CN114605262A - A kind of efficient and selective synthesis method of phenylallyl ether compounds - Google Patents
A kind of efficient and selective synthesis method of phenylallyl ether compounds Download PDFInfo
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- POSICDHOUBKJKP-UHFFFAOYSA-N prop-2-enoxybenzene Chemical class C=CCOC1=CC=CC=C1 POSICDHOUBKJKP-UHFFFAOYSA-N 0.000 title claims abstract description 15
- 238000001308 synthesis method Methods 0.000 title claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 28
- 238000000034 method Methods 0.000 claims abstract description 12
- 238000004440 column chromatography Methods 0.000 claims abstract description 8
- 239000011261 inert gas Substances 0.000 claims abstract description 8
- 239000003054 catalyst Substances 0.000 claims abstract description 7
- 239000002904 solvent Substances 0.000 claims abstract description 6
- CQRYARSYNCAZFO-UHFFFAOYSA-N salicyl alcohol Chemical compound OCC1=CC=CC=C1O CQRYARSYNCAZFO-UHFFFAOYSA-N 0.000 claims abstract description 5
- 238000003756 stirring Methods 0.000 claims abstract description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims abstract 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- 239000012046 mixed solvent Substances 0.000 claims description 7
- 239000003208 petroleum Substances 0.000 claims description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- 238000001311 chemical methods and process Methods 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 238000002360 preparation method Methods 0.000 claims 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- -1 benzene Allyl ether compounds Chemical class 0.000 abstract description 3
- 239000000758 substrate Substances 0.000 abstract description 3
- 239000012043 crude product Substances 0.000 abstract 1
- 238000012805 post-processing Methods 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- 238000005937 allylation reaction Methods 0.000 description 5
- 239000007810 chemical reaction solvent Substances 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000007872 degassing Methods 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- HBENZIXOGRCSQN-VQWWACLZSA-N (1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylpentan-2-yl]-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol Chemical compound N1([C@@H]2CC=3C4=C(C(=CC=3)O)O[C@H]3[C@@]5(OC)CC[C@@]2([C@@]43CC1)C[C@@H]5[C@](C)(O)C(C)(C)CC)CC1CC1 HBENZIXOGRCSQN-VQWWACLZSA-N 0.000 description 1
- PHDIJLFSKNMCMI-ITGJKDDRSA-N (3R,4S,5R,6R)-6-(hydroxymethyl)-4-(8-quinolin-6-yloxyoctoxy)oxane-2,3,5-triol Chemical compound OC[C@@H]1[C@H]([C@@H]([C@H](C(O1)O)O)OCCCCCCCCOC=1C=C2C=CC=NC2=CC=1)O PHDIJLFSKNMCMI-ITGJKDDRSA-N 0.000 description 1
- JNPGUXGVLNJQSQ-BGGMYYEUSA-M (e,3r,5s)-7-[4-(4-fluorophenyl)-1,2-di(propan-2-yl)pyrrol-3-yl]-3,5-dihydroxyhept-6-enoate Chemical compound CC(C)N1C(C(C)C)=C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)C(C=2C=CC(F)=CC=2)=C1 JNPGUXGVLNJQSQ-BGGMYYEUSA-M 0.000 description 1
- HIHOEGPXVVKJPP-JTQLQIEISA-N 5-fluoro-2-[[(1s)-1-(5-fluoropyridin-2-yl)ethyl]amino]-6-[(5-methyl-1h-pyrazol-3-yl)amino]pyridine-3-carbonitrile Chemical compound N([C@@H](C)C=1N=CC(F)=CC=1)C(C(=CC=1F)C#N)=NC=1NC=1C=C(C)NN=1 HIHOEGPXVVKJPP-JTQLQIEISA-N 0.000 description 1
- 238000005821 Claisen rearrangement reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/317—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
- C07C67/32—Decarboxylation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/31—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of functional groups containing oxygen only in singly bound form
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Abstract
本发明公开了一种属于有机合成领域，涉及一种苯基烯丙基醚类化合物的高效选择性合成方法。所述方法为：于惰性气体氛围下，向反应器中依次加入羟甲基苯酚、GMDVs、催化剂及溶剂，一定温度下搅拌至反应完毕，浓缩溶剂得到粗产品，经柱层析分离可得到苯基烯丙基醚类化合物。本发明合成方法具有收率高、化学选择性好、底物适用面广、反应条件温和及后处理方便等优点。其反应方程式如下：
Description
技术领域technical field
本发明公开了属于有机合成技术领域的一种苯基烯丙基醚类化合物的高效选择性合成方法。The invention discloses an efficient and selective synthesis method of phenylallyl ether compounds belonging to the technical field of organic synthesis.
背景技术Background technique
苯基烯丙基醚是一种十分重要的有机合成中间体，可以合成一系列生物活性分子或者天然产物(Chem.Rev.,2003,103,2921.)。此外，苯基烯丙基醚类化合物还是众多重要反应的前体，例如克莱森重排反应。Phenyl allyl ether is a very important intermediate in organic synthesis, which can synthesize a series of biologically active molecules or natural products (Chem. Rev., 2003, 103, 2921.). In addition, phenylallyl ethers are the precursors of many important reactions, such as the Claisen rearrangement.
目前苯基烯丙基醚类化合物的合成，多数采用酚类化合物与烯丙基卤代物在强碱的作用下的亲核取代反应，或者利用过渡金属(例如钯)催化下的烯丙基酯、烯丙醇或者其它烯丙基前体参与的烯丙基化反应。当反应底物中同时存在酚羟基和醇羟基时，上述方法并没有表现出很好的选择性。由于苯基烯丙基醚的合成方法较为局限，大大的限制了其在有机合成上的应用。因此，寻找一种新的烯丙基化试剂，发展一类高效、高选择性的构建苯基烯丙基醚类化合物的方法就显得尤为重要了。At present, the synthesis of phenyl allyl ether compounds mostly adopts the nucleophilic substitution reaction of phenolic compounds and allyl halides under the action of strong bases, or allyl esters catalyzed by transition metals (such as palladium). , allyl alcohol or other allyl precursors involved in the allylation reaction. When both phenolic and alcoholic hydroxyl groups are present in the reaction substrate, the above method does not show good selectivity. Because the synthetic method of phenyl allyl ether is relatively limited, its application in organic synthesis is greatly limited. Therefore, it is very important to find a new allylation reagent and develop a kind of efficient and highly selective method for the construction of phenylallyl ether compounds.
发明内容SUMMARY OF THE INVENTION
本发明的目的是为了克服现有的苯基烯丙基醚类化合物的选择性合成方法较为局限的问题，提供了一种高效、高选择性的合成苯基烯丙基醚类化合物的方法。The purpose of the present invention is to overcome the relatively limited problem of the selective synthesis method of the existing phenyl allyl ether compounds, and provide a method for synthesizing phenyl allyl ether compounds with high efficiency and high selectivity.
为了实现上述目的，本发明利用GMDVs作为烯丙基化试剂，提供了一种高效、高选择性的合成苯基烯丙基醚类化合物的方法。所述苯基烯丙基醚类化合物具有式I所示的结构：In order to achieve the above object, the present invention provides a method for synthesizing phenyl allyl ether compounds with high efficiency and high selectivity by using GMDVs as an allylation reagent. Described phenyl allyl ether compound has the structure shown in formula I:
其中，R1选自饱和烷基、烷氧基、卤素中的任意一种，位于苯环的4#、5#、6#其中一个位置上；Wherein, R 1 is selected from any one of saturated alkyl, alkoxy, halogen, and is located at one of the positions of 4 # , 5 # and 6 # of the benzene ring;
R2均为选自芳基、取代芳基、饱和烷基、氢原子中的任意一种；R 2 is any one selected from aryl group, substituted aryl group, saturated alkyl group and hydrogen atom;
所述芳基为苯基或萘基；The aryl group is phenyl or naphthyl;
所述取代芳基的取代基为卤素原子、饱和烷基、烷氧基、芳基中的任意一种；The substituent of the substituted aryl group is any one of a halogen atom, a saturated alkyl group, an alkoxy group, and an aryl group;
于惰性气体氛围下，向反应器中依次加入羟甲基苯酚、GMDVs、催化剂及溶剂，一定温度下搅拌至反应完毕；其化学过程见反应式II：Under the inert gas atmosphere, add methylol phenol, GMDVs, catalyst and solvent successively to the reactor, and stir until the reaction is completed at a certain temperature; its chemical process is shown in Reaction Formula II:
所述催化剂选自四三苯基膦钯(Pd(PPh3)4)，醋酸钯、三(二亚苄基丙酮)二钯(Pd2(dba)3)中的任意一种。The catalyst is selected from any one of tetrakistriphenylphosphine palladium (Pd(PPh 3 ) 4 ), palladium acetate and tris(dibenzylideneacetone)dipalladium (Pd 2 (dba) 3 ).
所述溶剂选自二氯甲烷、四氢呋喃、乙酸乙酯、乙醇、乙腈、丙酮、N,N-二甲基甲酰胺、1,4-二氧六环中的任意一种。The solvent is selected from any one of dichloromethane, tetrahydrofuran, ethyl acetate, ethanol, acetonitrile, acetone, N,N-dimethylformamide and 1,4-dioxane.
所述羟甲基苯酚、GMDVs及催化剂的摩尔比为1.0:(1.0-2.0):(0.01-0.1)。The molar ratio of the methylol phenol, the GMDVs and the catalyst is 1.0:(1.0-2.0):(0.01-0.1).
反应时间为1-24h。The reaction time is 1-24h.
反应温度为0-60℃。The reaction temperature is 0-60°C.
在反应后用石油醚和乙酸乙酯的混合溶剂进行柱层析分离。After the reaction, column chromatography was performed with a mixed solvent of petroleum ether and ethyl acetate.
本发明的有益效果为：本发明提供的苯基烯丙基醚类化合物的高效选择性合成方法科学合理，相较于传统方法，具有如下显著优点：The beneficial effects of the present invention are as follows: the high-efficiency selective synthesis method of the phenylallyl ether compounds provided by the present invention is scientific and reasonable, and compared with the traditional method, it has the following significant advantages:
(1)利用GMDVs作为烯丙基化试剂，可实现酚羟基的选择性烯丙基化；(1) Selective allylation of phenolic hydroxyl groups can be achieved by using GMDVs as allylation reagents;
(2)反应收率高，操作简单，条件温和，产物易于分离，适合大规模生产；(2) The reaction yield is high, the operation is simple, the conditions are mild, and the product is easy to separate, which is suitable for large-scale production;
(3)底物适用面广，可对苯基烯丙基醚类化合物进行多样化合成。(3) The substrate has a wide range of applications, and the phenylallyl ether compounds can be synthesized in a variety of ways.
附图说明Description of drawings
图1为实施例1制备的化合物(3a)的NMR图谱；Fig. 1 is the NMR spectrum of compound (3a) prepared in Example 1;
图2为实施例2制备的化合物(3b)的NMR图谱；Figure 2 is the NMR spectrum of compound (3b) prepared in Example 2;
图3为实施例3制备的化合物(3c)的NMR图谱；Figure 3 is the NMR spectrum of compound (3c) prepared in Example 3;
图4为实施例4制备的化合物(3d)的NMR图谱；Figure 4 is the NMR spectrum of compound (3d) prepared in Example 4;
图5为实施例5制备的化合物(3e)的NMR图谱。FIG. 5 is the NMR spectrum of compound (3e) prepared in Example 5. FIG.
具体实施方式Detailed ways
在本文中通过具体实施例对本发明的方法进行说明，但本发明并不局限于此，在本发明的技术构思范围内，进行任何的修改、等同替换和改进等，均应包括在本发明的保护范围之内。The method of the present invention will be described herein through specific embodiments, but the present invention is not limited thereto, and any modifications, equivalent replacements and improvements within the scope of the technical concept of the present invention shall be included in the scope of the present invention. within the scope of protection.
实施例1：Example 1:
反应方程式如下：The reaction equation is as follows:
将化合物1a(5mmol)、GMDVs(7.5mmol)、Pd(PPh3)4(0.25mmol)于惰性气体氛围下依次加入反应器中，加入无水四氢呋喃50毫升后进行脱气，室温反应12小时。反应完成后，旋干反应溶剂，用石油醚和乙酸乙酯的体积比8:1的混合溶剂柱层析，得到纯3a。3a的产率为78％。Compound 1a (5 mmol), GMDVs (7.5 mmol), and Pd(PPh 3 ) 4 (0.25 mmol) were successively added to the reactor under an inert gas atmosphere, 50 ml of anhydrous tetrahydrofuran was added, and then degassed, and the reaction was carried out at room temperature for 12 hours. After the completion of the reaction, the reaction solvent was spin-dried, and purified by column chromatography with a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 8:1 to obtain pure 3a. The yield of 3a was 78%.
3a的核磁数据如下：The NMR data of 3a are as follows:
1H NMR(500MHz,CDCl3)δ7.50(d,J＝2.5Hz,1H),7.36-7.22(m,10H),7.19(t,J＝7.5Hz,1H),6.61(d,J＝9.0Hz,1H),6.04(dd,J＝9.5,4.5Hz,1H),5.03(s,1H),4.99(s,1H),4.37-4.28(m,2H),3.82-3.74(m,1H),3.62(d,J＝2.5Hz,3H),2.89-2.74(m,2H),2.47-2.36(m,1H)ppm. 1 H NMR (500MHz, CDCl 3 ) δ 7.50 (d, J=2.5Hz, 1H), 7.36-7.22 (m, 10H), 7.19 (t, J=7.5Hz, 1H), 6.61 (d, J= 9.0Hz, 1H), 6.04(dd, J=9.5, 4.5Hz, 1H), 5.03(s, 1H), 4.99(s, 1H), 4.37-4.28(m, 2H), 3.82-3.74(m, 1H) ),3.62(d,J＝2.5Hz,3H),2.89-2.74(m,2H),2.47-2.36(m,1H)ppm.
13C NMR(125MHz,CDCl3)δ173.66,154.45,142.63,141.32,138.18,134.40,134.29,131.13,130.45,128.72,128.31,127.84,127.55,127.50,126.50,114.87,114.80,113.43,71.27,71.20,71.13,52.14,49.98,36.29ppm. 13 C NMR(125MHz,CDCl 3 )δ173.66,154.45,142.63,141.32,138.18,134.40,134.29,131.13,130.45,128.72,128.31,127.84,127.55,127.50,126.50,114.87,114.80,113.43,71.27,71.20,71.13 ,52.14,49.98,36.29ppm.
实施例2Example 2
反应方程式如下：The reaction equation is as follows:
将化合物1b(5mmol)、GMDVs(7.5mmol)、Pd2(dba)3(0.25mmol)于惰性气体氛围下依次加入反应器中，加入无水四氢呋喃50毫升后进行脱气，室温反应12小时。反应完成后，旋干反应溶剂，用石油醚和乙酸乙酯的体积比5:1的混合溶剂柱层析，得到纯3b。3b的产率为70％。Compound 1b (5 mmol), GMDVs (7.5 mmol), and Pd 2 (dba) 3 (0.25 mmol) were successively added to the reactor under an inert gas atmosphere, and 50 ml of anhydrous tetrahydrofuran was added, followed by degassing, and the reaction was carried out at room temperature for 12 hours. After the completion of the reaction, the reaction solvent was spin-dried, and purified by column chromatography with a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 5:1 to obtain pure 3b. The yield of 3b was 70%.
3b的核磁数据如下：The NMR data of 3b are as follows:
1H NMR(500MHz,CDCl3)δ7.40-7.33(m,2H),7.33-7.22(m,7H),7.17(t,J＝7.5Hz,1H),7.13(d,J＝8.5Hz,1H),6.46(dd,J＝8.5,2.0Hz,1H),6.40(d,J＝1.5Hz,1H),6.03(t,J＝6.0Hz,1H),5.09(s,1H),5.00(s,1H),4.42-4.30(m,2H),3.84-3.74(m,4H),3.62(d,J＝4.0Hz,3H),2.94-2.80(m,2H),2.51-2.39ppm. 1 H NMR (500 MHz, CDCl 3 ) δ 7.40-7.33 (m, 2H), 7.33-7.22 (m, 7H), 7.17 (t, J=7.5Hz, 1H), 7.13 (d, J=8.5Hz, 1H), 6.46(dd, J＝8.5, 2.0Hz, 1H), 6.40(d, J＝1.5Hz, 1H), 6.03(t, J＝6.0Hz, 1H), 5.09(s, 1H), 5.00( s, 1H), 4.42-4.30(m, 2H), 3.84-3.74(m, 4H), 3.62(d, J=4.0Hz, 3H), 2.94-2.80(m, 2H), 2.51-2.39ppm.
13C NMR(125MHz,CDCl3)δ173.74,173.69,160.22,156.64,143.55,141.58,138.28,128.74,128.70,128.09,127.84,127.48,127.01,126.39,124.90,124.82,114.80,114.76,104.51,104.48,99.68,71.69,71.56,70.96,55.35,52.10,49.95,49.94,36.43ppm. 13 C NMR(125MHz,CDCl 3 )δ173.74,173.69,160.22,156.64,143.55,141.58,138.28,128.74,128.70,128.09,127.84,127.48,127.01,126.39,124.90,124.82,114.80,114.76,104.51,104.48,99.68 ,71.69,71.56,70.96,55.35,52.10,49.95,49.94,36.43ppm.
实施例3Example 3
反应方程式如下：The reaction equation is as follows:
将化合物1c(5mmol)、GMDVs(7.5mmol)、Pd(PPh3)4(0.25mmol)于惰性气体氛围下依次加入反应器中，加入无水乙酸乙酯50毫升后进行脱气，室温反应12小时。反应完成后，旋干反应溶剂，用石油醚和乙酸乙酯的体积比8:1的混合溶剂柱层析，得到纯3c。3c的产率为73％。Compound 1c (5 mmol), GMDVs (7.5 mmol), and Pd(PPh 3 ) 4 (0.25 mmol) were successively added to the reactor under an inert gas atmosphere, and 50 mL of anhydrous ethyl acetate was added, followed by degassing, and the reaction was carried out at room temperature for 12 Hour. After the reaction was completed, the reaction solvent was spin-dried, and purified by column chromatography with a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 8:1 to obtain pure 3c. The yield of 3c was 73%.
3c的核磁数据如下：The NMR data of 3c are as follows:
1H NMR(500MHz,CDCl3)δ7.58-7.52(m,2H),7.50(dd,J＝8.0,2.0Hz,2H),7.46-7.38(m,4H),7.37-7.29(m,2H),7.28-7.20(m,6H),6.97(t,J＝7.5Hz,1H),6.79(d,J＝8.0Hz,1H),6.17-6.09(m,1H),5.09(s,1H),5.00(s,1H),4.46-4.33(m,2H),3.89-3.78(m,1H),3.59(d,J＝5.0Hz,3H),3.02(dd,J＝14.5,5.5Hz,1H),2.97-2.86(m,1H),2.56-2.47(m,1H)ppm. 1 H NMR (500 MHz, CDCl 3 ) δ 7.58-7.52 (m, 2H), 7.50 (dd, J=8.0, 2.0 Hz, 2H), 7.46-7.38 (m, 4H), 7.37-7.29 (m, 2H) ),7.28-7.20(m,6H),6.97(t,J=7.5Hz,1H),6.79(d,J=8.0Hz,1H),6.17-6.09(m,1H),5.09(s,1H) ,5.00(s,1H),4.46-4.33(m,2H),3.89-3.78(m,1H),3.59(d,J＝5.0Hz,3H),3.02(dd,J＝14.5,5.5Hz,1H ),2.97-2.86(m,1H),2.56-2.47(m,1H)ppm.
13C NMR(125MHz,CDCl3)δ173.74,173.68,155.55,142.41,141.67,140.90,139.97,138.26,132.13,132.04,128.70,128.67,127.90,127.89,127.80,127.49,127.12,127.05,126.94,126.90,121.04,114.74,114.67,111.74,71.81,71.68,70.95,52.09,50.01,36.53,36.49ppm. 13 C NMR(125MHz,CDCl 3 )δ173.74,173.68,155.55,142.41,141.67,140.90,139.97,138.26,132.13,132.04,128.70,128.67,127.90,127.89,127.80,127.49,127.12,127.05,126.94,126.90,121.04 ,114.74,114.67,111.74,71.81,71.68,70.95,52.09,50.01,36.53,36.49ppm.
实施例4Example 4
反应方程式如下：The reaction equation is as follows:
将化合物1d(5mmol)、GMDVs(7.5mmol)、Pd(PPh3)4(0.25mmol)于惰性气体氛围下依次加入反应器中，加入无水四氢呋喃50毫升后进行脱气，0摄氏度下反应12小时。反应完成后，旋干反应溶剂，用石油醚和乙酸乙酯的体积比8:1的混合溶剂柱层析，得到纯3d。3d的产率为74％。Compound 1d (5 mmol), GMDVs (7.5 mmol), and Pd(PPh 3 ) 4 (0.25 mmol) were sequentially added to the reactor under an inert gas atmosphere, and 50 ml of anhydrous tetrahydrofuran was added, followed by degassing, and the reaction was carried out at 0 degrees Celsius for 12 Hour. After the reaction is completed, the reaction solvent is spin-dried, and pure 3d is obtained by column chromatography with a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 8:1. The yield of 3d was 74%.
3d的核磁数据如下：The 3d NMR data are as follows:
1H NMR(500MHz,CDCl3)δ7.86(d,J＝7.5Hz,1H),7.82-7.68(m,3H),7.53-7.38(m,3H),7.34-7.16(m,7H),6.94(t,J＝7.5Hz,1H),6.79(d,J＝8.0Hz,1H),6.28(dd,J＝10.0,5.0Hz,1H),5.09(s,1H),5.00(s,1H),4.45-4.35(m,2H),3.90-3.75(m,1H),3.58(d,J＝4.5Hz,3H),3.13(dd,J＝22.0,5.0Hz,1H),3.00-2.82(m,1H),2.64-2.41(m,1H)ppm. 1 H NMR (500MHz, CDCl 3 ) δ 7.86(d, J=7.5Hz, 1H), 7.82-7.68(m, 3H), 7.53-7.38(m, 3H), 7.34-7.16(m, 7H), 6.94(t,J＝7.5Hz,1H),6.79(d,J＝8.0Hz,1H),6.28(dd,J＝10.0,5.0Hz,1H),5.09(s,1H),5.00(s,1H ),4.45-4.35(m,2H),3.90-3.75(m,1H),3.58(d,J=4.5Hz,3H),3.13(dd,J=22.0,5.0Hz,1H),3.00-2.82( m,1H),2.64-2.41(m,1H)ppm.
13C NMR(125MHz,CDCl3)δ173.74,173.68,155.68,155.66,141.65,141.64,140.66,140.64,138.25,133.21,132.70,132.13,132.04,128.70,128.10,128.07,128.03,127.81,127.79,127.57,127.47,125.89,125.63,124.98,124.95,121.05,121.03,114.77,114.69,111.76,77.25,77.00,76.75,71.87,71.71,70.99,70.98,52.10,52.09,50.02,36.60,36.54ppm. 13 C NMR(125MHz,CDCl 3 )δ173.74,173.68,155.68,155.66,141.65,141.64,140.66,140.64,138.25,133.21,132.70,132.13,132.04,128.70,128.10,128.07,128.03,127.81,127.79,127.57,127.47 ,125.89,125.63,124.98,124.95,121.05,121.03,114.77,114.69,111.76,77.25,77.00,76.75,71.87,71.71,70.99,70.98,52.10,52.09,36.54ppm.
实施例5Example 5
反应方程式如下：The reaction equation is as follows:
将化合物1e(5mmol)、GMDVs(7.5mmol)、Pd(PPh3)4(0.25mmol)于惰性气体氛围下依次加入反应器中，加入无水四氢呋喃50毫升后进行脱气，室温反应2小时。反应完成后，旋干反应溶剂，用石油醚和乙酸乙酯的体积比3:1的混合溶剂柱层析，得到纯3e。3e的产率为57％。Compound 1e (5 mmol), GMDVs (7.5 mmol), and Pd(PPh 3 ) 4 (0.25 mmol) were successively added to the reactor under an inert gas atmosphere, 50 ml of anhydrous tetrahydrofuran was added, and then degassed, and the reaction was carried out at room temperature for 2 hours. After the reaction was completed, the reaction solvent was spin-dried, and purified by column chromatography with a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 3:1 to obtain pure 3e. The yield of 3e was 57%.
3e的核磁数据如下：The NMR data of 3e are as follows:
1H NMR(500MHz,CDCl3)δ7.35-7.19(m,7H),6.94(t,J＝7.5Hz,1H),6.78(d,J＝8.5Hz,1H),5.18(s,1H),5.05(s,1H),4.71(d,J＝6.0Hz,2H), 1 H NMR (500MHz, CDCl 3 ) δ 7.35-7.19 (m, 7H), 6.94 (t, J=7.5Hz, 1H), 6.78 (d, J=8.5Hz, 1H), 5.18 (s, 1H) ,5.05(s,1H),4.71(d,J＝6.0Hz,2H),
4.52-4.41(m,2H),3.91(dd,J＝9.5,6.5Hz,1H),3.63(s,3H),3.00(dd,J＝14.5,9.0Hz,1H),2.58(dd,J＝15.0,6.5Hz,1H),2.48(t,J＝6.0Hz,1H)ppm.4.52-4.41(m, 2H), 3.91(dd, J=9.5, 6.5Hz, 1H), 3.63(s, 3H), 3.00(dd, J=14.5, 9.0Hz, 1H), 2.58(dd, J= 15.0,6.5Hz,1H),2.48(t,J=6.0Hz,1H)ppm.
13C NMR(125MHz,CDCl3)δ173.79,156.28,141.67,138.30,129.29,128.86,128.81,128.72,127.81,127.51,120.86,114.70,111.25,77.25,77.00,76.75,70.72,61.87,52.12,50.06,36.77ppm. 13 C NMR(125MHz,CDCl 3 )δ173.79,156.28,141.67,138.30,129.29,128.86,128.81,128.72,127.81,127.51,120.86,114.70,111.25,77.25,77.00,76.75,70.72,61.87,52.12,50.06,36.77 ppm.
由上述实例可以看出，按照本发明所述的利用GMDVs合成苯基烯丙基醚类化合物的方法，可在温和条件下，高效高选择性的获得多样化的产物。It can be seen from the above examples that according to the method for synthesizing phenylallyl ether compounds using GMDVs according to the present invention, diversified products can be obtained with high efficiency and selectivity under mild conditions.
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