A method for preparing a non-conjugated functionalized olefin compound

Abstract

The application discloses a preparation method of a non-conjugated functionalized olefin compound, and the method is carried out in a cobalt / photocatalysis dual catalytic system which is composed of a cobalt catalyst, a ligand, a photocatalyst, a hydrogen source, a base and a solvent. β The target product is efficiently and selectively synthesized through reaction of an ethylenic compound or a halogenated compound or an electron-deficient olefin represented by formula (2) with acetylene as a C2 synthetic unit. The application adopts a cobalt / photocatalysis dual catalytic synergistic mechanism, has mild conditions (normal temperature and pressure, visible light driving), uses water as a green hydrogen source, uses acetylene as a cheap C2 source, has high atom economy, has good substrate universality, and the compound represented by formula (1) is easy to be prepared through Friedel-Crafts acylation or is commercially available, and the compound represented by formula (1) is easy to generate the compound (III) represented by formula (2) under the action of a base. The obtained non-conjugated olefin is a key intermediate for synthesizing high-value-added fine chemicals such as fragrances and insect pheromones, and has wide application prospects.

Description

Technical Field

[0001] This invention relates to the field of chemical synthesis, and more specifically to a method for preparing non-conjugated functionalized olefin compounds. Background Technology

[0002] Non-conjugated functionalized olefin compounds, as shown in formula (3), are important chemical synthesis intermediates and are widely used in the fields of pharmaceuticals, fragrances, dyes and other fine chemicals.

[0003]

[0004] For example, dihydromarigoldone (2,6-dimethyl-7-octen-4-one) is a typical non-conjugated enone fragrance, possessing aromas that combine marigold characteristics with fruity and herbal sweetness. It is widely used in cosmetics and tobacco flavorings, serving as a high-quality alternative to natural marigold essential oil. More importantly, this type of non-conjugated enone structure is a key intermediate in the synthesis of many high-value compounds: for instance, tetradec-1-en-5-one can be used to synthesize insect pheromones (eicos-13-en-10-one); furthermore, 3-methyl-1-phenylpent-4-en-1-one is a key precursor in the synthesis of the important fragrance molecule doliether. This further highlights the broad value of the products obtained by this method.

[0005] Currently, the synthetic routes for non-conjugated functionalized alkenes (i.e., alkenes where the double bond and functional group are not conjugated) are generally quite complex. Because different functional groups (such as ketones and esters) are compatible with different reaction conditions, their synthesis often requires multiple steps, resulting in lengthy processes and low overall yields. For example, traditional synthetic methods rely on strategies such as nucleophilic addition with metal reagents, Wittig reactions, alkene metathesis, and the protection and deprotection of functional groups to introduce alkene bonds and specific functional groups. For instance, when the target molecule contains a ketone functional group, the synthesis often requires the use of an equivalent amount of Grignard reagent (such as butenyl magnesium bromide) for nucleophilic addition (IV). Angew. Chem. Int. Ed 2013, 52 , 8597-8601.). This not only significantly increases the cost of raw materials, but also requires harsh reaction conditions, demanding strictly anhydrous and oxygen-free operation, limiting the feasibility of its large-scale application. For molecules containing ester functional groups, their synthesis typically involves the use of stoichiometric condensing agents (V) ( Angew. Chem. Int. Ed 2017, 56 , 12692-12696.) or water-sensitive and expensive precursors (such as butenoyl chloride) (VI)( Org. Lett. 2015, 17 (6090-6093.), the former may lead to product purification difficulties and reagent residues, while the latter has expensive raw materials and is accompanied by certain safety and storage risks.

[0006]

[0007] In summary, existing synthetic methods have significant limitations in terms of procedural economy, functional group compatibility, ease of operation, and cost control. There is an urgent need to develop a general synthetic strategy that is simpler, operates under milder conditions, has broader functional group tolerance, and is more cost-effective. Therefore, developing a simple, efficient, mild, and environmentally friendly general method for synthesizing non-conjugated functionalized olefin compounds is of great significance. Summary of the Invention

[0008] To overcome the shortcomings of the prior art, the present invention aims to provide a method for preparing non-conjugated functionalized olefin compounds.

[0009] Specifically, the present invention provides two reaction pathways: one is as shown in equation (1). β - Using halogenated compounds as starting materials, they participate in the reaction after generating an electron-deficient olefin intermediate (2) in situ in the reaction system. The target product (3) is constructed in one step through a dehalogenation / homogenization tandem process. This "slow-release strategy" can effectively control the concentration of highly active olefin intermediates, thereby inhibiting side reactions such as self-polymerization, which is the key to achieving high selectivity. The second method is to directly use the electron-deficient olefin shown in formula (2) as a substrate and construct the target product (3) in one step through its homogenization reaction with acetylene.

[0010] The core innovation of this method lies in using widely available and inexpensive acetylene gas as the C2 synthon to replace the expensive and stoichiometric metal reagents required in traditional methods, thereby significantly reducing raw material costs and operational complexity. The method described in this invention features mild conditions, simple steps, and broad functional group compatibility, demonstrating promising prospects for industrial application.

[0011] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0012] This invention provides a method for preparing a non-conjugated functionalized olefin compound, comprising one of the following methods: Method 1: As shown in equation (1) β - Using halogenated compounds as starting materials, a cobalt / photocatalytic dual-catalytic system consisting of a cobalt catalyst, ligand, photocatalyst, hydrogen source, base, and solvent is reacted to obtain a non-conjugated functionalized olefin compound of formula (3).

[0013] Method 2: Using electron-deficient olefins and acetylene as shown in formula (2) as starting materials, the reaction is carried out in a cobalt / photocatalytic dual-catalytic system consisting of a cobalt catalyst, ligand, photocatalyst, hydrogen source, base and solvent to obtain non-conjugated functionalized olefin compounds (3).

[0014] The reaction synthesis route is shown below:

[0015] in, X is a chlorine or bromine atom; R is a hydrogen atom, a substituted or unsubstituted C1-C30 alkyl group, or a substituted or unsubstituted C6-C30 aryl group. EWG is an electron-withdrawing group with the structure: -WL; where W is carbonyl, ester, amide, cyano, sulfone, phosphonate, or imine; and L is a substituted or unsubstituted C1-C30 alkyl, substituted or unsubstituted C6-C30 aryl, or substituted or unsubstituted C3-C30 heteroaryl. The substituents in the "substituted" group are one or more, each independently selected from C1-C4 alkyl, C1-C2 alkoxy, C1-C2 alkylthio, diphenylamino, halogen, C2-C10 ester, trifluoromethyl, pinacol diboronic acid ester, hydroxy or cyano; two adjacent substituents are optionally connected to each other to form a ring.

[0016] When there are multiple substituents among the substituted C6-C30 aryl, substituted C3-C30 heteroaryl, and substituted C1-C30 alkyl groups, the substituents may be the same or different.

[0017] R is a hydrogen atom, a substituted or unsubstituted C1-C30 alkyl group, or a substituted or unsubstituted C6-C30 aryl group.

[0018] Preferably, R is a hydrogen atom, a substituted or unsubstituted C1-C10 alkyl group, or a substituted or unsubstituted C6-C14 aryl group.

[0019] More preferably, R is a hydrogen atom, a substituted or unsubstituted C1-C6 alkyl group, or a substituted or unsubstituted C6-C10 aryl group.

[0020] More preferably, R is a hydrogen atom, a methyl group, or a phenyl group.

[0021] The cobalt catalyst is one or more of cobalt acetylacetonate, cobalt acetate, and cobalt chloride.

[0022] The ligand is selected from one or more of 1,10-phenanthroline ligands, 2,2'-bipyridine ligands, or oxazoline ligands.

[0023] Preferably, the ligand is a 1,10-phenanthroline ligand, wherein the 2nd and 9th positions are hydrogen atoms, substituted or unsubstituted C1-C6 alkyl groups, or substituted or unsubstituted C6-C10 aryl groups.

[0024] More preferably, in the 1,10-phenanthroline ligand, the 2nd and 9th positions are hydrogen atoms or C1-C3 alkyl groups.

[0025] More preferably, the 1,10-phenanthroline ligand is 2,9-dimethyl-1,10-phenanthroline.

[0026] The photocatalyst is selected from one or more of organic photocatalysts, iridium complex photocatalysts, or ruthenium complex photocatalysts.

[0027] More preferably, the organic photocatalyst is 2,4,5,6-tetra(9-carbazolyl)-isophthalonitrile.

[0028] More preferably, the iridium complex photocatalyst is fac -Ir(ppy)3.

[0029] More preferably, the ruthenium complex photocatalyst is Ru(bpy)3(PF6)2.

[0030] The hydrogen source is one or more of hansyl ester, water, or triethylamine.

[0031] More preferably, the hydrogen source is Hans ester (2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylic acid diethyl ester, CAS No. 1149-23-1).

[0032] The alkali is triethylamine. N,N -One or more of diisopropylethylamine, 1,8-diazabicycloundec-7-ene or tetramethylethylenediamine; and / or an organic ammonium salt.

[0033] More preferably, the base is triethylamine, N,N-diisopropylethylamine; and / or the corresponding hydrochloride salt of the base.

[0034] The solvent is acetonitrile, tetrahydrofuran, N,N One or more of dimethylformamide, 1,4-dioxane, ethylene glycol dimethyl ether, toluene, or a mixture thereof with water.

[0035] More preferably, the solvent is a mixture of acetonitrile and water, wherein the volume ratio of acetonitrile to water is 3:1.

[0036] The concentration of the compound of formula (1) or the compound of formula (2) in the solvent is 0.01-0.1 mol / L.

[0037] The reaction was carried out under inert gas protection and an acetylene atmosphere of 1-5 atm.

[0038] The reaction temperature is 30℃-100℃, and the reaction time is 3-24 hours.

[0039] As used in this invention, the term "aryl" refers to a monocyclic or bicyclic system containing 6-30 ring atoms, wherein at least one ring system is aromatic. Examples of aryl groups may include phenyl, naphthyl, etc.

[0040] As used in this invention, the term "heteroaryl" refers to a monocyclic or bicyclic system containing 3 to 30 carbon atoms, wherein at least one ring system contains one or more heteroatoms. Examples of heteroaryl groups include, but are not limited to, 2-furanyl, 2-thienyl, 2-pyridyl, 8-quinolinyl, etc.

[0041] The term "halogen" as used in this invention refers to fluorine, chlorine, bromine, and iodine.

[0042] Formula (1) of this invention β - Some halogenated compounds can be purchased directly, while others can be easily synthesized through Friedel-Crafts acylation.

[0043] Specifically, the Friedel-Crafts acylation synthesis method is as follows: under nitrogen protection, in an aluminum trichloride / dichloromethane system, an aromatic hydrocarbon reacts with an acyl chloride to prepare the product. β - Halogenated compounds.

[0044]

[0045] The electron-deficient olefin compounds shown in formula (2) can be referred to the literature method ( Angew. Chem. Int. Ed 2013, 52 , 5818-5821.), through formula (1) β - Halogenated compounds are synthesized under alkaline conditions.

[0046]

[0047] Specifically, formula (1) β The mass ratio of the halogenated compound to the base was 1:2. The reaction was carried out at room temperature for 2 hours.

[0048] The non-conjugated functionalized olefin compounds obtained by the above preparation method are important chemical synthesis intermediates, which are widely used in the fields of pharmaceuticals, fragrances, dyes and other fine chemicals.

[0049] Compared with the prior art, the beneficial effects of the present invention are: (1) The present invention adopts a cobalt / photocatalytic dual synergistic mechanism, with mild conditions (room temperature and pressure, visible light driven); water is used as a green hydrogen source and acetylene is used as a cheap C2 source, with high atom economy; the substrate has good universality, and the compound of formula (1) is easy to prepare or obtain commercially through Friedel-Crafts acylation, and the compound of formula (1) is easy to generate compound (III) of formula (2) under the action of base.

[0050] (2) This invention avoids the use of metal reagents, and the post-processing is simpler, greener, and cheaper, and can realize the construction of non-conjugated functionalized olefins.

[0051] (3) The conditions of this invention are simple and mild, the raw materials are readily available, there are few by-products, it is green and environmentally friendly, and it has good functional group compatibility. It can be used for the synthesis of fragrances, and can also be used to prepare high-value-added compounds such as insect pheromones through later functionalization. It has good application prospects. Attached Figure Description

[0052] Figure 1(a) and Figure 1(b) are the 1H and 1C spectra of the non-conjugated functionalized olefins synthesized in Example 3, respectively.

[0053] Figure 2(a) and Figure 2(b) are the 1H and 1C spectra of the non-conjugated functionalized olefins synthesized in Example 16, respectively.

[0054] Figures 3(a), 3(b), and 3(c) are the proton, carbon, and phosphorus spectra of the non-conjugated functionalized olefins synthesized in Example 23, respectively.

[0055] Figures 4(a) and 4(b) are the proton and carbon spectra of the non-conjugated functionalized olefins synthesized in Example 25, respectively.

[0056] Figures 5(a) and 5(b) are the proton and carbon spectra of the non-conjugated functionalized olefins synthesized in Example 27, respectively.

[0057] Figures 6(a) and 6(b) are the 1H and 1C spectra of the non-conjugated functionalized olefins synthesized in Example 36, respectively.

[0058] Figures 7(a) and 7(b) are the 1H and 1C spectra of the non-conjugated functionalized olefins synthesized in Example 37, respectively. Detailed Implementation

[0059] The present invention will be further illustrated below with reference to specific embodiments, but the embodiments do not limit the present invention in any way. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in this technical field, and can be purchased directly or synthesized by methods known in the literature.

[0060] Example 1 This embodiment provides a method for preparing 1-(4-methoxyphenyl)pent-4-en-1-one (3a), the steps of which are as follows:

[0061] Method 1: Using 3-chloro-1-(4-methoxyphenyl)prop-1-one (1a, 39.6 mg, 0.2 mmol, 1.0 eq.) as a substrate: Under nitrogen protection, cobalt acetylacetonate (5.2 mg, 0.02 mmol, 10 mol%) and L1 ligand 2,9-dimethyl-1,10-phenanthroline (6.2 mg, 0.03 mmol, 15 mol%), acetonitrile (2.5 mL) were added to a reaction flask. The mixture was stirred at room temperature for 10 minutes, then 3-chloro-1-(4-methoxyphenyl)prop-1-one (39.6 mg, 0.2 mmol, 1.0 eq.), 4CzIPN (1.9 mg, 0.0024 mmol, 1.2 mol%), acetonitrile (0.5 mL), water (1 mL), and triethylamine (98 μL, 0.7 mmol, 3.5 eq.) were added. (eq.). The acetylene was replaced three times, and the mixture was irradiated with a blue LED lamp (40 W) at room temperature while stirring for 3 hours. After the reaction was complete, the mixture was concentrated under reduced pressure to remove the solvent, and the crude product was purified by silica gel column chromatography using a mixture of petroleum ether / ethyl acetate (20:1 v / v) as the eluent to give the product 1-(4-methoxyphenyl)pent-4-en-1-one (3a, 29.2 mg, 77%).

[0062] Method 2: Using 1-(4-methoxyphenyl)prop-2-en-1-one (2a, 32.4 mg, 0.2 mmol, 1.0 eq.) as a substrate: Under nitrogen protection, cobalt acetylacetonate (5.2 mg, 0.02 mmol, 10 mol%), L1 ligand 2,9-dimethyl-1,10-phenanthroline (6.2 mg, 0.03 mmol, 15 mol%), 1-(4-methoxyphenyl)prop-2-en-1-one (2a, 32.4 mg, 0.2 mmol, 1.0 eq.), 4CzIPN (1.9 mg, 0.0024 mmol, 1.2 mol%), Et3N (70 μL, 0.5 mmol, 2.5 eq.), and Et3N·HCl (27.4 mg, 0.2 mmol, 1.0 eq.) were added to the reaction flask. The reaction was carried out under a solvent of CH3CN / H2O (3 / 1, v / v, 0.05 M) and an acetylene atmosphere, with blue light irradiation at room temperature for 3 hours. After the reaction was completed, the product 1-(4-methoxyphenyl)pent-4-en-1-one (3a, 28.6 mg, 75%) was obtained by standard post-treatment and column chromatography (PE / EA = 20:1).

[0063] NMR identification data of compound 3a: 1H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 8.9 Hz, 2H), 6.93 (d, J = 8.9 Hz, 2H), 5.90 (ddt, J = 16.9, 10.2, 6.5 Hz, 1H), 5.12 –4.97 (m, 2H), 3.86 (s, 3H), 3.02 (t, J = 7.0 Hz, 2H), 2.53 – 2.44 (m, 2H). 13 CNMR (101 MHz, CDCl3) δ 198.1, 163.4, 137.5, 130.3, 130.1, 115.2, 113.7, 55.5,37.4, 28.4. Examples 2-26 This embodiment provides a series of non-conjugated functionalized olefins, using the same method as described in Example 1, but employing different... β Using chloro compounds or electron-deficient alkenes as substrates, a series of non-conjugated functionalized alkenes can be obtained, as shown in Table 1: Table 1

[0064] Example 27 This embodiment provides a method for preparing phenyl pent-4-enoic acid (3aa), the steps of which are as follows:

[0065] Method 1: Using phenyl 3-chloropropionate (1aa, 36.8 mg, 0.2 mmol, 1.0 eq.) as a substrate: Under nitrogen protection, cobalt acetylacetonate (5.2 mg, 0.02 mmol, 10 mol%) and L1 ligand 2,9-dimethyl-1,10-phenanthroline (6.2 mg, 0.03 mmol, 15 mol%), acetonitrile (2.5 mL) were added to the reaction flask. The mixture was stirred at room temperature for 10 minutes, and then phenyl 3-chloropropionate (1aa, 36.8 mg, 0.2 mmol, 1.0 eq.), 4CzIPN (1.9 mg, 0.0024 mmol, 1.2 mol%), acetonitrile (1.5 mL), water (72 μL, 20 eq.), and triethylamine (98 μL, 0.7 mmol, 3.5 eq.) were added. The acetylene was replaced three times, and the mixture was irradiated with a blue LED lamp (40 W) at room temperature while stirring for 5 hours. After the reaction was complete, the mixture was concentrated under reduced pressure to remove the solvent. The crude product was purified by silica gel column chromatography using a mixture of petroleum ether / ethyl acetate (20:1 v / v) as the eluent to give 4-enoic acid phenyl ester (3 aa, 27.0 mg, 77%).

[0066] Method 2: Using phenyl acrylate (2aa, 29.6 mg, 0.2 mmol, 1.0 eq.) as a substrate, under nitrogen protection, the following were added to the reaction flask: cobalt acetylacetonate (5.2 mg, 0.02 mmol, 10 mol%), L1 ligand 2,9-dimethyl-1,10-phenanthroline (6.2 mg, 0.03 mmol, 15 mol%), phenyl acrylate (2aa, 29.6 mg, 0.2 mmol, 1.0 eq.), 4CzIPN (1.9 mg, 0.0024 mmol, 1.2 mol%), triethylamine (70 μL, 0.5 mmol, 2.5 eq.), water (72 μL, 20 eq.), and triethylamine hydrochloride (27.4 mg, 0.2 mmol, 1.0 eq.). The solvent was CH3CN. The reaction was carried out under acetylene atmosphere (4 mL, 0.05 M) and blue light irradiation at room temperature for 5 hours. After the reaction was completed, the product 4-enoic acid phenyl ester (3aa, 19.6 mg, 56%) was obtained by standard post-treatment and column chromatography (PE / EA = 20:1).

[0067] NMR identification data of compound 3aa: 1H NMR (400 MHz, CDCl3) δ 7.42 – 7.33 (m, 2H), 7.27 – 7.19 (m, 1H), 7.11 – 7.04 (m, 2H), 5.90 (ddt, J = 16.7, 10.2, 6.4 Hz,1H), 5.20 – 5.04 (m, 2H), 2.67 (t, J = 7.2 Hz, 2H), 2.55 – 2.47 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 171.5, 150.7, 136.3, 129.4, 125.8, 121.5, 115.9, 33.6,28.9. Example 28 This embodiment provides a method for preparing benzylpent-4-enoate (3ab), the steps of which are as follows:

[0068] Method 1: Replace phenyl 3-chloropropionate in Example 27 with benzyl 3-chloropropionate, and keep the rest of the operation unchanged, to finally obtain benzylpent-4-enoate (3ab, 31.6 mg, 83%).

[0069] Method 2: Replace phenyl acrylate in Example 27 with benzyl acrylate, and keep the rest of the operation unchanged, to finally obtain benzylpent-4-enoate (3ab, 30.8 mg, 81%).

[0070] NMR identification data of compound 3ab: 1 H NMR (400 MHz, CDCl3) δ 7.42 – 7.32 (m, 5H),5.83 (ddt, J = 16.5, 10.2, 6.2 Hz, 1H), 5.13 (s, 2H), 5.10 – 4.97 (m, 2H), 2.51 – 2.44 (m, 2H), 2.44 – 2.36 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 172.9, 136.6, 136.0, 128.5, 128.2, 115.6, 66.2, 33.5, 28.8. Example 29 This embodiment provides a method for preparing cyclohexylpent-4-enoate (3ac), the steps of which are as follows:

[0071] Method 1: Replace phenyl 3-chloropropionate in Example 27 with cyclohexyl 3-chloropropionate, while keeping the rest of the operation unchanged, and finally obtain cyclohexylpent-4-enoate (3ac, 24.6 mg, 68%).

[0072] Method 2: Replace phenyl acrylate in Example 27 with cyclohexyl acrylate, while keeping the other operations unchanged, to finally obtain cyclohexylpent-4-enoate (3ac, 25.4 mg, 70%).

[0073] NMR identification data of compound 3ac: 1 H NMR (400 MHz, CDCl3) δ 5.88 – 5.76 (m, 1H), 5.09 – 4.96 (m, 2H), 4.80 – 4.71 (m, 1H), 2.42 – 2.33 (m, 4H), 1.88 – 1.78(m, 2H), 1.75 – 1.67 (m, 2H), 1.58 – 1.48 (m, 1H), 1.46 – 1.24 (m, 5H). 13 C NMR (101 MHz, CDCl3) δ 172.5, 136.8, 115.3, 72.5, 33.9, 31.6, 29.0, 25.4, 23.7. Example 30 This embodiment provides a method for preparing 4-pentenoic acid hexyl ester (3ad), the steps of which are as follows:

[0074] Method 1: Replace phenyl 3-chloropropionate in Example 27 with hexyl 3-chloropropionate, and keep the rest of the operation unchanged, to finally obtain hexyl 4-pentenoate (3ad, 25.8 mg, 70%).

[0075] Method 2: Replace phenyl acrylate in Example 27 with n-hexyl acrylate, with the rest of the operation unchanged, and finally obtain hexyl 4-pentenoate (3ad, 23.6 mg, 64%).

[0076] NMR identification data of compound 3ad: NMR identification data of compound 3ad: 1 H NMR (400 MHz, CDCl3) δ 5.83 (ddt, J = 16.2, 11.5, 5.8 Hz, 1H), 5.10 – 4.95 (m, 2H), 4.06 (t, J= 6.7 Hz, 2H), 2.43 – 2.32 (m, 4H), 1.66 – 1.55 (m, 2H), 1.37 – 1.23 (m, 6H), 0.88 (t, J = 6.7 Hz, 3H). 13 C NMR (101 MHz, CDCl3)δ 173.0, 136.7, 115.3, 64.5, 33.5, 31.4, 28.9, 28.6, 25.5, 22.5, 13.9. Example 31 This embodiment provides a method for preparing decane-1,10-dimethylbis(4-pentenoate) (3ae), the steps of which are as follows:

[0077] Method 1: Replace phenyl 3-chloropropionate in Example 27 with decane-1,10-dimethylbis(3-chloropropionate), double the equivalent of all reagents except decane-1,10-dimethylbis(3-chloropropionate), and keep the other operations unchanged to finally obtain decane-1,10-dimethylbis(4-pentenoate) (3ae, 31.0 mg, 46%).

[0078] Method 2: Replace phenyl acrylate in Example 27 with decane-1,10-dimethyldiacrylate. Except for decane-1,10-dimethyldiacrylate, double the equivalent of all reagents and keep the rest of the operation unchanged to finally obtain decane-1,10-dimethylbis(4-pentenoate) (3ae, 33.8 mg, 50%).

[0079] NMR identification data of compound 3ae: 1 H NMR (400 MHz, CDCl3) δ 5.88 – 5.76 (m, 2H), 5.09 – 4.96 (m, 4H), 4.06 (t, J = 6.7 Hz, 4H), 2.43 – 2.34 (m, 8H), 1.65 – 1.58 (m, 4H), 1.35 – 1.27 (m, 12H). 13 C NMR (101 MHz, CDCl3) δ 173.0, 136.6, 115.3, 64.4, 33.4, 29.3, 29.1, 28.8, 28.5, 25.8. Example 32 This embodiment provides a method for preparing 4-pentenoic acid-4-methoxyphenyl ester (3af), the steps of which are as follows:

[0080] The 3-chloropropionic acid phenyl ester in Method 1 of Example 27 was replaced with 3-chloropropionic acid-4-methoxyphenyl ester, and the rest of the operation remained unchanged, finally yielding 4-pentenoic acid-4-methoxyphenyl ester (3af, 28.8 mg, 70%).

[0081] NMR identification data of compound 3af: 1 H NMR (400 MHz, CDCl3) δ 7.03 – 6.97 (m, 2H), 6.94 – 6.84 (m, 2H), 5.90 (ddt, J = 16.8, 10.2, 6.4 Hz, 1H), 5.18 – 5.03 (m,2H), 3.79 (s, 3H), 2.65 (t, J = 7.1 Hz, 2H), 2.55 – 2.45 (m, 2H). 13 C NMR (101MHz, CDCl3) δ 171.9, 157.2, 144.1, 136.3, 122.2, 115.8, 114.4, 55.5, 33.5,28.9. Example 33 This embodiment provides a method for preparing 4-pentenoic acid-4-fluorophenyl ester (3ag), the steps of which are as follows:

[0082] By replacing 3-chloropropionic acid phenyl ester in Method 1 of Example 27 with 3-chloropropionic acid-4-fluorophenyl ester, and keeping the rest of the operation unchanged, 4-pentenoic acid-4-fluorophenyl ester (3 ag, 25.2 mg, 65%) was finally obtained.

[0083] NMR identification data of compound 3ag: 1 H NMR (400 MHz, CDCl3) δ 7.09 – 7.00 (m, 4H),5.90 (ddt, J = 16.8, 10.3, 6.4 Hz, 1H), 5.20 – 5.04 (m, 2H), 2.66 (t, J = 7.6 Hz, 2H), 2.55 – 2.45 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 171.6, 160.2 (d, J = 244.0Hz), 146.5 (d, J= 2.9 Hz), 136.2, 123.0 (d, J = 8.5 Hz), 116.1, 116.0 (d, J = 8.0Hz), 33.5, 28.8. 19 F NMR (471 MHz, CDCl3) δ -117.11. Example 34 This embodiment provides a method for preparing 4-pentenoic acid-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl ester (3ah), the steps of which are as follows:

[0084] The 3-chloropropionic acid phenyl ester in Method 1 of Example 27 was replaced with 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl ester of 3-chloropropionic acid, while the rest of the operation remained unchanged, and the final product was 4-pentenoic acid 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl ester (3ah, 16.4 mg, 47%).

[0085] NMR identification data of compound 3ah: 1 H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 8.2 Hz, 2H), 7.08 (d, J = 8.1 Hz, 2H), 5.90 (ddt, J = 16.8, 10.3, 6.4 Hz, 1H), 5.21 –5.00 (m, 2H), 2.66 (t, J = 7.4 Hz, 2H), 2.50 (m, 2H), 1.34 (s, 12H). 13 C NMR (101MHz, CDCl3) δ 171.3, 153.2, 136.3, 136.2, 120.9, 115.9, 83.9, 33.6, 28.8,24.8. Example 35 This embodiment provides a method for preparing 4-pentenoic acid (8S,9R,13R,14R)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopentadieno[a]phenanthrene-3-yl ester (3ai), the steps of which are as follows:

[0086] The phenyl 3-chloropropionic acid in Method 1 of Example 27 was replaced with (8S,9R,13R,14R)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopentadieno[a]phenanthrene-3-yl ester, with all other operations remaining unchanged, to finally obtain (8S,9R,13R,14R)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopentadieno[a]phenanthrene-3-yl ester (3 ai, 32.4 mg, 46%). NMR identification data of compound 3ai: 1 H NMR (400 MHz, CDCl3) δ 7.31 – 7.26 (m, 1H), 6.87 – 6.77 (m, 2H), 5.90 (ddt, J = 16.8, 10.2, 6.4 Hz, 1H), 5.19 – 5.03 (m,2H), 2.96 – 2.86 (m, 2H), 2.69 – 2.61 (m, 2H), 2.53 – 2.48 (m, 2H), 2.44 –2.36 (m, 1H), 2.36 – 2.24 (m, 1H), 2.21 – 1.92 (m, 5H), 1.70 – 1.35 (m, 9H). 13 C NMR (101 MHz, CDCl3) δ 171.8, 148.6, 138.0, 137.3, 136.3, 126.4, 121.5,118.7, 115.9, 50.4, 47.9, 44.1, 38.0, 35.8, 33.6, 31.5, 29.4, 28.9, 26.3,25.7, 21.6, 13.8. Example 36 This embodiment provides ( E The preparation method of 1-phenylpent-4-en-1-one oxime (3aj) is as follows:

[0087] by( E Replacing phenyl acrylate in Method 2 of Example 27 with 1-phenylprop-2-en-1-one oxime, with all other operations remaining unchanged, finally yields ( E 1-Phenylacet-4-ene-1-one oxime (3aj, 6.4 mg, 20%).

[0088] NMR identification data of compound 3aj:1 H NMR (400 MHz, CDCl3) δ 9.99 (s, 1H), 7.69 –7.60 (m, 2H), 7.46 – 7.39 (m, 3H), 5.91 (ddt, J = 16.9, 10.2, 6.5 Hz, 1H), 5.15– 4.99 (m, 2H), 2.97 (t, J = 8.4 Hz, 2H), 2.44 – 2.34 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 159.1, 137.4, 135.6, 129.2, 128.6, 126.3,115.2, 30.2, 25.8. Example 37 This embodiment provides N -methyl- N The preparation method of 3-phenyl-4-pentenamide (3ak) is as follows:

[0089] by N -methyl- N - Phenylacetamide replaces phenyl acrylate in Method 2 of Example 27, with all other operations remaining unchanged, ultimately yielding... N -methyl- N -Phenylacetamide (3ak, 34.6 mg, 92%).

[0090] NMR identification data of compound 3ak: 1 H NMR (400 MHz, CDCl3) δ 7.46 – 7.39 (m, 2H), 7.38 – 7.30 (m, 1H), 7.23 – 7.15 (m, 2H), 5.73 (ddt, J = 16.9, 10.2, 6.6 Hz,1H), 4.99 – 4.85 (m, 2H), 3.27 (s, 3H), 2.39 – 2.29 (m, 2H), 2.24 – 2.11 (m,2H). 13 C NMR (101 MHz, CDCl3) δ 172.3, 144.0, 137.5, 129.7, 127.7, 127.3, 114.9,37.3, 33.4, 29.4. Examples 38-51 Using 3-chloro-1-(p-tolyl)prop-1-one as the raw material, different cobalt catalysts, ligands, solvents and hydrogen sources were used (Table 2). Other conditions were the same as in Example 1. The product yields are shown in Table 2.

[0091] Table 2

[0092] The optimal combination of conditions—cobalt acetylacetonate as the catalyst, 2,9-dimethyl-1,10-phenanthroline as the ligand, acetonitrile as the solvent, and hansyl ester as the hydrogen source—resulted in the highest reaction yield (Example 48, yield 90%). This indicates that this combination offers the highest catalytic efficiency within the scope of implementation. However, replacing hansyl ester with water is a greener, milder, and atom-economical method (Example 51, yield 83%). Examples 52-68 Using 1-(4-methoxyphenyl)prop-2-en-1-one as the raw material, different solvents, bases, and photosensitizers (Table 3) were used. Other aspects were the same as in Example 1. The product yield is shown in Table 3.

[0093] Table 3

[0094] Optimal combination of conditions: The highest yield was achieved (Example 62, yield 77%) when using 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (4CzIPN) as a photosensitizer in a mixed solvent of acetonitrile / water (volume ratio 3:1), with the simultaneous addition of triethylamine (Et3N) and triethylamine hydrochloride (Et3N·HCl) as base and additive. Examples 69-76 Using 3-chloro-1-(p-tolyl)prop-1-one as the raw material, different pressures, light sources, and temperatures (Table 4) were applied, while other conditions were the same as in Example 1. The product yields are shown in Table 4.

[0095] Table 4

[0096] The optimal combination of conditions was: a pressure of 1 atm, a blue light source, and a temperature of 30°C, resulting in the highest yield (Example 69, yield 83%). Pressure and temperature had little effect on the reaction yield.

[0097] Examples 77-82 Using 3-chloro-1-(p-tolyl)prop-1-one as a raw material, different powers of blue light were used, and the ratio of cobalt catalyst to ligand (Table 5) was the same as in Example 1. The product yield is shown in Table 5.

[0098] Table 5

[0099] The optimal combination of conditions was: the highest yield was achieved when the blue light power was 40W, the cobalt acetylacetone equivalent was 10%, and the 2,9-dimethyl-1,10-phenanthroline equivalent was 15% (Example 79, yield 83%).

[0100] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the implementation of the present invention. Those skilled in the art can make other variations or modifications based on the above description. It is neither necessary nor possible to exhaustively describe all embodiments here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the scope of protection of the claims of the present invention.

Claims

1. A method for preparing a non-conjugated functionalized olefin compound, characterized in that, As shown in equation (1) β - Using halogenated compounds as starting materials, the reaction is carried out in a cobalt / photocatalytic dual-catalytic system consisting of a cobalt catalyst, ligand, photocatalyst, hydrogen source, base and solvent to obtain a non-conjugated functionalized olefin compound of formula (3). The synthesis route is as follows: in, X is a chlorine or bromine atom; R is a hydrogen atom, a substituted or unsubstituted C1-C30 alkyl group, or a substituted or unsubstituted C6-C30 aryl group. R is a hydrogen atom, a substituted or unsubstituted C1-C30 alkyl group, or a substituted or unsubstituted C6-C30 aryl group; The substituents in the "substituted" group are one or more, each independently selected from C1-C4 alkyl, C1-C2 alkoxy, C1-C2 alkylthio, diphenylamino, halogen, C2-C10 ester, trifluoromethyl, pinacol diboronic acid ester, hydroxy or cyano; two adjacent substituents are optionally connected to each other to form a ring; EWG is an electron-withdrawing group with the structure: -WL; where W is a carbonyl, ester, amide, cyano, sulfone, phosphonate, or imine group; and L is a substituted or unsubstituted C1-C30 alkyl, substituted or unsubstituted C6-C30 aryl, or substituted or unsubstituted C3-C30 heteroaryl group.

2. A method for preparing a non-conjugated functionalized olefin compound, characterized in that, Using electron-deficient olefins and acetylene as shown in formula (2) as starting materials, the reaction was carried out in a cobalt / photocatalytic dual-catalytic system consisting of a cobalt catalyst, ligand, photocatalyst, hydrogen source, base and solvent to obtain non-conjugated functionalized olefin compounds (3). The synthesis route is as follows: in, X is a chlorine or bromine atom; R is a hydrogen atom, a substituted or unsubstituted C1-C30 alkyl group, or a substituted or unsubstituted C6-C30 aryl group. EWG is an electron-withdrawing group with the structure: -WL; where W is carbonyl, ester, amide, cyano, sulfone, phosphonate, or imine; and L is a substituted or unsubstituted C1-C30 alkyl, substituted or unsubstituted C6-C30 aryl, or substituted or unsubstituted C3-C30 heteroaryl. R is a hydrogen atom, a substituted or unsubstituted C1-C30 alkyl group, or a substituted or unsubstituted C6-C30 aryl group; The substituents in the "substituted" group are one or more, each independently selected from C1-C4 alkyl, C1-C2 alkoxy, C1-C2 alkylthio, diphenylamino, halogen, C2-C10 ester, trifluoromethyl, pinacol diboronic acid ester, hydroxy or cyano; two adjacent substituents are optionally connected to each other to form a ring.

3. The preparation method according to claim 1 or 2, characterized in that, The cobalt catalyst is selected from one or more of cobalt acetylacetonate, cobalt chloride, cobalt bromide, cobalt iodide, and cobalt acetate.

4. The preparation method according to claim 1 or 2, characterized in that, The ligand is selected from one or more of 1,10-phenanthroline ligands, 2,2'-bipyridine ligands, or oxazoline ligands.

5. The preparation method according to claim 1 or 2, characterized in that, The photocatalyst is selected from one or more of organic photocatalysts, iridium complex photocatalysts, or ruthenium complex photocatalysts.

6. The preparation method according to claim 1 or 2, characterized in that, The hydrogen source is selected from one or more of hesperidin, triethylamine, and water.

7. The preparation method according to claim 1 or 2, characterized in that, The alkali is selected from triethylamine, N,N -One or more of diisopropylethylamine, 1,8-diazabicycloundec-7-ene or tetramethylethylenediamine; and / or an organic ammonium salt.

8. The preparation method according to claim 1 or 2, characterized in that, The solvent is selected from acetonitrile, tetrahydrofuran, etc. N, N One or more of dimethylformamide, 1,4-dioxane, ethylene glycol dimethyl ether, toluene, or a mixture thereof with water.

9. The preparation method according to claim 1 or 2, characterized in that, The concentration of the compound of formula (1) or the compound of formula (2) in the solvent is 0.01-0.1 mol / L.

10. The preparation method according to claim 1 or 2, characterized in that, The reaction is carried out under an inert gas atmosphere and a 1-5 atm acetylene atmosphere, at a temperature of 30℃-100℃, and for a time of 3-24 h.

Images