CN110950850B - Free-radical cyclization reaction method of 1, 6-eneyne compound and ether compound - Google Patents
Free-radical cyclization reaction method of 1, 6-eneyne compound and ether compound Download PDFInfo
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- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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Abstract
The invention relates to a regioselective free-radical cyclization reaction method of a 1, 6-eneyne compound and an ether compound under a transition metal-free catalyst system. The method comprises the steps of adding a 1, 6-eneyne compound, an ether compound, an alkali additive and an oxidant into a Schlenk reaction bottle, and stirring and reacting at a certain temperature under the air atmosphere condition to obtain a cyclized product 2-pyrrolidone compound.
Description
Technical Field
The application belongs to the field of organic synthesis, and particularly relates to a regioselective free-radical cyclization reaction method of a 1, 6-eneyne compound and a (thio) ether compound under a transition metal-free catalyst system.
Background
α -functionalized ether derivatives are widely present in pharmaceuticals, natural products, and agrochemicals, exhibiting various biological activities, and formula 1 is a representative biologically active α -functionalized ether derivative. Therefore, the preparation of the skeleton by the alpha-C-H functionalization reaction of the ether compound which is cheap and easy to obtain is imminent. In recent years, chemists have developed functionalization reactions of ether compounds with ketones, carboxylic acids, amines, aromatics, heteroarenes, alkenes, alkynes, and eneyne derivatives. Among them, the reaction of ether compounds with enyne derivatives is of great interest, on the one hand, because of its simplicity and high efficiency, it is possible to construct multiple chemical bonds simultaneously. On the other hand, this reaction enables the preparation of complex cyclic compounds with high atom economy.
Biologically active alpha-functionalized ether derivatives represented by formula 1
The conventional cyclization reaction method of the eneyne derivative and the ether compound generally requires the use of a transition metal catalyst or high temperature, so that the realization of the cyclization reaction without any transition metal catalyst and at a relatively mild reaction temperature is considered to be one of the promising synthetic strategies due to the characteristics of economy and environmental friendliness. Furthermore, the reactions reported in the past are usually accompanied by intramolecular tandem cyclization reactions, which greatly limits the diversity construction of organic molecules. The inventor carries out intensive research on ether free radical reaction under a transition metal-free catalyst system, and in the invention, the inventor provides a novel method for carrying out high-regioselectivity cyclization reaction on a 1, 6-eneyne compound and a (thio) ether compound serving as reaction raw materials through a free radical process under the promotion of an oxidant and an alkali additive.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a free cyclization reaction method of a green, high-efficiency, low-cost and high-selectivity 1, 6-eneyne compound and a (thio) ether compound, and the method prepares and obtains the 2-pyrrolidone compound with high yield at high regioselectivity at mild temperature by using an oxidant/alkali additive catalytic system which is cheap and easy to obtain and without using a transition metal catalyst.
The invention provides a free radical cyclization reaction method, which takes 1, 6-eneyne compounds and (thio) ether compounds as raw materials and is prepared by the following steps:
adding a 1, 6-eneyne compound shown in a formula 1, a compound shown in a formula 2, an alkali additive and an oxidant into a Schlenk reaction bottle, placing the reaction bottle at a certain temperature under the condition of air atmosphere, stirring for reaction, monitoring the reaction process by TLC or GC until the raw materials are completely reacted, and performing post-treatment to obtain a cyclized product 2-pyrrolidone compound (I).
The chemical reaction formula of the high-regioselectivity free radical cyclization reaction method of the 1, 6-eneyne and the ether compound provided by the invention can be expressed as (see formula I):
in the reaction of the first formula, the reaction atmosphere may be an air atmosphere of 1atm, and a nitrogen atmosphere of 1atm or other inert gas atmosphere may be used instead.
The post-treatment operation is as follows: and (3) extracting the reaction liquid after the reaction is finished with ethyl acetate, drying an organic phase with anhydrous sodium sulfate, filtering, concentrating under reduced pressure to remove a solvent, and performing column chromatography separation on the residue (the elution solvent is ethyl acetate/n-hexane) to obtain the target product 2-pyrrolidone compound (I).
In the compounds represented by formula 1 and formula I, R 1 Selected from hydrogen, C 5 -C 14 Aryl radical, C 1 -C 10 Alkyl radical, C 1 -C 6 An acyl group;
R 2 selected from hydrogen, C 1 -C 6 Alkyl radical, C 5 -C 14 An aryl group;
R 3 is selected from C 1 -C 6 Alkyl radical, C 5 -C 14 An aryl group;
R 4 selected from hydrogen, C 1 -C 6 Alkyl radical, C 5 -C 14 An aryl group;
wherein each R is 1 -R 4 The aryl, alkyl and acyl groups having the number of carbon atoms in the substituents are optionally substituted by a substituent selected from the group consisting of halogen, C 1 -C 6 Alkyl radical, C 1 -C 6 Alkoxy radical, C 5 -C 14 Aryl, halogen substituted C 1 -C 6 Alkyl, -NO 2 、-CN、C 1 -C 6 alkyl-C (= O) -, C 1 -C 6 alkyl-OC (O =) -;
n =1 or 2;
the compound shown in the formula 2 is selected from any one of tetrahydrofuran, tetrahydropyran, 1, 4-dioxane, diethyl ether, dimethyl glycol and ethyl sulfide.
Preferably, R 1 Is selected from C 1 -C 10 Alkyl radical, C 5 -C 14 An aryl group; wherein said C 1 -C 10 Alkyl radical, C 5 -C 14 Aryl is optionally substituted by a substituent selected from halogen, C 1 -C 6 Alkyl radical, C 1 -C 6 Alkoxy radical, C 5 -C 14 Aryl, halogen substituted C 1 -C 6 Alkyl, -NO 2 、-CN、C 1 -C 6 alkyl-C (= O) -, C 1 -C 6 alkyl-OC (O =) -;
R 2 selected from hydrogen, C 1 -C 6 An alkyl group;
R 3 is selected from C 1 -C 6 Alkyl radical, C 5 -C 14 Aryl, wherein said C 1 -C 6 Alkyl radical, C 5 -C 14 Aryl is optionally substituted by a substituent selected from halogen, C 1 -C 6 Alkyl radical, C 1 -C 6 Alkoxy radical, C 5 -C 14 Aryl, halogen substituted C 1 -C 6 Alkyl, -NO 2 、-CN、C 1 -C 6 alkyl-C (= O) -, C 1 -C 6 alkyl-OC (O =) -;
R 4 selected from hydrogen.
Preferably, the compound represented by formula 2 is selected from tetrahydrofuran.
In the reaction of the invention, the oxidant is selected from any one or a mixture of more of tert-butyl peroxybenzoate, benzoyl peroxide and tert-butyl peroxide. Preferably tert-butyl peroxybenzoate.
In the reaction of the invention, the alkali additive is any one or a mixture of more of cesium carbonate, sodium acetate, 1, 8-diazabicycloundecen-7-ene and triethylamine. Cesium carbonate is preferred.
In the reaction of the present invention, the certain temperature is 60 to 100 ℃ and the temperature is most preferably 85 ℃.
In the reaction of the present invention, the time required for complete conversion of the reaction raw materials is 10 to 30 hours, preferably 20 hours.
In the reaction of the present invention, the molar ratio of the compound of formula 1, the base additive and the oxidizing agent is 1: 1 to 2: 3 to 5, and preferably, the molar ratio of the compound of formula 1, the base additive and the oxidizing agent is 1: 1.2: 4.
The invention has the beneficial effects that: a process for the high-regioselectivity free-radical cyclization reaction of 1, 6-eneyne compound and (thio) ether compound in the presence of transition metal-free catalyst system features that a cheap and easily available oxidant/alkali additive is used as catalyst system to obtain a series of target products in high yield. The method has the advantages of wide reaction substrate application range, simplicity, high efficiency, economy and greenness, and is particularly suitable for industrial production.
Detailed Description
The present invention will be described in further detail with reference to specific examples, but the present invention is not limited thereto.
The experimental methods described in the following examples are all conventional methods unless otherwise specified; the reagents and starting materials, if not otherwise specified, are commercially available and/or may be prepared according to known methods.
Examples 1-16 were experiments optimized for reaction conditions.
Example 1
A Schlenk bottle was charged with a 1, 6-enyne compound represented by formula 1a (39.8mg, 0.2mmol), tetrahydrofuran (0.5 mL), tert-butyl peroxybenzoate (TBPB, 155.2mg, 0.8mmol), and cesium carbonate (Cs) 2 CO 3 78.2mg, 0.24mmol), then the reactor was stirred under an air atmosphere at 85 ℃ for reaction, progress of the reaction was monitored by TLC until the raw material disappeared (reaction time was 20 hours), after completion of the reaction, the reaction solution was concentrated under reduced pressure to remove the solvent, and the residue was separated by column chromatography (elution solvent: ethyl acetate/n-hexane) to give the target product I-1 (78% yield, d.r. = 5.7: 1); 1 H NMR(400MHz，DMSO-d6)δ：7.74(d，J＝8.4Hz，0.3H)，7.69(d，J＝8.0Hz，1.7H)，7.42-7.36(m，2H)，7.17-7.12(m，1H)，5.29-5.02(m，2H)，4.51(d，J＝14.4Hz，1H)，4.38(d，J＝16.0Hz，1H)，3.90-3.84(m，1H)，3.60-3.54(m，1H)，3.45-3.40(m，1H)，2.01-1.95(m，1H)，1.89-1.82(m，1H)，1.78-1.63(m，3H)，1.44-1.37(m，1H)，1.26(s，0.5H)，1.22(s，2.6H)； 13 C NMR(100MHz，DMSO-d6)δ：177.0，176.6，146.3，139.9，139.4，129.3，129.1，124.7，124.4，120.3，120.1，108.4，108.1，76.0，75.7，66.9(2)，52.0，51.9，48.4，48.1，45.1，44.9，32.0，31.8，26.5，25.7，25.4；HRMS m/z(ESI)calcd for C 17 H 22 NO 2 ([M+H] + )272.1645，found 272.1649。
example 2
The yield of the objective product I-1 was 0% by the same procedure as in example 1 except that no oxidizing agent was added.
Example 3
The procedure of example 1 was repeated except that no base was added, whereby the yield of the objective product I-1 was 23%.
Example 4
The procedure of example 1 was repeated except that di-t-butyl peroxide (DTBP, 116.8mg,0.8 mmol) was used as the oxidizing agent in place of t-butyl peroxybenzoate, to obtain the desired product I-1 in a yield of 5%.
Example 5
The procedure of example 1 was repeated except that benzoyl peroxide (BPO, 193.6mg, 0.8mmol) was used in place of tert-butyl peroxybenzoate as an oxidizing agent, whereby the yield of the objective product I-1 was 18%.
Example 6
tert-Butanol peroxide (TBHP, 72.0mg,0.8 mmol) was used as an oxidizing agent in place of tert-butylperoxybenzoate, and the same procedure as in example 1 was repeated to give the desired product I-1 in a yield of 32%.
Example 7
With the oxidant hydrogen peroxide (H) 2 O 2 30% in water,90.7mg, 0.8mmol) in place of tert-butyl peroxybenzoate, and under the same conditions as in example 1, the yield of the objective product I-1 was 0%.
Example 8
The target product I-1 was obtained in a yield of 51% under the same conditions as in example 1 except that the amount of the oxidizing agent tert-butyl peroxybenzoate used was 3 equivalents (TBPB, 116.4mg,0.6 mmol).
Example 9
The amount of tert-butyl peroxybenzoate used as the oxidizing agent was 5 equivalents (TBPB, 194.0mg,1.0 mmol), and the other conditions were the same as in example 1, whereby the yield of the objective product I-1 was 78%.
Example 10
With sodium carbonate (Na) 2 CO 3 25.4mg, 0.24mmol) in place of cesium carbonate under the same conditions as in example 1 to obtain the desired product I-1 in a yield of 71%.
Example 11
The desired product I-1 was obtained in 49% yield under the same conditions as in example 1 except that sodium acetate (NaOAc, 19.7mg, 0.24mmol) was used in place of cesium carbonate.
Example 12
The desired product I-1 was obtained in a yield of 72% under the same conditions as in example 1 except that 1, 8-diazabicycloundecen-7-ene (DBU, 36.5mg, 0.24mmol) was used in place of cesium carbonate.
Example 13
With triethylamine (Et) 3 N,24.0mg, 0.24mmol) in place of cesium carbonate, and the same conditions as in example 1 were repeated to obtain the desired product I-1 in a yield of 45%.
Example 14
The amount of cesium carbonate is 2 equivalents (Cs) 2 CO 3 130.4mg,0.4 mmol) under the same conditions as in example 1 to obtain the target product I-1 with a yield of 79%.
Example 15
The reaction temperature was reduced to 60 ℃ and the other conditions were the same as in example 1, giving a yield of 23% of the desired product I-1.
Example 16
The reaction temperature was raised to 100 ℃ and the other conditions were the same as in example 1, giving the desired product I-1 in 67% yield.
As can be seen from the above examples 1-16, the optimum reaction conditions were those of example 1, i.e., tert-butyl peroxybenzoate (4 equivalents) as the oxidizing agent and cesium carbonate (1.2 equivalents) as the base additive, and the reaction temperature was 85 ℃. On the basis of obtaining the optimal reaction condition, the inventor further selects 1, 6-eneyne compounds and (thio) ether compounds with different substituents as raw materials under the optimal reaction condition to develop a high-area-selectivity free radical cyclization reaction method.
Example 17 reaction with tetrahydropyran
A Schlenk bottle was charged with a 1, 6-enyne compound represented by formula 1a (39.8mg, 0.2mmol), tetrahydropyran (0.5 mL), tert-butyl peroxybenzoate (TBPB, 155.2mg, 0.8mmol), and cesium carbonate (Cs) 2 CO 3 78.2mg, 0.24mmol), and then the reactor was placed under an air atmosphere,Stirring the reaction at 85 deg.C, monitoring the progress of the reaction by TLC until the starting material disappeared (reaction time was 20 hours), after completion of the reaction, concentrating the reaction solution under reduced pressure to remove the solvent, and subjecting the residue to column chromatography (elution solvent: ethyl acetate/n-hexane) to obtain the objective product I-2 (65% yield, d.r. > 20: 1); 1 H NMR(400MHz，DMSO-d6)δ：7.63(d，J＝7.6Hz，2H)，7.36(t，J＝7.2Hz，2H)，7.12(t，J＝7.0Hz，1H)，5.29(s，1H)，5.16(s，1H)，4.48(d，J＝14.4Hz，1H)，4.31(d，J＝14.0Hz，1H)，3.50(d，J＝10.8Hz，1H)，3.30-3.22(m，1H)，3.15-3.07(m，1H)，2.02-1.92(m，1H)，1.74-1.57(m，2H)，1.45-1.32(m，4H)，1.20(s，3H)，1.14-1.06(m，1H)； 13 C NMR(100MHz，DMSO-d6)δ：177.2，146.6，139.9，129.0，124.4，120.5，108.4，75.1，68.1，52.3，47.5，46.3，32.1，26.4，25.8，23.4；HRMS m/z(ESI)calcd for C 18 H 24 NO 2 ([M+H] + )286.1802，found 286.1800。
example 18 reaction with 1, 4-dioxane
A Schlenk bottle was charged with a 1, 6-enyne compound represented by formula 1a (39.8mg, 0.2mmol), 1, 4-dioxane (0.5 mL), tert-butyl peroxybenzoate (TBPB, 155.2mg, 0.8mmol), and cesium carbonate (Cs) 2 CO 3 78.2mg, 0.24mmol), then the reactor is stirred under an air atmosphere at 85 ℃ for reaction, the progress of the reaction is monitored by TLC until the raw material disappears (the reaction time is 20 hours), after the reaction is completed, the reaction solution is concentrated under reduced pressure to remove the solvent, and the residue is separated by column chromatography (the eluting solvent is: ethyl acetate/n-hexane) to yield the target product I-3 (61% yield, d.r. > 20: 1); 1 H NMR(400MHz，DMSO-d6)δ：7.65(d，J＝7.6Hz，2H)，7.37(t，J＝7.0Hz，2H)，7.14(t，J＝6.8Hz，1H)，5.31(s，1H)，5.19(s，1H)，4.51(d，J＝14.4Hz，1H)，4.38(d，J＝14.0Hz，1H)，3.57-3.50(m，3H)，3.46-3.41(m，1H)，3.39-3.36(m，2H)，3.12(t，J＝10.2Hz，1H)，1.87(t，J＝12.0Hz，1H)，1.53(d，J＝13.6Hz，1H)，1.22(s，3H)； 13 C NMR(100MHz，DMSO-d6)δ：176.7，146.2，139.8，129.1，124.6，120.6，108.7，73.1，70.7，66.5，66.1，52.2，47.2，26.3；HRMS m/z(ESI)calcd for C 17 H 22 NO 3 ([M+H] + )288.1594，found 288.1599。
example 19 reaction with Ether
A Schlenk bottle was charged with 1, 6-eneyne compound represented by formula 1a (39.8mg, 0.2mmol), diethyl ether (0.5 mL), tert-butyl peroxybenzoate (TBPB, 155.2mg, 0.8mmol), and cesium carbonate (Cs) 2 CO 3 78.2mg, 0.24mmol), then the reactor was stirred under an air atmosphere at 85 ℃ for reaction, progress of the reaction was monitored by TLC until the raw material disappeared (reaction time was 20 hours), after completion of the reaction, the reaction solution was concentrated under reduced pressure to remove the solvent, and the residue was separated by column chromatography (elution solvent: ethyl acetate/n-hexane) to give the desired product I-4 (66% yield, d.r. > 20: 1); 1 H NMR(500MHz，CDCl 3 )δ：7.77(d，J＝10.0Hz，2H)，7.36(t，J＝10.0Hz，2H)，7.11(t，J＝9.0Hz，1H)，5.28(t，J＝2.5Hz，1H)，5.07(t，J＝3.0Hz，1H)，4.52-4.47(m，1H)，4.39-4.35(m，1H)，3.58-3.53(m，1H)，3.48-3.42(m，1H)，3.08-3.01(m，1H)，2.30-2.24(m，1H)，1.61-1.57(m，1H)，1.32(s，3H)，1.11(d，J＝7.5Hz，3H)，0.81(t，J＝8.5Hz，3H)； 13 C NMR(125MHz，CDCl 3 )δ：177.7，145.9，139.6，128.8，123.9，119.2，107.6，71.9，63.3，51.7，48.1，46.2，27.0，19.5，15.2；HRMS m/z(ESI)calcd for C 17 H 24 NO 2 ([M+H] + )274.1802，found 274.1800。
example 20 reaction with Dimethylethylene glycol
A Schlenk bottle was charged with 1, 6-eneyne compound represented by formula 1a (39.8mg, 0.2mmol), dimethyl glycol (0.5 mL), tert-butyl peroxybenzoate (TBPB, 155.2mg, 0.8mmol), and cesium carbonate (Cs) 2 CO 3 78.2mg, 0.24mmol), then the reactor was stirred under an air atmosphere at 85 ℃ for reaction, progress of the reaction was monitored by TLC until the raw material disappeared (reaction time was 20 hours), after completion of the reaction, the reaction solution was concentrated under reduced pressure to remove the solvent, and the residue was separated by column chromatography (elution solvent: ethyl acetate/n-hexane) to yield the target product I-5 (69% yield, d.r. = 1: 1); 1 H NMR(400MHz，DMSO-d6)δ：7.74-7.62(m，2H)，7.40-7.36(m，2H)，7.16-7.11(m，1H)，5.32-5.16(m，2H)，4.58-4.37(m，2H)，3.30(d，J＝3.6Hz，3H)，3.25(t，J＝20.4Hz，3H)，3.09(s，1.5H)，3.03(s，1.5H)，2.06-1.96(m，1H)，1.79-1.65(m，1H)，1.25(s，1.5H)，1.22(s，1.5H)； 13 C NMR(100MHz，DMSO-d6)δ：177.0，176.7，146.1，145.9，139.8，139.6，129.3，129.1，124.5，124.3，120.2，120.1，108.5，108.3，77.0(2)，74.4(2)，58.9，58.4，51.8(2)，38.6(2)，26.7，26.1，25.7；HRMS m/z(ESI)calcd for C 17 H 24 NO 3 ([M+H] + )290.1751，found 290.1755。
example 21 reaction with Ethyl sulfide
A Schlenk bottle was charged with a 1, 6-enyne compound represented by formula 1a (39.8mg, 0.2mmol), ethyl sulfide (0.5 mL), tert-butyl peroxybenzoate (TBPB, 155.2mg, 0.8mmol), and cesium carbonate (Cs) 2 CO 3 78.2mg, 0.24mmol), then the reactor was stirred under an air atmosphere at 85 ℃ for reaction, progress of the reaction was monitored by TLC until the raw material disappeared (reaction time was 20 hours), after completion of the reaction, the reaction solution was concentrated under reduced pressure to remove the solvent, and the residue was separated by column chromatography (elution solvent: ethyl acetate/n-hexane) to yield the desired product I-6 (71% yield)，d.r.＝4∶1)； 1 H NMR(500MHz，CDCl 3 )δ：7.72-7.69(m，1.6H)，7.67-7.62(m，0.4H)，7.41-7.36(m，2H)，7.19-7.13(m，1H)，5.30-5.25(m，1H)，5.20-5.14(m，0.8H)，5.09(t，J＝3.0Hz，0.2H)，4.56-4.42(m，2H)，3.06-2.98(m，0.8H)，2.87-2.80(m，1H)，2.58-2.43(m，2H)，2.33-2.27(m，0.2H)，1.78-1.62(m，1H)，1.39(s，2.5H)，1.33(s，0.6H)，1.29-1.20(m，3H)，1.17(t，J＝9.0Hz，2.4H)，1.08(t，J＝9.0Hz，0.6H)； 13 C NMR(125MHz，CDCl 3 )δ：176.9，176.0，145.7，145.1，139.4，139.0，128.9，128.8，124.8，124.4，120.1，120.0，108.8，108.2，52.6，52.1，52.0，41.5，36.5，36.2，24.3，24.1，23.0，22.7，15.0，14.4；HRMS m/z(ESI)calcd for C 17 H 24 NOS([M+H] + )290.1573，found 290.1569。
Example 22
A Schlenk bottle was charged with 1, 6-eneyne compound represented by formula 1b (45.8mg, 0.2mmol), tetrahydrofuran (0.5 mL), tert-butyl peroxybenzoate (TBPB, 155.2mg, 0.8mmol), and cesium carbonate (Cs) 2 CO 3 78.2mg, 0.24mmol), then the reactor was stirred under an air atmosphere at 85 ℃ for reaction, progress of the reaction was monitored by TLC until the raw material disappeared (reaction time was 20 hours), after completion of the reaction, the reaction solution was concentrated under reduced pressure to remove the solvent, and the residue was separated by column chromatography (elution solvent: ethyl acetate/n-hexane) to give the target product I-7 (84% yield, d.r. = 14: 1); 1 H NMR(500MHz，CDCl 3 )δ：7.60(d，J＝9.0Hz，0.2H)，7.53(d，J＝9.0Hz，1.9H)，6.91(t，J＝8.5Hz，2H)，5.26(t，J＝2.0Hz，1H)，5.09(t，J＝2.5Hz，1H)，4.43-4.37(m，2H)，4.05-3.99(m，1H)，3.80(s，3H)，3.74(t，J＝11.0Hz，1H)，3.58-3.54(m，1H)，2.19-2.14(m，1H)，1.95-1.85(m，2H)，1.79-1.74(m，1H)，1.63-1.59(m，1H)，1.50(t，J＝8.5Hz，1H)，1.36(s，0.2H)，1.32(s，2.8H)； 13 C NMR(125MHz，CDCl 3 )δ：177.1，156.6，146.5，132.7，122.4，121.7，114.1，114.0，107.8，107.7，75.8，67.3，55.5，52.8，48.0，45.0，31.9，26.3，25.3；HRMS m/z(ESI)calcd for C 18 H 24 NO 3 ([M+H] + )302.1751，found 302.1753。
example 23
A Schlenk bottle was charged with a 1, 6-enyne compound represented by formula 1c (42.6 mg, 0.2mmol), tetrahydrofuran (0.5 mL), tert-butyl peroxybenzoate (TBPB, 155.2mg, 0.8mmol), and cesium carbonate (Cs) 2 CO 3 78.2mg, 0.24mmol), then the reactor was stirred under an air atmosphere at 85 ℃ for reaction, progress of the reaction was monitored by TLC until the raw material disappeared (reaction time was 20 hours), after completion of the reaction, the reaction solution was concentrated under reduced pressure to remove the solvent, and the residue was separated by column chromatography (elution solvent: ethyl acetate/n-hexane) to give the target product I-8 (81% yield, d.r. = 2.3: 1); 1 H NMR(500MHz，CDCl 3 )δ：7.59(d，J＝5.0Hz，0.6H)，7.53(d，J＝5.0Hz，1.4H)，7.18(t，J＝9.5Hz，2H)，5.26-5.21(m，1H)，5.15-5.08(m，1H)，4.53-4.36(m，2H)，4.04-3.99(m，0.7H)，3.80-3.71(m，1.3H)，3.60-3.54(m，1H)，2.34(s，0.9H)，2.33(s，2.1H)，2.19-2.14(m，1H)，2.05-2.00(m，0.7H)，1.94-1.84(m，2.3H)，1.78-1.74(m，1H)，1.51-1.46(m，1H)，1.33(s，0.9H)，1.33(s，2.1H)； 13 C NMR(125MHz，CDCl 3 )δ：177.2，176.6，146.4，146.2，137.0，136.6，134.4，134.0，129.5，129.3，120.5，119.9，107.8，107.7，76.4，75.7，67.3，52.4，52.3，48.6，48.2，45.5，44.9，31.9(2)，26.3，25.9，25.6，25.3，20.9；HRMS m/z(ESI)calcd for C 18 H 24 NO 2 ([M+H] + )286.1802，found 286.1798。
example 24
A Schlenk bottle was charged with 1, 6-eneyne compound represented by formula 1d (51.0 mg, 0.2mmol), tetrahydrofuran (0.5 mL), tert-butyl peroxybenzoate (TBPB, 155.2mg, 0.8mmol), and cesium carbonate (Cs) 2 CO 3 78.2mg, 0.24mmol), then the reactor was stirred under an air atmosphere at 85 ℃ for reaction, progress of the reaction was monitored by TLC until the raw material disappeared (reaction time was 20 hours), after completion of the reaction, the reaction solution was concentrated under reduced pressure to remove the solvent, and the residue was separated by column chromatography (elution solvent: ethyl acetate/n-hexane) to yield the target product I-9 (82% yield, d.r. = 1: 1); 1 H NMR(500MHz，CDCl 3 )δ：7.65-7.62(m，0.5H)，7.58-7.57(m，1H)，7.42-7.35(m，2H)，7.14-7.12(m，0.5H)，5.27(t，J＝2.0Hz，0.5H)，5.22-5.15(m，0.5H)，5.10-5.08(m，1H)，4.55-4.50(m，1H)，4.44-4.38(m，1.5H)，4.04-4.01(m，0.5H)，3.80-3.75(m，1H)，3.72-3.55(m，1H)，2.23-2.14(m，1H)，2.04-2.01(m，0.5H)，1.94-1.86(m，2H)，1.78-1.73(m，1.5H)，1.51-1.44(m，1H)，1.32(s，6H)，1.31(s，6H)； 13 C NMR(125MHz，CDCl 3 )δ：177.3，176.7，146.4，146.1，140.1，139.8，136.9，136.5，125.8，125.7，120.1，119.6，107.8(2)，76.4，75.7，67.3(2)，52.3，52.2，48.6，48.2，45.4，44.8，31.9(2)，31.4(2)，31.3，26.8，26.0，25.6，25.3；HRMS m/z(ESI)calcd for C 21 H 30 NO 2 ([M+H] + )328.2271，found 328.2275。
example 25
A Schlenk bottle was charged with 1, 6-enyne compound represented by formula 1e (43.4 mg, 0.2mmol), tetrahydrofuran (0.5 mL), tert-butyl peroxybenzoate (TBPB, 155.2mg, 0.8mmol), and cesium carbonate (Cs) 2 CO 3 78.2mg, 0.24mmol), and then the reactor was put under an air atmosphere at 85 ℃Stirring the reaction, monitoring the reaction progress by TLC until the raw material disappears (the reaction time is 20 hours), concentrating the reaction solution under reduced pressure to remove the solvent after the reaction is completed, and separating the residue by column chromatography (the elution solvent is ethyl acetate/n-hexane) to obtain the target product I-10 (75% yield, d.r. = 2.3: 1); 1 H NMR(500MHz，CDCl 3 )δ：7.69-7.66(m，0.6H)，7.62-7.59(m，1.4H)，7.09-7.04(m，2H)，5.29-5.22(m，1H)，5.16-5.11(m，1H)，4.55-4.35(m，2H)，4.03-3.99(m，0.7H)，3.88-3.84(m，0.3H)，3.80-3.70(m，1H)，3.62-3.52(m，1H)，2.19-2.14(m，1H)，1.94-1.85(m，3H)，1.63-1.60(m，1H)，1.52-1.46(m，1H)，1.36(s，0.9H)，1.33(s，2.1H)； 13 C NMR(125MHz，CDCl 3 )δ：177.5，176.8，160.0(d，J C-F ＝242.3Hz)，159.9(d，J C-F ＝242.9Hz)，146.0，145.9，135.6(2)，122.3(d，J C-F ＝7.9Hz)，121.7(d，J C-F ＝7.9Hz)，115.6(d，J C-F ＝19.4Hz)，115.4(d，J C-F ＝19.4Hz)，108.0，107.9，76.3，75.7，67.4，67.3，52.6，52.4，48.5，48.1，45.5，45.1，32.0，31.8，26.4，25.8，25.5，25.3； 19 F NMR(471MHz，DMSO-d6)δ：-117.5，-118.0；HRMS m/z(ESI)calcd for C 17 H 21 FNO 2 ([M+H] + )290.1551，found 290.1553。
example 26
A Schlenk bottle was charged with a 1, 6-enyne compound represented by formula 1f (46.6 mg, 0.2mmol), tetrahydrofuran (0.5 mL), tert-butyl peroxybenzoate (TBPB, 155.2mg, 0.8mmol), and cesium carbonate (Cs) 2 CO 3 78.2mg, 0.24mmol), then the reactor is stirred under an air atmosphere at 85 ℃ for reaction, the progress of the reaction is monitored by TLC until the raw material disappears (the reaction time is 20 hours), after the reaction is completed, the reaction solution is concentrated under reduced pressure to remove the solvent, and the residue is separated by column chromatography (the eluting solvent is: ethyl acetate/n-hexane) to yield the desired product I-11 (73% yield, d.r.＝9∶1)； 1 H NMR(500MHz，CDCl 3 )δ：7.70-7.67(m，1H)，7.62(d，J＝9.0Hz，1H)，7.36-7.32(m，2H)，5.29-5.23(m，1H)，5.16-5.09(m，1H)，4.54-4.35(m，2H)，4.13-4.01(m，1H)，3.79-3.69(m，1H)，3.61-3.51(m，1H)，2.00-1.84(m，3H)，1.76-1.58(m，2H)，1.51-1.42(m，1H)，1.33(s，2.7H)，1.29(s，0.3H)； 13 C NMR(125MHz，CDCl 3 )δ：177.7，177.0，145.7，145.1，138.1，137.5，129.0，128.9，128.8，121.4，120.8，108.2，108.0，76.3，75.7，67.4(2)，52.2，52.1，48.6，48.2，45.5，45.1，32.0，31.8，26.4，25.8，25.5，25.3；HRMS m/z(ESI)calcd for C 17 H 21 ClNO 2 ([M+H] + )306.1255，found 306.1251。
Example 27
A Schlenk bottle was charged with 1g of a 1, 6-enyne compound (55.4 mg, 0.2mmol) represented by the formula (1 g), tetrahydrofuran (0.5 mL), tert-butyl peroxybenzoate (TBPB, 155.2mg, 0.8mmol), and cesium carbonate (Cs) 2 CO 3 78.2mg, 0.24mmol), then the reactor was stirred under an air atmosphere at 85 ℃ for reaction, progress of the reaction was monitored by TLC until the raw material disappeared (reaction time was 20 hours), after completion of the reaction, the reaction solution was concentrated under reduced pressure to remove the solvent, and the residue was separated by column chromatography (elution solvent: ethyl acetate/n-hexane) to yield the target product I-12 (74% yield, d.r. = 5: 1); 1 H NMR(500MHz，CDCl 3 )δ：7.64-7.62(m，1H)，7.58(d，J＝9.0Hz，1H)，7.50-7.46(m，2H)，5.33-5.23(m，1H)，5.16-5.08(m，1H)，4.54-4.37(m，2H)，4.13-3.98(m，1H)，3.86-3.69(m，1H)，3.60-3.51(m，1H)，2.01-1.85(m，3H)，1.75-1.60(m，2H)，1.51-1.42(m，1H)，1.32(s，2.5H)，1.29(s，0.5H)； 13 C NMR(125MHz，CDCl 3 )δ：177.7，177.2，145.6，145.1，138.6，138.0，131.9，131.7，121.7，121.1，117.4，117.1，108.3，108.2，76.3，75.6，67.4，67.0，52.1，52.0，48.7，48.3，45.6，45.1，32.0，31.8，26.4，25.8，25.5，25.3；HRMS m/z(ESI)calcd for C 17 H 21 BrNO 2 ([M+H] + )350.0750，found 350.0752。
example 28
To a Schlenk bottle were added a 1, 6-enyne compound represented by formula 1h (53.4 mg, 0.2mmol), tetrahydrofuran (0.5 mL), tert-butyl peroxybenzoate (TBPB, 155.2mg, 0.8mmol), and cesium carbonate (Cs) 2 CO 3 78.2mg, 0.24mmol), then the reactor was stirred under an air atmosphere at 85 ℃ for reaction, progress of the reaction was monitored by TLC until the raw material disappeared (reaction time was 20 hours), after completion of the reaction, the reaction solution was concentrated under reduced pressure to remove the solvent, and the residue was separated by column chromatography (elution solvent: ethyl acetate/n-hexane) to yield the target product I-13 (71% yield, d.r. = 4: 1); 1 H NMR(500MHz，CDCl 3 )δ：7.88(d，J＝8.5Hz，0.4H)，7.82(d，J＝8.5Hz，1.6H)，7.63(t，J＝20.5Hz，2H)，5.33-5.26(m，1H)，5.18-5.13(m，1H)，4.60-4.40(m，2H)，4.05-4.00(m，0.8H)，3.82-3.67(m，1.2H)，3.60-3.49(m，1H)，2.17-1.85(m，3H)，1.76-1.62(m，2H)，1.52-1.44(m，1H)，1.38(s，0.6H)，1.34(s，2.4H)； 13 C NMR(125MHz，CDCl 3 )δ：178.2，177.6，145.4，145.3，142.5，141.9，126.1(q，J C-F ＝2.7Hz)，126.0(q，J C-F ＝2.8Hz)，125.8(q，J C-F ＝30.0Hz)，119.5，119.2，119.1，108.4，108.2，76.2，75.6，67.4，52.0，48.8，48.4，45.6，45.2，32.0，31.7，26.5，25.8，25.5，25.3； 19 F NMR(471MHz，DMSO-d6)δ：-62.1(2)；HRMS m/z(ESI)calcd for C 18 H 21 F 3 NO 2 ([M+H] + )340.1519，found 340.1515。
example 29
A Schlenk bottle was charged with a 1, 6-enyne compound represented by formula 1i (42.6 mg, 0.2mmol), tetrahydrofuran (0.5 mL), tert-butyl peroxybenzoate (TBPB, 155.2mg, 0.8mmol), and cesium carbonate (Cs) 2 CO 3 78.2mg, 0.24mmol), then the reactor was stirred under an air atmosphere at 85 ℃ for reaction, progress of the reaction was monitored by TLC until the raw material disappeared (reaction time was 20 hours), after completion of the reaction, the reaction solution was concentrated under reduced pressure to remove the solvent, and the residue was separated by column chromatography (elution solvent: ethyl acetate/n-hexane) to give the target product I-14 (80% yield, d.r. = 4: 1); 1 H NMR(500MHz，CDCl 3 )δ：7.59(s，0.2H)，7.53(s，0.8H)，7.47(d，J＝8.5Hz，0.2H)，7.41(d，J＝8.0Hz，0.8H)，7.28-7.23(m，1H)，6.99-6.95(m，1H)，5.27-5.22(m，1H)，5.15-5.09(m，1H)，4.53-4.40(m，2H)，4.04-3.99(m，0.8H)，3.80-3.72(m，1.2H)，3.61-3.52(m，1H)，2.38(s，0.6H)，2.36(s，2.4H)，2.19-2.14(m，1H)，1.95-1.85(m，2H)，1.79-1.74(m，1H)，1.64-1.61(m，1H)，1.51-1.46(m，1H)，1.36(s，0.6H)，1.33(s，2.4H)； 13 C NMR(125MHz，CDCl 3 )δ：177.4，176.9，146.3，146.1，139.4，139.0，138.8，138.6，128.8，128.6，125.5，125.3，121.2，120.7，117.4，117.0，107.8，107.7，76.4，75.7，67.4，67.3，52.4，52.3，48.7，48.3，45.4，44.9，31.9(2)，26.4，25.9，25.6，25.3，21.7(2)；HRMS m/z(ESI)calcd for C 18 H 24 NO 2 ([M+H] + )286.1802，found 286.1800。
example 30
A Schlenk bottle was charged with a 1, 6-eneyne compound represented by formula 1j (46.6 mg, 0.2mmol), tetrahydrofuran (0.5 mL), tert-butyl peroxybenzoate (TBPB, 155.2mg, 0.8mmol), and cesium carbonate (Cs) 2 CO 3 78.2mg, 0.24mmol), and then the reactor was emptiedStirring the mixture under the conditions of gas atmosphere and 85 ℃ for reaction, monitoring the reaction progress by TLC until the raw materials disappear (the reaction time is 20 hours), concentrating the reaction solution under reduced pressure to remove the solvent after the reaction is finished, and carrying out column chromatography separation on the residue (the elution solvent is ethyl acetate/n-hexane) to obtain a target product I-15 (71 percent yield, d.r. = 4: 1); 1 H NMR(500MHz，CDCl 3 )δ：7.80(s，0.2H)，7.73(s，0.8H)，7.64(d，J＝5.0Hz，0.2H)，7.58(d，J＝10.0Hz，0.8H)，7.32-7.28(m，1H)，7.15-7.05(m，1H)，5.31-5.23(m，1H)，5.16-5.11(m，1H)，4.564.35(m，2H)，4.043.99(m，1H)，3.80-3.70(m，1H)，3.61-3.52(m，1H)，2.18-2.14(m，1H)，2.06-1.98(m，1H)，1.94-1.79(m，3H)，1.64-1.60(m，1H)，1.36(s，0.6H)，1.33(s，2.4H)； 13 C NMR(125MHz，CDCl 3 )δ：177.8(2)，145.6，140.2(2)，134.5，129.9，129.8，124.6，124.3，120.2，119.8，118.1，117.6，108.2，108.0，76.3，75.6，67.4(2)，52.2，52.1，48.8，48.3，45.5，45.1，32.0，31.8，26.4，25.8，25.5，25.3；HRMS m/z(ESI)calcd for C 17 H 21 ClNO 2 ([M+H] + )306.1255，found 306.1251。
example 31
A Schlenk bottle was charged with a 1, 6-enyne compound represented by formula 1k (42.6 mg, 0.2mmol), tetrahydrofuran (0.5 mL), tert-butyl peroxybenzoate (TBPB, 155.2mg, 0.8mmol), and cesium carbonate (Cs) 2 CO 3 78.2mg, 0.24mmol), then the reactor is stirred under an air atmosphere at 85 ℃ for reaction, the progress of the reaction is monitored by TLC until the raw material disappears (the reaction time is 20 hours), after the reaction is completed, the reaction solution is concentrated under reduced pressure to remove the solvent, and the residue is separated by column chromatography (the eluting solvent is: ethyl acetate/n-hexane) to give the target product I-16 (63% yield, d.r. = 5.7: 1); 1 H NMR(500MHz，CDCl 3 )δ：7.72-7.70(m，0.3H)，7.67-7.65(m，1.7H)，7.37(t，J＝12.5Hz，2H)，7.16-7.11(m，1H)，5.64-5.60(m，1H)，4.42-4.34(m，2H)，4.02-3.97(m，0.8H)，3.79-3.69(m，1.2H)，3.63-3.52(m，1H)，2.26-2.21(m，1H)，2.07-2.01(m，1H)，1.95-1.83(m，4H)，1.78(d，J＝5.0Hz，3H)，1.48(s，0.4H)，1.42(s，2.5H)； 13 C NMR(125MHz，CDCl 3 )δ：178.4，139.7(2)，135.3，135.2，128.9，128.8，124.6，124.2，120.3，120.0，119.8，119.2，76.1，67.3，67.2，52.5，52.4，48.1，48.0，43.0，42.8，31.9，31.5，25.5，25.4，24.8(2)，14.1，13.7；HRMS m/z(ESI)calcd for C 18 H 24 NO 2 ([M+H] + )286.1802，found 286.1800。
example 32
A Schlenk bottle was charged with 1l of a 1, 6-eneyne compound represented by the formula 1 (55.0 mg, 0.2mmol), tetrahydrofuran (0.5 mL), tert-butyl peroxybenzoate (TBPB, 155.2mg, 0.8mmol), and cesium carbonate (Cs) 2 CO 3 78.2mg, 0.24mmol), then the reactor was stirred under an air atmosphere at 85 ℃ for reaction, progress of the reaction was monitored by TLC until the raw material disappeared (reaction time was 20 hours), after completion of the reaction, the reaction solution was concentrated under reduced pressure to remove the solvent, and the residue was separated by column chromatography (elution solvent: ethyl acetate/n-hexane) to yield the target product I-17 (60% yield, d.r. > 20: 1); 1 H NMR(500MHz，CDCl 3 )δ：7.41(d，J＝8.0Hz，2H)，7.34-7.29(m，2H)，7.18-7.09(m，6H)，5.33(s，1H)，5.24(s，1H)，4.14(d，J＝13.5Hz，1H)，3.88-3.84(m，1H)，3.80-3.76(m，1H)，3.63-3.59(m，1H)，3.50(d，J＝13.5Hz，1H)，3.25(d，J＝13.0Hz，1H)，2.74(d，J＝12.5Hz，1H)，2.26-2.20(m，1H)，2.14-2.10(m，1H)，2.03-1.99(m，1H)，1.90-1.75(m，3H)； 13 C NMR(125MHz，CDCl 3 )δ：175.2，142.9，138.6，136.4，130.3，128.8，127.8，126.6，124.9，120.6，109.2，76.3，67.2，54.8，52.6，46.8，43.7，31.8，25.9；HRMS m/z(ESI)calcd for C 23 H 26 NO 2 ([M+H] + )348.1958，found 348.1960。
example 33
A Schlenk bottle was charged with 1, 6-eneyne compound represented by formula 1m (52.2 mg,0.2 mmol), tetrahydrofuran (0.5 mL), tert-butyl peroxybenzoate (TBPB, 155.2mg,0.8 mmol), and cesium carbonate (Cs) 2 CO 3 78.2mg, 0.24mmol), then the reactor was stirred under an air atmosphere at 85 ℃ for reaction, progress of the reaction was monitored by TLC until the raw material disappeared (reaction time was 20 hours), after completion of the reaction, the reaction solution was concentrated under reduced pressure to remove the solvent, and the residue was separated by column chromatography (elution solvent: ethyl acetate/n-hexane) to yield the target product I-18 (67% yield, d.r. = 1.5: 1); 1 H NMR(500MHz，CDCl 3 )δ：7.65(d，J＝9.0Hz，1.2H)，7.59(d，J＝9.0Hz，0.8H)，7.47(d，J＝8.5Hz，0.8H)，7.43(d，J＝8.0Hz，1.2H)，7.33-7.28(m，2H)，7.26-7.22(m，2H)，7.16-7.05(m，2H)，5.50-5.40(m，1H)，5.19-5.16(m，1H)，4.48-4.40(m，2H)，4.14-4.09(m，0.4H)，3.91-3.88(m，0.6H)，3.76-3.72(m，1H)，3.58-3.51(m，1H)，2.63-2.49(m，1H)，2.35-2.31(m，1H)，2.04-1.82(m，3H)，1.75-1.68(m，1H)； 13 C NMR(125MHz，CDCl 3 )δ：173.8，173.4，142.7，142.5，141.1，141.0，138.5，138.0，127.9，127.8，127.5，127.4，126.1，126.0，125.6，125.4，123.8，123.4，119.2，118.9，110.5，110.3，74.5，66.4，66.3，56.3，55.7，51.4，42.6，42.1，31.3，31.0，24.8，24.4；HRMS m/z(ESI)calcd for C 22 H 24 NO 2 ([M+H] + )334.1802，found 334.1804。
example 34 reaction mechanism control experiment
Experiment of dynamicsShows the reaction K H /K D And =1.5, the cutting reaction of the C-H bond at the alpha position of the oxygen atom of the ether compound is the rate-determining step of the whole reaction process. I-1 and I-1-d7 (75% yield, d.r. = 5.7: 1); 1 H NMR(500MHz，CDCl 3 )δ：7.72(d，J＝8.5Hz，0.3H)，7.67(d，J＝7.5Hz，1.7H)，7.40-7.35(m，2H)，7.17-7.12(m，1H)，5.28-5.22(m，1H)，5.16-5.10(m，1H)，4.54-4.39(m，2H)，4.05-3.99(m，0.6H)，3.77-3.72(m，0.6H)，3.59-3.53(m，0.6H)，2.20-2.15(m，1H)，2.03-2.00(m，0.6H)，1.93-1.85(m，1.8H)，1.52-1.46(m，1H)，1.37(s，0.5H)，1.33(s，2.5H)。
to the reaction of example 1, 4.2 equivalents of tetramethylpiperidine nitroxide (TEMPO) was added as a radical scavenger, the yield of the target product of the reaction was almost 0%, and intermediate II-1 was obtained in a yield of 73%, indicating that the reaction did proceed through the radical reaction. II-1 (73% yield); 1 H NMR(500MHz，CDCl 3 )δ：5.39-5.36(m，1H)，3.79-3.73(m，1H)，3.60-3.53(m，1H)，1.48-1.44(m，6H)，1.29(d，J＝5.5Hz，3H)，1.20(t，J＝8.0Hz，1H)，1.15(s，3H)，1.12(s，3H)，1.09(s，3H)，1.08(s，3H)； 13 C NMR(125MHz，CDCl 3 )δ：109.8，66.8，60.4，59.0，40.4，40.0，33.7，33.6，33.5，20.4，19.9，19.2，17.2。
it follows that the possible reaction mechanism of the present invention can be deduced as shown in the following formula:
the embodiments described above are only preferred embodiments of the invention and are not exhaustive of the possible implementations of the invention. Any obvious modifications thereof, which would occur to one skilled in the art, without departing from the principles and spirit of the invention, are to be considered as included within the scope of the appended claims.
Claims (8)
1. A free cyclization reaction method of a 1, 6-eneyne compound and an ether compound is characterized by comprising the following steps:
adding a 1, 6-eneyne compound shown in a formula 1, a compound shown in a formula 2, an alkali additive and an oxidant into a Schlenk reaction bottle, placing the reaction bottle at a certain temperature under the air atmosphere condition, stirring for reaction, monitoring the reaction process by TLC or GC until the raw materials are completely reacted, and performing post-treatment to obtain a cyclized product 2-pyrrolidone compound I;
in the compounds represented by formula 1 and formula I, R 1 Is selected from C 5 -C 14 An aryl group;
R 2 selected from hydrogen, C 1 -C 6 An alkyl group;
R 3 is selected from C 1 -C 6 Alkyl radical, C 5 -C 14 An aryl group;
R 4 selected from hydrogen;
wherein R is as defined above 1 The aryl group having the number of carbon atoms among the substituents is optionally substituted by a substituent selected from the group consisting of halogen, C 1 -C 6 Alkyl radical, C 1 -C 6 Alkoxy, halogen substituted C 1 -C 6 An alkyl group;
n＝1；
the compound shown in the formula 2 is selected from any one of tetrahydrofuran, tetrahydropyran, 1, 4-dioxane, diethyl ether, dimethyl glycol or ethyl sulfide;
the oxidant is tert-butyl peroxybenzoate; the alkali additive is selected from one or a mixture of more of cesium carbonate, sodium acetate, 1, 8-diazabicycloundecen-7-ene and triethylamine; the certain temperature is 60-100 ℃.
2. The method of claim 1, wherein the base additive is cesium carbonate.
3. The method according to any one of claims 1-2, wherein the certain temperature is 85 ℃.
4. The method according to any one of claims 1 to 2, wherein the time required for complete reaction of the starting materials is 10 to 30 hours.
5. The method according to claim 4, wherein the time required for complete reaction of the starting materials is 20 hours.
6. The process according to any one of claims 1 to 2, wherein the molar ratio of the 1, 6-enyne compound of formula 1, the base additive and the oxidizing agent is from 1: 1 to 2: 3 to 5.
7. The process of claim 6, wherein the molar ratio of the 1, 6-enyne compound of formula 1, the base additive, and the oxidizing agent is 1: 1.2: 4.
8. A method according to any one of claims 1-2, characterized in that the post-processing operation is as follows: extracting the reaction solution after the reaction is finished with ethyl acetate, drying an organic phase with anhydrous sodium sulfate, filtering, concentrating under reduced pressure to remove a solvent, and separating the residue by column chromatography, wherein the elution solvent is: ethyl acetate/n-hexane to obtain the target product 2-pyrrolidone compound I.
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