JP3905340B2 - New preparation method of organometallic compounds - Google Patents

Description

（式中、Ｒ^１，Ｒ^２，Ｒ^３は、それぞれ独立して置換基を有していてもよい炭化水素基を表す。）で示される有機ガリウム反応剤（有機ガリウム試薬）が挙げられる。
また、インジウムよりも還元力の強い金属としてアルミニウムを用いた場合に得られる有機金属化合物としては、例えば下記一般式［３］
【化４】

（式中、Ｒ^１，Ｒ^２，Ｒ^３は前記と同じ。）で示される有機アルミニウム反応剤（有機アルミニウム試薬）が挙げられる。
なお、一般式［２］及び［３］において、Ｒ^１，Ｒ^２，Ｒ^３で表される置換基を有していてもよい炭化水素基の定義及び具体例は、前記一般式［１］におけるＲのそれと全く同じである。
【００１４】
本発明に係る反応は、１０℃前後の比較的低温で反応が十分に進行し、対応する有機金属化合物が高収率で得られる。反応に用いられる溶媒としては、例えばジエチルエーテル、テトラヒドロフラン（ＴＨＦ）等のエーテル系溶媒や、ジメチルホルムアミド（ＤＭＦ）、例えばベンゼン、トルエン等の芳香族炭化水素系溶媒等が挙げられるが、これらに限定されるものではない。反応時間は、通常数１０分〜数時間程度である。
なお、反応に用いる１種以上の有機ハロゲン化合物とインジウムよりも還元力の強い金属との使用割合は、例えば当該金属としてガリウム又はアルミニウムを用いた場合には、当該金属２当量に対し、有機ハロゲン化合物の使用量は合計で３当量乃至その１〜１．２倍量程度である。
【００１５】
本発明に係る有機金属化合物、即ち、例えば有機ガリウム反応剤、有機アルミニウム反応剤等は、炭素−炭素結合を生成する種々の有機合成反応、例えば、当該反応剤のカルボニル化合物への求核付加反応や当該反応剤のアルキンへの付加反応等に効果的に供せられる。
即ち、より具体的には、例えばアリルガリウム反応剤、アリルアルミニウム反応剤等は、アルデヒドやケトン等のカルボニル化合物に付加してホモアリルアルコールを与える。
また、これらの反応剤は、室温下、アミンの添加により速やかにアセチレンに付加し、１，４−ジエンを与える。ここで用いられるアミンとしては、例えば、トリエチルアミンやジイソプロピルエチルアミンのような嵩高いアミンが好ましい。
【００１６】
本発明に係る有機金属化合物は、本発明の製造方法により製造、単離した後、これを反応剤（反応試薬）として炭素−炭素結合生成反応に供してもよいが（所謂グリニャール型反応）、次ステップの炭素−炭素結合生成反応を試薬調製と同時に行う所謂バルビエ（Barbier）型反応によりこれを行うこともまた可能である。
このような場合には、当該有機金属化合物製造反応を炭素−炭素結合生成反応に用いる原料化合物の共存下に行えばよい。
即ち、例えば、本発明に係る有機金属化合物の、アルデヒドやケトン等のカルボニル化合物への求核付加反応により、ホモアリルアルコールを製造しようとする場合には、当該アルデヒド類やケトン類の共存下に当該有機金属化合物製造反応を行えばよいし、また、例えば、アルキンに本発明に係る有機金属化合物を付加して１，４−ジエン類を得ようとする場合には、当該アルキン類の共存下に当該有機金属化合物製造反応を行えばよい。なお、後者の場合には、反応系にトリエチルアミンやジイソプロピルエチルアミン等のアミンを添加することが望ましい。
【００１７】
【実施例】
以下、実験例、実施例により本発明をより詳細に説明するが、本発明はこれら実験例、実施例により何ら限定されるものではない。
【００１８】
実験例１
ガリウム金属の活性化を、シクロドデカノンのバルビエ型のアリル化をプローブとして、種々の金属塩を添加して反応を行ない検討した。その結果、ガリウム金属の活性化にインジウム金属の添加が有効であることを見出した。そこで、ガリウムに対するインジウムおよび臭化アリルの当量を検討した。
ガリウム０．７５当量、インジウム金属０．１５当量、臭化アリル１．５当量を用い、ＴＨＦ溶媒中、２５℃で反応させたところ、アリル化体の収率は９５％という結果を得た。
なお、インジウム金属のみで反応を行なってもその収率は３８％と、両者を使うより低い結果が得られている。
ガリウム金属を使用したこれらの実験結果を表１に、また、反応スキームを以下に示す。
【化５】

【００１９】
【表１】

【００２０】
実験例２
臭化アリルを用いるバルビエ型反応において、反応の進行状況と温度を調べたところ、興味深い結果が観察された。反応は、シクロドデカノンに対して、臭化アリルを１．５当量用い、ＴＨＦ溶媒中で２時間反応させた。ガリウム金属のみを用いた場合、温度を上げると反応が進行するようになったが、７０℃でも収率は２８％どまりであった。ガリウムとインジウムの５：１の系でも高温で収率が高くなるが、５５℃で９０％を越える収率となった。反応温度を下げると収率は徐々に低下したが、１０℃になると、逆に収率が８２％に急上昇した。
反応スキームを以下に示す。
【化６】

また、これらの実験結果を図１に示す。なお、図１中、−×−はガリウム金属のみの系、また、−●−はガリウム/インジウム＝５/１の系における結果をそれぞれ示す。
【００２１】
実験例３
先の結果からインジウム金属は触媒量でよいのではないかと考え、その当量数を減らしてみた。反応はバルビエ型でシクロドデカノンに対して臭化アリルを１．５当量用い、１０℃で５時間反応させた。ガリウム金属に対してインジウム金属を１０mol％、５mol％、１mol％と減らしても、収率９０％以上で反応は進行した。また、インジウム金属を添加しないと予想通り、反応は全く進行しなかった。なお、インジウム金属のみでの収率は６４％と、ガリウム−インジウムの系よりも低かった。
これらの実験結果を表２に、また、反応スキームを以下に示す。
【化７】

【００２２】
【表２】

【００２３】
実験例４
アリルガリウム化合物を先に調製し、グリニャール型の反応が行なえないかを検討した。アルゴン雰囲気下、ガリウム(０．９０mmol)と触媒量のインジウム(０．０４５mmol)をＴＨＦ溶媒中１０℃で攪拌した。臭化アリル(１．５mmol)を加え、２時間攪拌したところ、ガリウムとインジウムの金属粉末は完全に消え、無色透明の溶液が得られた。ここにシクロドデカノン(１．０mmol)を加えると、ほぼ定量的に付加反応が進行した。このことから、反応はバルビエ型だけでなくグリニャール型でも行なえることが判った。ベンズアルデヒドでは反応はどちらで行なっても高収率で付加体が得られた。シクロヘキサンカルバルデヒドではバルビエ型で反応させると副生成物が生じたため収率が５８％に低下したが、グリニャール型で行なうことで副生成物を抑えることができた。このようなメチルケトンでもグリニャール型とバルビエ型ともに高収率で付加体を得た。なおこの反応は、ＴＨＦ溶媒中、熱をかけずに１０℃で行なった。
これらの実験結果を表３及び表４に、また、反応スキームをそれぞれ以下に示す。
【化８】

【化９】

【００２４】
【表３】

【００２５】
【表４】

【００２６】
なお、上記実験において、触媒量のインジウム金属の添加で、臭化アリルを加えたときに、ガリウム金属が全て溶け、グリニャール型で反応が行えたことから、アリルガリウム種が生じていることが示唆される。この反応のメカニズムは次のように考えられる。
【化１０】

即ち、ガリウムに触媒量のインジウムを加えると、インジウム粉末表面が金属光沢を帯びる。このことは、活性なインジウム金属が徴量生じたことを示唆する。反応では、このインジウムにより臭化アリルが還元され、先ずアリルインジウム種が生成する。次に３価のガリウムとのトランスメタル化（金属交換）によりアリルガリウム種が生じるとともに、３価のインジウムが再生する。３価のインジウムはガリウム金属によって還元され、元のインジウム金属が再生すると考えられる。
【００２７】
実験例５
重ＴＨＦ中でアリルガリウム種を調製し、^１ＨＮＭＲを測定した。
結果を図２に示す。
アリル位のメチレンが、２．０ppmと１．７ppmにほぼ１対２のダブレットとして観測されたことからこのようなアリルガリウム種が調製できたと考えられる。
【００２８】
実験例６ アリルガリウムの安定性
調製したアリルガリウム種の安定性を調べた。
臭化アリルに対してガリウム金属を０．６７当量、インジウム金属を０．０３３当量加え、ＴＨＦ溶媒中、１０℃で２時間攪拌し、完全に金属を消失させ、アリルガリウム種を調製した。これを室温、アルゴン雰囲気下で保存した。調製したアリルガリウム種に対して、ノナナールを１当量加えて反応させ、その収率を比較した。アリルガリウムを調製した直後のものと１ヶ月間室温で保存したものとで、収率に全く変化がなかった（前者：７５％、後者：７７％）ことから、アリルガリウム種は室温では熱的に安定でつぶれないことが判った。
【００２９】
実施例１ アリルガリウムの調製
アルゴン雰囲気下、ガリウム金属(０．１３ｇ，１．８mmol)、インジウム金属(１０mg，０．０９０mmol)のＴＨＦ(７mL)懸濁液を１０℃に冷却し、１０分間攪拌した。そこへ臭化アリル(０．２６mL，３．０mmol)を滴下し、２時間攪拌したところ、ガリウム金属は消失し見えなくなった。
【００３０】
実施例２ アリルガリウムのカルボニル化合物への付加反応
実施例１と同様にして得られたアリルガリウムに、シクロドデカノン(０．３７ｇ，２．０mmol)のＴＨＦ(３mL)溶液を加え、１０℃で攪拌した。５時間後、反応混合物を氷水にあけ、後処理した。水層をエーテル(５mＬ×３)で抽出し、有機層をまとめて、無水硫酸マグネシウムで乾燥後、減圧下(１Torr)で溶媒を留去した。
粗生成物をシリカゲルカラムクロマトグラフィー(ヘキサン／酢酸エチル＝１００／１)により精製し、１−アリルシクロドデカノール０．４４ｇ(１．９８mmol，収率９９％)を得た。
【００３１】
実施例３ アリルガリウムの末端アセチレンへの付加反応(グリニャール型反応)
実施例１と同様にして得られたアリルガリウムに、４−フェニル−１−ブチン(０．１３ｇ，１．０mmol)のＴＨＦ(２mL)溶液とジイソプロピルエチルアミン(０．１７mL，１．０mmol)を加え、２５℃で攪拌した。２時間後、反応混合物を希塩酸(６Ｍ)にあけ、後処理した。水層をへキサン(５mＬ×３)で抽出し、食塩水で洗浄後、無水硫酸マグネシウムで乾燥した。減圧下(１Torr)で溶媒を留去し、粗生成物をシリカゲルカラムクロマトグラフィー(ヘキサン)により精製し、２−(２−フェニルエチル)−１，４−ペンタジエン０．１７ｇ(０．９７mmol，収率９７％)を得た。
【００３５】
【発明の効果】
本発明は、例えば、有機ガリウム反応剤、有機アルミニウム反応剤等の有機金属化合物をインジウムを触媒量添加することにより、当該金属を活性化して、室温等の穏やかな条件下で調製する方法を提供するものであり、このようにして得られた本発明に係る有機金属化合物、例えば有機ガリウム反応剤、有機アルミニウム反応剤等は、炭素−炭素結合を生成する種々の有機合成反応、例えば、当該反応剤のカルボニル化合物への求核付加反応や当該反応剤のアルキンへの付加反応等に効果的に供せられる。
本発明に係る有機ガリウム試薬、有機アルミニウム試薬等を用いることにより、従来の金属系反応剤では合成が困難であった、種々の有用な有機化合物が、新規に、或いはより容易に、高選択的に得られるようになる。
本発明に係る有機金属化合物は、本発明の製造方法により製造、単離した後、これを反応剤（反応試薬）として炭素−炭素結合生成反応に供してもよいが（所謂グリニャール型反応）、次ステップの炭素−炭素結合生成反応を試薬調製と同時に行う所謂バルビエ（Barbier）型反応によりこれを行うこともまた可能である。
【図面の簡単な説明】
【図１】図１は、臭化アリルを用いるバルビエ型反応において、ガリウム金属のみの系、及びガリウム/インジウム＝５/１の系それぞれについて、反応の進行状況と温度との関係について調べた結果を示す。
【図２】図２は、本発明の方法により、重ＴＨＦ中でアリルガリウム種を調製し、^１ＨＮＭＲを測定した結果を示す。[0001]
BACKGROUND OF THE INVENTION
The present invention provides a novel preparation of organometallic compounds such as organogallium reactants and organoaluminum reactants used in carbon-carbon bond formation reactions such as nucleophilic addition reactions to carbonyl compounds and addition reactions to alkynes. Regarding the law.
[0002]
[Prior art]
Many metals are used in organic synthesis reactions, and Grignard reaction using magnesium and Refomatsky reaction using zinc are well known.
Reaction using metal is one of the most effective means in organic synthesis. However, since the metal surface is covered with an oxide film, the reaction often does not proceed even if the metal is used as it is. There is a problem that it must be activated for use in the reaction. For example, since manganese manganese exhibits almost no reducing power as it is, one method is an active method that can reduce benzyl bromide by reducing manganese (2) salt with lithium naphthalenide by Rieke's activation method. Manganese is gained. In addition, the present inventors have previously found activation of manganese metal that causes catalytic amounts of lead chloride (2) and Me ₃ SiCl to act on manganese metal. This is an example in which the addition of a small amount of different metal is effective in activating the metal.
Examples of using gallium metal include, for example, a method of adding lead (2) (J. Chem. Soc., Perkin Trans. 1, 1995, 189-191) and a method of adding potassium iodide (Tetrahedron). Letters, Vol. 35, No. 50, 9433-9434, 1994), etc., are known, but in any case, the reaction hardly proceeds at room temperature, and all require heating conditions. However, it is difficult to produce at high temperatures due to side reactions and the like, and the efficiency is poor.
[0003]
[Problems to be solved by the invention]
The present invention, for example, activates metals such as gallium and aluminum by adding a catalytic amount of a metal different from gallium, aluminum or the like to an organometallic compound such as an organic gallium reactant or an organoaluminum reactant, and so on. It is an object of the present invention to provide a process for preparing this under mild conditions.
[0004]
[Means for Solving the Problems]
The present invention relates to a method for producing an organometallic compound, which comprises reacting an organohalogen compound with a metal having a reducing power stronger than indium in the presence of a catalytic amount of indium or an indium compound.
[0005]
Moreover, this invention relates to the reaction reagent used for the carbon-carbon bond production | generation reaction obtained by the said manufacturing method.
[0006]
Furthermore, this invention relates to the said manufacturing method which performs the said manufacturing reaction in coexistence of the raw material compound used for a carbon-carbon bond production | generation reaction.
[0007]
Furthermore, the present invention relates to a method for producing a carbon-carbon bond by a Barbier-type reaction, characterized in that the above production method is carried out in the presence of a raw material compound used for a carbon-carbon bond producing reaction.
[0008]
That is, the present inventor cooled and stirred a suspension obtained by adding a catalytic amount of indium metal to gallium metal or aluminum metal to 10 ° C., and further dropped and stirred allyl bromide. Gallium or aluminum metal disappears and allyl gallium bromide or allyl aluminum bromide is found (confirmed by NMR). This Grignard type gallium and aluminum reagent (reactant) is It was confirmed that the addition reaction to a strong carbonyl compound, acetylene, etc. can be carried out in high yield. By adopting this method, not only the Grignard type reagent but also the next step addition reaction can be carried out. In order to complete the present invention, it has been found that a Barbier-type reaction can be effectively performed simultaneously with reagent preparation. Arrived.
By using the organic gallium reagent, organoaluminum reagent, etc. according to the present invention, various useful organic compounds, which were difficult to synthesize with conventional metal-based reactants, are newly or more easily and highly selective. Will be obtained.
[0009]
DETAILED DESCRIPTION OF THE INVENTION
Examples of the organic halogen compound used in the present invention include the following general formula [1].
RX [1]
(Wherein, R represents a hydrocarbon group which may have a substituent, and X represents a halogen atom).
In the general formula [1], examples of the hydrocarbon group that may have a substituent represented by R include an alkyl group, an alkenyl group, an alkynyl group, an aralkyl group, and an aryl group. It is done.
Examples of the alkyl group include linear, branched or cyclic alkyl groups having 1 to 20 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms. , Methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, secondary butyl group, tertiary butyl group, pentyl group, hexyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclooctyl group Etc.
Examples of the alkenyl group include those having an unsaturated group such as one or more double bonds in the above-mentioned alkyl group having 2 or more carbon atoms, and more specifically, vinyl group, allyl group, 1- Examples include propenyl group, isopropenyl group, 2-butenyl group, 1,3-butadienyl group, 2-pentenyl group, 2-hexenyl group, cyclopropenyl group, cyclopentenyl group, cyclohexenyl group and the like.
Examples of the alkynyl group include those having an unsaturated group such as one or more triple bonds in the aforementioned alkyl group having 2 or more carbon atoms, and more specifically, an ethynyl group, 1-propynyl group, 2 -A propynyl group etc. are mentioned.
Examples of the aralkyl group include monocyclic, polycyclic or condensed cyclic aralkyl groups having 7 to 30 carbon atoms, preferably 7 to 20 carbon atoms, more preferably 7 to 15 carbon atoms. Examples include a benzyl group, a phenethyl group, a naphthylmethyl group, and a naphthylethyl group.
Examples of the aryl group include monocyclic, polycyclic or condensed cyclic aromatic hydrocarbon groups having 6 to 30 carbon atoms, preferably 6 to 20 carbon atoms, more preferably 6 to 14 carbon atoms, and more specifically. Examples thereof include a phenyl group, a tolyl group, a xylyl group, a naphthyl group, a methylnaphthyl group, an anthryl group, a phenanthryl group, and a biphenyl group.
These substituents such as an alkyl group, an alkenyl group, an alkynyl group, an aralkyl group, and an aryl group may be any group as long as they do not hinder the reaction. For example, a methoxycarbonyl group, an ethoxycarbonyl group And the like, for example, alkoxy groups such as methoxy group and ethoxy group.
[0010]
In the general formula [1], examples of the halogen atom represented by X include chlorine, bromine, iodine and the like, and bromine is particularly preferable.
Specific examples of the organic halogen compound represented by the general formula [1] include, for example, allyl bromide (allyl bromide), bromoacetate ester, benzyl bromide, and the like. Absent.
[0011]
The reaction according to the present invention proceeds most effectively in the presence of metallic indium, but the reaction proceeds effectively even in the presence of an indium compound such as indium chloride. A so-called catalytic amount is sufficient for the use amount of these metal indium or indium compound.
[0012]
Examples of the metal having a reducing power stronger than that of indium used in the present invention include gallium and aluminum.
[0013]
In the present invention, as the organometallic compound obtained when gallium is used as the metal having a reducing power stronger than that of indium, for example, the following general formula [2]
[Chemical 3]

(Wherein R ¹ , R ² , and R ³ each independently represents a hydrocarbon group that may have a substituent), an organic gallium reagent (an organic gallium reagent) is exemplified.
Moreover, as an organometallic compound obtained when aluminum is used as a metal having a stronger reducing power than indium, for example, the following general formula [3]
[Formula 4]

(In the formula, R ¹ , R ² , and R ³ are the same as described above).
In the general formulas [2] and [3], the definition and specific examples of the hydrocarbon group which may have a substituent represented by R ¹ , R ² , R ³ are as described in the general formula [1]. Is exactly the same as that of R.
[0014]
The reaction according to the present invention sufficiently proceeds at a relatively low temperature of about 10 ° C., and the corresponding organometallic compound is obtained in a high yield. Examples of the solvent used in the reaction include ether solvents such as diethyl ether and tetrahydrofuran (THF), and dimethylformamide (DMF) such as aromatic hydrocarbon solvents such as benzene and toluene, but are not limited thereto. Is not to be done. The reaction time is usually about several tens of minutes to several hours.
In addition, the use ratio of the one or more organic halogen compounds used for the reaction and the metal having a stronger reducing power than indium is, for example, when gallium or aluminum is used as the metal, The total amount of the compound used is about 3 equivalents or about 1 to 1.2 times the amount.
[0015]
The organometallic compound according to the present invention, that is, for example, an organic gallium reactant, an organoaluminum reactant, and the like are various organic synthesis reactions that generate a carbon-carbon bond, for example, a nucleophilic addition reaction of the reactant to a carbonyl compound. And can be effectively used for the addition reaction of the reactant to the alkyne.
That is, more specifically, for example, an allyl gallium reagent, an allyl aluminum reagent, or the like is added to a carbonyl compound such as an aldehyde or a ketone to give homoallyl alcohol.
In addition, these reactants are quickly added to acetylene by addition of amine at room temperature to give 1,4-diene. As the amine used here, for example, bulky amines such as triethylamine and diisopropylethylamine are preferable.
[0016]
The organometallic compound according to the present invention may be produced and isolated by the production method of the present invention, and then subjected to a carbon-carbon bond formation reaction using this as a reactant (reaction reagent) (so-called Grignard type reaction). It is also possible to carry out this by a so-called Barbier type reaction in which the carbon-carbon bond formation reaction of the next step is performed simultaneously with the preparation of the reagent.
In such a case, the organometallic compound production reaction may be performed in the presence of a raw material compound used for the carbon-carbon bond generation reaction.
That is, for example, when homoallylic alcohol is to be produced by the nucleophilic addition reaction of the organometallic compound according to the present invention to a carbonyl compound such as an aldehyde or a ketone, The organometallic compound production reaction may be carried out. For example, when an organometallic compound according to the present invention is added to alkyne to obtain 1,4-dienes, The organometallic compound production reaction may be carried out. In the latter case, it is desirable to add an amine such as triethylamine or diisopropylethylamine to the reaction system.
[0017]
【Example】
EXAMPLES Hereinafter, although this invention is demonstrated in detail by an experiment example and an Example, this invention is not limited at all by these experiment examples and Examples.
[0018]
Experimental example 1
The activation of gallium metal was examined by adding various metal salts and using the Barbie type allylation of cyclododecanone as a probe. As a result, it has been found that the addition of indium metal is effective for the activation of gallium metal. Therefore, the equivalents of indium and allyl bromide to gallium were examined.
When 0.75 equivalent of gallium, 0.15 equivalent of indium metal, and 1.5 equivalent of allyl bromide were used and reacted in THF solvent at 25 ° C., the yield of allylated product was 95%.
In addition, even if it reacts only with an indium metal, the yield is 38% and the result lower than using both is obtained.
The results of these experiments using gallium metal are shown in Table 1, and the reaction scheme is shown below.
[Chemical formula 5]

[0019]
[Table 1]

[0020]
Experimental example 2
In the Barbier-type reaction using allyl bromide, when the progress of the reaction and the temperature were investigated, interesting results were observed. In the reaction, 1.5 equivalents of allyl bromide was used for cyclododecanone and reacted in THF solvent for 2 hours. When only gallium metal was used, the reaction proceeded when the temperature was raised, but the yield was only 28% even at 70 ° C. Even in a 5: 1 system of gallium and indium, the yield increased at high temperatures, but exceeded 55% at 55 ° C. When the reaction temperature was lowered, the yield gradually decreased, but at 10 ° C., the yield rose sharply to 82%.
The reaction scheme is shown below.
[Chemical 6]

The results of these experiments are shown in FIG. In FIG. 1, − × − indicates a result in a gallium metal-only system, and − ● − indicates a result in a gallium / indium = 5/1 system.
[0021]
Experimental example 3
From the previous results, we thought that the amount of indium metal may be a catalytic amount, and tried to reduce the number of equivalents. The reaction was a Barbier type, using 1.5 equivalents of allyl bromide with respect to cyclododecanone, and allowed to react at 10 ° C. for 5 hours. Even if the indium metal was reduced to 10 mol%, 5 mol%, and 1 mol% with respect to gallium metal, the reaction proceeded with a yield of 90% or more. Further, the reaction did not proceed at all as expected without adding indium metal. The yield of indium metal alone was 64%, which was lower than that of the gallium-indium system.
The results of these experiments are shown in Table 2, and the reaction scheme is shown below.
[Chemical 7]

[0022]
[Table 2]

[0023]
Experimental Example 4
An allyl gallium compound was prepared in advance and examined whether a Grignard type reaction could be performed. In an argon atmosphere, gallium (0.90 mmol) and a catalytic amount of indium (0.045 mmol) were stirred in a THF solvent at 10 ° C. When allyl bromide (1.5 mmol) was added and stirred for 2 hours, the metal powder of gallium and indium disappeared completely, and a colorless and transparent solution was obtained. When cyclododecanone (1.0 mmol) was added thereto, the addition reaction proceeded almost quantitatively. From this, it was found that the reaction can be performed not only in the Barbier type but also in the Grignard type. With benzaldehyde, the adduct was obtained in high yield regardless of the reaction. In cyclohexane carbaldehyde, by-product was produced when the reaction was performed in the Barbier type, and the yield was reduced to 58%. However, by-product in the Grignard type could be suppressed. Even with such methyl ketones, adducts were obtained in high yields for both the Grignard type and the Barbier type. This reaction was carried out in a THF solvent at 10 ° C. without applying heat.
The experimental results are shown in Tables 3 and 4, and the reaction scheme is shown below.
[Chemical 8]

[Chemical 9]

[0024]
[Table 3]

[0025]
[Table 4]

[0026]
In the above experiment, when allyl bromide was added with the addition of a catalytic amount of indium metal, all the gallium metal was dissolved and the reaction was performed in the Grignard type, suggesting that allyl gallium species were generated. Is done. The mechanism of this reaction is considered as follows.
[Chemical Formula 10]

That is, when a catalytic amount of indium is added to gallium, the surface of the indium powder has a metallic luster. This suggests that an active indium metal has been produced. In the reaction, allyl bromide is reduced by this indium, and first allylindium species are generated. Next, allylgallium species are generated by transmetalation (metal exchange) with trivalent gallium, and trivalent indium is regenerated. It is considered that trivalent indium is reduced by gallium metal and the original indium metal is regenerated.
[0027]
Experimental Example 5
Allylgallium species were prepared in deuterated THF and ¹ HNMR was measured.
The results are shown in FIG.
It is considered that such allylgallium species could be prepared because allylic methylene was observed as a one-to-two doublet at 2.0 ppm and 1.7 ppm.
[0028]
Experimental Example 6 Stability of Allyl Gallium The stability of the prepared allyl gallium species was examined.
0.67 equivalents of gallium metal and 0.033 equivalents of indium metal were added to allyl bromide, and the mixture was stirred in a THF solvent at 10 ° C. for 2 hours to completely eliminate the metal to prepare an allylgallium species. This was stored at room temperature under an argon atmosphere. One equivalent of nonanal was added to the prepared allylgallium species and reacted, and the yields were compared. There was no change in yield between the one immediately after the preparation of allylgallium and the one stored at room temperature for one month (the former: 75%, the latter: 77%). It was found to be stable and unbreakable.
[0029]
Example 1 Preparation of allylgallium A suspension of gallium metal (0.13 g, 1.8 mmol) and indium metal (10 mg, 0.090 mmol) in THF (7 mL) was cooled to 10 ° C. and stirred for 10 minutes under an argon atmosphere. did. When allyl bromide (0.26 mL, 3.0 mmol) was added dropwise thereto and stirred for 2 hours, the gallium metal disappeared and disappeared.
[0030]
Example 2 Addition reaction of allylgallium to a carbonyl compound To allylgallium obtained in the same manner as in Example 1, a solution of cyclododecanone (0.37 g, 2.0 mmol) in THF (3 mL) was added at 10 ° C. Stir. After 5 hours, the reaction mixture was poured into ice water and worked up. The aqueous layer was extracted with ether (5 mL × 3), the organic layers were combined, dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure (1 Torr).
The crude product was purified by silica gel column chromatography (hexane / ethyl acetate = 100/1) to obtain 0.44 g (1.98 mmol, yield 99%) of 1-allylcyclododecanol.
[0031]
Example 3 Addition reaction of allyl gallium to terminal acetylene (Grignard type reaction)
To allyl gallium obtained in the same manner as in Example 1, 4-phenyl-1-butyne (0.13 g, 1.0 mmol) in THF (2 mL) and diisopropylethylamine (0.17 mL, 1.0 mmol) were added. And stirred at 25 ° C. After 2 hours, the reaction mixture was poured into dilute hydrochloric acid (6M) and worked up. The aqueous layer was extracted with hexane (5 mL × 3), washed with brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure (1 Torr), and the crude product was purified by silica gel column chromatography (hexane) to give 0.17 g (0.97 mmol, yield of 2- (2-phenylethyl) -1,4-pentadiene. 97%).
[0035]
【The invention's effect】
The present invention provides a method for preparing an organometallic compound such as an organic gallium reactant and an organoaluminum reactant under a mild condition such as room temperature by activating the metal by adding a catalytic amount of indium. The organometallic compound according to the present invention thus obtained, for example, an organic gallium reactant, an organoaluminum reactant, and the like are used in various organic synthesis reactions that generate a carbon-carbon bond, for example, the reaction. It can be effectively used for the nucleophilic addition reaction of the agent to the carbonyl compound and the addition reaction of the reagent to the alkyne.
By using the organic gallium reagent, organoaluminum reagent, etc. according to the present invention, various useful organic compounds, which were difficult to synthesize with conventional metal-based reactants, are newly or more easily and highly selective. Will be obtained.
The organometallic compound according to the present invention may be produced and isolated by the production method of the present invention, and then subjected to a carbon-carbon bond formation reaction using this as a reactant (reaction reagent) (so-called Grignard type reaction). It is also possible to carry out this by a so-called Barbier type reaction in which the carbon-carbon bond formation reaction of the next step is performed simultaneously with the preparation of the reagent.
[Brief description of the drawings]
BRIEF DESCRIPTION OF DRAWINGS FIG. 1 shows the results of investigating the relationship between the progress of reaction and temperature in a gallium metal-only system and a gallium / indium = 5/1 system in a Barbier-type reaction using allyl bromide. Indicates.
FIG. 2 shows the results of ¹ HNMR measurement of allylgallium species prepared in deuterated THF by the method of the present invention.

Claims (12)

  A method for producing an organic gallium compound, comprising reacting an organic halogen compound with gallium metal in the presence of a catalytic amount of indium or an indium compound. The organic halogen compound is represented by the following general formula [1]
RX [1]
(In the formula, R represents a hydrocarbon group which may have a substituent, and X represents a halogen atom.)
The manufacturing method of Claim 1 which is 1 or more types of compounds shown by these. The organic gallium compound is represented by the following general formula [2]

(In the formula, R ¹ , R ² and R ³ each independently represents a hydrocarbon group which may have a substituent.)
The manufacturing method of Claim 1 or 2 which is a compound shown by these. The method according to any one of claims 2 to 3 , wherein the organic halogen compound represented by the general formula [1] is allyl bromide.   The manufacturing method in any one of Claims 1-4 which perform the said manufacturing reaction in the coexistence of the raw material compound used for a carbon-carbon bond production | generation reaction.   The production method according to claim 5, wherein the raw material compound used in the carbon-carbon bond formation reaction is a carbonyl compound.   The production method according to claim 5, wherein the raw material compound used for the carbon-carbon bond formation reaction is alkyne.   The production method according to claim 7, wherein the reaction is carried out in the presence of an amine.   A method for producing a carbon-carbon bond by a Barbier-type reaction, wherein the production method according to any one of claims 1 to 4 is carried out in the presence of a raw material compound used for a carbon-carbon bond producing reaction.   A method for nucleophilic addition of an organometallic compound to a carbonyl compound by a Barbier-type reaction, wherein the production method according to any one of claims 1 to 4 is carried out in the presence of a carbonyl compound.   A method for adding an organometallic compound to an alkyne by a Barbier-type reaction, wherein the production method according to any one of claims 1 to 4 is carried out in the presence of alkyne.   The addition method according to claim 11, wherein the reaction is carried out in the presence of an amine.

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