A method for synthesizing a beta-keto ester compound

Abstract

The application discloses a kind of β-carbonyl ester compound synthesis method, carboxylic acid, alkenyl ester, catalyst, ligand, silane, reducing agent, organic solvent are mixed at 20~120 DEG C stirring reaction 4~24h to obtain reaction liquid, reaction liquid is separated and purified by silica gel column to obtain β-carbonyl ester compound.The application has high yield, high regioselectivity, mild reaction condition, reaction raw material is simple and easy to obtain, cheap, stable, no irritating smell, environmental protection.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing beta-carbonyl ester compounds. Background Art

[0002] β-Carboxyl esters are a class of important structural units found in a wide range of natural products and active pharmaceutical ingredients, and are also crucial intermediates for chemical processing. Alkenyl esters and carboxylic acids are widely available basic chemical raw materials, and the hydroacylation of alkenes has become an important method for the industrial production of fine chemicals such as aldehydes and alcohols. Palladium-, silver-, and copper-catalyzed decarboxylative coupling strategies have made aromatic carboxylic acids an inexpensive source of aromatic groups, while carboxylic acids as acyl groups remain relatively unrecognized. Previously, most methods involved preactivating aromatic carboxylic acids and converting them into intermediates such as acyl chlorides, esters, anhydrides, and amides, which were then used in various metal-catalyzed coupling reactions to synthesize acyl compounds. In 2006, Chul-Ho Jun's group reported the rhodium-catalyzed hydroacylation of alkenyl esters, using more active aromatic aldehydes as carbonyl sources (Eur. J. Org. Chem. 2006, 11, 2504-2507). In 2018, Yang Hua's group reported the photocatalytic hydroacylation of alkenyl esters to synthesize 1,4-dicarbonyl compounds, using more active aromatic chlorides as carbonyl sources (Chem Asian J. 2018, 13, 271-274). In 2021, Zhu Shaolin's group reported the nickel-catalyzed three-component asymmetric reductive hydroacylation of simple alkenes, using ethyl chloroformate as a specific carbonyl source (J. Am. Chem. Soc. 2021, 143, 14089). Hydroacylation reactions reported by previous researchers are currently limited to specific, more active carbonyl sources. Currently, the dehydroxylation of unactivated carboxylic acids to provide carbonyl sources is only reported as a free radical process. The present invention proposes a nickel-catalyzed hydroacylation reaction of α,β-unsaturated olefins, in which unactivated carboxylic acid is used as the acyl source, and develops an efficient and inexpensive catalytic system to achieve the preparation of acyl ester derivatives, which has important research significance and potential application value. Summary of the Invention

[0003] In view of the above problems, the object of the present invention is to provide a method for synthesizing β-carbonyl ester compounds.

[0004] In order to achieve the above objectives, the following technical solutions are proposed:

[0005] The present invention provides a method for synthesizing a β-carbonyl ester compound. The specific method is as follows: under a nitrogen atmosphere, a carboxylic acid represented by formula (I), an alkenyl ester represented by formula (II), a catalyst, a ligand, a silane, a reducing agent, and an organic solvent are mixed, and the mixture is stirred and reacted at 20° C. to 120° C. for 4 to 24 hours (preferably at 60° C. for 12 hours) to obtain a reaction solution, and the reaction solution is separated and purified by silica gel column chromatography to obtain a β-carbonyl ester compound represented by formula (III).

[0006]

[0007] Wherein, R in formula (I) or formula (III) 1 is selected from phenyl, p-methoxybenzene, p-phenylbenzene, p-cyanobenzene, hexyl, decyl, chloropropyl, cyclohexanemethyl, benzyl, cyclopentyl, naphthyl or furan, R in formula (II) or formula (III) 2 is selected from hydrogen, methyl or phenyl, R 3 Selected from ethyl or benzyl, the catalyst is NiBr2, NiCl2, or NiBr2(DME), the ligand is triphenylphosphine, 2,2'-bipyridine, 1,10-phenanthroline or α,α,α-terpyridine, and the molar ratio of the carboxylic acid compound represented by formula (I) to the alkenyl ester represented by formula (II), the catalyst, the ligand, the silane, and the reducing agent is 1:1~2:0.02~0.1:0.05~0.2:1~5:1~5.

[0008] Furthermore, the silane is diphenylsilane, diethoxysilane or triethoxysilane (preferably triethoxysilane).

[0009] Furthermore, the reducing agent is zinc, magnesium or manganese (preferably zinc).

[0010] Furthermore, the organic solvent is dioxane, anisole or tetrahydrofuran (preferably tetrahydrofuran).

[0011] Furthermore, the volume of the organic solvent is 20.5 to 123.0 ml / g (preferably 41 ml / g) based on the mass of the carboxylic acid represented by formula (I).

[0012] Furthermore, the molar ratio of the carboxylic acid compound represented by formula (I) to the alkenyl ester represented by formula (II), the catalyst, the ligand, the silane, and the reducing agent is 1:1.2:0.05:0.1:3:3.

[0013] Furthermore, the catalyst is NiBr2(DME).

[0014] Furthermore, the ligand is α,α,α-terpyridine.

[0015] Furthermore, the specific operation process of the silica gel column chromatography separation and purification is: concentrating the reaction solution, performing column chromatography, eluting with a mixture of petroleum ether and ethyl acetate in a volume ratio of 30 to 15:1 as an eluent, collecting the eluate containing the target compound, concentrating, distilling and drying.

[0016] Furthermore, the β-carbonyl ester compound is one of the following:

[0017]

[0018] The beneficial effects of the present invention are: high yield, high regioselectivity, mild reaction conditions, simple and easy to obtain reaction raw materials, low price, stable properties, no irritating odor, and environmental protection. DETAILED DESCRIPTION

[0019] The present invention will be further described in detail with reference to the following specific examples, and the protection content of the present invention is not limited to the following examples. Without departing from the spirit and scope of the inventive concept, the changes and advantages that those skilled in the art can think of are included in the present invention, and are protected by the appended claims. The process, conditions, reagents, experimental methods, etc. for implementing the present invention, except for the contents specifically mentioned below, are common knowledge and common common sense in the art, and the present invention has no special restrictions. The data given in the following examples include specific operations and reaction conditions and products, and the product purity is identified by nuclear magnetic resonance.

[0020] Example 1

[0021] Synthesis of compound 3a:

[0022]

[0023] Under nitrogen atmosphere, benzoic acid 1a (0.2 mmol, 24.4 mg, 1.0 equiv), ethyl methacrylate 2a (0.24 mmol, 27.4 mg, 1.2 equiv), (EtO)3SiH (0.6 mmol, 98.4 mg, 3.0 equiv), zinc (0.6 mmol, 39.0 mg, 3.0 equiv), NiBr2(DME) (0.01 mmol, 3.1 mg, 5 mol%), α,α,α-terpyridine (0.02 mmol, 4.70 mg, 10 mol%) and 1 ml of tetrahydrofuran were added to a reaction tube. The reaction system was allowed to react at 60°C for 12 hours. After completion of the reaction, the reaction solution was concentrated and subjected to column chromatography (100-mesh silica gel) using a mixture of petroleum ether and ethyl acetate (300 ml, 10 ml, by volume) in a 30:1 ratio (volume ratio). The eluate containing the target compound was collected, concentrated, distilled, and dried to obtain product 3a (yield 84%). (Eluent polarity: petroleum ether / ethyl acetate = 30:1). 1 H NMR (400MHz, CDCl3) δ7.82 (d, J = 7.7Hz, 2H), 7.50 (t, J = 7.2Hz, 1H), 7.39 (t, J = 7.8Hz, 2H), 4.09 (q, J = 7.1Hz, 2H), 1.53 (s, 6H), 1.02 (t, J = 7.1Hz, 3H).

[0024] Example 2:

[0025] NiBr2(DME) was replaced with NiBr2, and other operations were carried out as in Example 1 to obtain product 3a (26.8 mg) with a yield of 61%.

[0026] Example 3:

[0027] NiBr2(DME) was replaced with NiCl2, and other operations were carried out as in Example 1 to obtain product 3a (26.4 mg) with a yield of 60%.

[0028] Example 4:

[0029] The amount of NiBr2(DME) was changed to (6.2 mg, 0.02 mmol), and the other operations were the same as in Example 1 to obtain product 3a (36.5 mg) with a yield of 83%.

[0030] Example 5:

[0031] The amount of NiBr2(DME) was changed to (1.8 mg, 0.005 mmol), and the other operations were the same as in Example 1 to obtain product 3a (36.5 mg) with a yield of 26%.

[0032] Example 6:

[0033] The amount of triethoxysilane was changed to (32.8 mg, 0.2 mmol), and the other operations were the same as in Example 1 to obtain product 3a (2.2 mg) with a yield of 5%.

[0034] Example 7:

[0035] The amount of triethoxysilane was changed to (164 mg, 1.0 mmol), and the other operations were the same as in Example 1 to obtain product 3a (32.6 mg) with a yield of 74%.

[0036] Example 8:

[0037] Triethoxysilane was replaced with diphenylsilane, and other operations were carried out as in Example 1 to obtain product 3a (22.9 mg) with a yield of 52%.

[0038] Example 9:

[0039] Triethoxysilane was replaced with diethoxysilane, and other operations were carried out as in Example 1 to obtain product 3a (22.4 mg) with a yield of 51%.

[0040] Example 10:

[0041] The amount of zinc was changed to (13 mg, 0.2 mmol), and the other operations were the same as in Example 1 to obtain product 3a (6.6 mg) with a yield of 15%.

[0042] Example 11:

[0043] The amount of zinc was changed to (65 mg, 1.0 mmol), and the other operations were the same as in Example 1 to obtain product 3a (26.4 mg) with a yield of 60%.

[0044] Example 12:

[0045] Zinc was replaced with magnesium, and other operations were carried out as in Example 1 to obtain product 3a (13.2 mg) with a yield of 30%.

[0046] Example 13:

[0047] Zinc was replaced with manganese, and other operations were carried out as in Example 1 to obtain product 3a (14.1 mg) with a yield of 32%.

[0048] Example 14:

[0049] The solvent tetrahydrofuran was replaced with anisole, and other operations were carried out as in Example 1 to obtain product 3a (17.6 mg) with a yield of 40%.

[0050] Example 15:

[0051] The solvent tetrahydrofuran was replaced with dioxane, and other operations were carried out as in Example 1 to obtain product 3a (13.2 mg) with a yield of 30%.

[0052] Example 16:

[0053] The solvent tetrahydrofuran was changed from 41 ml / g to 20.5 ml / g based on the mass of benzoic acid. Other operations were carried out as in Example 1 to obtain product 3a (26.4 mg) with a yield of 60%.

[0054] Example 17:

[0055] The solvent tetrahydrofuran was changed from 41 ml / g to 123.0 ml / g based on the mass of benzoic acid. Other operations were carried out as in Example 1 to obtain product 3a (24.6 mg) with a yield of 56%.

[0056] Example 18:

[0057] The temperature was lowered to 20°C, and other operations were carried out as in Example 1 to obtain product 3a (24.6 mg) with a yield of 56%.

[0058] Example 19:

[0059] The temperature was raised to 120° C. and other operations were carried out as in Example 1 to obtain product 3a (32.1 mg) with a yield of 73%.

[0060] Example 20:

[0061] The reaction time was shortened to 4 hours, and other operations were carried out the same as in Example 1 to obtain product 3a (22.0 mg) with a yield of 50%.

[0062] Example 21:

[0063] The reaction time was extended to 24 hours, and other operations were carried out the same as in Example 1 to obtain product 3a (37.4 mg) with a yield of 85%.

[0064] Example 22:

[0065] The amount of α,α,α-terpyridine was changed to (2.9 mg, 0.01 mmol), and the other operations were the same as in Example 1 to obtain product 3a (26.8 mg) with a yield of 61%.

[0066] Example 23:

[0067] The amount of α,α,α-terpyridine was changed to (9.4 mg, 0.04 mmol), and the other operations were the same as in Example 1 to obtain product 3a (36.1 mg) with a yield of 82%.

[0068] Example 24:

[0069] Example 1, except that the amount of ethyl methacrylate was changed to (0.2 mmol, 22.8 mg, 1 equiv), to give product 3a (26.8 mg) in 61% yield.

[0070] Example 25:

[0071] Example 1, except that the amount of ethyl methacrylate was changed to (0.2 mmol, 22.8 mg, 1 equiv), to give product 3a (26.8 mg) in 61% yield.

[0072] Example 26:

[0073] Example 1, except that the amount of ethyl methacrylate was changed to (0.2 mmol, 22.8 mg, 1 equiv), to give product 3a (26.8 mg) in 61% yield.

[0074] Example 27:

[0075] Example 1, except that the amount of ethyl methacrylate was changed to (0.2 mmol, 22.8 mg, 1 equiv), to give product 3a (26.8 mg) in 61% yield.

[0076] Example 28:

[0077] Example 1, except that the amount of ethyl methacrylate was changed to (0.2 mmol, 22.8 mg, 1 equiv), to give product 3a (26.8 mg) in 61% yield.

[0078] Example 29:

[0079] Synthesis of compound 3b:

[0080]

[0081] Under nitrogen atmosphere, p-methoxybenzoic acid 1b (0.2 mmol, 30.4 mg, 1.0 equiv), ethyl methacrylate 2a (0.24 mmol, 27.4 mg, 1.2 equiv), (EtO)3SiH (0.6 mmol, 98.4 mg, 3.0 equiv), zinc (0.6 mmol, 39.0 mg, 3.0 equiv), NiBr2(DME) (0.01 mmol, 3.1 mg, 5 mol%), α,α,α-terpyridine (0.02 mmol, 4.7 mg, 10 mol%) and 1 ml of tetrahydrofuran were added to a reaction tube. The reaction system was allowed to react at 60°C for 12 hours. After completion of the reaction, the reaction solution was concentrated and subjected to column chromatography (100-mesh silica gel) using a mixture of petroleum ether and ethyl acetate (300 ml petroleum ether, 10 ml ethyl acetate) in a 30:1 volume ratio as the eluent. The eluate containing the target compound was collected, concentrated, distilled, and dried to obtain product 3b (yield 68%). (Eluent polarity: petroleum ether / ethyl acetate 30:1). 1 HNMR (400MHz, CDCl3) δ7.83(d,J=8.8Hz,2H),6.88(d,J=8.8Hz,2H),4.10(q,J=7.0Hz,2H),3.84(s,3H),1.51(s,6H),1.06(t,J=7.1Hz,3H).

[0082] Example 30:

[0083] Synthesis of compound 3c:

[0084]

[0085] Under nitrogen atmosphere, p-methoxybenzoic acid 1c (0.2 mmol, 30.4 mg, 1.0 equiv), ethyl methacrylate 2a (0.24 mmol, 27.4 mg, 1.2 equiv), (EtO)3SiH (0.6 mmol, 98.4 mg, 3.0 equiv), zinc (0.6 mmol, 39.0 mg, 3.0 equiv), NiBr2(DME) (0.01 mmol, 3.1 mg, 5 mol%), α,α,α-terpyridine (0.02 mmol, 4.7 mg, 10 mol%) and 1 ml of tetrahydrofuran were added to a reaction tube. The reaction system was allowed to react at 60°C for 12 hours. After completion of the reaction, the reaction solution was concentrated and subjected to column chromatography (100-mesh silica gel) using a mixture of petroleum ether and ethyl acetate (300 ml, 10 ml, by volume) in a 30:1 ratio (volume ratio). The eluate containing the target compound was collected, concentrated, distilled, and dried to obtain product 3c (yield 65%). (Eluent polarity: petroleum ether / ethyl acetate = 30:1). 1 HNMR(400MHz, CDCl3)δ7.93(d,J=8.5Hz,2H),7.67–7.60(m,4H),7.47(t,J=7.1Hz,2 H),7.39(t,J=7.3Hz,1H),4.15(q,J=7.1Hz,2H),1.58(s,6H),1.08(t,J=7.1Hz,3H). 13 C NMR(101MHz, CDCl3)δ197.32(s),175.12(s),145.32(s),139.72(s),133.85(s),129.31(s) ,128.98(s),128.28(s),127.23(s),127.06(s),61.44(s),53.32(s),23.97(s),13.83(s).

[0086] Example 31:

[0087] Synthesis of compound 3d:

[0088]

[0089] Under nitrogen atmosphere, p-cyanobenzoic acid 1d (0.2 mmol, 29.4 mg, 1.0 equiv), ethyl methacrylate 2a (0.24 mmol, 27.4 mg, 1.2 equiv), (EtO)3SiH (0.6 mmol, 98.4 mg, 3.0 equiv), zinc (0.6 mmol, 39.0 mg, 3.0 equiv), NiBr2(DME) (0.01 mmol, 3.1 mg, 5 mol%), α,α,α-terpyridine (0.02 mmol, 4.7 mg, 10 mol%), and 1 ml of tetrahydrofuran were added to a reaction tube. The reaction system was allowed to react at 60°C for 12 hours. After completion of the reaction, the reaction solution was concentrated and subjected to column chromatography (100-mesh silica gel) using a mixture of petroleum ether and ethyl acetate (300 ml petroleum ether, 10 ml ethyl acetate) in a 30:1 volume ratio as the eluent. The eluate containing the target compound was collected, concentrated, distilled, and dried to obtain product 3d (yield 41%). (Eluent polarity: petroleum ether / ethyl acetate = 30:1). 1 H NMR (400MHz, CDCl3) δ7.90 (d, J = 8.5Hz, 2H), 7.72 (d, J = 8.6Hz, 2H), 4.11 (q, J = 7.1Hz, 2H), 1.53 (s, 6H), 1.05 (t, J = 7.1Hz, 3H). 13 C NMR(101MHz, CDCl3)δ196.66(s),174.30(s),138.53(s),132.33(s),128.99(s),117 .82(s),115.99(s),61.70(s),53.54(s),23.66(s),13.78(s).HRMS(ESI)m / z:[M+Na + ]Calcd for C 14 H 15 NNaO3 + :268.0950;Found:268.0951.

[0090] Example 32:

[0091] Synthesis of compound 3e:

[0092]

[0093] Under nitrogen atmosphere, 2-naphthoic acid 1e (0.2 mmol, 34.4 mg, 1.0 equiv), ethyl methacrylate 2a (0.24 mmol, 27.4 mg, 1.2 equiv.), (EtO)3SiH (0.6 mmol, 98.4 mg, 3.0 equiv), zinc (0.6 mmol, 39.0 mg, 3.0 equiv), NiBr2(DME) (0.01 mmol, 3.1 mg, 5 mol%), α,α,α-terpyridine (0.02 mmol, 4.7 mg, 10 mol%) and 1 ml of tetrahydrofuran were added to a reaction tube. The reaction system was allowed to react at 60°C for 12 hours. After completion of the reaction, the reaction solution was concentrated and eluted by column chromatography (100-mesh silica gel) using a mixture of petroleum ether and ethyl acetate (300 ml petroleum ether, 10 ml ethyl acetate) in a volume ratio of 30:1. The eluate containing the target compound was collected, concentrated, distilled, and dried to obtain product 3e (yield 64%). (Eluent polarity: petroleum ether / ethyl acetate = 30:1). 1 H NMR (400MHz, CDCl3) δ8.37(s,1H),7.92(d,J=8.5Hz,2H),7.85(d,J=9.2Hz,2H),7.56(m,2H),4.12(q,J=7.1Hz,2H),1.62(s,6H),1.02(t,J=7.1Hz,3H).

[0094] Example 33:

[0095] Synthesis of compound 3f:

[0096]

[0097] Under nitrogen atmosphere, furanoic acid 1f (0.2 mmol, 22.4 mg, 1.0 equiv), ethyl methacrylate 2a (0.24 mmol, 27.4 mg, 1.2 equiv), (EtO)3SiH (0.6 mmol, 98.4 mg, 3.0 equiv), zinc (0.6 mmol, 39.0 mg, 3.0 equiv), NiBr2(DME) (0.01 mmol, 3.1 mg, 5 mol%), α,α,α-terpyridine (0.02 mmol, 4.7 mg, 10 mol%) and 1 ml of tetrahydrofuran were added to a reaction tube. The reaction system was allowed to react at 60°C for 12 hours. After completion of the reaction, the reaction solution was concentrated and eluted by column chromatography (100-mesh silica gel) using a mixture of petroleum ether and ethyl acetate (300 ml by volume, 10 ml by volume) in a 30:1 ratio. The eluate containing the target compound was collected, concentrated, distilled, and dried to obtain product 3f (yield 69%). (Eluent polarity: petroleum ether / ethyl acetate = 30:1). 1 H NMR (400MHz, CDCl3) δ7.51(d,J=0.8Hz,1H),7.20(d,J=3.6Hz,1H),6.50(dd,J=3.6,1.6Hz,1H),4.11(q,J=7.1Hz,2H),1.48(s,6H),1.07(t,J=7.1Hz,3H).

[0098] Example 34:

[0099] Synthesis of compound 3g:

[0100]

[0101] Under nitrogen atmosphere, benzoic acid 1a (0.2 mmol, 24.4 mg, 1.0 equiv), ethyl phenylacrylate 2 g (0.24 mmol, 42.2 mg, 1.2 equiv), (EtO)3SiH (0.6 mmol, 98.4 mg, 3.0 equiv), zinc (0.6 mmol, 39.0 mg, 3.0 equiv), NiBr2(DME) (0.01 mmol, 3.1 mg, 5 mol%), α,α,α-terpyridine (0.02 mmol, 4.7 mg, 10 mol%) and 1 ml of tetrahydrofuran were added to a reaction tube. The reaction system was allowed to react at 60°C for 12 hours. After completion of the reaction, the reaction solution was concentrated and subjected to column chromatography (100-mesh silica gel) using a mixture of petroleum ether and ethyl acetate (300 ml petroleum ether, 10 ml ethyl acetate) in a volume ratio of 30:1 as the eluent. The eluate containing the target compound was collected, concentrated, distilled, and dried to obtain 3 g of the product (yield 47%). (Eluent polarity: petroleum ether / ethyl acetate = 30:1). 1 H NMR (400MHz, CDCl3) δ7.70(d,J=7.3Hz,2H),7.54–7.43(m,3H),7.38–7.28(m,6H),4.20–4.12(m,2H),1.93(s,3H),1.07(t,J=7.1Hz,3H).

[0102] Example 35:

[0103] Synthesis of compound 3h:

[0104]

[0105] Under nitrogen atmosphere, benzoic acid 1a (0.2 mmol, 24.4 mg, 1.0 equiv), benzyl methacrylate 2h (0.24 mmol, 42.2 mg, 1.2 equiv), (EtO)3SiH (0.6 mmol, 98.4 mg, 3.0 equiv), zinc (0.6 mmol, 39.0 mg, 3.0 equiv), NiBr2(DME) (0.01 mmol, 3.1 mg, 5 mol%), α,α,α-terpyridine (0.02 mmol, 4.7 mg, 10 mol%) and 1 ml of tetrahydrofuran were added to a reaction tube. The reaction system was allowed to react at 60°C for 12 hours. After completion of the reaction, the reaction solution was concentrated and subjected to column chromatography (100-mesh silica gel) using a mixture of petroleum ether and ethyl acetate (300 ml petroleum ether, 10 ml ethyl acetate) in a volume ratio of 30:1 as the eluent. The eluate containing the target compound was collected, concentrated, distilled, and dried to obtain the product (yield 71%). (Eluent polarity: petroleum ether / ethyl acetate = 30:1). 1 H NMR(400MHz, CDCl3) δ7.79(d,J=7.5Hz,2H),7.50(t,J=7.4Hz,1H),7.38–7.3 2(m,2H),7.28–7.23(m,3H),7.09(d,J=6.3Hz,2H),5.10(s,2H),1.59(s,6H). 13 C NMR(101MHz, CDCl3)δ197.55(s),174.80(s),135.09(s),135.05(s),132.65(s),128. 61(s),128.48(s),128.43(s),128.26(s),128.25(s),67.14(s),53.34(s),23.99(s).

[0106] Example 36:

[0107] Synthesis of compound 3i:

[0108]

[0109] Under nitrogen atmosphere, benzoic acid 1a (0.2 mmol, 24.4 mg, 1.0 equiv), ethyl acrylate 2i (0.24 mmol, 24.0 mg, 1.2 equiv), (EtO)3SiH (0.6 mmol, 98.4 mg, 3.0 equiv), zinc (0.6 mmol, 39.0 mg, 3.0 equiv), NiBr2(DME) (0.01 mmol, 3.1 mg, 5 mol%), α,α,α-terpyridine (0.02 mmol, 4.7 mg, 10 mol%) and 1 ml of tetrahydrofuran were added to a reaction tube. The reaction system was allowed to react at 60°C for 12 hours. After completion of the reaction, the reaction solution was concentrated and subjected to column chromatography (100-mesh silica gel) using a mixture of petroleum ether and ethyl acetate (300 ml by volume, 10 ml by volume) as the eluent. The eluate containing the target compound was collected, concentrated, distilled, and dried to obtain product 3i (yield 61%). (Eluent polarity: petroleum ether / ethyl acetate = 30:1). 1 H NMR (400MHz, CDCl3) δ7.97(d,J=7.6Hz,2H),7.57(t,J=7.3Hz,1H),7.47(t,J=7.8Hz,2H), 4.37(q,J=7.1Hz,1H), 4.14(q,J=7.1Hz,2H), 1.49(d,J=7.1Hz,3H), 1.16(t,J=7.1Hz,3H). 13 C NMR (101MHz, CDCl3) δ195.94(s), 170.92(s), 135.88(s), 133.46(s), 128.73(s), 128.59(s), 61.38(s), 48.37(s), 13.96(s), 13.75(s).

[0110] Example 37:

[0111] Synthesis of compound 3j:

[0112]

[0113] Under nitrogen atmosphere, heptanoic acid 1j (0.2 mmol, 26.0 mg, 1.0 equiv), ethyl methacrylate 2a (0.24 mmol, 27.4 mg, 1.2 equiv), (EtO)3SiH (0.6 mmol, 98.4 mg, 3.0 equiv), zinc (0.6 mmol, 39.0 mg, 3.0 equiv), NiBr2(DME) (0.01 mmol, 3.1 mg, 5 mol%), α,α,α-terpyridine (0.02 mmol, 4.7 mg, 10 mol%) and 1 ml of tetrahydrofuran were added to a reaction tube. The reaction system was allowed to react at 60°C for 12 hours. After completion of the reaction, the reaction solution was concentrated and subjected to column chromatography (100-mesh silica gel) using a mixture of petroleum ether and ethyl acetate (300 ml petroleum ether, 10 ml ethyl acetate) in a volume ratio of 30:1 as the eluent. The eluate containing the target compound was collected, concentrated, distilled, and dried to obtain product 3j (yield 67%). (Eluent polarity: petroleum ether / ethyl acetate = 30:1). 1 H NMR (400MHz, CDCl3) δ4.15 (q, J = 7.1Hz, 2H), 2.41 (t, J = 7.3Hz, 2H), 1.58–1.51 (m, 2H), 1.33 (s, 6H), 1.28–1.21 (m, 9H), 0.85 (t, J = 6.7Hz, 3H). 13 C NMR(101MHz, CDCl3)δ208.20(s),173.80(s),61.23(s),55.57(s),37.95(s),31. 59(s),28.80(s),23.84(s),22.47(s),21.86(s),13.99(s).HRMS(ESI)m / z:[M+Na + ]Calcd for C 13 H 24 NaO3 + :251.1623;Found:251.1629.

[0114] Example 38:

[0115] Synthesis of compound 3k:

[0116]

[0117] Under nitrogen atmosphere, undecanoic acid 1c (0.2 mmol, 37.3 mg, 1.0 equiv), ethyl methacrylate 2a (0.24 mmol, 27.4 mg, 1.2 equiv), (EtO)3SiH (0.6 mmol, 98.4 mg, 3.0 equiv), zinc (0.6 mmol, 39.0 mg, 3.0 equiv), NiBr2(DME) (0.01 mmol, 3.1 mg, 5 mol%), α,α,α-terpyridine (0.02 mmol, 4.7 mg, 10 mol%), and 1 ml of tetrahydrofuran were added to a reaction tube. The reaction system was allowed to react at 60°C for 12 hours. After completion of the reaction, the reaction solution was concentrated and subjected to column chromatography (100-mesh silica gel) using a mixture of petroleum ether and ethyl acetate (300 ml petroleum ether, 10 ml ethyl acetate) in a 30:1 volume ratio as the eluent. The eluate containing the target compound was collected, concentrated, distilled, and dried to obtain product 3k (yield 41%). (Eluent polarity: petroleum ether / ethyl acetate = 30:1). 1 H NMR (400MHz, CDCl3) δ4.15 (q, J = 7.1Hz, 2H), 2.40 (t, J = 7.2Hz, 2H), 1.59–1.47 (m, 2H), 1.32 (s, 6H), 1.29–1.15 (m, 17H), 0.84 (t, J = 6.6Hz, 3H). 13 C NMR(101MHz, CDCl3)δ208.14(s),173.78(s),61.20(s),55.55(s),37.94(s),31.86(s),29.53(s) ,29.45(s),29.40(s),29.28(s),29.14(s),23.88(s),22.64(s),21.85(s),14.06(s),13.99(s).

[0118] Example 39:

[0119] Synthesis of compound 3l:

[0120]

[0121] Into a reaction tube was placed 4-chlorobutyric acid 1l (0.2 mmol, 24.5 mg, 1.0 equiv), ethyl methacrylate 2a (0.24 mmol, 27.4 mg, 1.2 equiv), (EtO)3SiH (0.6 mmol, 98.4 mg, 3.0 equiv), zinc (0.6 mmol, 39.0 mg, 3.0 equiv), NiBr2(DME) (0.01 mmol, 3.1 mg, 5 mol%), a, a, a-tripyridyl (0.02 mmol, 4.7 mg, 10 mol%), tetrahydrofuran 1 ml under nitrogen atmosphere. The reaction was stirred at 60 °C for 12 h. After the reaction was completed, the reaction solution was concentrated and column chromatography (100 mesh silica gel) was performed with petroleum ether and ethyl acetate (volume ratio 30:1, petroleum ether 300 ml, ethyl acetate 10 ml) as the eluent to obtain the product 3l (yield 75%). 1 H NMR (400 MHz, CDC13) δ 4.16 (q, J = 7.1 Hz, 2H), 3.53 (t, J = 6.2 Hz, 2H), 2.64 (t, J = 6.8 Hz, 2H), 2.04 (p, J = 6.5 Hz, 2H), 1.35 (s, 6H), 1.24 (t, J = 7.1 Hz, 3H). 13 C NMR (101 MHz, CDC13) δ 207.16 (s), 173.49 (s), 61.44 (s), 55.50 (s), 44.24 (s), 34.68 (s), 26.58 (s), 21.89 (s), 13.99 (s). HRMS (ESI) m / z: [M + Na + ] Calcd for C 10 H 17 ClNaO3 + : 243.0764; Found: 243.0769.

[0122] Example 40:

[0123] Synthesis of compound 3m:

[0124]

[0125] Under nitrogen atmosphere, cyclohexyl acetic acid 1m (0.2mmol, 28.4mg, 1.0equiv), ethyl methacrylate 2a (0.24mmol, 27.4mg, 1.2equiv), (EtO)3SiH (0.6mmol, 98.4mg, 3.0equiv), zinc (0.6mmol, 39.0mg, 3.0equiv), NiBr2(DME) (0.01mmol, 3.1mg, 5mol%), α,α,α-terpyridine (0.02mmol, 4.7mg, 10mol%) and tetrahydrofuran 1ml were added to the reaction tube. The reaction system was allowed to react at 60°C for 12 hours. After completion of the reaction, the reaction solution was concentrated and subjected to column chromatography (100-mesh silica gel) using a mixture of petroleum ether and ethyl acetate (300 ml petroleum ether, 10 ml ethyl acetate) in a volume ratio of 30:1 as the eluent. The eluate containing the target compound was collected, concentrated, distilled, and dried to obtain product 3m (yield 57%). (Eluent polarity: petroleum ether / ethyl acetate = 30:1). 1 H NMR(400MHz, CDCl3)δ4.14(q,J=7.1Hz,2H),2.27(d,J=6.7Hz,2H),1.87–1.83(m,1H),1.6 2(d,J=8.9Hz,5H),1.30(s,6H),1.25–1.19(m,5H),1.13–1.03(m,1H),0.90–0.77(m,2H). 13 CNMR(101MHz, CDCl3)δ207.37(s),173.72(s),61.23(s),55.71(s),45.51(s),33.19(s),33.06(s),26.20(s),26.08(s),21.76(s),13.99(s).

[0126] Example 41:

[0127] Synthesis of compound 3n:

[0128]

[0129] Under nitrogen atmosphere, phenylacetic acid 1n (0.2 mmol, 27.2 mg, 1.0 equiv), ethyl methacrylate 2a (0.24 mmol, 27.4 mg, 1.2 equiv), (EtO)3SiH (0.6 mmol, 98.4 mg, 3.0 equiv), zinc (0.6 mmol, 39.0 mg, 3.0 equiv), NiBr2(DME) (0.01 mmol, 3.1 mg, 5 mol%), α,α,α-terpyridine (0.02 mmol, 4.7 mg, 10 mol%), and 1 ml of tetrahydrofuran were added to a reaction tube. The reaction system was allowed to react at 60°C for 12 hours. After completion of the reaction, the reaction solution was concentrated and subjected to column chromatography (100-mesh silica gel) using a mixture of petroleum ether and ethyl acetate (300 ml by volume, 10 ml by volume) as the eluent. The eluate containing the target compound was collected, concentrated, distilled, and dried to obtain product 3n (yield 51%). (Eluent polarity: petroleum ether / ethyl acetate = 30:1). 1 H NMR (400MHz, CDCl3) δ7.35–7.25(m,3H),7.20(d,J=7.0Hz,2H),4.19(q,J=7.1Hz,2H),3.80(s,2H),1.44(s,6H),1.26(t,J=7.1Hz,3H). 13 C NMR(101MHz, CDCl3)δ205.24(s),173.58(s),134.10(s),129.52(s),128.44(s),126.92(s),61.48(s),55.86(s),44.68(s),21.96(s),14.02(s).

[0130] Example 42:

[0131] Synthesis of compound 3o:

[0132]

[0133] Under nitrogen atmosphere, cyclopentanoic acid 1o (0.2 mmol, 22.8 mg, 1.0 equiv), ethyl methacrylate 2a (0.24 mmol, 27.4 mg, 1.2 equiv), (EtO)3SiH (0.6 mmol, 98.4 mg, 3.0 equiv), zinc (0.6 mmol, 39.0 mg, 3.0 equiv), NiBr2(DME) (0.01 mmol, 3.1 mg, 5 mol%), α,α,α-terpyridine (0.02 mmol, 4.7 mg, 10 mol%), and 1 ml of tetrahydrofuran were added to a reaction tube. The reaction system was allowed to react at 60°C for 12 hours. After completion of the reaction, the reaction solution was concentrated and subjected to column chromatography (100-mesh silica gel) using a mixture of petroleum ether and ethyl acetate (300 ml, 10 ml, by volume) in a 30:1 ratio (volume ratio). The eluate containing the target compound was collected, concentrated, distilled, and dried to obtain product 3o (yield 46%). (Eluent polarity: petroleum ether / ethyl acetate = 30:1). 1 H NMR(500MHz, CDCl3)δ4.15(q,J=7.5Hz,2H),2.95(p,J=7.5Hz,1H),1.80–1.70(m ,4H),1.69–1.61(m,2H),1.58–1.48(m,2H),1.33(s,6H),1.23(t,J=7.0Hz,3H). 13 C NMR (101MHz, CDCl3) δ212.61(s),173.85(s),61.21(s),55.93(s),47.46(s),32.31(s),26.46(s),21.61(s),14.06(s).HRMS(ESI)m / z:[M+Na + ]Calcd for C 12 H 20 NaO3 + :235.1310;Found:235.1315.

Claims

1. A method for synthesizing a β-carbonyl ester compound, comprising: mixing a carboxylic acid represented by formula (I), an alkenyl ester represented by formula (II), a catalyst, a ligand, a silane, a reducing agent, and an organic solvent under a nitrogen atmosphere, stirring and reacting the mixture at 20°C to 120°C for 4 to 24 hours to obtain a reaction solution, and separating and purifying the reaction solution by silica gel column chromatography to obtain a β-carbonyl ester compound represented by formula (III). in, In formula (I) or formula (III), R 1 is selected from phenyl, p-methoxybenzene, p-phenylbenzene, p-cyanobenzene, hexyl, decyl, chloropropyl, cyclohexanemethyl, benzyl, cyclopentyl, naphthyl or furan, R in formula (II) or formula (III) 2 is selected from hydrogen, methyl or phenyl, R 3 The invention relates to a method for preparing a novel silane-containing compound comprising: a silane selected from an ethyl group and a benzyl group; a catalyst selected from NiBr2, NiCl2, or NiBr2(DME); a ligand selected from triphenylphosphine, 2,2'-bipyridine, 1,10-phenanthroline, or α,α,α-terpyridine; a molar ratio of the carboxylic acid compound represented by formula (I) to the alkenyl ester represented by formula (II), the catalyst, the ligand, the silane, and the reducing agent is 1:1-2:0.02-0.1:0.05-0.2:1-5:1-5; the silane is diphenylsilane, diethoxysilane, or triethoxysilane; and the reducing agent is zinc.

2. The method for synthesizing β-carbonyl ester compounds according to claim 1, wherein: The organic solvent is dioxane, anisole or tetrahydrofuran.

3. The method for synthesizing β-carbonyl ester compounds according to claim 1, wherein: The volume of the organic solvent is 20.5-123.0 ml / g based on the mass of the carboxylic acid represented by formula (I).

4. The method for synthesizing β-carbonyl ester compounds according to claim 1, wherein: The molar ratio of the carboxylic acid compound represented by formula (I) to the alkenyl ester represented by formula (II), the catalyst, the ligand, the silane, and the reducing agent is 1:1.2:0.05:0.1:3:

3.

5. The method for synthesizing β-carbonyl ester compounds according to claim 1, wherein: The catalyst is NiBr2(DME).

6. The method for synthesizing β-carbonyl ester compounds according to claim 1, wherein: The ligand is α,α,α-terpyridine.

7. The method for synthesizing β-carbonyl ester compounds according to claim 1, wherein: The specific operation process of the silica gel column separation and purification is as follows: the reaction solution is concentrated, column chromatography is performed, and a mixture of petroleum ether and ethyl acetate with a volume ratio of 30 to 15:1 is used as an eluent for elution, and the eluate containing the target compound is collected, concentrated, distilled and dried.

8. The method for synthesizing β-carbonyl ester compounds according to claim 1, wherein: The β-carbonyl ester compound is one of the following: 。

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