 to 100:5. The reaction temperature is 25 to 100°C, the reaction time is 1 to 6 hours, the initial pressure of carbon dioxide is 0.05 to 1.5 MPa, and the reaction is carried out in an organic solvent medium. The reaction vessel is treated to be anhydrous and oxygen-free before the reaction and filled with carbon dioxide. The organic solvent is toluene, N,N-dimethylformamide, 1,4-dioxane, chlorobenzene, or acetonitrile.

[0027] The preferred reaction temperature of the present invention is 80°C, the preferred reaction time is 1 h, the initial pressure of carbon dioxide is 0.1 MPa, and the molar ratio of the epoxide amine shown in formula (II) to the halogen-free catalyst shown in formula (I) is 100:5.

[0028] Beneficial effects

[0029] This invention develops a halogen-free organic ion-pair catalyst containing pyridine anions to catalyze the intramolecular cycloaddition reaction of epoxides with CO2, efficiently preparing 5-hydroxymethyloxazolidinone. This invention is the first to propose using a halogen-free organic ion-pair catalyst composed of hydroxypyridine and a common organic base to catalyze the reaction of epoxides with CO2 to produce 5-hydroxymethyloxazolidinone. The technical solution of this invention can achieve at least one of the following beneficial effects:

[0030] (1) The catalytic system provided by this invention can efficiently synthesize 5-hydroxymethyloxazolidinone, a pharmaceutically active intermediate with modifiable side chain groups. Compared with the 5-hydroxymethyloxazolidinone synthesized using metal catalysts or halogen-containing catalysts in the prior art, it has the advantages of high yield, no metal residue, no halogen residue, and mild conditions. It has great commercial application potential in fields such as biomedicine where there are strict requirements for metal and halogen residues.

[0031] (2) The catalytic system of this invention uses an ion-pair bifunctional catalyst. Hydrogen bonding via HBD activates the epoxide, and hydrogen bonding between the oxyanion of the pyridine anion and the proton of the NH4+ hydrogen atom enhances the nucleophilicity of the nitrogen atom, subsequently activating carbon dioxide. Compared to other methods of synthesizing 5-hydroxymethyloxazolidinone under high temperature, high pressure, and high catalyst loading conditions, the reaction conditions of this invention are very mild, and the catalyst system is relatively simple.

[0032] (3) The catalytic reaction of the catalytic system of the present invention is simple, the required equipment is simple, and it is suitable for industrial scale-up.

[0033] (4) The catalytic system used in this invention is inexpensive and easy to prepare, and requires a small amount of catalyst, thus exhibiting the characteristics of efficient quantitative conversion. Some literature currently reports a conversion time of 20 hours (Org. Chem. Front., 2022, 9:4294) or even longer (Angew. Chem. Int. Ed., 2016, 55:3972).

[0034] In summary, compared with other existing catalytic systems, the present invention has significant advantages such as mild reaction conditions, low catalyst dosage, high efficiency, easy preparation, inexpensive and easy-to-prepare catalyst, and absence of metals and halogens. Attached Figure Description

[0035] The embodiments of the present invention will be described in detail with reference to the accompanying drawings, wherein...

[0036] Figures 1-2 : The 1H and 1C NMR spectra of the oxazolidinone obtained in Example 1;

[0037] Figures 3-24 The following are the 1H and 1C NMR spectra of the oxazolidinones obtained in Examples 16-26, respectively.

[0038] Figures 25-26 : The 1H and 1C NMR spectra of the catalyst used in Example 1;

[0039] Figures 27-31 : 1H NMR spectra of the catalysts used in Examples 2-6;

[0040] Figure 32 : The 1H NMR spectrum of the reaction solution in Example 1; Figure 33-37 The following are the 1H NMR spectra of the reaction solutions in Examples 2-6; Figures 38-48 The images show the 1H NMR spectra of the reaction solutions in Examples 16-26. Detailed Implementation

[0041] The present invention can be further illustrated by the following embodiments, which are for illustrative purposes only and not for limiting the invention. Any person skilled in the art will understand that these embodiments do not limit the invention in any way, and that appropriate modifications and data transformations can be made thereto without departing from the spirit and scope of the invention.

[0042] The 1H NMR spectra involved in the examples were measured using a Bruker Ascend TM-400 NMR spectrometer, and the deuterated reagents used were deuterated chloroform (CDCl3) or deuterated DMSO (DMSO-d6).

[0043] All raw materials used in the following examples were purchased from Anaiji Chemical.

[0044] The synthesis method of the epoxide shown in formula (II) is an improvement on the method in the literature (Synlett, 2011(2011)1831-1834), and the synthetic route is shown in the following reaction formula (using aniline without substituents as template substrate):

[0045]

[0046] We improved the original synthetic method, and the specific synthetic steps are shown in the reaction formula below. In the first step, isopropanol was used as the reaction solvent, and the intermediate product was separated and purified after the reaction. In the second step, excess potassium hydroxide was added, and the product was separated and purified to obtain the epoxyamine shown in Formula II.

[0047]

[0048] The structure of the catalytic system used in the examples is as follows:

[0049]

[0050] The structure of the epoxyamine used in the examples is as follows:

[0051]

[0052] The formula for calculating the yield of oxazolidinone described in the examples is: Yield = Selectivity × Conversion

[0053] Example 1:

[0054] The Schlenk procedure was performed to remove water and oxygen from the reaction system. The reaction flask was evacuated and then purged with 1 atm of CO2. This process was repeated three times to ensure a CO2 atmosphere was maintained. A CO2-filled balloon was inserted into the flask. Catalyst 1 (5.8 mg, 0.025 mmol, 0.05 equiv) was dissolved in N,N-dimethylformamide (0.5 ml), and finally epoxide A (75 mg, 0.5 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 80°C and reacted for 1 hour. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The results are shown in the attached figure. Figure 32As shown, apart from DMF (peak positions at 7.79 ppm, 2.75 ppm, and 2.65 ppm), only the characteristic peaks corresponding to epoxide A were detected. This indicates a reaction selectivity greater than 99% as determined by 1H NMR spectroscopy. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution. This solution was then evaporated to dryness using a rotary evaporator and dried in a vacuum oven at 45°C to constant weight, yielding a pure white solid with a yield of 90%. The 1H NMR spectrum of the product is attached. Figure 1 As shown (H NMR spectrum, 400 Hz, CDCl3). The spectral data are as follows: 1 ¹H NMR (400MHz, Chloroform-d) δ 7.51–7.44 (m, 2H), 7.36–7.26 (m, 2H), 7.08 (ddt, J = 8.5, 7.3, 1.1 Hz, 1H), 4.68 (dddd, J = 8.8, 7.1, 4.2, 3.3 Hz, 1H), 4.03–3.87 (m, 3H), 3.70 (ddd, J = 12.5, 6.8, 4.1 Hz, 1H), 2.21 (t, J = 6.5 Hz, 1H). The carbon spectrum of the product is shown below. Figure 2 As shown, the spectral data is as follows: 13 C NMR (101MHz, Chloroform-d) δ154.74,138.09,129.11,124.22,118.32,72.80,62.88,46.35.

[0055] The catalyst 1 was prepared as follows: 4-hydroxypyridine (3 mmol, 0.2853 g, 1.0 equiv) was dissolved in 15 ml of methanol and stirred until homogeneous. TBD (3 mmol, 0.4176 g, 1 equiv) was dissolved in 10 ml of methanol. At 0 °C, the methanol solution of TBD was added dropwise to the methanol solution of 4-hydroxypyridine while stirring. After the TBD solution was completely added, the mixture was stirred at room temperature for 12 hours. After the reaction was complete, the methanol solvent was removed under reduced pressure, and the mixture was dried under vacuum for several days to obtain a yellow oily catalyst 1. The proton NMR spectrum is shown below. Figure 25 As shown (1H NMR spectrum, 400Hz, DMSO-d6). Spectral data are as follows: 1 ¹H NMR (400MHz, DMSO-d⁶) δ 7.72 (d, J = 5.7Hz, 2H), 6.69 (s, 2H), 6.10 (d, J = 5.7Hz, 2H), 3.19 (d, J = 13.8Hz, 8H), 1.85 (p, J = 5.9Hz, 4H). The carbon spectrum of the product is shown below. Figure 26 As shown (H NMR spectrum, 101 Hz, DMSO-d6). Spectral data are as follows: 13C NMR (101MHz, DMSO-d6) δ173.84,151.04,148.63,115.59,46.24,37.57,20.57.

[0056] Example 2:

[0057] The Schlenk procedure was performed to remove water and oxygen from the reaction system. The reaction flask was evacuated and then purged with 1 atm of CO2. This process was repeated three times to ensure a CO2 atmosphere was maintained. A CO2-filled balloon was inserted into the flask. Catalyst 2 (5.8 mg, 0.025 mmol, 0.05 equiv) was dissolved in N,N-dimethylformamide (0.5 ml), and finally, epoxide A (75 mg, 0.5 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 80°C and reacted for 1 hour. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The results are shown in the attached figure. Figure 33 As shown, apart from DMF (peak positions at 7.79 ppm, 2.75 ppm, and 2.65 ppm), only the characteristic peaks corresponding to epoxide A were detected. This indicates a reaction selectivity greater than 99% as determined by 1H NMR spectroscopy. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution. This solution was then evaporated to dryness using a rotary evaporator and dried in a vacuum oven at 45°C to constant weight, yielding a pure white solid with a yield of 84%.

[0058] The catalyst 2 was prepared as follows: 3-hydroxypyridine (3 mmol, 0.2853 g, 1.0 equiv) was dissolved in 15 ml of methanol and stirred until homogeneous. TBD (3 mmol, 0.4176 g, 1 equiv) was dissolved in 10 ml of methanol. At 0 °C, the methanol solution of TBD was added dropwise to the methanol solution of 3-hydroxypyridine while stirring. After the TBD solution was completely added, the mixture was stirred at room temperature for 12 hours. After the reaction was complete, the methanol solvent was removed under reduced pressure, and the mixture was dried under vacuum for several days to obtain a yellow oily catalyst 2. The proton NMR spectrum is shown below. Figure 27 As shown (H NMR spectrum, 400 MHz, DMSO-d6). Spectral data are as follows: 1 H NMR (400MHz, DMSO-d6) δ8.04(s,2H),7.76(d,J=2.9Hz,1H),7.48(dd,J=4.5,1.4Hz,1H),6.87(dd ,J=8.2,4.4Hz,1H),6.66(ddd,J=8.3,3.0,1.5Hz,1H),3.25–3.13(m,8H),1.83(p,J=5.9Hz,4H).

[0059] Example 3:

[0060] The Schlenk procedure was performed to remove water and oxygen from the reaction system. The reaction flask was evacuated and then purged with 1 atm of CO2. This process was repeated three times to ensure a CO2 atmosphere was maintained. A CO2-filled balloon was inserted into the flask. Catalyst 3 (5.8 mg, 0.025 mmol, 0.05 equiv) was dissolved in N,N-dimethylformamide (0.5 ml), and finally, epoxide A (75 mg, 0.5 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 80°C and reacted for 1 hour. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The results are shown in the attached figure. Figure 34 As shown, apart from DMF (peak positions at 7.79 ppm, 2.75 ppm, and 2.65 ppm), only the characteristic peaks corresponding to epoxide A were detected. This indicates a reaction selectivity greater than 99% as determined by 1H NMR spectroscopy. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution. This solution was then evaporated to dryness using a rotary evaporator and dried in a vacuum oven at 45°C to constant weight, yielding a pure white solid with a yield of 80%.

[0061] The catalyst 3 was prepared as follows: 2-hydroxypyridine (3 mmol, 0.2853 g, 1.0 equiv) was dissolved in 15 ml of methanol and stirred until homogeneous. TBD (3 mmol, 0.4176 g, 1 equiv) was dissolved in 10 ml of methanol. At 0 °C, the methanol solution of TBD was added dropwise to the methanol solution of 2-hydroxypyridine while stirring. After the TBD solution was completely added, the mixture was stirred at room temperature for 12 hours. After the reaction was complete, the methanol solvent was removed under reduced pressure, and the mixture was dried under vacuum for several days to obtain a yellow oily catalyst 3. The proton NMR spectrum is shown below. Figure 28 As shown (1H NMR spectrum, 400Hz, DMSO-d6). Spectral data are as follows: 1 H NMR(400MHz,DMSO-d6)δ8.81(s,2H),7.61–7.53(m,1H),7.18(ddd,J=8.9,6 .9, 2.4Hz, 1H), 6.08–5.99 (m, 2H), 3.26–3.17 (m, 8H), 1.85 (p, J = 5.9Hz, 4H).

[0062] Example 4:

[0063] The Schlenk procedure was performed to remove water and oxygen from the reaction system. The reaction flask was evacuated and then purged with 1 atm of CO2. This process was repeated three times to ensure a CO2 atmosphere was maintained. A CO2-filled balloon was inserted into the flask. Catalyst 4 (6.2 mg, 0.025 mmol, 0.05 equiv) was dissolved in N,N-dimethylformamide (0.5 ml), and finally, epoxide A (75 mg, 0.5 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 80°C and reacted for 1 hour. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The results are shown in the attached figure. Figure 35 As shown, apart from DMF (peak positions at 7.79 ppm, 2.75 ppm, and 2.65 ppm), only the characteristic peaks corresponding to epoxide A were detected. This indicates a reaction selectivity greater than 99% as determined by 1H NMR spectroscopy. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution. This solution was then evaporated to dryness using a rotary evaporator and dried in a vacuum oven at 45°C to constant weight, yielding a pure white solid with a yield of 85%.

[0064] Catalyst 4 was prepared as follows: 4-hydroxypyridine (3 mmol, 0.2853 g, 1.0 equiv) was dissolved in 15 ml of methanol and stirred until homogeneous. MTBD (3 mmol, 0.4597 g, 1 equiv) was dissolved in 10 ml of methanol. At 0 °C, the methanol solution of MTBD was added dropwise to the methanol solution of 4-hydroxypyridine while stirring. After the MTBD solution was completely added, the mixture was stirred at room temperature for 12 hours. After the reaction was complete, the methanol solvent was removed under reduced pressure, and the mixture was dried under vacuum for several days to obtain a yellow oily catalyst 4. The proton NMR spectrum is shown below. Figure 29 As shown (1H NMR spectrum, 400Hz, DMSO-d6). Spectral data are as follows: 1 HNMR(400MHz,DMSO-d6)δ7.83–7.72(m,2H),6.28–6.19(m,2H),6.06(s,2H), 3.23–3.12(m,8H),2.85(s,3H),1.89(p,J=6.0Hz,2H),1.79(p,J=5.9Hz,2H).

[0065] Example 5:

[0066] The Schlenk procedure was performed to remove water and oxygen from the reaction system. The reaction flask was evacuated and then purged with 1 atm of CO2. This process was repeated three times to ensure a CO2 atmosphere was maintained. A CO2-filled balloon was inserted into the flask. Catalyst 5 (6.2 mg, 0.025 mmol, 0.05 equiv) was dissolved in N,N-dimethylformamide (0.5 ml), and finally epoxide A (75 mg, 0.5 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 80°C and reacted for 1 hour. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The results are shown in the attached figure. Figure 36 As shown, apart from DMF (peak positions at 7.79 ppm, 2.75 ppm, and 2.65 ppm), only the characteristic peaks corresponding to epoxide A were detected. This indicates a reaction selectivity greater than 99% as determined by 1H NMR spectroscopy. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution. This solution was then evaporated to dryness using a rotary evaporator and dried in a vacuum oven at 45°C to constant weight, yielding a pure white solid with a yield of 65%.

[0067] The catalyst 5 was prepared as follows: 4-hydroxypyridine (3 mmol, 0.2853 g, 1.0 equiv) was dissolved in 15 ml of methanol and stirred until homogeneous. DBU (3 mmol, 0.4586 g, 1 equiv) was dissolved in 10 ml of methanol. At 0 °C, the methanol solution of DBU was added dropwise to the methanol solution of 4-hydroxypyridine while stirring. After the DBU solution was completely added, the mixture was stirred at room temperature for 12 hours. After the reaction was complete, the methanol solvent was removed under reduced pressure, and the mixture was dried under vacuum for several days to obtain a yellow oily catalyst 5. The proton NMR spectrum is shown below. Figure 30 As shown (1H NMR spectrum, 400Hz, DMSO-d6). Spectral data are as follows: 1 H NMR(400MHz,DMSO-d6)δ8.24(s,2H),7.86–7.73(m,2H),6.27–6.13(m,2H),3.3 7–3.27(m,4H),3.15(d,J=5.8Hz,4H),1.79(p,J=5.8Hz,2H),1.62–1.51(m,6H).

[0068] Example 6:

[0069] The Schlenk procedure was performed to remove water and oxygen from the reaction system. The reaction flask was evacuated and then purged with 1 atm of CO2. This process was repeated three times to ensure a CO2 atmosphere was maintained. A CO2-filled balloon was inserted into the flask. Catalyst 6 (5.4 mg, 0.025 mmol, 0.05 equiv) was dissolved in N,N-dimethylformamide (0.5 ml), and finally epoxide A (75 mg, 0.5 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 80°C and reacted for 1 hour. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The results are shown in the attached figure. Figure 37 As shown, apart from DMF (peak positions at 7.79 ppm, 2.75 ppm, and 2.65 ppm), only the characteristic peaks corresponding to epoxide A were detected. This indicates a reaction selectivity greater than 99% as determined by 1H NMR spectroscopy. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution. This solution was then evaporated to dryness using a rotary evaporator and dried in a vacuum oven at 45°C to constant weight, yielding a pure white solid with a yield of 50%.

[0070] The catalyst 6 was prepared as follows: 4-hydroxypyridine (3 mmol, 0.2853 g, 1.0 equiv) was dissolved in 15 ml of methanol and stirred until homogeneous. DMAP (3 mmol, 0.3365 g, 1 equiv) was dissolved in 10 ml of methanol. At 0 °C, the methanol solution of DMAP was added dropwise to the methanol solution of 4-hydroxypyridine while stirring. After the DMAP solution was completely added, the mixture was stirred at room temperature for 12 hours. After the reaction was complete, the methanol solvent was removed under reduced pressure, and the mixture was dried under vacuum for several days to obtain a yellow oily catalyst 6. The proton NMR spectrum is shown below. Figure 31 As shown (1H NMR spectrum, 400Hz, DMSO-d6). Spectral data are as follows: 1 HNMR (400MHz, DMSO-d6) δ8.16–8.03(m,2H),7.70(d,J=6.9Hz,2H),6.66–6.53(m,2H),6.17(d,J=6.8Hz,2H),3.51–3.25(m,2H),2.94(s,6H).

[0071] Example 7:

[0072] The Schlenk procedure was performed to remove water and oxygen from the reaction system. The reaction flask was evacuated and purged with 1 atm of CO2, then repeated three times to ensure a CO2 atmosphere. A CO2-filled balloon was inserted into the flask. Catalyst 1 (5.8 mg, 0.025 mmol, 0.05 equiv) was dissolved in N,N-dimethylformamide (0.5 ml), and finally epoxide A (75 mg, 0.5 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 60°C for 1 hour. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution. This mixed solution was evaporated to dryness using a rotary evaporator and then dried in a vacuum drying oven at 45°C to constant weight, yielding a pure white solid with a yield of 84%.

[0073] Example 8:

[0074] The Schlenk procedure was performed to remove water and oxygen from the reaction system. The reaction flask was evacuated and purged with 1 atm of CO2, then repeated three times to ensure a CO2 atmosphere. A CO2-filled balloon was inserted into the flask. Catalyst 1 (5.8 mg, 0.025 mmol, 0.05 equiv) was dissolved in N,N-dimethylformamide (0.5 ml), and finally epoxide A (75 mg, 0.5 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 100°C and reacted for 1 hour. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution. This mixed solution was evaporated to dryness using a rotary evaporator and then dried in a vacuum drying oven at 45°C to constant weight, yielding a pure white solid with a yield of 92%.

[0075] Example 9:

[0076] The Schlenk procedure was performed to remove water and oxygen from the reaction system. The reaction flask was evacuated and purged with 1 atm of CO2, then repeated three times to ensure a CO2 atmosphere. A CO2-filled balloon was inserted into the flask. Catalyst 1 (5.8 mg, 0.025 mmol, 0.05 equiv) was dissolved in N,N-dimethylformamide (0.5 ml), and finally epoxide A (75 mg, 0.5 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 80°C for 2 hours. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution. This mixed solution was evaporated to dryness using a rotary evaporator and then dried in a vacuum drying oven at 45°C to constant weight, yielding a pure white solid with a yield of 93%.

[0077] Example 10:

[0078] The Schlenk procedure was performed to remove water and oxygen from the reaction system. The reaction flask was evacuated and purged with 1 atm of CO2, and this process was repeated three times to ensure a CO2 atmosphere. A CO2-filled balloon was inserted into the flask. Catalyst 1 (5.8 mg, 0.025 mmol, 0.05 equiv) was dissolved in N,N-dimethylformamide (0.5 ml), and finally epoxide A (75 mg, 0.5 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 80°C for 4 hours. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution. This mixed solution was evaporated to dryness using a rotary evaporator and then dried in a vacuum drying oven at 45°C to constant weight, yielding a pure white solid with a yield of 99%.

[0079] Example 11:

[0080] The Schlenk procedure was performed to remove water and oxygen from the reaction system. The reaction flask was evacuated and purged with 1 atm of CO2, and this process was repeated three times to ensure a CO2 atmosphere. A CO2-filled balloon was inserted into the flask. Catalyst 1 (5.8 mg, 0.025 mmol, 0.05 equiv) was dissolved in acetonitrile (0.5 ml), and finally, epoxide A (75 mg, 0.5 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 80°C for 1 hour. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution. This mixed solution was evaporated to dryness using a rotary evaporator and then dried in a vacuum drying oven at 45°C to constant weight, yielding a pure white solid with a yield of 35%.

[0081] Example 12:

[0082] The Schlenk procedure was performed to remove water and oxygen from the reaction system. The reaction flask was evacuated and purged with 1 atm of CO2, then this process was repeated three times to ensure a CO2 atmosphere. A CO2-filled balloon was inserted into the flask. Catalyst 1 (5.8 mg, 0.025 mmol, 0.05 equiv) was dissolved in chlorobenzene (0.5 ml), and finally, epoxide A (75 mg, 0.5 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 80°C for 1 hour. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution. This mixed solution was evaporated to dryness using a rotary evaporator and then dried in a vacuum drying oven at 45°C to constant weight, yielding a pure white solid with a yield of 42%.

[0083] Example 13:

[0084] The Schlenk procedure was performed to remove water and oxygen from the reaction system. The reaction flask was evacuated and purged with 1 atm of CO2, repeated three times to ensure a CO2 atmosphere. A CO2-filled balloon was inserted into the flask. Catalyst 1 (5.8 mg, 0.025 mmol, 0.05 equiv) was dissolved in 1,4-dioxane (0.5 ml), and finally epoxide A (75 mg, 0.5 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 80°C for 1 hour. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution. This mixed solution was evaporated to dryness using a rotary evaporator and then dried in a vacuum drying oven at 45°C to constant weight, yielding a pure white solid with a yield of 23%.

[0085] Example 14:

[0086] The Schlenk procedure was performed under anhydrous and oxygen-free conditions to remove water and oxygen from the reaction system. The reaction flask was evacuated and purged with 1 atm of CO2, and this process was repeated three times to ensure a CO2 atmosphere. A CO2-filled balloon was inserted into the flask. Catalyst 1 (1.2 mg, 0.0125 mmol, 0.025 equiv) was dissolved in N,N-dimethylformamide (0.5 ml), and finally, epoxide A (75 mg, 0.5 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 80°C and reacted for 1 hour. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution. This mixed solution was evaporated to dryness using a rotary evaporator and then dried in a vacuum drying oven at 45°C to constant weight, yielding a pure white solid with a yield of 74%.

[0087] Example 15:

[0088] The Schlenk procedure was performed to remove water and oxygen from the reaction system. The reaction flask was evacuated and purged with 1 atm of CO2, then repeated three times to ensure a CO2 atmosphere. A CO2-filled balloon was inserted into the flask. Catalyst 1 (2.9 mg, 0.005 mmol, 0.01 equiv) was dissolved in N,N-dimethylformamide (0.5 ml), and finally epoxide A (75 mg, 0.5 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 80°C for 1 hour. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution. This mixed solution was evaporated to dryness using a rotary evaporator and then dried in a vacuum drying oven at 45°C to constant weight, yielding a pure white solid with a yield of 48%.

[0089] Example 16:

[0090] The Schlenk procedure was performed to remove water and oxygen from the reaction system. The reaction flask was evacuated and then filled with 1 atm of CO2. This process was repeated three times to ensure a CO2 atmosphere was maintained. A CO2-filled balloon was inserted into the flask. Catalyst 1 (5.8 mg, 0.025 mmol, 0.05 equiv) was dissolved in N,N-dimethylformamide (0.5 ml), and finally epoxide B (82 mg, 0.5 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 80°C and reacted for 1 hour. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The results are shown in the attached figure. Figure 38 As shown, apart from DMF (peak positions at 7.79 ppm, 2.75 ppm, and 2.65 ppm), only the characteristic peaks corresponding to epoxide B were detected. This indicates a reaction selectivity greater than 99% as determined by 1H NMR spectroscopy. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution. This solution was then evaporated to dryness using a rotary evaporator and dried in a vacuum oven at 45°C to constant weight, yielding a pure white solid with a yield of 80%. The 1H NMR spectrum of the product is attached. Figure 3 As shown (H NMR spectrum, 400 Hz, CDCl3). The spectral data are as follows: 1¹H NMR (400MHz, Chloroform-d) δ 7.24–7.15 (m, 4H), 4.71 (ddt, J = 9.6, 6.7, 3.4Hz, 1H), 3.95–3.78 (m, 3H), 3.66 (d, J = 12.4Hz, 1H), 2.55 (s, 1H), 2.24 (s, 3H). The carbon spectrum of the product is shown below. Figure 4 As shown, the spectral data is as follows: 13 C NMR (101MHz, Chloroform-d) δ156.65,136.22,135.89,131.47,128.46,127.11,126.92,74.07,62.97,49.02,17.90.

[0091] Example 17

[0092] The Schlenk procedure was performed to remove water and oxygen from the reaction system. The reaction flask was evacuated and then purged with 1 atm of CO2. This process was repeated three times to ensure a CO2 atmosphere was maintained. A CO2-filled balloon was inserted into the flask. Catalyst 1 (5.8 mg, 0.025 mmol, 0.05 equiv) was dissolved in N,N-dimethylformamide (0.5 ml), and finally epoxide C (82 mg, 0.5 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 80°C and reacted for 1 hour. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The results are shown in the attached figure. Figure 39 As shown, apart from DMF (peak positions at 7.79 ppm, 2.75 ppm, and 2.65 ppm), only the characteristic peaks corresponding to epoxide C were detected. This indicates a reaction selectivity greater than 99% as determined by 1H NMR spectroscopy. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution. This solution was then evaporated to dryness on a rotary evaporator and dried in a vacuum oven at 45°C to constant weight, yielding a pure white solid with a yield of 88%. The 1H NMR spectrum of the product is attached. Figure 5 As shown (H NMR spectrum, 400 Hz, CDCl3). The spectral data are as follows: 1 ¹H NMR (400MHz, Chloroform-d) δ 7.23–7.08 (m, 2H), 6.84 (d, J = 7.4 Hz, 1H), 4.60 (tt, J = 7.6, 3.5 Hz, 1H), 3.87 (ddd, J = 18.0, 13.6, 5.9 Hz, 3H), 3.62 (dd, J = 12.3, 3.9 Hz, 1H), 2.63 (s, 1H), 2.24 (s, 3H). The carbon spectrum of the product is shown below. Figure 6As shown, the spectral data is as follows: 13 C NMR (101MHz, Chloroform-d) δ155.03,139.15,138.13,129.00,125.17,119.24,115.63,73.02,62.92,46.60,21.75.

[0093] Example 18:

[0094] The Schlenk procedure was performed to remove water and oxygen from the reaction system. The reaction flask was evacuated and then purged with 1 atm of CO2. This process was repeated three times to ensure a CO2 atmosphere was maintained. A CO2-filled balloon was inserted into the flask. Catalyst 1 (5.8 mg, 0.025 mmol, 0.05 equiv) was dissolved in N,N-dimethylformamide (0.5 ml), and finally epoxide D (82 mg, 0.5 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 80°C and reacted for 1 hour. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The results are shown in the attached figure. Figure 40 As shown, apart from DMF (peak positions at 7.79 ppm, 2.75 ppm, and 2.65 ppm), only the characteristic peaks corresponding to epoxide D were detected. This indicates a reaction selectivity greater than 99% as determined by 1H NMR spectroscopy. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution. This solution was then evaporated to dryness on a rotary evaporator and dried in a vacuum oven at 45°C to constant weight, yielding a pure white solid with a yield of 81%. The 1H NMR spectrum of the product is attached. Figure 7 As shown (H NMR spectrum, 400 Hz, CDCl3). The spectral data are as follows: 1 ¹H NMR (400MHz, Chloroform-d) δ 7.39–7.29 (m, 2H), 7.11 (d, J = 8.2 Hz, 2H), 4.67 (ddt, J = 9.0, 7.2, 3.7 Hz, 1H), 4.01–3.85 (m, 3H), 3.70 (dd, J = 12.5, 4.3 Hz, 1H), 2.26 (s, 3H), 1.57 (s, 1H). The carbon spectrum of the product is shown below. Figure 8 As shown, the spectral data is as follows: 13 C NMR (101MHz, Chloroform-d) δ 137.22, 132.06, 119.71, 117.05, 72.74, 62.76, 46.17.

[0095] Example 19:

[0096] The Schlenk procedure was performed to remove water and oxygen from the reaction system. The reaction flask was evacuated and then purged with 1 atm of CO2. This process was repeated three times to ensure a CO2 atmosphere was maintained. A CO2-filled balloon was inserted into the flask. Catalyst 1 (5.8 mg, 0.025 mmol, 0.05 equiv) was dissolved in N,N-dimethylformamide (0.5 ml), and finally epoxide E (92 mg, 0.5 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 80°C and reacted for 1 hour. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The results are shown in the attached figure. Figure 41 As shown, apart from DMF (peak positions at 7.79 ppm, 2.75 ppm, and 2.65 ppm), only the characteristic peaks corresponding to epoxide E were detected. This indicates a reaction selectivity greater than 99% as determined by 1H NMR spectroscopy. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution. This solution was then evaporated to dryness on a rotary evaporator and dried in a vacuum oven at 45°C to constant weight, yielding a pure white solid with a yield of 87%. The 1H NMR spectrum of the product is attached. Figure 9 As shown (H NMR spectrum, 400 Hz, CDCl3). The spectral data are as follows: 1 ¹H NMR (400MHz, Chloroform-d) δ 7.57 (t, J = 2.1 Hz, 1H), 7.40 (dd, J = 8.4, 2.2 Hz, 1H), 7.30–7.22 (m, 1H), 7.08 (dd, J = 7.9, 1.9 Hz, 1H), 4.72 (tt, J = 7.4, 3.4 Hz, 1H), 3.97 (td, J = 9.5, 9.0, 3.7 Hz, 3H), 3.72 (dd, J = 12.7, 3.7 Hz, 1H), 2.74 (s, 1H). The carbon spectrum of the product is shown below. Figure 10 As shown, the spectral data is as follows: 13 CNMR(101MHz,Chloroform-d)δ154.83,139.33,134.95,130.19,124.24,118.40,116.24,73.19,62.67,46.29.

[0097] Example 20:

[0098] The Schlenk procedure was performed to remove water and oxygen from the reaction system. The reaction flask was evacuated and then purged with 1 atm of CO2. This process was repeated three times to ensure a CO2 atmosphere was maintained. A CO2-filled balloon was inserted into the flask. Catalyst 1 (5.8 mg, 0.025 mmol, 0.05 equiv) was dissolved in N,N-dimethylformamide (0.5 ml), and finally epoxide F (92 mg, 0.5 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 80°C and reacted for 1 hour. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The results are shown in the attached figure. Figure 42 As shown, apart from DMF (peak positions at 7.79 ppm, 2.75 ppm, and 2.65 ppm), only the characteristic peaks corresponding to epoxide F were detected. This indicates a reaction selectivity greater than 99% as determined by 1H NMR spectroscopy. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution. This solution was then evaporated to dryness using a rotary evaporator and dried in a vacuum oven at 45°C to constant weight, yielding a pure white solid with a yield of 91%. The 1H NMR spectrum of the product is attached. Figure 11 As shown (H NMR spectrum, 400 Hz, CDCl3). The spectral data are as follows: 1 ¹H NMR (400MHz, Chloroform-d) δ 7.53–7.45 (m, 2H), 7.37–7.29 (m, 2H), 4.75 (ddt, J = 8.8, 7.0, 3.5Hz, 1H), 4.06–3.94 (m, 3H), 3.76 (dd, J = 12.7, 3.9Hz, 1H), 2.09 (s, 1H). The carbon spectrum of the product is shown below. Figure 12 As shown, the spectral data is as follows: 13 C NMR (101MHz, Chloroform-d) δ154.61,136.69,129.43,129.11,119.41,72.82,62.71,46.24.

[0099] Example 21:

[0100] The Schlenk procedure was performed to remove water and oxygen from the reaction system. The reaction flask was evacuated and then purged with 1 atm of CO2. This process was repeated three times to ensure a CO2 atmosphere was maintained. A CO2-filled balloon was inserted into the flask. Catalyst 1 (5.8 mg, 0.025 mmol, 0.05 equiv) was dissolved in N,N-dimethylformamide (0.5 ml), and finally epoxide G (108 mg, 0.5 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 80°C and reacted for 1 hour. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The results are shown in the attached figure. Figure 43 As shown, apart from DMF (peak positions at 7.79 ppm, 2.75 ppm, and 2.65 ppm), only the characteristic peaks corresponding to epoxide G were detected. This indicates a reaction selectivity greater than 99% as determined by 1H NMR spectroscopy. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution. This solution was then evaporated to dryness on a rotary evaporator and dried in a vacuum oven at 45°C to constant weight, yielding a pure white solid with a yield of 85%. The 1H NMR spectrum of the product is attached. Figure 13 As shown (H NMR spectrum, 400 Hz, CDCl3). The spectral data are as follows: 1 ¹H NMR (400MHz, Chloroform-d) δ 7.50 (d, J = 1.8 Hz, 2H), 7.12 (t, J = 1.8 Hz, 1H), 4.76 (dq, J = 8.6, 3.5 Hz, 1H), 4.06–3.94 (m, 3H), 3.75 (dd, J = 12.7, 3.6 Hz, 1H). The carbon spectrum of the product is shown below. Figure 14 As shown, the spectral data is as follows: 13 C NMR (101MHz, Chloroform-d) δ154.37,140.02,135.63,124.12,116.44,73.09,62.67,46.17.

[0101] Example 22:

[0102] The Schlenk procedure was performed to remove water and oxygen from the reaction system. The reaction flask was evacuated and then purged with 1 atm of CO2. This process was repeated three times to ensure a CO2 atmosphere was maintained. A CO2-filled balloon was inserted into the flask. Catalyst 1 (5.8 mg, 0.025 mmol, 0.05 equiv) was dissolved in N,N-dimethylformamide (0.5 ml), and finally epoxide H (114 mg, 0.5 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 80°C and reacted for 1 hour. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The results are shown in the attached figure. Figure 44 As shown, apart from DMF (peak positions at 7.79 ppm, 2.75 ppm, and 2.65 ppm), only the characteristic peak corresponding to epoxide H was detected. This indicates a reaction selectivity greater than 99% as determined by 1H NMR spectroscopy. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution. This solution was then evaporated to dryness on a rotary evaporator and dried in a vacuum oven at 45°C to constant weight, yielding a pure white solid with a yield of 92%. The 1H NMR spectrum of the product is attached. Figure 15 As shown (H NMR spectrum, 400 Hz, CDCl3). The spectral data are as follows: 1 ¹H NMR (400MHz, Chloroform-d) δ 7.52–7.41 (m, 4H), 4.75 (ddt, J = 8.7, 7.0, 3.6Hz, 1H), 4.06–3.93 (m, 3H), 3.76 (dd, J = 12.6, 3.9Hz, 1H), 1.81 (s, 1H). The carbon spectrum of the product is shown below. Figure 16 As shown, the spectral data is as follows: 13 C NMR (101MHz, Chloroform-d) δ 133.94, 129.63, 118.41, 72.68, 63.02, 46.50, 20.77.

[0103] Example 23:

[0104] The Schlenk procedure was performed to remove water and oxygen from the reaction system. The reaction flask was evacuated and then purged with 1 atm of CO2. This process was repeated three times to ensure a CO2 atmosphere was maintained. A CO2-filled balloon was inserted into the flask. Catalyst 1 (5.8 mg, 0.025 mmol, 0.05 equiv) was dissolved in N,N-dimethylformamide (0.5 ml), and finally epoxide I (83.6 mg, 0.5 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 80°C and reacted for 1 hour. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The results are shown in the attached figure. Figure 45 As shown, apart from DMF (peak positions at 7.79 ppm, 2.75 ppm, and 2.65 ppm), only the characteristic peaks corresponding to epoxide I were detected. This indicates a reaction selectivity greater than 99% as determined by 1H NMR spectroscopy. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution. This solution was then evaporated to dryness on a rotary evaporator and dried in a vacuum oven at 45°C to constant weight, yielding a pure white solid with a yield of 84%. The 1H NMR spectrum of the product is attached. Figure 17 As shown (H NMR spectrum, 400 Hz, CDCl3). The spectral data are as follows: 1 ¹H NMR (400MHz, Chloroform-d) δ 7.50 (s, 2H), 7.07 (s, 2H), 4.75 (s, 1H), 3.99 (d, J = 11.1 Hz, 3H), 3.76 (d, J = 12.4 Hz, 1H), 2.26 (s, 1H). The carbon spectrum of the product is shown below. Figure 18 As shown, the spectral data is as follows: 13 CNMR(101MHz,Chloroform-d)δ160.69,158.26,155.12,134.25,120.33,120.25,116.04,115.81,73.03,62.79,46.69.

[0105] Example 24:

[0106] The Schlenk procedure was performed to remove water and oxygen from the reaction system. The reaction flask was evacuated and then purged with 1 atm of CO2. This process was repeated three times to ensure a CO2 atmosphere was maintained. A CO2-filled balloon was inserted into the flask. Catalyst 1 (5.8 mg, 0.025 mmol, 0.05 equiv) was dissolved in N,N-dimethylformamide (0.5 ml), and finally epoxide J (116.7 mg, 0.5 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 80°C and reacted for 1 hour. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The results are shown in the attached figure. Figure 46 As shown, apart from DMF (peak positions at 7.79 ppm, 2.75 ppm, and 2.65 ppm), only the characteristic peaks corresponding to epoxide J were detected. This indicates a reaction selectivity greater than 99% as determined by 1H NMR spectroscopy. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution. This solution was then evaporated to dryness on a rotary evaporator and dried in a vacuum oven at 45°C to constant weight, yielding a pure white solid with a yield of 88%. The 1H NMR spectrum of the product is attached. Figure 19 As shown (H NMR spectrum, 400 Hz, CDCl3). The spectral data are as follows: 1 ¹H NMR (400MHz, Chloroform-d) δ 7.35 (t, J = 7.7Hz, 1H), 7.21 (d, J = 7.7Hz, 2H), 4.83 (ddt, J = 9.8, 6.9, 3.5Hz, 1H), 4.07–3.99 (m, 1H), 3.83–3.73 (m, 3H), 3.02 (dp, J = 20.4, 6.9Hz, 2H), 1.25 (dd, J = 7.1, 1.3Hz, 12H). The carbon spectrum of the product is shown below. Figure 20 As shown, the spectral data is as follows: 13 C NMR(101MHz,Chloroform-d)δ157.15,147.84,147.53,131.26,129.67,124.52, 124.40,73.68,63.27,49.91,29.85,28.91,28.72,24.65,24.51,24.32,24.26.

[0107] Example 25:

[0108] The Schlenk procedure was performed to remove water and oxygen from the reaction system. The reaction flask was evacuated and then purged with 1 atm of CO2. This process was repeated three times to ensure a CO2 atmosphere. A CO2-filled balloon was inserted into the flask. Catalyst 1 (5.8 mg, 0.025 mmol, 0.05 equiv) was dissolved in N,N-dimethylformamide (0.5 ml), and finally epoxide K (103.6 mg, 0.5 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 80°C and reacted for 1 hour. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The results are shown in the attached figure. Figure 47 As shown, apart from DMF (peak positions at 7.79 ppm, 2.75 ppm, and 2.65 ppm), only the characteristic peaks corresponding to epoxide K were detected. This indicates a reaction selectivity greater than 99% as determined by 1H NMR spectroscopy. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution. This solution was then evaporated to dryness on a rotary evaporator and dried in a vacuum oven at 45°C to constant weight, yielding a pure white solid with a yield of 71%. The 1H NMR spectrum of the product is attached. Figure 21 As shown (H NMR spectrum, 400 Hz, CDCl3). The spectral data are as follows: 1 ¹H NMR (400MHz, DMSO-d⁶) δ 8.01–7.95 (m, 2H), 7.75–7.69 (m, 2H), 5.23 (t, J = 5.6 Hz, 1H), 4.74 (ddt, J = 9.5, 6.3, 3.6 Hz, 1H), 4.14 (t, J = 9.1 Hz, 1H), 3.88 (dd, J = 9.0, 6.1 Hz, 1H), 3.84 (s, 3H), 3.69 (ddd, J = 12.4, 5.5, 3.3 Hz, 1H), 3.57 (ddd, J = 12.4, 5.8, 3.9 Hz, 1H). The carbon spectrum of the product is shown below. Figure 22 As shown, the spectral data is as follows: 13 C NMR (101MHz, DMSO-d6) δ165.78,154.30,142.74,130.25,123.83,117.06,73.41,61.59,51.98,45.89.

[0109] Example 26:

[0110] The Schlenk procedure was performed to remove water and oxygen from the reaction system. The reaction flask was evacuated and then purged with 1 atm of CO2. This process was repeated three times to ensure a CO2 atmosphere. A CO2-filled balloon was inserted into the flask. Catalyst 1 (5.8 mg, 0.025 mmol, 0.05 equiv) was dissolved in N,N-dimethylformamide (0.5 ml), and finally, epoxide L (126.1 mg, 0.5 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 80°C and reacted for 1 hour. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The 1H NMR spectroscopy analysis showed a reaction selectivity greater than 99%. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution, which was then evaporated to dryness on a rotary evaporator and dried in a vacuum oven at 45°C to constant weight to obtain a pure white solid with a yield of 86%. The proton NMR spectrum of the product is attached. Figure 23 As shown (H NMR spectrum, 400 Hz, CDCl3). The spectral data are as follows: 1 ¹H NMR (400MHz, Chloroform-d) δ 7.41 (dd, J = 14.4, 2.6 Hz, 1H), 7.08 (dd, J = 8.9, 2.7 Hz, 1H), 6.89 (t, J = 9.1 Hz, 1H), 4.69 (ddt, J = 10.2, 7.3, 3.5 Hz, 1H), 3.96–3.89 (m, 3H), 3.87–3.80 (m, 4H), 3.70 (dd, J = 12.6, 3.9 Hz, 1H), 3.05–2.98 (m, 4H). The carbon spectrum of the product is shown below. Figure 24 As shown, the spectral data is as follows: 13 C NMR (101MHz, Chloroform-d) δ156.74,154.44,136.45,133.21,118.85,113.91,107.49,72.77,66.97,62.78,51.03,46.39.

[0111] Example 27:

[0112] The Schlenk procedure was performed to remove water and oxygen from the reaction system. The reaction flask was evacuated and then purged with 1 atm of CO2. This process was repeated three times to ensure a CO2 atmosphere was maintained. A CO2-filled balloon was inserted into the flask. Catalyst 1 (292.9 mg, 1.25 mmol, 0.05 equiv) was dissolved in N,N-dimethylformamide (25 ml), and finally epoxide A (3.7298 g, 25 mmol, 1 equiv) was added and thoroughly mixed before being injected into the reaction flask. The reaction flask was placed on a heated stirrer at 80°C for 4 hours. After the reaction was complete, the reaction tube was removed and allowed to cool naturally. 0.1 ml of the reaction solution was analyzed by 1H NMR spectroscopy. The results are shown in the attached figure. Figure 48 As shown, apart from DMF (peak positions at 7.79 ppm, 2.75 ppm, and 2.65 ppm), only the characteristic peaks corresponding to epoxide A were detected. This indicates a reaction selectivity greater than 99% as determined by 1H NMR spectroscopy. The remaining solution was purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain a mixed solution. This solution was then evaporated to dryness using a rotary evaporator and dried in a vacuum oven at 45°C to constant weight, yielding a pure white solid with a yield of 98%.

Claims

1. A method for synthesizing 5-hydroxymethyloxazolidinone, characterized in that, The epoxide of formula (II) and carbon dioxide are used to generate 5-hydroxymethyloxazolidinone under the catalysis of the catalyst of formula (I). The catalyst shown in formula (I) is selected from the following structures: When R 1 ~R 5 When one of the substituents is selected from fluorine, chlorine, bromine, methyl, or ester, the other substituents are selected from hydrogen; the ester group is selected from methyl acetate or ethyl acetate. Or when R 2 R 4 When all are selected from fluorine, chlorine, or bromine, the other substituents are selected from hydrogen; or when R 1 R 5 When both are selected from isopropyl, the other substituents are selected from hydrogen; or when R 2 R 4 When both are selected from isopropyl, the other substituents are selected from hydrogen; or when R 3 When selected from morpholino, R 4 The molecule is selected from fluorine, and other substituents are selected from hydrogen.

2. The method as described in claim 1, characterized in that, The epoxide shown in formula (II) is selected from the following structures: 。 3. The method as described in claim 2, characterized in that, 5-hydroxymethyloxazolidinone was generated by using the epoxide shown in Formula A and carbon dioxide under the catalysis of the catalysts shown in Formulas 1 to 6; Alternatively, epoxides of formulas A to L and carbon dioxide can be used to generate 5-hydroxymethyloxazolidinone under the catalysis of the catalyst shown in formula 1.

4. The method as described in claim 1, characterized in that, The method for synthesizing 5-hydroxymethyloxazolidinone is as follows: the epoxide shown in formula (II) and the catalyst shown in formula (I) are mixed and reacted in a reaction vessel at a molar ratio of 100:0.5 to 100:

5. The reaction temperature is 60 to 100°C, the reaction time is 1 to 6 hours, the initial pressure of carbon dioxide is 0.05 to 1.5 MPa, and the reaction is carried out in an organic solvent medium. The reaction vessel is treated to be anhydrous and oxygen-free and filled with carbon dioxide before the reaction.

5. The method as described in claim 4, characterized in that, The organic solvents mentioned are toluene, N,N-dimethylformamide, 1,4-dioxane, chlorobenzene, and acetonitrile.

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