CN114014869B - Chiral 2,2' -bipyridine ligand and preparation method and application thereof - Google Patents

Chiral 2,2' -bipyridine ligand and preparation method and application thereof Download PDF

Info

Publication number
CN114014869B
CN114014869B CN202111434132.1A CN202111434132A CN114014869B CN 114014869 B CN114014869 B CN 114014869B CN 202111434132 A CN202111434132 A CN 202111434132A CN 114014869 B CN114014869 B CN 114014869B
Authority
CN
China
Prior art keywords
formula
chiral
reaction
stirring
ligand
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202111434132.1A
Other languages
Chinese (zh)
Other versions
CN114014869A (en
Inventor
李鹏飞
欧阳彝钊
张帅
茜姆勃玟
宋沛东
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Xian Jiaotong University
Original Assignee
Xian Jiaotong University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Xian Jiaotong University filed Critical Xian Jiaotong University
Priority to CN202111434132.1A priority Critical patent/CN114014869B/en
Publication of CN114014869A publication Critical patent/CN114014869A/en
Application granted granted Critical
Publication of CN114014869B publication Critical patent/CN114014869B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/113—Spiro-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
    • B01J31/1805—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing nitrogen
    • B01J31/181—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine
    • B01J31/1825—Ligands comprising condensed ring systems, e.g. acridine, carbazole
    • B01J31/183—Ligands comprising condensed ring systems, e.g. acridine, carbazole with more than one complexing nitrogen atom, e.g. phenanthroline
    • B01J31/1835—Ligands comprising condensed ring systems, e.g. acridine, carbazole with more than one complexing nitrogen atom, e.g. phenanthroline comprising aliphatic or saturated rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/36—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal
    • C07C29/38—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal by reaction with aldehydes or ketones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
    • C07C41/30—Preparation of ethers by reactions not forming ether-oxygen bonds by increasing the number of carbon atoms, e.g. by oligomerisation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
    • B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
    • B01J2231/4205—C-C cross-coupling, e.g. metal catalyzed or Friedel-Crafts type
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
    • B01J2531/0261—Complexes comprising ligands with non-tetrahedral chirality
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
    • B01J2531/84—Metals of the iron group
    • B01J2531/847—Nickel
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Pyridine Compounds (AREA)

Abstract

The invention provides a chiral 2,2' -bipyridyl ligand and a preparation method and application thereof, wherein the chiral 2,2' -bipyridyl ligand is shown in a formula (1) or a formula (1 '),

Description

Chiral 2,2' -bipyridine ligand and preparation method and application thereof
Technical Field
The invention belongs to the technical field of fine chemical engineering, and relates to a chiral 2,2' -bipyridyl ligand and a preparation method and application thereof.
Background
The construction of molecules is a difficult art, but is at the heart of chemistry, upon which many areas and industries of research, including biomedical and materials science, rely. Among them, the construction of chiral molecules has long been a goal to be overcome by chemists. First, chirality is closely related to life phenomena, and the development of chirality science is not known in the aspects of exploring mystery and evolutionary mechanisms of life origin and operation, researching and developing drugs, pesticides, biological detection reagents, bionic materials and the like related to life. With the development of the field of material science, chiral materials have shown unique values in molecular machines, nonlinear optics, three-dimensional display and information storage and transmission. Whether oriented to scientific and technological application or life health, the efficient and accurate preparation of chiral substances is always the most important one.
Transition metal catalytic reactions, enzyme catalytic reactions and small organic molecule catalytic reactions are three ways of constructing chiral molecules, and transition metal catalysis is the most widely studied and applied class of them. The ligand is an important component of the metal complex, and has a key regulation function on the electronic structure of the central metal, the spatial structure of the complex and the physicochemical properties of the complex.
However, most of the chiral ligands widely used at present rely on the chiral skeleton provided by natural molecules, and most of artificially designed ligand skeletons are difficult to synthesize, expensive in raw materials and narrow in application range. Especially chiral 2, 2-bipyridine type ligands are more slowly developed. Therefore, it is of far-reaching interest to design a 2, 2-bipyridyl ligand skeleton which is easy to synthesize and has cheap raw materials.
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides a chiral 2,2' -bipyridine ligand, a preparation method and application thereof, wherein the ligand has the advantages of low synthesis raw material cost, simplicity and easy obtainment and convenient synthesis.
The invention is realized by the following technical scheme:
a chiral 2,2 '-bipyridine ligand has a structural formula shown in formula (1) or formula (1'):
Figure BDA0003381016020000021
wherein R is aryl or alkyl.
The preparation method of the chiral 2,2' -bipyridyl ligand comprises the following steps:
(1) Brominating 2-cyclopentene-1-one under the action of liquid bromine, and reacting with diethyl malonate to obtain a pair of enantiomers;
(2) Reacting the obtained enantiomer with (R) -tert-butyl sulfinamide and tetraethyl titanate, then separating and purifying the product to obtain sulfinyl imine, and then hydrolyzing with hydrochloric acid to obtain chiral ketone shown in formula (2) and/or formula (2');
Figure BDA0003381016020000022
(3) Placing chiral ketone shown in a formula (2) and hydroxylamine into ethanol for reaction to obtain oxime shown in a formula (3);
or, placing the chiral ketone shown in the formula (2 ') and hydroxylamine into ethanol for reaction to obtain oxime shown in the formula (3');
Figure BDA0003381016020000023
(4) Adding oxime shown in a formula (3) into toluene, and then adding iron powder, acetic anhydride and acetic acid to react to obtain amide shown in a formula (4);
or adding the oxime shown in the formula (3 ') into toluene, and then adding iron powder, acetic anhydride and acetic acid to react to obtain the amide shown in the formula (4');
Figure BDA0003381016020000031
(5) Dissolving amide shown in a formula (4) in N, N-dimethylformamide, then dropwise adding phosphorus oxychloride, and reacting to obtain a chloropyridine derivative shown in a formula (5);
or dissolving the amide shown in the formula (4 ') in N, N-dimethylformamide, and then dropwise adding phosphorus oxychloride to react to obtain the chloropyridine derivative shown in the formula (5');
Figure BDA0003381016020000032
(6) Dissolving a chloropyridine derivative shown in formula (5) in tetrahydrofuran, and then dropwise adding the solution into a toluene solution of DIBAL-H at a low temperature to react to obtain a diol derivative shown in formula (6);
or dissolving the chloropyridine derivative shown in the formula (5 ') in tetrahydrofuran, and then dropwise adding the solution into a toluene solution of DIBAL-H at a low temperature to react to obtain a diol derivative shown in the formula (6');
Figure BDA0003381016020000033
(7) Reacting the diol obtained in the formula (6) with p-toluenesulfonic acid, stannous chloride, a molecular sieve and methyl ketal under the reflux condition of 1, 2-dichloroethane to obtain a ketal derivative shown in a formula (7);
or reacting the diol obtained in the formula (6 ') with p-toluenesulfonic acid, tin dichloride, a molecular sieve and methyl ketal under the reflux condition of 1, 2-dichloroethane to obtain the ketal derivative shown in the formula (7').
Figure BDA0003381016020000041
(8) Adding manganese powder, nickel chloride hexahydrate and triphenylphosphine into N, N-dimethylformamide, heating and stirring for 1 hour, then adding a chloropyridine derivative shown in a formula (7) or a formula (7 ') dissolved in the N, N-dimethylformamide, and reacting to obtain the chiral 2,2' -bipyridine ligand.
Preferably, the specific process of step (1) is as follows: under the protection of nitrogen, 2-cyclopentene-1-ketone and liquid bromine react in dichloromethane at 0 ℃ to room temperature for 4-8 hours to obtain 2-bromo-2-cyclopentene-1-ketone, the 2-bromo-2-cyclopentene-1-ketone and diethyl malonate react in 1, 2-dichloroethane solvent under the catalysis of alkali, the temperature is heated to 90 ℃ for 12-24 hours, and a pair of enantiomers are obtained by filtration and column chromatography separation.
Preferably, the specific process of step (3) is as follows: placing the chiral ketone shown in the formula (2) or the formula (2 ') and hydroxylamine into an ethanol solution, heating, refluxing and stirring for 18-24 hours, then washing with water, extracting with dichloromethane, drying the obtained organic phase with anhydrous sodium sulfate, and removing the solvent to obtain the oxime shown in the formula (3) or the formula (3').
Preferably, the specific process of step (4) is as follows: adding oxime shown in a formula (3) or a formula (3 ') into toluene, cooling to 0 ℃, adding iron powder, adding a mixture of acetic anhydride and acetic acid, heating to room temperature for reaction, stirring for 18-24 hours, filtering out the iron powder, adding an ammonium chloride aqueous solution, extracting by using ethyl acetate, and performing silica gel column chromatography separation to obtain amide shown in a formula (4) or a formula (4').
Preferably, the specific process of step (5) is as follows: dissolving the amide shown in the formula (4) or the formula (4 ') in N, N-dimethylformamide, then dropwise adding phosphorus oxychloride in an ice bath, stirring at the temperature of 80-100 ℃ for 18-24 hours, and separating the mixture by using column chromatography to obtain the chloropyridine derivative shown in the formula (5) or the formula (5').
The chiral 2,2' -bipyridyl ligand is used as a catalyst ligand in the preparation of chiral diaryl methanol.
Preferably, the method comprises the following steps:
under the condition of argon, stirring and mixing a nickel dibromide ethylene glycol dimethyl ether complex, a chiral 2,2' -bipyridine ligand and 2-methyltetrahydrofuran at room temperature, adding zinc powder and sodium tetraphenyltetrafluoroborate, and continuously stirring and mixing at room temperature; adding aldehyde and aryl halide into a reaction system, and stirring the obtained reaction mixture at-30-0 ℃ for reaction; after the reaction is finished, removing the solvent; the obtained crude reaction product is separated and purified to obtain the chiral diaryl methanol.
The chiral 2,2' -bipyridine ligand is used as a catalyst ligand in the preparation of chiral self-coupling diaryl compounds.
Preferably, the method comprises the following steps:
under the condition of argon, heating, stirring and mixing a nickel dichloride triphenylphosphine complex, a chiral 2,2' -bipyridine ligand and N, N-dimethylacetamide, adding manganese powder and aryl chloride, and stirring and reacting the obtained reaction mixture at 60-80 ℃; and after the reaction is finished, removing the solvent, and separating and purifying the obtained crude reaction product to obtain the chiral biaryl compound.
Compared with the prior art, the invention has the following beneficial technical effects:
the chiral 2,2' -bipyridine ligand has the advantages of low cost of raw materials, simplicity, easy obtainment and convenient synthesis. In the process of synthesizing the ligand, the substituent group of the ligand can be randomly regulated and controlled so as to regulate and control the electrical property and the steric hindrance condition of the ligand, so that the ligand disclosed by the invention can use different groups according to different reactions so as to meet the requirement of wide applicability. The ligand of the invention has been used for preparing chiral diaryl methanol and chiral self-coupling diaryl compounds, and the effectiveness and the applicability of the ligand are verified. When the method is applied to preparing chiral diaryl methanol and self-coupling diaryl, the yield and enantioselectivity of products can be kept at a high level when cheap metallic nickel is used as a catalyst.
The chiral 2,2' -bipyridyl ligand has the advantages of low cost of raw materials, simplicity, easy obtainment and convenient synthesis.
The ligand of the invention is adopted to prepare chiral diaryl methanol, cheap aryl aldehyde and aryl halide can be adopted as raw materials, the catalyst is cheap metal nickel, the product has good stereoselectivity and high yield, and the purification is easy.
The ligand of the invention is adopted to prepare the chiral self-coupling diaryl product, cheap aryl chloride can be adopted as the raw material, the catalyst is cheap metallic nickel, the product has good stereoselectivity and high yield, and the purification is easy.
Drawings
FIG. 1 shows chiral 2,2' -bipyridine ligands of formula (1) in example 1 of the present invention, R is phenyl substituted 1 H NMR spectrum.
FIG. 2 shows a chiral 2,2 '-bipyridine ligand of formula (1') R in example 2 of the present invention is methyl-substituted 1 H NMR spectrum.
Detailed Description
The present invention will now be described in further detail with reference to specific examples, which are intended to be illustrative, but not limiting, of the invention.
A chiral 2,2 '-bipyridine ligand with different substituents has a structural formula shown as a formula (1) or a formula (1'):
Figure BDA0003381016020000061
wherein R is aryl or alkyl.
A method for preparing chiral 2,2' -bipyridine ligands with different substituents comprises the following steps:
the first step is as follows: under the protection of nitrogen, liquid bromine is dissolved in dichloromethane and then is dripped into dichloromethane solution of 2-cyclopentene-1-ketone under the condition of ice water bath, and triethylamine is added after 2-5 hours of reaction. Washing with water after reaction, extracting with dichloromethane, combining organic phases, drying with anhydrous magnesium sulfate, filtering, decompressing and evaporating the solvent to dryness, and further purifying the obtained crude product to obtain the 2-bromo-2-cyclopentene-1-ketone. Under the catalysis of alkali and phase transfer catalyst, 2-bromo-2-cyclopentene-1-ketone and diethyl malonate react in 1, 2-dichloroethane to obtain a pair of enantiomers.
The second step: the enantiomer obtained was stirred with (R) -tert-butylsulfinamide and a certain amount of tetraethyl titanate in 1, 2-dichloroethane at 90 ℃ overnight, and then the product was isolated and purified using a silica gel column to obtain optically pure sulfinimide. Subsequent hydrolysis with aqueous hydrochloric acid affords the chiral ketones of formula (2) and/or formula (2'), respectively.
Figure BDA0003381016020000071
The third step: placing the chiral ketone shown in the formula (2) or the formula (2') and excess hydroxylamine into an ethanol solution, refluxing and stirring for 18-24 hours, then washing with water, and extracting with dichloromethane. The organic phase was dried over anhydrous sodium sulfate, and the solvent was removed to obtain an oxime represented by the formula (3) or (3') in which the ketone was converted.
Figure BDA0003381016020000072
The fourth step: an oxime represented by the formula (3) or the formula (3') is added to an appropriate amount of toluene. The toluene solution was then cooled to 0 ℃ and excess iron powder was added. Then a mixture of the appropriate acetic anhydride and acetic acid is slowly added to the solution and allowed to warm to room temperature. After reacting for 18-24 hours, filtering the iron powder, adding a proper amount of ammonium chloride aqueous solution into the filtrate, extracting by using ethyl acetate, and then carrying out silica gel column chromatography separation to obtain the corresponding amide product shown in the formula (4) or the formula (4').
Figure BDA0003381016020000081
The fifth step: an amide represented by the formula (4) or (4') is dissolved in N, N-dimethylformamide. Then dropping phosphorus oxychloride into the ice bath. After stirring at 80-100 ℃ for 18-24 hours, the mixture is separated by column chromatography to obtain the chloropyridine derivative which is an important intermediate shown in formula (5) or formula (5').
Figure BDA0003381016020000082
And a sixth step: dissolving the chloropyridine derivative shown in the formula (5) or the formula (5 ') in tetrahydrofuran, dropwise adding the solution into a toluene solution of diisobutylaluminum hydride (DIBAL-H) at a temperature of between 20 ℃ below zero and 0 ℃, stirring for 2 to 4 hours, quenching, extracting by using dichloromethane, collecting an organic phase, concentrating, and recrystallizing by using acetone to obtain the diol derivative shown in the formula (6) or the formula (6').
Figure BDA0003381016020000083
The seventh step: the diol obtained by the formula (6) or the formula (6 ') reacts with p-toluenesulfonic acid, tin dichloride, a molecular sieve and methyl ketal with different substituents for 4 to 8 hours under the reflux condition of 1, 2-dichloroethane at 90 ℃, and after the reaction is finished, silica gel column chromatography separation is carried out to obtain ketal derivatives with different substituent protections, namely the formula (7) or the formula (7').
Figure BDA0003381016020000091
Eighth step: adding manganese powder and a nickel dichloride triphenylphosphine complex into N, N-dimethylformamide, heating and stirring for 1 hour, recovering to room temperature, adding a chloropyridine derivative shown in a formula (7) or a formula (7 ') dissolved in the N, N-dimethylformamide, heating to 60 ℃, stirring for 12-18 hours, and separating by silica gel column chromatography to obtain chiral 2,2' -bipyridine ligand formula (1) or formula (1 ') with different substituents.
Figure BDA0003381016020000092
The application of the chiral 2,2' -bipyridyl ligand as a catalyst ligand in preparing diaryl methanol comprises the following steps:
under the condition of argon, adding a nickel dibromide ethylene glycol dimethyl ether complex, a chiral 2,2 '-bipyridine ligand of a formula (1) or a formula (1') and 2-methyltetrahydrofuran, stirring at room temperature for 1 hour, adding zinc powder and sodium tetraphenyltetrafluoroborate, and continuing stirring at room temperature for 1 hour. After fully stirring, adding aldehyde and aryl halide into the reaction system in turn, and placing the reaction mixture at-30-0 ℃ for stirring for 24-48 hours. After completion of the reaction, the reaction mixture was warmed to room temperature and then distilled under reduced pressure to remove 2-methyltetrahydrofuran. And separating the crude reaction product by silica gel column chromatography to obtain a chiral diaryl methanol product.
The structure of the chiral diaryl methanol compound is shown as the formula (8):
Figure BDA0003381016020000101
wherein R is 1 Represents an aromatic ring, a substituted aromatic ring or a naphthalene ring, R 2 Represents an aromatic ring, a substituted aromatic ring or a naphthalene ring.
The application of the chiral 2,2' -bipyridyl ligand as a catalyst ligand in preparing the chiral self-coupling diaryl product comprises the following steps:
under argon, adding nickel dichloride triphenylphosphine complex, chiral 2,2 '-bipyridine ligand of formula (1) or formula (1'), and N, N-dimethylacetamide, stirring at 60 deg.C for 1 hr, adding manganese powder and aryl chloride, and stirring the reaction mixture at 60-80 deg.C for 24-48 hr. After completion of the reaction, the reaction mixture was returned to room temperature, and then N, N-dimethylacetamide was removed by extraction with dichloromethane and water, and dichloromethane was removed by rotary evaporation. And separating the crude reaction product by silica gel column chromatography to obtain a chiral self-coupling diaryl product.
The structure of the chiral self-coupling diaryl compound is shown as the formula (9):
Figure BDA0003381016020000102
wherein R is 3 Represents an aromatic ring, a substituted aromatic ring or a naphthalene ring.
Example 1
Synthesis of chiral 2,2' -bipyridine ligand:
1.1
Figure BDA0003381016020000103
2-cyclopenten-1-one was dissolved in 60mL of Dichloromethane (DCM) and Br was added at 0 deg.C 2 (liquid bromine is stored under water seal, the lowest liquid bromine is required to be sucked up) is dissolved in 60mL of DCM, and the system is added through a constant pressure dropping funnel (dropping is carried out, and the temperature of the system is controlled to be less than 5 ℃). About 30min after the addition was complete, the temperature was maintained at 0 ℃ for 10min. Adding Et 3 Dissolving N in 60mL DCM, quickly dropwise adding the system through a constant-pressure dropping funnel (about 10 min), stirring the system at room temperature for 4h after the addition is finished, adding saturated ammonium chloride aqueous solution (20 mL) to quench the reaction after the reaction is finished, extracting with 50-60mL DCM for 3 times each time, combining organic phases, drying with anhydrous sodium sulfate, filtering, concentrating under reduced pressure, and separating and purifying the obtained crude product by column chromatography to obtain the 2-bromo-2-cyclopentene-1-one.
1.2
Figure BDA0003381016020000111
2-bromo-2-cyclopenten-1-one (240mmol, 1.0 equiv), 39g diethyl malonate (480mmol, 2.0 equiv), 15.6g tetrahexylammonium bromide (36mmol, 15mol%) and 200g potassium carbonate (1440mmol, 6.0 equiv) were added to 240mL of 1, 2-dichloroethane. The reaction mixture was stirred at 90 ℃ for 20 hours, cooled to room temperature, filtered and the solvent was evaporated off. The crude reaction product was chromatographed on silica gel to separate a group of mixed enantiomeric products, ethyl (1R, 5S) -2-oxobicyclo [3.1.0] hexane-6, 6-diacetate and ethyl (1S, 5R) -2-oxobicyclo [3.1.0] hexane-6, 6-diacetate.
1.3
Figure BDA0003381016020000112
The above enantiomer (3.9g, 15mmol) was taken and reacted with (R) - (+) -tert-butylsulfinamide (1.81g, 15mmol) and tetraethyltitanate (6.8g, 30mmol) in dichloroethane (75 mL) at 90 ℃ for 20 hours. And (3) cooling the materials to room temperature, adding saturated ammonium chloride aqueous solution (20 mL) to quench the materials for reaction, extracting the materials for 3 times by using 20-30mL ethyl acetate each time, combining organic phases, drying the organic phases by using anhydrous sodium sulfate, filtering the organic phases, concentrating the organic phases under reduced pressure, and separating and purifying the obtained crude product by using column chromatography to obtain optically pure sulfinylimine intermediates respectively. Hydrolysis of the intermediate with aqueous hydrochloric acid (20 mL) gave ethyl (1R, 5S) -2-oxobicyclo [3.1.0] hexane-6, 6-diacetate and ethyl (1S, 5R) -2-oxobicyclo [3.1.0] hexane-6, 6-diacetate, respectively.
1.4
Figure BDA0003381016020000121
(1S, 5R) -2-oxobicyclo [3.1.0] hexane-6, 6-diacetic acid ethyl ester (3.6 g, 15mmol) was dissolved in 20mL of ethanol, and hydroxylamine (1.5g, 45mmol) was added thereto, followed by heating to 80 ℃ and stirring under reflux overnight. After the system was cooled to room temperature, 20mL of water was added thereto, followed by extraction with 20 to 30mL of methylene chloride each time for 3 times, and the organic phases were combined and dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product (1S, 5R) -2-isonitrobicyclo [3.1.0] hexane-6, 6-diacetic acid ethyl ester.
1.5
Figure BDA0003381016020000122
(1S, 5R) -2-isonitrobicyclo [3.1.0] hexane-6, 6-diacetic acid ethyl ester (2.5g, 10mmol) obtained in the previous step was dissolved in toluene (20 mL) and iron powder (3.35g, 60mmol) was added thereto and then cooled to 0 ℃. A mixture of acetic anhydride (3.1g, 30mmol) and acetic acid (1.8g, 30mmol) was then slowly added to the system and allowed to return to room temperature. After stirring for 18-24 hours, adding saturated ammonium chloride aqueous solution (20 mL) to quench the reaction, extracting 3 times with 20-30mL ethyl acetate each time, combining organic phases, drying with anhydrous sodium sulfate, filtering, concentrating under reduced pressure, and separating and purifying the obtained crude product by column chromatography to obtain (1S, 5R) -2-acetamido-bicyclo [3.1.0] -2-alkene-hexane-6, 6-ethyl diacetate.
1.6
Figure BDA0003381016020000131
Ethyl (1S, 5R) -2-acetylaminobicyclo [3.1.0] -2-ene-hexane-6, 6-diacetate (11.2g, 40mmol) obtained in the above step and N, N-dimethylformamide (17.5g, 240mmol) were charged into a round-bottomed flask, and after replacing nitrogen gas, phosphorus oxychloride (42g, 280mmol) was added dropwise. After the completion of the dropwise addition, the mixture was heated to 100 ℃ and stirred for 24 hours. Cooling to room temperature, and directly separating and purifying by column chromatography to obtain the chloropyridine diester derivative shown in formula (5).
1.7
Figure BDA0003381016020000132
The chloropyridine diester derivative of formula (5) (4.8 g,15.8 mmol) obtained in the previous step was dissolved in 80mL of tetrahydrofuran and sufficiently stirred at 0 ℃. Diisobutylaluminum hydride (1.5M in toluene, 63mL, 95mmol) was diluted to 1M with 32mL of tetrahydrofuran, and then slowly added dropwise to the reaction solution. After the addition was complete, the reaction mixture was slowly warmed to room temperature and stirring was continued for 2 hours. After completion of the reaction, the reaction mixture was quenched by slowly dropping distilled water under cooling in an ice-water bath, extracted with dichloromethane, and then the organic phases were combined and the solvent was removed by rotary evaporation. The crude reaction product is subjected to silica gel column chromatography to obtain the chloropyridine diol derivative shown in the formula (6).
1.8
Figure BDA0003381016020000133
Phenyl is exemplified as the substituent in this step. Taking the chloropyridine diol derivative of formula (6) (450mg, 2mmol), benzophenone dimethyl ketal (3.0 equiv), p-toluenesulfonic acid (5 mol%), stannous chloride (5 mol%) and
Figure BDA0003381016020000142
molecular sieves (400mg, 200mg/mmol) and dry 1, 2-dichloroethane (1.0M) were added. The reaction mixture was stirred at 100 ℃ for 24 hours. After completion of the reaction, the reaction mixture was filtered to collect the filtrate, and the solvent was distilled off under reduced pressure. The crude reaction product was subjected to silica gel column chromatography to isolate the chloropyridine derivative of formula (7-Ph).
1.9
Figure BDA0003381016020000141
Manganese powder (440mg, 8mmol) and nickel dichloride triphenylphosphine complex (131mg, 0.2mmol) were added to N, N-dimethylformamide (15 mL), and the mixture was heated to 70 ℃ and stirred for 2 hours. After the color was observed to turn green, the chloropyridine derivative represented by the formula (7-Ph) (778mg, 2mmol) was dissolved in N, N-dimethylformamide (3 mL), and the chloropyridine derivative represented by the formula (7-Ph) was added dropwise to the reaction system and stirred for 36 hours. Filtering after the reaction is finished, combining organic phases, drying by using anhydrous sodium sulfate, filtering, decompressing and concentrating, and separating and purifying the obtained crude product by using column chromatography to obtain the chiral 2,2' -bipyridyl ligand Ph-Sbpy of the formula (1) with the R group being phenyl. Preparation of the resulting chiral 2,2' -bipyridyl ligand Ph-Sbpy 1 The H NMR spectrum is shown in FIG. 1.
Example 2
Synthesis of chiral 2,2' -bipyridine ligand:
2.1
Figure BDA0003381016020000151
the reaction time of 1.1 in example 1 was shortened to 2 hours, and the reaction results were the same under the same conditions.
2.2
Figure BDA0003381016020000152
The reaction stirring time of 1.2 in example 1 was shortened to 12 hours, and the reaction results were the same under the same conditions.
2.3
Figure BDA0003381016020000153
The reaction stirring time of 1.3 in example 1 was shortened to 12 hours, and the reaction results were the same under the same conditions.
2.4
Figure BDA0003381016020000154
The reaction time was shortened to 6 hours by replacing ethyl (1S, 5R) -2-oxobicyclo [3.1.0] hexane-6, 6-diacetate in the reaction of 1.4 in example 1 with ethyl (1R, 5S) -2-oxobicyclo [3.1.0] hexane-6, 6-diacetate, and the other conditions were the same, whereby ethyl (1R, 5S) -2-isonitrosobicyclo [3.1.0] hexane-6, 6-diacetate, which is a crude product, was obtained.
2.5
Figure BDA0003381016020000161
(1S, 5R) -2-isonitrosobicyclo [3.1.0] hexane-6, 6-diacetic acid ethyl ester in the 1.5 reaction in example 1 was replaced with (1R, 5S) -2-isonitrosobicyclo [3.1.0] hexane-6, 6-diacetic acid ethyl ester obtained in the 2.4 step, and the remaining conditions were the same to obtain (1R, 5S) -2-acetamidobicyclo [3.1.0] -2-ene-hexane-6, 6-diacetic acid ethyl ester.
2.6
Figure BDA0003381016020000162
Ethyl (1R, 5S) -2-acetylaminobicyclo [3.1.0] -2-ene-hexane-6, 6-diacetate (11.2g, 40mmol) obtained in the above step and N, N-dimethylformamide (17.5g, 240mmol) were charged into a round-bottomed flask, and after replacing nitrogen gas, phosphorus oxychloride (42g, 280mmol) was added dropwise. After the completion of the dropwise addition, the mixture was heated to 100 ℃ and stirred for 16 hours. Cooling to room temperature, and directly separating and purifying by column chromatography to obtain the chloropyridine diester derivative formula (5').
2.7
Figure BDA0003381016020000163
The chloropyridine diester derivative of formula (5') (4.8 g,15.8 mmol) obtained in the previous step was dissolved in 80mL of tetrahydrofuran and sufficiently stirred at 0 ℃. Diisobutylaluminum hydride (1.5M in toluene, 63mL, 95mmol) was diluted to 1M with 32mL of tetrahydrofuran, and then slowly added dropwise to the reaction solution. After the addition was complete, the reaction mixture was slowly warmed to room temperature and stirring was continued for 2 hours. After completion of the reaction, the reaction mixture was quenched by slowly dropping distilled water under cooling in an ice-water bath, extracted with dichloromethane, and then the organic phases were combined and the solvent was distilled off under reduced pressure. The crude reaction product is separated by silica gel column chromatography to obtain the chloropyridine diol derivative formula (6').
2.8
Figure BDA0003381016020000171
Methyl groups are exemplified as substituents in this step. Collecting chloropyridine diol derivative (6') (450mg, 2mmol), 2-dimethoxypropane (3.0 equiv), p-toluenesulfonic acid (5 mol%), stannous chloride(5 mol%) and
Figure BDA0003381016020000173
molecular sieves (400mg, 200mg/mmol) and dry 1, 2-dichloroethane (1.0M) were added. The reaction mixture was stirred at 100 ℃ for 24 hours. After completion of the reaction, the reaction mixture was filtered to collect the filtrate, and the solvent was distilled off under reduced pressure. The crude reaction product was subjected to silica gel column chromatography to isolate the chloropyridine derivative of formula (7' -Me).
2.9
Figure BDA0003381016020000172
Manganese powder (440mg, 8mmol) and nickel dichloride triphenylphosphine complex (131mg, 0.2mmol) were added to N, N-dimethylformamide (15 mL), and the mixture was heated to 70 ℃ and stirred for 2 hours. After the color was observed to turn green, the chloropyridine derivative of formula (7' -Me) (531mg, 2mmol) was dissolved in N, N-dimethylformamide (3 mL), and the chloropyridine derivative of formula (7-Ph) solution was added dropwise to the reaction system, followed by stirring for 36 hours. Filtering after the reaction is finished, combining organic phases, drying by using anhydrous sodium sulfate, filtering, decompressing and concentrating, and separating and purifying the obtained crude product by using column chromatography to obtain the chiral 2,2 '-bipyridyl ligand Me-Sbpy of the formula (1') with the R group being methyl. Preparation of the chiral 2,2' -bipyridyl ligand Me-Sbpy 1 The H NMR spectrum is shown in FIG. 2.
The following examples further illustrate the use of the invention and do not therefore limit the scope of the invention described.
Preparation of chiral diaryl methanol
Preparation of example 1
This example is for the preparation of (S) - (4-methoxyphenyl) -phenylmethanol, comprising in particular the following steps: nickel-ethylene-glycol-dimethyl-dibromide complex (7.0 mg,0.02mmol, 10mol%), ph-SBpy (17.0 mg,0.024mmol, 12mol%) and 2-methyltetrahydrofuran (0.5 mL) were mixed under argon and stirred at 33 ℃ for 1 hour. Tetrabutylammonium tetraphenylborate (28.0mg, 0.05mmol, 25mol%) and zinc powder (19.6mg, 0.3mmol, 1.5equiv) were added under protection of a nitrogen streamThe reaction solution was added and stirring was continued at 33 ℃ for 1 hour. After sufficient stirring, the reaction system was a dark blue-green mixture. Subsequently, benzaldehyde (0.2mmol, 1.0 equiv), 4-iodoanisole (0.5mmol, 2.5 equiv), 1, 4-dioxane (0.5 mL) and methylene chloride (0.1 mL) were added to the reaction system in this order, and the reaction mixture was left to stand at-30 ℃ for 24 hours with stirring. After the reaction was completed, the solvent was removed by a rotary evaporator, and the product was purified by a silica gel column chromatography method (using 200-300 mesh size silica gel, the mass ratio of silica gel to the substance to be purified was 50-100, the eluent was petroleum ether and ethyl acetate, and the volume ratio was 5-10) to obtain ((S) - (4-methoxyphenyl) -phenylmethanol (88% yield, 91% ee). 1 H NMR(400MHz,CDCl 3 )δ7.21–7.39(m,2H),6.85(d,J＝8.4Hz,2H),5.79(s,1H),3.78(s,3H),2.25(s,1H). 13 C NMR(100MHz,CDCl 3 )δ159.0,144.0,136.2,128.5,127.9,127.4,126.4,113.9,75.8,55.3.
Preparation of example 2
The reaction was carried out under the same conditions except for using 4-methylbenzaldehyde instead of benzaldehyde in preparation example 1 to give (S) - (4-methoxyphenyl) - (4-methylphenyl) -methanol (92% yield, 88% ee). 1 H NMR(400MHz,CDCl 3 )δ7.28-7.23(m,4H),7.14(d,J＝8.0Hz,2H),6.85(d,J＝8.4Hz,2H),5.76(d,J＝1.6Hz,1H),3.78(s,3H),2.32(s,3H),2.18(d,J＝3.2Hz,1H). 13 C NMR(100MHz,CDCl 3 )δ159.0,141.2,137.1,136.4,129.2,127.8,126.4,113.8,75.7,55.3,21.1.
Preparation of example 3
The reaction was carried out under the same conditions except for using 4-t-butyliodobenzene instead of 4-iodoanisole in production example 1 to give (S) - (4-t-butylphenyl) -phenylmethanol (91% yield, 88% ee). 1 H NMR(400MHz,CDCl 3 )δ7.51–7.08(m,9H),5.72(s,1H),2.21(s,1H),1.22(s,9H). 13 C NMR(100MHz,CDCl 3 )δ150.5,143.9,140.9,128.5,127.5,126.5,126.3,125.5,76.1,34.5,31.4.
Preparation of example 4
The reaction was carried out under the same conditions except for using 2-methoxyiodobenzene instead of 4-iodoanisole in preparation example 1 to give (S) - (2-methylphenyl) -phenylmethanol (77% yield, 84% ee). 1 H NMR(400MHz,CDCl 3 )δ7.39(d,J＝7.6Hz,2H),7.32(t,J＝7.6Hz,2H),7.29–7.19(m,3H),6.94(t,J＝7.6Hz,1H),6.89(d,J＝8.0Hz,1H),6.05(d,J＝5.2Hz,1H),3.81(s,3H),3.06(d,J＝5.6Hz,1H). 13 C NMR(100MHz,CDCl 3 )δ156.8,143.2,131.9,128.8,128.2,127.9,127.2,126.6,120.8,110.8,72.3,55.4.
Preparation of chiral biaryl products
Preparation of example 5
This example is a preparation of (S) -5,5', 6' -tetramethoxy- [1,1' -biphenyl]-2,2' -dicarboxaldehyde, comprising in particular the following steps: 2-chloro-3, 4-dimethoxybenzaldehyde (0.1mmol, 1.0equiv), niCl, under argon 2 (PPh3) 2 (6.5mg, 0.01mmol, 10mol%), ph-SBpy (11.6mg, 0.01mmol, 10mol%), zinc powder (3.1mg, 0.2mmol, 2.0equiv) and TBAI (18.5mg, 0.05mmol, 0.5equiv) were mixed. Adding dry NMP, placing the mixture into an oil bath at 45 ℃ for heating and stirring for 16 hours, removing the solvent by using a rotary evaporator after the reaction is finished, purifying the product by using a silica gel column chromatography method (using 200-300 mesh silica gel, the mass ratio of the silica gel to the substance to be purified is 50-100, and an eluent is petroleum ether and ethyl acetate, and the volume ratio is 5-10)]-2,2' -diformaldehyde (92% yield, 91% ee). 1 H NMR(400MHz,CDCl 3 )δ9.55(s,2H),7.84(d,J＝8.6Hz,2H),7.12(d,J＝8.6Hz,2H),4.00(s,6H),3.60(s,6H). 13 C NMR(100MHz,CDCl 3 )δ190.1,157.7,146.7,131.5,128.6,126.1,112.1,60.6,56.1.
Preparation of example 6
Preparation of 2-chloro-3, 4-dimethoxybenzaldehyde in example 5 was replaced with 1-chloro-2-naphthaldehyde under the same conditions as above, and reacted to (R) - [1,1' -binaphthyl]-2,2' -dicarbaldehyde (81% yield, 86% ee). 1 H NMR(400MHz,CDCl 3 )δ9.62(s,2H),8.21(d,J＝8.6Hz,2H),8.13(d,J＝8.7Hz,2H),8.02(d,J＝8.2Hz,2H),7.64(t,J＝7.5Hz,2H),7.38(t,J＝7.7Hz,2H),7.24(d,J＝8.5Hz,2H). 13 C NMR(100MHz,CDCl 3 )δ191.2,139.8,136.1,133.6,133.4,129.9,129.6,128.7,128.1,127.4,122.5.
Preparation of example 7
By 1-chloro-6-cyclopropyl-2-Naphthalenealdehyde instead of 2-chloro-3, 4-dimethoxybenzaldehyde in preparation example 5, the same conditions were followed to react to give (R) -6,6 '-dicyclopropyl- [1,1' -binaphthyl]-2,2' -diformaldehyde (91% yield, 92% ee). 1 H NMR(400MHz,CDCl 3 )δ9.56(s,2H),8.14(d,J＝8.7Hz,2H),7.99(d,J＝8.7Hz,2H),7.66(d,J＝1.4Hz,2H),7.11(d,J＝8.8Hz,2H),7.04–7.01(m,2H),2.09–2.02(m,2H),1.12–1.05(m,4H),0.85–0.79(m,4H). 13 C NMR(100MHz,CDCl 3 )δ191.3,146.4,140.0,136.3,132.5,131.9,129.0,127.5,126.4,124.3,122.6,16.0,10.3,10.2.
The chiral diaryl carbinol and the chiral biaryl products obtained by the preparation method have higher yield and stereoselectivity. The product can be used for synthesizing intermediates of medicines/pesticides, and the preparation method can be used for preparing a plurality of similar products and has industrial application value.

Claims (10)

1. A chiral 2,2' -bipyridine ligand having the formula Ph-Sbpy or Me-Sbpy:
Figure FDA0003915193700000011
2. a process for the preparation of a chiral 2,2' -bipyridine ligand according to claim 1, comprising the steps of:
(1) Brominating 2-cyclopentene-1-one under the action of liquid bromine, and reacting with diethyl malonate to obtain a pair of enantiomers;
(2) Reacting the obtained enantiomer with (R) -tert-butyl sulfinamide and tetraethyl titanate, then separating and purifying the product to obtain sulfinyl imine, and then hydrolyzing with hydrochloric acid to obtain chiral ketone shown in formula (2) and/or formula (2');
Figure FDA0003915193700000012
(3) Placing chiral ketone shown in a formula (2) and hydroxylamine into ethanol for reaction to obtain oxime shown in a formula (3);
or, placing the chiral ketone shown in the formula (2 ') and hydroxylamine into ethanol for reaction to obtain oxime shown in the formula (3');
Figure FDA0003915193700000021
(4) Adding oxime shown in a formula (3) into toluene, and then adding iron powder, acetic anhydride and acetic acid to react to obtain amide shown in a formula (4);
or adding the oxime shown in the formula (3 ') into toluene, and then adding iron powder, acetic anhydride and acetic acid to react to obtain the amide shown in the formula (4');
Figure FDA0003915193700000022
(5) Dissolving amide shown in a formula (4) in N, N-dimethylformamide, then dropwise adding phosphorus oxychloride, and reacting to obtain a chloropyridine derivative shown in a formula (5);
or dissolving the amide shown in the formula (4 ') in N, N-dimethylformamide, and then dropwise adding phosphorus oxychloride to react to obtain the chloropyridine derivative shown in the formula (5');
Figure FDA0003915193700000023
(6) Dissolving the chloropyridine derivative shown in the formula (5) in tetrahydrofuran, and then dropwise adding the solution into a toluene solution of DIBAL-H at a temperature of between 20 ℃ below zero and 0 ℃ to react to obtain a diol derivative shown in the formula (6);
or dissolving the chloropyridine derivative shown in the formula (5 ') in tetrahydrofuran, and then dropwise adding the solution into a toluene solution of DIBAL-H at a temperature of between 20 ℃ below zero and 0 ℃ to react to obtain a diol derivative shown in the formula (6');
Figure FDA0003915193700000031
(7) Reacting the diol obtained in the formula (6) with p-toluenesulfonic acid, tin dichloride, a molecular sieve and benzophenone dimethyl ketal under the reflux condition of 1, 2-dichloroethane to obtain a ketal derivative shown in a formula (7-Ph);
or reacting the diol obtained in the formula (6 ') with 2, 2-dimethoxypropane, tin dichloride, a molecular sieve and p-toluenesulfonic acid under the reflux condition of 1, 2-dichloroethane to obtain a ketal derivative shown in a formula (7' -Me);
Figure FDA0003915193700000032
(8) Adding manganese powder, nickel chloride hexahydrate and triphenylphosphine into N, N-dimethylformamide, heating and stirring for 1 hour, then adding a chloropyridine derivative shown in a formula (7-Ph) or a formula (7 '-Me) dissolved in the N, N-dimethylformamide, and reacting to obtain the chiral 2,2' -bipyridyl ligand.
3. The method for preparing chiral 2,2' -bipyridine ligand according to claim 2, wherein the specific process of step (1) is as follows: under the protection of nitrogen, 2-cyclopentene-1-ketone and liquid bromine react in dichloromethane at 0 ℃ to room temperature for 4-8 hours to obtain 2-bromo-2-cyclopentene-1-ketone, the 2-bromo-2-cyclopentene-1-ketone and diethyl malonate react in 1, 2-dichloroethane solvent under the catalysis of alkali, the temperature is heated to 90 ℃ for 12-24 hours, and a pair of enantiomers are obtained by filtration and column chromatography separation.
4. The method for preparing chiral 2,2' -bipyridine ligand according to claim 2, wherein the step (3) comprises the following steps: placing the chiral ketone shown in the formula (2) or the formula (2 ') and hydroxylamine into an ethanol solution, heating, refluxing and stirring for 18-24 hours, then washing with water, extracting with dichloromethane, drying the obtained organic phase with anhydrous sodium sulfate, and removing the solvent to obtain the oxime shown in the formula (3) or the formula (3').
5. The method for preparing chiral 2,2' -bipyridine ligand according to claim 2, wherein the step (4) comprises the following steps: adding oxime shown in a formula (3) or a formula (3 ') into toluene, cooling to 0 ℃, adding iron powder, adding a mixture of acetic anhydride and acetic acid, heating to room temperature for reaction, stirring for 18-24 hours, filtering out the iron powder, adding an ammonium chloride aqueous solution, extracting by using ethyl acetate, and performing silica gel column chromatography separation to obtain amide shown in a formula (4) or a formula (4').
6. The method for preparing chiral 2,2' -bipyridine ligand according to claim 2, wherein the step (5) comprises the following steps: dissolving the amide shown in the formula (4) or the formula (4 ') in N, N-dimethylformamide, then dropwise adding phosphorus oxychloride in an ice bath, stirring at the temperature of 80-100 ℃ for 18-24 hours, and separating the mixture by using column chromatography to obtain the chloropyridine derivative shown in the formula (5) or the formula (5').
7. Use of the chiral 2,2' -bipyridine ligand of claim 1 as a catalyst ligand in the preparation of chiral diaryl methanol.
8. The use according to claim 7, comprising:
under the condition of argon, stirring and mixing a nickel dibromide ethylene glycol dimethyl ether complex, a chiral 2,2' -bipyridine ligand and 2-methyltetrahydrofuran at room temperature, adding zinc powder and sodium tetraphenyltetrafluoroborate, and continuously stirring and mixing at room temperature; adding aldehyde and aryl halide into a reaction system, and stirring the obtained reaction mixture at-30-0 ℃ for reaction; after the reaction is finished, removing the solvent; the obtained crude reaction product is separated and purified to obtain the chiral diaryl methanol.
9. Use of the chiral 2,2' -bipyridine ligand of claim 1 as a catalyst ligand in the preparation of chiral self-coupled diaryl compounds.
10. The use according to claim 9, comprising:
under the condition of argon, heating, stirring and mixing a nickel dichloride triphenylphosphine complex, a chiral 2,2' -bipyridine ligand and N, N-dimethylacetamide, adding manganese powder and aryl chloride, and stirring and reacting the obtained reaction mixture at 60-80 ℃; and after the reaction is finished, removing the solvent, and separating and purifying the obtained crude reaction product to obtain the chiral biaryl compound.
CN202111434132.1A 2021-11-29 2021-11-29 Chiral 2,2' -bipyridine ligand and preparation method and application thereof Active CN114014869B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202111434132.1A CN114014869B (en) 2021-11-29 2021-11-29 Chiral 2,2' -bipyridine ligand and preparation method and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202111434132.1A CN114014869B (en) 2021-11-29 2021-11-29 Chiral 2,2' -bipyridine ligand and preparation method and application thereof

Publications (2)

Publication Number Publication Date
CN114014869A CN114014869A (en) 2022-02-08
CN114014869B true CN114014869B (en) 2023-03-24

Family

ID=80067082

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202111434132.1A Active CN114014869B (en) 2021-11-29 2021-11-29 Chiral 2,2' -bipyridine ligand and preparation method and application thereof

Country Status (1)

Country Link
CN (1) CN114014869B (en)

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004269490A (en) * 2003-02-19 2004-09-30 Kyushu Univ Production method of optically active lactone compound
GB2456298A (en) * 2008-01-07 2009-07-15 Anthony Ian Newman Electroluminescent materials comprising oxidation resistant fluorenes
CN104496736B (en) * 2014-10-23 2016-09-28 北京理工大学 A kind of cross-coupling reaction based on rare earth compound and application
CN110128341B (en) * 2019-05-13 2020-08-18 西安交通大学 Chiral 2, 2' -bipyridyl ligand, preparation method thereof and application thereof in preparation of chiral cyclopropane derivative
CN112724168B (en) * 2020-12-29 2021-12-28 西安交通大学 Chiral pyridine derived N, B ligand, preparation method and application in iridium-catalyzed asymmetric boronation reaction

Also Published As

Publication number Publication date
CN114014869A (en) 2022-02-08

Similar Documents

Publication Publication Date Title
CN108069934B (en) Method for preparing polyaromatic substituted naphthalene derivative by reaction of biphenyl type arone and tolane catalyzed by ruthenium
CN114409515B (en) Preparation method of gem-difluoroolefin compound
CN110483252B (en) Method for synthesizing asymmetric triarylmethane derivative
CN100482644C (en) Chiral diene ligand, synthesis method and its application in asymmetric reaction
CN110128341B (en) Chiral 2, 2' -bipyridyl ligand, preparation method thereof and application thereof in preparation of chiral cyclopropane derivative
CN111925356B (en) Synthesis method and application of chiral quinoline-imidazoline ligand
CN114014869B (en) Chiral 2,2' -bipyridine ligand and preparation method and application thereof
CN105504305B (en) One kind contains 3（4 pyridines）Coordination polymer of pyrazoles propionic acid and preparation method thereof, purposes
CN111995554A (en) Method for preparing asymmetric organic selenium ether compound by metal-free chemical oxidation method
CN114768866B (en) Chiral deuterated Maruoka phase transfer catalyst, preparation method thereof and application thereof in asymmetric catalytic reaction
CN111848480A (en) Method for synthesizing aryl difluoromethyl seleno ether from arylboronic acid and application thereof
CN116178336A (en) Method for synthesizing N-aryl ketimine by acid catalytic ketal method and application
CN112920072B (en) NOBIN biaryl compound and synthetic method thereof
CN112979523B (en) Preparation method of chiral 1, 4-diphenyl-2-hydroxy-1, 4-dibutyl ketone compound
CN102491888B (en) Acyl-substituted triptycene and preparation method thereof
CN112299981B (en) Preparation method of alpha, alpha-difluoroketone derivative
CN111116450B (en) Axial chiral naphthylamine squaramide organic catalyst, and preparation method and application thereof
CN105209435A (en) Pyridine- or pyrazine-containing compounds
CN110437277B (en) Synthetic method of phosphoalkenyl ester compound
CN114644663A (en) Chiral tridentate nitrogen phosphine ligand and application thereof in asymmetric hydrogenation reaction of ketone
CN109666041A (en) The chiral monophosphorus ligand HP-Phos and preparation method and application of a kind of hexichol ether skeleton
CN117720537B (en) Axial chiral indole-furan catalyst and preparation method and application thereof
CN111732508B (en) Synthesis method of spiro compound
CN107892669A (en) A kind of method by reacting synthesis of quinoline derivatives by means of hydrogen
CN114736108B (en) Allyl carbonyl enol compound and synthesis method thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant