JP5072030B2

JP5072030B2 - Cyclic α-hydroxy-α, β-unsaturated ketone compound and method for producing cyclopentenone compound

Info

Publication number: JP5072030B2
Application number: JP2008059203A
Authority: JP
Inventors: 修小林; 雅也小久保
Original assignee: Japan Science and Technology Agency; National Institute of Japan Science and Technology Agency
Current assignee: Japan Science and Technology Agency; National Institute of Japan Science and Technology Agency
Priority date: 2008-03-10
Filing date: 2008-03-10
Publication date: 2012-11-14
Anticipated expiration: 2028-03-10
Also published as: JP2009215204A

Description

この発明は、水中で、ルイス酸触媒を用いて、２−オキソ−１，４−ペンタジエニル−３−オン化合物から、環状α−ヒドロキシ−α，β−不飽和ケトン化合物及びシクロペンテノン化合物を合成する方法に関する。 The present invention synthesizes cyclic α-hydroxy-α, β-unsaturated ketone compounds and cyclopentenone compounds from 2-oxo-1,4-pentadienyl-3-one compounds in water using a Lewis acid catalyst. On how to do.

１，４−ペンタジエニル−３−オン化合物からシクロペンテノン誘導体を得る有用な方法としてナザロフ反応が知られている(非特許文献１など)。 A Nazaroff reaction is known as a useful method for obtaining a cyclopentenone derivative from a 1,4-pentadienyl-3-one compound (Non-patent Document 1, etc.).

Org. Lett. 2003, 5, 4931-4934Org. Lett. 2003, 5, 4931-4934

従来のナザロフ反応(非特許文献１など)においては有機溶媒を用い、アルゴンや窒素のような不活性ガス存在下、モレキュラーシーブスのような脱水剤を用いることで極限まで酸素、水を取り除いて反応を行う必要があった。
従って、本発明は、ナザロフ反応を改良して、水中で環状α−ヒドロキシ−α，β−不飽和ケトン化合物及びシクロペンテノン化合物を合成する方法を提供することを目的とする。 In the conventional Nazaroff reaction (Non-Patent Document 1, etc.), an organic solvent is used, and in the presence of an inert gas such as argon or nitrogen, a dehydrating agent such as molecular sieve is used to remove oxygen and water to the limit. Had to do.
Accordingly, it is an object of the present invention to provide a method for synthesizing cyclic α-hydroxy-α, β-unsaturated ketone compounds and cyclopentenone compounds in water by improving the Nazaroff reaction.

水溶媒中で、ルイス酸触媒を用いて、２−オキソ−１，４−ペンタジエニル−３−オン化合物に対してナザロフ反応を行うと、有機溶媒中で反応を行った場合とは異なる反応経路を通り、環状α−ヒドロキシ−α，β−不飽和ケトン化合物を選択的に与えることを見出した。すなわち、反応中間体であるペンタジエニルカチオンに対して溶媒として用いた水が反応することによって対応する環状α−ヒドロキシ−α，β−不飽和ケトン化合物が生成した。
また、同じ反応系中に２級アミンを加えると、有機溶媒中で反応を行った時と同様に(非特許文献１など)、シクロペンテノン化合物を生成できることを見出した。 When a Nazaroff reaction is performed on a 2-oxo-1,4-pentadienyl-3-one compound using a Lewis acid catalyst in an aqueous solvent, a reaction route different from that in the case of performing the reaction in an organic solvent is obtained. As described above, it has been found that a cyclic α-hydroxy-α, β-unsaturated ketone compound is selectively provided. That is, the corresponding cyclic α-hydroxy-α, β-unsaturated ketone compound was produced by the reaction of water used as a solvent with the pentadienyl cation, which is a reaction intermediate.
Further, it has been found that when a secondary amine is added to the same reaction system, a cyclopentenone compound can be produced in the same manner as when the reaction is carried out in an organic solvent (Non-patent Document 1, etc.).

即ち、本発明は、水中で、触媒として下記一般式
Ｍ（ＸＲ ^５）_３
（式中、ＭはＳｃを表し、Ｒ^５は、炭素数が８〜３０の脂肪族炭化水素基を表し、Ｘは−ＯＳＯ_２−又は−ＯＳＯ_３ −を表す。）で表されるルイス酸と、下式（式１）

（式中、Ｒ^１〜Ｒ^４は、それぞれ独立に、水素原子、置換基を有していてもよい芳香族炭化水素基若しくは芳香族複素環基、又は置換基を有していてもよい、アルキル基、シクロアルキル基又はアルケニル基を表し、Ｒ^１とＲ^２は共同でヘテロ原子を含んでもよい４〜１０員環を形成してよく、またＲ^３とＲ^４は共同でヘテロ原子を含んでもよい４〜１０員環を形成してよい。）で表される２−オキソ−１，４−ペンタジエニル−３−オン化合物を共存させることから成る、下式（化２）

（式中、Ｒ^２〜Ｒ^４は、上記と同様に定義される。但し、Ｒ ^１とＲ ^２が共同でヘテロ原子を含んでもよい４〜１０員環を形成していない場合には、（ａ）が生成し、Ｒ ^１とＲ ^２が共同でヘテロ原子を含んでもよい４〜１０員環を形成する場合には、（ｂ）が生成し、式中、Ｒ ^７は、形成した当該４〜１０員環中のＲ ^１及びＲ ^２に相当する基を表す。）で表される環状α−ヒドロキシ−α，β−不飽和ケトン化合物の製造方法である。
That is, the present invention provides the following general formula M ( XR ⁵ ) ₃ as a catalyst in water.
(Wherein, M represents S c, ^{R 5} has a carbon number represents an aliphatic hydrocarbon group having 8 to 30, X is -OSO ₂ - represents a. - or -OSO ₃₎ Lewis represented by Acid and the following formula (Formula 1)

(Wherein R ^{1 to} R ⁴ each independently have a hydrogen atom, an aromatic hydrocarbon group or an aromatic heterocyclic group which may have a substituent, or a substituent , Represents an alkyl group, a cycloalkyl group or an alkenyl group , R ¹ and R ² may together form a 4- to 10-membered ring which may contain a hetero atom, and R ³ and R ⁴ jointly contain a hetero atom. Or a 4- to 10-membered ring may be formed.), And a 2-oxo-1,4-pentadienyl-3-one compound represented by the following formula (Formula 2):

(Wherein R ^{2 to} R ⁴ are defined in the same manner as described above, provided that when R ¹ and R ² do not form a 4- to 10-membered ring which may contain a hetero atom together, ( When a) is formed and R ¹ and R ² together form a 4 to 10 membered ring that may contain a hetero atom, (b) is formed, wherein R ⁷ is the 4 And represents a group corresponding to R ¹ and R ² in a 10-membered ring .

更に、本発明は、水中で、触媒として下記一般式
Ｍ（ＸＲ ^５）_３
（式中、ＭはＳｃを表し、Ｒ^５は、炭素数が８〜３０の脂肪族炭化水素基を表し、Ｘは−ＯＳＯ_２−又は−ＯＳＯ_３ −を表す。）で表されるルイス酸、下式（式１）

（式中、Ｒ^１〜Ｒ^４は、それぞれ独立に、水素原子、置換基を有していてもよい芳香族炭化水素基若しくは芳香族複素環基、又は置換基を有していてもよい、アルキル基、シクロアルキル基又はアルケニル基を表し、Ｒ^１とＲ^２は共同でヘテロ原子を含んでもよい４〜１０員環を形成してよく、またＲ^３とＲ^４は共同でヘテロ原子を含んでもよい４〜１０員環を形成してよい。）で表される２−オキソ−１，４−ペンタジエニル−３−オン化合物、及び下式
Ｒ^６ _２−ＮＨ
（式中、Ｒ^６は、同じであっても異なってもよく、アルキル基、シクロアルキル基又はアルケニル基を表す。）で表される２級アミンを共存させることから成る、下式（化３）

（式中、Ｒ^１〜Ｒ^４は、上記と同様に定義される。）で表されるシクロペンテノン化合物の製造方法である。
Furthermore, the present invention provides the following general formula M ( XR ⁵ ) ₃ as a catalyst in water.
(Wherein, M represents S c, ^{R 5} has a carbon number represents an aliphatic hydrocarbon group having 8 to 30, X is -OSO ₂ - represents a. - or -OSO ₃₎ Lewis represented by Acid, the following formula (Formula 1)

(Wherein R ^{1 to} R ⁴ each independently have a hydrogen atom, an aromatic hydrocarbon group or an aromatic heterocyclic group which may have a substituent, or a substituent , Represents an alkyl group, a cycloalkyl group or an alkenyl group , R ¹ and R ² may together form a 4- to 10-membered ring which may contain a hetero atom, and R ³ and R ⁴ jointly contain a hetero atom. But may form a good 4-10 membered ring.) 2-oxo-1,4-pentadienyl-3-one compound represented by, and the following formula R ⁶ ₂ -NH
(Wherein R ⁶ may be the same or different and each represents an alkyl group, a cycloalkyl group, or an alkenyl group). )

(Wherein R ^{1 to} R ⁴ are defined in the same manner as described above).

本発明の製法は、有害な有機溶媒を用いることなく効率的に５員環α−ヒドロキシ−α，β−不飽和ケトン誘導体やシクロペンテノン誘導体を合成することができるため、これらの化合物の環境調和型プロセスとして有用である。
本発明の製法は、ルイス酸触媒を用いることにより、溶媒として水のみを用いてナザロフ反応を行うことで有機溶媒中とは異なる生成物（即ち、α−ヒドロキシ−α，β−不飽和ケトン化合物）を与える。
また、反応系中に２級アミンが存在すると有機溶媒中で反応を行った時と同じ化合物（即ち、シクロペンテノン化合物）を合成することもできる。
本発明の製法を用いることにより、５員環α−ヒドロキシ−α，β−不飽和ケトン化合物を１工程で合成することができる。これらの化合物の中には下式に示すような有用な天然物も含まれているため、これらの天然物の環境調和型プロセスを提供することが可能となる。これらの化合物は、従来のナザロフ反応(非特許文献１など)では合成することができなかったものである。

The production method of the present invention can efficiently synthesize 5-membered ring α-hydroxy-α, β-unsaturated ketone derivatives and cyclopentenone derivatives without using harmful organic solvents. Useful as a harmonized process.
In the production method of the present invention, a Lewis acid catalyst is used to carry out a Nazaroff reaction using only water as a solvent, resulting in a product different from that in an organic solvent (that is, an α-hydroxy-α, β-unsaturated ketone compound). )give.
In addition, when a secondary amine is present in the reaction system, the same compound (that is, cyclopentenone compound) as when the reaction is performed in an organic solvent can be synthesized.
By using the production method of the present invention, a 5-membered ring α-hydroxy-α, β-unsaturated ketone compound can be synthesized in one step. Since these compounds include useful natural products as shown in the following formula, it is possible to provide an environmentally conscious process for these natural products. These compounds cannot be synthesized by the conventional Nazaroff reaction (Non-patent Document 1, etc.).

本発明で用いる触媒であるルイス酸は、下記一般式で表される。
Ｍ（ＸＲ ^５）_３
ＭはＳｃを表す。
Ｒ^５は、炭素数が８〜３０の脂肪族炭化水素基である。またこの脂肪族炭化水素基は、任意の置換基を有していてもよい。置換基としては、アルキル基、アリール基等の炭化水素基、ハロゲン原子、ヒドロキシル基、アルコキシ基、アシルオキシ基、アミノ基、ニトロ基、シアノ基等が挙げられる。
Ｘは、−ＯＳＯ_２−又は−ＯＳＯ_３−である。
このルイス酸は、有機酸のアルカリ金属塩又はアルカリ土類金属塩と上記金属のハロゲン化物とを水中で混合するか、あるいは有機酸と上記金属の酸化物又は水酸化物とを水中で混合することにより製造することができる。
The Lewis acid that is a catalyst used in the present invention is represented by the following general formula.
M ^(XR _{5) 3}
M represents a S c.
R ⁵ is an aliphatic hydrocarbon group having a carbon number of 8-30. Aliphatic hydrocarbon group Matako may have an arbitrary substituent. Examples of the substituent include hydrocarbon groups such as alkyl groups and aryl groups, halogen atoms, hydroxyl groups, alkoxy groups, acyloxy groups, amino groups, nitro groups, and cyano groups.
X is, - OSO ₂ - or -OSO ₃ - a.
In this Lewis acid, an alkali metal salt or alkaline earth metal salt of an organic acid and a halide of the metal are mixed in water, or an organic acid and an oxide or hydroxide of the metal are mixed in water. Can be manufactured.

本発明の反応の基質である２−オキソ−１，４−ペンタジエニル−３−オン化合物は下式（式１）で表される。

本願発明の反応においては、この２−オキソ−１，４−ペンタジエニル−３−オン構造が重要なのであり、当該反応において置換基Ｒ^１〜Ｒ^４は重要な要素ではなく、特に制限はない。 The 2-oxo-1,4-pentadienyl-3-one compound which is a substrate for the reaction of the present invention is represented by the following formula (Formula 1).

In the reaction of the present invention, the 2-oxo-1,4-pentadienyl-3-one structure is important. In the reaction, the substituents R ^{1 to} R ⁴ are not important elements and are not particularly limited.

Ｒ^１〜Ｒ^４は、それぞれ独立に、水素原子、置換基を有していてもよい芳香族炭化水素基若しくは芳香族複素環基、又は置換基を有していてもよい非芳香族炭化水素基を表す。
芳香族炭化水素基としては、アリール基が挙げられ、アリール基としては、フェニル基、α又はβ−ナフチル基が挙げられる。芳香族複素環基としては、ピリジル、ピリミジニル、チアゾリル、オキサゾリル、イソオキサゾリル、イソチアゾリル、フリル、イミダゾリル等の単環の芳香族複素環基、ベンズイソチアゾリル、ベンズイソオキサゾリル、ベンズフリル、キノリル、イソキノリル、インドリル、インダゾリル、ベンズイミダゾリル、ベンズオキサゾリル、ナフチリジニル、プテリジニル、チエノフラニル、イミダゾチオフェン−イル、イミダゾフラニル等の二環性の芳香族複素環基が挙げられる。
また、これらは置換基を有していてもよく、特に制限はないが、直鎖又は分岐のアルキル基、アルコキシル基、アリール基、ハロゲン原子などが挙げられる。 R ^{1 to} R ⁴ are each independently a hydrogen atom, an aromatic hydrocarbon group or aromatic heterocyclic group that may have a substituent, or a non-aromatic hydrocarbon that may have a substituent. Represents a group.
Examples of the aromatic hydrocarbon group include an aryl group, and examples of the aryl group include a phenyl group and an α or β-naphthyl group. Aromatic heterocyclic groups include monocyclic aromatic heterocyclic groups such as pyridyl, pyrimidinyl, thiazolyl, oxazolyl, isoxazolyl, isothiazolyl, furyl, imidazolyl, benzisothiazolyl, benzisoxazolyl, benzfuryl, quinolyl, isoquinolyl And bicyclic aromatic heterocyclic groups such as indolyl, indazolyl, benzimidazolyl, benzoxazolyl, naphthyridinyl, pteridinyl, thienofuranyl, imidazothiophenyl, and imidazolofuranyl.
These may have a substituent and are not particularly limited, and examples thereof include a linear or branched alkyl group, an alkoxyl group, an aryl group, and a halogen atom.

この非芳香族炭化水素基は、アルキル基、シクロアルキル基又はアルケニル基であり、好ましくはアルキル基である。アルキル基は、直鎖又は分岐でもよく、特に制限はないが、通常炭素数が１〜２０である。シクロアルキル基として、シクロブチル、シクロペンチル、シクロヘキシル、シクロヘプチル基等を挙げることができる。アルケニル基としては、例えば、ビニル基、プロペニル基、１−メチルビニル基、アリル基等をあげることができる。
これらはまた、上記と同様の置換基を有していてもよい。
また、Ｒ^１とＲ^２は共同でヘテロ原子を含んでもよい４〜１０員環を形成してよく、またＲ^３とＲ^４は共同でヘテロ原子を含んでもよい４〜１０員環を形成してよい。ヘテロ原子としては、−Ｏ−、−Ｓ−、−ＮＨ−が挙げられる。
The non-aromatic hydrocarbon group, an alkyl group, a cycloalkyl group or an alkenyl group, preferably an alkyl group. The alkyl group may be linear or branched and is not particularly limited, but usually has 1 to 20 carbon atoms. Examples of the cycloalkyl group include cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl groups. Examples of the alkenyl group include a vinyl group, a propenyl group, a 1-methylvinyl group, and an allyl group.
These may also have the same substituents as described above.
R ¹ and R ² may jointly form a 4- to 10-membered ring that may contain a hetero atom, and R ³ and R ⁴ jointly form a 4- to 10-membered ring that may contain a hetero atom. It's okay. Examples of the hetero atom include —O—, —S—, and —NH—.

本発明の反応で用いる二級アミンは下式で表される。
Ｒ^６ _２−ＮＨ
Ｒ^６は、同じであっても異なってもよく、直鎖又は分岐の、好ましくは分岐のアルキル基、シクロアルキル基、アルケニル基、好ましくは炭素数が３〜２０の分岐のアルキル基又は炭素数が５〜２０のシクロアルキル基を表す。
このような二級アミンとして、例えば、ジイソプロピルアミン、ジシクロヘキシルアミン等をあげることができる。 The secondary amine used in the reaction of the present invention is represented by the following formula.
R ⁶ ₂ -NH
R ⁶ may be the same or different, and may be a linear or branched, preferably branched alkyl group, cycloalkyl group, alkenyl group, preferably a branched alkyl group having 3 to 20 carbon atoms, or a carbon number. Represents a cycloalkyl group of 5 to 20.
Examples of such secondary amines include diisopropylamine and dicyclohexylamine.

本発明の第一の実施態様として、水中で、触媒として上記ルイス酸を用いて、２−オキソ−１，４−ペンタジエニル−３−オン化合物を共存させると、下式に従って、環状α−ヒドロキシ−α，β−不飽和ケトン化合物が生成する（式中、Ｒ^１〜Ｒ^４は、上記で定義したとおりである。）。

但し、Ｒ ^１とＲ ^２が共同でヘテロ原子を含んでもよい４〜１０員環を形成する場合には、下式に従って、環状α−ヒドロキシ−α，β−不飽和ケトン化合物が生成する。（式中、Ｒ ^７は、形成した当該４〜１０員環中のＲ ^１及びＲ ^２に相当する基を表す。）

反応条件は以下のとおりである
溶媒は、水である。
基質の濃度は、０．００１〜１０Ｍ、好ましくは０．００５〜１Ｍである。
触媒の使用量は、基質に対して、０．０００１〜１当量、好ましくは０．００５〜０．２当量である。
反応温度は、０〜１００℃、好ましくは０〜４０℃である。
反応時間は、通常１〜１２０時間である。
このように、本願発明の製法により、環状α−ヒドロキシ−α，β−不飽和ケトン化合物を得ることができるが、この生成物は従来の有機溶媒を用いたナザロフ反応(非特許文献１など)では得ることのできなかったものである。

As a first embodiment of the present invention, when a 2-oxo-1,4-pentadienyl-3-one compound is allowed to coexist in water using the above Lewis acid as a catalyst, a cyclic α-hydroxy- An α, β-unsaturated ketone compound is produced (wherein R ^{1 to} R ⁴ are as defined above).

However, when R ¹ and R ² jointly form a 4- to 10-membered ring that may contain a hetero atom, a cyclic α-hydroxy-α, β-unsaturated ketone compound is formed according to the following formula. (In the formula, R ⁷ represents a group corresponding to R ¹ and R ² in the formed 4- to 10-membered ring .)

The reaction conditions are as follows: The solvent is water.
The concentration of the substrate is 0.001 to 10M, preferably 0.005 to 1M.
The usage-amount of a catalyst is 0.0001-1 equivalent with respect to a substrate, Preferably it is 0.005-0.2 equivalent.
The reaction temperature is 0 to 100 ° C, preferably 0 to 40 ° C.
The reaction time is usually 1 to 120 hours.
Thus, although the cyclic α-hydroxy-α, β-unsaturated ketone compound can be obtained by the production method of the present invention, this product is a Nazaroff reaction using a conventional organic solvent (Non-patent Document 1, etc.). It was something that could not be obtained.

本発明の第二の実施態様として、水中で、触媒として上記ルイス酸を用いて、２−オキソ−１，４−ペンタジエニル−３−オン化合物を共存させ、更に二級アミンを加えると、下式に従って、シクロペンテノン化合物が生成する（式中、Ｒ^１〜Ｒ^４、Ｒ^６は、上記で定義したとおりである。）。

反応条件は以下のとおりである
溶媒は、水である。
基質の濃度は、０．００１〜１０Ｍ、好ましくは０．００５〜１Ｍである。
触媒の使用量は、基質に対して、０．０００１〜１当量、好ましくは０．００５〜０．２当量である。
二級アミンの使用量は、基質に対して、０．１〜１０当量、好ましくは０．１〜３当量である。
反応温度は、０〜１００℃、好ましくは０〜４０℃である。
反応時間は、通常１〜１２０時間である。
このように、溶媒として水を用いるにもかかわらず、二級アミンを加えることにより、従来の有機溶媒を用いたナザロフ反応(非特許文献１など)と同様にシクロペンテノン化合物を得ることができる。 As a second embodiment of the present invention, when a 2-oxo-1,4-pentadienyl-3-one compound is allowed to coexist in water using the above Lewis acid as a catalyst and a secondary amine is further added, To form a cyclopentenone compound (wherein R ^{1 to} R ⁴ and R ⁶ are as defined above).

The reaction conditions are as follows: The solvent is water.
The concentration of the substrate is 0.001 to 10M, preferably 0.005 to 1M.
The usage-amount of a catalyst is 0.0001-1 equivalent with respect to a substrate, Preferably it is 0.005-0.2 equivalent.
The usage-amount of a secondary amine is 0.1-10 equivalent with respect to a substrate, Preferably it is 0.1-3 equivalent.
The reaction temperature is 0 to 100 ° C, preferably 0 to 40 ° C.
The reaction time is usually 1 to 120 hours.
In this way, a cyclopentenone compound can be obtained in the same manner as in the conventional Nazaroff reaction using an organic solvent (Non-patent Document 1, etc.) by adding a secondary amine in spite of using water as a solvent. .

以下、実施例にて本発明を例証するが本発明を限定することを意図するものではない。
以下の実施例において、¹H NMR及び¹³C NMRは、溶媒としてCDCl₃を内部標準としてテトラメチルシランを用い、日本電子株式会社製JNM-LA400又はJNM-ECA-500を用いて測定した。IRスペクトルは、日本分光社製FT/IR-610を用いて測定した。
また、実施例に用いた基質は公知文献（Org. Lett. 2003, 5 (26), 4931-4934.）に記載の製法に従って合成した。 The following examples illustrate the invention but are not intended to limit the invention.
In the following examples, ¹ H NMR and ¹³ C NMR were measured using JNM-LA400 or JNM-ECA-500 manufactured by JEOL Ltd., using CDCl ₃ as a solvent and tetramethylsilane as an internal standard. The IR spectrum was measured using FT / IR-610 manufactured by JASCO Corporation.
The substrates used in the examples were synthesized according to the production method described in known literature (Org. Lett. 2003, 5 (26), 4931-4934.).

製造例１
スカンジウムトリスドデシルサルフェート（Sc(DS)₃）を公知の方法（J. Am. Chem. Soc. 2000, 122 (30), 7202-7207）によって合成した。
ドデシル硫酸ナトリウム（和光純薬工業株式会社製、1.49 g）を水（25 mL）に溶解した。この溶液に塩化スカンジウム六水和物（添川化学製、500 mg）の水（5 mL）溶液を室温で滴下した。反応液を室温で１時間攪拌した。現れた結晶をろ取し水（100 mL x 3）で洗浄した。結晶を減圧下乾燥して、Sc(DS)₃（1.32 g, 91%）を白色結晶として得た。
元素分析計算値：C₃₃H₆₉O₉S₃Sc・2.5H₂O C:49.79, H:9.37
観測値： C:49.81, H:9.14 Production Example 1
Scandium trisdodecyl sulfate (Sc (DS) ₃ ) was synthesized by a known method (J. Am. Chem. Soc. 2000, 122 (30), 7202-7207).
Sodium dodecyl sulfate (Wako Pure Chemical Industries, Ltd., 1.49 g) was dissolved in water (25 mL). To this solution, a solution of scandium chloride hexahydrate (Zoegawa Chemical, 500 mg) in water (5 mL) was added dropwise at room temperature. The reaction was stirred at room temperature for 1 hour. The appeared crystals were collected by filtration and washed with water (100 mL × 3). The crystals were dried under reduced pressure to obtain Sc (DS) ₃ (1.32 g, 91%) as white crystals.
Elemental analysis Calculated value: C ₃₃ H ₆₉ O ₉ S ₃ Sc ・ 2.5H ₂ OC: 49.79, H: 9.37
Observations: C: 49.81, H: 9.14

実施例１
10mLのフラスコに製造例１で得たSc(DS)₃（25.2 mg）を水（1.8 mL）中で懸濁した。この溶液に１−（３，４−ジヒドロ−２Ｈ−ピラン−６−イル）−２−メチルプロプ−２−エン−１−オン（45.7 mg）を加えた。反応液を室温で１６時間攪拌した。反応液に飽和炭酸水素ナトリウム水（5 mL）、飽和食塩水（5 mL）を加えた。水層をジクロロメタン（20 mL x 3）で抽出した。有機層を合わせて飽和食塩水（10 mL x 2）で洗浄し、無水硫酸水素ナトリウムで乾燥した。無水硫酸水素ナトリウムをろ別し、減圧下濃縮した。残渣を分取用TLC（溶出液：ｎ−ヘキサン／酢酸エチル＝1/2）で精製し、２−ヒドロキシ−５−（３−ヒドロキシプロピル）−３−メチルシクロペント−２−エノン（45.5 mg、89%）を無色液体として得た。
反応式を下式に示す。

Example 1
Sc (DS) ₃ (25.2 mg) obtained in Production Example 1 was suspended in water (1.8 mL) in a 10 mL flask. To this solution was added 1- (3,4-dihydro-2H-pyran-6-yl) -2-methylprop-2-en-1-one (45.7 mg). The reaction was stirred at room temperature for 16 hours. Saturated aqueous sodium hydrogen carbonate (5 mL) and saturated brine (5 mL) were added to the reaction solution. The aqueous layer was extracted with dichloromethane (20 mL x 3). The organic layers were combined, washed with saturated brine (10 mL × 2), and dried over anhydrous sodium hydrogen sulfate. Anhydrous sodium hydrogensulfate was filtered off and concentrated under reduced pressure. The residue was purified by preparative TLC (eluent: n-hexane / ethyl acetate = 1/2) to give 2-hydroxy-5- (3-hydroxypropyl) -3-methylcyclopent-2-enone (45.5 mg). 89%) as a colorless liquid.
The reaction formula is shown below.

反応基質の分析データを以下に示す：
¹H NMR δ 1.86-1.90 (m, 2H), 1.96 (s, 3H), 4.13 (t, J = 5.2 Hz, 2H), 5.64 (d, J = 1.2 Hz, 1H), 5.68 (d, J = 1.2 Hz, 1H), 5.86 (t, J = 4.8 Hz, .1H); ¹³C NMR δ 19.0, 20.9, 21.4, 66.3, 114.0, 123.9, 142.8, 150.9; IR (neat, cm^-1): 2930, 2877, 1658, 1624, 1448, 1320, 1289, 1234, 1172, 1064, 1020, 991, 925, 768; HRMS(ESI-TOF, Pos.) calced for C₉H₁₂O₂Na ([M+Na]⁺): 175.0735, found: 175.0723.
生成物の分析データを以下に示す：
¹H NMR δ 1.47-1.53 (m, 1H), 1.62-1.68 (m, 2H), 1.76-1.87 (m, 2H), 2.00 (s, 3H), 2.10 (dd, J = 1.7, 14.3 Hz, 1H), 2.13-2.42 (m, 1H), 2.61-2.66 (m, 1H), 3.66 (t, J = 6.3 Hz, 2H), 5.79 (s, 1H); ¹³C NMR δ 14.2, 27.6, 29.9, 34.6, 42.4, 62.5, 142.9, 148.1, 204.9; IR (neat) 3419, 2939, 1700, 1644, 1517, 1446, 1373, 1294, 1217, 1167, 1120, 1043, 987, 814 cm^-1; HRMS(EI, Pos.) calced for C₉H₁₂O₂ ([M-H₂O]⁺): 152.0840, found: 152.0837. Analytical data for the reaction substrate is shown below:
¹ H NMR δ 1.86-1.90 (m, 2H), 1.96 (s, 3H), 4.13 (t, J = 5.2 Hz, 2H), 5.64 (d, J = 1.2 Hz, 1H), 5.68 (d, J = 1.2 Hz, 1H), 5.86 (t, J = 4.8 Hz, .1H); ¹³ C NMR δ 19.0, 20.9, 21.4, 66.3, 114.0, 123.9, 142.8, 150.9; IR (neat, cm ^-1 ): 2930, 2877, 1658, 1624, 1448, 1320, 1289, 1234, 1172, 1064, 1020, 991, 925, 768; HRMS (ESI-TOF, Pos.) Calced for C ₉ H ₁₂ O ₂ Na ([M + Na] ⁺ ): 175.0735, found: 175.0723.
The analytical data of the product is shown below:
¹ H NMR δ 1.47-1.53 (m, 1H), 1.62-1.68 (m, 2H), 1.76-1.87 (m, 2H), 2.00 (s, 3H), 2.10 (dd, J = 1.7, 14.3 Hz, 1H ), 2.13-2.42 (m, 1H), 2.61-2.66 (m, 1H), 3.66 (t, J = 6.3 Hz, 2H), 5.79 (s, 1H); ¹³ C NMR δ 14.2, 27.6, 29.9, 34.6 , 42.4, 62.5, 142.9, 148.1, 204.9; IR (neat) 3419, 2939, 1700, 1644, 1517, 1446, 1373, 1294, 1217, 1167, 1120, 1043, 987, 814 cm ^-1 ; HRMS (EI, Pos.) Calced for C ₉ H ₁₂ O ₂ ([MH ₂ O] ⁺ ): 152.0840, found: 152.0837.

実施例２
基質を等モルの１−（３，４−ジヒドロ−２Ｈ−ピラン−６−イル）−３，３−ジメチル−２−メチレンブタン−１−オンに代えて、実施例１と同様の反応を行ない、３−tert−ブチル−２−ヒドロキシ−５−（３−ヒドロキシプロピル）シクロペント−２−エノンを得た（収率８８％）。
反応式を下式に示す。

反応基質の分析データを以下に示す：
¹H NMR δ 1.17 (s, 9H), 1.84-1.89 (m, 2H), 2.22-2.26 (m, 2H), 4.11-4.13 (m, 2H), 5.16 (s, 1H), 5.44 (s, 1H), 5.91-5.95 (m, 1H); ¹³C NMR δ 21.1, 21.4, 29.6, 35.4, 66.4, 115.6, 116.6, 152.0, 155.8, 194.7; IR (neat) 2959, 2871, 1666, 1623, 1462, 1361, 1287, 1214, 1143, 1085, 1062, 997, 918, 771 cm^-1; HRMS(ESI-TOF, Pos.) calced for C₁₂H₁₉O₂ ([M+H]⁺): 195.1385, found: 195.1364.
生成物の分析データを以下に示す：
¹H NMR δ 1.25 (s, 9H), 1.45-1.50 (m, 1H), 1.62-1.68 (m, 2H), 1.79-1.92 (m,1H), 1.97 (brs, 1H), 2.13 (dd, J = 6.6, 17.8 Hz, 1H), 2.35-2.40 (m, 1H), 2.69 (dd, J = 6.3, 17.8 Hz, 2H), 3.67 (t, J = 6.3 Hz, 1H), 5.76 (brs, 1H); ¹³C NMR δ 27.7, 28.1, 29.8, 30.9, 34.0, 41.5, 62.5, 146.6, 152.5, 206.0; IR (neat) 3480, 2959, 2250, 1699, 1650, 1472, 1398, 1366, 1292, 1169, 1114, 1075, 956, 911, 733 cm^-1; HRMS(EI, Pos.) calced for C₁₂H₁₈O₂ ([M-H₂O]⁺): 194.1307, found: 194.1307. Example 2
The same reaction as in Example 1 was performed by replacing the substrate with equimolar 1- (3,4-dihydro-2H-pyran-6-yl) -3,3-dimethyl-2-methylenebutan-1-one. 3-tert-butyl-2-hydroxy-5- (3-hydroxypropyl) cyclopent-2-enone was obtained (88% yield).
The reaction formula is shown below.

Analytical data for the reaction substrate is shown below:
¹ H NMR δ 1.17 (s, 9H), 1.84-1.89 (m, 2H), 2.22-2.26 (m, 2H), 4.11-4.13 (m, 2H), 5.16 (s, 1H), 5.44 (s, 1H ), 5.91-5.95 (m, 1H); ¹³ C NMR δ 21.1, 21.4, 29.6, 35.4, 66.4, 115.6, 116.6, 152.0, 155.8, 194.7; IR (neat) 2959, 2871, 1666, 1623, 1462, 1361 , 1287, 1214, 1143, 1085, 1062, 997, 918, 771 cm ^-1 ; HRMS (ESI-TOF, Pos.) Calced for C ₁₂ H ₁₉ O ₂ ([M + H] ⁺ ): 195.1385, found: 195.1364.
The analytical data of the product is shown below:
¹ H NMR δ 1.25 (s, 9H), 1.45-1.50 (m, 1H), 1.62-1.68 (m, 2H), 1.79-1.92 (m, 1H), 1.97 (brs, 1H), 2.13 (dd, J = 6.6, 17.8 Hz, 1H), 2.35-2.40 (m, 1H), 2.69 (dd, J = 6.3, 17.8 Hz, 2H), 3.67 (t, J = 6.3 Hz, 1H), 5.76 (brs, 1H) ; ¹³ C NMR δ 27.7, 28.1, 29.8, 30.9, 34.0, 41.5, 62.5, 146.6, 152.5, 206.0; IR (neat) 3480, 2959, 2250, 1699, 1650, 1472, 1398, 1366, 1292, 1169, 1114 , 1075, 956, 911, 733 cm ^-1 ; HRMS (EI, Pos.) Calced for C ₁₂ H ₁₈ O ₂ ([MH ₂ O] ⁺ ): 194.1307, found: 194.1307.

実施例３
基質を等モルの（Ｅ）−（３，４−ジヒドロ−２Ｈ−ピラン−６−イル）−２−メチルブト−２−エン−１−オンに代えて、実施例１と同様の反応を行ない、２−ヒドロキシ−５−（３−ヒドロキシプロピル）−３，４−ジメチルシクロペント−２−エノンを得た（収率７９％）。
反応式を下式に示す。

反応基質の分析データを以下に示す：
¹H NMR δ 1.82-1.90 (m, 8H), 2.19-2.23 (m, 2H), 4.10-4.12 (m, 2H), 5.65 (t, J = 4.6 Hz, 1H), 6.48-6.52 (m, 1H); ¹³C NMR δ 12.4, 14.4, 20.7, 21.6, 66.3, 111.7, 136.2, 137.7, 151.4; IR (neat, cm^-1): 2930, 1648, 1445, 1391, 1346, 1281, 1226, 1158, 1065, 920, 893, 742, 661; HRMS(ESI-TOF, Pos.) calced for C₁₀H₁₅O₂ ([M+H]⁺): 167.1072, found: 167.1034.
生成物の分析データを以下に示す：
¹H NMR δ 1.18 (d, J = 7.5 Hz, 3H), 1.47-1.54 (m, 1H), 1.65-1.70 (m, 2H), 1.76-1.83 (m, 1H), 1.95 (s, 3H), 2.31-2.36 (m, 1H), 2.63 (brs, 1H), 3.65 (t, J = 6.9 Hz, 2H), 6.86 (brs, 1H); ¹³C NMR δ 11.9, 18.5, 27.0, 40.5, 51.2, 62.4, 147.8, 148.2, 204.7; IR (neat) 3433, 2965, 2876, 1703, 1646, 1455, 1402, 1290, 1146, 1041, 964 cm^-1; HRMS(EI, Pos.) calced for C₁₀H₁₄O₂ ([M-H₂O]⁺): 184.1100, found: 184.1099. Example 3
The same reaction as in Example 1 was performed by replacing the substrate with equimolar (E)-(3,4-dihydro-2H-pyran-6-yl) -2-methylbut-2-en-1-one, 2-hydroxy-5- (3-hydroxypropyl) -3,4-dimethylcyclopent-2-enone was obtained (yield 79%).
The reaction formula is shown below.

Analytical data for the reaction substrate is shown below:
¹ H NMR δ 1.82-1.90 (m, 8H), 2.19-2.23 (m, 2H), 4.10-4.12 (m, 2H), 5.65 (t, J = 4.6 Hz, 1H), 6.48-6.52 (m, 1H ); ¹³ C NMR δ 12.4, 14.4, 20.7, 21.6, 66.3, 111.7, 136.2, 137.7, 151.4; IR (neat, cm ^-1 ): 2930, 1648, 1445, 1391, 1346, 1281, 1226, 1158, 1065 , 920, 893, 742, 661; HRMS (ESI-TOF, Pos.) Calced for C ₁₀ H ₁₅ O ₂ ([M + H] ⁺ ): 167.1072, found: 167.1034.
The analytical data of the product is shown below:
¹ H NMR δ 1.18 (d, J = 7.5 Hz, 3H), 1.47-1.54 (m, 1H), 1.65-1.70 (m, 2H), 1.76-1.83 (m, 1H), 1.95 (s, 3H), 2.31-2.36 (m, 1H), 2.63 (brs, 1H), 3.65 (t, J = 6.9 Hz, 2H), 6.86 (brs, 1H); ¹³ C NMR δ 11.9, 18.5, 27.0, 40.5, 51.2, 62.4 , 147.8, 148.2, 204.7; IR (neat) 3433, 2965, 2876, 1703, 1646, 1455, 1402, 1290, 1146, 1041, 964 cm ^-1 ; HRMS (EI, Pos.) Calced for C ₁₀ H ₁₄ O ₂ ([MH ₂ O] ⁺ ): 184.1100, found: 184.1099.

実施例４
基質を等モルのシクロヘキセニル（３，４−ジヒドロ−２Ｈ−ピラン−６−イル）メタノンに代えて、実施例１と同様の反応を行ない、３−ヒドロキシ−１−（３−ヒドロキシプロピル）−５，６，７，７ａ−テトラヒドロ−１Ｈ−インデン−２（４Ｈ）−オンを得た（収率９３％）。
反応式を下式に示す。

反応基質の分析データを以下に示す：
¹H NMR δ 1.60-1.67 (m, 4H), 1.85-1.90 (m, 2H), 2.19-2.40 (m, 6H), 4.10-4.12 (m, 2H), 5.67 (t, J = 4.6 Hz, 1H), 6.71 (m, 1H); ¹³C NMR δ 20.7, 21.6, 21.9, 24.2, 66.3, 111.5, 137.6, 140.3, 151.5, 192.3; IR (neat) 2932, 1648, 1446, 1388, 1345, 1277, 1252, 1218, 1055, 983, 923, 892, 745, 703 cm^-1; HRMS(ESI-TOF, Pos.) calced for C₁₂H₁₆O₂Na ([M+H]⁺): 215.1048, found: 215.1035.
生成物の分析データを以下に示す：
¹H NMR δ 1.01-1.09 (m, 1H), 1.29-1.36 (m, 1H), 1.40-1.53 (m, 2H), 1.62-1.69 (m, 2H), 1.70-1.86 (m, 2H), 1.93-2.04 (m, 3H), 2.14-2.19 (m, 2H), 2.50 (brs, 1H), 2.95-3.00 (m, 1H), 3.66 (t, J = 6.9 Hz, 2H), 6.24 (brs, 1H); ¹³C NMR δ 25.4, 25.5, 26.7, 30.1, 34.3, 43.4, 49.9, 62.5, 145.1, 149.5, 204.5; IR (neat) 3392, 2933, 2860, 1693, 1647, 1447, 1395, 1291, 1166, 1139, 1117, 1062, 954, 910, 882, 732 cm^-1; HRMS(EI, Pos.) calced for C₁₂H₁₆O₂ ([M-H₂O]⁺): 192.1151, found: 192.1150. Example 4
The substrate was replaced with equimolar cyclohexenyl (3,4-dihydro-2H-pyran-6-yl) methanone, and the same reaction as in Example 1 was performed to obtain 3-hydroxy-1- (3-hydroxypropyl)- 5,6,7,7a-Tetrahydro-1H-indene-2 (4H) -one was obtained (yield 93%).
The reaction formula is shown below.

Analytical data for the reaction substrate is shown below:
¹ H NMR δ 1.60-1.67 (m, 4H), 1.85-1.90 (m, 2H), 2.19-2.40 (m, 6H), 4.10-4.12 (m, 2H), 5.67 (t, J = 4.6 Hz, 1H ), 6.71 (m, 1H); ¹³ C NMR δ 20.7, 21.6, 21.9, 24.2, 66.3, 111.5, 137.6, 140.3, 151.5, 192.3; IR (neat) 2932, 1648, 1446, 1388, 1345, 1277, 1252 , 1218, 1055, 983, 923, 892, 745, 703 cm ^-1 ; HRMS (ESI-TOF, Pos.) Calced for C ₁₂ H ₁₆ O ₂ Na ([M + H] ⁺ ): 215.1048, found: 215.1035 .
The analytical data of the product is shown below:
¹ H NMR δ 1.01-1.09 (m, 1H), 1.29-1.36 (m, 1H), 1.40-1.53 (m, 2H), 1.62-1.69 (m, 2H), 1.70-1.86 (m, 2H), 1.93 -2.04 (m, 3H), 2.14-2.19 (m, 2H), 2.50 (brs, 1H), 2.95-3.00 (m, 1H), 3.66 (t, J = 6.9 Hz, 2H), 6.24 (brs, 1H ); ¹³ C NMR δ 25.4, 25.5, 26.7, 30.1, 34.3, 43.4, 49.9, 62.5, 145.1, 149.5, 204.5; IR (neat) 3392, 2933, 2860, 1693, 1647, 1447, 1395, 1291, 1166, 1139, 1117, 1062, 954, 910, 882, 732 cm ^-1 ; HRMS (EI, Pos.) Calced for C ₁₂ H ₁₆ O ₂ ([MH ₂ O] ⁺ ): 192.1151, found: 192.1150.

実施例５
基質を等モルの（Ｅ）−２−メチル−１−フェニル−４−プロポキシペンタ−１，４−ジエン−３−オンに代えて、実施例１と同様の反応を行ない、２−ヒドロキシ−３−メチル−４−フェニルシクロペント−２−エノンを得た（収率８７％）。
反応式を下式に示す。

反応基質の分析データを以下に示す：
¹H NMR δ 1.02 (t, J = 7.5 Hz, 3H), 1.76-1.84 (m, 2H), 2.14 (s, 3H), 3.78 (t, J = 6.9 Hz, 2H), 4.58 (d, J = 2.9 Hz, 1H), 4.84 (d, J = 2.9 Hz, 1H), 7.26-7.45 (m, 6H); ¹³C NMR δ 10.7, 14.0, 22.1, 69.7, 91.9, 128.4, 128.5, 129.7, 135.7, 135.9, 141.3, 194.3.; IR (neat, cm^-1): 3056, 2965, 2878, 1656, 1606, 1491, 1448, 1374, 1295, 1192, 1050, 928, 838, 781, 696, 615, 515; HRMS(ESI-TOF, Pos.) calced for C₁₅H₁₈O₂Na ([M+Na]⁺): 253.1204, found: 253.1180.
生成物の分析データを以下に示す：
¹H NMR δ 1.81 (s, 3H), 2.35 (d, J = 19.5, 1H), 2.93 (dd, J = 5.7, 19.5 Hz, 1H), 3.78-3.80 (m, 1H), 6.41 (s, 1H), 7.11-7.13 (m, 2H), 7.23-7.27 (m, 1H), 7.30-7.34 (m, 2H); ¹³C NMR δ 12.6, 42.3, 44.9, 127.1, 128.9, 141.7, 146.4, 149.6, 202.4; IR (neat) 3247, 1699, 1651, 1405, 1356, 1293, 1154, 1115, 929, 770, 702 cm^-1; HRMS(EI, Pos.) calced for C₁₂H₁₂O₂ ([M]⁺): 188.0838, found: 188.0837. Example 5
The substrate was replaced with an equimolar amount of (E) -2-methyl-1-phenyl-4-propoxypenta-1,4-dien-3-one, and the same reaction as in Example 1 was performed to give 2-hydroxy-3 -Methyl-4-phenylcyclopent-2-enone was obtained (yield 87%).
The reaction formula is shown below.

Analytical data for the reaction substrate is shown below:
¹ H NMR δ 1.02 (t, J = 7.5 Hz, 3H), 1.76-1.84 (m, 2H), 2.14 (s, 3H), 3.78 (t, J = 6.9 Hz, 2H), 4.58 (d, J = 2.9 Hz, 1H), 4.84 (d, J = 2.9 Hz, 1H), 7.26-7.45 (m, 6H); ¹³ C NMR δ 10.7, 14.0, 22.1, 69.7, 91.9, 128.4, 128.5, 129.7, 135.7, 135.9 , 141.3, 194.3 .; IR (neat, cm ^-1 ): 3056, 2965, 2878, 1656, 1606, 1491, 1448, 1374, 1295, 1192, 1050, 928, 838, 781, 696, 615, 515; HRMS (ESI-TOF, Pos.) Calced for C ₁₅ H ₁₈ O ₂ Na ([M + Na] ⁺ ): 253.1204, found: 253.1180.
The analytical data of the product is shown below:
¹ H NMR δ 1.81 (s, 3H), 2.35 (d, J = 19.5, 1H), 2.93 (dd, J = 5.7, 19.5 Hz, 1H), 3.78-3.80 (m, 1H), 6.41 (s, 1H ), 7.11-7.13 (m, 2H), 7.23-7.27 (m, 1H), 7.30-7.34 (m, 2H); ¹³ C NMR δ 12.6, 42.3, 44.9, 127.1, 128.9, 141.7, 146.4, 149.6, 202.4 ; IR (neat) 3247, 1699, 1651, 1405, 1356, 1293, 1154, 1115, 929, 770, 702 cm ^-1 ; HRMS (EI, Pos.) Calced for C ₁₂ H ₁₂ O ₂ ([M] ⁺ ): 188.0838, found: 188.0837.

実施例６
１０ｍLのフラスコに製造例１で得たSc(DS)₃（25.2 mg）を水（0.3 mL）中で懸濁した。この溶液にＮ，Ｎ−ジイソプロピルアミン（東京化成製）（0.084 mL）と１−（３，４−ジヒドロ−２Ｈ−ピラン−６−イル）−２−メチルプロプ−２−エン−１−オン（45.7 mg）を加えた。反応液を室温で２４時間攪拌した。反応液に飽和炭酸水素ナトリウム水（5 mL）、飽和食塩水（5 mL）を加えた。水層をジクロロメタン（20 mL x 3）で抽出した。有機層を合わせて飽和食塩水（10 mL x 2）で洗浄し、無水硫酸水素ナトリウムで乾燥した。無水硫酸水素ナトリウムをろ別し、減圧下濃縮した。残渣を分取用TLC（溶出液：ｎ−ヘキサン／酢酸エチル＝１／２）で精製し、６−メチル−３，４，５，６−テトラヒドロ−２Ｈ−シクロペンタ[ｂ]ピラン−７−オン（44.4 mg、82%）を無色液体として得た。 Example 6
Sc (DS) ₃ (25.2 mg) obtained in Production Example 1 was suspended in water (0.3 mL) in a 10 mL flask. To this solution, N, N-diisopropylamine (manufactured by Tokyo Chemical Industry) (0.084 mL) and 1- (3,4-dihydro-2H-pyran-6-yl) -2-methylprop-2-en-1-one (45.7 mg). The reaction was stirred at room temperature for 24 hours. Saturated aqueous sodium hydrogen carbonate (5 mL) and saturated brine (5 mL) were added to the reaction solution. The aqueous layer was extracted with dichloromethane (20 mL x 3). The organic layers were combined, washed with saturated brine (10 mL × 2), and dried over anhydrous sodium hydrogen sulfate. Anhydrous sodium hydrogensulfate was filtered off and concentrated under reduced pressure. The residue was purified by preparative TLC (eluent: n-hexane / ethyl acetate = 1/2) and 6-methyl-3,4,5,6-tetrahydro-2H-cyclopenta [b] pyran-7-one (44.4 mg, 82%) was obtained as a colorless liquid.

反応式を下式に示す。

反応基質の分析データを以下に示す：
¹H NMR δ 1.86-1.90 (m, 2H), 1.96 (s, 3H), 4.13 (t, J = 5.2 Hz, 2H), 5.64 (d, J = 1.2 Hz, 1H), 5.68 (d, J = 1.2 Hz, 1H), 5.86 (t, J = 4.8 Hz, .1H); ¹³C NMR δ 19.0, 20.9, 21.4, 66.3, 114.0, 123.9, 142.8, 150.9; IR (neat, cm^-1): 2930, 2877, 1658, 1624, 1448, 1320, 1289, 1234, 1172, 1064, 1020, 991, 925, 768; HRMS(ESI-TOF, Pos.) calced for C₉H₁₂O₂Na ([M+Na]⁺): 175.0735, found: 175.0723.
生成物の分析データを以下に示す：
¹H NMR δ 1.20 (d, J = 7.2 Hz, 3H), 1.93-1.99 (m, 2H), 2.02-2.07 (m, 1H), 2.32-2.07 (m, 3H), 2.67-2.74 (m, 1H), 4.11 (t, J = 4.0 Hz, 2H); ¹³C NMR δ 16.5, 21.6, 24.0, 34.8, 38.0, 66.7, 143.9, 150.2, 203.5; IR (neat) 2956, 2880, 1760, 1648, 1465, 1401, 1291, 1168, 1113, 1073, 953, 858, 721cm^-1. The reaction formula is shown below.

Analytical data for the reaction substrate is shown below:
¹ H NMR δ 1.86-1.90 (m, 2H), 1.96 (s, 3H), 4.13 (t, J = 5.2 Hz, 2H), 5.64 (d, J = 1.2 Hz, 1H), 5.68 (d, J = 1.2 Hz, 1H), 5.86 (t, J = 4.8 Hz, .1H); ¹³ C NMR δ 19.0, 20.9, 21.4, 66.3, 114.0, 123.9, 142.8, 150.9; IR (neat, cm ^-1 ): 2930, 2877, 1658, 1624, 1448, 1320, 1289, 1234, 1172, 1064, 1020, 991, 925, 768; HRMS (ESI-TOF, Pos.) Calced for C ₉ H ₁₂ O ₂ Na ([M + Na] ⁺ ): 175.0735, found: 175.0723.
The analytical data of the product is shown below:
¹ H NMR δ 1.20 (d, J = 7.2 Hz, 3H), 1.93-1.99 (m, 2H), 2.02-2.07 (m, 1H), 2.32-2.07 (m, 3H), 2.67-2.74 (m, 1H ), 4.11 (t, J = 4.0 Hz, 2H); ¹³ C NMR δ 16.5, 21.6, 24.0, 34.8, 38.0, 66.7, 143.9, 150.2, 203.5; IR (neat) 2956, 2880, 1760, 1648, 1465, 1401, 1291, 1168, 1113, 1073, 953, 858, 721cm ^-1 .

実施例７
基質を等モルの（Ｅ）−（３，４−ジヒドロ−２Ｈ−ピラン−６−イル）−２−メチルブト−２−エン−１−オンに代えて、実施例６と同様の反応を行ない、５，６−ジメチル−３，４，５，６−テトラヒドロ−２Ｈ−シクロペンタ[ｂ]ピラン−７−オンを得た（収率８０％）。
反応式を下式に示す。

反応基質の分析データを以下に示す：
¹H NMR δ 1.82-1.90 (m, 8H), 2.19-2.23 (m, 2H), 4.10-4.12 (m, 2H), 5.65 (t, J = 4.6 Hz, 1H), 6.48-6.52 (m, 1H); ¹³C NMR δ 12.4, 14.4, 20.7, 21.6, 66.3, 111.7, 136.2, 137.7, 151.4; IR (neat, cm^-1): 2930, 1648, 1445, 1391, 1346, 1281, 1226, 1158, 1065, 920, 893, 742, 661; HRMS(ESI-TOF, Pos.) calced for C₁₀H₁₅O₂ ([M+H]⁺): 167.1072, found: 167.1034.
生成物の分析データを以下に示す：
¹H NMR δ 1.05-1.09 (m, 3H), 1.17-1.20 (m, 3H), 1.86-2.00 (m, 3H), 2.18-2.28 (m, 1H), 2.24-2.85 (m, 2H), 4.00-4.19 (m, 2H); ¹³C NMR δ 11.1, 14.6, 14.7, 21.4, 21.5, 21.5, 21.8, 35.9, 41.2, 42.0, 47.2, 66.5, 66.7, 147.6, 148.8, 149.4, 202.6, 203.3; IR (neat) 2965, 2874, 1707, 1648, 1456, 1289, 1145, 1082, 1043, 962, 943 cm^-1. Example 7
The same reaction as in Example 6 was performed by replacing the substrate with equimolar (E)-(3,4-dihydro-2H-pyran-6-yl) -2-methylbut-2-en-1-one, 5,6-Dimethyl-3,4,5,6-tetrahydro-2H-cyclopenta [b] pyran-7-one was obtained (yield 80%).
The reaction formula is shown below.

Analytical data for the reaction substrate is shown below:
¹ H NMR δ 1.82-1.90 (m, 8H), 2.19-2.23 (m, 2H), 4.10-4.12 (m, 2H), 5.65 (t, J = 4.6 Hz, 1H), 6.48-6.52 (m, 1H ); ¹³ C NMR δ 12.4, 14.4, 20.7, 21.6, 66.3, 111.7, 136.2, 137.7, 151.4; IR (neat, cm ^-1 ): 2930, 1648, 1445, 1391, 1346, 1281, 1226, 1158, 1065 , 920, 893, 742, 661; HRMS (ESI-TOF, Pos.) Calced for C ₁₀ H ₁₅ O ₂ ([M + H] ⁺ ): 167.1072, found: 167.1034.
The analytical data of the product is shown below:
¹ H NMR δ 1.05-1.09 (m, 3H), 1.17-1.20 (m, 3H), 1.86-2.00 (m, 3H), 2.18-2.28 (m, 1H), 2.24-2.85 (m, 2H), 4.00 -4.19 (m, 2H); ¹³ C NMR δ 11.1, 14.6, 14.7, 21.4, 21.5, 21.5, 21.8, 35.9, 41.2, 42.0, 47.2, 66.5, 66.7, 147.6, 148.8, 149.4, 202.6, 203.3; IR ( neat) 2965, 2874, 1707, 1648, 1456, 1289, 1145, 1082, 1043, 962, 943 cm ^-1 .

実施例８
基質を等モルのシクロヘキセニル（３，４−ジヒドロ−２Ｈ−ピラン−６−イル）メタノンに代えて、実施例６と同様の反応を行ない、３，４，３ｂ，５，６，７，８，８ａ−オクタヒドロ−２Ｈ−オキサ−フルオレン−９−オンを得た（収率８０％）。
反応式を下式に示す。

反応基質の分析データを以下に示す：
¹H NMR δ 1.60-1.67 (m, 4H), 1.85-1.90 (m, 2H), 2.19-2.40 (m, 6H), 4.10-4.12 (m, 2H), 5.67 (t, J = 4.6 Hz, 1H), 6.71 (m, 1H); ¹³C NMR δ 20.7, 21.6, 21.9, 24.2, 66.3, 111.5, 137.6, 140.3, 151.5, 192.3; IR (neat) 2932, 1648, 1446, 1388, 1345, 1277, 1252, 1218, 1055, 983, 923, 892, 745, 703 cm^-1; HRMS(ESI-TOF, Pos.) calced for C₁₂H₁₆O₂Na ([M+H]⁺): 215.1048, found: 215.1035.
生成物の分析データを以下に示す：
¹H NMR δ 1.15-1.55 (m, 5H), 1.68-1.98 (m, 5H), 2.18-2.46 (m, 3H), 2.72-2.77 (m, 1H), 4.03-4.17 (m, 2H); ¹³C NMR δ 20.3, 20.4, 21.5, 21.9, 22.4, 26.6, 37.4, 43.6, 66.7, 148.3, 150.2, 202.8; IR (neat) 2932, 2862, 1705, 1644, 1446, 1400, 1290, 1165, 1081, 955, 910 cm^-1 Example 8
The substrate was replaced with equimolar cyclohexenyl (3,4-dihydro-2H-pyran-6-yl) methanone, and the same reaction as in Example 6 was performed to obtain 3,4,3b, 5,6,7,8. , 8a-Octahydro-2H-oxa-fluoren-9-one was obtained (yield 80%).
The reaction formula is shown below.

Analytical data for the reaction substrate is shown below:
¹ H NMR δ 1.60-1.67 (m, 4H), 1.85-1.90 (m, 2H), 2.19-2.40 (m, 6H), 4.10-4.12 (m, 2H), 5.67 (t, J = 4.6 Hz, 1H ), 6.71 (m, 1H); ¹³ C NMR δ 20.7, 21.6, 21.9, 24.2, 66.3, 111.5, 137.6, 140.3, 151.5, 192.3; IR (neat) 2932, 1648, 1446, 1388, 1345, 1277, 1252 , 1218, 1055, 983, 923, 892, 745, 703 cm ^-1 ; HRMS (ESI-TOF, Pos.) Calced for C ₁₂ H ₁₆ O ₂ Na ([M + H] ⁺ ): 215.1048, found: 215.1035 .
The analytical data of the product is shown below:
¹ H NMR δ 1.15-1.55 (m, 5H), 1.68-1.98 (m, 5H), 2.18-2.46 (m, 3H), 2.72-2.77 (m, 1H), 4.03-4.17 (m, 2H); ¹³ C NMR δ 20.3, 20.4, 21.5, 21.9, 22.4, 26.6, 37.4, 43.6, 66.7, 148.3, 150.2, 202.8; IR (neat) 2932, 2862, 1705, 1644, 1446, 1400, 1290, 1165, 1081, 955 , 910 cm ^-1

実施例９
基質を等モルの１−（５，６−ジヒドロ−１，４−ジオキサン−２−イル）−３−メチル−２−メチレンブタン−１−オンに代えて、実施例６と同様の反応を行ない、６−イソプロピル−２，３，６，７−テトラヒドロ−シクロペンテナル[１，４]ジオキサン−５−オンを得た（収率７２％）。
反応式を下式に示す。

反応基質の分析データを以下に示す：
¹H NMR δ 1.06 (d, J = 6.8 Hz, 6H), 2.86 sept, J = 6.8 Hz, 1H), 4.20 (s, 4H), 5.36-5.38 (m, 2H), 7.17 (s, 1H); ¹³C NMR δ 21.1, 30.5, 63.5, 65.2, 116.8, 142.4, 153.3, 191.8; IR (neat) 3478, 3100, 2963, 1728, 1610, 1460, 1370, 1299, 1240, 1174, 1091, 1023, 980, 922, 872, 802, 747, 703, 577 cm^-1; HRMS(ESI-TOF, Pos.) calced for C₁₀H₁₄O₃Na ([M+Na]⁺): 205.0841, found: 205.0816.
生成物の分析データを以下に示す：
¹H NMR δ 0.80 (d, J = 6.9 Hz, 3H), 0.98 (d, J = 7.5 Hz, 3H), 2.27-2.33 (m, 2H), 2.41-2.44 (m, 1H), 2.51 (dd, J = 6.9, 18.1 Hz, 1H), 4.14 (t, J = 4.1 Hz, 2H), 4.32-4.35 (m, 2H); ¹³C NMR δ 16.5, 20.4, 24.8, 28.0, 47.6, 63.8, 66.8, 134.3, 165.0, 196.9; IR (neat) 2957, 1705, 1647, 1459, 1402, 1323, 1241, 1132, 1074, 1025, 995, 867 cm^-1 Example 9
The same reaction as in Example 6 was performed by replacing the substrate with equimolar 1- (5,6-dihydro-1,4-dioxan-2-yl) -3-methyl-2-methylenebutan-1-one. 6-isopropyl-2,3,6,7-tetrahydro-cyclopentenal [1,4] dioxan-5-one was obtained (yield 72%).
The reaction formula is shown below.

Analytical data for the reaction substrate is shown below:
¹ H NMR δ 1.06 (d, J = 6.8 Hz, 6H), 2.86 sept, J = 6.8 Hz, 1H), 4.20 (s, 4H), 5.36-5.38 (m, 2H), 7.17 (s, 1H); ¹³ C NMR δ 21.1, 30.5, 63.5, 65.2, 116.8, 142.4, 153.3, 191.8; IR (neat) 3478, 3100, 2963, 1728, 1610, 1460, 1370, 1299, 1240, 1174, 1091, 1023, 980, 922, 872, 802, 747, 703, 577 cm ^-1 ; HRMS (ESI-TOF, Pos.) Calced for C ₁₀ H ₁₄ O ₃ Na ([M + Na] ⁺ ): 205.0841, found: 205.0816.
The analytical data of the product is shown below:
¹ H NMR δ 0.80 (d, J = 6.9 Hz, 3H), 0.98 (d, J = 7.5 Hz, 3H), 2.27-2.33 (m, 2H), 2.41-2.44 (m, 1H), 2.51 (dd, J = 6.9, 18.1 Hz, 1H), 4.14 (t, J = 4.1 Hz, 2H), 4.32-4.35 (m, 2H); ¹³ C NMR δ 16.5, 20.4, 24.8, 28.0, 47.6, 63.8, 66.8, 134.3 , 165.0, 196.9; IR (neat) 2957, 1705, 1647, 1459, 1402, 1323, 1241, 1132, 1074, 1025, 995, 867 cm ^-1

Claims

The following general formula M ( XR ⁵ ) ₃ as a catalyst in water
(Wherein, M represents S c, ^{R 5} has a carbon number represents an aliphatic hydrocarbon group having 8 to 30, X is -OSO ₂ - represents a. - or -OSO ₃₎ Lewis represented by Acid and the following formula (Formula 1)

(Wherein R ^{2 to} R ⁴ are defined in the same manner as described above, provided that when R ¹ and R ² do not form a 4- to 10-membered ring which may contain a hetero atom together, ( When a) is formed and R ¹ and R ² together form a 4 to 10 membered ring that may contain a hetero atom, (b) is formed, wherein R ⁷ is the 4 Represents a group corresponding to R ¹ and R ² in a 10-membered ring, and a method for producing a cyclic α-hydroxy-α, β-unsaturated ketone compound represented by

The following general formula M ( XR ⁵ ) ₃ as a catalyst in water
(Wherein, M represents S c, ^{R 5} has a carbon number represents an aliphatic hydrocarbon group having 8 to 30, X is -OSO ₂ - represents a. - or -OSO ₃₎ Lewis represented by Acid, the following formula (Formula 1)

(Wherein R ^{1 to} R ⁴ are defined in the same manner as described above).