A catalytic asymmetric synthesis of chiral 3-alkyl substituted pyrrolidines

Abstract

The application provides a catalytic asymmetric synthesis method of chiral 3-alkyl substituted pyrrolidine, and belongs to the technical field of asymmetric organic synthesis, and comprises the following steps: acyl-protected 3-pyrroline is reacted with alkyl iodide under the catalysis of cobalt and a chiral oxazoline ligand, under the action of a base and a silicon hydride reagent, in an organic solvent, and at 0 DEG C to obtain a chiral 3-alkyl substituted pyrrolidine product. The chiral 3-alkyl substituted pyrrolidine product is obtained in one step, the operation is simple, the regioselectivity is high, the method is cheap and has good application prospect, and can be applied to the efficient synthesis of natural products, drugs and materials.

Description

Technical Field

[0001] This invention belongs to the field of asymmetric organic synthesis technology, and specifically relates to a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines. Background Technology

[0002] Chiral 3-substituted pyrrolidine skeletons are widely found in active natural products and pharmaceutical intermediates, and are also important skeletons for natural products, materials and pharmaceutical intermediates, such as 3-hydroxymethylpyrrolidine, chiral pyrrolidine-3-carboxylic acid, chiral n-boc-3-hydroxymethylpyrrolidine, chiral n-boc-3-aminopyrrolidine, chiral n-boc-3-cyanopyrrolidine, etc. Therefore, the synthesis of this type of compound has always been of great interest to researchers and is one of the hot topics in the field of organic synthesis. At present, the synthesis methods of this type of chiral compound include: asymmetric hydrogenation method, enzyme catalysis method, etc. However, these methods have great limitations, and the reaction conditions are basically very harsh, which greatly limits their application in drug development, natural product synthesis and other fields. Therefore, the development of efficient asymmetric synthesis methods to construct chiral 3-substituted pyrrolidine structures in one step has also been valued. For example: (1) Chiral 3-substituted pyrrolidine compounds can be synthesized by direct hydrogenation or hydrogenation-relay cyclization. In 2006, Krische et al. obtained pyrrolidone with a chiral center at the 4-position through rhodium-catalyzed intramolecular hydrogenation cyclization of aldehydes and acetylacetonates with good enantioselectivity (jurhee, mjkrische, j.am.chem.soc.2006, 128, 10674.). Subsequently, Zhang and Liu et al. successfully synthesized pyrrolidone structures with a chiral center at the 5-position by direct hydrogenation reduction of β,γ-unsaturated γ-lactams using phosphonamide ligands under iridium catalysis (q.yuan, d.liu, w.zhang, org.lett.2017, 19, 1144.). (2) With the continuous development of organic synthesis methodology, ch-bond activation has been widely used in organic synthesis chemistry as a simple and efficient synthetic method, and the synthesis of chiral pyrrolidone skeletons by asymmetric ch-bond activation is also a widely used synthetic method. For example, Shibata et al. reported the synthesis of asymmetric sp pyrrolidone skeletons by a chiral iridium catalyst. 3Chiral pyrrolidone structures were synthesized by chemihydride (y.tahara, m.michino, m.ito, kskanyiva, t. shibata, chem.commun. 2015, 51, 16660.). Subsequently, Chang et al. reported the successful construction of 5-substituted chiral pyrrolidone structures by intramolecular asymmetric chemihydride insertion of 1,4-dioxo-2-oxazol-5-one catalyzed by iridium with chiral diamine as ligand. This method has high atom utilization and good step economy, but because it is an intramolecular reaction, it has certain limitations on the substrate (y.park, s.chang, nat.catal. 2019, 2, 219.). (3) Other methods, such as CPR (i)-catalyzed asymmetric allyl substitution, can also synthesize chiral pyrrolidone structures. In 2012, Kitamura et al. used cpru(i) as a catalyst and pyridine containing axial chirality as a ligand to construct a pyrrolidone structure containing a chiral quaternary carbon center via an intramolecular allyl substitution reaction. However, its enantiomeric excess was only 86%. (T. Seki, S. Tanaka, M. Kitamura, org. Lett. 2012, 14, 608.).

[0003] The above methods usually require the pre-preparation of metal alkyl reagents or the use of expensive transition metal catalysts. Most synthetic methods have difficulties in controlling the regioselectivity and enantioselectivity of the products, and have drawbacks such as the difficulty in preparing raw materials and the instability and mutability of enzymes. Therefore, developing a low-cost metal-catalyzed method for highly selective synthesis of chiral 3-substituted pyrrolidines has important research significance and application value. Summary of the Invention

[0004] This invention addresses the technical problems existing in the prior art by providing a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines. Using acyl-protected 3-pyrrolidines and alkyl iodides as raw materials, the method involves reacting the chiral 3-alkyl-substituted pyrrolidine products in an organic solvent at 0 degrees Celsius under the catalysis of cobalt and chiral oxazoline ligands, and in the presence of a base and a silane reagent.

[0005] The technical solution adopted in this invention is: a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: reacting acyl-protected 3-pyrrolidines with alkyl iodides in an organic solvent at 0 degrees Celsius under the catalysis of cobalt and chiral oxazoline ligands, and in the presence of a base and a silane reagent, to obtain chiral 3-alkyl-substituted pyrrolidine products.

[0006] .

[0007] Further, cobalt, chiral oxazoline ligand and organic solvent were added to the reaction flask and stirred evenly at room temperature. Then, acyl-protected 3-pyrrolidone, alkyl iodide, base and organic solvent were added. After cooling to zero degrees Celsius, silane reagent was added dropwise, and the reaction was carried out at zero degrees Celsius for 12-36 hours.

[0008] Further, after the reaction was completed, ethyl acetate was added, the mixture was filtered, the filter cake was washed with ethyl acetate 2-3 times, the solvent was removed under reduced pressure, and the chiral 3-alkyl-substituted pyrrolidine products were separated by column chromatography.

[0009] Furthermore, the acyl protecting group of the acyl-protected 3-pyrrolidone is a benzoyl group with different substitutions, and the substituent R on the benzene ring of the benzoyl group is chlorine, alkyl, methoxy, naphthyl, phenyl or ester group;

[0010] The substituent R1 on the alkyl iodide is alkyl, ester, naphthyl, phenyl, chlorine, carbazole, benzyl, or amide.

[0011] Furthermore, the molar ratio of the acyl-protected 3-pyrrolidone to the alkyl iodide is 1:2, and the concentration is 0.05 mol / L.

[0012] Furthermore, the cobalt used is at least one of CoBr2, CoCl2, CoI2, Co(DME)Br2, CoCl2(PPh3)3, Co(acac)2, Co(OAc)2(H2O)4, CoBr2, and Co(OAc)2, and the amount of cobalt is 2-15 mol of acyl-protected 3-pyrrolline.

[0013] Furthermore, the chiral oxazoline ligand used is at least one of L1-L8.

[0014]

[0015] The amount of chiral oxazoline ligand is 10-15 mol of acyl-protected 3-pyrrolline.

[0016] Furthermore, the base used is at least one selected from diisopropylamine, triethylamine, tetramethylethylenediamine, N,N-dimethylethylamine, N,N-diisopropylethylamine, piperidine, 2,2,6,6-tetramethylpiperidine, 1,2,2,6,6-pentamethylpiperidine, potassium fluoride, potassium phosphate, cesium carbonate, cesium fluoride, potassium carbonate, or sodium carbonate, and the amount of base is 2-3 eq of acyl-protected 3-pyrroline.

[0017] Furthermore, the silane reagent used is at least one of dimethoxymethylsilane, methylphenyldichlorosilane, trimethoxysilane, phenyldimethylsilane, or triethoxysilane, and the amount of the silane reagent is 2-3 eq of acyl-protected 3-pyrrolline.

[0018] Furthermore, the organic solvent used is at least one of tetrahydrofuran, toluene, chlorobenzene, xylene, mesitylene, pentafluorobenzene, fluorobenzene, cyclopentyl methyl ether, ethylene glycol dimethyl ether, methyl tert-butyl ether, tert-butylmethylene ether, N,N-dimethylformamide, or 1,4-dioxane.

[0019] Compared with the prior art, the beneficial effects of this invention are as follows: This invention uses acyl-protected 3-pyrrolidine and alkyl iodide as raw materials, and obtains chiral 3-alkyl-substituted pyrrolidine products in one step under the catalysis of cobalt and chiral bisoxazoline ligands and the action of base and silane reagent. The operation is simple, the regioselectivity is high, and it is an inexpensive method with good application prospects. It can be applied to the efficient synthesis of natural products, drugs and materials. Attached Figure Description

[0020] Figure 1 The 1H NMR spectrum of the sample obtained in Example 1 of this invention;

[0021] Figure 2 The carbon NMR spectrum of the sample obtained in Example 1 of this invention;

[0022] Figure 3 The 1H NMR spectrum of the sample obtained in Example 2 of this invention;

[0023] Figure 4 The carbon NMR spectrum of the sample obtained in Example 2 of this invention;

[0024] Figure 5 The 1H NMR spectrum of the sample obtained in Example 3 of this invention;

[0025] Figure 6 The carbon NMR spectrum of the sample obtained in Example 3 of this invention;

[0026] Figure 7 The hydrogen NMR spectrum of the sample obtained in Example 27 of this invention;

[0027] Figure 8 The carbon NMR spectrum of the sample obtained in Example 27 of this invention;

[0028] Figure 9 The 1H NMR spectrum of the sample obtained in Example 28 of this invention;

[0029] Figure 10 The carbon NMR spectrum of the sample obtained in Example 28 of this invention;

[0030] Figure 11 The 1H NMR spectrum of the sample obtained in Example 29 of this invention;

[0031] Figure 12This is the carbon NMR spectrum of the sample obtained in Example 29 of the present invention. Detailed Implementation

[0032] To enable those skilled in the art to better understand the technical solution of the present invention, the present invention will be described in detail below with reference to specific embodiments. Example 1

[0033] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1a (0.2 mmol, 1.0 equiv.), 2a (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, followed by column chromatography to obtain target product 1 (45.1 mg, yield 81%, ee value 95%). Figures 1-2 As shown, the proton and carbon spectrum data are as follows: 1 H NMR (500MHz, CDCl3) δ 7.51 – 7.48 (m, 2H), 7.42 – 7.36 (m, 3H), 7.30 (t, J = 7.6Hz, 1H), 7.27 – 7.23 (m, 1H), 7.23 – 7.14 (m, 2H), 7.11 (d, J = 7.7 Hz, 1H),3.93 – 3.72 (m, 1H), 3.63 – 3.37 (m, 2H), 3.30 – 3.04 (m, 1H), 2.75 – 2.50(m, 2H), 2.27 – 1.98 (m, 2H), 1.79 (q, J = 7.6 Hz, 1H), 1.74 – 1.50 (m, 2H). 13C NMR (126 MHz, CDCl3) δ 169.8, 169.7, 141.8, 141.6, 137.1, 137.0, 129.8,128.5, 128.5, 128.4, 128.3, 128.2, 127.1, 126.0, 55.1, 51.7, 49.4, 45.9,39.2, 37.2, 35.2, 34.5, 34.3, 32.5, 30.5. Example 2

[0034] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1a (0.2 mmol, 1.0 equiv.), 2b (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain target product 2 (38.6 mg, yield 66%, ee value 94%). Figures 3-4 As shown, the proton and carbon spectrum data are as follows: 1 H NMR(500MHz, CDCl3) δ 7.53 – 7.48 (m, 2H), 7.43 – 7.37 (m, 3H), 7.22 – 6.95 (m,4H), 3.98 – 3.73 (m, 1H), 3.67 – 3.40 (m, 2H), 3.32 – 3.07 (m, 1H), 2.73 –2.47 (m, 2H), 2.37 – 1.97 (m, 5H), 1.73 (q, J = 7.8 Hz, 1H), 1.69 – 1.51 (m,2H). 13C NMR (126 MHz, CDCl3) δ 169.8, 169.7, 140.0, 139.8, 137.1, 137.0,135.8, 135.6, 130.3, 130.3, 129.9, 128.7, 128.6, 128.3, 127.1, 126.2, 126.1,126.0, 55.1, 51.8, 49.4, 45.9, 39.6, 37.7, 34.0, 33.3, 32.6, 31.9, 31.7,30.5, 19.3, 19.2. Example 3

[0035] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1a (0.2 mmol, 1.0 equiv.), 2c (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain target product 3 (30.9 mg, yield 50%, ee value 93%). Figures 5-6 As shown, the proton and carbon spectrum data are as follows: 1 H NMR(500MHz, CDCl3) 7.54 – 7.47 (m, 2H), 7.47 – 7.33 (m, 3H), 7.22 – 7.03 (m, 2H), 6.94 – 6.76 (m, 2H), 3.94 – 3.81 (m, 2H), 3.78 – 3.71 (m, 2H), 3.62 – 3.52(m, 1H), 3.52 – 3.37 (m, 1H), 3.34 – 3.05 (m, 1H), 2.74 – 2.50 (m, 2H), 2.27– 2.00 (m, 2H), 1.74 (q, J= 7.6 Hz, 1H), 1.69 – 1.53 (m, 2H). 13 C NMR (126MHz, CDCl3) δ 169.7, 169.7, 157.4, 157.3, 137.2, 137.1, 130.2, 130.0, 129.8,129.7, 129.6, 128.3, 127.2, 127.2, 127.1, 120.4, 110.3, 110.2, 55.3, 55.2,55.1, 51.8, 49.4, 45.9, 39.4, 37.6, 33.6, 33.0, 32.5, 30.6, 28.9, 28.6. Example 4

[0036] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1a (0.2 mmol, 1.0 equiv.), 2d (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 4 (37.7 mg, yield 61%, ee value 95%). The 1H and 1C spectral data are as follows: 1 H NMR (500MHz, CDCl3) δ7.50 – 7.48 (m, 2H), 7.42 – 7.36 (m, 3H), 7.19 (dt, J = 22.9, 8.1 Hz, 1H), 6.80 – 6.66 (m, 3H), 3.92 – 3.71 (m, 4H), 3.62 – 3.38 (m, 2H), 3.30 – 3.03(m, 1H), 2.72 – 2.48 (m, 2H), 2.24 – 1.98 (m, 2H), 1.78 (q, J= 7.6 Hz, 1H),1.74 – 1.49 (m, 2H). 13 C NMR (126 MHz, CDCl3) δ 169.8, 169.7, 159.7, 159.7,143.4, 143.2, 137.1, 137.0, 129.8, 129.5, 129.4, 128.3, 127.1, 120.8, 120.6,114.2, 114.2, 111.2, 111.1, 55.2, 55.1, 55.1, 51.7, 49.4, 45.9, 39.2, 37.2,35.0, 34.5, 34.3, 34.3, 32.5, 30.5. Example 5

[0037] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1a (0.2 mmol, 1.0 equiv.), 2e (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 5 (51.6 mg, yield 88%, ee value 95%). The 1H and 1C spectral data are as follows: 1 H NMR(500MHz, CDCl3) δ7.59 – 7.28 (m, 5H), 7.17 – 6.93 (m, 4H), 3.92 – 3.71 (m, 1H), 3.62 – 3.37(m, 2H), 3.33 – 2.99 (m, 1H), 2.71 – 2.43 (m, 2H), 2.31 (d, J = 13.8 Hz, 3H),2.25 – 1.96 (m, 2H), 1.76 (q, J = 7.6 Hz, 1H), 1.71 – 1.49 (m, 2H).13 C NMR(126 MHz, CDCl3) δ 169.7, 169.6, 138.7, 138.5, 137.2, 137.0, 135.5, 129.8,129.2, 129.1, 128.3, 128.2, 128.1, 127.1, 55.1, 51.7, 49.4, 45.9, 39.2, 37.2,35.3, 34.6, 34.0, 33.9, 32.5, 30.5, 21.0. Example 6

[0038] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1a (0.2 mmol, 1.0 equiv.), 2f (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 6 (40.3 mg, yield 60%, ee value 93%). The 1H and 1C spectral data are as follows: 1 H NMR (500MHz, CDCl3) δ7.53 – 7.46 (m, 2H), 7.42 – 7.37 (m, 3H), 7.32 (d, J = 8.3 Hz, 1H), 7.28 (d, J = 8.2 Hz, 1H), 7.13 (d, J = 8.1 Hz, 1H), 7.05 (d, J= 8.0 Hz, 1H), 3.94 – 3.72 (m, 1H), 3.64 – 3.38 (m, 2H), 3.30 – 3.06 (m, 1H), 2.71 – 2.48 (m, 2H), 2.30 – 1.98 (m, 2H), 1.80 – 1.75 (m, 1H), 1.71 – 1.51 (m, 2H), 1.30 (d, J =11.3 Hz, 9H). 13 C NMR (126 MHz, CDCl3) δ 169.8, 169.7, 148.8, 138.7, 138.5,137.1, 137.0, 129.8, 128.3, 128.2, 128.0, 127.9, 127.1, 125.4, 125.3, 55.1,51.7, 49.4, 45.9, 39.2, 37.3, 35.2, 34.4, 34.4, 34.3, 33.9, 33.7, 32.5, 31.4,31.4, 30.5, 29.7. Example 7

[0039] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1a (0.2 mmol, 1.0 equiv.), 2 g (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 7 (53.8 mg, yield 87%, ee value 96%). The 1H and 1C spectral data are as follows: 1 H NMR (500MHz, CDCl3) δ7.51 – 7.47 (m, 2H), 7.43 – 7.36 (m, 3H), 7.11 (d, J = 8.1 Hz, 1H), 7.03 (d,J = 8.1 Hz, 1H), 6.82 (dd, J = 24.9, 8.2 Hz, 2H), 3.95 – 3.71 (m, 4H), 3.63 –3.37 (m, 2H), 3.29 – 3.03 (m, 1H), 2.70 – 2.45 (m, 2H), 2.27 – 1.97 (m, 2H),1.78 – 1.51 (m, 4H). 13 C NMR (126 MHz, CDCl3) δ 169.8, 169.7, 157.9, 137.1,137.0, 133.8, 133.6, 129.8, 129.2, 129.1, 128.3, 127.1, 113.9, 113.8, 55.3,55.3, 55.1, 51.7, 49.4, 45.9, 39.2, 37.1, 35.4, 34.7, 33.5, 33.4, 32.5, 30.5. Example 8

[0040] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1a (0.2 mmol, 1.0 equiv.) is added, followed by 2 h (0.4 mmol, 2.0 equiv.), CsF (91.1 mg, 0.6 mmol, 3.0 equiv.), and then another 2 ml of ethylene glycol dimethyl ether is added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 h. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 8 (70.9 mg, yield 92%, ee value 94%). The 1H and 1C spectral data are as follows: 1 H NMR (500MHz, CDCl3) δ7.51 – 7.48 (m, 2H), 7.46 – 7.26 (m, 8H), 7.11 (d, J = 8.2 Hz, 1H), 7.02 (d, J= 8.2 Hz, 1H), 6.91 (d, J = 8.4 Hz, 1H), 6.87 (d, J = 8.5 Hz, 1H), 5.03 (d, J = 13.0 Hz, 2H), 3.92 – 3.71 (m, 1H), 3.63 – 3.36 (m, 2H), 3.28 – 3.03 (m,1H), 2.71 – 2.42 (m, 2H), 2.25 – 1.95 (m, 2H), 1.75 (q, J = 7.6 Hz, 1H), 1.70– 1.49 (m, 2H). 13 C NMR (126 MHz, CDCl3) δ 169.8, 169.7, 157.2, 137.2, 137.2,137.1, 137.0, 134.1, 134.0, 129.8, 129.3, 129.2, 128.6, 128.3, 128.0, 127.5,127.5, 127.1, 114.9, 114.8, 70.1, 70.1, 55.1, 51.7, 49.4, 45.9, 39.2, 37.2,35.4, 34.7, 33.6, 33.4, 32.5, 30.5, 29.7. Example 9

[0041] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1a (0.2 mmol, 1.0 equiv.), 2i (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 9 (43.4 mg, yield 73%, ee value 95%). The 1H and 1C spectral data are as follows:1 1H NMR (500 MHz, CDCl3) δ 7.51 – 7.48 (m, 2H), 7.43 – 7.36 (m, 3H), 7.15 – 7.12 (m, 1H), 7.07 – 7.05 (m, 1H), 6.95 (dt, J J = 24.3, 8.5 Hz, 2H), 3.93 – 3.72 (m, 1H), 3.63 – 3.39 (m, 2H), 3.29 – 3.03 (m, 1H), 2.72 – 2.47 (m, 2H), 2.27 – 1.97 (m, 2H), 1.76 (q, J J = 7.6 Hz, 1H), 1.70 – 1.53 (m, 2H). 13 13C NMR (126 MHz, CDCl3) 169.8, 169.6, 161.3 (d, J J = 243.6 Hz), 137.3 (d, J J = 17.0 Hz), 137.0 (d, J J = 16.9 Hz), 129.8, 129.6 (d, J J = 7.9 Hz), 129.5 (d, J J = 7.8 Hz), 128.3, 127.1, 115.3 (d, J J = 3.5 Hz), 115.1 (d, J J = 3.5 Hz), 55.0, 51.6, 49.3, 45.8, 39.2, 37.1, 35.3, 34.6, 33.6, 33.5, 32.5, 30.5. 19 19F NMR (471 MHz, CDCl3) δ -117.4, -117.5。 Example 10

[0042] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1a (0.2 mmol, 1.0 equiv.), 2j (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 10 (43.4 mg, yield 73%, ee value 95%). The 1H and 1C spectral data are as follows: 1 H NMR(500MHz, CDCl3)δ 7.56 – 7.46 (m, 2H), 7.46 – 7.33 (m, 3H), 7.25 – 7.12 (m, 1H), 7.09 – 6.91(m, 2H), 3.93 – 3.73 (m, 1H), 3.65 – 3.41 (m, 2H), 3.31 – 3.02 (m, 1H), 2.70 – 2.46 (m, 2H), 2.26 – 1.98 (m, 2H), 1.76 (q, J = 7.7 Hz, 1H), 1.72 – 1.50(m, 2H). 13 C NMR (126 MHz, CDCl3) δ 169.8, 169.7, 156.59 (d, J = 246.9 Hz), 156.57 (d, J = 246.9 Hz), 138.68 (d, J = 4.1 Hz), 138.55 (d, J = 3.7 Hz), 136.9 (d, J = 18.1 Hz), 130.2, 130.1, 129.9, 128.3, , 127.89 (d, J = 6.7 Hz), 127.78 (d, J= 6.7 Hz), 127.1, 127.1, 120.7 (d, J = 17.4 Hz), 116.46 (d, J =21.0 Hz), 116.42 (d, J = 21.0 Hz), 55.0, 51.6, 49.3, 45.8, 39.2, 37.1, 35.0,34.3, 33.5, 33.4, 32.4, 30.5. 19 F NMR (471 MHz, CDCl3) δ -119.5, -119.7. Example 11

[0043] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1a (0.2 mmol, 1.0 equiv.), 2k (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 11 (47.5 mg, yield 70%, ee value 96%). The 1H and 1C spectral data are as follows: 1 H NMR(500MHz, CDCl3)δ 7.65 – 7.30 (m, 5H), 6.44 – 6.17 (m, 3H), 3.92 – 3.36 (m, 9H), 3.31 – 3.02(m, 1H), 2.70 – 2.43 (m, 2H), 2.27 – 1.99 (m, 2H), 1.77 (q, J = 7.6 Hz, 1H),1.73 – 1.50 (m, 2H). 13C NMR (126 MHz, CDCl3) δ 169.7, 169.6, 160.9, 160.8,144.2, 144.0, 137.1, 137.0, 129.8, 128.3, 127.1, 106.5, 106.4, 97.9, 97.8,55.3, 55.2, 55.0, 51.7, 49.4, 45.9, 39.2, 37.2, 34.9, 34.7, 34.6, 34.2, 32.5,30.5. Example 12

[0044] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1a (0.2 mmol, 1.0 equiv.), 2l (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 12 (47.5 mg, yield 70%, ee value 96%). The 1H and 1C spectral data are as follows: 1 H NMR(500MHz, CDCl3)δ 7.97 (dd, J = 49.3, 8.1 Hz, 1H), 7.88 – 7.79 (m, 1H), 7.70 (dd, J = 18.5,8.2 Hz, 1H), 7.60 – 7.18 (m, 9H), 4.02 – 3.73 (m, 1H), 3.66 – 3.52 (m, 1H), 3.52 – 3.39 (m, 1H), 3.38 – 2.92 (m, 3H), 2.38 – 2.01 (m, 2H), 1.94 – 1.88(m, 1H), 1.80 (q, J = 7.5 Hz, 1H), 1.72 – 1.51 (m, 1H).13 C NMR (126 MHz, CDCl3) δ 169.8, 169.7, 137.9, 137.7, 137.1, 137.0, 134.0, 133.9, 131.7,131.6, 129.9, 128.9, 128.3, 127.1, 127.1, 126.9, 126.9, 126.0, 125.9, 125.9,125.8, 125.6, 125.6, 125.5, 123.6, 123.5, 55.1, 51.7, 49.4, 45.9, 39.7, 37.7,34.6, 33.8, 32.6, 31.7, 31.5, 30.5. Example 13

[0045] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1a (0.2 mmol, 1.0 equiv.), 2m (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 13 (46.8 mg, yield 71%, ee value 96%). The 1H and 1C spectral data are as follows: 1 H NMR(500MHz, CDCl3)δ 7.74 – 7.59 (m, 2H), 7.59 – 7.44 (m, 3H), 7.45 – 7.33 (m, 3H), 7.32 – 7.18(m, 1H), 7.17 – 7.02 (m, 2H), 3.95 – 3.73 (m, 4H), 3.63 – 3.37 (m, 2H), 3.34 – 3.03 (m, 1H), 2.87 – 2.62 (m, 2H), 2.29 – 1.96 (m, 2H), 1.85 (q, J= 7.6Hz, 1H), 1.80 – 1.70 (m, 1H), 1.68 – 1.51 (m, 1H). 13 C NMR (126 MHz, CDCl3) δ169.8, 169.7, 157.3, 137.1, 137.0, 136.9, 136.7, 133.1, 129.8, 129.1, 129.1,128.9, 128.9, 128.3, 127.6, 127.5, 127.1, 126.9, 126.9, 126.3, 126.1, 118.8,105.7, 55.3, 55.1, 51.7, 49.4, 45.9, 39.3, 37.2, 35.1, 34.4, 34.4, 34.3,32.5, 30.5. Example 14

[0046] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1a (0.2 mmol, 1.0 equiv.), 2n (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 14 (13.0 mg, yield 28%, ee value 91%). The 1H and 1C spectral data are as follows: 1H NMR(500MHz, CDCl3)δ 7.53 – 7.48 (m, 2H), 7.46 – 7.30 (m, 3H), 3.92 – 3.70 (m, 1H), 3.64 – 3.36(m, 2H), 3.23 – 2.97 (m, 1H), 2.36 – 2.16 (m, 1H), 2.15 – 1.93 (m, 1H), 1.67 – 1.44 (m, 2H), 1.37 – 1.18 (m, 2H), 0.94 – 0.85 (m, 6H). 13 C NMR (126 MHz, CDCl3) δ 169.8, 169.6, 137.2, 137.1, 129.8, 129.8, 128.3, 127.1, 127.1, 55.4,52.0, 49.4, 46.1, 42.7, 42.1, 37.7, 35.8, 32.8, 30.8, 26.8, 26.6, 22.9, 22.8,22.7, 22.6. Example 15

[0047] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1a (0.2 mmol, 1.0 equiv.), 2o (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 15 (32.0 mg, yield 58%, ee value 96%). The 1H and 1C spectral data are as follows: 1 H NMR(500MHz, CDCl3)δ 7.50 – 7.49 (m, 2H), 7.43 – 7.36 (m, 3H), 4.84 (dt, J= 36.7, 4.6 Hz, 1H),4.01 – 3.91 (m, 2H), 3.89 – 3.74 (m, 3H), 3.63 – 3.41 (m, 2H), 3.24 – 3.05(m, 1H), 2.29 – 2.00 (m, 2H), 1.76 – 1.72 (m, 1H), 1.66 – 1.43 (m, 4H). 13 CNMR (126 MHz, CDCl3) δ 169.8, 169.7, 137.0, 136.9, 129.8, 129.8, 128.3,127.1, 104.2, 104.0, 64.9, 55.1, 51.8, 49.3, 46.0, 39.5, 37.7, 32.4, 32.4,32.2, 30.5, 27.4, 26.8. Example 16

[0048] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1a (0.2 mmol, 1.0 equiv.), 2p (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 16 (49.3 mg, yield 84%, ee value 96%). The 1H and 1C spectral data are as follows: 1 H NMR(500MHz, CDCl3)δ 7.50 – 7.47 (m, 2H), 7.39 – 3.35 (m, 3H), 7.29 – 7.24 (m, 2H), 7.22 – 7.05(m, 3H), 3.87 – 3.70 (m, 1H), 3.62 – 3.37 (m, 2H), 3.22 – 3.00 (m, 1H), 2.60(dt, J= 32.7, 7.6 Hz, 2H), 2.26 – 1.96 (m, 2H), 1.75 – 1.65 (m, 1H), 1.64 –1.44 (m, 3H), 1.41 – 1.34 (m, 1H). 13 C NMR (126 MHz, CDCl3) δ 169.8, 169.7,142.2, 142.0, 137.2, 137.0, 129.8, 128.4, 128.4, 128.4, 128.3, 128.3, 127.1,125.9, 125.8, 55.2, 51.8, 49.4, 46.0, 39.7, 37.8, 36.0, 35.9, 32.9, 32.5,32.3, 30.5, 30.1, 29.9. Example 17

[0049] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1a (0.2 mmol, 1.0 equiv.), 2q (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 17 (51.1 mg, yield 71%, ee value 94%). The 1H and 1C spectral data are as follows: 1 H NMR(500MHz, CDCl3)δ 7.83 – 7.62 (m, 3H), 7.57 – 7.46 (m, 2H), 7.46 – 7.35 (m, 4H), 7.32 (t, J=7.5 Hz, 1H), 7.21 – 7.02 (m, 2H), 4.18 – 3.97 (m, 2H), 3.95 – 3.74 (m, 1H), 3.67 – 3.56 (m, 1H), 3.54 – 3.41 (m, 1H), 3.31 – 3.04 (m, 1H), 2.36 – 2.01(m, 2H), 1.99 – 1.87 (m, 1H), 1.87 – 1.75 (m, 1H), 1.72 – 1.56 (m, 3H). 13 CNMR (126 MHz, CDCl3) δ 169.8, 169.7, 156.9, 156.8, 137.1, 137.0, 134.6,134.6, 129.8, 129.4, 129.0, 128.3, 127.7, 127.1, 126.7, 126.7, 126.4, 123.6,123.6, 118.9, 118.8, 106.6, 106.6, 67.7, 67.6, 55.2, 51.8, 49.4, 46.0, 39.6,37.7, 32.5, 30.6, 30.0, 29.4, 28.0, 27.8. Example 18

[0050] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1a (0.2 mmol, 1.0 equiv.), 2r (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 18 (45.4 mg, yield 78%, ee value 94%). The 1H and 1C spectral data are as follows: 1H NMR(500MHz, CDCl3)δ 7.62 – 7.46(m, 2H), 7.45 – 7.31 (m, 3H), 4.22 – 4.02 (m, 2H), 3.90 – 3.72(m, 1H), 3.65 – 3.39 (m, 2H), 3.27 – 3.01 (m, 1H), 2.34 (t, J = 7.4 Hz, 1H), 2.27 (t, J = 7.4 Hz, 1H), 2.18 – 2.07 (m, 1H), 2.06 – 1.92 (m, 1H), 1.77 –1.66 (m, 1H), 1.66 – 1.45 (m, 3H), 1.44 – 1.34 (m, 1H), 1.25 (dt, J = 14.4, 7.1 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 173.4, 173.3, 169.7, 169.7, 137.1,137.0, 129.8, 129.8, 128.3, 128.2, 127.1, 60.3, 55.0, 51.7, 49.3, 45.9, 39.5,37.6, 34.3, 34.2, 32.7, 32.3, 32.2, 30.4, 23.6, 23.4, 14.3, 14.2. Example 19

[0051] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1a (0.2 mmol, 1.0 equiv.), 2s (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 19 (52.0 mg, yield 68%, ee value 95%). The 1H and 1C spectral data are as follows: 1 H NMR(500MHz, CDCl3)δ 8.08 (t, J = 7.7 Hz, 2H), 7.59 – 7.31 (m, 9H), 7.25 – 7.19 (m, 2H), 4.27(dt, J = 31.4, 7.1 Hz, 2H), 3.84 – 3.64 (m, 1H), 3.56 – 3.31 (m, 2H), 3.19 –2.88 (m, 1H), 2.19 – 1.73 (m, 4H), 1.54 – 1.33 (m, 3H). 13 C NMR (126 MHz, CDCl3) δ 169.7, 169.7, 140.4, 140.3, 137.0, 136.9, 129.9, 128.3, 128.3,127.1, 127.1, 125.8, 125.7, 122.9, 120.5, 119.0, 108.6, 108.5, 54.9, 51.7, 49.3, 45.9, 43.0, 42.9, 39.6, 37.7, 32.4, 31.0, 30.4, 30.3, 27.8, 27.6. Example 20

[0052] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1a (0.2 mmol, 1.0 equiv.), 2t (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 20 (50.8 mg, yield 70%, ee value 94%). The 1H and 1C spectral data are as follows: 1 H NMR(500MHz, CDCl3)δ 7.91 – 7.77 (m, 2H), 7.76 – 7.64 (m, 2H), 7.58 – 7.45 (m, 2H), 7.44 – 7.31(m, 3H), 3.89 – 3.69 (m, 2H), 3.66 (t, J = 7.1 Hz, 1H), 3.63 – 3.39 (m, 2H), 3.23 – 3.00 (m, 1H), 2.32 – 2.02 (m, 2H), 1.80 – 1.38 (m, 5H). 13 C NMR (126MHz, CDCl3) δ 169.6, 168.4, 137.0, 134.0, 132.1, 132.0, 129.8, 128.3, 128.2,127.1, 123.2, 55.0, 51.7, 49.3, 45.9, 39.4, 37.8, 37.4, 32.3, 30.4, 29.9,29.7, 27.3, 27.2. Example 21

[0053] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1a (0.2 mmol, 1.0 equiv.), 2u (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 21 (39.9 mg, yield 77%, ee value 95%). The 1H and 1C spectral data are as follows: 1 H NMR(500MHz, CDCl3)δ 7.52 – 7.49 (m, 2H), 7.41 – 7.36 (m, 3H), 3.89 – 3.71 (m, 1H), 3.62 – 3.38(m, 2H), 3.22 – 3.02 (m, 1H), 2.25 – 1.96 (m, 2H), 1.63 – 1.17 (m, 12H), 0.88(dt, J = 16.3, 6.6 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 169.7, 169.6, 137.2,137.1, 129.8, 128.2, 127.1, 127.1, 55.2, 51.9, 49.4, 46.0, 39.8, 37.9, 33.4,32.8, 32.5, 31.8, 31.7, 30.6, 29.4, 29.3, 28.2, 28.1, 22.6, 22.6, 14.1, 14.1. Example 22

[0054] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1a (0.2 mmol, 1.0 equiv.), 2v (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 22 (49.8 mg, yield 85%, ee value 95%). The 1H and 1C spectral data are as follows: 1 H NMR(500MHz, CDCl3)δ 7.51 – 7.36 (m, 5H), 3.88 – 3.71 (m, 1H), 3.63 – 3.38 (m, 4H), 3.23 – 2.99(m, 1H), 2.26 – 1.96 (m, 2H), 1.80 – 1.70 (m, 2H), 1.56 – 1.24 (m, 9H). 13 CNMR (126 MHz, CDCl3) δ 169.7, 169.6, 137.2, 137.1, 129.8, 128.3, 128.2,127.1, 127.1, 55.2, 51.8, 49.4, 46.0, 45.1, 45.0, 39.7, 37.8, 33.2, 32.6,32.5, 32.5, 30.5, 28.9, 28.1, 27.9, 26.8, 26.7. Example 23

[0055] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1a (0.2 mmol, 1.0 equiv.), 2w (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, followed by column chromatography to obtain the target product 23 (69.6 mg, yield 58%, dr value 95:5). The 1H and 1C spectral data are as follows: 1 H NMR(500MHz, CDCl3)δ 7.56 – 7.47 (m, 2H), 7.44 – 7.35 (m, 3H), 7.30 – 7.23 (m, 1H), 6.86 – 6.72(m, 2H), 4.70 (t, J = 8.4 Hz, 1H), 3.92 – 3.73 (m, 1H), 3.66 – 3.55 (m, 1H), 3.53 – 3.40 (m, 1H), 3.28 – 3.05 (m, 1H), 2.95 – 2.77 (m, 2H), 2.55 (dt, J =32.4, 7.3 Hz, 2H), 2.35 – 2.01 (m, 7H), 1.95 – 1.24 (m, 19H), 0.93 (t, J =7.4 Hz, 3H), 0.82 (d, J = 2.2 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 173.9,172.1, 172.1, 169.8, 169.7, 148.4, 148.3, 138.2, 137.9, 137.9, 137.1, 136.9,129.9, 129.8, 128.3, 128.3, 127.1, 126.4, 121.5, 121.4, 118.5, 118.5, 82.4,55.0, 51.7, 49.8, 49.3, 46.0, 44.0, 42.9, 39.5, 38.2, 37.6, 36.9, 34.3, 34.3,34.2, 32.7, 32.3, 32.2, 30.5, 29.5, 27.6, 27.2, 27.0, 26.0, 23.6, 23.4, 23.3,22.3, 13.8, 12.1. Example 24

[0056] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1a (0.2 mmol, 1.0 equiv.), 2x (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 24 (57.5 mg, yield 56%, dr value 95:5). The 1H and 1C spectral data are as follows: 1 H NMR(500MHz, CDCl3)δ 7.57 – 7.47 (m, 2H), 7.42 – 7.37 (m, 3H), 7.29 (d, J= 7.8 Hz, 1H), 6.92 – 6.74 (m, 2H), 3.93 – 3.74 (m, 1H), 3.66 – 3.55 (m, 1H), 3.54 – 3.41 (m, 1H), 3.27 – 3.07 (m, 1H), 2.93 – 2.88 (m, 2H), 2.59 (t, J = 7.3 Hz, 1H), 2.56 –2.47 (m, 2H), 2.42 – 2.38 (m, 1H), 2.33 – 2.09 (m, 4H), 2.07 – 1.94 (m, 3H),1.88 – 1.79 (m, 1H), 1.78 – 1.42 (m, 11H), 0.91 (d, J = 2.3 Hz, 3H). 13 C NMR(126 MHz, CDCl3) δ 220.8, 220.7, 172.1, 172.1, 169.8, 169.7, 148.5, 148.5,138.1, 137.4, 137.0, 136.9, 129.9, 128.3, 128.3, 127.1, 126.4, 121.5, 121.5,118.7, 118.7, 55.0, 51.7, 50.4, 49.3, 48.0, 46.0, 44.2, 39.5, 38.0, 37.6,35.9, 34.3, 34.2, 32.7, 32.4, 32.2, 31.6, 30.5, 29.4, 26.3, 25.8, 23.6, 23.4, 21.6, 13.8. Example 25

[0057] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1a (0.2 mmol, 1.0 equiv.), 2y (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 25 (48.4 mg, yield 50%, ee value 90%). The 1H and 1C spectral data are as follows: 1 H NMR (500MHz, CDCl3) δ8.12 (dd, J = 11.5, 2.4 Hz, 1H), 7.90 – 7.87 (m, 1H), 7.60 – 7.52 (m, 1H), 7.51 – 7.44 (m, 3H), 7.43 – 7.33 (m, 5H), 7.05 – 7.00 (m, 1H), 5.18 (d, J =6.4 Hz, 2H), 4.10 (dt, J = 32.1, 6.5 Hz, 2H), 3.87 – 3.70 (m, 1H), 3.65 (s,1H), 3.61 (s, 1H), 3.59 – 3.36 (m, 2H), 3.21 – 3.01 (m, 1H), 2.24 – 1.97 (m,2H), 1.70 (p, J = 7.2 Hz, 1H), 1.66 – 1.45 (m, 3H), 1.41 – 1.35 (m, 1H). 13CNMR (126 MHz, CDCl3) δ 190.8, 171.4, 171.4, 169.7, 169.6, 160.5, 140.4,140.4, 137.0, 136.9, 136.3, 136.3, 135.6, 135.6, 132.9, 132.8, 132.4, 129.9,129.8, 129.5, 129.3, 129.3, 128.3, 128.3, 127.9, 127.8, 127.1, 125.2, 121.1,121.1, 73.7, 64.8, 64.7, 55.0, 51.7, 49.3, 46.0, 40.3, 40.3, 39.4, 37.4, 32.4, 30.5, 29.6, 29.1, 27.3, 27.2. Example 26

[0058] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1a (0.2 mmol, 1.0 equiv.), 2z (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, followed by column chromatography to obtain the target product 26 (67.9 mg, yield 61%, dr value 94:6). The 1H and 1C spectral data are as follows: 1 H NMR(500MHz, CDCl3)δ 7.51 – 7.48 (m, 2H), 7.45 – 7.31 (m, 3H), 7.16 (t, J = 8.1 Hz, 1H), 6.98(t, J = 8.6 Hz, 1H), 6.89 (d, J = 6.3 Hz, 1H), 5.48 (dt, J= 30.0, 6.5 Hz,1H), 3.86 – 3.68 (m, 1H), 3.61 – 3.36 (m, 2H), 3.28 – 2.96 (m, 3H), 2.95 –2.72 (m, 3H), 2.30 – 2.26 (m, 1H), 2.19 – 2.05 (m, 3H), 2.00 – 1.80 (m, 2H), 1.79 – 1.24 (m, 16H), 1.24 – 1.15 (m, 9H), 0.92 (d, J = 7.4 Hz, 3H). 13 C NMR(126 MHz, CDCl3) δ 173.0, 172.9, 169.8, 169.7, 147.2, 145.7, 137.1, 137.0,134.8, 129.8, 129.8, 128.3, 127.1, 127.1, 126.9, 126.9, 124.2, 123.9, 55.2,51.8, 49.7, 49.6, 49.4, 46.0, 45.3, 45.3, 39.7, 38.4, 37.8, 37.5, 37.3, 36.9,36.8, 36.2, 33.4, 33.1, 32.6, 32.5, 30.5, 30.2, 29.3, 27.9, 27.8, 25.7, 25.6, 25.3, 24.0, 23.9, 23.9, 19.0, 18.8, 18.6. Example 27

[0059] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1b (0.2 mmol, 1.0 equiv.), 2a (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, followed by column chromatography to obtain the target product 27 (44.0 mg, yield 75%, ee value 95%). Figures 7-8 As shown, the proton and carbon spectrum data are as follows: 1 H NMR(500MHz, CDCl3) δ 7.36 – 7.13 (m, 8H), 7.13 – 7.06 (m, 1H), 3.98 – 3.76 (m,1H), 3.60 – 3.17 (m, 2H), 3.16 – 2.75 (m, 1H), 2.74 – 2.49 (m, 2H), 2.30 (d, J = 3.1 Hz, 3H), 2.26 – 1.96 (m, 2H), 1.78 (q, J = 7.6 Hz, 1H), 1.72 – 1.49(m, 2H). 13 C NMR (126 MHz, CDCl3) δ 170.0, 169.9, 141.7, 141.6, 137.8, 137.6,133.8, 130.5, 130.4, 128.8, 128.5, 128.5, 128.3, 128.2, 126.0, 125.9, 125.9,125.6, 53.8, 50.8, 48.1, 45.0, 38.9, 37.4, 35.2, 34.5, 34.4, 34.3, 32.1,30.6, 19.0. Example 28

[0060] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1c (0.2 mmol, 1.0 equiv.), 2a (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, followed by column chromatography to obtain the target product 28 (53.8 mg, yield 87%, ee value 97%). Figures 9-10 As shown, the proton and carbon spectrum data are as follows: 1 HNMR(500MHz,CDCl3) δ 7.41 – 7.07 (m, 7H), 7.08 – 6.83 (m, 2H), 4.02 – 3.69 (m,4H), 3.59 – 2.83 (m, 3H), 2.74 – 2.48 (m, 2H), 2.26 – 1.94 (m, 2H), 1.81 –1.73 (m, 1H), 1.73 – 1.47 (m, 2H). 13 C NMR (126 MHz, CDCl3) δ 167.8, 167.8,155.3, 141.9, 141.7, 130.3, 128.5, 128.4, 128.4, 128.2, 127.8, 127.4, 127.2,126.0, 120.9, 120.9, 111.2, 111.1, 55.6, 53.1, 51.0, 47.4, 45.2, 38.6, 37.4,35.2, 34.5, 34.4, 34.3, 32.0, 30.6. Example 29

[0061] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1d (0.2 mmol, 1.0 equiv.), 2a (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, followed by column chromatography to obtain the target product 29 (49.3 mg, yield 84%, ee value 94%). Figures 11-12 As shown, the proton and carbon spectrum data are as follows: 1 HNMR (500MHz, CDCl3) δ 7.36 – 7.14 (m, 8H), 7.12 (d, J = 7.5 Hz, 1H), 3.93 –3.70 (m, 1H), 3.62 – 3.37 (m, 2H), 3.29 – 3.03 (m, 1H), 2.75 – 2.51 (m, 2H),2.36 (d, J = 4.3 Hz, 3H), 2.27 – 1.97 (m, 2H), 1.78 (q, J = 7.6 Hz, 1H), 1.73– 1.49 (m, 2H). 13 C NMR (126 MHz, CDCl3) δ 170.0, 169.9, 141.8, 141.6, 138.1,137.1, 137.0, 130.5, 128.5, 128.4, 128.4, 128.2, 128.1, 127.8, 126.0, 124.0,55.1, 51.7, 49.4, 45.9, 39.2, 37.2, 35.2, 34.5, 34.3, 32.5, 30.5, 21.4. Example 30

[0062] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1e (0.2 mmol, 1.0 equiv.), 2a (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 30 (50.8 mg, yield 81%, ee value 95%). The 1H and 1C spectral data are as follows: 1 H NMR(500MHz, CDCl3)δ 7.50 – 7.47 (m, 1H), 7.43 – 7.04 (m, 8H), 3.93 – 3.69 (m, 1H), 3.62 – 3.36(m, 2H), 3.27 – 3.00 (m, 1H), 2.78 – 2.50 (m, 2H), 2.28 – 1.99 (m, 2H), 1.78(q, J = 7.6 Hz, 1H), 1.74 – 1.49 (m, 2H). 13 C NMR (126 MHz, CDCl3) δ 168.2,168.1, 141.7, 141.5, 138.8, 138.6, 134.4, 130.0, 129.7, 128.5, 128.5, 128.3,128.2, 127.4, 126.1, 126.0, 125.3, 125.2, 55.0, 51.8, 49.4, 46.0, 39.3, 37.2,35.1, 34.4, 34.4, 34.3, 32.4, 30.5. Example 31

[0063] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1f (0.2 mmol, 1.0 equiv.), 2a (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 31 (52.8 mg, yield 90%, ee value 95%). The 1H and 1C spectral data are as follows: 1 H NMR(500MHz, CDCl3)δ 7.42 – 7.40 (m, 2H), 7.32 – 7.08 (m, 7H), 3.91 – 3.70 (m, 1H), 3.62 – 3.39(m, 2H), 3.29 – 3.07 (m, 1H), 2.74 – 2.51 (m, 2H), 2.37 (d, J = 5.2 Hz, 3H),2.25 – 1.97 (m, 2H), 1.78 (q, J = 7.6 Hz, 1H), 1.73 – 1.49 (m, 2H). 13 C NMR (126 MHz, CDCl3) δ 169.9, 169.8, 141.8, 141.6, 140.0, 134.2, 134.0, 128.9,128.5, 128.4, 128.4, 128.2, 127.3, 126.0, 55.2, 51.8, 49.5, 46.0, 39.3, 37.2,35.2, 34.5, 34.4, 34.3, 32.5, 30.5, 21.4. Example 32

[0064] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1f (0.2 mmol, 1.0 equiv.), 2a (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 32 (57.9 mg, yield 88%, ee value 93%). The 1H and 1C spectral data are as follows: 1 H NMR(500MHz, CDCl3)δ 7.93 – 7.77 (m, 3H), 7.56 – 7.38 (m, 4H), 7.34 – 7.28 (m, 1H), 7.24 – 6.97(m, 4H), 4.11 – 3.90 (m, 1H), 3.74 – 3.35 (m, 1H), 3.26 – 2.75 (m, 2H), 2.75 – 2.65 (m, 1H), 2.55 – 2.40 (m, 1H), 2.30 – 1.91 (m, 2H), 1.86 – 1.77 (m,1H), 1.70 – 1.47 (m, 2H). 13 C NMR (126 MHz, CDCl3) δ 169.3, 169.2, 141.7,141.5, 135.7, 135.5, 133.6, 133.5, 129.3, 129.2, 128.5, 128.5, 128.4, 128.4,128.2, 127.0, 126.4, 126.3, 126.1, 126.0, 125.3, 125.2, 124.9, 124.9, 123.8,123.8, 53.9, 51.2, 48.3, 45.4, 38.9, 37.4, 35.2, 34.5, 34.4, 34.2, 32.1, 30.7. Example 33

[0065] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, 1 g (0.2 mmol, 1.0 equiv.) of substrate, 2a (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 33 (57.9 mg, yield 88%, ee value 93%). The 1H and 1C spectral data are as follows: 1 H NMR(500MHz, CDCl3)δ 7.93 – 7.77 (m, 3H), 7.56 – 7.38 (m, 4H), 7.34 – 7.28 (m, 1H), 7.24 – 6.97(m, 4H), 4.11 – 3.90 (m, 1H), 3.74 – 3.35 (m, 1H), 3.26 – 2.75 (m, 2H), 2.75 – 2.65 (m, 1H), 2.55 – 2.40 (m, 1H), 2.30 – 1.91 (m, 2H), 1.86 – 1.77 (m,1H), 1.70 – 1.47 (m, 2H). 13 C NMR (126 MHz, CDCl3) δ 169.3, 169.2, 141.7,141.5, 135.7, 135.5, 133.6, 133.5, 129.3, 129.2, 128.5, 128.5, 128.4, 128.4,128.2, 127.0, 126.4, 126.3, 126.1, 126.0, 125.3, 125.2, 124.9, 124.9, 123.8,123.8, 53.9, 51.2, 48.3, 45.4, 38.9, 37.4, 35.2, 34.5, 34.4, 34.2, 32.1, 30.7. Example 34

[0066] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1h (0.2 mmol, 1.0 equiv.), 2a (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 34 (52.4 mg, yield 79%, ee value 95%). The 1H and 1C spectral data are as follows: 1 H NMR(500MHz, CDCl3)δ 7.36 – 6.95 (m, 7H), 6.80 (d, J = 7.9 Hz, 1H), 5.97 (d, J = 4.4 Hz, 2H),3.87 – 3.67 (m, 1H), 3.61 – 3.38 (m, 2H), 3.29 – 3.04 (m, 1H), 2.75 – 2.49(m, 2H), 2.22 – 1.98 (m, 2H), 1.82 – 1.50 (m, 3H). 13 C NMR (126 MHz, CDCl3) δ169.0, 168.9, 148.9, 147.4, 141.8, 141.6, 130.8, 130.7, 128.5, 128.3, 128.2,126.0, 121.8, 108.1, 108.0, 101.4, 55.3, 51.9, 49.6, 46.1, 39.3, 37.2, 35.1,34.5, 34.3, 32.5, 30.5. Example 35

[0067] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1i (0.2 mmol, 1.0 equiv.), 2a (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 35 (38.4 mg, yield 83%, ee value 92%). The 1H and 1C spectral data are as follows: 1 H NMR(500MHz, CDCl3)δ 7.32 – 7.25 (m, 2H), 7.24 – 7.11 (m, 3H), 3.81 – 3.63 (m, 1H), 3.59 – 3.47(m, 1H), 3.39 – 3.28 (m, 1H), 3.06 – 2.94 (m, 1H), 2.72 – 2.58 (m, 2H), 2.28 – 2.20 (m, 2H), 2.14 – 1.99 (m, 2H), 1.73 (p, J = 7.5 Hz, 2H), 1.66 – 1.46(m, 1H), 1.14 (td, J = 7.4, 2.2 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 172.4,172.4, 141.8, 141.7, 128.5, 128.4, 128.3, 128.3, 126.0, 125.9, 52.1, 51.1,46.3, 45.4, 39.0, 37.1, 35.0, 34.9, 34.4, 32.2, 30.5, 27.8, 27.6, 9.1. Example 36

[0068] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1j (0.2 mmol, 1.0 equiv.), 2a (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 36 (29.9 mg, yield 61%, ee value 97%). The 1H and 1C spectral data are as follows: 1 H NMR(500MHz, CDCl3)δ 7.33 – 7.24 (m, 2H), 7.24 – 7.11 (m, 3H), 3.82 – 3.62 (m, 1H), 3.60 – 3.48(m, 1H), 3.41 – 3.28 (m, 1H), 3.07 – 2.95 (m, 1H), 2.73 – 2.58 (m, 2H), 2.21(q, J = 6.8, 6.4 Hz, 1H), 2.14 – 1.91 (m, 2H), 1.77 – 1.46 (m, 5H), 0.96 (t, J = 7.4 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 171.8, 171.7, 141.8, 141.7, 128.5,128.4, 128.3, 128.3, 126.1, 126.0, 52.3, 51.0, 46.4, 45.3, 39.0, 37.1, 36.7,36.5, 35.0, 34.9, 34.4, 32.2, 30.5, 18.4, 14.1. Example 37

[0069] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1k (0.2 mmol, 1.0 equiv.), 2a (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 37 (34.7 mg, yield 67%, ee value 94%). The 1H and 1C spectral data are as follows: 1 H NMR(500MHz, CDCl3)δ 7.33 – 7.24 (m, 2H), 7.23 – 7.11 (m, 3H), 3.81 – 3.62 (m, 1H), 3.60 – 3.50(m, 1H), 3.40 – 3.28 (m, 1H), 3.06 – 2.94 (m, 1H), 2.72 – 2.59 (m, J = 7.7,7.2 Hz, 2H), 2.25 – 2.03 (m, 5H), 1.73 (p, J = 7.2 Hz, 2H), 1.66 – 1.46 (m,1H), 0.96 (d, J = 6.4 Hz, 6H). 13 C NMR (126 MHz, CDCl3) δ 171.3, 171.2, 141.8,141.7, 128.5, 128.4, 128.3, 128.3, 126.0, 125.9, 52.5, 51.0, 46.6, 45.3,43.7, 43.4, 39.0, 37.1, 35.1, 34.8, 34.4, 32.2, 30.5, 25.6, 22.8, 22.8. Example 38

[0070] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1L (0.2 mmol, 1.0 equiv.), 2a (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 38 (60.7 mg, yield 90%, ee value 94%). The 1H and 1C spectral data are as follows: 1 H NMR (500 MHz, CDCl3, 50) o C) δ 7.34 – 7.23 (m, 2H), 7.19 – 7.15 (m, 3H), 3.85 – 3.66 (m, 2H), 3.53 – 3.40 (m, 1H), 3.13 (dd, J = 11.0, 8.4 Hz, 1H), 2.71 – 2.60 (m, 2H), 2.09 – 1.90 (m, 11H), 1.77 – 1.66 (m, 8H), 1.54 – 1.42 (m, 1H). 13 C NMR (126MHz, CDCl3, 50 o C) δ 175.8, 141.8, 128.4, 128.3, 125.9, 53.5, 47.6, 41.8, 38.4,36.8, 34.8, 34.5, 28.5. Example 39

[0071] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1m (0.2 mmol, 1.0 equiv.), 2a (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 39 (37.2 mg, yield 65%, ee value 91%). The 1H and 1C spectral data are as follows: 1 H NMR (500 MHz, CDCl3) δ 7.32 – 7.25 (m, 2H), 7.20 – 7.17 (m, 3H), 3.46 – 3.35 (m, 3H), 3.23– 3.14 (m, 4H), 3.04 (t, J = 9.6 Hz, 1H), 2.69 – 2.60 (m, 2H), 2.13 – 2.03(m, 1H), 2.00 – 1.95 (m, 1H), 1.72 (q, J = 7.6 Hz, 2H), 1.62 – 1.40 (m, 7H). 13 C NMR (126 MHz, CDCl3) δ 163.2, 142.0, 128.4, 128.3, 125.9, 54.1, 48.1,47.2, 38.3, 34.9, 34.5, 31.6, 25.9, 24.8. Example 40

[0072] This invention provides a catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, comprising the following steps: Under a nitrogen atmosphere, 4.4 mg CoBr2, 13.1 mg chiral ligand L1, and 2 ml of ethylene glycol dimethyl ether are added to a reaction flask. The mixture is stirred at room temperature for 10 minutes. Then, substrate 1n (0.2 mmol, 1.0 equiv.), 2a (0.4 mmol, 2.0 equiv.), and CsF (91.1 mg, 0.6 mmol, 3.0 equiv.) are added. Another 2 ml of ethylene glycol dimethyl ether is then added. The reaction system is cooled to 0°C, and (MeO)2MeSiH (63.7 mg, 0.6 mmol, 3.0 equiv.) is added dropwise. The reaction is then carried out at 0°C for 12 hours. After the reaction is complete, the reaction system is allowed to return to room temperature, and 5 ml of ethyl acetate is added. The mixture is filtered, and the filter cake is washed three times with ethyl acetate. Solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain the target product 40 (55.6 mg, yield 75%, ee value 94%). The 1H and 1C spectral data are as follows: 1 H NMR (500 MHz, CDCl3, 50) o C) δ 7.29 – 7.23 (m, 6H), 7.16 (t, J = 7.4 Hz, 1H), 7.13 – 7.01 (m,8H), 3.44 (dd, J = 11.0, 7.2 Hz, 1H), 3.36 – 3.32 (m, 1H), 3.11 (q, J = 10.5, 9.3 Hz, 1H), 2.83 (t, J = 9.5 Hz, 1H), 2.61 – 2.51 (m, 2H), 2.09 – 1.99 (m,1H), 1.93 – 1.88 (m, 1H), 1.62 (q, J = 7.6 Hz, 2H), 1.48 – 1.41 (m, 1H). 13 CNMR (126 MHz, CDCl3, 50 o C) δ 158.6, 144.6, 141.8, 129.2, 128.5, 128.3, 126.0,125.7, 124.7, 53.2, 47.4, 37.9, 34.8, 34.4, 31.4.

[0073] Table 1. Structural formulas of raw materials and target products in Examples 1-40

[0074] ;

[0075] ;

[0076] ;

[0077] ;

[0078] ;

[0079] ;

[0080] ;

[0081] ;

[0082] .

[0083] The present invention has been described in detail above through embodiments, but the content described is only an exemplary embodiment of the present invention and should not be considered as limiting the scope of the present invention. The scope of protection of the present invention is defined by the claims. Any technical solutions designed by those skilled in the art using the technical solutions described in the present invention, or designed by those skilled in the art under the inspiration of the technical solutions of the present invention, within the substance and protection scope of the present invention, to achieve the above-mentioned technical effects, or any equivalent changes and improvements made to the scope of the application, should still fall within the patent protection scope of the present invention.

Claims

1. A catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines, characterized in that, The reaction includes the following steps: acyl-protected 3-pyrrolidine reacts with an alkyl iodide in an organic solvent at 0°C under the catalysis of cobalt and a chiral oxazoline ligand, in the presence of a base and a silane reagent, to yield a chiral 3-alkyl-substituted pyrrolidine product. ； The chiral oxazoline ligand used is at least one of L1-L8. ； The amount of chiral oxazoline ligand is 10-15 mol% of the acyl-protected 3-pyrrolline; Structural formulas of raw materials and target products ； ； ； ； ； ； ； 。 2. The catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines as described in claim 1, characterized in that, Add cobalt, chiral oxazoline ligand and organic solvent to the reaction flask, stir until homogeneous at room temperature, then add acyl-protected 3-pyrrolidone, alkyl iodide, base and organic solvent, cool to zero degrees Celsius, add silane reagent dropwise, and then react at zero degrees Celsius for 12-36 hours.

3. The catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines as described in claim 1 or 2, characterized in that, After the reaction was completed, ethyl acetate was added, the mixture was filtered, and the filter cake was washed with ethyl acetate 2-3 times. The solvent was removed under reduced pressure, and the chiral 3-alkyl-substituted pyrrolidine products were separated by column chromatography.

4. The catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines as described in claim 1, characterized in that, The molar ratio of the acyl-protected 3-pyrrolidone to the alkyl iodide is 1:2, and the concentration is 0.05 mol / L.

5. The catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines as described in claim 1, characterized in that, The cobalt used is at least one of CoBr2, CoCl2, CoI2, Co(DME)Br2, CoCl2(PPh3)3, Co(acac)2, Co(OAc)2(H2O)4, and Co(OAc)2, and the amount of cobalt is 2-15 mol of acyl-protected 3-pyrrolline.

6. The catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines as described in claim 1, characterized in that, The base used is at least one of diisopropylamine, triethylamine, tetramethylethylenediamine, N,N-dimethylethylamine, N,N-diisopropylethylamine, piperidine, 2,2,6,6-tetramethylpiperidine, 1,2,2,6,6-pentamethylpiperidine, potassium fluoride, potassium phosphate, cesium carbonate, cesium fluoride, potassium carbonate, or sodium carbonate, and the amount of base is 2-3 eq of acyl-protected 3-pyrroline.

7. The catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines as described in claim 1, characterized in that, The silane reagent used is at least one of dimethoxymethylsilane, methylphenyldichlorosilane, trimethoxysilane, phenyldimethylsilane, or triethoxysilane, and the amount of silane reagent is 2-3 eq of acyl-protected 3-pyrrolline.

8. The catalytic asymmetric synthesis method for chiral 3-alkyl-substituted pyrrolidines as described in claim 1, characterized in that, The organic solvent used is at least one of tetrahydrofuran, toluene, chlorobenzene, xylene, mesitylene, pentafluorobenzene, fluorobenzene, cyclopentyl methyl ether, ethylene glycol dimethyl ether, methyl tert-butyl ether, tert-butylmethylene ether, N,N-dimethylformamide, or 1,4-dioxane.

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