KR100941174B1 - Furan derivatives, and process for preparing them using Ag catalyst - Google Patents

Abstract

The present invention relates to a furan derivative and a method for preparing the same using a silver catalyst. More specifically, an intramolecular cyclization reaction between allene-in-1,6-diol derivatives under oxygen (Ag) catalyst conditions is performed. It relates to a furan derivative represented by the following formula (1) of the novel structure prepared by performing and a method for producing the same.

In Formula 1, A and B are as defined in the detailed description of the invention, respectively.

Silver catalyst, allene-1,6-diol, intramolecular cyclization reaction, furan

Description

Furan derivatives, and process for preparing them using Ag catalyst}

The present invention relates to a furan derivative of a novel structure prepared by selective intramolecular cyclization reaction of allene-in-1,6-diol derivatives under oxygen (Ag) catalyst condition and a method for preparing the same.

Furan derivatives form a basic skeleton for synthesizing important natural products, and because they have biological activities, are widely used as intermediates for synthesizing pharmaceuticals, perfumes, spices, and the like.

Research on the preparation of furan derivatives is extensive, many synthesis methods have been developed by organic synthesis chemists and reported in many documents. In particular, the synthesis of furan derivatives using transition metals such as palladium (Pd), chromium (Cr), copper (Cu), and the like as catalysts is well known to have excellent stereoselectivity and site selectivity. In the synthesis of organic compounds through the reaction of unsaturated compounds with nucleophiles, silver (Ag) is known in the literature to act as a Lewis acid to activate the π-bond of unsaturated carbon to enhance its reactivity with nucleophiles. However, the synthesis of furan compounds using silver (Ag) catalysts is rare.

Recently, however, many organic synthesis methods have been developed utilizing the excellent reactivity of silver (Ag) catalysts. J. Org. Chem. 1984 , 49 , 3762; Angew. Chem. Int. Ed. Engl . 1980 , 19 , 461; Tetrahedron . 1987 , 43 , 3309; Chem. Eur. J. 1997 , 3 , 1170; J. Org. Chem. 2000 , 65 , 4198; J. Am. Chem. Soc . 2000 , 122 , 4992; Org. Lett. 2000 , 2 , 297; Org. Lett . 2001 , 3 , 2537; Org. Lett . 2002 , 4 , 289; Org. Lett. 2002 , 4 , 1387 ; J. Am. Chem. Soc . 2004 , 126 , 11164; Org. Lett . 2005 , 7 , 3367].

The present inventors have completed the present invention by confirming that the silver (Ag) catalyst exhibits excellent stereoselectivity and site selectivity in the intramolecular cyclization reaction of the allene-1,6-diol derivative. As reported so far, no examples of synthesizing furan derivatives from allene-1,6-diol compounds by intramolecular cyclization using silver (Ag) catalysts have been reported in any literature.

It is an object of the present invention to provide an allene-1,6-diol derivative having a novel structure.

Another object of the present invention is to provide a method for selectively preparing a furan derivative by carrying out a cyclization reaction of an allene-1,6-diol derivative using a silver (Ag) catalyst.

The present invention is characterized by a furan derivative represented by the following formula (1) and a method for producing the same.

[Formula 1]

In Formula 1, A and B are each a hydrogen atom; C ₁ -C ₆ Alkyl groups; C ₅ -C ₈ Cycloalkyl group; Halogen, nitro, C ₁ -C ₆ Alkyl, C ₁ -C ₆ Alkoxy, C ₂ -C ₆ Alkylcarbonyl, C ₂ -C ₆ A phenyl group in which a substituent selected from alkoxycarbonyl and C ₂ -C ₆ alkanoate is substituted or unsubstituted; Phenyl-C ₁ -C ₆ alkylene group; Or a 5 to 8 pentagonal heterocycle group containing an oxygen atom.

The present invention provides a selective intramolecular cyclization reaction under a silver (Ag) catalyst using a furan derivative having a novel structure represented by Chemical Formula 1 and the above-mentioned novel compound as an allene-1-1,6-diol derivative. It relates to a method for producing.

Hereinafter, the substituents in the furan derivative represented by Chemical Formula 1 according to the present invention will be described in more detail.

"Alkyl" in the present invention represents a straight or pulverized saturated carbon chain having 1 to 6 carbon atoms. Specifically, methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, secondary-butyl, t-butyl, pentyl, neo-pentyl, hexyl, isohexyl and the like can be included.

'Cycloalkyl' in the present invention refers to a group comprising saturated or partially saturated mono- or poly-carbocyclic rings having 5 to 8 ring carbon atoms. Specifically, cycloalkyl may include cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, and the like.

Heterocycle in the present invention refers to an aromatic hydrocarbon ring composed of 5 to 8 elements including oxygen as a hetero atom. Specifically, furan, pyran, isobenzofuran, chromene, and the like may be included.

Preferred compounds in the furan derivative represented by Formula 1 according to the present invention, wherein A and B are each a hydrogen atom; C ₁ -C ₄ alkyl group; C ₅ -C ₇ cycloalkyl group; Phenyl group; Or a substituent selected from halogen, nitro, C ₁ -C ₄ alkyl, C ₁ -C ₄ alkoxy, C ₂ -C ₄ alkylcarbonyl, C ₂ -C ₄ alkoxycarbonyl and C ₂ -C ₄ alkanoate Phenyl group; Except for compounds in which A and B are hydrogen atoms at the same time.

More preferred compounds in the furan derivative represented by Formula 1 according to the present invention, A and B are each a hydrogen atom; Methyl group; Ethyl group; n-propyl group; Isopropyl group; Butyl group; Isobutyl group; Hexyl group; Cyclohexyl group; Phenyl group; Or chloro, iodo, bromo, nitro, methyl, ethyl, n-propyl, isopropyl, butyl, methoxy, ethoxy, propoxy, butoxy, acetyl, methoxycarbonyl, ethoxycarbonyl and acetoxy A substituent selected from represents a substituted phenyl group; Except for compounds in which A and B are hydrogen atoms at the same time.

Specific examples of the furan derivative represented by Chemical Formula 1 according to the present invention are as follows: 1- (5-propyl-4-vinylfuran-2-yl) -pentan-2-ol and 1-cyclohexyl-2 -(5-cyclohexyl-4-vinylfuran-2-yl) -ethanol, 1-phenyl-2- (5-phenyl-4-vinylfuran-2-yl) -ethanol, 1- (4-chlorophenyl) -2- [5- (4-chlorophenyl) -4-vinylfuran-2-yl] -ethanol, 1- (3-methoxyphenyl) -2- [5- (3-methoxyphenyl) -4- Vinylfuran-2-yl] -ethanol, or 1- (4-acetylphenyl) -2- [5- (4-acetylphenyl) -4-vinylfuran-2-yl] -ethanol.

On the other hand, the present invention includes a method for producing a furan derivative represented by the formula (1) as a scope.

The preparation method according to the present invention is performed by performing an intramolecular cyclization reaction of an allene-1,6-diol compound represented by Formula 2 under silver (Ag) catalyst conditions.

[Formula 2]

In Formula 2, A and B are as defined above, respectively.

In the preparation method of the present invention, in performing the intramolecular cyclization reaction between oxygen and carbon, a furan derivative represented by Chemical Formula 1 is synthesized by performing the selective intramolecular cyclization reaction by the selective use of silver (Ag) catalyst. There is a characteristic. The silver (Ag) catalyst used in the present invention may be any silver compound containing silver ions (Ag ⁺ ), specifically, selected from the group consisting of AgOTf, AgBF ₄ , AgSbF ₆ , and AgAsF ₆ . Preferably, in the embodiment of the present invention, the example using AgOTf as a catalyst representatively. The silver (Ag) catalyst can be sufficiently added even if a small amount is added as a catalytic amount, the present invention is not particularly limited in the amount of the silver (Ag) catalyst used, in consideration of various conditions of the formula (3) It is preferable to use it in 0.01-0.5 equivalent range with respect to the allene 1, 6- diol compound represented by the following.

The solvent used in the cyclization reaction of the present invention is a conventional organic solvent, and may be used acetonitrile, aliphatic nitriles including nitromethane, dichloromethane, halogenated aliphatic hydrocarbons including dichloroethane, and the like. In the examples, dichloromethane is typically used.

The cyclization reaction is carried out in the temperature range of 15 ℃ to 30 ℃, even if the reaction is carried out at room temperature can be sufficiently completed.

The cyclization reaction time may vary depending on the reactants, the type of solvent, and the amount of solvent. The starting material through TLC confirms that allene-1,6-diol compounds are consumed and then completes the reaction. . After the reaction is completed, the solvent may be distilled off under reduced pressure, and then the target product may be separated and purified through a conventional method such as column chromatography.

In addition, the allene-in-1,6-diol compound represented by Chemical Formula 2 used as a starting material in carrying out the intramolecular cyclization reaction of the present invention is also a novel compound. The present inventors have applied for the allene-in-1,6-diol compound represented by Chemical Formula 2 and a method for preparing the compound as Korean Patent Application No. 10-2007-0058871, which is represented by Chemical Formula 2 For specific preparation methods of the compounds, reference should be made to the previously published specification.

The allene-in-1,6-diol compound represented by Formula 2 may be reacted with an organic indium reagent by reacting indium (In) with 1,6-dibromo-2,4-hexadiin represented by Formula 3 below: And (ii) reacting the carbonyl compound represented by the following Formula 4 with or without in situ after separation and purification of the prepared organic indium reagent. 1,6-diol derivatives can be prepared.

In Formula 4, A and B are as defined in Formula 1, respectively.

Indium (In) in the reaction is used in the range of 2 to 3 equivalents, preferably 2.1 to 2.5 equivalents relative to 1,6-dibromo-2,4-hexadiyne represented by the formula (3). The reaction solvent is a conventional organic solvent, and it is performed using dimethylformamide (DMF) and tetrahydrofuran (THF), preferably using tetrahydrofuran (THF). The reaction temperature is to maintain 15 ℃ to 30 ℃, the reaction can be carried out smoothly even at room temperature. The reaction time may vary depending on the reactants, the type of solvent, and the amount of the solvent, and then complete the reaction after confirming that all the starting materials are consumed through TLC. After the reaction is completed, the solvent may be distilled off under reduced pressure through the extraction process, and then the target product may be separated and purified through conventional methods such as column chromatography. In addition, when the carbonyl compound represented by Chemical Formula 4 is an aldehyde compound, it may be more preferable to add a halide metal salt, and the halide metal salt may be 1,6-dibromo-2,4-hexa represented by Chemical Formula 2 above. The diyne is used in the amount of 2 to 3 equivalents, preferably in the range of 2.1 to 2.5 equivalents. The halide metal salt refers to a halide compound of alkali metal, and specifically, lithium iodide (LiI), sodium iodide (NaI), potassium iodide (KI), lithium chloride (LiCl), sodium chloride (NaCl), potassium chloride ( KCl) and the like can be used.

The present invention as described above will be described in more detail through the following Preparation Examples and Examples, but the following Preparation Examples and Examples to help the understanding of the present invention, the scope of the present invention is limited thereto It is not.

[Production example]

The present invention is a typical synthesis example of the allene-1,6-diol compound represented by the formula (2) used as a starting material.

Preparation Example 1 Preparation of 3-vinylidene-4-octin-2,7-diol

Dissolve indium (126 mg, 1.1 mmol) and lithium chloride (147 mg, 1.1 mmol) in THF (2 mL) solvent in a nitrogen atmosphere, and add 1,6-dibromo-2,4-hexadiyne (130 mg). 0.55 mmol) was dissolved in THF (3 mL), stirred at room temperature for 15 minutes, and then acetyl aldehyde (44 mg, 1.0 mmol) was added to the reaction solvent and stirred at room temperature for 1 hour, followed by 10% aqueous hydrochloric acid solution (3 mL). Was added to terminate the reaction. The mixture was extracted with Et ₂ O (20 mL × 3) and washed with water (20 mL) and saturated aqueous NaCl solution (20 mL). The extracted organic layer was dried over anhydrous MgSO ₄ and filtered. The solvent was removed and the residue was separated by column chromatography to obtain 3-vinylidene-4-octyne-2,7-diol (70 mg, 84%).

¹ H NMR (400 MHz, CDCl _3, 25 ° C., TMS) δ 5.08 (s, 2H), 4.33 (q, J = 6.25 Hz, 1H), 4.03-3.96 (m, 1H), 2.71 (s, 2H) , 2.59-2.45 (m, 1H), 1.36 (d, J = 6.25 Hz, 3H), 1.28 (d, J = 6.10 Hz, 3H)

Preparation Example 2 Preparation of 5-vinylidene-6-dodecine-4,9-diol

Dissolve indium (126 mg, 1.1 mmol) and lithium chloride (147 mg, 1.1 mmol) in THF (2 mL) solvent in a nitrogen atmosphere, and add 1,6-dibromo-2,4-hexadiyne (130 mg). 0.55 mmol) was dissolved in THF (3 mL) and stirred at room temperature for 15 minutes. Butyryl aldehyde (106 mg, 1.0 mmol) was added to the reaction solvent, which was stirred at room temperature for 1 hour, followed by 10% aqueous hydrochloric acid solution (3 mL). ) To terminate the reaction. The mixture was extracted with Et ₂ O (20 mL × 3) and washed with water (20 mL) and saturated aqueous NaCl solution (20 mL). The extracted organic layer was dried over anhydrous MgSO ₄ and filtered. The solvent was removed and the residue was separated by column chromatography to obtain 5-vinylidene-6-dodecine-4,9-diol (95 mg, 85%).

¹ H NMR (400 MHz, CDCl _3, 25 ° C., TMS) δ 5.07 (s, 2H), 4.13 (t, J = 6.42 Hz, 1H), 3.82-3.76 (m, 1H), 2.59 (dd, J = 4.60, 4.60 Hz, 1H), 2.47 (dd, 6.81, 6.81 Hz, 1H), 1.93 (s, 2H), 1.72-1.63 (m, 4H), 1.60-1.25 (m, 4H)

Preparation Example 3 Preparation of 1,6-dicyclohexyl-2-vinylidene-3-hexine-1,6-diol

Dissolve indium (126 mg, 1.1 mmol) and lithium chloride (147 mg, 1.1 mmol) in THF (2 mL) solvent in a nitrogen atmosphere, and add 1,6-dibromo-2,4-hexadiyne (130 mg). 0.55 mmol) was dissolved in THF (3 mL), stirred at room temperature for 15 minutes, and cyclohexylcarbaaldehyde (112 mg, 1.0 mmol) was added to the reaction solvent, which was stirred at room temperature for 1 hour, followed by 10% aqueous hydrochloric acid solution (3 mL) was added to terminate the reaction. The mixture was extracted with Et ₂ O (20 mL × 3) and washed with water (20 mL) and saturated aqueous NaCl solution (20 mL). The extracted organic layer was dried over anhydrous MgSO ₄ and filtered. The solvent was removed and the residue was separated by column chromatography to obtain 1,6-dicyclohexyl-2-vinylidene-3-hexine-1,6-diol (95 mg, 63%).

¹ H NMR (400 MHz, CDCl _3, 25 ° C, TMS) δ 5.03 (s, 2H), 3.82 (d, J = 7.17 Hz, 1H), 3.53-3.49 (m, 1H), 2.60 (dd, J = 4.27, 4.27 Hz, 1H), 2.51 (dd, J = 6.78, 7.39 Hz, 1H) 2.08 (s, 2H), 1.93 (t, J = 14.2 Hz, 2H), 1.78-1.65 (m, 8H), 1.64 -1.45 (m, 2H), 1.28-1.12 (m, 6H), 1.08-0.98 (m, 4H)

Preparation Example 4 Preparation of 1,6-diphenyl-2-vinylidene-3-hexine-1,6-diol

Dissolve indium (126 mg, 1.1 mmol) and lithium chloride (147 mg, 1.1 mmol) in THF (2 mL) solvent in a nitrogen atmosphere, and add 1,6-dibromo-2,4-hexadiyne (130 mg). 0.55 mmol) was dissolved in THF (3 mL), stirred at room temperature for 15 minutes, and benzaldehyde (106 mg, 1.0 mmol) was added to the reaction solvent, which was stirred at room temperature for 1 hour, followed by 10% aqueous hydrochloric acid solution (3 mL). Was added to terminate the reaction. The mixture was extracted with Et ₂ O (20 mL × 3) and washed with water (20 mL) and saturated aqueous NaCl solution (20 mL). The extracted organic layer was dried over anhydrous MgSO ₄ and filtered. The solvent was removed and the residue was separated by column chromatography to obtain the title compound 1,6-diphenyl-2-vinylidene-3-hexine-1,6-diol (125 mg, 63%).

¹ H NMR (400 MHz, CDCl _3, 25 ° C., TMS) δ 7.36-7.25 (m, 10H), 5.21 (d, J = 2.06 Hz, 1H), 5.10 (s, 2H), 4.75 (t, J = 6.3 Hz, 1H), 2.69 (d, J = 6.3 Hz, 2H), 2.27 (s, 2H)

Preparation Example 5 Preparation of 1,10-diphenyl-2-vinylidene-1,9-decadiene-5-phosphor-3,8-diol

Dissolve indium (126 mg, 1.1 mmol) and lithium chloride (147 mg, 1.1 mmol) in THF (2 mL) solvent in a nitrogen atmosphere, and add 1,6-dibromo-2,4-hexadiyne (130 mg). 0.55 mmol) was dissolved in THF (3 mL), stirred at room temperature for 15 minutes, and then trans-cinnaaldehyde (132 mg, 1.0 mmol) was added to the reaction solvent and stirred at room temperature for 1 hour, followed by 10% aqueous hydrochloric acid solution (3 mL) was added to terminate the reaction. The mixture was extracted with Et ₂ O (20 mL × 3) and washed with water (20 mL) and saturated aqueous NaCl solution (20 mL). The extracted organic layer was dried over anhydrous MgSO ₄ and filtered. The solvent was removed and the residue was separated by column chromatography to obtain the title compound 1,10-diphenyl-2-vinylidene-1,9-decadiene-5-phosphine-3,8-diol (153 mg, 70%) Got.

¹ H NMR (400 MHz, CDCl _3, 25 ° C., TMS) δ 7.40-7.34 (m, 4H), 7.32-7.28 (m, 4H), 7.25-7.22 (m, 2H), 6.65 (dd, J = 11.4 , 11.4 Hz, 2H), 6.28 (ddd, J = 15.9, 11.6, 6.2 Hz, 2H), 5.15 (s, 2H), 4.81 (d, J = 6.2 Hz, 1H), 2.78-2.65 (m, 2H) , 2.20 (s, 2H)

Preparation Example 6 Preparation of 1,6-bis- (4-chlorophenyl) -2-vinylidene-3-hexine-1,6-diol

Dissolve indium (126 mg, 1.1 mmol) and lithium chloride (147 mg, 1.1 mmol) in THF (2 mL) solvent in a nitrogen atmosphere, and add 1,6-dibromo-2,4-hexadiyne (130 mg). 0.55 mmol) was dissolved in THF (3 mL), stirred at room temperature for 15 minutes, and 4-chlorobenzaldehyde (140 mg, 1.0 mmol) was added to the reaction solvent and stirred at room temperature for 1 hour, followed by 10% aqueous hydrochloric acid solution ( 3 mL) was added to terminate the reaction. The mixture was extracted with Et ₂ O (20 mL × 3) and washed with water (20 mL) and saturated aqueous NaCl solution (20 mL). The extracted organic layer was dried over anhydrous MgSO ₄ and filtered. The solvent was removed and the residue was separated by column chromatography to obtain the title compound 6-bis- (4-chlorophenyl) -2-vinylidene-3-hexine-1,6-diol (154 mg, 86%).

¹ H NMR (400 MHz, CDCl _3, 25 ° C., TMS) δ 7.29-7.26 (m, 6H), 7.21-7.18 (m, 2H), 5.16 (s, 1H), 5.09 (s, 2H), 4.76- 4.72 (m, 1H), 2.82 (s, 2H), 2.72 (d, J = 5.55 Hz, 2H)

Preparation Example 7 Preparation of 1,6-bis- (2-iodophenyl) -2-vinylidene-3-hexine-1,6-diol

Dissolve indium (63 mg, 0.55 mmol) and lithium chloride (74 mg, 0.55 mmol) in THF (1 mL) solvent in a nitrogen atmosphere, and add 1,6-dibromo-2,4-hexadiyne (65 mg). 0.275 mmol) was dissolved in THF (1.0 mL), stirred at room temperature for 15 minutes, and 2-iodobenzaldehyde (116 mg, 1.0 mmol) was dissolved in THF (0.5 mL) and added to the reaction solvent to obtain 4 at room temperature. After stirring for 10 hours, 10% aqueous hydrochloric acid solution (3 mL) was added to terminate the reaction. The mixture was extracted with Et ₂ O (20 mL × 3) and washed with water (20 mL) and saturated aqueous NaCl solution (20 mL). The extracted organic layer was dried over anhydrous MgSO ₄ and filtered. After the solvent was removed, the residue was separated by column chromatography to obtain the title compound 1,6-bis- (2-iodophenyl) -2-vinylidene-3-hexine-1,6-diol (104 mg, 77%). Got it.

¹ H NMR (400 MHz, CDCl _3, 25 ° C., TMS) δ 7.69-7.63 (m, 4H), 7.10 (d, J = 8.05 Hz, 2H), 7.05-7.01 (m, 2H), 5.14 (s, 1H), 5.12 (s, 2H), 4.73-4.71 (m, 1H), 2.67 (d, J = 6.75 Hz, 2H), 2.35 (s, 2H)

Preparation Example 8 Preparation of 1,6-bis- (2-methoxyphenyl) -2-vinylidene-3-hexine-1,6-diol

Dissolve indium (126 mg, 1.1 mmol) and lithium chloride (147 mg, 1.1 mmol) in THF (1 mL) solvent in a nitrogen atmosphere, and add 1,6-dibromo-2,4-hexadiyne (130 mg). 0.55 mmol) was dissolved in THF (1.5 mL), stirred at room temperature for 15 minutes, and 2-methoxybenzaldehyde (68 mg, 0.5 mmol) was added to the reaction solvent and stirred at room temperature for 8 hours, followed by 10% aqueous hydrochloric acid solution. (3 mL) was added to terminate the reaction. The mixture was extracted with Et ₂ O (20 mL × 3) and washed with water (20 mL) and saturated aqueous NaCl solution (20 mL). The extracted organic layer was dried over anhydrous MgSO ₄ and filtered. The solvent was removed and the residue was separated by column chromatography to obtain 1,6-bis- (2-methoxyphenyl) -2-vinylidene-3-hexine-1,6-diol (71 mg, 82%) as a title compound. Got it.

¹ H NMR (400 MHz, CDCl _3, 25 ° C., TMS) δ 7.33-7.29 (m, 2H), 7.27-7.22 (m, 2H), 6.97-6.92 (m, 2H), 6.90-6.84 (m, 2H ), 5.41 (s, 1H), 5.03-4.97 (m, 3H), 3.83 (s, 3H), 3.81 (s, 3H), 3.22 (s, 1H), 2.86-2.81 (m, 2H), 2.66 ( dd, J = 7.56, 7.61 Hz, 1H)

Preparation Example 9 Preparation of 1,6-bis- (3-methoxyphenyl) -2-vinylidene-3-hexine-1,6-diol

Dissolve indium (126 mg, 1.1 mmol) and lithium chloride (147 mg, 1.1 mmol) in THF (1 mL) solvent in a nitrogen atmosphere, and add 1,6-dibromo-2,4-hexadiyne (130 mg). 0.55 mmol) was dissolved in THF (1.5 mL), stirred at room temperature for 15 minutes, and 3-methoxybenzaldehyde (136 mg, 1.0 mmol) was added to the reaction solvent and stirred at room temperature for 6 hours, followed by 10% aqueous hydrochloric acid solution. (3 mL) was added to terminate the reaction. The mixture was extracted with Et ₂ O (20 mL × 3) and washed with water (20 mL) and saturated aqueous NaCl solution (20 mL). The extracted organic layer was dried over anhydrous MgSO ₄ and filtered. The solvent was removed and the residue was separated by column chromatography to obtain 1,6-bis- (3-methoxyphenyl) -2-vinylidene-3-hexine-1,6-diol (142 mg, 81%) as a title compound. Got it.

¹ H NMR (400 MHz, CDCl _3, 25 ° C., TMS) δ 7.28-7.21 (m, 4H), 6.98-6.95 (m, 2H), 6.95-6.80 (m, 2H), 5.19 (s, 1H), 5.11 (s, 2H), 4.76-4.73 (m, 1H), 3.80 (s, 3H), 3.79 (s, 3H), 2.69 (d, J = 6.69 Hz, 2H), 2.48 (s, 2H)

Preparation Example 10 Preparation of 1,6-bis- (4-methoxyphenyl) -2-vinylidene-3-hexine-1,6-diol

Dissolve indium (126 mg, 1.1 mmol) and lithium chloride (147 mg, 1.1 mmol) in THF (1 mL) solvent in a nitrogen atmosphere, and add 1,6-dibromo-2,4-hexadiyne (130 mg). 0.55 mmol) was dissolved in THF (1.5 mL), stirred at room temperature for 15 minutes, and 4-methoxybenzaldehyde (136 mg, 1.0 mmol) was added to the reaction solvent and stirred at room temperature for 3 hours, followed by 10% aqueous hydrochloric acid solution. (3 mL) was added to terminate the reaction. The mixture was extracted with Et ₂ O (20 mL × 3) and washed with water (20 mL) and saturated aqueous NaCl solution (20 mL). The extracted organic layer was dried over anhydrous MgSO ₄ and filtered. The solvent was removed and the residue was separated by column chromatography to obtain 1,6-bis- (4-methoxyphenyl) -2-vinylidene-3-hexine-1,6-diol (136 mg, 78%) as a title compound. Got it.

¹ H NMR (400 MHz, CDCl _3, 25 ° C., TMS) δ 7.30 (d, J = 8.59 Hz, 1H), 7.29 (d, J = 8.59 Hz, 1H), 7.23 (d, J = 8.7 Hz, 1H ), 7.22 (d, J = 8.7 Hz, 1H), 6.89-6.83 (m, 4H), 5.16 (s, 1H), 5.11 (s, 2H), 4.74 (t, J = 6.32 Hz, 1H), 3.80 (s, 3H), 3.79 (s, 3H), 2.70 (d, J = 6.32 Hz, 2H), 2.28 (s, 2H)

Preparation Example 11 Preparation of 1,6-bis- (4-methylphenyl) -2-vinylidene-3-hexine-1,6-diol

Dissolve indium (126 mg, 1.1 mmol) and lithium chloride (147 mg, 1.1 mmol) in THF (1 mL) solvent in a nitrogen atmosphere, and add 1,6-dibromo-2,4-hexadiyne (130 mg). 0.55 mmol) was dissolved in THF (1.5 mL), stirred at room temperature for 15 minutes, and 4-methylbenzaldehyde (60 mg, 0.5 mmol) was added to the reaction solvent and stirred at room temperature for 4 hours, followed by 10% aqueous hydrochloric acid solution ( 3 mL) was added to terminate the reaction. The mixture was extracted with Et ₂ O (20 mL × 3) and washed with water (20 mL) and saturated aqueous NaCl solution (20 mL). The extracted organic layer was dried over anhydrous MgSO ₄ and filtered. The solvent was removed and the residue was separated by column chromatography to obtain 1,6-bis- (4-methylphenyl) -2-vinylidene-3-hexine-1,6-diol (69 mg, 81%) as a title compound.

¹ H NMR (400 MHz, CDCl _3, 25 ° C., TMS) δ 7.25-7.23 (m, 2H), 7.17-7.08 (m, 6H), 5.15 (s, 1H), 5.06 (s, 2H), 4.71 ( t, J = 6.28 Hz, 1H), 3.03 (s, 2H), 2.66 (d, J = 6.28 Hz, 2H), 2.33 (s, 3H), 2.32 (s, 3H)

Preparation Example 12 Preparation of 2,6-bis- (2,4,6-trimethylphenyl) -2-vinylidene-3-hexine-1,6-diol

Dissolve indium (126 mg, 1.1 mmol) and lithium chloride (147 mg, 1.1 mmol) in THF (1 mL) solvent in a nitrogen atmosphere, and add 1,6-dibromo-2,4-hexadiyne (130 mg). 0.55 mmol) was dissolved in THF (1.5 mL), stirred at room temperature for 15 minutes, and then 2,4,6-trimethylbenzaldehyde (74 mg, 0.5 mmol) was added to the reaction solvent and stirred at room temperature for 34 hours. Aqueous solution of% hydrochloric acid (3 mL) was added to terminate the reaction. The mixture was extracted with Et ₂ O (20 mL × 3) and washed with water (20 mL) and saturated aqueous NaCl solution (20 mL). The extracted organic layer was dried over anhydrous MgSO ₄ and filtered. The solvent was removed and the residue was separated by column chromatography to obtain the title compound 1,6-bis- (2,4,6-trimethylphenyl) -2-vinylidene-3-hexine-1,6-diol (77 mg, 82 %) Was obtained.

¹ H NMR (400 MHz, CDCl _3, 25 ° C., TMS) δ 6.80 (d, J = 8.14 Hz, 4H), 5.72 (q, J = 4.23 Hz, 1H), 5.13-5.09 (m, 1H), 5.07 (d, J = 4.46 Hz, 2H), 2.89 (dd, J = 9.7, 9.7 Hz, 1H), 2.59-2.50 (m, 1H), 2.37 (s, 3H), 2.36 (s, 3H), 2.34 ( s, 6H), 2.23 (s, 4H), 2.22 (s, 4H)

Preparation Example 13 Preparation of 1,6-bis- (4-nitrophenyl) -2-vinylidene-3-hexine-1,6-diol

Dissolve indium (126 mg, 1.1 mmol) and lithium chloride (147 mg, 1.1 mmol) in THF (2 mL) solvent in a nitrogen atmosphere, and add 1,6-dibromo-2,4-hexadiyne (130 mg). 0.55 mmol) was dissolved in THF (3 mL), stirred at room temperature for 15 minutes, and 4-nitrobenzaldehyde (151 mg, 1.0 mmol) was added to the reaction solvent, followed by stirring at room temperature for 15 minutes, followed by 10% aqueous hydrochloric acid solution ( 3 mL) was added to terminate the reaction. The mixture was extracted with Et ₂ O (20 mL × 3) and washed with water (20 mL) and saturated aqueous NaCl solution (20 mL). The extracted organic layer was dried over anhydrous MgSO ₄ and filtered. The solvent was removed and the residue was separated by column chromatography to obtain the title compound 1,6-bis- (4-nitrophenyl) -2-vinylidene-3-hexine-1,6-diol (180 mg, 95%). .

¹ H NMR (400 MHz, CDCl _3, 25 ° C., TMS) δ 8.22-8.11 (m, 4H), 7.59-7.49 (m, 4H), 5.34 (s, 1H), 5.16 (s, 2H), 4.94- 4.92 (m, 1H), 2.96 (s, 1H), 2.88 (s, 1H), 2.71-2.69 (m, 2H)

Preparation Example 14 Preparation of 1,6-bis- (3-hydroxyphenyl) -2-vinylidene-3-hexine-1,6-diol

Dissolve indium (126 mg, 1.1 mmol) and lithium chloride (147 mg, 1.1 mmol) in THF (1 mL) solvent in a nitrogen atmosphere, and add 1,6-dibromo-2,4-hexadiyne (130 mg). 0.55 mmol) was dissolved in THF (1.5 mL), stirred at room temperature for 15 minutes, and 3-hydroxybenzaldehyde (122 mg, 1.0 mmol) was added to the reaction solvent and stirred at room temperature for 8 hours, followed by 10% aqueous hydrochloric acid solution. (3 mL) was added to terminate the reaction. The mixture was extracted with Et ₂ O (20 mL × 3) and washed with water (20 mL) and saturated aqueous NaCl solution (20 mL). The extracted organic layer was dried over anhydrous MgSO ₄ and filtered. The solvent was removed and the residue was separated by column chromatography to obtain the title compound 1,6-bis- (3-hydroxyphenyl) -2-vinylidene-3-hexine-1,6-diol (128 mg, 80%). Got it.

¹ H NMR (400 MHz, DMSO-d ₆ , 25 ° C.) δ 9.24 (s, 2H), 7.11-7.03 (m, 2H), 6.79-6.69 (m, 4H), 6.67-6.61 (m, 2H), 5.70-5.67 (m, 1H), 5.37 (d, J = 4.35 Hz, 1H), 5.12 (s, 2H), 4.91 (s, 1H), 4.55-4.49 (m, 1H), 2.60-2.49 (m, 2H)

Preparation Example 15 Preparation of 1,6-bis- (4-acetylphenyl) -2-vinylidene-3-hexine-1,6-diol

Dissolve indium (126 mg, 1.1 mmol) and lithium chloride (147 mg, 1.1 mmol) in THF (2 mL) solvent in a nitrogen atmosphere, and add 1,6-dibromo-2,4-hexadiyne (130 mg). 0.55 mmol) was dissolved in THF (3 mL), stirred at room temperature for 15 minutes, and 4-acetylbenzaldehyde (148 mg, 1.0 mmol) was added to the reaction solvent and stirred at room temperature for 8 hours, followed by 10% aqueous hydrochloric acid solution ( 3 mL) was added to terminate the reaction. The mixture was extracted with Et ₂ O (20 mL × 3) and washed with water (20 mL) and saturated aqueous NaCl solution (20 mL). The extracted organic layer was dried over anhydrous MgSO ₄ and filtered. The solvent was removed and the residue was separated by column chromatography to obtain the title compound 1,6-bis- (4-acetylphenyl) -2-vinylidene-3-hexine-1,6-diol (154 mg, 82%). .

¹ H NMR (400 MHz, CDCl _3, 25 ° C., TMS) δ 7.95-7.89 (m, 4H), 7.37 (d, J = 8.23 Hz, 2H), 7.40 (d, J = 8.23 Hz, 1H), 7.39 (d, J = 8.23 Hz, 1H), 5.28 (s, 1H), 5.15 (s, 2H), 4.86 (dd, J = 5.73, 4.68 Hz, 1H), 2.74 (dd, J = 5.73, 4.68 Hz, 1H), 2.61 (s, 1H), 2.51 (s, 1H)

Preparation Example 16 Preparation of 1,6-bis- (4-methoxycarbonylphenyl) -2-vinylidene-3-hexine-1,6-diol

Dissolve indium (126 mg, 1.1 mmol) and lithium chloride (147 mg, 1.1 mmol) in THF (2 mL) solvent in a nitrogen atmosphere, and add 1,6-dibromo-2,4-hexadiyne (130 mg). 0.55 mmol) was dissolved in THF (3 mL), stirred at room temperature for 15 minutes, and methyl 4-formylbenzoate (164 mg, 1.0 mmol) was added to the reaction solvent and stirred at room temperature for 7 hours, followed by 10% aqueous hydrochloric acid solution. (3 mL) was added to terminate the reaction. The mixture was extracted with Et ₂ O (20 mL × 3) and washed with water (20 mL) and saturated aqueous NaCl solution (20 mL). The extracted organic layer was dried over anhydrous MgSO ₄ and filtered. The solvent was removed and the residue was separated by column chromatography to obtain 1,6-bis- (4-methoxycarbonylphenyl) -2-vinylidene-3-hexine-1,6-diol (190 mg, 82%). .

¹ H NMR (400 MHz, CDCl _3, 25 ° C., TMS) δ 8.00-7.94 (m, 4H), 7.43 (d, J = 8.23 Hz, 1H), 7.42 (d, J = 8.32 Hz, 1H), 7.35 (d, J = 8.27 Hz, 1H), 7.34 (d, J = 8.27 Hz, 1H), 5.25 (s, 1H), 5.09 (s, 2H), 4.82 (dd, J = 5.06, 5.73 Hz, 1H) , 3.90 (s, 6H), 2.99 (s, 2H), 2.71-2.69 (m, 2H)

Preparation Example 17 Preparation of 1,6-bis- (4-acetoxyphenyl) -2-vinylidene-3-hexine-1,6-diol

Dissolve indium (126 mg, 1.1 mmol) and lithium chloride (147 mg, 1.1 mmol) in THF (2 mL) solvent in a nitrogen atmosphere, and add 1,6-dibromo-2,4-hexadiyne (130 mg). 0.55 mmol) was dissolved in THF (3 mL), stirred at room temperature for 15 minutes, and 4-acetoxybenzaldehyde (164 mg, 1.0 mmol) was added to the reaction solvent and stirred at 0 ° C. for 24 hours, followed by 10% hydrochloric acid. An aqueous solution (3 mL) was added to terminate the reaction. The mixture was extracted with Et ₂ O (20 mL × 3) and washed with water (20 mL) and saturated aqueous NaCl solution (20 mL). The extracted organic layer was dried over anhydrous MgSO ₄ and filtered. The solvent was removed and the residue was separated by column chromatography to obtain 1,6-bis- (4-acetoxyphenyl) -2-vinylidene-3-hexine-1,6-diol (140 mg, 69%).

¹ H NMR (400 MHz, CDCl _3, 25 ° C., TMS) δ 7.40 (d, J = 8.51 Hz, 2H), 7.32-7.29 (m, 2H), 7.08-7.01 (m, 4H), 5.21 (s, 1H), 5.11 (s, 2H), 4.74 (dd, J = 5.42, 6.16 Hz, 1H), 2.68 (d, J = 6.16 Hz, 2H), 2.29 (s, 6H)

Preparation Example 18 Preparation of 1,6-Difuran-2-yl-2-vinylidene-3-hexine-1,6-diol

Dissolve indium (126 mg, 1.1 mmol) and lithium chloride (147 mg, 1.1 mmol) in THF (2 mL) solvent in a nitrogen atmosphere, and add 1,6-dibromo-2,4-hexadiyne (130 mg). 0.55 mmol) was dissolved in THF (3 mL), stirred at room temperature for 15 minutes, and 2-furylaldehyde (96 mg, 1.0 mmol) was added to the reaction solvent and stirred at room temperature for 2 hours, followed by 10% aqueous hydrochloric acid solution (3 mL) was added to terminate the reaction. The mixture was extracted with Et ₂ O (20 mL × 3) and washed with water (20 mL) and saturated aqueous NaCl solution (20 mL). The extracted organic layer was dried over anhydrous MgSO ₄ and filtered. The solvent was removed and the residue was separated by column chromatography to obtain 1,6-difuran-2-yl-2-vinylidene-3-hexine-1,6-diol (123 mg, 91%).

¹ H NMR (400 MHz, CDCl _3, 25 ° C., TMS) δ 7.38 (d, J = 10.1 Hz, 2H), 6.35-6.32 (m, 3H), 6.28 (t, J = 3.90 Hz, 1H), 5.20 -5.18 (m, 3H), 4.84 (t, J = 6.10 Hz, 1H), 2.88 (d, J = 6.10 Hz, 2H), 2.43 (s, 2H)

Preparation Example 19 Preparation of 3,8-dimethyl-1,10-diphenyl-4-vinylidene-5-decine-3,8-diol

Dissolve indium (189 mg, 1.65 mmol) in THF (1 mL) solvent under nitrogen atmosphere, and add 1,6-dibromo-2,4-hexadiyne (195 mg. 0.825 mmol) to THF (1.5 mL). After dissolving in, stirred for 15 minutes at room temperature, 4-phenyl-2-butanone (75 mg, 0.5 mmol) was added to the reaction solvent and stirred for 7 hours at room temperature, followed by adding 10% aqueous hydrochloric acid solution (3 mL). Terminated. The mixture was extracted with Et ₂ O (20 mL × 3) and washed with water (20 mL) and saturated aqueous NaCl solution (20 mL). The extracted organic layer was dried over anhydrous MgSO ₄ and filtered. The solvent was removed and then separated by column chromatography to obtain 3,8-dimethyl-1,10-diphenyl-4-vinylidene-5-decine-3,8-diol (61 mg, 65%).

¹ H NMR (400 MHz, CDCl _3, 25 ° C., TMS) δ 7.28-7.24 (m, 4H), 7.18 (d, J = 7.06 Hz, 6H), 5.17 (s, 2H), 2.74-2.67 (m, 4H), 2.60 (s, 2H), 2.03-1.97 (m, 2H), 1.90 (ddd, J = 6.16, 7.2, 6.53 Hz, 2H), 1.44 (s, 3H), 1.35 (s, 3H)

Preparation Example 20 Preparation of 1,6-dicyclohexyl-2-vinylidene-3-hexine-1,6-diol

Dissolve indium (189 mg, 1.65 mmol) in THF (1 mL) solvent under nitrogen atmosphere, and then add 1,6-dibromo-2,4-hexadiyne (195 mg. 0.825 mmol) to THF (1.5 mL). After dissolving in, stirred for 15 minutes at room temperature, cyclohexanone (49 mg, 0.5 mmol) was added to the reaction solvent and stirred for 7 hours at room temperature, 10% hydrochloric acid aqueous solution (3 mL) was added to terminate the reaction. The mixture was extracted with Et ₂ O (20 mL × 3) and washed with water (20 mL) and saturated aqueous NaCl solution (20 mL). The extracted organic layer was dried over anhydrous MgSO ₄ and filtered. The solvent was removed and the residue was separated by column chromatography to obtain 1,6-dicyclohexyl-2-vinylidene-3-hexine-1,6-diol (50 mg, 73%).

¹ H NMR (400 MHz, CDCl _3, 25 ° C., TMS) δ 5.09 (s, 2H), 2.52 (s, 2H), 1.74-1.60 (m, 12H), 1.59-1.48 (m, 4H), 1.28- 1.26 (m, 2 H)

Preparation Example 21 Preparation of 2,7-diphenyl-3-vinylidene-4-octin-2,7-diol

Dissolve indium (189 mg, 1.65 mmol) in THF (1 mL) solvent under nitrogen atmosphere, and add 1,6-dibromo-2,4-hexadiyne (195 mg. 0.825 mmol) to THF (1.5 mL). After dissolving in the solution, the mixture was stirred at room temperature for 15 minutes, and then acetophenone (60 mg, 0.5 mmol) was added to the reaction solvent, and the mixture was stirred at room temperature for 20 hours, and 10% aqueous hydrochloric acid solution (3 mL) was added to terminate the reaction. The mixture was extracted with Et ₂ O (20 mL × 3) and washed with water (20 mL) and saturated NaCl solution (20 mL). The extracted organic layer was dried over anhydrous MgSO ₄ and filtered. The solvent was removed and then separated by column chromatography to obtain 2,7-diphenyl-3-vinylidene-4-octin-2,7-diol (108 mg, 68%).

¹ H NMR (400 MHz, CDCl _3, 25 ° C., TMS) δ 7.40-7.26 (m, 10H), 5.17 (s, 1H), 2.87-2.64 (m, 2H), 1.90 (s, 2H), 1.54 ( d, J = 10.4 Hz, 3H), 1.41 (d, J = 12.5 Hz, 3H)

EXAMPLE

Using the allene-1,6-diol derivative synthesized by the above preparation as a starting material, it is a representative example of synthesizing the furan derivative represented by the formula (1) by performing an intramolecular cyclization reaction.

Example 1 Preparation of 1- (5-propyl-4-vinylfuran-2-yl) -pentan-2-ol

Silver triflate (AgOTf, 7.7 mg, 0.03 mmol) was dissolved in a CH ₂ Cl ₂ (0.5 mL) solvent under nitrogen atmosphere, and then 5-vinylidene-6-dodecine-4,9-diol (44 mg, 0.2 mmol) was dissolved in CH ₂ Cl ₂ (1 mL) solvent, stirred at room temperature for 2.5 hours, and the reaction was terminated. After removing the solvent of the reaction product was separated by column chromatography to give the title compound 1- (5-propyl-4-vinylfuran-2-yl) -pentan-2-ol (30 mg, 68%).

¹ H NMR (400 MHz, CDCl _3, 25 ° C., TMS) δ 6.50 (dd, J = 17.4, 10.9 Hz, 1H), 6.21 (s, 1H), 5.32 (d, J = 17.4 Hz, 1H), 5.05 (d, J = 10.9 Hz, 1H), 3.91-3.84 (m, 1H), 2.78 (dd, J = 4.02, 4.02 Hz, 1H), 2.65 (dd, J = 7.92, 7.92 Hz, 1H), 2.59 ( t, J = 7.3 Hz, 2H), 1.80 (d, J = 4.02, 1H), 1.68-1.60 (m, 2H), 1.55-1.36 (m, 4H), 0.92 (t, J = 7.49 Hz, 6H)

Example 2. Preparation of 1-cyclohexyl-2- (5-cyclohexyl-4-vinylfuran-2-yl) -ethanol

Dissolve silver triflate (7.7 mg, 0.03 mmol) in CH ₂ Cl ₂ (0.5 mL) solvent under nitrogen atmosphere and add 1,6-dicyclohexyl-2-vinylidene-3-hexine-1,6-di All (60 mg, 0.2 mmol) was dissolved in CH ₂ Cl ₂ (1 mL) solvent, stirred at room temperature for 1.5 hours, and then the reaction was terminated. After removing the solvent of the reaction product was separated by column chromatography to give the title compound 1-cyclohexyl-2- (5-cyclohexyl-4- vinylfuran-2-yl)-ethanol (52 mg, 86%).

¹ H NMR (400 MHz, CDCl _3, 25 ° C., TMS) δ 6.49 (dd, J = 17.4, 10.8 Hz, 1H), 6.14 (s, 1H), 5.24 (d, J = 17.4 Hz, 1H), 4.96 (d, J = 10.8 Hz, 1H), 3.57-3.52 (m, 1H), 2.76-2.54 (m, 3H), 1.81-1.30 (m, 13H), 1.29-1.10 (m, 10H)

Example 3. Preparation of 1-phenyl-2- (5-phenyl-4-vinylfuran-2-yl) -ethanol

Dissolve silver triflate (7.7 mg, 0.03 mmol) in CH ₂ Cl ₂ (0.5 mL) solvent under nitrogen atmosphere and add 1,6-diphenyl-2-vinylidene-3-hexine-1,6-diol (58 mg, 0.2 mmol) was dissolved in CH ₂ Cl ₂ (1 mL) solvent, stirred at room temperature for 1.5 hours, and the reaction was terminated. After removing the solvent of the reaction product was separated by column chromatography to give the title compound 1-phenyl-2- (5-phenyl-4-vinylfuran-2-yl) -ethanol (46 mg, 80%).

¹ H NMR (400 MHz, CDCl _3, 25 ° C., TMS) δ 7.55 (d, J = 8.58 Hz, 2H), 7.43-7.34 (m, 6H), 7.32-7.27 (m, 2H), 6.84 (dd, J = 17.3, 10.8 Hz, 1H), 6.39 (s, 1H), 5.50 (d, J = 17.3 Hz, 1H), 5.20 (d, J = 10.8 Hz, 1H), 5.05 (t, J = 6.5 Hz, 1H), 3.07 (d, J = 6.5 Hz, 2H), 2.29 (s, 1H)

Example 4. Preparation of 1- (4-chlorophenyl) -2- [5- (4-chlorophenyl) -4-vinylfuran-2-yl] -ethanol

Dissolve silver triflate (7.7 mg, 0.03 mmol) in CH ₂ Cl ₂ (0.5 mL) solvent under nitrogen atmosphere and add 1,6-bis- (4-chlorophenyl) -2-vinylidene-3-hexyne-. 1,6-diol (72 mg, 0.2 mmol) was dissolved in CH ₂ Cl ₂ (1 mL) solvent, stirred at room temperature for 3 hours, and the reaction was terminated. The solvent of the reaction was removed and then separated by column chromatography to give the title 1- (4-chlorophenyl) -2- [5- (4-chlorophenyl) -4-vinylfuran-2-yl] -ethanol (57 mg, 79 %) Was obtained.

¹ H NMR (400 MHz, CDCl _3, 25 ° C, TMS) δ 7.45 (d, J = 8.59 Hz, 2H), 7.38 (d, J = 8.59 Hz, 2H), 7.33 (s, 4H), 6.77 (dd) , J = 17.4, 10.8 Hz, 1H), 6.38 (s, 1H), 5.52 (d, J = 17.3 Hz, 1H), 5.24 (d, J = 10.8 Hz, 1H), 5.02 (t, J = 6.51 Hz , 1H), 3.04 (d, J = 6.51 Hz, 2H), 2.25 (s, 1H)

Example 5. Preparation of 1- (3-methoxyphenyl) -2- [5- (3-methoxyphenyl) -4-vinylfuran-2-yl] -ethanol

Dissolve silver triflate (7.7 mg, 0.03 mmol) in CH ₂ Cl ₂ (0.5 mL) solvent under nitrogen atmosphere and add 1,6-bis- (3-methoxyphenyl) -2-vinylidene-3-hexyne -1,6-diol (70 mg, 0.2 mmol) was dissolved in a solvent of CH ₂ Cl ₂ (1 mL), stirred at room temperature for 5 hours, and the reaction was terminated. The solvent of the reaction product was removed and then separated by column chromatography to obtain the title compound 1- (3-methoxyphenyl) -2- [5- (3-methoxyphenyl) -4-vinylfuran-2-yl] -ethanol ( 57 mg, 81%).

¹ H NMR (400 MHz, CDCl _3, 25 ° C., TMS) δ 7.35 (m, 1H), 7.16 (d, J = 7.83 Hz, 1H), 7.10-7.09 (m, 1H), 6.99-6.97 (m, 2H), 6.89-6.82 (m, 4H), 6.41 (s, 1H), 5.51 (d, J = 17.4 Hz, 1H), 5.21 (d, J = 10.8 Hz, 1H), 5.04 (t, J = 6.5 Hz, 1H), 3.85 (s, 3H), 3.81 (s, 3H), 3.39 (s, 1H), 3.08 (d, J = 6.5 Hz, 2H)

Example 6. Preparation of 1- (4-acetylphenyl) -2- [5- (4-acetylphenyl) -4-vinylfuran-2-yl] -ethanol

Dissolve silver triflate (7.7 mg, 0.03 mmol) in CH ₂ Cl ₂ (0.5 mL) solvent under nitrogen atmosphere and add 1,6-bis- (4-acetylphenyl) -2-vinylidene-3-hexyne-. 1,6-diol (75 mg, 0.2 mmol) was dissolved in a solvent of CH ₂ Cl ₂ (1 mL), stirred at room temperature for 4.5 hours, and the reaction was terminated. After removing the solvent of the reaction product was separated by column chromatography to give the title compound 1- (4-acetylphenyl) -2- [5- (4-acetylphenyl) -4-vinylfuran-2-yl] -ethanol (64 mg) , 85%).

¹ H NMR (400 MHz, CDCl _3, 25 ° C, TMS) δ 7.96 (dd, J = 7.02, 7.02 Hz, 4H), 7.63 (d, J = 8.37 Hz, 2H), 7.51 (d, J = 8.25 Hz , 2H), 6.86 (dd, J = 17.3, 10.8 Hz, 1H), 6.43 (s, 1H), 5.57 (d, J = 17.3 Hz, 1H), 5.30 (d, J = 10.8 Hz, 1H), 5.16 (t, J = 6.48 Hz, 1H), 3.11 (d, J = 6.48 Hz, 1H) 2.61 (s, 3H), 2.60 (s, 3H), 1.90 (s, 1H)

As described above, the furan derivative represented by Chemical Formula 1 according to the present invention is a novel compound, and the oxygen- caused by intramolecular cyclization reaction of allene-in-1,6-diol compound under silver (Ag) catalyst condition. It can be obtained in high yield through the carbon bonding method.

In addition, the furan derivatives of the present invention thus prepared are useful as intermediates in the synthesis of medicaments or perfumes, which form a basic skeleton of natural products.

Claims (7)

Furan derivative represented by the following formula (1): [Formula 1]

In Formula 1, A and B are each a hydrogen atom; C ₁ -C ₆ alkyl group; C ₅ -C ₈ cycloalkyl group; A substituent selected from halogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, and C ₂ -C ₆ alkylcarbonyl represents a substituted or unsubstituted phenyl group; Except for compounds in which A and B are hydrogen atoms at the same time. The method of claim 1, A and B are each hydrogen atoms; C ₁ -C ₄ alkyl group; C ₅ -C ₇ cycloalkyl group; Phenyl group; Or a substituent selected from halogen, C ₁ -C ₄ alkyl, C ₁ -C ₄ alkoxy, and C ₂ -C ₄ alkylcarbonyl is a substituted phenyl group; However, the compound characterized in that A and B at the same time excludes a compound having a hydrogen atom. The method of claim 2, A and B are each hydrogen atoms; Methyl group; Ethyl group; n-propyl group; Isopropyl group; Butyl group; Isobutyl group; Hexyl group; Cyclohexyl group; Phenyl group; Or a phenyl group substituted with a substituent selected from chloro, iodo, bromo, methyl, ethyl, n-propyl, isopropyl, butyl, methoxy, ethoxy, propoxy, butoxy, and acetyl; However, the compound characterized in that A and B at the same time excludes a compound that is a hydrogen atom. The method of claim 1, 1- (5-propyl-4-vinylfuran-2-yl) -pentan-2-ol, 1-cyclohexyl-2- (5-cyclohexyl-4-vinylfuran-2-yl) -ethanol, 1-phenyl-2- (5-phenyl-4-vinylfuran-2-yl) -ethanol, 1- (4-chlorophenyl) -2- [5- (4-chlorophenyl) -4-vinylfuran-2-yl] -ethanol, 1- (3-methoxyphenyl) -2- [5- (3-methoxyphenyl) -4-vinylfuran-2-yl] -ethanol, and 1- (4-acetylphenyl) -2- [5- (4-acetylphenyl) -4-vinylfuran-2-yl] -ethanol. An allene-1,6-diol derivative represented by the following formula (2) is an intramolecular ring in the presence of a silver (Ag) catalyst selected from Ag ⁺ ion-containing compounds consisting of AgOTf, AgBF ₄ , AgSbF ₆ , and AgAsF ₆ Method of preparing a furan derivative represented by the following Chemical Formula 1 by carrying out a reaction: [Formula 2]

[Formula 1]

In Formula 1 or 2, A and B are each a hydrogen atom; C ₁ -C ₆ alkyl group; C ₅ -C ₈ cycloalkyl group; A substituent selected from halogen, nitro, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, C ₂ -C ₆ alkylcarbonyl, C ₂ -C ₆ alkoxycarbonyl and C ₂ -C ₆ alkanoate is substituted or Unsubstituted phenyl group; Phenyl-C ₁ -C ₆ alkylene group; Or a 5 to 8 pentagonal heterocycle group containing an oxygen atom. delete The method according to claim 5, wherein the silver (Ag) catalyst is used in an amount of 0.01 to 0.5 equivalents based on the allene-1,6-diol derivative represented by Chemical Formula 2.