Solid-supported manganese catalyst and its manufacturing method and use

Abstract

To provide an immobilized manganese catalyst as well as a preparation method and application thereof.SOLUTION: A preparation process of the immobilized manganese catalyst comprises the following steps: complexing an organic ligand and a metal manganese salt to form a catalytic activity unit, and polymerizing the catalytic activity unit with a comonomer to obtain the immobilized manganese catalyst as shown in the formula I or II. The immobilized manganese catalyst belongs to a heterogeneous chiral catalyst, has high catalytic activity and excellent enantioselectivity (ee value is as high as 98.3%), is insoluble in a reaction solvent, is easy to separate from a reaction system and recover, and has good stability. And the catalyst can be combined with continuous flow catalysis, can maintain high catalytic activity for a long time, and can be applied to asymmetric epoxidation reaction of α,β-unsaturated carbonyl compounds.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to the technical field of catalytic chemistry, and in particular to a solid supported manganese catalyst and its method of preparation and use. [Background technology]

[0002] Asymmetric epoxidation of olefins is an important type of organic synthesis reaction, and the chiral epoxy compounds produced are important pharmaceutical intermediates. Therefore, it is very important to develop an efficient catalyst for such epoxidation reactions. Many researchers have developed biomimetic catalysts by mimicking the active sites of metal oxidase P450, and among these catalysts, Salen ligands have attracted the attention of researchers due to their characteristics such as the ease of preparation of the complexes formed with metals and high catalytic activity. Later, scientists discovered that the reaction catalyzed by manganese complexes formed by non-heme N4 chiral ligands and manganese metal has higher reaction selectivity and enantioselectivity, and has been proven to be an efficient catalyst for asymmetric epoxidation reactions.

[0003] In 1990, Jacobson et al. reported a reaction system using a chiral Schiff base complex as a catalyst (Non-Patent Document 1), and the obtained epoxide had a yield of 93% and an ee value of 93%, which was a very good result in the asymmetric epoxidation reaction of non-functional olefins. However, this homogeneous catalyst has defects such as being difficult to separate, recover, and reuse, and being prone to dimer deactivation in the reaction system. To solve these problems, in 2000, Kim's research group developed a heterogeneous JandaJel catalyst that can be attached to resin, and the obtained epoxide had an ee value of 97%, but this complex was only cycled three times (Non-Patent Document 2). In 2008, Bao Hebin's research group used the asymmetric epoxidation of styrene as a probe reaction, a Salen-Mn(III) complex as a catalyst, metachloroperbenzoic acid as an oxygen source, and NMO as an axial ligand, and found that the catalytic effect was optimal, and the product had a conversion rate of 85%, a selectivity of 90%, and an ee value of 60%. In this reaction, the solid-supported chiral Salen-Mn(III) catalyst had stable properties and could be cycled six times (Non-Patent Document 3). In 2021, Sun's research group reported the design and synthesis of a non-heme manganese N4 catalyst supported on an organic porous framework. This POP-based manganese catalyst has high reaction activity for the asymmetric epoxidation of olefins, and the product can reach an ee value of 96% and is easy to recover and reuse, but the types of catalyst substrates are small, and the catalyst can only be cycled five times, and there is a certain amplification effect in gram-scale reactions (Non-Patent Document 4). [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] J. Am. Chem. Soc. 1990, 112, 2801-2803. [Non-Patent Document 2] J. Am. Chem. Soc. 2000, 122, 6929-6934. [Non-Patent Document 3] High School Chemistry Bulletin, 2008, 29, 927-931. [Non-Patent Document 4] ACS Catal. 2021, 11, 10964-10973. Summary of the Invention [Problem to be solved by the invention]

[0005] In response to the above problems in the prior art, the present invention provides a method for producing a solid-supported manganese catalyst, which solves the problem that homogeneous catalysts cannot be recovered and reused, and also solves the problem that the yield and enantioselectivity decrease in amplification reactions when used in continuous flow catalysis. This catalyst has high catalytic activity and excellent enantioselectivity, and can be used in asymmetric epoxidation reactions of α,β-unsaturated carbonyl compounds. [Means for solving the problem]

[0006] The technical solutions adopted by the present invention are as follows:

[0007] A solid-supported manganese catalyst having the structure shown in formula (I) or (II): [ka] In general formula I, R 1 is selected from hydrogen, C1-C6 linear or branched alkyl, C3-C6 cycloalkyl, substituted aryl or heterocyclic aryl; R 2 is one selected from hydrogen, C1-C6 linear or branched alkyl, C3-C6 cycloalkyl, substituted aryl or heterocyclic aryl, and halogen; In the general formulas I and II, n is a natural number selected from 1 to 200, and X is OTf -1 , OAc -1 , ClO4 -1 , NO3 -1 , a halogen anion.

[0008] The solid supported manganese catalysts of the present invention as shown in formula I or II are obtained by polymerizing the catalytically active units C1 or C2, respectively, with divinylbenzene (DVB).

[0009] A method for producing the solid-supported manganese catalyst, comprising the steps of: Step (1) of reacting Boc-L-prolinal with 4-vinylbenzylamine shown in formula 1 to generate an imine intermediate, which is then reduced with NaBH4 to obtain intermediate 2; (2) removing the Boc protecting group of intermediate 2 by trifluoroacetic acid (TFA) catalysis to give intermediate 3; (3) adding a substituted 2-chloromethylbenzimidazole or 2-chloromethylpyridine in the presence of K2CO3 to carry out a nucleophilic substitution to generate an organic ligand L1 or L2 having an N4 center; Step (4) of adding a metal manganese salt MnX2 to L1 or L2 to effect a coordination reaction to obtain a catalytically active unit C1 or C2; and (5) adding divinylbenzene (DVB) and azobisisobutyronitrile (AIBN) to C1 or C2 to carry out a copolymerization reaction to obtain a solid-supported manganese catalyst I or II; [ka] In step (3), the substituent R of the substituted 2-chloromethylbenzimidazole 1 , R 2 is the same as Formula I, and in step (4), the anion X of the metal manganese salt MnX2 is the same as Formula I or II.

[0010] In the step (1), the molar ratio of Boc-L-prolinal to 4-vinylbenzylamine is 0.8-1.5:1, the reaction is carried out in a dichloromethane solution, the reaction temperature is 0-40°C, and the reaction time is 0.5-12 hours, the molar ratio of NaBH4 to 4-vinylbenzylamine is 2-6:1, the NaBH4 reduction reaction is carried out in a methanol solution, the reaction temperature is -10-40°C, and the reaction time is 0.5-12 hours.

[0011] In the step (2), the molar ratio of TFA to intermediate 2 is 5 to 50:1, preferably 15 to 25:1, the reaction is carried out in a dichloromethane solution, the reaction temperature is −10 to 40° C., and the reaction time is 0.5 to 24 hours.

[0012] In the step (3), the molar ratio of the substituted 2-chloromethylbenzimidazole or 2-chloromethylpyridine to the intermediate 3 is 2.0-4.0:1, the molar ratio of the K2CO3 to the intermediate 3 is 1.0-4.0:1, the reaction is carried out in an acetonitrile solution, the reaction temperature is 20-70°C, and the reaction time is 1-12 hours.

[0013] In the step (4), the molar ratio of the metal manganese salt MnX2 to the organic ligand L1 or L2 is 1.0 to 1.5:1, the reaction is carried out in an acetonitrile solution, the reaction temperature is 20 to 70° C., and the reaction time is 0.5 to 12 hours.

[0014] In the step (5), the molar ratio of DVB to the catalytically active unit C1 or C2 is 10-100:1, preferably 20-40:1, the molar ratio of AIBN to DVB is 0.1%-10%:1, preferably 1%-3%:1, the reaction is carried out in a tetrahydrofuran solution, the reaction temperature is 60-120°C, and the reaction time is 8-48 hours.

[0015] In addition, the present invention further provides the use of the solid-supported manganese catalyst prepared by the above technical solution in the asymmetric epoxidation reaction of α,β-unsaturated carbonyl compounds; The α,β-unsaturated carbonyl compound is dissolved in acetonitrile solvent, and the solid-supported manganese catalyst I or II is added. At the same time, an acid additive and an oxidizing agent are added. The reaction temperature is -45 to 30°C. After reaction and purification, an epoxy compound with high enantioselectivity is produced. The solid-supported manganese catalyst I or II is centrifuged and collected. After the catalyst is washed with ethyl acetate, it can be re-introduced into the next reaction. The reaction formula is as follows: [ka] R 3 is C1-C6 linear or branched alkyl, C3-C6 cycloalkyl, substituted aryl or heterocyclic aryl; R 4 is C1 to C6 linear or branched alkyl, C3 to C6 cycloalkyl, substituted aryl or heterocyclic aryl, alkoxy, amino, or substituted amino.

[0016] The oxide is one of hydrogen peroxide, metachloroperbenzoic acid, t-butyl peroxide, and iodosylbenzene, and the molar ratio of the oxide to the α,β-unsaturated carbonyl compound is 1.2 to 2:1. The acid added to the reaction is one of acetic acid, 2,2-dimethylbutyric acid, 2-ethylhexanoic acid, butyric acid, 4-methylvaleric acid, 4-phenylbutyric acid, 2-ethylbutyric acid, and 2,2-dimethylpropionic acid, and the molar ratio of the oxide to the α,β-unsaturated carbonyl compound is 2 to 8:1.

[0017] In addition, the present invention further provides the use of the solid-supported manganese catalyst prepared by the above technical solution in continuous flow catalysis of asymmetric epoxidation reaction of α,β-unsaturated carbonyl compounds; The solid-supported manganese catalyst I or II and silica gel are thoroughly ground in a mortar and then loaded into a fixed-bed reactor. One channel contains solution A prepared by dissolving α,β-unsaturated carbonyl compounds and acid additives in acetonitrile, and the concentrations of α,β-unsaturated carbonyl compounds and acid additives in solution A are 0.2-0.4mol / L and 0.8-2mol / L, respectively. The other channel contains solution B prepared by dissolving oxidizing agent in acetonitrile, and the concentration of oxidizing agent in solution B is 0.5-2mol / L. The liquid flow rate is controlled by a syringe pump, respectively. The reaction temperature is -45-30℃, and the residence time of the reaction system is 10-30min. After reaction and purification, an epoxy compound with high enantioselectivity is produced. Effect of the Invention

[0018] By using the above techniques, the present invention has the following features compared to the conventional techniques.

[0019] The present invention provides a method for preparing a solid-supported manganese catalyst, which includes complexing an organic ligand with a metal manganese salt to form a catalytically active unit, and then polymerizing with a comonomer to obtain a solid-supported manganese catalyst as shown in formula I or II. The solid-supported manganese catalyst belongs to a heterogeneous chiral catalyst, has high catalytic activity and excellent enantioselectivity (ee value up to 98.3%), is insoluble in the reaction solvent, is easy to separate and recover from the reaction system, and is highly stable. In addition, by combining with a continuous flow catalyst, it can maintain high catalytic activity for a long period of time and can be used in the asymmetric epoxidation reaction of α,β-unsaturated carbonyl compounds. [Brief description of the drawings]

[0020] [Figure 1] 1 shows the results of scanning electron microscopy characterization (500 nm) of solid supported manganese catalyst I-1. [Diagram 2] The solid supported manganese catalyst I-1 was characterized by transmission electron microscopy (10 nm), X-ray energy spectrum (100 nm), and elemental characterization (100 nm). [Diagram 3] 1 is a nitrogen adsorption / desorption curve of solid-supported manganese catalyst I-1. [Figure 4] 1 shows the pore size pattern of solid-supported manganese catalyst I-1. [Diagram 5] 1 shows the results of a thermogravimetric analysis pattern of solid-supported manganese catalyst I-1. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0021] The present invention will be further described below with reference to specific examples, but the scope of the present invention is not limited thereto.

[0022] [Example 1: Preparation of solid-supported manganese catalyst I-1] [ka] (1) Boc-L-prolinal (996 mg, 5.0 mmol), 4-vinylbenzylamine (595 mg, 5.0 mmol) and 10 mL of dichloromethane solution were added to a 100 mL one-neck flask, and the mixture was reacted at 40°C for 8 h in a nitrogen gas atmosphere. The solvent was recovered to obtain a yellow oily liquid. 20 mL of methanol solution was added, and NaBH4 (908 mg, 24.0 mmol) was added in batches at 0°C. After reacting for 8 h, the solvent was recovered, and 20 mL of water was added to dissolve the mixture. The mixture was then extracted three times with dichloromethane (20 mL x 3). The organic phases were combined and dried to obtain intermediate 2 (1.45 g, 4.6 mmol, yield 92%) as a yellow oily liquid. (2) 20 mL of dichloromethane solution was added to a 100 mL one-neck flask to dissolve the obtained intermediate 2 (1.0 g, 3.2 mmol), and TFA (7.21 g, 63.2 mmol) was added at 25°C. The reaction was allowed to proceed for 12 hours, and quenched by adding 20 mL of saturated NaHCO3. The mixture was extracted twice with dichloromethane (20 mL x 2). The organic phases were combined and dried to obtain intermediate 3 (608 mg, 2.8 mmol, 88% yield) as a yellow oily liquid. (3) In a 100 mL one-neck flask, add intermediate 3 (216 mg, 1.0 mmol), 2-(chloromethyl)-1-methyl-1H-benzimidazole (451 mg, 2.5 mmol), and KCO. 3( The mixture was dissolved in 20 mL of acetonitrile solution (415 mg, 3.0 mmol), and reacted at 60° C. in a nitrogen gas atmosphere. After reacting for 8 h, the solvent was recovered, and 20 mL of water was added to dissolve the mixture. The mixture was then extracted three times with dichloromethane (20 mL×3). The organic phases were combined, dried, and purified by column chromatography to obtain a yellow foamy solid L1-1 (352 mg, 0.7 mmol, yield 70%).

[0023] The structural characteristics of L1-1 are as follows: Yellow solid; 1 H NMR (400 MHz, Chloroform-d) δ 7.72 - 7.67 (m, 2H), 7.34 (d, J = 8.0 Hz, 2H), 7.26 - 7.20 (m, 8H), 6.68 (dd, J = 17.6, 3.2 Hz, 1H), 5.72 (dd, J = 17.6, 1.2 Hz, 1H), 5.23 (dd, J = 11.2, 1.2 Hz, 1H), 4.20 (d, J = 13.6 Hz, 1H), 3.79 (d, J = 13.6 Hz, 1H), 3.71 (d, J = 13.6 Hz, 1H), 3.67 - 3.56 (m, 5H), 3.55 - 3.52 (m, 1H), 3.48 (s, 3H), 2.77 - 2.64 (m, 3H), 2.50 (dd, J = 12.4, 7.2 Hz, 1H), 2.28 (td, J = 9.2, 7.2 Hz, 2H), 2.02 - 1.91 (m, 1H), 1.67 - 1.46 (m, 2H); 13C NMR (100 MHz, Chloroform-d) δ 152.27, 151.72, 142.17, 142.12, 137.98, 136.80, 136.42, 136.20, 129.77, 126.17, 122.63, 122.38, 121.97, 121.80, 119.53, 119.46, 113.87, 109.12, 109.10, 62.33, 59.85, 59.38, 54.82, 52.38, 52.10, 30.49, 30.00, 29.72, 22.37; HRMS-ESI (m / z): calcd for C 32 H 37 N6[M + H] + : 505.3074, found: 505.3073.

[0024] (4) Place L1-1 (352 mg, 0.7 mmol) and Mn(OTf) in a 100 mL one-neck flask. 2( The reaction was carried out in a nitrogen gas atmosphere at 60°C for 6 hours to obtain a pale yellow solid C1-1 (458 mg, 0.67 mmol, yield 97%).

[0025] The structural features of C1-1 are as follows: HRMS-ESI (m / z): calcd for C 34 H 36 F6MnN6NaO6S2[M + Na] + : 880.1315, found: 880.1295.

[0026] (5) C1-1 (172 mg, 0.2 mmol) was added with DVB (780 mg, 6.0 mmol), AIBN (15 mg), and 10 mL of tetrahydrofuran solution, and reacted at room temperature for 1 h and then at 100°C for 24 h. After filtration, solid-supported manganese catalyst I-1 was obtained in a yield of 75%.

[0027] In the structure of catalyst I-1, the number of DVB is 30 (see ACS Catal. 2021, 11, 10964-10973), and the polymerization reaction is a free radical polymerization, so by default the ratio of DVB to catalyst C1-1 in the supported catalyst is the feed ratio for the polymerization reaction, which is 30:1.

[0028] The scanning electron microscopy characterization (500 nm) of the solid supported manganese catalyst I-1 is shown in Fig. 1, which intuitively indicates that the solid supported manganese catalyst I-1 has a large amount of mesoporous structure, which is more favorable for the transport of raw materials and products during the catalytic reaction.

[0029] The results of transmission electron microscopy characterization (10 nm), X-ray energy spectrum (100 nm) and elemental characterization (100 nm) of the solid-supported manganese catalyst I-1 are summarized in Figure 2, which shows that the catalytic monomer C1-1 in the solid-supported catalyst I-1 is successfully solid-supported and distributed singly and uniformly on the porous organic polymeric support.

[0030] The nitrogen adsorption / desorption curve of the solid-supported manganese catalyst I-1 is shown in Figure 3. This supported catalyst has a high specific surface area (98.78 m 2 / g).

[0031] The pore size pattern of the solid supported manganese catalyst I-1 is shown in FIG. 4, which indicates that the pore size range of this supported catalyst is mainly in the range of 7-20 nm, which belongs to mesoporous support materials.

[0032] The thermogravimetric analysis pattern of the solid supported manganese catalyst I-1 is shown in FIG. 5, which indicates that the supported catalyst has good thermodynamic stability.

[0033] [Example 2: Preparation of solid-supported manganese catalyst I-2] [ka] (1) In a 100 mL single-neck flask, add intermediate 3 (216 mg, 1.0 mmol), 2-(chloromethyl)-1-ethyl-1H-benzimidazole (487 g, 2.5 mmol), and KCO. 3( The mixture was dissolved in 20 mL of acetonitrile solution (415 mg, 3.0 mmol), and reacted at 60° C. in a nitrogen gas atmosphere. After reacting for 8 h, the solvent was recovered, and 20 mL of water was added to dissolve the mixture. The mixture was then extracted three times with dichloromethane (20 mL×3). The organic phases were combined, dried, and purified by column chromatography to obtain a yellow foamy solid L1-2 (330 mg, 0.62 mmol, yield 62%).

[0034] The structural characteristics of L1-2 are as follows: Yellow solid; 1 H NMR (400 MHz, Chloroform-d) δδ 7.90 - 7.59 (m, 2H), 7.44 - 7.28 (m, 4H), 7.26 - 7.19 (m, 6H), 6.70 (dd, J = 17.6, 10.8 Hz, 1H), 5.74 (d, J = 17.6 Hz, 1H), 5.24 (d, J = 10.8 Hz, 1H), 4.26 (d, J = 12.8 Hz, 1H), 4.17 - 3.96 (m, 2H), 3.85 - 3.78 (m, 2H), 3.76 - 3.72 (m, 2H), 3.65 - 3.56 (m, 3H), 2.83 - 2.75 (m, 1H), 2.76 - 2.60 (m, 2H), 2.58 - 2.52 (m, 1H), 2.30 - 2.21 (m, 1H), 2.00 - 1.93 (m, 1H), 1.62 - 1.57 (m, 1H), 1.50 - 1.36 (m, 2H), 1.28 - 1.16 (m, 3H), 1.14 - 1.05 (m, 3H); 13C NMR (100 MHz, Chloroform-d) δ 151.86, 150.99, 142.42, 142.30, 137.85, 136.87, 136.39, 135.13, 135.10, 129.87, 126.17, 122.58, 122.31, 121.88, 121.68, 119.62, 119.53, 113.90, 109.39, 109.33, 62.18, 59.79, 59.57, 54.77, 52.33, 51.83, 38.44, 38.27, 30.56, 22.34, 14.79, 14.72; HRMS-ESI (m / z): calcd for C 34 H 41 N6[M + H] + : 533.3387, found: 533.3387.

[0035] (2) L1-2 (330 mg, 0.62 mmol), Mn(OTf)2 (241 mg, 0.68 mmol), and 30 mL of acetonitrile solution were added to a 100 mL single-neck flask, and the mixture was reacted at 60 °C in a nitrogen gas atmosphere for 6 h. After the reaction was completed, the solvent was recovered to obtain a pale yellow solid C1-2 (424 mg, 0.6 mmol, yield 97%).

[0036] The structural features of C1-2 are as follows: HRMS-ESI (m / z): calcd for C 36 H 40 F6MnN6NaO6S2[M + Na] + : 908.1628, found: 908.1619.

[0037] (3) C1-2 (177 mg, 0.2 mmol) was added with DVB (780 mg, 6.0 mmol), AIBN (15 mg), and 10 mL of tetrahydrofuran solution, and reacted at room temperature for 1 h and then at 100°C for 24 h. After filtration, solid-supported manganese catalyst I-2 was obtained in a yield of 72%.

[0038] [Example 3: Preparation of solid-supported manganese catalyst I-3] [ka] (1) In a 100 mL single-neck flask, add intermediate 3 (216 mg, 1.0 mmol), 2-(chloromethyl)-1-cyclohexyl-1H-benzimidazole (622 mg, 2.5 mmol), and KCO. 3( The mixture was dissolved in 20 mL of acetonitrile solution (415 mg, 3.0 mmol), and reacted at 60° C. in a nitrogen gas atmosphere for 8 h. The solvent was then recovered, dissolved in 20 mL of water, and extracted three times with dichloromethane (20 mL×3). The organic phases were combined, dried, and purified by column chromatography to obtain a yellow foamy solid L1-3 (340 mg, 0.53 mmol, yield 53%).

[0039] The structural characteristics of L1-3 are as follows: Yellow solid; 1H NMR (400 MHz, Chloroform-d) δ 7.71 - 7.67 (m, 2H), 7.59 - 7.48 (m, 2H), 7.38 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 7.21 - 7.15 (m, 4H), 6.70 (dd, J = 17.6, 10.8 Hz, 1H), 5.73 (d, J = 17.6 Hz, 1H), 5.23 (d, J = 10.8 Hz, 1H), 4.43 (tdt, J = 12.0, 7.6, 4.0 Hz, 2H), 4.11 (d, J = 13.2 Hz, 1H), 3.94 (d, J = 13.2 Hz, 1H), 3.80 (d, J = 13.2 Hz, 1H), 3.69 (d, J = 13.2 Hz, 1H), 3.59 (d, J = 13.2 Hz, 1H), 3.44 (d, J = 13.2 Hz, 1H), 2.79 - 2.67 (m, 2H), 2.67 - 2.48 (m, 2H), 2.37 - 2.19 (m, 2H), 2.17 - 2.00 (m, 3H), 1.98 - 1.84 (m, 5H), 1.81 - 1.72 (m, 3H), 1.56 - 1.47 (m, 1H), 1.36 - 1.20 (m, 5H), 1.17 - 1.05 (m, 2H); 13 C NMR (100 MHz, Chloroform-d) δ 151.77, 150.90, 143.08, 142.94, 138.05, 136.86, 136.44, 134.11, 134.09, 129.60, 126.33, 122.04, 121.83, 121.45, 121.27, 119.96, 119.84, 113.80, 112.43, 112.27, 62.22, 59.93, 59.21, 56.16, 55.62, 54.34, 52.85, 52.48, 31.40, 31.34, 31.31, 31.10, 30.76, 26.20, 25.95, 25.83, 25.76, 25.47, 25.40, 22.59; HRMS-ESI (m / z): calcd for C42 H 53 N6[M + H] + : 641.4326, found: 641.4325.

[0040] (2) Place L1-3 (340 mg, 0.53 mmol) and Mn(OTf) in a 100 mL one-neck flask. 2( A solution of C1-3 (206 mg, 0.58 mmol) in 30 mL of acetonitrile was added and reacted at 60° C. in a nitrogen gas atmosphere for 6 hours. After the reaction was completed, the solvent was recovered to obtain a pale yellow solid C1-3 (510 mg, 0.51 mmol, yield 96%).

[0041] The structural features of C1-3 are as follows: HRMS-ESI (m / z): calcd for C 44 H 52 F6MnN6NaO6S2[M + Na] + : 1016.2567, found: 1016.2560.

[0042] (3) C1-3 (199 mg, 0.2 mmol) was added with DVB (780 mg, 6.0 mmol), AIBN (15 mg), and 10 mL of tetrahydrofuran solution, and reacted at room temperature for 1 h and then at 100°C for 24 h. After filtration, solid-supported manganese catalyst I-3 was obtained in a yield of 70%.

[0043] [Example 4: Preparation of solid-supported manganese catalyst I-4] [ka] (1) In a 100 mL single-neck flask, add intermediate 3 (216 mg, 1.0 mmol), 2-(chloromethyl)-1-methyl-4-bromo-1H-benzimidazole (649 mg, 2.5 mmol), and KCO. 3(The mixture was dissolved in 20 mL of acetonitrile solution (415 mg, 3.0 mmol), and reacted at 60° C. in a nitrogen gas atmosphere. After reacting for 8 h, the solvent was recovered, and 20 mL of water was added to dissolve the mixture. The mixture was then extracted three times with dichloromethane (20 mL×3). The organic phases were combined, dried, and purified by column chromatography to obtain a yellow foamy solid L1-4 (240 mg, 0.36 mmol, yield 36%).

[0044] The structural characteristics of L1-4 are as follows: Yellow solid; 1 H NMR (400 MHz, Chloroform-d) δ 7.82 - 7.80 (m, 2H), 7.38 - 7.27 (m, 4H), 7.25 - 7.18 (m, 2H), 7.12 - 7.08 (m, 1H), 7.06 - 7.02 (m, 1H), 6.68 (ddd, J = 18.0, 11.2, 2.8 Hz, 1H), 5.72 (d, J = 17.6 Hz, 1H), 5.23 (d, J = 11.2 Hz, 1H), 4.18 - 4.10 (m, 1H), 3.81 - 3.72 (m, 1H), 3.71 - 3.58 (m, 3H), 3.53 - 3.48 (m, 7H), 2.70 (t, J = 8.4 Hz, 2H), 2.63 - 2.54 (m, 2H), 2.50 - 2.45 (m, 1H), 2.32 - 2.22 (m, 1H), 2.11 - 1.87 (m, 3H); 13 C NMR (100 MHz, Chloroform-d) δ 153.35, 152.87, 143.37, 137.72, 136.92, 136.35, 135.14, 135.08, 129.73, 126.18, 125.66, 125.46, 122.31, 122.23, 114.96, 114.83, 113.96, 110.35, 110.32, 62.33, 59.88, 59.37, 54.83, 52.21, 51.83, 30.43, 30.11, 29.97, 22.43; HRMS-ESI (m / z): calcd for C 32 H35 Br2N6[M + H] + : 661.1284, found: 661.1283.

[0045] (2) Place L1-4 (240 mg, 0.36 mmol) and Mn(OTf) in a 100 mL one-neck flask. 2( The reaction was carried out in a nitrogen gas atmosphere at 60° C. for 6 hours. After the reaction was completed, the solvent was recovered to obtain a pale yellow solid C1-4 (346 mg, 0.34 mmol, yield 95%).

[0046] The structural features of C1-4 are as follows: HRMS-ESI (m / z): calcd for C 34 H 34 Br2F6MnN6NaO6S2[M + Na] + : 1035.9525, found: 1035.9523.

[0047] (3) C1-4 (346 mg, 0.34 mmol) was added with DVB (1.33 g, 10.2 mmol), AIBN (15 mg), and 10 mL of tetrahydrofuran solution, and reacted at room temperature for 1 h and then at 100°C for 24 h. After filtration, solid-supported manganese catalyst I-4 was obtained in a yield of 68%.

[0048] [Example 5: Preparation of solid-supported manganese catalyst II] [ka] (1) Place intermediate 3 (216 mg, 1.0 mmol), 2-(chloromethyl)pyridine (319 mg, 2.5 mmol), and KCO in a 100 mL single-neck flask. 3(The crude product L2 (415 mg, 3.0 mmol) was dissolved in 20 mL of acetonitrile solution, and reacted at 60° C. in a nitrogen gas atmosphere. After reacting for 8 h, the solvent was recovered, and 20 mL of water was added to dissolve the crude product. The crude product was extracted three times with dichloromethane (20 mL×3). The organic phases were combined, dried, and then purified by column chromatography to obtain a yellow foamy solid L2 (279 mg, 0.7 mmol, yield 70%).

[0049] The structural characteristics of L2 are: Yellow solid; 1 H NMR (400 MHz, Chloroform-d) δ 8.52 - 8.48 (m, 2H), 7.64 - 7.56 (m, 2H), 7.55 - 7.49 (m, 1H), 7.39 - 7.24 (m, 5H), 7.16 - 7.06 (m, 2H), 6.68 (dd, J = 17.6, 10.8 Hz, 1H), 5.71 (d, J = 17.6 Hz, 1H), 5.20 (d, J = 11.2 Hz, 1H), 4.37 - 4.10 (m, 1H), 3.82 - 3.68 (m, 2H), 3.68 - 3.39 (m, 3H), 2.82 - 2.37 (m, 3H), 2.25 - 2.14 (m, 1H), 2.10 - 1.83 (m, 2H), 1.76 - 1.50 (m, 3H); 13 C NMR (100 MHz, Chloroform-d) δ 160.22, 148.92, 148.78, 139.04, 136.66, 136.37, 136.35, 136.32, 129.19, 126.09, 123.07, 123.00, 121.89, 121.79, 113.35, 62.35, 61.30, 61.16, 59.44, 59.02, 54.87, 30.11, 22.57; HRMS-ESI (m / z): calculation 26 H 31 N4[M + H] + : 399.2543, found: 399.2540.

[0050] (5) Place L2 (279 mg, 0.7 mmol) and Mn(OTf) in a 100 mL one-neck flask. 2( A solution of C2 (270 mg, 0.77 mmol) in 30 mL of acetonitrile was added, and the reaction was carried out at 60° C. in a nitrogen gas atmosphere for 6 hours. After the reaction was completed, the solvent was recovered to obtain a pale yellow solid C2 (499 mg, 0.67 mmol, yield 96%).

[0051] The structural features of C2 are as follows: HRMS-ESI (m / z): calcd for C 28 H 30 F6MnN4NaO6S2[M + Na] + : 774.0784, found: 774.0777.

[0052] (3) C2 (150 mg, 0.2 mmol) was added with DVB (780 mg, 6.0 mmol), AIBN (15 mg), and 10 mL of tetrahydrofuran solution, and reacted at room temperature for 1 h and then at 100°C for 24 h. After filtration, solid-supported manganese catalyst II was obtained in an 80% yield.

[0053] [Example 6: Preparation of solid-supported manganese catalyst I-5] [ka] To C1-1 (172 mg, 0.2 mmol), DVB (261 mg, 2 mmol), AIBN (5 mg), and 10 mL of tetrahydrofuran solution were added, and the mixture was reacted at room temperature for 1 h and then at 100° C. for 24 h. After filtration, solid-supported manganese catalyst I-5 was obtained.

[0054] [Example 7: Preparation of solid-supported manganese catalyst I-6] [ka] To C1-1 (172 mg, 0.2 mmol), DVB (1.57 g, 12 mmol), AIBN (30 mg), and 10 mL of tetrahydrofuran solution were added, and the mixture was reacted at room temperature for 1 h and then at 100° C. for 24 h. After filtration, solid-supported manganese catalyst I-6 was obtained.

[0055] [Example 8: Use of solid-supported manganese catalyst I-1 in asymmetric epoxidation reaction of α,β-unsaturated carbonyl compounds] [ka] Dissolve chalcone 4 (52 mg, 0.25 mmol) in 1 mL of acetonitrile solution, add solid-supported manganese catalyst I-1 (11.9 mg) and 2,2-dimethylbutyric acid (145 mg, 1.25 mmol), cool to -40 ° C, dilute 50% hydrogen peroxide (26 mg, 0.375 mmol) with acetonitrile to 0.5 mL, and react for 2 h after dropping. After the reaction is completed, collect catalyst I-1 by centrifugal filtration, concentrate the filtrate to dryness under reduced pressure, and separate the residue by column chromatography (ethyl acetate: n-hexane = 1: 20, v / v) to obtain a yellow solid (53.2 mg, 0.237 mmol, yield 95%, ee value 95.7%).

[0056] [Example 9: Use of solid-supported manganese catalyst I-2 in asymmetric epoxidation reaction of α,β-unsaturated carbonyl compounds] [ka] Dissolve chalcone 4 (52 mg, 0.25 mmol) in 1 mL of acetonitrile solution, add solid-supported manganese catalyst I-2 (12.0 mg) and 2,2-dimethylbutyric acid (145 mg, 1.25 mmol), cool to -40 ° C, dilute 50% hydrogen peroxide (26 mg, 0.375 mmol) with acetonitrile to 0.5 mL, and react for 2 h after dropping. After the reaction is completed, collect catalyst I-2 by centrifugal filtration, concentrate the filtrate to dryness under reduced pressure, and separate the residue by column chromatography (ethyl acetate: n-hexane = 1: 20, v / v) to obtain a yellow solid (52.7 mg, 0.235 mmol, yield 94%, ee value 94.5%).

[0057] [Example 10: Use of solid-supported manganese catalyst I-3 in asymmetric epoxidation reaction of α,β-unsaturated carbonyl compounds] [ka] Dissolve chalcone 4 (52 mg, 0.25 mmol) in 1 mL of acetonitrile solution, add solid-supported manganese catalyst I-3 (12.2 mg) and 2,2-dimethylbutyric acid (145 mg, 1.25 mmol), cool to -40 ° C, dilute 50% hydrogen peroxide (26 mg, 0.375 mmol) with acetonitrile to 0.5 mL, and react for 2 h after dropping. After the reaction is completed, collect catalyst I-3 by centrifugal filtration, concentrate the filtrate to dryness under reduced pressure, and separate the residue by column chromatography (ethyl acetate: n-hexane = 1: 20, v / v) to obtain a yellow solid (52.1 mg, 0.232 mmol, yield 93%, ee value 94.6%).

[0058] [Example 11: Use of solid-supported manganese catalyst I-4 in asymmetric epoxidation reaction of α,β-unsaturated carbonyl compounds] [ka] Dissolve chalcone 4 (52 mg, 0.25 mmol) in 1 mL of acetonitrile solution, add solid-supported manganese catalyst I-4 (12.3 mg) and 2,2-dimethylbutyric acid (145 mg, 1.25 mmol), cool to -40 ° C, dilute 50% hydrogen peroxide (26 mg, 0.375 mmol) with acetonitrile to 0.5 mL, and react for 2 h after dropping. After the reaction is completed, collect catalyst I-4 by centrifugal filtration, concentrate the filtrate to dryness under reduced pressure, and separate the residue by column chromatography (ethyl acetate: n-hexane = 1: 20, v / v) to obtain a yellow solid (37.5 mg, 0.167 mmol, yield 67%, ee value 91.3%).

[0059] [Example 12: Use of solid-supported manganese catalyst II in asymmetric epoxidation reaction of α,β-unsaturated carbonyl compounds] [ka] Dissolve chalcone 4 (52 mg, 0.25 mmol) in 1 mL of acetonitrile solution, add solid-supported manganese catalyst II (11.6 mg) and 2,2-dimethylbutyric acid (145 mg, 1.25 mmol), cool to -40 ° C, dilute 50% hydrogen peroxide (26 mg, 0.375 mmol) with acetonitrile to 0.5 mL, and react for 2 h after dropping. After the reaction is completed, collect catalyst II by centrifugal filtration, concentrate the filtrate to dryness under reduced pressure, and separate the residue by column chromatography (ethyl acetate: n-hexane = 1: 20, v / v) to obtain a yellow solid (51.6 mg, 0.230 mmol, yield 92%, ee value 89.5%).

[0060] [Example 13: Use of solid-supported manganese catalyst I-5 in asymmetric epoxidation reaction of α,β-unsaturated carbonyl compounds] [ka] Dissolve chalcone 4 (52 mg, 0.25 mmol) in 1 mL of acetonitrile solution, add solid-supported manganese catalyst I-5 (5.4 mg) and 2,2-dimethylbutyric acid (145 mg, 1.25 mmol), cool to -40 ° C, dilute 50% hydrogen peroxide (26 mg, 0.375 mmol) with acetonitrile to 0.5 mL, and react for 2 h after dropping. After the reaction is completed, collect catalyst I-5 by centrifugal filtration, concentrate the filtrate to dryness under reduced pressure, and separate the residue by column chromatography (ethyl acetate: n-hexane = 1: 20, v / v) to obtain a yellow solid (52.1 mg, 0.232 mmol, yield 93%, ee value 95.4%).

[0061] [Example 14: Use of solid-supported manganese catalyst I-6 in asymmetric epoxidation reaction of α,β-unsaturated carbonyl compounds] [ka] Dissolve chalcone 4 (52 mg, 0.25 mmol) in 1 mL of acetonitrile solution, add solid-supported manganese catalyst I-6 (21.7 mg) and 2,2-dimethylbutyric acid (145 mg, 1.25 mmol), cool to -40 ° C, dilute 50% hydrogen peroxide (26 mg, 0.375 mmol) with acetonitrile to 0.5 mL, and react for 2 h after dropping. After the reaction is completed, collect catalyst I-6 by centrifugal filtration, concentrate the filtrate to dryness under reduced pressure, and separate the residue by column chromatography (ethyl acetate: n-hexane = 1: 20, v / v) to obtain a yellow solid (44.8 mg, 0.200 mmol, yield 80%, ee value 95.5%).

[0062] [Example 15: Recovery cycle experiment of solid-supported manganese catalyst I-1] According to the experimental process in Example 8, after centrifugation, catalyst I-1 was washed with 1 mL of ethyl acetate, dried, and then put into the reaction, and this experimental process was repeated. Since it was found that the yield significantly decreased and there was a problem of metal loss after the fifth cycle, the recovered I-1 was put into 1 mL of acetonitrile before the sixth cycle reaction, and Mn(OTf)2 (0.4 mg) was added, and the reaction was carried out at 60°C for 6 h in a nitrogen gas atmosphere to re-coordinate, and after centrifugation drying, it was re-put into the reaction. The yield and ee value of the recovery cycle experiment are shown in Table 1.

[0063] [Table 1]

[0064] [Example 16: Use of solid-supported manganese catalyst I-1 in continuous flow catalysis] I-1 (238 mg) and silica gel (2.0 g) were thoroughly ground in a mortar and filled into the piping of a fixed-bed reactor. Chalcone 4 (2.08 g, 10 mmol) and 2,2-dimethylbutyric acid (5.8 g, 50 mmol) were dissolved in acetonitrile and diluted to 36 mL, and then injected into the fixed-bed reactor by injection pump 1 (flow rate, 40 μL / min). At the same time, 50% hydrogen peroxide solution (816 mg, 12 mmol) was diluted to 18 mL with acetonitrile and injected into the fixed-bed reactor by injection pump 2 (flow rate, 20 μL / min). The reaction temperature was controlled at -40°C, the residence time of the reaction solution in the fixed bed was 20 min, and the operation was continuous for 90 to 900 min. The yield and ee value are shown in Table 2.

[0065] [Table 2]

[0066] Table 2 shows the yield and ee value of the continuous operation time of the catalyst in the continuous flow catalyst. As can be seen from the reaction results, when the continuous operation time of the catalyst is 900 min, the reaction yield still reaches 87%, indicating that the catalyst has very high stability.

[0067] The operation steps described in Examples 17-44 were repeated in Example 8, except that the structures of the α,β-unsaturated carbonyl compound derivatives as the reaction raw materials were changed, and the yields, purities and ee values ​​of the corresponding epoxidation products were as shown in Table 3.

[0068] [Table 3A] [Table 3B] [Table 3C] [Table 3D]

[0069] (Examples 17 to 44 are all known substances.) The contents described in this specification are merely enumerated embodiments of the inventive concept, and the scope of protection of the present invention should not be considered as being limited to the specific forms described in the examples.

[0070] (Additional Note) (Appendix 1) A solid supported manganese catalyst having the structure shown in Formula I or Formula II: [ka] In general formula I, R 1 is selected from hydrogen, C1-C6 linear or branched alkyl, C3-C6 cycloalkyl, substituted aryl or heterocyclic aryl, preferably methyl, ethyl or cyclohexyl; R 2 is one selected from hydrogen, C1-C6 linear or branched alkyl, C3-C6 cycloalkyl, substituted aryl or heterocyclic aryl, and halogen, preferably hydrogen or Br; In the general formulas I and II, n is a natural number selected from 1 to 200, preferably 30, and X is - OTF, - OAc, ClO4 -1 , NO3 -1 , halogen anions, preferably - 1. A solid supported manganese catalyst, characterized in that it is OTf.

[0071] (Appendix 2) Step (1) is a reaction of Boc-L-prolinal with 4-vinylbenzylamine shown in formula 1 to generate an imine intermediate, which is then reduced with NaBH4 to obtain intermediate 2; (2) removing the Boc protecting group from intermediate 2 by trifluoroacetic acid catalysis to give intermediate 3; (3) a nucleophilic substitution reaction of intermediate 3 with a substituted 2-chloromethylbenzimidazole or 2-chloromethylpyridine in the presence of KCO to produce an organic ligand L1 or L2 having an N4 center; (4) a step in which an organic ligand L1 or L2 undergoes a coordination reaction with a manganese metal salt MnX2 to obtain a catalytically active unit C1 or C2; and step (5) of the catalytically active unit C1 or C2 reacting with divinylbenzene (DVB) and azobisisobutyronitrile (AIBN) to produce a solid-supported manganese catalyst as shown in formula I or formula II, the reaction formula being as follows: [ka] In step (3), the substituent R of the substituted 2-chloromethylbenzimidazole 1 , R 2 is the same as Formula I, and in step (4), the anion X of the metal manganese salt MnX2 is the same as Formula I or II.

[0072] (Appendix 3) The method for producing a solid supported manganese catalyst according to Appendix 2, characterized in that in the step (1), the molar ratio of Boc-L-prolinal to 4-vinylbenzylamine is 0.8-1.5:1, the reaction is carried out in a dichloromethane solution, the reaction temperature is 0-40°C, and the reaction time is 0.5-12 hours, the molar ratio of NaBH4 to 4-vinylbenzylamine is 2-6:1, and the NaBH4 reduction reaction is carried out in a methanol solution, the reaction temperature is -10-40°C, and the reaction time is 0.5-12 hours.

[0073] (Appendix 4) The method for producing a solid supported manganese catalyst according to Appendix 2, wherein in the step (2), a molar ratio of TFA to intermediate 2 is 5 to 50:1, and preferably 15 to 25:1, the reaction is carried out in a dichloromethane solution, the reaction temperature is −10 to 40° C., and the reaction time is 0.5 to 24 hours.

[0074] (Appendix 5) The method for producing a solid supported manganese catalyst according to Appendix 2, characterized in that in the step (3), the molar ratio of the substituted 2-chloromethylbenzimidazole or 2-chloromethylpyridine to the intermediate 3 is 2.0-4.0:1, the molar ratio of the K2CO3 to the intermediate 3 is 1.0-4.0:1, the reaction is carried out in an acetonitrile solution, the reaction temperature is 20-70°C, and the reaction time is 1-12 hours.

[0075] (Appendix 6) The method for producing a solid supported manganese catalyst according to Appendix 2, wherein in the step (4), a molar ratio of the metal manganese salt MnX2 to the organic ligand L1 or L2 is 1.0-1.5:1, the reaction is carried out in an acetonitrile solution, the reaction temperature is 20-70°C, and the reaction time is 0.5-12 hours.

[0076] (Appendix 7) The method for producing a solid supported manganese catalyst according to Appendix 2, characterized in that in the step (5), the molar ratio of DVB to the catalytically active unit C1 or C2 is 10-100:1, preferably 20-40:1, the molar ratio of AIBN to DVB is 0.1%-10%:1, preferably 1%-3%:1, the reaction is carried out in a tetrahydrofuran solution, the reaction temperature is 60-120°C, and the reaction time is 8-48 hours.

[0077] (Appendix 8) The α,β-unsaturated carbonyl compound is dissolved in an organic solvent, and the solid-supported manganese catalyst I or II is added. At the same time, an acid additive and an oxidizing agent are added. The reaction temperature is -45 to 30°C. After reaction and purification, an epoxy compound with high enantioselectivity is produced. The solid-supported manganese catalyst I or II is centrifuged and collected. The reaction formula is as follows: [ka] In the structure of the α,β-unsaturated carbonyl compound in the above reaction formula, R 3 is C1-C6 linear or branched alkyl, C3-C6 cycloalkyl, substituted aryl or heterocyclic aryl; R 4 is C1 to C6 linear or branched alkyl, C3 to C6 cycloalkyl, substituted aryl or heterocyclic aryl, alkoxy, amino or substituted amino, in an asymmetric epoxidation reaction of an α,β-unsaturated carbonyl compound.

[0078] (Appendix 9) The method for use according to appendix 8, wherein the oxidant is one of hydrogen peroxide, metachloroperbenzoic acid, t-butyl peroxide, and iodosylbenzene, and the molar ratio of the oxidant to the α,β-unsaturated carbonyl compound is 1.2 to 2:1; the acid added to the reaction is one of acetic acid, 2,2-dimethylbutyric acid, 2-ethylhexanoic acid, butyric acid, 4-methylvaleric acid, 4-phenylbutyric acid, 2-ethylbutyric acid, and 2,2-dimethylpropionic acid, and the molar ratio of the oxidant to the α,β-unsaturated carbonyl compound is 2 to 8:1; and the organic solvent is acetonitrile.

[0079] (Appendix 10) The method of use according to appendix 8 is characterized in that the solid-supported manganese catalyst I or II and silica gel are thoroughly ground in a mortar and then loaded into a fixed-bed reactor; one channel contains solution A prepared by dissolving an α,β-unsaturated carbonyl compound and an acid additive in an organic solvent, the concentrations of the α,β-unsaturated carbonyl compound and the acid additive in solution A being 0.2-0.4 mol / L and 0.8-2 mol / L, respectively; the other channel contains solution B prepared by dissolving an oxidizing agent in an organic solvent, the concentration of the oxidizing agent in solution B being 0.5-2 mol / L; the flow rate of the liquid is controlled by a syringe pump; the reaction temperature is -45-30°C; the residence time of the reaction system is 10-30 min; and after reaction and purification, an epoxy compound with high enantioselectivity is produced.

Claims

1. A solid-supported manganese catalyst for use in the asymmetric epoxidation reaction of an α,β-unsaturated carbonyl compound, comprising: The solid-supported manganese catalyst is a copolymer of a catalytically active unit C1 represented by the following formula C1 or a catalytically active unit C2 represented by the following formula C2 and divinylbenzene (DVB), 【Chemistry 1】 Having the structure shown in general formula I or general formula II, 【Chemistry 2】 In formulae C1 and C2 and general formulae I and II, R １ is hydrogen, C １ ~C ６ Linear or branched alkyl, C ３ ~C ６ cycloalkyl, substituted aryl, or heterocyclic aryl of the formula R ２ is hydrogen, C １ ~C ６ Linear or branched alkyl, C ３ ~C ６ X is one selected from the group consisting of --OTf, --OAc, ClO 4 --1, NO 3 --1, and halogen anions; A solid supported manganese catalyst, characterized in that in general formula I or II, n is a natural number selected from 10 to 60.

2. The solid supported manganese catalyst according to claim 1, wherein R 1 is methyl, ethyl or cyclohexyl.

3. The solid supported manganese catalyst according to claim 1, wherein R 2 is hydrogen or Br.

4. The solid supported manganese catalyst as described in claim 1, characterized in that n is 30.

5. The solid supported manganese catalyst according to claim 1, wherein X is −OTf.

6. Boc-L-prolinal reacts with 4-vinylbenzylamine shown in formula 1 to produce an imine intermediate, followed by NaBH ４ to obtain intermediate 2; (2) subjecting intermediate 2 to a Boc protecting group removal reaction catalyzed by trifluoroacetic acid to give intermediate 3; K ２ CO ３ In the presence of ４ (3) forming an organic ligand L1 or L2 having a center; The organic ligand L1 or L2 is a metal manganese salt MnX ２ (4) a coordination reaction with the above to obtain catalytically active unit C1 or C2; and step (5) of the catalytically active unit C1 or C2 reacting with divinylbenzene (DVB) and azobisisobutyronitrile (AIBN) to produce a solid-supported manganese catalyst as shown in general formula I or general formula II, the reaction formula being as follows: 【Chemistry 3】 In step (3), the substituent R of the substituted 2-chloromethylbenzimidazole １ , R ２ is the same as general formula I, and in step (4), a metal manganese salt MnX ２ 2. The method for preparing a solid supported manganese catalyst according to claim 1, wherein the anion X is the same as that of general formula I or II.

7. In the step (1), the molar ratio of Boc-L-prolinal to 4-vinylbenzylamine is 0.8-1.5:1, the reaction is carried out in a dichloromethane solution, the reaction temperature is 0-40° C., the reaction time is 0.5-12 h, and NaBH ４ and 4-vinylbenzylamine in a molar ratio of 2 to 6:1, ４ The method for producing a solid supported manganese catalyst according to claim 6, characterized in that the reduction reaction is carried out in a methanol solution, the reaction temperature is -10 to 40°C, and the reaction time is 0.5 to 12 hours.

8. 7. The method for producing a solid supported manganese catalyst according to claim 6, wherein in step (2), the molar ratio of TFA to intermediate 2 is 5-50:1, the reaction is carried out in a dichloromethane solution, the reaction temperature is -10-40°C, and the reaction time is 0.5-24h.

9. The method for producing a solid supported manganese catalyst as described in claim 8, characterized in that in step (2), the molar ratio of TFA to intermediate 2 is 15-25:

1.

10. In the step (3), the molar ratio of the substituted 2-chloromethylbenzimidazole or 2-chloromethylpyridine to the intermediate 3 is 2.0-4.0:1; ２ CO ３ The method for producing a solid supported manganese catalyst according to claim 6, characterized in that the molar ratio of the intermediate 3 to the supported manganese catalyst is 1.0-4.0:1, the reaction is carried out in an acetonitrile solution, the reaction temperature is 20-70°C, and the reaction time is 1-12h.

11. In the step (4), the metal manganese salt MnX ２ and the organic ligand L1 or L2 is 1.0-1.5:1, the reaction is carried out in an acetonitrile solution, the reaction temperature is 20-70°C, and the reaction time is 0.5-12h.

12. 7. The method for preparing a solid supported manganese catalyst according to claim 6, wherein in step (5), the molar ratio of DVB to the catalytically active unit C1 or C2 is 10-100:1, the molar ratio of AIBN to DVB is 0.1%-10%:1, the reaction is carried out in a tetrahydrofuran solution, the reaction temperature is 60-120° C., and the reaction time is 8-48 h.

13. The method for producing a solid supported manganese catalyst according to claim 12, wherein the molar ratio of DVB to the catalytically active unit C1 or C2 is 20-40:

1.

14. The method for producing a solid supported manganese catalyst according to claim 12, characterized in that the molar ratio of AIBN to DVB is 1%-3%:

1.

15. The α,β-unsaturated carbonyl compound is dissolved in an organic solvent, and the solid-supported manganese catalyst I or II is added, and at the same time, an acid additive and an oxidizing agent are added. The reaction temperature is -45 to 30°C. After reaction and purification, an epoxy compound with high enantioselectivity is produced, and the solid-supported manganese catalyst I or II is centrifuged and collected. The reaction formula is as follows: 【Chemistry 4】 In the structure of the α,β-unsaturated carbonyl compound in the above reaction formula, R ３ is C １ ~C ６ Linear or branched alkyl, C ３ ~C ６ is a cycloalkyl, substituted aryl or heterocyclic aryl of the formula R ４ is C １ ~C ６ Linear or branched alkyl, C ３ ~C ６ 2. The method of using the solid supported manganese catalyst according to claim 1 in asymmetric epoxidation reaction of an α,β-unsaturated carbonyl compound, wherein the aryl group is cycloalkyl, substituted aryl or heterocyclic aryl, alkoxy, amino or substituted amino of the formula (I).

16. The method according to claim 15, characterized in that the oxidizing agent is one of hydrogen peroxide, metachloroperbenzoic acid, t-butyl peroxide, and iodosylbenzene, and the molar ratio of the oxidizing agent to the α,β-unsaturated carbonyl compound is 1.2 to 2:1; the acid added to the reaction is one of acetic acid, 2,2-dimethylbutyric acid, 2-ethylhexanoic acid, butyric acid, 4-methylvaleric acid, 4-phenylbutyric acid, 2-ethylbutyric acid, and 2,2-dimethylpropionic acid, and the molar ratio of the oxidizing agent to the α,β-unsaturated carbonyl compound is 2 to 8:1; and the organic solvent is acetonitrile.

17. The method of use according to claim 15, characterized in that: the solid-supported manganese catalyst I or II and silica gel are thoroughly ground in a mortar and then packed into a fixed-bed reactor; one channel contains solution A prepared by dissolving an α,β-unsaturated carbonyl compound and an acid additive in an organic solvent, the concentrations of the α,β-unsaturated carbonyl compound and the acid additive in solution A are 0.2-0.4 mol / L and 0.8-2 mol / L, respectively; the other channel contains solution B prepared by dissolving an oxidant in an organic solvent, the concentration of the oxidant in solution B is 0.5-2 mol / L; the flow rate of the liquid is controlled by a syringe pump; the reaction temperature is -45-30°C; the residence time of the reaction system is 10-30 min; and after reaction and purification, an epoxy compound with high enantioselectivity is prepared.

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