A method for preparing chiral pyrrolizine-3-one compounds

Abstract

The invention discloses a method for preparing a chiral pyrrolizine-3-one compound. N The pyrrole derivatives are used as raw materials, and the corresponding chiral pyrrolazine-3-one compounds are reacted in an organic solvent at a temperature of 40-140°C under the combined action of a hydrogen source, a palladium salt and a ligand. N The chiral pyrrolazine-3-one compounds were rapidly constructed by using pyrroloacylpyrrole derivatives as raw materials and constructing a ring and two chemical bonds in one step. The reaction conditions are mild and the operation is simple. It has the advantages of easy availability of reaction raw materials, wide applicability of substrates and easy separation of target products.

Description

Technical Field

[0001] The invention belongs to the technical field of catalytic synthesis and relates to a method for preparing a chiral pyrrolizine-3-one compound, and more specifically, to a method for synthesizing a chiral pyrrolizine-3-one compound by a palladium-catalyzed intramolecular asymmetric cycloisomerization reaction of N-alkynoylpyrrole. Background Art

[0002]

[0003] As mentioned above, chiral pyrrolizine-3-one skeletons are widely present in natural products or drug molecules. Such compounds have medicinal value such as anti-cancer, anti-inflammatory, and strong protease inhibitory activity. Some pyrrolizine-3-one derivatives also have excellent photophysical and chemical properties and can be used to prepare nonlinear optical materials, fluorescent materials, photosensitive materials, photoinitiators, etc. Therefore, the asymmetric synthesis of such compounds is of great research significance.

[0004] Enyne cycloisomerization can efficiently synthesize a series of cyclic compounds. By changing the substrate structure or choosing a suitable metal catalyst, monocyclic, cyclo- or spirocyclic products can be obtained. Although there have been many excellent works in the field of palladium-catalyzed enyne cycloisomerization, there are few reports on the asymmetric cycloisomerization reaction using 1,5-enyne as a substrate. In addition, most of the known reports use classic 1,5-enyne as a substrate. When the double bond is located in the aromatic system, it is more challenging to achieve asymmetric cycloisomerization reactions of 1,5-enyne substrates such as N-alkynoylpyrrole. Based on this, we used N-alkynoylpyrrole derivatives as raw materials and developed a palladium-catalyzed intramolecular asymmetric dearomatization cycloisomerization reaction to quickly synthesize chiral pyrrolazine-3-one compounds with unique structures, and established a library of potential biologically active molecules, which has great research value. Summary of the invention

[0005] The object of the present invention is to provide a method for preparing a chiral pyrrolazine-3-one compound, which utilizes easily prepared reaction raw materials and synthesizes the chiral pyrrolazine-3-one compound in one step through a palladium-catalyzed intramolecular dearomatization cycloisomerization reaction of an N-alkynoylpyrrole derivative.

[0006] The method for preparing a chiral pyrrolazine-3-one compound is characterized in that an N-alkynoyl pyrrole derivative is used as a raw material, and a reaction is carried out in an organic solvent at a temperature of 40-140° C. under the joint action of a hydrogen source, a palladium salt and a ligand. After the reaction is completed, a chiral pyrrolazine-3-one compound is obtained by post-treatment. The general reaction formula is as follows:

[0007]

[0008] Where: R 1 is one of an alkyl group or a phenyl group; R 2 It is an alkyl group or a substituted phenyl group.

[0009] The method for preparing the chiral pyrrolizine-3-one compound is characterized in that R 1 and R 2 The alkyl groups in R are all selected from C1 to C10 straight or branched alkanes; 2 The substituted phenyl group is monosubstituted or polysubstituted, and the substituent is a C1-C10 straight chain or branched alkane, alkoxy or halogen.

[0010] The method for preparing the chiral pyrrolizine-3-one compound is characterized in that the solvent is selected from any one of dichloromethane, dichloroethane, toluene, m-xylene, methanol, ethanol, methyl tert-butyl ether, ether, tetrahydrofuran or 1,4-dioxane, and the volume ratio of the solvent to the substance amount of the N-alkynoyl pyrrole derivative is 1 to 100:1, preferably 5 to 20:1, the volume unit is milliliter, and the substance amount unit is millimole.

[0011] The preparation method of the chiral pyrrolazine-3-one compound is characterized in that the palladium catalyst is selected from any one of tetrakistriphenylphosphine palladium, di(tri-tert-butylphosphine) palladium, tri(dibenzylideneacetone)dipalladium, bis(dibenzylideneacetone)palladium, palladium acetate, tetraacetonitrile ditetrafluoroborate palladium, diacetonitrile dichloropalladium, and allylpalladium chloride dimer.

[0012] The method for preparing the chiral pyrrolizine-3-one compound is characterized in that the ligand is selected from (S)-Monophos, (S)-Segphos, (S)-Binap, (S)- t Any one of Bu-Phox, (R,R)-Ph-BPE, and (R)-4-phenoxybinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphine.

[0013] The method for preparing the chiral pyrrolizine-3-one compound is characterized in that the hydrogen source is selected from any one of benzoic acid, acetic acid, p-toluenesulfonic acid monohydrate, triethylamine hydrochloride, triethylamine hydrobromide, triethylamine hydroiodide, triethylamine p-toluenesulfonate, water or formic acid.

[0014] The method for preparing the chiral pyrrolizine-3-one compound is characterized in that the molar ratio of the N-alkynoyl pyrrole derivative, the palladium catalyst, the ligand and the hydrogen source is 1:0.05-0.4:0.1-0.8:1-5.

[0015] The method for preparing the chiral pyrrolizine-3-one compound is characterized in that the reaction temperature is 80-140° C. and the reaction time is 3-72 hours, preferably 12 hours.

[0016] The preparation method of the chiral pyrrolizine-3-one compound is characterized in that the post-treatment step is: after the reaction is completed, the solvent is removed by rotary evaporation and then separated by column chromatography to obtain the target product; the mobile phase of the column chromatography is a mixture of petroleum ether and ethyl acetate in a volume ratio of 1 to 10:1.

[0017] By adopting the above technology, compared with the prior art, the beneficial effects of the present invention are as follows:

[0018] The present invention uses N-alkynoyl pyrrole derivatives as raw materials, and under the joint action of a palladium catalyst, a ligand and a hydrogen source, etc., an intramolecular cycloisomerization reaction is carried out to efficiently synthesize chiral pyrrolazine-3-one compounds in one step. The reaction raw materials are simple and easy to obtain, the operation is simple, the conditions are mild, and it has the advantages of good functional group tolerance and wide substrate universality. DETAILED DESCRIPTION

[0019] The present invention will be further described below in conjunction with specific embodiments, but the protection scope of the present invention is not limited thereto;

[0020] Example 1

[0021] Under nitrogen atmosphere, N-alkynoyl pyrrole derivative 1a (44.6 mg, 0.2 mmol), palladium tetraacetonitrile tetrafluoroborate (8.8 mg, 0.02 mmol), (R)-4-phenoxy dinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphine heterocycloheptatriene (16.8 mg, 0.04 mmol), triethylamine hydroiodide (57.2 mg, 0.25 mmol) were added to a dry Schlenk tube in sequence. Then tetrahydrofuran (2.0 mL) was added via a syringe, and the reaction mixture was reacted at 120°C for 12 h. The reaction solution was then concentrated under reduced pressure and the residue was purified by silica gel chromatography, eluted with ethyl acetate / petroleum ether 1:10 (v / v) to obtain product 2a with a yield of 60%. The er was determined to be 92 / 8 by HPLC. [Lux 5u Cellulose-3 C1 column (25cm×0.46cm ID), n-hexane / i-PrOH=90 / 10, 0.7mL / min, 254nm; t major =16.4min,t minor =17.5min]; 1H NMR (400MHz, CDCl3) δ7.61-7.56(m,2H),7.50-7.46(m,3H),6.56(d,J=5.8Hz,1 H),6.27(s,1H),6.20(d,J=5.8Hz,1H),5.26(s,1H),4.77(s,1H),1.58(s,3H). 13 CNMR(100MHz, CDCl3)δ173.9,166.3,145.2,135.4,131.0,130.6,129.1,127.6,120.8,95.9,34.1,22.4,14.1.MS m / z(ESI+):Calculated for C 15 H 14 NO + ([M+H] + ):224.1,found224.1.

[0022] Example 2

[0023] Under nitrogen atmosphere, N-alkynoyl pyrrole derivative 1b (48.2 mg, 0.2 mmol), palladium acetate (4.5 mg, 0.02 mmol), (S)-BINAP (12.4 mg, 0.02 mmol), triethylamine hydroiodide (57.2 mg, 0.25 mmol) were added to a dry Schlenk tube in sequence. Tetrahydrofuran (2.0 mL) was then added via a syringe, and the reaction mixture was reacted at 120°C for 12 h. The reaction solution was then concentrated under reduced pressure and the residue was purified by silica gel chromatography, eluted with ethyl acetate / petroleum ether 1:10 (v / v), to give product 2b with a yield of 80%. The er was determined to be 84 / 16 by HPLC. [Lux5u Cellulose-3 C1 column (25 cm × 0.46 cm ID), n-hexane / i-PrOH = 90 / 10, 0.7 mL / min, 254 nm; t major =14.9min,t minor =18.7min]; 1 H NMR (400MHz, CDCl3) δ7.60-7.54(m,2H),7.19-7.14(m,2H),6.51(d,J=6.5Hz,1H ),6.201(s,2H),6.198(d,J=5.6Hz,1H),5.26(s,1H),4.76(s,1H),1.56(s,3H). 13C NMR (100MHz, CDCl3) δ173.6,165.1,145.1,135.0,131.2,129.6(d,J=8.5Hz),120.7(d,J=1.7Hz),116.3(d,J=21.8Hz),96.1,80.0,27.5,22.3,14.1.MS m / z(ESI+):Calculated for C 15 H 13 NO + ([M+H] + ):242.1,found242.1.

[0024] Embodiment 3:

[0025] Under nitrogen atmosphere, N-alkynoyl pyrrole derivative 1c (51.4 mg, 0.2 mmol), palladium acetate (4.5 mg, 0.02 mmol), (S)-Monophos (14.4 mg, 0.04 mmol), triethylamine hydroiodide (57.2 mg, 0.25 mmol) were added to a dry Schlenk tube in sequence. Tetrahydrofuran (2.0 mL) was then added via a syringe, and the reaction mixture was reacted at 120°C for 12 h. The reaction solution was then concentrated under reduced pressure and the residue was purified by silica gel chromatography, eluted with ethyl acetate / petroleum ether 1:10 (v / v), to give product 2c with a yield of 60%. The er was determined to be 89 / 11 by HPLC. [Lux5u Cellulose-3 C1 column (25 cm × 0.46 cm ID), n-hexane / i-PrOH = 90 / 10, 0.7 mL / min, 254 nm; t minor =16.1min,t major =21.4min]; 1 H NMR (400MHz, CDCl3) δ7.52-7.49(m,2H),7.46-7.41(m,2H),6.50(d,J=5.7Hz,1 H),6.24(s,1H),6.20(d,J=5.8Hz,1H),5.26(s,1H),4.77(s,1H),1.55(s,3H). 13 C NMR (100MHz, CDCl3) δ173.5,165.0,145.0,136.7,134.9,131.3,129.8,129.4,128.8,121.3,96.2,79.9,27.5.MS m / z(ESI+):Calculated for C 15 H 13ClNO + ([M+H] + ):258.1,found258.0.

[0026] Example 4

[0027] Under nitrogen atmosphere, N-alkynoylpyrrole derivative 1d (47.4 mg, 0.2 mmol), palladium tetraacetonitrile tetrafluoroborate (8.8 mg, 0.02 mmol), (R,R)-Ph-BPE (20.2 mg, 0.04 mmol), triethylamine hydroiodide (57.2 mg, 0.25 mmol) were added to a dry Schlenk tube in sequence. Tetrahydrofuran (2.0 mL) was then added via a syringe, and the reaction mixture was reacted at 110° C. for 24 h, and then the reaction solution was concentrated under reduced pressure and the residue was purified by silica gel chromatography, eluted with ethyl acetate / petroleum ether 1:10 (v / v), to give product 2d with a yield of 38%. The er was determined to be 91 / 9 by HPLC. [Lux 5u Cellulose-3 C1 column (25cm×0.46cmID), n-hexane / i-PrOH=90 / 10, 0.7mL / min, 254nm; t major =11.8min,t minor =15.8min]; 1 H NMR (400MHz, CDCl3) δ7.50-7.46(m,2H),7.29-7.26(m,2H),6.55(d,J=5.0Hz,1H),6. 22(s,1H),6.18(d,J=5.8Hz,1H),5.25(s,1H),4.75(s,1H),2.41(s,3H),1.57(s,3H). 13 C NMR (100MHz, CDCl3) δ174.0,166.3,145.3,141.1,135.5,130.9,129.8,127.5,119.8,95.7,80.1,29.7,27.6,21.4.MSm / z(ESI+):Calculated for C 16 H 16 NO + ([M+H] + ):238.1,found238.1.

[0028] Example 5

[0029] Under nitrogen atmosphere, N-alkynoyl pyrrole derivative 1e (50.6 mg, 0.2 mmol), palladium acetate (4.5 mg, 0.02 mmol), (S)-Monophos (14.4 mg, 0.04 mmol), triethylamine hydrochloride (34.3 mg, 0.25 mmol) were added to a dry Schlenk tube in sequence. Tetrahydrofuran (2.0 mL) was then added via a syringe, and the reaction mixture was reacted at 100 °C for 24 h. The reaction solution was then concentrated under reduced pressure and the residue was purified by silica gel chromatography, eluted with ethyl acetate / petroleum ether 1:10 (v / v), to give product 2e with a yield of 31%. The product was determined to be 87 / 13 by HPLC. [Lux5u Cellulose-3 C1 column (25 cm × 0.46 cm ID), n-hexane / i-PrOH = 90 / 10, 0.7 mL / min, 254 nm; t minor =20.0min,t major =26.0min]; 1 H NMR (400MHz, CDCl3) δ7.57-7.51(m,2H),7.01-6.95(m,2H),6.53(d,J=5.0Hz,1H),6. 18(d,J=5.8Hz,1H),6.16(s,1H),5.25(s,1H),4.74(s,1H),3.87(s,3H),1.58(s,3H). 13 C NMR (100MHz, CDCl3) δ173.1,164.9,160.4,144.3,134.4,129.9,128.2,117.5,113.5,94.6,54.4,26.7.MS m / z(ESI+):Calculated forC 16 H 16 NO2 + ([M+H] + ):254.1,found254.1

[0030] Example 6

[0031] Under nitrogen atmosphere, N-alkynoyl pyrrole derivative 1f (55.8 mg, 0.2 mmol), palladium tetraacetonitrile tetrafluoroborate (8.8 mg, 0.02 mmol), (R)-4-phenoxy dinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphine heterocycloheptatriene (16.8 mg, 0.04 mmol), triethylamine hydroiodide (57.2 mg, 0.25 mmol) were added to a dry Schlenk tube in sequence. Then tetrahydrofuran (2.0 mL) was added via a syringe, and the reaction mixture was reacted at 100°C for 12 h. The reaction solution was then concentrated under reduced pressure and the residue was purified by silica gel chromatography, eluted with ethyl acetate / petroleum ether 1:10 (v / v) to obtain the product 2f with a yield of 41%. The er was determined to be 87 / 13 by HPLC. [Lux 5u Cellulose-3 C1 column (25cm×0.46cm ID), n-hexane / i-PrOH=90 / 10, 0.7mL / min, 254nm; t major =10.8min,t minor =11.7min]; 1 H NMR (400MHz, CDCl3) δ7.55-7.51(m,2H),7.50-7.47(m,2H),6.55(d,J=5.0Hz,1H),6. 24(s,1H),6.18(d,J=5.8Hz,1H),5.25(s,1H),4.74(s,1H),1.59(s,3H),1.35(s,9H). 13 C NMR (100MHz, CDCl3) δ174.1,166.2,154.2,145.3,135.5,130.9,128.4,127.4,126.1,119.8,95.7,80.1,60.4,34.9,31.1,29.7,27.7.MS m / z(ESI+):Calculatedfor C 19 H 22 NO + ([M+H] + ):280.2,found280.2.

[0032] Example 7

[0033] Under nitrogen atmosphere, 1 g (58.2 mg, 0.2 mmol) of N-alkynoylpyrrole derivative, palladium diacetylacetonate (6.1 mg, 0.02 mmol), (S)- tBu-Phox (9.3 mg, 0.024 mmol), triethylamine hydrochloride (34.3 mg, 0.25 mmol). Then toluene (2.0 mL) was added through a syringe, and the reaction mixture was reacted at 120 ° C for 12 h, and then the reaction solution was concentrated under reduced pressure and the residue was purified by silica gel chromatography, eluted with ethyl acetate / petroleum ether 1:10 (v / v) to obtain 2 g of product with a yield of 46%. The er was determined to be 82 / 18 by HPLC. [Lux5u Cellulose-3 C1 column (25cm×0.46cm ID), n-hexane / i-PrOH=90 / 10, 0.7mL / min, 254nm; t major =13.6min,t minor =17.5min]; 1 H NMR (400MHz, CDCl3) δ7.75-7.72(m,2H),7.70-7.66(m,2H),6.52(d,J=5.0Hz,1 H),6.32(s,1H),6.22(d,J=5.8Hz,1H),5.28(s,1H),4.79(s,1H),1.57(s,3H). 13 C NMR(100MHz, CDCl3)δ144.9,134.7,131.4,127.8,126.1,123.0,96.5,29.7,27.3,1.0.MS m / z(ESI+):Calculated for C 16 H 13 F3NO + ([M+H] + ):292.1,found292.1.

[0034] Example 8

[0035] Under nitrogen atmosphere, N-alkynoylpyrrole derivative 1h (61.4 mg, 0.2 mmol), palladium acetate (4.5 mg, 0.02 mmol), (S)- tBu-Phox (9.3 mg, 0.024 mmol), triethylamine hydroiodide (57.2 mg, 0.25 mmol). Then toluene (2.0 mL) was added by syringe, the reaction mixture was reacted at 100 ° C for 12 h, and then the reaction solution was concentrated under reduced pressure and the residue was purified by silica gel chromatography, eluted with ethyl acetate / petroleum ether 1:10 (v / v) to obtain the product 2h, with a yield of 50%. The er was determined to be 89 / 11 by HPLC. [Lux 5uCellulose-3 C1 column (25cm×0.46cm ID), n-hexane / i-PrOH=90 / 10, 0.7mL / min, 254nm; t major =12.1min,t minor =14.9min]; 1 H NMR (400MHz, CDCl3) δ7.63-7.59(m,2H),7.34-7.30(m,2H),6.50(d,J=5.0Hz,1 H),6.25(s,1H),6.21(d,J=5.8Hz,1H),5.27(s,1H),4.78(s,1H),1.57(s,3H). 13 C NMR (100MHz, CDCl3) δ173.4, 164.7, 150.55 (q, J = 2.0Hz), 145.0, 134.8, 131.3, 129.9, 129.2, 121.6, 121.3, 119.1, 96.3, 80.0, 27.4.MS m / z(ESI+):Calculated for C 16 H 13 F3NO + ([M+H] + ):308.1,found308.0.

[0036] Example 9

[0037] Under nitrogen atmosphere, N-alkynoyl pyrrole derivative 1i (59.8 mg, 0.2 mmol), palladium tetraacetonitrile tetrafluoroborate (8.8 mg, 0.02 mmol), (R)-4-phenoxy dinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphine heterocycloheptatriene (16.8 mg, 0.04 mmol), triethylamine hydroiodide (57.2 mg, 0.25 mmol) were added to a dry Schlenk tube in sequence. Then tetrahydrofuran (2.0 mL) was added via a syringe, and the reaction mixture was reacted at 80°C for 24 h. The reaction solution was then concentrated under reduced pressure and the residue was purified by silica gel chromatography, eluted with ethyl acetate / petroleum ether 1:10 (v / v) to obtain product 2i with a yield of 35%. The er was determined to be 93 / 7 by HPLC. [Lux 5u Cellulose-3 C1 column (25cm×0.46cm ID), n-hexane / i-PrOH=90 / 10, 0.7mL / min, 254nm; t minor =19.9min,t major =27.3min]; 1 H NMR (400MHz, CDCl3) δ7.71-7.60(m,6H),7.50-7.44(m,2H),7.42-7.37(m,1H),6.58(d,J =5.0Hz,1H),6.30(s,1H),6.20(d,J=5.8Hz,1H),5.27(s,1H),4.76(s,1H),1.62(s,3H). 13 C NMR (100MHz, CDCl3) δ173.9,165.9,145.2,143.4,139.8,135.4,131.1,130.1,129.0,128.13,128.05,127.7,127.1,120.6,95.9,80.1,27.7.MS m / z(ESI+):Calculated for C 21 H 18 NO + ([M+H] + ):300.1,found300.1.

[0038] Example 10

[0039] Under nitrogen atmosphere, N-alkynoylpyrrole derivative 1j (57.0 mg, 0.2 mmol), palladium acetate (4.5 mg, 0.02 mmol), (R)-4-phenoxy dinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphine heterocycloheptatriene (16.8 mg, 0.04 mmol), triethylamine hydroiodide (57.2 mg, 0.25 mmol) were added to a dry Schlenk tube in sequence. Then tetrahydrofuran (2.0 mL) was added via a syringe, and the reaction mixture was reacted at 120°C for 24 h. The reaction solution was then concentrated under reduced pressure and the residue was purified by silica gel chromatography, eluted with ethyl acetate / petroleum ether 1:10 (v / v) to obtain product 2j with a yield of 42%. Theer was determined to be 89 / 11 by HPLC. [Lux 5u Cellulose-3 C3 column (25cm×0.46cm ID), nhexane / i-PrOH=95 / 05, 0.7mL / min, 254nm; t minor =28.3min,t major =32.6min]; 1 H NMR (400MHz, CDCl3) δ7.41-7.26(m,10H),6.74(d,J=6.7Hz,1H),6.51(s,1H),6.41(d,J=5.8Hz,1H),5.21(s,1H),4.76(s,1H). 13 C NMR (100MHz, CDCl3) δ175.0,165.4,145.3,140.0,132.9,132.7,130.4,128.9,128.3,127.7,126.3,121.4,97.0,83.9,68.2,38.8.MS m / z(ESI+):Calculated for C 20 H 16 NO + ([M+H] + ):286.1,found286.0.

[0040] The experimental results corresponding to the synthesis methods of specific chiral pyrrolizine-3-one compounds in Examples 1 to 10 are listed in Table 1:

[0041] Table 1 Palladium-catalyzed synthesis of chiral spiro[furan-3,3'-indolenine]-2-one reaction results [a]

[0042]

[0043]

[0044] [a] The reaction conditions are shown in the examples; [b] Isolated yield.

[0045] The above are only several specific embodiments of the present invention, and the description is relatively specific and detailed, but the protection scope of the present invention is not limited thereto. Any changes or substitutions that can be easily thought of by any technician familiar with the technical field within the technical scope disclosed by the present invention should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the attached claims.

Claims

1. A method for preparing a chiral pyrrolizine-3-one compound, characterized in that by N -Alkynoyl pyrrole derivatives are used as raw materials, and the reaction is carried out in an organic solvent under the joint action of a hydrogen source, a palladium catalyst and a ligand. After the reaction is completed, a chiral pyrrolazine-3-one compound is obtained by post-treatment. The general reaction formula is as follows: ； The chiral pyrrolizine-3-one compound is one of compounds 2a-2j; ； The palladium catalyst is selected from any one of palladium acetate, palladium tetraacetonitrile ditetrafluoroborate, and palladium diacetylacetonate; The ligand is selected from ( S )-Monophos, ( S )-Binap, ( S )- t Bu-Phox, R,R )-Ph-BPE, ( R Any one of )-4-phenoxy dinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphine heterocycloheptatriene; The hydrogen source is selected from any one of triethylamine hydrochloride and triethylamine hydroiodide; N - The molar ratio of the acetyloyl pyrrole derivative, the palladium catalyst, the ligand, and the hydrogen source is 1:0.05-0.4:0.1-0.8:1-5; The reaction temperature is 80-140°C and the reaction time is 12-72 h.

2. The method for preparing a chiral pyrrolizine-3-one compound according to claim 1, characterized in that The solvent is selected from any one of dichloromethane, dichloroethane, toluene, m-xylene, methanol, ethanol, methyl tert-butyl ether, ether, tetrahydrofuran or 1,4-dioxane, and the volume amount of the solvent is N The molar ratio of the -alkyne acyl pyrrole derivative is 1 to 100:1, the volume unit is milliliter, and the molar unit is millimole.

3. The method for preparing a chiral pyrrolizine-3-one compound according to claim 2, characterized in that The volume of solvent used is N The molar ratio of the -alkyne acyl pyrrole derivative is 5 to 20:1, the volume unit is milliliter, and the molar unit is millimole.

4. The method for preparing a chiral pyrrolizine-3-one compound according to claim 1, characterized in that The post-treatment step is: after the reaction is completed, the solvent is removed by rotary evaporation and then separated by column chromatography to obtain the target product; the mobile phase of the column chromatography is a mixture of petroleum ether and ethyl acetate in a volume ratio of 1 to 10:1.

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