CN117185925A - Preparation method of polysubstituted aryl carboxylate compound - Google Patents

Preparation method of polysubstituted aryl carboxylate compound Download PDF

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CN117185925A
CN117185925A CN202310458655.2A CN202310458655A CN117185925A CN 117185925 A CN117185925 A CN 117185925A CN 202310458655 A CN202310458655 A CN 202310458655A CN 117185925 A CN117185925 A CN 117185925A
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CN117185925B (en
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章晓炜
何晓琳
马馨然
杨舒
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Jiangxi Normal University
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Abstract

The invention belongs to the technical field of synthesis of pharmaceutical intermediates, and particularly relates to a preparation method of a polysubstituted aryl carboxylate compound. Cesium carbonate, palladium acetate and tris (5-methoxy-1-indolyl) phosphine are replaced by nitrogen for three times, then an organic solvent is added, then aryl iodide, water, chloroformate, olefin and 2-cyano-5-norbornene are sequentially added, and the mixture reacts under the protection of inert gas, and after the reaction is finished, the organic solvent is removed and purified, so that the polysubstituted aryl carboxylate compound is obtained; the invention adopts chloroformate, aryl iodide and ethyl acrylate to carry out domino coupling reaction under the synergistic catalysis of palladium and norbornene, and the polysubstituted aryl carboxylate compound is obtained by a one-pot method.

Description

Preparation method of polysubstituted aryl carboxylate compound
Technical Field
The invention belongs to the technical field of synthesis of pharmaceutical intermediates, and particularly relates to a preparation method of a polysubstituted aryl carboxylate compound.
Background
It is well known that polysubstituted aryl carboxylic acids and derivatives thereof are very important building blocks, which are widely used in various valuable active substances such as natural products, medicines, pesticides, pigments, fragrances and leather. For example, the bioactive medicine molecule molugin separated from the madder shows good anticancer effect clinically; amorfrutin C separated from Glycyrrhrizae radix is a natural substance for anti-diabetic treatment, and has effects in reducing blood sugar and relieving inflammation; ataluren can promote the read-through of stop codon, and can effectively treat Dunaliella muscular dystrophy and cystic fibrosis. Therefore, the rapid and efficient preparation of poly-substituted aryl carboxylic acids and derivatives thereof (particularly poly-substituted aryl carboxylic esters) has been one of the key research directions for workers in the field of synthesis.
(1) The traditional methods for preparing aryl carboxylic esters mainly comprise two methods, namely: is mainly prepared by an esterification reaction method of aryl carboxylic acid and alcohol under the catalysis of strong acid or by a method of using aryl acyl chloride and alcohol to act in strong alkali. However, the two methods need to use strong acid/alkali, the reaction conditions are severe, the requirements on equipment are high, the functional groups sensitive to the strong acid/alkali are not compatible, and only a single ester group can be introduced. (J. Otera et al, analysis 2009; pp 3-157)
(2) In 2009, fumitoshi Kakiuchi, using chloroformate as an esterification reagent, and introducing an ester group onto 7, 8-benzoquinoline under the action of a ruthenium catalyst, was successful in synthesizing various polysubstituted aromatic esters. However, this method requires the use of quinoline as a directing group and at present only alkyl esters, benzyl esters and phenyl esters are introduced, which are not mentioned. (Kakiuchi, F.et al, J.am. Chem. Soc.2009, 131, 2792)
(3) In 2012, the Shi Bingfeng group used carbon monoxide and alcohol as the ester group sources, and synthesized aryl carboxylic acid esters by palladium catalysis. The reaction is insensitive to oxygen, has wide application range of the substrate and has great potential in the later modification of complex molecules. However, the method also uses pyridine as a guiding group, and the reagent has high toxicity, inconvenient operation and lack of environmental friendliness. (F. B.Shi et al, org. Biomol. Chem.,2014, 12, 2538)
(4) The problem of Dong Anbin in 2016 is that a self-made mixed anhydride is used as an electrophile, a sterically hindered ester group is used as a leaving group, and selective cleavage of a C-O bond is realized through Pd/NBE synergic catalysis, so that a polysubstituted aryl carboxylic acid derivative is obtained. Although this method exhibits a broad substrate range and high functional group compatibility, the atom economy is not high. (Dong, G.et al, chem.2016,1, 581-591)
Although there are many synthetic routes to synthesize aryl carboxylates, the reaction conditions are severe, directing groups are required, reagents are highly toxic, only one group can be singly introduced, and the atom economy is not high, so that the application of the reaction is greatly limited. Therefore, it is necessary to develop a novel method for synthesizing a polysubstituted aryl carboxylate compound with high atom economy.
Disclosure of Invention
The invention aims to solve the defects in the prior art and provides a preparation method of a polysubstituted aryl carboxylic ester compound, which adopts the following technical scheme:
a preparation method of a polysubstituted aryl carboxylic ester compound specifically comprises the following steps:
cesium carbonate, palladium acetate and tris (5-methoxy-1-indolyl) phosphine are added with an organic solvent after nitrogen is replaced for three times, then aryl iodide, water, chloroformate, olefin and 2-cyano-5-norbornene are sequentially added, and the mixture is reacted under the protection of inert gas for 12 h-48 h, and after the reaction is finished, the organic solvent is removed and the mixture is purified to obtain a polysubstituted aryl carboxylate compound; the structural formula of the aryl iodide is shown as formula I; the structural formula of the polysubstituted aryl carboxylic ester compound is shown as a formula II;
a formula I; />A formula II; wherein R is 1 ，R 2 Are each independently selected from aryl or alkyl.
The invention adopts chloroformate, aryl iodide and ethyl acrylate to carry out domino coupling reaction under the synergistic catalysis of palladium and norbornene to obtain the polysubstituted aryl carboxylate compound by a one-pot method, and solves the defects of high toxicity of reaction raw materials, low raw material utilization rate, harsh reaction conditions and the like in the prior art.
As a further preferred embodiment, R 1 At least one selected from methyl, ethyl, isopropyl, phenyl, oxytrifluoromethyl, methoxy, trifluoromethyl, halogen, nitro and alkoxycarbonyl.
As a further preferred embodiment, R 2 Selected from butyl, heptyl, isopropyl, sec-butyl, isobutyl, cyclopentyl, 9-fluorenylmethoxycarbonyl, [1S- (1. Alpha., 2. Alpha., 5. Beta.)]-at least one of 5-methyl-2- (1-methylethyl) cyclohexyl, benzyl, 4-fluorobenzyl, 4-trifluoromethylbenzyl, 2-chlorobenzyl, 4-cyanobenzyl, 4-nitrobenzyl, 4-methoxybenzyl, 4-t-butylbenzyl.
As a further preferred embodiment, the molar ratio of aryl iodide species, cesium carbonate, palladium acetate, tris (5-methoxy-1-indolyl) phosphine, water, chloroformate, alkene and 2-cyano-5-norbornene is 1:3:0.1:0.2:2:2:2:2.
as a further preferred embodiment, the reaction time is 24 h; the reaction temperature is 60-100 ℃; a more preferred reaction temperature is 60 ℃. The higher the temperature, the more readily the starting chloroformate will degrade, resulting in a reduced final yield.
As a further preferred embodiment, the organic solvent is toluene; the inert gas is nitrogen.
The beneficial effects of the invention are as follows: (1) The process for preparing the polysubstituted aryl carboxylic ester compound is simple to operate and mild in condition, and chloroformate is stable under the condition of the reaction system;
(2) The commercially-available aryl iodide and terminal olefin used for preparing the polysubstituted aryl carboxylate compound can be simply synthesized by adopting the existing mature process, has high safety, and avoids the preparation process of complex raw materials;
(3) The method has high atom economy in the process of preparing the polysubstituted aryl carboxylic ester compound, reduces the production cost and is beneficial to environmental protection;
(4) The method for preparing the polysubstituted aryl carboxylic ester compound has less side reaction and the yield reaches 32-90%;
(5) The method for preparing the polysubstituted aryl carboxylate compound is not limited by substrates, so that a polysubstituted aryl carboxylate library is established, and a raw material source is provided for drug screening and new drug synthesis.
Detailed Description
The conception, specific structure, and technical effects produced by the present invention will be clearly and completely described in connection with the embodiments below to fully understand the objects, aspects, and effects of the present invention.
The synthesis method comprises the following steps:
。
the method comprises the following specific steps:
palladium acetate (0.03 mmol,0.1 eq), tris (5-methoxy-1-indolyl) phosphine (0.06 mmol,0.2 eq) and Cs were added sequentially to the reaction flask 2 CO 3 (0.6 mmol,3 eq.) after nitrogen was replaced three times, 3 mL toluene, aryl iodide (0.3 mmol,1 eq.), chloroformate (0.6 mmol,2 eq.), alkene (0.6 mmol,2 eq.), 2-cyano-5-norbornene (0.6 mmol,2 eq.) and water (0.6 mmol,2 eq.) were added sequentially under nitrogen, stirred at 60 ℃ for 24 hours, after the reaction was completed, the mixture was cooled to room temperature, the reaction mixture was filtered with celite, the filter cake was washed with ethyl acetate, and the filtrate was concentrated and isolated by column chromatography to give the target product.
Examples 1 to 17 according to the above method, the polysubstituted aryl carboxylic ester compounds represented by the following formulas 1 to 17 can be prepared by changing the types of aryl iodide compound substrates and keeping other conditions unchanged:。
example 1
A substrate:；
compound 1:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=25:1, rf=0.4), yellow oil (64.3 mg,70% yield); 1H NMR (400 MHz, CHCl 3) delta 8.06 (d, J=16.2 Hz, 1H), 7.68 (dd, J=7.6, 1.5 Hz, 1H), 7.38 (d, J=6.2 Hz, 3H), 7.32 (t, J=7.6 Hz, 1H), 5.90 (d, J=16.1 Hz, 1H), 4.25 (q, J=7.1 Hz, 2H), 4.02 (d, J=6.6 Hz, 2H), 2.69 (q, J=7.5 Hz, 2H), 2.05-1.95 (M, 1H), 1.32 (t, J=7.1 Hz, 3H), 1.17 (t, J=7.6 Hz, 3H), 0.96 (d, J=6. Hz, 6H), 13C {1H (100 MHz, 3.6.6 Hz, 2H), 2.37 (q, J=7.15, 2H), 2.69 (q, J=7.5 Hz, 2H), 2.05-1.95 (M, 1H), 1.7.3H), 1.1.35 (t, 1.35, 3H), 1.35 (t, 3H), 1.96 (j=7.37, 37, 37.143, 3H), 0.143, 37.143, 37, 37.35 (37H), 1.15+3.15, 37, 37.15, 37.15+3H, 37.15.15, 37.15.13, 37, 37.15.13.15.g.
Example 2
A substrate:；
compound 2:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=25:1, rf=0.4), yellow oil (64.3 mg,70% yield); 1 H NMR(400 MHz, CHCl 3 ) δ 8.06 (d,J=16.2 Hz, 1H), 7.68 (dd,J= 7.6, 1.5 Hz, 1H), 7.38 (d,J= 6.2Hz, 1H), 7.32 (t,J= 7.6 Hz, 1H), 5.90 (d,J= 16.1 Hz, 1H),4.25 (q,J= 7.1 Hz, 2H), 4.02 (d,J= 6.6 Hz, 2H), 2.69 (q,J= 7.5 Hz, 2H), 2.05 – 1.95 (m, 1H), 1.32 (t,J= 7.1 Hz, 3H), 1.17 (t,J= 7.6 Hz, 3H), 0.96 (d,J= 6.7 Hz, 6H); 13 C{ 1 H}NMR(100 MHz, CHCl 3 ) δ 168.2, 166.3, 144.0, 143.1, 135.2, 132.1,131.3, 128.3, 127.7, 123.5, 71.63, 60.6, 27.8, 26.6, 19.3, 15.4, 15.4, 14.4;HRMS(ESI): m/z calcd for C 18 H 24 NaO 4 + [M+Na] + 327.1567 found 327.1560。
example 3
A substrate:；
compound 3:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=25:1, rf=0.4), yellow oil (68.7 mg,75% yield); 1 H NMR(400 MHz, CHCl 3 ) δ 8.08 (d,J=16.2 Hz, 1H), 7.63 (d,J= 7.9 Hz, 1H), 7.17 (d,J= 7.9 Hz, 1H),5.83 (d,J= 16.2 Hz, 1H), 4.25 (d,J= 7.2 Hz, 2H), 4.00 (d,J= 6.6 Hz, 2H), 2.28 (d,J= 35.0 Hz, 6H), 2.05 – 1.95 (m, 1H), 1.32 (t,J= 7.1 Hz, 3H), 0.96 (d,J= 6.7 Hz, 6H); 1313 C{ 1 H}NMR(100 MHz, CHCl 3 ) δ 167.9, 166.3, 145.3, 141.6, 136.2, 135.2,129.5, 128.7, 127.5, 123.6, 123.6, 71.4, 60.5, 27.8, 21.0, 19.3, 17.0, 14.4;HRMS(ESI): m/z calcd for C 18 H 24 NaO 4 + [M+Na] + 327.1567 found 327.1576。
example 4
A substrate:；
compound 4:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=15:1, rf=0.4), brown oil (71.3 mg,78% yield); 1 H NMR(400 MHz, CHCl 3 ) δ 8.00 (d,J=16.2 Hz, 1H), 7.49 (s, 1H), 7.18 (d,J= 1.8 Hz, 1H), 5.90 (d,J= 16.3 Hz, 1H), 4.25 (q,J= 7.1 Hz, 2H), 4.03 (d,J= 6.6 Hz,2H), 2.34 (d,J= 5.5 Hz, 6H), 2.07 – 1.96 (m, 1H), 1.32 (t,J=7.1 Hz, 3H), 0.97 (d,J= 6.7 Hz, 6H); 13 C{ 1 H}NMR(100 MHz, CHCl 3 ) δ 168.4, 166.5, 144.0, 138.2, 137.0, 134.7,132.6, 131.4, 128.4, 123.4, 71.7, 60.6, 27.8, 21.1, 20.9, 19.4, 14.4;HRMS(ESI): m/z calcd for C 18 H 24 NaO 4 + [M+Na] + 327.1567 found 327.1557。
example 5
A substrate:；
compound 5:；
product characterization data: purified by flash columnchromatography (petroleum ether/acoet=25:1, rf=0.4), yellow oil (66.8 mg,61% yield); 1 H NMR(400 MHz, CHCl 3 ) δ 8.10 (d,J=16.1 Hz, 1H), 7.66 (dd,J= 7.7, 1.4 Hz, 1H), 7.47 (dd,J= 7.9,1.4 Hz, 1H), 7.36 (t,J= 7.7 Hz, 1H), 5.86 (d,J= 16.1 Hz, 1H),4.25 (q,J= 7.2 Hz, 2H), 4.01 (d,J= 6.6 Hz, 2H), 3.24 – 3.18(m, 1H), 2.03 – 1.03 (m, 1H), 1.32 (t,J= 7.1 Hz, 3H), 1.20 (d,J= 6.9 Hz, 6H), 0.96 (d,J= 6.7 Hz, 6H); 13 C{ 1 H}NMR(100 MHz, CHCl 3 ) δ 168.3, 166.2, 147.7, 144.4, 134.6, 131.2,128.9, 128.4, 127.5, 123.6, 71.6, 60.7, 29.8, 27.8, 23.9, 19.3, 14.4;HRMS(ESI): m/z calcd for C 19 H 26 NaO 4 + [M+Na] + 341.1723 found 341.1722。
example 6
A substrate:
compound 6:；
characterization data of the product compounds: purified by flash columnchromatography (petroleum ether/acoet=15:1, rf=0.4), colorless oil (91.5 mg, 87% yield); 1 H NMR(400 MHz, CHCl 3 ) δ 7.90(d,J= 16.2 Hz, 1H), 7.78 (dd,J= 7.2, 1.9 Hz, 1H), 7.48 – 7.31(m, 5H), 7.28 – 7.23 (m, 2H), 5.66 (d,J= 16.3 Hz, 1H), 4.13 (q,J= 7.1 Hz, 2H), 4.06 (d,J= 6.7 Hz, 2H), 2.07 – 1.97 (m, 1H), 1.22 (t,J= 7.1 Hz, 3H), 0.97 (d,J= 6.7 Hz, 6H); 13 C{ 1 H}NMR(100 MHz, CHCl 3 ) δ 168.5, 166.1, 143.5, 142.7, 140.2, 134.1,133.6, 132.2, 129.8, 128.9, 128.4, 127.6, 124.5, 71.9, 60.5, 27.8, 19.3, 14.3;HRMS(ESI): m/z calcd for C 22 H 24 NaO 4 + [M+Na] + 375.1567 found 375.1560。
example 7
A substrate:
compound 7:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=25:1, rf=0.4), yellow oil (66.8 mg,61% yield); 1 H NMR(400 MHz, CHCl 3 ) δ 7.94 (d,J=16.3 Hz, 1H), 7.83 (dd,J= 6.9, 2.1 Hz, 1H), 7.47 – 7.41 (m, 2H), 6.24(d,J= 16.3 Hz, 1H), 4.26 (q,J= 7.1 Hz, 2H), 4.09 (d,J= 6.6 Hz, 2H), 2.08 – 2.01 (m, 1H), 1.33 (t,J= 7.1 Hz, 3H), 0.98 (d,J= 6.7 Hz, 6H); 13 C{ 1 H} NMR(100 MHz, CHCl 3 )δ 166.5, 166.2, 147.1, 137.6, 133.3, 129.8, 129.6, 128.8, 125.7, 124.6, 120.44(q,J= 259.0 Hz), 72.2, 60.8, 27.8, 19.3, 14.4; 19 F{ 1 H}NMR(376 MHz, CDCl 3 ) δ -57.1;HRMS (ESI):m/z calcd for C 17 H 19 F 3 NaO 5 + [M+Na] + 383.1077 found 383.1085。
example 8
A substrate:
compound 8:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=15:1, rf=0.2), brown oil (60.1 mg,65% yield); 1 H NMR(400 MHz, CHCl 3 ) δ 8.00 (d,J=16.1 Hz, 1H), 7.36 – 7.33 (m, 2H), 7.05 (dd,J= 6.9, 2.6 Hz, 1H), 6.54(d,J= 16.2 Hz, 1H), 4.23 (d,J= 7.1 Hz, 2H), 4.08 (d,J= 6.6 Hz, 2H), 3.87 (s, 3H), 2.08 – 1.98 (m, 1H), 1.31 (t,J= 7.2 Hz,3H), 0.97 (d,J= 6.7 Hz, 6H); 13 C{ 1 H}NMR(100 MHz, CHCl 3 ) δ 168.1, 167.3, 158.6, 138.7, 134.0, 129.9,123.9, 123.5, 121.9, 114.0, 71.8, 60.4, 55.9, 27.8, 19.3, 14.4;HRMS (ESI):m/z calcd for C 17 H 22 NaO 5 + [M+Na] + 329.1359 found 329.1352。
example 9
A substrate:
compound 9:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=25:1, rf=0.4), yellow oil (71.0 mg,68% yield); 1 H NMR(400 MHz, CHCl 3 ) δ 8.07 (dd,J=16.2, 2.1 Hz, 1H), 8.00 (d,J= 7.8 Hz, 1H), 7.83 (d,J= 7.8 Hz,1H), 7.52 (t,J= 7.9 Hz, 1H), 5.92 (d,J= 16.1 Hz, 1H), 4.25(q,J= 7.1 Hz, 2H), 4.04 (d,J= 6.6 Hz, 2H), 2.04 – 1.98 (m,1H), 1.32 (t,J= 7.1 Hz, 3H), 0.97 (d,J= 6.7 Hz, 6H); 13 C{ 1 H}NMR(100 MHz, CHCl 3 ) δ 166.9, 165.6, 141.0, 135.7 (d,J=1.8 Hz), 133.2, 133.1, 129.6 (q,J= 30.40 Hz), 129.0 (q,J= 5.3Hz), 128.3, 125.2 (d,J= 2.1 Hz), 123.6 (q,J= 274.2 Hz), 72.2,60.9, 27.8, 19.3, 14.3; 19 F{ 1 H}NMR(376 MHz, CDCl 3 ) δ -58.1;HRMS (ESI):m/z calcd for C 17 H 19 F 3 NaO 4 + [M+Na] + 367.1128 found 367.1137。
example 10
A substrate:；
compound 10:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=15:1, rf=0.5), colorless oil (31.3 mg, 33% yield); 1 H NMR(400 MHz, CHCl 3 ) δ 7.94(d,J= 16.3 Hz, 1H), 7.73 (dd,J= 7.8, 1.3 Hz, 1H), 7.56 (dd,J= 8.1, 1.3 Hz, 1H), 7.33 (t,J= 7.9 Hz, 1H), 6.12 (d,J= 16.3Hz, 1H), 4.26 (q,J= 7.1 Hz, 2H), 4.05 (d,J= 6.6 Hz, 2H), 2.06– 1.96 (m, 1H), 1.33 (t,J= 7.1 Hz, 3H), 0.97 (d,J= 6.7 Hz,6H); 13 C{ 1 H} NMR(100 MHz, CHCl 3 )δ 167.1, 166.0, 140.9, 134.5, 134.2, 133.2, 133.1, 129.3, 128.6, 125.5, 72.1,60.8, 27.8, 19.3, 14.4;HRMS (ESI): m/z calcd for C 16 H 19 ClNaO 4 + [M+Na] + 333.0864 found 333.0872。
example 11
A substrate:；
compound 11:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=25:1, rf=0.4), yellow oil (83.6 mg,90% yield); 1 H NMR(400 MHz, CHCl 3 ) δ 8.00 (d,J=16.3 Hz, 1H), 7.78 (dd,J= 8.7, 5.6 Hz, 1H), 7.04 (t,J= 8.7Hz, 1H), 5.88 (d,J= 16.3 Hz, 1H), 4.25 (q,J= 7.1 Hz, 2H),4.02 (d,J= 6.7 Hz, 2H), 2.24 (d,J= 2.6 Hz, 3H), 2.06 – 1.96(m, 1H), 1.32 (t,J= 7.1 Hz, 3H), 0.96 (d,J= 6.8 Hz, 6H); 13 C{ 1 H} NMR(100 MHz,CHCl 3 ) δ 166.8, 166.1, 163.4 (d,J= 251.3 Hz), 143.2 (d,J= 2.5 Hz), 139.2 (d,J= 5.5 Hz), 129.8 (d,J= 10.0 Hz), 126.6(d,J= 3.4 Hz), 124.4, 124.3 (d,J= 17.4 Hz), 114.7 (d,J= 23.8 Hz), 71.7, 60.8, 27.8, 19.3, 14.4, 12.3 (d,J= 5.5 Hz); 19 F{ 1 H}NMR(376 MHz, CDCl 3 ) δ -107.7;HRMS (ESI):m/z calcd for C 17 H 21 FNaO 4 + [M+Na] + 331.1316 found 331.1313。
example 12
A substrate:；
compound 12:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=15:1, rf=0.5), colorless oil (78.5 mg, 81% yield); 1 H NMR(400 MHz, CHCl 3 ) δ 8.02(d,J= 16.2 Hz, 1H), 7.66 (d,J= 8.4 Hz, 1H), 7.39 (d,J= 8.4 Hz, 1H), 5.85 (d,J= 16.3 Hz, 1H), 4.26 (q,J= 7.1 Hz,2H), 4.02 (d,J= 6.6 Hz, 2H), 2.38 (s, 3H), 2.07 – 1.93 (m, 1H), 1.32(t,J= 7.1 Hz, 3H), 0.96 (d,J= 6.7 Hz, 6H); 13 C{ 1 H}NMR(100 MHz, CHCl 3 ) δ 167.1, 166.0, 143.9, 139.1, 138.1, 134.9,129.5, 128.9, 128.6, 124.5, 71.8, 60.8, 27.8, 19.3, 18.0, 14.4;HRMS (ESI):m/z calcd for C 17 H 21 ClNaO 4 + [M+Na] + 347.1021 found 347.1022。
example 13
A substrate:；
compound 13；
Compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=15:1, rf=0.2), brown oil (74.1 mg,74% yield); 1 H NMR(400 MHz, CHCl 3 ) δ 8.54 (s, 1H), 8.23 (s,1H), 8.00 (d,J= 16.3 Hz, 1H), 5.96 (d,J= 16.3 Hz, 1H), 4.27(q,J= 7.1 Hz, 2H), 4.09 (d,J= 6.7 Hz, 2H), 2.47 (s, 3H), 2.10– 2.00 (m, 1H), 1.33 (t,J= 7.1 Hz, 3H), 0.98 (d,J= 6.7 Hz,6H); 13 C{ 1 H} NMR(100 MHz, CHCl 3 )δ 165.9, 165.6, 147.0, 142.3, 141.9, 139.3, 132.5, 127.8, 125.3, 122.9, 72.4,61.1, 27.8, 21.3, 19.3, 14.4;HRMS (ESI): m/z calcd for C 17 H 22 NO 6 + [M+H] + 336.1442 found 336.1443。
example 14
A substrate:；
compound 14:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=15:1, rf=0.2), brown oil (92.1 mg,88% yield); 1 H NMR(400 MHz, CHCl 3 ) δ 8.34 (d,J= 1.8Hz, 1H), 8.04 – 8.00 (m, 2H), 5.94 (d,J= 16.3 Hz, 1H), 4.26 (q,J= 7.1 Hz, 2H), 4.06 (d,J= 6.7 Hz, 2H), 3.93 (s, 3H), 2.40 (s, 3H),2.08 – 1.98 (m, 1H), 1.32 (t,J= 7.1 Hz, 3H), 0.97 (d,J= 6.8Hz, 6H); 13 C{ 1 H} NMR(100 MHz, CHCl 3 )δ 167.2, 166.1, 166.0, 143.1, 140.2, 137.6, 134.5, 131.6, 129.7, 128.9, 124.5,72.0, 60.8, 52.5, 27.8, 21.0, 19.3, 14.4;HRMS (ESI): m/z calcd for C 19 H 24 NaO 6 + [M+Na] + 371.1465 found 371.1461。
example 15
A substrate:；/>
compound 15:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=15:1, rf=0.5), colorless oil (57.8 mg, 51% yield); 1 H NMR(400 MHz, CHCl 3 ) δ 8.01 –7,96 (m, 2H), 7.82 (d,J= 2.2 Hz, 1H), 5.92 (d,J= 16.2 Hz,1H), 4.26 (q,J= 7.1 Hz, 2H), 4.05 (d,J= 6.7 Hz, 2H), 2.07 –1.97 (m, 1H), 1.32 (t,J= 7.1 Hz, 3H), 0.97 (d,J= 6.7 Hz, 6H); 13 C{ 1 H} NMR(100 MHz, CHCl 3 ) δ165.7, 165.4, 139.8, 134.7, 134.6, 134.0, 133.2, 131.2 (q,J= 31.0 Hz),129.3 (q,J= 5.6 Hz), 125.8, 122.8 (q,J= 274.5 Hz), 72.6,61.0, 27.8, 19.3, 14.3; 19 F{ 1 H}NMR(376 MHz, CDCl 3 ) δ -58.5;HRMS (ESI):m/z calcd for C 17 H 18 ClF 3 NaO 4 + [M+Na] + 401.0738 found 401.0730。
example 16
A substrate:；
compound 16:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=25:1, rf=0.2), pale yellow oil (36.8 mg, 32% yield); 1 H NMR(400 MHz, CHCl 3 ) δ 8.08(d,J= 16.2 Hz, 1H), 7.98 (d,J= 8.5 Hz, 1H), 7.47 (d,J= 8.5 Hz, 1H), 6.04 (d,J= 16.2 Hz, 1H), 4.23 (q,J= 7.1 Hz,2H), 4.07 (dd,J= 9.1, 6.6 Hz, 4H), 2.08 – 1.97 (m, 2H), 1.30 (t,J= 7.1 Hz, 3H), 0.99 – 0.96 (m, 12H); 13 C{ 1 H}NMR(100 MHz, CHCl 3 ) δ 166.2, 165.6, 165.6, 142.3, 136.6, 135.5,134.8, 132.3, 129.6, 128.70, 124.0, 72.6, 72.2, 60.8, 27.8, 27.7, 19.3, 19.3,14.4;HRMS (ESI): m/z calcd for C 21 H 27 ClNaO 6 + [M+Na] + 433.1388 found 433.1391。
example 17
A substrate:；
compound 17:
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=15:1, rf=0.2), pale yellow oil (46.9 mg, 42% yield); 1 H NMR(400 MHz, CHCl 3 ) δ 8.30(d,J= 16.0 Hz, 1H), 7.96 (d,J= 7.8 Hz, 2H), 7.46 (t,J= 7.8 Hz, 1H), 5.80 (d,J= 16.1 Hz, 1H), 4.22 (q,J= 7.1 Hz,2H), 4.03 (d,J= 6.6 Hz, 4H), 2.06 – 1.77 (m, 2H), 1.30 (t,J=7.1 Hz, 3H), 0.96 (d,J= 6.8 Hz, 12H), 13 C{ 1 H}NMR(100 MHz, CHCl 3 ) δ 167.3, 165.8, 144.7, 137.1, 132.9, 132.3,128.3, 122.6, 72.0, 60.6, 27.8, 19.3, 14.4;HRMS (ESI): m/z calcd for C 21 H 28 NaO 6 + [M+Na] + 399.1778 found 399.1784。
examples 18 to 33 according to the above method, the polysubstituted aryl carboxylic ester compounds represented by the following formulas 18 to 33 can be prepared by changing the types of chloroformate compound substrates and keeping the other conditions unchanged:。
example 18
A substrate:；
compound 18:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=15:1, rf=0.3), pale yellow solid (71.3 mg,73% yield); 1 H NMR(400 MHz, CDCl 3 )δ8.42 (d,J= 16.2 Hz, 1H), 8.17 (d,J= 8.6 Hz, 1H), 7.95 (d,J= 8.7 Hz, 1H), 7.88 – 7.84 (m, 2H), 7.60 – 7.52 (m, 2H), 6.08 (d,J=16.2 Hz, 1H), 4.35 – 4.30 (m, 4H), 1.77 – 1.72 (m, 2H), 1.49 – 1.44 (m, 2H),1.37 (t,J= 7.1 Hz, 3H), 0.97 (t,J= 7.4 Hz, 3H); 13 C{ 1 H}NMR(100 MHz, CDCl 3 )δ167.7, 166.3, 143.5, 136.0, 135.1,131.0, 128.6, 128.4, 128.0, 127.3, 127.2, 126.8, 125.7, 125.2, 65.5, 60.8,30.7, 19.4, 14.4, 13.8;HRMS (ESI): m/z calcd for C 20 H 22 NaO 4 + [M+Na] + 349.1410, found 349.1410。
example 19
A substrate:；
compound 19:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=50:1, rf=0.2), yellow oil (71.9 mg,65% yield); 1 H NMR(400 MHz, CDCl 3 )δ8.42 (d,J= 16.2Hz, 1H), 8.17 (d,J= 8.1 Hz, 1H), 7.95 (d,J= 8.6 Hz, 1H), 7.87– 7.84 (m, 2H), 7.59 – 7.51 (m, 2H), 6.08 (d,J= 16.2 Hz, 1H), 4.35 –4.30 (m, 4H), 1.80 – 1.73 (m, 2H), 1.42 – 1.29 (m, 11H), 0.89 (t,J=6.7 Hz, 3H); 13 C{ 1 H} NMR(100 MHz, CDCl 3 )δ167.6, 166.2, 143.5, 136.1, 135.1, 131.0, 128.6, 128.3, 128.0, 127.3,127.1, 126.8, 125.7, 125.1, 65.8, 60.8, 31.8, 29.1, 28.7, 26.1, 22.7, 14.4,14.1;HRMS (ESI): m/z calcd for C 23 H 28 NaO 4 + [M+Na] + 391.1880 found 391.1876。
example 20
A substrate:；
compound 20:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=15:1, rf=0.4), pale yellow oil (77.3 mg, 82% yield); 1 H NMR(400 MHz, CDCl 3 )δ8.41 (d,J= 16.2 Hz, 1H), 8.15 (d,J= 7.8 Hz, 1H),7.92 (d,J= 8.6 Hz, 1H), 7.87 – 7.83 (m, 2H), 7.58 – 7.51 (m, 2H), 6.08(d,J= 16.2 Hz, 1H), 5.33 -5.23 (m, 1H), 4.33 (q,J= 7.1 Hz,2H), 1.37 (d,J= 6.0 Hz, 8H); 13 C{ 1 H}NMR(100 MHz, CDCl 3 )δ167.2, 166.2, 143.5, 135.6, 135.0,131.00, 128.6, 128.3, 127.9, 127.8, 127.1, 126.7, 125.7, 125.1, 69.2, 60.7,21.9, 14.4;HRMS (ESI): m/z calcd for C 19 H 20 NaO 4 + [M+Na] + 335.1254 found 335.1248。
example 21
A substrate:；/>
compound 21:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=25:1, rf=0.2), colorless oil (71.3 mg,73% yield); 1 H NMR(400 MHz, CDCl 3 )δ8.42(d,J= 16.2 Hz, 1H), 8.16 (d,J= 1.6 Hz, 1H), 7.94 (d,J= 8.7 Hz, 1H), 7.87 – 7.84 (m, 2H), 7.59 – 7.51 (m, 2H), 6.09 (d,J=16.3 Hz, 1H), 5.17 – 5.10 (m,J= 6.3 Hz, 1H), 4.33 (q,J= 7.2Hz, 2H), 1.80 -1.73 (dt,J= 14.3, 7.1 Hz, 1H), 1.70 – 1.61 (m, 1H),1.39 – 1.34 (m, 6H), 0.97 (t,J= 7.5 Hz, 3H); 13 C{ 1 H}NMR(100 MHz, CDCl 3 )δ167.3, 166.2, 143.6, 135.6, 135.0,131.0, 128.6, 128.3, 127.9, 127.8, 127.1, 126.7, 125.7, 125.2, 73.8, 60.7,28.9, 19.5, 14.4, 9.8;HRMS (ESI): m/z calcd for C 20 H 22 NaO 4 + [M+Na] + 349.1410 found 349.1402。
example 22
A substrate:；
compound 22:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=15:1, rf=0.2), pale yellow oil (90.3 mg, 83% yield); 1 H NMR(400 MHz, CDCl 3 )δ8.43 (d,J= 16.3 Hz, 1H), 8.18 (d,J= 8.2 Hz, 1H),7.97 (d,J= 8.6 Hz, 1H), 7.89 – 7.85 (m, 2H), 7.60 – 7.52 (m, 2H), 6.09(d,J= 16.3 Hz, 1H), 4.32 (q,J= 7.2 Hz, 2H), 4.12 (d,J= 6.6 Hz, 2H), 2.13 – 2.03 (m, 1H), 1.37 (t,J= 7.1 Hz, 3H), 1.02 (d,J= 6.7 Hz, 6H); 13 C{ 1 H} NMR(100 MHz, CDCl 3 )δ167.6, 166.3, 143.5, 136.1, 135.2, 131.1, 128.7, 128.4, 128.0, 127.3,127.2, 126.8, 125.8, 125.3, 71.8, 60.8, 27.9, 19.4, 14.4;HRMS (ESI):m/z calcd for C 20 H 22 NaO 4 + [M+Na] + 349.1410 found 349.1415。
example 23
A substrate:；
compound 23:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=25:1, rf=0.2), pale yellow oil (72.5 mg, 71% yieldd); 1 H NMR(400 MHz, CDCl 3 )δ8.39 (d,J= 16.2 Hz, 1H), 8.16 (d,J= 8.2 Hz, 1H),7.93 (d,J= 8.6 Hz, 1H), 7.88 – 7.84 (m, 2H), 7.60 – 7.52 (m, 2H), 6.08(d,J= 16.2 Hz, 1H), 5.46 – 5.42 (m, 1H), 4.33 (q,J= 7.1 Hz,2H), 1.96 – 1.77 (m, 6H), 1.68 – 1.61 (m, 2H), 1.37 (t,J= 7.1 Hz, 3H); 13 C{ 1 H} NMR(100 MHz, CDCl 3 )δ167.5, 166.2, 143.6, 135.7, 135.1, 131.1, 128.6, 128.4, 127.9, 127.7,127.1, 126.7, 125.9, 125.2, 78.7, 60.8, 32.8, 23.9, 14.5;HRMS (ESI): m/zcalcd for C 21 H 22 NaO 4 + [M+Na] + 361.1410 found 361.1409。
example 24
A substrate:；
compound 24:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=15:1, rf=0.2), yellow solid (82.9 mg,62% yield); 1 H NMR(400 MHz, CDCl 3 )δ8.51 (d,J= 16.3 Hz, 1H), 8.25 (d,J= 8.2 Hz, 1H), 7.97 (d,J= 8.7 Hz,1H), 7.91 (d,J= 7.8 Hz, 2H), 7.80 (d,J= 7.5 Hz, 2H), 7.66 (d,J= 7.6 Hz, 2H), 7.63 – 7.56 (m, 2H), 7.43 (t,J= 7.4 Hz, 2H),7.35 – 7.31 (m, 2H), 6.17 (d,J= 16.3 Hz, 1H), 4.67 (d,J= 7.2Hz, 2H), 4.40 (t,J= 7.1 Hz, 1H), 4.29 (q,J= 7.1 Hz, 2H), 1.32(t,J= 7.1 Hz, 3H); 13 C{ 1 H} NMR(100MHz, CDCl 3 )δ167.2, 166.2, 143.9, 143.3, 141.4, 136.7,135.3, 131.1, 128.9, 128.4, 128.2, 127.9, 127.3, 126.9, 126.7, 125.5, 125.4,125.2, 120.2, 67.5, 60.8, 47.0, 14.4;HRMS (ESI): m/z calcd for C 30 H 24 NaO 4 + [M+Na] + 471.1567 found 471.1564。
example 25
A substrate:；
compound 25:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=25:1, rf=0.3), yellow oil (110.3 mg,90% yield); 1 H NMR(400 MHz, CHCl 3 ) δ 8.41 (d,J=16.2 Hz, 1H), 8.16 (d,J= 8.2 Hz, 1H), 7.94 (d,J= 8.6 Hz, 1H),7.89 – 7.85 (m, 2H), 7.60 – 7.52 (m, 2H), 6.09 (d,J= 16.2 Hz, 1H),4.98 (td,J= 10.9, 4.4 Hz, 1H), 4.32 (q,J= 7.1 Hz, 2H), 217 –2.12 (m, 1H), 1.94 (td,J= 7.0, 2.8 Hz, 1H), 1.75 – 1.70 (m, 2H), 1.57– 1.50 (m, 2H), 1.38 (t,J= 7.1 Hz, 3H), 1.12 (q,J= 12.1 Hz,2H), 0.92 (dd,J= 14.5, 6.8 Hz, 7H), 0.80 (d,J= 6.9 Hz, 3H); 13 C{ 1 H}NMR(100 MHz, CHCl 3 ) δ 167.3, 166.2, 143.6, 135.7, 135.0, 131.1,128.6, 128.4, 127.9, 127.9, 127.2, 126.8, 125.7, 125.2, 75.7, 60.8, 47.3, 41.0,34.4, 31.6, 26.5, 23.5, 22.2, 20.9, 16.4, 14.5;HRMS (ESI): m/z calcdfor C 26 H 32 NaO 4 + [M+Na] + 431.2193 found 431.2202。
example 26
A substrate:；
compound 26:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=10:1, rf=0.3), pale yellow oil (68.5 mg, 63% yield); 1 H NMR(400 MHz, CDCl 3 )δ8.43 (d,J= 16.2 Hz, 1H), 8.18 (d,J= 8.3 Hz, 1H), 7.99 (d,J= 8.7 Hz, 1H), 7.88 – 7.84 (m, 2H), 7.61 – 7.53 (m, 2H), 7.48 – 7.46 (m, 2H),7.42 – 7.34 (m, 3H), 6.08 (d,J= 16.2 Hz, 1H), 5.38 (s, 2H), 4.31 (q,J= 7.1 Hz, 2H), 1.37 (t,J= 7.1 Hz, 3H); 13 C{ 1 H}NMR(100 MHz, CDCl 3 )δ167.3, 166.2, 143.4, 136.5, 135.7,135.2, 131.1, 128.72, 128.7, 128.6, 128.4, 128.4, 128.1, 127.2, 126.8, 126.8,125.8, 125.3, 67.4, 60.8, 14.4;HRMS (ESI): m/z calcd for C 23 H 21 O 4 + [M+H] + 361.1434 found 361.1444。
example 27
A substrate:；
compound 27:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=15:1, rf=0.4), yellow oil (68.1 mg, 60% yield); 1 H NMR(400 MHz, CDCl 3 )δ8.40 (d,J= 16.2Hz, 1H), 8.16 (d,J= 8.3 Hz, 1H), 7.95 (d,J= 8.7 Hz, 1H), 7.87– 7.83 (m, 2H), 7.60 – 7.52 (m, 2H), 7.46 – 7.42 (m, 2H), 7.07 (t,J=8.7 Hz, 2H), 6.05 (d,J= 16.2 Hz, 1H), 5.33 (s, 2H), 4.31 (q,J= 7.1 Hz, 2H), 1.36 (t,J= 7.2 Hz, 3H); 13 C{ 1 H}NMR(100 MHz, CDCl 3 )δ167.2, 166.1, 162.8 (d,J=247.0 Hz), 143.2, 136.4, 135.2, 131.6 (d,J= 3.3 Hz), 131.0, 130.6 (d,J= 8.2 Hz), 128.7, 128.4, 128.1, 127.2, 126.8, 126.7, 125.7, 125.4, 115.6 (d,J= 21.6 Hz), 66.6, 60.8, 14.38; 19 F{ 1 H}NMR(376 MHz, CDCl 3 )δ-113.4;HRMS(ESI): m/z calcd for C 23 H 20 FO 4 + [M+H] + 379.1340 found 379.1347。
example 28
A substrate:；
compound 28:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=15:1, rf=0.2), brown oil (56.4 mg,44% yield); 1 H NMR(400 MHz, CHCl 3 ) δ 8.34 (d,J=16.2 Hz, 1H), 8.10 (d,J= 8.5 Hz, 1H), 7.91 (d,J= 8.6 Hz, 1H),7.82 –7.79 (m, 2H), 7.59 – 7.4 (m, 6H), 6.00 (d,J= 16.3 Hz, 1H), 5.34(s, 2H), 4.21 (d,J= 7.1 Hz, 2H), 1.27 (t,J= 7.1 Hz, 3H); 13 C{ 1 H}NMR(100 MHz, CHCl 3 ) δ167.11, 166.15, 143.29,139.74, 136.72, 135.34, 131.07, 130.59 (q,J= 32.5 Hz), 128.81, 128.55,128.43, 128.33, 127.36, 126.91, 126.31, 125.73 (q,J= 3.9 Hz), 125.68,125.49, 121.43 (q,J= 272.3 Hz), 66.40, 60.88, 14.40; 19 F{ 1 H}NMR(376 MHz, CDCl 3 ) δ -62.6;HRMS (ESI):m/z calcd for C 24 H 19 F 3 NaO 4 + [M+Na] + 451.1128 found 451.1119。
example 29
A substrate:；
compound 29:；
compound characterization data: purified by flash columnchromatography (petroleum ether/AcOEt = 15:1, rf = 0.2), yellow oil (87.7 mg,74% yield); 1 H NMR(400 MHz, CHCl 3 ) δ 8.43 (d,J= 16.3 Hz,1H), 8.18 (d,J= 8.3 Hz, 1H), 8.01 (d,J= 8.6 Hz, 1H), 7.89 –7.85 (m, 2H), 7.61 – 7.51 (m, 3H), 7.44 – 7.40 (m, 1H), 7.32 – 7.25 (m, 2H),6.09 (d,J= 16.3 Hz, 1H), 5.48 (s, 2H), 4.30 (q,J= 7.1 Hz,2H), 1.36 (t,J= 7.1 Hz, 3H); 13 C{ 1 H}NMR(100 MHz, CHCl 3 ) δ 167.0, 166.1, 143.2, 136.7, 135.3, 134.1,133.5, 131.1, 130.3, 129.8, 129.8, 128.7, 128.4, 128.2, 127.2, 127.1, 126.9,126.5, 125.8, 125.5, 64.7, 60.8, 14.4;HRMS (ESI): m/z calcd for C 23 H 19 ClNaO 4+ [M+Na] + 417.0864 found 417.0873。
Example 30
A substrate:；
compound 30:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=5:1, rf=0.2), yellow oil (57.0 mg,49% yield); 1 H NMR(400 MHz, CHCl 3 ) δ 8.40 (d,J= 16.2Hz, 1H), 8.17 (d,J= 8.5 Hz, 1H), 7.98 (d,J= 8.7 Hz, 1H), 7.90– 7.87 (m, 2H), 7.68 (d,J= 8.3 Hz, 2H), 7.62 – 7.55 (m, 4H), 6.07 (d,J= 16.3 Hz, 1H), 5.41 (s, 2H), 4.30 (q,J= 7.2 Hz, 2H), 1.35 (t,J= 7.1 Hz, 3H); 13 C{ 1 H} NMR(100 MHz, CHCl 3 )δ 167.0, 166.1, 143.2, 141.1, 136.8, 135.4, 132.6, 131.1, 128.9, 128.7, 128.4,128.4, 127.4, 126.9, 126.2, 125.6, 125.5, 118.7, 112.3, 66.2, 60.9, 14.4;HRMS(ESI): m/z calcd for C 24 H 19 NNaO 4 + [M+Na] + 408.1206 found 408.1193。
example 31
A substrate:；
compound 31:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=5:1, rf=0.3), white solid (52.7 mg,43% yield); 1 H NMR(400 MHz, CDCl 3 )δ8.41 (d,J= 16.3 Hz, 1H), 8.25 (d,J= 8.8 Hz, 2H), 8.17 (d,J= 8.4 Hz,1H), 7.99 (d,J= 8.7 Hz, 1H), 7.90 – 7.88 (m, 2H), 7.63 – 7.55 (m, 4H),6.07 (d,J= 16.3 Hz, 1H), 5.46 (s, 2H), 4.29 (q,J= 7.1 Hz,2H), 1.35 (t,J= 7.1 Hz, 3H); 13 C{ 1 H}NMR(100 MHz, CDCl 3 )δ167.0, 166.1, 147.9, 148.0, 143. 2,143.2, 143.0, 136.8, 135.4, 131.1, 128.9, 128. 4, 127.4, 126.9, 126.1, 125.6,124.0, 65.9, 60.9, 14.4;HRMS (ESI): m/z calcd for C 23 H 19 NNaO 6 + [M+Na] + 428.1105 found 428.1107。
example 32
A substrate:；/>
compound 32:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=5:1, rf=0.3), yellow oil (82.9 mg,66% yield); 1 H NMR(400 MHz, CHCl 3 )δ8.41 (d,J= 16.3 Hz, 1H), 8.17 (d,J= 8.5 Hz, 1H), 8.06 (d,J= 8.4 Hz,2H), 7.99 (d,J= 8.7 Hz, 1H), 7.89 – 7.86 (m, 2H), 7.62 – 7.55 (m, 2H),7.51 (d,J= 8.3 Hz, 2H), 6.07 (d,J= 16.3 Hz, 1H), 5.42 (s,2H), 4.29 (q,J= 7.1 Hz, 2H), 3.92 (s, 3H), 1.34 (t,J= 7.1 Hz,3H); 13 C{ 1 H} NMR(100 MHz, CHCl 3 )δ167.1, 166.9, 166.2, 143.2, 140.8, 136.7, 135.3, 131.1, 130.2, 130.1,128.8, 128.4, 128.3, 128.1, 127.3, 126.9, 126.5, 125.7, 125.5, 66.6, 60.9,52.3, 14.4;HRMS (ESI): m/z calcd for C 25 H 22 NaO 6 + [M+Na] + 441.1309 found 441.1310。
example 33
A substrate:；
compound 33:；
compound characterization data: purified by flash columnchromatography (petroleum ether/acoet=25:1, rf=0.2), pale yellow oil (66.8 mg, 53% yield); 1 H NMR(400 MHz, CDCl 3 )δ8.46 (d,J= 16.3 Hz, 1H), 8.19 (d,J= 7.8 Hz, 1H),8.00 (d,J= 8.6 Hz, 1H), 7.86 (t,J= 8.9 Hz, 2H), 7.61 – 7.53(m, 2H), 7.45 – 7.40 (m, 4H), 6.11 (d,J= 16.3 Hz, 1H), 5.36 (s, 2H),4.34 (q,J= 7.1 Hz, 2H), 1.40 – 1.35 (m, 12H); 13 C{ 1 H}NMR(100 MHz, CDCl 3 )δ167.3, 166.2, 151.5, 143.4, 136.5,135.2, 132.8, 131.1, 128.6, 128.4, 128.4, 128.1, 127.2, 126.9, 126.8, 125.8,125.6, 125.3, 67.2, 60.8, 34.7, 31.4, 14.4;HRMS (ESI): m/z calcd for C 27 H 28 NaO 4 + [M+Na] + 439.1880 found 439.1887。
furthermore, we have attempted to use other reaction systems:
comparative example 1
The palladium acetate in example 22 was removed, reacted for 24 hours, suction filtered, and the solvent was distilled off under reduced pressure, and other conditions were kept unchanged, whereby the objective poly-substituted aryl carboxylate could not be obtained.
Comparative example 2
The ethyl acrylate in example 22 was removed, reacted for 24 hours, suction filtered, and the solvent was distilled off under reduced pressure, and other conditions were kept unchanged, so that the objective poly-substituted aryl carboxylate could not be obtained.
Comparative example 3
The tris (5-methoxy-1-indolyl) phosphine reagent of example 22 was replaced with tris (4-methoxyphenyl) phosphine reagent (0.6 mmol,0.2 equiv), reacted for 24 hours, suction filtered, the solvent was distilled off under reduced pressure, other conditions were kept unchanged, and the product compound 24 was obtained in 12% yield by flash column chromatography.
Comparative example 4
The water in example 22 was removed, the solvent toluene reagent was changed to an N, N-dimethylformamide reagent, and the reaction was carried out for 24 hours, suction filtration and distillation under reduced pressure were carried out to remove the solvent, and other conditions were kept unchanged, whereby the objective polysubstituted aryl carboxylate could not be obtained.
While the present invention has been described in considerable detail and with particularity with respect to several described embodiments, it is not intended to be limited to any such detail or embodiments or any particular embodiment, but is to be construed as providing broad interpretation of such claims by reference to the appended claims in view of the prior art so as to effectively encompass the intended scope of the invention. Furthermore, the foregoing description of the invention has been presented in its embodiments contemplated by the inventors for the purpose of providing a useful description, and for the purposes of providing a non-essential modification of the invention that may not be presently contemplated, may represent an equivalent modification of the invention.

Claims (10)

1. The preparation method of the polysubstituted aryl carboxylic ester compound is characterized by comprising the following steps:
cesium carbonate, palladium acetate and tris (5-methoxy-1-indolyl) phosphine are replaced by nitrogen for three times, then an organic solvent is added, then aryl iodide, water, chloroformate, ethyl acrylate and 2-cyano-5-norbornene are sequentially added, and the mixture is reacted under the protection of inert gas for 12 h-48 h, and after the reaction is finished, the organic solvent is removed and purified, so that the polysubstituted aryl carboxylate compound is obtained; the structural formula of the aryl iodide is shown as a formula I; the structural formula of the polysubstituted aryl carboxylic ester compound is shown in a formula II;
a formula I; />A formula II; wherein R is 1 ，R 2 Are each independently selected from aryl or alkyl.
2. The process of claim 1, wherein R is 1 At least one selected from methyl, ethyl, isopropyl, phenyl, oxytrifluoromethyl, methoxy, trifluoromethyl, halogen, nitro and alkoxycarbonyl.
3. The process of claim 1, wherein R is 2 Selected from butyl, heptyl, isopropyl, sec-butyl, isobutyl, cyclopentyl, 9-fluorenylmethoxycarbonyl, [1S- (1. Alpha., 2. Alpha., 5. Beta.)]-at least one of 5-methyl-2- (1-methylethyl) cyclohexyl, benzyl, 4-fluorobenzyl, 4-trifluoromethylbenzyl, 2-chlorobenzyl, 4-cyanobenzyl, 4-nitrobenzyl, 4-methoxybenzyl, 4-t-butylbenzyl.
4. The preparation method according to claim 1, wherein the molar ratio of the aryl iodide compound, cesium carbonate, palladium acetate, tris (5-methoxy-1-indolyl) phosphine, water, chloroformate, olefin and 2-cyano-5-norbornene is 1:3:0.1:0.2:2:2:2:2.
5. the method of claim 1, wherein the reaction time is 24 h.
6. The process according to claim 1, wherein the reaction temperature is from 60 ℃ to 100 ℃.
7. The process of claim 6, wherein the reaction temperature is 60 ℃.
8. The method according to claim 1, wherein the organic solvent is toluene.
9. The method according to claim 1, wherein the inert gas is nitrogen.
10. A process according to any one of claims 1 to 9, wherein the polysubstituted aryl carboxylate compound has the structure as described in any one of the following compounds 1 to 33:
。
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