JP2002145842A - Optically active cobalt (ii), cobalt (iii) complex and production complex thereof - Google Patents
Optically active cobalt (ii), cobalt (iii) complex and production complex thereofInfo
- Publication number
- JP2002145842A JP2002145842A JP2000344191A JP2000344191A JP2002145842A JP 2002145842 A JP2002145842 A JP 2002145842A JP 2000344191 A JP2000344191 A JP 2000344191A JP 2000344191 A JP2000344191 A JP 2000344191A JP 2002145842 A JP2002145842 A JP 2002145842A
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- optically active
- complex
- cobalt
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
- B01J31/2204—Organic complexes the ligands containing oxygen or sulfur as complexing atoms
- B01J31/2208—Oxygen, e.g. acetylacetonates
- B01J31/2226—Anionic ligands, i.e. the overall ligand carries at least one formal negative charge
- B01J31/2243—At least one oxygen and one nitrogen atom present as complexing atoms in an at least bidentate or bridging ligand
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/02—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups
- C07C251/04—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C251/10—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of an unsaturated carbon skeleton
- C07C251/12—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of an unsaturated carbon skeleton being acyclic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/02—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups
- C07C251/04—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C251/10—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of an unsaturated carbon skeleton
- C07C251/16—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of an unsaturated carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
- C07C29/143—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones
- C07C29/145—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones with hydrogen or hydrogen-containing gases
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/60—Reduction reactions, e.g. hydrogenation
- B01J2231/64—Reductions in general of organic substrates, e.g. hydride reductions or hydrogenations
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
- B01J2531/0238—Complexes comprising multidentate ligands, i.e. more than 2 ionic or coordinative bonds from the central metal to the ligand, the latter having at least two donor atoms, e.g. N, O, S, P
- B01J2531/0241—Rigid ligands, e.g. extended sp2-carbon frameworks or geminal di- or trisubstitution
- B01J2531/0252—Salen ligands or analogues, e.g. derived from ethylenediamine and salicylaldehyde
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/84—Metals of the iron group
- B01J2531/845—Cobalt
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
【0001】[0001]
【発明の属する技術分野】本発明は光学活性β-ケトイ
ミン化合物、及び光学活性サレン化合物を配位子とする
光学活性コバルト錯体、並びに光学活性アルコール、光
学活性アミン、光学活性シクロプロパン等の光学活性化
合物の製造に用いられる触媒として有用な光学活性コバ
ルト錯体触媒に関する。The present invention relates to an optically active β-ketoimine compound, an optically active cobalt complex having an optically active salen compound as a ligand, and an optically active alcohol, an optically active amine, an optically active cyclopropane and the like. The present invention relates to an optically active cobalt complex catalyst useful as a catalyst used in the production of a compound.
【0002】[0002]
【従来の技術】これまでに光学活性遷移金属錯体を触媒
とする不斉合成反応が数多く開発され、医薬・農薬等の
重要中間体製造に活用されてきた。特に、光学活性ホス
フィン化合物を配位子とする遷移金属錯体触媒が不斉水
素化反応に有効であることが報告されて以来、研究が大
きく進展し、不斉触媒を用いるオレフィンの不斉異性化
反応や不斉水素化反応を工業的な生産に利用する例が数
多く報告されるようになった。2. Description of the Related Art Hitherto, many asymmetric synthesis reactions using an optically active transition metal complex as a catalyst have been developed and utilized for producing important intermediates such as pharmaceuticals and agricultural chemicals. In particular, since the report was made that a transition metal complex catalyst having an optically active phosphine compound as a ligand was effective for asymmetric hydrogenation, a great deal of research has been carried out, and asymmetric isomerization of olefins using asymmetric catalysts has been carried out. There have been many reports of the use of reactions and asymmetric hydrogenation reactions for industrial production.
【0003】一方、近年、窒素2原子と酸素2原子から
なる4座の配位子を用いる金属錯体触媒の開発の進展も
著しく、実用性の高い不斉触媒反応が報告されるように
なった。例えば、2分子のサリチルアルデヒド誘導体と
1分子のエチレンジアミン誘導体の縮合反応により得ら
れる、サレン型と呼ばれる4座の配位子を用いて、特開
平5−301878号公報には光学活性マンガン錯体に
よるオレフィンの不斉エポキシ化反応が、特開平9−6
7312号公報には下記式(9)[化13]On the other hand, in recent years, the development of metal complex catalysts using a tetradentate ligand consisting of two atoms of nitrogen and two atoms of oxygen has been remarkably progressed, and highly practical asymmetric catalysis has been reported. . For example, Japanese Unexamined Patent Publication (Kokai) No. 5-301878 discloses an olefin comprising an optically active manganese complex using a tetradentate ligand called salen type obtained by a condensation reaction of two molecules of a salicylaldehyde derivative and one molecule of an ethylenediamine derivative. Asymmetric epoxidation reaction of JP-A-9-6
No. 7312 discloses the following formula ( 9 ):
【0004】[0004]
【化13】 Embedded image
【0005】に代表されるコバルト錯体による不斉シク
ロプロパン化反応が、WO 00/09463号公報には
下記式(10)[化14]An asymmetric cyclopropanation reaction using a cobalt complex represented by a cobalt complex is described in WO 00/09463 in the following formula ( 10 ):
【0006】[0006]
【化14】 Embedded image
【0007】に代表されるコバルト錯体を用いる、ラセ
ミ体のエポキシドの光学分割による光学活性エポキシド
の合成反応等が開示されている。[0007] A synthesis reaction of an optically active epoxide by optical resolution of a racemic epoxide using a cobalt complex typified by, for example, is disclosed.
【0008】また、2分子のβ-ジケトン誘導体と1分
子のエチレンジアミン誘導体の縮合反応により得られ
る、β-ケトイミン型と呼ばれる4座の配位子を用いる
不斉金属錯体触媒に関しては、本発明者らにより種々の
不斉反応が開発されている。例えば、特開平6−247
993号公報にはオレフィン類の不斉酸素酸化反応によ
る光学活性エポキシドの製造法が、特開平9−1511
43号公報にはケトン類の不斉還元反応による光学活性
アルコールの製造法が、WO98/39276号公報には
イミン類の不斉還元反応による光学活性アミンの製造法
が、特開平11−246501号公報にはα,β-不飽和
カルボン酸アミド類の不斉1,4-還元反応による光学活性
カルボン酸アミドの製造法が、また、Heterocycles, 5
2, 1041 (2000) には不斉ヘテロ Diels-Alder反応によ
る光学活性ジヒドロピラン誘導体の製造法が開示されて
いる。The asymmetric metal complex catalyst using a tetradentate ligand called β-ketoimine type, which is obtained by a condensation reaction of two molecules of β-diketone derivative and one molecule of ethylenediamine derivative, is disclosed by the present inventors. Have developed various asymmetric reactions. For example, JP-A-6-247
Japanese Patent Application Laid-Open No. 9-1511 discloses a method for producing an optically active epoxide by asymmetric oxygen oxidation of olefins.
No. 43 discloses a method for producing an optically active alcohol by an asymmetric reduction reaction of ketones, and WO 98/39276 discloses a method for producing an optically active amine by an asymmetric reduction reaction of imines, which is disclosed in JP-A-11-246501. The publication discloses a method for producing optically active carboxylic acid amides by asymmetric 1,4-reduction reaction of α, β-unsaturated carboxylic acid amides, and Heterocycles, 5
2 , 1041 (2000) discloses a method for producing an optically active dihydropyran derivative by an asymmetric hetero Diels-Alder reaction.
【0009】しかし、対象となる反応、あるいは基質に
よっては、化学選択性、ジアステレオ選択性、エナンチ
オ選択性などの選択性や、触媒効率が不十分であり、触
媒の配位子や金属、対イオン等に改良や変更を加える必
要のある場合がある。本発明者らは、より高いエナンチ
オ選択性を有する光学活性コバルト錯体触媒を開発すべ
く検討を重ね、立体的に嵩高いジアミンより誘導して得
られるβ-ケトイミン型コバルト錯体、すなわち、下記
式(11)[化15]However, depending on the target reaction or the substrate, the selectivity such as chemoselectivity, diastereoselectivity, and enantioselectivity, and the catalytic efficiency are insufficient. In some cases, it is necessary to make improvements or changes to ions or the like. The present inventors have been studying to develop an optically active cobalt complex catalyst having higher enantioselectivity, and have obtained a β-ketoimine type cobalt complex derived from a sterically bulky diamine, that is, the following formula ( 11 ) [Formula 15]
【0010】[0010]
【化15】 Embedded image
【0011】で表される光学活性コバルト錯体が、高い
エナンチオ選択性を示すことを見出し、Synlett, 1996,
1076 (1996) 等に報告した。ところが、この錯体は反
応点の近傍が立体的に嵩高い基質には不適切であり、場
合によっては不斉還元反応が全く進行しないという問題
点が残されていた。さらに検討を重ねた結果、下記式
(3a)または(3a')[化16]It has been found that the optically active cobalt complex represented by the formula (1) exhibits high enantioselectivity, and is described in Synlett, 1996 ,
1076 (1996). However, this complex is unsuitable for a substrate whose reaction point is sterically bulky in the vicinity, and in some cases, there remains a problem that the asymmetric reduction reaction does not proceed at all. As a result of further study, the following formula ( 3a ) or ( 3a ' ) [Formula 16]
【0012】[0012]
【化16】 Embedded image
【0013】で表される光学活性コバルト(II)錯体
が、種々の基質に対し有効であることが判明した。すな
わち、この錯体は不斉シクロプロパン化反応、及び不斉
ボロヒドリド還元反応の触媒として高い性能を有し、こ
れらの反応において高い立体(エナンチオ、及びジアス
テレオ)選択性を示すことが明らかになった。これらの
結果は特願平11−163426号公報、特願2000
−70712号公報、及びChem. Lett., 1999, 1345 (1
999)、Synlett, 2000, 535 (2000)に報告されている。It has been found that the optically active cobalt (II) complex represented by the formula is effective for various substrates. That is, it was revealed that this complex has high performance as a catalyst for asymmetric cyclopropanation reaction and asymmetric borohydride reduction reaction, and shows high steric (enantio- and diastereo-) selectivity in these reactions. . These results are disclosed in Japanese Patent Application Nos. 11-163426 and 2000
-70712, and Chem. Lett., 1999 , 1345 (1
999), Synlett, 2000 , 535 (2000).
【0014】しかしながら、上記錯体の不斉源である光
学活性ジアミン、すなわち、下記式(12)または(1
2')[化17]However, the optically active diamine which is an asymmetric source of the above complex, ie, the following formula ( 12 ) or ( 1 )
2 ' ) [Formula 17]
【0015】[0015]
【化17】 Embedded image
【0016】で表される光学活性1,2-ビス(2,4,6-トリ
メチルフェニル)-1,2-エタンジアミンに関しては、不
斉酸化反応用のマンガン錯体の原料として使用された例
が米国イリノイ大学のZhang, Weiによる学位論文(Ph.
D. thesis, University of Illinois, 1991)に開示さ
れているものの、絶対構造(絶対立体配置)については
明らかにされていなかった。そのためこのジアミンを不
斉源として使用する触媒開発を系統的に行うことが困難
であるばかりでなく、生理活性の高い一方のエナンチオ
マーのみが必要とされる医薬品の合成においては、合成
時に使用している触媒の絶対構造がわからず、製造管理
の上で著しく不便が生じるという問題点があった。With respect to the optically active 1,2-bis (2,4,6-trimethylphenyl) -1,2-ethanediamine represented by the following formula, an example used as a raw material of a manganese complex for an asymmetric oxidation reaction is shown. Ph.D. dissertation by Zhang, Wei, University of Illinois, USA
D. thesis, University of Illinois, 1991), but the absolute structure (absolute configuration) was not disclosed. For this reason, it is not only difficult to systematically develop a catalyst using this diamine as an asymmetric source, but also in the synthesis of a drug that requires only one enantiomer having high physiological activity, However, there is a problem that the absolute structure of the catalyst is not known, resulting in significant inconvenience in production control.
【0017】[0017]
【発明が解決しようとする課題】上述のように、不斉還
元反応、及び不斉シクロプロパン化反応の触媒として、
種々の基質に対して高い選択性を示す錯体の提供が望ま
れており、併せて触媒の絶対構造を明らかにし、開発、
及び製造上の管理が容易になることが強く望まれてい
る。本発明はこれらの要望を満足せしめることを課題と
するものである。As described above, as a catalyst for an asymmetric reduction reaction and an asymmetric cyclopropanation reaction,
It is desired to provide a complex having high selectivity for various substrates, and together with clarifying the absolute structure of the catalyst,
There is a strong demand for easy management in manufacturing. An object of the present invention is to satisfy these needs.
【0018】[0018]
【課題を解決するための手段】そこで本発明者らは、前
記課題を解決するために、不斉源に光学活性なトランス
-1,2-ビス(2,4,6-トリメチルフェニル)-1,2-エタンジ
アミンを有する4座のコバルト錯体を触媒に用いて鋭意
検討を重ねてきた。その結果、光学活性N,N'-ビス(2-
アセチル-3-オキソブチリデン)-1,2-ビス(2,4,6-トリ
メチルフェニル)エチレンジアミナト臭化コバルト(I
II)錯体のX線構造解析により光学活性1,2-ビス(2,
4,6-トリメチルフェニル)-1,2-エタンジアミンの絶対
構造を明らかにした上、この光学活性N,N'-ビス(2-ア
セチル-3-オキソブチリデン)-1,2-ビス(2,4,6-トリメ
チルフェニル)エチレンジアミン、及び光学活性N,N'
-ビス(サリシリデン)-1,2-ビス(2,4,6-トリメチルフェ
ニル)エチレンジアミン等の4座の配位子を含むコバル
ト錯体触媒が、不斉ボロヒドリド還元反応、及び不斉シ
クロプロパン化反応に有効であることを見出し、本発明
に到達した。In order to solve the above-mentioned problems, the present inventors have developed an optically active transformer as an asymmetric source.
Intensive studies have been conducted using a tetradentate cobalt complex having -1,2-bis (2,4,6-trimethylphenyl) -1,2-ethanediamine as a catalyst. As a result, the optically active N, N'-bis (2-
Acetyl-3-oxobutylidene) -1,2-bis (2,4,6-trimethylphenyl) ethylenediaminatocobalt bromide (I
II) The X-ray structure analysis of the complex reveals the optically active 1,2-bis (2,
After clarifying the absolute structure of 4,6-trimethylphenyl) -1,2-ethanediamine, the optically active N, N′-bis (2-acetyl-3-oxobutylidene) -1,2-bis (2, 4,6-trimethylphenyl) ethylenediamine and optically active N, N '
Asymmetric borohydride reduction reaction and asymmetric cyclopropanation reaction using cobalt complex catalysts containing tetradentate ligands such as -bis (salicylidene) -1,2-bis (2,4,6-trimethylphenyl) ethylenediamine And found that the present invention was effective.
【0019】[0019]
【発明の実施の形態】以下、本発明を詳細に説明する。
本発明の光学活性コバルト(II)錯体は、下記一般式
(1)または(1')[化18]BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail.
The optically active cobalt (II) complex of the present invention has the following general formula ( 1 ) or ( 1 ′ ):
【0020】[0020]
【化18】 Embedded image
【0021】〔式中、R1及びR2は、同一でも異なって
いてもよく、水素原子、直鎖もしくは分岐状のアルキル
基、直鎖もしくは分岐状のアルケニル基、直鎖もしくは
分岐状のアリール基、アシル基またはアルコキシカルボ
ニル基、アリールオキシカルボニル基またはアラルキル
オキシカルボニル基であり、前記アルキル基、アルケニ
ル基、アリール基、アシル基、アルコキシカルボニル
基、アリールオキシカルボニル基及びアラルキルオキシ
カルボニル基は置換基を有していてもよく、また、R1
及びR2は、相互に連結して、R1及びR2がそれぞれ結
合している炭素原子と共同して環を形成してもよい。〕
で表される。[In the formula, R 1 and R 2 may be the same or different and each represents a hydrogen atom, a linear or branched alkyl group, a linear or branched alkenyl group, a linear or branched aryl group. A group, an acyl group or an alkoxycarbonyl group, an aryloxycarbonyl group or an aralkyloxycarbonyl group, wherein the alkyl group, alkenyl group, aryl group, acyl group, alkoxycarbonyl group, aryloxycarbonyl group and aralkyloxycarbonyl group are And R 1
And R 2 may be linked to each other to form a ring in cooperation with the carbon atom to which R 1 and R 2 are each bonded. ]
It is represented by
【0022】上記R1及びR2のアルキル基としては、メ
チル基、エチル基、イソプロピル基、tert-ブチル基、
sec-ブチル基、n-プロピル基、n-ブチル基等が代表的
である。The alkyl groups for R 1 and R 2 include a methyl group, an ethyl group, an isopropyl group, a tert-butyl group,
Typical examples include a sec-butyl group, an n-propyl group, and an n-butyl group.
【0023】アリール基としては、フェニル基、p-メ
トキシフェニル基、p-クロロフェニル基、p-フルオロ
フェニル基、3,5-ジメチルフェニル基、3,5-ジメトキシ
フェニル基、2,4,6-トリメチルフェニル基、ナフチル基
等の置換または非置換の芳香族炭化水素基;フリル基、
チエニル基、ピリジル基、ピロリル基、オキサゾリル
基、イソオキサゾル基、チアゾリル基、イソチアゾリル
基、イミダゾリル基、ピラゾリル基、ピリミジル基、ピ
リダジニル基、ピラリジニル基、キノリル基、イソキノ
リル基等の置換または非置換の芳香族複素環基が代表的
である。The aryl group includes a phenyl group, a p-methoxyphenyl group, a p-chlorophenyl group, a p-fluorophenyl group, a 3,5-dimethylphenyl group, a 3,5-dimethoxyphenyl group, a 2,4,6- A substituted or unsubstituted aromatic hydrocarbon group such as a trimethylphenyl group or a naphthyl group; a furyl group,
Substituted or unsubstituted aromatic groups such as thienyl group, pyridyl group, pyrrolyl group, oxazolyl group, isoxazole group, thiazolyl group, isothiazolyl group, imidazolyl group, pyrazolyl group, pyrimidyl group, pyridazinyl group, pyraridinyl group, quinolyl group, isoquinolyl group Heterocyclic groups are representative.
【0024】アシル基としては、アセチル基、トリフル
オロアセチル基、プロピオニル基、ブチリル基、イソブ
チリル基、ピバロイル基等の脂肪族アシル基;ベンゾイ
ル基、3,5-ジメチルベンゾイル基、2,4,6-トリメチルベ
ンゾイル基、2,6-ジメトキシベンゾイル基、2,4,6-トリ
メトキシベンゾイル基、2,6-ジイソプロポキシベンゾイ
ル基、1-ナフチルカルボニル基、2-ナフチルカルボニル
基、9-アントリルカルボニル基等の芳香族アシル基が代
表的であり、アルコキシカルボニル基の代表例として
は、メトキシカルボニル基、エトキシカルボニル基、n
-ブトキシカルボニル基、n-オクチルオキシカルボニル
基、シクロペンチルオキシカルボニル基、シクロヘキシ
ルオキシカルボニル基、シクロオクチルオキシカルボニ
ル基、tert-ブトキシカルボニル基が挙げられ、アリー
ルオキシカルボニル基の代表例としては、フェノキシカ
ルボニル基が挙げられ、アラルキルオキシカルボニル基
の代表例としては、ベンジルオキシカルボニル基、フェ
ネチルオキシカルボニル基等が挙げられる。Examples of the acyl group include aliphatic acyl groups such as acetyl, trifluoroacetyl, propionyl, butyryl, isobutyryl, and pivaloyl; benzoyl, 3,5-dimethylbenzoyl, 2,4,6 -Trimethylbenzoyl group, 2,6-dimethoxybenzoyl group, 2,4,6-trimethoxybenzoyl group, 2,6-diisopropoxybenzoyl group, 1-naphthylcarbonyl group, 2-naphthylcarbonyl group, 9-anthryl Aromatic acyl groups such as a carbonyl group are typical, and typical examples of the alkoxycarbonyl group include a methoxycarbonyl group, an ethoxycarbonyl group,
-Butoxycarbonyl group, n-octyloxycarbonyl group, cyclopentyloxycarbonyl group, cyclohexyloxycarbonyl group, cyclooctyloxycarbonyl group, tert-butoxycarbonyl group, and a typical example of the aryloxycarbonyl group is a phenoxycarbonyl group. And a benzyloxycarbonyl group, a phenethyloxycarbonyl group and the like are typical examples of the aralkyloxycarbonyl group.
【0025】また、R1及びR2は、相互に連結して、R
1及びR2がそれぞれ結合している炭素原子と共同して環
を形成してもよい。例えば、R1及びR2が相互に連結し
て、-(CH2)4-または-CH=CH-CH=CH-となる場
合、それぞれシクロヘキサン環またはベンゼン環が形成
され、このように形成されたシクロヘキサン環、ベンゼ
ン環等の環は、例えば、メチル基、エチル基、n-プロ
ピル基、イソプロピル基、sec-ブチル基、tert-ブチル
基等のアルキル基;フェニル基、ナフチル基等のアリー
ル基;メトキシ基、エトキシ基、イソプロピルオキシ基
等のアルキルオキシ基;フェノキシ基、2,6-ジメチルフ
ェノキシ基等のアリールオキシ基;ベンジルオキシ基、
フェネチルオキシ基等のアラルキルオキシ基;フッ素、
塩素、臭素等のハロゲン原子;シアノ基;ニトロ基から
選ばれる1または2以上の置換基で置換されていてもよ
く、また、前記ベンゼン環は縮合し、ナフタレン環等の
縮合多環を形成してもよい。R 1 and R 2 are linked to each other to form R 1
1 and R 2 may form a ring together with the carbon atom to which they are attached. For example, when R 1 and R 2 are linked together to form-(CH 2 ) 4 -or -CH = CH-CH = CH-, a cyclohexane ring or a benzene ring is formed, respectively. Rings such as cyclohexane ring and benzene ring are, for example, alkyl groups such as methyl group, ethyl group, n-propyl group, isopropyl group, sec-butyl group and tert-butyl group; aryl groups such as phenyl group and naphthyl group. An alkyloxy group such as a methoxy group, an ethoxy group, and an isopropyloxy group; an aryloxy group such as a phenoxy group and a 2,6-dimethylphenoxy group; a benzyloxy group;
An aralkyloxy group such as a phenethyloxy group; fluorine,
A halogen atom such as chlorine or bromine; a cyano group; a nitro group, which may be substituted with one or more substituents, and the benzene ring is condensed to form a condensed polycyclic ring such as a naphthalene ring. You may.
【0026】この一般式(1)または(1')で表され
る光学活性コバルト(II)錯体の具体例として、下記
式(3a)〜(3f)、(6a)〜(6j)([化1
9]〜[化22])で表されるもの、及びそれらの鏡像
異性体等が挙げられる。As specific examples of the optically active cobalt (II) complex represented by the general formula ( 1 ) or ( 1 ' ), the following formulas ( 3a ) to ( 3f ), ( 6a ) to ( 6j ) ( 1
9] to [Formula 22]), their enantiomers, and the like.
【0027】[0027]
【化19】 Embedded image
【0028】[0028]
【化20】 Embedded image
【0029】[0029]
【化21】 Embedded image
【0030】[0030]
【化22】 Embedded image
【0031】また、本発明の光学活性コバルト(II
I)錯体は、下記一般式(2)または(2')[化2
3]The optically active cobalt (II) of the present invention
I) The complex is represented by the following general formula ( 2 ) or ( 2 ′ )
3]
【0032】[0032]
【化23】 Embedded image
【0033】〔式中、R1及びR2は、前記一般式(1)
または(1')について定義したとおりであり、式中X-
は塩を形成し得る陰イオン対である。〕で表される。[In the formula, R 1 and R 2 are the same as those in the general formula ( 1 ).
Or (1 ') are as defined for in formula X -
Is an anion pair capable of forming a salt. ] Is represented.
【0034】上記X-としては、F-、Cl-、Br-、
I-、OH-、CH3CO2 -、p-CH3C 6H4SO3 -、CF
3SO3 -、PF6 -、BF4 -、BPh4 -、SbF6 -、Cl
O4 -等が代表的である。The above X-As F-, Cl-, Br-,
I-, OH-, CHThreeCOTwo -, P-CHThreeC 6HFourSOThree -, CF
ThreeSOThree -, PF6 -, BFFour -, BPhFour -, SbF6 -, Cl
OFour -Etc. are typical.
【0035】前記式(2)または(2')で表される光
学活性コバルト(III)錯体の具体例として、下記式
(4aA)〜(4aH)、(7aB)〜(7aE)
([化24]〜[化26])で表されるもの、及びそれ
らの鏡像異性体等が挙げられる。As specific examples of the optically active cobalt (III) complex represented by the above formula ( 2 ) or ( 2 ' ), the following formulas ( 4aA ) to ( 4aH ), ( 7aB ) to ( 7aE )
([Chemical Formula 24] to [Chemical Formula 26]) and their enantiomers.
【0036】[0036]
【化24】 Embedded image
【0037】[0037]
【化25】 Embedded image
【0038】[0038]
【化26】 Embedded image
【0039】前記一般式(1)または(1')で表され
る光学活性コバルト(II)錯体、及び一般式(2)ま
たは(2')で表される光学活性コバルト(III)錯
体は、公知の方法に従って調製することができる。例え
ば、Y. Nishidaら、 Inorg.Chim. Acta, 38, 213 (198
0); L. Claisen, Ann. Chem., 297, 57 (1897); E. G.
Jager, Z. Chem., 8, 30, 392, および 475 (1968)に報
告された方法に従って調製することができ、特開平9−
151143号公報にも開示されている。例えば、式
(5a)で表されるβ-ケトイミン化合物、及びそれに
対応する、式(3a)で表される光学活性コバルト(I
I)錯体、及び式(4aB)で表される光学活性コバル
ト(III)錯体は、下記式(A)[化27]に示す工
程に従って調製することができる。The optically active cobalt (II) complex represented by the general formula ( 1 ) or ( 1 ′ ) and the optically active cobalt (III) complex represented by the general formula ( 2 ) or ( 2 ′ ) It can be prepared according to a known method. See, for example, Y. Nishida et al., Inorg. Chim. Acta, 38 , 213 (198
0); L. Claisen, Ann. Chem., 297 , 57 (1897); EG
It can be prepared according to the method reported in Jager, Z. Chem., 8 , 30, 392, and 475 (1968).
It is also disclosed in JP-A-151143. For example, the β-ketoimine compound represented by the formula ( 5a ) and the corresponding optically active cobalt (I) represented by the formula ( 3a )
I) The complex and the optically active cobalt (III) complex represented by the formula ( 4aB ) can be prepared according to the steps shown in the following formula ( A ).
【0040】[0040]
【化27】 Embedded image
【0041】このβ-ケトイミン型光学活性コバルト錯
体の製造において、原料合成工程となる3-メトキシメチ
レン-2,4-ペンタンジオン(式(A)中の化合物(13
a))の調製は、例えば、アセチルアセトンに1〜5モ
ル当量のオルトギ酸トリメチルを加え、無水酢酸溶媒中
で、加熱・還流することにより行うことができる。In the production of the β-ketoimine type optically active cobalt complex, 3-methoxymethylene-2,4-pentanedione (compound ( 13)
a )) can be prepared, for example, by adding 1 to 5 molar equivalents of trimethyl orthoformate to acetylacetone and heating and refluxing in an acetic anhydride solvent.
【0042】光学活性ジアミンとの脱水縮合反応は、ア
ルコール溶媒中、3-メトキシメチレン-2,4-ペンタンジ
オン(13a)を2当量加え、室温で1〜2時間撹拌し
た後、さらに50℃に加熱することにより行うことがで
きる。濃縮して得られる粗生成物は、シリカゲルカラム
クロマトグラフィー、再沈殿、再結晶等の通常の精製方
法によって精製することができる。The dehydration-condensation reaction with an optically active diamine is carried out by adding 2 equivalents of 3-methoxymethylene-2,4-pentanedione ( 13a ) in an alcohol solvent, stirring the mixture at room temperature for 1 to 2 hours, and then heating at 50 ° C. It can be performed by heating. The crude product obtained by concentration can be purified by a conventional purification method such as silica gel column chromatography, reprecipitation, and recrystallization.
【0043】配位子の錯形成工程に使用する塩基性化合
物としては水酸化ナトリウム、水酸化カリウム等が挙げ
られ、その使用量は、配位子に対して2.0モル当量以上
であり、好ましくは2.0〜2.5モル当量である。Examples of the basic compound used in the ligand complex formation step include sodium hydroxide, potassium hydroxide and the like. The amount of the basic compound to be used is at least 2.0 molar equivalents to the ligand, and is preferably 2.0 to 2.5 molar equivalents.
【0044】コバルトカチオン源としては、塩化コバル
ト(II)、酢酸コバルト(II)等、コバルトの2価
イオンを含む化合物が挙げられ、これらは水溶液として
使用できる。配位子に対して1.0モル当量、もしくはそ
れ以上のコバルトカチオンを添加すればよく、好ましく
は1.0〜1.5モル当量となる量が使用される。Examples of the cobalt cation source include compounds containing divalent ions of cobalt, such as cobalt (II) chloride and cobalt (II) acetate, and these can be used as an aqueous solution. It is sufficient to add 1.0 molar equivalent or more of the cobalt cation to the ligand, and preferably, an amount that gives 1.0 to 1.5 molar equivalent is used.
【0045】錯形成反応は、窒素またはアルゴン等の不
活性ガス雰囲気下で行い、塩基、コバルトカチオン、配
位子を溶かすための水、及び溶媒は脱気したものを使用
する。また、反応温度は0℃以上であれば反応が進行す
るが、30〜80℃程度に加熱することにより反応時間を短
縮することができ、好ましくは40〜60℃である。The complex formation reaction is carried out in an atmosphere of an inert gas such as nitrogen or argon, and degassed water is used for dissolving the base, the cobalt cation and the ligand, and the solvent is used. The reaction proceeds when the reaction temperature is 0 ° C. or higher, but the reaction time can be shortened by heating to about 30 to 80 ° C., and preferably 40 to 60 ° C.
【0046】溶媒としては、メタノール、エタノール、
2-プロパノール等のアルコール系溶媒が好ましい。As the solvent, methanol, ethanol,
Alcohol solvents such as 2-propanol are preferred.
【0047】上記式(A)に示す錯形成工程において、
塩化コバルト(II)水溶液の添加後間もなく、1〜10
分程度でコバルト(II)錯体が析出を開始するが、さ
らに加熱・撹拌を30分〜2時間程度継続して行う。その
後、反応混合物を室温まで冷却し、必要に応じて水を添
加して反応生成物を析出させる。次に窒素などの不活性
ガス下で濾別し、水または水−アルコールの混合溶液に
より洗浄した後、真空乾燥を行い、目的の光学活性コバ
ルト(II)錯体を得ることができる。In the complex forming step represented by the above formula (A),
Shortly after the addition of the aqueous cobalt (II) chloride solution, 1-10
The cobalt (II) complex starts to precipitate in about a minute, but heating and stirring are further continued for about 30 minutes to 2 hours. Thereafter, the reaction mixture is cooled to room temperature, and water is added as necessary to precipitate a reaction product. Next, the mixture is filtered off under an inert gas such as nitrogen, washed with water or a mixed solution of water-alcohol, and then dried under vacuum to obtain a target optically active cobalt (II) complex.
【0048】上記の方法により得られた光学活性コバル
ト(II)錯体に、塩素、臭素、ヨウ素等のハロゲンを
添加することにより、対応するハロゲン化された光学活
性コバルト(III)錯体へと変換できる。例えば、ジ
クロロメタン溶媒中で、光学活性コバルト(II)錯体
に臭素(Br2)0.5モル当量を加え、室温で撹拌して反応
させ、濃縮すると粗生成物が得られる。この粗生成物は
シリカゲルカラムクロマトグラフィー、再沈殿、再結晶
等の精製操作により精製できる。By adding a halogen such as chlorine, bromine or iodine to the optically active cobalt (II) complex obtained by the above-mentioned method, it can be converted to the corresponding halogenated optically active cobalt (III) complex. . For example, in a dichloromethane solvent, 0.5 mol equivalent of bromine (Br 2 ) is added to the optically active cobalt (II) complex, reacted at room temperature with stirring, and concentrated to obtain a crude product. This crude product can be purified by purification operations such as silica gel column chromatography, reprecipitation, and recrystallization.
【0049】一方、例えば、式(8a)で表されるサレ
ン化合物、及びそれに対応する、式(6a)で表される
光学活性コバルト(II)錯体、及び式(7aB)で表
される光学活性コバルト(III)錯体は、前記式
(A)と同様に下記式(B)[化28]に示す工程に従
って調製することができる。On the other hand, for example, the salen compound represented by the formula ( 8a ), the corresponding optically active cobalt (II) complex represented by the formula ( 6a ), and the optically active compound represented by the formula ( 7aB ) The cobalt (III) complex can be prepared according to the process shown in the following formula ( B ) [Formula 28] in the same manner as in the above formula ( A ).
【0050】[0050]
【化28】 Embedded image
【0051】このサレン型光学活性コバルト錯体の製造
は、前述の式(A)における化合物(13)の代わりに
サリチルアルデヒド(式(B)中の化合物(14a))
を出発原料として用い、同様の工程を経て製造できる。The salen type optically active cobalt complex is produced by replacing the compound ( 13 ) in the above formula ( A ) with salicylaldehyde (the compound ( 14a ) in the formula ( B )).
Can be produced as a starting material through the same steps.
【0052】このようにして得られる、前記式(3a)
または(6a)に代表される光学活性コバルト(II)
錯体、及び前記式(4aB)または(7aB)に代表さ
れる光学活性コバルト(III)錯体は、共にケトンや
イミンを基質とする不斉ボロヒドリド還元反応の触媒と
して、あるいはオレフィンの不斉シクロプロパン化反応
の触媒として有効である。また、これらの錯体は空気中
で非常に安定であり、3〜5年間保管したものでも触媒と
して問題なく使用できる。The above formula ( 3a ) thus obtained is obtained.
Or optically active cobalt (II) represented by ( 6a )
The complex and the optically active cobalt (III) complex represented by the formula ( 4aB ) or ( 7aB ) are both used as a catalyst for an asymmetric borohydride reduction reaction using a ketone or imine as a substrate, or for asymmetric cyclopropanation of an olefin. It is effective as a catalyst for the reaction. In addition, these complexes are very stable in the air, and can be used without problems even if stored for 3 to 5 years as a catalyst.
【0053】特にコバルト(III)錯体の場合は、溶
媒に溶かして水や空気に曝しても全く問題がないほど安
定である。安定かつ取り扱いが容易であるという特性が
あるため、X線による構造解析を行うことが容易であ
る。すなわち、光学活性コバルト(III)錯体をテト
ラヒドロフラン(THF)-ヘキサン溶液中で結晶化さ
せてX線分析可能な単結晶を得、これをX線構造解析に
供することができる。実際に、式(4aB)で表される
光学活性コバルト(III)錯体の単結晶を用いてX線
分析を行い、これまで明らかにされていなかった光学活
性ジアミン部分の絶対立体配置を決定することができ
た。Particularly, in the case of the cobalt (III) complex, it is stable so that there is no problem even when it is dissolved in a solvent and exposed to water or air. Since it has the characteristics of being stable and easy to handle, it is easy to perform structural analysis using X-rays. That is, the optically active cobalt (III) complex is crystallized in a tetrahydrofuran (THF) -hexane solution to obtain a single crystal capable of X-ray analysis, which can be subjected to X-ray structural analysis. Actually, X-ray analysis is performed using a single crystal of the optically active cobalt (III) complex represented by the formula ( 4aB ) to determine the absolute configuration of the optically active diamine moiety, which has not been clarified until now. Was completed.
【0054】次に、本発明の光学活性コバルト錯体の不
斉源として使用する、前記式(12)で表される光学活
性ジアミン(1,2-ビス(2,4,6-トリメチルフェニル)-
1,2-エタンジアミン)の合成法、及び光学活性コバルト
(III)錯体の絶対立体配置決定方法について、参考
までに説明する。 光学活性ジアミン(12)の合成法:まず、ラセミ体の
トランス-1,2-ビス(2,4,6-トリメチルフェニル)-1,2-
エタンジアミンの製造法について説明する。ラセミ体の
トランス-1,2-ビス(2,4,6-トリメチルフェニル)-1,2-
エタンジアミンは、下記式(C)[化29]に示す工程
(Pedersenらによる方法:J.Am.Chem.Soc., 109, 3
152 (1987))に従って調製することができる。Next, the optically active diamine (1,2-bis (2,4,6-trimethylphenyl)-) represented by the above formula ( 12 ), which is used as an asymmetric source of the optically active cobalt complex of the present invention.
A method for synthesizing (1,2-ethanediamine) and a method for determining the absolute configuration of an optically active cobalt (III) complex will be described for reference. Synthesis method of optically active diamine ( 12 ): First, racemic trans-1,2-bis (2,4,6-trimethylphenyl) -1,2-
A method for producing ethanediamine will be described. Racemic trans-1,2-bis (2,4,6-trimethylphenyl) -1,2-
Ethanediamine can be obtained by a process represented by the following formula ( C ) (Method by Pedersen et al .: J. Am. Chem. Soc., 109 , 3).
152 (1987)).
【0055】[0055]
【化29】 Embedded image
【0056】すなわち、2,4,6-トリメチルベンズアルデ
ヒド(15)をリチウムビス(トリメチルシリル)アミ
ドと反応させた、塩化トリメチルシランを加えて撹拌を
続けた後、濃縮して析出する塩を濾別、除去し、濾液を
減圧蒸留するとシリルイミン(16)が得られる。次
に、等モル量の四塩化ニオブ−テトラヒドロフラン錯体
の存在下、1,2-ジメトキシエタン溶媒中、上記で得たシ
リルイミン(16)を室温で反応させ、塩基で処理する
ことにより、目的とするラセミ体のトランス-1,2-ビス
(2,4,6-トリメチルフェニル)-1,2-エタンジアミン
((±)-12)が収率よく得られる。次に光学活性マ
ンデル酸による光学分割を行い、光学活性ジアミンを単
離する事ができる。すなわち、(+)-マンデル酸を分
割剤として使用した場合には(−)-1,2-ビス(2,4,6-
トリメチルフェニル)-1,2-エタンジアミンが、一方、
(−)-マンデル酸を使用した場合には(+)-1,2-ビス
(2,4,6-トリメチルフェニル)-1,2-エタンジアミンが
得られる。That is, 2,4,6-trimethylbenzaldehyde ( 15 ) was reacted with lithium bis (trimethylsilyl) amide, trimethylsilane chloride was added, stirring was continued, and the salt precipitated by concentration was separated by filtration. The filtrate is distilled off under reduced pressure to obtain silylimine ( 16 ). Next, in the presence of an equimolar amount of a niobium tetrachloride-tetrahydrofuran complex, the silylimine ( 16 ) obtained above is reacted in a 1,2-dimethoxyethane solvent at room temperature and treated with a base to obtain the desired compound. racemic trans-1,2-bis (2,4,6-trimethylphenyl) -1,2-ethanediamine ((±) - 12) are obtained in good yield. Next, optical resolution with optically active mandelic acid is performed to isolate the optically active diamine. That is, when (+)-mandelic acid is used as a resolving agent, (−)-1,2-bis (2,4,6-
Trimethylphenyl) -1,2-ethanediamine,
When (-)-mandelic acid is used, (+)-1,2-bis (2,4,6-trimethylphenyl) -1,2-ethanediamine is obtained.
【0057】絶対配置決定の原理:X線の散乱と吸収が
同時に強く起ると、X線の異常散乱が生じる。これを利
用することにより、対称心を持たない結晶の絶対構造が
決定できる。最近では、最小二乗法のパラメータとして
次式[数式1]で定義される変数xを精密化する方法が
標準的に使用されている。Principle of determining the absolute configuration: If X-ray scattering and absorption occur simultaneously, abnormal X-ray scattering occurs. By utilizing this, the absolute structure of a crystal having no center of symmetry can be determined. Recently, a method of refining a variable x defined by the following equation [Equation 1] as a parameter of the least squares method has been used as a standard.
【数式1】 変数xをFlack のパラメータという。(Flack, H. D.,
Acta Cryst. A39, 876-881 (1983). ) xが0に近ければ絶対構造は正しいが、1に近ければ反
転構造のほうが正しいことになる。このFlack のパラメ
ータを利用すれば絶対構造の解析を行うことができる。
絶対配置を決定する際には、Flack のパラメータxが
-0.2以上0.3以下であること、その標準偏差が0.5以下
であること、という2つの条件を満足している必要があ
る。本発明では、このFlackのパラメータを利用して錯
体の絶対立体配置を明らかにすることができた。なお、
絶対配置を決定するためには、フリーデル対(hklと-h,
-k,-lの反射の組)をできるだけ多く測定する必要があ
る。[Formula 1] The variable x is called a Flack parameter. (Flack, HD,
Acta Cryst. A39 , 876-881 (1983).) If x is close to 0, the absolute structure is correct, but if it is close to 1, the inverted structure is correct. Using these Flack parameters, you can analyze the absolute structure.
When determining the absolute configuration, the Flack parameter x
It is necessary to satisfy two conditions, that is, -0.2 or more and 0.3 or less and its standard deviation is 0.5 or less. In the present invention, the absolute configuration of the complex could be clarified using the Flack parameter. In addition,
To determine the absolute configuration, the Friedel pair (hkl and -h,
-k, -l reflection set) must be measured as much as possible.
【0058】[0058]
【実施例】以下、実施例により本発明を具体的に説明す
るが、本発明は、これらの実施例に限定されるものでは
ない。EXAMPLES The present invention will be described below in detail with reference to examples, but the present invention is not limited to these examples.
【0059】(参考例1) 3-メトキシメチレン-2,4-ペンタンジオン(13a)の
合成:反応器に入れたアセチルアセトン 21.6 g (0.216
mol)とオルトギ酸トリメチル 40.0 g (0.377 mol)の無
水酢酸(66.0 g, 0.647 mol)溶液を120℃で5時間加熱し
た。副生する低沸点成分を留去した後、減圧蒸留する
と、3-メトキシメチレン-2,4-ペンタンジオン 29.8 g
が得られた(収率96%)。 沸点 110〜112 ℃/0.7 mmHg。1 H NMR (CDCl3)δ = 7.63 (1H, s), 4.05 (3H, s), 2.3
8 (3H, s), 2.33 (3H, s); IR 2998, 2946, 2852, 167
8, 1623, 1587, 1388, 1360, 1292, 1134 cm-1.Reference Example 1 Synthesis of 3-methoxymethylene-2,4-pentanedione ( 13a ): 21.6 g (0.216 g) of acetylacetone in a reactor
mol) and 40.0 g (0.377 mol) of trimethyl orthoformate in acetic anhydride (66.0 g, 0.647 mol) were heated at 120 ° C. for 5 hours. After distilling off low-boiling components produced as by-products, distillation under reduced pressure gives 3-methoxymethylene-2,4-pentanedione 29.8 g
Was obtained (96% yield). Boiling point 110-112 ° C / 0.7 mmHg. 1 H NMR (CDCl 3 ) δ = 7.63 (1H, s), 4.05 (3H, s), 2.3
8 (3H, s), 2.33 (3H, s); IR 2998, 2946, 2852, 167
8, 1623, 1587, 1388, 1360, 1292, 1134 cm -1 .
【0060】(実施例1) β-ケトイミン型配位子(5a)の合成:ナトリウムのD
線に対してプラスの旋光性を示す1,2-ビス(2,4,6-トリ
メチルフェニル)エチレンジアミン 2.96 g (10 mmol)の
エタノール溶液(60 ml)に、撹拌しながら、室温で3-メ
トキシメチレン-2,4-ペンタンジオン2.98 g (21 mmol)
のエタノール溶液(40 ml)を滴下した。室温で1時間撹拌
した後、50℃に昇温して2時間撹拌を続けた。反応終了
後、溶媒を減圧留去すると粗生成物が得られた。粗生成
物をジクロロメタン/エーテル/ヘキサンにより再結晶を
行い、濾別、洗浄、真空乾燥するとβ-ケトイミン型配
位子(5a) 4.88 gが白色粉末として得られた(単離収
率 95%)。1 H NMR (CDCl3)δ = 1.73 (6H, br), 2.21 (6H, s), 2.
22 (6H, s), 2.46 (6H,s), 2.72 (6H, br), 5.20 (2H,
m), 6.60-6.90 (4H, m), 7.65 (2H, d, J = 12.2 Hz);
比旋光度 [α]D 27 −186° (c 1.02, CHCl3)Example 1 Synthesis of β-ketoimine type ligand ( 5a ): D of sodium
1,2-bis (2,4,6-trimethylphenyl) ethylenediamine 2.96 g (10 mmol) in ethanol solution (60 ml) showing a positive optical rotation with respect to the line Methylene-2,4-pentanedione 2.98 g (21 mmol)
An ethanol solution (40 ml) was added dropwise. After stirring at room temperature for 1 hour, the temperature was raised to 50 ° C., and stirring was continued for 2 hours. After completion of the reaction, the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was recrystallized from dichloromethane / ether / hexane, filtered, washed and dried under vacuum to obtain 4.88 g of β-ketoimine type ligand ( 5a ) as a white powder (isolation yield: 95%) . 1 H NMR (CDCl 3 ) δ = 1.73 (6H, br), 2.21 (6H, s), 2.
22 (6H, s), 2.46 (6H, s), 2.72 (6H, br), 5.20 (2H,
m), 6.60-6.90 (4H, m), 7.65 (2H, d, J = 12.2 Hz);
Specific rotation [α] D 27 −186 ° (c 1.02, CHCl 3 )
【0061】(実施例2) β-ケトイミナトコバルト(II)錯体(3a)の合
成:反応器に入れたβ-ケトイミン型配位子(5a) 4.
1 g (8 mmol)にメタノール(140 ml)を加え、窒素流通下
で撹拌して溶解させた。30分間撹拌した後、水酸化ナト
リウム0.72 g (18 mmol)水溶液 (2.8 ml)を加え、50℃
で撹拌した。30分後、塩化コバルト・6水和物2.1 g (9
mmol)水溶液(3.7 ml)を滴下すると黄褐色の沈殿が析出
した。更に30分間撹拌した後、室温に冷却して水を加え
た(40 ml×2回)。窒素雰囲気下で反応液を濾過し、析出
物を水洗し、窒素流通により乾燥させた。窒素ボックス
内で生成物を取り出し、120℃で2時間減圧乾燥を行なう
と、黄褐色のコバルト(II)錯体(3a)4.3 gが得
られた(収率93%)。 融点 276-282 ℃Example 2 Synthesis of β-ketoiminatocobalt (II) complex ( 3a ): β-ketoimine type ligand ( 5a ) placed in a reactor 4.
Methanol (140 ml) was added to 1 g (8 mmol), and dissolved by stirring under a nitrogen flow. After stirring for 30 minutes, an aqueous solution (2.8 ml) of sodium hydroxide 0.72 g (18 mmol) was added, and the mixture was added at 50 ° C.
And stirred. After 30 minutes, 2.1 g of cobalt chloride hexahydrate (9
mmol) aqueous solution (3.7 ml) was added dropwise to precipitate a tan precipitate. After further stirring for 30 minutes, the mixture was cooled to room temperature and water was added (40 ml × 2). The reaction solution was filtered under a nitrogen atmosphere, the precipitate was washed with water, and dried by flowing nitrogen. The product was taken out in a nitrogen box, and dried under reduced pressure at 120 ° C. for 2 hours to obtain 4.3 g of a yellow-brown cobalt (II) complex ( 3a ) (93% yield). Melting point 276-282 ℃
【0062】(実施例3) β-ケトイミナト臭化コバルト(III)錯体(4aB)
の合成:β-ケトイミナトコバルト(II)錯体(3
a) 1.15 g (2 mmol)にジクロロメタン(23 ml)を加
え、窒素流通下で臭素168 mg (1.05 mmol)を含むジクロ
ロメタン溶液(5 ml)を滴下した。室温で1時間撹拌した
後、溶媒を留去し、シリカゲルカラムクロマトグラフィ
ー(CH2Cl2/MeOH=30/1)による精製を行った。目的物を
含む留分を濃縮後、さらに少量のジクロロメタンに溶か
し、ヘキサンを加えたところ、茶色の析出物が得られ
た。濾過、洗浄、乾燥操作を行い、目的とする臭化コバ
ルト(III)錯体(4aB)1.17 gを回収できた(収
率90%)。Example 3 β-ketoiminate cobalt (III) bromide complex ( 4aB )
Synthesis of β-ketoiminatocobalt (II) complex ( 3
a ) Dichloromethane (23 ml) was added to 1.15 g (2 mmol), and a dichloromethane solution (5 ml) containing 168 mg (1.05 mmol) of bromine was added dropwise under nitrogen flow. After stirring at room temperature for 1 hour, the solvent was distilled off, and purification was performed by silica gel column chromatography (CH 2 Cl 2 / MeOH = 30/1). After concentrating the fraction containing the target substance, it was further dissolved in a small amount of dichloromethane, and hexane was added, whereby a brown precipitate was obtained. By performing filtration, washing and drying operations, 1.17 g of the target cobalt (III) bromide complex ( 4aB ) was recovered (yield 90%).
【0063】(実施例4)(-)D-β-ケトイミナト臭化コ
バルト(III)錯体(4aB)(N,N'-ビス(2-アセチ
ル-2-ブテンジイル-3-オラト)-1,2-ビス(2,4,6-トリメ
チルフェニル)エチレンジアミン-臭化コバルト(II
I))のX線結晶構造解析による絶対立体配置の決定(Example 4) (-) D -β-ketiminato cobalt (III) bromide complex ( 4aB ) (N, N'-bis (2-acetyl-2-butenediyl-3-orato) -1,2 -Bis (2,4,6-trimethylphenyl) ethylenediamine-cobalt bromide (II
I)) Determination of absolute configuration by X-ray crystal structure analysis
【0064】X線構造解析:X線構造解析には、前記式
(4aB)で表されるN,N'-ビス(2-アセチル-2-ブテンジ
イル-3-オラト)-1,2-ビス(2,4,6-トリメチルフェニ
ル)エチレンジアミン-臭化コバルト(III)錯体、
あるいはその鏡像異性体のうち、ナトリウムのD線に対
してマイナスの旋光性([α]D 27 = -1440°(c 0.022, T
HF))を示すサンプルを用いた。分析に使用する単結晶
は、錯体のTHF(テトラヒドロフラン)溶液にヘキサ
ンを少量加えて拡散させることにより調製した。得られ
た褐色の柱状晶(0.5×0.3×0.1 mm)を母液と共にキャ
ピラリーに封入し、4軸型X線回折計Rigaku AFC-7Rにの
せた。線源にはMoKα(波長λ=0.71073Å)を用いて、2
θm ax=55°まで+h,+k,±lの反射のX線回折強度を測定
した。また、2θ≦40°の領域については、+h ,−k,±
lの反射の測定も行った。全部で12278反射を測定し、11
744個の独立反射を得た。なお、この中には3169個のフ
リーデル対も含まれている。結晶学的データを表1[表
1]に示す。X-ray structure analysis: For X-ray structure analysis, N, N'-bis (2-acetyl-2-butenediyl-3-orato) -1,2-bis () represented by the above formula ( 4aB ) was used. 2,4,6-trimethylphenyl) ethylenediamine-cobalt (III) bromide complex,
Alternatively, among its enantiomers, a negative optical rotation ([α] D 27 = -1440 ° (c 0.022, T
HF)). The single crystal used for the analysis was prepared by adding a small amount of hexane to a THF (tetrahydrofuran) solution of the complex and diffusing it. The obtained brown columnar crystals (0.5 × 0.3 × 0.1 mm) were sealed in a capillary together with the mother liquor, and placed on a 4-axis X-ray diffractometer Rigaku AFC-7R. Using MoKα (wavelength λ = 0.71073Å) as the source, 2
θ m ax = 55 ° to + h, + k, measurement of X-ray diffraction intensity of the reflection of ± l. In addition, for the region of 2θ ≦ 40 °, + h, −k, ±
l reflection measurements were also made. A total of 12278 reflections were measured and 11
744 independent reflections were obtained. This includes 3169 Friedel pairs. The crystallographic data is shown in Table 1 [Table 1].
【0065】[0065]
【表1】 [Table 1]
【0066】構造は直接法を用いて解いた。結晶溶媒と
して2分子独立なTHFが含まれていたが、原子変位パラ
メータが非常に大きかったため、THFの非水素原子は等
方性温度因子を用いて解析し、C-CおよびC-O結合距離が
妥当な値になるように束縛した。なお、THF中の酸素原
子の割り付けは、それがもし炭素原子ならば近接する錯
体との間に異常に短いH…H間距離が生じてしまうことよ
り判定した。配位している水分子の水素位置はD合成の
ピークをもとに計算で(sp2混成を仮定し)理想化した。
その他の水素原子も幾何学的計算で導入し固定した。水
素の温度因子Uiso(H)は、それが結合している非水素原
子の等価等方性温度因子Ueqの1.2倍に固定した。結晶構
造が近似的に対称心のある構造(空間群が疑似的にP21/
c)であったため、原子パラメータ間の相関が強く、最
小二乗法(SHELXL97; Sheldrick, G. M., Program for
the Refinement of Crystal Structure, University of
Goettingen, Germany, 1997)が収束させにくかった。
異方性温度因子が非正値あるいは異常な値(max/min AD
P が4以上)になるのを避けるために、さらに6個の非
水素原子(O8, O13, C31, C63, C71, C72原子)には等
方性温度因子を用いた。吸収補正は多面体の数値積分に
より行った(透過因子Tの範囲は0.619 から0.854)。
消衰効果の影響はなかった。The structure was solved using the direct method. Two independent molecules of THF were included as a crystallization solvent, but the non-hydrogen atoms of THF were analyzed using the isotropic temperature factor because the atomic displacement parameter was very large, and the CC and CO bond distances were reasonable values. Tied up. The assignment of oxygen atoms in THF was judged from the fact that if it was a carbon atom, an unusually short distance between H and H would occur between adjacent complexes. The hydrogen position of the coordinated water molecule was idealized by calculation (assuming sp 2 hybridization) based on the peak of D synthesis.
Other hydrogen atoms were introduced and fixed by geometric calculation. The hydrogen temperature factor U iso (H) was fixed at 1.2 times the equivalent isotropic temperature factor U eq of the non-hydrogen atom to which it was bonded. The crystal structure is a structure with an approximate symmetry center (space group is pseudo P2 1 /
c), the correlation between the atomic parameters is strong, and the least squares method (SHELXL97; Sheldrick, GM, Program for
the Refinement of Crystal Structure, University of
Goettingen, Germany, 1997).
Non-positive or abnormal value of anisotropic temperature factor (max / min AD
In order to avoid P becoming 4 or more), an isotropic temperature factor was used for 6 more non-hydrogen atoms (O8, O13, C31, C63, C71, C72 atoms). The absorption correction was performed by numerical integration of the polyhedron (the transmission factor T ranged from 0.619 to 0.854).
There was no effect of the extinction effect.
【0067】精密化に用いた反射数11744に対して、精
密化したパラメータ数は749。R(F) =0.064, wR(F2)=0.1
86, S=1.035, (Δ/σ)max=0.020, Δρmax=0.70 e
Å-3, Δρmin= -0.60 eÅ-3, Flack のパラメータは0.
04(2)であった。The number of refined parameters is 749 for the number of reflections 11744 used for refinement. R (F) = 0.064, wR (F 2 ) = 0.1
86, S = 1.035, (Δ / σ) max = 0.020, Δρ max = 0.70 e
Å -3 , Δρ min = -0.60 eÅ -3 , Flack parameter is 0.
04 (2).
【0068】以上の結果より、この錯体の構造が次に示
すとおり明らかになった。結晶中には2分子の独立なコ
バルト錯体(図1及び図2)が存在するが、絶対配置を
含めて分子構造は本質的に同一であり、図3に示される
通りである。Flack のパラメータ(0.04(2))は正常な
範囲(-0.2<x<0.3、及び標準偏差<0.5)に入ってお
り、その標準偏差も充分小さい。構造解析の精度も標準
的な水準に達している(R=0.064)。したがって、ナトリ
ウムD線に対してマイナスの旋光性を示すこの錯体につ
いて、配位子の不斉炭素原子まわりの絶対配置は(R,R)
であることが明確に決定できた。From the above results, the structure of this complex was clarified as follows. Although there are two independent cobalt complexes (FIGS. 1 and 2) in the crystal, the molecular structure including the absolute configuration is essentially the same, as shown in FIG. Flack's parameter (0.04 (2)) is in the normal range (-0.2 <x <0.3 and standard deviation <0.5), and its standard deviation is small enough. The accuracy of structural analysis has also reached the standard level (R = 0.064). Therefore, for this complex that exhibits a negative optical rotation for the sodium D line, the absolute configuration of the ligand around the asymmetric carbon atom is (R, R)
Was clearly determined.
【0069】また、このことから、これまでに明らかに
なっていなかった、対応する光学活性配位子、及び光学
活性ジアミンの絶対立体配置が判明し、表2[表2]に
示す通り、旋光度と関連づけることができた。From this, the absolute configuration of the corresponding optically active ligand and the corresponding optically active diamine, which had not been clarified, was determined. As shown in Table 2, the optical rotation was shown. Could be linked to degrees.
【0070】[0070]
【表2】 [Table 2]
【0071】(実施例5) 光学活性コバルト(III)錯体(4aF)の合成:前
記式(4aB)で表される光学活性臭化コバルト(II
I)錯体327 mg(0.501 mmol)にジクロロメタン(15 ml)
を加え、銀紙でフラスコを遮光する。錯体が溶解したこ
とを確認した後、ヘキサフルオロリン酸銀(I) 210 m
g (0.862 mmol, 1.66 当量)を加えて90分間撹拌する。
その後生成した沈殿をろ別し、ジクロロメタンで洗浄し
た。濾液を濃縮し、残渣を最少量のジクロロメタンに溶
解し、この溶液を大量のヘキサンに加えて再沈殿・精製
し、式(4aF)で表される光学活性コバルト(II
I)錯体(淡褐色固体327 mg、収率91%)を得た。Example 5 Synthesis of Optically Active Cobalt (III) Complex ( 4aF ): Optically active cobalt (II) bromide (II) represented by the above formula ( 4aB )
I) Dichloromethane (15 ml) was added to 327 mg (0.501 mmol) of the complex.
And shield the flask from light with silver paper. After confirming that the complex was dissolved, the silver (I) hexafluorophosphate 210 m
g (0.862 mmol, 1.66 equivalents) and stir for 90 minutes.
Thereafter, the formed precipitate was separated by filtration and washed with dichloromethane. The filtrate is concentrated, the residue is dissolved in a minimum amount of dichloromethane, and this solution is added to a large amount of hexane to reprecipitate and purify the optically active cobalt (II) represented by the formula ( 4aF ).
I) A complex (327 mg of a light brown solid, yield 91%) was obtained.
【0072】(実施例6) サレン型配位子(8a)の合成:ナトリウムのD線に対
してプラスの旋光性を示す1,2-ビス(2,4,6-トリメチル
フェニル)エチレンジアミン 296 mg (1 mmol)のエタノ
ール溶液(6 ml)に、撹拌しながら室温でサリチルアルデ
ヒド244 mg (2 mmol)のエタノール溶液(6 ml)を滴下し
た。室温で1時間撹拌した後、溶媒を減圧留去すると粗
生成物が得られた。粗生成物をジクロロメタン/エーテ
ル/ヘキサンにより再結晶を行い、濾別、洗浄、真空乾
燥するとサレン型配位子(8a) 485 mgが淡黄色粉末と
して得られた(単離収率 96%)。1 H NMR (CDCl3)δ = 1.85 (6H, s), 2.20 (6H, s), 2.6
6 (6H, s), 5.65 (2H, s), 6.63-7.27 (12H, m), 8.40
(2H, s), 13.16 (2H, s); 比旋光度 [α]D 27 +214°
(c 0.60, CHCl3)Example 6 Synthesis of salen-type ligand ( 8a ): 296 mg of 1,2-bis (2,4,6-trimethylphenyl) ethylenediamine showing a positive optical rotation for sodium D line A solution of salicylaldehyde (244 mg, 2 mmol) in ethanol (6 ml) was added dropwise with stirring to a solution of ethanol (1 mmol) in ethanol (6 ml) at room temperature. After stirring at room temperature for 1 hour, the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was recrystallized from dichloromethane / ether / hexane, filtered, washed and dried under vacuum to obtain 485 mg of a salen-type ligand ( 8a ) as a pale yellow powder (isolation yield: 96%). 1 H NMR (CDCl 3 ) δ = 1.85 (6H, s), 2.20 (6H, s), 2.6
6 (6H, s), 5.65 (2H, s), 6.63-7.27 (12H, m), 8.40
(2H, s), 13.16 (2H, s); specific rotation [α] D 27 + 214 °
(c 0.60, CHCl 3 )
【0073】(実施例7) サレンコバルト(II)錯体(6a)の合成:反応器に
入れたサレン型配位子(8a) 404 mg (0.8 mmol)にメ
タノール(30ml)を加え、窒素流通下で撹拌して溶解させ
た。30分間撹拌した後、水酸化ナトリウム80 mg (2.0 m
mol)水溶液 (0.4 ml)を加え、60℃で撹拌した。30分
後、塩化コバルト・6水和物228 mg (0.96 mmol)水溶液
(0.6 ml)を滴下すると茶色の沈殿が析出した。更に30分
間撹拌した後、室温に冷却して水を加えた(10 ml)。窒
素雰囲気下で反応液を濾過し、析出物を水洗し、窒素流
通により乾燥させた。窒素ボックス内で生成物を取り出
し、120℃で2時間減圧乾燥を行なうと、明るい茶色のコ
バルト(II)錯体(6a)451 mgが得られた(収率
>99%)。Example 7 Synthesis of Salen Cobalt (II) Complex ( 6a ): Methanol (30 ml) was added to 404 mg (0.8 mmol) of salen type ligand ( 8a ) placed in a reactor, and the mixture was allowed to flow under nitrogen. To dissolve. After stirring for 30 minutes, sodium hydroxide 80 mg (2.0 m
mol) aqueous solution (0.4 ml) and stirred at 60 ° C. After 30 minutes, 228 mg (0.96 mmol) aqueous solution of cobalt chloride hexahydrate
(0.6 ml) was added dropwise to precipitate a brown precipitate. After stirring for another 30 minutes, it was cooled to room temperature and water was added (10 ml). The reaction solution was filtered under a nitrogen atmosphere, the precipitate was washed with water, and dried by flowing nitrogen. The product was taken out in a nitrogen box and dried under reduced pressure at 120 ° C. for 2 hours to obtain 451 mg of a light brown cobalt (II) complex ( 6a ) (yield).
> 99%).
【0074】(参考例2) 光学活性コバルト(II)錯体触媒(3a)を用いる不
斉還元反応:水素化ホウ素ナトリウム 28 mg (0.75 mmo
l)のクロロホルム懸濁液(22 ml)に、窒素雰囲気下、-20
℃でエタノール 0.13 ml (2.25 mmol)、ついでテトラ
ヒドロフルフリルアルコール 1.0 ml (10.5 mmol)を滴
下し、15分間攪拌して修飾ボロヒドリド還元剤を調製し
た。この還元剤溶液に対し、前記式(3a)で表される
(R,R)の絶対立体配置を有する光学活性コバルト(I
I)錯体 1.4 mg (0.0025 mmol)のクロロホルム溶液(4
ml)、さらにジベンゾイルメタン 56 mg (0.25 mmol)の
クロロホルム溶液(4 ml)を滴下し、-20 ℃で40時間反
応させた。リン酸緩衝液を加えて反応を停止し、生成物
をジクロロメタンで抽出した。有機層を飽和食塩水で洗
浄し、無水硫酸ナトリウムで乾燥した。溶液をろ過し、
溶媒を減圧留去した。得られた混合物をシリカゲルカラ
ムクロマトグラフィーで分離精製したところ、1,3-ジフ
ェニル-1,3-プロパンジオールを定量的に得た(57mg)。
この生成物の光学純度を高速液体クロマトグラフィー
(光学活性カラム:ダイセル化学工業社製、CHIRALPAK A
D; Ethanol 1.2 % in Hexane, 流速1.0 ml/min, 保持
時間 32.4 min, 52.9 min)で分析したところ、98%eeで
あった。dl/meso比は、生成物の水酸基をアセチル化し
た誘導体の1H NMRの積分値から、84/16であること
がわかった。また、生成物の絶対立体配置は、文献値と
の旋光度の比較により(R,R)であることが判明した。Reference Example 2 Asymmetric reduction reaction using an optically active cobalt (II) complex catalyst ( 3a ): sodium borohydride 28 mg (0.75 mmo)
l) in a chloroform suspension (22 ml) under a nitrogen atmosphere under -20.
0.13 ml (2.25 mmol) of ethanol and then 1.0 ml (10.5 mmol) of tetrahydrofurfuryl alcohol were added dropwise at ℃, and the mixture was stirred for 15 minutes to prepare a modified borohydride reducing agent. This reducing agent solution is represented by the above formula ( 3a ).
Optically active cobalt (I) having the absolute configuration of (R, R)
I) A solution of 1.4 mg (0.0025 mmol) of the complex in chloroform (4
ml) and a chloroform solution (4 ml) of 56 mg (0.25 mmol) of dibenzoylmethane were added dropwise, and the mixture was reacted at -20 ° C for 40 hours. The reaction was stopped by adding a phosphate buffer, and the product was extracted with dichloromethane. The organic layer was washed with brine and dried over anhydrous sodium sulfate. Filter the solution,
The solvent was distilled off under reduced pressure. The obtained mixture was separated and purified by silica gel column chromatography to give 1,3-diphenyl-1,3-propanediol quantitatively (57 mg).
The optical purity of this product is determined by high performance liquid chromatography.
(Optically active column: Daicel Chemical Industries, CHIRALPAK A
D; Ethanol 1.2% in Hexane, flow rate 1.0 ml / min, retention time 32.4 min, 52.9 min), it was 98% ee. The dl / meso ratio was found to be 84/16 from the 1 H NMR integrated value of the derivative obtained by acetylating the hydroxyl group of the product. The absolute configuration of the product was found to be (R, R) by comparison of the optical rotation with literature values.
【0075】(比較例1)前記参考例2において、コバ
ルト(II)錯体触媒(3a)の代わりに、下記に示す
コバルト(II)錯体(17)[化30]を使用した以
外は、参考例2と同様にして反応を行った。その結果、
定量的に目的物は得られたものの、生成物のdl/meso比
は29/71、dl体の光学収率は61%eeであった。(Comparative Example 1) The same procedure as in Reference Example 2 was carried out except that the cobalt (II) complex ( 17 ) shown below was used instead of the cobalt (II) complex catalyst ( 3a ). The reaction was carried out in the same manner as in Example 2. as a result,
Although the desired product was obtained quantitatively, the dl / meso ratio of the product was 29/71, and the optical yield of the dl form was 61% ee.
【0076】[0076]
【化30】 Embedded image
【0077】(参考例3) 光学活性コバルト(III)錯体触媒(4aB)を用い
る不斉還元反応:前記参考例2において、コバルト(I
I)錯体触媒(3a)の代わりに、前記コバルト(II
I)錯体(4aB)を使用した以外は、参考例2と同様
にして反応を行った。その結果、定量的に目的物が得ら
れ、dl/meso比は82/18、dl体の光学収率は98%eeであっ
た。Reference Example 3 Asymmetric reduction reaction using an optically active cobalt (III) complex catalyst ( 4aB ):
I) Instead of the complex catalyst ( 3a ), the cobalt (II)
I) The reaction was carried out in the same manner as in Reference Example 2 except that the complex ( 4aB ) was used. As a result, the desired product was obtained quantitatively, the dl / meso ratio was 82/18, and the optical yield of the dl form was 98% ee.
【0078】(参考例4) 光学活性コバルト(II)錯体(6a)を用いる不斉還
元反応:前記参考例2において、コバルト(II)錯体
触媒(3a)の代わりに、前記光学活性コバルト(I
I)錯体(6a)を触媒に用い、ジベンゾイルメタンの
代わりにアセトフェノンを用い、反応温度を0 ℃とする
以外は参考例2と同様にして反応を行った。その結果、
反応は1時間以内に完結して定量的に目的物が得られ、
光学収率は84%eeであった。Reference Example 4 Asymmetric reduction reaction using optically active cobalt (II) complex ( 6a ): In the above-mentioned Reference Example 2, instead of the cobalt (II) complex catalyst ( 3a ), the optically active cobalt (I) was used.
I) The reaction was carried out in the same manner as in Reference Example 2 except that the complex ( 6a ) was used as a catalyst, acetophenone was used instead of dibenzoylmethane, and the reaction temperature was set to 0 ° C. as a result,
The reaction is completed within 1 hour and the desired product is obtained quantitatively.
The optical yield was 84% ee.
【0079】(比較例2、3)各例において、コバルト
(II)錯体触媒(6a)の代わりに、表3に示すコバ
ルト(II)錯体(18)または(19)を使用した以
外は、参考例4と同様にして反応を行った。反応は比較
例2においては1時間以内に完結して定量的に目的物が
得られたが、比較例3では3時間をかけても完結しなか
った。得られた生成物の光学純度を表3[表3]に示
す。(Comparative Examples 2 and 3) In each of the examples, a cobalt (II) complex ( 18 ) or ( 19 ) shown in Table 3 was used instead of the cobalt (II) complex catalyst ( 6a ). The reaction was carried out in the same manner as in Example 4. In Comparative Example 2, the reaction was completed within 1 hour, and the target product was obtained quantitatively. In Comparative Example 3, the reaction was not completed even after 3 hours. The optical purity of the obtained product is shown in Table 3 [Table 3].
【0080】[0080]
【表3】 [Table 3]
【0081】(参考例5)前記参考例2において、コバ
ルト(II)錯体触媒(R,R)-(3a)を基質に対して
2mol%用い、ジベンゾイルメタンの代わりに2-フェナシ
ルピリジンを用いる以外は参考例2と同様にして12時間
反応を行った。得られたアルコールの収率と光学純度及
び主エナンチオマーの絶対立体配置を表4[表4]に示
す。(Reference Example 5) In Reference Example 2, the cobalt (II) complex catalyst (R, R)-( 3a ) was added to the substrate.
The reaction was performed for 12 hours in the same manner as in Reference Example 2 except that 2 mol% was used and 2-phenacylpyridine was used instead of dibenzoylmethane. Table 4 [Table 4] shows the yield, optical purity, and absolute configuration of the main enantiomer of the obtained alcohol.
【0082】(参考例6〜8)各例において、コバルト
(II)錯体触媒(3a)の代わりに、表4[表4]に
示すコバルト(II)錯体(3c)、(3d)、及び
(11)を用いる以外は参考例5と同様にして反応を行
った。得られたアルコールの収率と光学純度及び絶対立
体配置を表4[表4]に示す。Reference Examples 6 to 8 In each of the examples, instead of the cobalt (II) complex catalyst ( 3a ), the cobalt (II) complexes ( 3c ), ( 3d ), and ( 3d ) shown in Table 4 [Table 4] were used. The reaction was carried out in the same manner as in Reference Example 5, except that 11 ) was used. Table 4 [Table 4] shows the yield, optical purity and absolute configuration of the obtained alcohol.
【0083】(比較例4)コバルト(II)錯体触媒
(3a)の代わりに、表4[表4]に示すコバルト(I
I)錯体(20)を用いる以外は、参考例5と同様にし
て反応を行った。得られたアルコールの収率と光学純度
を表4[表4]に示す。Comparative Example 4 Instead of the cobalt (II) complex catalyst ( 3a ), cobalt (I) shown in Table 4 was used.
I) The reaction was carried out in the same manner as in Reference Example 5 except that the complex ( 20 ) was used. Table 4 [Table 4] shows the yield and optical purity of the obtained alcohol.
【0084】[0084]
【表4】 [Table 4]
【0085】(参考例9) 光学活性コバルト(II)錯体触媒(3a)を用いる不
斉シクロプロパン化反応:反応器にコバルト(II)錯
体触媒(3a)29mg(0.05 mmol)を計り取り、反応容
器内を窒素ガス雰囲気に置換した後、テトラヒドロフラ
ン1mlを加え、コバルト錯体を溶解させる。あらかじめ2
5℃に調整した油浴中に容器を浸けこの容器にさらに、
スチレン0.57 ml(5.0 mmol)を加え、引き続きジアゾ
酢酸tert-ブチル148 μl(1.0 mmol)を滴下、N-メチル
イミダゾール8 μl(0.1 mmol)を加え、同反応温度で
2時間撹拌した。反応の進行はガスクロマトグラフィー
分析で確認し、シリカゲルカラムクロマトグラフィーで
過剰のスチレンと錯体触媒、N-メチルイミダゾールを除
去、生成物を油状物質として得た(174 mg, 80% 収率)。
得られた2-フェニルシクロプロピルカルボン酸tert-ブ
チルエステルの異性体比(トランス:シス)は、ガスク
ロマトグラフィーによる分析の結果、83:17であった。
生成物を分取薄層クロマトグラフィーでトランス/シス
体それぞれを分離した。トランス体の光学収率は、水素
化アルミニウムリチウムで処理しカラムクロマトグラフ
ィーで生成、得られた還元体を高速液体クロマトグラフ
ィー(光学活性カラム : ダイセル化学工業社製, Chiral
cel OB-H)により分析した結果、96%eeであった。シス体
の光学収率は、薄層クロマトグラフィーで分離精製した
後、同じく高速液体クロマトグラフィー(光学活性カラ
ム : Chiralcel OB-H )で分析した結果、91%eeであっ
た。(Reference Example 9) Asymmetric cyclopropanation reaction using optically active cobalt (II) complex catalyst ( 3a ): 29 mg (0.05 mmol) of cobalt (II) complex catalyst ( 3a ) was measured in a reactor, and the reaction was carried out. After replacing the atmosphere in the vessel with a nitrogen gas atmosphere, 1 ml of tetrahydrofuran is added to dissolve the cobalt complex. 2 in advance
Immerse the container in an oil bath adjusted to 5 ° C.
0.57 ml (5.0 mmol) of styrene was added, followed by 148 μl (1.0 mmol) of tert-butyl diazoacetate dropwise, 8 μl (0.1 mmol) of N-methylimidazole was added, and the mixture was stirred at the same reaction temperature for 2 hours. The progress of the reaction was confirmed by gas chromatography analysis, and excess styrene, the complex catalyst and N-methylimidazole were removed by silica gel column chromatography to obtain the product as an oil (174 mg, 80% yield).
The isomer ratio (trans: cis) of the obtained 2-phenylcyclopropylcarboxylic acid tert-butyl ester was 83:17 as a result of analysis by gas chromatography.
The product was separated in trans / cis form by preparative thin-layer chromatography. The optical yield of the trans form is determined by treating with lithium aluminum hydride and producing the reduced form by column chromatography.
The result of analysis by cel OB-H) was 96% ee. The optical yield of the cis form was 91% ee as a result of separation and purification by thin layer chromatography and analysis by high performance liquid chromatography (optically active column: Chiralcel OB-H).
【0086】(参考例10)コバルト(II)錯体触媒
(3a)の代わりに、前記コバルト(II)錯体(3
e)を用いる以外は、参考例9と同様にして反応を行っ
た。得られた2-フェニルシクロプロピルカルボン酸tert
-ブチルエステルの収率は99%、異性体比(トランス:シ
ス)は91:9であった。また、トランス体、シス体の光
学収率は、それぞれ96%ee、77%eeであった。Reference Example 10 Instead of the cobalt (II) complex catalyst ( 3a ), the cobalt (II) complex ( 3
The reaction was carried out in the same manner as in Reference Example 9 except that e ) was used. The obtained 2-phenylcyclopropylcarboxylic acid tert
The yield of -butyl ester was 99%, and the isomer ratio (trans: cis) was 91: 9. The optical yields of the trans form and the cis form were 96% ee and 77% ee, respectively.
【0087】[0087]
【発明の効果】本発明の光学活性コバルト錯体は、不斉
ボロヒドリド還元反応、及び不斉シクロプロパン化反応
において、触媒活性、エナンチオ選択性に優れ、しかも
空気中での安定性が高く、取り扱いが容易なものであ
る。したがって、この光学活性コバルト錯体、およびそ
の製造中間体となる配位子は、医薬品、農薬などの光学
活性な生理活性化合物の製造において有用である。The optically active cobalt complex of the present invention has excellent catalytic activity and enantioselectivity in asymmetric borohydride reduction reaction and asymmetric cyclopropanation reaction, and has high stability in the air, and is easy to handle. It's easy. Therefore, this optically active cobalt complex and a ligand which is an intermediate for producing the optically active cobalt complex are useful for producing optically active physiologically active compounds such as pharmaceuticals and agricultural chemicals.
【図1】 式(4aB)で表される光学活性コバルト(I
II)錯体のX線構造解析によって求められた構造図。FIG. 1 shows an optically active cobalt (I) represented by the formula ( 4aB ).
II) Structural diagram obtained by X-ray structural analysis of the complex.
【図2】 図1に示した錯体と同じ結晶中に含まれる、
もう一方の独立したコバルト錯体の構造を表すORTEP
図。FIG. 2 is contained in the same crystal as the complex shown in FIG. 1,
ORTEP representing the structure of the other independent cobalt complex
FIG.
【図3】 図1及び図2に示したコバルト錯体の模式
図。FIG. 3 is a schematic diagram of the cobalt complex shown in FIGS. 1 and 2.
【図4】 図1及び図2に示したコバルト錯体を含む単
結晶中での錯体の配列状態を示すa軸投影図。FIG. 4 is an a-axis projection view showing an arrangement state of the complexes in the single crystal containing the cobalt complex shown in FIGS. 1 and 2;
【図5】 図1及び図2に示したコバルト錯体を含む単
結晶中での錯体の配列状態を示すb軸投影図。FIG. 5 is a b-axis projection view showing an arrangement state of the complexes in the single crystal containing the cobalt complex shown in FIGS. 1 and 2.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.7 識別記号 FI テーマコート゛(参考) C07C 69/753 C07C 69/753 A 251/16 251/16 C07F 15/06 C07F 15/06 // C07B 41/02 C07B 41/02 Z 53/00 53/00 B 61/00 300 61/00 300 C07M 7:00 C07M 7:00 Fターム(参考) 4G069 AA02 BA21A BA21B BA27A BA27B BC67A BC67B BE10A BE10B BE13A BE13B BE37A BE37B BE38A BE38B CB57 4H006 AA01 AB84 4H039 CA60 CB20 4H050 AB40 WB13 WB14 WB21 ──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. 7 Identification symbol FI Theme coat ゛ (Reference) C07C 69/753 C07C 69/753 A 251/16 251/16 C07F 15/06 C07F 15/06 // C07B 41 / 02 C07B 41/02 Z 53/00 53/00 B 61/00 300 61/00 300 C07M 7:00 C07M 7:00 F term (reference) 4G069 AA02 BA21A BA21B BA27A BA27B BC67A BC67B BE10A BE10B BE13A BE13B BE37A BE37B BE38A BE38B CB57 4H006 AA01 AB84 4H039 CA60 CB20 4H050 AB40 WB13 WB14 WB21
Claims (12)
水素原子、直鎖もしくは分岐状のアルキル基、直鎖もし
くは分岐状のアルケニル基、直鎖もしくは分岐状のアリ
ール基、アシル基またはアルコキシカルボニル基、アリ
ールオキシカルボニル基またはアラルキルオキシカルボ
ニル基であり、前記アルキル基、アルケニル基、アリー
ル基、アシル基、アルコキシカルボニル基、アリールオ
キシカルボニル基またはアラルキルオキシカルボニル基
は置換基を有していてもよく、また、R1及びR2は、相
互に連結して、R1及びR2がそれぞれ結合している炭素
原子と共同して環を形成してもよい。〕で表される光学
活性コバルト(II)錯体。1. A compound represented by the following formula ( 1 ) or ( 1 ′ ): Wherein R 1 and R 2 may be the same or different;
A hydrogen atom, a linear or branched alkyl group, a linear or branched alkenyl group, a linear or branched aryl group, an acyl group or an alkoxycarbonyl group, an aryloxycarbonyl group or an aralkyloxycarbonyl group, The alkyl group, alkenyl group, aryl group, acyl group, alkoxycarbonyl group, aryloxycarbonyl group or aralkyloxycarbonyl group may have a substituent, and R 1 and R 2 are mutually linked. , R 1 and R 2 may form a ring together with the carbon atom to which each is attached. ] The optically active cobalt (II) complex represented by these.
形成し得る陰イオン対である。〕で表される光学活性コ
バルト(III)錯体。2. A compound represented by the following formula ( 2 ) or ( 2 ′ ): [Wherein, R 1 and R 2 are as defined above, and X − is an anion pair capable of forming a salt. ] The optically active cobalt (III) complex represented by these.
ール基、またはアルコキシ基、アリールオキシ基であ
り、前記アルキル基、アリール基、アルコキシ基及びア
リールオキシ基は置換基を有していてもよい。〕で表さ
れる光学活性コバルト(II)錯体。3. The compound represented by the following formula ( 3 ) or ( 3 ′ ): [In the formula, R 3 is a linear or branched alkyl group, aryl group, or alkoxy group, aryloxy group, and the alkyl group, aryl group, alkoxy group, and aryloxy group have a substituent. Is also good. ] The optically active cobalt (II) complex represented by these.
光学活性コバルト(III)錯体。4. The compounds of the following formulas ( 4 ) and ( 4 ′ ): [Wherein, R 3 and X − are as defined above. ] The optically active cobalt (III) complex represented by these.
5] 【化5】 で表される光学活性コバルト(II)錯体。5. A compound represented by the following formula ( 3a ) or ( 3a ′ ): An optically active cobalt (II) complex represented by the formula:
6] 【化6】 〔式中、X-は前記と同義である。〕で表される光学活
性コバルト(III)錯体。6. A compound represented by the following formula ( 4a ) or ( 4a ′ ): [Wherein, X - has the same meaning as described above. ] The optically active cobalt (III) complex represented by these.
7] 【化7】 で表される光学活性β-ケトイミン化合物。7. A compound represented by the following formula ( 5a ) or ( 5a ′ ): An optically active β-ketoimine compound represented by
いてもよく、水素原子、直鎖もしくは分岐状のアルキル
基、直鎖もしくは分岐状のアルケニル基、直鎖もしくは
分岐状のもしくはアリール基、アルコキシ基、シアノ
基、またはニトロ基、またはハロゲン原子であり、前記
アルキル基、アルケニル基、アリール基、アルコキシ基
は置換基を有していてもよく、また、R4〜R7のうちい
ずれか二つが相互に連結し、それぞれ結合している炭素
原子と共同して環を形成してもよく、ナフチル環等の縮
合環を形成していてもよい。〕で表される光学活性コバ
ルト(II)錯体。8. A compound represented by the following formula ( 6 ) or ( 6 ′ ): [In the formula, R 4 , R 5 , R 6 , and R 7 may be the same or different and are each a hydrogen atom, a linear or branched alkyl group, a linear or branched alkenyl group, a linear or branched or aryl group, an alkoxy group, a cyano group or a nitro group, or a halogen atom, the alkyl group, an alkenyl group, an aryl group, an alkoxy group may have a substituent, and, R 4, Any two of R 7 to R 7 may be mutually connected to form a ring together with the carbon atoms to which they are bonded, or may form a condensed ring such as a naphthyl ring. ] The optically active cobalt (II) complex represented by these.
る。〕で表される光学活性コバルト(III)錯体。9. A compound represented by the following formula ( 7 ) or ( 7 ′ ): [Wherein, R 4 , R 5 , R 6 , R 7 and X − are as defined above. ] The optically active cobalt (III) complex represented by these.
10] 【化10】 で表される光学活性コバルト(II)錯体。10. A compound represented by the following formula ( 6a ) or ( 6a ′ ): An optically active cobalt (II) complex represented by the formula:
11] 【化11】 〔式中、X-は前記と同義である。〕で表される光学活
性コバルト(III)錯体。11. A compound represented by the following formula ( 7a ) or ( 7a ′ ): [Wherein, X - has the same meaning as described above. ] The optically active cobalt (III) complex represented by these.
12] 【化12】 で表される光学活性サレン化合物。12. A compound represented by the following formula ( 8a ) or ( 8a ′ ): An optically active salen compound represented by the formula:
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KR100675983B1 (en) | 2006-03-06 | 2007-01-30 | 한국화학연구원 | Novel cobalt amino-alkoxide complexes and process for preparing thereof |
JP2009091337A (en) * | 2007-10-12 | 2009-04-30 | Keio Gijuku | Method for producing optically active secondary alcohol |
CN105254786A (en) * | 2015-07-17 | 2016-01-20 | 南昌大学 | C-C bridged [ONNO]-beta-ketoimine metal catalyst and preparation method thereof |
CN113024342A (en) * | 2021-03-16 | 2021-06-25 | 温州大学 | Method for regio-and stereoselectively synthesizing (E) -2,4, 4-trisubstituted conjugated diene |
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CN111747972A (en) * | 2020-06-16 | 2020-10-09 | 苏州大学 | Deprotonated beta-ketimine lithium compound and preparation method thereof |
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US5756790A (en) * | 1995-09-29 | 1998-05-26 | Mitsui Petrochemical Industries, Ltd. | Optically active cobalt (II) complexes and method for the preparation of optically active alcohols |
EP0901996B1 (en) * | 1997-03-06 | 2006-02-01 | Mitsui Chemicals, Inc. | Process for producing optically active amines |
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100675983B1 (en) | 2006-03-06 | 2007-01-30 | 한국화학연구원 | Novel cobalt amino-alkoxide complexes and process for preparing thereof |
JP2009091337A (en) * | 2007-10-12 | 2009-04-30 | Keio Gijuku | Method for producing optically active secondary alcohol |
CN105254786A (en) * | 2015-07-17 | 2016-01-20 | 南昌大学 | C-C bridged [ONNO]-beta-ketoimine metal catalyst and preparation method thereof |
CN113024342A (en) * | 2021-03-16 | 2021-06-25 | 温州大学 | Method for regio-and stereoselectively synthesizing (E) -2,4, 4-trisubstituted conjugated diene |
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