JP5309318B2 - Process for producing esters, carboxylic acids and amides - Google Patents

Description

  The present invention relates to a method for producing esters, carboxylic acids and amides using 1,3-dicarbonyl compounds as raw materials. Specifically, a method for producing an ester from a 1,3-dicarbonyl compound and an alcohol, a method for producing a carboxylic acid from a 1,3-dicarbonyl compound and water, and a thioester from a 1,3-dicarbonyl compound and a thiol. The present invention relates to a production method and a method for producing an amide from a 1,3-dicarbonyl compound and an amine. Moreover, it is related with the manufacturing method of the ketone which remove | eliminates an acyl group from a 1, 3- dicarbonyl compound.

  Esters, carboxylic acids, amides, and the like are widely used in various structures and are practically important compounds. For example, esters are useful as fragrances because they are often scented components such as fruits, and are also used as solvents such as paints and adhesives and plasticizers for plastics. Carboxylic acids and carboxylic acid amides are also very widely used. These compounds are also important as precision synthetic products used in pharmaceuticals and electronic materials.

  As a conventional ester synthesis method, dehydration condensation of a carboxylic acid and an alcohol is most common. However, since it is often necessary to add a strong acid such as sulfuric acid as a catalyst, it has been difficult to synthesize esters having acid-sensitive functional groups. Also, the reaction of acid chlorides or acid anhydrides with alcohols is often used. However, since hydrogen chloride and carboxylic acid are by-produced after the reaction, there is a problem that the system becomes acidic. Therefore, there has been a demand for an ester synthesis reaction under neutral conditions without addition of acid or by-product. This is the same in the synthesis of amides.

  1,3-dicarbonyl compounds (β-dicarbonyl compounds) have been used as raw materials for synthesis reactions. For example, Non-Patent Document 1 discloses a reaction in which a 1,3-diketone (β-diketone) and an alcohol are reacted in the presence of an indium chloride catalyst to introduce a carbon-carbon bond at the α-position of the 1,3-diketone. Has been reported (see the following formula (1)). According to this reaction, a carbon-carbon bond is introduced in such a form that a hydroxyl group of alcohol is eliminated.

  Non-Patent Document 2 reports a reaction in which 1,3-diketone and alcohol are reacted in the presence of ytterbium triflate to synthesize β-ketoenol ether (see the following formula (2)). . According to this reaction, a dehydration reaction proceeds after a hydroxyl group of the alcohol undergoes a nucleophilic attack on one of the carbonyl groups of the 1,3-diketone, and a carbon-oxygen bond is formed.

M. Yasuda, two others, Angewandte Chemie Int. Ed., 2006, 45, p. 793-796 M. Curini, two others, Tetrahedron Letters, 2006, 47, p. 4697-4700

  An object of this invention is to provide the novel manufacturing method of new ester, carboxylic acid, and amide. Specifically, a method of synthesizing an ester, a carboxylic acid and an amide in a high yield under mild conditions by reacting an alcohol, water, thiol or amine with a 1,3-dicarbonyl compound as a raw material. It is intended to provide.

［式中、Ｒ^１及びＲ^４は、それぞれ独立して水素原子、置換基を有してもよいアルキル基、置換基を有してもよいアルケニル基、置換基を有してもよいアルキニル基、置換基を有してもよいアリール基、置換基を有してもよいアリールアルキル基、置換基を有してもよいアリールアルケニル基、置換基を有してもよいアリールアルキニル基、置換基を有してもよいシクロアルキル基、置換基を有してもよい複素環基であり；Ｒ^２及びＲ^３は、それぞれ独立して水素原子、ハロゲン原子、置換基を有してもよいアルキル基、置換基を有してもよいアルケニル基、置換基を有してもよいアルキニル基、置換基を有してもよいアリール基、置換基を有してもよいアリールアルキル基、置換基を有してもよいアリールアルケニル基、置換基を有してもよいアリールアルキニル基、置換基を有してもよいシクロアルキル基、置換基を有してもよい複素環基、保護されていてもよい水酸基、アルコキシ基、アリーロキシ基、アルデヒド基、保護されていてもよいカルボキシル基又はその塩、アルキルカルボニル基、アリールカルボニル基、アルキロキシカルボニル基、アリーロキシカルボニル基、アルキルカルボニロキシ基、アリールカルボニロキシ基、保護されていてもよいアミノ基、アルキルアミノ基、アリールアミノ基、アンモニウム基、アルキルアンモニウム基、アリールアンモニウム基、保護されていてもよいチオール基、アルキルチオ基、アリールチオ基、保護されていてもよいスルフィン酸基又はその塩、アルキルスルフィニル基、アリールスルフィニル基、保護されていてもよいスルホン酸基又はその塩、アルキルスルホニル基、アリールスルホニル基、アルキルアゾ基、アリールアゾ基、保護されていてもよいリン酸基又はその塩、保護されていてもよい亜リン酸基又はその塩、シアノ基、ニトロ基又はアジド基であり；Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は、相互に結合して環を形成してもよい。］
で示される１，３−ジカルボニル化合物と、下記式（II）

［式中、−Ｘ−は、−Ｏ−、−Ｓ−又は−ＮＲ^６−を示し；Ｒ^５及びＲ^６は、それぞれ独立して水素原子、置換基を有してもよいアルキル基、置換基を有してもよいアルケニル基、置換基を有してもよいアルキニル基、置換基を有してもよいアリール基、置換基を有してもよいアリールアルキル基、置換基を有してもよいアリールアルケニル基、置換基を有してもよいアリールアルキニル基、置換基を有してもよいシクロアルキル基、置換基を有してもよい複素環基であり；Ｒ^５及びＲ^６は、相互に結合して環を形成してもよく、Ｒ^５又はＲ^６が式（I）におけるＲ^１、Ｒ^２、Ｒ^３又はＲ^４と結合していてもよい。］
で示される化合物を、インジウムトリフラート又は銅トリフラートから選択されるルイス酸触媒の存在下に反応させることを特徴とする、下記式（III）

［式中、Ｘ、Ｒ^１及びＲ^５は、上記式（I）及び式（II）と同じ。］
で示される、エステル、カルボン酸及びアミドからなる群から選択される１種の化合物の製造方法である。 The present invention relates to the following formula (I)

[Wherein, R ¹ and R ⁴ each independently represent a hydrogen atom, an alkyl group which may have a substituent, an alkenyl group which may have a substituent, or an alkynyl group which may have a substituent. An aryl group which may have a substituent, an arylalkyl group which may have a substituent, an arylalkenyl group which may have a substituent, an arylalkynyl group which may have a substituent, a substituent A cycloalkyl group that may have a heterocyclic group that may have a substituent; R ² and R ³ each independently represent a hydrogen atom, a halogen atom, or an alkyl that may have a substituent; A group, an alkenyl group which may have a substituent, an alkynyl group which may have a substituent, an aryl group which may have a substituent, an arylalkyl group which may have a substituent, a substituent An arylalkenyl group that may have a substituent Arylalkynyl group which may be substituted, cycloalkyl group which may have substituent, heterocyclic group which may have substituent, hydroxyl group which may be protected, alkoxy group, aryloxy group, aldehyde group, protected May be a carboxyl group or a salt thereof, an alkylcarbonyl group, an arylcarbonyl group, an alkyloxycarbonyl group, an aryloxycarbonyl group, an alkylcarbonyloxy group, an arylcarbonyloxy group, an amino group which may be protected, an alkylamino Group, arylamino group, ammonium group, alkylammonium group, arylammonium group, thiol group which may be protected, alkylthio group, arylthio group, sulfinic acid group which may be protected or its salt, alkylsulfinyl group, aryl Sulfinyl group, even if protected Sulfonic acid groups or salts thereof, alkylsulfonyl groups, arylsulfonyl groups, alkylazo groups, arylazo groups, optionally protected phosphoric acid groups or salts thereof, optionally protected phosphorous acid groups or salts thereof, cyano A group, a nitro group or an azide group; R ¹ , R ² , R ³ and R ⁴ may be bonded to each other to form a ring. ]
1,3-dicarbonyl compound represented by the following formula (II)

[Wherein, -X- represents -O-, -S- or -NR ^6- ; R ⁵ and R ⁶ each independently represents a hydrogen atom, an alkyl group which may have a substituent, or a substituent; An alkenyl group which may have a group, an alkynyl group which may have a substituent, an aryl group which may have a substituent, an arylalkyl group which may have a substituent, and a substituent An arylalkenyl group which may have a substituent, an arylalkynyl group which may have a substituent, a cycloalkyl group which may have a substituent, a heterocyclic group which may have a substituent; R ⁵ and R ⁶ are , ^May be bonded to each other to form a ring, and R ⁵ or R ⁶ may be bonded to R ¹ , R ² , R ³ or R ⁴ in formula (I). ]
The compound represented by formula (III) is reacted in the presence of a Lewis acid catalyst selected from indium triflate or copper triflate:

[Wherein, X, R ¹ and R ⁵ are the same as those in the above formulas (I) and (II). ]
Is a method for producing one compound selected from the group consisting of esters, carboxylic acids and amides.

At this time, in the 1,3-dicarbonyl compound represented by the formula (I), R ¹ , R ² , R ³ and R ⁴ are bonded to each other to form a ring, which is represented by the formula (III). It is preferred that the compound is one compound selected from the group consisting of ketoesters, ketocarboxylic acids and ketoamides .

In the above manufacturing method, reacting the formula (I) shown are 1,3-dicarbonyl compound of the formula (II) at a concentration both above 1 mol / L of the compound represented by are preferred. Moreover, it is also preferable to make it react at the reaction temperature of 60-200 degreeC.

［式中、Ｒ^１及びＲ^４は、それぞれ独立して水素原子、置換基を有してもよいアルキル基、置換基を有してもよいアルケニル基、置換基を有してもよいアルキニル基、置換基を有してもよいアリール基、置換基を有してもよいアリールアルキル基、置換基を有してもよいアリールアルケニル基、置換基を有してもよいアリールアルキニル基、置換基を有してもよいシクロアルキル基、置換基を有してもよい複素環基であり；Ｒ^２及びＲ^３は、それぞれ独立して水素原子、ハロゲン原子、置換基を有してもよいアルキル基、置換基を有してもよいアルケニル基、置換基を有してもよいアルキニル基、置換基を有してもよいアリール基、置換基を有してもよいアリールアルキル基、置換基を有してもよいアリールアルケニル基、置換基を有してもよいアリールアルキニル基、置換基を有してもよいシクロアルキル基、置換基を有してもよい複素環基、保護されていてもよい水酸基、アルコキシ基、アリーロキシ基、アルデヒド基、保護されていてもよいカルボキシル基又はその塩、アルキルカルボニル基、アリールカルボニル基、アルキロキシカルボニル基、アリーロキシカルボニル基、アルキルカルボニロキシ基、アリールカルボニロキシ基、保護されていてもよいアミノ基、アルキルアミノ基、アリールアミノ基、アンモニウム基、アルキルアンモニウム基、アリールアンモニウム基、保護されていてもよいチオール基、アルキルチオ基、アリールチオ基、保護されていてもよいスルフィン酸基又はその塩、アルキルスルフィニル基、アリールスルフィニル基、保護されていてもよいスルホン酸基又はその塩、アルキルスルホニル基、アリールスルホニル基、アルキルアゾ基、アリールアゾ基、保護されていてもよいリン酸基又はその塩、保護されていてもよい亜リン酸基又はその塩、シアノ基、ニトロ基又はアジド基であり；Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は、相互に結合して環を形成してもよい。］
で示される１，３−ジカルボニル化合物と、下記式（II）

［式中、−Ｘ−は、−Ｏ−、−Ｓ−又は−ＮＲ^６−を示し；Ｒ^５及びＲ^６は、それぞれ独立して水素原子、置換基を有してもよいアルキル基、置換基を有してもよいアルケニル基、置換基を有してもよいアルキニル基、置換基を有してもよいアリール基、置換基を有してもよいアリールアルキル基、置換基を有してもよいアリールアルケニル基、置換基を有してもよいアリールアルキニル基、置換基を有してもよいシクロアルキル基、置換基を有してもよい複素環基であり；Ｒ^５及びＲ^６は、相互に結合して環を形成してもよく、Ｒ^５又はＲ^６が式（I）におけるＲ^１、Ｒ^２、Ｒ^３又はＲ^４と結合していてもよい。］
で示される化合物を、インジウムトリフラート又は銅トリフラートから選択されるルイス酸触媒の存在下に反応させることを特徴とする、下記式（IV）

［式中、Ｒ^２、Ｒ^３及びＲ^４は、上記式（I）及び式（II）と同じ。］
で示されるケトンの製造方法である。 The present invention also provides the following formula (I)

[Wherein, R ¹ and R ⁴ each independently represent a hydrogen atom, an alkyl group which may have a substituent, an alkenyl group which may have a substituent, or an alkynyl group which may have a substituent. An aryl group which may have a substituent, an arylalkyl group which may have a substituent, an arylalkenyl group which may have a substituent, an arylalkynyl group which may have a substituent, a substituent A cycloalkyl group that may have a heterocyclic group that may have a substituent; R ² and R ³ each independently represent a hydrogen atom, a halogen atom, or an alkyl that may have a substituent; A group, an alkenyl group which may have a substituent, an alkynyl group which may have a substituent, an aryl group which may have a substituent, an arylalkyl group which may have a substituent, a substituent An arylalkenyl group that may have a substituent Arylalkynyl group which may be substituted, cycloalkyl group which may have substituent, heterocyclic group which may have substituent, hydroxyl group which may be protected, alkoxy group, aryloxy group, aldehyde group, protected May be a carboxyl group or a salt thereof, an alkylcarbonyl group, an arylcarbonyl group, an alkyloxycarbonyl group, an aryloxycarbonyl group, an alkylcarbonyloxy group, an arylcarbonyloxy group, an amino group which may be protected, an alkylamino Group, arylamino group, ammonium group, alkylammonium group, arylammonium group, thiol group which may be protected, alkylthio group, arylthio group, sulfinic acid group which may be protected or its salt, alkylsulfinyl group, aryl Sulfinyl group, even if protected Sulfonic acid groups or salts thereof, alkylsulfonyl groups, arylsulfonyl groups, alkylazo groups, arylazo groups, optionally protected phosphoric acid groups or salts thereof, optionally protected phosphorous acid groups or salts thereof, cyano A group, a nitro group or an azide group; R ¹ , R ² , R ³ and R ⁴ may be bonded to each other to form a ring. ]
1,3-dicarbonyl compound represented by the following formula (II)

[Wherein, -X- represents -O-, -S- or -NR ^6- ; R ⁵ and R ⁶ each independently represents a hydrogen atom, an alkyl group which may have a substituent, or a substituent; An alkenyl group which may have a group, an alkynyl group which may have a substituent, an aryl group which may have a substituent, an arylalkyl group which may have a substituent, and a substituent An arylalkenyl group which may have a substituent, an arylalkynyl group which may have a substituent, a cycloalkyl group which may have a substituent, a heterocyclic group which may have a substituent; R ⁵ and R ⁶ are , ^May be bonded to each other to form a ring, and R ⁵ or R ⁶ may be bonded to R ¹ , R ² , R ³ or R ⁴ in formula (I). ]
Wherein the compound represented by formula (IV) is reacted in the presence of a Lewis acid catalyst selected from indium triflate or copper triflate:

[Wherein R ² , R ³ and R ⁴ are the same as those in the above formulas (I) and (II). ]
It is a manufacturing method of the ketone shown by these.

  According to the production method of the present invention, a 1,3-dicarbonyl compound is used as a raw material, and an alcohol, water, thiol, or amine is reacted with this to produce an ester, a carboxylic acid and an amide in a good yield under mild conditions. Can be synthesized.

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は、前記の通り。］
で示される１，３−ジカルボニル化合物と、下記式（II）

［式中、−Ｘ−及びＲ^５は、前記の通り。］
で示される化合物を反応させることを特徴とする、下記式（III）

［式中、Ｘ、Ｒ^１及びＲ^５は、前記の通り。］
で示される、エステル、カルボン酸及びアミドからなる群から選択される１種の化合物の製造方法である。ここで、エステルはチオエステルを、カルボン酸はチオカルボン酸を、それぞれ含む概念である。 The reaction of the present invention has the following formula (I)

[Wherein, R ¹ , R ² , R ³ and R ⁴ are as described above. ]
1,3-dicarbonyl compound represented by the following formula (II)

[Wherein, -X- and R ⁵ are as defined above. ]
A compound represented by the following formula (III):

[Wherein, X, R ¹ and R ⁵ are as defined above. ]
Is a method for producing one compound selected from the group consisting of esters, carboxylic acids and amides. Here, ester is a concept including thioester, and carboxylic acid is including thiocarboxylic acid.

［式中、Ｒ^２、Ｒ^３及びＲ^４は、前記の通り。］
で示されるケトンも生成する。したがって、上記式（III）で示される化合物ではなく、上記式（IV）で示される化合物を目的化合物としてもよい。なお、Ｒ^４が水素の場合には、ケトンではなくアルデヒドが得られる。 Further, when the 1,3-dicarbonyl compound represented by the above formula (I) and the compound represented by the above formula (II) are reacted, the ester, carboxylic acid and amide represented by the above formula (III) One compound selected from the group consisting of the following formula (IV)

[Wherein R ² , R ³ and R ⁴ are as described above. ]
Is also produced. Therefore, not the compound represented by the above formula (III) but the compound represented by the above formula (IV) may be used as the target compound. When R ⁴ is hydrogen, an aldehyde is obtained instead of a ketone.

  Non-patent literature 1 and non-patent literature 2 report that alcohol reacts with a 1,3-dicarbonyl compound in the presence of a metal catalyst. However, all the reactions described in these documents only form a new carbon-carbon bond or carbon-oxygen bond, and break the carbon-carbon bond in the 1,3-dicarbonyl compound. There is no mention of what to do. At this time, the present inventor reacted alcohol, water or amine with 1,3-dicarbonyl compound and cleaved carbon-carbon bond in 1,3-dicarbonyl compound to produce ester, carboxylic acid or We found a new reaction to synthesize amides. Heretofore, it has not been reported at all that such a reaction proceeds with good yield.

The estimation mechanism of this reaction is as shown in the following formula (3). Here, a mechanism in the case of synthesizing an ester and a ketone by reacting an alcohol with a 1,3-diketone in which R ³ is a hydrogen atom in the presence of the metal catalyst (M) is shown.

  In the reaction mechanism represented by the above formula (3), first, the 1,3-dicarbonyl compound is coordinated to the metal catalyst and the carbon of the carbonyl group is activated, whereby the nucleophilic attack of the alcohol proceeds. Then, the carbon-carbon bond is cleaved by the subsequent reverse aldol reaction to produce an ester and a metal enolate. Thereafter, the metal enolate is protonated to produce enol, which is obtained as a ketone. At the same time, the catalyst is regenerated. By this reaction, an ester is synthesized from a 1,3-dicarbonyl compound and an alcohol, a carboxylic acid is synthesized from a 1,3-dicarbonyl compound and water, and an amide is synthesized from a 1,3-dicarbonyl compound and an amine, respectively. In any case, a ketone from which an acyl group is eliminated from a 1,3-dicarbonyl compound is obtained at the same time.

  The inventor reacted with alcohol at 80 ° C. in the presence of an indium triflate catalyst using a ketone having only one carbonyl group instead of the 1,3-dicarbonyl compound represented by the formula (I). As a result, the reaction did not proceed. When β-ketoester was used, a complicated mixture was obtained, and the target product of the present invention could not be confirmed. In addition, when 1,3-diester was used, the target compound was not obtained due to the progress of the transesterification reaction. Therefore, in the production method of the present invention, it is important to use the 1,3-dicarbonyl compound represented by the formula (I) as a raw material.

［式中、Ｒ^１及びＲ^４は、それぞれ独立して水素原子、置換基を有してもよいアルキル基、置換基を有してもよいアルケニル基、置換基を有してもよいアルキニル基、置換基を有してもよいアリール基、置換基を有してもよいアリールアルキル基、置換基を有してもよいアリールアルケニル基、置換基を有してもよいアリールアルキニル基、置換基を有してもよいシクロアルキル基、置換基を有してもよい複素環基であり；Ｒ^２及びＲ^３は、それぞれ独立して水素原子、ハロゲン原子、置換基を有してもよいアルキル基、置換基を有してもよいアルケニル基、置換基を有してもよいアルキニル基、置換基を有してもよいアリール基、置換基を有してもよいアリールアルキル基、置換基を有してもよいアリールアルケニル基、置換基を有してもよいアリールアルキニル基、置換基を有してもよいシクロアルキル基、置換基を有してもよい複素環基、保護されていてもよい水酸基、アルコキシ基、アリーロキシ基、アルデヒド基、保護されていてもよいカルボキシル基又はその塩、アルキルカルボニル基、アリールカルボニル基、アルキロキシカルボニル基、アリーロキシカルボニル基、アルキルカルボニロキシ基、アリールカルボニロキシ基、保護されていてもよいアミノ基、アルキルアミノ基、アリールアミノ基、アンモニウム基、アルキルアンモニウム基、アリールアンモニウム基、保護されていてもよいチオール基、アルキルチオ基、アリールチオ基、保護されていてもよいスルフィン酸基又はその塩、アルキルスルフィニル基、アリールスルフィニル基、保護されていてもよいスルホン酸基又はその塩、アルキルスルホニル基、アリールスルホニル基、アルキルアゾ基、アリールアゾ基、保護されていてもよいリン酸基又はその塩、保護されていてもよい亜リン酸基又はその塩、シアノ基、ニトロ基又はアジド基であり；Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は、相互に結合して環を形成してもよい。］
で示されるものである。 Hereinafter, this reaction will be described in more detail. The 1,3-dicarbonyl compound used in the present invention has the following formula (I)

[Wherein, R ¹ and R ⁴ each independently represent a hydrogen atom, an alkyl group which may have a substituent, an alkenyl group which may have a substituent, or an alkynyl group which may have a substituent. An aryl group which may have a substituent, an arylalkyl group which may have a substituent, an arylalkenyl group which may have a substituent, an arylalkynyl group which may have a substituent, a substituent A cycloalkyl group that may have a heterocyclic group that may have a substituent; R ² and R ³ each independently represent a hydrogen atom, a halogen atom, or an alkyl that may have a substituent; A group, an alkenyl group which may have a substituent, an alkynyl group which may have a substituent, an aryl group which may have a substituent, an arylalkyl group which may have a substituent, a substituent An arylalkenyl group that may have a substituent Arylalkynyl group which may be substituted, cycloalkyl group which may have substituent, heterocyclic group which may have substituent, hydroxyl group which may be protected, alkoxy group, aryloxy group, aldehyde group, protected May be a carboxyl group or a salt thereof, an alkylcarbonyl group, an arylcarbonyl group, an alkyloxycarbonyl group, an aryloxycarbonyl group, an alkylcarbonyloxy group, an arylcarbonyloxy group, an amino group which may be protected, an alkylamino Group, arylamino group, ammonium group, alkylammonium group, arylammonium group, thiol group which may be protected, alkylthio group, arylthio group, sulfinic acid group which may be protected or its salt, alkylsulfinyl group, aryl Sulfinyl group, even if protected Sulfonic acid groups or salts thereof, alkylsulfonyl groups, arylsulfonyl groups, alkylazo groups, arylazo groups, optionally protected phosphoric acid groups or salts thereof, optionally protected phosphorous acid groups or salts thereof, cyano A group, a nitro group or an azide group; R ¹ , R ² , R ³ and R ⁴ may be bonded to each other to form a ring. ]
It is shown by.

Here, the carbon number of each substituent of the substituents R ¹ , R ² , R ³ and R ⁴ is not particularly limited, and may be a polymer chain, but is usually 50 or less, preferably 20 It is as follows. It is preferable that at least one of R ² and R ³ is a hydrogen atom because a 1,3-dicarbonyl compound can easily form an enol form. When R ¹ and R ⁴ are different, different products are obtained depending on the carbonyl group subjected to the nucleophilic attack, but the selectivity is good as shown in the following examples. The reaction product is considered to be determined by the stability of the reaction intermediate and steric hindrance. In addition, when R ¹ , R ² , R ³ and R ⁴ are bonded to each other to form a ring, the compound represented by the formula (III) and the compound represented by the formula (IV) are the same molecule. It may become. In such cases, ketoesters, ketocarboxylic acids or ketoamides will be synthesized and are useful.

［式中、−Ｘ−は、−Ｏ−、−Ｓ−又は−ＮＲ^６−を示し；Ｒ^５及びＲ^６は、それぞれ独立して水素原子、置換基を有してもよいアルキル基、置換基を有してもよいアルケニル基、置換基を有してもよいアルキニル基、置換基を有してもよいアリール基、置換基を有してもよいアリールアルキル基、置換基を有してもよいアリールアルケニル基、置換基を有してもよいアリールアルキニル基、置換基を有してもよいシクロアルキル基、置換基を有してもよい複素環基であり；Ｒ^５及びＲ^６は、相互に結合して環を形成してもよく、Ｒ^５又はＲ^６が式（I）におけるＲ^１、Ｒ^２、Ｒ^３又はＲ^４と結合していてもよい。］
で示されるものである。 In the present invention, the compound used for reacting with the 1,3-dicarbonyl compound is represented by the following formula (II):

[Wherein, -X- represents -O-, -S- or -NR ^6- ; R ⁵ and R ⁶ each independently represents a hydrogen atom, an alkyl group which may have a substituent, or a substituent; An alkenyl group which may have a group, an alkynyl group which may have a substituent, an aryl group which may have a substituent, an arylalkyl group which may have a substituent, and a substituent An arylalkenyl group which may have a substituent, an arylalkynyl group which may have a substituent, a cycloalkyl group which may have a substituent, a heterocyclic group which may have a substituent; R ⁵ and R ⁶ are , ^May be bonded to each other to form a ring, and R ⁵ or R ⁶ may be bonded to R ¹ , R ² , R ³ or R ⁴ in formula (I). ]
It is shown by.

In the above formula (II), the carbon number of each substituent of R ⁵ and R ⁶ is not particularly limited, and may be a polymer chain, but is usually 50 or less, and preferably 20 or less. In the formula (II), when -X- is -O- and R ⁵ is not a hydrogen atom, the compound represented by the formula (II) is an alcohol, which is reacted with a 1,3-dicarbonyl compound. Gives an ester of the following formula (V). As will be described in later examples, it has been confirmed that the reaction proceeds even when various alcohols are used. However, the yield decreases when a tertiary alcohol is used as compared with a primary alcohol or a secondary alcohol. As R ⁵ , not only a saturated hydrocarbon group but also those containing a double bond, a triple bond, an aromatic ring and the like can be used. Furthermore, what contains various functional groups, such as a halogen atom and an ether group, can also be used. In the formula (II), when -X- is -O- and R ⁵ is a hydrogen atom, the compound represented by the formula (II) is water and reacting it with a 1,3-dicarbonyl compound. To obtain a carboxylic acid represented by the following formula (V).

［式中、Ｒ^１及びＲ^５は、上記式（I）及び式（II）と同じ。］

[Wherein, R ¹ and R ⁵ are the same as those in the above formulas (I) and (II). ]

In the above formula (II), when -X- is -S-, the compound represented by formula (II) is a thiol (hydrogen sulfide when R ⁵ is a hydrogen atom), and 1,3-di- By reacting the carbonyl compound, a thioester represented by the following formula (VI) (thiocarboxylic acid when R ⁵ is a hydrogen atom) is obtained.

［式中、Ｒ^１及びＲ^５は、上記式（I）及び式（II）と同じ。］

[Wherein, R ¹ and R ⁵ are the same as those in the above formulas (I) and (II). ]

In the above formula (II), when -X- is -NR ^6- , the compound represented by formula (II) is an amine (ammonia when both R ⁵ and R ⁶ are hydrogen atoms), and 1 By reacting the 1,3-dicarbonyl compound, an amide represented by the following formula (VII) is obtained.

［式中、Ｒ^１、Ｒ^５及びＲ^６は、上記式（I）及び式（II）と同じ。］

[Wherein R ¹ , R ⁵ and R ⁶ are the same as those in the above formulas (I) and (II). ]

R ⁵ or R ⁶ in formula (II) may be bonded to R ¹ , R ² , R ³ or R ⁴ in formula (I). That is, one compound may be a compound represented by the formula (I) and a compound represented by the formula (II). In this case, the intramolecular reaction proceeds to synthesize ketoester, ketocarboxylic acid or ketoamide, which is useful.

  In the production method of the present invention, the compounding ratio of the compound represented by the formula (II) to the compound represented by the formula (I) is not particularly limited. The mixing ratio is determined in consideration of the cost of the raw material and the target product. In the present invention, the reaction is preferably carried out at a relatively high concentration, and preferably the concentration of the 1,3-dicarbonyl compound represented by the formula (I) and the compound represented by the formula (II) is 1 mol. / L or more is preferable, and it is more preferable that the reaction is performed at 2 mol / L or more. The solvent used is not particularly limited as long as it can dissolve the raw material, but an aprotic organic solvent such as hexane, benzene, toluene, dichloroethane, and tetrahydrofuran is preferable. Of these, halogen-containing hydrocarbon solvents are preferably used. However, in the production method of the present invention, it is preferable to carry out the reaction in a substantially solvent-free manner. This is because the reaction in the absence of solvent proceeds more favorably and is more advantageous from the viewpoint of solvent recovery and energy requirement.

  The reaction temperature is not particularly limited, but heating is preferable. Preferably it is heated to 40 ° C. or higher. In order to obtain the target compound in high yield, the reaction temperature is more preferably 60 ° C. or higher, and further preferably 80 ° C. or higher. On the other hand, if the reaction temperature is too high, side reactions and thermal decomposition may occur, and it is disadvantageous in terms of energy. Therefore, the reaction temperature is usually 300 ° C. or lower, preferably 200 ° C. or lower, and more preferably 150 ° C. or lower. In the production method of the present invention, the reaction proceeds under relatively mild conditions.

  This reaction is preferably carried out in the presence of a Lewis acid catalyst comprising a metal compound. According to the presumed mechanism, it is presumed that the oxygen atoms of the two carbonyl groups of the 1,3-dicarbonyl compound are coordinated to the metal atom of the catalyst and promote the nucleophilic attack on the carbon atom of the carbonyl group. Is done. Therefore, it is considered important that the metal compound functions as a Lewis acid and the oxygen atoms of the two carbonyl groups can be coordinated. As shown in the following examples, the metal species included in the catalyst in which this reaction has been confirmed to proceed are group 3 scandium and lanthanum, group 7 rhenium, group 11 copper and silver, group 13 It has been confirmed that the reaction proceeds with various metal compounds. Therefore, it is considered that any metal compound having moderate Lewis acidity can be a catalyst for this reaction. Although the metal seed | species used for a metal compound is not specifically limited, Based on the result of the said Example, It is a compound of the metal which belongs to the periodic table group 3-13 suitably. Among these, indium compounds, copper compounds, scandium compounds, and rhenium compounds are preferably used, indium compounds and copper compounds are more preferably used, and indium compounds are particularly preferably used.

  The valence of the metal compound is not particularly limited, and may be zero or may be a salt having a positive valence. In the present invention, a salt, particularly a metal salt of an organic acid is preferable. As the organic acid, carboxylic acid, sulfonic acid and the like are used. Here, examples of the carboxylic acid include acetic acid and trifluoroacetic acid. Examples of the sulfonic acid include trifluoromethanesulfonic acid, p-toluenesulfonic acid, methanesulfonic acid and the like. From the viewpoint of reactivity, a salt of trifluoromethanesulfonic acid, that is, triflate is particularly preferably used.

  The amount of the metal compound used as the catalyst is preferably 0.001 times or more with respect to the smaller number of moles of the compounds represented by formula (I) or formula (II), more preferably It is 0.005 times or more, and more preferably 0.01 times or more. On the other hand, from the viewpoint of reducing production costs and waste, the amount of metal compound used is more preferably 0 with respect to the smaller number of moles of the compounds represented by formula (I) or formula (II). .2 times or less, and more preferably 0.1 times or less.

  According to the production method of the present invention, the target compound can be obtained with good yield. The yield is preferably 20% or more, more preferably 50% or more, further preferably 80% or more, and particularly preferably 90% or more. As shown in the following examples, depending on the raw materials and reaction conditions, the reaction proceeds almost quantitatively without solvent, so that purification is easy. Here, the yield is a value (%) obtained by dividing the number of moles of the obtained target compound by the smaller number of moles of the compound represented by formula (I) or formula (II) and multiplying by 100. is there.

Example 1 (Representative reaction example)
A stir bar was added, and 4.2 mg (0.0075 mmol: 3.0 mol%) of indium triflate: In (OTf) ₃ was added to the heat-dried test tube, and the atmosphere was replaced with argon. 2,5-pentanedione (25.0 mg, 0.250 mmol) and 2-phenylethanol (30.5 mg, 0.250 mmol) were added using a microsyringe, and the mixture was heated and stirred at 80 ° C. for 24 hours under solvent-free conditions. The obtained reaction mixture was isolated and purified by silica gel column chromatography (developing solvent, hexane: ethyl acetate = 50: 1) to obtain 41.1 mg (0.250 mmol:> 99%) of 2-phenylethyl acetate. It was. It was found that the reaction proceeds quantitatively without solvent. The reaction formula is as shown in the following formula (4).

Example 2 (Examination of catalyst)
In Example 1, the reaction was conducted in the same manner as in Example 1 except that the catalyst shown in Table 1 was used, and the yield was determined from the resulting reaction mixture using ¹ H-NMR without isolation. . The results are summarized in Table 1. However, in Example 2-1, no catalyst was used. In Example 2-2 using a rhenium complex, the amount of catalyst added was 1.5 mol%.

  As can be seen from Table 1, the reaction did not proceed without catalyst (Example 2-1). When indium triflate was used, the reaction proceeded almost quantitatively (Example 2-8). Even when copper triflate was used, the yield exceeded 90% (Example 2-5). The yield when silver triflate was used was low (Example 2-7), but the yield was improved when copper triflate was formed in the reaction system using silver triflate and copper iodide in combination (Example 2). -6). It can be seen that indium chloride has a low yield (Example 2-9), and triflate is preferable. In addition, the reaction proceeded with rhenium salts, scandium salts, and lanthanum salts (Examples 2-2, 3, and 4).

Example 3 (Solvent and reaction temperature)
In Example 1, except that using a solvent shown in Table 2 were reacted at a temperature shown in Table 2 was reacted in the same manner as in Example 1, from the reaction mixture obtained, ¹ H- without isolation The yield was determined using NMR. The results are summarized in Table 2.

  As can be seen from Table 2, the reaction proceeds with good yield in the absence of solvent. When a solvent is used, a halogen-containing hydrocarbon solvent is preferable. It can also be seen that the optimum reaction temperature is around 80 ° C.

Example 4 (Examination of 1,3-diketone)
In Example 1, the reaction was carried out in the same manner as in Example 1 except that the alcohol was fixed to the same 2-phenylethanol as in Example 1 and the 1,3-diketone was changed to the compounds shown in Table 3. The reaction mixture was isolated and purified by silica gel column chromatography to determine the isolation yield. In addition, the yield using ¹ H-NMR was also determined without isolation. The results are summarized in Table 3. Here, in Example 4-2, 1.2 equivalent of 2-phenylethanol was added and reacted at 115 ° C. In Example 4-3, 1.5 equivalent of 2-phenylethanol was added and reacted at 115 ° C. In Example 4-5, 1.2 equivalent of 2-phenylethanol was added.

The reaction proceeded with good yield even with 1,3-diketone (Example 4-1) having an alkyl group at the α-position. In the case of 1,3-diketone having an aromatic ring in R ¹ and R ⁴ (Example 4-2), the ester was obtained in good yield by increasing the reaction temperature by increasing the amount of alcohol used. Also in the case of cyclic 1,3-diketone (Example 4-3), by increasing the amount of alcohol used and raising the reaction temperature, the reaction proceeds with a ring-opening reaction, and the ketoester yield is good. Obtained. In the case of an asymmetric 1,3-diketone (Examples 4-4 and 4-5), the reaction proceeded in a regioselective manner. In Example 4-4, priority was given to alcohol nucleophilic attack over the carbonyl group contained in the acetyl group rather than the carbonyl group contained in the benzoyl group. The benzoyl group is more stable in the enol form and has a larger steric hindrance, so it is considered that the carbonyl group contained in the acetyl group was selectively subjected to nucleophilic attack. In Example 4-5, the enol form of the carbonyl group contained in the 5-membered ring is unstable due to steric constraints. Therefore, the acetyl group is more likely to form an enol form, and as a result, the carbonyl group contained in the 5-membered ring is more susceptible to nucleophilic attack, and the ring-opening reaction proceeds selectively to obtain a keto ester in a high yield. It was. That is, as in Examples 4-3 and 4-5, when a carbonyl group is contained in the ring, the reaction proceeds with a ring-opening reaction, and a ketoester is obtained.

Example 5 (Study of alcohol)
In Example 1, 1,3-diketone was fixed to the same 2,4-pentanedione as in Example 1, alcohol was changed to the compounds shown in Table 4, and 1,3-diketone was equivalent to 1 equivalent of alcohol. The reaction was carried out in the same manner as in Example 1 except that was used, and the resulting reaction mixture was isolated and purified by silica gel column chromatography to determine the isolation yield. In addition, the yield using ¹ H-NMR was also determined without isolation. The results are summarized in Table 4.

  Esters were obtained in high yields for both primary and secondary alcohols (Examples 5-1, 5-2). With tertiary alcohol and benzyl alcohol, although the ester was obtained, the yield was low, and alkylation with dehydration was prioritized (Examples 5-3 and 5-4). Even in the case of an alcohol having a double bond, a triple bond, a halogen atom, or an ether group, an ester was obtained with good yield (Examples 5-5 to 5-10).

The structural data of 1-methyl-3-phenylpropyl acetate obtained in Example 5-2 is as follows.
¹ H NMR (400 MHz, CDCl ₃ ) δ 1.24 (d, J = 6.3 Hz, 2H), 2.05 (s, 1H), 1.74-1.84 (m, 1H), 1.88-1.98 (m, 1H), 2.56- 2.72 (m, 2H), 4.88-4.99 (m, 1H), 7.13-7.20 (m, 3H), 7.24-7.35 (m, 2H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 19.96, 21.25, 31.76 , 37.51, 70.46, 125.85, 128.35, 141.46, 170.66; IR (nujol, ν / cm ^-1 ) 3086 (w), 3028 (s), 2935 (s), 2864 (w), 1740 (s), 1604 ( w), 1496 (m), 1437 (w), 1372 (m), 1240 (s), 1131 (m), 1106 (w), 1051 (m), 917 (w), 806 (w), 749 ( m), 670 (m), 629 (w), 610 (m), 578 (m); Anal Calcd for C ₁₂ H ₁₆ O ₂ : C, 74.97; H, 8.39; Found: C, 75.16; H, 8.32 .

The structural data of 6-bromo-1-hexyl acetate obtained in Example 5-6 is as follows.
¹ H NMR (400 MHz, CDCl ₃ ) δ 1.38-1.42 (m, 2H), 1.42-1.52 (m, 2H), 1.65 (quint, J = 7.1 Hz, 2H), 1.87 (quint, J = 7.1 Hz 2H ), 2.04 (s, 3H), 3.41 (t, J = 6.8 Hz, 2H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 20.97, 25.08, 25.72, 28.35, 32.54, 33.74, 64.29, 171.16; IR ( nujol, ν / cm ^-1 ) 3086 (w), 3028 (s), 2935 (s), 2864 (w), 1740 (s), 1604 (w), 1496 (m), 1437 (w), 1372 ( m), 1240 (s), 1131 (m), 1106 (w), 1051 (m), 917 (w), 806 (w), 749 (m), 670 (m), 629 (w), 610 ( m), 578 (m); Anal Calcd for C ₁₂ H ₁₆ O ₂ : C, 74.97; H, 8.39; Found: C, 75.16; H, 8.32.

The structural data of 3-Benzoyloxy-propyl acetate obtained in Example 5-7 is as follows.
¹ H NMR (400 MHz, CDCl ₃ ) δ 1.94 (quint, J = 6.8 Hz, 2H), 2.02 (s, 3H), 3.55 (t, J = 6.3 Hz, 2H), 4.19 (t, J = 6.3 Hz 2H), 4,50 (s, 2H), 7.25-7.37 (m, 5H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 20.83, 28.90, 61.58, 66.50, 72.86, 127.50, 128.27, 138.21, 171.00; IR (nujol, ν / cm ^-1 ) 3088 (m), 2860 (S), 2780 (m), 1739 (S), 1653 (w), 1496 (m), 1455 (m), 1386 (w), 1243 (w), 1075 (w), 1045 (w), 970 (w), 738 (m), 699 (m), 607 (m): Anal Calcd forC ₁₂ H ₁₆ O ₃ : C, 69.21; H, 7.74; Found: C, 69.19; H, 7.84.

The structural data of 2-decynyl acetate obtained in Example 5-9 is as follows.
¹ H NMR (400 MHz, CDCl ₃ ) δ 0.88 (t, J = 6.8 Hz, 3H), 1.22-1.34 (m, 8H), 1.51 (quint, J = 7.3 Hz, 2H), 2.10 (s, 3H) , 2.22 (dt, J = 2.1 Hz, 2H), 4.66 (t, J = 2.1 Hz, 2H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 14.07, 18.72, 20.79, 22.56, 28.33, 28.70, 31.55, 31.66, 52.87, 73.75, 87.75, 170.38; IR (nujol, ν / cm ^-1 ) 2931 (s), 2858 (s), 1751 (s), 1465 (m), 1437 (m), 1378 (m), 1359 (m), 1224 (s), 1150 (m), 1025 (m), 967 (m), 625 (w): Anal Calcd for C ₁₂ H ₂₀ O ₂ : C, 73.43; H, 10.27; Found: C, 73.54; H, 10.11.

The structural data of 9-dodecynyl acetate obtained in Example 5-10 are as follows.
¹ H NMR (400 MHz, CDCl ₃ ) δ 1.12 (t, J = 7.4 Hz, 3H), 1.22-1.40 (quint, J = 6.9 Hz, 2H), 1.61 (quint, J = 6.9 Hz, 2H), 2.45 (s, 3H), 2.15-2.20 (m, 4H), 4.05 (t, J = 6.8 Hz, 2H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 12.38, 14.34, 18.67, 21.01, 25.81, 28.69, 28.99, 29.03, 29.10, 64.61, 79.44, 81.60, 171.27; IR (nujol, ν / cm ^-1 ) 2973 (w), 2932 (s), 2857 (m), 1742 (s), 1464 (w), 1387 (w), 1241 (s), 1037 (m), 665 (w), 605 (m).

Example 6 (Reaction of cyclic diketone and allyl alcohol)
In Example 1, 2 equivalents of 2-acetylcyclohexanone was used as the 1,3-diketone, 1 equivalent of allyl alcohol was used as the alcohol, and the addition amount of indium triflate was changed to 5 mol%. The keto ester represented by the following formula (5) was synthesized. The yield obtained by isolating and purifying the obtained reaction mixture by silica gel column chromatography was 93%, and the yield determined using ¹ H-NMR without isolation was 96%. A keto ester in which the carbonyl group contained in the 6-membered ring was selectively subjected to nucleophilic attack was obtained in good yield.

Example 7 (Examination of water)
In Example 1, 1 equivalent of dibenzoylmethane was used as 1,3-diketone, 5 equivalents of water was used as a nucleophile, and the reaction temperature was 115 ° C. The resulting reaction mixture was isolated and purified by silica gel column chromatography, and benzoic acid was obtained in a yield of 60% as shown in the following formula (6). This is considered to be the result of water performing a nucleophilic attack similar to alcohol, and it was confirmed that carboxylic acid can be synthesized from 1,3-diketone. Moreover, the production | generation of acetophenone was also confirmed simultaneously at this time, and the production | generation of the ketone by the deacylation reaction from a 1, 3- diketone was also confirmed.

Example 8 (Study of amine)
In Example 1, 2 equivalents of 2,4-pentanedione was used, 1 equivalent of morpholine was used as the nucleophile, and the amount of indium triflate was changed to 5 mol%. The resulting reaction mixture was isolated and purified by silica gel column chromatography to obtain an amide represented by the following formula (7) in a yield of 89%. This is considered to be a result of the nucleophilic attack of the amine in the same manner as the alcohol, and it was confirmed that the amide can be synthesized from the 1,3-diketone with high yield.

Claims (5)

Formula (I) below

[Wherein, R ¹ and R ⁴ each independently represent a hydrogen atom, an alkyl group which may have a substituent, an alkenyl group which may have a substituent, or an alkynyl group which may have a substituent. An aryl group which may have a substituent, an arylalkyl group which may have a substituent, an arylalkenyl group which may have a substituent, an arylalkynyl group which may have a substituent, a substituent A cycloalkyl group that may have a heterocyclic group that may have a substituent; R ² and R ³ each independently represent a hydrogen atom, a halogen atom, or an alkyl that may have a substituent; A group, an alkenyl group which may have a substituent, an alkynyl group which may have a substituent, an aryl group which may have a substituent, an arylalkyl group which may have a substituent, a substituent An arylalkenyl group that may have a substituent Arylalkynyl group which may be substituted, cycloalkyl group which may have substituent, heterocyclic group which may have substituent, hydroxyl group which may be protected, alkoxy group, aryloxy group, aldehyde group, protected May be a carboxyl group or a salt thereof, an alkylcarbonyl group, an arylcarbonyl group, an alkyloxycarbonyl group, an aryloxycarbonyl group, an alkylcarbonyloxy group, an arylcarbonyloxy group, an amino group which may be protected, an alkylamino Group, arylamino group, ammonium group, alkylammonium group, arylammonium group, thiol group which may be protected, alkylthio group, arylthio group, sulfinic acid group which may be protected or its salt, alkylsulfinyl group, aryl Sulfinyl group, even if protected Sulfonic acid groups or salts thereof, alkylsulfonyl groups, arylsulfonyl groups, alkylazo groups, arylazo groups, optionally protected phosphoric acid groups or salts thereof, optionally protected phosphorous acid groups or salts thereof, cyano A group, a nitro group or an azide group; R ¹ , R ² , R ³ and R ⁴ may be bonded to each other to form a ring. ]
1,3-dicarbonyl compound represented by the following formula (II)

[Wherein, -X- represents -O-, -S- or -NR ^6- ; R ⁵ and R ⁶ each independently represents a hydrogen atom, an alkyl group which may have a substituent, or a substituent; An alkenyl group which may have a group, an alkynyl group which may have a substituent, an aryl group which may have a substituent, an arylalkyl group which may have a substituent, and a substituent An arylalkenyl group which may have a substituent, an arylalkynyl group which may have a substituent, a cycloalkyl group which may have a substituent, a heterocyclic group which may have a substituent; R ⁵ and R ⁶ are , ^May be bonded to each other to form a ring, and R ⁵ or R ⁶ may be bonded to R ¹ , R ² , R ³ or R ⁴ in formula (I). ]
The compound represented by formula (III) is reacted in the presence of a Lewis acid catalyst selected from indium triflate or copper triflate:

[Wherein, X, R ¹ and R ⁵ are the same as those in the above formulas (I) and (II). ]
The manufacturing method of 1 type of compounds selected from the group which consists of ester, carboxylic acid, and amide shown by these. In the 1,3-dicarbonyl compound represented by the formula (I), R ¹ , R ² , R ³ and R ⁴ are bonded to each other to form a ring, and the compound represented by the formula (III) is The production method according to claim 1, which is one compound selected from the group consisting of ketoesters, ketocarboxylic acids and ketoamides. The production method according to claim 1 or 2, wherein the 1,3-dicarbonyl compound represented by the formula (I) and the compound represented by the formula (II) are reacted at a concentration of 1 mol / L or more. The production method according to any one of claims 1 to 3 , wherein the reaction is performed at a reaction temperature of 60 to 200 ° C. Formula (I) below

[Wherein, R ¹ and R ⁴ each independently represent a hydrogen atom, an alkyl group which may have a substituent, an alkenyl group which may have a substituent, or an alkynyl group which may have a substituent. An aryl group which may have a substituent, an arylalkyl group which may have a substituent, an arylalkenyl group which may have a substituent, an arylalkynyl group which may have a substituent, a substituent A cycloalkyl group that may have a heterocyclic group that may have a substituent; R ² and R ³ each independently represent a hydrogen atom, a halogen atom, or an alkyl that may have a substituent; A group, an alkenyl group which may have a substituent, an alkynyl group which may have a substituent, an aryl group which may have a substituent, an arylalkyl group which may have a substituent, a substituent An arylalkenyl group that may have a substituent Arylalkynyl group which may be substituted, cycloalkyl group which may have substituent, heterocyclic group which may have substituent, hydroxyl group which may be protected, alkoxy group, aryloxy group, aldehyde group, protected May be a carboxyl group or a salt thereof, an alkylcarbonyl group, an arylcarbonyl group, an alkyloxycarbonyl group, an aryloxycarbonyl group, an alkylcarbonyloxy group, an arylcarbonyloxy group, an amino group which may be protected, an alkylamino Group, arylamino group, ammonium group, alkylammonium group, arylammonium group, thiol group which may be protected, alkylthio group, arylthio group, sulfinic acid group which may be protected or its salt, alkylsulfinyl group, aryl Sulfinyl group, even if protected Sulfonic acid groups or salts thereof, alkylsulfonyl groups, arylsulfonyl groups, alkylazo groups, arylazo groups, optionally protected phosphoric acid groups or salts thereof, optionally protected phosphorous acid groups or salts thereof, cyano A group, a nitro group or an azide group; R ¹ , R ² , R ³ and R ⁴ may be bonded to each other to form a ring. ]
1,3-dicarbonyl compound represented by the following formula (II)

[Wherein, -X- represents -O-, -S- or -NR ^6- ; R ⁵ and R ⁶ each independently represents a hydrogen atom, an alkyl group which may have a substituent, or a substituent; An alkenyl group which may have a group, an alkynyl group which may have a substituent, an aryl group which may have a substituent, an arylalkyl group which may have a substituent, and a substituent An arylalkenyl group which may have a substituent, an arylalkynyl group which may have a substituent, a cycloalkyl group which may have a substituent, a heterocyclic group which may have a substituent; R ⁵ and R ⁶ are , ^May be bonded to each other to form a ring, and R ⁵ or R ⁶ may be bonded to R ¹ , R ² , R ³ or R ⁴ in formula (I). ]
Wherein the compound represented by formula (IV) is reacted in the presence of a Lewis acid catalyst selected from indium triflate or copper triflate:

[Wherein R ² , R ³ and R ⁴ are the same as those in the above formulas (I) and (II). ]
The manufacturing method of the ketone shown by these.