Method for preparing conjugated enol ester compound

Abstract

The invention relates to a method for preparing a conjugated enol ester compound. Specifically, under the catalysis of transition metal, eneyne and acid are used as raw materials to construct the conjugated enol ester compound in one step. The method used in the invention has the advantages of mild reaction conditions, simple operation and wide substrate application range.

Description

Technical Field

[0001] The present invention relates to a method for preparing a conjugated enol ester compound Background Art

[0002] As a common structural unit, multifunctional olefins are widely present in various drug molecules and natural products. Among them, ester compounds containing conjugated diene structural units have attracted widespread attention because they can serve as C4 synthons and contain easily leaving acyl groups. They are widely used as raw materials in organic synthesis, such as Diels-Alder reaction (reference [1] J. Org. Chem., 1985, 50, 1955; reference [2] Org. Lett., 2009, 11, 5658), other cyclization reactions (reference [3] Synth. Commun., 1989, 19, 1463), hydrogenation reactions to obtain chiral allyl ester compounds (reference [4] Tetrahedron Lett., 1998, 39, 5505) or coupling reactions (reference [5] Bull. Chem. Soc. Jpn., 1984, 57, 242) to synthesize high value-added fine chemicals.

[0003] Compared with the existing and potential application values, the methods reported so far for constructing conjugated enol esters are relatively few. They mainly include: (1) the reaction of ketones with acyl chlorides or anhydrides (reference [6] Synth. Commun., 2002, 32, 3181; reference [7] J. Org. Chem., 1966, 31, 2105) to form enol esters. Although this reaction does not require a metal catalyst, it generally requires high temperature and strong acid or base conditions; (2) transition metal-catalyzed isomerization reactions, such as the gold-catalyzed isomerization of propargyl esters (reference [8] Chem. .Commun., 2010, 46, 9179; Reference [9] J.Am.Chem.Soc., 2008, 130, 3740; Reference

[10] Org.Lett., 2006, 8, 4585.), Isomerization of propadiene catalyzed by gold or rhodium (Reference

[11] Org.Lett., 2007, 9, 985; Reference

[12] Org.Lett., 2011, 13, 1920)

[107] ; (3) Transition metal catalyzed coupling reactions, such as ruthenium-catalyzed coupling of propargyl esters with diazo compounds (reference

[13] Angew. Chem. Int. Ed., 2009, 48, 1439), gold-catalyzed coupling of propargyl esters with azides (reference

[14] Chem. Commun., 2015, 51, 15462); (4) Using transition metals as catalysts to achieve the hydroacyloxylation of enynes with acids. This method has the advantages of high efficiency and atom economy. However, the hydroacyloxylation of enynes reported so far mainly uses ruthenium as a catalyst, and the reaction substrates are limited to enynes with triple bonds at the terminal positions (reference

[15] Tetrahedron Lett., 1982, 23, 1523; reference

[16] Organometallics, 2011, 30, 852). Gold can be used to catalyze the hydroacyloxylation of internal enynes, but the selectivity of the reaction is relatively poor (reference

[17] Org. Biomol. Chem., 2017, 15, 1670; reference

[18] ACS Catal., 2015, 5, 6918). Literature research shows that the traditional method for synthesizing conjugated enol esters has the problem of harsh reaction conditions. The problem of obtaining conjugated enol esters by isomerization or coupling is that the raw materials are difficult to obtain. The direct construction of conjugated enol esters from simple enynes by hydrogen functionalization has the disadvantages of poor selectivity and limited substrate applicability. Therefore, the selective construction of conjugated enol esters by improving hydrogen functionalization has become a valuable research direction. Summary of the invention

[0004] The object of the present invention is to provide a method for preparing a conjugated enol ester compound.

[0005]

[0006] The specific steps are as follows:

[0007] Under nitrogen or argon protection conditions, a catalyst, a ligand, an additive and a solvent are added to a reactor, and then 1,3-enyne (1) and an acid (2) are added, and the reaction is carried out at 0°C-100°C, preferably 60°C, for 5-24 hours, preferably 18 hours; after the reaction is completed, a conjugated enol ester compound (3) is separated and obtained.

[0008] The catalyst is one or two of tri(triphenylphosphine)carbonyl rhodium hydride, (1,5-cyclooctadiene)chlororhodium (I) dimer, rhodium chloride and triphenylphosphine rhodium chloride, preferably (1,5-cyclooctadiene)chlororhodium (I) dimer; the ligand is one or two of triphenylphosphine, bisdiphenylphosphinomethane, 1,1'-binaphthyl-2,2'-bisdiphenylphosphine, bis(2-diphenylphosphophenyl) ether and 4,5-bisdiphenylphosphine-9,9-dimethylxanthene, preferably 1,1'-binaphthyl-2,2'-bisdiphenylphosphine; the additive is one or two or more of triethylamine, cesium carbonate, cesium acetate, sodium tert-butoxide, sodium carbonate, potassium phosphate and sodium ethoxide, preferably sodium tert-butoxide; the molar ratio of the acid (2) to the additive is 5:1-100:1, preferably 10:1. The solvent is one or more of 1,2-dichloroethane, dichloromethane, chloroform, tetrahydrofuran, 1,4-dioxane, and N,N-dimethylformamide, preferably dichloromethane; the amount of the solvent is 5-50 ml, preferably 5 ml, per mmol of the raw material 2. The molar ratio of 1,3-enyne (1) to acid (2) is 5:1-1:1, preferably 1.5:1.

[0009] The method used in the invention has mild reaction conditions, simple operation and a wide range of substrate applications. DETAILED DESCRIPTION

[0010] In order to better understand the present invention, the following examples are provided for illustration.

[0011] Embodiment 1:

[0012]

[0013] Under nitrogen protection, (1,5-cyclooctadiene)chlororhodium (I) dimer (0.005mmol, 2.5mol%), 1,1'-binaphthyl-2,2'-bisdiphenylphosphine (0.010mmol, 5.0mol%), sodium tert-butoxide (0.020mmol, 10.0mol%), and then dichloromethane (0.5mL) were added to the reaction tube. After stirring at room temperature for 1 minute, ene 1a (0.30mmol, 1.5 equivalents) and substrate acid 2a (0.20mmol, 1.0 equivalents) were added, and the reaction tube was sealed and stirred at 60°C for 18 hours. After the reaction was completed, it was cooled to room temperature, and the solvent was removed by rotary evaporation. Petroleum ether and ethyl acetate were used as developing agents (petroleum ether: ethyl acetate = 20:1), and silica gel was used for purification and separation, and the target product 3aa was finally obtained. The product structure was determined by nuclear magnetic resonance. The reaction yield was 77%.

[0014] Characterization data of Example 3aa:

[0015] 3aa, white solid. 1 H NMR (700 MHz, CDCl3 )δ8.30–8.17(m,2H),7.67(td,J=7.4,1.4Hz,1H),7.54(t,J=7.8Hz,2H),7.49–7.44(m,2H),7.29–7.22(m,2H), 7.22–7.15(m,1H),6.51(dd,J=17.1,10.9Hz,1H),6.36(s,1H),5.32(d,J=17.1Hz,1H),5.22(d,J=10.9Hz,1H). 13 C NMR (175 MHz, CDCl 3 )δ163.9,146.1,134.0,133.9,132.3,130.4,129.2,128.9,128.88,128.7,128.0,121.4,114.7.

[0016] Embodiment 2:

[0017]

[0018] Under nitrogen protection, (1,5-cyclooctadiene)chlororhodium (I) dimer (0.005mmol, 2.5mol%), 1,1'-binaphthyl-2,2'-bisdiphenylphosphine (0.010mmol, 5.0mol%), sodium tert-butoxide (0.020mmol, 10.0mol%), and then dichloromethane (0.5mL) were added to the reaction tube. After stirring at room temperature for 1 minute, enyne 1b (0.30mmol, 1.5 equivalents) and substrate acid 2a (0.20mmol, 1.0 equivalents) were added, and the reaction tube was sealed and stirred at 60°C for 18 hours. After the reaction was completed, it was cooled to room temperature, and the solvent was removed by rotary evaporation. Petroleum ether and ethyl acetate were used as developing agents (volume ratio, petroleum ether: ethyl acetate = 20:1), and silica gel was used for purification and separation, and the target product 3ba was finally obtained. The product structure was determined by nuclear magnetic resonance. The reaction yield was 68%.

[0019] Characterization data of Example 3ba:

[0020] 3ba, white solid. 1 H NMR (400 MHz, CDCl 3)δ8.28–8.23(m,2H),7.70–7.62(m,1H),7.60–7.49(m,2H),7.40(d,J=8.2Hz,2H),7.09(d,J=8.3Hz,2H),6.50(dd,J=17. 1,10.9Hz,1H),6.34(s,1H),5.28(d,J=17.1Hz,1H),5.19(d,J=10.9Hz,1H),2.58(q,J=7.6Hz,2H),1.18(t,J=7.6Hz,3H). 13 C NMR (100 MHz, CDCl 3 )δ163.9,145.4,144.3,133.9,132.3,131.4,130.4,129.3,128.9,128.9,128.3,121.4,114.1,28.7,15.4.

[0021] Embodiment 3:

[0022]

[0023] Under nitrogen protection, (1,5-cyclooctadiene)chlororhodium (I) dimer (0.005mmol, 2.5mol%), 1,1'-binaphthyl-2,2'-bisdiphenylphosphine (0.010mmol, 5.0mol%), sodium tert-butoxide (0.020mmol, 10.0mol%), and then dichloromethane (0.5mL) were added to the reaction tube. After stirring at room temperature for 1 minute, enyne 1c (0.30mmol, 1.5 equivalents) and substrate acid 2a (0.20mmol, 1.0 equivalents) were added, and the reaction tube was sealed and stirred at 60°C for 18 hours. After the reaction was completed, it was cooled to room temperature, and the solvent was removed by rotary evaporation. Petroleum ether and ethyl acetate were used as developing agents (petroleum ether: ethyl acetate = 20:1), and silica gel was used for purification and separation, and the target product 3ca was finally obtained. The product structure was determined by nuclear magnetic resonance. The reaction yield was 77%.

[0024] Characterization data of Example 3ca:

[0025] 3ca, white solid. 1 H NMR (400 MHz, CDCl 3)δ8.28–8.23(m,2H),7.70–7.63(m,1H),7.57–7.52(m,2H),7.44–7.37(m,2H),6.83–6.73(m,2H),6.4 8(dd,J=17.1,10.8Hz,1H),6.30(s,1H),5.25(d,J=17.1Hz,1H),5.16(d,J=10.8Hz,1H),3.75(s,3H). 13 C NMR (100 MHz, CDCl 3 )δ163.9,159.3,144.6,133.9,132.3,130.34,130.29,129.2,128.9,126.7,121.0,114.2,113.5,55.3.

[0026] Embodiment 4:

[0027]

[0028] Under nitrogen protection, (1,5-cyclooctadiene)chlororhodium (I) dimer (0.005mmol, 2.5mol%), 1,1'-binaphthyl-2,2'-bisdiphenylphosphine (0.010mmol, 5.0mol%), sodium tert-butoxide (0.020mmol, 10.0mol%), and then dichloromethane (0.5mL) were added to the reaction tube. After stirring at room temperature for 1 minute, enyne 1d (0.30mmol, 1.5 equivalents) and substrate acid 2a (0.20mmol, 1.0 equivalents) were added, and the reaction tube was sealed and stirred at 60°C for 18 hours. After the reaction was completed, it was cooled to room temperature, and the solvent was removed by rotary evaporation. Petroleum ether and ethyl acetate were used as developing agents (petroleum ether: ethyl acetate = 20:1), and silica gel was used for purification and separation, and the target product 3da was finally obtained. The product structure was determined by nuclear magnetic resonance. The reaction yield was 58%.

[0029] Characterization data of Example 3da:

[0030] 3da, white solid. 1 H NMR (400 MHz, CDCl 3)δ8.28(d,J=7.6Hz,2H),7.69(t,J=7.7Hz,1H),7.59–7.53(m,6H),7.50(d,J=8.1Hz,2H),7.41(t,J=7.5Hz,2H),7 .33(t,J=7.3Hz,1H),6.54(dd,J=17.1,10.8Hz,1H),6.41(s,1H),5.35(d,J=17.1Hz,1H),5.25(d,J=10.8Hz,1H). 13 C NMR (100 MHz, CDCl 3 )δ163.9,146.2,140.6,140.5,134.0,133.1,132.3,130.4,129.3,129.2,128.9,128.9,127.5,127.4,127.0,121.0,114.7.

[0031] Embodiment 5:

[0032]

[0033] Under nitrogen protection, (1,5-cyclooctadiene)chlororhodium (I) dimer (0.005mmol, 2.5mol%), 1,1'-binaphthyl-2,2'-bisdiphenylphosphine (0.010mmol, 5.0mol%), sodium tert-butoxide (0.020mmol, 10.0mol%), and then dichloromethane (0.5mL) were added to the reaction tube. After stirring at room temperature for 1 minute, ene 1e (0.30mmol, 1.5 equivalents) and substrate acid 2a (0.20mmol, 1.0 equivalents) were added, and the reaction tube was sealed and stirred at 60°C for 18 hours. After the reaction was completed, it was cooled to room temperature, and the solvent was removed by rotary evaporation. Petroleum ether and ethyl acetate were used as developing agents (petroleum ether: ethyl acetate = 20:1), and silica gel was used for purification and separation, and the target product 3ea was finally obtained. The product structure was determined by nuclear magnetic resonance. The reaction yield was 91%.

[0034] Characterization data of Example 3ea:

[0035] 3ea, white solid. 1 H NMR (400 MHz, CDCl 3)δ8.37–8.14(m,2H),7.73–7.62(m,1H),7.57–7.51(m,2H),7.48–7.42(m,2H),6.97–6.90(m,2 H),6.48(dd,J=17.1,10.9Hz,1H),6.32(s,1H),5.31(d,J=17.1Hz,1H),5.22(d,J=10.8Hz,1H). 13 C NMR (100 MHz, CDCl 3 )δ163.8,162.2(d,J=248.7Hz),145.8(d,J=2.4Hz),134.0,132.1,130.6(d,J=8.1 Hz), 130.3, 130.2 (d, J = 3.6Hz), 129.0, 128.9, 120.2, 115.8 (d, J = 21.6Hz), 114.8. 19 F NMR (376 MHz, CDCl 3 )δ-112.86.

[0036] Embodiment 6:

[0037]

[0038] Under nitrogen protection, (1,5-cyclooctadiene)chlororhodium (I) dimer (0.005mmol, 2.5mol%), 1,1'-binaphthyl-2,2'-bisdiphenylphosphine (0.010mmol, 5.0mol%), sodium tert-butoxide (0.020mmol, 10.0mol%), and then dichloromethane (0.5mL) were added to the reaction tube. After stirring at room temperature for 1 minute, ene 1f (0.30mmol, 1.5 equivalents) and substrate acid 2a (0.20mmol, 1.0 equivalents) were added, and the reaction tube was sealed and stirred at 60°C for 18 hours. After the reaction was completed, it was cooled to room temperature, and the solvent was removed by rotary evaporation. Petroleum ether and ethyl acetate were used as developing agents (petroleum ether: ethyl acetate = 20:1), and silica gel was used for purification and separation, and the target product 3fa was finally obtained. The product structure was determined by nuclear magnetic resonance. The reaction yield was 92%.

[0039] Characterization data of Example 3fa:

[0040] 3fa, white solid. 1 H NMR (400 MHz, CDCl 3)δ8.31–8.26(m,2H),7.95(s,1H),7.77–7.61(m,5H),7.59–7.54(m,2H),7.45–7.36(m,2H), 6.58(dd,J=17.1,10.9Hz,1H),6.53(s,1H),5.38(d,J=17.1Hz,1H),5.27(d,J=10.8Hz,1H). 13 C NMR (100 MHz, CDCl 3 )δ163.9,146.4,133.9,133.5,132.9,132.3,131.6,130.4,129.2,128.9,128.6,128.3,127.6,126.4,126.33,126.30,121.4,114.8.

[0041] Embodiment 7:

[0042]

[0043] Under nitrogen protection, (1,5-cyclooctadiene)chlororhodium (I) dimer (0.005mmol, 2.5mol%), 1,1'-binaphthyl-2,2'-bisdiphenylphosphine (0.010mmol, 5.0mol%), sodium tert-butoxide (0.020mmol, 10.0mol%), and then dichloromethane (0.5mL) were added to the reaction tube. After stirring at room temperature for 1 minute, 1g of enyne (0.30mmol, 1.5 equivalents) and substrate acid 2a (0.20mmol, 1.0 equivalents) were added, and the reaction tube was sealed and stirred at 60°C for 18 hours. After the reaction was completed, it was cooled to room temperature, and the solvent was removed by rotary evaporation. Petroleum ether and ethyl acetate were used as developing agents (petroleum ether: ethyl acetate = 20:1), and silica gel was used for purification and separation, and the target product 3ga was finally obtained. The product structure was determined by nuclear magnetic resonance. The reaction yield was 70%.

[0044] Characterization data of Example 3ga:

[0045] 3ga, white solid. 1 H NMR (400 MHz, CDCl 3)δ8.35–8.28(m,2H),7.76–7.65(m,1H),7.61–7.51(m,2H),7.21(d,J=5.1,1H),7.10(d,J=3.6Hz,1H),6.96(dd ,J=5.1,3.6Hz,1H),6.65(s,1H),6.48(dd,J=17.1,10.9Hz,1H),5.26(d,J=17.1Hz,1H),5.21(d,J=10.9Hz,1H). 13 C NMR (100 MHz, CDCl 3 )δ164.0,144.3,136.5,133.9,131.1,130.6,129.4,128.9,128.8,127.5,126.9,115.4,114.6.

[0046] Embodiment 8:

[0047]

[0048] Under nitrogen protection, (1,5-cyclooctadiene)chlororhodium (I) dimer (0.005mmol, 2.5mol%), 1,1'-binaphthyl-2,2'-bisdiphenylphosphine (0.010mmol, 5.0mol%), sodium tert-butoxide (0.020mmol, 10.0mol%), and then dichloromethane (0.5mL) were added to the reaction tube. After stirring at room temperature for 1 minute, ene 1h (0.30mmol, 1.5 equivalents) and substrate acid 2a (0.20mmol, 1.0 equivalents) were added, and the reaction tube was sealed and stirred at 60°C for 18 hours. After the reaction was completed, it was cooled to room temperature, and the solvent was removed by rotary evaporation. Petroleum ether and ethyl acetate were used as developing agents (petroleum ether: ethyl acetate = 20:1), and silica gel was used for purification and separation, and the target product 3ha was finally obtained. The product structure was determined by nuclear magnetic resonance. The reaction yield was 75%.

[0049] Characterization data of Example 3ha:

[0050] 3ha, white solid. 1 H NMR (400 MHz, CDCl 3)δ8.19(d,J=7.7Hz,2H),7.63(t,J=7.4Hz,1H),7.51(t,J=7.6Hz,2H),6.34(dd,J=17.1,10.9Hz,1H),5.47(t,J=7.5Hz ,1H),5.15(d,J=17.2Hz,1H),5.04(d,J=10.9Hz,1H),2.08(q,J=7.3Hz,2H),1.45–1.23(m,4H),0.87(t,J=7.1Hz,3H). 13 C NMR (100 MHz, CDCl 3 )δ164.2,146.0,133.6,131.5,130.2,129.4,128.7,123.5,112.7,31.0,25.8,22.4,14.0.

[0051] Embodiment 9:

[0052]

[0053] Under nitrogen protection, (1,5-cyclooctadiene)chlororhodium (I) dimer (0.005mmol, 2.5mol%), 1,1'-binaphthyl-2,2'-bisdiphenylphosphine (0.010mmol, 5.0mol%), sodium tert-butoxide (0.020mmol, 10.0mol%), and then dichloromethane (0.5mL) were added to the reaction tube. After stirring at room temperature for 1 minute, ene 1a (0.30mmol, 1.5 equivalents) and substrate acid 2b (0.20mmol, 1.0 equivalents) were added, and the reaction tube was sealed and stirred at 60°C for 18 hours. After the reaction was completed, it was cooled to room temperature, and the solvent was removed by rotary evaporation. Petroleum ether and ethyl acetate were used as developing agents (petroleum ether: ethyl acetate = 20:1), and silica gel was used for purification and separation, and the target product 3ab was finally obtained. The product structure was determined by nuclear magnetic resonance. The reaction yield was 64%.

[0054] Characterization data of Example 3ab:

[0055] 3ab, white solid. 1 H NMR (400 MHz, CDCl 3)δ8.17(d,J=7.8Hz,2H),7.518(d,J=7.5Hz,2H),7.37(d,J=7.9Hz,2H),7.31–7.25(m,2H),7.25–7.19(m,1H ),6.54(dd,J=17.1,10.9Hz,1H),6.38(s,1H),5.35(d,J=17.1Hz,1H),5.25(d,J=10.9Hz,1H),2.51(s,3H). 13 C NMR (100 MHz, CDCl 3 )δ163.9,146.1,144.8,134.1,132.3,130.4,129.6,128.9,128.7,127.9,126.4,121.3,114.6,21.9.

[0056] Embodiment 10:

[0057]

[0058] Under nitrogen protection, (1,5-cyclooctadiene)chlororhodium (I) dimer (0.005mmol, 2.5mol%), 1,1'-binaphthyl-2,2'-bisdiphenylphosphine (0.010mmol, 5.0mol%), sodium tert-butoxide (0.020mmol, 10.0mol%), and then dichloromethane (0.5mL) were added to the reaction tube. After stirring at room temperature for 1 minute, enyne 1a (0.30mmol, 1.5 equivalents) and substrate acid 2c (0.20mmol, 1.0 equivalents) were added, and the reaction tube was sealed and stirred at 60°C for 18 hours. After the reaction was completed, it was cooled to room temperature, and the solvent was removed by rotary evaporation. Petroleum ether and ethyl acetate were used as developing agents (petroleum ether: ethyl acetate = 20:1), and silica gel was used for purification and separation, and the target product 3ac was finally obtained. The product structure was determined by nuclear magnetic resonance. The reaction yield was 81%.

[0059] Characterization data of Example 3ac:

[0060] 3ac, white solid. 1 H NMR (400 MHz, CDCl 3 )δ8.23–8.10(m,2H),7.58–7.53(m,2H),7.51–7.47(m,2H),7.29–7.22(m,2H),7.22–7.16(m,1H),6.5 0(dd,J=17.1,10.8Hz,1H),6.35(s,1H),5.31(d,J=17.3Hz,1H),5.21(d,J=10.8Hz,1H),1.40(s,9H).13 C NMR (100 MHz, CDCl 3 )δ163.9,157.7,146.1,134.1,132.4,130.3,128.9,128.7,127.9,126.4,125.9,121.4,114.6,35.4,31.3.

[0061] Embodiment 11:

[0062]

[0063] Under nitrogen protection, (1,5-cyclooctadiene)chlororhodium (I) dimer (0.005mmol, 2.5mol%), 1,1'-binaphthyl-2,2'-bisdiphenylphosphine (0.010mmol, 5.0mol%), sodium tert-butoxide (0.020mmol, 10.0mol%), and then dichloromethane (0.5mL) were added to the reaction tube. After stirring at room temperature for 1 minute, enyne 1a (0.30mmol, 1.5 equivalents) and substrate acid 2d (0.20mmol, 1.0 equivalents) were added, and the reaction tube was sealed and stirred at 60°C for 18 hours. After the reaction was completed, it was cooled to room temperature, and the solvent was removed by rotary evaporation. Petroleum ether and ethyl acetate were used as developing agents (petroleum ether: ethyl acetate = 20:1), and silica gel was used for purification and separation, and the target product 3ad was finally obtained. The product structure was determined by nuclear magnetic resonance. The reaction yield was 84%.

[0064] Characterization data of Example 3ad:

[0065] 3ad, white solid. 1 H NMR (400 MHz, CDCl 3 )δ7.47(d,J=7.0Hz,2H),7.36(t,J=7.6Hz,2H),7.29(t,J=3.7Hz,1H),6.44(dd,J=17.1 ,10.8Hz,1H),6.27(s,1H),5.31(d,J=17.1Hz,1H),5.25(d,J=10.8Hz,1H),2.33(s,3H). 13 C NMR (100 MHz, CDCl 3 )δ168.2,146.0,134.1,132.2,128.8,128.7,128.0,121.0,114.5,21.0.

[0066] Embodiment 12:

[0067]

[0068] Under nitrogen protection, (1,5-cyclooctadiene)chlororhodium (I) dimer (0.005mmol, 2.5mol%), 1,1'-binaphthyl-2,2'-bisdiphenylphosphine (0.010mmol, 5.0mol%), sodium tert-butoxide (0.020mmol, 10.0mol%), and then dichloromethane (0.5mL) were added to the reaction tube. After stirring at room temperature for 1 minute, enyne 1a (0.30mmol, 1.5 equivalents) and substrate acid 2e (0.20mmol, 1.0 equivalents) were added, and the reaction tube was sealed and stirred at 60°C for 18 hours. After the reaction was completed, it was cooled to room temperature, and the solvent was removed by rotary evaporation. Petroleum ether and ethyl acetate were used as developing agents (petroleum ether: ethyl acetate = 20:1), and silica gel was used for purification and separation, and the target product 3ae was finally obtained. The product structure was determined by nuclear magnetic resonance. The reaction yield was 44%.

[0069] Characterization data of Example 3ae:

[0070] 3ae, white solid. 1 H NMR (400 MHz, CDCl 3 )δ7.91(d,J=16.0Hz,1H),7.66–7.57(m,2H),7.52–7.42(m,5H),7.33–7.28(m,2H),7.25–7.20(m,1H),6.69( d,J=16.0Hz,1H),6.47(dd,J=17.1,10.9Hz,1H),6.31(s,1H),5.33(d,J=17.1Hz,1H),5.23(d,J=10.9Hz,1H). 13 C NMR (100 MHz, CDCl 3 )δ164.2,147.3,145.9,134.14,134.07,132.3,131.0,129.2,128.9,128.7,128.5,128.0,121.2,116.7,114.7.

[0071] Embodiment 13:

[0072]

[0073] Under nitrogen protection, (1,5-cyclooctadiene)chlororhodium (I) dimer (0.005mmol, 2.5mol%), 1,1'-binaphthyl-2,2'-bisdiphenylphosphine (0.010mmol, 5.0mol%), sodium tert-butoxide (0.020mmol, 10.0mol%), and then dichloromethane (0.5mL) were added to the reaction tube. After stirring at room temperature for 1 minute, enyne 1a (0.30mmol, 1.5 equivalents) and phenol 2f (0.20mmol, 1.0 equivalents) were added, and the reaction tube was sealed and stirred at 60°C for 18 hours. After the reaction was completed, it was cooled to room temperature, and the solvent was removed by rotary evaporation. Petroleum ether and ethyl acetate were used as developing agents (petroleum ether: ethyl acetate = 20:1), and silica gel was used for purification and separation, and the target product 3af was finally obtained. The product structure was determined by nuclear magnetic resonance. The reaction yield was 84%.

[0074] Characterization data of Example 3af:

[0075] 3af, white solid. 1 H NMR (400 MHz, CDCl 3 )δ7.54(d,J=8.4Hz,2H),7.31–7.20(m,4H),7.16(t,J=7.3Hz,1H),7.01(d,J=8.1Hz,2H),6.97(t,J=7 .4Hz,1H),6.37(dd,J=17.1,10.8Hz,1H),6.24(s,1H),5.32(d,J=17.1Hz,1H),5.14(d,J=10.8Hz,1H). 13 C NMR (100 MHz, CDCl 3 )δ156.5,148.9,134.4,132.6,129.8,129.3,128.6,127.7,121.9,121.0,116.5,115.5.

[0076] Comparative Example 1:

[0077] The operation process is the same as that of Example 1, except that the reaction does not occur when the solvent is replaced with an equal volume of methanol.

[0078] Comparative Example 2:

[0079] The operation process is the same as that of Example 1, except that an equimolar amount of triethylenediamine is used as an additive, and the yield of 3aa is significantly reduced to 15%.

[0080] Comparative Example 3:

[0081] The operation process is the same as that of Example 1, except that if no catalyst is added to the system, 3aa cannot be generated.

Claims

1. A method for preparing a conjugated enol ester compound, characterized in that: As shown in the following reaction formula, 1,3-enyne (1) reacts with one or more of an acid (2) and / or a phenol as raw materials to generate a conjugated enol ester compound (3). The reaction formula is as follows: wherein R is selected from one or more of phenyl, phenyl containing substituents (the substituents include methyl, ethyl, methoxy, phenyl, halogen (one or more of fluorine, chlorine, bromine or iodine), nitro, trifluoromethoxy), naphthyl, thiophene, alkyl (wherein the alkyl carbon content is less than or equal to six) substituents, benzyl substituents; R ’ One or more selected from methyl, ethyl, tert-butyl, adamantyl, phenyl, phenyl containing substituents (the substituents include one or more of methyl, methoxy, tert-butyl, isopropyl, halogen); wherein compound 2 may also be phenol.

2. The method for preparing a conjugated enol ester compound according to claim 1, characterized in that: The specific steps are as follows: Under the protection of one or more of nitrogen or inert gas (such as argon), a catalyst, a ligand, an additive and a solvent are added to a reactor, and 1,3-enyne (1) and an acid (2) and / or phenol are added to react at 0°C-100°C (preferably 40-80°C) for 5-24 hours (preferably 18-22 hours); after the reaction is completed, a conjugated enol ester (3) is separated and obtained.

3. The method according to claim 2, characterized in that: The catalyst is one or more of tris(triphenylphosphine)carbonyl rhodium hydride, (1,5-cyclooctadiene)rhodium chloride (I) dimer, rhodium chloride and triphenylphosphine rhodium chloride, preferably (1,5-cyclooctadiene)rhodium chloride (I) dimer; The ligand is one or more of triphenylphosphine, bisdiphenylphosphinomethane, 1,1'-binaphthyl-2,2'-bisdiphenylphosphine, bis(2-diphenylphosphophenyl)ether and 4,5-bisdiphenylphosphino-9,9-dimethylxanthene, preferably 1,1'-binaphthyl-2,2'-bisdiphenylphosphine; The molar ratio of catalyst to ligand is 1:1–1:5, preferably 1:1-1:3; The molar ratio of catalyst to acid (2) and / or phenol is 1:10-1:50, preferably 1:30-1:

45.

4. The method according to claim 2, characterized in that: The additive is one or more of triethylamine, cesium carbonate, cesium acetate, sodium tert-butoxide, sodium carbonate, potassium phosphate and sodium ethoxide, preferably sodium tert-butoxide; The molar ratio of the acid (2) and / or phenol to the additive is 5:1-100:1, preferably 10:1-25:

1.

5. The method according to claim 2, characterized in that: The solvent is one or more of 1,2-dichloroethane, dichloromethane, chloroform, tetrahydrofuran, 1,4-dioxane, and N,N-dimethylformamide, preferably dichloromethane; the amount of the solvent is 5-50 ml, preferably 3-8 ml, per mmol of the raw acid (2) and / or phenol.

6. The method according to claim 1 or 2, characterized in that: The molar ratio of 1,3-enyne (1) to acid (2) and / or phenol is 5:1-1:1, preferably 2:1-1:1.

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