JP2010173958A

JP2010173958A - New diphosphine compound, method for producing the same and metal complex containing the same

Info

Publication number: JP2010173958A
Application number: JP2009017385A
Authority: JP
Inventors: Toshinobu Korenaga; 敏伸是永; Takashi Sakai; 貴志酒井; Kazutaka Osaki; 和隆大崎
Original assignee: Okayama University NUC
Current assignee: Okayama University NUC
Priority date: 2009-01-28
Filing date: 2009-01-28
Publication date: 2010-08-12
Anticipated expiration: 2029-01-28
Also published as: JP5283175B2

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new diphosphine compound showing a good reaction yield and enantio-selectivity in using it as a ligand of a transition metal complex which is a catalyst for asymmetric synthesis, and also easily synthesized. <P>SOLUTION: This representative diphosphine compound and the metal complex by using the same as the ligand are expressed by formulae. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

本発明は、新規なジホスフィン化合物、その製造方法及びそれを含む金属錯体に関する。当該ジホスフィン化合物が配位子として遷移金属に配位した金属錯体は、不斉合成用触媒として好適に用いられる。 The present invention relates to a novel diphosphine compound, a method for producing the same, and a metal complex containing the same. A metal complex in which the diphosphine compound is coordinated to a transition metal as a ligand is suitably used as a catalyst for asymmetric synthesis.

従来、ジホスフィン化合物は遷移金属錯体における配位子として広く使用されてきた。このとき、光学活性なジホスフィン化合物を配位子として用いた光学活性な遷移金属錯体は、不斉合成に用いることができる。そのようなジホスフィン化合物において不斉触媒として優れた性能を有するものとして、ビフェニル基やビナフチル基を有する軸不斉光学活性体が提案されている。 Conventionally, diphosphine compounds have been widely used as ligands in transition metal complexes. At this time, an optically active transition metal complex using an optically active diphosphine compound as a ligand can be used for asymmetric synthesis. As such a diphosphine compound having an excellent performance as an asymmetric catalyst, an axially asymmetric optically active substance having a biphenyl group or a binaphthyl group has been proposed.

非特許文献１には、そのような軸不斉光学活性体であるジホスフィン化合物が提案されている。なかでも、下記式に示すBINAP［(1,1-binaphthalene)-2,2-diylbis(diphenylphosphine)］を配位子として用いた遷移金属錯体は、不斉合成用触媒として優れた性能を示すことが知られていて、最も汎用的に用いられている不斉配位子の一つである。しかしながら、反応の種類や条件によっては、BINAPを含む不斉触媒を用いた場合に、反応の進行が不十分となったり、エナンチオ選択性が不十分となったりする場合があった。一方、下記式に示すMeO-BIPHEP［(6,6'-dimethoxybiphenyl-2,2'-diyl)bis(diphenylphosphine)］を配位子として用いた遷移金属錯体も、不斉合成用触媒として広く用いられているが、反応収率やエナンチオ選択性の面で不十分な場合があった。MeO-BIPHEPについては、特許文献１にも記載されている。 Non-Patent Document 1 proposes a diphosphine compound which is such an axially asymmetric optically active substance. In particular, transition metal complexes using BINAP [(1,1-binaphthalene) -2,2-diylbis (diphenylphosphine)] shown in the following formula as a ligand exhibit excellent performance as a catalyst for asymmetric synthesis. Is one of the most widely used asymmetric ligands. However, depending on the type and conditions of the reaction, when an asymmetric catalyst containing BINAP is used, the progress of the reaction may be insufficient or the enantioselectivity may be insufficient. On the other hand, transition metal complexes using MeO-BIPHEP [(6,6'-dimethoxybiphenyl-2,2'-diyl) bis (diphenylphosphine)] represented by the following formula as a ligand are also widely used as catalysts for asymmetric synthesis. However, the reaction yield and enantioselectivity were sometimes insufficient. MeO-BIPHEP is also described in Patent Document 1.

特許文献２には、MeO-BIPHEPのリン原子に結合している４個のフェニル基の全てが、３，５−ビス（トリフルオロメチル）フェニル基に置き換わっているジホスフィン化合物を不斉配位子として用いて、環状ケトンの不斉還元反応を行った例が記載されている。しかしながら、本願実施例にも示すように、このような電子求引基を有するジホスフィン化合物を用いた場合であっても、やはり反応の種類や条件によっては反応収率やエナンチオ選択性の面で不十分な場合があった。 In Patent Document 2, a diphosphine compound in which all four phenyl groups bonded to the phosphorus atom of MeO-BIPHEP are replaced with 3,5-bis (trifluoromethyl) phenyl groups is an asymmetric ligand. As an example, an asymmetric reduction reaction of a cyclic ketone is described. However, as shown in the Examples of the present application, even when such a diphosphine compound having an electron withdrawing group is used, depending on the type and conditions of the reaction, the reaction yield and enantioselectivity are not satisfactory. There were enough cases.

特表平６−５０６４７５号公報JP-T 6-506475 特開２００１−２７０８６５号公報JP 2001-270865 A

Helvetica Chimica Acta, vol. 74, p.370-389 (1991)Helvetica Chimica Acta, vol. 74, p.370-389 (1991)

本発明は、上記課題を解決するためになされたものであり、不斉合成用触媒である遷移金属錯体の配位子として用いた際に、反応収率及びエナンチオ選択性が良好であって、しかも容易に合成できる新規ジホスフィン化合物を提供することを目的とするものである。また、そのようなジホスフィン化合物の製造方法及びそれを含む金属錯体を提供することを目的とするものである。さらには、そのような金属錯体からなる不斉合成用触媒を提供することを目的とするものである。 The present invention has been made to solve the above problems, and when used as a ligand of a transition metal complex that is a catalyst for asymmetric synthesis, the reaction yield and enantioselectivity are good, And it aims at providing the novel diphosphine compound which can be synthesize | combined easily. Moreover, it aims at providing the manufacturing method of such a diphosphine compound, and a metal complex containing the same. Furthermore, it aims at providing the catalyst for asymmetric synthesis which consists of such a metal complex.

本発明は、下記式（１）で表されるジホスフィン化合物である。 The present invention is a diphosphine compound represented by the following formula (1).

［式中、Ｒ^１、Ｒ^２及びＲ^３は、それぞれ独立して水素原子、ハロゲン原子、炭素数１〜６のアルキル基、炭素数１〜６のアルコキシ基、炭素数１〜１０のフッ素化アルキル基又は炭素数１〜１０のフッ素化アルコキシ基を示す。Ｒ^４は、炭素数１〜６のアルキル基又は炭素数１〜１０のフッ素化アルキル基を示す。同一のベンゼン環に結合しているＲ^１、Ｒ^２、Ｒ^３及びＲ^４は、互いに結合して環を形成していてもよい。Ａｒは、下記式（２）で表される置換フェニル基を示す。］ [Wherein R ¹ , R ² and R ³ are each independently a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, or a fluorination having 1 to 10 carbon atoms. An alkyl group or a fluorinated alkoxy group having 1 to 10 carbon atoms is shown. R ⁴ represents an alkyl group having 1 to 6 carbon atoms or a fluorinated alkyl group having 1 to 10 carbon atoms. R ¹ , R ² , R ³ and R ⁴ bonded to the same benzene ring may be bonded to each other to form a ring. Ar represents a substituted phenyl group represented by the following formula (2). ]

［式中、Ｒ^５、Ｒ^６、Ｒ^７、Ｒ^８及びＲ^９で示される置換基のうち、３〜５個の置換基がフッ素原子又は炭素数１〜６のパーフルオロアルキル基であり、０〜２個の置換基が水素原子である。］ [Wherein, among the substituents represented by R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ , 3 to 5 substituents are a fluorine atom or a C 1-6 perfluoroalkyl group, 0 to 2 substituents are hydrogen atoms. ]

このとき、Ｒ^５、Ｒ^６、Ｒ^７、Ｒ^８及びＲ^９で示される置換基のうち、３〜５個の置換基がフッ素原子であることが好ましい。また、前記ジホスフィン化合物が、軸不斉光学活性体であることも好ましい。 In this ^{^{^{case, R 5, R 6, R}}} 7, among the substituents represented by ^{R 8} and ^{R 9,} is preferably 3-5 substituents are fluorine atoms. The diphosphine compound is preferably an axially asymmetric optically active substance.

本発明の好適な実施態様は、前記ジホスフィン化合物が配位子として遷移金属に配位した金属錯体である。このとき、当該遷移金属が、周期律表の第８族、第９族又は第１０族に属する金属であることが好ましい。また、軸不斉光学活性体である前記金属錯体は、不斉合成用触媒として好適に用いることができる。 A preferred embodiment of the present invention is a metal complex in which the diphosphine compound is coordinated to a transition metal as a ligand. In this case, the transition metal is preferably a metal belonging to Group 8, Group 9, or Group 10 of the periodic table. Moreover, the said metal complex which is an axially asymmetric optically active substance can be used suitably as a catalyst for asymmetric synthesis.

また本発明は、下記式（３） Further, the present invention provides the following formula (3)

［式中、Ｒ^１、Ｒ^２及びＲ^３は、それぞれ独立して水素原子、ハロゲン原子、炭素数１〜６のアルキル基、炭素数１〜６のアルコキシ基、炭素数１〜１０のフッ素化アルキル基又は炭素数１〜１０のフッ素化アルコキシ基を示す。Ｒ^４は、炭素数１〜６のアルキル基又は炭素数１〜１０のフッ素化アルキル基を示す。同一のベンゼン環に結合しているＲ^１、Ｒ^２、Ｒ^３及びＲ^４は、互いに結合して環を形成していてもよい。］ [Wherein R ¹ , R ² and R ³ are each independently a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, or a fluorination having 1 to 10 carbon atoms. An alkyl group or a fluorinated alkoxy group having 1 to 10 carbon atoms is shown. R ⁴ represents an alkyl group having 1 to 6 carbon atoms or a fluorinated alkyl group having 1 to 10 carbon atoms. R ¹ , R ² , R ³ and R ⁴ bonded to the same benzene ring may be bonded to each other to form a ring. ]

で表される光学活性なジホスフィン化合物を、トリホスゲンと四級アンモニウム塩とを混合して調製された反応剤と反応させる、下記式（４） The optically active diphosphine compound represented by formula (4) is reacted with a reaction agent prepared by mixing triphosgene and a quaternary ammonium salt.

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は前記式（３）に同じ。］
で表される光学活性なジホスフィン化合物の製造方法である。 [Wherein R ¹ , R ² , R ³ and R ⁴ are the same as those in the formula (3). ]
Is an optically active diphosphine compound production method.

このとき、上記製造方法によって得られた前記式（４）で表される光学活性なジホスフィン化合物に、下記式（５） At this time, the optically active diphosphine compound represented by the above formula (4) obtained by the above production method is added to the following formula (5).

［式中、Ａｒは、下記式（２）で表される置換フェニル基を示し、Ｍは、Ｌｉ又はＭｇ−Ｘを示す。ここでＸはハロゲン原子を示す。］ [In the formula, Ar represents a substituted phenyl group represented by the following formula (2), and M represents Li or Mg—X. Here, X represents a halogen atom. ]

［式中、Ｒ^５、Ｒ^６、Ｒ^７、Ｒ^８及びＲ^９で示される置換基のうち、３〜５個の置換基がフッ素原子又は炭素数１〜６のパーフルオロアルキル基であり、０〜２個の置換基が水素原子である。］
で表される有機金属化合物と反応させる下記式（１） [Wherein, among the substituents represented by R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ , 3 to 5 substituents are a fluorine atom or a C 1-6 perfluoroalkyl group, 0 to 2 substituents are hydrogen atoms. ]
The following formula (1) is reacted with an organometallic compound represented by

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は、前記式（３）に同じ。Ａｒは、前記式（２）に同じ。］
で表される光学活性なジホスフィン化合物の製造方法が、好適な実施態様である。 [Wherein R ¹ , R ² , R ³ and R ⁴ are the same as those in the formula (3). Ar is the same as the formula (2). ]
A method for producing an optically active diphosphine compound represented by the formula is a preferred embodiment.

本発明のジホスフィン化合物は、不斉合成用触媒である遷移金属錯体の配位子として用いた際に、反応収率及びエナンチオ選択性が良好であって、しかも容易に合成できる。したがって、各種の不斉合成反応に好適に用いることができる。また、本発明のジホスフィン化合物の合成方法は、そのようなジホスフィン化合物などを、高い光学純度で容易に合成できるものである。 The diphosphine compound of the present invention has good reaction yield and enantioselectivity when used as a ligand of a transition metal complex that is a catalyst for asymmetric synthesis, and can be easily synthesized. Therefore, it can be suitably used for various asymmetric synthesis reactions. The method for synthesizing a diphosphine compound of the present invention can easily synthesize such a diphosphine compound and the like with high optical purity.

本発明のジホスフィン化合物は、下記式（１）で表されるものである。 The diphosphine compound of the present invention is represented by the following formula (1).

本発明のジホスフィン化合物の特徴は、MeO-BIPHEPに代表されるような、６位及び６’位にアルコキシ基を有するビフェニル骨格を含む芳香族ジホスフィンにおいて、リン原子に結合しているフェニル基の３〜５個の水素原子がフッ素原子又はパーフルオロアルキル基に置換されていることである。リン原子に結合している４個のフェニル基の全てにおいて、強力な電子求引基をそれぞれ３個以上有することによってホスフィンの電子密度が制御される。本発明のジホスフィン化合物を不斉合成用触媒の配位子として用いた場合には、このような強力な電子求引効果によって、高活性の不斉触媒を提供することができる。また、水素原子よりも大きいフッ素原子あるいはパーフルオロアルキル基の存在によって、配位子の立体制御能が向上することも期待できる。さらに、ビフェニル骨格において、６位及び６’位にアルコキシ基を有することによって、ジホスフィン化合物の合成が容易になる。 The diphosphine compound of the present invention is characterized in that an aromatic diphosphine containing a biphenyl skeleton having alkoxy groups at the 6-position and 6′-position, represented by MeO-BIPHEP, has 3 phenyl groups bonded to a phosphorus atom. ˜5 hydrogen atoms are substituted with fluorine atoms or perfluoroalkyl groups. In all of the four phenyl groups bonded to the phosphorus atom, the electron density of the phosphine is controlled by having at least three strong electron withdrawing groups. When the diphosphine compound of the present invention is used as a ligand for the catalyst for asymmetric synthesis, such a strong electron-withdrawing effect can provide a highly active asymmetric catalyst. In addition, the presence of a fluorine atom or perfluoroalkyl group larger than a hydrogen atom can be expected to improve the stereocontrollability of the ligand. Furthermore, since the biphenyl skeleton has alkoxy groups at the 6-position and 6'-position, synthesis of the diphosphine compound is facilitated.

上記式（１）において、Ｒ^１、Ｒ^２及びＲ^３は、それぞれ独立して水素原子、ハロゲン原子、炭素数１〜６のアルキル基、炭素数１〜６のアルコキシ基、炭素数１〜１０のフッ素化アルキル基又は炭素数１〜１０のフッ素化アルコキシ基を示す。 In the above formula (1), R ¹ , R ² and R ³ each independently represent a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, or 1 to 10 carbon atoms. Or a fluorinated alkoxy group having 1 to 10 carbon atoms.

ここで、ハロゲン原子としては、フッ素原子、塩素原子、臭素原子などが例示される。炭素数１〜６のアルキル基としては、メチル基、エチル基、１−プロピル基、２−プロピル基、１−ブチル基、２−ブチル基、２−メチル−２−プロピル基、１−ペンチル基、１−ヘキシル基などが例示される。炭素数１〜６のアルコキシ基としては、メトキシ基、エトキシ基、１−プロポキシル基、２−プロポキシ基、１−ブトキシ基、２−ブトキシ基、２−メチル−２−プロポキシ基、１−ペンチルオキシ基、１−ヘキシルオキシ基などが例示される。 Here, examples of the halogen atom include a fluorine atom, a chlorine atom, and a bromine atom. Examples of the alkyl group having 1 to 6 carbon atoms include methyl group, ethyl group, 1-propyl group, 2-propyl group, 1-butyl group, 2-butyl group, 2-methyl-2-propyl group, and 1-pentyl group. And 1-hexyl group. Examples of the alkoxy group having 1 to 6 carbon atoms include methoxy group, ethoxy group, 1-propoxyl group, 2-propoxy group, 1-butoxy group, 2-butoxy group, 2-methyl-2-propoxy group, and 1-pentyl. Examples include an oxy group and a 1-hexyloxy group.

炭素数１〜１０のフッ素化アルキル基は、アルキル基中の全ての水素原子がフッ素原子に置換されたもの（パーフルオロアルキル基）と、アルキル基中の一部の水素原子がフッ素原子で置換されたものを含み、直鎖状でも分岐状でもよい。本発明のジホスフィン化合物を触媒の配位子として用い、フッ素系の溶媒を用いる不斉合成反応などにおいて触媒の溶解性が良好である。アルキル基中の一部の水素原子がフッ素原子で置換されたものとしては、例えば、下記式（６）で示されるものなどを用いることができる。 The fluorinated alkyl group having 1 to 10 carbon atoms is one in which all hydrogen atoms in the alkyl group are substituted with fluorine atoms (perfluoroalkyl group), and some hydrogen atoms in the alkyl group are substituted with fluorine atoms. It may be linear or branched. The solubility of the catalyst is good in the asymmetric synthesis reaction using the diphosphine compound of the present invention as a catalyst ligand and using a fluorine-based solvent. As what substituted some hydrogen atoms in the alkyl group by the fluorine atom, what is shown by following formula (6) etc. can be used, for example.

［式中、ｍは１〜９の整数であり、ｎは０〜８の整数であり、ｍ＋ｎは１〜９の整数である。］ [Wherein, m is an integer of 1 to 9, n is an integer of 0 to 8, and m + n is an integer of 1 to 9. ]

炭素数１〜１０のフッ素化アルコキシ基は、アルコキシ基中の全ての水素原子がフッ素原子に置換されたもの（パーフルオロアルコキシ基）と、アルコキシ基中の一部の水素原子がフッ素原子で置換されたものを含み、直鎖状でも分岐状でもよい。本発明のジホスフィン化合物を触媒の配位子として用い、フッ素系の溶媒を用いる不斉合成反応などにおいて触媒の溶解性が良好である。アルコキシ基中の一部の水素原子がフッ素原子で置換されたものとしては、例えば、下記式（７）で示されるものなどを用いることができる。 The fluorinated alkoxy group having 1 to 10 carbon atoms is one in which all hydrogen atoms in the alkoxy group are substituted with fluorine atoms (perfluoroalkoxy group), and some hydrogen atoms in the alkoxy group are substituted with fluorine atoms. It may be linear or branched. The solubility of the catalyst is good in the asymmetric synthesis reaction using the diphosphine compound of the present invention as a catalyst ligand and using a fluorine-based solvent. As what substituted some hydrogen atoms in an alkoxy group by the fluorine atom, what is shown by following formula (7) etc. can be used, for example.

合成しやすさの面からは、Ｒ^１、Ｒ^２及びＲ^３が、いずれも水素原子であることが好ましい。 From the viewpoint of ease of synthesis, it is preferable that R ¹ , R ² and R ³ are all hydrogen atoms.

Ｒ^４は、炭素数１〜６のアルキル基又は炭素数１〜１０のフッ素化アルキル基を示す。炭素数１〜６のアルキル基及び炭素数１〜１０のフッ素化アルキル基としては、Ｒ^１、Ｒ^２及びＲ^３と同じものを使用することができる。このように、ビフェニル骨格の６位及び６’位にアルコキシ基を有することによって、ジホスフィン化合物の合成が容易になる。中でも、Ｒ^４がメチル基であること、すなわち、ビフェニル骨格の６位及び６’位にメトキシ基が結合していることが、合成しやすくて好ましい。 R ⁴ represents an alkyl group having 1 to 6 carbon atoms or a fluorinated alkyl group having 1 to 10 carbon atoms. As the alkyl group having 1 to 6 carbon atoms and the fluorinated alkyl group having 1 to 10 carbon atoms, the same groups as R ¹ , R ² and R ³ can be used. Thus, having an alkoxy group at the 6-position and 6′-position of the biphenyl skeleton facilitates the synthesis of the diphosphine compound. Among them, it is preferable that R ⁴ is a methyl group, that is, that a methoxy group is bonded to the 6-position and 6′-position of the biphenyl skeleton because of easy synthesis.

同一のベンゼン環に結合しているＲ^１、Ｒ^２、Ｒ^３及びＲ^４は、互いに結合して環を形成していてもよい。この場合、Ｒ^３及びＲ^４が互いに結合して環を形成していることが好ましい。 R ¹ , R ² , R ³ and R ⁴ bonded to the same benzene ring may be bonded to each other to form a ring. In this case, it is preferable that R ³ and R ⁴ are bonded to each other to form a ring.

上記式（２）において、Ｒ^５、Ｒ^６、Ｒ^７、Ｒ^８及びＲ^９で示される５つの置換基のうち、３〜５個の置換基がフッ素原子又は炭素数１〜６のパーフルオロアルキル基であり、０〜２個の置換基が水素原子であることが重要である。このような強力な電子求引基を多数有することによって、触媒の配位子として用いた際に、従来の電子供与性を有する不斉配位子では反応性が不十分であったり、エナンチオ選択性が不十分であったりした反応においても、不斉合成反応の収率及びエナンチオ選択性を大きく改善できる場合がある。 In the above formula (2), among the five substituents represented by R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ , 3 to 5 substituents are fluorine atoms or C 1-6 perfluoro. It is an alkyl group, and it is important that 0 to 2 substituents are hydrogen atoms. By having a large number of such strong electron-withdrawing groups, when used as a catalyst ligand, conventional asymmetric ligands having electron-donating properties are not sufficiently reactive or enantioselective. Even in reactions where the properties are insufficient, the yield and enantioselectivity of the asymmetric synthesis reaction may be greatly improved.

炭素数１〜６のパーフルオロアルキル基としては、トリフルオロメチル基、ペンタフルオロエチル基、ヘプタフルオロプロピル基などが例示される。なかでも合成しやすさや立体障害の面からトリフルオロメチル基が好適である。 Examples of the C 1-6 perfluoroalkyl group include a trifluoromethyl group, a pentafluoroethyl group, a heptafluoropropyl group, and the like. Of these, a trifluoromethyl group is preferred from the viewpoint of ease of synthesis and steric hindrance.

Ｒ^５、Ｒ^６、Ｒ^７、Ｒ^８及びＲ^９で示される５つの置換基のうち、少なくとも１つがフッ素原子であることが、立体障害の面から好ましい。フッ素原子の数は２個以上であることがより好ましく、３個以上であることがさらに好ましい。 Of the five substituents represented by R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ , at least one is preferably a fluorine atom from the viewpoint of steric hindrance. The number of fluorine atoms is more preferably 2 or more, and further preferably 3 or more.

以上説明した本発明のジホスフィン化合物は、ラセミ体であってもよい。この場合には、例えば遷移金属に配位させて錯体を形成させてから光学分割して光学活性な金属錯体を得ることもできる。しかしながら、金属錯体の調製の容易性の観点からはジホスフィン化合物自体が光学活性体であることが好ましく、この場合、軸不斉光学活性体となる。すなわち、下記式（１−Ｒ）又は下記式（１−Ｓ）からなる光学活性体であることが好ましい。 The diphosphine compound of the present invention described above may be a racemate. In this case, for example, an optically active metal complex can be obtained by coordinating with a transition metal to form a complex and then optically resolving. However, from the viewpoint of ease of preparation of the metal complex, the diphosphine compound itself is preferably an optically active substance, and in this case, it becomes an axially asymmetric optically active substance. That is, an optically active substance composed of the following formula (1-R) or the following formula (1-S) is preferable.

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は前記式（１）に同じ。］ [Wherein R ¹ , R ² , R ³ and R ⁴ are the same as those in the formula (1). ]

本発明の好適な実施態様は光学活性体であるジホスフィン化合物が遷移金属に配位した金属錯体である。 A preferred embodiment of the present invention is a metal complex in which a diphosphine compound as an optically active substance is coordinated to a transition metal.

このような金属錯体に用いられる好適な遷移金属は、周期律表の第８族、第９族又は第１０族に属する金属である。具体的には、ロジウム、白金、パラジウム、ルテニウム、ニッケル、鉄、イリジウムなどが例示される。この場合、ハロゲン化物、カルボニル錯体、オレフィン錯体、エノラート錯体などの遷移金属塩又は遷移金属錯体に本発明のジホスフィン化合物を配位させた金属錯体が好適である。 Suitable transition metals used for such metal complexes are those belonging to Group 8, Group 9 or Group 10 of the Periodic Table. Specifically, rhodium, platinum, palladium, ruthenium, nickel, iron, iridium and the like are exemplified. In this case, a metal complex in which the diphosphine compound of the present invention is coordinated to a transition metal salt or transition metal complex such as a halide, a carbonyl complex, an olefin complex, or an enolate complex is preferable.

このような遷移金属錯体は、予め錯体として単離したものを準備してから不斉合成反応に用いてもよいし、本発明のジホスフィン化合物と遷移金属化合物とを混合することによって反応系中で金属錯体を形成させてもよい。操作の容易性の観点からは、後者の方法が好適に採用される。触媒の使用量は、通常、原料化合物に対して０．１〜１０モル％であり、好適には１〜５モル％である。用いられる溶媒は、原料化合物、反応剤及び本発明のジホスフィン化合物を溶解させることのできる溶媒であればよく、トルエンなどの芳香族炭化水素；テトラヒドロフラン、ジオキサンなどのエーテル；塩化メチレンなどの含ハロゲン炭化水素などが例示される。このとき、水を共存させた混合溶媒とすることもできる。反応によって様々な溶媒を選択することができる。 Such a transition metal complex may be prepared in advance as a complex and then used for the asymmetric synthesis reaction, or in the reaction system by mixing the diphosphine compound of the present invention and the transition metal compound. A metal complex may be formed. From the viewpoint of ease of operation, the latter method is preferably employed. The usage-amount of a catalyst is 0.1-10 mol% normally with respect to a raw material compound, Preferably it is 1-5 mol%. The solvent used may be any solvent that can dissolve the raw material compound, the reactant, and the diphosphine compound of the present invention; aromatic hydrocarbon such as toluene; ether such as tetrahydrofuran and dioxane; halogen-containing carbonization such as methylene chloride. Hydrogen etc. are illustrated. At this time, a mixed solvent in which water coexists can also be used. Various solvents can be selected depending on the reaction.

本発明のジホスフィン化合物を配位子とする触媒を使用した不斉合成反応は特に限定されない。不斉水素化反応、不斉付加反応、不斉異性化反応、不斉交差カップリング反応などの各種の不斉合成反応に用いることができる。本願実施例では、ホウ素化合物（ボロン酸）のα，β−不飽和化合物（α，β−不飽和ケトン）への１，４−付加反応の例において、光学収率よく反応が進行することが示されている。 The asymmetric synthesis reaction using the catalyst having the diphosphine compound of the present invention as a ligand is not particularly limited. It can be used for various asymmetric synthesis reactions such as asymmetric hydrogenation reaction, asymmetric addition reaction, asymmetric isomerization reaction, and asymmetric cross-coupling reaction. In Examples of the present application, in the example of 1,4-addition reaction of a boron compound (boronic acid) to an α, β-unsaturated compound (α, β-unsaturated ketone), the reaction proceeds with good optical yield. It is shown.

本発明のジホスフィン化合物を合成する方法は特に限定されるものではないが、好適な合成方法は、下記式（４） The method for synthesizing the diphosphine compound of the present invention is not particularly limited, but a suitable synthesis method is represented by the following formula (4).

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は前記式（１）に同じ。］
で表される光学活性なジホスフィン化合物に、下記式（５） [Wherein R ¹ , R ² , R ³ and R ⁴ are the same as those in the formula (1). ]
In the optically active diphosphine compound represented by the following formula (5)

［式中、Ａｒは、前記式（２）で表される置換フェニル基を示し、Ｍは、Ｌｉ又はＭｇ−Ｘを示す。ここでＸはハロゲン原子を示す。］
で表される有機金属化合物と反応させる下記式（１） [Wherein Ar represents a substituted phenyl group represented by the formula (2), and M represents Li or Mg-X. Here, X represents a halogen atom. ]
The following formula (1) is reacted with an organometallic compound represented by

［式中、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４及びＡｒは、既に説明したとおり。］
で表される光学活性なジホスフィン化合物の製造方法である。 [Wherein R ¹ , R ² , R ³ , R ⁴ and Ar are as described above. ]
Is an optically active diphosphine compound production method.

この方法によれば、ラセミ化を起こすことなく、上記式（４）で表される光学活性なジホスフィン化合物から、上記式（１）で表される光学活性なジホスフィン化合物を得ることができる。 According to this method, the optically active diphosphine compound represented by the above formula (1) can be obtained from the optically active diphosphine compound represented by the above formula (4) without causing racemization.

式（５）において、Ｍがリチウム原子である場合には、式（５）で表される化合物は有機リチウム化合物である。また、ＭがＭｇ−Ｘである場合には、式（５）で表される化合物はグリニャール化合物である。グリニャール化合物におけるハロゲン原子としては、塩素原子、臭素原子、ヨウ素原子などを採用することができる。 In Formula (5), when M is a lithium atom, the compound represented by Formula (5) is an organolithium compound. When M is Mg—X, the compound represented by the formula (5) is a Grignard compound. As the halogen atom in the Grignard compound, a chlorine atom, a bromine atom, an iodine atom or the like can be employed.

式（５）で表される有機リチウム化合物は、Ａｒ−Ｈで示される置換ベンゼン又はＡｒ−Ｘで示される置換ベンゼンに対してｎ−ブチルリチウムなどのアルキルリチウム化合物を反応させて、前記置換ベンゼン中の水素原子又はハロゲン原子をリチウム原子に置き換える方法などによって合成される。また、式（５）で表されるグリニャール化合物は、Ａｒ−Ｘで示される置換ベンゼンに対して金属マグネシウムを反応させる方法などによって合成される。これらの場合の反応溶媒としては、非プロトン性の有機溶媒が用いられ、テトラヒドロフラン（ＴＨＦ）やジエチルエーテルなどのエーテルが好適に用いられる。 The organolithium compound represented by the formula (5) is obtained by reacting an alkyllithium compound such as n-butyllithium with a substituted benzene represented by Ar-H or a substituted benzene represented by Ar-X. It is synthesized by a method in which a hydrogen atom or a halogen atom in the inside is replaced with a lithium atom. Further, the Grignard compound represented by the formula (5) is synthesized by a method of reacting magnesium metal with a substituted benzene represented by Ar-X. As a reaction solvent in these cases, an aprotic organic solvent is used, and ethers such as tetrahydrofuran (THF) and diethyl ether are preferably used.

このようにして合成された式（５）で表される化合物は、そのまま式（４）で表される化合物と反応させることが好ましい。このときの反応溶媒は、式（５）で表される化合物を合成した時の溶媒をそのまま用いることができるし、他の有機溶媒を加えてもよい。ラセミ化や副反応を防止する観点からは、反応温度は−８０〜２０℃であることが好ましい。式（４）で表される化合物に対する収率を向上させるためには、式（４）で表される化合物に対して過剰量の式（５）で表される化合物を反応させることが好ましい。具体的には、式（４）で表される化合物１モルに対して４〜５０モルの式（５）で表される化合物を反応させることが好ましく、８〜２０モルの式（５）で表される化合物を反応させることがより好ましい。 The compound represented by the formula (5) synthesized in this manner is preferably reacted with the compound represented by the formula (4) as it is. As the reaction solvent at this time, the solvent when the compound represented by the formula (5) is synthesized can be used as it is, or another organic solvent may be added. From the viewpoint of preventing racemization and side reactions, the reaction temperature is preferably −80 to 20 ° C. In order to improve the yield with respect to the compound represented by Formula (4), it is preferable to react an excess amount of the compound represented by Formula (5) with respect to the compound represented by Formula (4). Specifically, it is preferable to react 4 to 50 mol of the compound represented by the formula (5) with respect to 1 mol of the compound represented by the formula (4), and 8 to 20 mol of the formula (5). It is more preferable to react the represented compound.

また、式（４）で示される化合物の製造方法としては、下記式（３） Moreover, as a manufacturing method of the compound shown by Formula (4), following formula (3)

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は前記式（１）に同じ。］
で表される光学活性なジホスフィン化合物を、トリホスゲンと四級アンモニウム塩とを混合して調製された反応剤と反応させる、下記式（４） [Wherein R ¹ , R ² , R ³ and R ⁴ are the same as those in the formula (1). ]
The optically active diphosphine compound represented by formula (4) is reacted with a reaction agent prepared by mixing triphosgene and a quaternary ammonium salt.

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は前記式（１）に同じ。］
で表される光学活性なジホスフィン化合物の製造方法が好適である。この製造方法によって、危険性の高いホスゲンを使用することなく、しかもラセミ化を起こすことなく、光学的に純粋な式（４）で表される光学活性なジホスフィン化合物を得ることができる。なお、この製造方法によって得られる式（４）で表される化合物は、式（１）で示されるジホスフィン化合物を製造するのに用いられるのみならず、その他の化合物を合成する中間体として用いることもできる。 [Wherein R ¹ , R ² , R ³ and R ⁴ are the same as those in the formula (1). ]
A method for producing an optically active diphosphine compound represented by the formula: By this production method, an optically active diphosphine compound represented by the formula (4) can be obtained without using highly dangerous phosgene and without causing racemization. The compound represented by formula (4) obtained by this production method is not only used for producing the diphosphine compound represented by formula (1), but also used as an intermediate for synthesizing other compounds. You can also.

ここで、式（３）で表される化合物は、既知の方法にしたがって合成することができる。その製造方法の一例を下記式（Ｉ）に示す。

Here, the compound represented by the formula (3) can be synthesized according to a known method. An example of the manufacturing method is shown in the following formula (I).

従来の合成方法では、式（３）で表される化合物から、式（４）で表される化合物を合成するときに、毒性の高いホスゲンが用いられている。本発明者らがホスゲンの代わりに、固体であって、取扱いの容易なトリホスゲン（炭酸ビス（トリクロロメチル））を用いたところ、単にトリホスゲンを用いたのでは、得られる式（４）で示されるジホスフィン化合物の一部がラセミ化してしまうことが明らかになった。これに対し、トリホスゲンと四級アンモニウム塩とを予め混合して調製した反応剤を用いることによって、ラセミ化を防止することができ、光学的に純粋な式（４）で表される化合物を得ることができた。 In a conventional synthesis method, highly toxic phosgene is used when a compound represented by formula (4) is synthesized from a compound represented by formula (3). When the present inventors used triphosgene (bis (trichloromethyl carbonate)) that is solid and easy to handle instead of phosgene, when triphosgene is simply used, the formula (4) is obtained. It became clear that a part of the diphosphine compound was racemized. In contrast, by using a reactant prepared by mixing triphosgene and a quaternary ammonium salt in advance, racemization can be prevented and an optically pure compound represented by the formula (4) is obtained. I was able to.

トリホスゲンと混合される四級アンモニウム塩は、特に限定されないが、脂肪族四級アンモニウム塩であることが好ましく、有機溶媒への溶解性の観点から、炭素数が１０以上であることが好ましく、２０以上であることがより好ましい。炭素数は、通常５０以下である。四級アンモニウム塩のカウンタアニオンは特に限定されないが、ハロゲンイオン、例えば塩素イオンが代表的である。このような四級アンモニウム塩としては、例えば、Ｎ−メチル−Ｎ，Ｎ−ジオクチルオクタン−１−アミニウムクロライド（コグニス社から「アリコート（Aliquat：登録商標）３３６」として市販されている。）などが、特に好適に用いられる。 The quaternary ammonium salt mixed with triphosgene is not particularly limited, but is preferably an aliphatic quaternary ammonium salt, and preferably has 10 or more carbon atoms from the viewpoint of solubility in an organic solvent. More preferably. Carbon number is usually 50 or less. The counter anion of the quaternary ammonium salt is not particularly limited, but a halogen ion such as a chlorine ion is typical. Examples of such a quaternary ammonium salt include N-methyl-N, N-dioctyloctane-1-aminium chloride (commercially available as “Aliquat® 336” from Cognis). Are particularly preferably used.

トリホスゲンと四級アンモニウム塩を混合する際には、密封した容器中で両者を十分に混合する。このとき、トリホスゲン１モルに対して四級アンモニウム塩を０．０１〜０．２モル使用することが好ましく、０．０５〜０．０７モル使用することがより好ましい。反応温度は好適には０〜７０℃であり、より好適には３０〜４０℃である。反応時間は好適には２〜１００時間であり、より好適には２４〜４８時間である。用いられる溶媒は、両者を溶解する有機溶媒であれば特に限定されず、トルエン、ヘキサンなどが例示される。 When mixing triphosgene and a quaternary ammonium salt, both are mixed thoroughly in a sealed container. At this time, it is preferable to use 0.01-0.2 mol of quaternary ammonium salts with respect to 1 mol of triphosgene, and it is more preferable to use 0.05-0.07 mol. The reaction temperature is preferably 0 to 70 ° C, more preferably 30 to 40 ° C. The reaction time is preferably 2 to 100 hours, more preferably 24 to 48 hours. The solvent used is not particularly limited as long as it is an organic solvent that dissolves both, and examples thereof include toluene and hexane.

こうして予め調製された反応剤の溶液と、式（３）で表される化合物とを反応させる。このとき、式（３）で表される化合物の溶液を予め調製しておき、溶液同士を混合して反応させることが好ましい。混合時の温度は、好適には−８０〜０℃であり、より好適には−８０〜−７０℃である。その後必要に応じて昇温させて、好適には０〜５０℃、より好適には２０〜３０℃で反応させる。このときの反応時間は好適には２〜１００時間であり、より好適には２４〜４８時間である。反応に用いられる溶媒は、両者を溶解する有機溶媒であれば特に限定されず、トルエン、塩化メチレンなどが例示される。反応終了後は、必要に応じて溶媒を除去して、前述の要領で有機リチウム化合物やグリニャール化合物と反応させることができる。また、それ以外の反応に用いることもできる。 In this way, the solution of the reactant prepared in advance is reacted with the compound represented by the formula (3). At this time, it is preferable to prepare a solution of the compound represented by the formula (3) in advance, and mix and react the solutions. The temperature at the time of mixing is preferably −80 to 0 ° C., and more preferably −80 to −70 ° C. Thereafter, the temperature is raised as necessary, and the reaction is preferably carried out at 0 to 50 ° C., more preferably at 20 to 30 ° C. The reaction time at this time is preferably 2 to 100 hours, more preferably 24 to 48 hours. The solvent used in the reaction is not particularly limited as long as it is an organic solvent that dissolves both, and examples thereof include toluene and methylene chloride. After completion of the reaction, the solvent can be removed as necessary and reacted with the organolithium compound or the Grignard compound as described above. It can also be used for other reactions.

合成例１
300 ml三つ口フラスコを十分に乾燥させ、不活性ガス雰囲気下で水素化アルミニウムリチウム (95％) (760 mg、20.0 mmol) を加え、-78℃に冷却しTHF (12 ml) を加えた。次いで、トリメチルシリルクロライド(2.50 ml、19.7 mmol) を約5分かけて滴下し、-78℃で15分攪拌後、室温でさらに2時間攪拌した。その後、-30℃まで冷却し、(R)-[6’-(ジエトキシホスホリル)-6,2’-ジメトキシビフェニル-2-イル]リン酸ジエチルエステル (1.56 g、3.21 mmol)のTHF溶液 (12.0 ml) を10分以上かけて滴下し、30℃の恒温槽で72時間反応させた。十分に脱気した水 (4.0 ml) を、注意深く滴下して反応を停止し、さらに十分に脱気した水酸化ナトリウム水溶液 (30 wt%) (12.0 ml) を加えた。反応器内の固体成分が白色に変化するまで攪拌し、THF (約20 ml × 3回) を用いて抽出及び残渣の洗浄を行い、別途用意した三つ口フラスコ (不活性ガス雰囲気)に移した。そこへ、十分脱気した飽和塩化ナトリウム水溶液を加え、洗浄操作を行った。水層を除去した後、有機層を硫酸ナトリウムで脱水し、有機層のみを別のフラスコに移し、溶媒留去・減圧乾燥を行うことで、目的化合物を得、そのまま、下記合成例２の反応に移った。¹H NMR (300 MHz, CDCl₃) : δ = 3.57 (d, ¹J_P-H = 204.6 Hz, 4H), 3.73 (s, 6H), 6.92 - 6.95 (m, 2H), 7.24 - 7.29 (m, 4H). ³¹P NMR (121 MHz, CDCl₃) : δ = -127.2 (s). Synthesis example 1
The 300 ml three-necked flask was thoroughly dried, lithium aluminum hydride (95%) (760 mg, 20.0 mmol) was added under an inert gas atmosphere, cooled to −78 ° C., and THF (12 ml) was added. . Next, trimethylsilyl chloride (2.50 ml, 19.7 mmol) was added dropwise over about 5 minutes, and the mixture was stirred at -78 ° C for 15 minutes, and further stirred at room temperature for 2 hours. Thereafter, the mixture was cooled to −30 ° C. and (R)-[6 ′-(diethoxyphosphoryl) -6,2′-dimethoxybiphenyl-2-yl] phosphoric acid diethyl ester (1.56 g, 3.21 mmol) in a THF solution ( 12.0 ml) was added dropwise over 10 minutes and reacted in a thermostatic bath at 30 ° C. for 72 hours. Sufficiently degassed water (4.0 ml) was carefully added dropwise to stop the reaction, and further sufficiently degassed aqueous sodium hydroxide solution (30 wt%) (12.0 ml) was added. Stir until the solid component in the reactor turns white, extract with THF (about 20 ml × 3 times) and wash the residue, then transfer to a separately prepared three-necked flask (inert gas atmosphere). did. A saturated sodium chloride aqueous solution sufficiently deaerated was added thereto, and a washing operation was performed. After removing the aqueous layer, the organic layer is dehydrated with sodium sulfate, and only the organic layer is transferred to another flask, and the target compound is obtained by performing solvent distillation and drying under reduced pressure. Moved on. ¹ H NMR (300 MHz, CDCl ₃ ): δ = 3.57 (d, ¹ J _PH = 204.6 Hz, 4H), 3.73 (s, 6H), 6.92-6.95 (m, 2H), 7.24-7.29 (m, 4H ³¹ P NMR (121 MHz, CDCl ₃ ): δ = -127.2 (s).

合成例２
30 ml 耐圧試験管を充分に乾燥させ、トリホスゲン (1.83 g、6.17 mmol)を入れ、「Aliquat（登録商標）336」 (170 mg、0.421 mmol) のトルエン溶液 (10.0 ml) を加え、すばやく栓をし、35℃で2日間、激しく攪拌した。その後、その反応溶液及び、上記合成例１で合成した(R)-[6,6’-ジメトキシ[1,1’-ビフェニル]-2,2’-ジイル]ビスホスフィンの塩化メチレン溶液 (20.0 ml) を-78℃に冷却し、カニュラーを用いて、トルエン溶液を、塩化メチレン溶液に混合させた。ゆっくりと室温に戻してからさらに2日間攪拌し、溶媒を留去することで目的化合物とAliquat（登録商標） 336の混合物を得た。Aliquat（登録商標） 336は取り除かずに、そのまま下記合成例３の反応に移った。¹H NMR (300 MHz, CDCl₃) : δ = 3.77 (s, 6H), 7.11(d, J = 8.4 Hz, 2H), 7.63 (m, 2H), 7.86 (d, J = 8.1 H, 2H). ³¹P NMR (121 MHz, CDCl₃) : δ = 158.1 (s). Synthesis example 2
Thoroughly dry the 30 ml pressure test tube, add triphosgene (1.83 g, 6.17 mmol), add the toluene solution (10.0 ml) of “Aliquat® 336” (170 mg, 0.421 mmol), and plug it quickly. And stirred vigorously at 35 ° C. for 2 days. Then, the reaction solution and a methylene chloride solution of (R)-[6,6′-dimethoxy [1,1′-biphenyl] -2,2′-diyl] bisphosphine synthesized in Synthesis Example 1 (20.0 ml) ) Was cooled to −78 ° C. and the toluene solution was mixed with the methylene chloride solution using a cannula. After slowly returning to room temperature, the mixture was further stirred for 2 days, and the solvent was distilled off to obtain a mixture of the target compound and Aliquat (registered trademark) 336. Aliquat (registered trademark) 336 was not removed, and the reaction was directly carried out in the following Synthesis Example 3. ¹ H NMR (300 MHz, CDCl ₃ ): δ = 3.77 (s, 6H), 7.11 (d, J = 8.4 Hz, 2H), 7.63 (m, 2H), 7.86 (d, J = 8.1 H, 2H) ³¹ P NMR (121 MHz, CDCl ₃ ): δ = 158.1 (s).

合成例３
200 ml三つ口フラスコを十分に乾燥させ、不活性ガス雰囲気下で、マグネシウム (542 mg、22.3 mmol) 及び、触媒量のヨウ素を加え、THF (5.0 ml) を加えた。1-ブロモ-3,4,5-トリフルオロベンゼン (0.20 ml、1.7 mmol) を加え、ヨウ素の色が消失したことを確認した。そこへ、1-ブロモ-3,4,5-トリフルオロベンゼン (2.0 ml、17 mmol) のTHF溶液(14.0 ml) を約25分かけて滴下し、更に室温下で1時間攪拌した。その後、反応溶液を-78℃まで冷却し、上記合成例２で合成した(R)-[6,6’-ジメトキシ[1,1’-ビフェニル]-2,2’-ジイル]ホスフォナスジクロライドのTHF溶液 (37.5 ml) を約30分かけて滴下した。滴下終了後、徐々に室温まで戻し、18時間反応させた。飽和塩化アンモニウム水溶液を加えて反応を停止し、THFを留去後、残渣を酢酸エチルに溶解させて抽出操作を行い、飽和塩化ナトリウム水溶液で洗浄、硫酸ナトリウムで脱水の後、セライト濾過を行い、濃縮・乾固させた。カラムクロマトグラフィー (ヘキサン/酢酸エチル = 8/1及びヘキサン/塩化メチレン = 3/1) によって精製することにより、目的化合物を得た。(43% Yield (合成例１からの3step)、>99% ee) ¹H NMR (300 MHz, CDCl₃) : δ = 3.44 (s, 6H), 6.60 (d, J = 7.4 Hz, 2H), 6.66 - 6.72 (m, 4H), 6.74 - 6.81 (m, 4H), 6.89 (d, J = 8.2 Hz, 2H), 7.35 - 7.40 (m, 2H). ¹³C NMR (75 MHz, CDCl₃): δ = 55.0, 112.1, 116.3 - 117.6 (m), 125.5, 130.1, 131.5 - 132.1 (m), 132.5 - 133.0 (m), 135.8, 139.9 (dt, ¹J_F-C = 255.4 Hz, ²J_F-C = 15.3 Hz), 140.1 (dt, ¹J_F-C = 255.1 Hz, ²J_F-C = 15.3 Hz), 151.2 (dm, ¹J_F-C = 254.2 Hz), 157.4 - 157.5 (m). ¹⁹F NMR (282 MHz, CDCl₃) : δ = -159.7 - -159.3 (m, 4F), -134.3 (dd, ³J = 21.0 Hz, ⁴J = 7.0 Hz, 4F), -133.7 (dd, ³J = 21.0 Hz, ⁴J = 7.0 Hz, 4F). ³¹P NMR (121 MHz, CDCl₃) : δ = 10.2 (s). IR (KBr) : 1610, 1518, 1410, 1317, 1256, 1082, 1045, 856, 754 cm^-1. M.p. 131 - 132°. Anal. calc. for C₃₈H₂₀F₂₄O₂P₂ : C 57.16, H 2.52%. Found : C 56.99, H 2.91. [α]_D ^29.0 = -25.5°. HPLC (Daicel Chiralcel OD-H, Hexane/i-PrOH = 200 : 1, flow rate = 0.4 ml/min) : t_R = 14.1 min ((S)-isomer), t_R = 15.9 min ((R)-isomer). Synthesis example 3
The 200 ml three-necked flask was fully dried, magnesium (542 mg, 22.3 mmol) and a catalytic amount of iodine were added under an inert gas atmosphere, and THF (5.0 ml) was added. 1-Bromo-3,4,5-trifluorobenzene (0.20 ml, 1.7 mmol) was added and it was confirmed that the color of iodine disappeared. Thereto was added dropwise a THF solution (14.0 ml) of 1-bromo-3,4,5-trifluorobenzene (2.0 ml, 17 mmol) over about 25 minutes, and the mixture was further stirred at room temperature for 1 hour. Thereafter, the reaction solution was cooled to −78 ° C. and the (R)-[6,6′-dimethoxy [1,1′-biphenyl] -2,2′-diyl] phosphonas dichloride synthesized in Synthesis Example 2 was synthesized. A THF solution (37.5 ml) was added dropwise over about 30 minutes. After completion of the dropping, the temperature was gradually returned to room temperature and reacted for 18 hours. Saturated aqueous ammonium chloride solution was added to stop the reaction, THF was distilled off, the residue was dissolved in ethyl acetate and extracted, washed with saturated aqueous sodium chloride solution, dehydrated with sodium sulfate, filtered through celite, Concentrated to dryness. The target compound was obtained by purification by column chromatography (hexane / ethyl acetate = 8/1 and hexane / methylene chloride = 3/1). (43% Yield (3step from Synthesis Example 1),> 99% ee) ¹ H NMR (300 MHz, CDCl ₃ ): δ = 3.44 (s, 6H), 6.60 (d, J = 7.4 Hz, 2H), 6.66-6.72 (m, 4H), 6.74-6.81 (m, 4H), 6.89 (d, J = 8.2 Hz, 2H), 7.35-7.40 (m, 2H). ¹³ C NMR (75 MHz, CDCl ₃ ): δ = 55.0, 112.1, 116.3-117.6 (m), 125.5, 130.1, 131.5-132.1 (m), 132.5-133.0 (m), 135.8, 139.9 (dt, ¹ J _FC = 255.4 Hz, ² J _FC = 15.3 Hz ), 140.1 (dt, ¹ J _FC = 255.1 Hz, ² J _FC = 15.3 Hz), 151.2 (dm, ¹ J _FC = 254.2 Hz), 157.4-157.5 (m). ¹⁹ F NMR (282 MHz, CDCl ₃ ) : δ = -159.7--159.3 (m, 4F), -134.3 (dd, ³ J = 21.0 Hz, ⁴ J = 7.0 Hz, 4F), -133.7 (dd, ³ J = 21.0 Hz, ⁴ J = 7.0 Hz ³¹ P NMR (121 MHz, CDCl ₃ ): δ = 10.2 (s). IR (KBr): 1610, 1518, 1410, 1317, 1256, 1082, 1045, 856, 754 cm ^-1 . Mp 131 -132 °. Anal. Calc. For C ₃₈ H ₂₀ F ₂₄ O ₂ P ₂ : C 57.16, H 2.52%. Found: C 56.99, H 2.91. [Α] _D ^29.0 = -25.5 °. HPLC (Daicel Chiralcel OD -H, Hexane / i-PrOH = 200: 1, flow rate = 0.4 ml / min): t _R = 14.1 min ((S) -isomer), t _R = 15.9 min ((R) -isomer).

合成例４
30 ml 耐圧試験管を充分に乾燥させ、トリホスゲン (1.13 g、3.81 mmol)を入れ、Aliquat（登録商標） 336 (92.5 mg、0.229 mmol) のトルエン溶液 (6.5 ml) を加え、すばやく栓をし、35℃で2日間、激しく攪拌した。その後、その反応溶液及び、別途単離した(S)-[6,6’-ジメトキシ[1,1’-ビフェニル]-2,2’-ジイル]ビスホスフィン (570 mg、2.05 mmol)の塩化メチレン溶液 (15.0 ml) を-78℃に冷却し、カニュラーを用いて、トルエン溶液を、塩化メチレン溶液に混合させた。ゆっくりと室温に戻してからさらに2日間攪拌し、溶媒を留去することで目的化合物とAliquat（登録商標） 336の混合物を得た。Aliquat（登録商標） 336は取り除かずに、そのまま下記合成例５の反応に移った。¹H NMR (300 MHz, CDCl₃) : δ = 3.77 (s, 6H), 7.11(d, J = 8.4 Hz, 2H), 7.63 (m, 2H), 7.86 (d, J = 8.1 H, 2H). ³¹P NMR (121 MHz, CDCl₃) : δ = 158.1 (s). Synthesis example 4
Thoroughly dry the 30 ml pressure test tube, add triphosgene (1.13 g, 3.81 mmol), add Aliquat® 336 (92.5 mg, 0.229 mmol) in toluene (6.5 ml), cap quickly, Stir vigorously at 35 ° C. for 2 days. Then the reaction solution and separately isolated (S)-[6,6′-dimethoxy [1,1′-biphenyl] -2,2′-diyl] bisphosphine (570 mg, 2.05 mmol) in methylene chloride The solution (15.0 ml) was cooled to −78 ° C., and the toluene solution was mixed with the methylene chloride solution using a cannula. After slowly returning to room temperature, the mixture was further stirred for 2 days, and the solvent was distilled off to obtain a mixture of the target compound and Aliquat (registered trademark) 336. The Aliquat (registered trademark) 336 was not removed, and the reaction was directly carried out in the following Synthesis Example 5. ¹ H NMR (300 MHz, CDCl ₃ ): δ = 3.77 (s, 6H), 7.11 (d, J = 8.4 Hz, 2H), 7.63 (m, 2H), 7.86 (d, J = 8.1 H, 2H) ³¹ P NMR (121 MHz, CDCl ₃ ): δ = 158.1 (s).

合成例５
200 ml三つ口フラスコを十分に乾燥させ、不活性ガス雰囲気下で、マグネシウム (320.9 mg、13.2 mmol) 及び、触媒量のヨウ素を加え、Et₂O (1.5 ml) を加えた。1-ブロモ-3,4,5-トリフルオロベンゼン (1.4 ml、12 mmol) のEt₂O溶液 (11.5 ml) を約25分かけて滴下し、更に室温下で30分攪拌した。その後、Et₂O (26.0 ml) を加えて反応液を希釈し、-78℃まで冷却した。そこへ上記合成例４で合成した(S)-[6,6’-ジメトキシ[1,1’-ビフェニル]-2,2’-ジイル]ホスフォナスジクロライドのTHF溶液 (20.0 ml) を約30分かけて滴下した。滴下終了後、徐々に室温まで戻し、2時間反応させた。飽和塩化アンモニウム水溶液を加えて反応を停止し、THFを留去後、残渣を酢酸エチルに溶解させて抽出操作を行い、飽和塩化ナトリウム水溶液で洗浄、硫酸ナトリウムで脱水の後、セライト濾過を行い、濃縮・乾固させた。カラムクロマトグラフィー(ヘキサン/酢酸エチル = 8/1及びヘキサン/塩化メチレン = 3/1) によって精製することにより、目的化合物を得た。(32% Yield (合成例４からの2step)、>99% ee) ¹H NMR (300 MHz, CDCl₃) : δ = 3.44 (s, 6H), 6.60 (d, J = 7.4 Hz, 2H), 6.66 - 6.72 (m, 4H), 6.74 - 6.81 (m, 4H), 6.89 (d, J = 8.2 Hz, 2H), 7.35 - 7.40 (m, 2H). ¹³C NMR (75 MHz, CDCl₃) : δ = 55.0, 112.1, 116.3 - 117.6 (m), 125.5, 130.1, 131.5 - 132.1 (m), 132.5 - 133.0 (m), 135.8, 139.9 (dt, ¹J_F-C = 255.4 Hz, ²J_F-C = 15.3 Hz), 140.1 (dt, ¹J_F-C = 255.1 Hz, ²J_F-C = 15.3 Hz), 151.2 (dm, ¹J_F-C = 254.2 Hz), 157.4 - 157.5 (m). ¹⁹F NMR (282 MHz, CDCl₃) : δ = -159.7 - -159.3 (m, 4F), -134.3 (dd, ³J = 21.0 Hz, ⁴J = 7.0 Hz, 4F), -133.7 (dd, ³J = 21.0 Hz, ⁴J = 7.0 Hz, 4F). ³¹P NMR (121 MHz, CDCl₃) : δ = 10.2 (s). IR (KBr) : 1610, 1518, 1410, 1317, 1256, 1082, 1045, 856, 754 cm^-1. M.p. 131 - 132°. Anal. calc. for C₃₈H₂₀F₂₄O₂P₂ : C 57.16, H 2.52%. Found : C 56.99, H 2.91. [α]_D ^22.1 = +22.3°. HPLC (Daicel Chiralcel OD-H, Hexane/i-PrOH = 200 : 1, flow rate = 0.4 ml/min) : t_R = 14.1 min ((S)-isomer), t_R = 15.9 min ((R)-isomer). Synthesis example 5
The 200 ml three-necked flask was fully dried, magnesium (320.9 mg, 13.2 mmol) and a catalytic amount of iodine were added under an inert gas atmosphere, and Et ₂ O (1.5 ml) was added. An Et ₂ O solution (11.5 ml) of 1-bromo-3,4,5-trifluorobenzene (1.4 ml, 12 mmol) was added dropwise over about 25 minutes, and the mixture was further stirred at room temperature for 30 minutes. Thereafter, Et ₂ O (26.0 ml) was added to dilute the reaction solution and cooled to −78 ° C. Thereto was added a THF solution (20.0 ml) of (S)-[6,6′-dimethoxy [1,1′-biphenyl] -2,2′-diyl] phosphorous dichloride synthesized in Synthesis Example 4 for about 30 minutes. It was dripped over. After completion of the dropping, the temperature was gradually returned to room temperature and reacted for 2 hours. Saturated aqueous ammonium chloride solution was added to stop the reaction, THF was distilled off, the residue was dissolved in ethyl acetate and extracted, washed with saturated aqueous sodium chloride solution, dehydrated with sodium sulfate, filtered through celite, Concentrated to dryness. The target compound was obtained by purification by column chromatography (hexane / ethyl acetate = 8/1 and hexane / methylene chloride = 3/1). (32% Yield (2step from Synthesis Example 4),> 99% ee) ¹ H NMR (300 MHz, CDCl ₃ ): δ = 3.44 (s, 6H), 6.60 (d, J = 7.4 Hz, 2H), . 6.66 - 6.72 (m, 4H ), 6.74 - 6.81 (m, 4H), 6.89 (d, J = 8.2 Hz, 2H), 7.35 - 7.40 (m, 2H) 13 C NMR (75 MHz, CDCl 3): δ = 55.0, 112.1, 116.3-117.6 (m), 125.5, 130.1, 131.5-132.1 (m), 132.5-133.0 (m), 135.8, 139.9 (dt, ¹ J _FC = 255.4 Hz, ² J _FC = 15.3 Hz ), 140.1 (dt, ¹ J _FC = 255.1 Hz, ² J _FC = 15.3 Hz), 151.2 (dm, ¹ J _FC = 254.2 Hz), 157.4-157.5 (m). ¹⁹ F NMR (282 MHz, CDCl ₃ ) : δ = -159.7--159.3 (m, 4F), -134.3 (dd, ³ J = 21.0 Hz, ⁴ J = 7.0 Hz, 4F), -133.7 (dd, ³ J = 21.0 Hz, ⁴ J = 7.0 Hz ³¹ P NMR (121 MHz, CDCl ₃ ): δ = 10.2 (s). IR (KBr): 1610, 1518, 1410, 1317, 1256, 1082, 1045, 856, 754 cm ^-1 . Mp 131 -132 °. Anal. Calc. For C ₃₈ H ₂₀ F ₂₄ O ₂ P ₂ : C 57.16, H 2.52%. Found: C 56.99, H 2.91. [Α] _D ^22.1 = + 22.3 °. HPLC (Daicel Chiralcel OD -H, Hexane / i-PrOH = 200: 1, flow rate = 0.4 ml / min): t _R = 14.1 min ((S) -isomer), t _R = 15.9 min ((R) -isomer).

合成例６
300 ml三つ口フラスコを十分に乾燥させ、不活性ガス雰囲気下で水素化アルミニウムリチウム (95％) (949 mg、23.8 mmol) を加え、-78℃に冷却しTHF (15 ml) を加えた。次いで、トリメチルシリルクロライド(3.10 ml、24.4 mmol) を約5分かけて滴下し、-78℃で15分攪拌後、室温でさらに2時間攪拌した。その後、-30℃まで冷却し、(S)-[6’-(ジエトキシホスホリル)-6,2’-ジメトキシビフェニル-2-イル]リン酸ジエチルエステル (1.95 g、4.01 mmol)のTHF溶液 (15.0 ml) を10分以上かけて滴下し、30℃の恒温槽で72時間反応させた。十分に脱気した水 (4.0 ml) を、注意深く滴下して反応を停止し、さらに十分に脱気した水酸化ナトリウム水溶液 (30 wt%) (12.0 ml) を加えた。反応器内の固体成分が白色に変化するまで攪拌し、THF (約20 ml × 3回) を用いて抽出及び残渣の洗浄を行い、別途用意した三つ口フラスコ (不活性ガス雰囲気)に移した。そこへ、十分脱気した飽和塩化ナトリウム水溶液を加え、洗浄操作を行った。水層を除去した後、有機層を硫酸ナトリウムで脱水し、有機層のみを別のフラスコに移し、溶媒留去・減圧乾燥を行うことで、目的化合物を得、そのまま下記合成例７の反応に移った。¹H NMR (300 MHz, CDCl₃) : δ = 3.57 (d, ¹J_P-H = 204.6 Hz, 4H), 3.73 (s, 6H), 6.92 - 6.95 (m, 2H), 7.24 - 7.29 (m, 4H). ³¹P NMR (121 MHz, CDCl₃) : δ = -127.2 (s). Synthesis Example 6
The 300 ml three-necked flask was thoroughly dried, lithium aluminum hydride (95%) (949 mg, 23.8 mmol) was added under an inert gas atmosphere, cooled to −78 ° C., and THF (15 ml) was added. . Next, trimethylsilyl chloride (3.10 ml, 24.4 mmol) was added dropwise over about 5 minutes, and the mixture was stirred at -78 ° C for 15 minutes, and further stirred at room temperature for 2 hours. Then, it was cooled to −30 ° C. and (S)-[6 ′-(diethoxyphosphoryl) -6,2′-dimethoxybiphenyl-2-yl] phosphoric acid diethyl ester (1.95 g, 4.01 mmol) in a THF solution ( 15.0 ml) was added dropwise over 10 minutes and the reaction was carried out in a thermostatic bath at 30 ° C. for 72 hours. Sufficiently degassed water (4.0 ml) was carefully added dropwise to stop the reaction, and further sufficiently degassed aqueous sodium hydroxide solution (30 wt%) (12.0 ml) was added. Stir until the solid component in the reactor turns white, extract with THF (about 20 ml × 3 times) and wash the residue, then transfer to a separately prepared three-necked flask (inert gas atmosphere). did. A saturated sodium chloride aqueous solution sufficiently deaerated was added thereto, and a washing operation was performed. After removing the aqueous layer, the organic layer was dehydrated with sodium sulfate, only the organic layer was transferred to another flask, and the target compound was obtained by performing solvent evaporation and drying under reduced pressure. Moved. ¹ H NMR (300 MHz, CDCl ₃ ): δ = 3.57 (d, ¹ J _PH = 204.6 Hz, 4H), 3.73 (s, 6H), 6.92-6.95 (m, 2H), 7.24-7.29 (m, 4H ³¹ P NMR (121 MHz, CDCl ₃ ): δ = -127.2 (s).

合成例７
30 ml 耐圧試験管を充分に乾燥させ、トリホスゲン (2.37 g、7.99 mmol)を入れ、Aliquat（登録商標） 336 (190 mg、0.470 mmol) のトルエン溶液 (13.4 ml) を加え、すばやく栓をし、35℃で2日間、激しく攪拌した。その後、その反応溶液及び、上記合成例６で合成した(S)-[6,6’-ジメトキシ[1,1’-ビフェニル]-2,2’-ジイル]ビスホスフィンの塩化メチレン溶液 (25.0 ml) を-78℃に冷却し、カニュラーを用いて、トルエン溶液を、塩化メチレン溶液に混合させた。ゆっくりと室温に戻してからさらに2日間攪拌し、溶媒を留去することで目的化合物とAliquat（登録商標） 336の混合物を得た。Aliquat（登録商標） 336は取り除かずに、そのまま下記合成例８の反応に移った。¹H NMR (300 MHz, CDCl₃) : δ = 3.77 (s, 6H), 7.11(d, J = 8.4 Hz, 2H), 7.63 (m, 2H), 7.86 (d, J = 8.1 H, 2H). ³¹P NMR (121 MHz, CDCl₃) : δ = 158.1 (s). Synthesis example 7
Thoroughly dry the 30 ml pressure test tube, add triphosgene (2.37 g, 7.99 mmol), add a solution of Aliquat® 336 (190 mg, 0.470 mmol) in toluene (13.4 ml), cap quickly, Stir vigorously at 35 ° C. for 2 days. Thereafter, the reaction solution and a methylene chloride solution of (S)-[6,6′-dimethoxy [1,1′-biphenyl] -2,2′-diyl] bisphosphine synthesized in Synthesis Example 6 (25.0 ml) ) Was cooled to −78 ° C. and the toluene solution was mixed with the methylene chloride solution using a cannula. After slowly returning to room temperature, the mixture was further stirred for 2 days, and the solvent was distilled off to obtain a mixture of the target compound and Aliquat (registered trademark) 336. Aliquat (registered trademark) 336 was not removed, and the reaction was directly carried out in the following Synthesis Example 8. ¹ H NMR (300 MHz, CDCl ₃ ): δ = 3.77 (s, 6H), 7.11 (d, J = 8.4 Hz, 2H), 7.63 (m, 2H), 7.86 (d, J = 8.1 H, 2H) ³¹ P NMR (121 MHz, CDCl ₃ ): δ = 158.1 (s).

合成例８
300 ml三つ口フラスコを十分に乾燥させ、不活性ガス雰囲気下で、2,3,5,6-テトラフルオロベンゾトリフルオリド(8.83 g、40.5 mmol) をTHF(40 ml)に溶解させ、-85℃まで冷却した。次いで、1.63 M n-ブチルリチウム (24.5 ml、39.9 mmol) を約25分かけて滴下し、更に90分攪拌した。この後、上記合成例７で合成した(S)-[6,6’-ジメトキシ[1,1’-ビフェニル]-2,2’-ジイル]ホスフォナスジクロライドのTHF溶液 (50.0 ml) を約40分かけて滴下し、-85℃のまま48時間反応させた。その後、飽和塩化アンモニウム水溶液を加えて反応を停止し、THFを留去後、残渣を酢酸エチルに溶解させて抽出操作を行い、飽和塩化ナトリウム水溶液で洗浄、硫酸ナトリウムで脱水の後、セライト濾過を行い、濃縮・乾固させた。カラムクロマトグラフィー(ヘキサン/酢酸エチル = 8/1)によって精製することにより、目的化合物を得た。(65% Yield (合成例６からの3step)、>99% ee) ¹H NMR (300 MHz, CDCl₃) : δ = 3.30 (s, 6H), 6.81 (d, J = 8.4 Hz, 2H), 7.06 (d, J = 7.6 Hz, 2H), 7.40 - 7.45 (m, 2H). ¹³C NMR (75 MHz, CDCl₃) : δ = 54.9, 110.5 - 111.5 (m), 112.1, 117.2 - 118.3 (m), 120.6 (q, ¹J_F-C = 275.6 Hz), 124.8, 127.9 - 128.4 (m), 130.5, 130.7, 143.1 (dd, ¹J_F-C = 263.1 Hz, ²J_F-C = 18.6 Hz), 144.1 (dd, ¹J_F-C = 263.6 Hz, ²J_F-C = 17.6 Hz), 146.9 (dm, ¹J_F-C = 246.2 Hz), 148.8 (dm, ¹J_F-C = 251.6 Hz), 157.8 - 158.0 (m). ¹⁹F NMR (282 MHz, CDCl₃) : δ = -141.7 - -141.6 (m, 4F), -140.1 - -139.9 (m, 4F), -127.9 - -127.7 (m, 4F), -125.4 - -125.2 (m, 4F), -57.7 (t, ⁴J = 21.0 Hz, 6F), -57.6 (t, ⁴J = 21.0 Hz, 6F). ³¹P NMR (121 MHz, CDCl₃) : δ = -49.3 (m). IR (KBr) : 1651, 1568, 1475, 1327, 1263, 1184, 1157, 1043, 978, 935, 716 cm^-1. M.p. > 200°(dec., darkening from 200°). Anal. calc. for C₄₂H₁₂F₂₈O₂P₂ : C 44.16, H 1.06%. Found : C 44.05, H 1.28. [α]_D ^19.3 = -55.7°(c 1.0, CHCl₃). HPLC (Daicel Chiralcel OD-H, Hexane/i-PrOH = 200 : 1, flow rate = 0.5 ml/min) : t_R = 9.8 min ((S)-isomer), t_R = 13.8 min ((R)-isomer). Synthesis example 8
The 300 ml three-necked flask was thoroughly dried, and 2,3,5,6-tetrafluorobenzotrifluoride (8.83 g, 40.5 mmol) was dissolved in THF (40 ml) under an inert gas atmosphere. Cooled to 85 ° C. Next, 1.63 M n-butyllithium (24.5 ml, 39.9 mmol) was added dropwise over about 25 minutes, and the mixture was further stirred for 90 minutes. Thereafter, a THF solution (50.0 ml) of (S)-[6,6′-dimethoxy [1,1′-biphenyl] -2,2′-diyl] phosphorous dichloride synthesized in Synthesis Example 7 was about 40%. The solution was added dropwise over a period of 48 minutes and allowed to react for 48 hours at -85 ° C. Then, saturated ammonium chloride aqueous solution was added to stop the reaction, THF was distilled off, the residue was dissolved in ethyl acetate and extracted, washed with saturated sodium chloride aqueous solution, dehydrated with sodium sulfate, and filtered through Celite. And concentrated to dryness. The target compound was obtained by purification by column chromatography (hexane / ethyl acetate = 8/1). (65% Yield (3step from Synthesis Example 6),> 99% ee) ¹ H NMR (300 MHz, CDCl ₃ ): δ = 3.30 (s, 6H), 6.81 (d, J = 8.4 Hz, 2H), 7.06 (d, J = 7.6 Hz , 2H), 7.40 - 7.45 (m, 2H) 13 C NMR (75 MHz, CDCl 3):. δ = 54.9, 110.5 - 111.5 (m), 112.1, 117.2 - 118.3 (m ), 120.6 (q, ¹ J _FC = 275.6 Hz), 124.8, 127.9-128.4 (m), 130.5, 130.7, 143.1 (dd, ¹ J _FC = 263.1 Hz, ² J _FC = 18.6 Hz), 144.1 (dd, ¹ J _FC = 263.6 Hz, ² J _FC = 17.6 Hz), 146.9 (dm, ¹ J _FC = 246.2 Hz), 148.8 (dm, ¹ J _FC = 251.6 Hz), 157.8-158.0 (m). ¹⁹ F NMR ( 282 MHz, CDCl ₃ ): δ = -141.7--141.6 (m, 4F), -140.1--139.9 (m, 4F), -127.9--127.7 (m, 4F), -125.4--125.2 (m, . 4F), -57.7 (t, 4 J = 21.0 Hz, 6F), -57.6 (t, 4 J = 21.0 Hz, 6F) 31 P NMR (121 MHz, CDCl 3): δ = -49.3 (m). IR (KBr): 1651, 1568, 1475, 1327, 1263, 1184, 1157, 1043, 978, 935, 716 cm ^-1 .Mp> 200 ° (dec., Darkening from 200 °). Anal. Calc. For C ₄₂ H ₁₂ F ₂₈ O ₂ P ₂ : C 44.16, H 1.06%. Found: C 44.05, H 1.28. [Α] _D ^19.3 = -55.7 ° (c 1.0, CHCl ₃ ). HPLC (Dai cel Chiralcel OD-H, Hexane / i-PrOH = 200: 1, flow rate = 0.5 ml / min): t _R = 9.8 min ((S) -isomer), t _R = 13.8 min ((R) -isomer) .

合成例９
30 ml 耐圧試験管を充分に乾燥させ、トリホスゲン (1.13 g、3.81 mmol)を入れ、Aliquat（登録商標） 336 (100 mg、0.248 mmol) のトルエン溶液 (6.5 ml) を加え、すばやく栓をし、35℃で2日間、激しく攪拌した。その後、その反応溶液及び、別途単離した(R)-[6,6’-ジメトキシ[1,1’-ビフェニル]-2,2’-ジイル]ビスホスフィン (533 mg、1.91mmol)の塩化メチレン溶液 (15.0 ml) を-78℃に冷却し、カニュラーを用いて、トルエン溶液を、塩化メチレン溶液に混合させた。徐々に室温に戻し、さらに2日間攪拌し、溶媒を留去することで目的化合物とAliquat（登録商標） 336の混合物を得た。Aliquat（登録商標） 336は取り除かずに、そのまま下記合成例１０の反応に移った。¹H NMR (300 MHz, CDCl₃) : δ = 3.77 (s, 6H), 7.11(d, J = 8.4 Hz, 2H), 7.63 (m, 2H), 7.86 (d, J = 8.1 H, 2H). ³¹P NMR (121 MHz, CDCl₃) : δ = 158.1 (s). Synthesis Example 9
Thoroughly dry the 30 ml pressure test tube, add triphosgene (1.13 g, 3.81 mmol), add Aliquat® 336 (100 mg, 0.248 mmol) in toluene (6.5 ml), cap quickly, Stir vigorously at 35 ° C. for 2 days. Thereafter, the reaction solution and separately isolated (R)-[6,6′-dimethoxy [1,1′-biphenyl] -2,2′-diyl] bisphosphine (533 mg, 1.91 mmol) in methylene chloride The solution (15.0 ml) was cooled to −78 ° C., and the toluene solution was mixed with the methylene chloride solution using a cannula. The mixture was gradually returned to room temperature, further stirred for 2 days, and the solvent was distilled off to obtain a mixture of the target compound and Aliquat (registered trademark) 336. The Aliquat (registered trademark) 336 was not removed, and the reaction was carried out as it was in Synthesis Example 10 below. ¹ H NMR (300 MHz, CDCl ₃ ): δ = 3.77 (s, 6H), 7.11 (d, J = 8.4 Hz, 2H), 7.63 (m, 2H), 7.86 (d, J = 8.1 H, 2H) ³¹ P NMR (121 MHz, CDCl ₃ ): δ = 158.1 (s).

合成例１０
300 mlの三つ口フラスコを十分に乾燥させ、不活性ガス雰囲気下で、2,3,5,6-テトラフルオロベンゾトリフルオリド(4.37 g、20.0 mmol) をTHF(20 ml)に溶解させ、-85℃まで冷却した。次いで、1.59 M n-ブチルリチウム (12.5 ml、19.9 mmol) を約25分かけて滴下し、更に130分攪拌した。この後、上記合成例９で合成した(R)-[6,6’-ジメトキシ[1,1’-ビフェニル]-2,2’-ジイル]ホスフォナスジクロライドのTHF溶液 (25.0 ml) を約40分かけて滴下し、-85℃のまま14時間反応させた。その後、飽和塩化アンモニウム水溶液を加えて反応を停止し、THFを留去後、残渣を酢酸エチルに溶解させて抽出操作を行い、飽和塩化ナトリウム水溶液で洗浄後、セライト濾過を行い、濃縮・乾固させた。カラムクロマトグラフィー(ヘキサン/酢酸エチル = 15/1) によって精製することにより、目的化合物を得た。(52% Yield (合成例９からの2step)、>99% ee) ¹H NMR (300 MHz, CDCl₃) : δ = 3.30 (s, 6H), 6.81 (d, J = 8.4 Hz, 2H), 7.06 (d, J = 7.6 Hz, 2H), 7.40 - 7.45 (m, 2H). ¹³C NMR (75 MHz, CDCl₃) : δ = 54.9, 110.5 - 111.5 (m), 112.1, 117.2 - 118.3 (m), 120.6 (q, ¹J_F-C = 275.6 Hz), 124.8, 127.9 - 128.4 (m), 130.5, 130.7, 143.1 (dd, ¹J_F-C = 263.1 Hz, ²J_F-C = 18.6 Hz), 144.1 (dd, ¹J_F-C = 263.6 Hz, ²J_F-C = 17.6 Hz), 146.9 (dm, ¹J_F-C = 246.2 Hz), 148.8 (dm, ¹J_F-C = 251.6 Hz), 157.8 - 158.0 (m). ¹⁹F NMR (282 MHz, CDCl₃) : δ = -141.7 - -141.6 (m, 4F), -140.1 - -139.9 (m, 4F), -127.9 - -127.7 (m, 4F), -125.4 - -125.2 (m, 4F), -57.7 (t, ⁴J = 21.0 Hz, 6F), -57.6 (t, ⁴J = 21.0 Hz, 6F). ³¹P NMR (121 MHz, CDCl₃) : δ = -49.3 (m). IR (KBr) : 1651, 1568, 1475, 1327, 1263, 1184, 1157, 1043, 978, 935, 716 cm^-1. M.p. > 200° (dec., darkening from 200°). Anal. calc. for C₄₂H₁₂F₂₈O₂P₂ : C 44.16, H 1.06%. Found : C 44.05, H 1.28. [α]_D ^25.4 = +53.7°(c 1.0, CHCl₃). HPLC (Daicel Chiralcel OD-H, Hexane/i-PrOH = 200 : 1, flow rate = 0.5 ml/min) : t_R = 9.8 min ((S)-isomer), t_R = 13.8 min ((R)-isomer). Synthesis Example 10
The 300 ml three-necked flask was thoroughly dried and 2,3,5,6-tetrafluorobenzotrifluoride (4.37 g, 20.0 mmol) was dissolved in THF (20 ml) under an inert gas atmosphere. Cooled to -85 ° C. Next, 1.59 M n-butyllithium (12.5 ml, 19.9 mmol) was added dropwise over about 25 minutes, and the mixture was further stirred for 130 minutes. Thereafter, a THF solution (25.0 ml) of (R)-[6,6′-dimethoxy [1,1′-biphenyl] -2,2′-diyl] phosphorous dichloride synthesized in Synthesis Example 9 was about 40%. The solution was added dropwise over a period of time and reacted at -85 ° C for 14 hours. Then, saturated ammonium chloride aqueous solution was added to stop the reaction, THF was distilled off, the residue was dissolved in ethyl acetate, extracted, washed with saturated sodium chloride aqueous solution, filtered through celite, concentrated and dried. I let you. The target compound was obtained by purification by column chromatography (hexane / ethyl acetate = 15/1). (52% Yield (2step from Synthesis Example 9),> 99% ee) ¹ H NMR (300 MHz, CDCl ₃ ): δ = 3.30 (s, 6H), 6.81 (d, J = 8.4 Hz, 2H), 7.06 (d, J = 7.6 Hz , 2H), 7.40 - 7.45 (m, 2H) 13 C NMR (75 MHz, CDCl 3):. δ = 54.9, 110.5 - 111.5 (m), 112.1, 117.2 - 118.3 (m ), 120.6 (q, ¹ J _FC = 275.6 Hz), 124.8, 127.9-128.4 (m), 130.5, 130.7, 143.1 (dd, ¹ J _FC = 263.1 Hz, ² J _FC = 18.6 Hz), 144.1 (dd, ¹ J _FC = 263.6 Hz, ² J _FC = 17.6 Hz), 146.9 (dm, ¹ J _FC = 246.2 Hz), 148.8 (dm, ¹ J _FC = 251.6 Hz), 157.8-158.0 (m). ¹⁹ F NMR ( 282 MHz, CDCl ₃ ): δ = -141.7--141.6 (m, 4F), -140.1--139.9 (m, 4F), -127.9--127.7 (m, 4F), -125.4--125.2 (m, . 4F), -57.7 (t, 4 J = 21.0 Hz, 6F), -57.6 (t, 4 J = 21.0 Hz, 6F) 31 P NMR (121 MHz, CDCl 3): δ = -49.3 (m). IR (KBr): 1651, 1568, 1475, 1327, 1263, 1184, 1157, 1043, 978, 935, 716 cm ^-1 .Mp> 200 ° (dec., Darkening from 200 °). Anal.calc. For C ₄₂ H ₁₂ F ₂₈ O ₂ P ₂ : C 44.16, H 1.06%. Found: C 44.05, H 1.28. [Α] _D ^25.4 = + 53.7 ° (c 1.0, CHCl ₃ ). HPLC (Da icel Chiralcel OD-H, Hexane / i-PrOH = 200: 1, flow rate = 0.5 ml / min): t _R = 9.8 min ((S) -isomer), t _R = 13.8 min ((R) -isomer) .

合成例１１
20 mlシュレンク管を十分に乾燥させ、アルゴン雰囲気下で、上記合成例３で合成したジホスフィン (9.6 mg、12 μmol)、μ-ジクロロテトラエチレンロジウム(I) (2.3 mg、6.0 μmol)、塩化メチレン (0.5 ml) を加え、室温下で2時間攪拌した。その後、塩化メチレンを留去することで、目的化合物を得た。¹H NMR (300 MHz,CDCl₃) : δ = 3.53 (s, 12H), 6.53 - 6.60 (m, 8H), 7.04 - 7.09 (m, 4H), 7.16 - 7.22 (m, 8H), 7.62 (br s, 8H). ¹³C NMR (75 MHz, CDCl₃) : δ = 55.1, 111.5, 118.6 - 118.9 (m), 122.2, 126.0 - 126.6 (m), 127.6 - 128.2 (m), 129.5, 133.3 - 134.0 (m), 140.2 (dt, ¹J_F-C = 257.7 Hz, ²J_F-C = 15.0 Hz,), 141.1 (dt, ¹J_F-C = 257.1 Hz, ²J_F-C = 15.5 Hz), 149.8 (dm, ¹J_F-C = 253.1 Hz), 157.5. ¹⁹F NMR (282 MHz, CDCl₃) : δ = -157.9 - -157.7 (m, 4F), -157.3 - -157.1 (m, 4F), -134.7 - 134.6 (m, 8F), -134.3 (br s, 8F). ³¹P NMR (121 MHz, CDCl₃) : δ = 50.2 (d, ¹J_Rh-P = 196 Hz). Synthesis Example 11
The 20 ml Schlenk tube was thoroughly dried, and the diphosphine (9.6 mg, 12 μmol), μ-dichlorotetraethylenerhodium (I) (2.3 mg, 6.0 μmol), methylene chloride synthesized in Synthesis Example 3 above under an argon atmosphere. (0.5 ml) was added and stirred at room temperature for 2 hours. Then, the target compound was obtained by distilling off methylene chloride. ¹ H NMR (300 MHz, CDCl ₃ ): δ = 3.53 (s, 12H), 6.53-6.60 (m, 8H), 7.04-7.09 (m, 4H), 7.16-7.22 (m, 8H), 7.62 (br ¹³ C NMR (75 MHz, CDCl ₃ ): δ = 55.1, 111.5, 118.6-118.9 (m), 122.2, 126.0-126.6 (m), 127.6-128.2 (m), 129.5, 133.3-134.0 (m), 140.2 (dt, ¹ J _FC = 257.7 Hz, ² J _FC = 15.0 Hz,), 141.1 (dt, ¹ J _FC = 257.1 Hz, ² J _FC = 15.5 Hz), 149.8 (dm, ¹ J _FC = 253.1 Hz), 157.5. ¹⁹ F NMR (282 MHz, CDCl ₃ ): δ = -157.9--157.7 (m, 4F), -157.3--157.1 (m, 4F), -134.7-134.6 (m, 8F .), -134.3 (br s, 8F) 31 P NMR (121 MHz, CDCl 3): δ = 50.2 (d, 1 J Rh-P = 196 Hz).

合成例１２
30 mlフラスコに、上記合成例１０で合成したジホスフィン (183 mg、0.160 mmol) 、テトラカルボニルジ-μ-クロロ二ロジウム(I) (31.1 mg、80.2 μmol)、エタノール (約20 ml) を加え、室温下で20時間攪拌した。エタノールを留去し、残渣をヘキサン (約10 ml) で3回洗浄し、乾燥させることで、目的化合物を得た。ここで得られた錯体は空気中で非常に安定であったため、下記反応例２において、ここで得られた錯体をそのまま触媒として用いた。(71% Yield) ¹H NMR (300 MHz, acetone-d₆) : δ = 3.45 (s, 12H), 6.86 - 6.90 (m, 4H), 7.27 - 7.38 (m, 8H). ¹³C NMR (75 MHz, acetone-d₆) : δ = 55.9, 111.2 - 112.9 (m), 113.5, 116.5 - 117.5 (m), 121.6 (q, ¹J_F-C = 274.0 Hz), 123.0, 124.7 - 125.0 (m), 130.5 - 130.6 (m), 132.4 - 133.3 (m), 141.5 - 150.5 (m), 158.8 - 158.9 (m). ¹⁹F NMR (282 MHz, acetone-d₆) : δ = -139.6 - -139.2 (m, 4F), -138.1 (br s, 4F), -137.4 (br s, 4F), -136.2 (br s, 4F), -129.9 (br s, 4F), -121.7 (br s, 4F), -118.6 - -118.5 (m, 4F), -106.8 - -106.7 (m, 4F), -53.9 - -53.8 (m, 12F), -53.3 - -53.1 (m, 12F). ³¹P NMR (121 MHz, acetone-d₆) : δ = 8.3 (d, ¹J_Rh-P = 206 Hz). IR (KBr) : 1475, 1329, 1186, 1155, 982, 937, 716, 669 cm^-1. Anal. calc. for C₈₄H₂₄Cl₂F₅₆O₄P₄Rh₂ : C 41.03, H 0.98%. Found : C 40.76, H 1.35. Synthesis Example 12
To the 30 ml flask was added diphosphine (183 mg, 0.160 mmol) synthesized in Synthesis Example 10 above, tetracarbonyldi-μ-chlorodirhodium (I) (31.1 mg, 80.2 μmol), ethanol (about 20 ml), The mixture was stirred at room temperature for 20 hours. Ethanol was distilled off, and the residue was washed three times with hexane (about 10 ml) and dried to obtain the target compound. Since the complex obtained here was very stable in the air, in the following reaction example 2, the complex obtained here was used as a catalyst as it was. (71% Yield) ¹ H NMR (300 MHz, acetone-d ₆ ): δ = 3.45 (s, 12H), 6.86-6.90 (m, 4H), 7.27-7.38 (m, 8H). ¹³ C NMR (75 MHz, acetone-d ₆ ): δ = 55.9, 111.2-112.9 (m), 113.5, 116.5-117.5 (m), 121.6 (q, ¹ J _FC = 274.0 Hz), 123.0, 124.7-125.0 (m), 130.5 - 130.6 (m), 132.4 - 133.3 (m), 141.5 - 150.5 (m), 158.8 - 158.9 (m) 19 F NMR (282 MHz, acetone-d 6):. δ = -139.6 - -139.2 (m, 4F), -138.1 (br s, 4F), -137.4 (br s, 4F), -136.2 (br s, 4F), -129.9 (br s, 4F), -121.7 (br s, 4F), -118.6 --118.5 (m, 4F), -106.8--106.7 (m, 4F), -53.9--53.8 (m, 12F), -53.3--53.1 (m, 12F). ³¹ P NMR (121 MHz, acetone -d ₆ ): δ = 8.3 (d, ¹ J _Rh-P = 206 Hz). IR (KBr): 1475, 1329, 1186, 1155, 982, 937, 716, 669 cm ^-1 . Anal. calc. for C ₈₄ H ₂₄ Cl ₂ F ₅₆ O ₄ P ₄ Rh ₂ : C 41.03, H 0.98%. Found: C 40.76, H 1.35.

合成例１３
20 mlシュレンク管を十分に乾燥させ、アルゴン雰囲気下で、ジホスフィン (13.5 mg、12 μmol)、μ-ジクロロテトラエチレンロジウム(I) (2.3 mg、6.0 μmol)、塩化メチレン (0.5 ml) を加え、室温下で2時間攪拌した。その後、塩化メチレンを留去することで、目的化合物を得た。¹H NMR (300 MHz, CDCl₃) : δ = 3.33 (s, 12H), 6.33 (d, J = 8.4 Hz, 4H), 6.43 - 6.49 (m, 4H), 6.90 - 6.95 (m, 4H), 7.49 (s, 4H), 7.76 - 7.79 (m, 8H), 7.84 (s, 4H), 8.48 (br s, 8H). ¹³C NMR (75 MHz, CDCl₃) : δ = 55.4, 112.3, 121.8, 122.7 (q, ¹J_F-C = 272.8 Hz), 122.9 (q, ¹J_F-C = 272.8 Hz), 123.2, 125.8 - 125.9 (m), 129.3 - 133.3 (m), 134.3, 157.7. ¹⁹F NMR (282 MHz, CDCl₃) : δ = -65.1 (s, 24F), -64.4 (s, 24F). ³¹P NMR (121 MHz, CDCl₃) : δ = 51.1 (d, ¹J_Rh-P = 193 Hz). Synthesis Example 13
Thoroughly dry the 20 ml Schlenk tube and add diphosphine (13.5 mg, 12 μmol), μ-dichlorotetraethylenerhodium (I) (2.3 mg, 6.0 μmol), methylene chloride (0.5 ml) under an argon atmosphere. The mixture was stirred at room temperature for 2 hours. Then, the target compound was obtained by distilling off methylene chloride. ¹ H NMR (300 MHz, CDCl ₃ ): δ = 3.33 (s, 12H), 6.33 (d, J = 8.4 Hz, 4H), 6.43-6.49 (m, 4H), 6.90-6.95 (m, 4H), 7.49 (s, 4H), 7.76 - 7.79 (m, 8H), 7.84 (s, 4H), 8.48 (br s, 8H) 13 C NMR (75 MHz, CDCl 3):. δ = 55.4, 112.3, 121.8, 122.7 (q, ¹ J _FC = 272.8 Hz), 122.9 (q, ¹ J _FC = 272.8 Hz), 123.2, 125.8-125.9 (m), 129.3-133.3 (m), 134.3, 157.7. ¹⁹ F NMR (282 MHz _{, CDCl 3): δ = -65.1} (s, 24F), -64.4 (s, 24F) 31 P NMR (121 MHz, CDCl 3):. δ = 51.1 (d, 1 J Rh-P = 193 Hz).

合成例１４
20 mlシュレンク管を十分に乾燥させ、アルゴン雰囲気下で、上記合成例５で合成したジホスフィン (86.5 mg、0.108 mmol)、ビス(ベンゾニトリル)ジクロロ白金(II) (51.9 mg、0.109 mmol)、1,2-ジクロロエタン (5.0 ml) を加え、60℃で26時間攪拌した。その後、1,2-ジクロロエタンを留去し、塩化メチレン/ヘキサンを用いて再結晶を行うことにより、目的化合物を得た。(88 % Yield) ¹H NMR (300 MHz, CDCl₃) : δ = 3.66 (s, 6H), 6.57 - 6.63 (m, 2H), 6.77 (d, J = 8.3 Hz, 2H), 7.15 - 7.25 (m, 6H), 7.51 (br s, 4H). ¹³C NMR (75 MHz, CDCl₃) : δ = 55.7, 114.1, 118.9 - 119.8 (m), 121.7 - 122.0 (m), 122.8 - 123.0 (m), 124.5 -124.6 (m), 126.2 - 126.4 (m), 127.2 - 128.3 (m), 130.7 - 130.9 (m), 141.7 (dt, ¹J_F-C = 260.5 Hz, ²J_F-C = 15.2 Hz,), 142.3 (dt, ¹J_F-C = 261.7 Hz, ²J_F-C = 15.2 Hz), 150.3 (dm, ¹J_F-C = 257.1 Hz), 157.9 - 158.0 (m). ¹⁹F NMR (282 MHz, CDCl₃) : δ = -153.8 - -153.7 (m, 2F), -152.4 - -152.3 (m, 2F), -132.3 - -132.2 (m, 4F), -131.1 (br s, 4F). ³¹P NMR (121 MHz, CDCl₃) : δ = 9.9 (s, ¹J_Pt-P = 3621 Hz). IR (KBr) : 1616, 1589, 1524, 1464, 1418, 1290, 1269, 1242, 1153, 1088, 1049, 853, 762, 644, 629 cm^-1. Synthesis Example 14
The 20 ml Schlenk tube was sufficiently dried, and the diphosphine (86.5 mg, 0.108 mmol), bis (benzonitrile) dichloroplatinum (II) (51.9 mg, 0.109 mmol), 1 , 2-dichloroethane (5.0 ml) was added, and the mixture was stirred at 60 ° C. for 26 hours. Thereafter, 1,2-dichloroethane was distilled off and recrystallization was performed using methylene chloride / hexane to obtain the target compound. (88% Yield) ¹ H NMR (300 MHz, CDCl ₃ ): δ = 3.66 (s, 6H), 6.57-6.63 (m, 2H), 6.77 (d, J = 8.3 Hz, 2H), 7.15-7.25 ( . m, 6H), 7.51 ( br s, 4H) 13 C NMR (75 MHz, CDCl 3): δ = 55.7, 114.1, 118.9 - 119.8 (m), 121.7 - 122.0 (m), 122.8 - 123.0 (m) , 124.5 -124.6 (m), 126.2-126.4 (m), 127.2-128.3 (m), 130.7-130.9 (m), 141.7 (dt, ¹ J _FC = 260.5 Hz, ² J _FC = 15.2 Hz,), 142.3 ^{_{. (dt, 1 J FC =}} 261.7 Hz, 2 J FC = 15.2 Hz), 150.3 (dm, 1 J FC = 257.1 Hz), 157.9 - 158.0 (m) 19 F NMR (282 MHz, CDCl 3): δ = -153.8 - -153.7 (m, 2F) , -152.4 - -152.3 (m, 2F), -132.3 -. -132.2 (m, 4F), -131.1 (br s, 4F) 31 P NMR (121 MHz, CDCl ₃ ): δ = 9.9 (s, ¹ J _Pt-P = 3621 Hz) .IR (KBr): 1616, 1589, 1524, 1464, 1418, 1290, 1269, 1242, 1153, 1088, 1049, 853, 762, 644, 629 cm ^-1 .

合成例１５
20 mlシュレンク管を十分に乾燥させ、アルゴン雰囲気下で、上記合成例８で合成したジホスフィン (171 mg、0.150 mmol)、ビス(ベンゾニトリル)ジクロロ白金(II) (71.5 mg、0.151 mmol)、1,2-ジクロロエタン (9.0 ml) を加え、80℃で3日間攪拌した。その後、1,2-ジクロロエタンを留去し、塩化メチレン/ヘキサンを用いて再結晶を行うことにより、目的化合物を得た。(83 % Yield) ¹H NMR (300 MHz, acetone-d₆) : δ = 3.61 (s, 6H), 7.12 - 7.15 (m, 2H), 7.48 - 7.58 (m, 4H). ¹³C NMR (75 MHz, acetone-d₆) : δ = 56.6, 108.1 - 109.5 (m), 111.2 - 112.5 (m), 113.9 - 115.1 (m), 116.0, 121.3 (q, ¹J_F-C = 274.6 Hz), 121.4 (q, ¹J_F-C = 274.6 Hz), 124.7, 125.0 - 125.6 (m), 130.6, 132.0 - 132.2 (m), 134.8, 136.6, 142.3 - 151.0 (m), 159.1 - 159.3 (m). ¹⁹F NMR (282 MHz, acetone-d₆) : δ = -137.4 - -137.2 (m, 2F), -136.4 - -136.0 (m, 4F), -135.7 - -135.4 (m, 2F), -129.6 - -129.5 (m, 2F), -119.7 - -119.5 (m, 2F), -116.6 - -116.5 (m, 2F), -107.5 - -107.3 (m, 2F), -53.6 - -53.5 (m, 6F), -53.4 - -53.2 (m, 6F). ³¹P NMR (121 MHz, acetone-d₆) : δ = -26.1 (s, ¹J_Pt-P = 3745 Hz). IR (KBr) : 1479, 1464, 1329, 1271, 1155, 1038, 982, 943, 770, 716 cm^-1. Anal. calc. for C₄₂H₁₂Cl₂F₂₈O₂P₂Pt : C 35.82, H 0.86%. Found : C 36.07, H 1.12. Synthesis Example 15
The 20 ml Schlenk tube was thoroughly dried, and the diphosphine (171 mg, 0.150 mmol), bis (benzonitrile) dichloroplatinum (II) (71.5 mg, 0.151 mmol), 1 , 2-dichloroethane (9.0 ml) was added, and the mixture was stirred at 80 ° C. for 3 days. Thereafter, 1,2-dichloroethane was distilled off and recrystallization was performed using methylene chloride / hexane to obtain the target compound. (83% Yield) ¹ H NMR (300 MHz, acetone-d ₆ ): δ = 3.61 (s, 6H), 7.12-7.15 (m, 2H), 7.48-7.58 (m, 4H). ¹³ C NMR (75 MHz, acetone-d ₆ ): δ = 56.6, 108.1-109.5 (m), 111.2-112.5 (m), 113.9-115.1 (m), 116.0, 121.3 (q, ¹ J _FC = 274.6 Hz), 121.4 (q , ¹ J _FC = 274.6 Hz), 124.7, 125.0-125.6 (m), 130.6, 132.0-132.2 (m), 134.8, 136.6, 142.3-151.0 (m), 159.1-159.3 (m). ¹⁹ F NMR (282 MHz, acetone-d ₆ ): δ = -137.4--137.2 (m, 2F), -136.4--136.0 (m, 4F), -135.7--135.4 (m, 2F), -129.6--129.5 (m , 2F), -119.7--119.5 (m, 2F), -116.6--116.5 (m, 2F), -107.5--107.3 (m, 2F), -53.6--53.5 (m, 6F), -53.4 --53.2 (m, 6F). ³¹ P NMR (121 MHz, acetone-d ₆ ): δ = -26.1 (s, ¹ J _Pt-P = 3745 Hz). IR (KBr): 1479, 1464, 1329, 1271, 1155, 1038, 982, 943, 770, 716 cm ^-1 . Anal.calc. For C ₄₂ H ₁₂ Cl ₂ F ₂₈ O ₂ P ₂ Pt: C 35.82, H 0.86%. Found: C 36.07, H 1.12 .

反応例１
20 mlシュレンク管を十分に乾燥させ、アルゴン雰囲気下で、上記合成例３で合成したジホスフィン(19.2 mg、24.0 μmol)、μ-ジクロロテトラエチレンロジウム(I) (4.7 mg、12 μmol)、塩化メチレン (1.0 ml) を加え、室温下で2時間攪拌した。その後、塩化メチレンを留去し、KOH (22.8 mg、0.40 mmol)、充分に脱気したトルエン (1.6 ml) 及び水 (0.16 ml) を加え、室温で1時間激しく攪拌した。次いで、20℃以下に冷却し、フェニルボロン酸 (107.3 mg、0.880 mmol) 及び2-シクロヘキセン-1-オン (77 μl、0.80 mmol) を加え、20℃で3時間反応させた。飽和炭酸水素ナトリウム水溶液を加え、酢酸エチルで抽出後、カラムクロマトグラフィー(ヘキサン/酢酸エチル = 5/1) によって精製することにより、目的化合物を得た。(99% Yield、99 %ee) Reaction example 1
A 20 ml Schlenk tube was thoroughly dried, and the diphosphine (19.2 mg, 24.0 μmol), μ-dichlorotetraethylenerhodium (I) (4.7 mg, 12 μmol), methylene chloride synthesized in Synthesis Example 3 above under an argon atmosphere. (1.0 ml) was added and stirred at room temperature for 2 hours. Thereafter, methylene chloride was distilled off, KOH (22.8 mg, 0.40 mmol), sufficiently degassed toluene (1.6 ml) and water (0.16 ml) were added, and the mixture was vigorously stirred at room temperature for 1 hour. Next, the mixture was cooled to 20 ° C. or lower, phenylboronic acid (107.3 mg, 0.880 mmol) and 2-cyclohexen-1-one (77 μl, 0.80 mmol) were added, and the mixture was reacted at 20 ° C. for 3 hours. A saturated aqueous sodium hydrogen carbonate solution was added, the mixture was extracted with ethyl acetate, and purified by column chromatography (hexane / ethyl acetate = 5/1) to obtain the target compound. (99% Yield, 99% ee)

反応例２
20 mlシュレンク管を十分に乾燥させ、アルゴン雰囲気下で、上記合成例１２で合成した[(diphosphine)RhCl]₂(14.8 mg、6.0 μmol)、KOH (11.3 mg、0.20 mmol)、充分に脱気したトルエン (0.80 ml) 及び水 (80 μl) を加え、室温で1時間激しく攪拌した。次いで、20℃以下に冷却し、フェニルボロン酸 (53.6 mg 、0.440 mmol) 及び2-シクロヘキセン-1-オン (39 μl、0.40 mmol) を加え、20℃で3時間反応させた。飽和炭酸水素ナトリウム水溶液を加え、酢酸エチルで抽出後、カラムクロマトグラフィー(ヘキサン/酢酸エチル = 5/1)によって精製することにより、目的化合物を得た。(86 % Yield、96% ee) Reaction example 2
The 20 ml Schlenk tube was fully dried, and [(diphosphine) RhCl] ₂ (14.8 mg, 6.0 μmol), KOH (11.3 mg, 0.20 mmol), fully degassed in the above Synthesis Example 12 under an argon atmosphere. Toluene (0.80 ml) and water (80 μl) were added and stirred vigorously at room temperature for 1 hour. Next, the mixture was cooled to 20 ° C. or lower, phenylboronic acid (53.6 mg, 0.440 mmol) and 2-cyclohexen-1-one (39 μl, 0.40 mmol) were added, and the mixture was reacted at 20 ° C. for 3 hours. A saturated aqueous sodium hydrogen carbonate solution was added, the mixture was extracted with ethyl acetate, and purified by column chromatography (hexane / ethyl acetate = 5/1) to obtain the target compound. (86% Yield, 96% ee)

反応例３
20 mlシュレンク管を十分に乾燥させ、アルゴン雰囲気下で、上記合成例１０で合成したジホスフィン (13.5 mg、12.0 μmol)、μ-ジクロロテトラエチレンロジウム(I) (2.3 mg、6.0 μmol)、塩化メチレン (0.5 ml) を加え、室温下で2時間攪拌した。その後、塩化メチレンを留去し、KOH (11.4 mg、0.20 mmol)、充分に脱気したトルエン (0.80 ml) 及び水 (80 μl) を加え、室温で1時間激しく攪拌した。次いで、20℃以下に冷却し、フェニルボロン酸 (53.6 mg、0.440 mmol) 及び2-シクロヘキセン-1-オン (39 μl、0.40 mmol) を加え、20℃で5時間反応させた。飽和炭酸水素ナトリウム水溶液を加え、酢酸エチルで抽出後、カラムクロマトグラフィー (ヘキサン/酢酸エチル = 5/1)によって精製することにより、目的化合物を得た。(76% Yield、97 %ee) Reaction example 3
A 20 ml Schlenk tube was sufficiently dried, and diphosphine (13.5 mg, 12.0 μmol), μ-dichlorotetraethylenerhodium (I) (2.3 mg, 6.0 μmol), methylene chloride synthesized in Synthesis Example 10 above under an argon atmosphere. (0.5 ml) was added and stirred at room temperature for 2 hours. Thereafter, methylene chloride was distilled off, KOH (11.4 mg, 0.20 mmol), sufficiently degassed toluene (0.80 ml) and water (80 μl) were added, and the mixture was vigorously stirred at room temperature for 1 hour. Next, the mixture was cooled to 20 ° C. or lower, phenylboronic acid (53.6 mg, 0.440 mmol) and 2-cyclohexen-1-one (39 μl, 0.40 mmol) were added, and the mixture was reacted at 20 ° C. for 5 hours. A saturated aqueous sodium hydrogen carbonate solution was added, the mixture was extracted with ethyl acetate, and purified by column chromatography (hexane / ethyl acetate = 5/1) to obtain the target compound. (76% Yield, 97% ee)

反応例４
20 mlシュレンク管を十分に乾燥させ、アルゴン雰囲気下で、(R)-BINAP (7.5 mg、12 μmol)、μ-ジクロロテトラエチレンロジウム(I) (2.3 mg、6.0 μmol)、塩化メチレン (0.5 ml) を加え、室温下で2時間攪拌した。その後、塩化メチレンを留去し、KOH (11.2 mg、0.200 mmol)、充分に脱気したトルエン (0.80 ml) 及び水 (80 μl) を加え、室温で1時間激しく攪拌した。次いで、20℃以下に冷却し、フェニルボロン酸 (53.6 mg、0.440 mmol) 及び2-シクロヘキセン-1-オン (39 μl、0.40 mmol) を加え、20℃で3時間反応させた。飽和炭酸水素ナトリウム水溶液を加え、酢酸エチルで抽出を行い、¹H NMR測定を行ったところ、目的物が全く生成していないと分かった。 Reaction example 4
Thoroughly dry the 20 ml Schlenk tube, and under an argon atmosphere, (R) -BINAP (7.5 mg, 12 μmol), μ-dichlorotetraethylenerhodium (I) (2.3 mg, 6.0 μmol), methylene chloride (0.5 ml ) Was added and stirred at room temperature for 2 hours. Thereafter, methylene chloride was distilled off, KOH (11.2 mg, 0.200 mmol), sufficiently degassed toluene (0.80 ml) and water (80 μl) were added, and the mixture was vigorously stirred at room temperature for 1 hour. Next, the mixture was cooled to 20 ° C. or lower, phenylboronic acid (53.6 mg, 0.440 mmol) and 2-cyclohexen-1-one (39 μl, 0.40 mmol) were added, and the mixture was reacted at 20 ° C. for 3 hours. A saturated aqueous sodium hydrogen carbonate solution was added, extraction was performed with ethyl acetate, and ¹ H NMR measurement was performed. As a result, it was found that the target product was not produced at all.

上記表にも示されるように、Ａｒで示される置換フェニル基の置換基のうち３〜５個の置換基がフッ素原子又はパーフルオロアルキル基である反応例１及び２では、２個の置換基がフッ素原子又はパーフルオロアルキル基である反応例３に比べて、収率が良好である。また、得られる反応生成物の光学純度も高い。一方、(R)-BINAPを用いた反応例４では、反応が進行しなかった。
As shown in the above table, in Reaction Examples 1 and 2 in which 3 to 5 substituents among the substituents of the substituted phenyl group represented by Ar are fluorine atoms or perfluoroalkyl groups, two substituents Compared to Reaction Example 3 in which is a fluorine atom or a perfluoroalkyl group, the yield is good. Moreover, the optical purity of the reaction product obtained is high. On the other hand, in Reaction Example 4 using (R) -BINAP, the reaction did not proceed.

Claims

The diphosphine compound represented by following formula (1).

[Wherein R ¹ , R ² and R ³ are each independently a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, or a fluorination having 1 to 10 carbon atoms. An alkyl group or a fluorinated alkoxy group having 1 to 10 carbon atoms is shown. R ⁴ represents an alkyl group having 1 to 6 carbon atoms or a fluorinated alkyl group having 1 to 10 carbon atoms. R ¹ , R ² , R ³ and R ⁴ bonded to the same benzene ring may be bonded to each other to form a ring. Ar represents a substituted phenyl group represented by the following formula (2). ]

[Wherein, among the substituents represented by R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ , 3 to 5 substituents are a fluorine atom or a C 1-6 perfluoroalkyl group, 0 to 2 substituents are hydrogen atoms. ]

^{^{^{R 5, R 6, R 7}}} , among the substituents represented by ^{R 8} and ^{R 9,} diphosphine compound of claim 1 wherein 3-5 substituents fluorine atom.

The diphosphine compound according to claim 1, which is an axially asymmetric optically active substance.

A metal complex in which the diphosphine compound according to claim 3 is coordinated to a transition metal as a ligand.

The metal complex according to claim 4, wherein the transition metal is a metal belonging to Group 8, Group 9, or Group 10 of the Periodic Table.

A catalyst for asymmetric synthesis comprising the metal complex according to claim 4 or 5.

Following formula (3)

[Wherein R ¹ , R ² and R ³ are each independently a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, or a fluorination having 1 to 10 carbon atoms. An alkyl group or a fluorinated alkoxy group having 1 to 10 carbon atoms is shown. R ⁴ represents an alkyl group having 1 to 6 carbon atoms or a fluorinated alkyl group having 1 to 10 carbon atoms. R ¹ , R ² , R ³ and R ⁴ bonded to the same benzene ring may be bonded to each other to form a ring. ]
The optically active diphosphine compound represented by formula (4) is reacted with a reaction agent prepared by mixing triphosgene and a quaternary ammonium salt.

[Wherein R ¹ , R ² , R ³ and R ⁴ are the same as those in the formula (3). ]
The manufacturing method of the optically active diphosphine compound represented by these.

The optically active diphosphine compound represented by the formula (4) obtained by the production method according to claim 7 is added to the following formula (5):

[In the formula, Ar represents a substituted phenyl group represented by the following formula (2), and M represents Li or Mg—X. Here, X represents a halogen atom. ]

[Wherein, among the substituents represented by R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ , 3 to 5 substituents are a fluorine atom or a C 1-6 perfluoroalkyl group, 0 to 2 substituents are hydrogen atoms. ]
The following formula (1) is reacted with an organometallic compound represented by

[Wherein R ¹ , R ² , R ³ and R ⁴ are the same as those in the formula (3). Ar is the same as the formula (2). ]
The manufacturing method of the optically active diphosphine compound represented by these.