CN112500254A - Polyene cyclization initiated by protonation of acetylenic amides - Google Patents

Polyene cyclization initiated by protonation of acetylenic amides Download PDF

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CN112500254A
CN112500254A CN201910870454.7A CN201910870454A CN112500254A CN 112500254 A CN112500254 A CN 112500254A CN 201910870454 A CN201910870454 A CN 201910870454A CN 112500254 A CN112500254 A CN 112500254A
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polycyclic compound
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phenyl
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benzenesulfonyl
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赵军锋
姚家盛
马诗强
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Jiangxi Normal University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
    • C07C303/40—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reactions not involving the formation of sulfonamide groups
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    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B37/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving either the formation of a carbon-to-carbon bond between two carbon atoms not directly linked already or the disconnection of two directly linked carbon atoms
    • C07B37/10—Cyclisation
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/78—Ring systems having three or more relevant rings
    • C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
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    • C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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    • C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
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Abstract

The invention relates to an efficient polycyclic series reaction initiated by alkynylamide, and provides a polycyclic compound with a structure shown in a formula II, and a preparation method and application thereof. Taking alkynylamide as a raw material, and directly obtaining the complex polycyclic compound by reaction under the condition of Bronsted acid. The product is a cis-tricyclic framework product which is opposite to the stereoselectivity rule of the traditional polyene cyclization reaction (cis-olefin obtains a cis-fused framework, and trans-olefin obtains a trans-fused framework), the cis-structured fused-ring product is a structural framework which is difficult to realize by the traditional polyene cyclization reaction, and the structural framework is widely existed in natural products such as terpene alkaloids, such as morphine and the like. The invention not only provides a new method for the total synthesis of the natural products, but also provides a new idea for synthesizing the terpene alkaloids, thereby having great development potential.

Description

Polyene cyclization initiated by protonation of acetylenic amides
Technical Field
The invention relates to an efficient polycyclic series reaction initiated by alkynylamide, in particular to a method for preparing a complex polycyclic compound by directly initiating the polycyclic series reaction by protonation of alkynylamide under the condition of Bronsted acid.
Background
With the development of economy and the progress of society, the human world will enter the era of sustainable development and intense competition of comprehensive national forces. In order to meet the requirements of sustainable development strategy, efficient, highly selective and atom-economical green chemical reactions are gradually becoming the trend of modern organic synthetic chemistry development. The synthesis of some complex molecules by harsh reaction conditions and complex synthetic steps has no longer been the goal of contemporary organic synthesis pursuits. People pay more attention to how to realize the synthesis of target molecules quickly, concisely and efficiently, namely, the efficiency and atom economy in the synthesis process are more important. The research finds that the biogenic synthesis of a plurality of natural products with complex structures involves enzyme-catalyzed high-efficiency tandem reactions, and if the enzyme-catalyzed tandem reactions in organisms can be simulated in a laboratory, the chemoselectivity, the regioselectivity and the stereoselectivity of the reactions can be controlled very efficiently. Because the reaction intermediate does not need to be separated and purified, the generation of chemical waste is indirectly reduced, the atom economy is improved, and the method conforms to the trend that modern organic synthetic chemistry develops towards high efficiency and green.
Alkyne amides are very specific molecules with a nitrogen atom directly attached to the carbon atom of the triple bond between carbon and carbon of the alkyne and an electron withdrawing group attached to the nitrogen atom, and the first synthesis of alkyne amides was first achieved by the teaching of viewhe in 1972 (angelw.chem.int.ed.1972, 11,917.). Due to the unstable nature of the acetylenic amines, which are the parent compounds, acetylenic amide chemistry has not received academic attention. Since the 21 st century, a batch of organic chemists represented by Richard Hsung (chem.Rev.2010,110, 5064-5106.) and Evano Gwilherm (Angew.chem.Int.Ed.2010,49, 2840-2859.) have studied the chemistry of alkynylamides again, and found that most of alkynylamides are stable and many new reaction properties are developed gradually. Thus, the use of acetylenic amides in organic synthesis has been rapidly developed in the past two decades, from the initial synthesis of simple small molecules to the total synthesis of now complex heterocyclic compounds and even natural products. As the synthesis of alkynylamides itself becomes more mature, their use in medicinal chemistry has also begun to evolve slowly. The alkyne amide chemistry gradually becomes an important field at the front of the research of organic synthetic chemistry, and a plurality of new reactions involving the alkyne amide are developed. In 2016, the subject group of applicants discovered that alkynylamides can act as condensing agents to facilitate formation of amide bonds, which has attracted a great deal of interest to both academia and industry (J.Am.chem.Soc.,2016,138, 13135-13138.).
Disclosure of Invention
The invention aims to provide a polycyclic compound with a structure shown as a formula II, and a preparation method and application thereof.
The polycyclic compound provided by the invention has a structure shown as a formula II:
Figure BDA0002202657310000021
wherein the content of the first and second substances,
the A ring is selected from benzene ring and naphthalene ring;
x is selected from-CH2-、-O-；
R1Selected from alkyl of H, C1-C8, alkoxy of C1-C8, halogen and aryl;
R2selected from alkyl and aryl of C1-C8;
EWG is selected from the group consisting of alkylsulfonyl, substituted alkylsulfonyl, benzenesulfonyl, substituted benzenesulfonyl.
In some preferred embodiments, ring a is selected from a benzene ring;
x is selected from-CH2-、-O-；
R1Selected from H, methyl, ethyl, n-propyl, methoxy, ethoxy, fluorine, chlorine, bromine, iodine, phenyl;
R2selected from methyl, ethyl, n-propyl, phenyl;
EWG is selected from the group consisting of methanesulfonyl, benzenesulfonyl, p-toluenesulfonyl, p-chlorobenzenesulfonyl.
In some preferred embodiments, the polycyclic compound has a structure represented by any one of the following formulas:
Figure BDA0002202657310000022
Figure BDA0002202657310000031
the preparation method of the polycyclic compound with the structure shown in the formula II comprises the following steps:
taking alkynylamide with a structure shown as a formula I as a raw material, and reacting under the participation of Bronsted acid to obtain a polycyclic compound with a structure shown as a formula II, wherein the reaction formula is (1);
Figure BDA0002202657310000032
wherein the content of the first and second substances,
the A ring is selected from benzene ring and naphthalene ring;
x is selected from-CH2-、-O-；
R1Selected from alkyl of H, C1-C8, alkoxy of C1-C8, halogen and aryl;
R2selected from alkyl and aryl of C1-C8;
R3selected from phenyl, naphthyl, substituted phenyl, substituted naphthyl;
EWG is selected from the group consisting of alkylsulfonyl, substituted alkylsulfonyl, benzenesulfonyl, substituted benzenesulfonyl.
In some preferred embodiments, ring a is selected from a benzene ring;
x is selected from-CH2-、-O-；
R1Selected from H, methyl, ethyl, n-propyl, methoxy, ethoxy, fluorine, chlorine, bromine, iodine, phenyl;
R2selected from methyl, ethyl, n-propyl, phenyl;
R3selected from phenyl, methylphenyl, ethylphenyl, n-propylphenyl, p-methoxyphenyl, p-ethoxyphenyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-iodophenyl, p-phenylphenyl;
EWG is selected from the group consisting of methanesulfonyl, benzenesulfonyl, p-toluenesulfonyl, p-chlorobenzenesulfonyl.
In some preferred embodiments, the bronsted acid is selected from the group consisting of trifluoromethanesulfonic acid (TfOH), bis-trifluoromethylsulfonyl imide (Tf)2NH)。
In some preferred embodiments, the solvent used for the reaction is Dichloromethane (DCM).
In some preferred embodiments, the reaction temperature is-80 to 0 ℃.
The polycyclic compound having the structure shown in formula II can be applied to the field of medicinal chemistry, for example, in the synthesis of natural products such as terpene alkaloids, e.g., morphine.
The invention has the beneficial effects that: the method realizes the efficient polycyclic series reaction initiated by the alkyne amide, and the complex polycyclic product is synthesized by directly initiating the polycyclic series reaction under the action of the Bronsted acid by taking the alkyne amide as a raw material. The product is a cis-tricyclic framework product which is opposite to the stereoselectivity rule of the traditional polyene cyclization reaction (cis-olefin obtains a cis-fused framework, and trans-olefin obtains a trans-fused framework), the cis-structured fused-ring product is a structural framework which is difficult to realize by the traditional polyene cyclization reaction, and the structural framework is widely existed in natural products such as terpene alkaloids, such as morphine and the like. The method not only provides a new method for the total synthesis of the natural products, but also provides a new idea for synthesizing the terpene alkaloids, thereby having great development potential.
Detailed Description
The invention is further illustrated by the following examples, which are intended only for a better understanding of the invention and therefore do not limit the scope of the invention by way of example.
The experimental methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials are commercially available.
Example 1
Figure BDA0002202657310000051
Adding 0.1mmol of alkynylamide 1a and a stirrer into a clean reaction tube, adding 1mL of DCM, stirring at 0 ℃ for 10min, adding 0.2mL of TfOH, and continuously stirring for 10 min; after the reaction is finished, adding a sodium bicarbonate aqueous solution into the reaction liquid for quenching, extracting the reaction liquid for 3 times by using ethyl acetate, concentrating an organic layer, and separating by column chromatography to obtain a pure polycyclic compound 2a, a white solid with the yield of 89%.
[2a]1H NMR(400MHz,CDCl3)δ7.69(d,J＝8.2Hz,2H),7.31(t,J＝7.8Hz,3H),7.19–7.04(m,3H),5.04(t,J＝3.7Hz,1H),2.97(s,3H),2.86–2.63(m,3H),2.45(s,3H),2.25–2.17(m,1H),2.08–1.88(m,3H),1.81–1.64(m,1H),1.39(s,3H)；
13C NMR(100MHz,CDCl3)δ144.9,143.5,143.3,136.2,133.6,129.2,128.9,128.1,126.9,126.0,125.4,124.4,46.9,39.8,36.9,32.8,29.8,26.8,24.8,22.5,21.5.
HRMS(ESI)calcd for C23H27NNaO2S(M+Na)+:404.1655,found:404.1661.
Example 2
Figure BDA0002202657310000052
Adding 0.1mmol of alkynylamide 1a and a stirrer into a clean reaction tube, adding 1mL of DCM, stirring at 0 ℃ for 10min, adding Tf2NH (5eq.), and continuously stirring for 30 min; after the reaction is finished, adding a sodium bicarbonate aqueous solution into the reaction liquid for quenching, extracting the reaction liquid for 3 times by using ethyl acetate, concentrating an organic layer, and separating by column chromatography to obtain a pure polycyclic compound 2a, a white solid with the yield of 37%.
[2a]1H NMR(400MHz,CDCl3)δ7.69(d,J＝8.2Hz,2H),7.31(t,J＝7.8Hz,3H),7.19–7.04(m,3H),5.04(t,J＝3.7Hz,1H),2.97(s,3H),2.86–2.63(m,3H),2.45(s,3H),2.25–2.17(m,1H),2.08–1.88(m,3H),1.81–1.64(m,1H),1.39(s,3H)；
13C NMR(100MHz,CDCl3)δ144.9,143.5,143.3,136.2,133.6,129.2,128.9,128.1,126.9,126.0,125.4,124.4,46.9,39.8,36.9,32.8,29.8,26.8,24.8,22.5,21.5.
HRMS(ESI)calcd for C23H27NNaO2S(M+Na)+:404.1655,found:404.1661.
Example 3
Figure BDA0002202657310000061
Adding 0.1mmol of alkynylamide 1b and a stirrer into a clean reaction tube, adding 1mL of DCM, stirring for 10min at-20 ℃, adding 0.2mL of TfOH, and continuously stirring for 30 min; after the reaction is finished, adding a sodium bicarbonate aqueous solution into the reaction liquid for quenching, extracting the reaction liquid for 3 times by using ethyl acetate, concentrating an organic layer, and separating by using column chromatography to obtain a pure polycyclic compound 2b which is a white solid with the yield of 82%.
[2b]1H NMR(400MHz,CDCl3)δ7.29(d,J＝7.8Hz,1H),7.16(t,J＝7.4Hz,1H),7.12–7.03(m,2H),5.76(t,J＝3.7Hz,1H),3.11(s,3H),2.90(s,3H),2.82–2.73(m,2H),2.54(d,J＝10.3Hz,1H),2.24–2.08(m,3H),1.86–1.77(m,1H),1.74–1.62(m,2H),1.33(s,3H).
13C NMR(100MHz,CDCl3)δ144.7,143.8,136.0,128.9,126.9,126.1,125.5,123.9,46.6,39.4,37.0,34.7,32.7,29.8,26.7,24.7,22.6.
HRMS(ESI)calcd for C17H23NNaO2S(M+Na)+:328.1342,found 328.1335.
Example 4
Figure BDA0002202657310000062
Adding 0.1mmol of alkynylamide 1c and a stirrer into a clean reaction tube, adding 1mL of DCM, stirring for 10min at-60 ℃, adding 0.2mL of TfOH, and continuously stirring for 1 h; after the reaction is finished, adding a sodium bicarbonate aqueous solution into the reaction liquid for quenching, extracting the reaction liquid for 3 times by using ethyl acetate, concentrating an organic layer, and separating by using column chromatography to obtain a pure polycyclic compound 2c which is a white solid with the yield of 60%.
[2c]1H NMR(400MHz,CDCl3)δ7.77–7.71(m,2H),7.54–7.49(m,2H),7.30(d,J＝7.4Hz,1H),7.20–7.14(m,1H),7.13–7.04(m,2H),5.06(t,J＝3.7Hz,1H),2.99(s,3H),2.86–2.74(m,2H),2.66(d,J＝10.9Hz,1H),2.25–2.16(m,1H),2.10–1.88(m,3H),1.82–1.67(m,2H),1.39(s,3H).
13C NMR(100MHz,CDCl3)δ144.6,143.4,139.1,136.0,135.0,129.4,128.9,128.9,126.8,126.1,125.4,124.8,46.9,39.9,36.9,32.7,29.7,26.8,24.8,22.5.
HRMS(ESI)calcd for C22H25ClNO2S(M+H)+:402.1289,found 402.1283.
Example 5
Figure BDA0002202657310000071
Adding 0.1mmol of alkynylamide 1d and a stirrer into a clean reaction tube, adding 1mL of DCM, stirring for 10min at-78 ℃, adding 0.2mL of TfOH, and continuously stirring for 2 h; after the reaction is finished, adding a sodium bicarbonate aqueous solution into the reaction liquid for quenching, extracting the reaction liquid for 3 times by using ethyl acetate, concentrating an organic layer, and separating by using column chromatography to obtain a pure polycyclic compound 2d, a white solid and the yield of 91%.
[2d]1H NMR(400MHz,CDCl3)δ7.69(d,J＝8.1Hz,2H),7.32(d,J＝8.0Hz,2H),7.10(s,1H),6.93(dd,J＝18.1,7.5Hz,2H),5.05(t,J＝3.4Hz,1H),2.97(s,3H),2.82–2.69(m,2H),2.65(d,J＝11.3Hz,1H),2.45(s,3H),2.31(s,3H),2.24–2.16(m,1H),2.08–1.90(m,2H),1.79–1.60(m,3H),1.38(s,3H).
13C NMR(100MHz,CDCl3)δ144.7,143.6,143.3,135.2,133.7,133.1,129.3,128.8,128.1,127.4,126.4,124.4,47.0,39.9,36.9,32.7,29.5,26.7,25.0,22.6,21.5,21.3.
HRMS(ESI)calcd for C24H29NNaO2S(M+Na)+:418.1811,found 418.1820.
Example 6
Figure BDA0002202657310000081
Adding 0.1mmol of alkynylamide 1e and a stirrer into a clean reaction tube, adding 1mL of DCM, stirring at 0 ℃ for 10min, adding 0.2mL of TfOH, and continuously stirring for 3 h; after the reaction is finished, adding a sodium bicarbonate aqueous solution into the reaction liquid for quenching, extracting the reaction liquid for 3 times by using ethyl acetate, concentrating an organic layer, and separating by using column chromatography to obtain a pure polycyclic compound 2e, wherein the yield is 72 percent.
[2e]1H NMR(400MHz,CDCl3)δ7.69(d,J＝8.2Hz,2H),7.56(d,J＝7.5Hz,2H),7.51(d,J＝1.1Hz,1H),7.42(t,J＝7.6Hz,2H),7.35–7.28(m,4H),7.13(d,J＝7.9Hz,1H),5.04(t,J＝3.6Hz,1H),2.97(s,3H),2.88–2.67(m,3H),2.44(s,3H),2.28–2.20(m,1H),2.12–1.87(m,3H),,1.86–1.63(m,2H),1.44(s,3H).
13C NMR(100MHz,CDCl3)δ145.3,143.5,143.4,141.7,139.1,135.5,133.5,129.4,129.3,128.7,128.2,127.1,127.0,125.8,124.4,124.4,47.0,39.9,37.2,32.9,29.6,26.9,24.9,22.6,21.6.
HRMS(ESI)calcd for C29H32NO2S(M+H)+:458.2148,found 458.2145.
Example 7
Figure BDA0002202657310000082
Adding 0.1mmol of alkynylamide 1f and a stirrer into a clean reaction tube, adding 1mL of DCM, stirring for 10min at-50 ℃, adding 0.2mL of TfOH, and continuously stirring for 2 h; after the reaction is finished, adding a sodium bicarbonate aqueous solution into the reaction liquid for quenching, extracting the reaction liquid for 3 times by using ethyl acetate, concentrating an organic layer, and separating by using column chromatography to obtain a pure polycyclic compound 2f, wherein the yield is 86 percent.
[2f]1H NMR(400MHz,CDCl3)δ7.67(d,J＝8.2Hz,2H),7.39(d,J＝1.7Hz,1H),7.31(d,J＝8.0Hz,2H),7.18(dd,J＝8.2,1.9Hz,1H),6.92(d,J＝8.2Hz,1H),5.02(t,J＝3.7Hz,1H),2.95(s,3H),2.79–2.62(m,3H),2.44(s,3H),2.25–2.14(m,1H),2.07–1.87(m,2H),1.77–1.56(m,3H),1.37(s,3H).
13C NMR(100MHz,CDCl3)δ147.3,143.4,143.2,135.2,133.4,130.7,129.9,129.3,128.5,128.1,124.4,119.6,46.6,39.9,37.2,32.7,29.3,26.8,24.6,22.4,21.6.
HRMS(ESI)calcd for C23H26BrNNaO2S(M+Na)+:482.0760,found 482.0765.
Example 8
Figure BDA0002202657310000091
Adding 1g of 0.1mmol of alkynylamide and a stirrer into a clean reaction tube, adding 1mL of DCM, stirring for 10min at-50 ℃, adding 0.2mL of TfOH, and continuously stirring for 2 h; after the reaction is finished, adding a sodium bicarbonate aqueous solution into the reaction liquid for quenching, extracting the reaction liquid for 3 times by using ethyl acetate, concentrating an organic layer, and separating by using column chromatography to obtain a pure polycyclic compound 2g, a white solid and the yield of 80%.
[2f]1H NMR(400MHz,CDCl3)δ7.99(d,J＝8.4Hz,1H),7.78–7.75(m,1H),7.71–7.66(m,3H),7.51–7.41(m,4H),7.32(s,1H),5.04(t,J＝3.3Hz,1H),3.20–3.04(m,2H),2.98(s,3H),2.78(d,J＝8.8Hz,1H),2.43(s,4H),2.40–2.33(m,2H),1.94–1.83(m,3H),1.44(s,3H).
13C NMR(100MHz,CDCl3)δ143.5,143.4,141.3,133.5,132.2,131.7,131.1,129.3,128.2,128.2,126.4,125.9,125.1,125.1,124.7,123.5,46.3,39.8,37.4,32.4,27.2,25.6,24.3,22.6,21.6.
HRMS(ESI)calcd for C23H26BrNNaO2S(M+H)+:432.1992,found 432.2001.
Example 9
Figure BDA0002202657310000092
Adding 0.1mmol of alkynylamide into a clean reaction tube for 1 hour and a stirrer, adding 1mL of DCM, stirring for 10min at-40 ℃, adding 0.2mL of TfOH, and continuously stirring for 12 hours; after the reaction is finished, adding a sodium bicarbonate aqueous solution into the reaction liquid for quenching, extracting the reaction liquid for 3 times by using ethyl acetate, concentrating an organic layer, and separating by using column chromatography to obtain a pure polycyclic compound for 2 hours, wherein the yield is 63 percent.
[2g]1H NMR(400MHz,CDCl3)δ7.67(d,J＝8.1Hz,2H),7.30(d,J＝8.0Hz,2H),7.19(d,J＝7.8Hz,1H),7.06(t,J＝7.7Hz,1H),6.88(t,J＝7.5Hz,1H),6.78(d,J＝8.2Hz,1H),5.06(s,1H),4.49(dd,J＝11.1,4.8Hz,1H),4.26(dd,J＝11.0,2.1Hz,1H),2.92(s,3H),2.87(s,1H),2.43(s,3H),2.07–2.00(m,1H),1.89–1.61(m,3H),1.43(s,3H).
13C NMR(100MHz,CDCl3)δ154.7,143.4,139.4,133.4,129.2,128.6,128.5,128.0,127.0,126.8,120.8,116.8,64.1,45.4,38.8,34.3,33.4,30.6,22.0,21.5.
HRMS(ESI)calcd for C22H25NNaO3S(M+Na)+:406.1747,found 406.1439.
Example 10
Figure BDA0002202657310000101
Adding 0.1mmol of alkynylamide 1i and a stirrer into a clean reaction tube, adding 1mL of DCM, stirring for 10min at-10 ℃, adding 0.2mL of TfOH, and continuously stirring for 18 h; after the reaction is finished, adding a sodium bicarbonate aqueous solution into the reaction liquid for quenching, extracting the reaction liquid for 3 times by using ethyl acetate, concentrating an organic layer, and separating by using column chromatography to obtain a pure polycyclic compound 2i, a white solid and the yield of 58%.
[2h]1H NMR(400MHz,CDCl3)δ7.67(d,J＝7.9Hz,2H),7.30(d,J＝7.8Hz,2H),6.97(s,1H),6.86(d,J＝8.2Hz,1H),6.67(d,J＝8.2Hz,1H),5.06(s,1H),4.44(dd,J＝11.0,4.7Hz,1H),4.22(d,J＝11.0Hz,1H),2.91(s,3H),2.84(d,J＝1.6Hz,1H),2.43(s,3H),2.25(s,3H),2.05–1.96(m,1H),1.88–1.63(m,3H),1.41(s,3H).
13C NMR(100MHz,CDCl3)δ152.5,143.4,139.5,133.3,129.8,129.2,128.5,128.3,128.0,127.8,127.0,116.6,64.1,45.5,38.8,34.3,33.3,30.6,22.0,21.5,20.8.
HRMS(ESI)calcd for C23H28NO3S(M+H)+:398.1784,found 398.1779.
Example 11
Figure BDA0002202657310000111
Adding 0.1mmol of alkynylamide 1j and a stirrer into a clean reaction tube, adding 1mL of DCM, stirring for 10min at-20 ℃, adding 0.2mL of TfOH, and continuously stirring for 20 h; after the reaction is finished, adding a sodium bicarbonate aqueous solution into the reaction liquid for quenching, extracting the reaction liquid for 3 times by using ethyl acetate, concentrating an organic layer, and separating by using column chromatography to obtain a pure polycyclic compound 2j, a white solid with the yield of 63%.
[2i]1H NMR(400MHz,CDCl3)δ7.66(d,J＝7.7Hz,2H),7.34–7.26(m,3H),7.14(d,J＝8.7Hz,1H),6.67(d,J＝8.7Hz,1H),5.06(s,1H),4.49(dd,J＝11.1,4.6Hz,1H),4.23(d,J＝11.1Hz,1H),2.90(s,3H),2.87(s,1H),2.44(s,3H),2.03–1.95(m,1H),1.91–1.80(m,1H),1.77–1.64(m,2H),1.41(s,3H).
13C NMR(100MHz,CDCl3)δ153.9,143.6,139.2,133.1,131.0,130.1,129.6,129.3,128.5,128.1,118.9,112.9,64.2,45.0,38.8,34.6,33.3,30.6,22.0,21.6.
HRMS(ESI)calcd for C22H25BrNO3S(M+H)+:462.0733,found 462.0727.
Example 12
Figure BDA0002202657310000112
Adding 0.1mmol of alkynylamide 1k and a stirrer into a clean reaction tube, adding 1mL of DCM, stirring for 10min at-40 ℃, adding 0.2mL of TfOH, and continuously stirring for 24 h; after the reaction is finished, adding a sodium bicarbonate aqueous solution into the reaction liquid for quenching, extracting the reaction liquid for 3 times by using ethyl acetate, concentrating an organic layer, and separating by using column chromatography to obtain a pure polycyclic compound 2k which is a white solid with the yield of 61%.
[2j]1H NMR(400MHz,CDCl3)δ7.67(d,J＝8.0Hz,2H),7.30(d,J＝8.0Hz,2H),6.78–6.63(m,3H),5.07(s,1H),4.44(dd,J＝11.0,4.8Hz,1H),4.21(dd,J＝11.0,1.7Hz,1H),3.75(s,3H),2.92(s,3H),2.84(s,1H),2.43(s,3H),2.04–1.95(m,1H),1.91–1.78(m,1H),1.78–1.67(m,2H),1.42(s,3H).
13C NMR(100MHz,CDCl3)δ153.7,148.8,143.4,139.4,133.3,129.6,129.2,128.4,128.0,117.3,112.5,112.2,64.1,55.7,45.4,38.8,34.7,33.5,30.6,22.0,21.5.
HRMS(ESI)calcd for C23H28NO4S(M+H)+:414.1734,found 414.1729.
Example 13
Figure BDA0002202657310000121
Adding 0.1mmol of alkynylamide 1l and a stirrer into a clean reaction tube, adding 1mL of DCM, stirring for 10min at-30 ℃, adding 0.2mL of TfOH, and continuously stirring for 18 h; after the reaction is finished, adding a sodium bicarbonate aqueous solution into the reaction liquid for quenching, extracting the reaction liquid for 3 times by using ethyl acetate, concentrating an organic layer, and separating by using column chromatography to obtain 2l of a pure polycyclic compound, namely a white solid with the yield of 60%.
[2k]1H NMR(400MHz,CDCl3)δ7.66(d,J＝7.7Hz,2H),7.31(d,J＝7.4Hz,2H),7.14(s,1H),7.00(d,J＝8.6Hz,1H),6.71(d,J＝8.6Hz,1H),5.07(s,1H),4.48(d,J＝7.1Hz,1H),4.23(d,J＝11.0Hz,1H),2.90(s,3H),2.87(s,1H),2.43(s,3H),2.03–1.94(m,1H),1.91–1.81(m,1H),1.78–1.61(m,2H),1.41(s,3H).
13C NMR(100MHz,CDCl3)δ153.4,143.5,139.3,133.2,130.4,129.3,128.5,128.1,127.2,126.6,125.5,118.4,64.3,45.0,38.8,34.7,33.3,30.5,22.0,21.5.
HRMS(ESI)calcd for C22H25ClNO3S(M+H)+:418.1238,found 418.1230.
Example 14
Figure BDA0002202657310000122
Adding 0.1mmol of alkynylamide 1m and a stirrer into a clean reaction tube, adding 1mL of DCM, stirring for 10min at-78 ℃, adding 0.2mL of TfOH, and continuously stirring for 24 h; after the reaction is finished, adding a sodium bicarbonate aqueous solution into the reaction liquid for quenching, extracting the reaction liquid for 3 times by using ethyl acetate, concentrating an organic layer, and separating by using column chromatography to obtain a pure polycyclic compound 2m, a white solid with the yield of 59%.
[2l]1H NMR(400MHz,CDCl3)δ7.67(d,J＝8.1Hz,2H),7.51(d,J＝8.0Hz,2H),7.40(t,J＝7.6Hz,3H),7.30(d,J＝8.4Hz,4H),6.85(d,J＝8.4Hz,1H),5.08(s,1H),4.53(dd,J＝11.1,4.6Hz,1H),4.29(d,J＝11.1Hz,1H),2.93(s,3H),2.91(s,1H),2.43(s,3H),2.14–2.06(m,1H),1.91–1.68(m,3H),1.48(s,3H).
13C NMR(100MHz,CDCl3)δ154.5,143.5,141.3,139.4,134.0,133.3,129.3,128.7,128.6,128.1,126.8,126.6,126.0,125.6,117.3,115.7,64.3,45.5,38.9,34.6,33.5,30.8,22.1,21.6.
HRMS(ESI)calcd for C28H30NO3S(M+H)+:460.1941,found 460.1941.
The above-mentioned embodiments are merely illustrative of the preferred embodiments of the present invention, and do not limit the scope of the present invention, and various modifications and improvements of the technical solution of the present invention by those skilled in the art should fall within the protection scope defined by the claims of the present invention without departing from the spirit of the present invention.

Claims (10)

1. A polycyclic compound having a structure according to formula II:
Figure FDA0002202657300000011
wherein the content of the first and second substances,
the A ring is selected from benzene ring and naphthalene ring;
x is selected from-CH2-、-O-；
R1Selected from alkyl of H, C1-C8, alkoxy of C1-C8, halogen and aryl;
R2selected from alkyl and aryl of C1-C8;
EWG is selected from the group consisting of alkylsulfonyl, substituted alkylsulfonyl, benzenesulfonyl, substituted benzenesulfonyl.
2. Polycyclic compound according to claim 1,
ring A is selected from benzene ring;
x is selected from-CH2-、-O-；
R1Selected from H, methyl, ethyl, n-propyl, methoxy, ethoxy, fluorine, chlorine, bromine, iodine, phenyl;
R2selected from methyl, ethyl, n-propyl, phenyl;
EWG is selected from the group consisting of methanesulfonyl, benzenesulfonyl, p-toluenesulfonyl, p-chlorobenzenesulfonyl.
3. The polycyclic compound of claim 2, wherein the polycyclic compound has a structure according to any one of the following formulae:
Figure FDA0002202657300000012
Figure FDA0002202657300000021
4. a method of preparing a polycyclic compound according to claim 1, comprising the steps of:
taking alkynylamide with a structure shown as a formula I as a raw material, and reacting under the participation of Bronsted acid to obtain a polycyclic compound with a structure shown as a formula II, wherein the reaction formula is (1);
Figure FDA0002202657300000022
wherein the content of the first and second substances,
the A ring is selected from benzene ring and naphthalene ring;
x is selected from-CH2-、-O-；
R1Selected from alkyl of H, C1-C8, alkoxy of C1-C8, halogen and aryl;
R2selected from alkyl and aryl of C1-C8;
R3selected from phenyl, naphthyl, substituted phenyl, substituted naphthyl;
EWG is selected from the group consisting of alkylsulfonyl, substituted alkylsulfonyl, benzenesulfonyl, substituted benzenesulfonyl.
5. The method of claim 4,
ring A is selected from benzene ring;
x is selected from-CH2-、-O-；
R1Selected from H, methyl, ethyl, n-propyl, methoxy, ethoxy, fluorine, chlorine, bromine, iodine, phenyl;
R2selected from methyl, ethyl, n-propyl, phenyl;
R3selected from phenyl, methylphenyl, ethylphenyl, n-propylphenyl, p-methoxyphenyl, p-ethoxyphenyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-iodophenyl, p-phenylphenyl;
EWG is selected from the group consisting of methanesulfonyl, benzenesulfonyl, p-toluenesulfonyl, p-chlorobenzenesulfonyl.
6. The method of claim 4, wherein the Bronsted acid is selected from the group consisting of trifluoromethanesulfonic acid (TfOH), bis-trifluoromethylsulfonyl imide (Tf)2NH)。
7. The process according to claim 4, wherein the solvent used for the reaction is Dichloromethane (DCM).
8. The method according to claim 4, wherein the reaction temperature is-80 to 0 ℃.
9. Use of a polycyclic compound according to claim 1.
10. Use according to claim 9, wherein the polycyclic compound is used for the synthesis of terpene alkaloids.
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