KR20090088173A - Dihydrofuran derivatives and synthesis of them using gold-catalyst - Google Patents

Abstract

A dihydrofuran derivative is provided to improve yield of the dihydrofuran derivative through intramolecular cyclization of alenyl alcohol compound and use as a precursor in synthesis of medicine or perfume. A dihydrofuran derivative is denoted by the chemical formula 1. In the chemical formula 1, R is independently (C1-C7) alkyl group, A is hydrogen, (C1-C7)alkyl, (C3-C8)cycloalkyl, (C6-C20)aryl or (C6-C20)aryl(C1-C7)alkyl. The dihydrofuran derivative is a compound of the chemical formula 2 or 3. The dihydrofuran derivative of the chemical formula 1 is produced through intramolecular cyclization of homoalenyl alcohol compound.

Description

Dihydrofuran derivatives and synthesis of them using gold-catalyst}

The present invention relates to a dihydrofuran derivative and a method for preparing the same. More specifically, the present invention relates to a method for selectively preparing a dihydrofuran derivative through an intramolecular cyclization reaction of an allenyl alcohol compound using a gold (Au) catalyst.

Dihydrofuran derivatives form a basic skeleton for synthesizing natural products, and because they have biological activities, they are used as important precursors for making medicines, perfumes, spices, and the like. In the past, the dihydrofuran compound was synthesized through a 1,3-dicarbonyl compound, and recently, a transition metal catalyst, palladium (Pd), nickel (Ni), copper (Cu), or molybdenum ( An example of synthesis using Mo) was also reported. In particular, the synthesis of dihydrofuran derivatives using the transition metal catalyst as described above is very important for the synthesis of natural products because it has the advantages of excellent stereoselectivity or site selectivity, has been studied by many chemists.

Recently, a dihydrofuran compound was synthesized using a gold (Au) catalyst, which is known to be able to synthesize various organic compounds through reaction with nucleophiles by acting as a Lewis acid to activate π-bonding of unsaturated carbon. And many studies have been conducted ( J. Org. Chem . 1984, 49 , 3762; Angew . Chem . Int . Ed . Engl . 1980, 19 , 461; Tetrahedron . 1987, 43 , 3309; J. Org . Chem 1990, 55, 2995;. . J. Am Chem Soc 1995, 117, 12895;... Chem Eur J. 1997, 3, 1170;. J. Am Chem Soc 1998, 120, 9720;... J. Comb Chem 1999, 1, 181; .. 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 . 2001, 3 , 2717; Org . Lett . 2002, 4 , 289; Org . Lett . 2002, 4 , 1387 ; J. Am . Chem . Soc . 2004, 126 , 11164; Org . Lett . 2005, 7 , 3367; J. Am . Chem . Soc . 2007, 129 , 1046). Such a gold (Au) catalyst has the disadvantage of being expensive compared to other transition metal catalysts, but has the advantage of being more reactive than other metal catalysts, the reaction proceeds even using a very small amount of catalyst.

In the literature, N. Krause and A. Hoffmann-Roder et al . ( Org . Lett . , 2001, 3 , 2537; Synthesis , 2002, 1759; Org . Biomol . Chem . , 2005, 3 , 387-391) In the following schemes, a compound in which alkyl is substituted such as methyl at the 3-position of dihydrofuran and a method for preparing the same are known.

However, in order for the dihydrofuran derivative to be applied to synthesis of various natural products, it is necessary to develop a substance having various functional groups. Accordingly, the present invention provides a new dihydrofuran derivative having an ester group at the 3-position of dihydrofuran. It is intended to provide useful intermediates for the synthesis of natural and bioactive substances.

It is an object of the present invention to provide new intermediates useful for the synthesis of natural and bioactive substances by preparing new dihydrofuran derivatives having ester groups at the 3-position of dihydrofuran.

In another aspect, the present invention provides a method for producing a dihydrofuran derivative having an ester group in the 3-position through the intramolecular cyclization reaction of the allylyl alcohol compound having an ester group using a gold (Au) catalyst There is a purpose.

The present invention provides a dihydrofuran derivative represented by the following Chemical Formula 1 and a preparation method thereof.

[Formula 1]

Dihydrofuran derivative manufacturing method of the formula (1) according to the present invention is characterized by inducing a carbon-oxygen bond through the intramolecular cyclization reaction of the allylyl alcohol compound represented by the following formula (4) under a gold (Au) catalyst .

[Formula 4]

In Formula 1 and Formula 4, R is independently selected from a (C1-C7) alkyl group; A is hydrogen, or is selected from (C 1 -C 7) alkyl, (C 3 -C 8) cycloalkyl, (C 6 -C 20) aryl, or (C 6 -C 20) aryl (C 1 -C 7) alkyl, in which A is alkyl, cyclo Alkyl, aryl or arylalkyl is a halogen element, nitro group, hydroxy group, (C1-C7) alkyl, (C1-C7) alkoxy, (C1-C7) alkylcarbonyl, (C1-C7) alkoxycarbonyl, and formyl group May be substituted with one or more substituents selected from (-CHO); n is an integer of 1-3.

Hereinafter, the present invention will be described in more detail.

It provides a dihydrofuran derivative of the formula (1) according to the present invention.

[Formula 1]

In Formula 1, R is independently selected from (C1-C7) alkyl group; A is hydrogen, or is selected from (C 1 -C 7) alkyl, (C 3 -C 8) cycloalkyl, (C 6 -C 20) aryl, or (C 6 -C 20) aryl (C 1 -C 7) alkyl, in which A is alkyl, cyclo Alkyl, aryl or arylalkyl is a halogen element, nitro group, hydroxy group, (C1-C7) alkyl, (C1-C7) alkoxy, (C1-C7) alkyl carbonyl, (C1-C7) alkoxycarbonyl, and formyl group May be substituted with one or more substituents selected from (-CHO); n is an integer of 1-3. In Formula 1, when n is 2 or 3, R may be different from each other, and a compound in which R has a different ester group is also included in the scope of the present invention.

The dihydrofuran derivative of Chemical Formula 1 is more specifically selected from the dihydrofuran derivatives of Chemical Formula 2 and Chemical Formula 3 below.

[Formula 2]

[Formula 3]

[In Formula 2 and Formula 3, R and R 'are independently selected from (C1-C7) alkyl group;

B ¹ in formula (2) is hydrogen or selected from (C ¹ -C 7) alkyl, (C 3 -C 8) cycloalkyl, (C 6 -C 20) aryl, or (C 6 -C 20) aryl (C 1 -C 7) alkyl;

B ² in formula (3) is selected from (C1-C7) alkylene, (C3-C8) cycloalkylene, (C6-C20) arylene, or (C6-C20) aryl (C1-C7) alkylene;

Alkyl, cycloalkyl, aryl or arylalkyl of B ¹ and B ² may be a halogen element, a nitro group, a hydroxy group, (C 1 -C 7) alkyl, (C 1 -C 7) alkoxy, (C 1 -C 7) alkylcarbonyl, (C 1 Or C1) alkoxycarbonyl, and one or more substituents selected from formyl groups (-CHO).]

Alkyl in R and A, B ¹ and B ² of Formulas 1 to 3 includes all linear or pulverized carbon chains, and aryl in A, B ¹ and B ² is phenyl, naphthyl, anthryl, etc. Examples of the arylalkyl in A, B ¹ and B ² include (C 1 -C 7) alkyl in which aryl groups such as phenyl, naphthyl and anthryl are substituted.

Substituents which may be substituted in A, B ¹ and B ² of Formulas 1 to 3 are more specifically, for example, chloro, iodo, methyl, methoxy. Nitro, hydroxy, acetyl, methoxycarbonyl, formyl and the like.

The dihydrofuran derivative of Chemical Formula 1 according to the present invention may be more specifically selected from compounds having the following structure.

[Wherein R and R 'are independently selected from (C1-C7) alkyl groups.]

Hereinafter, a method for preparing a dihydrofuran derivative according to the present invention will be described in detail.

Method for preparing a dihydrofuran derivative according to the present invention is to prepare a dihydrofuran derivative of the general formula (1) through an intramolecular cyclization reaction of the allylyl alcohol compound represented by the following formula (4) under a gold (Au) catalyst It is characterized by.

[Formula 1]

[Formula 4]

[In Formula 1 and Formula 4, R is independently selected from a (C1-C7) alkyl group; A is hydrogen, or is selected from (C 1 -C 7) alkyl, (C 3 -C 8) cycloalkyl, (C 6 -C 20) aryl, or (C 6 -C 20) aryl (C 1 -C 7) alkyl, in which A is alkyl, cyclo Alkyl, aryl or arylalkyl is a halogen element, nitro group, hydroxy group, (C1-C7) alkyl, (C1-C7) alkoxy, (C1-C7) alkylcarbonyl, (C1-C7) alkoxycarbonyl, and formyl group May be substituted with one or more substituents selected from (-CHO); n is an integer of 1 to 3.]

When n is 2 or 3 in Formulas 1 and 4, two or three allylyl alcohol groups may be cyclized at the same time, or a cyclization reaction may be performed step by step after generating the allenyl alcohol group. For example, the compound of Formula 3 may be composed of two reaction processes as in Scheme 1 below.

Scheme 1

The gold (Au) catalyst used in the preparation method of the present invention uses a monovalent or trivalent halide-based gold (Au) compound, and the monovalent gold catalyst is, for example, AuBr, AuCl, PPh ₃ AuCl (Ph = phenyl) And the like. As the trivalent gold catalyst, AuBr ₃ , AuCl ₃ , and the like may be used, and PPh ₃ AuCl is more preferably used as a catalyst.

In the production method of the present invention, when the silver (Ag) catalyst is used in addition to the gold (Au) catalyst, the Lewis acidity of the gold (Au) catalyst is increased to further improve the selectivity and yield of the reaction. In the case of the silver (Ag) catalyst, AgOTf (OTf = trifluoromethane sulfonate), AgBF ₄ , AgSbF ₆ , AgAsF ₆ , AgPF ₆ is preferably selected from the group, and AgOTf is more preferably used as a catalyst.

The silver (Ag) catalyst used in the preparation method of the present invention is a gold catalyst (Ag) when using a trivalent gold (Au) catalyst, such as AuBr ₃ , AuCl ₃ is 2 to 4 mol ( mole) times, more preferably 3 moles times. In the case of monovalent gold (Au) catalysts such as AuBr, AuCl, and PPh ₃ AuCl, silver (Ag) catalysts should use 0.5 to 1.5 mole times, more preferably the same amount of catalyst, for gold (Au) catalysts. .

The amount of the gold (Au) catalyst used in the preparation method of the present invention is to be used in the range of 0.05 equivalents to 0.1 equivalents to the allylyl alcohol compound represented by Formula 4.

The reaction solvent used in the production method of the present invention is a conventional organic solvent, one or two or more selected from acetonitrile, dichloromethane, dichloroethane, nitromethane, and the like. Mixed solvents can be used. It is more preferable to use dichloromethane and a mixed solvent including the same.

The reaction temperature is carried out at room temperature, preferably 15 to 30 degrees, the reaction time may vary depending on the reactants, the type of solvent and the amount of the solvent, the starting material through the TLC homoalylyl alcohol Complete the reaction after confirming that all compounds have been consumed. When 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.

Dihydrofuran derivatives prepared through the oxygen-carbon bonding method due to the intramolecular cyclization reaction of the allylyl alcohol compound using the gold (Au) catalyst according to the present invention can be obtained with high yield.

In addition, the dihydrofuran derivative thus prepared forms a basic skeleton of natural products and can be used as an important precursor for synthesis of medicine or perfume.

Hereinafter, the configuration of the present invention in more detail through examples, the following examples are provided to help the understanding of the present invention, the scope of the present invention is not limited thereto.

Example 1 Preparation of 3-ethoxycarbonyl-2,5-dihydrofuran (3-ethoxycarbonyl-2,5-dihydrofuran)

In a nitrogen atmosphere, PPh ₃ AuCl (7.4 mg, 0.015 mmol) and AgOTf (3.9 mg, 0.015 mmol) were dissolved in a solvent of CH ₂ Cl ₂ (0.5 ml), and then 2-hydroxymethyl-buta-2,3-diene was added thereto. Ouck acid ethyl ester (43 mg, 0.3 mmol) was dissolved in a solvent of CH ₂ Cl ₂ (0.7 ml), stirred at room temperature for 1 hour, and the reaction was terminated. After removing the solvent of the reaction product was separated by column chromatography to give the title compound 3-ethoxycarbonyl-2,5-dihydrofuran (32 mg, 75%). ¹ H NMR (400 MHz, CDCl _{3 ,} 25 ° C., TMS) data values ( d ) of the title compound obtained are listed in Table 1.

Example 2 Preparation of 2-propyl-3-ethoxycarbonyl-2,5-dihydrofuran (2-propyl-3-ethoxycarbonyl-2,5-dihydrofuran)

Using 2- (1-hydroxybutyl) -buta-2,3-dienoic acid ethyl ester (55 mg, 0.3 mmol) instead of 2-hydroxymethyl-buta-2,3-dienoic acid ethyl ester The title compound was obtained in the same manner as in Example 1 except that the title compound (52 mg, 95%) was obtained.

Example 3 Preparation of 2-phenethyl-3-ethoxycarbonyl-2,5-dihydrofuran (2-phenethyl-3-ethoxycarbonyl-2,5-dihydrofuran)

2- (1-hydroxy-3-phenylpropyl) -buta-2,3-dienoic acid ethyl ester (74 mg, 0.3 mmol) instead of 2-hydroxymethyl-buta-2,3-dienoic acid ethyl ester The title compound (61 mg, 83%) was obtained in the same manner as in Example 1 except for using).

Example 4 Preparation of 2-cyclohexyl-3-ethoxycarbonyl-2,5-dihydrofuran (2-cyclohexyl-3-ethoxycarbonyl-2,5-dihydrofuran)

Using 2- (cyclohexylhydroxymethyl) -buta-2,3-dienoic acid ethyl ester (67 mg, 0.3 mmol) instead of 2-hydroxymethyl-buta-2,3-dienoic acid ethyl ester The title compound was obtained in the same manner as in Example 1, except that 59 mg (88%) of the title compound was obtained.

Example 5 Preparation of 2-phenyl-3-ethoxycarbonyl-2,5-dihydrofuran (2-phenyl-3-ethoxycarbonyl-2,5-dihydrofuran)

The use of 2- (hydroxyphenylmethyl) -buta-2,3-dienoic acid ethyl ester (65 mg, 0.3 mmol) in place of 2-hydroxymethyl-buta-2,3-dienoic acid ethyl ester The same procedure as in Example 1 except for the title compound (55 mg, 85%).

Example 6 Preparation of 2- (4-chlorophenyl) -3-ethoxycarbonyl-2,5-dihydrofuran (2- (4-chlorophenyl) -3-ethoxycarbonyl-2,5-dihydrofuran)

2-[(4-chlorophenyl) -hydroxymethyl] -buta-2,3-dienoic acid ethyl ester (76 mg, 0.3) instead of 2-hydroxymethyl-buta-2,3-dienoic acid ethyl ester mmol) was used in the same manner as in Example 1 to obtain the title compound (69 mg, 91%).

Example 7 Preparation of 2- (2-iodophenyl) -3-ethoxycarbonyl-2,5-dihydrofuran (2- (2-iodophenyl) -3-ethoxycarbonyl-2,5-dihydrofuran)

2- [hydroxy-2- (iodophenyl) -methyl] -buta-2,3-dienoic acid ethyl ester (103 mg instead of 2-hydroxymethyl-buta-2,3-dienoic acid ethyl ester , 0.3 mmol) was used in the same manner as in Example 1 to obtain the title compound (98 mg, 95%).

Example 8 Preparation of 2- (4-methylphenyl) -3-ethoxycarbonyl-2,5-dihydrofuran (2- (4-methylphenyl) -3-ethoxycarbonyl-2,5-dihydrofuran)

Under nitrogen atmosphere, PPh ₃ AuCl (13 mg, 0.03 mmol) and AgOTf (8.0 mg, 0.03 mmol) were dissolved in a solvent of CH ₂ Cl ₂ (0.5 ml), and then 2- [hydroxy- (4-methylphenyl) -methyl ] -Buta-2,3-dieoic acid ethyl ester (70 mg, 0.3 mmol) was dissolved in a solvent of CH ₂ Cl ₂ (0.7 ml), stirred at room temperature for 1 hour, and the reaction was terminated. After removing the solvent of the reaction product was separated by column chromatography to give the title compound 2- (4-methylphenyl) -3-ethoxycarbonyl-2,5-dihydrofuran (62 mg, 88%).

Example 9 2- (2,4,6-trimethylphenyl) -3-ethoxycarbonyl-2,5-dihydrofuran (2- (2,4,6-trimethylphenyl) -3-ethoxycarbonyl-2 , 5-dihydrofuran)

Under nitrogen atmosphere, PPh ₃ AuCl (13 mg, 0.03 mmol) and AgOTf (8.0 mg, 0.03 mmol) were added to CH ₂ Cl ₂ (0.5 ml) dissolved in a solvent, and then added 2- [hydroxy- (2,4,6-trimethylphenyl) -methyl] -buta-2,3-dienoic acid ethyl ester (78 mg, 0.3 mmol) in CH ₂ Cl ₂ (0.7 ml) was dissolved in a solvent and stirred at room temperature for 1 hour to terminate the reaction. After removing the solvent of the reaction product was separated by column chromatography to give the title compound 2- (2,4,6-trimethylphenyl) -3-ethoxycarbonyl-2,5-dihydrofuran (64 mg, 82%). Got it.

Example 10 2- (3-methoxyphenyl) -3-ethoxycarbonyl-2,5-dihydrofuran (2- (3-methoxyphenyl) -3-ethoxycarbonyl-2,5-dihydro-furan) Manufacture

2- [hydroxy- (3-methoxyphenyl) -methyl] -buta-2,3-dienoic acid ethyl ester (75 mg) instead of 2-hydroxymethyl-buta-2,3-dienoic acid ethyl ester , 0.3 mmol) was obtained in the same manner as in Example 1 to obtain the title compound (62 mg, 83%).

Example 11 Preparation of 2- (3-hydroxyphenyl) -3-ethoxycarbonyl-2,5-dihydrofuran (2- (3-hydroxyphenyl) -3-ethoxycarbonyl-2,5-dihydrofuran)

2- [hydroxy- (3-hydroxyphenyl) -methyl] -buta-2,3-dienoic acid ethyl ester (70 mg) instead of 2-hydroxymethyl-buta-2,3-dienoic acid ethyl ester , 0.3 mmol) was obtained in the same manner as in Example 1 to obtain the title compound (18 mg, 26%).

Example 12 Preparation of 2- (4-nitrophenyl) -3-ethoxycarbonyl-2,5-dihydrofuran (2- (4-nitrophenyl) -3-ethoxycarbonyl-2,5-dihydrofuran)

2- [hydroxy- (4-nitrophenyl) -methyl] -buta-2,3-dienoic acid ethyl ester (79 mg, instead of 2-hydroxymethyl-buta-2,3-dienoic acid ethyl ester In the same manner as in Example 1 except for using 0.3 mmol), the title compound (71 mg, 90%) was obtained.

Example 13 Preparation of 2- (4-formylphenyl) -3-ethoxycarbonyl-2,5-dihydrofuran (2- (4-formylphenyl) -3-ethoxycarbonyl-2,5-dihydrofuran)

2-[(4-formylphenyl) -hydroxymethyl] -buta-2,3-dienoic acid ethyl ester (74 mg, 0.3 instead of 2-hydroxymethyl-buta-2,3-dienoic acid ethyl ester The title compound (67 mg, 90%) was obtained in the same manner as in Example 1 except that mmol) was used.

Example 14 Preparation of 2- (4-acetylphenyl) -3-ethoxycarbonyl-2,5-dihydrofuran (2- (4-acetylphenyl) -3-ethoxycarbonyl-2,5-dihydrofuran)

2- [hydroxy- (4-acetylphenyl) -methyl] -buta-2,3-dienoic acid ethyl ester (78 mg, instead of 2-hydroxymethyl-buta-2,3-dienoic acid ethyl ester In the same manner as in Example 1 except for using 0.3 mmol), the title compound (73 mg, 94%) was obtained.

Example 15 2- (4-methoxycarbonylphenyl) -3-ethoxycarbonyl-2,5-dihydrofuran (2- (4-methoxycarbonylphenyl) -3-ethoxycarbonyl-2,5-dihydro- manufacture of furan

2- [hydroxy- (4-methoxycarbonylphenyl) -methyl] -buta-2,3-dienoic acid ethyl ester instead of 2-hydroxymethyl-buta-2,3-dienoic acid ethyl ester 83 mg, 0.3 mmol) was used in the same manner as in Example 1 to obtain the title compound (81 mg, 97%).

Example 16 1,4- (di-3-ethoxycarbonyl-2,5-dihydrofuranyl) -benzene, (1,4- (di-3-ethoxycarbonyl-2,5-dihydrofuranyl)- benzene)

In a nitrogen atmosphere, indium (57.4 mg, 0.5 mmol) and lithium chloride (100 mg, 1.5 mmol) were dissolved in a solvent of DMF (1 ml), and then ethyl 4-bromobutinate (143 mg. 0.75 mmol) was added to DMF ( 1.0 ml), stirred at room temperature for 30 minutes, then thiophthalaldehyde (67 mg, 0.5 mmol) was added to the reaction solvent, stirred at room temperature for 5 hours, and then saturated sodium hydrogencarbonate aqueous solution (3 ml) was added to terminate the reaction. I was. The mixture was extracted with Et ₂ O (10 mL × 3) and washed with saturated sodium bicarbonate (10 ml) and saturated aqueous sodium chloride solution (10 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 2-[(4-formylphenyl) -hydroxymethyl] -buta-2,3-dienoic acid ethyl ester (101 mg, 82%).

Under nitrogen atmosphere, PPh ₃ AuCl (7.4 mg, 0.015 mmol) and AgOTf (3.9 mg, 0.015 mmol) were dissolved in a solvent of CH ₂ Cl ₂ (0.5 ml), and then 2-[(4-formylphenyl) -hydroxymethyl ] -Buta-2,3-dieoic acid ethyl ester (74 mg, 0.3 mmol) was dissolved in a solvent of CH ₂ Cl ₂ (0.7 ml), stirred at room temperature for 1 hour, and the reaction was terminated. After removing the solvent of the reaction product was separated by column chromatography to give the title compound 2- (4-formylphenyl) -2,5-dihydrofuran-3-carboxylic acid ethyl ester (67 mg, 90%).

In a nitrogen atmosphere, indium (57.4 mg, 0.5 mmol) and lithium chloride (100 mg, 1.5 mmol) were dissolved in a solvent of DMF (1 ml), and then ethyl 4-bromobutinate (143 mg. 0.75 mmol) was added to DMF ( 1.0 ml), stirred at room temperature for 30 minutes, and then 3- (4-formylphenyl) -2,5-dihydrofuran-2-carboxylic acid ethyl ester (123 mg, 0.5 mmol) was added to the reaction solvent. After stirring for 18 hours at room temperature, saturated aqueous sodium hydrogen carbonate solution (3 ml) was added to terminate the reaction. The mixture was extracted with Et ₂ O (10 mL × 3) and washed with saturated sodium bicarbonate (10 ml) and saturated aqueous sodium chloride solution (10 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, 3- [4- (2-ethoxycarbonyl-1-hydroxy-buta-2,3-dienyl) -phenyl] -2,5-dihydro. Furan-2-carboxylic acid ethyl ester (116 mg, 65%) was obtained.

2- [4- (2-ethoxycarbonyl-1-hydroxybuta-2,3-enyl) -phenyl] -2, instead of 2-hydroxymethyl-buta-2,3-dienoic acid ethyl ester The title compound (87 mg, 81%) was obtained in the same manner as in Example 1 except using 5-dihydrofuran-3-carboxylic acid ethyl ester (108 mg, 0.3 mmol).

TABLE 1 ¹ H NMR data of Example Compound

Claims (8)

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

[In Formula 1, R is independently selected from a (C1-C7) alkyl group; A is hydrogen, or is selected from (C 1 -C 7) alkyl, (C 3 -C 8) cycloalkyl, (C 6 -C 20) aryl, or (C 6 -C 20) aryl (C 1 -C 7) alkyl, in which A is alkyl, cyclo Alkyl, aryl or arylalkyl is a halogen element, nitro group, hydroxy group, (C1-C7) alkyl, (C1-C7) alkoxy, (C1-C7) alkylcarbonyl, (C1-C7) alkoxycarbonyl, and formyl group May be substituted with one or more substituents selected from (-CHO); n is an integer of 1 to 3.] The method of claim 1, Dihydrofuran derivative is a dihydrofuran derivative characterized in that it is selected from a compound of formula (2) or (3): [Formula 2]

[Formula 3]

[In Formula 2 and Formula 3, R and R 'are independently selected from (C1-C7) alkyl group; B ¹ in formula (2) is hydrogen or selected from (C ¹ -C 7) alkyl, (C 3 -C 8) cycloalkyl, (C 6 -C 20) aryl, or (C 6 -C 20) aryl (C 1 -C 7) alkyl; B ² in formula (3) is selected from (C1-C7) alkylene, (C3-C8) cycloalkylene, (C6-C20) arylene, or (C6-C20) aryl (C1-C7) alkylene; Alkyl, cycloalkyl, aryl or arylalkyl of B ¹ and B ² may be a halogen element, a nitro group, a hydroxy group, (C 1 -C 7) alkyl, (C 1 -C 7) alkoxy, (C 1 -C 7) alkylcarbonyl, (C 1 Or C1) alkoxycarbonyl, and one or more substituents selected from formyl groups (-CHO).] The method of claim 2, Dihydrofuran derivatives are selected from compounds of the structure:

[Wherein R and R 'are independently selected from (C1-C7) alkyl groups.] Preparation of a dihydrofuran derivative comprising preparing a dihydrofuran derivative of the general formula (1) through an intramolecular cyclization reaction of a homoalenyl alcohol compound represented by the following general formula (4) under a gold (Au) catalyst Way. [Formula 1]

[Formula 4]

[In Formula 1 and Formula 4, R is independently selected from a (C1-C7) alkyl group; A is hydrogen, or is selected from (C 1 -C 7) alkyl, (C 3 -C 8) cycloalkyl, (C 6 -C 20) aryl, or (C 6 -C 20) aryl (C 1 -C 7) alkyl, in which A is alkyl, cyclo Alkyl, aryl or arylalkyl is a halogen element, nitro group, hydroxy group, (C1-C7) alkyl, (C1-C7) alkoxy, (C1-C7) alkylcarbonyl, (C1-C7) alkoxycarbonyl, and formyl group May be substituted with one or more substituents selected from (-CHO); n is an integer of 1 to 3.] The method of claim 4, wherein The gold (Au) catalyst is selected from AuBr, AuCl or PPh ₃ AuCl as a monovalent gold catalyst, AuBr ₃ or AuCl ₃ as a trivalent gold catalyst, a method for producing a derivative. The method of claim 5, wherein A method for producing a dihydrofuran derivative, characterized by using a silver (Ag) catalyst selected from the group consisting of AgOTf, AgBF ₄ , AgSbF ₆ , AgAsF ₆ , and AgPF ₆ in addition to the gold (Au) catalyst. The method of claim 6, The use amount of the silver catalyst is 2 to 4 mole times with respect to the gold (Au) catalyst when using a trivalent gold (Au) catalyst, 0.5 to 1.5 mole times when using a monovalent gold (Au) catalyst, characterized in that Method for preparing a dihydrofuran derivative. The method of claim 4, wherein The cyclization reaction is carried out under a solvent selected from acetonitrile, dichloromethane, dichloroethane, nitromethane dichloromethane (CH ₂ Cl ₂ ), and a mixed solvent thereof. Method for producing a dihydrofuran derivative, characterized in that.