JP7303502B2 - Method for producing allylsilane compound using palladium nanoparticle catalyst - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for producing an allylsilane compound using a palladium nanoparticle catalyst.

Allylsilane compounds are known as allylating agents in asymmetric allylation reactions of, for example, carbonyl compounds and imine compounds, and are used in the synthesis of pharmaceuticals and pharmaceutical intermediates. Allylsilane compounds have low toxicity and are more stable to water and air than allylating agents such as allylmagnesium halide and allyllithium. Therefore, allylsilane compounds are in high demand as useful reagents for organic synthesis, and the development of methods for their production has been actively pursued.

For example, in Non-Patent Document 1, an allyl alcohol compound is reacted with trifluoroacetic anhydride in the presence of N,N-dimethylaminopyridine (DMAP) to synthesize a trifluoroacetate ester of an allyl alcohol compound as an intermediate. and a silylation step of reacting the synthesized intermediate with a disilane compound in the presence of bis(dibenzylideneacetone)palladium(0). However, in this method, the allyl substrate undergoes two steps, the esterification step and the silylation step, resulting in a decrease in yield and an increase in production cost.
Non-Patent Document 2 discloses a method of reacting an allyl alcohol compound and a disilane compound in the presence of a catalyst, tetrakis(acetonitrile)palladium(II)bis(tetrafluoroborate). This method requires as much as 5 mol % of the catalyst with respect to the substrate, and there is a problem that the yield decreases when the amount of the catalyst is reduced. Therefore, further improvement is desired from the viewpoint of manufacturing cost and environmental friendliness.
Non-Patent Document 3 discloses a method of reacting an allyl halide compound with copper trimethylsilyl. In this method, in order to obtain trimethylsilylcopper as a substrate, it is necessary to react hexamethyldisilane with methyllithium to form trimethylsilyllithium, which is further reacted with copper (I) iodide. Thus, methyllithium, which is unstable to water and air, must be used for the synthesis of the substrate, and the number of steps is large, so this method is not suitable as an industrial production method.
Non-Patent Document 4 discloses a method of reacting allylmagnesium bromide with triphenylsilane. However, since highly reactive and unstable to water and air organometallics are used, it is difficult to control the reaction, and a large amount of organometallic reagents is required, resulting in workability, production cost and environmental problems. left.
Further, Patent Document 1 discloses a method of reacting an allyl halide compound with a disilane compound in the presence of palladium element-containing nanoparticles having a surface coordinated with a solvent. In this method, since the allyl halide compound used as a substrate is expensive, there is room for improvement in terms of production cost.

JP 2017-088576 A

Yuan Ma, Heteroatom Chemistry, 2002, 13, 310-315 Nicklas Selander, et al., J. Am. Chem. Soc. 2011, 133, 3, 409-411 Janice Gorzynski Smith, et al., J. Org. Chem. 1984, 49, 22, 4112-4120 Henry Gilman, et al., J. Am. Chem. Soc. 1959, 81, 22, 5925-5928

An object of the present invention is to provide a method for efficiently producing an allylsilane compound in one step from a substrate that is inexpensive and easy to handle without using a large amount of metal catalyst.

The present inventors have made intensive studies to solve the above problems. As a result, in the presence of a palladium nanoparticle catalyst and a cocatalyst, the inventors found that silylation of an allyl alcohol compound proceeds to produce allylsilane, thereby completing the present invention.

（式（Ａ）～（Ｃ）中、Ｒ^１～Ｒ^３は、それぞれ独立して水素原子、炭素数１～２０の脂肪族炭化水素基、炭素数６～２０の芳香族炭化水素基又は炭素数３～２０の芳香族複素環基を表し；Ｒ^４、Ｒ^５は、それぞれ独立して水素原子、炭素数１～２０の脂肪族炭化水素基、炭素数６～２０の芳香族炭化水素基又は炭素数３～２０の芳香族複素環基を表し；Ｒ^６～Ｒ^８は、それぞれ独立して水素原子、ハロゲン原子、炭素数１～２０の脂肪族炭化水素基又は炭素数６～２０の芳香族炭化水素基を表す。）
（２）
前記共触媒が、トリフルオロ酢酸である、（１）に記載のアリルシラン化合物の製造方法。
（３）
配位性有機溶媒が、エチレングリコール、ジメチルアセトアミド（ＤＭＡ）、Ｎ，Ｎ－ジメチルホルムアミド（ＤＭＦ）、Ｎ－メチルピロリドン（ＮＭＰ）及びジメチルスルホキシド（ＤＭＳＯ）からなる群より選択される１以上の有機化合物である、（１）又は（２）に記載のアリルシラン化合物の製造方法。
（４）
前記反応が、反応溶媒中で行われる、（１）～（３）の何れかに記載のアリルシラン化合物の製造方法。
（５）
前記反応溶媒が、１，４－ジオキサン、ジグリム、Ｎ，Ｎ－ジメチルホルムアミド（ＤＭＦ）、酢酸、トルエン、シクロペンチルメチルエーテル（ＣＰＭＥ）及びベンゾニトリルからなる群より選択される１以上の反応溶媒である、（４）に記載のアリルシラン化合物の製造方法。 That is, the present invention is as follows.
(1)
In the presence of a palladium nanoparticle catalyst and a co-catalyst formed by coordinating a coordinating organic solvent on the surface of the palladium nanoparticles, an allyl alcohol compound represented by the formula (A) and a disilane represented by the formula (B) A method for producing an allylsilane compound represented by formula (C), comprising a silylation step of reacting with a compound.

(In formulas (A) to (C), R ¹ to R ³ are each independently a hydrogen atom, an aliphatic hydrocarbon group having 1 to 20 carbon atoms, an aromatic hydrocarbon group having 6 to 20 carbon atoms, or a carbon represents an aromatic heterocyclic group of 3 to 20; R ⁴ and R ⁵ each independently represents a hydrogen atom, an aliphatic hydrocarbon group of 1 to 20 carbon atoms, an aromatic hydrocarbon group of 6 to 20 carbon atoms; or an aromatic heterocyclic group having 3 to 20 carbon atoms; R ⁶ to R ⁸ each independently represent a hydrogen atom, a halogen atom, an aliphatic hydrocarbon group having 1 to 20 carbon atoms, or represents an aromatic hydrocarbon group.)
(2)
The method for producing an allylsilane compound according to (1), wherein the co-catalyst is trifluoroacetic acid.
(3)
coordinating organic solvent, one or more selected from the group consisting of ethylene glycol, dimethylacetamide (DMA), N,N-dimethylformamide (DMF), N-methylpyrrolidone (NMP) and dimethylsulfoxide (DMSO) A method for producing the allylsilane compound according to (1) or (2), which is a compound.
(4)
The method for producing an allylsilane compound according to any one of (1) to (3), wherein the reaction is carried out in a reaction solvent.
(5)
The reaction solvent is one or more reaction solvents selected from the group consisting of 1,4-dioxane, diglyme, N,N-dimethylformamide (DMF), acetic acid, toluene, cyclopentyl methyl ether (CPME) and benzonitrile. , a method for producing an allylsilane compound according to (4).

According to the production method of the present invention, an allylsilane compound can be efficiently produced in one step in the presence of a small amount of a palladium nanoparticle catalyst from an inexpensive and easy-to-handle allyl alcohol compound.

In describing the details of the present invention, a specific example will be described, but the present invention is not limited to the following content as long as it does not deviate from the gist of the present invention, and can be implemented with appropriate modifications.

<1. Allylsilane compound>
According to the production method of the present embodiment, an allylsilane compound represented by formula (C) (sometimes referred to as “allylsilane compound (C)”) is provided.

(R ¹ to R ³ )
R ¹ to R ³ each independently represent a hydrogen atom, an aliphatic hydrocarbon group having 1 to 20 carbon atoms, an aromatic hydrocarbon group having 6 to 20 carbon atoms or an aromatic heterocyclic group having 3 to 20 carbon atoms. show.

Examples of aliphatic hydrocarbon groups having 1 to 20 carbon atoms represented by R ¹ to R ³ include methyl group, ethyl group, n-propyl group, iso-propyl group, n-butyl group, sec-butyl group, iso Alkyl groups such as -butyl group, tert-butyl group, n-pentyl group, iso-pentyl group, neopentyl group, n-hexyl group, n-octyl group; cyclopentyl group, cyclohexyl group, 1-adamantyl group, 2-adamantyl cycloalkyl groups such as groups; alkenyl groups such as vinyl groups, allyl groups, isopropenyl groups, 2-butenyl groups, and 3-pentenyl groups;

Examples of aromatic hydrocarbon groups having 6 to 20 carbon atoms represented by R ¹ to R ³ include phenyl group, biphenylyl group, terphenylyl group, naphthyl group, anthracenyl group, phenanthrenyl group, fluorenyl group, indenyl group, pyrenyl group, fluoranthenyl group, triphenylenyl group, perylenyl group and the like.

The aromatic heterocyclic group having 3 to 20 carbon atoms represented by R ¹ to R ³ includes pyridyl group, pyrimidinyl group, triazinyl group, thienyl group, furyl group, pyrrolyl group, quinolyl group, isoquinolyl group, benzofuranyl group, benzothienyl group, indolyl group, carbazolyl group, benzoxazolyl group, benzothiazolyl group, quinoxalinyl group, benzimidazolyl group, pyrazolyl group, dibenzofuranyl group, dibenzothienyl group, carbolinyl group and the like.

The aliphatic hydrocarbon group having 1 to 20 carbon atoms, the aromatic hydrocarbon group having 6 to 20 carbon atoms or the aromatic heterocyclic group having 3 to 20 carbon atoms may have a substituent or may be unsubstituted. may be Substituents include deuterium atom; amino group; methoxy group, ethoxy group, n-propyloxy group, iso-propyloxy group, n-butoxy group, sec-butoxy group, isobutoxy group, tert-butoxy group, n- Alkyloxy groups having 1 to 6 carbon atoms such as hexyloxy group; Aryloxy groups such as phenyloxy group and tolyloxy group; Arylalkyloxy groups such as benzyloxy group and phenethyloxy group; Dimethylamino group, diethylamino group and dibutylamino dialkylamino group: pyridyl group, pyrimidinyl group, triazinyl group, thienyl group, furyl group, pyrrolyl group, quinolyl group, isoquinolyl group, indolyl group, carbazolyl group, and other aromatic heterocyclic groups;
In addition, when the aliphatic hydrocarbon group having 1 to 20 carbon atoms, the aromatic hydrocarbon group having 6 to 20 carbon atoms or the aromatic heterocyclic group having 3 to 20 carbon atoms has a substituent, the carbon number is substituted It means the total carbon number of the group and the carbon number of the aliphatic hydrocarbon group, aromatic hydrocarbon group or aromatic heterocyclic group.

Preferred embodiments of R ¹ to R ³ are described below.
When R ¹ to R ³ are aliphatic hydrocarbon groups having 1 to 20 carbon atoms, the number of carbon atoms is preferably 15 or less, more preferably 12 or less, still more preferably 10 or less, and particularly preferably 6 or less. .
When R ¹ to R ³ are aromatic hydrocarbon groups having 6 to 20 carbon atoms, the number of carbon atoms is preferably 18 or less, more preferably 16 or less, and still more preferably 10 or less.
When R ¹ to R ³ are aromatic heterocyclic groups having 3 to 20 carbon atoms, the number of carbon atoms is preferably 15 or less, more preferably 10 or less, and even more preferably 5 or less.
More specifically, R ¹ is preferably a hydrogen atom, a methyl group, a 4-methyl-3-penten-1-yl group or a phenyl group, and a 4-methyl-3-penten-1-yl group or a phenyl group. more preferred.
R ² is preferably a hydrogen atom, a methyl group or a phenyl group, more preferably a hydrogen atom or a methyl group.
A hydrogen atom is preferred as R ³ .

( ^R4 , ^R5 )
R ⁴ and R ⁵ each independently represents a hydrogen atom, an aliphatic hydrocarbon group having 1 to 20 carbon atoms, an aromatic hydrocarbon group having 6 to 20 carbon atoms or an aromatic heterocyclic group having 3 to 20 carbon atoms. show.

The aliphatic hydrocarbon group having 1 to 20 carbon atoms, the aromatic hydrocarbon group having 6 to 20 carbon atoms or the aromatic heterocyclic group having 3 to 20 carbon atoms represented by R ⁴ and R ⁵ may be the above R ¹ The same group as the C 1-20 aliphatic hydrocarbon group, C 6-20 aromatic hydrocarbon group or C 3-20 aromatic heterocyclic group represented by ~R ³ can be mentioned. Moreover, these groups may have a substituent or may be unsubstituted. As the substituent, the same substituents as those which R ¹ to R ³ may have can be mentioned.

Preferred embodiments of R ⁴ are described below.
When R ⁴ is an aliphatic hydrocarbon group having 1 to 20 carbon atoms, the number of carbon atoms is preferably 15 or less, more preferably 10 or less, even more preferably 5 or less, and particularly preferably 5 or less.
When R ⁴ is an aromatic hydrocarbon group having 6 to 20 carbon atoms, the number of carbon atoms is preferably 18 or less, more preferably 16 or less, still more preferably 10 or less.
More specifically, R ⁴ is preferably a hydrogen atom, a methyl group or a phenyl group, more preferably a hydrogen atom or a phenyl group.

(R ⁶ to R ⁸ )
R ⁶ to R ⁸ each independently represent a hydrogen atom, a halogen atom, an aliphatic hydrocarbon group having 1 to 20 carbon atoms or an aromatic hydrocarbon group having 6 to 20 carbon atoms.

Halogen atoms represented by R ⁶ to R ⁸ include fluorine, chlorine, bromine and iodine atoms.

Examples of aliphatic hydrocarbon groups having 1 to 20 carbon atoms represented by R ⁶ to R ⁸ include methyl group, ethyl group, n-propyl group, iso-propyl group, n-butyl group, sec-butyl group, iso Alkyl groups such as -butyl group, tert-butyl group, n-pentyl group, iso-pentyl group, neopentyl group, n-hexyl group, n-octyl group; cyclopentyl group, cyclohexyl group, 1-adamantyl group, 2-adamantyl cycloalkyl groups such as groups; alkenyl groups such as vinyl groups, allyl groups, isopropenyl groups and 2-butenyl groups;

Examples of aromatic hydrocarbon groups having 6 to 20 carbon atoms represented by R ⁶ to R ⁸ include phenyl group, biphenylyl group, terphenylyl group, naphthyl group, anthracenyl group, phenanthrenyl group, fluorenyl group, indenyl group, pyrenyl group, fluoranthenyl group, triphenylenyl group, perylenyl group and the like.

Preferred embodiments of R ⁶ to R ⁸ are described below.
When R ⁶ to R ⁸ are aliphatic hydrocarbon groups having 1 to 20 carbon atoms, the number of carbon atoms is preferably 15 or less, more preferably 10 or less, still more preferably 5 or less, and particularly preferably 3 or less. .
When R ⁶ to R ⁸ are aromatic hydrocarbon groups having 6 to 20 carbon atoms, the number of carbon atoms is preferably 18 or less, more preferably 16 or less, still more preferably 10 or less.
When R ⁶ to R ⁸ are aromatic heterocyclic groups having 3 to 20 carbon atoms, the number of carbon atoms is preferably 15 or less, more preferably 10 or less, and even more preferably 5 or less.
More specifically, R ⁶ to R ⁸ are preferably a hydrogen atom, a methyl group, an ethyl group, a tert-butyl group or a phenyl group, more preferably a methyl group.
Also, R ⁶ to R ⁸ may be the same or different, but are preferably the same.

Specific examples of the allylsilane compound (C) include the following allylsilane compounds.

<2. Method for Producing Allylsilane Compound>
In the method for producing the allylsilane compound (C) according to the present embodiment, as shown in the scheme below, a palladium nanoparticle catalyst (also called “PdNPs”) in which a coordinating organic solvent is coordinated to the surface of palladium nanoparticles ) and a cocatalyst, an allyl alcohol compound represented by formula (A) (sometimes referred to as "allyl alcohol compound (A)") and a disilane compound represented by formula (B) ("disilane compound ( B)” is sometimes referred to as a silylation step.

(In formulas (A) to (C), R ¹ to R ³ are each independently a hydrogen atom, an aliphatic hydrocarbon group having 1 to 20 carbon atoms, an aromatic hydrocarbon group having 6 to 20 carbon atoms, or a carbon represents an aromatic heterocyclic group of 3 to 20; R ⁴ and R ⁵ each independently represents a hydrogen atom, an aliphatic hydrocarbon group of 1 to 20 carbon atoms, an aromatic hydrocarbon group of 6 to 20 carbon atoms; or an aromatic heterocyclic group having 3 to 20 carbon atoms; R ⁶ to R ⁸ each independently represent a hydrogen atom, a halogen atom, an aliphatic hydrocarbon group having 1 to 20 carbon atoms, or represents an aromatic hydrocarbon group.)

<2-1. Substrate>
(allyl alcohol compound)
The specific type of allyl alcohol compound (A) used as a substrate is not particularly limited, and can be appropriately selected according to the allylsilane compound (C) that is the purpose of production. Moreover, the allyl alcohol compound (A) is known or can be easily produced by a method according to a known production method.

R ¹ to R ⁵ each represent the same group as R ¹ to R ⁵ in formula (C), and preferred embodiments are also the same.

Specific examples of the allyl alcohol compound (A) include the following allyl alcohol compounds.

(Disilane compound)
The specific type of the disilane compound (B) used as the substrate is not particularly limited, and can be appropriately selected according to the allylsilane compound (C) that is the purpose of production. Moreover, the disilane compound (B) is known or can be easily produced by a method according to a known production method.

R ⁶ to R ⁸ each represent the same group as R ⁶ to R ⁸ in formula (C), and preferred embodiments are also the same. R ⁶ to R ⁸ may be the same or different, but are preferably the same. In addition, each of two R ⁶ , R ⁷ , or R ⁸ in one molecule of the disilane compound (B) may be the same or different, but is preferably the same. .

Specific examples of the disilane compound (B) include the following disilane compounds.

<2-2. Palladium Nanoparticle Catalyst>
The palladium nanoparticle catalyst in this embodiment is a catalyst in which a coordinating organic solvent is coordinated to the surface of palladium nanoparticles. The palladium nanoparticle catalyst has the advantage that it can be recovered and reused as a catalyst after being used in the silylation process. In addition, it is believed that the coordinating organic solvent coordinating on the surface of the palladium nanoparticles protects the palladium nanoparticles from deterioration and maintains the catalytic activity.

"Palladium nanoparticles" means particles containing a palladium element as a constituent element. Therefore, the specific composition is not particularly limited as long as it contains palladium, and in addition to metallic palladium particles, palladium alloy particles, particles in which metallic palladium particles are doped with other atoms such as oxygen atoms and carbon atoms, Alternatively, inorganic palladium compound particles such as palladium oxide are also included.

The palladium nanoparticles preferably contain oxygen atoms in addition to palladium. Specifically, metallic palladium particles doped with oxygen atoms, palladium alloy particles doped with oxygen atoms, or palladium oxide particles are preferred.

The particle diameter (cumulative median diameter) of the palladium nanoparticles is not particularly limited as long as it is in the range of 0.5 nm or more and 100 nm or less, preferably 0.8 nm or more, more preferably 1 nm or more. is 50 nm or less, more preferably 10 nm or less, still more preferably 5 nm or less. The cumulative median diameter can be measured with a transmission electron microscope (TEM).

In addition, "a coordinating organic solvent is coordinated to the surface" means that molecules of the coordinating organic solvent are coordinated to the surface of the palladium nanoparticles.
The coordinating organic solvent that coordinates to the palladium nanoparticles can be appropriately selected according to the intended reaction. Regarding whether the coordinating organic solvent is coordinated to the palladium nanoparticles, the palladium nanoparticle catalyst is stably dispersed in the coordinating organic solvent without surface treatment with a dispersant or the like. It can be judged whether or not That is, for example, a palladium nanoparticle catalyst coordinated with N,N-dimethylformamide (DMF) as a coordinating organic solvent can be stably dispersed in a coordinating organic solvent that has an affinity for DMF.

Examples of coordinating organic solvents include ethylene glycol, dimethylacetamide (DMA
), N,N-dimethylformamide (DMF), N-methylpyrrolidone (NMP), dimethylsulfoxide (DMSO) and the like. Among these, N,N-dimethylformamide (DMF) is particularly preferred from the viewpoint of catalytic activity.

The method for preparing the palladium nanoparticle catalyst is not particularly limited, but examples include a method of heating and refluxing a precursor containing palladium element in a polar solvent. Specifically, a palladium nanoparticle catalyst can be prepared by the method described in Japanese Patent No. 6459126 or Japanese Patent Application Laid-Open No. 2017-088576.

<2-3. Cocatalyst>
The silylation step is carried out in the presence of a co-catalyst in addition to the palladium nanoparticle catalyst. The co-catalyst is not particularly limited as long as it promotes the catalytic silylation reaction of the allyl alcohol compound. It should be noted that promoting the catalytic silylation reaction of the allyl alcohol compound specifically means coordinating with palladium of the palladium nanoparticle catalyst to improve the catalytic activity, or acting on the hydroxyl group of the allyl alcohol compound. It is to increase the leaving ability of the hydroxyl group and increase the reactivity of the allyl alcohol compound.

Examples of co-catalysts include trifluoroacetic acid; acetic acid; potassium tetrafluoroborate; potassium fluoride; Lewis acids such as iron (III) chloride and aluminum chloride; Among these, trifluoroacetic acid is particularly preferred from the viewpoint of improving catalytic activity, suppressing side reactions, and improving reactivity of allyl alcohol compounds.

<2-4. Reaction Conditions in Silylation Step>
The silylation step is performed by reacting the allyl alcohol compound (A) and the disilane compound (B) in the presence of a palladium nanoparticle catalyst and a co-catalyst.

(amount of palladium nanoparticle catalyst)
The amount of the palladium nanoparticle catalyst used in the silylation step is not particularly limited, but is usually 0.01 mol% or more, preferably 0.05 mol% or more, or more in terms of the amount of palladium element relative to the allyl alcohol compound (A). It is preferably 0.1 mol % or more, and usually 5.0 mol % or less, more preferably 3.0 mol % or less, further preferably 1.0 mol % or less.

(amount of co-catalyst)
The amount of the co-catalyst used in the silylation step is usually 1 mol % or more and 150 mol % or less relative to the allyl alcohol compound (A), although it depends on the amount of the palladium nanoparticle catalyst, the reaction concentration, and the like. From the viewpoint of the yield of the allylsilane compound (C), the lower limit of the cocatalyst amount is preferably 5 mol% or more, more preferably 10 mol% or more, and still more preferably 15 mol%, relative to the allyl alcohol compound (A). More preferably, it is 20 mol % or more. From the viewpoint of ease of purification, the upper limit of the amount of the cocatalyst is preferably 120 mol% or less, more preferably 100 mol% or less, and still more preferably 50 mol% or less with respect to the allyl alcohol compound (A). .
Specifically, for example, when 0.5 mmol of allyl alcohol compound (A) is reacted in 0.4 mL of 1,4-dioxane in the presence of 1 μmol of palladium nanoparticle catalyst, the amount of cocatalyst is is preferably about 20 mol %.

(molar ratio of substrate)
In the silylation step, the amount of the disilane compound (B) relative to the allyl alcohol compound (A) is not particularly limited, but is usually 1.0 equivalent or more and 6.0 equivalents relative to 1.0 equivalent of the allyl alcohol compound (A). It is below. From the viewpoint of suppression of side reactions and ease of purification, the amount of the disilane compound (B) is preferably 4.0 equivalents or less, more preferably 3.0 equivalents or less, relative to 1.0 equivalents of the allyl alcohol compound (A). , more preferably 2.0 equivalents or less.

(reaction solvent)
The silylation step may be performed without solvent or in a reaction solvent. From the viewpoint of suppressing side reactions, it is preferable to carry out the reaction without a solvent, and from the viewpoint of yield of the allylsilane compound (C), it is preferable to carry out the reaction in a reaction solvent.

The reaction solvent is not particularly limited, and examples include hydrocarbon solvents such as hexane, benzene, and toluene; ether solvents such as diethyl ether, 1,4-dioxane, diglyme, cyclopentylmethyl ether (CPME), and tetrahydrofuran (THF); acetic acid. Ester solvents such as ethyl and butyl acetate; Halogenated hydrocarbon solvents such as 1,2-dichloroethane and chloroform; Nitrile solvents such as acetonitrile and benzonitrile; Protic polar solvents such as acetic acid, ethanol, butanol, ethylene glycol and glycerin; aprotic polar solvents such as acetone, dimethylacetamide (DMA), N,N-dimethylformamide (DMF), N-methylpyrrolidone (NMP), dimethylsulfoxide (DMSO); These reaction solvents are not limited to one type, and may be a mixed solvent in which two or more types are combined. The reaction solvent is preferably used after being dehydrated and deoxygenated.

Among these reaction solvents, 1,4-dioxane, diglyme, N,N-dimethylformamide (DMF), acetic acid, toluene, cyclopentyl methyl ether (CPME) or benzonitrile are preferred. In particular, from the viewpoint of the yield of the allylsilane compound (C), 1,4-dioxane is more preferable, and from the viewpoint of suppressing side reactions, diglyme, N,N-dimethylformamide (DMF), acetic acid, toluene or benzonitrile. is more preferred.

(reaction temperature)
Although the reaction temperature is not particularly limited, it is usually 70°C or higher and 150°C or lower. From the viewpoint of the yield of the allylsilane compound (C), the lower limit of the reaction temperature is preferably 100° C. or higher, more preferably 110° C. or higher, and still more preferably 120° C. or higher. Moreover, the upper limit of the reaction temperature is preferably 145° C. or lower, more preferably 140° C. or lower, from the viewpoint of suppressing side reactions. In particular, setting the reaction temperature to about 130° C. is preferable in terms of improving the yield of the allylsilane compound (C) and suppressing side reactions.

(reaction time)
Although the reaction time is not particularly limited, it is usually from 1 hour to 24 hours. From the viewpoint of improving the yield of the allylsilane compound (C) and suppressing side reactions, the lower limit of the reaction time is preferably 4 hours or longer, more preferably 10 hours or longer, and still more preferably 15 hours or longer. Moreover, the upper limit of the reaction time is preferably 22 hours or less, more preferably 20 hours or less, in terms of facilitating purification.

(atmospheric gas, etc.)
The silylation step may be performed under normal pressure or under pressure. The silylation step does not require strict water-free conditions, but is usually carried out under an inert atmosphere such as nitrogen or argon.

<2-5. Other processes>
The method for producing the allylsilane compound (C) according to the present embodiment may include an optional step in addition to the silylation step. An optional step includes a purification step for increasing the purity of the allylsilane compound (C). In the purification step, purification methods commonly used in the field of organic synthesis, such as filtration, adsorption, column chromatography, and distillation, can be employed.

The present invention will be described in more detail with reference to examples below, but modifications can be made as appropriate without departing from the gist of the present invention. Therefore, the scope of the present invention should not be construed to be limited by the specific examples shown below.
The measurement method of gas chromatography (GC-MS) in the examples is as follows.

<Measurement method of GC-MS>
(GC-MS measurement conditions)
Gas chromatograph: GC2010 GC-MS QP2010 (manufacturer: Shimadzu Corporation)
Column: BP5 (manufacturer: SGE Analytical Science, inner diameter: 0.22 mm, film thickness: 0.25 μm, length: 25 m)
Carrier gas: He (column flow rate 0.98 mL/min)
Column temperature conditions: After holding at 40°C for 4 minutes, temperature was raised to 280°C at 15°C/min Ion source temperature: 200°C
Interface temperature: 280°C
Injection temperature: 280°C
Injection volume: 1.0 μL
Injection mode: Split Ionization method: EI method Internal standard substance: Undecane Detector: Secondary electron multiplier with conversion dynode

<Synthesis of palladium nanoparticle catalyst>
(Synthesis example 1)
Put 15 mL of dehydrated N,N-dimethylformamide (DMF) in an air atmosphere in a 100 mL three-necked flask connected to a Dimroth condenser, immerse in an oil bath heated to 140 ° C., stir bar in an air atmosphere. Preheating was performed for about 10 minutes under reflux conditions while rotating at 1500 rpm.
Then, 150 μL of a 0.1 molar (0.1 M) palladium (II) chloride (PdCl ₂ ) aqueous solution was added in an air atmosphere using a microsyringe, and the mixture was heated under reflux at 140° C. for 10 hours while stirring. . After 10 hours had passed, the mixture was cooled to room temperature to obtain a dispersion.

DMF was distilled off from the resulting dispersion using a rotary evaporator, and the dispersion was sufficiently dried (conditions: 10 hPa, 40° C.). As a result, a palladium nanoparticle catalyst was obtained.

<Production of allylsilane compound>
(Experimental Example 1-1: Investigation of catalyst)

A branched Schlenk flask was charged with 2 μmol of the palladium nanoparticle catalyst obtained in Synthesis Example 1 (0.4 mol % with respect to cinnamyl alcohol), and the inside of the branched Schlenk flask was replaced with argon. Next, 0.5 mmol of cinnamyl alcohol and 1 mL of 1,4-dioxane were added to the palladium nanoparticle catalyst, and the mixture was stirred for 20 minutes to obtain a dispersion in which the palladium nanoparticle catalyst was uniformly dispersed.
To the resulting dispersion, 1.5 mmol of hexamethyldisilane and 0.5 mmol of trifluoroacetic acid (100 mol % with respect to cinnamyl alcohol) were sequentially added to obtain a reaction liquid. Subsequently, the obtained reaction solution was stirred while being heated in an oil bath at 130°C. After 15 hours from the start of heating, a sample was taken from the reaction solution, and the progress of the reaction was confirmed by GC-MS. Table 1 shows the conversion of the substrate and the yield of the product calculated from the GC-MS measurement results. After that, the reaction liquid was cooled, and 10 mL of diethyl ether was added to the cooled reaction liquid to obtain a reaction mixture.
The resulting reaction mixture was filtered and concentrated by an evaporator. The residue obtained by concentration was purified by medium-pressure silica gel chromatography (device: SP1-A1A0 manufactured by Biotage, column: SNAP Ultra 10 g manufactured by Biotage, developing solvent: hexane/ethyl acetate = 100/0), and allylsilane was added. The compound was obtained as a colorless liquid.

(Experimental Examples 1-2 to 1-6: Investigation of catalyst)
The reaction was carried out in the same manner as in Experimental Example 1-1, except that the palladium nanoparticle catalyst and its amount were changed as shown in Table 1. Table 1 shows the conversion of the substrate and the yield of the product calculated from the GC-MS measurement results.

From the results shown in Table 1, only a small amount of the allylsilane compound was obtained from the allyl alcohol compound and the disilane compound without the reaction catalyst.
In addition, in the presence of a palladium catalyst other than the palladium nanoparticle catalyst, both allyl alcohol compound 1 and disilane compound 2 exhibited sufficient conversion rates, but the yield of allylsilane compound 3 was small.
On the other hand, in the presence of the palladium nanoparticle catalyst, the reaction between allyl alcohol compound 1 and disilane compound 2 proceeded, and allylsilane compound 3 was obtained. In addition, in the presence of the palladium nanoparticle catalyst, although the by-product 4 was also produced, the ratio of the yield of the allylsilane compound 3 to the yield of the by-product 4 (sometimes referred to as “reaction selectivity”) was , was greater than or equal to 2. That is, according to the production method according to the present embodiment, it was shown that the side reactions are suppressed and the desired silylation proceeds selectively.

(Experimental Example 2-1: Examination of amount of palladium nanoparticle catalyst)

A branched Schlenk flask was charged with 1 μmol of the palladium nanoparticle catalyst (0.2 mol % relative to cinnamyl alcohol) obtained in Synthesis Example 1, and the inside of the branched Schlenk flask was replaced with argon. Next, 0.5 mmol of cinnamyl alcohol and 1 mL of 1,4-dioxane were added to the palladium nanoparticle catalyst, and the mixture was stirred for 20 minutes to obtain a dispersion in which the palladium nanoparticle catalyst was uniformly dispersed.
To the resulting dispersion, 3 mmol of hexamethyldisilane and 0.5 mmol of trifluoroacetic acid (100 mol % with respect to cinnamyl alcohol) were sequentially added to obtain a reaction liquid. Subsequently, the obtained reaction solution was stirred while being heated in an oil bath at 130°C. After 15 hours from the start of heating, a sample was taken from the reaction solution, and the progress of the reaction was confirmed by GC-MS. Table 2 shows the conversion of the substrate and the yield of the product calculated from the GC-MS measurement results. After that, the reaction liquid was cooled, and 10 mL of diethyl ether was added to the cooled reaction liquid to obtain a reaction mixture.
The resulting reaction mixture was purified in the same manner as in Experimental Example 1-1 to obtain an allylsilane compound as a colorless liquid.

(Experimental Examples 2-2 to 2-3: Examination of amount of palladium nanoparticle catalyst)
The reaction was carried out in the same manner as in Experimental Example 2-1, except that the amount of the palladium nanoparticle catalyst was changed as shown in Table 2. Table 2 shows the conversion of the substrate and the yield of the product calculated from the GC-MS measurement results.

From the results shown in Table 2, when the amount of palladium nanoparticle catalyst was varied within the range of 0.2 to 0.4 mol% with respect to allyl alcohol compound 1 in silylation, the amount of palladium nanoparticle catalyst was increased. It was found that the conversion rate of allyl alcohol compound 1, which is a substrate, is improved by increasing the temperature. Further, even when the amount of the palladium nanoparticle catalyst was varied within the above range, no significant change was observed in either the yield of the allylsilane compound 3 or the yield of the by-product 4.
That is, according to the production method according to this embodiment, even if the amount of the palladium nanoparticle catalyst is 0.2 mol% with respect to the allyl alcohol compound 1 that is the substrate, high catalytic activity and high reaction selectivity are exhibited. I understand.

(Experimental Example 3-1: Examination of substrate amount)

A branched Schlenk flask was charged with 1 μmol of the palladium nanoparticle catalyst (0.2 mol % relative to cinnamyl alcohol) obtained in Synthesis Example 1, and the inside of the branched Schlenk flask was replaced with argon. Next, 0.5 mmol of cinnamyl alcohol and 1 mL of 1,4-dioxane were added to the palladium nanoparticle catalyst, and the mixture was stirred for 20 minutes to obtain a dispersion in which the palladium nanoparticle catalyst was uniformly dispersed.
To the resulting dispersion, 0.5 mmol of hexamethyldisilane and 0.5 mmol of trifluoroacetic acid (100 mol % with respect to cinnamyl alcohol) were sequentially added to obtain a reaction liquid. Subsequently, the obtained reaction solution was stirred while being heated in an oil bath at 130°C. After 15 hours from the start of heating, a sample was taken from the reaction solution, and the progress of the reaction was confirmed by GC-MS. Table 3 shows the conversion of the substrate and the yield of the product calculated from the GC-MS measurement results. After that, the reaction liquid was cooled, and 10 mL of diethyl ether was added to the cooled reaction liquid to obtain a reaction mixture.
The resulting reaction mixture was purified in the same manner as in Experimental Example 1-1 to obtain an allylsilane compound as a colorless liquid.

(Experimental Examples 3-2 to 3-5: Examination of Substrate Amount)
A reaction was carried out in the same manner as in Experimental Example 3-1, except that the amount of hexamethyldisilane was changed as shown in Table 3. Table 3 shows the conversion of the substrate and the yield of the product calculated from the GC-MS measurement results.

From the results shown in Table 3, when the amount of disilane compound 2 was varied in the range of 0.5 to 3 mmol (that is, 1 to 6 equivalents relative to allyl alcohol compound 1), the amount of disilane compound 2 was increased. , the conversion rate of disilane compound 2 decreases, but the yield of allylsilane compound 1 is not significantly affected. It was also found that when the disilane compound 2 is used in an excessive amount relative to the allyl alcohol compound 1, the yield of the by-product 4 increases, which tends to lower the reaction selectivity.

(Experimental Example 4-1: Examination of co-catalyst)

A branched Schlenk flask was charged with 2 μmol of the palladium nanoparticle catalyst obtained in Synthesis Example 1 (0.4 mol % with respect to cinnamyl alcohol), and the inside of the branched Schlenk flask was replaced with argon. Next, 0.5 mmol of cinnamyl alcohol and 1 mL of 1,4-dioxane were added to the palladium nanoparticle catalyst, and the mixture was stirred for 20 minutes to obtain a dispersion in which the palladium nanoparticle catalyst was uniformly dispersed.
3 mmol of hexamethyldisilane and 0.15 mmol of trifluoroacetic acid (30 mol % with respect to cinnamyl alcohol) were sequentially added to the resulting dispersion to obtain a reaction liquid. Subsequently, the obtained reaction solution was stirred while being heated in an oil bath at 130°C. After 15 hours from the start of heating, a sample was taken from the reaction solution, and the progress of the reaction was confirmed by GC-MS. Table 4 shows the conversion of the substrate and the yield of the product calculated from the GC-MS measurement results. After that, the reaction liquid was cooled, and 10 mL of diethyl ether was added to the cooled reaction liquid to obtain a reaction mixture.
The resulting reaction mixture was purified in the same manner as in Experimental Example 1-1 to obtain an allylsilane compound as a colorless liquid.

(Experimental Examples 4-2 to 4-5: Examination of co-catalyst)
The reaction was carried out in the same manner as in Experimental Example 4-1, except that the cocatalyst was changed as shown in Table 4. Table 4 shows the conversion of the substrate and the yield of the product calculated from the GC-MS measurement results.

From the results shown in Table 4, it was found that the silylation reaction did not progress when no cocatalyst was added to the reaction system. It was also shown that the allylsilane compound 3 can be obtained in a higher yield when trifluoroacetic acid is used as a cocatalyst than when other cocatalysts are used.

(Experimental Example 5-1: Examination of reaction solvent)

A branched Schlenk flask was charged with 2 μmol of the palladium nanoparticle catalyst obtained in Synthesis Example 1 (0.4 mol % with respect to cinnamyl alcohol), and the inside of the branched Schlenk flask was replaced with argon. Next, 0.5 mmol of cinnamyl alcohol and 1 mL of diglyme were added to the palladium nanoparticle catalyst and stirred for 20 minutes to obtain a dispersion in which the palladium nanoparticle catalyst was uniformly dispersed.
To the resulting dispersion, 3 mmol of hexamethyldisilane and 0.5 mmol of trifluoroacetic acid (100 mol % with respect to cinnamyl alcohol) were sequentially added to obtain a reaction liquid. Subsequently, the obtained reaction solution was stirred while being heated in an oil bath at 130°C. After 15 hours from the start of heating, a sample was taken from the reaction solution, and the progress of the reaction was confirmed by GC-MS. Table 5 shows the conversion of the substrate and the yield of the product calculated from the GC-MS measurement results. After that, the reaction liquid was cooled, and 10 mL of diethyl ether was added to the cooled reaction liquid to obtain a reaction mixture.
The resulting reaction mixture was purified in the same manner as in Experimental Example 1-1 to obtain an allylsilane compound as a colorless liquid.

(Experimental Examples 5-2 to 5-9: Examination of reaction solvent)
A reaction was carried out in the same manner as in Experimental Example 5-1, except that the reaction solvent was changed as shown in Table 5. Table 5 shows the conversion of the substrate and the yield of the product calculated from the GC-MS measurement results.

From the results shown in Table 5, it was found that the allylsilane compound 3 can be obtained in high yield by using 1,4-dioxane as the reaction solvent.
In addition, when diglyme, N,N-dimethylformamide, acetic acid, toluene or benzonitrile, especially acetic acid, toluene or benzonitrile is used as a reaction solvent, or when no reaction solvent is used, the yield of allylsilane compound 3 is not high. , the progress of side reactions was effectively suppressed, and high reaction selectivity was shown.

(Experimental Example 6-1: Examination of reaction temperature)

A branched Schlenk flask was charged with 2 μmol of the palladium nanoparticle catalyst obtained in Synthesis Example 1 (0.4 mol % with respect to cinnamyl alcohol), and the inside of the branched Schlenk flask was replaced with argon. Next, 0.5 mmol of cinnamyl alcohol and 1 mL of 1,4-dioxane were added to the palladium nanoparticle catalyst, and the mixture was stirred for 20 minutes to obtain a dispersion in which the palladium nanoparticle catalyst was uniformly dispersed.
To the resulting dispersion, 1.5 mmol of hexamethyldisilane and 0.5 mmol of trifluoroacetic acid (100 mol % with respect to cinnamyl alcohol) were sequentially added to obtain a reaction liquid. Subsequently, the obtained reaction solution was stirred while being heated in an oil bath at 100°C. After 15 hours from the start of heating, a sample was taken from the reaction solution, and the progress of the reaction was confirmed by GC-MS. Table 6 shows the conversion of the substrate and the yield of the product calculated from the GC-MS measurement results. After that, the reaction liquid was cooled, and 10 mL of diethyl ether was added to the cooled reaction liquid to obtain a reaction mixture.
The resulting reaction mixture was purified in the same manner as in Experimental Example 1-1 to obtain an allylsilane compound as a colorless liquid.

(Experimental Examples 6-2 to 6-5: Examination of reaction temperature)
A reaction was carried out in the same manner as in Experimental Example 6-1, except that the reaction temperature was changed as shown in Table 6. Table 6 shows the conversion of the substrate and the yield of the product calculated from the GC-MS measurement results.

From the results in Table 6, it was found that the yield and reaction selectivity of allylsilane compound 3 were highest when the reaction temperature was around 130°C, and gradually decreased as the temperature became higher or lower than 130°C.

(Experimental Example 7-1: Examination of reaction time)

A branched Schlenk flask was charged with 2 μmol of the palladium nanoparticle catalyst obtained in Synthesis Example 1 (0.4 mol % with respect to cinnamyl alcohol), and the inside of the branched Schlenk flask was replaced with argon. Next, 0.5 mmol of cinnamyl alcohol and 1 mL of 1,4-dioxane were added to the palladium nanoparticle catalyst, and the mixture was stirred for 20 minutes to obtain a dispersion in which the palladium nanoparticle catalyst was uniformly dispersed.
To the resulting dispersion, 1.5 mmol of hexamethyldisilane and 0.5 mmol of trifluoroacetic acid (100 mol % with respect to cinnamyl alcohol) were sequentially added to obtain a reaction liquid. Subsequently, the obtained reaction solution was stirred while being heated in an oil bath at 130°C. After 4 hours from the start of heating, a sample was taken from the reaction solution, and the progress of the reaction was confirmed by GC-MS. Table 7 shows the conversion of the substrate and the yield of the product calculated from the GC-MS measurement results. After that, the reaction liquid was cooled, and 10 mL of diethyl ether was added to the cooled reaction liquid to obtain a reaction mixture.
The resulting reaction mixture was purified in the same manner as in Experimental Example 1-1 to obtain an allylsilane compound as a colorless liquid.

(Experimental Examples 7-2 to 7-5: Examination of reaction time)
The reaction was carried out in the same manner as in Experimental Example 7-1, except that the reaction time was changed as shown in Table 7. Table 7 shows the conversion of the substrate and the yield of the product calculated from the GC-MS measurement results.

From the results in Table 7, it was found that the longer the reaction time, the higher the conversion rate of allyl alcohol compound 1 and the higher the yield of allylsilane compound 3. In addition, as the reaction time increased, the yield of the by-product 4 also increased slightly, but the yield of the allylsilane compound 3 increased to a greater extent, and as a result, the longer the reaction time, the higher the reaction selectivity. It was found that the

(Experimental Example 8-1 to Experimental Example 8-2: Examination of types of substrates)

The reaction was carried out in the same manner as in Experimental Example 1-1, except that cinnamyl alcohol was changed to allyl alcohol compound 5 shown in Table 8. Table 8 shows the conversion of the substrate and the yield of the product calculated from the GC-MS measurement results. For comparison, Table 8 also shows the results of Experimental Example 1-1.

From the results in Table 8, it was found that the allyl alcohol compound 5 exhibited high reaction selectivity due to the phenyl group being bonded to the carbon to which the OH group was bonded, and the allylsilane compound 6 was obtained efficiently. .

According to the present invention, the silylation reaction of an inexpensive and easy-to-handle allyl alcohol compound proceeds in the presence of a small amount of a palladium nanoparticle catalyst, and an allylsilane compound can be efficiently produced in one step. The allylsilane compound produced by the production method of the present invention can be used as a useful allylating agent in, for example, the organosilicon chemical industry.

Claims (4)

In the presence of a palladium nanoparticle catalyst and a co-catalyst formed by coordinating a coordinating organic solvent on the surface of the palladium nanoparticles, an allyl alcohol compound represented by the formula (A) and a disilane represented by the formula (B) a silylation step of reacting with a compound ,
A method for producing an allylsilane compound represented by formula (C) , wherein the co-catalyst is trifluoroacetic acid .

(In formulas (A) to (C), R ¹ to R ³ are each independently a hydrogen atom, an aliphatic hydrocarbon group having 1 to 20 carbon atoms, an aromatic hydrocarbon group having 6 to 20 carbon atoms, or a carbon represents an aromatic heterocyclic group of 3 to 20; R ⁴ and R ⁵ each independently represents a hydrogen atom, an aliphatic hydrocarbon group of 1 to 20 carbon atoms, an aromatic hydrocarbon group of 6 to 20 carbon atoms; or an aromatic heterocyclic group having 3 to 20 carbon atoms; R ⁶ to R ⁸ each independently represent a hydrogen atom, a halogen atom, an aliphatic hydrocarbon group having 1 to 20 carbon atoms, or represents an aromatic hydrocarbon group.) coordinating organic solvent, one or more selected from the group consisting of ethylene glycol, dimethylacetamide (DMA), N,N-dimethylformamide (DMF), N-methylpyrrolidone (NMP) and dimethylsulfoxide (DMSO) The method for producing an allylsilane compound according to claim 1 , which is a compound. 3. The method for producing an allylsilane compound according to claim 1 , wherein the reaction is carried out in a reaction solvent. The reaction solvent is one or more reaction solvents selected from the group consisting of 1,4-dioxane, diglyme, N,N-dimethylformamide (DMF), acetic acid, toluene, cyclopentyl methyl ether (CPME) and benzonitrile. The method for producing an allylsilane compound according to claim 3 .