KR102321935B1 - Cyclic ketone-fused γ-butenolide compounds and preparation method thereof - Google Patents

Abstract

The present invention relates to a novel gamma-butenoride compound having a cyclic ketone compound and a method for preparing the same. The one-pot synthesis method used has the advantage of efficiently synthesizing a gamma-butenoride compound conjugated to a cyclic ketone compound having various substituents at once, and is a novel method synthesized by the above synthesis method. The gamma-butenoride compound is used as a natural product synthesis and pharmaceutical agent, or has antioxidant, antibacterial insecticidal and bactericidal effects, and thus can be widely used in herbicides and pesticides.

Description

Gamma-butenolide compound having a cyclic ketone compound and a preparation method thereof {Cyclic ketone-fused γ-butenolide compounds and preparation method thereof}

The present invention relates to a novel gamma-butenoride compound having a cyclic ketone compound and a method for preparing the same. The one-pot synthesis method used has the advantage of efficiently synthesizing a gamma-butenoride compound conjugated to a cyclic ketone compound having various substituents at once, and is a novel method synthesized by the above synthesis method. The gamma-butenoride compound is used as a natural product synthesis and pharmaceutical agent, or has antioxidant, antibacterial insecticidal and bactericidal effects, and thus can be widely used in herbicides and pesticides.

Gamma-butenolide compounds are compounds with important structural motifs widely found in natural and synthetic compounds. Compounds containing these structures possess a wide range of biological activities, and some have been used in traditional medicine. . It can also serve as a building block for the synthesis of novel functional substances for the synthesis of complex materials and pharmaceuticals.

For example, a gamma-butenoride compound with a cyclohexane ring conjugated is a characteristic skeleton core of a physiologically active natural product, and because of their importance and usefulness, intramolecular and intermolecular cyclization protocols have been adopted. Many efforts have been made to prepare these heterocyclic structures using

A typical synthesis method is within a molecular gold catalyst cascade cyclization (gold-catalyzed cascade cyclization) / (Z) - Enigma oxidative decomposition reaction of the play (oxidative cleavage reaction of (Z) -enynols), carbonyl dioxide and 2,3-oleic play carboxylation of 2,3-allenols with carbondioxide, diphenyldiselenide-catalyzed cyclization of β,δ-butenoicacids, and meta A ruthenium-catalyzed ring-closing metathesis of methallylacrylates and the like are known.

Further, intermolecular synthesis include crotonaldehyde, or by organic or Lewis acid catalyst p-Kui nonme lactide and Mukai Yamato of silica oxy furan-Michael reaction (organo- or Lewis acid-catalyzed Mukaiyama-Michael reaction of crotonaldehyde or silyloxy furans to p -quinone methides), tandem reactions of trifluoromethyl ketone or nitrogen nucleophiles with vinyl epoxides, tertiary catalyzed by Lewis and Bronsted acids Lewis and Brønsted acid-promoted annulation of ketoacids with tertiary alcohols, tandems of allylic carbonates and trifluoromethyl ketones promoted by phosphine tandem reactions, and boron-catalyzed aldol reactions of benzyl aldehyde and pyruvic acid.

Although various synthesis methods of gamma-butenolide have been reported, the development of a novel gamma-butenoride compound conjugated with a cyclic ketone compound has been limited.

On the other hand, as the synthesis of gamma-butenolide conjugated with cyclohexane, it has been reported as a process of 4 steps starting from pyrrolidine enamine (SK Bagal, RM Adlington, JE Baldwin and R. Marquez) , J. Org. Chem ., 2004, 69 , 9100.), a one-pot synthesis method of gamma-butenolide conjugated with cyclohexane has not yet been reported.

Therefore, it is very urgent to develop a new synthesis method capable of synthesizing a gamma-butenoride compound having various substituents and conjugated with a cyclic ketone compound more easily and efficiently.

S. K. Bagal, R. M. Adlington, J. E. Baldwin and R. Marquez, J. Org. Chem., 2004, 69, 9100.) Org Biomol Chem. 2017 Jul 26;15(29):6098-6103 (2017.07.26. Released)

The present inventors have found that when a cyclic diazodicarbonyl compound and a beta-ketoamide compound are reacted under a ruthenium catalyst, the cyclic diazocarbonyl compound and the beta-ketoamide compound are coupled at once. Thus, the present invention was completed by confirming that a gamma-butenoride compound conjugated with a cyclic ketone compound having various substituents can be easily prepared in a simple and excellent yield by a one-pot reaction.

Accordingly, an object of the present invention is to provide a gamma-butenoride compound in which a cyclic ketone compound having various substituents is conjugated.

Another object of the present invention is to provide a method for preparing the gamma-butenoride compound.

The present invention solves the above problem by providing a compound selected from gamma-butenolides compounds represented by the following formula (I) and pharmaceutically acceptable salts thereof.

[Formula Ⅰ]

In the above formula (I),

Wherein X is a substituted or unsubstituted C ₁ to C ₄ alkyl group; and NRR' (wherein, R and R' are each independently a hydrogen atom; or a substituent _{selected from a substituted or unsubstituted C 1} to C ₄ alkyl group); an aliphatic cyclic compound as any one selected from the group consisting of ( A) to form,

Each of R ₁ or R ₂ may be the same or different, and may be a hydrogen atom; C _{1 To} C ₁₀ Alkyl group; a substituted or unsubstituted aryl group; And 5- to 6-membered heterocyclic compound; represents any one selected from the group consisting of,

wherein R ₃ is a substituted or unsubstituted C ₁ to C ₁₀ alkyl group; and a substituted or unsubstituted aryl group; represents any one selected from the group consisting of,

Each of R ₄ or R ₅ may be the same or different, and may be a hydrogen atom; or a substituted or unsubstituted C ₁ to C ₄ alkyl group;

The R ₁ or R ₂ may _{be connected to each other with R 4} or R ₅ to form a substituted or unsubstituted aryl group.

In addition, the present invention is characterized in that the cyclic diazodicarbonyl compounds represented by the following formula (1) and beta-ketoamide compounds (β-ketoamide compounds) represented by the following formula (2) are reacted under a ruthenium catalyst. By providing a method for producing a gamma-butenolides (γ-butenolides) compound represented by the following formula (I), the above problems are solved.

[Formula 1]

[Formula 2]

[Formula Ⅰ]

(In Formula 1, Formula 2, and Formula I, X, and R ₁ to R ₅ are each as defined above.)

The novel gamma-butenoride compound according to the present invention can be widely used for synthesizing natural products and used as pharmaceuticals, or as herbicides and pesticides due to its antioxidant, antibacterial, and bactericidal effects.

In addition, the method for preparing a novel gamma-butenoride compound according to the present invention uses a cyclic diazocarbonyl compound and a beta-ketoamide compound as starting materials, but uses ruthenium catalysts in a polar solvent; AgSbF ₆ phosphorus Gamma having various substituents by coupling a cyclic diazocarbonyl compound and a beta-ketoamide compound through a one-pot reaction by using a co-catalyst and an additive together in a predetermined amount -It has the advantage of being able to easily generate a butenolide compound. In addition, this reaction has the advantage that the synthesis is simple, and the chemical and stereoselectivity are high, so that it is excellent in terms of yield and thus excellent in economic terms.

1 is a view showing a ruthenium-catalyzed reaction between a cyclic diazocarbonyl compound and a beta-ketoamide compound according to the present invention to synthesize a novel gamma-butenoride compound.

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

The present inventors have a one-pot method by coupling cyclic diazodicarbonyl compounds and beta-ketoamide compounds under a ruthenium catalyst with a diazocarbonyl compound and beta-ketoamide compound at once. The present invention was completed by confirming that a gamma-butenoride compound conjugated with a cyclic ketone compound having various substituents can be prepared simply and easily by a one-pot reaction (see FIG. 1).

More specifically, the present invention provides a compound selected from gamma-butenolides compounds represented by the following formula (I) and pharmaceutically acceptable salts thereof.

[Formula Ⅰ]

In Formula 1, X is a substituted or unsubstituted C ₁ to C ₄ alkyl group; and NRR' (wherein, R and R' are each independently a hydrogen atom; or a substituent _{selected from a substituted or unsubstituted C 1} to C ₄ alkyl group); an aliphatic cyclic compound as any one selected from the group consisting of ( A), wherein R ₁ or R ₂ may each be the same or different, and may be a hydrogen atom; C _{1 To} C ₁₀ Alkyl group; a substituted or unsubstituted aryl group; And any one selected from the group consisting of a pentacyclic heterocyclic compound, wherein R ₃ is a substituted or unsubstituted C ₁ to C ₁₀ alkyl group; represents a substituted or unsubstituted aryl group, wherein R ₄ or R ₅ may be the same or different, respectively, and a hydrogen atom; or a substituted or unsubstituted C ₁ to C ₄ alkyl group; wherein R ₁ or R ₂ is _{connected to each other with R 4} or R ₅ to form a substituted or unsubstituted aryl group.

Preferably, X represents any one selected from the group consisting _{of -CH 2} -, -CH ₂ CH ₂ -, -NH-, and -N(CH _{3 ), wherein R 1} or R ₂ is a hydrogen atom; halogen atom; C _{1 To} C ₁₀ Alkyl group; C _{1 To} C ₄ An aryl group having an alkoxy alkyl or halogen atom as a substituent or unsubstituted; and a pentacyclic to hexagonal heterocyclic compound having an oxygen atom as a hetero element; represents any one selected from the group consisting of, wherein R ₃ is a substituted or unsubstituted C ₁ to C ₁₀ alkyl group; and a nitro group (NO ₂ ) or _{a phenyl group having a C 1} to C ₄ alkoxyalkyl as a substituent; represents any one selected from the group consisting of, wherein R ₁ or R ₂ is R ₄ or R ₅ It is formed by being connected to each other The aryl group may be a benzene ring.

로서, 상기 R₆ 내지 R₁₀은 각각 동일하거나 다를 수 있고, 수소 원자; 할로겐 원자; 및 C₁ 내지 C₄의 알콕시 알킬;로 이루어진 군에서 선택된 어느 하나의 치환기를 갖거나, R₇ 내지 R₈이 서로 연결되고 헤테로 원자인 산소 원자가 1 내지 2개 포함된 5각 내지 6각의 헤테로 시클로알킬을 포함할 수 있다. 바람직하게는, 상기 헤테로 시클로알킬은 R₇ 내지 R₈이 서로 연결된 것으로,

일 수 있다.More preferably, the aryl group in _{R 1} or R ₂

, wherein R ₆ to R ₁₀ may be the same or different, respectively, and may be a hydrogen atom; halogen atom; And C _{1 To} C ₄ Alkoxy alkyl; or having any one substituent selected from the group consisting of, or R _{7 To} R ₈ are connected to each other and a pentagonal to hexagonal hetero atom containing 1 to 2 oxygen atoms that are hetero atoms cycloalkyl. Preferably, the heterocycloalkyl is R ₇ to R ₈ are connected to each other,

can be

The gamma butenolides (γ-butenolides) compound is ( E )-3-(1-hydroxyethylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2, 4-dione [( E )-3-(1-Hydroxyethylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 3a]; ( E )-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione[( E )-3-(1-Hydroxyethylidene)-3,5 ,6,7-tetrahydrobenzofuran-2,4-dione, compound 3b]; ( E )-3-(1-hydroxyethylidene)-6-methyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-3-(1-Hydroxyethylidene) -6-methyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 3c]; ( E )-3-(1-hydroxyethylidene)-6-isopropyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-3-(1-Hydroxyethylidene) )-6-isopropyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 3d]; ( E )-3-(1-hydroxyethylidene)-6-phenyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-3-(1-Hydroxyethylidene) -6-phenyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 3e]; ( E )-6-(3,4-dimethoxyphenyl)-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E ) -6-(3,4-Dimethoxyphenyl)-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 3f]; ( E )-6-(benzo[d][1,3]dioxol-5-yl)-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2 ,4-dione[( E )-6-(Benzo[ d ][1,3]dioxol-5-yl)-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2,4- dione, compound 3 g]; ( E )-6-(4-chlorophenyl)-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-6- (4-Chlorophenyl)-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 3h]; ( E )-6-(furan-2-yl)-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione[( E )-6 -(Furan-2-yl)-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 3i]; ( E )-3-(1-hydroxypropylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-3-(1-Hydroxypropylidene) )-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4a]; ( E )-6-(4-chlorophenyl)-3-(1-hydroxypropylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione[( E )-6-( 4-Chlorophenyl)-3-(1-hydroxypropylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4b]; ( E )-6-(furan-2-yl)-3-(1-hydroxypropylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione[( E )-6- (Furan-2-yl)-3-(1-hydroxypropylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4c]; ( E )-3-(1-hydroxybutylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione[( E )-3-(1- Hydroxybutylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4d]; ( E )-3-(1-Hydroxybutylidene)-6-methyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-3-(1-Hydroxybutylidene) -6-methyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4e]; ( E )-6-(furan-2-yl)-3-(1-hydroxybutylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione[( E )-6 -(Furan-2-yl)-3-(1-hydroxybutylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4f]; ( E )-3-(1-hydroxy-2-methylpropylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione[( E )-3- (1-Hydroxy-2-methylpropylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4g]; ( E )-3-(1-hydroxy-2-methylpropylidene)-6-methyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione[( E )-3-(1) -Hydroxy-2-methylpropylidene)-6-methyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4h]; ( E )-6-(furan-2-yl)-3-(1-hydroxy-2-methylpropylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-6-(Furan-2-yl)-3-(1-hydroxy-2-methylpropylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4i]; ( E )-3-(1-hydroxy-2,2-dimethylpropylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione[( E )- 3-(1-Hydroxy-2,2-dimethylpropylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4j]; ( E )-3-(1-hydroxy-2,2-dimethylpropylidene)-6-phenyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione[( E )-3- (1-Hydroxy-2,2-dimethylpropylidene)-6-phenyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4k]; ( E )-3-(1-hydroxyhexylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione[( E )-3-(1) -Hydroxyhexylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4l]; (E)-3-(1-hydroxyhexylidene)-6-isopropyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [ E )-3-(1-Hydroxyhexylidene) -6-isopropyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4m]; ( E )-6-(benzo[d][1,3]dioxol-5-yl)-3-(1-hydroxyhexylidene)-3,5,6,7-tetrahydrobenzofuran-2 ,4-dione[( E )-6-(Benzo[ d ][1,3]dioxol-5-yl)-3-(1-hydroxyhexylidene)-3,5,6,7-tetrahydrobenzofuran-2,4- dione, compound 4n]; ( E ) 3-(1-Hydroxydodecylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-3-(1-Hydroxydodecylidene) )-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4o]; ( E )-3-(1-Hydroxydodecylidene)-6-phenyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-3-(1-Hydroxydodecylidene) -6-phenyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4p]; ( E )-3-(hydroxy(phenyl)methylene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione[( E )-3-(Hydroxy(phenyl) )methylene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4q]; ( E )-3-(hydroxy(phenyl)methylene)-6-isopropyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione[( E )-3-(Hydroxy(phenyl) methylene)-6-isopropyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4r]; ( E )-3-(hydroxy(4-methoxyphenyl)methylene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione[( E )-3- (Hydroxy(4-methoxyphenyl)methylene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4s]; ( E )-3-(hydroxy(4-nitrophenyl)methylene)-6-isopropyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione[( E )-3-(Hydroxy (4-nitrophenyl)methylene)-6-isopropyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4t]; ( E )-3-(1-hydroxyethylidene)-5,6,7,8-tetrahydro-2H-cyclohepta[b]furan-2,4(3H)-dione[( E )-3 -(1-hydroxyethylidene)-5,6,7,8-tetrahydro- 2H- cyclohepta[ b ]furan-2,4( 3H )-dione, compound 5b]; ( E )-3-(1-hydroxyethylidene)-5-methyl-3,5-dihydrofuro[3,2-c]quinoline-2,4-dione[( E )-3-( 1-Hydroxyethylidene)-5-methyl-3,5-dihydrofuro[3,2-c]quinoline-2,4-dione, compound 5c]; and ( E )-3-(1-hydroxyhexylidene)-5-methyl-3,5-dihydrofuro[3,2-c]quinoline-2,4-dione[( E )-3- (1-Hydroxyhexylidene)-5-methyl-3,5-dihydrofuro[3,2-c]quinoline-2,4-dione, compound 5d]; may be any one selected from the group consisting of, but is not limited thereto .

In addition, the present invention reacts cyclic diazodicarbonyl compounds represented by the following formula (1) and beta-ketoamide compounds (β-ketoamide compounds) represented by the following formula (2) under a ruthenium catalyst, A method for preparing a gamma-butenolide (γ-butenolides) compound represented by I is provided.

[Formula 1]

[Formula 2]

In Formulas 1 and 2 and Formula I, X, and R ₁ to R ₅ are each as defined above.

In addition, the cyclic diazocarbonyl compound represented by Formula 1 is 2-diazo-5,5-dimethylcyclohexane-1,3-dione (2-diazo-5,5-dimethylcyclohexane-1,3-dione) , compound 1a); 2-diazo-cyclohexane-1,3-dione (2-diazo-cyclohexane-1,3-dione, compound 1b); 2-diazo-5-methylcyclohexane-1,3-dione (2-diazo-5-methylcyclohexane-1,3-dione, compound 1c); 2-diazo-5-isopropylcyclohexane-1,3-dione (2-diazo-5-isopropylcyclohexane-1,3-dione, compound 1d); 2-diazo-5-phenylcyclohexane-1,3-dione (2-diazo-5-phenylclohexane-1,3-dione, compound 1e); 2-diazo-5-(3,4-dimethoxyphenyl)cyclohexane-1,3-dione (2-diazo-5-(3,4-dimethoxyphenyl)cyclohexane-1,3-dione, compound 1f); 5-(benzo[d][1,3]dioxol-5-yl)-2-diazocyclohexane-1,3-dione (5-(benzo[d][1,3]dioxol-5-yl )-2-diazocyclohexane-1,3-dione, compound 1 g); 5-(4-chlorophenyl)-2-diazocyclohexane-1,3-dione (5-(4-chlorophenyl)-2-diazocyclohexane-1,3-dione, compound 1h); and 2-diazo-5-(furan-2-yl)cyclohexane-1,3-dione (2-diazo-5-(furan-2-yl)cyclohexane-1,3-dione, compound 1i). It may be selected from the group, but is not limited thereto.

The beta-ketoamide compound represented by Formula 2 is 3-oxo- N- phenylbutanamide (3-oxo-N-phenylbutanamide, compound 2a); 3-oxo-N- phenylpentanamide (3-oxo-N-phenylpentanamide, compound 2b); 3-oxo- N- phenylhexanamide (compound 2c); 4-methyl-3-oxo-N- phenylpentanamide (4-methyl-3-oxo-N-phenylpentanamide, compound 2d); 4,4-dimethyl-3-oxo-N- phenylpentanamide (4,4-dimethyl-3-oxo-N-phenylpentanamide, compound 2e); 3-oxo-N- phenyloctanamide (3-oxo-N-phenyloctanamide, compound 2f); 3-oxo-N- phenyltridecanamide (3-oxo-N-phenyltridecanamide, compound 2g); 3-oxo-N,3-diphenylpropanamide (3-oxo- N,3- diphenylpropanamide, compound 2h); 3-(4-methoxyphenyl)-3-oxo-N-phenyl propanamide (3-(4-metho xyphenyl)-3-oxo- N- phenylpropanamide, compound 2i); and 3-(4-nitrophenyl)-3-oxo-N-phenyl propanamide (3-(4-nitrophenyl)-3-oxo- N- phenylpropanamide, compound 2j), but is limited thereto it's not going to be

A representative manufacturing method according to the present invention is as shown in Scheme 1 below.

[Scheme 1]

The reaction is [RhCp*Cl ₂ ] ₂ or [RuCl ₂ ( p -cymene)] ₂ selected from ruthenium catalysts and AgSbF ₆ phosphorus Reactivity can be improved by using a co-catalyst together. The concentration of the ruthenium catalyst is 0.5 to 10 mol%, and it is possible to obtain an optimal yield to use the cocatalyst of 5 to 20 mol%. In this case, the polar solvent may be a dichloroethylene (DCE) solvent.

In addition, in addition to the ruthenium catalyst and the co-catalyst, the reaction is performed with any one additive selected from the group consisting of silver acetate (AgOAc), pivalic acid (PivOH), and acetic acid (AcOH) in a polar solvent. Reactivity can be improved by using additionally to react.

The concentration of the additive may be used in the range of 50 to 300 mol% to obtain an optimal yield.

The reaction may be carried out at 50 to 90° C. for 3 to 24 hours, but may be changed depending on the reactants and conditions.

The reaction is a one-pot reaction, whereby a cyclic diazocarbonyl compound and a beta-ketoamide compound are coupled to obtain a gamma-butenolide compound in which a cyclic ketone compound having various substituents is conjugated. However, it can be produced in high yield.

Hereinafter, preferred examples are presented to help the understanding of the present invention, but the following examples are only illustrative of the present invention, and the scope of the present invention is not limited to the following examples. The embodiments of the present invention are provided to more completely explain the present invention to those of ordinary skill in the art.

(Example 1)

1. Common Experimental Analysis Method

All experiments below were performed under a nitrogen atmosphere. To measure TLC for analysis, pre-coated silica gel plates (Art. 5554) with a fluorescent indicator from Merck were used. Flash column chromatography was performed using silica gel 9385 (Merck). Melting points were measured using a Fisher-Johns melting point apparatus and were not calibrated. ¹ H NMR and ¹³ C NMR analyzes were recorded using a Varian VNS or DPX (600 MHz or 300 MHz and 150 MHz or 75 MHz, respectively) spectrometer in _{CDCl 3} with solvochemical shifts of 7.24 ppm and 77.00 ppm. Chemical shift is reported in units of ppm (units of ppm), and the coupling constant value (J) is expressed in Hz. Multiplicity was summarized as follows: s = singlet, d = doublet, t = triplet, q = triplet, m = multiplet, and dd = doublet of doublet. IR analysis (infrared analysis) was recorded with a PerkinElmer Spectrum Two ^{TM IR spectrometer whose frequency is expressed in cm -1} , and high-resolution mass spectrometry (HR-MS) was performed with a Jeol JMS 700 spectrometer through the Korea Basic Science Institute.

2. Identification of optimal reaction conditions

[Table 1]

Referring to Table 1, the cyclic diazo of 2-diazo-5,5-dimethylcyclohexane-1,3-dione (2-diazo-5,5-dimethylcyclohexane-1,3-dione, compound 1a) is By performing a ruthenium metal catalyzed reaction from a carbonyl compound and a beta-ketoamide compound, which is 3-oxo-N- phenylbutanamide (compound 2a), a gamma-butenoride reaction for compound 3a Optimization of the conditions is shown.

More specifically, when 10 mol% RuCl ₃ or Ru(PPh ₃ ) ₃ Cl ₂ was first tried in a DCE solvent at 70° C. for 12 hours, it was confirmed that compound 3a was not produced (entries 1 and 2). It was confirmed that compound 3a could not be synthesized even in reaction with other catalysts such as _{RhCp*Cl 2} (5 mol%), [RuCl ₂ ( p -cymene)] ₂ (2.5 _{mol%), AgSbF 6 (10 mol%).} (entries 3-5).

However, the reaction of binding _{[RhCp*Cl 2} ] ₂ (5 mol%) or [RuCl ₂ ( p -cymene)] ₂ (2.5 mol%) together with _{AgSbF 6} (10 mol%) as a co-catalyst was 21% and 46, respectively. It was confirmed that compound 3a can be obtained in a yield of % (entries 6 and 7).

It was confirmed that the reaction was further improved by additives such as AgOAc, PivOH and AcOH except for NaOAc (entries 8-11).

_{[RuCl 2} ( p -cymene)] ₂ (2.5 _{mol%) and AgSbF 6} (10 mol%) as a catalyst in the presence of AcOH (200 mol%) in a dichloroethylene (DCE) solvent at 70 ° C. for 5 hours 94% of compound 3a was obtained as an optimal yield during the reaction (entries 12). On the other hand, lowering the temperature to room temperature resulted in significantly lower yields (entries 13 and 14).

In addition, reactions in non-polar or other polar solvents such as toluene, dioxane, acenitrile and dimethylformamide (DMF) solvents have given poor results (entries 15-18).

The gamma-butenoride compound 3a was confirmed by irradiation analysis using a spectrometer and comparison with a structurally related compound, and as a ^{result of 1} H NMR analysis, the enol proton (s = 13.31 ppm), the methyl peak of the vinyl moiety (d = 2.40 ppm), and two identical methyl peaks (d = 1.14 ppm). In addition, ₁₃ C NMR analysis showed a carbonyl carbon of the enone moiety (δ 196.7 ppm) and an ester carbonyl carbon on the lactone nucleus (δ 175.7 ppm).

Therefore, the optimal condition is entry 12, using [RuCl ₂ ( p- cymene)] ₂ (2.5 mol%) and AgSbF ₆ (10 mol%) in the presence of AcOH (200 mol%) in DCE solvent 5 at 70° C. (E )-3-(1-hydroxyethylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione in the highest yield when reacted for a period of time It was confirmed that compound 3a could be obtained.

3. Preparation using a cyclic diazocarbonyl compound having various substituents (Compound 1)

[Scheme 2]

compound 1 R1 R2 compound name

1a Me Me 2-diazo-5,5-dimethylcyclohexane-1,3-dione 2-diazo-5,5-dimethylcyclohexane-1,3-dione 1b H H 2-diazocyclohexane-1,3-dione 2-diazo-cyclohexane-1,3-dione 1c Me H 2-diazo-5-methylcyclohexane-1,3-dione 2-diazo-5-methylcyclohexane-1,3-dione 1d i- Pr H 2-diazo-5-isopropylcyclohexane-1,3-dione 2-diazo-5-isopropylcyclohexane-1,3-dione 1e Ph H 2-diazo-5-phenylclohexane-1,3-dione 2-diazo-5-phenylcyclohexane-1,3-dione 1f 3,4dimethoxyphenyl H 2-diazo-5-(3,4-dimethoxyphenyl)cyclohexane-1,3-dione 2-diazo-5-(3,4-dimethoxyphenyl)cyclohexane-1,3-dione 1 g benzo[d][1,3]dioxol-5-yl H 5-(benzo[d][1,3]dioxol-5-yl)-2-diazocyclohexane-1,3-dione 5-(benzo[d][1,3]dioxol-5-yl)-2-diazocyclohexane-1,3-dione 1h 4-chlorophenyl H 5-(4-chlorophenyl)-2-diazocyclohexane-1,3-dione 5-(4-Chlorophenyl)-2-diazocyclohexane-1,3-dione 1i furan-2-yl H 2-diazo-5-(furan-2-yl)cyclohexane-1,3-dione 2-diazo-5-(furan-2-yl)cyclohexane-1,3-dione

After obtaining the optimized conditions, referring to Scheme 2 and Table 2, the reactivity was obtained using the cyclic diazocarbonyl compound 1b-1i having various substituents and the 3-oxo-N-phenylbutanamide compound 2a. evaluated.

Specifically, 92% of compound 3b could be obtained through the reaction of diazo compound 1b having no substituent at the 5-position of the 2-diazo-1,3-cyclohexanedione ring. In addition, when compound 1c or compound 1d having a methyl or isopropyl group at position 5 on the 1,3-cyclohexanedione ring was reacted, 92% of compound 3c and 90% of compound 3d were obtained, respectively. In addition, in the case of compound 3e-3i, it was confirmed that it could be successfully obtained in a yield of 74 to 83%.

4. Preparation using beta-ketoamide compound (Compound 2) having various substituents

[Scheme 3]

compound 2 R3 compound name

2a Me 3-oxo- N- phenylbutanamide 3-oxo-N-phenylbutanamide 2b It's 3-oxo- N- phenylpentanamide 3-oxo-N-phenylpentanamide 2c Pr 3-oxo- N- phenylhexanamide 3-oxo-N-phenylhexanamide 2d i- Pr 4-methyl-3-oxo- N -phenylpentanamide 4-Methyl-3-oxo-N-phenylpentanamide 2e t-Bu 4,4-dimethyl-3-oxo- N- phenylpentanamide 4,4-Dimethyl-3-oxo-N-phenylpentanamide 2f n-pentyl 3-oxo- N- phenyloctanamide 3-oxo-N-phenyloctanamide 2g n-undecanyl 3-oxo- N- phenyltridecanamide 3-oxo-N-phenyltridecanamide 2h Ph 3-oxo- N,3- diphenylpropanamide 3-oxo-N,3-diphenylpropanamide 2i 4-OMePh 3-(4-metho xyphenyl)-3-oxo- N- phenylpropanamide 3-(4-Methoxyphenyl)-3-oxo-N-phenylpropanamide 2j 4-NO ₂ PH 3-(4-nitrophenyl)-3-oxo- N- phenylpropanamide 3-(4-nitrophenyl)-3-oxo-N-phenylpropanamide

Referring to Scheme 3 and Table 3, cyclic diazocarbonyl compounds 1a, 1c-1e, 1h-1i, and 1g having various substituents and beta-ketoamide compound 2b-2j having various substituents were used for reactivity evaluated.

More specifically, the reaction of compound 1a, compound 1h or compound 1i with compound 2b, which is 3-oxo-N-phenylpentanamide, yields compound 4a (91%), compound 4b (87%) and compound 4c (83%), respectively could be obtained

Similarly, the reaction of compound 1a, compound 1c and compound 1i with the diazo carbonyl compound of compound 1i with compound 2c, which is 3-oxo-N phenylhexanamide, yielded compound 4d-4f in the range of 82 to 92%, compound 2d is compound By reaction with 1e-1i, compounds 4g to 4i were obtained in a yield of 86 to 90%.

As a result to be noted here, when reacted using compound 2e, which is 4,4-dimethyl-3-oxo-N-pentylpentanamide having a bulky t-butyl group with steric hindrance, compound 4j and compound 4k are each 78 and a yield of 79%. For example, treatment of compound 1a, compound 1d or compound 1g with compound 2f, which is 3-oxo-N-phenyloctanamide, gave compounds 4l to 4n in a yield of 83 to 94%, and compound 1a or compound 1e and It was confirmed that compound 2g, which is 3-oxo-N-phenyltetradecanamide, can be obtained in 95% and 91% yields of compound 4o and compound 4p, respectively.

In addition, the desired products were successfully obtained using keto-amide compounds 2g to 2i having phenyl and aryl groups. When compound 1a or compound 1d and 3-oxo-N,3-diphenylpropanamide (2h) were reacted, compounds 4q (90%) and 4r (92%) were obtained, and 3- (4-methoxyphenyl) When compound 2i which is -3-oxo-N-phenylpropanamide and compound 2j which is 3-(4-nitrophenyl)-3-oxo-N-phenylpropanamide are reacted, compound 4s and compound 4t are 93% and 72 respectively % yield could be obtained.

5. Confirmation of Effect of Ring Size of Diazo Compounds

[Scheme 4]

The reaction of compound 1j and compound 2a under standard conditions did not synthesize the desired compound 5a, but when compound 1k and compound 2a were reacted, compound 5b was successfully synthesized in a yield of 78%. As a result, it can be confirmed that the gamma-butenoride of the present invention can form a hexagonal or more ketone ring compound.

6. Proof of diversity: Synthesis of gamma-butenolide conjugated to a quinoline ring

[Scheme 5]

In order to further demonstrate the versatility of the synthesis method according to the present invention, quinoline is conjugated by reacting compound 11, which is 3-diazochromane-2,4-dione as a diazo carbonyl compound. It was confirmed whether the gamma-butenolide compound was synthesized.

As a result of the reaction, when compound 2a or compound 2f and compound 11 were reacted in a dichloroethane solvent at 70° C. for 6 hours, compound 5c and compound 5d were obtained in yields of 85% and 89%, respectively.

Therefore, it was confirmed that various gamma-butenolides can be prepared when a ruthenium (II) catalyst capable of activating cyclic diazodicarbonyl is used for coupling with a β-ketoamide compound.

7. Confirmation of large-scale reactivity of diazo compound 1c and β-ketoamide compound 2a

[Scheme 6]

As a result of confirming the yield by reacting the synthesis method according to the present invention on a large scale, it was possible to confirm an excellent yield of 84% even in the large-scale reaction of compound 1c and compound 2a. Therefore, it can be confirmed that the synthesis method according to the present invention is an economical method capable of scale-up production.

(Example 2)

Cyclic diazo carbonyl compound ( 1 , 1.1 mmol), β- ketoamide compound ( 2 , 1 mmol), and [RuCl ₂ ( p- cymene)] ₂ (2.5 _{mol%), AgSbF 6} (10 mol%), and AcOH (2 mmol) was added to DCE solvent (5 mL), and the mixture was stirred at 70° C. under a nitrogen atmosphere for a predetermined time. When the reaction was complete as indicated by TLC, water (10 mL) was added and the solution was extracted with ethyl acetate (10 mL×3) and dried over anhydrous Na ₂ SO ₄ . The product (compound 3-5 ) was obtained after purification through column chromatography on silica gel and evaporation of the solvent. Compounds 5c and 5d conjugated with quinoline were also obtained through the same method.

(One) ( E )-3-(1-hydroxyethylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-3-(1-Hydroxyethylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 3a]

It was prepared according to the previous general experimental procedure, and the product was obtained as a white solid (yield: 94% (209 mg), melting point: 162-164° C.): ¹ H NMR (600 MHz, CDCl ₃ ) d 13.31 (1H, s) ), 2.57 (2H, s), 2.41 (2H, s), 2.40 (3H, s), 1.14 (6H, s); ¹³ CNMR (150 MHz, CDCl ₃ ) d 196.7, 175.7, 167.0, 166.5, 115.3, 94.4, 49.6, 36.7, 34.5, 28.4, 18.7; IR (ATR) 2962, 1773, 1625, 1264, 1320, 847, 573 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₂ H ₁₄ O ₄ Na: 245.0790. Found: 245.0788.

(2) ( E )-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-3-(1-Hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 3b]

It was prepared according to the previous general experimental procedure, and the product was obtained as a white solid (yield: 92% (179 mg), melting point: 98-100° C.): ¹ H NMR (600 MHz, CDCl ₃ ) d 13.47 (1H, s) ), 2.71 (2H, t, J = 6.6 Hz), 2.56 (2H, t, J = 6.6 Hz), 2.41 (3H, s), 2.18-1.13 (2H, m); ¹³ CNMR (150 MHz, CDCl ₃ ) d 197.4, 175.9, 167.8, 166.8, 116.6, 94.3, 35.5, 22.8, 21.2, 18.8; IR (ATR) 2958, 1768, 1620, 1312, 866, 567 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₀ H ₁₀ O ₄ Na: 217.0477. Found: 217.0474.

(3)( E )-3-(1-hydroxyethylidene)-6-methyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-3-(1-Hydroxyethylidene)-6-methyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 3c]

It was prepared according to the previous general experimental procedure, and the product was obtained as a white solid (yield: 92% (208 mg), melting point: 84-86° C.): ¹ H NMR (600 MHz, CDCl ₃ ) d 13.41 (1H, s) ), 2.79-2.74 (1H, m), 2.61 (1H, dd, J = 16.9, 2.4 Hz), 2.41-2.38 (5H, m), 2.28 (1H, dd, J = 17.0, 11.0 Hz), 1.17 ( 3H, d, J = 6.2 Hz); ¹³ CNMR (150 MHz, CDCl ₃ ) d 197.0, 175.9, 167.3, 166.9, 116.3, 94.5, 43.8, 30.88, 29.3, 20.8, 18.8; IR (ATR) 2956, 1766, 1612, 1317, 895, 579 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₁ H ₁₂ O ₄ Na: 231.0634. Found: 231.0630.

(4) ( E )-3-(1-hydroxyethylidene)-6-isopropyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-3-(1-Hydroxyethylidene)-6-isopropyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 3d]

It was prepared according to the previous general experimental procedure, and the product was obtained as a white solid (yield: 90% (213 mg), melting point: 168-170° C.): ¹ H NMR (600 MHz, CDCl ₃ ) d 13.37 (1H, s) ), 2.71 (1H, dd, J = 18.4, 4.9 Hz), 2.61 (1H, dd, J = 16.9, 3.9 Hz), 2.45 (1H, dd, J = 18.4, 11.3 Hz), 2.39 (3H, s) , 2.29 (1H, dd, J = 16.9, 12.8 Hz), 2.10-2.04 (1H, m), 1.71-1.64 (1H, m), 0.95 (6H, d, J = 6.8 Hz); ¹³ CNMR (150 MHz, CDCl ₃ ) d 197.4, 175.7, 167.8, 166.9, 116.2, 94.4, 40.9, 39.5, 31.7, 26.5, 19.6, 19.4, 18.7; IR (ATR) 2952, 1714, 1610, 1315, 892, 571 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₃ H ₁₆ O ₄ Na: 259.0947. Found: 259.0943.

(5) ( E )-3-(1-hydroxyethylidene)-6-phenyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-3-(1-Hydroxyethylidene)-6-phenyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 3e]

It was prepared according to the previous general experimental procedure, and the product was obtained as a white solid (yield: 78% (212 mg), melting point: 190-192° C.): ¹ H NMR (600 MHz, CDCl ₃ ) d 13.37 (1H, s) ), 7.36 (2H, t, J = 7.6 Hz), 7.29 (1H, t, J = 7.4 Hz), 7.25 (2H, d, J = 7.5 Hz), 3.57-3.51 (1H, m), 3.01-2.90 (2H, m), 2.83-2.81 (2H, m), 2.44 (3H, s); ¹³ CNMR (150 MHz, CDCl ₃ ) d 196.1, 176.2, 166.8, 166.7, 141.1, 129.0, 127.6, 126.6, 116.5, 94.4, 42.7, 40.0, 30.5, 18.8; IR (ATR) 2960, 1769, 1619, 1321, 911, 768, 702 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₆ H ₁₄ O ₄ Na:293.0790. Found: 293.0787.

(6) ( E )-6-(3,4-dimethoxyphenyl)-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-6-(3,4-Dimethoxyphenyl)-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 3f]

It was prepared according to the previous general experimental procedure, and the product was obtained as a white solid (yield: 74% (245 mg), melting point: 208-210° C.): ¹ H NMR (600 MHz, CDCl ₃ ) d 13.37 (1H, s) ), 6.84 (1H, d, J = 8.3 Hz), 6.79 (1H, dd, J = 8.3, 1.9 Hz), 6.74 (1H, d, J = 2.0 Hz), 3.87 (3H, s), 3.86 (3H) , s), 3.49 (1H, m), 2.99 (1H, dd, J = 18.5, 5.3 Hz), 2.90 (1H, dd, J = 18.5, 10.8 Hz), 2.85-2.75 (2H, m), 2.45 ( 3H, s); ¹³ CNMR (150 MHz, CDCl ₃ ) d 196.1, 176.2, 166.8, 166.8, 149.2, 148.5, 133.7, 118.5, 116.5, 111.5, 110.0, 94.4, 55.9, 43.0, 39.7, 30.8, 18.9; IR (ATR) 2965, 1755, 1608, 1519, 1311, 1252, 1022, 761, 574 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₈ H ₁₈ O ₆ Na: 353.1001. Found: 353.0998.

(7) ( E )-6-(benzo[d][1,3]dioxol-5-yl)-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2,4 -Dion[( E )-6-(Benzo[ d ][1,3]dioxol-5-yl)-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 3g]

It was prepared according to the previous general experimental procedure, and the product was obtained as a white solid (yield: 83% (263 mg), melting point: 215-217° C.): ¹ H NMR (600 MHz, CDCl ₃ ) d 13.35 (1H, s) ), 6.77 (1H, d, J = 8.0 Hz), 6.72 (1H, d, J = 1.6 Hz), 6.69 (1H, dd, J = 8.0, 1.6 Hz), 5.94 (2H, s), 3.48-3.42 (1H, m), 2.95 (1H, dd, J = 18.5, 5.2 Hz), 2.85 (1H, dd, J = 18.5, 10.9 Hz), 2.81-2.70 (2H, m), 2.43 (3H, s); ¹³ CNMR (150 MHz, CDCl ₃ ) d 196.0, 176.2, 166.8, 166.7, 148.0, 146.9, 135.0, 119.8, 116.4, 108.5, 106.96, 101.2, 94.3, 43.0, 39.8, 30.8, 18.8; IR (ATR) 2907, 1780, 1614, 1311, 1241, 1032, 763, 583 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₇ H ₁₄ O ₆ Na: 337.0688. Found: 337.0686.

(8) ( E )-6-(4-chlorophenyl)-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-6-(4-Chlorophenyl)-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 3h]

It was prepared according to the previous general experimental procedure, and the product was obtained as a white solid (yield: 77% (235 mg), melting point: 197-200° C.): ¹ H NMR (600 MHz, CDCl ₃ ) d 13.31 (1H, s) ), 7.33 (2H, d, J = 8.1 Hz), 7.19 (2H, d, J = 8.1 Hz), 3.55-3.50 (1H, m), 2.98 (1H, dd, J = 18.5, 5.1 Hz,), 2.89 (1H, dd, J = 18.4, 10.8 Hz), 2.83-2.74 (2H, m), 2.43 (3H, s); ¹³ CNMR (150 MHz, CDCl ₃ ) d 195.6, 176.3, 166.6, 166.4, 139.5, 133.4, 129.2, 128.0, 116.5, 94.3, 42.6, 39.4, 30.4, 18.8; IR (ATR) 2957, 1766, 1609, 1319, 906, 826, 589 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₆ H ₁₃ O ₄ ClNa: 327.0400. Found: 327.0397.

(9) ( E )-6-(furan-2-yl)-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-6-(Furan-2-yl)-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 3i]

It was prepared according to the previous general experimental procedure, and the product was obtained as a white solid (yield: 81% (212 mg), melting point: 142-144° C.): ¹ H NMR (600 MHz, CDCl ₃ ) d 13.31 (1H, s) ), 7.33 (1H, d, J = 1.1 Hz), 6.30 (1H, dd, J = 3.2, 1.9 Hz), 6.09 (1H, d, J = 3.2 Hz), 3.67-3.62 (1H, m), 3.07 (1H, dd, J = 18.5, 5.4 Hz), 2.96 (1H, dd, J = 18.6, 9.2 Hz), 2.90 (1H, dd, J = 17.2, 4.5 Hz), 2.80 (1H, dd, J = 17.2) , 10.4 Hz), 2.41 (3H, s); ¹³ CNMR (150 MHz, CDCl ₃ ) d 195.4, 176.2, 166.6, 166.0, 154.1, 142.0, 116.5, 110.2, 105.5, 94.3, 40.0, 33.2, 27.9, 18.8; IR (ATR) 3118, 1762, 1623, 1318, 906, 853, 758, 580 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₄ H ₁₂ O ₅ Na: 283.0583. Found: 283.0580.

(10) ( E )-3-(1-hydroxypropylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-3-(1-Hydroxypropylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4a]

Prepared according to the previous general experimental procedure, the product was obtained as a yellow liquid (yield: 91% (216 mg)): ¹ H NMR (600 MHz, CDCl ₃ ) d 13.41 (1H, s), 2.85 (2H, q, J = 7.5 Hz), 2.57 (2H, s), 2.42 (2H, s), 1.18 (3H, t, J = 7.6 Hz), 1.15 (6H, s); ¹³ CNMR (150 MHz, CDCl ₃ ) d 196.7, 180.5, 166.6, 115.4, 93.5, 49.7, 36.8, 34.5, 28.5, 25.2, 10.6; IR (ATR) 2961, 1718, 1621, 1452, 1340, 868, 571 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₃ H ₁₆ O ₄ Na: 259.0947. Found: 259.0944.

(11) ( E )-6-(4-chlorophenyl)-3-(1-hydroxypropylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-6-(4-Chlorophenyl)-3-(1-hydroxypropylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4b]

It was prepared according to the previous general experimental procedure, and the product was obtained as a white solid (yield: 87% (280 mg), melting point: 171-173° C.): ¹ H NMR (600 MHz, CDCl ₃ ) d 13.42 (1H, s) ), 7.32 (2H, d, J = 8.3 Hz), 7.19 (2H, d, J = 8.4 Hz), 3.55-3.49 (1H, m), 2.97 (1H, dd, J = 18.4, 5.2 Hz), 2.90 -2.84 (3H, m), 2.82-2.73 (2H, m), 1.19 (3H, t, J = 7.5 Hz); ¹³ CNMR (150 MHz, CDCl ₃ ) d 195.6, 181.1, 166.5, 166.3, 139.5, 133.4, 129.1, 128.0, 116.6, 93.3, 42.6, 39.3, 30.4, 25.3, 10.6; IR (ATR) 2980, 1771, 1605, 1319, 821, 590 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₇ H ₁₅ ClO ₄ Na: 341.0557. Found: 341.0551.

(12) ( E )-6-(furan-2-yl)-3-(1-hydroxypropylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-6-(Furan-2-yl)-3-(1-hydroxypropylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4c]

It was prepared according to the previous general experimental procedure, and the product was obtained as a white solid (yield: 83% (230 mg), melting point: 116-118° C.): ¹ H NMR (600 MHz, CDCl ₃ ) d 13.41 (1H, s) ), 7.33(1H, s), 6.30 (1H, dd, J = 3.0, 1.9 Hz), 6.10 (1H, d, J = 3.2 Hz), 3.67-3.62 (1H, m), 3.07 (1H, dd, J = 18.5, 5.3 Hz), 2.96 (1H, dd, J = 18.5, 9.2 Hz), 2.90 (1H, dd, J = 17.2, 4.5 Hz), 2.86 (2H, q, J = 7.6 Hz), 2.80 ( 1H, dd, J = 17.1, 10.5 Hz), 1.18 (3H, t, J = 7.5 Hz); ¹³ C NMR (150 MHz, CDCl ₃ ) d 195.4, 181.0, 166.3, 166.1, 154.2, 142.0, 116.6, 110.2, 105.5, 93.3, 40.0, 33.2, 27.9, 25.3, 10.6; IR (ATR) 2992, 1765, 1612, 1318, 856, 746, 590 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₅ H ₁₄ O ₅ Na: 297.0739. Found: 297.0735.

(13) ( E )-3-(1-hydroxybutylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-3-(1-Hydroxybutylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4d]

Prepared according to the previous general experimental procedure, the product was obtained as a yellow liquid (yield: 90% (225 mg)): ¹ H NMR (600 MHz, CDCl ₃ ) d 13.37 (1H, s), 2.79 (2H, t, J = 7.2 Hz), 2.56 (2H, s), 2.40 (2H, s), 1.67-1.61 (2H, m), 1.13 (6H, s), 0.96 (3H, t, J = 7.4 Hz); ¹³ C NMR (150 MHz, CDCl ₃ ) d 196.6, 179.4, 166.7, 166.6, 115.4, 94.0, 49.6, 36.7, 34.4, 33.4, 28.4, 20.1, 13.7; IR (ATR) 2964, 1726, 1659, 1573, 1216, 748 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₄ H ₁₈ O ₄ Na: 273.1103. Found: 273.1100.

(14) ( E )-3-(1-hydroxybutylidene)-6-methyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-3-(1-Hydroxybutylidene)-6-methyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4e]

It was prepared according to the previous general experimental procedure, and the product was obtained as a white solid (yield: 92% (218 mg), melting point: 80-82° C.): ¹ H NMR (600 MHz, CDCl ₃ ) d 13.46 (1H, s) ), 2.80 (2H, t, J = 7.8 Hz), 2.75 (1H, d, J = 13.5 Hz), 2.60 (1H, dd, J = 17.0, 3.7 Hz), 2.44-2.37 (2H, m), 2.27 (1H, dd, J = 16.9, 11.9 Hz), 1.68-1.62 (2H, m), 1.16 (3H, d, J = 6.2 Hz), 0.96 (3H, t, J = 7.4 Hz); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 197.0, 179.7, 167.3, 166.6, 116.3, 94.1, 43.8, 33.5, 30.9, 29.8, 20.7, 20.1, 13.7; IR (ATR) 2967, 1750, 1599, 1323, 870, 840, 582 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₃ H ₁₆ O ₄ Na: 259.0947. Found: 259.0944.

(15) ( E )-6-(furan-2-yl)-3-(1-hydroxybutylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-6-(Furan-2-yl)-3-(1-hydroxybutylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4f]

It was prepared according to the previous general experimental procedure, and the product was obtained as a white solid (yield: 82% (237 mg), melting point: 104-106° C.): ¹ H NMR (600 MHz, CDCl ₃ ) d 13.39 (1H, s) ), 7.34 (1H, d, J = 1.7 Hz), 6.30 (1H, dd, J = 3.2, 1.9 Hz), 6.10 (1H, d, J = 3.3 Hz), 3.67-3.62 (1H, m), 3.07 (1H, dd, J = 18.5, 5.3 Hz), 2.96 (1H, dd, J = 18.5, 9.3 Hz), 2.91 (1H, dd, J = 17.2, 4.5 Hz), 2.84-2.78 (3H, m), 1.70-1.63 (2H, m), 0.98 (3H, t, J = 7.4 Hz); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 195.4, 180.0, 166.4, 166.1, 154.2, 142.0, 116.5, 110.2, 105.5, 93.9, 40.1, 33.5, 33.2, 27.9, 20.1, 13.7; IR (ATR) 2965, 1764, 1620, 1326, 851, 740, 592 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₆ H ₁₆ O ₅ Na: 311.0896. Found: 311.0893.

(16) ( E )-3-(1-hydroxy-2-methylpropylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-3-(1-Hydroxy-2-methylpropylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4g]

It was prepared according to the previous general experimental procedure, and the product was obtained as a white solid (yield: 89% (223 mg), melting point: 101-103° C.): ¹ H NMR (600 MHz, CDCl ₃ ) d 13.53 (1H, s) ), 3.89-3.83 (1H, m), 2.56 (2H, s), 2.40 (2H, s), 1.14 (3H, s), 1.13 (9H, s); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 196.7, 183.9, 166.6, 166.4, 115.5, 92.6, 49.7, 36.8, 34.4, 29.4, 28.4, 19.2; IR (ATR) 2967, 1757, 1604, 1304, 858, 579 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₄ H ₁₈ O ₄ Na: 273.1103. Found: 273.1099.

(17) ( E )-3-(1-hydroxy-2-methylpropylidene)-6-methyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-3-(1-Hydroxy-2-methylpropylidene)-6-methyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4h]

It was prepared according to the general experimental procedure above, and the product was obtained as a white solid (yield: 90% (210 mg), melting point: 117-119° C.): ¹ H NMR (600 MHz, CDCl ₃ ) d 13.67 (1H, s) ), 3.91-3.84 (1H, m), 2.78-2.73 (1H, m), 2.60 (1H, dd, J = 16.9, 3.8 Hz), 2.44-2.38 (2H, m), 2.37-2.25 (1H, m) ), 1.16 (3H, d, J = 6.4 Hz), 1.15 (6H, d, J = 6.8 Hz); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 197.1, 184.2, 167.3, 166.3, 116.4, 92.6, 43.8, 30.9, 29.6, 29.4, 20.8, 19.2, 19.2; IR (ATR) 2965, 1767, 1613, 1314, 843, 583 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₃ H ₁₆ O ₄ Na: 259.0947. Found: 259.0944.

(18) ( E )-6-(furan-2-yl)-3-(1-hydroxy-2-methylpropylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-6-(Furan-2-yl)-3-(1-hydroxy-2-methylpropylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4i]

Prepared according to the previous general experimental procedure, the product was obtained as a brown solid (yield: 86% (203 mg), melting point: 85-87° C.): ¹ H NMR (300 MHz, CDCl ₃ ) d 13.60 (1H, s) ), 7.35 (1H, s), 6.31 (1H, dd, J = 3.0, 1.9 Hz), 6.10 (1H, d, J = 2.6 Hz), 3.93-3.84 (1H, m), 3.69-3.59 (1H, m), 3.11-2.93 (2H, m), 2.90-2.75 (2H, m), 1.16 (6H, d, J = 6.8 Hz); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 195.5, 184.5, 166.1, 166.1, 154.1, 142.0, 116.6, 110.2, 105.5, 92.5, 40.0, 33.2, 29.5, 27.9, 19.2, 19.2; IR (ATR) 2973, 1767, 1611, 1312, 912, 770 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₆ H ₁₆ O ₅ Na: 311.0896. Found: 311.0892.

(19) ( E )-3-(1-hydroxy-2,2-dimethylpropylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-3-(1-Hydroxy-2,2-dimethylpropylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4j]

It was prepared according to the previous general experimental procedure, and the product was obtained as a white solid (yield: 78% (208 mg), melting point: 109-111° C.): ¹ H NMR (600 MHz, CDCl ₃ ) d 14.64 (1H, s) ), 2.58 (2H, s), 2.44 (2H, s), 1.37 (9H, s), 1.15 (6H, s); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 197.1, 189.0, 167.2, 165.0, 116.0, 93.3, 49.9, 39.2, 37.1, 34.2, 28.4, 26.1; IR (ATR) 2960, 1759, 1589, 1306, 845, 578 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₅ H ₂₀ O ₄ Na:287.1260. Found: 287.1258.

(20) ( E )-3-(1-hydroxy-2,2-dimethylpropylidene)-6-phenyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-3-(1-Hydroxy-2,2-dimethylpropylidene)-6-phenyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4k]

It was prepared according to the previous general experimental procedure, and the product was obtained as a white solid (yield: 79% (247 mg), melting point: 110-112° C.): ¹ H NMR (600 MHz, CDCl ₃ ) d 14.66 (1H, s) ), 7.30 (2H, t, J = 7.6 Hz), 7.22 (1H, t, J = 7.4 Hz), 7.19 (2H, d, J = 7.7 Hz), 3.50-3.44 (1H, m), 2.94 (1H) , dd, J = 18.4, 5.3 Hz), 2.86 (1H, dd, J = 18.4, 10.9 Hz), 2.84-2.73 (2H, m), 1.32 (9H, s); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 196.5, 189.4, 167.5, 164.8, 141.0, 129.0, 127.6, 126.6, 117.1, 93.2, 42.9, 39.7, 39.2, 30.8, 26.1; IR (ATR) 2941, 1763, 1580, 1309, 867, 769, 698 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₉ H ₂₀ O ₄ Na:335.1260. Found: 335.1257.

(21) ( E )-3-(1-hydroxyhexylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-3-(1-Hydroxyhexylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4l]

Prepared according to the previous general experimental procedure, the product was obtained as a yellow liquid (yield: 94% (262 mg)): ¹ H NMR (600 MHz, CDCl ₃ ) d 13.37 (1H, s), 2.82 (2H, t, J = 7.7 Hz), 2.57 (2H, s), 2.41 (2H, s), 1.64-1.59 (2H, m), 1.36-1.28 (4H, m), 1.14 (6H, s), 0.86 (3H, t) , J = 6.6 Hz); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 196.6, 179.8, 166.7, 166.6, 115.4, 93.9, 49.7, 36.8, 34.4, 31.6, 31.4, 28.5, 26.4, 22.3, 13.8; IR (ATR) 2957, 1723, 1573, 1453, 755, 573 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₆ H ₂₂ O ₄ Na:301.1416. Found: 301.1412.

(22) (E)-3-(1-hydroxyhexylidene)-6-isopropyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-3-(1-Hydroxyhexylidene)-6-isopropyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4m]

Prepared according to the previous general experimental procedure, the product was obtained as a brown solid (yield: 92% (270 mg), melting point: 44-46° C.): ¹ H NMR (600 MHz, CDCl ₃ ) d 13.46 (1H, s) ), 2.85-2.78 (2H, m), 2.71 (1H, dd, J = 18.4, 4.9 Hz), 2.62 (1H, dd, J = 16.9, 3.9 Hz), 2.45 (1H, dd, J = 18.4, 11.3) Hz), 2.30 (1H, dd, J = 16.9, 12.8 Hz), 2.10-2.04 (1H, m), 1.71-1.66 (1H, m), 1.63-1.59 (2H, m), 1.36-1.27 (4H, m), 0.96 (6H, d, J = 6.8 Hz), 0.86 (3H, t, J = 7.0 Hz); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 197.4, 179.9, 167.9, 166.6, 116.3, 93.9, 40.9, 39.6, 31.8, 31.6, 31.3, 26.6, 26.4, 22.3, 19.6, 19.4, 13.8; IR (ATR) 2956, 1770, 1619, 1336, 826, 590 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₇ H ₂₄ O ₄ Na: 315.1573. Found: 315.1569.

(23) ( E )-6-(benzo[d][1,3]dioxol-5-yl)-3-(1-hydroxyhexylidene)-3,5,6,7-tetrahydrobenzofuran-2,4 -Dion[( E )-6-(Benzo[ d ][1,3]dioxol-5-yl)-3-(1-hydroxyhexylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4n]

It was prepared according to the previous general experimental procedure, and the product was obtained as a white solid (yield: 83% (310 mg), melting point: 144-146° C.): ¹ H NMR (600 MHz, CDCl ₃ ) d 13.43 (1H, s) ), 6.77 (1H, d, J = 7.8 Hz), 6.72 (1H, s), 6.69 (1H, d, J = 7.9 Hz), 5.94 (2H, s), 3.47-3.42 (1H, m), 2.94 (1H, dd, J = 18.5, 5.1 Hz), 2.87-2.79 (3H, m), 2.79-2.70 (2H, m), 1.66-1.61 (2H, m), 1.36-1.30 (4H, m), 0.88 (3H, t, J = 6.7 Hz); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 196.0, 180.3, 166.7, 166.4, 148.0, 146.9, 135.0, 119.8, 116.5, 108.5, 106.9, 101.2, 93.8, 43.0, 39.8, 31.7, 31.3, 30.9, 26.4, 22.3 , 13.8; IR (ATR) 2928, 1765, 1611, 1341, 1239, 1036, 769, 577 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₂₁ H ₂₂ O ₆ Na: 393.1314. Found: 393.1312.

(24) ( E ) 3-(1-hydroxydodecylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-3-(1-Hydroxydodecylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4o]

Prepared according to the previous general experimental procedure, the product was obtained as a yellow liquid (yield: 95% (345 mg)): ¹ H NMR (600 MHz, CDCl ₃ ) d 13.37 (1H, s), 2.81 (2H, t, J = 7.8 Hz), 2.56 (2H, s), 2.41 (2H, s), 1.63-1.58 (2H, m), 1.37-1.33 (2H, m), 1.27-1.21 (14H, m), 1.14 (6H) , s), 0.84 (3H, t, J = 7.0 Hz); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 196.6, 179.8, 166.6, 166.5, 115.4, 93.9, 49.7, 36.8, 34.4, 31.8, 31.7, 29.5, 29.5, 29.4, 29.3, 29.2, 28.4, 26.7, 22.6, 14.0 ; IR (ATR) 2924, 1727, 1573, 1455, 1215, 754 cm ^-1 ;HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₂₂ H ₃₄ O ₄ Na:385.2355. Found: 385.2352.

(25) ( E )-3-(1-hydroxydodecylidene)-6-phenyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione[( E )-3-(1-Hydroxydodecylidene)-6-phenyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4p]

It was prepared according to the previous general experimental procedure, and the product was obtained as a white solid (yield: 91% (375 mg), melting point: 112-114° C.): ¹ H NMR (600 MHz, CDCl ₃ ) d 13.40 (1H, s), 7.31 (2H, t, J = 7.7 Hz), 7.23 (1H, t, J = 6.8 Hz), 7.20 (2H, d, J = 8.6 Hz), 3.52-3.46 (1H, m), 2.94 ( 1H, dd, J = 18.5, 5.2 Hz), 2.87 (1H, dd, J = 18.5, 10.8 Hz), 2.82-2.73 (4H, m), 1.61-1.56 (2H, m), 1.34-1.31 (2H, m), 1.24-1.19 (14H, m), 0.81 (3H, t, J = 7.0 Hz); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 170.4, 163.0, 148.8, 135.7, 134.9, 130.4, 128.6, 128.3, 128.1, 114.0, 52.1, 51.4, 33.4; IR (ATR) 2918, 1766, 1621, 1336, 914, 697 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₂₆ H ₃₄ O ₄ Na:433.2355. Found: 433.2353.

(26) ( E )-3-(hydroxy(phenyl)methylene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-3-(Hydroxy(phenyl)methylene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4q]

It was prepared according to the previous general experimental procedure, and the product was obtained as a white solid (yield: 90% (256 mg), melting point: 177-180° C.): ¹ H NMR (600 MHz, CDCl ₃ ) d 13.94 (1H, s) ), 7.70 (2H, d, J = 8.0 Hz), 7.48 (1H, t, J = 7.4 Hz), 7.42 (2H, t, J = 7.7 Hz), 2.62 (2H, s), 2.50 (2H, s) ), 1.19 (6H, s); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 196.9, 172.7, 168.2, 165.7, 132.5, 131.4, 129.1, 127.7, 115.7, 94.1, 49.8, 37.0, 34.4, 28.5; IR (ATR) 2957, 1773, 1617, 1594, 1326, 1284, 968, 852, 695 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₇ H ₁₆ O ₄ Na: 307.0947. Found: 307.0944.

(27) ( E )-3-(Hydroxy(phenyl)methylene)-6-isopropyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-3-(Hydroxy(phenyl)methylene)-6-isopropyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4r]

Prepared according to the previous general experimental procedure, the product was obtained as a yellow solid (yield: 92% (298 mg), melting point: 193-195 ° C.): ¹ H NMR (600 MHz, CDCl ₃ ) d 7.70 (2H, d , J = 8.3 Hz), 7.49-7.46 (1H, m), 7.41 (2H, t, J = 7.8 Hz), 2.75 (1H, dd, J = 18.5, 5.0 Hz), 2.68 (1H, dd, J = 16.9, 3.9 Hz), 2.48 (1H, dd, J = 18.5, 11.3 Hz), 2.35 (1H, dd, J = 16.9, 12.8 Hz), 2.13-2.07 (1H, m), 1.73-1.67 (1H, m) ), 0.96 (6H, d, J = 6.8 Hz); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 197.5, 172.7, 169.6, 165.6, 132.6, 131.4, 129.1, 127.7, 116.6, 94.1, 40.7, 39.8, 31.7, 26.8, 19.6, 19.4; IR (ATR) 2967, 1765, 1595, 1328, 760, 696, 596 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₈ H ₁₈ O ₄ Na: 321.1103. Found: 321.1110.

(28) ( E )-3-(hydroxy(4-methoxyphenyl)methylene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-3-(Hydroxy(4-methoxyphenyl)methylene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4s]

Prepared according to the previous general experimental procedure, the product was obtained as a yellow liquid (yield: 93% (292 mg)): ¹ H NMR (600 MHz, CDCl ₃ ) d 13.94 (1H, s), 7.76 (2H, d, J = 8.9 Hz), 6.91 (2H, d, J = 8.8 Hz), 3.83 (3H, s), 2.60 (2H, s), 2.48 (2H, s), 1.17 (6H, s); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 196.8, 172.6, 167.7, 166.0, 162.3, 131.3, 124.7, 115.9, 113.0, 93.2, 55.3, 49.9, 37.0, 34.3, 28.4; IR (ATR) 2958, 1724, 1673, 1598, 1254, 1165, 1025, 845, 610 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₈ H ₁₈ O ₅ Na: 337.1052. Found: 337.1048.

(29) ( E )-3-(Hydroxy(4-nitrophenyl)methylene)-6-isopropyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [( E )-3-(Hydroxy(4-nitrophenyl)methylene)-6-isopropyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione, compound 4t]

It was prepared according to the previous general experimental procedure, and the product was obtained as a yellow solid (yield: 72% (247 mg), melting point: 159-161° C.): ¹ H NMR (600 MHz, CDCl ₃ ) d 8.24 (2H, d) , J = 7.6 Hz), 7.84 (2H, d, J = 7.6 Hz), 2.78 (1H, dd, J = 18.7, 4.9 Hz), 2.72 (1H, dd, J = 17.0, 3.9 Hz), 2.53 (1H) , dd, J = 18.6, 11.2 Hz), 2.39 (1H, dd, J = 16.9, 12.9 Hz), 2.17-2.11 (1H, m), 1.76-1.70 (1H, m), 0.99 (6H, d, J) = 6.7 Hz); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 197.8, 170.6, 169.2, 165.2, 149.1, 138.6, 130.3, 128.9, 123.0, 120.2, 116.4, 95.8, 40.7, 39.7, 31.7, 26.8, 19.6, 19.4; IR (ATR) 2968, 1767, 1621, 1590, 1516, 1315, 1296, 846 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₈ H ₁₇ NO ₆ Na: 366.0954. Found: 366.0950.

(30) ( E )-3-(1-hydroxyethylidene)-5,6,7,8-tetrahydro-2H-cyclohepta[b]furan-2,4(3H)-dione[( E )-3-(1-hydroxyethylidene)-5,6,7,8-tetrahydro-2 H -cyclohepta[ b ]furan-2,4(3 H )-dione, compound 5b]

It was prepared according to the previous general experimental procedure, and the product was obtained as a white solid (yield: 78% (163 mg), melting point: 112-114° C.): ¹ H NMR (600 MHz, CDCl ₃ ) δ 14.39 (1H, s) ), 2.88 (2H, t, J = 6.3 Hz), 2.80-2.76 (2H, m), 2.44 (3H, s), 1.97-1.93 (2H, m), 1.91-1.87 (2H, m); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 201.1, 177.2, 167.1, 166.0, 118.9, 95.6, 42.1, 28.7, 23.0, 21.4, 20.1; IR (ATR) 2960, 1768, 1620, 1315, 866, 567 cm ^-1 ; HRMS (ESI) m/z (M ⁺ )calcd for C ₁₁ H ₁₂ O ₄ :208.0736. Found: 208.0732.

(31) ( E )-3-(1-hydroxyethylidene)-5-methyl-3,5-dihydrofuro[3,2-c]quinoline-2,4-dione [( E )-3-(1-Hydroxyethylidene)-5-methyl-3,5-dihydrofuro[3,2-c]quinoline-2,4-dione, compound 5c]

Prepared according to the previous general experimental procedure, the product was obtained as a white solid (yield: 85% (219 mg), melting point: 213-215° C.): ¹ H NMR (600 MHz, CDCl ₃ ) d 7.87 (1H, d , J = 7.9 Hz), 7.61 (1H, t, J = 7.8 Hz), 7.48 (1H, d, J = 8.6 Hz), 7.36 (1H, t, J = 7.5 Hz), 3.80 (3H, s), 2.51 (3H, s); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 178.9, 167.1, 160.1, 150.8, 137.9, 130.8, 123.8, 122.6, 115.3, 112.1, 110.4, 95.1, 30.1, 19.5; IR (ATR) 2951, 1755, 1643, 1609, 1609, 1375, 908, 867, 749 cm ^-1 ; HRMS (ESI) m/z [M+Na] ⁺ calcd for C ₁₄ H ₁₁ NO ₄ Na: 280.0586. Found: 280.0583.

(32) ( E )-3-(1-hydroxyhexylidene)-5-methyl-3,5-dihydrofuro[3,2-c]quinoline-2,4-dione[( E )-3-(1-Hydroxyhexylidene)-5-methyl-3,5-dihydrofuro[3,2-c]quinoline-2,4-dione, compound 5d]

Prepared according to the previous general experimental procedure, the product was obtained as a yellow solid (yield: 89% (280 mg), melting point: 102-104 ° C.): ¹ H NMR (600 MHz, CDCl ₃ ) d 7.91 (1H, d , J = 8.0 Hz), 7.62-7.59 (1H, m), 7.49 (1H, d, J = 8.6 Hz), 7.37 (1H, t, J = 7.6 Hz), 3.81 (3H, s), 2.94 (2H) , t, J = 7.8 Hz), 1.72-1.67 (2H, m), 1.42-1.31 (4H, m), 0.89 (3H, t, J = 7.2 Hz); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 183.0, 166.9, 160.3, 150.9, 137.9, 130.8, 123.8, 122.6, 115.3, 112.2, 110.6, 94.7, 32.3, 31.4, 30.1, 26.4, 22.4, 13.9; IR (ATR) 2927, 1774, 1638, 1605, 1378, 755, 728 cm ^-1 ; HRMS m/z (M ⁺ )calcd for C ₁₈ H ₁₉ NO ₄ :313.1314. Found: 313.1318.

As described above in detail a specific part of the content of the present invention, for those of ordinary skill in the art, it is clear that this specific description is only a preferred embodiment, and the scope of the present invention is not limited thereby. something to do. Accordingly, the substantial scope of the present invention will be defined by the appended claims and their equivalents.

Claims (16)

A compound selected from gamma-butenolides compounds represented by the following formula (I) and pharmaceutically acceptable salts thereof:
[Formula Ⅰ]

In the above formula (I),
wherein X is a C ₁ to C ₄ alkyl group; And -NR- (wherein, R is a hydrogen atom; or a C ₁ to C ₄ alkyl group; a substituent selected from); to form an aliphatic cyclic compound (A) as any one selected from the group consisting of;
Each of R ₁ or R ₂ may be the same or different, and may be a hydrogen atom; C _{1 To} C ₁₀ Alkyl group;

an aryl group represented by ; And 5- to 6-membered heterocyclic compound; represents any one selected from the group consisting of (provided that when X is -CH ₂ -Excluding that R ₁ and R ₂ are both hydrogen or a methyl group), the R _{Any one of 1} or R ₂ may be connected to each other with any one of R ₄ or R _{5 to form an aryl group,}
wherein R ₃ is a C ₁ to C ₁₁ alkyl group; and a nitro group (NO ₂ ) or an aryl group unsubstituted or substituted with an alkoxyl group of _{C 1} to C _{4; represents any one selected from the group consisting of,}
Each of R ₄ or R ₅ may be the same or different, and may be a hydrogen atom; or a C ₁ to C ₄ alkyl group; or, wherein _{any one of R 4} or R ₅ is connected to any one of R ₁ or R ₂ to form an aryl group; may be formed.
The method of claim 1,
Wherein X represents any one selected from the group consisting _{of -CH 2} -, -CH ₂ CH ₂ -, -NH-, and -N(CH _{3 ),}
wherein R ₁ or R ₂ is a hydrogen atom; C _{1 To} C ₁₀ Alkyl group;

an aryl group represented by ; and a pentacyclic to hexagonal heterocyclic compound having an oxygen atom as a hetero element; or represents any one selected from the group consisting of (provided that when X is -CH ₂ -, R ₁ and R ₂ are both hydrogen or a methyl group except that), _{any one of R 1} or R ₂ may be connected to each other with any one of R ₄ or R _{5 to form a benzene ring,}
wherein R ₄ or R ₅ is a hydrogen atom, or _{any one of R 4} or R ₅ may be connected to any one of R ₁ or R ₂ to form a benzene ring.
3. The method of claim 2,
In the R ₁ or R ₂

In the aryl group represented by
R ₆ to R ₁₀ may each be the same or different, and may be a hydrogen atom; halogen atom; And C _{1 To} C ₄ An alkoxyl group; has any one substituent selected from the group consisting of, or R _{7 To} R ₈ are connected to each other

A compound that forms
The method of claim 1,
The gamma butenolide (γ-butenolides) compound is
( E )-3-(1-hydroxyethylidene)-6-methyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 3c]; ( E )-3-(1-hydroxyethylidene)-6-isopropyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 3d]; ( E )-3-(1-hydroxyethylidene)-6-phenyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 3e]; ( E )-6-(3,4-dimethoxyphenyl)-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 3f] ; ( E )-6-(benzo[d][1,3]dioxol-5-yl)-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2 ,4-dione [compound 3g]; ( E )-6-(4-Chlorophenyl)-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione [Compound 3h]; ( E )-6-(furan-2-yl)-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione [Compound 3i]; ( E )-3-(1-hydroxypropylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [Compound 4a]; ( E )-6-(4-Chlorophenyl)-3-(1-hydroxypropylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione [Compound 4b]; ( E )-6-(furan-2-yl)-3-(1-hydroxypropylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4c]; ( E )-3-(1-hydroxybutylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4d]; ( E )-3-(1-hydroxybutylidene)-6-methyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4e]; ( E )-6-(furan-2-yl)-3-(1-hydroxybutylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4f]; ( E )-3-(1-hydroxy-2-methylpropylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4g]; ( E )-3-(1-hydroxy-2-methylpropylidene)-6-methyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4h]; ( E )-6-(furan-2-yl)-3-(1-hydroxy-2-methylpropylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4i ]; ( E )-3-(1-hydroxy-2,2-dimethylpropylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4j]; ( E )-3-(1-hydroxy-2,2-dimethylpropylidene)-6-phenyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4k]; ( E )-3-(1-hydroxyhexylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [Compound 41]; (E)-3-(1-hydroxyhexylidene)-6-isopropyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4m]; ( E )-6-(benzo[d][1,3]dioxol-5-yl)-3-(1-hydroxyhexylidene)-3,5,6,7-tetrahydrobenzofuran-2 ,4-dione [compound 4n]; ( E ) 3-(1-hydroxydodecylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [Compound 4o]; ( E )-3-(1-hydroxydodecylidene)-6-phenyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4p]; ( E )-3-(hydroxy(phenyl)methylene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4q]; ( E )-3-(hydroxy(phenyl)methylene)-6-isopropyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4r]; ( E )-3-(hydroxy(4-methoxyphenyl)methylene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4s]; ( E )-3-(hydroxy(4-nitrophenyl)methylene)-6-isopropyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4t]; ( E )-3-(1-Hydroxyethylidene)-5,6,7,8-tetrahydro-2H-cyclohepta[b]furan-2,4(3H)-dione [compound 5b]; ( E )-3-(1-hydroxyethylidene)-5-methyl-3,5-dihydrofuro[3,2-c]quinoline-2,4-dione [compound 5c]; and ( E )-3-(1-hydroxyhexylidene)-5-methyl-3,5-dihydrofuro[3,2-c]quinoline-2,4-dione [compound 5d]; Any one selected from the group, the compound.
The following formula I, characterized in that the cyclic diazodicarbonyl compounds represented by the following formula (1) and the beta-ketoamide compounds (β-ketoamide compounds) represented by the following formula (2) are reacted under a ruthenium catalyst A method for preparing a gamma-butenolide (γ-butenolides) compound represented by:
[Formula 1]

[Formula 2]

[Formula Ⅰ]

In Formula 1, Formula 2, and Formula I,
wherein X is a C ₁ to C ₄ alkyl group; And -NR- (wherein, R is a hydrogen atom; or a C ₁ to C ₄ alkyl group; a substituent selected from); to form an aliphatic cyclic compound (A) as any one selected from the group consisting of;
Each of R ₁ or R ₂ may be the same or different, and may be a hydrogen atom; C _{1 To} C ₁₀ Alkyl group;

an aryl group represented by ; And 5- to 6-membered heterocyclic compound; represents any one selected from the group consisting of (provided that when X is -CH ₂ -Excluding that R ₁ and R ₂ are both hydrogen or a methyl group), the R _{Any one of 1} or R ₂ may be connected to each other with any one of R ₄ or R _{5 to form an aryl group,}
wherein R ₃ is a C ₁ to C ₁₁ alkyl group; and a nitro group (NO ₂ ) or an aryl group unsubstituted or substituted with an alkoxyl group of _{C 1} to C _{4; represents any one selected from the group consisting of,}
Each of R ₄ or R ₅ may be the same or different, and may be a hydrogen atom; or a C ₁ to C ₄ alkyl group; or, wherein _{any one of R 4} or R ₅ is connected to any one of R ₁ or R ₂ to form an aryl group; may be formed.
6. The method of claim 5,
Wherein X represents any one selected from the group consisting _{of -CH 2} -, -CH ₂ CH ₂ -, -NH-, and -N(CH _{3 ),}
wherein R ₁ or R ₂ is a hydrogen atom; C _{1 To} C ₁₀ Alkyl group;

an aryl group represented by ; and a pentacyclic to hexagonal heterocyclic compound having an oxygen atom as a hetero element; represents any one selected from the group consisting of, or any one of R ₁ or R ₂ is connected to any one of R ₄ or R ₅ may form a benzene ring,
wherein R ₄ or R ₅ is a hydrogen atom, or _{any one of R 4} or R ₅ may be connected to any one of R ₁ or R ₂ to form a benzene ring, gamma-butenolide A method for preparing a compound.
7. The method of claim 6,
In the R ₁ or R ₂

In the aryl group represented by
R ₆ to R ₁₀ may each be the same or different, and may be a hydrogen atom; halogen atom; and C ₁ to C ₄ having any one substituent selected from the group consisting of an alkoxyl group, or R ₇ to R ₈ are connected to each other

A method for producing a gamma-butenolide compound, characterized in that to form a.
6. The method of claim 5,
The cyclic diazo carbonyl compound represented by Formula 1 is
2-diazo-5,5-dimethylcyclohexane-1,3-dione (2-diazo-5,5-dimethylcyclohexane-1,3-dione, compound 1a); 2-diazo-cyclohexane-1,3-dione (2-diazo-cyclohexane-1,3-dione, compound 1b); 2-diazo-5-methylcyclohexane-1,3-dione (2-diazo-5-methylcyclohexane-1,3-dione, compound 1c); 2-diazo-5-isopropylcyclohexane-1,3-dione (2-diazo-5-isopropylcyclohexane-1,3-dione, compound 1d); 2-diazo-5-phenylcyclohexane-1,3-dione (2-diazo-5-phenylclohexane-1,3-dione, compound 1e); 2-diazo-5-(3,4-dimethoxyphenyl)cyclohexane-1,3-dione (2-diazo-5-(3,4-dimethoxyphenyl)cyclohexane-1,3-dione, compound 1f); 5-(benzo[d][1,3]dioxol-5-yl)-2-diazocyclohexane-1,3-dione (5-(benzo[d][1,3]dioxol-5-yl )-2-diazocyclohexane-1,3-dione, compound 1 g); 5-(4-chlorophenyl)-2-diazocyclohexane-1,3-dione (5-(4-chlorophenyl)-2-diazocyclohexane-1,3-dione, compound 1h); and 2-diazo-5-(furan-2-yl)cyclohexane-1,3-dione (2-diazo-5-(furan-2-yl)cyclohexane-1,3-dione, compound 1i); A method for producing a gamma-butenolide compound, characterized in that it is selected from the group consisting of.
6. The method of claim 5,
The beta-ketoamide compound represented by Formula 2 is
3-oxo-N- phenylbutanamide (3-oxo-N-phenylbutanamide, compound 2a); 3-oxo-N- phenylpentanamide (3-oxo-N-phenylpentanamide, compound 2b); 3-oxo- N- phenylhexanamide (compound 2c); 4-methyl-3-oxo-N- phenylpentanamide (4-methyl-3-oxo-N-phenylpentanamide, compound 2d); 4,4-dimethyl-3-oxo-N- phenylpentanamide (4,4-dimethyl-3-oxo-N-phenylpentanamide, compound 2e); 3-oxo-N- phenyloctanamide (3-oxo-N-phenyloctanamide, compound 2f); 3-oxo-N- phenyltridecanamide (3-oxo-N-phenyltridecanamide, compound 2g); 3-oxo-N,3-diphenylpropanamide (3-oxo- N,3- diphenylpropanamide, compound 2h); 3-(4-methoxyphenyl)-3-oxo-N-phenyl propanamide (3-(4-metho xyphenyl)-3-oxo- N- phenylpropanamide, compound 2i); and 3-(4-nitrophenyl)-3-oxo-N-phenyl propanamide (3-(4-nitrophenyl)-3-oxo- N- phenylpropanamide, compound 2j); characterized in that it is selected from the group consisting of; , A method for preparing a gamma-butenolide compound.
6. The method of claim 5,
The gamma butenolide (γ-butenolides) compound is
( E )-3-(1-hydroxyethylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [Compound 3a]; ( E )-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 3b]; ( E )-3-(1-hydroxyethylidene)-6-methyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 3c]; ( E )-3-(1-hydroxyethylidene)-6-isopropyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 3d]; ( E )-3-(1-hydroxyethylidene)-6-phenyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 3e]; ( E )-6-(3,4-dimethoxyphenyl)-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 3f] ; ( E )-6-(benzo[d][1,3]dioxol-5-yl)-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2 ,4-dione [compound 3g]; ( E )-6-(4-Chlorophenyl)-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione [Compound 3h]; ( E )-6-(furan-2-yl)-3-(1-hydroxyethylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione [Compound 3i]; ( E )-3-(1-hydroxypropylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [Compound 4a]; ( E )-6-(4-Chlorophenyl)-3-(1-hydroxypropylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione [Compound 4b]; ( E )-6-(furan-2-yl)-3-(1-hydroxypropylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4c]; ( E )-3-(1-hydroxybutylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4d]; ( E )-3-(1-hydroxybutylidene)-6-methyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4e]; ( E )-6-(furan-2-yl)-3-(1-hydroxybutylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4f]; ( E )-3-(1-hydroxy-2-methylpropylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4g]; ( E )-3-(1-hydroxy-2-methylpropylidene)-6-methyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4h]; ( E )-6-(furan-2-yl)-3-(1-hydroxy-2-methylpropylidene)-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4i ]; ( E )-3-(1-hydroxy-2,2-dimethylpropylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4j]; ( E )-3-(1-hydroxy-2,2-dimethylpropylidene)-6-phenyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4k]; ( E )-3-(1-hydroxyhexylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [Compound 41]; (E)-3-(1-hydroxyhexylidene)-6-isopropyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4m]; ( E )-6-(benzo[d][1,3]dioxol-5-yl)-3-(1-hydroxyhexylidene)-3,5,6,7-tetrahydrobenzofuran-2 ,4-dione [compound 4n]; ( E ) 3-(1-hydroxydodecylidene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [Compound 4o]; ( E )-3-(1-hydroxydodecylidene)-6-phenyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4p]; ( E )-3-(hydroxy(phenyl)methylene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4q]; ( E )-3-(hydroxy(phenyl)methylene)-6-isopropyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4r]; ( E )-3-(hydroxy(4-methoxyphenyl)methylene)-6,6-dimethyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4s]; ( E )-3-(hydroxy(4-nitrophenyl)methylene)-6-isopropyl-3,5,6,7-tetrahydrobenzofuran-2,4-dione [compound 4t]; ( E )-3-(1-Hydroxyethylidene)-5,6,7,8-tetrahydro-2H-cyclohepta[b]furan-2,4(3H)-dione [compound 5b]; ( E )-3-(1-hydroxyethylidene)-5-methyl-3,5-dihydrofuro[3,2-c]quinoline-2,4-dione [compound 5c]; and ( E )-3-(1-hydroxyhexylidene)-5-methyl-3,5-dihydrofuro[3,2-c]quinoline-2,4-dione [compound 5d]; A method for producing a gamma-butenolide compound, characterized in that it is any one selected from the group.
6. The method of claim 5,
The reaction is [RhCp*Cl ₂ ] ₂ or [RuCl ₂ ( p -cymene)] ₂ selected from ruthenium catalysts and AgSbF ₆ phosphorus A method for producing a gamma-butenoride compound, characterized in that the reaction is performed by adding a co-catalyst together.
12. The method of claim 11,
The concentration of the ruthenium catalyst is 0.5 to 10 mol%, characterized in that the co-catalyst is 5 to 20 mol%, gamma- a method for producing a butenolide compound.
6. The method of claim 5,
In the reaction, any one additive selected from the group consisting of silver acetate (AgOAc), pivalic acid (PivOH), and acetic acid (AcOH) in a dichloroethylene (DCE) polar solvent was added. A method for producing a gamma-butenoride compound, characterized in that the reaction is added.
14. The method of claim 13,
The concentration of the additive is characterized in that 50 to 300 mol%, gamma- a method of producing a butenolide compound.
6. The method of claim 5,
The reaction is characterized in that it is carried out at 50 to 90 ℃ for 3 to 24 hours, gamma- a method for producing a butenolide compound.
6. The method of claim 5,
The reaction is a one-pot reaction (one-pot reaction) to the cyclic diazo carbonyl compound and beta- ketoamide compound is characterized in that the coupling, gamma- a method of producing a butenolide compound.

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