CN107602320B - Synthesis method for preparing tri-substituted olefin based on nickel catalysis - Google Patents
Synthesis method for preparing tri-substituted olefin based on nickel catalysis Download PDFInfo
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Abstract
The invention discloses a synthesis method for preparing tri-substituted olefin based on nickel catalysis, which takes alkyl halide compound and intramolecular alkyne as raw materials, and reacts in a solvent according to the following reaction formula under the action of nickel catalyst, ligand, alkali and silane to obtain the tri-substituted olefin compound with single configuration. The tri-substituted olefin synthesized by the method has high regioselectivity and stereoselectivity, can completely obtain the tri-substituted olefin with a single configuration, and solves the separation problem of the obtained mixed olefin product. Meanwhile, the reaction system has a simple feeding mode, does not need to use a metal reagent sensitive to moisture and air, and is more convenient in actual use. The alkyl halide compound can be directly synthesized from alkyl alcohol, and the alkyne in the molecule has wide source and is easy to obtain. The reaction condition is mild, some groups sensitive to alkali can be well compatible, and the functional group compatibility is excellent.
Description
Technical Field
The invention relates to the technical field of compound substance preparation, in particular to a synthetic method of a single-configuration tri-substituted olefin compound.
Background
Olefins are an important structural segment in organic chemistry and are widely used in the industries of materials, petrochemical industry, medicine and the like. Research on olefin synthesis methods has been the focus of attention, and conventional synthesis methods include elimination reaction, reduction reaction, Wittig reaction, Julia olefination reaction, and the like. The reactions generally have the defects of harsh reaction conditions, high reaction temperature, need of using stronger alkali in a reaction system, and the most important point is that the cis-trans selectivity of the synthesized olefin is not high, so that the product is difficult to separate, and the like.
In addition to the above non-metal catalyzed methods of olefin synthesis, a number of transition metal catalyzed synthetic methods have been reported in recent years, such as Heck reactions, olefin metathesis reactions, and cross-coupling reactions involving alkenyl metal reagents or alkenyl halides. These reactions also have the disadvantages of limited substrate range, low cis-trans selectivity of the synthesized olefin, difficult product separation, and difficult synthesis of single-configuration alkenyl metal reagents or alkenyl halides.
Recently, methods for synthesizing olefins by the hydro-carbonization reaction of a transition metal catalyzed alkyne and an electrophile have been sought. The method has the advantages of easily available raw material sources, mild reaction conditions and high efficiency of obtaining the olefin with single configuration by controlling the reaction region and stereoselectivity. Avoiding the need for further separation to obtain a mixed olefin product. Prior work on alkyne hydro-carbonation reactions has dominated by pi-type electrophiles, such as CO2The method described in formula (1) is a method for synthesizing disubstituted alkenes by copper-catalyzed coupling of terminal alkynes and primary alkyl mesylates as reported by Lalic et al in J.Am.chem.Soc.2015,137,1424-1427, and the method described in formula (2) is a method for synthesizing disubstituted alkenes by iron-catalyzed coupling of aryl acetylenes and alkyl electrophiles as reported by Hu et al in J.Am.chem.Soc.2015,137, 4932-4935.
Formula (3) is a method for synthesizing 1, 1-disubstituted alkene by nickel-catalyzed mah-selective hydrogen-alkylation reaction of alkyne and alkyl electrophilic reagent reported by Friedel. The formula (4) is a copper-catalyzed aryl acetylene hydrogen-alkylated cis-and trans-olefin disubstituted olefin synthesis method reported by Nishikata group in ACS Catalysis 2017,7, 1049-1052.
Although there have been several reports of transition metal catalyzed alkyne hydro-alkylation reactions in recent years, the previous work clearly shows that the substrate is only suitable for terminal alkynes, and that no product is obtained by using intramolecular alkynes as raw materials under the same reaction conditions, so the reports can only be used for synthesizing disubstituted alkenes. The tri-substituted olefin has great demand in the material, petrochemical and pharmaceutical industries, at present, the Wittig reaction and the carbon-carbon bond cross coupling reaction participated by the tri-substituted alkenyl metal reagent catalyzed by the transition metal or the tri-substituted alkenyl halide are generally used for synthesizing the tri-substituted olefin, but the defects are that the cis-trans selectivity of the product is not high, the separation is difficult, the synthesis of the tri-substituted alkenyl synthon with single configuration is difficult, the source of the raw material is limited, and the functional groups are compatible. Therefore, the synthesis of trisubstituted olefins of a single configuration with high regio-stereoselectivity has always been a challenge in chemical synthesis.
Disclosure of Invention
Aiming at the problems of low cis-trans ratio and difficult separation of products caused by limited raw material sources, difficult synthesis, harsh reaction conditions, low reaction area and stereoselectivity in the synthesis of tri-substituted olefin, the invention provides a nickel-based catalytic synthesis method for preparing tri-substituted olefin, which has the advantages of simple reaction use of a nickel catalyst, wide raw material sources, mild reaction conditions and good functional group compatibility.
In order to solve the technical problems, the invention adopts the following technical scheme: a synthetic method for preparing tri-substituted olefin based on nickel catalysis is characterized by comprising the following steps: taking an alkyl halide compound and intramolecular alkyne as raw materials, and reacting in a solvent according to the following reaction formula under the action of a nickel catalyst, a ligand, alkali and silane to obtain a tri-substituted alkene compound with a single configuration in a general formula (I):
wherein R is1、R2Are the same or different alkyl or aryl substituents; r3、R4Are different alkyl substituents or cyclic substituents;
the nickel catalyst is a nickel (II) bromide diethylene glycol dimethyl ether compound;
the ligand is one of 4,4 '-di-tert-butyl-2, 2' -bipyridine, phenanthroline ligands, tri-tert-butyl bipyridine and dicyclohexyl phenylphosphonium;
the solvent is one or a mixture of more than two of dioxane, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone and methyl tert-butyl ether;
the silane is one of polymethylhydrosilane, phenylsilane, trimethoxysilane and methyldiethoxysilane.
Preferably, the base is one of cesium carbonate, sodium acetate, cesium fluoride, lithium methoxide, and potassium carbonate.
Preferably, the amount of the substance of intramolecular alkyne is 2 times the amount of the alkyl halide substance.
Preferably, the amount of the material of the nickel catalyst is 12% of the amount of the material of the alkyl halide.
Preferably, the amount of the substance of the ligand is 12% of the amount of the substance of the alkyl halide.
Preferably, the amount of the substance of the silane is 3 times the amount of the substance of the alkyl halide.
Preferably, the reaction temperature in the solvent is 30 ℃ and the reaction time is 4-10 h.
Compared with the existing technology for synthesizing the tri-substituted olefin, the tri-substituted olefin synthesized by the method has high regioselectivity and stereoselectivity, can completely obtain the tri-substituted olefin with a single configuration, and solves the problem of separation of the obtained mixed olefin product. Meanwhile, the reaction system has a simple feeding mode, does not need to use a metal reagent sensitive to moisture and air, and is more convenient in actual use. The alkyl halide compound can be directly synthesized from alkyl alcohol, and the alkyne in the molecule has wide source and is easy to obtain.
In addition, the reaction system has mild reaction conditions, can be well compatible with some groups sensitive to alkali, is difficult to realize in the prior reaction system, has excellent functional group compatibility, and provides an efficient preparation method for tri-substituted olefin with a single configuration.
Drawings
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of a tri-substituted olefin 1 prepared according to the present invention;
FIG. 2 shows the NMR spectrum of tri-substituted olefin 1 prepared according to the invention
FIG. 3 is a NMR spectrum of trisubstituted olefin 2 prepared according to the present invention;
FIG. 4 is a NMR carbon spectrum of trisubstituted olefin 2 prepared according to the present invention;
FIG. 5 is a NMR spectrum of tri-substituted olefin 3 prepared according to the present invention;
FIG. 6 shows the NMR carbon spectrum of tri-substituted olefin 3 prepared according to the present invention
FIG. 7 is a NMR spectrum of tri-substituted olefin 4 prepared according to the present invention;
FIG. 8 is a NMR carbon spectrum of tri-substituted olefin 4 prepared according to the present invention;
FIG. 9 is a NMR spectrum of tri-substituted olefin 5 prepared according to the present invention;
FIG. 10 shows NMR spectra of trisubstituted olefin 5 prepared according to the invention
FIG. 11 is a NMR carbon spectrum of tri-substituted olefin 5 prepared according to the present invention;
FIG. 12 is a NMR spectrum of trisubstituted olefin 6 prepared according to the present invention;
FIG. 13 is a NMR carbon spectrum of trisubstituted olefin 6 prepared according to the present invention;
FIG. 14 shows NMR spectra of tri-substituted olefin 7 prepared according to the present invention
FIG. 15 is a NMR carbon spectrum of trisubstituted olefin 7 prepared according to the present invention;
FIG. 16 is a NMR spectrum of tri-substituted olefin 8 prepared according to the present invention;
FIG. 17 is a NMR carbon spectrum of tri-substituted olefin 8 prepared according to the present invention
FIG. 18 is a NMR spectrum of trisubstituted olefin 9 prepared according to the present invention;
FIG. 19 is a NMR carbon spectrum of trisubstituted olefin 9 prepared according to the present invention;
FIG. 20 is a NMR spectrum of tri-substituted olefin 10 prepared according to the present invention;
FIG. 21 is a NMR carbon spectrum of tri-substituted olefin 10 prepared according to the present invention
FIG. 22 is a NMR spectrum of a tri-substituted olefin 11 prepared according to the present invention;
FIG. 23 is a NMR carbon spectrum of a tri-substituted olefin 11 prepared in accordance with the present invention;
FIG. 24 shows NMR spectra of tri-substituted olefin 12 prepared according to the present invention
FIG. 25 is a nuclear magnetic resonance fluorine spectrum of a tri-substituted olefin 12 prepared in accordance with the present invention;
FIG. 26 is a NMR carbon spectrum of tri-substituted olefin 12 prepared according to the present invention;
FIG. 27 is a NMR spectrum of tri-substituted olefin 13 prepared according to the present invention;
FIG. 28 is a NMR carbon spectrum of tri-substituted olefin 13 prepared according to the present invention;
FIG. 29 is a NMR spectrum of tri-substituted olefin 14 prepared according to the present invention;
FIG. 30 is a NMR carbon spectrum of tri-substituted olefin 14 prepared according to the present invention;
FIG. 31 is a NMR spectrum of tri-substituted olefin 15 prepared according to the present invention;
FIG. 32 is a NMR carbon spectrum of tri-substituted olefin 15 prepared according to the present invention.
Detailed Description
The technical solution of the present invention is further explained by the following embodiments:
example 1, the reaction formula for this example is as follows:
(1) under the air, nickel (II) bromide-diethylene glycol dimethyl ether complex (12 mol%), 4,4 '-di-tert-butyl-2, 2' -bipyridine (12 mol%) and potassium carbonate (2.5eq) are added into a sealed reaction tube with branch tubes and containing magnetons, and the reaction tube is pumped with argon for three times. Under the protection of argon, 0.7mL of N, N-dimethylacetamide is added into a reaction tube, the mixture is stirred for 5 minutes at room temperature, then phenylpropyne (2eq), cyclohexyl iodide (0.2mmol) and methyldiethoxysilane (3eq) are sequentially added into the reaction solution under the protection of argon, a piston is plugged, and the mixture is placed in a 30 ℃ oil bath and stirred for reaction for 10 hours.
(2) Adding ethyl acetate into the material obtained in the step (1), fully mixing, filtering solid residues by using a short silica gel column, and keeping an organic phase.
(3) The solvent in the organic phase obtained in step (2) was spin-dried to obtain a crude product, which was then purified by a silica gel column. The eluent is petroleum ether, the separation yield is 81 percent, and the product purity is 100 percent.
Example 2
The reaction formula for this example is shown below:
(1) under the air, nickel (II) bromide-diethylene glycol dimethyl ether complex (12 mol%), 4,4 '-di-tert-butyl-2, 2' -bipyridine (12 mol%) and potassium carbonate (2.5eq) are added into a sealed reaction tube with branch tubes and containing magnetons, and the reaction tube is pumped with argon for three times. Under the protection of argon, 0.7mL of N, N-dimethylacetamide is added into a reaction tube, the mixture is stirred for 5 minutes at room temperature, then phenylpropyne (2eq), N- (2-iodopropyl) -N-methylaniline (0.2mmol) and methyldiethoxysilane (3eq) are added into the reaction solution in sequence under the protection of argon, a piston is plugged, and the mixture is placed in a 30 ℃ oil bath and stirred for reaction for 10 hours.
(2) Adding ethyl acetate into the material obtained in the step (1), fully mixing, filtering solid residues by using a short silica gel column, and keeping an organic phase.
(3) The solvent in the organic phase obtained in step (2) was spin-dried to obtain a crude product, which was then purified by a silica gel column. The eluent is petroleum ether: ethyl acetate 50:1, isolated in 77% yield and product purity 100%.
Example 3
The reaction formula for this example is shown below:
(1) under the air, nickel (II) bromide-diethylene glycol dimethyl ether complex (12 mol%), 4,4 '-di-tert-butyl-2, 2' -bipyridine (12 mol%) and potassium carbonate (2.5eq) are added into a sealed reaction tube with branch tubes and containing magnetons, and the reaction tube is pumped with argon for three times. Under the protection of argon, 0.7mL of N, N-dimethylacetamide is added into a reaction tube, the mixture is stirred for 5 minutes at room temperature, then 4-octyne (2eq), 3-iodo-1-p-toluenesulfonyl pyrrolidine (0.2mmol) and methyldiethoxysilane (3eq) are added into the reaction solution in sequence under the protection of argon, a piston is plugged, and the mixture is placed in a 30 ℃ oil bath and stirred for reaction for 10 hours.
(2) Adding ethyl acetate into the material obtained in the step (1), fully mixing, filtering solid residues by using a short silica gel column, and keeping an organic phase.
(3) The solvent in the organic phase obtained in step (2) was spin-dried to obtain a crude product, which was then purified by a silica gel column. The eluent is petroleum ether: ethyl acetate 15:1, isolated in 75% yield and product purity 100%.
The nmr spectrum 2 of the trisubstituted olefin prepared is shown in table 1.
TABLE 1
The amounts of the substances and the reaction conditions used were experimentally expanded as in the examples to show that the technical solution of the invention has good functional group compatibility, and the respective expanded reaction formulas are as follows:
the present invention has been described in detail, and it should be understood that the detailed description and specific examples, while indicating the preferred embodiment of the invention, are intended for purposes of illustration only and are not intended to limit the scope of the invention.
Claims (7)
1. A synthetic method for preparing tri-substituted olefin based on nickel catalysis is characterized by comprising the following steps: taking a substrate 2 and a substrate 1 as raw materials, and reacting in a solvent according to the following reaction formula under the action of a nickel catalyst, a ligand, alkali and silane to obtain a tri-substituted olefin compound with a single configuration of a general formula (I):
wherein R is1、R2Are the same or different alkyl or aryl substituents; r3、R4Are different alkyl substituents or cyclic substituents;
the nickel catalyst is a nickel (II) bromide diethylene glycol dimethyl ether compound;
the ligand is one of 4,4 '-di-tert-butyl-2, 2' -bipyridine, phenanthroline ligands, tri-tert-butyl bipyridine and dicyclohexyl phenylphosphonium;
the solvent is one or a mixture of more than two of dioxane, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone and methyl tert-butyl ether;
the silane is one of polymethylhydrosilane, phenylsilane, trimethoxysilane and methyldiethoxysilane.
2. The synthesis method for preparing tri-substituted olefin based on nickel catalysis as claimed in claim 1, wherein: the alkali is one of cesium carbonate, sodium acetate, cesium fluoride, lithium methoxide and potassium carbonate.
3. The synthesis method for preparing tri-substituted olefin based on nickel catalysis as claimed in claim 1, wherein: the amount of substance of the substrate 1 is 2 times the amount of substance of the substrate 2.
4. The synthesis method for preparing tri-substituted olefin based on nickel catalysis as claimed in claim 1, wherein: the amount of the material of the nickel catalyst was 12% of the amount of the material of the substrate 2.
5. The synthesis method for preparing tri-substituted olefin based on nickel catalysis as claimed in claim 1, wherein: the amount of substance of the ligand is 12% of the amount of substance of the substrate 2.
6. The synthesis method for preparing tri-substituted olefin based on nickel catalysis as claimed in claim 1, wherein: the amount of the substance of the silane is 3 times the amount of the substance of the substrate 2.
7. The synthesis method for preparing tri-substituted olefin based on nickel catalysis as claimed in claim 1, wherein: the reaction temperature in the solvent was 30 deg.CoAnd C, the reaction time is 4-10 h.
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| CN108658717B (en) * | 2018-06-08 | 2021-01-05 | 滁州学院 | Synthetic method for preparing tri-substituted olefin through decarboxylation reaction |
| CN109678673B (en) * | 2018-11-07 | 2021-10-22 | 滁州学院 | Synthetic method of aryl-substituted homoallyl alcohol |
| CN110330446A (en) * | 2019-07-21 | 2019-10-15 | 滁州学院 | A kind of preparation method of the unnatural amino acid of alkenyl containing γ or β alkenyl |
| CN113563224A (en) * | 2020-12-31 | 2021-10-29 | 滁州学院 | Synthesis method of tri-substituted olefin containing gamma-cyano |
| CN113831216B (en) * | 2021-10-15 | 2024-05-24 | 滁州学院 | Synthetic method for preparing monofluoroolefin by taking aldehyde compound as raw material |
| CN115819207B (en) * | 2022-11-24 | 2024-03-22 | 宁波工程学院 | Method for synthesizing 1, 1-disubstituted diene by nickel catalysis |
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| CN105315181A (en) * | 2015-09-22 | 2016-02-10 | 湖南大学 | Synthetic method for sulfo trisubstituted alkenes compound |
| CN105859495A (en) * | 2016-05-05 | 2016-08-17 | 陕西师范大学 | Acetyenic-ketone-promoted CuI-catalyzed method for conducting Sonogashira coupled reaction |
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| US20040097745A9 (en) * | 2001-03-30 | 2004-05-20 | Grubbs Robert H. | Cross-metathesis reaction of functionalized and substituted olefins using group 8 transition metal carbene complexes as metathesis catalysts |
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| CN105315181A (en) * | 2015-09-22 | 2016-02-10 | 湖南大学 | Synthetic method for sulfo trisubstituted alkenes compound |
| CN105859495A (en) * | 2016-05-05 | 2016-08-17 | 陕西师范大学 | Acetyenic-ketone-promoted CuI-catalyzed method for conducting Sonogashira coupled reaction |
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| Stereoselective Synthesis of Trisubstituted Alkenes through Sequential Iron-Catalyzed Reductive anti-Carbozincation of Terminal Alkynes and Base-Metal-Catalyzed Negishi Cross-Coupling;Chi Wai Cheung et al.;《Chemistry - A European Journal》;20151104;第21卷(第50期);第18439-18444,S14,S51页 * |
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