JP2009215240A - Method for producing homo allyl alcohol, and asymmetric catalyst - Google Patents

Method for producing homo allyl alcohol, and asymmetric catalyst Download PDF

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JP2009215240A
JP2009215240A JP2008061580A JP2008061580A JP2009215240A JP 2009215240 A JP2009215240 A JP 2009215240A JP 2008061580 A JP2008061580 A JP 2008061580A JP 2008061580 A JP2008061580 A JP 2008061580A JP 2009215240 A JP2009215240 A JP 2009215240A
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Osamu Kobayashi
修 小林
Schneider Uwe
シュナイダー ウーベ
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Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing a homo allyl alcohol, comprising allylating a ketone in the presence of indium as a catalyst in water, and to provide an asymmetric catalyst. <P>SOLUTION: Provided is the method for producing the homo allyl alcohol, such as 3-methyl-2-phenylpent-4-en-2-ol, which comprises reacting a ketophenone represented by formula I, such as acetophenone, with an α-substituted allyl boronate represented by formula II, such as pinacolyl α-methyl allyl borate, in the presence of zero-valent indium as a catalyst in water. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

この発明は、ケトンを不斉アリル化するホモアリルアルコールの製造方法及び不斉触媒に関する。   The present invention relates to a method for producing homoallylic alcohol for asymmetrically allylating a ketone and an asymmetric catalyst.

水中でのケトンの不斉アリル化反応は報告例がなく、従来は厳密な無水条件を必要とし、有機溶媒中で行われていた。例えば、アリルホウ素試薬を用いた不斉アリル化としては、キラル銅触媒を用いた例（非特許文献１）やキラルジオールを用いた例（非特許文献２）が報告されているが、これらはいずれも有機溶媒中での反応である。また、アリル化剤としてアリルケイ素試薬やアリルスズ試薬を有機溶媒中で用いるケトンの不斉アリル化の例も報告されているが、アリルケイ素試薬には腐食性、アリルスズ試薬には毒性があることが知られており、これらの使用は望ましいものではない。
一方、インジウムの使用例に関しては、３価のインジウム触媒存在下でアリルスズ試薬を用いる例が報告されている（非特許文献３、４）。また、不斉源として当量のアミノアルコールを必要とするBarbier型アリル化反応（非特許文献５）も報告されているが、これらはいずれも有機溶媒中の反応であり、またジアステレオ選択的反応は報告されていない。 There has been no report on the asymmetric allylation reaction of ketones in water. Conventionally, strict anhydrous conditions are required and the reaction has been carried out in an organic solvent. For example, as an asymmetric allylation using an allyl boron reagent, an example using a chiral copper catalyst (Non-Patent Document 1) and an example using a chiral diol (Non-Patent Document 2) have been reported. Both are reactions in an organic solvent. In addition, examples of asymmetric allylation of ketones using an allyl silicon reagent or an allyl tin reagent as an allylating agent in an organic solvent have been reported, but allyl silicon reagents are corrosive and allyl tin reagents are toxic. These are known and their use is undesirable.
On the other hand, examples of using indium have been reported using allyltin reagents in the presence of a trivalent indium catalyst (Non-Patent Documents 3 and 4). Barbier-type allylation reaction (Non-Patent Document 5) that requires an equivalent amount of amino alcohol as an asymmetric source has also been reported. These are reactions in an organic solvent, and are diastereoselective reactions. Has not been reported.

Wada, R.; Oisaki, K.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2004, 126, 8910.Wada, R .; Oisaki, K .; Kanai, M .; Shibasaki, M. J. Am. Chem. Soc. 2004, 126, 8910. Lou, S.; Moquist, P. N.; Schaus, S. E. J. Am. Chem. Soc. 2006, 128, 12660.Lou, S .; Moquist, P. N .; Schaus, S. E. J. Am. Chem. Soc. 2006, 128, 12660. Lu, J.; Hong, M.-L.;Ji, S.- J.; Teo, Y.-C.; Loh, T.-P. Chem. Commun. 2005, 4217.Lu, J .; Hong, M.-L .; Ji, S.- J .; Teo, Y.-C .; Loh, T.-P. Chem. Commun. 2005, 4217. Lu, J.; Ji, S.- J. Chin. J. Chem. 2006, 24, 1439.Lu, J .; Ji, S.- J. Chin. J. Chem. 2006, 24, 1439. Haddad, T. D.; Hirayama, L. C.; Taynton, P.; Singaram, B. Tetrahedron Lett.2008, 49, 508.Haddad, T. D .; Hirayama, L. C .; Taynton, P .; Singaram, B. Tetrahedron Lett. 2008, 49, 508.

従って、本発明は、インジウムを触媒に用い、水中でケトンをアリル化するホモアリルアルコールの製造方法及び不斉触媒の提供を目的とする。   Therefore, an object of the present invention is to provide a method for producing homoallylic alcohol in which indium is used as a catalyst and allylates a ketone in water and an asymmetric catalyst.

このような課題を解決するために、本発明者らは鋭意研究した結果、0価のインジウム触媒と、ホウ素を含むアリル化剤とを用いることにより、水中でケトンのアリル化がエナンチオ選択的に進行することを見出し、本発明を完成するに至った。また、α位に置換基を有するアリル化剤を用いるとジアステレオ選択的かつα位選択的なアリル化反応も可能である。   In order to solve such a problem, the present inventors have conducted intensive research. It has been found that it has progressed, and the present invention has been completed. Further, when an allylating agent having a substituent at the α-position is used, a diastereoselective and α-selective allylation reaction is also possible.

即ち、本発明のホモアリルアルコールの製造方法は、水中で、触媒として０価のインジウムの存在下、式I

Figure 2009215240
で表されるケトン（R1, R2は、それぞれ同一でも異なっていてもよく、置換基を有していてもよい脂肪族炭化水素基、置換基を有していてもよい芳香族炭化水素基、又は置換基を有していてもよい複素環基；R1とR2は環を形成していてもよい）と、式II
Figure 2009215240
 で表されるアリルボロネート又はα-置換アリルボロネート（R3は、水素原子、置換基を有していてもよい脂肪族炭化水素基、置換基を有していてもよい芳香族炭化水素基、アルコキシ基、又はハロゲン基；R4は水素原子、置換基を有していてもよい脂肪族炭化水素基、置換基を有していてもよい芳香族炭化水素基、又は置換基を有していてもよい複素環基；R5はアルキル基）とを反応させることにより、式III
Figure 2009215240
 で表されるホモアリルアルコールを得る。 That is, the method for producing homoallylic alcohol of the present invention comprises a compound of formula I
Figure 2009215240
 (R 1 and R 2 , which may be the same or different, each may be an aliphatic hydrocarbon group which may have a substituent, or an aromatic hydrocarbon which may have a substituent A heterocyclic group which may have a group or a substituent; R 1 and R 2 may form a ring) and formula II
Figure 2009215240
 Allyl boronate or α-substituted allyl boronate represented by (R 3 is a hydrogen atom, an aliphatic hydrocarbon group which may have a substituent, an aromatic hydrocarbon which may have a substituent Group, alkoxy group, or halogen group; R 4 has a hydrogen atom, an aliphatic hydrocarbon group which may have a substituent, an aromatic hydrocarbon group which may have a substituent, or a substituent; By reacting with an optionally substituted heterocyclic group; R 5 is an alkyl group).
Figure 2009215240
 The homoallylic alcohol represented by this is obtained.

さらに、式IV

Figure 2009215240
又は、式V
Figure 2009215240
 で表される不斉配位子又はこれらの鏡像異性体（R6は、水素原子又はアルキル基；R7は、置換基を有していてもよい脂肪族炭化水素基、置換基を有していてもよい芳香族炭化水素基、又は置換基を有していてもよい複素環基；R8は、水素原子、置換基を有していてもよい脂肪族炭化水素基、置換基を有していてもよい芳香族炭化水素基、又は置換基を有していてもよい複素環基；R7とR8は環を形成していてもよい；R9は、それぞれ同じであっても異なっていてもよく、置換基を有していてもよい脂肪族炭化水素基、又は置換基を有していてもよい芳香族炭化水素基；R10はシアノ基またはアミノ基）を共存させると好ましい。 Furthermore, the formula IV
Figure 2009215240
 Or the formula V
Figure 2009215240
 Or an enantiomer thereof (R 6 is a hydrogen atom or an alkyl group; R 7 has an optionally substituted aliphatic hydrocarbon group or substituent. An aromatic hydrocarbon group which may have a substituent, or a heterocyclic group which may have a substituent; R 8 has a hydrogen atom, an aliphatic hydrocarbon group which may have a substituent, or a substituent; a good aromatic hydrocarbon group, or an optionally substituted heterocyclic group; R 7 and R 8 may form a ring; R 9 can be the respective same An aliphatic hydrocarbon group which may be different and may have a substituent, or an aromatic hydrocarbon group which may have a substituent; R 10 is a cyano group or an amino group) preferable.

本発明の不斉触媒は、式IV

Figure 2009215240
又は、式V
Figure 2009215240
 で表される不斉配位子又はこれらの鏡像異性体（R6は、水素原子又はアルキル基；R7は、置換基を有していてもよい脂肪族炭化水素基、置換基を有していてもよい芳香族炭化水素基、又は置換基を有していてもよい複素環基；R8は、水素原子、置換基を有していてもよい脂肪族炭化水素基、置換基を有していてもよい芳香族炭化水素基、又は置換基を有していてもよい複素環基；R7とR8は環を形成していてもよい；R9は、それぞれ同じであっても異なっていてもよく、置換基を有していてもよい脂肪族炭化水素基、又は置換基を有していてもよい芳香族炭化水素基；R10はシアノ基またはアミノ基）と、０価のインジウムからなる。 The asymmetric catalyst of the present invention has the formula IV
Figure 2009215240
 Or the formula V
Figure 2009215240
 Or an enantiomer thereof (R 6 is a hydrogen atom or an alkyl group; R 7 has an optionally substituted aliphatic hydrocarbon group or substituent. An aromatic hydrocarbon group which may have a substituent, or a heterocyclic group which may have a substituent; R 8 has a hydrogen atom, an aliphatic hydrocarbon group which may have a substituent, or a substituent; a good aromatic hydrocarbon group, or an optionally substituted heterocyclic group; R 7 and R 8 may form a ring; R 9 can be the respective same An aliphatic hydrocarbon group which may be different and may have a substituent, or an aromatic hydrocarbon group which may have a substituent; R 10 is a cyano group or an amino group) and zero valence Of indium.

本発明によれば、0価のインジウム触媒と、ホウ素を含むアリル化剤とを用いることにより、水中でケトンのアリル化をエナンチオ選択的に行うことができる。α位に置換基を有するアリル化剤を用いるとジアステレオ選択的かつα位選択的なアリル化反応も可能である。   According to the present invention, by using a zero-valent indium catalyst and an allylating agent containing boron, it is possible to enantioselectively perform ketone allylation in water. When an allylating agent having a substituent at the α-position is used, a diastereoselective and α-selective allylation reaction is also possible.

本発明は、0価のインジウム触媒と、ホウ素を含むアリル化剤とを用いることにより、水中でケトンをアリル化するものである。
ホウ素を含むアリル化剤としては、以下の式II
式II

Figure 2009215240
で表されるアリルボロネート又はα-置換アリルボロネート（R3は、水素原子、置換基を有していてもよい脂肪族炭化水素基、置換基を有していてもよい芳香族炭化水素基、アルコキシ基、又はハロゲン基；R4は水素原子、置換基を有していてもよい脂肪族炭化水素基、置換基を有していてもよい芳香族炭化水素基、又は置換基を有していてもよい複素環基；R5はアルキル基）を用いる。
ここで、式II において、R4が水素原子の場合は（α-無置換の）アリルボロネートであり、R4が水素原子以外の場合はα-置換アリルボロネートである。（α-無置換の）アリルボロネートは、後述する不斉配位子を用いるエナンチオ選択的反応に主に利用されるので、後述する不斉配位子と併用するのが好ましい。α-置換アリルボロネートは、ジアステレオ選択的かつα位選択的なアリル化反応に主に利用される。
R3は、望ましくはアルキル基又は水素原子である。R4は好ましくはアルキル基又は水素原子である。R5は好ましくは式VIで表される化合物である。 In the present invention, a ketone is allylated in water by using a zero-valent indium catalyst and an allylating agent containing boron.
As an allylating agent containing boron, the following formula II
Formula II
Figure 2009215240
 Allyl boronate or α-substituted allyl boronate represented by (R 3 is a hydrogen atom, an aliphatic hydrocarbon group which may have a substituent, an aromatic hydrocarbon which may have a substituent Group, alkoxy group, or halogen group; R 4 has a hydrogen atom, an aliphatic hydrocarbon group which may have a substituent, an aromatic hydrocarbon group which may have a substituent, or a substituent; An optionally substituted heterocyclic group; R 5 is an alkyl group).
Here, in the formula II, when R 4 is a hydrogen atom, it is an (α-unsubstituted) allyl boronate, and when R 4 is other than a hydrogen atom, it is an α-substituted allyl boronate. Since the (α-unsubstituted) allyl boronate is mainly used for enantioselective reaction using an asymmetric ligand described later, it is preferably used in combination with the asymmetric ligand described later. α-Substituted allyl boronates are mainly used for diastereoselective and α-selective allylation reactions.
R 3 is preferably an alkyl group or a hydrogen atom. R 4 is preferably an alkyl group or a hydrogen atom. R 5 is preferably a compound of formula VI.

式IIの化合物として、特に、

Figure 2009215240
で表される化合物を用いることが好ましい。 As compounds of formula II, in particular,
Figure 2009215240
 It is preferable to use the compound represented by these.

ケトンとしては、式I

Figure 2009215240
で表されるケトン（R1, R2は、それぞれ同一でも異なっていてもよく、置換基を有していてもよい脂肪族炭化水素基、置換基を有していてもよい芳香族炭化水素基、又は置換基を有していてもよい複素環基；R1とR2は環を形成していてもよい）を用いる。R1, R2のうち望ましくは一方が芳香族基である。
ケトンとしては、例えば、環式ケトン、非環式ケトン、芳香族ケトン、複素環ケトン、脂肪族ケトン等を用いることができる。つまり本発明は、広い基質一般性を有する。又、ケトンとしては、アミノ基、水酸基、メトキシ基、クロロ基、ブロモ基、ニトロ基、アミド基などの種々の官能基を構造に含むものを用いることができる。
特に、アセトフェノンを用いることが好ましい。 As a ketone, the formula I
Figure 2009215240
 (R 1 and R 2 , which may be the same or different, each may be an aliphatic hydrocarbon group which may have a substituent, or an aromatic hydrocarbon which may have a substituent A heterocyclic group which may have a group or a substituent; R 1 and R 2 may form a ring). One of R 1 and R 2 is preferably an aromatic group.
Examples of ketones that can be used include cyclic ketones, acyclic ketones, aromatic ketones, heterocyclic ketones, and aliphatic ketones. That is, the present invention has a broad substrate generality. In addition, as the ketone, those having various functional groups such as amino group, hydroxyl group, methoxy group, chloro group, bromo group, nitro group, amide group in the structure can be used.
In particular, acetophenone is preferably used.

ケトンのアリル化の触媒として、前記ケトンに対し１〜２０mol%の０価のインジウムを用いる。前記ケトンに対するインジウムの量は、好ましくは０．１〜２０mol%である。
０価のインジウムを触媒として用いると、０価のインジウムがα-置換アリルボロネートのホウ素原子と置換する（トランスメタル化）ことで高活性なアリルインジウムが生成するか、又は、インジウムから一電子がホウ素に移動することによりラジカル機構で反応が進行していると考えられる。 As a catalyst for the allylation of a ketone, 1 to 20 mol% of zero-valent indium is used with respect to the ketone. The amount of indium with respect to the ketone is preferably 0.1 to 20 mol%.
When zero-valent indium is used as a catalyst, high-activity allylindium is produced by replacing zero-valent indium with the boron atom of α-substituted allylboronate (transmetalation), or one electron from indium. It is considered that the reaction proceeds by a radical mechanism by moving to boron.

本発明において、反応溶媒は水であり、水中の各成分の濃度はそれぞれ0.01〜5mol/lであることが好ましい。但し、ケトンに対するアリルボロネートの当量は好ましくは１〜２当量、より好ましくは1.1〜1.5当量である。
この反応の温度は、好ましくは0〜50℃であり、より好ましくは0〜30℃である。
この反応時間は、好ましくは0〜48時間程度であり、より好ましくは8〜24時間程度である。
この反応系には上記成分のほか、適宜、触媒や界面活性剤等の公知の添加剤を添加してもよい。 In the present invention, the reaction solvent is water, and the concentration of each component in water is preferably 0.01 to 5 mol / l. However, the equivalent amount of allylboronate to ketone is preferably 1 to 2 equivalents, more preferably 1.1 to 1.5 equivalents.
The temperature of this reaction is preferably 0-50 ° C, more preferably 0-30 ° C.
This reaction time is preferably about 0 to 48 hours, more preferably about 8 to 24 hours.
In addition to the above components, known additives such as catalysts and surfactants may be added to this reaction system as appropriate.

本発明の製造方法によって得られるホモアリルアルコールは、
式III

Figure 2009215240
で表される。本発明によれば、アリル化がエナンチオ選択的に進行する。又、α位に置換基を有するアリル化剤を用いることにより、ジアステレオ選択的かつα位選択的なアリル化反応が進行する。
ホモアリルアルコールとしては、R1がフェニル基、R2がメチル基、R3=H、R4=Me又はHのものを例示することができる。
生成物は、抽出、カラムクロマトグラフィー、蒸留、再結晶等の一般的精製法を利用して回収できる。 Homoallyl alcohol obtained by the production method of the present invention is
Formula III
Figure 2009215240
 It is represented by According to the present invention, allylation proceeds enantioselectively. Further, by using an allylic agent having a substituent at the α-position, a diastereoselective and α-selective allylation reaction proceeds.
Examples of homoallylic alcohol include those in which R 1 is a phenyl group, R 2 is a methyl group, R 3 = H, R 4 = Me or H.
The product can be recovered using common purification methods such as extraction, column chromatography, distillation, recrystallization and the like.

反応系に、さらに、式IV

Figure 2009215240
又は、式V
Figure 2009215240
 で表される不斉配位子又はこれらの鏡像異性体（R6は、水素原子又はアルキル基；R7は、置換基を有していてもよい脂肪族炭化水素基、置換基を有していてもよい芳香族炭化水素基、又は置換基を有していてもよい複素環基；R8は、水素原子、置換基を有していてもよい脂肪族炭化水素基、置換基を有していてもよい芳香族炭化水素基、又は置換基を有していてもよい複素環基；R7とR8は環を形成していてもよい；R9は、それぞれ同じであっても異なっていてもよく、置換基を有していてもよい脂肪族炭化水素基、又は置換基を有していてもよい芳香族炭化水素基；R10はシアノ基またはアミノ基）を共存させて反応を行うことが好ましい。
上記不斉配位子を加えると、エナンチオ選択的な反応が可能になる。
R7は好ましくはフェニル基である。R8は、好ましくは水素原子又はフェニル基である。R9は、好ましくはフェニル基である。 In the reaction system, further formula IV
Figure 2009215240
 Or the formula V
Figure 2009215240
 Or an enantiomer thereof (R 6 is a hydrogen atom or an alkyl group; R 7 has an optionally substituted aliphatic hydrocarbon group or substituent. An aromatic hydrocarbon group which may have a substituent, or a heterocyclic group which may have a substituent; R 8 has a hydrogen atom, an aliphatic hydrocarbon group which may have a substituent, or a substituent; a good aromatic hydrocarbon group, or an optionally substituted heterocyclic group; R 7 and R 8 may form a ring; R 9 can be the respective same An aliphatic hydrocarbon group which may be different and may have a substituent, or an aromatic hydrocarbon group which may have a substituent; R 10 is a cyano group or an amino group) It is preferable to carry out the reaction.
Addition of the asymmetric ligand enables enantioselective reaction.
R 7 is preferably a phenyl group. R 8 is preferably a hydrogen atom or a phenyl group. R 9 is preferably a phenyl group.

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。   The following examples illustrate the invention but are not intended to limit the invention.

なお、以下の各実施例において、特に記載しない限り、NMRスペクトルはNMR装置（型式JEOL JNM-ECX400、日本電子社製）を用い、重クロロホルムを溶媒として測定した。1H NMRではテトラメチルシラン(TMS; d = 0.00 ppm)を、13C NMRでは非重水素化溶媒シグナル(CDCl3; d = 77.00 ppm)を内部標準とした。IRはIR装置（型式JASCO FT/IR-610、日本分光社製）を用いて測定した。ESI高分解能質量分析スペクトル(ESI-HRMS)はHRMS 装置（型式BRUKER DALTONICS BioTOF II、ブルカー・ダルトニクス社製）を用いて測定した。分取薄層クロマトグラフィーは薄層クロマトグラフィー装置（型式Wakogel B-5F、和光純薬工業社製）を用いて行った。
ケトンは市販品を使用前に蒸留精製して用いた。ピナコリルアリルボレートは文献（Y.-C. Teo, J.-D. Goh, T.-P. Loh, Org. Lett. 2005, 7, 2743-2745.）の方法を改良して調製した。ピナコリルa-メチルアリルボレートは文献（R. Wada, K. Oisaki, M. Kanai, M. Shibasaki, J. Am. Chem. Soc. 2004, 126, 8910-8911）の方法で調製した。金属インジウム(100 mesh-powder; 99.99%)はAldrich社から購入したものをそのまま用いた。 In the following examples, unless otherwise specified, NMR spectra were measured using an NMR apparatus (model JEOL JNM-ECX400, manufactured by JEOL Ltd.) and deuterated chloroform as a solvent. In 1 H NMR, tetramethylsilane (TMS; d = 0.00 ppm) was used as an internal standard, and in 13 C NMR, a non-deuterated solvent signal (CDCl 3 ; d = 77.00 ppm) was used as an internal standard. IR was measured using an IR apparatus (model JASCO FT / IR-610, manufactured by JASCO Corporation). ESI high resolution mass spectrometry spectrum (ESI-HRMS) was measured using an HRMS apparatus (model BRUKER DALTONICS BioTOF II, manufactured by Bruker Daltonics). Preparative thin layer chromatography was performed using a thin layer chromatography apparatus (model Wakogel B-5F, manufactured by Wako Pure Chemical Industries, Ltd.).
The ketone was used after being purified by distillation before use. Pinacolyl allyl borate was prepared by improving the method of literature (Y.-C. Teo, J.-D. Goh, T.-P. Loh, Org. Lett. 2005, 7, 2743-2745.). Pinacolyl a-methylallylborate was prepared by literature methods (R. Wada, K. Oisaki, M. Kanai, M. Shibasaki, J. Am. Chem. Soc. 2004, 126, 8910-8911). Indium metal (100 mesh-powder; 99.99%) purchased from Aldrich was used as it was.

１）ケトンとピナコリルアリルボレートの不斉アリル化反応の一般操作
撹拌子を入れた3 mLのスクリューバイアルに０価のインジウム(2.9 mg; 5mol%) およびインダ-ビス（オキサゾリン）配位子((+)-2,2'-methylenebis[(3aR,8aS)-3a,8a-dihydro-8H-indeno[1,2-d]oxazole] 8.3 mg; 5mol%)を加えた。これにケトン(0.5mmol) およびピナコリルアリルボレート(0.75 mmol; 1.5equiv)を順に加え、純水（Millipore製、0.5 mL; 1 M）を加えた。10度で24時間激しく撹拌した後、塩化メチレンを加え、有機相を分離したのち、水相から塩化メチレンで3回抽出した。有機相を合わせて硫酸ナトリウムで乾燥し、濾過後に減圧濃縮した。得られた粗生成物を分取薄層クロマトグラフィー（ヘキサン／酢酸エチル = 19:1 - 5:1）で精製し、生成物である三級ホモアリルアルコールを得た。 1) General operation of asymmetric allylation reaction between ketone and pinacolylallylborate A 0 mL indium (2.9 mg; 5 mol%) and inda-bis (oxazoline) ligand (into a 3 mL screw vial containing a stirring bar (+)-2,2′-methylenebis [(3aR, 8aS) -3a, 8a-dihydro-8H-indeno [1,2-d] oxazole] 8.3 mg; 5 mol%) was added. To this, ketone (0.5 mmol) and pinacolyl allyl borate (0.75 mmol; 1.5 equiv) were sequentially added, and pure water (Millipore, 0.5 mL; 1 M) was added. After vigorously stirring at 10 degrees for 24 hours, methylene chloride was added, the organic phase was separated, and extracted from the aqueous phase with methylene chloride three times. The organic phases were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting crude product was purified by preparative thin layer chromatography (hexane / ethyl acetate = 19: 1-5: 1) to obtain the product tertiary homoallyl alcohol.

この反応は原料のケトンとしてアセトフェノンを用い、15℃で反応を行い、以下の無色液体の生成物（2-Phenylpent-4-en-2-ol）を、収率68%、52% eeで得た。

Figure 2009215240
1H NMR (CDCl3, 400 MHz): δ = 1.55 (s, 3H), 2.08 (br s, 1H), 2.50 (dd, J = 8.4 Hz, J = 13.2 Hz, 1H), 2.69 (dd, J = 6.4 Hz, J = 13.2 Hz, 1H), 5.11-5.16 (m, 2H), 5.57-5.68 (m, 1H), 7.22-7.45 (m, 5H); 13C NMR (CDCl3, 100 MHz): δ= 29.87, 48.43, 73.59, 119.44, 124.73, 126.59, 128.14, 133.65, 147.61; IR (neat): n = 3433, 3075, 2978, 2930, 1639, 1494, 1446, 1374, 1069, 999, 915, 866, 767, 700, 658, 567 cm-1; HRMS (ESI) calcd. for C11H13 + = [M-OH]+: m/z = 145.1012, found: m/z = 145.1018; HPLC (DAICEL CHIRALPAK OJ-H, hexane/2-propanol = 98/2, 0.8 mL/min) tR = 15.2 min (minor), 18.0 min (major). In this reaction, acetophenone was used as a raw material ketone, and the reaction was carried out at 15 ° C to obtain the following colorless liquid product (2-Phenylpent-4-en-2-ol) with a yield of 68% and 52% ee. It was.
Figure 2009215240
 1 H NMR (CDCl 3 , 400 MHz): δ = 1.55 (s, 3H), 2.08 (br s, 1H), 2.50 (dd, J = 8.4 Hz, J = 13.2 Hz, 1H), 2.69 (dd, J = 6.4 Hz, J = 13.2 Hz, 1H), 5.11-5.16 (m, 2H), 5.57-5.68 (m, 1H), 7.22-7.45 (m, 5H); 13 C NMR (CDCl 3 , 100 MHz): δ = 29.87, 48.43, 73.59, 119.44, 124.73, 126.59, 128.14, 133.65, 147.61; IR (neat): n = 3433, 3075, 2978, 2930, 1639, 1494, 1446, 1374, 1069, 999, 915, 866 , 767, 700, 658, 567 cm -1 ; HRMS (ESI) calcd.for C 11 H 13 + = [M-OH] + : m / z = 145.1012, found: m / z = 145.1018; HPLC (DAICEL CHIRALPAK OJ-H, hexane / 2-propanol = 98/2, 0.8 mL / min) t R = 15.2 min (minor), 18.0 min (major).

２）ケトンとピナコリルα-メチルアリルボレートのジアステレオ選択的アリル化反応の一般操作
撹拌子を入れた3 mLのスクリューバイアルに０価のインジウム(2.9 mg; 5 mol%)を加えた。これに純水（Millipore製、0.5 mL; 1 M）を加え、ケトン(0.5 mmol) およびピナコリルa-メチルアリルボレート(0.55 mmol; 1.1 equiv)を順に加え、純水（Millipore製、0.5 mL; 1 M）を加えた。指定された温度で24時間激しく撹拌した後、塩化メチレンを加え、有機相を分離したのち、水相から塩化メチレンで3回抽出した。有機相を合わせて硫酸ナトリウムで乾燥し、濾過後に減圧濃縮した。得られた粗生成物を分取薄層クロマトグラフィー（ヘキサン／酢酸エチル = 19:1 - 5:1）で精製し、生成物であるα-置換三級ホモアリルアルコールを得た。 2) General procedure for diastereoselective allylation of ketone and pinacolyl α-methylallylborate Zero-valent indium (2.9 mg; 5 mol%) was added to a 3 mL screw vial containing a stir bar. To this was added pure water (Millipore, 0.5 mL; 1 M), ketone (0.5 mmol) and pinacolyl a-methylallylborate (0.55 mmol; 1.1 equiv) were added in this order, and pure water (Millipore, 0.5 mL; 1 M) was added. After vigorously stirring at the specified temperature for 24 hours, methylene chloride was added, the organic phase was separated, and then extracted from the aqueous phase with methylene chloride three times. The organic phases were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting crude product was purified by preparative thin layer chromatography (hexane / ethyl acetate = 19: 1-5: 1) to obtain the product α-substituted tertiary homoallyl alcohol.

この反応は原料のケトンとしてアセトフェノンを用い、0℃で反応を行い、以下の無色液体の生成物（3-Methyl-2-phenylpent-4-en-2-ol）を、収率98%、syn/anti = >50:1で得た。

Figure 2009215240
syn-isomer: 1H NMR (CDCl3, 400 MHz): δ= 0.85 (d, J = 7.5 Hz, 3H), 1.57 (s, 3H), 1.91 (s, 1H), 2.59 (quint, J = 7.5 Hz, 1H), 5.11-5.16 (m, 2H), 5.80-5.88 (m, 1H), 7.22-7.45 (m, 5H); 13C NMR (CDCl3, 100 MHz): δ= 14.78, 28.50, 48.94, 75.70, 116.3, 125.2, 126.4, 127.9, 139.9, 146.9; HRMS (ESI) calcd. for C12H15 + = [M-OH]+: m/z = 159.1168, found: m/z = 159.117;
anti-isomer: 1H NMR (CDCl3, 400 MHz): δ= 0.99 (d, J = 6.9 Hz, 3H), 1.55 (s, 3H), 2.00 (s, 1H), 2.60 (quint, J = 7.5 Hz, 1H), 5.10-5.16 (m, 2H), 5.70-5.76 (m, 1H), 7.22-7.45 (m, 5H); 13C NMR (CDCl3, 100 MHz): δ= 14.09, 25.85, 48.7, 75.75, 116.6, 125.4, 126.6, 127.9, 139.9, 147.0; HRMS (ESI) calcd. for C12H15 + = [M-OH]+: m/z = 159.1168, found: m/z = 159.1161. This reaction was carried out at 0 ° C. using acetophenone as a raw material ketone, and the following colorless liquid product (3-Methyl-2-phenylpent-4-en-2-ol) was obtained in a yield of 98%, syn / anti => 50: 1.
Figure 2009215240
 syn-isomer: 1 H NMR (CDCl 3 , 400 MHz): δ = 0.85 (d, J = 7.5 Hz, 3H), 1.57 (s, 3H), 1.91 (s, 1H), 2.59 (quint, J = 7.5 Hz, 1H), 5.11-5.16 (m, 2H), 5.80-5.88 (m, 1H), 7.22-7.45 (m, 5H); 13 C NMR (CDCl 3 , 100 MHz): δ = 14.78, 28.50, 48.94 , 75.70, 116.3, 125.2, 126.4, 127.9, 139.9, 146.9; HRMS (ESI) calcd.for C 12 H 15 + = [M-OH] + : m / z = 159.1168, found: m / z = 159.117;
anti-isomer: 1 H NMR (CDCl 3 , 400 MHz): δ = 0.99 (d, J = 6.9 Hz, 3H), 1.55 (s, 3H), 2.00 (s, 1H), 2.60 (quint, J = 7.5 Hz, 1H), 5.10-5.16 (m, 2H), 5.70-5.76 (m, 1H), 7.22-7.45 (m, 5H); 13 C NMR (CDCl 3 , 100 MHz): δ = 14.09, 25.85, 48.7 , 75.75, 116.6, 125.4, 126.6, 127.9, 139.9, 147.0; HRMS (ESI) calcd.for C 12 H 15 + = [M-OH] + : m / z = 159.1168, found: m / z = 159.1161.

Claims (3)

水中で、触媒として０価のインジウムの存在下、式I
Figure 2009215240
 で表されるケトン（R1, R2は、それぞれ同一でも異なっていてもよく、置換基を有していてもよい脂肪族炭化水素基、置換基を有していてもよい芳香族炭化水素基、又は置換基を有していてもよい複素環基；R1とR2は環を形成していてもよい）と、式II
Figure 2009215240
 で表されるアリルボロネート又はα-置換アリルボロネート（R3は、水素原子、置換基を有していてもよい脂肪族炭化水素基、置換基を有していてもよい芳香族炭化水素基、アルコキシ基、又はハロゲン基；R4は水素原子、置換基を有していてもよい脂肪族炭化水素基、置換基を有していてもよい芳香族炭化水素基、又は置換基を有していてもよい複素環基；R5はアルキル基）とを反応させることにより、式III
Figure 2009215240
 で表されるホモアリルアルコールを得るホモアリルアルコールの製造方法。 In water, in the presence of zerovalent indium as a catalyst, the formula I
Figure 2009215240
 (R 1 and R 2 , which may be the same or different, each may be an aliphatic hydrocarbon group which may have a substituent, or an aromatic hydrocarbon which may have a substituent A heterocyclic group which may have a group or a substituent; R 1 and R 2 may form a ring) and formula II
Figure 2009215240
 Allyl boronate or α-substituted allyl boronate represented by (R 3 is a hydrogen atom, an aliphatic hydrocarbon group which may have a substituent, an aromatic hydrocarbon which may have a substituent Group, alkoxy group, or halogen group; R 4 has a hydrogen atom, an aliphatic hydrocarbon group which may have a substituent, an aromatic hydrocarbon group which may have a substituent, or a substituent; By reacting with an optionally substituted heterocyclic group; R 5 is an alkyl group).
Figure 2009215240
 The manufacturing method of the homoallyl alcohol which obtains the homoallyl alcohol represented by these. さらに、式IV
Figure 2009215240
 又は、式V
Figure 2009215240
 で表される不斉配位子又はこれらの鏡像異性体（R6は、水素原子又はアルキル基；R7は、置換基を有していてもよい脂肪族炭化水素基、置換基を有していてもよい芳香族炭化水素基、又は置換基を有していてもよい複素環基；R8は、水素原子、置換基を有していてもよい脂肪族炭化水素基、置換基を有していてもよい芳香族炭化水素基、又は置換基を有していてもよい複素環基；R7とR8は環を形成していてもよい；R9は、それぞれ同じであっても異なっていてもよく、置換基を有していてもよい脂肪族炭化水素基、又は置換基を有していてもよい芳香族炭化水素基；R10はシアノ基またはアミノ基）を共存させる請求項１に記載のホモアリルアルコールの製造方法。 Furthermore, the formula IV
Figure 2009215240
 Or the formula V
Figure 2009215240
 Or an enantiomer thereof (R 6 is a hydrogen atom or an alkyl group; R 7 has an optionally substituted aliphatic hydrocarbon group or substituent. An aromatic hydrocarbon group which may have a substituent, or a heterocyclic group which may have a substituent; R 8 has a hydrogen atom, an aliphatic hydrocarbon group which may have a substituent, or a substituent; a good aromatic hydrocarbon group, or an optionally substituted heterocyclic group; R 7 and R 8 may form a ring; R 9 can be the respective same Claims that an aliphatic hydrocarbon group which may be different and may have a substituent, or an aromatic hydrocarbon group which may have a substituent; R 10 is a cyano group or an amino group) Item 2. A method for producing homoallyl alcohol according to Item 1. 式IV
Figure 2009215240
 又は、式V
Figure 2009215240
 で表される不斉配位子又はこれらの鏡像異性体（R6は、水素原子又はアルキル基；R7は、置換基を有していてもよい脂肪族炭化水素基、置換基を有していてもよい芳香族炭化水素基、又は置換基を有していてもよい複素環基；R8は、水素原子、置換基を有していてもよい脂肪族炭化水素基、置換基を有していてもよい芳香族炭化水素基、又は置換基を有していてもよい複素環基；R7とR8は環を形成していてもよい；R9は、それぞれ同じであっても異なっていてもよく、置換基を有していてもよい脂肪族炭化水素基、又は置換基を有していてもよい芳香族炭化水素基；R10はシアノ基またはアミノ基）と、０価のインジウムからなる不斉触媒。 Formula IV
Figure 2009215240
 Or the formula V
Figure 2009215240
 Or an enantiomer thereof (R 6 is a hydrogen atom or an alkyl group; R 7 has an optionally substituted aliphatic hydrocarbon group or substituent. An aromatic hydrocarbon group which may have a substituent, or a heterocyclic group which may have a substituent; R 8 has a hydrogen atom, an aliphatic hydrocarbon group which may have a substituent, or a substituent; a good aromatic hydrocarbon group, or an optionally substituted heterocyclic group; R 7 and R 8 may form a ring; R 9 can be the respective same An aliphatic hydrocarbon group which may be different and may have a substituent, or an aromatic hydrocarbon group which may have a substituent; R 10 is a cyano group or an amino group) and zero valence Asymmetric catalyst consisting of indium.
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JP2008255093A (en) * 2007-03-09 2008-10-23 Japan Science & Technology Agency Method for producing homoallyl alcohol or homoallyl hydrazide
JP2014514273A (en) * 2011-03-07 2014-06-19 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Method for asymmetric methylallylation in the presence of 2,2-substituted 1,1-bi-2-naphthol catalyst

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JPS63222123A (en) * 1987-03-11 1988-09-16 Kanto Denka Kogyo Kk Production of homoallyl alcohol
JP2006265127A (en) * 2005-03-22 2006-10-05 Fuji Photo Film Co Ltd Method for producing homoallyl alcohol compound
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008255093A (en) * 2007-03-09 2008-10-23 Japan Science & Technology Agency Method for producing homoallyl alcohol or homoallyl hydrazide
JP2014514273A (en) * 2011-03-07 2014-06-19 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Method for asymmetric methylallylation in the presence of 2,2-substituted 1,1-bi-2-naphthol catalyst

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