CN101298056B

CN101298056B - Asymmetric catalytic reaction catalyst and preparation and use thereof

Info

Publication number: CN101298056B
Application number: CN 200810132965
Authority: CN
Inventors: 戚明珠; 徐海鹏; 王宝林; 吕杨
Original assignee: Jiangsu Yangnong Chemical Co Ltd; Youth Chemical Co Ltd
Current assignee: Jiangsu Yangnong Chemical Co Ltd; Youth Chemical Co Ltd
Priority date: 2008-07-03
Filing date: 2008-07-03
Publication date: 2010-06-23
Anticipated expiration: 2028-07-03
Also published as: CN101298056A

Abstract

The invention provides a catalyst for unsymmetrical catalytic reactions, which is a composition formed by a novel chiral ligand and iridium metal precursor in situ; the structure of the chiral ligand is shown as the former formula I or II: wherein, R is a fatty group of H, C1-C40, a combination group of an aromatic group of C7-C60 and a fatty group or an aromatic group of C6-C60; Ar is the aromatic group of C6-C60; X is a fatty group, an aromatic group and a biphenyl or binaphthyl aromatic group. The invention also provides a preparation method for the catalyst and an application thereof in the catalytic reaction of catalyzing the bond of -C=N.

Description

Asymmetric catalytic reaction catalyst and preparation method and application thereof

Technical Field

The invention relates to a catalyst, in particular to an iridium metal complex catalyst in asymmetric catalytic reaction, a preparation method thereof and application thereof in catalytic hydrogenation reaction of asymmetric-C ═ N-double bonds.

Background

The hydrogenation of catalytic asymmetric C ═ N double bonds is a core technology in asymmetric synthesis, and is one of the most effective methods for synthesizing optical homochiral drugs, pesticides, food additives and perfumes, and the design and synthesis of chiral ligands are key factors for realizing the core technology. The chiral catalysts currently available for asymmetric hydrogenation of C ═ N double bonds are mainly iridium catalyst systems, and chiral ligands include bisphosphines and nitrogen-phosphine ligands. However, most of these chiral ligands are difficult to synthesize or have low catalytic activity and stereoselectivity, and thus are difficult to industrially apply. The most successful catalyst system at present is a catalyst system formed by JosiPhos ferrocene diphosphine ligand and iridium metal compound, and has been successfully applied to the industrial production of chiral herbicide Jindu with annual output of more than 10,000 tons. US5886225, US6008393, US5859300, WO9702232, US6527293, US5563308, US5466844 describe a process for the hydrogenation of imines, iridium catalysts with ferrocene as the parent chiral diphosphine ligand. The catalyst activity can be increased by tens of times or more by adding a halide and containing an acid to the reaction mixture. The deactivation of the catalyst can be reduced or avoided at the same time, and the reaction optical rotation yield can only reach 80% at the temperature higher than 50 ℃. US4994615 describes a process for the asymmetric hydrogenation of prochiral N-aryl ketimines, in which an iridium catalyst with a chiral diphosphine ligand is used. US5011995 describes a process for the asymmetric hydrogenation of prochiral N-aryl ketimines using the same catalyst. US5112999 discloses polynuclear iridium compounds and complex salts of iridium containing diphosphine ligands as catalysts for the hydrogenation of imines. At relatively large batch or process scales, the catalyst tends to deactivate to varying degrees depending on the catalyst precursor, matrix and diphosphine ligand used. Also at elevated temperatures, the reaction substrate is not completely converted. Therefore, the hydrogenation process has a catalyst yield that is too low for economic feasibility in industrial applications. The focus of current research is therefore on the development of novel catalyst systems.

Disclosure of Invention

One object of the present invention is: the new catalyst for asymmetric catalytic reaction has stable property, high optical selectivity and catalytic activity, and is favorable for wide application in various asymmetric hydrogenation reactions;

another object of the invention is: the preparation method of the catalyst is provided, the synthesis route of the method is simple, the required process conditions are easy to realize, and the cost for producing the catalyst is low;

yet another object of the present invention is: the use of the catalyst in catalytic hydrogenation reactions of asymmetric-C ═ N-double bonds is proposed.

The above object of the present invention is achieved by the following technical solutions:

a catalyst for asymmetric catalytic reaction is provided, which is a complex formed in situ by a novel chiral ligand and an iridium metal precursor, wherein the chiral ligand has a structure shown in the following formula I or formula II:

wherein,

r is H, C₁～C₄₀Aliphatic radical of (2), C₇～C₆₀A combination of aromatic and aliphatic groups of (a) or (C)₆～C₆₀An aromatic group of (a);

ar is C₆～C₆₀An aromatic group of (a);

x is aliphatic group, aromatic group, biphenyl or binaphthyl aromatic group.

R is preferably H, C₁～C₄₀Alkyl or cycloalkyl of (A) or (C)₇～C₆₀Benzyl group of (a);

x is preferably C₂～C₄₀Aliphatic radical of (2), C₆～C₆₀An aromatic group of (2), biphenyl or binaphthyl.

Said X is further preferably a group selected from one of the following structures:

wherein R1 and R2 are H, Me or Ph; r3 is alkyl or alkoxy; r4 is H, alkyl or alkoxy; r5 and R6 are H, alkyl, alkoxy or trialkyl silicon base; r7 and R8 are alkyl or alkoxy.

The invention also provides a preparation method of the catalyst for asymmetric catalytic reaction, which comprises the following steps:

1) synthesis of chiral ligands

1.1) synthesizing phosphine-primary amine key intermediate (S) -THNANH by direct ortho-metalation and phosphonylation of primary amine from chiral 1, 2, 3, 4-tetrahydro-1-naphthylamine₂Or (R) -THNANH₂The reaction is as follows:

wherein Ar is C₆～C₆₀An aromatic group of (a);

1.2) synthesizing a monoalkyl substituted phosphine-secondary amine intermediate (S) -THNANHR or (R) -THNANHR by acylating and reducing the intermediate obtained in the step 1.1), wherein the reaction formula is as follows;

wherein the R and R' groups are H, C₁～C₄₀Aliphatic radical of (2), C₇～C₆₀A combination of aromatic and aliphatic groups of (a) or (C)₆～C₆₀An aromatic group of (a);

1.3) condensing the phosphine-primary amine key intermediate obtained in the step 1.1) or the phosphine-secondary amine intermediate obtained in the step 1.2) with phosphite chloride with the structure shown as the following formula I to obtain the chiral ligand I or II with different chiral centers;

wherein X is an aliphatic group, an aromatic group, biphenyl or binaphthyl aromatic group;

the reaction in this step is briefly as follows:

wherein the R group is H, C₁～C₄₀Aliphatic radical of (2), C₇～C₆₀A combination of aromatic and aliphatic groups of (a) or (C)₆～C₆₀An aromatic group of (a);

2) synthesis of the catalyst for the asymmetric reaction

Mixing the chiral ligand synthesized in the step 1) and iridium metal salt in a solvent according to a molar ratio of 1-10: 1 to obtain an iridium metal complex of the chiral ligand, namely the catalyst for the asymmetric catalytic reaction. The solvent can be protonic alcohol solvent, and can also be CH₂Cl₂、CH₂ClCH₂Cl、CH₃Cl、CCl₄And aprotic solvents such as tetrahydrofuran, benzene, toluene, and ethyl acetate.

After the chiral ligand and the iridium metal salt in the catalyst are mixed in the solvent, the obtained mixed solution can be directly used for catalytic reaction, or the chiral ligand and the iridium metal salt can be mixed in the solvent to prepare a complex crystal for later use.

The invention also provides the application of the catalyst for asymmetric catalytic reaction in the catalytic hydrogenation reaction of asymmetric-C ═ N-double bonds.

In the catalysis process of the asymmetric hydrogenation reaction, the molar ratio of a reaction substrate to a catalyst is 100-1000,000: 1; the reaction is carried out at 1-100 atm and-20-200 ℃; the solvent can be protonic alcohol solvent, or CH₂Cl₂、CH₂ClCH₂Cl、CH₃Cl、CCl₄And aprotic solvents such as tetrahydrofuran, benzene, toluene, and ethyl acetate.

The catalysis of the asymmetric hydrogenation reaction is preferably carried out in the presence of an additive; the additive is any organic or inorganic compound capable of providing active protons, such as elementary iodine, an iodine-containing compound, an organic acid or an inorganic acid; the molar ratio of the additive to the catalyst is 0.1-1000: 1.

The catalytic hydrogenation of the asymmetric-C ═ N-double bond may be:

1) catalytic asymmetric hydrogenation of N-alkyl or N-aryl imines;

2) catalytic asymmetric hydrogenation of N-acylhydrazones, sulfonimides or phosphonimides; or,

3) catalytic asymmetric hydrogenation of aromatic or non-aromatic nitrogen heterocycles.

Wherein 1) the catalytic asymmetric hydrogenation of N-alkyl or N-aryl imine can be specifically asymmetric hydrogenation of refined toluylene imine with the structure shown as formula IV;

the invention also provides an application of the catalyst in the preparation of chiral herbicide Jindu: the catalyst is used for catalyzing refined methyl ethyl benzene imine with a structure shown in a formula IV to obtain a chiral hydrogenation product, and the chiral hydrogenation product is used as a raw material to prepare the chiral herbicide Jindu.

Thus, the process of the synthesis of the golden Dule can be shown as follows:

compared with the prior art, the catalyst provided by the invention has the following beneficial effects:

1. the catalyst of the invention has high catalytic activity and optical selectivity for hydrogenation of-C ═ N-double bonds.

The catalyst of the invention can present enantioselectivity of more than 90% to the asymmetric hydrogenation reaction of various C ═ N double bonds; the catalyst of the invention has high catalytic activity, TON can be up to more than 10000, and the catalyst can be compared favorably with a catalyst system formed by Josiphos ferrocene diphosphine ligand and iridium metal compound in the prior industrial application. .

2. The invention designs and synthesizesThe catalyst has wide application range and can be applied to asymmetric hydrogenation reaction of various-C ═ N-double bonds. Wherein the ligand and [ Ir (COD) Cl]₂The catalysts formed under in situ conditions are mainly used for catalytic asymmetric hydrogenation of the following classes of C ═ N double bonds:

(1) catalytic asymmetric hydrogenation of N-alkyl and N-aryl imines;

(2) catalytic asymmetric hydrogenation of N-acylhydrazones, sulfonimides, and phosphonimides;

(3) catalytic asymmetric hydrogenation of aromatic and non-aromatic nitrogen heterocycles.

The catalyst can be used for preparing chiral products of chiral amines and key chiral intermediates for synthesizing chiral medicines, pesticides and the like by an asymmetric catalytic hydrogenation method, has important application value in the industries of medicines, pesticides, spices, food and feed additives and the like, is particularly effective for asymmetric hydrogenation of a refined isopropyltoluidine intermediate, and has important significance for industrial production of herbicide Gordon.

3. The chiral ligand in the catalyst designed by the invention is stable to air and humidity, and is easy to operate and store; the ligand synthesis process route is simple, and violent operation conditions such as high temperature, high pressure and the like are not needed in the synthesis process; chiral sources for synthesis can be obtained in large quantities by asymmetric synthesis or resolution.

4. The catalyst has stable property, has good tolerance to air and humidity, has mild conditions for participating in asymmetric hydrogenation reaction, and can react at room temperature; the pressure of the hydrogen has wide application range, and the activity and the stereoselectivity of the catalyst are not influenced from normal pressure to high pressure.

Detailed Description

The technical means and effects of the present invention will be described in detail below by way of examples, but the present invention is not limited to the following examples.

Preparation examples

Example 1 Synthesis of chiral ligand intermediate A (phosphine-Primary amine Compound)

The structural formula of the chiral ligand intermediate A is as follows:

A

the chiral ligand intermediate a was prepared according to the following method:

into a 100ml three-necked flask were charged 1.47 g of (R) -1, 2, 3, 4-tetrahydro-1-naphthylamine and 10ml of diethyl ether, and 5.5ml of a 2.0mol/l n-BuLi hexane solution was slowly added at 0 ℃. After the addition, the reaction was stirred at 0 ℃ for a further 15 minutes, and then 1.09 g of trimethylchlorosilane were added. After 1 hour of reaction, 16.5ml of a 2.0mol/l n-BuLi hexane solution was slowly added, and the reaction mixture was slowly warmed to room temperature over a period of 5 hours. After 1 hour of reaction, the reaction mixture was cooled to-20 ℃ and a solution of 2.2 g of diphenylphosphinochloride and 10ml of diethyl ether was slowly added. The reaction was stirred at room temperature for 8 hours. 40ml of saturated NaHCO was added₃After the addition of the aqueous solution, the reaction was continued for 10 minutes with stirring. Separating, extracting water layer with 50ml diethyl ether twice, mixing ether layers, washing with 50ml water, and removing anhydrous Na₂SO₄And (5) drying. Filtering, removing the solvent under vacuum of 30mmHg, performing column chromatography on the residue to obtain viscous liquid, and recrystallizing 10ml of n-hexane to obtain white crystals, wherein 1.72 g of the phosphine-primary amine compound chiral ligand intermediate A is obtained, and the yield is 52%.¹H NMR(400MHz，CDCl₃)：δ＝7.31-7.28(8H，m；Ar-H)，7.25-7.22(2H，m；Ar-H)，7.08-7.02(2H，m；Ar-H)，6.80-6.77(1H，m；Ar-H)，4.64-4.63(1H，m；ArCH)，2.85-2.76(2H，m；Ar-CH₂)，2.00-1.86(2H，m；CH₂)，1.78-1.71(2H，m；CH₂)，1.65(2H，s；N-H)ppm；¹³C NMR(100MHz，CDCl₃)：δ＝145.47，137.66，137.16，137.07，136.68，136.62，134.21，134.01，133.55，133.36，132.61，130.93，128.82，128.73，128.66，128.59，128.52，126.87，46.34，31.48，29.81，17.18ppm；³¹P NMR(162MHz，CDCl₃)：δ＝-16.28ppm；HRMS(EI)：calcd for C₂₂H₂₂NP[M⁺]331.1490，found 331.1493.

Example 2 Synthesis of chiral ligand B (Phosphinophosphoramidate ligand)

The structural formula of the chiral ligand B is as follows:

the chiral ligand B is prepared according to the following method:

1) a100 ml three-necked flask was charged with 10 g of (R) -BINOL ((R) -2, 2 '-dihydroxy-1, 1' -binaphthyl) and 75 g of PCl₃And a catalytic amount of 2-methylpyrrolidone, the reaction is refluxed until the solid disappears (about 10 minutes). Removal of most of the PCl under reduced pressure of 30mmHg₃Small amount of PCl remaining₃Removed azeotropically with 50ml of toluene under reduced pressure. After removal of the toluene, the residue was recrystallized from 30ml of n-hexane to give 11.9 g of white chlorophosphite.

2) A100 ml three-necked flask was charged with 3.51 g of chlorophosphite prepared in step 1) and 30ml of anhydrous toluene, and a solution of 3.31 g of A prepared in example 1 and 3.03 g of triethylamine dissolved in 20ml of toluene was slowly dropped at 0 ℃. After the addition, the reaction mixture was warmed to room temperature and stirred for 8 hours. The residue was filtered and washed with 10ml of toluene. The residue was dissolved in 30ml CH₂Cl₂Washing with water, anhydrous Na₂SO₄And (5) drying. Removing the solvent CH₂Cl₂To obtain 5.18 g of chiral phosphine-phosphoramidite ligand B in the form of white powder.¹H NMR(400MHz，CD₂Cl₂)：δ＝7.85-7.80(4H，m；Ar-H)，7.29-7.11(18H，m；Ar-H)，6.95-6.94(2H，m；Ar-H)，6.72(1H，m；Ar-H)，5.35-5.34(1H，m；Ar-CH)，3.35-3.30(1H，m；N-H)，2.71-2.14(2H，m；Ar-CH₂)，2.18-2.14(1H，m；CH₂)，1.90-1.78(3H，m；CH₂)ppm；¹³C NMR(100MHz，CD₂Cl₂)：δ＝149.61，147.89，137.04，133.98，133.76，133.57，130.78，130.13，129.56，128.64，128.52，128.45，127.57，126.79，126.63，126.18，124.90，124.79，122.79，122.08，47.11，33.34，29.43，17.07ppm；³¹P NMR(162MHz，CD₂Cl₂)：δ＝155.4，-18.8ppm；HRMS(EI)：calcd for C₄₂H₃₃NO₂P₂[M⁺]645.1987，found 645.1979.

Example 3 Synthesis of chiral ligand C (Phosphinophosphoramidate ligand)

The structural formula of the chiral ligand C is as follows:

the chiral ligand C was prepared as follows:

1) a100 ml three-necked flask was charged with 10 g of (S) -BINOL and 75 g of PCl₃And a catalytic amount of 2-methylpyrrolidone, the reaction is refluxed until the solid disappears (about 10 minutes). Removal of most PCl under reduced pressure₃Small amount of PCl remaining₃Removed azeotropically with 50ml of toluene under reduced pressure. After removal of the toluene, the residue was recrystallized from 30ml of n-hexane to give 11.5 g of white chlorophosphite.

2) A100 ml three-necked flask was charged with 3.51 g of chlorophosphite prepared in step 1) and 30ml of anhydrous toluene, and a solution of 3.31 g of A prepared in example 1 and 3.03 g of triethylamine dissolved in 20ml of toluene was slowly dropped at 0 ℃. After the addition, the reaction mixture was warmed to room temperature and stirred for 8 hours. The residue was filtered and washed with 10ml of toluene. The residue was dissolved in 30ml CH₂Cl₂Washing with water, anhydrous Na₂SO₄And (5) drying. The solvent is removed, and 5.79 g of white powdery chiral phosphine-phosphoramidite ligand C is obtained.¹H NMR(400MHz，CDCl₃)：δ＝1.75-1.80(2H，m；CH₂)，1.97-2.05(2H，m；CH₂)，2.76-2.82(2H，m；CH₂)，3.34-3.38(1H，m；NH)，5.26-5.27(1H，m；CH)，6.64(1H，d，J＝8.8Hz；Ar-H)，6.89(1H，m；Ar-H)，7.11-7.41(20H，m；Ar-H)，7.65(1H，d，J＝8.8Hz；Ar-H)，7.82-7.89(2H，m；Ar-H)ppm；¹³C NMR(100MHz，CDCl₃)：δ＝16.6，28.8，31.7，47.3(t，J＝23.0Hz)，122.0，122.6，124.6(d，J＝7.0Hz)，125.9(d，J＝8.0Hz)，127.0(d，J＝4.0Hz)，127.6，128.2，128.3，128.4，128.5，128.6，128.7，129.2，130.0，130.7，130.8，131.3，132.8，132.9，133.4(d，J＝19Hz)，134.4(d，J＝20Hz)，136.4，136.9，137.0，138.2(d，J＝12Hz)，142.4，142.7，147.5，149.7ppm；³¹P NMR(162MHz，CDCl₃)：δ＝-18.41(d，J＝52.5Hz)，152.84(d，J＝52.5Hz)ppm.HRMS(EI)：calcdfor C₄₂H₃₃NO₂P₂[M⁺]645.1987，found 645.1981.

Example 4 Synthesis of chiral ligand D (Phosphinophosphoramidate ligand)

The structural formula of the chiral ligand D is as follows:

the chiral ligand D was prepared as follows:

1) a100 ml three-necked flask was charged with 10 g of (R) -3, 3 ' -dimethyl-2, 2 ' -dihydroxy-1, 1 ' -binaphthyl and 75 g of PCl₃And a catalytic amount of 2-methylpyrrolidone, the reaction is refluxed until the solid disappears (about 30 minutes). Removal of most PCl under reduced pressure₃Small amount of PCl remaining₃Removed azeotropically with 50ml of toluene under reduced pressure. After removal of the toluene, the residue was recrystallized from 30ml of n-hexane to give 10.8 g of white chlorophosphite.

2) At one endA100 ml three-necked flask was charged with 3.79 g of the phosphorochloridite prepared in the step 1) and 30ml of anhydrous toluene, and a solution of 3.31 g of A prepared in example 1 and 3.03 g of triethylamine dissolved in 20ml of toluene was slowly dropped at 0 ℃. After the addition, the reaction mixture was warmed to room temperature and stirred for 8 hours. Filtered and washed with 10ml of toluene. The residue was dissolved in 30ml CH₂Cl₂Washing with water, anhydrous Na₂SO₄And (5) drying. The solvent is removed, and 6.25 g of chiral phosphine-phosphoramidite ligand D in white powder is obtained.¹H NMR(400MHz，CD₂Cl₂)：δ＝6.77-7.83(23H，m；Ar-H)，5.36-5.34(1H，m；Ar-CH)，3.41-3.38(1H，m；N-H)，2.85-2.80(6H，m；Ar-CH₃)，2.74-2.43(2H，m；Ar-CH₂)，2.17-2.12(1H，m；CH₂)，1.94-1.77(3H，m；CH₂)ppm；¹³C NMR(100MHz，CD₂Cl₂)：δ＝148.60，147.81，134.85，133.17，133.11，133.07，129.24，129.11，128.96，128.34，128.10，128.05，126.99，126.52，126.43，126.09，124.82，124.56，122.91，122.74，45.81，31.76，28.23，22.51，22.72，16.97ppm；³¹P NMR(162MHz，CD₂Cl₂)：δ＝154.9，-18.1ppm；HRMS(EI)：calcd for C₄₄H₃₇NO₂P₂[M⁺]673.2300，found 673.2314.

Example 5 Synthesis of chiral ligand E (Phosphinophosphoramidate ligand)

The chiral ligand E has the following structure:

chiral ligand E was prepared as follows:

1) into a 100ml three-necked flask were charged 12g of (R) -3, 3 ' -diphenyl-2, 2 ' -dihydroxy-1, 1 ' -binaphthyl and 75 g of PCl₃And a catalytic amount of 2-methylpyrrolidone, and refluxing the reaction until the solid disappears (about 1 hour)). Removal of most PCl under reduced pressure₃Small amount of PCl remaining₃Removed azeotropically with 50ml of toluene under reduced pressure. After removal of the toluene, the residue was recrystallized from 30ml of n-hexane to give 12.1 g of white chlorophosphite.

2) A100 ml three-necked flask was charged with 5.03 g of chlorophosphite prepared in step 1) and 30ml of anhydrous toluene, and a solution of 3.31 g of A prepared in example 1 and 3.03 g of triethylamine dissolved in 20ml of toluene was slowly dropped at 0 ℃. After the addition, the reaction mixture was warmed to room temperature and stirred for 8 hours. Filtered and washed with 10ml of toluene. The residue was dissolved in 30ml CH₂Cl₂Washing with water, anhydrous Na₂SO₄And (5) drying. The solvent is removed, and 7.14 g of chiral phosphine-phosphoramidite ligand E in white powder is obtained.¹H NMR(400MHz，CD₂Cl₂)：δ＝6.92-7.83(33H，m；Ar-H)，5.35-5.31(1H，m；Ar-CH)，3.55-3.47(1H，m；N-H)，2.77-2.52(2H，m；Ar-CH₂)，2.21-2.16(1H，m；CH₂)，2.00-1.85(3H，m；CH₂)ppm；¹³C NMR(100MHz，CD₂Cl₂)：δ＝150.17，148.62，148.60，147.81，134.20，134.03，133.75，133.51，133.07，129.66，129.24，128.97，128.74，128.13，128.05，126.79，126.43，126.11，126.02，125.68，124.71，124.42，123.55，122.76，122.35，46.73，32.17，25.38，17.16ppm；³¹P NMR(162MHz，CD₂Cl₂)：δ＝157.2，-17.9ppm；HRMS(EI)：calcd for C₅₄H₄₁NO₂P₂[M⁺]797.2613，found 797.2609.

Example 6 Synthesis of chiral ligand F (phosphine-phosphoramidite ligand)

The chiral ligand F has the following structure:

the chiral ligand F was prepared as follows:

1) a50 ml three-necked flask was charged with 3.31 g of the intermediate A prepared in example 1 and 10ml of methyl formate, the mixture was reacted at 40 to 50 ℃ for 8 hours, and the unreacted methyl formate was removed under reduced pressure. The residue was taken up in a 50ml three-necked flask, 25ml of anhydrous THF was added, and 0.5 g of LiAlH was added under ice-bath conditions at 0 deg.C₄After the addition, the reaction was refluxed for 12 hours. Under ice-bath conditions, 10ml of saturated NH were slowly added₄Aqueous Cl solution. Transferring the reaction solution to a separating funnel, adding 10ml of water and 20ml of dichloromethane, separating, removing the solvent, carrying out column chromatography on residues, and recrystallizing by 10ml of n-hexane to obtain 3.08G of a white solid phosphine-secondary amine compound G;

2) a100 ml three-necked flask was charged with 3.51G of chlorophosphite prepared in step 1) of example 2 and 30ml of anhydrous toluene, and a solution of 3.45G of Compound G and 3.03G of triethylamine dissolved in 20ml of toluene was slowly dropped at 0 ℃. After the addition, the reaction mixture was warmed to room temperature and stirred for 8 hours. Filtered and washed with 10ml of toluene. The residue was dissolved in 30ml CH₂Cl₂Washing with water, anhydrous Na₂SO₄And (5) drying. The solvent was removed to give 6.05 g of chiral phosphine-phosphoramidite ligand F as a white powder.¹H NMR(400MHz，CD₂Cl₂)：δ＝7.84-7.79(4H，m；Ar-H)，7.28-7.07(18H，m；Ar-H)，6.93-6.92(2H，m；Ar-H)，6.79(1H，m；Ar-H)，5.33-5.31(1H，m；Ar-CH)，2.75-2.44(2H，m；Ar-CH₂)，2.21-2.17(1H，m；CH₂)，1.96-1.84(6H，m；CH₂，CH₃)ppm；¹³C NMR(100MHz，CD₂Cl₂)：δ＝150.59，147.50，136.88，133.82，133.67，133.17，130.58，129.67，129.11，128.24，127.97，127.91，127.01，126.48，126.17，125.98，124.65，123.99，122.83，121.79，49.42，34.58，30.11，27.75，19.01ppm；³¹P NMR(162MHz，CD₂Cl₂)：δ＝154.6，-18.4ppm；HRMS(EI)：calcd for C₄₃H₃₅NO₂P₂[M⁺]659.2143，found 659.2129.

Example 7 preparation of the catalyst

719mg of chiral ligand B prepared in example 2 in solution in 5ml of dichloromethane are slowly added to 38.6mg of [ Ir (COD) Cl]₂To a solution of 5ml of methylene chloride, the resulting yellow solution was stirred at room temperature for 1 hour. After removal of the solvent, the residue was washed twice with 10ml of diethyl ether and recrystallized from 20ml of dichloromethane/diethyl ether (1: 4) to yield 627mg of yellow crystals of a catalyst for asymmetric catalytic reactions according to the invention.¹H NMR(400MHz，CD₂Cl₂)：δ＝1.97(2H，m；CH₂)，2.18(6H，m；CH₂，CH)，2.38(3H，m；CH₂，CH)，2.50(1H，m；CH)，2.79(2H，m；CH₂)，4.10(1H，m；＝CH)，4.31(1H，br，s；＝CH)，4.84(1H，br，s；＝CH)，5.28(1H，br，s；＝CH)，5.39(1H，br，s；NH)，6.32(1H，d，J＝9.2Hz；Ar-H)，6.70(1H，t，J＝9.0Hz；Ar-H)，6.99(1H，t，J＝8.4Hz；Ar-H)，7.17(5H，m；Ar-H)，7.38(8H，m；Ar-H)，7.56(2H，m；Ar-H)，7.63(3H，d，J＝2.0Hz；Ar-H)，7.87(3H，m；Ar-H)，7.97(1H，d，J＝9.2Hz；Ar-H)；¹³C NMR(100MHz，CD₂Cl₂)：δ＝18.7，28.1，29.5，29.7，31.1，32.2，48.2(d，J(C，P)＝12Hz)，95.9，111.4，120.4，121.0，122.7，125.9(d，J(C，P)＝6Hz)，126.4，126.7，126.9，127.3(d，J(C，P)＝8Hz)，128.5，128.8(d，J(C，P)＝10Hz)，129.4(d，J(C，P)＝10Hz)，130.4，130.7，131.4，131.6，132.0，132.1，132.9，134.1(d，J(C，P)＝11Hz)，136.9，137.4，145.9(d，J(C，P)＝13Hz)，146.8ppm；³¹P NMR(162MHz，CD₂Cl₂)：δ＝14.40(dd，J(P，Rh)＝111.6Hz)，139.3(dd，J(P，Rh)＝229.1Hz，J(P，P)＝21.7Hz)ppm.。

Referring to the method, the chiral ligands C to F prepared in the previous embodiments and the corresponding iridium metal compound are used for preparing the complex according to the ratio of 1-10: 1, so that the catalyst for asymmetric catalytic reaction can be prepared, and the detailed method is not repeated here.

(II) application example

Example 8

Catalytic preparation of N-phenyl-1-phenylethylamine

6.7mg (0.01mmol) of [ Ir (COD) Cl]₂14.2mg (0.022mmol) of chiral ligand B prepared in example 2 and 2ml of methanol were stirred at room temperature for 30 minutes, and then a solution of N-phenyl-1-phenylethynylidene-amine (1.0mmol) as a substrate and 2ml of methanol was added thereto, and after 3 times of hydrogen substitution, the mixture was reacted under a hydrogen pressure of 10atm for 24 hours, and then the mixture was filtered through a short silica gel column, and the filtrate obtained by the filtration was concentrated and then subjected to content and optical purity measurement by GC to obtain N-phenyl-1-phenylethylamine in a yield of 100% and an enantiomeric excess of 90% ee or more.

Example 9

Catalytic preparation of N-phenyl-1-phenylethylamine

6.7mg (0.01mmol) of [ Ir (COD) Cl]₂14.2mg (0.022mmol) of chiral ligand B prepared in example 2, 8mg (0.05mmol) of I₂And 2ml of methanol were stirred at room temperature for 30 minutes, and then a solution of the substrate N-phenyl-1-phenylethynylidene-amine (1.0mmol) and 2ml of methanol was added thereto, and after 3 times of replacement with hydrogen gas, the mixture was reacted under a hydrogen pressure of 10atm for 24 hours. Filtering with short silica gel column, concentrating the filtrate, and determining content and optical purity with GC to obtain N-phenyl-1-phenylethylamine with yield of 100% and enantiomeric excess of more than 90% ee.

Example 10

Catalytic preparation of N-phenyl-1-phenylethylamine

6.7mg (0.01mmol) of [ Ir (COD) Cl]₂14.2mg (0.022mmol) of chiral ligand C prepared in example 3, 8mg (0.05mmol) of I₂After stirring 2ml of methanol at room temperature for 30 minutes, a solution of the substrate N-phenyl-1-phenylethynylidene-amine (100mmol) and 50ml of methanol was added, and the mixture was reacted at 50 ℃ for 24 hours under a hydrogen pressure of 50atm after 3 times of hydrogen substitution. Then filtering with a short silica gel columnAfter the filtrate obtained by filtration is concentrated, the content and the optical purity of the concentrated filtrate are measured by GC, the yield of the N-phenyl-1-phenylethylamine is 100 percent, and the enantiomeric excess is more than 80 percent ee.

Example 11

Catalytic preparation of N- (2 ' -methyl-6 ' -ethyl-benzene-1 ' -yl) -1- (methoxymethyl) ethylamine

1) 17.8mg (0.027mmol) of chiral ligand F prepared in example 6 and 40mg (0.108mmol) of tetrabutylammonium iodide were successively added to 8.8mg (0.013mmol) [ Ir (COD) Cl]₂To 10ml of acetic acid (degassed) solution and stirred for 15 minutes to obtain a catalyst solution.

2) 412g (2mol) of N- (2 ' -methyl-6 ' -ethyl-phen-1 ' -yl) -N- (1-methoxymethyl) ethan-1-ylamine are dissolved in 70ml of acetic acid (degassed).

3) The substrate solution obtained in step 2) and the catalyst solution obtained in step 1) were successively transferred to an inert gas (normal pressure). Then, a hydrogen pressure of 70atm was applied and the autoclave was heated to 50 ℃. After 18 hours of reaction, the reaction was stopped and the reaction solution was cooled to room temperature. The hydrogen pressure was released, and the reaction solution was discharged from the autoclave under pressure. The conversion was 100%. 100ml of toluene were added and then toluene and acetic acid were removed in a rotary evaporator. The residue was distilled under high vacuum (5mmHg) to give 401g (yield 97%) of pure N- (2 ' -methyl-6 ' -ethyl-phen-1 ' -yl) N- (1-methoxymethyl) ethylamine. Flash chromatography [ silica gel 0.040-0.063mm, eluent: ethane/Ethyl acetate (10: 1) to determine enantiomeric purity. The optical yield was 75.6% (S).

Example 12

1) 17.8mg (0.027mmol) of phosphine-phosphoramidite ligand F and 13.7mg (0.054mmol) of iodine were successively added to 8.8mg (0.013mmol) [ Ir (COD) Cl]₂To 10ml of acetic acid (degassed) solution and stirred for 15 minutes to obtain a catalyst solution.

2) 412g (2mol) of N- (2 ' -methyl-6 ' -ethyl-phen-1 ' -yl) N- (1-methoxymethyl) ethan-1-ylamine are dissolved in 70ml of acetic acid (degassed).

3) The substrate solution obtained in step 2) and the catalyst solution obtained in step 1) were successively transferred to an inert gas (normal pressure). Then, a hydrogen pressure of 70atm was applied and the autoclave was heated to 50 ℃. After 18 hours of reaction, the reaction was stopped and the reaction solution was cooled to room temperature. The hydrogen pressure was released, and the reaction solution was discharged from the autoclave under pressure. The conversion was 100%. 100ml of toluene were added and then toluene and acetic acid were removed in a rotary evaporator. The residue is distilled under high vacuum (5mmHg) to give 401g (yield 97%) of pure N- (2 ' -methyl-6 ' -ethyl-phen-1 ' -yl) -N- (1-methoxymethyl) ethylamine. Purification by flash chromatography [ silica gel 0.040-0.063mm, eluent: ethane/Ethyl acetate (10: 1) to determine enantiomeric purity. The optical yield was 80.7% (S).

Example 13

1) 10.4mg (0.0155mmol) of [ Ir (COD) Cl]₂22.1mg (0.0335mmol) of chiral ligand F prepared in example 6 and 50mg (0.136mmol) of tetrabutylammonium iodide were dissolved in 2.5ml of acetic acid (degassed) and stirred for 15 minutes to obtain a catalyst solution.

2) 17g (0.083mol) 2-methyl-6-ethylphenylammonia are dissolved in 9g of anhydrous methoxyacetone.

3) The methoxyacetone solution obtained in step 2) and the catalyst solution obtained in step 1) were transferred successively into a 50ml steel autoclave under an inert atmosphere. The inert gas (atmospheric pressure) was replaced with four cycles of hydrogen. Then, a hydrogen pressure of 40atm was applied and the autoclave was heated to 50 ℃. After 18 hours of reaction, the reaction was stopped and the reaction solution was cooled to room temperature. The hydrogen pressure was released, and the reaction solution was discharged from the autoclave under pressure. The conversion was 100%. 100ml of toluene were added and then toluene and acetic acid were removed in a rotary evaporator. The residue was distilled under high vacuum (5mmHg) to give N- (2 ' -methyl-6 ' -ethylphen-1 ' -yl) -1- (methoxymethyl) ethylamine 17g (yield 97%) in an optical yield of 85% (S).

Example 14 preparation of Goldur Using the catalyst of the invention

Preparation of (S) -2-chloro-N- (2-ethyl-6-methylphenyl) -N-2-methoxy-methylethylacetamide (Kindole)

433g (5.48mol) of pyridine were added to a solution of 936g (4.57mol) of (S) N- (2 ' -methyl-6 ' -ethyl-phen-1 ' -yl) -1- (methoxymethyl) ethylamine (ee 85%) prepared as catalyzed in example 13 in 1.8L of toluene at 15-20 ℃ over 25 minutes with stirring and introduction of ammonia gas. Then, 547g (4.84mol) of chloroacetyl chloride was added dropwise over 1.5 hours at 15 to 20 ℃ with ice cooling. After completion of the dropwise addition, the resulting suspension was stirred at room temperature for 1.5 hours. The reaction mixture was poured into 2L of water, the oil layer was separated after separation, and the aqueous layer was treated by extraction twice with 500ml of toluene each time. The combined organic phases were washed once with 500ml of 2mol/L hydrochloric acid, twice with 300ml of saturated sodium chloride solution, once with 600ml of saturated sodium bicarbonate solution, dried over anhydrous sodium sulfate and filtered, and the solvent was removed under a low vacuum of 30 mmHg. Rectifying and purifying the obtained crude product under 5mmHg to obtain 1193g of product with the content of 98.7 percent and the yield of 92.1 percent.

Claims

1. A catalyst for asymmetric catalytic reaction, which is a complex formed in situ by a chiral ligand and an iridium metal precursor, wherein the chiral ligand has the following structure formula I or formula II:

wherein,

r is H, C₁～C₄₀Aliphatic radical of (2), C₇～C₆₀A combination of aromatic and aliphatic radicals of (a) orC₆～C₆₀An aromatic group of (a);

ar is C₆～C₆₀The aromatic group of (a):

x is a group selected from one of the following structures:

2. The catalyst of claim 1 wherein R is H, C₁～C₄₀Alkyl or C₇～C₆₀Benzyl group of (a).

3. A method for preparing a catalyst for asymmetric catalytic reactions as claimed in claim 1, comprising the steps of:

1) synthesis of chiral ligands

wherein Ar is C₆～C₆₀An aromatic group of (a);

1.3) condensing the phosphine-primary amine key intermediate obtained in the step 1.1) or the phosphine-secondary amine intermediate obtained in the step 1.2) with phosphite chloride with the structure shown as the following formula III to obtain the chiral ligands I or II with different chiral centers;

wherein X is a group selected from one of the following structures:

the reaction in this step is briefly as follows:

2) synthesis of the catalyst for the asymmetric reaction

Mixing the chiral ligand synthesized in the step 1) and iridium metal salt in a solvent according to a molar ratio of 1-10: 1 to obtain an iridium metal complex of the chiral ligand, namely the catalyst for the asymmetric catalytic reaction; the solvent is an aprotic solvent.

4. Use of the catalyst for asymmetric catalytic reactions according to claim 1 for the catalytic hydrogenation of asymmetric-C ═ N-double bonds.

5. The use of claim 4, wherein: in the catalysis process of the asymmetric hydrogenation reaction, the molar ratio of a reaction substrate to a catalyst is 100-1000,000: 1.

6. The use of claim 5, wherein: the catalysis of the asymmetric hydrogenation reaction is carried out in the presence of an additive; the additive is any organic or inorganic compound capable of providing active protons; the molar ratio of the additive to the catalyst is 0.1-1000: 1.

7. Use according to claim 4, characterized in that the catalytic hydrogenation of the asymmetric-C ═ N-double bond is:

1) catalytic asymmetric hydrogenation of N-alkyl or N-aryl imines;

2) catalytic asymmetric hydrogenation of N-acylhydrazones, sulfonimides or phosphonimides; or

8. The use of claim 7, wherein: 1) the catalytic asymmetric hydrogenation of N-alkyl or N-aryl imines is the asymmetric hydrogenation of the fine toluylene imine of the structure IV below.

9. Use of the catalyst of claim 1 in the preparation of a chiral herbicide, aurantiol, characterized in that: the catalyst is used for catalyzing refined methyl ethyl benzene imine with a structure shown in a formula IV to obtain a chiral hydrogenation product, and the chiral hydrogenation product is used as a raw material to prepare the chiral herbicide Jindu.