CN117362190A - Preparation method of polysubstituted olefin - Google Patents

Preparation method of polysubstituted olefin Download PDF

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CN117362190A
CN117362190A CN202311113102.XA CN202311113102A CN117362190A CN 117362190 A CN117362190 A CN 117362190A CN 202311113102 A CN202311113102 A CN 202311113102A CN 117362190 A CN117362190 A CN 117362190A
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polysubstituted
under
reaction
amide
silver
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李先纬
陈亚博
张俏娅
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Guangdong University of Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/18—Systems containing only non-condensed rings with a ring being at least seven-membered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/56—Ring systems containing bridged rings
    • C07C2603/58—Ring systems containing bridged rings containing three rings
    • C07C2603/70—Ring systems containing bridged rings containing three rings containing only six-membered rings
    • C07C2603/74—Adamantanes
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
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Abstract

The present application provides a process for the preparation of polysubstituted olefins. The preparation method develops an alkenyl metal species from alkyne halogen for the first time, and finally, the polysubstituted olefin is formed by a strategy of hydrocarbon bond activation under the promotion of amide, so that the site-selective and stereoselective introduction of alkenyl fragments into amide molecules is realized to form the polysubstituted olefin. Under the condition of inert solvent, under the combined action of transition metal catalyst and oxidant, alkyne halogen firstly forms diketene, then under the action of metal, alkenyl metal species are generated, and then the strategy of activating carbon-hydrogen bonds is carried out to form polysubstituted olefin. Considering that the amide and the olefin are taken as ubiquitous functional groups in natural products, medicines and materials, the reaction is expected to provide a new idea for the development and application of related new medicines and new functional materials.

Description

Preparation method of polysubstituted olefin
Technical Field
The present application relates to the field of organic compound synthesis technology, and more particularly, to a method for preparing polysubstituted olefins.
Background
Polysubstituted olefins are widely available synthetic intermediates or products, and are widely used in organic chemistry, and there are many methods for synthesizing polysubstituted olefins today such as: wittig reactions of carbonyl compounds, heck reactions, alkyne carbon-metallizations, olefin isomerizations, olefin metathesis reactions, and the like. However, the above-mentioned methods generally have disadvantages of poor economy of steps, low productivity, need of preparing a substrate in advance, poor regio-or stereoselectivity, poor tolerance to functional groups, etc., so that the versatility of the substrate and the reaction selectivity are limited. In summary, the regio-and stereoselective synthetic methods of polysubstituted olefins remain worthy of exploration.
It is particularly pointed out that the introduction of electron rich alkyl (e.g., β -H containing alkyl) olefin backbones tends to be very challenging, mainly because metal catalyzed cross-coupling reactions for β -H containing alkenyl metal reagents or alkenyl halides tend to produce non-target isomers during the reaction, thereby reducing the efficiency and stereoselectivity of the overall reaction. In general, regio-and stereoselective introduction of alkenyl moieties into molecules, particularly polyalkyl-substituted olefins containing β -H, is extremely challenging and desirable.
Based on the research interest of subject group in the alkynylation of hydrocarbon bonds promoted by weak coordination, we realized Csp promoted by functional groups such as esters, ketones, sulfonamides, amides, alcohols, amine derivatives which are weakly coordinated and easily converted 2 -H and Csp 3 H alkynylation reaction (Angew.chem.Int.ed.2014, 53,14485-144895.Org.chem.front.,. 2021,8,6484-6490., (Front Cover); chem.Commun.,. 2020,56,11255-11258.Chin.J.chem.,. 2020,38,929-934.Org.chem.front.,. 2019,6,284-289.,. Front Cover.,. Hot Paper.; J.org.chem.,. 2017,82,13003-13011.) provides a new idea for the simple synthesis of multifunctional alkynes.
On the other hand, alkyne halides are available as multifunctional synthons, and in recent years, a simple path is provided for high-selectivity synthesis of various functional molecules in transition metal catalysis. Applicants have summarized herein a number of reaction modes for alkyne halides: firstly, under alkaline conditions, alkyne halogen is subjected to exchange of metal-halogen atoms, and C-X bond is broken to obtain alkyne anions; secondly, alkyne halogen is used as electrophilic alkyne reagent to react with nucleophilic reagent; thirdly, the alkyne halogen dissociates into halogen positive ions under the action of the organic lithium reagent to react as electrophilic halogenated reagent. Fourth, alkyne halides react simultaneously as electrophilic halogenating agents and nucleophilic alkynyl agents. In general, further development of more reactivity of the alkyne halides remains highly desirable.
The metal catalyzed hydrocarbon bond activation reaction under classical targeting strategies utilizes coordination between the targeting group and the metal catalyst to direct in situ formation of cyclometallated intermediates, thereby achieving their site selectivity. This also results in competing complexing for substrates containing multiple functional groups that tend to cause deactivation of the metal catalyst or non-targeted site selectivity.
In general, it is very challenging and desirable to develop novel reactivities for alkyne halides to compensate for certain deficiencies in the prior art of Heck reactions as well as oxidation of Heck reactions.
Content of the patent application
To overcome at least one of the problems of the prior art, the present application provides a process for the preparation of polysubstituted olefins. The preparation method utilizes the hydrocarbon bond activation promoted by the natural functional group amide to realize site selectivity and stereoselectivity to introduce alkenyl segments to construct polysubstituted olefin.
The present application provides a process for the preparation of polysubstituted olefins comprising the steps of: under the condition of inert solvent, under the combined action of catalyst and oxidant, alkyne halogen firstly forms alkenyl metal species, and finally, under the promotion of amide, the strategy of hydrocarbon bond activation is carried out to form polysubstituted olefin. The preparation method has the characteristics of easily obtained and easily converted raw materials and high-efficiency step economy.
In the preparation method of the patent application, a possible reaction mechanism flow is as follows:
the specific mechanism is as follows: the alkyne halogen leaves a group with large steric hindrance under the promotion of alkali to generate alkynyl carbonium ion A, which can undergo a Meyer-Schuster rearrangement reaction to be rearranged into a diallyl carbonium ion B, then generates C under the affinity attack of water, finally removes one hydrogen bromide to generate ketene, removes carbon monoxide under the action of metal to generate alkenyl metal species E, and then carries out hydrocarbon bond activation under the promotion of amide to realize the synthesis of polysubstituted olefin.
In order to solve the technical problems, the technical scheme adopted by the patent application is as follows:
a process for the preparation of a polysubstituted olefin comprising the steps of: under the condition of inert solvent, under the combined action of a catalyst and an oxidant, an alkenyl metal species is formed by alkyne halogen, and finally polysubstituted olefin (formula I) is formed by a strategy of hydrocarbon bond activation under the promotion of amide, wherein the reaction equation is as follows:
wherein Ar is benzene ring, condensed ring, heterocycle, biaryl ring containing different substituents, R is alkyl, R 1 、R 2 Are alkyl or aryl groups, and n is 0 or 1.
Preferably, the catalyst is used in an amount of 2mol% based on the amount of the amide compound (formula II).
Preferably, the catalyst is any one or combination of pentamethyl cyclopentadienyl rhodium chloride dimer, pentamethyl cyclopentadienyl iridium chloride dimer, palladium acetate, dichloro (p-cymene) ruthenium dimer, cobalt acetylacetonate and manganese pentacarbonyl bromide.
Preferably, the oxidant is any one or more of silver acetate, silver carbonate, silver oxide and potassium persulfate.
Preferably, the additive is any one or combination of silver hexafluoroantimonate, silver bistrifluoro-methylsulfonyl imide, sodium bicarbonate, lithium acetate and lithium hydrogen phosphate dipotassium carbonate.
Preferably, the inert solvent is any one or more of 1, 2-dichloroethane, toluene, tetrahydrofuran, 1, 4-dioxane, ethylene glycol dimethyl ether, N' -dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, acetonitrile and ethanol.
Preferably, the reaction is carried out at 80 to 120 ℃; the reaction is carried out for 6 to 24 hours.
More preferably, the preparation method of the polysubstituted olefin comprises the following specific steps:
s1: 22.7mg of N-t-butylnaphthalene-1-carboxamide, 49.5mg of ((1- (bromoethynyl) cycloheptyl) oxy) (t-butyl) dimethylsilane, 1.2mg of pentamethylcyclopentadiene rhodium dichloride dimer, 1.9mg of silver triflimide, 14.8mg of lithium carbonate, 33.4mg of silver acetate and 1.0mL of 1, 2-dichloroethane are sequentially added to the reactor in air;
s2: reacting the reaction solution at 100 ℃ for 12 hours;
s3: and separating the mixture by using a column chromatography separation technology after the reaction is finished to obtain the target compound.
More preferably, the developing agent or eluent selected in the column chromatography separation technique is petroleum ether: ethyl acetate.
More preferably, the developing agent or eluent is petroleum ether: the dosage proportion of the ethyl acetate is 20:1.
compared with the prior art, the beneficial effect of this patent application is:
the preparation method of the polysubstituted olefin provided by the application is that the alkyne halogen firstly forms an alkenyl metal species in an inert solvent under the action of a metal catalyst, and finally the polysubstituted olefin is formed by a strategy of hydrocarbon bond activation under the promotion of amide. The preparation method has the characteristics of easily available raw materials, easy conversion and high-efficiency step economy; in addition, the preparation method utilizes the hydrocarbon bond activation promoted by the natural functional group amide to realize site selectivity and stereoselectivity to introduce alkenyl segments to construct polysubstituted olefin.
Drawings
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of a compound 1a prepared in example 1 of the present patent application;
FIG. 2 is a nuclear magnetic resonance carbon spectrum of compound 1a prepared in example 1 of the present patent application;
FIG. 3 is a nuclear magnetic resonance hydrogen spectrum of compound 1b prepared in example 2 of the present patent application;
FIG. 4 is a nuclear magnetic resonance carbon spectrum of compound 1b prepared in example 2 of the present patent application;
FIG. 5 is a nuclear magnetic resonance hydrogen spectrum of compound 1c prepared in example 3 of the present patent application;
FIG. 6 is a nuclear magnetic resonance carbon spectrum of compound 1c prepared in example 3 of the present patent application;
FIG. 7 is a nuclear magnetic resonance hydrogen spectrum of compound 1d prepared in example 4 of the present patent application;
FIG. 8 is a nuclear magnetic resonance carbon spectrum of compound 1d prepared in example 4 of the present patent application;
FIG. 9 is a nuclear magnetic resonance hydrogen spectrum of compound 1e prepared in example 5 of the present patent application;
FIG. 10 is a nuclear magnetic resonance carbon spectrum of compound 1e prepared in example 5 of the present patent application;
FIG. 11 is a nuclear magnetic resonance hydrogen spectrum of compound 1f prepared in example 6 of the present patent application;
FIG. 12 is a nuclear magnetic resonance carbon spectrum of compound 1f prepared in example 6 of the present patent application;
FIG. 13 is a hydrogen nuclear magnetic resonance spectrum of 1g of the compound prepared in example 7 of the present patent application;
FIG. 14 is a nuclear magnetic resonance carbon spectrum of 1g of the compound prepared in example 7 of the present patent application.
Detailed Description
Embodiments of the present application will be described in detail below with reference to examples, but it will be understood by those skilled in the art that the following examples are only for illustration of the present application and should not be construed as limiting the scope of the present application. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.
It should be noted that:
in this patent application, all the embodiments mentioned herein and the preferred methods of implementation can be combined with each other to form new solutions, if not specifically stated.
In this application, unless otherwise indicated, the various reactions or steps may be performed sequentially or sequentially. Preferably, the reaction processes herein are performed sequentially.
Unless otherwise defined, the technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In addition, any method or material similar or equivalent to those described may be used in the present application.
The application develops an alkenyl metal species generated by alkyne halogen for the first time, and then under the assistance of natural functional group amide, the alkyne halogen is activated through aromatic ring hydrocarbon bond, so that the site-selective and stereoselective introduction of polysubstituted olefin into amide molecules is realized. The transformation has the following characteristics: 1) The amide is taken as a natural functional group, and is taken as a guiding group and a reactant in the application, so that the high-site and stereoselective synthesis of the polysubstituted olefin is realized; 2) The products containing alkenyl fragments obtained in this application have excellent stereoselectivity and the olefins contain alkyl substitution of β -H, which is also difficult to achieve with classical metal catalyzed cross-coupling reactions.
The present application provides a process for the preparation of polysubstituted olefins. The preparation method comprises the following steps: under the condition of inert solvent, under the combined action of a catalyst and an oxidant, an alkenyl metal species is formed by alkyne halogen, and finally polysubstituted olefin (formula I) is formed by a strategy of hydrocarbon bond activation under the promotion of amide, wherein the reaction equation is as follows:
wherein Ar is benzene ring, condensed ring, heterocycle, biaryl ring containing different substituents, R is alkyl, R 1 、R 2 Are alkyl or aryl groups, and n is 0 or 1.
The method utilizes the ubiquitous amide functional groups in human production and life, alkyne halogen firstly forms an alkenyl metal species, finally, the polysubstituted olefin is formed by a strategy of hydrocarbon bond activation under the promotion of amide, the reaction has excellent regio-stereoselectivity, and the polysubstituted alkenyl skeleton can be introduced into an amide molecule through trans-ring hydrocarbon bond activation, and the method is compatible with alkenyl fragments containing beta-H. The conversion not only makes up the defect that the classical Heck reaction and the oxidized Heck reaction are difficult to be compatible with polysubstituted and beta-H-containing alkyl fragments; in view of the utility of amides and polysubstituted olefins, this conversion offers potential for new syntheses and applications of drugs, materials.
In the preparation method of the patent application, a possible specific reaction mechanism flow is as follows:
under the condition of inert solvent, alkyne halogen leaves a group with large steric hindrance under the promotion of alkali to generate alkynyl carbonium ion A, which can undergo a Meyer-Schuster rearrangement reaction to form a diallyl carbonium ion B, then generates C under the affinity attack of water, finally removes one hydrogen bromide to generate dienone, and the dienone removes carbon monoxide to generate alkenyl metal species E under the action of metal, and then carries out hydrocarbon bond activation under the promotion of amide to realize the synthesis of polysubstituted olefin. The method has the characteristics of easily obtained and easily converted guide groups, good step economy and quick construction of various polysubstituted olefins, and realizes the regional and stereoselective synthesis of the polysubstituted olefins; the specific reaction mechanism flow is as follows:
the preparation method in the patent application is characterized in that the alkyne halogen firstly forms an alkenyl metal species through hydrocarbon bond activation promoted by the amide of a natural functional group, and finally the polysubstituted olefin is formed through a strategy of hydrocarbon bond activation under the promotion of the amide.
In some preferred embodiments, the catalyst is present in an amount of 2 mole% of the amide compound (formula II).
In some more preferred embodiments, the catalyst is any one of pentamethyl cyclopentadienyl rhodium chloride dimer, pentamethyl cyclopentadienyl iridium chloride dimer, palladium acetate, dichloro (p-cymene) ruthenium dimer, cobalt acetylacetonate, manganese pentacarbonyl bromide, or a combination thereof.
In some preferred embodiments, the oxidizing agent is any one or more of silver acetate, silver carbonate, silver oxide, and potassium persulfate.
In some preferred embodiments, the additive is any one of silver hexafluoroantimonate, silver bistrifluoro-methylsulfonimide, sodium bicarbonate, lithium acetate, lithium carbonate dipotassium hydrogen phosphate, or a combination thereof.
In some preferred embodiments, the inert solvent is any one or more of 1, 2-dichloroethane, toluene, tetrahydrofuran, 1, 4-dioxane, ethylene glycol dimethyl ether, N' -dimethylacetamide, N-methylpyrrolidone, dimethylsulfoxide, acetonitrile, ethanol.
In some preferred embodiments, the reaction is carried out at 80 to 120 ℃; the reaction is carried out for 6 to 24 hours.
In some more preferred embodiments, the developing agent or eluent is petroleum ether: the dosage proportion of the ethyl acetate is 20:1.
next, a method for producing the polysubstituted olefin according to the present application will be described in detail with specific examples.
1. Preparation example
Example 1 preparation of N-tert-butyl-2-cycloheptylmethylene-1-naphthalimide (1 a)
N-t-butylnaphthalene-1-carboxamide 2a (22.7 mg,0.10 mmol), ((1- (bromoethynyl) cycloheptyl) oxy) (t-butyl) dimethylsilane 3a (49.5 mg,0.15 mmol) pentamethylcyclopentadiene rhodium dichloride dimer [ Cp ] RhCl was added sequentially to a 15mL Schlenk tube under an atmospheric air atmosphere 2 ] 2 (1.2 mg, 0.002mmol), silver triflimide (1.9 mg,0.005 mmol), lithium carbonate (14.8 mg,0.20 mmol), silver oxide (46.2 mg,0.20 mmol), 1, 2-dichloroethane (DCE, 1.0 mL) and at 100℃for 12 hours. The crude product was chromatographed on prepared silica gel plates, the developing agent or eluent selected being Petroleum Ether (PE): ethyl Acetate (EA) =20: 1, N-tert-butyl product was obtained in 69% yield-2-cycloheptylmethylene-1-naphthamide (1 a). The chemical reaction equation corresponding to this example is as follows:
the nuclear magnetic hydrogen spectrum and the carbon spectrum of the compound prepared in the example 1 are shown in fig. 1 and 2. As can be seen from fig. 1: 1 H NMR(400MHz,CDCl 3 ) Delta 7.95 (d, j=8.0 hz, 1H), 7.78 (t, j=10.0 hz, 2H), 7.52-7.43 (m, 2H), 7.37 (d, j=8.4 hz, 1H), 6.50 (s, 1H), 5.56 (s, 1H), 2.46-2.40 (m, 4H), 1.73-1.68 (m, 2H), 1.65-1.59 (m, 6H), 1.51 (s, 9H). As can be seen from fig. 2: 13 C NMR(100MHz,CDCl 3 ) Delta 169.0,147.1,134.7,132.9,132.0,130.2,128.2,127.9,127.7,126.9,125.8,125.2,123.4,100.1,52.2,43.1,38.2,31.4,29.9,29.3,29.2,29.1,27.4,22.2 molecular carbon spectrum peaks can be in one-to-one correspondence with target products, and the quantity is reasonable. As a result of combining the above nuclear magnetic resonance spectrum and the carbon spectrum, the product obtained in example 1 was N-t-butyl-2-cycloheptylmethylene-1-naphthylamide (1 a).
The N-t-butylnaphthalene-1-carboxamide 2a in this example contains an amide function which is ubiquitous in human production and life, and under the promotion of this amide function, a polysubstituted alkenyl fragment was introduced into the hydrocarbon bond of arylcarboxamide N-t-butylnaphthalene-1-carboxamide 2a by activation of the aromatic ring hydrocarbon bond, activation of the carbon-carbon triple bond in the alkyne halo ((1- (bromoethynyl) cycloheptyl) oxy) (t-butyl) dimethylsilane 3 a. The reaction has excellent regio-and stereoselectivity, can introduce a polysubstituted alkenyl skeleton into an amide molecule through trans-ring hydrocarbon bond activation, and is compatible with alkenyl fragments containing beta-H. The reaction in this example was carried out at 100℃for 12 hours under an atmospheric air atmosphere and then a simple subsequent treatment was carried out to give the final target product N-tert-butyl-2-cycloheptylmethylene-1-naphthamide (1 a) in good yield (69%).
The chemical conversion in the embodiment can quickly construct condensed ring type polysubstituted olefin, and can be applied to organic photoelectric materials.
EXAMPLE 2 preparation of N-tert-butyl-2-cycloheptylmethylene-6-methylbenzamide (1 b)
N-t-butyl-2-methylbenzamide 2b (19.1 mg,0.10 mmol), ((1- (bromoethynyl) cycloheptyl) oxy) (t-butyl) dimethylsilane 3b (49.5 mg,0.15 mmol) pentamethylcyclopentadiene rhodium dichloride dimer [ Cp ] RhCl was added sequentially to a 15mL Schlenk tube under an atmospheric pressure air atmosphere 2 ] 2 (1.2 mg, 0.002mmol), silver triflimide (1.9 mg,0.005 mmol), lithium carbonate (14.8 mg,0.20 mmol), silver acetate (33.4 mg,0.20 mmol), 1, 2-dichloroethane (DCE, 1.0 mL) were reacted at 100℃for 12 hours. The crude product was chromatographed on prepared silica gel plates, the developing agent or eluent selected being Petroleum Ether (PE): ethyl Acetate (EA) =20: 1, N-tert-butyl-2-cycloheptylmethylene-6-methylbenzamide (1 b) was obtained in 62% yield. The chemical reaction equation corresponding to this example is as follows:
the nuclear magnetic hydrogen spectrum and the carbon spectrum of the compound prepared in the example 2 are shown in fig. 3 and 4. As can be seen from fig. 3: 1 H NMR(400MHz,CDCl 3 ) Delta 7.17 (t, j=7.6 hz, 1H), 7.03 (t, j=6.8 hz, 2H), 6.31 (s, 1H), 5.36 (s, 1H), 2.37 (t, j=5.6 hz, 4H), 2.34 (s, 3H), 1.67-1.65 (m, 2H), 1.61-1.54 (m, 6H), 1.43 (s, 9H). Molecular hydrogen spectrum peaks can be in one-to-one correspondence with the target products, and the quantity is reasonable. As can be seen from fig. 4: 13 C NMR(100MHz,CDCl 3 ) Delta 169.4,146.2,138.0,135.3,134.5,128.1,128.0,126.9,123.2,51.8,38.1,31.3,29.9,29.3,29.0,27.4,19.1 molecular carbon spectrum peaks can be in one-to-one correspondence with target products, and the quantity is reasonable. As a result of combining the above nuclear magnetic resonance spectrum and the carbon spectrum, the product obtained in example 2 was N-t-butyl-2-cycloheptylmethylene-6-methylbenzamide (1 b).
The N-tert-butyl-2-methylbenzamide 2b in this example contains an amide functional group which is ubiquitous in human production and life, and a polysubstituted alkenyl fragment was introduced into the hydrocarbon bond of the arylcarboxamide N-tert-butyl-2-methylbenzamide 2b by activation of an aromatic ring hydrocarbon bond, activation of a carbon-carbon triple bond in the alkyne halo ((1- (bromoethynyl) cycloheptyl) oxy) (tert-butyl) dimethylsilane 3b, and the promotion of the amide functional group. The reaction has excellent regio-and stereoselectivity, can introduce a polysubstituted alkenyl skeleton into an amide molecule through trans-ring hydrocarbon bond activation, and is compatible with alkenyl fragments containing beta-H. The reaction in this example was carried out at 100℃for 12 hours under an atmospheric air atmosphere and then a simple subsequent treatment was carried out to give the final target product N-tert-butyl-2-cycloheptylmethylene-6-methylbenzamide (1 b) in good yield (62%).
The chemical transformations in this example may be applied to benzamide substrates, providing a platform for the construction of more complex polysubstituted olefin molecules.
EXAMPLE 3 preparation of N-tert-butyl-2-chloro-6-cycloheptylmethylene benzamide (1 c)
N-t-butyl-2-chlorobenzamide 2c (21.1 mg,0.10 mmol), ((1- (bromoethynyl) cycloheptyl) oxy) (t-butyl) dimethylsilane 3c (49.5 mg,0.15 mmol) pentamethylcyclopentadiene rhodium dichloride dimer [ Cp ] RhCl was added sequentially to a 15mL Schlenk tube under an atmospheric pressure atmosphere 2 ] 2 (1.2 mg, 0.002mmol), silver triflimide (1.9 mg,0.005 mmol), lithium carbonate (14.8 mg,0.20 mmol), silver acetate (33.4 mg,0.20 mmol), 1, 2-dichloroethane (DCE, 1.0 mL) were reacted at 100℃for 12 hours. The crude product was chromatographed on prepared silica gel plates, the developing agent or eluent selected being Petroleum Ether (PE): ethyl Acetate (EA) =20: 1, N-tert-butyl-2-chloro-6-cycloheptylmethylene benzamide (1 c) was obtained in 62% yield. The chemical reaction equation corresponding to this example is as follows:
the nuclear magnetic hydrogen spectrum and the carbon spectrum of the compound prepared in example 3 are shown in fig. 5 and 6. As can be seen from fig. 5: 1 H NMR(400MHz,CDCl 3 ) Delta 7.20 (d, j=4.4 hz, 2H), 7.12 (t, j=4.4 hz, 1H), 6.32 (s, 1H), 5.23 (s, 1H), 2.39-2.34 (m, 4H), 2.10 (s, 9H), 1.67-1.64 (m, 2H), 1.60-1.52 (m, 6H). Molecular hydrogenThe spectrum peaks can be in one-to-one correspondence with the target products, and the quantity is reasonable. As can be seen from fig. 6: 13 C NMR(100MHz,CDCl 3 ) Delta 166.0,147.7,137.7,137.2,130.7,129.1,127.9,127.1,122.2,52.9,41.7,38.1,36.5,31.3,29.8,29.6,29.2,27.4 molecular carbon spectrum peaks can be in one-to-one correspondence with target products, and the quantity is reasonable. As a result of combining the above nuclear magnetic resonance spectrum and the carbon spectrum, the product obtained in example 3 was N-t-butyl-2-chloro-6-cycloheptylmethylene benzamide (1 c).
The N-tert-butyl-2-chlorobenzamide 2c in this example contains an amide functional group which is ubiquitous in human production and life, and under the promotion of the amide functional group, polysubstituted alkenyl fragments are introduced into the hydrocarbon bond of the N-tert-butyl-2-chlorobenzamide 2c through activation of an aromatic ring hydrocarbon bond and activation of a carbon-carbon triple bond in alkyne halogen ((1- (bromoethynyl) cycloheptyl) oxy) (tert-butyl) dimethylsilane 3 c. The reaction has excellent regio-and stereoselectivity, can introduce a polysubstituted alkenyl skeleton into an amide molecule through trans-ring hydrocarbon bond activation, and is compatible with alkenyl fragments containing beta-H. The reaction in this example was carried out at 100℃for 12 hours under an atmospheric air atmosphere and then a simple subsequent treatment was carried out to give the final target product N-tert-butyl-2-chloro-6-cycloheptylmethylene benzamide (1 c) in good yield (62%).
This example is compatible with halogen-chlorine functionality to facilitate subsequent transformations such as metal catalyzed coupling reactions, including Suziki reactions, buchwald-Hartwig couplings, and the like, to build complex molecules.
EXAMPLE 4 preparation of N-tert-butyl-2, 2-diphenylvinyl- [1,1' -biphenyl ] -2-carboxamide (1 d)
N-tert-butyl- [1,1' -biphenyl was added sequentially to a 15mL Schlenk tube under an atmospheric air atmosphere]-2-carboxamide 2d (25.3 mg,0.10 mmol), ((3-bromo-1, 1-diphenylprop-2-yn-1-yl) oxy) (tert-butyl) dimethylsilane 3d (60.4 mg,0.15 mmol), pentamethylcyclopentadiene rhodium dichloride dimer [ Cp ] 2 ] 2 (1.2 mg,0.002 mmol), silver triflimide (1.9 mg,0.005 mmol), lithium carbonate (14.8 mg,0.20 mmol), silver acetate (33.4 mg,0.20 mmol), N, N' -dimethylformamide (DMF, 1.0 mL),the reaction was carried out at 100℃for 12 hours. The crude product was chromatographed on prepared silica gel plates, the developing agent or eluent selected being Petroleum Ether (PE): ethyl Acetate (EA) =20: 1, N-tert-butyl-2, 2-diphenylvinyl- [1,1' -biphenyl was obtained as the product in 65% yield]-2-carboxamide (1 d). The chemical reaction equation corresponding to this example is as follows:
the nuclear magnetic hydrogen spectrum and the carbon spectrum of the compound prepared in example 4 are shown in fig. 7 and 8. As can be seen from fig. 7: 1 H NMR(400MHz,CDCl 3 ) Delta 7.47 (d, j=6.8 hz, 2H), 7.40-7.28 (m, 11H), 7.24-7.22 (m, 2H), 7.17 (s, 1H), 7.11 (d, j=7.6 hz, 1H), 7.03 (t, j=7.6 hz, 1H), 6.85 (d, j=8.0 hz, 1H), 5.10 (s, 1H), 1.09 (s, 9H) molecular hydrogen spectrum peaks can be in one-to-one correspondence with the target product, and the quantity is reasonable. As can be seen from fig. 8: 13 C NMR(100MHz,CDCl 3 ) Delta 168.6,144.1,143.2,140.5,140.3,139.1,138.1,135.6,130.7,129.0,128.9,128.5,128.4,128.3,128.2,128.0,127.9,127.7,127.5,125.6,51.6,28.4 molecular carbon spectrum peaks can be in one-to-one correspondence with target products, and the quantity is reasonable. As a result of combining the above nuclear magnetic resonance spectrum and carbon spectrum, the product obtained in example 4 was N-t-butyl-2, 2-diphenylvinyl- [1,1' -biphenyl]-2-carboxamide (1 d).
The N-tert-butyl- [1,1 '-biphenyl ] -2-carboxamide 2d in this example contains an amide function which is ubiquitous in human production and life, and the introduction of a polysubstituted alkenyl fragment to the hydrocarbon bond of N-tert-butyl- [1,1' -biphenyl ] -2-carboxamide 2d has been developed by activation of the carbon-carbon triple bond in alkyne halo ((3-bromo-1, 1-diphenylprop-2-yn-1-yl) oxy) (tert-butyl) dimethylsilane 3d under the promotion of this amide function. The reaction has excellent regio-and stereoselectivity, can introduce a polysubstituted alkenyl skeleton into an amide molecule through trans-ring hydrocarbon bond activation, and is compatible with alkenyl fragments containing beta-H. The reaction in this example was carried out at 100℃for 12 hours under atmospheric air atmosphere and then a simple subsequent treatment was carried out to give the final target product N-tert-butyl-2, 2-diphenylvinyl- [1,1' -biphenyl ] -2-carboxamide (1 d) in good yield (65%).
The embodiment can be compatible with alkynyl reagents with large steric hindrance, and provides thought for quickly constructing polyaromatic compounds and olefins with large steric hindrance. In addition, the conversion is via a macrocyclic metallation intermediate, effecting a trans-cyclic hydrocarbon bond oxyalkenyl reaction.
EXAMPLE 5 preparation of N-tert-butyl-2 '-cycloheptylmethylene- [1,1' -biphenyl ] -2-carboxamide (1 e)
N-tert-butyl- [1,1' -biphenyl was added sequentially to a 15mL Schlenk tube under an atmospheric air atmosphere]-2-carboxamide 2e (25.3 mg,0.10 mmol), ((1- (bromoethynyl) cycloheptyl) oxy) (tert-butyl) dimethylsilane 3e (49.5 mg,0.15 mmol), pentamethylcyclopentadiene rhodium dichloride dimer [ Cp ] RhCl 2 ] 2 (1.2 mg, 0.002mmol), silver triflimide (1.9 mg,0.005 mmol), lithium carbonate (14.8 mg,0.20 mmol), silver acetate (33.4 mg,0.20 mmol), 1, 2-dichloroethane (DCE, 1.0 mL) were reacted at 100℃for 12 hours. The crude product was chromatographed on prepared silica gel plates, the developing agent or eluent selected being Petroleum Ether (PE): ethyl Acetate (EA) =20: 1, N-tert-butyl-2 '-cycloheptylmethylene- [1,1' -biphenyl ] as a product in 68% yield]-2-carboxamide (1 e). The chemical reaction equation corresponding to this example is as follows:
the nuclear magnetic hydrogen spectrum and the carbon spectrum of the compound prepared in example 5 are shown in fig. 9 and 10. As can be seen from fig. 9: 1H NMR (400 MHz, CDCl 3) delta 7.49-7.46 (m, 2H), 7.39-7.32 (m, 4H), 7.24-7.19 (m, 2H), 6.45 (s, 1H), 5.05 (s, 1H), 2.42-2.37 (m, 4H), 1.68-1.62 (m, 4H), 1.59-1.52 (m, 4H), 1.12 (s, 9H) molecular hydrogen spectrum peaks can be in one-to-one correspondence with the target products, and the quantity is reasonable. As can be seen from fig. 10: 13C NMR (100 MHz, CDCl 3) delta 168.6,146.4,140.7,139.2,137.3,136.4,129.0,128.7,128.2,128.2,127.6,127.4,123.3,51.5,44.6,38.1,31.3,29.9,29.4,29.2,28.5,27.5 molecular carbon spectrum peaks can be in one-to-one correspondence with target products, and the quantity is reasonable. As a result of combining the above nuclear magnetic resonance spectrum and the carbon spectrum, the product obtained in example 5 was N-t-butyl-2 '-cycloheptylmethylene- [1,1' -biphenyl ] -2-carboxamide (1 e).
The N-tert-butyl- [1,1 '-biphenyl ] -2-carboxamide 2e in this example contains an amide function which is ubiquitous in human production and life, and under the promotion of this amide function, a polysubstituted alkenyl fragment was introduced into the hydrocarbon bond of N-tert-butyl- [1,1' -biphenyl ] -2-carboxamide 2e by activation of the carbon-carbon triple bond in the aromatic ring hydrocarbon bond activated alkyne halogen ((1- (bromoethynyl) cycloheptyl) oxy) (tert-butyl) dimethylsilane 3 e. The reaction has excellent regio-and stereoselectivity, can introduce a polysubstituted alkenyl skeleton into an amide molecule through trans-ring hydrocarbon bond activation, and is compatible with alkenyl fragments containing beta-H. The reaction in this example was carried out at 100℃for 12 hours under atmospheric air atmosphere and then a simple subsequent treatment was carried out to give the final target product N-tert-butyl-2 '-cycloheptylmethylene- [1,1' -biphenyl ] -2-carboxamide (1 e) in good yield (68%).
The embodiment can be modified at different sites of the o-benzene to realize the activation reaction of the trans-ring hydrocarbon bond, thereby providing a platform for constructing more complex polysubstituted olefin molecules.
EXAMPLE 6 preparation of N-tert-butyl-2- (3- (cycloheptylmethylene) thiophen-2-yl) acetamide (1 f)
N-tert-butyl-2-thiophen-2-ylacetamide 2f (19.7 mg,0.10 mmol), ((1- (bromoethynyl) cyclohepta) oxy) (tert-butyl) dimethylsilane 3f (49.5 mg,0.15 mmol) pentamethylcyclopentadiene rhodium dichloride dimer [ Cp ] RhCl was added sequentially to a 15mL Schlenk tube under an atmospheric air atmosphere 2 ] 2 (3.0 mg,0.005 mmol), silver triflimide (3.8 mg, 0.010mmol), lithium carbonate (14.8 mg,0.20 mmol), silver acetate (33.4 mg,0.25 mmol), 1, 2-dichloroethane (DCE, 1.0 mL) and reacted at 100℃for 12 hours. The crude product was chromatographed on prepared silica gel plates, the developing agent or eluent selected being Petroleum Ether (PE): ethyl Acetate (EA) =20: 1, N-tert-butyl-2- (3- (cycloheptylmethylene) thiophen-2-yl) acetamide (1 f) was obtained in a yield of 56%. The chemical reaction equation corresponding to this example is as follows:
the nuclear magnetic hydrogen spectrum and the carbon spectrum of the compound prepared in example 6 are shown in fig. 11 and 12. As can be seen from fig. 11: 1 H NMR(400MHz,CDCl 3 ) Delta 7.17 (d, j=5.2 hz, 1H), 7.03 (d, j=5.2 hz, 1H), 6.03 (s, 1H), 5.33 (s, 1H), 3.60 (s, 2H), 2.40-2.37 (m, 4H), 1.67-1.63 (m, 6H), 1.56-1.55 (m, 2H), 1.25 (s, 9H). Molecular hydrogen spectrum peaks can be in one-to-one correspondence with target products, and the quantity is reasonable. As can be seen from fig. 12: 13 C NMR(100MHz,CDCl 3 ) Delta 169.1,146.8,137.6,131.5,129.2,123.4,117.7,51.3,38.4,37.2,31.9,29.7,29.6,29.2,28.7,27.3 molecular carbon spectrum peaks can be in one-to-one correspondence with target products, and the quantity is reasonable. As a result of combining the above nuclear magnetic resonance spectrum and the carbon spectrum, the product obtained in example 6 was N-t-butyl-2- (3- (cycloheptylmethylene) thiophen-2-yl) acetamide (1 f).
The N-tert-butyl-2-thiophen-2-ylacetamide 2f in this example contains an amide functional group which is ubiquitous in the production and life of humans, and under the promotion of this amide functional group, a polysubstituted alkenyl fragment was introduced into the hydrocarbon bond of N-tert-butyl-2-thiophen-2-ylacetamide 2f by activation of an aromatic ring hydrocarbon bond and activation of a carbon-carbon triple bond in alkyne halogen ((1- (bromoethynyl) cycloheptyl) oxy) (tert-butyl) dimethylsilane 3 f. The reaction has excellent regio-and stereoselectivity, can introduce a polysubstituted alkenyl skeleton into an amide molecule through trans-ring hydrocarbon bond activation, and is compatible with alkenyl fragments containing beta-H. The reaction in this example was carried out at 100℃for 12 hours under atmospheric air atmosphere and then a simple subsequent treatment was carried out to give the final target product N-tert-butyl-2- (3- (cycloheptylmethylene) thiophen-2-yl) acetamide (1 f) in good yield (56%).
The chemical conversion in the embodiment can be compatible with heterocyclic acetamides substrates, and has extremely wide substrate practicability, so that a platform is provided for constructing more complex polysubstituted olefin molecules.
EXAMPLE 7 preparation of N-adamantan-1-yl-2 '-cycloheptylmethylene- [1,1' -biphenyl ] -2-carboxamide (1 g)
N-adamantan-1-yl adamantan- [1,1' -biphenyl ] was sequentially introduced into a 15mL Schlenk tube under an atmospheric air atmosphere]2-carboxamide 2g (33.1 mg,0.10 mmol), ((1- (bromoethynyl) cycloheptyl) oxy) (tert-butyl) dimethylsilane 3g (49.5 mg,0.15 mmol), pentamethylcyclopentadiene rhodium dichloride dimer [ Cp ] RhCl 2 ] 2 (3.0 mg,0.005 mmol), silver triflimide (3.8 mg,0.01 mmol), lithium carbonate (14.8 mg,0.20 mmol), silver oxide (58.7 mg,0.25 mmol), 1, 2-dichloroethane (DCE, 1.0 mL) and reacted at 100℃for 12 hours. The crude product was chromatographed on prepared silica gel plates, the developing agent or eluent selected being Petroleum Ether (PE): ethyl Acetate (EA) =20: 1, N-adamantan-1-yl-2 '-cycloheptylmethylene- [1,1' -biphenyl ] as a product in a yield of 66%]-2-carboxamide (1 g). The chemical reaction equation corresponding to this example is as follows:
the nuclear magnetic hydrogen spectrum and the carbon spectrum of the compound prepared in example 7 are shown in fig. 13 and 14. As can be seen from fig. 13: 1 H NMR(400MHz,CDCl 3 ) Delta 7.49 (d, j=6.8 hz, 2H), 7.40-7.31 (m, 4H), 7.21 (dd, j=12.8, 7.6hz, 2H), 6.46 (s, 1H), 4.93 (s, 1H), 2.43-2.39 (m, 4H), 1.97 (s, 3H), 1.76 (d, j=2.0 hz, 6H), 1.69-1.64 (m, 6H), 1.59 (s, 6H), 1.55 (d, j=8.8 hz, 2H). As can be seen from fig. 14: 13 C NMR(100MHz,CDCl 3 ) Delta 168.3,146.3,140.7,139.1,137.4,136.3,129.0,128.6,128.2,128.1,127.7,127.4,123.4,52.2,41.4,38.1,36.4,31.3,29.9,29.5,29.4,29.2,27.5 molecular carbon spectrum peaks can be in one-to-one correspondence with target products, and the quantity is reasonable. As a result of combining the above nuclear magnetic resonance spectrum and carbon spectrum, it is understood that the product obtained in example 7 is N-adamantan-1-yl-2 '-cycloheptylmethylene- [1,1' -biphenyl]-2-carboxamide (1 g).
2g of N-adamantan-1-yl adamantan- [1,1 '-biphenyl ] -2-carboxamide in this example contains an amide functional group which is ubiquitous in the production and life of humans, and a polysubstituted alkenyl fragment was introduced into 2g of N-adamantan-1-yl-adamantan- [1,1' -biphenyl ] -2-carboxamide by activation of an aromatic ring hydrocarbon bond, activation of a carbon-carbon triple bond in 3g of alkyne halo ((1- (bromoethynyl) cycloheptyl) oxy) (tert-butyl) dimethylsilane, and promotion of the amide functional group. The reaction has excellent regio-and stereoselectivity, can introduce a polysubstituted alkenyl skeleton into an amide molecule through trans-ring hydrocarbon bond activation, and is compatible with alkenyl fragments containing beta-H. The reaction in this example was carried out at 100℃for 12 hours under atmospheric air atmosphere and then a simple subsequent treatment was carried out to give the final target product N-adamantan-1-yl-2 '-cycloheptylmethylene- [1,1' -biphenyl ] -2-carboxamide (1 g) in good yield (66%).
The chemical transformations in this example are compatible with highly sterically hindered adamantyl groups, providing a platform for the construction of more complex, more sterically hindered polysubstituted olefin molecules.
In summary, the present application provides a process for the preparation of polysubstituted olefins. The preparation method comprises the following steps: under the condition of inert solvent, the amide compound (formula II) and the alkyne bromide compound (formula III) form polysubstituted olefin (formula I) through the strategy of forming a cyclometallated intermediate, breaking an alkynyl carbon-carbon triple bond and serving as an alkenyl synthon under the combined action of a catalyst and an oxidant, and the reaction equation is as follows:
wherein Ar is benzene ring, condensed ring, heterocycle, biaryl ring containing different substituents, R is alkyl, R 1 、R 2 Are alkyl or aryl groups, and n is 0 or 1.
The application develops an alkynyl carbon-carbon triple bond of alkyne halogen for the first time, breaks and is used as an alkenyl synthon, and under the assistance of natural functional group amide, polysubstituted olefin is introduced into amide molecules in a site-selective and stereoselective manner through activation of aromatic ring hydrocarbon bonds. The transformation has the following characteristics: 1) The amide is taken as a natural functional group, and is taken as a guiding group and a reactant in the application, so that the high-site and stereoselective synthesis of the polysubstituted olefin is realized; 2) The products containing alkenyl fragments obtained in this application have excellent stereoselectivity and the olefins contain alkyl substitution of β -H, which is also difficult to achieve with classical metal catalyzed cross-coupling reactions.
The application develops the introduction of polysubstituted alkenyl fragments into aryl formamide and acetamide hydrocarbon bonds through the activation of aromatic ring hydrocarbon bonds and the activation of alkyne halocarbon-carbon triple bonds under the promotion of ubiquitous amide functional groups in human production and life. The reaction has excellent regio-and stereoselectivity, can introduce a polysubstituted alkenyl skeleton into an amide molecule through trans-ring hydrocarbon bond activation, and is compatible with alkenyl fragments containing beta-H. The conversion not only makes up the defect that the classical Heck reaction and the oxidized Heck reaction are difficult to be compatible with polysubstituted and beta-H-containing alkyl fragments; in view of the utility of amides and polysubstituted olefins, this conversion offers potential for new syntheses and applications of drugs, materials.
In the description of the present specification, reference to the terms "one embodiment," "some embodiments," "illustrative embodiments," "examples," "specific examples," or "some examples," etc., means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the present patent application. In this specification, schematic representations of the above terms do not necessarily refer to the same embodiments or examples. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.
While several embodiments of the present patent application have been shown and described, it will be understood by those of ordinary skill in the art that: many changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the application, the scope of which is defined by the claims and their equivalents.

Claims (10)

1. A process for the preparation of a polysubstituted olefin, comprising the steps of: under the condition of inert solvent, under the combined action of a catalyst and an oxidant, an alkenyl metal species is formed by alkyne halogen, and finally polysubstituted olefin (formula I) is formed by a strategy of hydrocarbon bond activation under the promotion of amide, wherein the reaction equation is as follows:
wherein Ar is benzene ring, condensed ring, heterocycle, biaryl ring containing different substituents, R is alkyl, R 1 、R 2 Are alkyl or aryl groups, and n is 0 or 1.
2. The process for producing a polysubstituted olefin according to claim 1, wherein: the catalyst was used in an amount of 2mol% based on the amount of the amide compound (formula II).
3. The process for producing a polysubstituted olefin according to claim 2, wherein: the catalyst is any one or combination of pentamethyl cyclopentadienyl rhodium chloride dimer, pentamethyl cyclopentadienyl iridium chloride dimer, palladium acetate, dichloro (p-cymene) ruthenium dimer, cobalt acetylacetonate and pentacarbonyl manganese bromide.
4. The process for producing a polysubstituted olefin according to claim 1, wherein: the oxidant is any one or more of silver acetate, silver carbonate, silver oxide and potassium persulfate.
5. The process for producing a polysubstituted olefin according to claim 1, wherein: the additive is any one or combination of silver hexafluoroantimonate, silver bistrifluoro methanesulfonimide, sodium bicarbonate, lithium acetate and lithium carbonate dipotassium hydrogen phosphate.
6. The process for producing a polysubstituted olefin according to claim 1, wherein: the inert solvent is any one or more of 1, 2-dichloroethane, toluene, tetrahydrofuran, 1, 4-dioxane, ethylene glycol dimethyl ether, N' -dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, acetonitrile and ethanol.
7. The process for producing a polysubstituted olefin according to claim 1, wherein: the reaction is carried out at 80-120 ℃; the reaction is carried out for 6 to 24 hours.
8. The process for the preparation of polysubstituted olefins according to claim 1, characterized in that it comprises the following specific steps:
s1: 22.7mg of N-t-butylnaphthalene-1-carboxamide, 49.5mg of ((1- (bromoethynyl) cycloheptyl) oxy) (t-butyl) dimethylsilane, 1.2mg of pentamethylcyclopentadiene rhodium dichloride dimer, 1.9mg of silver triflimide, 14.8mg of lithium carbonate, 33.4mg of silver acetate and 1.0mL of 1, 2-dichloroethane are sequentially added to the reactor in air;
s2: reacting the reaction solution at 100 ℃ for 12 hours;
s3: and separating the mixture by using a column chromatography separation technology after the reaction is finished to obtain the target compound.
9. The process for producing a polysubstituted olefin according to claim 8, wherein: the developing agent or the eluent selected in the column chromatography separation technology is petroleum ether: ethyl acetate.
10. The process for the preparation of a polysubstituted olefin according to claim 9, characterized in that: the developing agent or the eluent is petroleum ether: the dosage proportion of the ethyl acetate is 20:1.
CN202311113102.XA 2023-08-30 2023-08-30 Preparation method of polysubstituted olefin Pending CN117362190A (en)

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