Synthesis method of substituted allyl alcohol compound

Abstract

The invention discloses a synthesis method of a substituted allyl alcohol compound, and belongs to the technical field of chemical synthesis, a titanocene compound and a nickel compound are used as bimetallic catalysts, and an epoxy compound can be promoted to react with beta-bromostyrene compounds containing different substituent groups to generate the corresponding substituted allyl alcohol compound. Metal organic reagents and noble metal catalysts are not used, the effect is good, and meanwhile the technical problems that the reaction needs high temperature and time is long are solved. The method is mild in reaction condition, wide in functional group compatibility, good in selectivity and easy to operate, and conforms to the development concept of green chemistry.

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis technology, specifically relating to a method for synthesizing substituted allyl alcohol compounds. Background Technology

[0002] Epoxides are essential electrophiles in organic synthesis; they are readily available and highly useful for ring-opening reactions with a wide variety of carbohydrate nucleophiles. The alcohol products obtained from the ring-opening reactions of epoxides are valuable starting chemicals that play a vital role in synthetic and medicinal chemistry.

[0003] Over the past few decades, various ring-opening reactions of epoxides with carbon-based nucleophiles have been studied. For example, in 2004, Oshima et al. reported a Heck-type reaction of epoxides and styrene using a cobalt catalyst linked to bis(diphenylphosphine)hexane, in which the use of a strong base Heck reagent leads to incompatibility with many polar groups. In 2018, Zhou JS's team reported a palladium-catalyzed intermolecular Heck-type reaction of epoxides and alkenes, which is compatible with many sensitive polar groups and acidic hydrogens, but requires the use of a noble palladium catalyst and a reaction time of 48 h at 110 °C. In 2019, Lu's team reported a Pd-catalyzed decarbonylation cross-coupling reaction of α,β-unsaturated carboxylic acids with epoxides, which provides a variety of synthetically valuable substituted allyl alcohols, but this reaction not only requires the use of a noble palladium catalyst, but also requires a high temperature of 90 °C for 30 h. In 2020, Lu's team reported an example of Ni-catalyzed Suzuki-type cross-coupling of boric acid and epoxides. This reaction does not use exogenous bases and has better substrate compatibility, but the organometallic boron reagent has poor stability.

[0004] It is evident that the synthesis of allyl alcohol compounds disclosed in the prior art requires the use of noble metals as catalysts, which increases the preparation cost. The organometallic reagents used have poor stability, and the reaction involves high temperature and long reaction time. Summary of the Invention

[0005] This invention provides a method for synthesizing substituted allyl alcohol compounds, effectively solving the technical problem that existing allyl alcohol compound synthesis methods require the use of organometallic reagents and noble metal catalysts, and the reaction requires high temperatures. This invention uses 1,2-epoxycyclohexane and β-bromostyrene compounds as reaction substrates, and a cheap, non-toxic, and abundant titanium and nickel metal compound as a catalyst to carry out the ring-opening alkenylation reaction of epoxide compounds at room temperature, avoiding high-temperature reaction conditions, shortening the reaction time, and having a wider functional group compatibility.

[0006] The present invention solves the above-mentioned technical problems through the following technical solutions.

[0007] The purpose of this invention is to provide a method for synthesizing substituted allyl alcohol compounds, comprising the following steps: Using 1,2-epoxycyclohexane of Formula 1 and β-bromostyrene compounds of Formula 2 as reaction substrates, with titanium-ceramic and nickel compounds as dual catalysts, and 4,4'-dimethyl-2,2'-bipyridine as a ligand, a photosensitizer and a base were added. In an organic solvent, under blue light-induced synergistic catalysis and at room temperature under a protective atmosphere, 1,2-epoxycyclohexane and β-bromostyrene compounds underwent a ring-opening alkenylation reaction to yield substituted allyl alcohol compounds. The synthetic route is as follows: R is selected from hydrogen atom, alkyl, cyano, methoxy, trifluoromethyl, methylthio, halogen, methyl formate, aryl or heterocyclic aryl.

[0008] In a preferred embodiment, the titanium cadmium compound is dichlorotitanium cadmium, and the nickel compound is nickel ethylene glycol dimethyl ether bromide (NiBr2·glyme), nickel diethylene glycol dimethyl ether bromide (NiBr2·diglyme), nickel bromide (NiBr2), nickel iodide (NiI2), nickel chloride (NiCl2), nickel acetylacetone (Ni(acac)2), or nickel trifluoromethanesulfonate (Ni(OTf)2).

[0009] In a preferred embodiment, the molar ratio of 1,2-epoxycyclohexane to β-bromostyrene is 1:1 to 3, the molar ratio of 1,2-epoxycyclohexane, the titanium oxycyclohexane compound, and the nickel compound is 1:0.25:0.1, and the molar ratio of 1,2-epoxycyclohexane to 4,4'-dimethyl-2,2'-bipyridine is 1:0.2.

[0010] In a preferred embodiment, the molar ratio of 1,2-epoxycyclohexane to the photosensitizer is 1:0.05.

[0011] In a preferred embodiment, the photosensitizer is 2,4,5,6-tetra(9-carbazolyl)-isophthalonitrile (4CzIPN), tri(2-phenylpyridine)iridium (Ir(ppy)3), tri(2,2'-bipyridine)ruthenium(II)hexafluorophosphate (Ru(bpy)3·PF6) or eosin B.

[0012] In a preferred embodiment, the wavelength of the blue light is 400nm~450nm.

[0013] In a preferred embodiment, the base is triethylamine, and the molar ratio of 1,2-epoxycyclohexane to the base is 0.2:1.

[0014] In a preferred embodiment, the organic solvent is toluene or tetrahydrofuran.

[0015] In a preferred embodiment, the ring-opening alkenylation reaction takes 10-20 hours.

[0016] In a preferred embodiment, after the ring-opening alkenylation reaction is completed, a mixture is obtained. The mixture is then filtered through a silica gel liner and purified by column chromatography using petroleum ether and ethyl acetate in a volume ratio as eluents to obtain substituted allyl alcohol compounds.

[0017] In a preferred embodiment, the substituted allyl alcohol compound is , , , , , , , , , , , , or .

[0018] Compared with the prior art, the beneficial effects of the present invention are as follows: This invention provides a method for synthesizing substituted allyl alcohols. Using 1,2-epoxycyclohexane and β-bromostyrene compounds as substrates, a titanoceramic compound and a nickel compound as dual catalysts, and 4,4'-dimethyl-2,2'-bipyridine as a ligand, a photosensitizer and a base are added. In an organic solvent, under blue light-induced synergistic catalysis and at room temperature under a protective atmosphere, 1,2-epoxycyclohexane and β-bromostyrene compounds undergo a ring-opening alkenylation reaction to yield substituted allyl alcohols. This invention uses a titanoceramic compound and a nickel compound as bimetallic catalysts, which can promote the reaction of epoxides with β-bromostyrene compounds containing different substituents to generate the corresponding substituted allyl alcohols. This avoids the use of organometallic reagents and noble metal catalysts, resulting in better performance. It also solves the technical problems of requiring high temperatures and long reaction times. The reaction conditions of this invention are mild, have broad functional group compatibility, good selectivity, are easy to operate, and conform to the development concept of green chemistry. Attached Figure Description

[0019] Figure 1 The hydrogen spectrum of the substituted allyl alcohol compound prepared in Example 1 of this invention.

[0020] Figure 2 The carbon spectrum of the substituted allyl alcohol compound prepared in Example 1 of this invention.

[0021] Figure 3 The hydrogen spectrum of the substituted allyl alcohol compound prepared in Example 2 of this invention.

[0022] Figure 4 The carbon spectrum of the substituted allyl alcohol compound prepared in Example 2 of this invention.

[0023] Figure 5 The hydrogen spectrum of the substituted allyl alcohol compound prepared in Example 3 of this invention.

[0024] Figure 6 The hydrogen spectrum of the substituted allyl alcohol compound prepared in Example 4 of this invention.

[0025] Figure 7 The hydrogen spectrum of the substituted allyl alcohol compound prepared in Example 5 of this invention.

[0026] Figure 8 The carbon spectrum of the substituted allyl alcohol compound prepared in Example 5 of this invention.

[0027] Figure 9 The hydrogen spectrum of the substituted allyl alcohol compound prepared in Example 6 of this invention.

[0028] Figure 10 The hydrogen spectrum of the substituted allyl alcohol compound prepared in Example 7 of this invention.

[0029] Figure 11 The hydrogen spectrum of the substituted allyl alcohol compound prepared in Example 8 of this invention.

[0030] Figure 12 The hydrogen spectrum of the substituted allyl alcohol compound prepared in Example 9 of this invention.

[0031] Figure 13 The carbon spectrum of the substituted allyl alcohol compound prepared in Example 9 of this invention.

[0032] Figure 14 The hydrogen spectrum of the substituted allyl alcohol compound prepared in Example 10 of this invention.

[0033] Figure 15 The carbon spectrum of the substituted allyl alcohol compound prepared in Example 10 of this invention.

[0034] Figure 16 The hydrogen spectrum of the substituted allyl alcohol compound prepared in Example 11 of this invention.

[0035] Figure 17 The hydrogen spectrum of the substituted allyl alcohol compound prepared in Example 12 of this invention.

[0036] Figure 18 The carbon spectrum of the substituted allyl alcohol compound prepared in Example 12 of this invention.

[0037] Figure 19 The hydrogen spectrum of the substituted allyl alcohol compound prepared in Example 13 of this invention.

[0038] Figure 20 The hydrogen spectrum of the substituted allyl alcohol compound prepared in Example 14 of this invention. Detailed Implementation

[0039] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0040] It should be noted that the technical terms used in this invention are only for the purpose of describing specific embodiments and are not intended to limit the scope of protection of this invention. Unless otherwise specified, all raw materials, reagents, instruments and equipment used in the following embodiments of this invention can be purchased from the market or prepared by existing methods.

[0041] In the prior art, the synthesis methods of substituted allyl alcohol derivatives have the problems of requiring the use of organometallic reagents and noble metal catalysts, low selectivity, and harsh reaction conditions. The present invention provides a synthesis method of substituted allyl alcohol compounds.

[0042] The technical content of the present invention will be described in detail below.

[0043] This invention provides a method for synthesizing substituted allyl alcohol compounds, comprising the following steps: Using 1,2-epoxycyclohexane of Formula 1 and β-bromostyrene compounds of Formula 2 as reaction substrates, with titanium-ceramic and nickel compounds as dual catalysts, and 4,4'-dimethyl-2,2'-bipyridine as a ligand, a photosensitizer and a base were added. In an organic solvent, under blue light-induced synergistic catalysis and at room temperature under a protective atmosphere, 1,2-epoxycyclohexane and β-bromostyrene compounds underwent a ring-opening alkenylation reaction to yield substituted allyl alcohol compounds. The synthetic route is as follows: R is selected from alkyl, cyano, methoxy, trifluoromethyl, methylthio, halogen, methyl formate, aryl or heterocyclic aryl.

[0044] In existing technologies, cross-coupling reactions using epoxides and aryl olefins as substrates require organometallic reagents, strongly basic Grignard reagents, or noble metal catalysts such as palladium. This invention, however, uses titanium and nickel compounds as bimetallic catalysts to synergistically catalyze the ring-opening alkenylation reaction of epoxides with β-bromoaryl olefins under blue light induction. This invention, using titanium and nickel compounds as bimetallic catalysts, effectively promotes the reaction of epoxides with β-bromostyrene compounds containing different substituents to generate corresponding substituted allyl alcohols. Furthermore, this invention allows the reaction to proceed at room temperature, with mild reaction conditions and ease of operation.

[0045] In the ring-opening alkenylation reaction of this invention, the photosensitizer becomes excited under blue light excitation. The excited-state photosensitizer donates electrons to generate a photosensitizer cation, and the tetravalent titanium in the titanoceramsite compound gains electrons to generate trivalent titanium. The trivalent titanium species reduces the oxygen-containing compound 1,2-epoxycyclohexane with a single electron to generate a carbon radical. On the other hand, the divalent nickel catalyst of the nickel compound reduces to an active zero-valent nickel species, which undergoes oxidative addition with the alkenyl bromine of β-bromostyrene compounds to generate divalent alkenyl nickel species. The divalent alkenyl nickel species combines with the carbon radical to generate a trivalent nickel species. Reductive elimination yields substituted allyl alcohol compounds and monovalent nickel species. The monovalent nickel species is reduced by the photosensitizer to generate a zero-valent nickel species.

[0046] It should be noted that the titanium-ceramic compound used in this invention is dichlorotitanocene, and the nickel compound is nickel ethylene glycol dimethyl ether bromide (NiBr2·glyme), nickel diethylene glycol dimethyl ether bromide (NiBr2·diglyme), nickel bromide (NiBr2), nickel iodide (NiI2), nickel chloride (NiCl2), nickel acetylacetonate (Ni(acac)2), or nickel trifluoromethanesulfonate (Ni(OTf)2). The photosensitizer used in this invention is 2,4,5,6-tetra(9-carbazolyl)-isophthalonitrile (4CzIPN), tris(2-phenylpyridinium)iridium (Ir(ppy)3), tris(2,2'-bipyridine)ruthenium(II) hexafluorophosphate (Ru(bpy)3·PF6), or Eosin B. The organic solvent used in this invention is toluene or tetrahydrofuran. The ligand 4,4'-dimethyl-2,2'-bipyridine used in this invention was purchased from Bidex Pharmaceuticals and had a purity of 98%.

[0047] To obtain sufficient yields of substituted allyl alcohol compounds, the molar ratio of 1,2-epoxycyclohexane to β-bromostyrene compounds is 1:1 to 3, the molar ratio of 1,2-epoxycyclohexane, the titanium dioxide compound, and the nickel compound is 1:0.25:0.1, the molar ratio of 1,2-epoxycyclohexane to 4,4'-dimethyl-2,2'-bipyridine is 1:0.2, and the molar ratio of 1,2-epoxycyclohexane to the photosensitizer is 1:0.05.

[0048] In order to induce the photosensitizer to change from the ground state to the excited state under the action of light, the present invention limits the wavelength of the blue light to 400nm~450nm.

[0049] To provide electrons to the reaction system, the base used in this invention is triethylamine, and the molar ratio of 1,2-epoxycyclohexane to the base is 0.2:1. This invention uses triethylamine as a reducing agent to provide electrons so that the photosensitizer can be cycled.

[0050] To obtain a product with optimal yield, the ring-opening alkenylation reaction time is limited to 10-20 hours in this invention. When the reaction time is less than 10 hours, the reactants are not fully reacted, resulting in a low product yield. When the reaction time exceeds 20 hours, the product yield no longer increases; therefore, 20 hours is the optimal reaction time.

[0051] To further improve the yield and purity of the target product, after the ring-opening alkenylation reaction is completed, a mixture is obtained. The mixture is then filtered through a silica gel liner and purified by column chromatography using petroleum ether and ethyl acetate in a volume ratio to obtain substituted allyl alcohol compounds.

[0052] The technical effects of the present invention will be further illustrated below through specific embodiments.

[0053] Example 1 A method for synthesizing substituted allyl alcohol compounds, comprising the following steps: 0.0062 g of ethylene glycol dimethyl ether nickel bromide, 0.0124 g of titanium dichlorophenoxyacetate (Cp₂TiCl₂), 0.0079 g of 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (4CzIPN), and 0.0076 g of 4,4'-dimethyl-2,2'-bipyridine were added to a reaction tube. Under nitrogen atmosphere, 0.6 mmol (0.1182 g) of (4-methyl)-β-bromostyrene and 0.2 mmol of... 20 μL of 1,2-epoxycyclohexane, 1 mmol (140 μL) of triethylamine, and 5 mL of tetrahydrofuran were reacted at 25 °C under blue light for 20 h. After the reaction, the reaction mixture was filtered through a silica gel liner and purified by rapid column chromatography using petroleum ether and ethyl acetate in a 5:1 volume ratio as eluents to obtain (1R,2S)-2-((E)-4-methylstyryl)cyclohexane-1-ol (21.8 mg), with the structural formula [insert structural formula here]. The yield was 50%.

[0054] Example 2 A method for synthesizing substituted allyl alcohol compounds, comprising the following steps: 0.0062 g of ethylene glycol dimethyl ether nickel bromide, 0.0124 g of Cp₂TiCl₂, 0.0079 g of 4CzIPN, and 0.0076 g of 4,4'-dimethyl-2,2'-bipyridine were added to a reaction tube. Under nitrogen atmosphere, 0.6 mmol (79 μL) of (4-fluoro)-β-bromostyrene, 0.2 mmol (20 μL) of 1,2-epoxycyclohexane, 1 mmol (140 μL) of triethylamine, and 5 mL of tetrahydrofuran were added sequentially. The reaction was carried out at 25 °C under blue light for 20 h. After the reaction, the reaction mixture was filtered through a silica gel liner and purified by rapid column chromatography using petroleum ether and ethyl acetate in a 5:1 volume ratio as eluents to obtain (1R,2S)-2-((E)-4-fluorostyrene)cyclohexane-1-ol (19.2 mg), with the structural formula [insert structural formula here]. The yield was 44%.

[0055] Example 3 A method for synthesizing substituted allyl alcohol compounds, comprising the following steps: 0.0062 g of ethylene glycol dimethyl ether nickel bromide, 0.0124 g of Cp₂TiCl₂, 0.0079 g of 4CzIPN, and 0.0076 g of 4,4'-dimethyl-2,2'-bipyridine were added to a reaction tube. Under nitrogen atmosphere, 0.6 mmol (3 equiv) of (4-cyano)-β-bromostyrene, 0.2 mmol (20 μL) of 1,2-epoxycyclohexane, 1 mmol (140 μL) of triethylamine, and 5 mL of tetrahydrofuran were added sequentially. The reaction was carried out at 25 °C under blue light for 20 h. After the reaction, the reaction mixture was filtered through a silica gel liner and purified by rapid column chromatography using petroleum ether and ethyl acetate in a 5:1 volume ratio as eluents to obtain 14.1 mg of 4-((E)-2-((1S,2R)-2-hydroxycyclohexyl)vinyl)benzonitrile, with the following structural formula: The yield was 31%.

[0056] Example 4 A method for synthesizing substituted allyl alcohol compounds, comprising the following steps: 0.0062 g of ethylene glycol dimethyl ether nickel bromide, 0.0124 g of Cp₂TiCl₂, 0.0079 g of 4CzIPN, and 0.0076 g of 4,4'-dimethyl-2,2'-bipyridine were added to a reaction tube. Under nitrogen atmosphere, 0.6 mmol (0.1278 g) of (4-methoxy)-β-bromostyrene, 0.2 mmol (20 μL) of 1,2-epoxycyclohexane, 1 mmol (140 μL) of triethylamine, and 5 mL of tetrahydrofuran were added sequentially. The reaction was carried out at 25 °C under blue light for 20 h. After the reaction, the reaction mixture was filtered through a silica gel liner and purified by rapid column chromatography using petroleum ether and ethyl acetate in a 5:1 volume ratio as eluents to obtain (1R,2S)-2-((E)-4-methoxystyrene)cyclohexane-1-ol (17.8 mg), with the structural formula [insert structural formula here]. The yield was 38%.

[0057] Example 5 A method for synthesizing substituted allyl alcohol compounds, comprising the following steps: 0.0062 g of ethylene glycol dimethyl ether nickel bromide, 0.0124 g of Cp₂TiCl₂, 0.0079 g of 4CzIPN, and 0.0076 g of 4,4'-dimethyl-2,2'-bipyridine were added to a reaction tube. Under nitrogen atmosphere, 0.6 mmol (96 μL) of (4-trifluoromethyl)-β-bromostyrene, 0.2 mmol (20 μL) of 1,2-epoxycyclohexane, 1 mmol (140 μL) of triethylamine, and 5 mL of tetrahydrofuran were added sequentially. The reaction was carried out at 25 °C under blue light for 20 h. After the reaction, the reaction mixture was filtered through a silica gel liner and purified by rapid column chromatography using petroleum ether and ethyl acetate in a 5:1 volume ratio as eluents to obtain (1R,2S)-2-((E)-4-(trifluoromethyl)styrene)cyclohexane-1-ol (27.6 mg), with the following structural formula: The yield was 51%.

[0058] Example 6 A method for synthesizing substituted allyl alcohol compounds, comprising the following steps: 0.0062 g of ethylene glycol dimethyl ether nickel bromide, 0.0124 g of Cp₂TiCl₂, 0.0079 g of 4CzIPN, and 0.0076 g of 4,4'-dimethyl-2,2'-bipyridine were added to a reaction tube. Under nitrogen atmosphere, 0.6 mmol (0.1428 g) of (4-tert-butyl)-β-bromostyrene, 0.2 mmol (20 μL) of 1,2-epoxycyclohexane, 1 mmol (140 μL) of triethylamine, and 5 mL of tetrahydrofuran were added sequentially. The reaction was carried out at 25 °C under blue light for 20 h. After the reaction, the reaction mixture was filtered through a silica gel liner and purified by rapid column chromatography using petroleum ether and ethyl acetate in a 5:1 volume ratio as eluents to obtain (1R,2S)-2-((E)-4-(tert-butyl)styrene)cyclohexane-1-ol (17.5 mg), with the structural formula [insert structural formula here]. The yield was 34%.

[0059] Example 7 A method for synthesizing substituted allyl alcohol compounds, comprising the following steps: 0.0062 g of ethylene glycol dimethyl ether nickel bromide, 0.0124 g of Cp₂TiCl₂, 0.0079 g of 4CzIPN, and 0.0076 g of 4,4'-dimethyl-2,2'-bipyridine were added to a reaction tube. Under nitrogen atmosphere, 0.6 mmol (96 μL) of (4-ethyl)-β-bromostyrene, 0.2 mmol (20 μL) of 1,2-epoxycyclohexane, 1 mmol (140 μL) of triethylamine, and 5 mL of tetrahydrofuran were added sequentially. The reaction was carried out at 25 °C under blue light for 20 h. After the reaction, the reaction mixture was filtered through a silica gel liner and purified by rapid column chromatography using petroleum ether and ethyl acetate in a 5:1 volume ratio as eluents to obtain (1R,2S)-2-((E)-4-ethylstyrene)cyclohexane-1-ol (14.8 mg), with the structural formula [insert structural formula here]. The yield was 32%.

[0060] Example 8 A method for synthesizing substituted allyl alcohol compounds, comprising the following steps: 0.0062 g of ethylene glycol dimethyl ether nickel bromide, 0.0124 g of Cp₂TiCl₂, 0.0079 g of 4CzIPN, and 0.0076 g of 4,4'-dimethyl-2,2'-bipyridine were added to a reaction tube. Under nitrogen atmosphere, 0.6 mmol (0.1368 g) of (4-methylthio)-β-bromostyrene, 0.2 mmol (20 μL) of 1,2-epoxycyclohexane, 1 mmol (140 μL) of triethylamine, and 5 mL of tetrahydrofuran were added sequentially. The reaction was carried out at 25 °C under blue light for 20 h. After the reaction, the reaction mixture was filtered through a silica gel liner and purified by rapid column chromatography using petroleum ether and ethyl acetate in a 5:1 volume ratio as eluents to obtain (1R,2S)-2-((E)-4-(methylthio)styrene)cyclohexane-1-ol (19.8 mg), with the structural formula [not provided in the original text]. The yield was 40%.

[0061] Example 9 A method for synthesizing substituted allyl alcohol compounds, comprising the following steps: 0.0062 g of ethylene glycol dimethyl ether nickel bromide, 0.0124 g of Cp₂TiCl₂, 0.0079 g of 4CzIPN, and 0.0076 g of 4,4'-dimethyl-2,2'-bipyridine were added to a reaction tube. Under nitrogen atmosphere, 0.6 mmol (0.1555 g) of (4-phenyl)-β-bromostyrene, 0.2 mmol (20 μL) of 1,2-epoxycyclohexane, and 1 mL of [unspecified substance] were added sequentially. 140 μL of triethylamine and 5 mL of tetrahydrofuran were reacted at 25 °C under blue light for 20 h. After the reaction, the reaction mixture was filtered through a silica gel liner and purified by rapid column chromatography using petroleum ether and ethyl acetate in a volume ratio of 5:1 to obtain (1R,2S)-2-((E)-2-([1,1'-biphenyl]-4-yl)vinyl)cyclohexane-1-ol (26.5 mg), with the structural formula [insert structural formula here]. The yield was 48%.

[0062] Example 10 A method for synthesizing substituted allyl alcohol compounds, comprising the following steps: 0.0062 g of ethylene glycol dimethyl ether nickel bromide, 0.0124 g of Cp₂TiCl₂, 0.0079 g of 4CzIPN, and 0.0076 g of 4,4'-dimethyl-2,2'-bipyridine were added to a reaction tube. Under nitrogen atmosphere, 0.6 mmol (0.1399 g) of β-bromonaphthylene, 0.2 mmol (20 μL) of 1,2-epoxycyclohexane (0.2 mmol), and 1... mmol, i.e., 140 μL of triethylamine (5 equiv) and 5 mL of tetrahydrofuran, were reacted at 25 °C under blue light for 20 h. After the reaction, the reaction mixture was filtered through a silica gel liner and purified by rapid column chromatography using petroleum ether and ethyl acetate in a volume ratio of 5:1 to obtain (1R,2S)-2-((E)-2-(naphth-2-yl)vinyl)cyclohexane-1-ol (21.0 mg), with the structural formula: The yield was 42%.

[0063] Example 11 A method for synthesizing substituted allyl alcohol compounds, comprising the following steps: 0.0062 g of ethylene glycol dimethyl ether nickel bromide, 0.0124 g of Cp₂TiCl₂, 0.0079 g of 4CzIPN, and 0.0076 g of 4,4'-dimethyl-2,2'-bipyridine were added to a reaction tube. Under nitrogen atmosphere, 0.6 mmol (81 μL) of (3,4-difluoro)-β-bromostyrene, 0.2 mmol (20 μL) of 1,2-epoxycyclohexane, 1 mmol (140 μL) of triethylamine, and 5 mL of tetrahydrofuran were added sequentially. The reaction was carried out at 25 °C under blue light for 20 h. After the reaction, the reaction mixture was filtered through a silica gel liner and purified by rapid column chromatography using petroleum ether, ethyl acetate, and dichloromethane in a volume ratio of 5:1:1 to obtain (1R,2S)-2-((E)-3,4-difluorostyrene)cyclohexane-1-ol (14.1 mg), with the structural formula [insert structural formula here]. The yield was 30%.

[0064] Example 12 A method for synthesizing substituted allyl alcohol compounds, comprising the following steps: 0.0062 g of ethylene glycol dimethyl ether nickel bromide, 0.0124 g of Cp₂TiCl₂, 0.0079 g of 4CzIPN, and 0.0076 g of 4,4'-dimethyl-2,2'-bipyridine were added to a reaction tube. Under nitrogen atmosphere, 0.6 mmol (0.1446 g) of (4-methoxycarbonyl)-β-bromostyrene and 0.2 mmol (20 μL) of 1,2-epoxycyclohexane were added sequentially. 1 mmol (140 μL) of triethylamine and 5 mL of tetrahydrofuran were reacted at 25 °C under blue light for 20 h. After the reaction, the reaction mixture was filtered through a silica gel liner and purified by rapid column chromatography using petroleum ether, ethyl acetate, and dichloromethane in a volume ratio of 5:1:1 to obtain methyl 4-((E)-2-((1S,2R)-2-hydroxycyclohexyl)vinyl)benzoic acid (27.1 mg), with the structural formula [insert structural formula here]. The yield was 52%.

[0065] Example 13 A method for synthesizing substituted allyl alcohol compounds, comprising the following steps: 0.0062 g of ethylene glycol dimethyl ether nickel bromide, 0.0124 g of Cp₂TiCl₂, 0.0079 g of 4CzIPN, and 0.0076 g of 4,4'-dimethyl-2,2'-bipyridine were added to a reaction tube. Under nitrogen atmosphere, 0.6 mmol (70 μL) of (E)-2-(2-bromovinyl)thiophene, 0.2 mmol (20 μL) of 1,2-epoxycyclohexane, 1 mmol (140 μL) of triethylamine, and 5 mL of tetrahydrofuran were added sequentially. The reaction was carried out at 25 °C under blue light for 20 h. After the reaction, the reaction mixture was filtered through a silica gel liner and purified by rapid column chromatography using petroleum ether and ethyl acetate in a 5:1 volume ratio as eluents to obtain (1S,2R)-2-((E)-2-(thiophen-2-yl)vinyl)cyclohexane-1-ol (12.3 mg), with the following structural formula: The yield was 30%.

[0066] Example 14 A method for synthesizing substituted allyl alcohol compounds, comprising the following steps: 0.0062 g of ethylene glycol dimethyl ether nickel bromide, 0.0124 g of Cp₂TiCl₂, 0.0079 g of 4CzIPN, and 0.0076 g of 4,4'-dimethyl-2,2'-bipyridine were added to a reaction tube. Under nitrogen atmosphere, 0.6 mmol (79 μL) of β-bromostyrene, 0.2 mmol (20 μL) of 1,2-epoxycyclohexane, 1 mmol (140 μL) of triethylamine, and 5 mL of tetrahydrofuran were added sequentially. The reaction was carried out at 25 °C under blue light for 20 h. After the reaction, the reaction mixture was filtered through a silica gel liner and purified by rapid column chromatography using petroleum ether and ethyl acetate in a 5:1 volume ratio as eluents to obtain (1R,2S)-2-((E)-styryl)-cyclohexane-1-ol (31.2 mg), with the following structural formula: The yield was 77%.

[0067] Based on Example 14 above, this invention further adjusts the type of ligand, resulting in lower product yields. For example, replacing 4,4'-dimethyl-2,2'-bipyridine with 2,4,6-triphenylpyridine in Example 14 yields only 8%. Using N1,N1,N2,N2-tetraethylethylenediamine as the ligand yields 16%. Using 2,2'-bipyridine as the ligand yields 42%. Using 6,6'-dimethyl-2,2'-bipyridine as the ligand yields 13%. Using 4,4'-dimethoxy-2,2'-bipyridine as the ligand yields 14%; using [2,2'-bipyridine]-4,4'-dicarboxylic acid dimethyl ester as the ligand yields 16%. Using 2,2'-biquinoline as the ligand yields only 6%. Using 1,10-phenanthroline as the ligand yields 25%. Using 4,7-diphenyl-1,10-phenanthroline as a ligand, the yield was 12%. Using di(pyridin-2-yl)amine as a ligand, the yield was 20%. Using 2,2':6',2''-terpyridine as a ligand, the yield was 9%. Using 4,4'-di-tert-butyl-2,2'-bipyridine as a ligand, the yield was 14%. Using 1,4-dimethylpiperazine as a ligand, the yield was only 4%.

[0068] The substituted allyl alcohol compounds prepared in the embodiments of the present invention were characterized, as shown in Table 1 below.

[0069] The physicochemical and structural parameters of the substituted allyl alcohol compounds in Examples 1 to 14 are shown in Table 1 below.

[0070] Table 1. Physicochemical and structural parameters of the 14 substituted allyl alcohol compounds of this invention. Based on the above carbon and hydrogen spectra, the products prepared in the embodiments of the present invention are all substituted allyl alcohol compounds.

[0071] Although preferred embodiments of the invention have been described, those skilled in the art, upon learning the basic inventive concept, can make other changes and modifications to these embodiments. Therefore, the appended claims are intended to be interpreted as including both the preferred embodiments and all changes and modifications falling within the scope of the invention.

[0072] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.

Claims

1. A method for synthesizing substituted allyl alcohol compounds, characterized in that, Includes the following steps: Using 1,2-epoxycyclohexane of Formula 1 and β-bromostyrene compounds of Formula 2 as reaction substrates, with titanium-ceramic and nickel compounds as dual catalysts, and 4,4'-dimethyl-2,2'-bipyridine as a ligand, a photosensitizer and a base were added. In an organic solvent, under blue light-induced synergistic catalysis and at room temperature under a protective atmosphere, 1,2-epoxycyclohexane and β-bromostyrene compounds underwent a ring-opening alkenylation reaction to yield substituted allyl alcohol compounds. The synthetic route is as follows: R is selected from hydrogen atom, alkyl, cyano, methoxy, trifluoromethyl, methylthio, halogen, methyl formate, aryl or heterocyclic aryl.

2. The method for synthesizing substituted allyl alcohol compounds according to claim 1, characterized in that, The titanium cadmium compound is titanium cadmium dichlorodi ...

3. The method for synthesizing substituted allyl alcohol compounds according to claim 1, characterized in that, The molar ratio of 1,2-epoxycyclohexane to β-bromostyrene compounds is 1:1 to 3, the molar ratio of 1,2-epoxycyclohexane, titanium staphylocene compound, and nickel compound is 1:0.25:0.1, and the molar ratio of 1,2-epoxycyclohexane to 4,4'-dimethyl-2,2'-bipyridine is 1:0.

2.

4. The method for synthesizing substituted allyl alcohol compounds according to claim 1, characterized in that, The molar ratio of 1,2-epoxycyclohexane to the photosensitizer is 1:0.

05.

5. The method for synthesizing substituted allyl alcohol compounds according to claim 1, characterized in that, The photosensitizer is 2,4,5,6-tetra(9-carbazolyl)-isophthalonitrile, tris(2-phenylpyridine)iridium, tris(2,2'-bipyridine)ruthenium(II)hexafluorophosphate, or eosin B.

6. The method for synthesizing substituted allyl alcohol compounds according to claim 1, characterized in that, The wavelength of the blue light is 400nm~450nm.

7. The method for synthesizing substituted allyl alcohol compounds according to claim 1, characterized in that, The base is triethylamine, and the molar ratio of 1,2-epoxycyclohexane to the base is 0.2:

1.

8. The method for synthesizing substituted allyl alcohol compounds according to claim 1, characterized in that, The organic solvent is toluene or tetrahydrofuran.

9. The method for synthesizing substituted allyl alcohol compounds according to claim 1, characterized in that, The ring-opening alkenylation reaction takes 10-20 hours. After the ring-opening alkenylation reaction is completed, a mixture is obtained. The mixture is filtered through a silica gel liner and purified by column chromatography using two or three of petroleum ether, ethyl acetate, and dichloromethane as eluents to obtain substituted allyl alcohol compounds.

10. The method for synthesizing substituted allyl alcohol compounds according to claim 1, characterized in that, The substituted allyl alcohol compound is , , , , 、 、 、 、 、 、 、 、 or .

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