Method for preparing beta, gamma unsaturated ester compound through ring opening of vinyl cyclopropane

Abstract

The invention relates to the technical field of organic medicine synthesis, and discloses a method for preparing beta, gamma unsaturated ester compounds through ring opening of vinyl cyclopropane. The method comprises the following steps: dispersing vinyl cyclopropane, formic acid aryl ester, a palladium catalyst and a phosphine ligand in an organic solvent under a protective atmosphere, reacting to obtain beta, gamma unsaturated ester compounds, and separating out a target product after the reaction is completed. Phenyl formate is used as a carbonyl source, the method does not need an autoclave, the reaction steps are simple and convenient, the operation is simple, the reaction is novel, and a series of gamma and delta unsaturated ester compounds and derivatives thereof can be synthesized with extremely high efficiency.

Description

Technical Field

[0001] The present invention relates to the technical field of organic drug synthesis, and in particular to a method for preparing β,γ-unsaturated ester compounds by ring-opening of vinylcyclopropane. This method uses vinylcyclopropane as a substrate and aryl formate as a carbonyl source to prepare β,γ-unsaturated esters through a ring-opening hydroesterification reaction. Background Art

[0002] Vinylcyclopropane is an important class of organic synthesis intermediates. A variety of important organic compounds can be obtained through the functionalization reaction of vinylcyclopropane. In addition, β,γ-unsaturated carbonyl compounds are also extremely widely used in disciplines such as fine chemical engineering and pharmaceutical chemistry. As the molecular skeleton of compounds such as drugs and fragrances, they play a huge role in people's daily lives.

[0003] However, there is little research on the ring-opening hydroesterification reaction of vinylcyclopropane in the prior art, and traditional methods mostly rely on carbon monoxide as a carbonyl source, which have problems such as complex operation and low safety. Therefore, it is of great significance to develop a mild, efficient and carbon monoxide-free synthesis method. Summary of the Invention

[0004] The technical problem to be solved by the present invention is: to overcome the deficiencies in the prior art and provide a method for preparing β,γ-unsaturated ester compounds by ring-opening of vinylcyclopropane. The present invention provides a method that does not involve carbon monoxide, uses phenyl formate as a carbonyl source, does not require the use of an autoclave, and successfully realizes the ring-opening hydroesterification reaction of vinylcyclopropane under mild conditions, thereby efficiently and highly selectively preparing a series of β,γ-unsaturated ester compounds.

[0005] The technical solution adopted by the present invention to solve its technical problems is:

[0006] A method for preparing β,γ-unsaturated ester compounds by ring-opening of vinylcyclopropane. Under a nitrogen protection atmosphere, vinylcyclopropane, aryl formate, metal palladium salt and phosphine ligand are dispersed in an organic solvent and then reacted to obtain a crude product of β,γ-unsaturated ester; after the reaction is completed, the crude product of β,γ-unsaturated ester is separated to obtain the target product β,γ-unsaturated ester.

[0007] The reaction formula of this preparation method is:

[0008]

[0009] Further, the structural formula of the vinylcyclopropane is

[0010] wherein, R is one of phenyl, p-fluorophenyl, p-methylphenyl, p-trifluoromethylphenyl, 2-naphthyl.

[0011] Further, the molar ratio of the vinyl cyclopropane, aryl formate, palladium metal salt and phosphine ligand is 1:(1-4):(0.001-0.05):(0.004-0.2).

[0012] Further, the aryl formate is preferably the following compound:

[0013]

[0014] Further, the palladium metal salt is one or more of palladium acetate, palladium chloride, palladium nitrate, palladium trifluoroacetate, and preferably palladium acetate.

[0015] Further, the phosphorus ligand is one of PPh3, (o-OMe-Ph)3P, (p-F-Ph)3P, PPh2Cy, PPhCy2, PCy3, dppm, dppb, dppf, Xantphos, DPEphos. The phosphorus ligand is preferably Xantphos, and its structural formula is as follows:

[0016]

[0017] Further, the organic solvent is one of toluene, n-hexane, 1,2-dichloroethane, dichloromethane, acetonitrile, acetone, tetrahydrofuran, 1,4-dioxane, ethyl acetate, and preferably toluene.

[0018] Further, the reaction temperature is 20-110°C, and preferably 90°C is used as the reaction temperature.

[0019] Further, the separation operation is silica gel column chromatography separation method.

[0020] The specific reaction mechanism of the present invention is as follows: First, Pd(0) coordinates with vinyl cyclopropane 1a to generate an allyl palladium intermediate M1. At the same time, another part of Pd(0) can promote the decomposition of phenyl formate into carbon monoxide and phenol by forming intermediate M4. The allyl palladium intermediate M1 can undergo an addition reaction with phenol and complex one molecule of carbon monoxide to form intermediate M2. Subsequently, intermediate M2 undergoes carbonyl insertion to generate intermediate M3, and then a reductive elimination reaction occurs to generate the final product 3a, and Pd(0) is released to participate in the next cycle. The specific reaction mechanism is as follows:

[0021]

[0022] The beneficial effects of the present invention are as follows: The present invention is reasonably designed and the preparation method is simple, and has the following advantages:

[0023] (1) The present invention reacts vinyl cyclopropane with an equivalent amount of phenyl formate using palladium metal salts and Xantphos as catalysts, and can obtain the corresponding β,γ-unsaturated ester compounds and their derivatives through reaction under very mild conditions;

[0024] (2) The present invention uses phenyl formate as a carbonyl source, successfully solves the problem of the selective ring-opening hydroesterification reaction of vinyl cyclopropane, and successfully realizes the synthesis of a series of β,γ-unsaturated ester compounds;

[0025] (3) The reaction conditions of the present invention are mild. Using phenyl formate as a carbonyl source avoids the use of carbon monoxide in traditional hydroesterification reactions, is easy to operate, has good yields, and can greatly save energy and improve synthesis efficiency. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the following will briefly introduce the drawings required for use in the description of the specific embodiments or the prior art. Obviously, the drawings in the following description are some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0027] Figure 1 1H NMR spectrum of 1,1-diethyl 5-phenyl (E)-2-phenylpent-3-ene-1,1,5-tris(β,γ-unsaturated ester) (structural formula 3a) synthesized in Example 1; 1 H NMR spectrum;

[0028] Figure 2 13C NMR spectrum of 1,1-diethyl 5-phenyl (E)-2-phenylpent-3-ene-1,1,5-tris(β,γ-unsaturated ester) (structural formula 3a) synthesized in Example 1; 13 13C NMR spectrum;

[0029] Figure 3 1H NMR spectrum of 1,1-diethyl 5-phenyl (E)-2-(p-tolyl)pent-3-ene-1,1,5-tris(β,γ-unsaturated ester) (structural formula 3b) synthesized in Example 2; 1 1H NMR spectrum;

[0030] Figure 4 13C NMR spectrum of 1,1-diethyl 5-phenyl (E)-2-(p-tolyl)pent-3-ene-1,1,5-tris(β,γ-unsaturated ester) (structural formula 3b) synthesized in Example 2; 13 13C NMR spectrum;

[0031] Figure 51,1 - Diethyl 5 - phenyl (E) - 2 - (4 - fluorophenyl) pent - 3 - en - 1,1,5 - tricarboxylic acid ester (structural formula 3c) synthesized in Example 3 1 H NMR spectrum;

[0032] Figure 6 1,1 - Diethyl 5 - phenyl (E) - 2 - (4 - fluorophenyl) pent - 3 - en - 1,1,5 - tricarboxylic acid ester (structural formula 3c) synthesized in Example 3 13 C NMR spectrum;

[0033] Figure 7 1,1 - Diethyl 5 - phenyl (E) - 2 - (4 - (trifluoromethyl)phenyl) pent - 3 - en - 1,1,5 - tricarboxylic acid ester (structural formula 3d) synthesized in Example 4 1 H NMR spectrum;

[0034] Figure 8 1,1 - Diethyl 5 - phenyl (E) - 2 - (4 - (trifluoromethyl)phenyl) pent - 3 - en - 1,1,5 - tricarboxylic acid ester (structural formula 3d) synthesized in Example 4 13 C NMR spectrum;

[0035] Figure 9 1,1 - Diethyl 5 - phenyl (E) - 2 - (naphthalen - 2 - yl) pent - 3 - en - 1,1,5 - tricarboxylic acid ester (structural formula 3e) synthesized in Example 5 1 H NMR spectrum;

[0036] Figure 10 1,1 - Diethyl 5 - phenyl (E) - 2 - (naphthalen - 2 - yl) pent - 3 - en - 1,1,5 - tricarboxylic acid ester (structural formula 3e) synthesized in Example 5 13 C NMR spectrum;

[0037] Figure 11 1,1 - Diethyl 5 - (4 - fluorophenyl) (E) - 2 - phenyl pent - 3 - en - 1,1,5 - tricarboxylic acid ester (structural formula 3f) synthesized in Example 6 1 H NMR spectrum;

[0038] Figure 12 1,1 - Diethyl 5 - (4 - fluorophenyl) (E) - 2 - phenyl pent - 3 - en - 1,1,5 - tricarboxylic acid ester (structural formula 3f) synthesized in Example 6 13 C NMR spectrum;

[0039] Figure 131,1 - Diethyl 5-(4 - chlorophenyl)(E)-2 - phenylpent - 3 - ene - 1,1,5 - tricarboxylate (structural formula 3g) synthesized in Example 7 1 H NMR spectrum;

[0040] Figure 14 1,1 - Diethyl 5-(4 - chlorophenyl)(E)-2 - phenylpent - 3 - ene - 1,1,5 - tricarboxylate (structural formula 3g) synthesized in Example 7 13 C NMR spectrum;

[0041] Figure 15 1,1 - Diethyl 5-(4 - (trifluoromethyl)phenyl)(E)-2 - phenylpent - 3 - ene - 1,1,5 - tricarboxylate (structural formula 3h) synthesized in Example 8 1 H NMR spectrum;

[0042] Figure 16 1,1 - Diethyl 5-(4 - (trifluoromethyl)phenyl)(E)-2 - phenylpent - 3 - ene - 1,1,5 - tricarboxylate (structural formula 3h) synthesized in Example 8 13 C NMR spectrum;

[0043] Figure 17 1,1 - Diethyl 5-(2,4,6 - trichlorophenyl)(E)-2 - phenylpent - 3 - ene - 1,1,5 - tricarboxylate (structural formula 3i) synthesized in Example 9 1 H NMR spectrum;

[0044] Figure 18 1,1 - Diethyl 5-(2,4,6 - trichlorophenyl)(E)-2 - phenylpent - 3 - ene - 1,1,5 - tricarboxylate (structural formula 3i) synthesized in Example 9 13 C NMR spectrum. Detailed implementation manners

[0045] It should be noted that the following detailed descriptions are all illustrative and are intended to provide further explanations for this application. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the technical field to which this application belongs.

[0046] It should be noted that the terms used herein are only for describing specific implementation manners and are not intended to limit the exemplary implementation manners according to this application. As used herein, unless the context clearly indicates otherwise, the singular forms also include the plural forms. In addition, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or their combinations.

[0047] The technical solution of the present invention will be clearly and completely described below in conjunction with embodiments. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of them. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts belong to the scope of protection of the present invention.

[0048] Example 1 1,1-Diethyl 5-phenyl (E)-2-phenylpent-3-ene-1,1,5-tri-β,γ-unsaturated ester (see Structural Formula 3a)

[0049] The synthesis reaction of 1,1-diethyl 5-phenyl (E)-2-phenylpent-3-ene-1,1,5-tri-β,γ-unsaturated ester 3a is as follows:

[0050]

[0051] Under argon protection, palladium acetate (0.0034 g, 0.015 mmol), diphosphine ligand Xantphos (0.0174 g, 0.030 mmol), 0.3 mL of toluene, phenyl formate (0.1099 g, 0.9 mmol) and 1a (0.0865 g, 0.3 mmol) were successively added to the reactor and mixed well. After sealing, the temperature of the mixed system in the reactor was raised to 90 °C by a heating plate and reacted for 24 hours. Then, the heating was stopped and it was naturally cooled to room temperature (25 °C, the same below). The target product (0.0886 g, yield 72%) was obtained by column chromatography separation (packed with petroleum ether, and the eluent was petroleum ether:ethyl acetate volume ratio 10:1 to 5:1) as a colorless oil.

[0052] The results of product structure confirmation are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.39 - 7.19 (m, 8H), 7.07 - 7.02 (m, 2H), 5.88 (dd, J = 15.6, 8.4 Hz, 1H), 5.82 - 5.73 (m, 1H), 4.22 - 4.12 (m, 3H), 3.99 - 3.90 (m, 2H), 3.84 (d, J = 10.8 Hz, 1H), 3.26 (d, J = 6.8 Hz, 2H), 1.24 (t, J = 7.2 Hz, 3H), 0.99 (t, J = 7.2 Hz, 3H); 1313C NMR (100 MHz, CDCl3) δ 169.8, 167.8, 167.5, 150.7, 140.1, 134.4, 129.5, 128.7, 128.1, 127.2, 126.0, 123.7, 121.6, 61.7, 61.5, 57.7, 48.8, 38.0, 14.2, 13.9; HRMS (ESI) calcd for C 24 H 27 O6 (M+H) + : 411.1802; found: 411.1801.

[0053] The synthesized compound was identified as the target compound 1,1 - diethyl 5 - phenyl (E) - 2 - phenyl pent - 3 - en - 1,1,5 - tri - β,γ - unsaturated ester 3a.

[0054] Example 2 1,1 - diethyl 5 - phenyl (E) - 2 - (p - tolyl) pent - 3 - en - 1,1,5 - tri - β,γ - unsaturated ester (see structural formula 3b)

[0055] The synthesis reaction of 1,1 - diethyl 5 - phenyl (E) - 2 - (p - tolyl) pent - 3 - en - 1,1,5 - tri - β,γ - unsaturated ester 3b is as follows:

[0056]

[0057] Under argon protection, palladium acetate (0.0034 g, 0.015 mmol), bisphosphine ligand Xantphos (0.0174 g, 0.030 mmol), 0.3 mL of toluene, phenyl formate (0.1099 g, 0.9 mmol) and 1b (0.0907 g, 0.3 mmol) were successively added to the reactor and mixed well. After sealing, the mixed system in the reactor was heated to 90 °C by a heating plate and reacted for 24 hours. Then, the heating was stopped and it was naturally cooled to room temperature (25 °C, the same below). The colorless oil was separated by column chromatography (using petroleum ether to pack the column, and the eluent was petroleum ether: ethyl acetate volume ratio 20:1 to 10:1), which was the target product (0.1093 g, yield 86%).

[0058] The results of product structure confirmation are as follows: 11H NMR (400 MHz, CDCl3) δ 7.39 - 7.33 (m, 2H), 7.25 - 7.19 (m, 1H), 7.16 - 7.08 (m, 4H), 7.07 - 7.02 (m, 2H), 5.86 (dd, J = 15.2, 8.0 Hz, 1H), 5.81 - 5.72 (m, 1H), 4.22 - 4.09 (m, 3H), 4.02 - 3.90 (m, 2H), 3.82 (d, J = 11.2 Hz, 1H), 3.25 (d, J = 6.4 Hz, 2H), 2.31 (s, 3H), 1.24 (t, J = 7.2 Hz, 3H), 1.02 (t, J = 7.2 Hz, 3H); 13 13C NMR (100 MHz, CDCl3) δ 170.0, 168.0, 167.6, 150.8, 137.2, 136.9, 134.7, 129.6, 129.5, 128.0, 126.0, 123.5, 121.7, 61.8, 61.6, 57.8, 48.5, 38.1, 21.2, 14.3; HRMS (ESI) calcd for C 25 H 28 O6Na (M + Na) + : 447.1778; found: 447.1777.

[0059] The synthesized compound was identified as the target compound 1,1 - diethyl 5 - phenyl (E) - 2 - (p - tolyl) pent - 3 - ene - 1,1,5 - tricarboxylate 3b by structural identification.

[0060] Example 3 1,1 - diethyl 5 - phenyl (E) - 2 - (4 - fluorophenyl) pent - 3 - ene - 1,1,5 - tricarboxylate (see Structural Formula 3c)

[0061] The synthesis reaction of 1,1 - diethyl 5 - phenyl (E) - 2 - (4 - fluorophenyl) pent - 3 - ene - 1,1,5 - tricarboxylate 3c is as follows:

[0062]

[0063] Under argon protection, palladium acetate (0.0034 g, 0.015 mmol), bisphosphine ligand Xantphos (0.0174 g, 0.030 mmol), 0.3 mL of toluene, phenyl formate (0.1099 g, 0.9 mmol) and 1c (0.0919 g, 0.3 mmol) were successively added to a reactor and mixed thoroughly. After sealing, the mixed system in the reactor was heated to 90 °C by a heating plate and reacted for 24 hours. Then, the heating was stopped and it was naturally cooled to room temperature (25 °C, the same below). The target product (0.1007 g, yield 78%) was obtained by column chromatography separation (packed with petroleum ether, and the eluent was petroleum ether: ethyl acetate volume ratio 10:1 to 5:1), which was a pale yellow oil.

[0064] The results of product structure confirmation are as follows: 1 H 1 H NMR (400 MHz, CDCl3) δ 7.39 - 7.33 (m, 2H), 7.25 - 7.19 (m, 3H), 7.06 - 6.96 (m, 4H), 5.85 (dd, J = 15.6, 8.0 Hz, 1H), 5.76 (dt, J = 15.6, 6.8 Hz, 1H), 4.23 - 4.11 (m, 3H), 4.02 - 3.92 (m, 2H), 3.79 (d, J = 10.8 Hz, 1H), 3.27 (d, J = 6.4 Hz, 2H), 1.24 (t, J = 7.2 Hz, 3H), 1.02 (t, J = 7.2 Hz, 3H); 13 C NMR (100 MHz, CDCl3) δ 169.9, 167.8, 167.5, 162.0 (d, J = 244.1 Hz), 150.8, 135.9 (d, J = 3.3 Hz), 134.3, 129.8 (d, J = 7.9 Hz), 129.6, 126.1, 123.9, 121.6, 115.7 (d, J = 21.3 Hz), 61.9, 61.7, 57.9, 48.0, 38.0, 14.3, 14.0. HRMS (ESI) calcd for C 24 H 26 FO6(M + H) + : 429.1708; found: 429.1715.

[0065] The synthesized compound was identified by structure as the target compound 1,1 - diethyl 5 - phenyl (E) - 2 - (4 - fluorophenyl) pent - 3 - en - 1,1,5 - tribeta, gamma - unsaturated ester 3c.

[0066] Example 4 1,1 - diethyl 5 - phenyl (E) - 2 - (4 - (trifluoromethyl)phenyl)penta - 3 - en - 1,1,5 - tri - β,γ - unsaturated ester (see Structural Formula 3d)

[0067] The synthesis reaction of 1,1 - diethyl 5 - phenyl (E) - 2 - (4 - (trifluoromethyl)phenyl)penta - 3 - en - 1,1,5 - tri - β,γ - unsaturated ester 3d is as follows:

[0068]

[0069] Under argon protection, palladium acetate (0.0034 g, 0.015 mmol), bisphosphine ligand Xantphos (0.0174 g, 0.030 mmol), 0.3 mL of toluene, phenyl formate (0.1099 g, 0.9 mmol) and 1d (0.1069 g, 0.3 mmol) were successively added to the reactor and mixed thoroughly. After sealing, the mixed system in the reactor was heated to 90 °C by a heating plate and reacted for 24 hours. Then, the heating was stopped and it was naturally cooled to room temperature (25 °C, the same below). The target product (0.0708 g, yield 49%) was obtained by column chromatography separation (using petroleum ether to pack the column, and the eluent was petroleum ether:ethyl acetate volume ratio 15:1 to 8:1), which was a pale yellow oil.

[0070] The results of product structure confirmation are as follows: 1 H NMR(400MHz,CDCl3)δ7.57(d,J = 8.0Hz,2H),7.42 - 7.33(m,4H),7.22(t,J = 7.6Hz,1H),7.04(d,J = 7.6Hz,2H),5.97 - 5.74(m,2H),4.28 - 4.15(m,3H),4.02 - 3.92(m,2H),3.85(d,J = 11.2Hz,1H),3.27(d,J = 6.4Hz,2H),1.25(t,J = 7.2Hz,3H),1.01(t,J = 7.2Hz,3H); 13 C NMR(100MHz,CDCl3)δ169.8,167.6,167.3,150.7,144.4,133.6,129.62(q,J = 32.3Hz),129.64,128.6,126.1,125.8(q,J = 3.7Hz),124.7,124.2(d,J = 270.3Hz),121.6,62.0,61.8,57.5,48.5,38.0,14.3,13.9;HRMS(ESI)calcdfor C 25 H 26 F3O6(M + H) +: 479.1676; found: 479.1677.

[0071] The compound synthesized by structural identification is the target compound 1,1 - diethyl 5 - phenyl (E) - 2 - (4 - (trifluoromethyl)phenyl)penta - 3 - en - 1,1,5 - tri - β,γ - unsaturated ester 3d.

[0072] Example 5 1,1 - diethyl 5 - phenyl (E) - 2 - (naphthalen - 2 - yl)penta - 3 - en - 1,1,5 - tri - β,γ - unsaturated ester (see structural formula 3e)

[0073] The synthesis reaction of 1,1 - diethyl 5 - phenyl (E) - 2 - (naphthalen - 2 - yl)penta - 3 - en - 1,1,5 - tri - β,γ - unsaturated ester 3e is as follows:

[0074]

[0075] Under argon protection, palladium acetate (0.0034 g, 0.015 mmol), bisphosphine ligand Xantphos (0.0174 g, 0.030 mmol), 0.3 mL of toluene, phenyl formate (0.1099 g, 0.9 mmol) and 1e (0.1015 g, 0.3 mmol) were successively added to the reactor and mixed thoroughly. After sealing, the mixed system in the reactor was heated to 90 °C by a heating plate and reacted for 24 hours. Then, the heating was stopped and it was naturally cooled to room temperature (25 °C, the same below). The colorless oil was separated by column chromatography (packed with petroleum ether, and the eluent was petroleum ether:ethyl acetate volume ratio 10:1), which is the target product (0.0834 g, yield 60%, the ratio of straight - chain to branched - chain is greater than 20:1).

[0076] The results of product structure confirmation are as follows: 1 H NMR(400 MHz, CDCl3) δ 7.84 - 7.77(m, 3H), 7.72(s, 1H), 7.50 - 7.32(m, 5H), 7.25 - 7.19(m, 1H), 7.08 - 7.02(m, 2H), 5.98(dd, J = 15.2, 8.0 Hz, 1H), 5.89 - 5.80(m, 1H), 4.36(dd, J = 10.8, 8.4 Hz, 1H), 4.22(q, J = 6.8 Hz, 2H), 4.00(d, J = 11.2 Hz, 1H), 3.97 - 3.88(m, 2H), 3.29(d, J = 6.8 Hz, 2H), 1.27(t, J = 7.2 Hz, 3H), 0.94(t, J = 7.2 Hz, 3H); 1313C NMR (100 MHz, CDCl3) δ 169.9, 167.9, 167.5, 150.8, 137.7, 134.4, 133.6, 132.7, 129.6, 128.5, 127.9, 127.8, 126.8, 126.32, 126.29, 126.02, 126.00, 124.0, 121.6, 61.9, 61.6, 57.7, 48.9, 38.1, 14.3, 13.9; HRMS (ESI) calcd for C 28 H 29 O6 (M + H) + : 461.1959; found: 461.1964.

[0077] The synthesized compound was identified as the target compound 1,1 - diethyl 5 - phenyl (E) - 2 - (naphthalen - 2 - yl) pent - 3 - en - 1,1,5 - tricarboxylate 3e by structural identification.

[0078] Example 6 1,1 - diethyl 5 - (4 - fluorophenyl) (E) - 2 - phenylpent - 3 - ene - 1,1,5 - tricarboxylate (see Structural Formula 3f)

[0079] The synthesis reaction of 1,1 - diethyl 5 - (4 - fluorophenyl) (E) - 2 - phenylpent - 3 - ene - 1,1,5 - tricarboxylate 3f is as follows:

[0080]

[0081] Under argon protection, palladium acetate (0.0034 g, 0.015 mmol), bisphosphine ligand Xantphos (0.0174 g, 0.030 mmol), 0.3 mL of toluene, phenyl 4 - fluorobenzoate 2b (0.1261 g, 0.9 mmol) and 1a (0.0865 g, 0.3 mmol) were successively added to the reactor and mixed thoroughly. After sealing, the mixed system in the reactor was heated to 90 °C by a heating plate and reacted for 24 hours. Then, the heating was stopped and it was allowed to cool naturally to room temperature (25 °C, the same below). The target product (0.1045 g, yield 81%) was obtained by column chromatography separation (using petroleum ether to pack the column, and the eluent was petroleum ether: ethyl acetate volume ratio 20:1 to 15:1) as a pale yellow oil.

[0082] The results of product structure confirmation are as follows: 11H NMR (400 MHz, CDCl3) δ 7.33 - 7.19 (m, 5H), 7.07 - 6.98 (m, 4H), 5.92 - 5.84 (m, 1H), 5.81 - 5.72 (m, 1H), 4.18 (q, J = 7.2 Hz, 2H), 4.16 (dd, J = 10.4, 8.0 Hz, 1H), 4.00 - 3.90 (m, 2H), 3.85 (d, J = 11.2 Hz, 1H), 3.25 (d, J = 6.8 Hz, 2H), 1.24 (t, J = 7.2 Hz, 3H), 0.99 (t, J = 6.8 Hz, 3H); 13 13C NMR (100 MHz, CDCl3) δ 170.0, 167.9, 167.5, 160.4 (d, J = 242.8), 146.5 (d, J = 2.8 Hz), 140.1, 134.6, 128.8, 128.1, 127.3, 123.5, 123.0 (d, J = 8.4 Hz), 116.2 (d, J = 23.3 Hz), 61.8, 61.6, 57.8, 48.8, 37.9, 14.3, 13.9; HRMS (ESI) calcd for C 24 H 25 FO6Na (M + Na) + : 451.1527; found: 451.1525.

[0083] The synthesized compound was identified as the target compound 1,1 - diethyl 5 - (4 - fluorophenyl)(E) - 2 - phenylpent - 3 - ene - 1,1,5 - tricarboxylate 3f.

[0084] Example 7 1,1 - Diethyl 5 - (4 - chlorophenyl)(E) - 2 - phenylpent - 3 - ene - 1,1,5 - tricarboxylate (see structural formula 3g)

[0085] The synthesis reaction of 1,1 - diethyl 5 - (4 - chlorophenyl)(E) - 2 - phenylpent - 3 - ene - 1,1,5 - tricarboxylate 3g is as follows:

[0086]

[0087] Under argon protection, palladium acetate (0.0034 g, 0.015 mmol), bisphosphine ligand Xantphos (0.0174 g, 0.030 mmol), 0.3 mL of toluene, phenyl chloroformate (0.1409 g, 0.9 mmol) and 1a (0.0865 g, 0.3 mmol) were successively added to the reactor and mixed thoroughly. After sealing, the mixed system in the reactor was heated to 90 °C by a heating plate and reacted for 24 hours. Then, the heating was stopped and it was naturally cooled to room temperature (25 °C, the same below). The colorless oil, namely the target product (0.0814 g, yield 61%), was obtained by column chromatography separation (using petroleum ether to pack the column, and the eluent was petroleum ether: ethyl acetate volume ratio 15:1).

[0088] The results of product structure confirmation are as follows: 1 H NMR(400MHz,CDCl3)δ7.34 - 7.28(m,4H),7.26 - 7.20(m,3H),7.02 - 6.97(m,2H),5.93 - 5.84(m,1H),5.80 - 5.71(m,1H),4.21 - 4.12(m,3H),4.00 - 3.91(m,2H),3.84(d,J=10.8Hz,1H);3.25(d,J=6.8Hz,2H),1.24(t,J=7.2Hz,3H),0.99(t,J=6.8Hz,3H). 13 C NMR(100MHz,CDCl3)δ169.7,167.9,167.5,149.2,140.1,134.7,131.4,129.6,128.8,128.1,127.3,123.4,123.0,61.8,61.5,57.7,48.8,37.9,14.2,13.9;HRMS(ESI)calcd for C 24 H 26 ClO6(M + H) + :445.1412;found:445.1416。

[0089] The synthesized compound was identified by structure as the target compound 5-(4-chlorophenyl)-1,1-diethyl (E)-2-phenylpent-3-ene-1,1,5-tricarboxylate 3g.

[0090] Example 8 1,1-Diethyl 5-(4-(trifluoromethyl)phenyl)(E)-2-phenylpent-3-ene-1,1,5-tricarboxylate (see structural formula 3h)

[0091] The synthesis reaction of 1,1 - diethyl 5-(4-(trifluoromethyl)phenyl)(E)-2-phenylpent-3-ene-1,1,5-tricarboxylate 3h is as follows:

[0092]

[0093] Under argon protection, palladium acetate (0.0034 g, 0.015 mmol), diphosphine ligand Xantphos (0.0174 g, 0.030 mmol), 0.3 mL of toluene, phenyl 4-(trifluoromethyl)formate (0.1711 g, 0.9 mmol) and 1a (0.0865 g, 0.3 mmol) were successively added to the reactor and mixed thoroughly. After sealing, the mixed system in the reactor was heated to 90 °C by a heating plate and reacted for 24 hours. Then, the heating was stopped, and after natural cooling to room temperature (25 °C, the same below), column chromatography separation (using petroleum ether to pack the column, and the eluent was petroleum ether:ethyl acetate volume ratio 15:1) was used to obtain a pale yellow oil, which was the target product (0.0786 g, yield 55%).

[0094] The results of product structure confirmation are as follows: 1 H NMR(400MHz,CDCl3)δ7.63(d,J=8.8Hz,2H),7.33 - 7.21(m,5H),7.18(d,J=8.4Hz,2H),5.94 - 5.87(m,1H),5.81 - 5.72(m,1H),4.22 - 4.13(m,3H),4.00 - 3.91(m,2H),3.85(d,J=10.8Hz,1H),3.28(d,J=7.2Hz,2H),1.25(t,J=7.2Hz,3H),1.00(t,J=7.2Hz,3H); 13 C NMR(100MHz,CDCl3)δ169.4,167.9,167.5,153.3,140.1,135.0,128.9,128.3(q,J=32.7),128.2,127.4,127.0(q,J=3.7Hz),124.0(q,J=270.2Hz),123.2,122.2,61.8,61.6,57.8,48.8,38.0,14.3,14.0;HRMS(ESI)calcd forC 25 H 26 F3O6(M+H) + :479.1676;found:479.1683。

[0095] The synthesized compound was identified structurally as the target compound 1,1 - diethyl 5-(4-(trifluoromethyl)phenyl)(E)-2-phenylpent-3-ene-1,1,5-tricarboxylate 3h.

[0096] Example 9 1,1 - diethyl 5-(2,4,6-trichlorophenyl)(E)-2-phenylpent-3-ene-1,1,5-tricarboxylate (see Structural Formula 3i)

[0097] The synthesis reaction of 1,1 - diethyl 5-(2,4,6-trichlorophenyl)(E)-2-phenylpent-3-ene-1,1,5-tricarboxylate 3i is as follows:

[0098]

[0099] Under argon protection, palladium acetate (0.0034 g, 0.015 mmol), bisphosphine ligand Xantphos (0.0174 g, 0.030 mmol), 0.3 mL of toluene, 2,4,6-trichlorobenzoate (0.2029 g, 0.9 mmol) and 1a (0.0865 g, 0.3 mmol) were successively added to the reactor and mixed thoroughly. After sealing, the temperature of the mixed system in the reactor was raised to 90 °C by a heating plate and reacted for 24 hours. Then, the heating was stopped and it was allowed to cool naturally to room temperature (25 °C, the same below). The target product (0.0960 g, yield 62%) was obtained by column chromatography separation (packed with petroleum ether, and the eluent was petroleum ether:ethyl acetate volume ratio 20:1 to 15:1) as a colorless oil.

[0100] The results of product structure confirmation are as follows: 1 H NMR(400MHz,CDCl3)δ7.35(s,2H),7.32 - 7.19(m,5H),5.97 - 5.88(m,1H),5.81 - 5.72(m,1H),4.23 - 4.13(m,3H),3.99 - 3.90(m,2H),3.84(d,J = 11.2Hz,1H),3.35(d,J = 6.8Hz,2H),1.25(t,J = 7.2Hz,3H),0.99(t,J = 7.2Hz,3H); 13 C NMR(100MHz,CDCl3)δ167.9,167.6,167.5,143.0,140.0,135.2,132.2,129.7,128.8,128.7,128.2,127.4,122.8,61.9,61.6,57.6,48.8,37.3,14.3,13.9;HRMS(ESI)calcd forC 24 H 24 Cl3O6(M + H)+ : 513.0633; found: 513.0642.

[0101] The compound synthesized through structural identification is the target compound 1,1 - diethyl 5-(2,4,6 - trichlorophenyl)(E)-2 - phenylpent - 3 - ene - 1,1,5 - tricarboxylate 3i.

[0102] Finally, it should be noted that the above - mentioned embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that they can still modify the technical solutions recorded in the foregoing embodiments, or perform equivalent replacements on some or all of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing β, γ unsaturated ester compounds by ring opening of vinyl cyclopropane, characterized in that: Under a nitrogen protective atmosphere, vinyl cyclopropane, aryl formate, metal palladium salt and phosphine ligand are dispersed in an organic solvent, and then reacted to obtain a preliminary β, γ unsaturated ester; after the reaction is completed, the preliminary β, γ unsaturated ester is separated to obtain the target product β, γ unsaturated ester.

2. The method for preparing β,γ unsaturated ester compounds by ring-opening of vinylcyclopropane according to claim 1, characterized in that: The structural formula of the vinyl cyclopropane is Wherein, R is one of phenyl, p-fluorophenyl, p-methylphenyl, p-trifluoromethylphenyl and 2-naphthyl.

3. A method for preparing β, γ unsaturated ester compounds by ring-opening of vinylcyclopropane according to claim 1, characterized in that: The molar ratio of the vinyl cyclopropane, aryl formate, metal palladium salt and phosphine ligand is 1:(1-4):(0.001-0.05):(0.004-0.2).

4. The method for preparing β,γ unsaturated ester compounds by ring-opening of vinylcyclopropane according to claim 1, characterized in that: The aryl formate is preferably the following compound:

5. The method for preparing β, γ unsaturated ester compounds by ring-opening of vinylcyclopropane according to claim 1, characterized in that: The metal palladium salt is one or more of palladium acetate, palladium chloride, palladium nitrate, and palladium trifluoroacetate.

6. The method for preparing β, γ unsaturated ester compounds by ring-opening of vinylcyclopropane according to claim 1, characterized in that: The phosphorus ligand is one of PPh3, (o-OMe-Ph)3P, (pF-Ph)3P, PPh2Cy, PPhCy2, PCy3, dppm, dppb, dppf, Xantphos, and DPEphos.

7. The method for preparing β, γ unsaturated ester compounds by ring-opening of vinylcyclopropane according to claim 1, characterized in that: The organic solvent is one of toluene, n-hexane, 1,2-dichloroethane, dichloromethane, acetonitrile, acetone, tetrahydrofuran, 1,4-dioxane, and ethyl acetate.

8. The method for preparing β, γ unsaturated ester compounds by ring-opening of vinylcyclopropane according to claim 1, characterized in that: The reaction temperature is 20-110°C.

9. The method for preparing β, γ unsaturated ester compounds by ring-opening of vinylcyclopropane according to claim 1, characterized in that: The separation operation is silica gel column chromatography separation method.

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