CN114014869A - 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

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CN114014869A
CN114014869A CN202111434132.1A CN202111434132A CN114014869A CN 114014869 A CN114014869 A CN 114014869A CN 202111434132 A CN202111434132 A CN 202111434132A CN 114014869 A CN114014869 A CN 114014869A
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李鹏飞
欧阳彝钊
张帅
茜姆勃玟
宋沛东
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Xian Jiaotong University
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Abstract

The invention provides a chiral 2,2 '-bipyridine ligand and a preparation method and application thereof, wherein the chiral 2,2' -bipyridine ligand is simple as shown in the formula(1) Or a compound represented by the 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 left in the aspects of exploring the mysterious and evolutionary mechanisms of life origin and operation, and developing drugs, pesticides, biological detection reagents, biomimetic 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 reaction, enzyme catalytic reaction and organic small molecule catalytic reaction are three ways of constructing chiral molecules, and transition metal catalysis is the most widely studied and applied type. 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 depend on chiral skeletons 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 for chiral 2, 2-bipyridine type ligands, the development is more slow. Therefore, it is of far-reaching significance 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' -bipyridyl ligand and a preparation method and application thereof, wherein the ligand has low synthesis raw material cost, is simple and easy to obtain, and is convenient to synthesize.
The invention is realized by the following technical scheme:
a chiral 2,2 '-bipyridine ligand has a structural formula shown as 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 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);
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, stannous chloride, 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 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' -bipyridyl 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' -bipyridyl ligand has the advantages of low raw material cost, 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 raw material cost, 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) R in example 1 of the present invention are phenyl-substituted1H NMR spectrum.
FIG. 2 shows that the chiral 2,2 '-bipyridine ligand of formula (1') R in example 2 of the present invention is methyl-substituted1H 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-one and diethyl malonate react in 1, 2-dichloroethane to obtain one pair of enantiomers.
The second step is that: the obtained enantiomer is stirred with (R) -tert-butyl sulfinamide and a certain amount of tetraethyl titanate in 1, 2-dichloroethane at 90 ℃ overnight, and then the product is separated and purified by using a silica gel chromatographic column to obtain optically pure sulfinyl imine. 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 the formula (5) or the 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 protected by different substituents, 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 ligands shown in the formula (1) or the 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 nickel dibromide ethylene glycol dimethyl ether complex, chiral 2,2 '-bipyridine ligand of formula (1) or 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 is1Represents an aromatic ring, a substituted aromatic ring or a naphthalene ring, R2Represents 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 the condition of argon, adding nickel dichloride triphenylphosphine complex, chiral 2,2 '-bipyridyl ligand of formula (1) or formula (1') and N, N-dimethylacetamide, stirring at 60 ℃ for 1 hour, adding manganese powder and aryl chloride, and placing the reaction mixture at 60-80 ℃ for stirring for 24-48 hours. 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 is3Represents 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 Dichloromethane (DCM) and Br was added at 0 deg.C2(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 10 min. Adding Et3Dissolving N in 60mL of DCM, quickly dropwise adding the N into the system through a constant-pressure dropping funnel (about 10min), stirring the system at room temperature for 4h after the addition is finished, adding a saturated ammonium chloride aqueous solution (20mL) to quench the reaction, extracting the combined organic phase for 3 times by using 50-60mL of DCM each time, drying the combined organic phase by using anhydrous sodium sulfate, filtering and concentrating under reduced pressure, and separating and purifying the obtained crude product by using column chromatography to obtain the 2-bromo-2-cyclopentene-1-one.
1.2
Figure BDA0003381016020000111
2-bromo-2-cyclopenten-1-one (240mmol, 1.0equiv), 39g diethyl malonate (480mmol,2.0equiv), 15.6g tetrahexylammonium bromide (36mmol, 15 mol%) and 200g potassium carbonate (1440mmol, 6.0equiv) were added to 240mL 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 subjected to silica gel column chromatography to separate a group of mixed enantiomer products of (1R,5S) -2-oxobicyclo [3.1.0] hexane-6, 6-diacetic acid ethyl ester and (1S,5R) -2-oxobicyclo [3.1.0] hexane-6, 6-diacetic acid ethyl ester.
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 (75mL) at 90 ℃ for 20 hours. And (3) cooling the materials to room temperature, adding saturated ammonium chloride aqueous solution (20mL) 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. The intermediate was hydrolyzed with an aqueous hydrochloric acid solution (20mL) to give 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 (3.6g, 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. The system is cooled to room temperature, 20mL of water is added, and the mixture is extracted 3 times with 20-30mL of dichloromethane each time, the organic phases are combined and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain a crude product of (1S,5R) -2-isonitrobicyclo [3.1.0] hexane-6, 6-diacetic acid ethyl ester.
1.5
Figure BDA0003381016020000122
Ethyl (1S,5R) -2-isonitrobicyclo [3.1.0] hexane-6, 6-diacetate (2.5g, 10mmol) obtained in the previous step was dissolved in toluene (20mL) and iron powder (3.35g, 60mmol) was added and 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. Stirring for 18-24 hr, adding saturated ammonium chloride aqueous solution (20mL), quenching, extracting with 20-30mL ethyl acetate for 3 times, mixing 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-ene-hexane-6, 6-diacetic acid ethyl ester.
1.6
Figure BDA0003381016020000131
Ethyl (1S,5R) -2-acetamido-bicyclo [3.1.0] -2-ene-hexane-6, 6-diacetate (11.2g, 40mmol) obtained in the previous step and N, N-dimethylformamide (17.5g, 240mmol) were taken out of the round-bottomed flask, and after nitrogen gas was replaced, 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) (4.8g, 15.8mmol) 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 obtained in the previous step of formula (6) (450mg, 2mmol), benzophenone dimethyl ketal (3.0equiv), p-toluenesulfonic acid (5 mol%), stannous chloride (5 mol%) and
Figure BDA0003381016020000142
molecular sieves (400mg, 200mg/mmol) were added dry 1, 2-dichloroethane (1.0M). 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 is subjected to silica gel column chromatography to separate chloropyridine derivativesFormula (7-Ph).
1.9
Figure BDA0003381016020000141
Manganese powder (440mg, 8mmol) and nickel dichloride triphenylphosphine complex (131mg, 0.2mmol) were added to N, N-dimethylformamide (15mL), and then heated to 70 ℃ and stirred for 2 hours. After the color was observed to turn green, the chloropyridine derivative of formula (7-Ph) (778mg, 2mmol) was dissolved in N, N-dimethylformamide (3mL), and the chloropyridine derivative of formula (7-Ph) solution was added dropwise to the above reaction system, followed by stirring for 36 hours. And filtering after the reaction is finished, combining organic phases, drying by using anhydrous sodium sulfate, filtering, and concentrating under reduced pressure to obtain a crude product, and separating and purifying 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 chiral 2,2' -bipyridyl ligand Ph-Sbpy1The 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, 5S) -2-oxobicyclo [3.1.0] hexane-6, 6-diacetate with ethyl (1R,5S) -2-oxobicyclo [3.1.0] hexane-6, 6-diacetate in the reaction of 1.4 in example 1, and the same conditions were applied to obtain ethyl (1R,5S) -2-isonitrosobicyclo [3.1.0] hexane-6, 6-diacetate as a crude product.
2.5
Figure BDA0003381016020000161
(1S, 5S) -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-isonitrobicyclo [3.1.0] hexane-6, 6-diacetic acid ethyl ester obtained in the 2.4 step, and the same conditions were used 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-acetamido-bicyclo [3.1.0] -2-ene-hexane-6, 6-diacetate (11.2g, 40mmol) obtained in the previous step and N, N-dimethylformamide (17.5g, 240mmol) were taken out of the round-bottomed flask, and after nitrogen gas was replaced, 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') (4.8g, 15.8mmol) obtained in the previous step was dissolved in 80mL of tetrahydrofuran and stirred well 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. The chloropyridine diol derivatives obtained in the previous step, formula (6') (450mg, 2mmol), 2, 2-dimethoxypropane (3.0equiv), p-toluenesulfonic acid (5 mol%), stannous chloride (5 mol%) and
Figure BDA0003381016020000173
molecular sieves (400mg, 200mg/mmol) were added dry 1, 2-dichloroethane (1.0M). 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 (15mL), and then 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 (3mL), and the chloropyridine derivative was addedThe solution of the formula (7-Ph) was added dropwise to the above 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-Sbpy1The 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 dibromide ethylene glycol dimethyl ether complex (7.0mg, 0.02mmol,10 mol%), Ph-SBpy (17.0mg,0.024mmol,12 mol%) and 2-methyltetrahydrofuran (0.5mL) were combined under argon and stirred at 33 ℃ for 1 hour. Tetrabutylammonium tetraphenylborate (28.0mg,0.05mmol,25 mol%) and zinc powder (19.6mg,0.3mmol,1.5equiv) were added to the reaction solution under the protection of a nitrogen stream 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,1.0equiv), 4-iodoanisole (0.5mmol,2.5equiv), 1, 4-dioxane (0.5mL) and methylene chloride (0.1mL) 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, the solvent was removed by a rotary evaporator, and the product was purified by silica gel column chromatography (using 200-300 mesh silica gel, the mass ratio of silica gel to the substance to be purified was 50-100: 1, and the eluent was petroleum ether and ethyl acetate, and the volume ratio was 5-10: 1) to obtain ((S) - (4-methoxyphenyl) -phenylmethanol (88% yield, 91% ee).1H NMR(400MHz,CDCl3)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).13C NMR(100MHz,CDCl3)δ159.0,144.0,136.2,128.5,127.9,127.4,126.4,113.9,75.8,55.3.
Preparation of example 2
Replacement of the benzyl radical in preparation example 1 with 4-methylbenzaldehydeAldehyde, otherwise under the same conditions, gave (S) - (4-methoxyphenyl) - (4-methylphenyl) -methanol (92% yield, 88% ee).1H NMR(400MHz,CDCl3)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).13C NMR(100MHz,CDCl3)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-tert-butyliodobenzene instead of 4-iodoanisole in preparation example 1 to give (S) - (4-tert-butylphenyl) -phenylmethanol (91% yield, 88% ee).1H NMR(400MHz,CDCl3)δ7.51–7.08(m,9H),5.72(s,1H),2.21(s,1H),1.22(s,9H).13C NMR(100MHz,CDCl3)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 using 2-methoxyiodobenzene instead of 4-iodoanisole in preparation example 1 to give (S) - (2-methylphenyl) -phenylmethanol (77% yield, 84% ee).1H NMR(400MHz,CDCl3)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).13C NMR(100MHz,CDCl3)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',6,6' -tetramethoxy- [1,1' -biphenyl]-2,2' -dicarboxaldehyde, comprising in particular the following steps: 2-chloro-3, 4-dimethoxybenzaldehyde (0.1mmol,1.0equiv), NiCl, under argon2(PPh3)2(6.5mg,0.01mmol,10 mol%), Ph-SBpy (11.6mg,0.01mmol,10 mol%), zinc powder (3.1mg,0.2mmol,2.0equiv) and TBAI (18.5mg,0.05mmol,0.5equiv) were mixed. Adding dry NMP, heating in 45 deg.C oil bath, stirring for 16 hr, removing solvent with rotary evaporator, and performing silica gel column chromatography (using 200-300 mesh silica gel)And (3) glue, wherein the mass ratio of the silica gel to the substance to be purified is 50-100: 1, eluent is petroleum ether and ethyl acetate, and the volume ratio is 5-10: 1) purifying the product to obtain (S) -5,5',6,6' -tetramethoxy- [1,1' -biphenyl]-2,2' -dicarboxaldehyde (92% yield, 91% ee).1H NMR(400MHz,CDCl3)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).13C NMR(100MHz,CDCl3)δ190.1,157.7,146.7,131.5,128.6,126.1,112.1,60.6,56.1.
Preparation of example 6
The 1-chloro-2-naphthaldehyde was used in place of the 2-chloro-3, 4-dimethoxybenzaldehyde of preparation example 5, under otherwise identical conditions, to react to (R) - [1,1' -binaphthyl]-2,2' -dicarboxaldehyde (81% yield, 86% ee).1H NMR(400MHz,CDCl3)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).13C NMR(100MHz,CDCl3)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
The 1-chloro-6-cyclopropyl-2-naphthaldehyde was used in place of the 2-chloro-3, 4-dimethoxybenzaldehyde of preparation example 5, and the reaction was carried out under the same conditions as for (R) -6,6 '-bicyclopropyl- [1,1' -binaphthyl ] -aldehyde]-2,2' -dicarboxaldehyde (91% yield, 92% ee).1H NMR(400MHz,CDCl3)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).13C NMR(100MHz,CDCl3)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 is characterized in that the structural formula is shown as a formula (1) or a formula (1'):
Figure FDA0003381016010000011
wherein R is aryl or alkyl.
2. A process for the preparation of chiral 2,2' -bipyridine ligands of 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 FDA0003381016010000012
(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 FDA0003381016010000021
(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 FDA0003381016010000022
(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 FDA0003381016010000023
(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 low temperature 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 low temperature to react to obtain a diol derivative shown in the formula (6');
Figure FDA0003381016010000031
(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, stannous chloride, 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 FDA0003381016010000032
(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.
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 diarylmethanol.
8. The use according to claim 7, comprising:
under the condition of argon, stirring and mixing a nickel dibromide 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 a 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.
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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1449840A1 (en) * 2003-02-19 2004-08-25 Kyushu University Method of producing optically active lactone compound
WO2009087364A1 (en) * 2008-01-07 2009-07-16 Lomox Limited Electroluminescent materials
CN104496736A (en) * 2014-10-23 2015-04-08 北京理工大学 Rare earth metal compound-based cross-coupling reaction and use thereof
CN110128341A (en) * 2019-05-13 2019-08-16 西安交通大学 A kind of chiral 2,2 '-bipyridine ligand and preparation method thereof and preparing the application in chiral cyclopropane derivative
CN112724168A (en) * 2020-12-29 2021-04-30 西安交通大学 Chiral pyridine derived N, B ligand, preparation method and application in iridium-catalyzed asymmetric boronation reaction

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1449840A1 (en) * 2003-02-19 2004-08-25 Kyushu University Method of producing optically active lactone compound
WO2009087364A1 (en) * 2008-01-07 2009-07-16 Lomox Limited Electroluminescent materials
CN104496736A (en) * 2014-10-23 2015-04-08 北京理工大学 Rare earth metal compound-based cross-coupling reaction and use thereof
CN110128341A (en) * 2019-05-13 2019-08-16 西安交通大学 A kind of chiral 2,2 '-bipyridine ligand and preparation method thereof and preparing the application in chiral cyclopropane derivative
CN112724168A (en) * 2020-12-29 2021-04-30 西安交通大学 Chiral pyridine derived N, B ligand, preparation method and application in iridium-catalyzed asymmetric boronation reaction

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
ALAKESH, B. ET AL.: "Benzenecarboperoxoic acid, 1, 1-dimethylethyl Ester", 《E-EROS ENCYCLOPEDIA OF REAGENTS FOR ORGANIC SYNTHESIS》 *
YIZHAO OUYANG ET AL.: "Z-bpy, a new C2-symmetric bipyridine ligand and its application in enantioselective copper(I)-catalyzed cyclopropanation of olefins", 《CHIN. J. CHEM.》 *
ZHANG, SHUAI ET AL.: "Design and Synthesis of Tunable Chiral 2,2"-Bipyridine Ligands:Application to the Enantioselective Nickel-Catalyzed Reductive Arylation of Aldehydes", 《ANGEWANDTE CHEMIE, INTERNATIONAL EDITION》 *

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