JP5046213B2

JP5046213B2 - Process for producing optically active alcohol compounds

Info

Publication number: JP5046213B2
Application number: JP2009059286A
Authority: JP
Inventors: 修小林; 雅也小久保; 武詩内藤
Original assignee: Japan Science and Technology Agency; National Institute of Japan Science and Technology Agency
Current assignee: Japan Science and Technology Agency; National Institute of Japan Science and Technology Agency
Priority date: 2009-03-12
Filing date: 2009-03-12
Publication date: 2012-10-10
Anticipated expiration: 2029-03-12
Also published as: JP2010207767A

Description

この発明は、エポキシドの開環反応により光学活性アルコールを製造する方法に関し、より詳細には、水溶液中でエポキシドを複素環化合物又はアミンにより不斉開環反応させて光学活性アルコール化合物を製造する方法に関する。 More particularly, the present invention relates to a method for producing an optically active alcohol compound by asymmetric ring-opening reaction of an epoxide with a heterocyclic compound or an amine in an aqueous solution. About.

近年、コストや安全性の観点からだけでなく、環境負荷の低減を目的として、従来は有機溶媒中で実施されていた合成反応を水中で達成しようとする試みが活発化している。既に本願発明者らは、界面活性剤型ルイス酸を用いた水溶液中での脱水エステル化反応や不斉ヒドロキシメチル化反応など種々の水系反応を開発している（非特許文献１）。
また、エポキシドは歪みが大きく、種々の求核剤と容易に反応して開環体を与えることから、アミンを求核剤とした水溶液中でのエポキシドの開環反応によるβ−アミノアルコールの合成方法が知られていた。
さらに近年、本願発明者らは、光学活性なビピリジン化合物を不斉配位子とした触媒を用いて、水溶液中での芳香族アミンを求核剤としたメソエポキシドの触媒的不斉開環反応を見出している（非特許文献２）。
一方、インドール誘導体などのヘテロ芳香族化合物には興味深い生理活性を示すものが多く、光学活性ヘテロ芳香族化合物を触媒的不斉反応により合成した例として、クロミウムーサレン錯体を用いたメソエポキシドのインドールによる触媒的不斉開環反応が知られている（非特許文献３）。
また、本発明者らは、光学活性なビピリジン化合物とＳｃ等を含むルイス酸とから成る不斉触媒を用いて、光学活性アルコールを合成する方法を開発した（特許文献１、２）。 In recent years, not only from the viewpoint of cost and safety, but also for the purpose of reducing environmental burden, attempts to achieve a synthesis reaction that has been conventionally performed in an organic solvent in water have become active. The present inventors have already developed various aqueous reactions such as a dehydration esterification reaction and an asymmetric hydroxymethylation reaction in an aqueous solution using a surfactant type Lewis acid (Non-patent Document 1).
Epoxides are highly distorted and easily react with various nucleophiles to give ring-opened products. Therefore, β-amino alcohols are synthesized by ring-opening reactions of epoxides in aqueous solutions containing amines as nucleophiles. The method was known.
More recently, the present inventors have used a catalyst having an optically active bipyridine compound as an asymmetric ligand, and a catalytic asymmetric ring-opening reaction of mesoepoxide using an aromatic amine as a nucleophile in an aqueous solution. (Non-Patent Document 2).
On the other hand, many heteroaromatic compounds such as indole derivatives have interesting physiological activities. Examples of synthesizing optically active heteroaromatic compounds by catalytic asymmetric reactions include mesoepoxide indoles using chromium-salen complexes. Catalytic asymmetric ring-opening reaction is known (Non-patent Document 3).
In addition, the present inventors have developed a method for synthesizing an optically active alcohol using an asymmetric catalyst comprising an optically active bipyridine compound and a Lewis acid containing Sc or the like (Patent Documents 1 and 2).

特開2007-238540JP2007-238540 特開2007-031344JP2007-031344

J. Am. Chem. Soc. 126, 12236-12237(2004).J. Am. Chem. Soc. 126, 12236-12237 (2004). Org. Lett. 7, 4593-4595(2005)Org. Lett. 7, 4593-4595 (2005) Angew. Chem. Int. Ed. 2004, 43, 84.Angew. Chem. Int. Ed. 2004, 43, 84.

本発明は、水溶液中で光学活性な配位子を有するルイス酸触媒を用いて、エポキシドの複素環化合物又はアミンによる不斉開環反応により、光学活性アルコール化合物を高収率かつ高立体選択的に製造する方法を提供することを目的とする。 The present invention provides an optically active alcohol compound in a high yield and a high stereoselectivity by an asymmetric ring-opening reaction of an epoxide with a heterocyclic compound or an amine using a Lewis acid catalyst having an optically active ligand in an aqueous solution. It aims at providing the method of manufacturing to.

本発明者らは、従来のＳｃを含むルイス酸と光学活性なビピリジン化合物とから成る不斉触媒（特許文献１、２）の金属種を銅族元素又は亜鉛族元素に変更することにより、従来得られていた光学活性アルコール（特許文献１、２）の鏡像異性体を合成できることを見出し、本発明を完成させるに至った。 The present inventors changed the metal species of the asymmetric catalyst (Patent Documents 1 and 2) composed of a conventional Lewis acid containing Sc and an optically active bipyridine compound to a copper group element or a zinc group element. The inventors have found that enantiomers of the obtained optically active alcohols (Patent Documents 1 and 2) can be synthesized, and have completed the present invention.

即ち、本発明は、下式(化１)

（式中、Ｒ^１は、炭素数が３以上のアルキル基又はアリール基を表し、Ｒ^２は、水素原子又は炭素数１〜４のアルキル基若しくはアルコキシ基を表し、Ｘは、−ＯＨ、又は−ＳＨを表す。）で表される配位子又はその対掌体とＭ（ＯＳＯ_２Ｒ^３）_２又はＭ（ＯＳＯ_３Ｒ^３）_２（式中、Ｍは銅族元素又は亜鉛族元素を表し、Ｒ^３は炭素数が６以上の脂肪族炭化水素基、芳香族炭化水素基又はパーフルオロアルキル基を表す。）で表されるルイス酸とを混合させて得られる、エポキシドの複素環化合物又はアミンによる不斉開環反応により、光学活性アルコール化合物を製造するための触媒である。

That is, the present invention has the following formula (Formula 1)

(Wherein R ¹ represents an alkyl group or aryl group having 3 or more carbon atoms, R ² represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms or an alkoxy group, and X represents —OH, or -SH represents a ligand or an enantiomer thereof and M (OSO ₂ R ³ ) ₂ or M (OSO ₃ R ³ ) ₂ (wherein M represents a copper group element or a zinc group element). R ³ represents an aliphatic hydrocarbon group having 6 or more carbon atoms, an aromatic hydrocarbon group or a perfluoroalkyl group.), And a heterocyclic compound of an epoxide obtained by mixing with a Lewis acid represented by Or it is a catalyst for manufacturing an optically active alcohol compound by asymmetric ring-opening reaction with an amine .

また、本発明は、水溶液中又は水と有機溶媒との混合溶媒中で、上記触媒の存在下で、下式（式２）

（式中、Ｒ^４及びＲ^５は、それぞれ同じであっても異なってもよく、置換基を有していてもよい脂肪族炭化水素基、芳香族炭化水素基又は複素環基を表す。）で表されるエポキシドと、
下式

（式中、Ｙ^１は＝ＣＨ−又は＝Ｎ−を表し、Ｙ^２は＝ＣＲ^８−又は＝Ｎ−（式中、Ｒ^８は水素原子又は炭化水素基を表す。）を表し、Ｚは−ＮＨ−、−ＮＲ^９−（式中、Ｒ^９は水素原子以外の炭化水素基を表す。）、−Ｏ−又は−Ｓ−を表す。但し、Ｙ^１が＝Ｎ−の場合には、Ｚは−ＮＨ−を表す。Ｒ^６及びＲ^７は共同して置換基を有していてもよい芳香環又は複素芳香環を形成する。）で表される複素環化合物とを反応させることから成る下式

（Ｙ^１が＝ＣＨ−の場合は式（１）又はその対掌体で表され、Ｙ^１が＝Ｎ−の場合は式（２）又はその対掌体で表され、式中、Ｙ^２、Ｒ^４〜Ｒ^７は上記と同様に定義される。）で表される光学活性アルコール化合物の製法である。
Further, the present invention provides the following formula (formula 2) in the presence of the above catalyst in an aqueous solution or a mixed solvent of water and an organic solvent.

(In the formula, R ⁴ and R ⁵ may be the same or different, and each represents an aliphatic hydrocarbon group, an aromatic hydrocarbon group or a heterocyclic group which may have a substituent.) An epoxide represented by
The following formula

(Wherein Y ¹ represents ═CH— or ═N—, Y ² represents ═CR ⁸ — or ═N— (wherein R ⁸ represents a hydrogen atom or a hydrocarbon group), and Z represents —NH—, —NR ⁹ — (wherein R ⁹ represents a hydrocarbon group other than a hydrogen atom), —O— or —S—, provided that when Y ¹ is ═N— Z represents —NH—, and R ⁶ and R ⁷ jointly form an aromatic ring or a heteroaromatic ring which may have a substituent. The following formula

(If ^{Y 1} is = CH- is represented by the formula (1) or its enantiomer, if ^{Y 1} is = N- in which formula (2) or its enantiomer, wherein, ^{Y 2} , R ^{4 to} R ⁷ are defined in the same manner as described above.).

更に、本発明は、水溶液中又は水と有機溶媒との混合溶媒中で、上記触媒の存在下で、下式（式２）

（式中、Ｒ^４及びＲ^５は、それぞれ同じであっても異なってもよく、置換基を有していてもよい脂肪族炭化水素基、芳香族炭化水素基又は複素環基を表す。）で表されるエポキシドと、Ｒ^１０Ｒ^１１ＮＨ（式中、Ｒ^１０及びＲ^１１は、それぞれ同じであっても異なってもよく、水素原子、置換基を有していてもよい脂肪族炭化水素基、芳香族炭化水素基又は複素環基を表し、但し、Ｒ^１０及びＲ^１１の少なくとも一方は、置換基を有していてもよい芳香族炭化水素基又は複素環基である。）で表される１級又は２級アミン化合物とを反応させることから成る下式（化５）

（式中、Ｒ^４、Ｒ^５、Ｒ^１０及びＲ^１１は上記と同様を表す。）又はその対掌体で表される光学活性β−アミノアルコール化合物の製法である。
Furthermore, the present invention provides the following formula (Formula 2) in the presence of the above catalyst in an aqueous solution or a mixed solvent of water and an organic solvent.

(In the formula, R ⁴ and R ⁵ may be the same or different, and each represents an aliphatic hydrocarbon group, an aromatic hydrocarbon group or a heterocyclic group which may have a substituent.) And an epoxide represented by R ¹⁰ R ¹¹ NH (wherein R ¹⁰ and R ¹¹ may be the same or different and each may be a hydrogen atom or an aliphatic hydrocarbon optionally having a substituent) A group, an aromatic hydrocarbon group or a heterocyclic group, provided that at least one of R ¹⁰ and R ¹¹ is an optionally substituted aromatic hydrocarbon group or heterocyclic group. Comprising the reaction of a primary or secondary amine compound

(Wherein R ⁴ , R ⁵ , R ¹⁰ and R ¹¹ represent the same as above) or a method for producing an optically active β-aminoalcohol compound represented by an enantiomer thereof.

本発明で用いる触媒は、下記構造

の配位子又はその対掌体とＭ（ＯＳＯ_２Ｒ^３）_２又はＭ（ＯＳＯ_３Ｒ^３）_２で表されるルイス酸とを混合させて得られる。
The catalyst used in the present invention has the following structure:

Or an enantiomer thereof and a Lewis acid represented by M (OSO ₂ R ³ ) ₂ or M (OSO ₃ R ³ ) ₂ are obtained.

Ｒ^１は、アルキル基又はアリール基を表す。このアルキル基は嵩高いこと、具体的には炭素数が３以上かつ分岐していることを要する。このアリール基はメトキシ基やハロゲン原子等の置換基を有していてもよい。
Ｒ^２は水素原子又は炭素数１〜４のアルキル基若しくはアルコキシ基、好ましくは水素原子を表す。
Ｘは−ＯＨ又は−ＳＨを、好ましくは−ＯＨを表す。 R ¹ represents an alkyl group or an aryl group. This alkyl group needs to be bulky, specifically having 3 or more carbon atoms and being branched. This aryl group may have a substituent such as a methoxy group or a halogen atom.
R ² represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms or an alkoxy group, preferably a hydrogen atom.
X represents —OH or —SH, preferably —OH.

一般式Ｍ（ＯＳＯ_２Ｒ^３）_２又はＭ（ＯＳＯ_３Ｒ^３）_２で表されるルイス酸において、金属Ｍは銅族元素又は亜鉛族元素、好ましくはＣｕ又はＺｎを表す。
Ｒ^３は、炭素数が６以上、好ましくは６〜２０の、脂肪族炭化水素基、芳香族炭化水素基又はパーフルオロアルキル基を表し、より好ましくは炭素数が６〜２０のアルキル基又はアルキルアリール基を表す。即ち、有機スルホン酸（−ＯＳＯ_２Ｒ^３）としてアルカンスルホン酸基やアルキルアレーンスルホン酸基が好ましく、例えば、ドデカンスルホン酸基、オクチルベンゼンスルホン酸基又はドデシルベンゼンスルホン酸基などが挙げられる。硫酸エステル（−ＯＳＯ_３Ｒ^３）としては、硫酸モノアルキルエステルが好ましく、例えば、硫酸ドデシルエステルが挙げられる。Ｒ^３の炭素鎖が短い場合、水溶媒中では収率が大きく低下する。 In the Lewis acid represented by the general formula M (OSO ₂ R ³ ) ₂ or M (OSO ₃ R ³ ) ₂ , the metal M represents a copper group element or a zinc group element, preferably Cu or Zn.
R ³ represents an aliphatic hydrocarbon group, an aromatic hydrocarbon group or a perfluoroalkyl group having 6 or more carbon atoms, preferably 6 to 20 carbon atoms, more preferably an alkyl group or alkyl having 6 to 20 carbon atoms. Represents an aryl group. That is, as the organic sulfonic acid (—OSO ₂ R ³ ), an alkanesulfonic acid group or an alkylarenesulfonic acid group is preferable, and examples thereof include a dodecanesulfonic acid group, an octylbenzenesulfonic acid group, and a dodecylbenzenesulfonic acid group. The sulfuric acid ester (-OSO _³ R _3), monoalkyl esters are preferable sulfate, for example, sulfuric acid dodecyl ester. When the carbon chain of R ³ is short, the yield is greatly reduced in an aqueous solvent.

触媒調整時の金属Ｍと配位子とのモル比は１：１〜１：２付近が好ましく、より好ましくは１：１〜１．０：１．２である。
溶媒は、水又は水と有機溶媒との混合溶媒、好ましくは水が用いられる。有機溶媒は基質が固体で水に分散または溶解しにくい場合などに使用する。有機溶媒としては水と混合する有機溶媒が好ましく、ジメトキシエタン（ＤＭＥ）、テトラヒドロフラン（ＴＨＦ）、アセトニトリル、ジオキサン、炭素数が４以下のアルコールなどが挙げられる。また、水と有機溶媒との混合比（体積）は、一般的には水が５０％以上、より好ましくは９０％以上である。
触媒の調整温度に制限はないが室温付近が好ましく、調整時間は通常１５分間〜３時間程度である。
この配位子とＭ（ＯＳＯ_２Ｒ^３）_２又はＭ（ＯＳＯ_３Ｒ^３）_２で表されるルイス酸とを溶媒中で混合すると、配位子がＭ^２＋に配位し、錯体を形成する。
反応に用いる触媒の量は、通常、エポキシドに対して０．３〜５モル％程度であるが、多くの場合１モル％で良好な結果を与える。 The molar ratio between the metal M and the ligand during catalyst preparation is preferably in the vicinity of 1: 1 to 1: 2, more preferably 1: 1 to 1.0: 1.2.
As the solvent, water or a mixed solvent of water and an organic solvent, preferably water is used. An organic solvent is used when the substrate is solid and difficult to disperse or dissolve in water. As the organic solvent, an organic solvent mixed with water is preferable, and examples thereof include dimethoxyethane (DME), tetrahydrofuran (THF), acetonitrile, dioxane, alcohol having 4 or less carbon atoms, and the like. The mixing ratio (volume) of water and organic solvent is generally 50% or more, more preferably 90% or more of water.
Although there is no restriction | limiting in the adjustment temperature of a catalyst, the room temperature vicinity is preferable and adjustment time is about 15 minutes-about 3 hours normally.
When this ligand and a Lewis acid represented by M (OSO ₂ R ³ ) ₂ or M (OSO ₃ R ³ ) ₂ are mixed in a solvent, the ligand coordinates to M ²⁺ to form a complex. To do.
The amount of the catalyst used in the reaction is usually about 0.3 to 5 mol% with respect to the epoxide, but in many cases 1 mol% gives good results.

本発明で用いるエポキシドの構造としては、下式(化２)

で表されるエポキシドが用いられる。
Ｒ^４及びＲ^５は、それぞれ同じであっても異なってもよく、好ましくは同じ（即ち、メソエポキシド）であって、置換基を有していてもよい脂肪族炭化水素基、芳香族炭化水素基又は複素環基、好ましくはアルキル基、アリール基又はアルキルアリール基、より好ましくはアリール基を表す。アリール基としてはフェニル基又ナフチル基が挙げられ、好ましくはフェニル基である。Ｒ^４及びＲ^５は、ハロゲン原子、水酸基、ニトロ基、シアノ基、エステル基、エーテル基、チオエーテル基、アミド基等の置換基を有していてもよい。 The structure of the epoxide used in the present invention is as follows:

The epoxide represented by these is used.
R ⁴ and R ⁵ may be the same or different, preferably the same (ie, meso epoxide), and may have an aliphatic hydrocarbon group or aromatic hydrocarbon which may have a substituent. Represents a group or a heterocyclic group, preferably an alkyl group, an aryl group or an alkylaryl group, more preferably an aryl group. Examples of the aryl group include a phenyl group and a naphthyl group, and a phenyl group is preferable. R ⁴ and R ⁵ may have a substituent such as a halogen atom, a hydroxyl group, a nitro group, a cyano group, an ester group, an ether group, a thioether group, or an amide group.

エポキシドへの求核剤となる複素環化合物は、下式

で表される。 Heterocyclic compounds that are nucleophiles for epoxides are

It is represented by

Ｙ^１は、＝ＣＨ−又は＝Ｎ−を表す。
Ｙ^２は＝ＣＲ^８−又は＝Ｎ−（式中、Ｒ^８は水素原子又は炭化水素基を表す。）を表す。
Ｚは−ＮＨ−、−ＮＲ^９−（式中、Ｒ^９は水素原子以外の炭化水素基を表す。）、−Ｏ−又は−Ｓ−を表す。但し、Ｙ^１が＝Ｎ−の場合には、Ｚは−ＮＨ−を表す。
これらの炭化水素基としては、特に限定は無いが、アルキル基、シクロアルキル基、アリール基及びアラルキル基等が挙げられる。
Ｒ^６及びＲ^７は共同して置換基を有していてもよい芳香環又は複素芳香環、好ましくは芳香環を形成する。
この芳香環としては、ベンゼン、ビフェニル、テルフェニル、ナフタレン、アントラセン等、好ましくはベンゼンを挙げることができる。
複素芳香環としては、ピリジン、ピリミジン等を挙げることができる。
これらは置換基として、任意の位置に、ハロゲン原子、アルキル基、アルケニル基、アルキニル基、シクロアルキル低級アルキル基、アラルキル基、アルコキシ基、ニトロ基、水酸基、低級アルコキシカルボニル基、ハロゲン原子等を有してもよい。 Y ¹ represents = CH- or = N-.
Y ² represents ═CR ⁸ — or ═N— (wherein R ⁸ represents a hydrogen atom or a hydrocarbon group).
Z represents —NH—, —NR ⁹ — (wherein R ⁹ represents a hydrocarbon group other than a hydrogen atom), —O— or —S—. However, when ^{Y 1} is = N- of, Z is representative of -NH-.
These hydrocarbon groups are not particularly limited, and examples thereof include alkyl groups, cycloalkyl groups, aryl groups, and aralkyl groups.
R ⁶ and R ⁷ together form an aromatic ring or a heteroaromatic ring which may have a substituent, preferably an aromatic ring.
Examples of the aromatic ring include benzene, biphenyl, terphenyl, naphthalene, anthracene, and the like, preferably benzene.
Examples of the heteroaromatic ring include pyridine and pyrimidine.
These have a halogen atom, alkyl group, alkenyl group, alkynyl group, cycloalkyl lower alkyl group, aralkyl group, alkoxy group, nitro group, hydroxyl group, lower alkoxycarbonyl group, halogen atom, etc. at any position as a substituent. May be.

また、エポキシドへの求核剤として、上記複素環化合物の代わりに、下式
Ｒ^１０Ｒ^１１ＮＨ
で表される一級又は二級アミンを使用してもよい。
Ｒ^１０及びＲ^１１は、それぞれ同じであっても異なってもよく、水素原子、置換基を有していてもよい脂肪族炭化水素基、芳香族炭化水素基又は複素環基を表し、但し、Ｒ^１０及びＲ^１１の少なくとも一方は、水素原子又は脂肪族炭化水素基ではなく、置換基を有していてもよい芳香族炭化水素基又は複素環基である。。これらのアミンの中でも特に芳香族アミンが好ましい。またＲ^１０及びＲ^１１は、ハロゲン原子、水酸基、ニトロ基、シアノ基、エステル基、エーテル基、チオエーテル基、アミド基等の置換基を有していてもよい。 Further, as a nucleophile to epoxide, instead of the above heterocyclic compound, the following formula R ¹⁰ R ¹¹ NH
A primary or secondary amine represented by the following formula may be used.
R ¹⁰ and R ¹¹ may be the same or different and each represents a hydrogen atom, an aliphatic hydrocarbon group which may have a substituent, an aromatic hydrocarbon group or a heterocyclic group, provided that At least one of R ¹⁰ and R ¹¹ is not a hydrogen atom or an aliphatic hydrocarbon group, but an aromatic hydrocarbon group or a heterocyclic group which may have a substituent. . Among these amines, aromatic amines are particularly preferable. R ¹⁰ and R ¹¹ may have a substituent such as a halogen atom, a hydroxyl group, a nitro group, a cyano group, an ester group, an ether group, a thioether group, or an amide group.

上記不斉触媒と基質であるエポキシド及び複素環化合物又はアミンを上記溶媒中で混合することで、複素環化合物又はアミンによるエポキシドの不斉開環反応が進行し、光学活性なアルコール化合物が高収率かつ高立体選択的に生成する。
反応溶液中のエポキシドの濃度は、０．１〜５モル／リットル、好ましくは、０．２〜１．０モル／リットルであり、エポキシドと複素環化合物又はアミンとの比率は、１：（０．５〜３）、好ましくは１：（１．２〜２）程度である。
反応温度は溶媒に水を用いることから通常は０℃以上であり、好ましくは室温付近である。反応温度を下げ過ぎると反応速度が低下し、上げすぎると立体選択性が低下する。反応時間は一般的には数時間〜数十時間程度である。 By mixing the asymmetric catalyst with the substrate epoxide and the heterocyclic compound or amine in the solvent, the asymmetric ring-opening reaction of the epoxide with the heterocyclic compound or amine proceeds, and the optically active alcohol compound has a high yield. Produces highly and stereoselectively.
The concentration of the epoxide in the reaction solution is 0.1 to 5 mol / liter, preferably 0.2 to 1.0 mol / liter, and the ratio of epoxide to heterocyclic compound or amine is 1: (0 .5-3), preferably about 1: (1.2-2).
The reaction temperature is usually 0 ° C. or higher because water is used as a solvent, and preferably around room temperature. If the reaction temperature is lowered too much, the reaction rate is lowered, and if it is raised too much, the stereoselectivity is lowered. The reaction time is generally about several hours to several tens of hours.

エポキシドでない基質が複素環化合物の場合には、生成物である光学活性アルコール化合物は、下式又はその対掌体で表される。化学式（化１）で表される配位子を用いた場合には、生成物として化学式（化４）で表される光学活性アルコール化合物が得られ、化学式（化１）で表される配位子の対掌体を用いた場合には、生成物として化学式（化４）で表される光学活性アルコール化合物の対掌体が得られる。

Ｙ^１が＝ＣＨ−の場合は式（１）又はその対掌体で表され、Ｙ^１が＝Ｎ−の場合は式（２）又はその対掌体で表され、式中、Ｙ^２、Ｒ^４〜Ｒ^７は上記と同様に定義される。
When the substrate that is not an epoxide is a heterocyclic compound, the product optically active alcohol compound is represented by the following formula or an enantiomer thereof. When the ligand represented by the chemical formula (Chemical formula 1) is used, an optically active alcohol compound represented by the chemical formula (Chemical formula 4) is obtained as a product, and the coordination represented by the chemical formula (Chemical formula 1) is obtained. In the case of using an enantiomer of a child, an enantiomer of an optically active alcohol compound represented by the chemical formula (Formula 4) is obtained as a product .

For Y ¹ is = CH- is represented by the formula (1) or its enantiomer, if ^{Y 1} is = N- in which formula (2) or its enantiomer, ^{wherein, Y} 2, R ^{4 to} R ⁷ are defined as described above.

一方、エポキシドでない基質がアミンの場合には、生成物である光学活性なアルコール化合物は、下式又はその対掌体で表される。化学式（化１）で表される配位子を用いた場合には、生成物として化学式（化５）で表される光学活性アルコール化合物が得られ、化学式（化１）で表される配位子の対掌体を用いた場合には、生成物として化学式（化５）で表される光学活性アルコール化合物の対掌体が得られる。

式中、Ｒ^４、Ｒ^５、Ｒ^１０及びＲ^１１は上記と同様に定義される。

On the other hand, when the substrate that is not an epoxide is an amine, the product optically active alcohol compound is represented by the following formula or an enantiomer thereof. When a ligand represented by the chemical formula (Chemical formula 1) is used, an optically active alcohol compound represented by the chemical formula (Chemical formula 5) is obtained as a product, and the coordination represented by the chemical formula (Chemical formula 1) is obtained. In the case of using an enantiomer of a child, an enantiomer of an optically active alcohol compound represented by the chemical formula (Formula 5) is obtained as a product .

In the formula, R ⁴ , R ⁵ , R ¹⁰ and R ¹¹ are defined as described above.

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。
本実施例では、溶媒としてイオン交換水を使用し、空気中で実施した。¹H NMR 及び ¹³C NMR はJEOL JNM-LA400(400 MHz)及びJNM-ECX600(600 MHz)を、赤外吸収スペクトルは JASCO FT/IR-610 を、質量分析には JEOL JMS-T100TD AccuTOF TLCを用いて測定した。光学純度はキラルカラムを用いたHPLC（Shimadzu VP-series）により決定した。 The following examples illustrate the invention but are not intended to limit the invention.
In this example, ion exchange water was used as a solvent, and the test was performed in air. ¹ H NMR and ¹³ C NMR are JEOL JNM-LA400 (400 MHz) and JNM-ECX600 (600 MHz), infrared absorption spectrum is JASCO FT / IR-610, and mass spectrometry is JEOL JMS-T100TD AccuTOF TLC. And measured. The optical purity was determined by HPLC (Shimadzu VP-series) using a chiral column.

合成例１
まず、キラルビピリジン配位子（化６（４））を、既報（Ishikawa, S.; Hamada, T.; Manabe, K.; Kobayashi, S. Synthesis 13, 2176-2182(2005).）に従って合成した。合成経路を下式(化６)に示す。

Synthesis example 1
First, a chiral bipyridine ligand (Chemical Formula 6 (4)) was synthesized according to a report (Ishikawa, S .; Hamada, T .; Manabe, K .; Kobayashi, S. Synthesis 13, 2176-2182 (2005).) did. The synthesis route is shown in the following formula (Formula 6).

2,6-ジブロムピリジン(１)をエーテル中でn-ブチルリチウムで処理した後、ピバロニトリルによりアシル化して化合物(２)を得た。化合物(２)のカルボニル基をRuCl[(S,S)-Tsdpen](p-cymene)により立体選択的に還元して(S)-体のアルコール(３)を ee > 99.5 % で得た。アルコール(３)をパラジウム触媒によるホモカップリング反応を行うことにより、C2対称の2,2'-ビピリジン体(４)(S,S)（以下「キラルビピリジン配位子」または「Bolm's ligand」という。）を得た。
¹H NMR(400 MHz, CDCl₃, TMS)δ 0.97(s, 18H), 4.43(brs, 4H), 7.23(d, J = 8.0 Hz, 2H), 7.79(dd, J = 7.8, 8.0 Hz, 2H), 8.31(d, J = 7.8 Hz, 2H); ¹³C NMR δ 25.9, 36.3, 80.2, 119.6, 123.1, 136.6, 153.8, 159.2 2,6-Dibromopyridine (1) was treated with n-butyllithium in ether and then acylated with pivalonitrile to give compound (2). The carbonyl group of the compound (2) was stereoselectively reduced with RuCl [(S, S) -Tsdpen] (p-cymene) to obtain the (S) -form alcohol (3) at ee> 99.5%. Alcohol (3) is subjected to a palladium-catalyzed homo-coupling reaction to produce a C2 symmetrical 2,2'-bipyridine (4) (S, S) (hereinafter referred to as "chiral bipyridine ligand" or "Bolm's ligand") .)
¹ H NMR (400 MHz, CDCl ₃ , TMS) δ 0.97 (s, 18H), 4.43 (brs, 4H), 7.23 (d, J = 8.0 Hz, 2H), 7.79 (dd, J = 7.8, 8.0 Hz, 2H), 8.31 (d, J = 7.8 Hz, 2H); ¹³ C NMR δ 25.9, 36.3, 80.2, 119.6, 123.1, 136.6, 153.8, 159.2

合成例２
本合成例ではルイス酸（Cu(O₃SC₁₂H₂₅)₂）を合成した。
ナス型フラスコにCH₃(CH₂)₁₁SO₃Na(東京化成工業, 2.02 g, 7.4 mmol)をとり、純水 70 ml を加え油浴にて 70℃に加熱し溶解した。これにCuCl₂(和光純薬工業, 0.50 g, 3.7 mmol)を加え 1 時間撹拌後、室温まで冷却し、生じた固体を濾取し純水 200 ml を用いて洗浄後、真空下乾燥して表題化合物を２水和物として得た(1.79 g)。生成物の分析結果を以下に示す。
Anal. Calcd: C, 48.17; H, 9.10. Found: C, 47.91; H, 8.93. Synthesis example 2
In this synthesis example, a Lewis acid (Cu (O ₃ SC ₁₂ H ₂₅ ) ₂ ) was synthesized.
CH ₃ (CH ₂ ) ₁₁ SO ₃ Na (Tokyo Chemical Industry, 2.02 g, 7.4 mmol) was placed in an eggplant-shaped flask, 70 ml of pure water was added, and the mixture was heated to 70 ° C. in an oil bath and dissolved. CuCl ₂ (Wako Pure Chemical Industries, 0.50 g, 3.7 mmol) was added thereto, stirred for 1 hour, cooled to room temperature, the resulting solid was collected by filtration, washed with 200 ml of pure water, and dried under vacuum. The title compound was obtained as a dihydrate (1.79 g). The analysis results of the product are shown below.
Anal.Calcd: C, 48.17; H, 9.10. Found: C, 47.91; H, 8.93.

合成例３
本合成例ではルイス酸（Zn(O₃SC₁₂H₂₅)₂）を合成した。
合成例２の手順に従い合成した。ただし、CH₃(CH₂)₁₁SO₃Na(東京化成工業, 4.00g, 14.7 mmol)、純水 75 ml、ZnCl₂(和光純薬工業, 1.00 g, 7.3 mmol）を用いて合成反応を行った。その結果、真空下乾燥し表題化合物を５水和物として得た(4.01g)。生成物の分析結果を以下に示す。
Anal. Calcd: C, 44.06; H, 9.24. Found: C, 44.61; H, 8.97 Synthesis example 3
In this synthesis example, a Lewis acid (Zn (O ₃ SC ₁₂ H ₂₅ ) ₂ ) was synthesized.
Synthesis was performed according to the procedure of Synthesis Example 2. However, CH ₃ (CH ₂ ) ₁₁ SO ₃ Na (Tokyo Chemical Industry, 4.00 g, 14.7 mmol), pure water 75 ml, ZnCl ₂ (Wako Pure Chemical Industries, 1.00 g, 7.3 mmol) was used for the synthesis reaction. It was. As a result, it was dried under vacuum to obtain the title compound as a pentahydrate (4.01 g). The analysis results of the product are shown below.
Anal. Calcd: C, 44.06; H, 9.24. Found: C, 44.61; H, 8.97

合成例４
本合成例ではルイス酸（Sc(O₃SC₁₂H₂₅)₃）を合成した。
合成例２の手順に従い合成した。ただし、CH₃(CH₂)₁₁SO₃Na(東京化成工業, 1.57g, 5.8 mmol)、純水 40 ml、 ScCl₃・6H₂O(和光純薬工業, 0.50 g, 1.9 mmol）を用いて合成反応を行った。その結果、真空下乾燥し表題化合物を３水和物として得た(1.47g)。生成物の分析結果を以下に示す。
Anal. Calcd: C, 51.04; H, 9.64. Found: C, 51.31; H, 9.40. Synthesis example 4
In this synthesis example, a Lewis acid (Sc (O ₃ SC ₁₂ H ₂₅ ) ₃ ) was synthesized.
Synthesis was performed according to the procedure of Synthesis Example 2. _{_{_{However, CH 3 (CH 2) 11}}} SO 3 Na ( Tokyo Kasei Kogyo, 1.57g, 5.8 mmol), pure water _{_{40 ml, ScCl 3 · 6H 2}} O ( Wako Pure Chemical, 0.50 g, 1.9 mmol) with A synthetic reaction was performed. As a result, it was dried under vacuum to obtain the title compound as a trihydrate (1.47 g). The analysis results of the product are shown below.
Anal.Calcd: C, 51.04; H, 9.64. Found: C, 51.31; H, 9.40.

合成例５〜８
本合成例では、文献(Tetrahedron, 1997, 53, 13727)にしたがって、各種エポキシドを合成した。各生成物の分析結果を以下に示す。
シス−スチルベンオキシド：
¹H NMR(400 MHz, CDCl₃, TMS)δ 4.36(s, 2H), 7.05-7.25(brs, 10H).
シス−1,2−ジ（ナフタレン−2−イル）エセンオキシド
¹H NMR (400 MHz, CDCl₃, TMS) δ 4.60 (s, 2H), 7.27 (d, J = 8.0 Hz, 2H), 7.34-7.41 (m, 4H). 7.59 (d, J = 8.0 Hz, 2H), 7.66-7.72 (m, 4H), 7.77 (s, 2H).
シス−1,2−ジ−p−トリルエセンオキシド
¹H NMR(400 MHz, CDCl₃, TMS)δ 2.25(s, 6H), 4.30(s, 2H), 6.99(d, J = 8.0 Hz, 4H), 7.06(d, J = 8.0 Hz, 4H).
シス−1,2−ジ−（p−ブロモフェニル）−エセンオキシド
¹H NMR(400 MHz, CDCl₃, TMS)δ 4.31(s, 2H), 7.03(d, J = 8.0 Hz, 4H), 7.32(d, J = 8.0 Hz, 4H). Synthesis Examples 5-8
In this synthesis example, various epoxides were synthesized according to the literature (Tetrahedron, 1997, 53, 13727). The analysis results of each product are shown below.
Cis-stilbene oxide:
¹ H NMR (400 MHz, CDCl ₃ , TMS) δ 4.36 (s, 2H), 7.05-7.25 (brs, 10H).
Cis-1,2-di (naphthalen-2-yl) ecene oxide
¹ H NMR (400 MHz, CDCl ₃ , TMS) δ 4.60 (s, 2H), 7.27 (d, J = 8.0 Hz, 2H), 7.34-7.41 (m, 4H). 7.59 (d, J = 8.0 Hz, 2H), 7.66-7.72 (m, 4H), 7.77 (s, 2H).
Cis-1,2-di-p-tolyl ecene oxide
¹ H NMR (400 MHz, CDCl ₃ , TMS) δ 2.25 (s, 6H), 4.30 (s, 2H), 6.99 (d, J = 8.0 Hz, 4H), 7.06 (d, J = 8.0 Hz, 4H) .
Cis-1,2-di- (p-bromophenyl) -ecene oxide
¹ H NMR (400 MHz, CDCl ₃ , TMS) δ 4.31 (s, 2H), 7.03 (d, J = 8.0 Hz, 4H), 7.32 (d, J = 8.0 Hz, 4H).

以下の実施例及び比較例では、触媒として合成例１で得たキラルビピリジン配位子（Bolm's ligand）及び合成例２〜４で得たルイス酸を用い、エポキシドとして合成例５〜８で得た化合物群を用いて光学活性アルコール化合物を合成した。 In the following Examples and Comparative Examples, the chiral bipyridine ligand (Bolm's ligand) obtained in Synthesis Example 1 and the Lewis acid obtained in Synthesis Examples 2 to 4 were used as catalysts, and the epoxide was obtained in Synthesis Examples 5 to 8. An optically active alcohol compound was synthesized using the compound group.

実施例１
本実施例では、下式に従って、光学活性アルコール化合物を合成した。

試験管に合成例１で合成したキラルビピリジン配位子(11.8 mg, 0.036 mmol)をとり、Cu(O₃SC₁₂H₂₅)₂(16.9 mg, 0.03 mmol)、純水 0.3 ml を加え、室温で1時間撹拌した。これにシス−スチルベンオキシド(58.9 mg, 0.30 mmol)、インドール(和光純薬工業, 42.2 mg, 0.36 mmol)を加え、室温で 22 時間撹拌した。撹拌を停止した後に飽和炭酸水素ナトリウム水溶液 6 ml、飽和食塩水 6 ml、ジクロロメタン 10 ml を加え分液操作を行った。更にジクロロメタン 20 ml を用いて二回抽出し、合わせた有機層に飽和食塩水 30 ml を加え分液操作を行った。有機層に無水硫酸ナトリウムを加え 10 分間静置した後に濾過し、真空下有機溶媒を留去した。薄層クロマトグラフィー(展開溶媒: n‐ヘキサン/酢酸エチル＝3/2)により精製し、(1S,2S)-2-(1H-indol-3-yl)-1,2-diphenylethanolを得た(75.6 mg, 80% yield, 96% ee)。生成物の分析結果を以下に示す。
¹H NMR(600 MHz, CDCl₃, TMS)δ 2.56(brs, 1H), 4.55(d, J = 8.2 Hz, 1H), 5.28(d, J = 8.2 Hz, 1H), 6.99-7.20(m, 14H), 7.42-7.43(m, 1H), 8.09(brs, 1H); ¹³C NMR δ 52.0, 77.6, 111.1, 115.2, 119.3, 119.6, 122.2, 122.4, 126.3, 126.8, 127.3, 127.5, 127.9, 128.0, 128.6, 136.3, 141.7, 142.4, ; FT-IR(KBr)3348, 3026, 2873, 1490, 1457, 1340, 1224, 1042, 744, 698 cm^-1; HRMS(ESI)calced for C₂₂H₂₀N₁O₁([M+H]⁺): 314.1545, found: 314.1578; HPLC(Daicel Chiralpak OD-H, n-hexane/i-PrOH = 4/1, flow rate 0.8 mL/min)t_R = 34.6 min(minor), t_R = 48.6 min(major). Example 1
In this example, an optically active alcohol compound was synthesized according to the following formula.

Take the chiral bipyridine ligand (11.8 mg, 0.036 mmol) synthesized in Synthesis Example 1 in a test tube, add Cu (O ₃ SC ₁₂ H ₂₅ ) ₂ (16.9 mg, 0.03 mmol), and 0.3 ml of pure water, For 1 hour. To this was added cis-stilbene oxide (58.9 mg, 0.30 mmol) and indole (Wako Pure Chemical Industries, 42.2 mg, 0.36 mmol), and the mixture was stirred at room temperature for 22 hours. After the stirring was stopped, 6 ml of saturated aqueous sodium hydrogen carbonate solution, 6 ml of saturated brine, and 10 ml of dichloromethane were added to carry out a liquid separation operation. Further, the mixture was extracted twice with 20 ml of dichloromethane, and 30 ml of saturated saline was added to the combined organic layer for liquid separation operation. Anhydrous sodium sulfate was added to the organic layer and the mixture was allowed to stand for 10 minutes and then filtered, and the organic solvent was distilled off under vacuum. Purification by thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 3/2) gave (1S, 2S) -2- (1H-indol-3-yl) -1,2-diphenylethanol ( 75.6 mg, 80% yield, 96% ee). The analysis results of the product are shown below.
¹ H NMR (600 MHz, CDCl ₃ , TMS) δ 2.56 (brs, 1H), 4.55 (d, J = 8.2 Hz, 1H), 5.28 (d, J = 8.2 Hz, 1H), 6.99-7.20 (m, 14H), 7.42-7.43 (m, 1H), 8.09 (brs, 1H); ¹³ C NMR δ 52.0, 77.6, 111.1, 115.2, 119.3, 119.6, 122.2, 122.4, 126.3, 126.8, 127.3, 127.5, 127.9, 128.0 , 128.6, 136.3, 141.7, 142.4,; FT-IR (KBr) 3348, 3026, 2873, 1490, 1457, 1340, 1224, 1042, 744, 698 cm ^-1 ; HRMS (ESI) calced for C ₂₂ H ₂₀ N ₁ O ₁ ([M + H] ⁺ ): 314.1545, found: 314.1578; HPLC (Daicel Chiralpak OD-H, n-hexane / i-PrOH = 4/1, flow rate 0.8 mL / min) t _R = 34.6 min (minor), t _R = 48.6 min (major).

実施例２
本実施例では、インドールに代えて5-メトキシインドール(和光純薬工業, 53.0 mg, 0.36 mmol）を用いて、実施例１と同様に合成反応を行った。その結果、(1S,2S)-2-(5-methoxy-1H-indol-3-yl)-1,2-diphenylethanolを得た(80.6 mg, 78% yield, 92% ee)。生成物の分析結果を以下に示す。
¹H NMR(600 MHz, CDCl₃, TMS)δ 2.04(brs, 1H), 3.72(s, 3H), 4.53(d, J = 7.6 Hz, 1H), 5.33(d, J = 7.6 Hz, 1H), 6.77-6.82(m, 2H), 7.08-7.30(m, 14H), 8.02(brs, 1H); ¹³C NMR δ 52.0, 55.8, 77.3, 101.4, 111.7, 112.6, 115.0, 123.4, 126.3, 126.7, 127.3, 127.9, 128.0, 128.6, 131.5, 141.9, 142.6, 154.1; FT-IR(KBr)3518, 3369, 3314, 3025, 1623, 1583, 1485, 1453, 1437, 1213, 1166, 1024, 926, 823, 808, 754, 727, 695 cm^-1; HRMS(ESI)calced for C₂₃H₂₂N₁O₂([M+H]+): 344.1651, found: 344.1679; HPLC(Daicel Chiralpak AD-H, n-hexane/i-PrOH = 7/3, flow rate 1.0 mL/min)t_R = 22.2 min(major),t_R = 28.7 min(minor). Example 2
In this example, the synthesis reaction was carried out in the same manner as in Example 1 using 5-methoxyindole (Wako Pure Chemical Industries, 53.0 mg, 0.36 mmol) instead of indole. As a result, (1S, 2S) -2- (5-methoxy-1H-indol-3-yl) -1,2-diphenylethanol was obtained (80.6 mg, 78% yield, 92% ee). The analysis results of the product are shown below.
¹ H NMR (600 MHz, CDCl ₃ , TMS) δ 2.04 (brs, 1H), 3.72 (s, 3H), 4.53 (d, J = 7.6 Hz, 1H), 5.33 (d, J = 7.6 Hz, 1H) , 6.77-6.82 (m, 2H), 7.08-7.30 (m, 14H), 8.02 (brs, 1H); ¹³ C NMR δ 52.0, 55.8, 77.3, 101.4, 111.7, 112.6, 115.0, 123.4, 126.3, 126.7, 127.3, 127.9, 128.0, 128.6, 131.5, 141.9, 142.6, 154.1; FT-IR (KBr) 3518, 3369, 3314, 3025, 1623, 1583, 1485, 1453, 1437, 1213, 1166, 1024, 926, 823, 808, 754, 727, 695 cm ^-1 ; HRMS (ESI) calced for C ₂₃ H ₂₂ N ₁ O ₂ ([M + H] +): 344.1651, found: 344.1679; HPLC (Daicel Chiralpak AD-H, n- hexane / i-PrOH = 7/3, flow rate 1.0 mL / min) t _R = 22.2 min (major), t _R = 28.7 min (minor).

実施例３
本実施例では、インドールに代えて5-メチルインドール(東京化成工業, 47.2 mg, 0.36 mmol)、純水 3 mlを用いて、実施例１と同様に合成反応を行った。その結果、(1S,2S)-2-(5-methyl-1H-indol-3-yl)-1,2-diphenylethanolを得た(79.2 mg, 81% yield, 92% ee)。生成物の分析結果を以下に示す。
¹H NMR(600 MHz, CDCl₃, TMS)δ 2.34(s, 3H), 2.49(brs, 1H), 4.56(d, J = 8.3 Hz, 1H), 5.31(d, J = 9.6 Hz, 1H), 6.97-6.99(m, 1H), 7.06-7.30(m, 13H), 8.03(brs, 1H); ¹³C NMR δ 21.5, 52.1, 77.7, 110.7, 113.5, 114.8, 119.0, 122.6, 124.0, 126.3, 126.8, 127.3, 127.9, 128.1, 128.6, 128.9, 134.7, 141.8, 142.4; FT-IR(KBr)3490, 3285, 3025, 1490, 1454, 1225, 1111, 1073, 1024, 797, 761, 729, 697, 647 cm^-1; HRMS(ESI)calced for C₂₃H₂₂N₁O₁([M+H]⁺): 328.1701, found: 328.1688; HPLC(Daicel Chiralpak OD-H, n-hexane/i-PrOH = 7/3, flow rate 0.7 mL/min)t_R = 29.6 min(major), t_R = 36.9 min(minor). Example 3
In this example, synthesis reaction was carried out in the same manner as in Example 1 using 5-methylindole (Tokyo Chemical Industry, 47.2 mg, 0.36 mmol) and 3 ml of pure water instead of indole. As a result, (1S, 2S) -2- (5-methyl-1H-indol-3-yl) -1,2-diphenylethanol was obtained (79.2 mg, 81% yield, 92% ee). The analysis results of the product are shown below.
¹ H NMR (600 MHz, CDCl ₃ , TMS) δ 2.34 (s, 3H), 2.49 (brs, 1H), 4.56 (d, J = 8.3 Hz, 1H), 5.31 (d, J = 9.6 Hz, 1H) , 6.97-6.99 (m, 1H), 7.06-7.30 (m, 13H), 8.03 (brs, 1H); ¹³ C NMR δ 21.5, 52.1, 77.7, 110.7, 113.5, 114.8, 119.0, 122.6, 124.0, 126.3, 126.8, 127.3, 127.9, 128.1, 128.6, 128.9, 134.7, 141.8, 142.4; FT-IR (KBr) 3490, 3285, 3025, 1490, 1454, 1225, 1111, 1073, 1024, 797, 761, 729, 697, 647 cm ^-1 ; HRMS (ESI) calculated for C ₂₃ H ₂₂ N ₁ O ₁ ([M + H] ⁺ ): 328.1701, found: 328.1688; HPLC (Daicel Chiralpak OD-H, n-hexane / i-PrOH = 7/3, flow rate 0.7 mL / min) t _R = 29.6 min (major), t _R = 36.9 min (minor).

実施例４
本実施例では、インドールに代えて5-ブロモインドール(東京化成工業, 70.6 mg, 0.36 mmol)を用い、純水 3 mlを用いて、実施例１と同様に合成反応を行った。その結果、(1S,2S)-2-(5-bromo-1H-indol-3-yl)-1,2-diphenylethanolを得た(68.7 mg, 58% yield, 90% ee)。生成物の分析結果を以下に示す。
¹H NMR(600 MHz, CDCl₃, TMS)δ 2.03(brs, 1H), 4.51(d, J = 7.6 Hz, 1H), 5.27(d, J = 7.6 Hz, 1H), 7.06-7.34(m, 13H), 7.47-7.48(m, 1H), 8.18(brs, 1H); ¹³C NMRδ 51.6, 77.6, 112.5, 112.9, 114.9, 121.9, 123.8, 125.1, 126.5, 126.6, 126.9, 127.4, 127.9, 128.0, 128.1, 128.2, 128.5, 129.4, 134.8, 141.4, 142.3; FT-IR(KBr)3396, 3347, 3243, 1603, 1491, 1455, 1332, 1048, 1034, 887, 798, 751, 741, 699 cm^-1; HRMS(ESI)calced for C₂₂H₁₉Br₁N₁O₁([M+H]⁺): 392.0650, found: 392.0638; HPLC(Daicel Chiralpak OD-H, n-hexane/i-PrOH = 7/3, flow rate 1.0 mL/min)t_R = 15.2 min(major), t_R = 20.9 min(minor). Example 4
In this example, 5-bromoindole (Tokyo Chemical Industry, 70.6 mg, 0.36 mmol) was used instead of indole, and 3 ml of pure water was used for the synthesis reaction as in Example 1. As a result, (1S, 2S) -2- (5-bromo-1H-indol-3-yl) -1,2-diphenylethanol was obtained (68.7 mg, 58% yield, 90% ee). The analysis results of the product are shown below.
¹ H NMR (600 MHz, CDCl ₃ , TMS) δ 2.03 (brs, 1H), 4.51 (d, J = 7.6 Hz, 1H), 5.27 (d, J = 7.6 Hz, 1H), 7.06-7.34 (m, 13H), 7.47-7.48 (m, 1H), 8.18 (brs, 1H); ¹³ C NMRδ 51.6, 77.6, 112.5, 112.9, 114.9, 121.9, 123.8, 125.1, 126.5, 126.6, 126.9, 127.4, 127.9, 128.0, 128.1, 128.2, 128.5, 129.4, 134.8, 141.4, 142.3; FT-IR (KBr) 3396, 3347, 3243, 1603, 1491, 1455, 1332, 1048, 1034, 887, 798, 751, 741, 699 cm ^-1 ; HRMS (ESI) calced for C ₂₂ H ₁₉ Br ₁ N ₁ O ₁ ([M + H] ⁺ ): 392.0650, found: 392.0638; HPLC (Daicel Chiralpak OD-H, n-hexane / i-PrOH = 7 / 3, flow rate 1.0 mL / min) t _R = 15.2 min (major), t _R = 20.9 min (minor).

実施例５
本実施例では、インドールに代えて2-メチルインドール(東京化成工業, 59.0mg, 0.45 mmol)を用いて48 時間撹拌を行い、実施例１と同様に合成反応を行った。その結果、(1S,2S)-2-(2-methyl-1H-indol-3-yl)-1,2-diphenylethanolを得た(76.0 mg, 77% yield, 92% ee)。生成物の分析結果を以下に示す。
¹H NMR(600 MHz, CDCl₃, TMS)δ 2.09(s, 3H), 2.50(brs, 1H), 4.11(d, J = 6.9 Hz, 1H), 5.71(d, J = 6.2 Hz, 1H), 7.04-7.23(m, 13H), 7.66-7.67(m, 1H), 7.91(brs, 1H); ¹³C NMR δ 11.9, 52.4, 76.0, 109.4, 110.5, 119.4, 119.8, 121.1, 126.0, 126.8, 127.3, 127.8, 127.9, 128.0, 128.1, 133.8, 135.4, 141.9, 142.8; FT-IR(KBr)3400, 3059, 3028, 2914, 1492, 1459, 1303, 1052, 909, 741, 699 cm^-1; HRMS(ESI)calced for C₂₃H₂₂N₁O₁([M+H]⁺): 328.1701, found: 328.1687; HPLC(Daicel Chiralpak AD-H, n-hexane/i-PrOH = 9/1, flow rate 1.0 mL/min)t_R = 47.5 min(major), t_R = 55.8 min(minor). Example 5
In this example, instead of indole, 2-methylindole (Tokyo Chemical Industry, 59.0 mg, 0.45 mmol) was used for 48 hours of stirring, and the synthesis reaction was carried out in the same manner as in Example 1. As a result, (1S, 2S) -2- (2-methyl-1H-indol-3-yl) -1,2-diphenylethanol was obtained (76.0 mg, 77% yield, 92% ee). The analysis results of the product are shown below.
¹ H NMR (600 MHz, CDCl ₃ , TMS) δ 2.09 (s, 3H), 2.50 (brs, 1H), 4.11 (d, J = 6.9 Hz, 1H), 5.71 (d, J = 6.2 Hz, 1H) , 7.04-7.23 (m, 13H), 7.66-7.67 (m, 1H), 7.91 (brs, 1H); ¹³ C NMR δ 11.9, 52.4, 76.0, 109.4, 110.5, 119.4, 119.8, 121.1, 126.0, 126.8, 127.3, 127.8, 127.9, 128.0, 128.1, 133.8, 135.4, 141.9, 142.8; FT-IR (KBr) 3400, 3059, 3028, 2914, 1492, 1459, 1303, 1052, 909, 741, 699 cm ^-1 ; HRMS (ESI) calced for C ₂₃ H ₂₂ N ₁ O ₁ ([M + H] ⁺ ): 328.1701, found: 328.1687; HPLC (Daicel Chiralpak AD-H, n-hexane / i-PrOH = 9/1, flow rate 1.0 mL / min) t _R = 47.5 min (major), t _R = 55.8 min (minor).

実施例６
本実施例では、シス−スチルベンオキシドに代えてシス−1,2−ジ（ナフタレン−2−イル）エセンオキシド(88.9 mg, 0.30 mmol）を用いて、実施例１と同様に合成反応を行った。その結果、(1S,2S)-2-(1H-indol-3-yl)-1,2-di(naphthalene-2-yl)ethanolを得た(66.3 mg, 53% yield, 85% ee)。生成物の分析結果を以下に示す。
¹H NMR(600 MHz, CDCl₃, TMS)δ 2.61(brs, 1H), 4.91(d, J = 7.6 Hz, 1H), 5.64(d, J = 7.6 Hz, 1H), 6.96-6.99(m, 1H), 7.12-7.15(m, 1H), 7.31-7.46(m, 9H), 7.59-7.74(m, 8H), 8.12(brs, 1H); ¹³C NMRδ 51.8, 77.5, 111.1, 115.1, 119.7, 122.4, 122.8, 124.8, 125.4, 125.6, 125.7, 127.1, 127.5, 127.6, 127.8, 128.0, 132.2, 132.9, 133.1, 133.4, 136.3, 139.3, 139.9; FT-IR(KBr)3423, 3335, 3051, 2879, 1599, 1508, 1457, 1420, 1342, 1271, 1122, 1100, 1034, 908, 815, 745 cm^-1; HRMS(ESI)calced for C₃₀H₂₄N₁O₁([M+H]⁺): 414.1858, found: 414.1886; HPLC(Daicel Chiralpak AD-H, n-hexane/i-PrOH = 4/1, flow rate 1.0 mL/min)t_R = 51.5 min(major), t_R = 70.2 min(minor). Example 6
In this example, the synthesis reaction was carried out in the same manner as in Example 1 using cis-1,2-di (naphthalen-2-yl) ecene oxide (88.9 mg, 0.30 mmol) instead of cis-stilbene oxide. As a result, (1S, 2S) -2- (1H-indol-3-yl) -1,2-di (naphthalene-2-yl) ethanol was obtained (66.3 mg, 53% yield, 85% ee). The analysis results of the product are shown below.
¹ H NMR (600 MHz, CDCl ₃ , TMS) δ 2.61 (brs, 1H), 4.91 (d, J = 7.6 Hz, 1H), 5.64 (d, J = 7.6 Hz, 1H), 6.96-6.99 (m, 1H), 7.12-7.15 (m, 1H), 7.31-7.46 (m, 9H), 7.59-7.74 (m, 8H), 8.12 (brs, 1H); ¹³ C NMRδ 51.8, 77.5, 111.1, 115.1, 119.7, 122.4, 122.8, 124.8, 125.4, 125.6, 125.7, 127.1, 127.5, 127.6, 127.8, 128.0, 132.2, 132.9, 133.1, 133.4, 136.3, 139.3, 139.9; FT-IR (KBr) 3423, 3335, 3051, 2879, 1599, 1508, 1457, 1420, 1342, 1271, 1122, 1100, 1034, 908, 815, 745 cm ^-1 ; HRMS (ESI) calced for C ₃₀ H ₂₄ N ₁ O ₁ ([M + H] ⁺ ): 414.1858, found: 414.1886; HPLC (Daicel Chiralpak AD-H, n-hexane / i-PrOH = 4/1, flow rate 1.0 mL / min) t _R = 51.5 min (major), t _R = 70.2 min (minor) .

実施例７
本実施例では、シス−スチルベンオキシドに代えてシス−1,2−ジ−p−トリルエセンオキシド(67.3 mg, 0.30 mmol）を用いて、実施例１と同様に合成反応を行った。その結果、(1S,2S)-2-(1H-indol-3-yl)-1,2-di-p-tolylethanolを得た(49.4 mg, 48% yield, 87% ee)。生成物の分析結果を以下に示す。
¹H NMR(600 MHz, CDCl₃, TMS)δ 2.21(s, 3H), 2.26(brs, 1H), 2.27(s, 3H), 4.55(d, J = 7.6 Hz, 1H), 5.28(d, J = 7.6 Hz, 1H), 6.94(d, J = 8.3 Hz, 2H), 7.00-7.04(m, 5H), 7.11-7.17(m, 3H), 7.22-7.24(m, 2H), 7.45(d, J = 6.9 Hz, 1H), 8.10(brs, 1H); ¹³C NMR δ 20.9, 21.1, 51.3, 60.4, 77.5, 111.0, 115.6, 119.4, 119.5, 122.2, 122.5, 126.7, 126.8, 127.0, 127.6, 128.5, 128.6, 128.8, 129.0, 135.6, 136.3, 136.8, 138.9, 139.5; FT-IR(KBr)3412, 3020, 2918, 1511, 1489, 1419, 1339, 1189, 1036, 813, 742, 576 cm^-1; HRMS(ESI)calced for C₃₄H₂₄N₁O₁([M+H]⁺): 342.1858, found: 342.1822; HPLC(Daicel Chiralpak OD-H, n-hexane/i-PrOH = 4/1, flow rate 1.0 mL/min)t_R = 25.9 min(minor), t_R = 31.7 min(major). Example 7
In this example, the synthesis reaction was carried out in the same manner as in Example 1 using cis-1,2-di-p-tolyl ecene oxide (67.3 mg, 0.30 mmol) instead of cis-stilbene oxide. As a result, (1S, 2S) -2- (1H-indol-3-yl) -1,2-di-p-tolylethanol was obtained (49.4 mg, 48% yield, 87% ee). The analysis results of the product are shown below.
¹ H NMR (600 MHz, CDCl ₃ , TMS) δ 2.21 (s, 3H), 2.26 (brs, 1H), 2.27 (s, 3H), 4.55 (d, J = 7.6 Hz, 1H), 5.28 (d, J = 7.6 Hz, 1H), 6.94 (d, J = 8.3 Hz, 2H), 7.00-7.04 (m, 5H), 7.11-7.17 (m, 3H), 7.22-7.24 (m, 2H), 7.45 (d , J = 6.9 Hz, 1H), 8.10 (brs, 1H); ¹³ C NMR δ 20.9, 21.1, 51.3, 60.4, 77.5, 111.0, 115.6, 119.4, 119.5, 122.2, 122.5, 126.7, 126.8, 127.0, 127.6, 128.5, 128.6, 128.8, 129.0, 135.6, 136.3, 136.8, 138.9, 139.5; FT-IR (KBr) 3412, 3020, 2918, 1511, 1489, 1419, 1339, 1189, 1036, 813, 742, 576 cm ^-1 HRMS (ESI) calced for C ₃₄ H ₂₄ N ₁ O ₁ ([M + H] ⁺ ): 342.1858, found: 342.1822; HPLC (Daicel Chiralpak OD-H, n-hexane / i-PrOH = 4/1, flow rate 1.0 mL / min) t _R = 25.9 min (minor), t _R = 31.7 min (major).

実施例８
本実施例では、シス−スチルベンオキシドに代えてシス−1,2−ジ−（p−ブロモフェニル）−エセンオキシド(106.2 mg, 0.30 mmol)、インドール(70.3 mg, 0.60 mmol)、純水 0.6 mlを用いて48時間撹拌を行い、実施例１と同様に合成反応を行った。その結果、(1S,2S)-2-(1H-indol-3-yl)-1,2-di(p-bromophenyl)-ethanolを得た(116.3 mg, 82% yield, 92% ee)。生成物の分析結果を以下に示す。
¹H NMR(600 MHz, CDCl₃, TMS)δ 2.60(brs, 1H), 4.42(d, J = 8.3 Hz, 1H), 5.17(d, J = 8.3 Hz, 1H), 6.93(d, J = 8.9 Hz, 2H), 7.01-7.04(m, 3H), 7.15-7.38(m, 8H), 8.18(brs, 1H); ¹³C NMR δ 51.4, 76.8, 111.3, 114.1, 119.1, 119.8, 120.3, 121.3, 122.3, 122.5, 127.2, 128.4, 128.6, 130.3, 131.1, 131.3, 136.3, 140.3, 141.0; FT-IR(KBr)3411, 3055, 2892, 1702, 1591, 1486, 1456, 1405, 1339, 1100, 1071, 1040, 1009, 907, 833, 817, 781, 743 cm^-1; HRMS(ESI)calced for C₃₂H₁₈Br₂N₁O₁([M+H]⁺): 471.9735, found: 471.9711; HPLC(Daicel Chiralpak AD-H, n-hexane/i-PrOH = 7/3, flow rate 1.0 mL/min)t_R = 15.0 min(major), t_R = 19.0 min(minor). Example 8
In this example, instead of cis-stilbene oxide, cis-1,2-di- (p-bromophenyl) -ecene oxide (106.2 mg, 0.30 mmol), indole (70.3 mg, 0.60 mmol), and 0.6 ml of pure water were added. The mixture was stirred for 48 hours, and the synthesis reaction was carried out in the same manner as in Example 1. As a result, (1S, 2S) -2- (1H-indol-3-yl) -1,2-di (p-bromophenyl) -ethanol was obtained (116.3 mg, 82% yield, 92% ee). The analysis results of the product are shown below.
¹ H NMR (600 MHz, CDCl ₃ , TMS) δ 2.60 (brs, 1H), 4.42 (d, J = 8.3 Hz, 1H), 5.17 (d, J = 8.3 Hz, 1H), 6.93 (d, J = 8.9 Hz, 2H), 7.01-7.04 (m, 3H), 7.15-7.38 (m, 8H), 8.18 (brs, 1H); ¹³ C NMR δ 51.4, 76.8, 111.3, 114.1, 119.1, 119.8, 120.3, 121.3 , 122.3, 122.5, 127.2, 128.4, 128.6, 130.3, 131.1, 131.3, 136.3, 140.3, 141.0; FT-IR (KBr) 3411, 3055, 2892, 1702, 1591, 1486, 1456, 1405, 1339, 1100, 1071 , 1040, 1009, 907, 833, 817, 781, 743 cm ^-1 ; HRMS (ESI) calced for C ₃₂ H ₁₈ Br ₂ N ₁ O ₁ ([M + H] ⁺ ): 471.9735, found: 471.9711; HPLC (Daicel Chiralpak AD-H, n-hexane / i-PrOH = 7/3, flow rate 1.0 mL / min) t _R = 15.0 min (major), t _R = 19.0 min (minor).

実施例９
本実施例では、Cu(O₃SC₁₂H₂₅)₂に代えてZn(O₃SC₁₂H₂₅)₂₍16.9 mg, 0.03 mmol）を用いて、実施例１と同様に合成反応を行った。その結果、(1S,2S)-2-(1H-indol-3-yl)-1,2-diphenylethanolを得た(7.3 mg, 8% yield, 80% ee)。生成物の分析結果を以下に示す。
HPLC(Daicel Chiralpak OD-H, n-hexane/i-PrOH = 4/1, flow rate 0.8 mL/min)t_R = 31.2 min(minor), t_R = 43.8 min(major).
反応式を下式に示す。

Example 9
In this example, the synthetic reaction was carried out in the same manner as in Example 1 using Zn (O ₃ SC ₁₂ H ₂₅ ) _{2 (} 16.9 mg, 0.03 mmol) instead of Cu (O ₃ SC ₁₂ H ₂₅ ) ₂ . . As a result, (1S, 2S) -2- (1H-indol-3-yl) -1,2-diphenylethanol was obtained (7.3 mg, 8% yield, 80% ee). The analysis results of the product are shown below.
HPLC (Daicel Chiralpak OD-H, n-hexane / i-PrOH = 4/1, flow rate 0.8 mL / min) t _R = 31.2 min (minor), t _R = 43.8 min (major).
The reaction formula is shown below.

実施例１０
試験管に合成例１で合成したキラルビピリジン配位子(11.8 mg, 0.036 mmol)をとり、Cu(O₃SC₁₂H₂₅)₂(16.9 mg, 0.03 mmol)、純水 3 ml を加え、室温で1時間撹拌した。これにシス−スチルベンオキシド(58.9 mg, 0.30 mmol)、アニリン(41.0 μl, 0.45 mmol)を加え、室温で 22 時間撹拌した。撹拌を停止した後に飽和炭酸水素ナトリウム水溶液 6 ml、飽和食塩水 6 ml、ジクロロメタン 10 ml を加え分液操作を行った。更にジクロロメタン 20 ml を用いて二回抽出し、合わせた有機層に飽和食塩水 30 ml を加え分液操作を行った。有機層に無水硫酸ナトリウムを加え 10 分間静置した後に濾過し、真空下有機溶媒を留去した。薄層クロマトグラフィー(展開溶媒: n‐ヘキサン/酢酸エチル＝3/1)により精製し、(1R,2R)-1,2-Diphenyl-2-(phenylamino)-ethanolを得た(70.9 mg, 82% yield, 80% ee)。
反応式を下式に示す。

生成物の分析結果を以下に示す。
¹H NMR(600 MHz, CDCl₃, TMS)δ 4.53(d, J = 6.2 Hz, 1H), 4.88(d, J = 5.5 Hz, 1H), 6.53(d, J = 7.6 Hz, 2H), 6.64(t, J = 6.8 Hz, 1H), 7.05(t, J = 6.8 Hz, 2H), 7.21-7.27(m, 10H); ¹³C NMR δ 64.8, 78.0, 114.2, 118.0, 126.5, 127.3, 127.5, 127.9, 128.2, 128.5, 128.8, 129.0, 140.2, 140.6, 147.2; FT-IR(KBr)3408, 3059, 3029, 1602, 1502, 1453, 1317, 1051, 768, 751, 699 cm^-1; HRMS(ESI)calced for C₂₀H₂₀N₁O₁([M+H]⁺): 290.1545, found: 290.1517; HPLC(Daicel Chiralpak AD, n-hexane/i-PrOH = 19/1, flow rate 1.0 mL/min)t_R = 24.7 min(minor), t_R = 28.7 min(major). Example 10
Take the chiral bipyridine ligand (11.8 mg, 0.036 mmol) synthesized in Synthesis Example 1 in a test tube, add Cu (O ₃ SC ₁₂ H ₂₅ ) ₂ (16.9 mg, 0.03 mmol), 3 ml of pure water, For 1 hour. To this was added cis-stilbene oxide (58.9 mg, 0.30 mmol) and aniline (41.0 μl, 0.45 mmol), and the mixture was stirred at room temperature for 22 hours. After the stirring was stopped, 6 ml of saturated aqueous sodium hydrogen carbonate solution, 6 ml of saturated brine, and 10 ml of dichloromethane were added to carry out a liquid separation operation. Further, the mixture was extracted twice with 20 ml of dichloromethane, and 30 ml of saturated saline was added to the combined organic layer for liquid separation operation. Anhydrous sodium sulfate was added to the organic layer and the mixture was allowed to stand for 10 minutes and then filtered, and the organic solvent was distilled off under vacuum. Purification by thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 3/1) gave (1R, 2R) -1,2-Diphenyl-2- (phenylamino) -ethanol (70.9 mg, 82 % yield, 80% ee).
The reaction formula is shown below.

The analysis results of the product are shown below.
¹ H NMR (600 MHz, CDCl ₃ , TMS) δ 4.53 (d, J = 6.2 Hz, 1H), 4.88 (d, J = 5.5 Hz, 1H), 6.53 (d, J = 7.6 Hz, 2H), 6.64 (t, J = 6.8 Hz, 1H), 7.05 (t, J = 6.8 Hz, 2H), 7.21-7.27 (m, 10H); ¹³ C NMR δ 64.8, 78.0, 114.2, 118.0, 126.5, 127.3, 127.5, 127.9, 128.2, 128.5, 128.8, 129.0, 140.2, 140.6, 147.2; FT-IR (KBr) 3408, 3059, 3029, 1602, 1502, 1453, 1317, 1051, 768, 751, 699 cm ^-1 ; HRMS (ESI ) calced for C ₂₀ H ₂₀ N ₁ O ₁ ([M + H] ⁺ ): 290.1545, found: 290.1517; HPLC (Daicel Chiralpak AD, n-hexane / i-PrOH = 19/1, flow rate 1.0 mL / min ) t _R = 24.7 min (minor), t _R = 28.7 min (major).

実施例１１
本実施例では、Cu(O₃SC₁₂H₂₅)₂に代えてZn(O₃SC₁₂H₂₅)₂₍16.9 mg, 0.03 mmol）を用いて、実施例１０と同様に合成反応を行った。その結果、(1R,2R)-1,2-Diphenyl-2-(phenylamino)-ethanol を得た(84.1 mg, 97% yield, 92% ee)。
HPLC(Daicel Chiralpak AD, n-hexane/i-PrOH = 19/1, flow rate 1.0 mL/min)t_R = 25.4 min(major), t_R = 29.7 min(minor). Example 11
In this example, the synthetic reaction was performed in the same manner as in Example 10 using Zn (O ₃ SC ₁₂ H ₂₅ ) _{2 (} 16.9 mg, 0.03 mmol) instead of Cu (O ₃ SC ₁₂ H ₂₅ ) ₂ . . As a result, (1R, 2R) -1,2-Diphenyl-2- (phenylamino) -ethanol was obtained (84.1 mg, 97% yield, 92% ee).
HPLC (Daicel Chiralpak AD, n-hexane / i-PrOH = 19/1, flow rate 1.0 mL / min) t _R = 25.4 min (major), t _R = 29.7 min (minor).

比較例１
本実施例では、Cu(O₃SC₁₂H₂₅)₂に代えてSc(O₃SC₁₂H₂₅)₃(23.8 mg, 0.03 mmol）を用いて、実施例１と同様に合成反応を行った。その結果、(1R,2R)-2-(1H-indol-3-yl)-1,2-diphenylethanolを得た(54.3 mg, 58% yield, 92% ee)。
HPLC(Daicel Chiralpak OD-H, n-hexane/i-PrOH = 4/1, flow rate 0.8 mL/min)t_R = 30.7 min(major),t_R = 43.7 min(minor).
反応式を下式に示す。

Comparative Example 1
In this example, the synthetic reaction was performed in the same manner as in Example 1 using Sc (O ₃ SC ₁₂ H ₂₅ ) ₃ (23.8 mg, 0.03 mmol) instead of Cu (O ₃ SC ₁₂ H ₂₅ ) ₂ . . As a result, (1R, 2R) -2- (1H-indol-3-yl) -1,2-diphenylethanol was obtained (54.3 mg, 58% yield, 92% ee).
HPLC (Daicel Chiralpak OD-H, n-hexane / i-PrOH = 4/1, flow rate 0.8 mL / min) t _R = 30.7 min (major), t _R = 43.7 min (minor).
The reaction formula is shown below.

比較例２
本実施例では、Cu(O₃SC₁₂H₂₅)₂に代えてSc(O₃SC₁₂H₂₅)₃(23.8 mg, 0.03 mmol）を用いて、実施例１０と同様に合成反応を行った。その結果、(1S,2S)-1,2-Diphenyl-2-(phenylamino)-ethanol を得た(75.7 mg, 87% yield, 95% ee)。
HPLC(Daicel Chiralpak AD, n-hexane/i-PrOH = 19/1, flow rate 1.0 mL/min)tR = 25.4 min(major), t_R = 29.7 min(minor).
反応式を下式に示す。

Comparative Example 2
In this example, the synthetic reaction was carried out in the same manner as in Example 10 using Sc (O ₃ SC ₁₂ H ₂₅ ) ₃ (23.8 mg, 0.03 mmol) instead of Cu (O ₃ SC ₁₂ H ₂₅ ) ₂ . . As a result, (1S, 2S) -1,2-Diphenyl-2- (phenylamino) -ethanol was obtained (75.7 mg, 87% yield, 95% ee).
HPLC (Daicel Chiralpak AD, n-hexane / i-PrOH = 19/1, flow rate 1.0 mL / min) tR = 25.4 min (major), t _R = 29.7 min (minor).
The reaction formula is shown below.

Claims

The following formula

(Wherein R ¹ represents an alkyl group or aryl group having 3 or more carbon atoms, R ² represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms or an alkoxy group, and X represents —OH, or -SH represents a ligand or an enantiomer thereof and M (OSO ₂ R ³ ) ₂ or M (OSO ₃ R ³ ) ₂ (wherein M represents a copper group element or a zinc group element). R ³ represents an aliphatic hydrocarbon group having 6 or more carbon atoms, an aromatic hydrocarbon group or a perfluoroalkyl group.), And a heterocyclic compound of an epoxide obtained by mixing with a Lewis acid represented by Alternatively, a catalyst for producing an optically active alcohol compound by an asymmetric ring-opening reaction with an amine .

The catalyst according to claim 1, wherein R ¹ is a t-butyl group and R ² is a hydrogen atom.

The catalyst according to claim 1 or 2, wherein R ³ is an alkyl group having 6 to 20 carbon atoms or an alkylaryl group.

In the presence of the catalyst according to any one of claims 1 to 3 in an aqueous solution or a mixed solvent of water and an organic solvent, the following formula (formula 2):

The process according to claim 4, wherein the epoxide is a meso form (that is, R ⁴ and R ⁵ are the same).

The process according to claim 4 or 5, wherein the heterocyclic compound is an indole derivative.

(Wherein R ⁴ , R ⁵ , R ¹⁰ and R ¹¹ represent the same as above) or a process for producing an optically active β-amino alcohol compound represented by an enantiomer thereof.

The process according to claim 7, wherein the epoxide is a meso form (that is, R ⁴ and R ⁵ are the same).

The process according to claim 7 or 8, wherein the amine compound is an aromatic amine.