WO2009043300A1 - 1,2-disubstituted ruthenocene plane chirality ligand - Google Patents

Abstract

A 1,2-disubstituted ruthenocene chiral ligand of formula(1)or(2)comprises central chirality and plane chirality which have S structure or R structure and its preparation. Substituent R of formula(1)or(2)represents linear alkyl or branch-alkyl .The ligand can be used in all kinds of metallic catalysis asymmetric reaction.

Description

 1,2-disubstituted porphyrin surface chiral ligand and synthesis method thereof

 The invention relates to a chiral ligand in the technical field of chemical industry and a synthesis method thereof, and particularly relates to a 1,2-disubstituted hafnoside chiral ligand for asymmetric catalytic reaction and a method for synthesizing the same. technical background

 The rapid rise of the chiral pharmaceutical industry is mainly due to the great development of asymmetric synthetic methodologies. In turn, the chiral pharmaceutical industry has promoted the study of asymmetric synthetic methodologies. Asymmetric catalytic organic synthesis is one of the most effective and advantageous methods for obtaining chiral compounds. In the asymmetric catalytic organic synthesis reaction, the key to achieving high reactivity and high enantioselectivity lies in the structure of the chiral ligand. The synthesis and application of chiral phosphine nitrogen ligands have always been valued by chemists.

 A search of the prior art literature found that Sammakia et al. published Transfer Hydrogenation with Ruthenium Complexes of Chiral (Phosphinoferrocenyl) oxazolines in J. Org. Chem. (Organic Chemistry), Vol. 62, No. 6104-6105, 1997. a ruthenium complex catalyzed by a ruthenium complex of a diphenylphosphinoxazoline ferrocene ligand, which is proposed in the context of a chiral ferrocene-based ruthenium-ligand-catalyzed simple ketone transfer hydrogenation reaction. The enantioselectivity of 96% ee was obtained. The deficiency is that the ligand has low reactivity and the asymmetric induction effect is still poor. Summary of the invention

 The object of the present invention is to provide a diphenylphosphonium oxazoline ligand based on hafnocene and a synthesis method thereof, which can be applied to various metal-catalyzed asymmetric reactions, in view of the deficiencies of the prior art. It has high catalytic activity and stereoselectivity and has good application prospects.

The present invention has been achieved by the following technical solutions. The present invention is a ligand having a 1,2-disubstituted chiral ferrocene having a chirality and having a central chirality of S type or type, and its structural formula is represented by the following formula (1) or (2).

(wherein R represents a linear or branched fluorenyl group.)

 The present invention also relates to a method for synthesizing the above ligand having a 1,2-disubstituted hafnocene chirality.

 The above-described synthesis method of a ligand having a chiral chirality of 1,2-disubstituted ferrocene, represented by the general formula (1), having the central chiral S-type, has the following steps:

 In the first step, 1-chlorocarbonyldifluorene represented by the following formula (3) is reacted with an optically active amino alcohol represented by the following formula (4) in the presence of a base to obtain a general formula (5) an amide compound,

 ^^•coci

通式 （5) 中， R的含义与上述相同； The meaning of R in the general formula (4) is the same as above.

In the formula (5), R has the same meaning as described above;

 In the second step, an activator capable of activating a hydroxyl group is added, and the reaction is carried out in the presence of a base to obtain a 1-oxazolinyl ferrocene represented by the following formula (6).

 In the formula (6), R has the same meaning as described above;

In the step A3, in the presence of hydrazine, hydrazine, hydrazine, Ν'-tetramethylethylenediamine, 1-oxazolinyl ferrocene and an organolithium compound are reacted, followed by addition of a halogenated diphenylphosphine Carry out the reaction. Further, the above-described method for synthesizing a ligand having a 1,2-disubstituted ferrocene surface chirality represented by the general formula (2) has the following steps:

 In the first step, 1-chlorocarbonyldifluorene represented by the following formula (3) is reacted with an optically active amino alcohol represented by the following formula (4) in the presence of a base to obtain a general formula (5) an amide compound,

 ^^•coci

通式 （5) 中， R的含义与上述相同； The meaning of R in the general formula (4) is the same as above.

In the formula (5), R has the same meaning as described above;

 In the second step, an activator capable of activating a hydroxyl group is added, and the reaction is carried out in the presence of a base to obtain a 1-oxazolinyl ferrocene represented by the following formula (6).

 In the formula (6), R has the same meaning as described above;

 In the step B3, in the presence of ruthenium, osmium, iridium, Ν'-tetramethylethylenediamine, the 1-oxazoline ferrocene and the organolithium compound are reacted, and then, a silicidation reagent is added, The base and the diphenylphosphine halide are reacted to obtain a hafnium having a silicon fluorenyl group having a chirality represented by the following general formula (7).

通式 （7) 中， R的含义与上述相同， R¹表示有机基团； 第 Β4工序， 使该面手性为 S型的具有硅垸基的二茂钌， 与脱硅垸 基化试剂进行反应。 具体实施方式

In the formula (7), R has the same meaning as described above, and R ¹ represents an organic group; and in the fourth step, the hafnium having a silicon fluorenyl group having an S-type chirality, and desiliconized germanium The base reagent is reacted. detailed description

 The ligand having a 1,2-disubstituted chiral ferrocene having a chirality and having a central chirality of S type or type according to the present invention has a structural formula represented by the following formula (1) or (2).

In the above formulae (1) and (2), R represents a linear or branched fluorenyl group, and preferably the fluorenyl group is a linear or branched fluorenyl group having 1 to 4 carbon atoms, particularly preferably isopropyl group. Base, tert-butyl.

The above-mentioned chiral chirality represented by the formula (1) is an S-type ligand having a 1,2-disubstituted hafnocene chirality, and the above-mentioned chirality represented by the formula (2) is an R-form. The ligand having a 1,2-disubstituted hafnocene chirality can be produced, for example, by the following reaction mechanism (1). In other words, the ligand having the chirality represented by the formula (1) and having a 1,2-disubstituted hafnium surface chirality can be carried out by sequentially performing the following first step and second step. The process is carried out in the step A3. Further, the ligand having a chirality represented by the formula (2) and having a 1,2-disubstituted hafnium surface chirality can be sequentially subjected to the following first step, second step, and The production is carried out in the B3 step and the B4 step.

Reaction sheme (1

 Step 1

Step A3 Step B4

 1

 First step: a 1-chlorocarbonyldifluorene represented by the above formula (3) and an optically active amino alcohol represented by the above formula (4) are reacted in a solvent in the presence of a base to obtain a solvent. An amide compound represented by the above formula (5).

 The 1-chlorocarbonylferrocene represented by the above formula (3) can be produced, for example, by the following reaction mechanism (2).

 Reaction sheme (2 )

CI 〇

 COOH

CI COCI

1) AIC CH ₇ CI'

Ru (C0CI) ₂

 Ru Ru

2) t-BuOK/DME/H ₂ 0

(8) (9) (3) Hereinafter, the method for producing 1-chlorocarbonyl ferrocene (compound (3)) is preferably described in detail. The hafnoic acid (8) and 2-chlorobenzoyl chloride are subjected to a Friedel acylation reaction, followed by hydrolysis in ethylene glycol dimethyl ether in the presence of potassium t-butoxide, followed by acidification. 1-carboxydoprene (compound (9)). In the above-mentioned Friedel acylation reaction, aluminum trichloride is used in an amount of 1 to 3 moles, preferably 1.5 times moles relative to hafnocene (compound (8)), relative to hafnocene (compound (8) The amount of 2-chlorobenzoyl chloride used is 1 to 15 moles, preferably 10 moles. In the reaction, the amount of water used is 0.8 to 1.5 equivalents, preferably 0.9 to 1.1 equivalents, and the amount of potassium t-butoxide used is 3 to 5 moles, preferably 3.8 to 4.2 moles.

 After completion of the reaction, the aqueous phase is extracted with a solvent such as dichloromethane or ether, and then acidified to obtain 1-carboxydoprene (compound (9)).

 Next, a halogenating agent such as the obtained 1-carboxyferrocene (compound (9)) and oxalyl chloride is reacted in a solvent such as chloroformin in the presence of a catalyst such as pyridine. The halogenating agent is preferably used in an amount of 3.5 to 4.5 equivalents based on the amount of the 1-carboxy ferrocene (compound (9)), and it is preferred to carry out the reaction under reflux. Further, the reaction conditions are 1 hour or longer, preferably 2 to 5 hours. After completion of the reaction, ether or a mixture of methylene chloride and n-hexidine is added to remove impurities such as an acid chloride compound to obtain 1-chlorocarbonyl hafnocene (compound (3)).

 In the production method of the present invention, the R of the optically active amino alcohol represented by the formula (4) used in the first step corresponds to 1, 2 in the above formulas (1) and (2). a group of R in the formula of a disubstituted chiral ferrocene chiral ligand. Specifically, R in the formula represents a linear or branched fluorenyl group, and it is particularly preferred that the fluorenyl group is a linear or branched fluorenyl group having 1 to 4 carbon atoms. The optically active amino alcohol is used in an amount of 1.0 to 2 equivalents, preferably 1 to 1.3 equivalents based on the 1-chlorocarbonylferrocene represented by the formula (3).

 The base to be used in the first step is not particularly limited, and examples thereof include metal hydroxides such as ammonia water and potassium hydroxide, metal carboxylates such as sodium acetate and potassium acetate, triethylamine, pyridine, and diiso. An organic tertiary amine such as propylethylamine. These may be used alone or in combination of two or more. The amount of the base to be used is not particularly limited, and is 1.5 to 3 equivalents, preferably 2.2 to 2.6 equivalents, based on 1-chlorocarbonyltetradecene represented by the formula (3).

The reaction solvent to be used in the first step is not particularly limited as long as it can dissolve the raw material and has no activity on the product, and examples thereof include trichloromethane, chloroform, dichloroacetamidine, and tetrachloride. Lower halogenated hydrocarbons such as carbon, aromatic hydrocarbons such as benzene and chlorobenzene, di-lower decyl ethers such as diethyl ether and dimethyl ether, cyclic ethers such as tetrahydrofuran and dioxane, 1,2-dimethoxy Di-lower methoxy acetamidine, dimethylformamide, such as acetamidine, 1,2-diethoxyacetamidine, 1,2-dibutoxyacetamidine, 1,2-dibenzyloxyacetamidine Such as aliphatic amides and the like. These may be used alone or in combination of two or more.

 The reaction conditions in the first step are such that the reaction temperature is -10 to 40 ° C, preferably -5 to 30 ° C, and the reaction time is 5 hours or longer, preferably 15 to 30 hours.

 After completion of the reaction, the solvent is removed to obtain an amide compound represented by the formula (5). Second step: reacting an amide compound represented by the above formula (5) and an activator capable of activating a hydroxyl group obtained in the first step in a solvent in the presence of a base to obtain the above formula ( 6) 1-oxazolinyl ferrocene shown.

 As the activator capable of activating the hydroxyl group, a mercaptohalogen sulfonium compound, an arylhalide sulfonium compound, phosphorus oxychloride, phosphorus pentachloride, thionyl chloride, or triphenylphosphine can be suitably used. Among them, methylsulfonyl chloride is particularly preferred. The activator capable of activating the hydroxyl group is used in an amount of 1.0 to 2.0 equivalents, preferably 1.3 to 1.5 equivalents, based on the amide compound represented by the formula (5).

 As the base used in the second step, the same base as in the first step can be used. The amount of the base used in the second step is 1.5 to 3.5 equivalents, preferably 2.6 to 3 equivalents based on the amide compound represented by the formula (5).

 The solvent used in the second step can use the same solvent as in the first step. The reaction temperature is 0 to 40 ° C, preferably room temperature. The reaction time is 0.5 hours or longer, preferably 1 to 10 hours.

 After completion of the reaction, it is purified by a usual method as necessary to obtain 1-oxazolinyl ferrocene represented by the above formula (6).

 Step A3: in the presence of hydrazine, hydrazine, hydrazine, Ν'-tetramethylethylenediamine, in the solvent, the 1-evil represented by the above formula (6) obtained in the second step The oxazolyl ferrocene and the organolithium compound are reacted, and then the diphenylphosphine halide is added, and the reaction is further carried out to obtain one of the target products, and the chirality represented by the above formula (1) is S-type, A 1,2-disubstituted chiral octagonal chiral chiral ligand.

Specific examples of the organolithium compound used in the step A3 include methyllithium, ethyllithium, n-propyllithium, isopropyllithium, n-butyllithium, isobutyllithium, and t-butyllithium. , lithium dimethylamide, lithium diethylamide, lithium diisopropylamide, lithium diphenylamide, lithium dibenzylamide. It is particularly preferable to use n-butyllithium or isobutyllithium. The amount of the organolithium compound to be used is preferably 1.0 to 2 with respect to the 1-oxazoline-based hafnocene represented by the formula (6). The equivalent weight is particularly preferably 1.0 to 1.5 equivalents.

 Ν,Ν,Ν',Ν'-tetramethylethylenediamine is used in an amount of 1.0 to 2 equivalents, particularly preferably 1 to oxazolinyl ferrocene represented by the formula (6). 1.0 to 1.5 equivalents.

 Solvents which can be used are those which are capable of dissolving the starting materials and which are not active towards the product. Specifically, an aromatic solvent such as xylene, an aliphatic solvent such as valproate or hexanyl, an ether solvent such as diethyl ether, methyl tert-butyl ether, methylcyclopentyl ether or tetrahydrofuran, and the like may be mentioned. . From the viewpoint of good optical yield, an ether solvent such as dimethyl ether is preferably used.

 In the step A3, an organolithium compound is used, and in the presence of hydrazine, hydrazine, hydrazine, Ν'-tetramethylethylenediamine, the reaction is preferably carried out at a temperature of -90 to -5 ° C for 1 hour or more, preferably. Lithification is carried out for 2 to 24 hours, and in order to more fully lithify, it is more preferable to carry out the reaction at a temperature of -5 to 5 ° C for 0.1 hour or longer, preferably 0.1 to 2 hours. After the end of the lithiation reaction, the halogenated diphenylphosphine is added, and the reaction is carried out at 0 to 40 ° C, preferably at 5 to 30 ° C for 5 hours or more, preferably 6 to 24 hours.

 The diphenylphosphine halide is suitable for use with chlorodiphenylphosphine. The amount of the diphenylphosphine halide to be used is preferably 1.0 to 2 equivalents, particularly preferably 1.0 to 1.5 equivalents, based on the 1-oxazolinyl ferrocene represented by the formula (6).

 After the completion of the reaction, the solvent is removed, and if necessary, purification by extraction, column chromatography, or the like is carried out according to a usual method to obtain a target product having a chirality represented by the above formula (1) as an S-type, having a 1,2-disubstituted hand. Chiral ligands.

 In the present production method, after the first step and the second step, the following low B3 step and step B4 are carried out, whereby the surface chirality represented by the above formula (2) is R-type and has 1, A 2-disubstituted chiral octagonal chiral chiral ligand.

 Step B3: in the presence of hydrazine, hydrazine, hydrazine, Ν'-tetramethylethylenediamine, the 1-oxazolyl ferrocene and organolithium compound obtained in the second step in a solvent The reaction is carried out, and then a silicidation reagent, a base, and a diphenylphosphine halide are added to carry out a reaction to obtain a hafnium group having a silicon fluorenyl group having a surface chirality represented by the above formula (7).

 The organolithium compound which can be used in the step (3) is the same as the organolithium compound used in the above step A3. In addition, the amount of the organolithium compound to be used is preferably 1.0 to 2 equivalents, particularly preferably 1.0 to 1.5 equivalents, based on the 1-oxazolineylferrocene represented by the formula (6).

Ν,Ν,Ν',Ν'-tetramethylethylenediamine is used in an amount relative to the formula (6) The 1-oxazolinyl ferrocene is preferably 1.0 to 2 equivalents, particularly preferably 1.0 to 1.5 equivalents.

 Solvents which can be used are those which are capable of dissolving the starting materials and which are not active towards the product. Specifically, an aromatic solvent such as xylene, an aliphatic solvent such as valproate or hexanyl, an ether solvent such as diethyl ether, methyl tert-butyl ether, methylcyclopentyl ether or tetrahydrofuran, and the like may be mentioned. . From the viewpoint of good optical yield, an ether solvent such as dimethyl ether is preferably used.

 In the step B3, an organolithium compound is used, and in the presence of ruthenium, osmium, iridium, Ν'-tetramethylethylenediamine, the reaction is preferably carried out at a temperature of -90 to -5 ° C for 1 hour or more, preferably. Lithification is carried out for 2 to 24 hours, and in order to more fully lithify, it is preferred to carry out the reaction at a temperature of -5 to 5 ° C for 0.1 hour or longer, preferably 0.1 to 2 hours. After completion of the lithiation reaction, a silicon oximation reagent is added, and the reaction is carried out at 0 to 40 ° C, preferably at 5 to 30 ° C for 5 hours or more, preferably 6 to 24 hours.

相当于 硅垸化试剂的反应残基， 通式中的 R根据硅垸化试剂的种类而不同， 对于通式中的 R¹没有特别限制、 是有机基团。 作为硅垸化试剂， 适于 使用三甲基氯硅垸、 三乙基氯硅垸等的三垸基氯硅垸， 三垸基碘硅垸、 三氟甲磺酸盐等。 硅垸化试剂的使用量为， 相对于以通式 （6 )所表示 的 1_噁唑啉基二茂钌， 优选 1.0〜2当量、 特别优选 1.0〜1.5当量。 The silicon oximation reagent which can be used is not particularly limited, and a known silicon oximation reagent can be used. Therefore, the above formula (7) is produced using a silicon deuteration reagent.

Corresponding to the reaction residue of the silicon oximation reagent, R in the general formula differs depending on the type of the silicon sulfonating reagent, and R ¹ in the general formula is not particularly limited and is an organic group. As the silicon deuteration reagent, trimethyl chlorosilane, trimethyl sulfonium iodide, trifluoromethanesulfonate or the like is preferably used, such as trimethylchlorosilane or triethyl chlorosilane. The amount of the silicon oximation reagent to be used is preferably 1.0 to 2 equivalents, particularly preferably 1.0 to 1.5 equivalents, based on the 1 oxazolinyl ferrocene represented by the formula (6).

 After the reaction with the silicon oximation reagent, the addition of a base and diphenylphosphine halide are continued to carry out the reaction. Specifically, after the addition of the base, the reaction is preferably carried out at a temperature of -90 to -5 ° C for 1 hour or more, preferably 2 to 24 hours, and then further carried out at a temperature of -5 to 5 ° C for 0.1 hour or more, preferably. After 0.1 to 2 hours, the halogenated diphenylphosphine is added, and the reaction is carried out at 0 to 40 ° C, preferably at 5 to 30 ° C for 5 hours or longer, preferably 6 to 24 hours.

 As the base which can be used, an organolithium compound is preferred. Specific examples of the organolithium compound include methyllithium, ethyllithium, n-propyllithium, isopropyllithium, n-butyllithium, isobutyllithium, t-butyllithium, and dimethylaminolithium. Lithium diethylamide, lithium diisopropylamide, lithium diphenylamide, lithium dibenzylamide. It is particularly preferable to use n-butyllithium or isobutyllithium. The amount of the base to be used is preferably 1.0 to 2 equivalents, particularly preferably 1.0 to 1.5 equivalents, based on the 1-oxazolinyl ferrocene represented by the formula (6).

The diphenylphosphine halide is suitable for use with chlorodiphenylphosphine. The amount of the diphenylphosphine halide to be used is preferably 1.0 to 2 equivalents per 1 oxazolinyl ferrocene represented by the formula (6). It is preferably 1.0 to 1.5 equivalents.

 After completion of the reaction, the solvent is removed to obtain a chirality represented by the above formula (7).

S-type hafnocene having a silicon fluorenyl group.

 Step B4: In the solvent, a silicon germanium-containing hafnoxene having an S-type chirality represented by the above formula (7) is reacted with a desiliconization thiolation reagent to obtain one of the target products. A chiral chiral ligand having a chirality represented by the above formula (2) and having a 1,2-disubstituted chiral octagonal surface.

 Examples of the desiliconization-based sulfhydryl reagent which can be used in the step B4 include tetradecyl ammonium chloride such as tetrabutylammonium chloride, boron trichloride, hydrogen fluoride, trichloroacetic acid or fumaric acid, and oxalic acid. An organic carboxylic acid compound of tartaric acid, maleic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, lactic acid, gluconic acid, acetic acid or the like. The desiliconization hydrazylation reagent is used in an amount of 1 equivalent or more based on the hafnium having a silicon fluorenyl group having an S-type chirality represented by the above formula (7).

 Examples of the solvent that can be used include an aromatic solvent such as toluene or xylene, an aliphatic solvent such as valproate or hexanyl, or diethyl ether, methyl tert-butyl ether, methylcyclopentyl ether or tetrahydrofuran. Ether solvent, etc.

 The reaction in the step B4 is preferably carried out under reflux conditions for 3 hours or longer, more preferably 10 to 30 hours.

 After completion of the reaction, the solvent is removed, and if necessary, purification by extraction, column chromatography, or the like is carried out in accordance with a conventional method to obtain a target product having a chirality represented by the above formula (2) and having a 1,2-disubstituted chirality. Chiral ligands.

The ligand having a 1,2-disubstituted chiral ferrocene surface chirality according to the present invention contains both a central chirality of oxazoline and a chirality. The ligand having a 1,2-disubstituted chiral ferrocene surface chirality according to the present invention preferably forms a ligand of ruthenium, rhodium, iridium, nickel, palladium, platinum or silver. Further, a transition metal catalyst which is complexed with a ligand having a 1,2-disubstituted chiral ferrocene surface chirality according to the present invention can be used as an asymmetric transition metal catalyst. For example, it can be used for carbon carbon bond formation reaction, asymmetric cyclopropene reaction, intramolecular Wacker-Type cyclization reaction, Heck reaction, asymmetric oxidation of olefin, intramolecular [2+1] cycloaddition reaction. And catalytic hydrogenation reaction, asymmetric reduction reaction, etc., have high reactivity and stereoselectivity, and have good application prospects. Example

 The embodiments are provided below in conjunction with the technical contents of the present invention, and the present invention is not limited to these embodiments. Further, in each of the examples, the "ligand having a 1,2-disubstituted chiral octagonal chiral chirality" is referred to as "1,2-substituted fluorene oxime, ruthenium-ligand".

 Embodiment 1

 (1) Preparation of 1-dicarboxy fluorene

In a 250 mL two-necked flask, add ferrocene (0.23 g, 1 mmol), m-chlorobenzoyl chloride (0.18 g, 1 mol) and dichloromethane (5 mL to 50 ° C. C, add anhydrous trichloride in batches). Aluminum (0.14g, lmmol), stir it at room temperature overnight. Cool down to 0~2 ° C, carefully add water (2mL), stir for 2h, then dilute the system with dichloromethane (20mL), in order The acylation product was obtained by washing with 10% sodium hydroxide solution, water and saturated brine, dried over anhydrous Na ₂ SO ₄ , and evaporated. 51.5mg, y=13.9

^J H NMR (400 MHz, CDC1 ₃ ): δ 4.64 (s, 5H), 4.83 (t J=2 Hz, 2H), 5.01 (t J=2 Hz, 2H), 7.28-7.55 (m, 4H), 7.99-8.05 (m, 1H).

 To a 500 mL two-necked flask was added 2-chlorobenzoyl ferrocene (8.2 g, 22 mmol) and potassium t-butoxide (9.9 g, 88 mmol), and ethylene glycol dimethyl ether (220 mL) and water were added under a nitrogen atmosphere. 0.44 mL, 23 mmol), then warmed to reflux for 18 hours to give a white paddle. The system was diluted with an equal volume of water, and then extracted once with dichloromethane (200 mL) and diethyl ether (200 mL), and then the pH of the aqueous phase was adjusted to 2, and a large amount of earthy color precipitated, filtered and dried to obtain a yellowish color. Solid 1-carboxyluminocene 1 (4.65 g, y = 90%).

^J H NMR (400 MHz, CDC1 ₃ ): δ 4.63 (s, 5H), 4.76 (t J=2 Hz, 2H), 5.17 (t J=2 Hz, 2H).

 (2) Preparation of 1-0S 4-isopropyloxazolyl-2-difluorene

 To the 1-carboxyluminocene (2.53 g, 10 mmol), dichloromethane (60 mL) was added, and oxalyl chloride (4.0 mL, 40 mmol) and a catalytic amount of pyridine.lmL were added dropwise to the system under ice-cooling for 3 hours. The system was evaporated to dryness. The title compound was washed with diethyl ether (50 mL &lt

L-Valinol (1. 33 g, 13 mmol) was dissolved in dichloromethane (20 mL). DIPEA (4.6 mL, 26 mmol) was added dropwise, and the solution of acid chloride in dichloromethane (40 mL) was slowly added and stirred at room temperature overnight. DIPEA (4.6 mL, 26 mmol) was added directly to the system. Methyl sulfonyl chloride (1.0 mL, 13 mmol) was incubated for 0.5 h then stirred at room temperature for 2 h. The system was diluted with methylene chloride (60 mL), washed with water and brine, dried over anhydrous sodium sulfate, filtered, evaporated and evaporated. 1-oxazoline ferrocene 4a (2.7g, y=79%) o

JH NMR (400 MHz, CDC1 ₃ ): δ 0.88 (d, J=6A Hz, 3H), 095 (d, J=6A)

Hz, 3H), 1.79-1.91(m, IH), 3.92-4.02(m, 2H), 4.20(dd, J=8.4, 9.2 Hz), 4.58(s, 5H), 4.67(brs, 2H), 5.09 (brs, IH), 5.14 (brs, IH). ¹³ C NMR (100 MHz, CDC1 ₃ ): δ 18.17, 18.96, 32.39, 69.34, 71.04, , 71.74 (5 C), 72.08, 72.16, 74.79, 164.88.

 (3) Preparation of (5 1-(diphenylphosphino)-2-[(5 4-isopropyloxazolinyl]-2-dimercapto

1. Oxazoline hafnocene (138 mg, 0.4 mmol) was dissolved in diethyl ether (7 mL) and cooled to -78. TMEDA (42 L, 0.52 mmol) s-BuLi (0.6 mL, 0.98 M in cyclohexane, 0.52 mmol) was slowly added thereto and kept for 3 hours. It was then stirred at 0 ° C for 40 min. Further, diphenylphosphonium chloride (0.1 mL, 0.52 mmol) was added thereto at this temperature and stirred at room temperature overnight. System dilute with ether, and then with saturated NaHC0 ₃ solution, respectively, water and saturated brine, dried over anhydrous N¾S0 _4, the solvent was distilled off under reduced pressure to give a yellow-green oily liquid. Column chromatography (ethyl acetate/petroleum ether = 1/10) gave a yellow-green solid, 1,2-disubstituted hafimidine, oxime-ligand 5a (0.162 g, y=77%) ₀

Mp 136-138 °C ; [a] ^D ₂₇ = -97.51 (c 0.46, CHC1 ₃ ); ^J H NMR (CDC1 ₃ , 400

Hz): δ 0.67 (d, J=6.8 Hz, 3H), 0.79 (d, J=6.8 Hz, 3H), 1.64-1.68 (m, IH), 3.67 (t, J=7.6 Hz, IH), 3.79 -3.84 (m, IH), 3.94 (brs, IH), 4.16-4.20 (dd, J=8, 10 Hz, IH), 4.59 (s, 5H), 4.67 (brs, IH), 5.31 (brs, IH ), 7.27-7.40 (m, 10H).

 Embodiment 2

 (1) Preparation of 1-dicarboxy fluorene

Into a 250 mL two-necked flask was added hafnocene (0.23 g, 1 mmol), m-chlorobenzoyl chloride (2.7 g, 15 mol) and dichloromethane (5 mL). Cool down to 0~2. C. Anhydrous aluminum trichloride (0.42 g, 3 mmol) was added portionwise, and stirred at ambient temperature overnight. Cool down to 0~2 °C, carefully add water (2mL), stir for 2 hours, then dilute the system with dichloromethane (20mL), wash with 10% sodium hydroxide solution, water and saturated brine. Dry with anhydrous Na ₂ SO ₄ and evaporate the solvent under reduced pressure. Residue column chromatography (ethyl acetate I petroleum ether = 1 / 20) Acylated product (168mg, y=65.4

^J H NMR (400 MHz, CDC1 ₃ ): δ 4.64 (s, 5H), 4.83 (t J=2 Hz, 2H), 5.01 (t J=2 Hz, 2H), 7.28-7.55 (m, 4H), 7.99-8.05 (m, 1H).

 To a 500 mL two-necked flask was added 2-chlorobenzoyl hafnocene (8.2 g, 22 mmol) and potassium t-butoxide (9.9 g, 88 mmol), and ethylene glycol dimethyl ether (220 mL) was added under a nitrogen atmosphere. Water (0.44 mL, 23 mmol) was then warmed to reflux for 18 hours to give a white paddle. The system was diluted with an equal volume of water, and then extracted once with dichloromethane (200 mL) and diethyl ether (200 mL), and then the pH of the aqueous phase was adjusted to 2, and a large amount of earthy color precipitated, filtered and dried to obtain a yellowish color. Solid 1-carboxyluminocene 1 (4.65 g, y = 90%).

JH NMR (400 MHz, CDC1 ₃ ): δ 4.63 (s, 5H), 4.76 (t J=2 Hz, 2H), 5.17

(t J=2 Hz, 2H).

 (2) Preparation of isopropyloxazolyl-2-dimercapto

 To the 1-carboxy ferrocene (2.53 g, 10 mmol), dichloromethane (60 mL) was added, and oxalyl chloride (4.0 mL, 40 mmol) and a catalytic amount of pyridine.lmL were added dropwise to the system under ice-cooling for 3 hours. The system was evaporated to dryness. The title compound was washed with diethyl ether (50 mL &lt

 L-Valinol (1. 33 g, 13 mmol) was dissolved in dichloromethane (20 mL), DIPEA (4.6 mL, 26 mmol) was added dropwise, and the solution of acid chloride in dichloromethane (40 mL) was slowly added and stirred at room temperature overnight. DIPEA (4.6 mL, 26 mmol), methyl sulfonyl chloride (1.0 mL, 13 mmol) was added to the mixture, and the mixture was stirred for 0.5 hour, and then stirred at room temperature for 2 hours. The system was diluted with methylene chloride (60 mL), washed with water and brine, dried over anhydrous sodium sulfate, filtered, evaporated and evaporated. 1-oxazoline ferrocene 4a (2.7g, y=79

^J H NMR (400 MHz, CDC1 ₃ ): δ 0.88 (d, J = 6A Hz, 3H), 095 (d, J = 6A Hz, 3H), 1.79-1.91 (m, 1H), 3.92-4.02 (m , 2H), 4.20 (dd, J=8.4, 9.2 Hz), 4.58 (s, 5H), 4.67 (brs, 2H), 5.09 (brs, 1H), 5.14 (brs, 1H). ¹³ C NMR (100 MHz , CDC1 ₃ ): δ 18.17, 18.96, 32.39, 69.34, 71.04, , 71.74 (5 C), 72.08, 72.16, 74.79, 164.88.

 Preparation of (5), (5 1-(diphenylphosphino)-2-[(5 4-isopropyloxazolyl)-2-dimercapto

1. Oxazoline hafnocene (138 mg, 0.4 mmol) was dissolved in diethyl ether (7 mL) and cooled to -78. Slowly add TMEDA (42μΙ, 0.52mmol), s-BuLi (0.6mL, 0.98M) In cyclohexane, 0.52 mmol), kept for 3 hours. It was then stirred at 0 ° C for 40 min. Further, diphenylphosphonium chloride (0.1 mL, 0.52 mmol) was added thereto at this temperature and stirred at room temperature overnight. System dilute with ether, and then with saturated NaHC0 ₃ solution, respectively, water and saturated brine, dried over anhydrous N¾S0 _4, the solvent was distilled off under reduced pressure to give a yellow-green oily liquid. Column chromatography (ethyl acetate/petroleum ether = 1/10) gave a yellow-green solid, 1,2-disubstituted hafimidine, oxime-ligand 5a (0.162 g, y=77%) ₀

Mp 136-138 °C; [a] ^D ₂₇ = -97.51 (c 0.46, CHC1 ₃ ); ^J H NMR (CDC1 ₃ , 400 Hz): δ 0.67 (d, J = 6.8 Hz, 3H), 0.79 (d , J=6.8 Hz, 3H), 1.64-1.68 (m, IH), 3.67 (t, J=7.6 Hz, IH), 3.79-3.84 (m, IH), 3.94 (brs, IH), 4.16-4.20 ( Dd, J=8, 10 Hz, IH), 4.59 (s, 5H), 4.67 (brs, IH), 5.31 (brs, IH), 7.27-7.40 (m, 10H).

 Embodiment 3

 (1) Preparation of 1-dicarboxy fluorene

Into a 250 mL two-necked flask was added hafnocene (11.6 g, 50 mmol), m-chlorobenzoyl chloride (63 mL, 0.5 mol) and dichloromethane (100 mL). The temperature was lowered to 0 to 2 ° C, and anhydrous aluminum trichloride (8.7 g, 65 mmol) was added portionwise, and stirred overnight while stirring. Cool down to 0~2 ° C, carefully add water (20 mL), stir for 2 hours, then dilute the system with toluene (200 mL), wash with 10% sodium hydroxide solution, water and saturated brine, anhydrous Na ₂ S0 _{4 was} dried, and the solvent was evaporated under reduced pressure. Residue column chromatography (ethyl acetate / petroleum ether = 1 / 20) gave acylated product (13.5 g, y=73

^J H NMR (400 MHz, CDC1 ₃ ): δ 4.64 (s, 5H), 4.83 (t J=2 Hz, 2H), 5.01 (t J=2 Hz, 2H), 7.28-7.55 (m, 4H), 7.99-8.05 (m, IH).

 To a 500 mL two-necked flask was added 2-chlorobenzoyl ferrocene (8.2 g, 22 mmol) and potassium t-butoxide (9.9 g, 88 mmol), and ethylene glycol dimethyl ether (220 mL) and water were added under a nitrogen atmosphere. 0.44 mL, 23 mmol), then warmed to reflux for 18 hours to give a white paddle. The system was diluted with an equal volume of water, and then extracted once with dichloromethane (200 mL) and diethyl ether (200 mL), and then the pH of the aqueous phase was adjusted to 2, and a large amount of earthy color precipitated, filtered and dried to obtain a yellowish color. Solid 1-carboxyluminocene 1 (4.65 g, y = 90%).

^J H NMR (400 MHz, CDC1 ₃ ): δ 4.63 (s, 5H), 4.76 (t J=2 Hz, 2H), 5.17 (t J=2 Hz, 2H).

 (2) Preparation of 1-0S 4-isopropyloxazolyl-2- fluorene

1-Carboxymonocene (2.53 g, 10 mmol) with methylene chloride (60 mL), ice bath The oxalyl chloride (4.0 mL, 40 mmol) and a catalytic amount of pyridine (0.1 mL) were added dropwise to the system under reflux for 3 hours, and the system was evaporated to dryness. The title compound was washed with diethyl ether (50 mL X 3 ) and dried in vacuo. After 2 hours, a yellow-chloro solid was obtained directly for the next reaction.

 L-Valinol (1.13 g, 11 mmol) was dissolved in dichloromethane (20 mL). DIPEA ( 3.9 mL, 22 mmol) was added dropwise, and the solution of the acid chloride in dichloromethane (40 mL) was slowly added and stirred at room temperature overnight. DIPEA (5.3 mL, 30 mmol), methyl sulfonyl chloride (1.2 mL, 15 mmol) was added to the system, and the mixture was kept for 0.5 hour, and then stirred at room temperature for 2 hours. The system was diluted with methylene chloride (60 mL), washed with water and brine, dried over anhydrous sodium sulfate, filtered, evaporated and evaporated. 1-oxazoline ferrocene 4a (2.7 g, y = 79%).

^J H NMR (400 MHz, CDC1 ₃ ): δ 0.88 (d, J = 6A Hz, 3H), 095 (d, J = 6A Hz, 3H), 1.79-1.91 (m, IH), 3.92-4.02 (m , 2H), 4.20 (dd, J=8.4, 9.2 Hz), 4.58 (s, 5H), 4.67 (brs, 2H), 5.09 (brs, IH), 5.14 (brs, IH). ¹³ C NMR (100 MHz , CDC1 ₃ ): δ 18.17, 18.96, 32.39, 69.34, 71.04, , 71.74 (5 C), 72.08, 72.16, 74.79, 164.88.

(3) Preparation of (5 1-(diphenylphosphino)-2-[(5 4-isopropyloxazolinyl]-2- fluorenium oxime] oxazoline ferrocene (138 mg, 0.4 Methyl acetate (7 mL) was cooled to -78 ° C. TMEDA (42 L, 0.52 mmol), s-BuLi (0.6 mL, 0.98M in cyclohexane, 0.52 mmol) was slowly added thereto and kept for 3 hours. the 0 ° C and then stirred 40min. at this temperature and thereto was added diphenylphosphine chloride (O. lmL, 0.52mmol) was stirred at room temperature overnight. dilute with ether system, respectively, and then with saturated NaHC0 ₃ solution, water and washed with brine, dried over anhydrous N¾S0 _4, the solvent was distilled off under reduced pressure to give a yellow-green oily liquid. column chromatography (ethyl acetate / petroleum ether = 1/10) to give a yellow-green solid, 2-substituted ruthenocene addition Ρ ,Ν-ligand 5a ( 0.162g, y=77%) ₀

Mp 136-138 °C ; [a] ^D ₂₇ = -97.51 (c 0.46, CHC1 ₃ ); ^J H NMR (CDC1 ₃ , 400

Hz): δ 0.67 (d, J=6.8 Hz, 3H), 0.79 (d, J=6.8 Hz, 3H), 1.64-1.68 (m, IH), 3.67 (t, J=7.6 Hz, IH), 3.79 -3.84 (m, IH), 3.94 (brs, IH), 4.16-4.20 (dd, J=8, 10 Hz, IH), 4.59 (s, 5H), 4.67 (brs, IH), 5.31 (brs, IH ), 7.27-7.40 (m, 10H).

 Embodiment 4:

 (1) Preparation of 1-carboxy ferrocene

In a 250 mL two-necked flask, ferrocene (11.6 g, 50 mmol), m-chlorobenzoyl peroxide was added. Chlorine (63 mL, 0.5 mol) and dichloromethane (100 mL). The temperature was lowered to 0 to 2 ° C, and anhydrous aluminum trichloride (8.7 g, 65 mmol) was added portionwise, and stirred overnight while stirring. Cool down to 0~2 ° C, carefully add water (20 mL), stir for 2 hours, then dilute the system with toluene (200 mL), wash with 10% sodium hydroxide solution, water and saturated brine, anhydrous Na ₂ S0 _{4 was} dried, and the solvent was evaporated under reduced pressure. The residue was by column chromatography (ethyl acetate I petroleum ether = 1/20) to give acylated product (13.5g, y = 73%) 0

^J H NMR (400 MHz, CDC1 ₃ ): δ 4.64 (s, 5H), 4.83 (t J=2 Hz, 2H), 5.01 (t J=2 Hz, 2H), 7.28-7.55 (m, 4H), 7.99-8.05 (m, 1H).

 To a 500 mL two-necked flask was added 2-chlorobenzoyl ferrocene (8.2 g, 22 mmol) and potassium t-butoxide (9.9 g, 88 mmol), and ethylene glycol dimethyl ether (220 mL) and water were added under a nitrogen atmosphere. 0.44 mL, 23 mmol), then warmed to reflux for 18 hours to give a white paddle. The system was diluted with an equal volume of water, and then extracted once with dichloromethane (200 mL) and diethyl ether (200 mL), and then the pH of the aqueous phase was adjusted to 2, and a large amount of earthy color precipitated, filtered and dried to obtain a yellowish color. Solid 1-carboxyluminocene 1 (4.65 g, y = 90%).

JH NMR (400 MHz, CDC1 ₃ ): δ 4.63 (s, 5H), 4.76 (t J=2 Hz, 2H), 5.17

(t J=2 Hz, 2H).

 Preparation of ( 2 ), 1 -[(5 4-tert-butyloxazolyl]-2- ferrocene

 Dichloromethane (15 mL) was added to 1-carboxy ferrocene (0.52 g, 2.5 mmol), and oxalyl chloride (1.0 mL, 40 mmol) and catalytic amount of pyridine (0.05 mL) were added dropwise to the system under ice-cooling. o After refluxing for 3 hours, the system was evaporated to dryness. The title compound was washed with diethyl ether (20 mL EtOAc)

The L-Leucinol (0.3g, 2.5mmol) was dissolved in of dichloromethane (50 mL), was added dropwise _{Et 3 N (0.8mL, 5.5mmol)} , was slowly added to the acid chloride of dichloromethane (10 mL) was stirred at room temperature overnight. Et ₃ N (1.1 mL, 7.5 mmol), formazansulfonyl chloride (0.3 mL, 3.75 mmol) was added to the system, and the mixture was kept for 0.5 hour, and then stirred at room temperature for 2 hours. The system was diluted with methylene chloride (20 mL), washed with water and brine, dried over anhydrous sodium sulfate, filtered, evaporated and evaporated. 1-oxazoline ferrocene 4b (0.49g,

^J H NMR (400 MHz, CDC1 ₃ ): δ: 0.90 (s, 9H), 3.83 (dd, J=6.8, 10 Hz, 1H), 4.08—4.18 (m, 2H), 4.57 (s, 5H), 4.65 (brs, 2H), 5.05 (brs, 1H,), 5.17 (brs, 1H). Preparation of (5), (5 1-(diphenylphosphino)-2-[(5 4-tert-butyloxazolinyl)-2-difluorene

4b (178 mg, 0.5 mmol) was dissolved in diethyl ether (10 mL) and cooled to -78. TMEDA (O.lmL, 0.63 mmol), s-BuLi (0.7 mL, 0.98 M in cyclohexane, 0.65 mmol) was slowly added thereto, and kept for 3 hours. Then, it was stirred at 0 ° C for 40 min, at which temperature diphenylphosphonium chloride (0.12 mL, 0.65 mmol) was added thereto, and the mixture was warmed and stirred overnight. System dilute with ether, and then with saturated NaHC0 ₃ solution, respectively, water and saturated brine, dried over anhydrous N¾S0 _4, the solvent was evaporated under reduced pressure to give a yellow-green oily liquid. Column chromatography (ethyl acetate I petroleum ether = 1 / 10) gave yellow-green solid 5b (0.162 g, y=77

 M.p. 176-178 °C;

 1H NMR (CDC13, 400 Hz): δ 0.77 (s, 9H), 3.69 (dd, J=7.2, 10 Hz, 1H), 3.85 (dd, J=7.6, 8.4 Hz, 1H), 3.95 (brs, 1H) ), 4.10 (dd, J=8.4, 10 Hz, 1H), 4.59 (s, 5H), 4.66 (brs, 1H), 5.28 (brs, 1H), 7.27-7.38 (m, 10H).

 Embodiment 5:

 (1) Preparation of 1-dicarboxy fluorene

Into a 250 mL two-necked flask was added hafnocene (11.6 g, 50 mmol), m-chlorobenzoyl chloride (63 mL, 0.5 mol) and dichloromethane (100 mL). The temperature was lowered to 0 to 2 ° C, and anhydrous aluminum trichloride (8.7 g, 65 mmol) was added portionwise, and stirred overnight while stirring. Cool down to 0~2 ° C, carefully add water (20 mL), stir for 2 hours, then dilute the system with toluene (200 mL), wash with 10% sodium hydroxide solution, water and saturated brine, anhydrous Na ₂ S0 _{4 was} dried, and the solvent was evaporated under reduced pressure. The residue was by column chromatography (ethyl acetate I petroleum ether = 1/20) to give acylated product (13.5g, y = 73%) 0

^J H NMR (400 MHz, CDC1 ₃ ): δ 4.64 (s, 5H), 4.83 (t J=2 Hz, 2H), 5.01 (t J=2 Hz, 2H), 7.28-7.55 (m, 4H), 7.99-8.05 (m, 1H).

 To a 500 mL two-necked flask was added 2-chlorobenzoyl ferrocene (8.2 g, 22 mmol) and potassium t-butoxide (9.9 g, 88 mmol), and ethylene glycol dimethyl ether (220 mL) and water were added under nitrogen. (0.44 mL, 23 mmol), then warmed to reflux for 18 hours to give a white paddle. The system was diluted with an equal volume of water, and then extracted once with dichloromethane (200 mL) and diethyl ether (200 mL), and then the pH of the aqueous phase was adjusted to 2, and a large amount of earthy color precipitated, filtered and dried to obtain a yellowish color. Solid 1-carboxyluminocene 1 (4.65g, y=90

^J H NMR (400 MHz, CDC1 ₃ ): δ 4.63 (s, 5H), 4.76 (t J=2 Hz, 2H), 5.17 (t J=2 Hz, 2H). Preparation of (2), 1-0^-4-isopropyloxazolinyl-2-dimercapto

 To the 1-carboxy ferrocene (2.53 g, 10 mmol), dichloromethane (60 mL) was added, and oxalyl chloride (4.0 mL, 40 mmol) and a catalytic amount of pyridine (0.1 mL) were added dropwise to the system under ice-cooling. After refluxing for 5 hours, the system was evaporated to dryness.

L-Valinol (1.13 g, llmmol) was dissolved in dichloromethane (20 mL). DIPEA (3.9 mL, 22 mmol) DIPEA (5.3 mL, 30 mmol), formazansulfonyl chloride (1.2 mL, 15 mmol) was added to the system, and the mixture was kept for 0.5 hour, and then stirred at room temperature for 2 hours. The system was diluted with methylene chloride (60 mL), washed with water and brine, dried over anhydrous sodium sulfate, filtered, evaporated and evaporated. 4a (2.7g, y=79%) ₀

^J H NMR (400 MHz, CDC1 ₃ ): δ 0.88 (d, J = 6A Hz, 3H), 095 (d, J = 6A Hz, 3H), 1.79-1.91 (m, IH), 3.92-4.02 (m , 2H), 4.20 (dd, J=8.4, 9.2 Hz), 4.58 (s, 5H), 4.67 (brs, 2H), 5.09 (brs, IH), 5.14 (brs, IH). ¹³ C NMR (100 MHz , CDC1 ₃ ): δ 18.17, 18.96, 32.39, 69.34, 71.04, , 71.74 (5 C), 72.08, 72.16, 74.79, 164.88.

 (3), "One-pot method" preparation (i?)-l-(diphenylphosphino)-2-(5 4-isopropyloxazolinyl-3-(-trimethylsilyl)钌

 1-oxazoline ferrocene 4a (276 mg, 0.8 mmol) was dissolved in diethyl ether (10 mL) and cooled to -78. TMEDA (0.17 mL, 1.04 mmol) and s-BuLi (1.06 mL, 0.98 M in cyclohexane, 1.04 mmol) were slowly added thereto, and kept for 3 hours. Then, it was stirred at 0 ° C for 20 min, and trimethylsilyl silane (0.13 mL, 1.04 mmol) was added.

After 2 hours of reaction, THF (10 mL) was added to the system, the system was again cooled to -78 ° C, n-BuLi (0.4 mL, 2.89 M in cyclohexane, 1.04 mmol) was added, and after 2 hours, it was further increased to 0 ° C. After 2 hours of reaction, the system was always opaque. Diphenylphosphonium chloride (0.19 mL, 1.04 mmol) was added, and the mixture was warmed and stirred overnight. In diethyl ether (20mL) dilute, and then were followed in order with saturated NaHC0 ₃ solution, water and saturated brine, dried over anhydrous N¾S0 _4, the solvent was distilled off under reduced pressure to give a yellow-green oily liquid. Column chromatography (ethyl acetate / petroleum ether = 1 / 15) gave a yellow-yellow, solid, 6 (0.22 g, y = 52.2%).

^J H NMR (CDC1 ₃ , 400 Hz): δ 0.22 (s, 9H), 0.58 (d, J = 6.4 Hz), 0.65 (d, J = 6.4 Hz), 1.42-1.50 (m, IH), 3.79- 3.89 (m, 2H), 3.96 (dd, J=8.4, 10 Hz, 1H), 4.01 (d, J=2A Hz), 4.54 (d, J=2A Hz), 4.56 (s, 5H).

(4), (i?)-l-(diphenylphosphino)-2-(5 4-isopropyloxazolinyl-2-bromofluorene, 6 (0.25 g, anhydrous, anaerobic) 0.42 mmol) was dissolved in THF (5 mL), then THF (1M, 5 mL) EtOAc EtOAc EtOAc EtOAc EtOAc was extracted twice, the combined organic phases were washed with water and brine, dried over anhydrous Na ₂ S0 _4, evaporate the solvent yellow-green solid residue by column chromatography (ethyl acetate I petroleum ether = 1/15) to give 7 ( 0.22g, y=74%).

Mp 169-171. C ; [a] ^D ₂₇ = +130.47 (c 0.46, CHC1 ₃ ); ^J H NMR (CDC1 ₃ , 400 Hz): δ 0.62 (d, J = 6.8 Hz, 3H), 0.64 (d, J = 6.8 Hz) , 3H), 1.51-1.57 (m, 1H), 3.85-4.02 (m, 4H), 4.60 (s, 5H), 4.67 (brs, 1H), 5.30 (brs, 1H), 7.26-7.42 (m, 10H ).

 Table 1

 <Preparation of Transition Metal Catalysts>

The ligands having the 1,2-disubstituted chiral hafnocene chirality (2.74 mg, 1.3 mol%) of Example 1, Example 4 and Example 5 were added to a two-necked flask under a nitrogen atmosphere. Ru(II)(PPh ₃ ) ₃ Cl ₂ (3.8 mg, 1 mol%). Then, isopropanol (5 mL) was added, and after degassing, the reaction was carried out under reflux in an argon atmosphere for 0.5 hour.

 <Asymmetric Reduction of Transfer Hydrogenation Using Isopropanol as a Source of Hydrogen>

 Evaluation 1

 The above ruthenium transition metal catalyst (1.0 mol% of the substrate shown in Table 2) was added to a Schlenk bottle under an argon atmosphere. Further, 4.0 mmol of the substrate shown in Table 2, 5.0 mol of isopropyl alcohol, and potassium t-butoxide as a base (1.0 mol% of the substrate shown in Table 2) were added, and the reaction was carried out while refluxing. The reaction time is shown in Table 2. Shown.

Purification by column chromatography (solvent: ethyl acetate) gave the product, and the ee value measured by the chiral column OJ-H is shown in Table 2.

 Table 22

评价 2

Evaluation 2

The evaluation was carried out under the same reaction conditions as in Evaluation 1 except that the reaction was carried out at room temperature for 20 hours under pressure (10 atm), and the results are shown in Table 3.

10 atm Matrix

Ligand used (L) Conversion rate (%) ee (%)

 Ar R'

Example 1 Ph CH ₃ 100 97.4 Example 4 Ph CH ₃ 100 98.6

Claims

Claim  A 1,2-disubstituted octagonal facet chiral ligand, characterized in that  The ligand is a ligand having a chiral chirality and a central chiral S type having a 1,2-disubstituted chiral fluorene, and the structural formula is as shown in the following formula (1) or (2):

In the formula, R represents a linear or branched fluorenyl group. 2. The 1,2-disubstituted hafnocene chiral ligand according to claim 1, which is characterized in that  R in the above formulae (1) and (2) is a fluorenyl group having 1 to 4 carbon atoms. 3. The 1,2-disubstituted hafnocene chiral ligand according to claim 1, which is characterized in that  This ligand serves as a ligand for the asymmetric catalyst. A method for producing a 1,2-disubstituted hafnocene chiral ligand, characterized in that the 1,2-disubstituted hafnocene chiral ligand is represented by the following formula (1) The chirality indicated is an S-type ligand having a 1,2-disubstituted chiral octagonal chiral chirality.

 In the formula (1), R represents a linear or branched fluorenyl group,  The manufacturing method sequentially has the following steps: In the first step, 1-chlorocarbonyldifluorene represented by the following formula (3) is reacted with an optically active amino alcohol represented by the following formula (4) in the presence of a base to obtain a formula (5) an amide compound, ^^•COCI Ru ( 3 ) In the formula (3 ), the meaning of R is the same as above.

In the general formula (4), R has the same meaning as described above.

In the formula (5), R has the same meaning as described above;  In the second step, an activator capable of activating a hydroxyl group is added, and the reaction is carried out in the presence of a base to obtain a 1-oxazolinyl ferrocene represented by the following formula (6).

 In the formula (6), R has the same meaning as described above;  In the step A3, the 1-oxazoline-based hafnocene and the organolithium compound are reacted in the presence of hydrazine, hydrazine, hydrazine, Ν'-tetramethylethylenediamine, and then halogenated Phenylphosphine is reacted. A method for producing a 1,2-disubstituted hafnocene chiral ligand, characterized in that the 1,2-disubstituted hafnocene chiral ligand is represented by the following formula (2) The indicated hand is an R-type ligand having a 1,2-disubstituted chiral octagonal chiral chirality.

In the formula (2), R represents a linear or branched fluorenyl group,  The manufacturing method sequentially has the following steps: In the first step, 1-chlorocarbonyldifluorene represented by the following formula (3) is reacted with an optically active amino alcohol represented by the following formula (4) in the presence of a base to obtain the following Amidation compound represented by the general formula (5)

The meaning of R in the general formula (3) is the same as above.

The meaning of R in the general formula (4) is the same as above.

In the formula (5), R has the same meaning as described above; In the second step, an activator capable of activating a hydroxyl group is added, and the reaction is carried out in the presence of a base to obtain a 1-oxazolinyl ferrocene represented by the following formula (6).

 In the formula (6), R has the same meaning as described above;  In the step B3, the 1-oxazoline-based hafnocene and the organolithium compound are reacted in the presence of ruthenium, rhodium, osmium, Ν'-tetramethylethylenediamine, and then silicon silicide is added. The reagent, the base, and the diphenylphosphine halide are reacted to obtain a lanthanum group having a silicon fluorenyl group having a surface chirality represented by the following formula (7).

In the formula (7), R has the same meaning as defined above, and R ¹ represents an organic group; In the fourth step, the silicon germanium-containing hafnoxene having an S-type chirality is reacted with the desiliconization sulfhydrylating reagent. The method for producing a 1,2-disubstituted hafnocene chiral ligand according to claim 4 or 5, wherein  The activator capable of activating a hydroxyl group is at least one selected from the group consisting of a mercaptohalogen sulfonium compound, an arylhalothio compound, phosphorus oxychloride, phosphorus pentachloride, thionyl chloride, and triphenylphosphine. 7. An asymmetric transition metal catalyst characterized in that  The 1,2-disubstituted hafnocene chiral ligand described in claim 1 is used as a ligand.