CN114478362A - Preparation method of chiral pyridinol derivative - Google Patents

Preparation method of chiral pyridinol derivative Download PDF

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CN114478362A
CN114478362A CN202011167070.8A CN202011167070A CN114478362A CN 114478362 A CN114478362 A CN 114478362A CN 202011167070 A CN202011167070 A CN 202011167070A CN 114478362 A CN114478362 A CN 114478362A
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chiral
cod
tert
diphosphine
pyridinol
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稂琪伟
丁小兵
高爽
苏伟
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Shenzhen Catalys Technology Co Ltd
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/30—Oxygen atoms
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    • 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
    • B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
    • B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
    • B01J31/2409—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring with more than one complexing phosphine-P atom
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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    • 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
    • B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
    • B01J2231/643—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes of R2C=O or R2C=NR (R= C, H)
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    • B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
    • B01J2531/0225—Complexes comprising pentahapto-cyclopentadienyl analogues
    • B01J2531/023—Phospholyl ligands, i.e. [CnP(5-n)Rn]- in which n is 0-4 and R is H or hydrocarbyl, or analogous condensed ring systems
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    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
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    • B01J2531/827—Iridium
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    • 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
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    • C07—ORGANIC CHEMISTRY
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Abstract

The invention discloses a preparation method of a chiral pyridinol derivative, in particular to a method for preparing pyridinol by catalyzing asymmetric hydrogenation of pyridone through a chiral ferrocene skeleton phosphine ligand-metal complex. The method has the advantages of simple steps, simple and convenient operation, mild conditions and wide substrate application range, can efficiently and asymmetrically synthesize a series of pyridine alcohol compounds, can use the catalyst only in an amount of 0.002 mol% (S/C-50000), and has huge industrial application value.

Description

Preparation method of chiral pyridinol derivative
Technical Field
The invention belongs to the technical field of organic synthesis preparation, relates to asymmetric catalysis of compounds, and particularly relates to a preparation method of a chiral pyridinol derivative.
Background
The chiral pyridinol structure widely exists in natural products, novel functional materials and other substances and is also an important skeleton of various medicaments, for example, carbaxamine containing the chiral pyridinol structure and bepotastine besilate are two common histamine receptor antagonists; the compound A with a chiral pyridine alkyl alcohol structure as a framework is an anticancer drug in research; in addition, various chiral pyridine alkyl alcohols are intermediate components of catalyst ligands for part of industrial applications.
Figure BDA0002746156410000011
How to simply, cheaply and efficiently obtain chiral pyridine secondary alcohol is a problem which needs to be solved urgently. At present, asymmetric synthesis methods of chiral pyridinol derivatives can be divided into three major classes: (1) asymmetric addition of aryl organometallic reagents to heteroaromatic aldehydes; (2) biocatalytic techniques; (3) asymmetric catalytic hydrogenation. Among them, the chiral pyridinol product obtained by homogeneous asymmetric catalysis has a single configuration, the chemical waste generated in the reaction process is less, and the by-product is not generated basically, so that the asymmetric catalytic hydrogenation method is most attractive from the viewpoint of practical application and atom economy.
In 2000, the Noyori group (Pure appl. chem.,2001,73(2):227-2-BINAP-diamine was used as a catalyst, and the asymmetric hydrogenation of 2,3, 4-pyridylalkyl ketone and pyridyldiketone was studied. The system is found in the aspect of B [ OCH (CH)3)3]Under the condition of using the pyridine diketone as an additive, the efficient reduction of the pyridone substrate can be realized (the ee value of the product is more than 94 percent under the condition that S/C is 2000), and the pyridine diketone with the best reaction effect can obtain 100 percent of conversion and chiral pyridine diol with the ee value of more than 99.9 percent under the condition that S/C is 10000.
Figure BDA0002746156410000021
Ru (II) X in 2003 and 2008, groups of Cheng-yi Chen (Organic Letters,2003,5(26):5039-2Asymmetric catalysis of pyridine aryl ketones by BINAP-diamine catalytic system. The experimental result shows that the system can realize high-efficiency asymmetric hydrogenation reduction of pyridine aryl ketone with substituent at the ortho-position of aromatic ring under proper conditions, and the ee value of the product reaches 99% (S/C ═ 1000). However, when there is no substituent on the benzene ring or the substituent is at other positions, the selectivity of the system is greatly reduced.
Figure BDA0002746156410000022
In 2012, The Journal of Organic Chemistry,2012,77(1): 612-. The system exhibits greater catalytic capacity than the Noyori bisphosphine diamine catalyst in the catalytic reduction of such substrates, but, similar to previous experimental results, the high selectivity of the system to the substrate is dependent on the presence of aromatic ring ortho substituents on the substrate.
Despite the great progress made in the preparation of pyridinol derivatives by transition metal-catalyzed asymmetric hydrogenation, several important problems remain unsolved: (1) the conversion number (TON) is too low, and the TON is less than or equal to 2000, so that the requirement of industrial production cannot be met; (2) the catalytic system is single and is limited to diphosphine ligand and ruthenium or rhodium metal salt; (3) the substrate universality is poor, and the position of a substituent on a pyridine ring has a large influence on the ee value. These are problems to be solved urgently in the industrial synthesis of pyridinol derivatives. Therefore, the method for asymmetric catalytic hydrogenation with high efficiency, high stereoselectivity and wide substrate applicability has important practical significance.
Disclosure of Invention
In view of the above problems in the prior art, the present invention aims to provide a method for preparing chiral pyridinol derivatives, which has high atom economy, is suitable for industrial production and application, and can conveniently prepare chiral pyridinol derivatives with high purity and high enantioselectivity in large quantities.
The invention is realized by the following technical scheme, and the preparation method of the chiral pyridinol derivative is characterized by comprising the following steps of:
Figure BDA0002746156410000031
in the formulae (I) and (II), the substituent R1And a substituent R2Each independently selected from hydrogen, halogen, C1-C12 alkyl, aryl or heteroatom-containing substituted alkyl and aryl.
Wherein [ M ]/L is a catalyst formed by coordination bonding of a metal M complex and a chiral ligand L, wherein the metal M is Ru, Rh, Ir, Pd or the like, and the structure of the chiral ligand L is a ferrocene ligand shown in a general formula (III), (IV), (V) or (VI):
Figure BDA0002746156410000032
in the general formula, R represents methyl, isopropyl, tert-butyl, phenyl, benzyl or other optional linear, branched or cyclic substituent of C1-C6; ar represents phenyl, 4-methylphenyl, 4-methoxyphenyl, 3, 5-dimethylphenyl, 3, 5-dimethyl-4-methoxyphenyl, 3,4, 5-trimethylphenyl, 3, 5-di-tert-butylphenyl, 3, 5-di-tert-butyl-4-methoxyphenyl or 3, 5-di-tert-butyl-4-methylphenyl.
As a preferred embodiment of the present invention, the method includes:
1) sequentially adding a metal M complex and a chiral ligand L into a protic organic solvent under the atmosphere of argon at the temperature of 10-40 ℃, and stirring for reaction for 0.5-6 hours to prepare a catalyst [ M ]/L ] in which the metal M complex and the chiral ligand L are coordinately bound, wherein the metal M is Ru, Rh, Ir, Pd or the like;
2) adding the pyridone derivative shown in the formula (I), the catalyst [ M ]/L obtained in the step 1), a solvent and an alkali into an autoclave in sequence, carrying out asymmetric hydrogenation reaction at 10-60 ℃ and 0.1-10 MPa of hydrogen pressure for 2-24 hours, and obtaining the chiral pyridinol derivative shown in the formula (II) after the reaction is finished.
Wherein, after the reaction is finished, the reaction solution is decompressed and concentrated, after a proper amount of water is added, ethyl acetate is used for extraction, and the organic phase is remained after liquid separation. And then drying and concentrating the organic phase to obtain the chiral pyridine alcohol derivative shown in the formula (II).
As a preferred technical scheme of the invention, the chemical structure of the chiral ligand L includes but is not limited to chiral ligands shown as any one of formulas III-1 to III-6, IV-1, IV-2, V-1, V-2, VI-1 or VI-2:
Figure BDA0002746156410000041
as a preferred embodiment of the present invention, the metal M complex is [ Rh (NBD) ]2]+BF4 -；[Rh(NBD)Cl]2；[Rh(COD)Cl]2；[Rh(COD)2]+X-；Rh(acac)(CO)2；Rh(ethylene)2(acac)；[Rh(ethylene)2Cl]2；RhCl(PPh3)3；Rh(CO)2Cl2；Ru(arylgroup)X2；RuHX(L)2(diphosphine)；RuX2(L)2(diphosphine)；Ru(arene)X2(diphosphine)；Ru(RCOO)2(diphosphine)；Ru(methallyl)2(diphosphine)；Ru(aryl group)X2(PPh3)3；Ru(COD)(COT)；Ru(COD)(COT)X；RuX2(cymene)；Ru(COD)n；RuCl2(＝CHR)(PR'3)2；Ru(arylgroup)X2(diphosphine)；RuCl2(COD)；[Ru(COD)2]X；RuX2(diphosphine)；Ru(ArH)Cl2；Ru(COD)(methallyl)2；Ir(NBD)Cl]2；[Ir(NBD)2]X；[Ir(COD)Cl]2；[Ir(COD)2]X；[Ni(allyl)X]2；Ni(acac)2；Ni(COD)2；NiX2；MnX2；Mn(acac)2；CoX2；FeX2；CuX；CuX2；AgX；[Pd(allyl)Cl]2；PdCl2；Pd(OAc)2；Pd(CF3COO)2. In the above transition metal precursors, R and R' may be independently alkyl, alkoxy or substituted alkyl, aryl is aryl, and X is a negative anion, such as Cl-、Br-、BF4 -、ClO4 -、SbF6 -、PF6 -、CF3SO3 -、RCOO-、B(Ar)4 -Wherein Ar can be 3, 5-bis (trifluoromethyl) benzene or fluorobenzene. L is a solvent molecule, such as CH3CN, and the like.
Further, the solvent in step 1) and step 2) is independently selected from one or more mixed solvents of dichloromethane, tetrahydrofuran, 2-methyltetrahydrofuran, methyl tert-butyl ether, toluene, methanol, ethanol, n-propanol, isopropanol and tert-butanol.
Further, in the step 2), the molar ratio of the catalyst [ M ]/L, the base and the pyridone derivative is 1:10 to 200:100 to 50000.
Further, in the step 2), the reaction temperature for carrying out the asymmetric hydrogenation is 10 ℃ to 60 ℃.
Further, in the step 2), the pressure of hydrogen for performing the asymmetric hydrogenation reaction is 0.1-10 MPa.
Further, in the step 2), the reaction time for performing the asymmetric hydrogenation reaction is 2 to 24 hours.
Further, in the step 2), the base is one of potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, potassium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate and sodium methoxide or a mixture of sodium methoxide in any proportion.
Compared with the prior art, the invention has the following beneficial effects:
(1) the catalyst composed of chiral ferrocene tridentate ligand and metal complex is adopted, and due to high stability and reaction activity of the catalyst, inactivation caused by coordination of pyridine to the metal center of the catalyst is overcome. Compared with the prior art, the process is more advanced.
(2) Through a large number of experiments, the technology of the invention can obtain the enantioselectivity of more than 99 percent and the catalyst conversion number of 50000 which is far higher than that reported in the prior known public.
(3) The method has the characteristics of simple operation, mild reaction conditions, wide substrate application range, high atom economy, environmental friendliness and the like, and has great implementation value and social and economic benefits.
Detailed Description
The present invention will be further described with reference to specific examples, but the present invention is not limited thereto.
The experimental methods in the examples, in which specific conditions are not specified, are generally performed under the conditions described in the manual and the conventional conditions, or under the conditions recommended by the manufacturer; the materials, reagents and the like used are commercially available unless otherwise specified.
Example 1 (ligand examination)
Figure BDA0002746156410000061
In an argon-protected glove box, 0.021mmol chiral ligand L and metal M precursor [ Ir (COD) Cl ] were weighed]2(0.01mmol, 6.7mg) was added to a 10mL volumetric flask, 2mL of isopropanol solution was added, and the mixture was stirred at room temperature for 1 hour until it was completely dissolved, and the catalyst solution was directly used in the homogeneous catalytic hydrogenation reaction.
Under argon atmosphere, compound 1a (0.1mmol, 15mg), potassium carbonate (0.01mmol, 1.4mg) and the prepared catalyst solution (100uL, 0.001mmol) were added in this order to a 5mL hydrogenation tube, 0.9mL isopropanol was added, the reaction tube was placed in an autoclave, the gas in the autoclave was replaced with hydrogen three times, and finally 50atm hydrogen was charged and reacted in a constant temperature oil bath at 50 ℃ for 12 hours. After the reaction, the gas in the autoclave was slowly released, the reaction mixture was purified by a silica gel column, the concentrated filtrate was vacuum-dried to obtain a white solid, i.e., compound 1b, and the conversion and ee values were measured by HPLC, and the results are shown in table 1 below.
Table 1.
Figure BDA0002746156410000062
Figure BDA0002746156410000071
Figure BDA0002746156410000072
Example 2 (solvent examination)
Figure BDA0002746156410000073
Figure BDA0002746156410000074
In a glove box protected by argon, 0.021mmol of chiral ligand III-3 and metal M precursor [ Ir (COD) Cl ] are weighed]2(0.01mmol, 6.7mg) was added to a 10mL volumetric flask, 2mL of isopropanol solution was added, and the mixture was stirred at room temperature for 1 hour until it was completely dissolved, and the catalyst solution was directly used in the homogeneous catalytic hydrogenation reaction.
Under argon atmosphere, compound 1a (0.1mmol, 15mg), potassium carbonate (0.01mmol, 1.4mg) and the prepared catalyst solution (100 μ L, 0.001mmol) were added in this order to a 5mL hydrogenation tube, then 0.9mL of solvent was added, the reaction tube was placed in an autoclave, the gas in the autoclave was replaced with hydrogen three times, finally 50atm hydrogen was charged, and the reaction was carried out in a constant temperature oil bath at 50 ℃ for 12 hours. After the reaction, the gas in the autoclave was slowly released, the reaction mixture was purified by a silica gel column, the concentrated filtrate was vacuum-dried to obtain a white solid, i.e., compound 1b, and the conversion and ee values were measured by HPLC, and the results are shown in table 2 below.
Table 2.
Figure BDA0002746156410000081
Example 3 (examination of base)
Figure BDA0002746156410000082
Figure BDA0002746156410000083
In a glove box protected by argon, 0.021mmol of chiral ligand III-3 and metal M precursor are weighed[Ir(COD)Cl]2(0.01mmol, 6.7mg) was added to a 10mL volumetric flask, 2mL of isopropanol solution was added, and the mixture was stirred at room temperature for 1 hour until it was completely dissolved, and the catalyst solution was directly used in the homogeneous catalytic hydrogenation reaction.
Under argon atmosphere, compound 1a (0.1mmol, 15mg), a base (0.001mmol) and a prepared catalyst solution (10 μ L, 0.0001mmol) were sequentially added to a 5mL hydrogenation tube, 1mL isopropyl alcohol was further added, the reaction tube was placed in an autoclave, the gas in the autoclave was replaced with hydrogen three times, and finally 50atm hydrogen was charged, and the reaction was carried out in a constant temperature oil bath at 50 ℃ for 12 hours. After the reaction, the gas in the autoclave was slowly released, the reaction mixture was purified by a silica gel column, the concentrated filtrate was vacuum-dried to obtain a white solid, i.e., compound 1b, and the conversion and ee values were measured by HPLC, and the results are shown in table 3 below.
Table 3.
Figure BDA0002746156410000091
Examples 4 to 19 (investigation of substrate Range)
Figure BDA0002746156410000092
Figure BDA0002746156410000093
In a glove box protected by argon, 0.021mmol of chiral ligand III-3 and metal M precursor [ Ir (COD) Cl ] are weighed]2(0.01mmol, 6.7mg) was added to a 10mL volumetric flask, 2mL of isopropanol solution was added and stirred at room temperature for 1 hour until it was completely dissolved, and the catalyst solution was directly used for homogeneous catalytic hydrogenation.
Under argon atmosphere, compound 1a (0.1mmol, 15mg), sodium methoxide (0.001mmol, 0.05mg) and the prepared catalyst solution (10 μ L, 0.0001mmol) were sequentially added to a 5mL hydrogenation tube, 1mL of a solvent was further added, the reaction tube was placed in an autoclave, the gas in the autoclave was replaced with hydrogen three times, and finally 50atm hydrogen was charged and reacted in a constant temperature oil bath at 50 ℃ for 12 hours. After the reaction, the gas in the autoclave was slowly released, the reaction mixture was purified by a silica gel column, the concentrated filtrate was vacuum-dried to obtain a white solid, i.e., compound 1b, and the conversion and ee values were measured by HPLC, and the results are shown in table 4 below.
Table 4.
Figure BDA0002746156410000101
Figure BDA0002746156410000111
Example 20 (enlargement, S/C50000)
Figure BDA0002746156410000112
Figure BDA0002746156410000113
In a glove box protected by argon, 0.021mmol of chiral ligand III-3 and metal M precursor [ Ir (COD) Cl ] are weighed]2(0.01mmol, 6.7mg) was added to a 10mL volumetric flask, 2mL of isopropanol solution was added, and the mixture was stirred at room temperature for 1 hour until it was completely dissolved, and the catalyst solution was directly used in the homogeneous catalytic hydrogenation reaction.
Under argon atmosphere, compound 1a (40mmol, 6g), sodium methoxide (0.4mmol, 21.6mg) and the prepared catalyst solution (80 μ L, 0.0008mmol) were sequentially added to a 5mL hydrogenation tube, 1mL of isopropanol was further added, the reaction tube was placed in an autoclave, the gas in the autoclave was replaced with hydrogen three times, and finally 50atm hydrogen was charged and reacted in a constant temperature oil bath at 50 ℃ for 12 hours. After the reaction is finished, slowly releasing the gas in the autoclave, purifying the reaction mixture by using a silica gel short column, concentrating the filtrate, and drying the filtrate in vacuum to obtain a white solid, namely the compound 1b, wherein the reaction yield is 97 percent, and the ee value is 99 percent by HPLC.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.

Claims (10)

1. A preparation method of chiral pyridinol derivatives is characterized by comprising the following steps:
Figure FDA0002746156400000011
in the formulae (I) and (II), the substituent R1And a substituent R2Each independently selected from hydrogen, halogen, C1-C12 alkyl, aryl or heteroatom-containing substituted alkyl, aryl;
wherein [ M ]/L is a catalyst formed by coordination bonding of a metal M complex and a chiral ligand L, wherein the metal M is Ru, Rh, Ir, Pd or the like, and the structure of the chiral ligand L is a ferrocene ligand shown in a general formula (III), (IV), (V) or (VI):
Figure FDA0002746156400000012
in the general formula, R represents methyl, isopropyl, tert-butyl, phenyl, benzyl or other optional linear, branched or cyclic substituent of C1-C6; ar represents phenyl, 4-methylphenyl, 4-methoxyphenyl, 3, 5-dimethylphenyl, 3, 5-dimethyl-4-methoxyphenyl, 3,4, 5-trimethylphenyl, 3, 5-di-tert-butylphenyl, 3, 5-di-tert-butyl-4-methoxyphenyl or 3, 5-di-tert-butyl-4-methylphenyl.
2. The method for preparing a chiral pyridinol derivative according to claim 1, characterized by comprising:
1) sequentially adding a metal M complex and a chiral ligand L into a protic organic solvent under the atmosphere of argon at the temperature of 10-40 ℃, and stirring for reaction for 0.5-6 hours to prepare a catalyst [ M ]/L ] in which the metal M complex and the chiral ligand L are coordinately bound, wherein the metal M is Ru, Rh, Ir, Pd or the like;
2) adding the pyridone derivative shown in the formula (I), the catalyst [ M ]/L obtained in the step 1), a solvent and an alkali into an autoclave in sequence, carrying out asymmetric hydrogenation reaction at 10-60 ℃ and 0.1-10 MPa of hydrogen pressure for 2-24 hours, and obtaining the chiral pyridinol derivative shown in the formula (II) after the reaction is finished.
3. The process according to claim 1, wherein the chiral ligand L has a chemical structure including but not limited to any one of the following structures:
Figure FDA0002746156400000021
4. the process for preparing a chiral pyridinol derivative according to claim 1, wherein the metal M complex is [ Rh (NBD) ]2]+BF4 -；[Rh(NBD)Cl]2；[Rh(COD)Cl]2；[Rh(COD)2]+X-；Rh(acac)(CO)2；Rh(ethylene)2(acac)；[Rh(ethylene)2Cl]2；RhCl(PPh3)3；Rh(CO)2Cl2；Ru(arylgroup)X2；RuHX(L)2(diphosphine)；RuX2(L)2(diphosphine)；Ru(arene)X2(diphosphine)；Ru(RCOO)2(diphosphine)；Ru(methallyl)2(diphosphine)；Ru(aryl group)X2(PPh3)3；Ru(COD)(COT)；Ru(COD)(COT)X；RuX2(cymene)；Ru(COD)n；RuCl2(＝CHR)(PR'3)2；Ru(arylgroup)X2(diphosphine)；RuCl2(COD)；[Ru(COD)2]X；RuX2(diphosphine)；Ru(ArH)Cl2；Ru(COD)(methallyl)2；Ir(NBD)Cl]2；[Ir(NBD)2]X；[Ir(COD)Cl]2；[Ir(COD)2]X；[Ni(allyl)X]2；Ni(acac)2；Ni(COD)2；NiX2；MnX2；Mn(acac)2；CoX2；FeX2；CuX；CuX2；AgX；[Pd(allyl)Cl]2；PdCl2；Pd(OAc)2；Pd(CF3COO)2(ii) a In the above transition metal precursors, R and R' may be independently alkyl, alkoxy or substituted alkyl, aryl is aryl, and X is a negative anion, such as Cl-、Br-、BF4 -、ClO4 -、SbF6 -、PF6 -、CF3SO3 -、RCOO-、B(Ar)4 -Wherein Ar can be 3, 5-bis (trifluoromethyl) benzene or fluorobenzene; l is a solvent molecule, such as CH3CN, and the like.
5. The method according to claim 1, wherein the solvent in step 1) and step 2) is one or more selected from dichloromethane, tetrahydrofuran, 2-methyltetrahydrofuran, methyl tert-butyl ether, toluene, methanol, ethanol, n-propanol, isopropanol, and tert-butanol.
6. The method according to claim 1, wherein in step 2), the molar ratio of the catalyst [ M ]/L ] to the base to the pyridone derivative is 1:10 to 200:100 to 50000.
7. The method for preparing chiral pyridinol derivative according to claim 1, wherein the asymmetric hydrogenation is carried out at a reaction temperature of 10 to 60 ℃ in step 2).
8. The method for preparing chiral pyridinol derivative according to claim 1, wherein the hydrogen pressure for the asymmetric hydrogenation in step 2) is 0.1 to 10 MPa.
9. The method for preparing chiral pyridinol derivative according to claim 1, wherein the reaction time for the asymmetric hydrogenation in step 2) is 2-24 hours.
10. The method for preparing chiral pyridinol derivative according to claim 1, wherein in step 2), the base is one or a mixture of potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, potassium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate and sodium methoxide in any proportion.
CN202011167070.8A 2020-10-27 2020-10-27 Preparation method of chiral pyridinol derivative Pending CN114478362A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112961194A (en) * 2021-03-08 2021-06-15 洛阳师范学院 PNO ligand containing chiral ferrocene and application thereof
WO2023206665A1 (en) * 2022-04-26 2023-11-02 凯特立斯（深圳）科技有限公司 Process for unprotected asymmetric preparation of nicotine

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105732725A (en) * 2016-01-30 2016-07-06 武汉凯特立斯科技有限公司 Chiral tridentate nitrogen-phosphine-oxygen ligands and application of related ligands in asymmetric catalytic reactions
CN106632511A (en) * 2016-12-01 2017-05-10 武汉凯特立斯科技有限公司 Chiral tridentate phosphonic amine ligand and application thereof in asymmetric catalytic reaction

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105732725A (en) * 2016-01-30 2016-07-06 武汉凯特立斯科技有限公司 Chiral tridentate nitrogen-phosphine-oxygen ligands and application of related ligands in asymmetric catalytic reactions
CN106632511A (en) * 2016-12-01 2017-05-10 武汉凯特立斯科技有限公司 Chiral tridentate phosphonic amine ligand and application thereof in asymmetric catalytic reaction

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
WEILONG WU等: ""Iridium Catalysts with f-Amphox Ligands: Asymmetric Hydrogenation of Simple Ketones"", 《ORG.LETT.》, vol. 18, pages 2938 - 2941 *
WEIPING CHEN等: ""Ferrocene-based aminophosphine ligands in the Ru(II)-catalysed asymmetric hydrogenation of ketones: assessment of the relative importance of planar versus carbon-centredchirality"", 《TETRAHEDRON: ASYMMETRY》, vol. 17, no. 8, pages 1161 - 1164 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112961194A (en) * 2021-03-08 2021-06-15 洛阳师范学院 PNO ligand containing chiral ferrocene and application thereof
CN112961194B (en) * 2021-03-08 2023-12-12 洛阳师范学院 PNO ligand containing chiral ferrocene and application thereof
WO2023206665A1 (en) * 2022-04-26 2023-11-02 凯特立斯（深圳）科技有限公司 Process for unprotected asymmetric preparation of nicotine

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