2, 2apos, which is precisely regulated and controlled in chirality; synthesis process of-[[(1S, 2S)-1, 2-(-)-1, 2-(-)]-di [6-(1, 1-(-)] phenol
By introducing chiral ligands into the synthesis process, the formation and configuration of chiral centers are accurately controlled, and the problem of difficult products with high optical purity in traditional synthesis methods is solved, and the products with precise chiral regulation and high optical purity are achieved, meeting the strict requirements in the fields of materials science and medicinal chemistry.
Patent Information
- Application Number
- CN202411985721.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-31
- Publication Date
- 2025-05-06
AI Technical Summary
Traditional synthesis methods have difficulty in precise control of chirality and cannot meet the needs of high optical purity products, especially in the fields of materials science and medicinal chemistry for specific chiral compounds.
Using 3-aminopyridine as the starting material, chiral ligand is introduced in the reaction step, and the complex structure of the target compound is gradually constructed through a series of organic reactions to ensure the accurate transmission and maintenance of chirality throughout the synthesis process.
Accurate chiral regulation is achieved, ensuring high optical purity of the product, meeting the strict requirements for specific chiral compounds in the fields of materials science and medicinal chemistry, and improving the selectivity and yield of the reaction.
Abstract
Description
Technical Field
[0001] The present invention relates to a chirality-precisely controlled synthesis process of 2,2'-[((1S,2S)-1,2-diphenyl-1,2-ethylene-bisiminoethyl)]-bis[6-(1,1-dimethylethyl)]phenol (abbreviation: 2,2'-[[(1S,2S)-1,2 - (-) - 1,2 -(-)]-bis[6-(1,1 - (-)] phenol). Background Art
[0002] 2,2'-[((1S,2S)-1,2-diphenyl-1,2-ethylene-bis-iminoethyl)]-bis[6-(1,1-dimethylethyl)]phenol is an organic compound with a unique structure and potential application value. In the field of materials science, its special molecular structure gives the material good optical, electrical and thermal properties, and can be used to prepare high-performance optical materials, electronic devices and thermally stable materials. In pharmaceutical chemistry, the specific structure of the compound may give it certain biological activities, such as antibacterial, antiviral, and antitumor, providing a potential lead compound for the development of new drugs.
[0003] Traditional synthesis methods face challenges in precisely controlling chirality and are unable to meet the demands of specific applications for products with high optical purity. Chiral boron-binding ligands have unique structures and properties and can provide an efficient chiral induction environment for chiral synthesis, thus helping to achieve precise control of the chirality of target compounds. Summary of the invention
[0004] In view of the deficiencies in the prior art, the present invention provides a synthesis process for 2,2'-[((1S,2S)-1,2-diphenyl-1,2-ethylene-bisiminoethyl)]-bis[6-(1,1-dimethylethyl)]phenol with precise chirality control.
[0005] To achieve the above-mentioned purpose, the present invention provides the following technical scheme: a chirality-precisely controlled 2,2'-[((1S,2S)-1,2-diphenyl-1,2-ethylene-bis-iminoethyl)]-bis[6-(1,1-dimethylethyl)]phenol synthesis process, using 3-aminopyridine as a starting material, introducing a chiral boron ligand in the reaction step, utilizing the specific interaction between the ligand and the reactants and the catalyst, precisely controlling the formation and configuration of the chiral center, and gradually constructing the complex structure of the target compound through a series of organic reactions, while ensuring the accurate transfer and maintenance of chirality in the entire synthesis process; Step 1, protecting the amino group of 3-aminopyridine; Step 2: Chlorination reaction involving chiral boron-linked ligand; Step 3, deprotection reaction of N-Boc-2-chloro-3-aminopyridine; Step 4: chiral matching condensation reaction with (1S,2S)-1,2-diphenyl-1,2-ethylenediamine; Step 5: Chiral-maintaining coupling reaction with 6-tert-butylphenol.
[0006] Preferably, the specific operation of step one is: Dissolve 3-aminopyridine (10 g, 0.109 mol) in 100 mL of dry dichloromethane, add di-tert-butyl dicarbonate (24.7 g, 0.114 mol) and triethylamine (11.1 g, 0.109 mol), and stir at room temperature for 4 hours; After the reaction, the reaction solution was transferred to a separatory funnel and washed with 5% hydrochloric acid solution (2×50 mL), saturated sodium bicarbonate solution (2×50 mL) and saturated brine (50 mL) in sequence. The organic phase was separated and dried over anhydrous sodium sulfate. After filtration, the solvent was removed by distillation under reduced pressure to obtain N-Boc-3-aminopyridine, which provided a stable amino protection form for subsequent reactions.
[0007] Preferably, the specific operation of step 2 is: dissolving N-Boc-3-aminopyridine (15 g, 0.072 mol) in 120 mL of carbon tetrachloride, adding a chiral boron ligand (0.5 g, the molar amount is determined according to the specific ligand), N-chlorosuccinimide (11 g, 0.082 mol) and azobisisobutyronitrile (AIBN, 0.1 g), stirring and reacting at 55 ° C for 10 hours under light conditions; After the reaction was completed, the mixture was cooled to room temperature, the insoluble matter was removed by filtration, the filtrate was distilled under reduced pressure to remove the solvent, and the obtained crude product was purified by column chromatography (petroleum ether: ethyl acetate = 4:1) to obtain N-Boc-2-chloro-3-aminopyridine, and its chiral purity was effectively controlled.
[0008] Preferably, in step 2, the chiral boron-linked ligand interacts with the active intermediate in the reaction system, and guides N-chlorosuccinimide to selectively chlorinate the pyridine ring through steric hindrance and electronic effects, while inducing the formation of a chiral center and controlling its configuration.
[0009] Preferably, the specific operation of step three is: dissolving N-Boc-2-chloro-3-aminopyridine (12 g, 0.051 mol) in 80 mL of 4M hydrochloric acid in dioxane solution, stirring at room temperature for 3 hours; After the reaction is completed, dioxane and excess hydrochloric acid are distilled off under reduced pressure, the residue is dissolved in water, the pH is adjusted to 8-9 with saturated sodium carbonate solution, and then extracted with dichloromethane (3×50 mL), the organic phases are combined, dried over anhydrous sodium sulfate, filtered, and the solvent is distilled off under reduced pressure to obtain 2-chloro-3-aminopyridine.
[0010] Preferably, the specific operation of step 4 is: add 2-chloro-3-aminopyridine (7 g, 0.05 mol), (1S, 2S)-1,2-diphenyl-1,2-ethylenediamine (4.5 g, 0.023 mol) and potassium carbonate (13.8 g, 0.1 mol) to 100 mL of ethanol, and heat under reflux for 12 hours; After the reaction, the mixture was cooled to room temperature, the insoluble matter was removed by filtration, and the filtrate was distilled under reduced pressure to remove ethanol. Water (50 mL) was added to the residue, and the mixture was extracted with dichloromethane (3×50 mL). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was distilled under reduced pressure to obtain 2,2'-[((1S,2S)-1,2-diphenyl-1,2-ethylene-bis(iminoethyl)]-bipyridine dichloride.
[0011] Preferably, in step 4, under alkaline conditions, the amino group of (1S,2S)-1,2-diphenyl-1,2-ethylenediamine performs nucleophilic substitution on the chlorine atom of 2-chloro-3-aminopyridine. Due to the chiral center introduced in the early stage and the chiral boron ligand-induced chiral environment, the reaction proceeds in a specific chiral matching manner, ensuring accurate chirality transfer.
[0012] Preferably, the specific operation of step 5 is: add 2,2'-[((1S,2S)-1,2-diphenyl-1,2-ethylene-bisiminoethyl)]-bipyridine dichloride (10 g, 0.018 mol), 6-tert-butylphenol (6 g, 0.036 mol), potassium carbonate (10 g, 0.072 mol), tetrakis(triphenylphosphine)palladium (Pd(PPh3)4, 0.6 g) and 150 mL of toluene into a reaction bottle, and heat under reflux for 24 hours under nitrogen protection; After the reaction is completed, the reaction mixture is cooled to room temperature, the insoluble matter is removed by filtration, the filtrate is washed with dilute hydrochloric acid (2×50 mL) and water (2×50 mL) in sequence, the organic phase is separated, and the mixture is dried over anhydrous sodium sulfate. After filtration, the solvent is removed by distillation under reduced pressure, and the mixture is purified by column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain high-purity and high-optical-purity 2,2'-[((1S,2S)-1,2-diphenyl-1,2-ethylene-bisiminoethyl)]-bis[6-(1,1-dimethylethyl)]phenol.
[0013] Preferably, in step five, under the action of a palladium catalyst, the phenol oxide anion of 6-tert-butylphenol undergoes a coupling reaction with 2,2'-[((1S,2S)-1,2-diphenyl-1,2-ethylene-bis(iminoethyl)]-bipyridine dichloride, and the chiral environment induced by the chiral boron ligand continues to play a role in this step, ensuring that the chirality does not change during the coupling process.
[0014] Compared with the prior art, the present invention provides a chirality-precisely controlled 2,2'-[((1S,2S)-1,2-diphenyl-1,2-ethylene-bis-iminoethyl)]-bis[6-(1,1-dimethylethyl)]phenol synthesis process, which has the following beneficial effects: 1. This chiral precisely controlled synthesis process of 2,2'-[((1S,2S)-1,2-diphenyl-1,2-ethylene-bis(iminoethyl)]-bis[6-(1,1-dimethylethyl)]phenol uses a chiral boron ligand. Since this ligand is prepared using the strategy of alkyl-substituted chiral diols and borate esters, it realizes the preparation of diaryl chiral diamines, which is highly efficient, low-cost, and green and environmentally friendly.
[0015] 2. This chiral precise control process for the synthesis of 2,2'-[((1S,2S)-1,2-diphenyl-1,2-ethylene-bis(iminoethyl)]-bis[6-(1,1-dimethylethyl)]phenol can precisely control the formation and configuration of the chiral center during the entire synthesis process by using a chiral boron ligand, ensuring that the final product has high optical purity and meets the strict requirements for specific chiral compounds in the fields of medicinal chemistry and materials science.
[0016] 3. This chiral precisely controlled synthesis process of 2,2'-[((1S,2S)-1,2-diphenyl-1,2-ethylene-bis(iminoethyl)]-bis[6-(1,1-dimethylethyl)]phenol protects the amino group of 3-aminopyridine, avoids possible side reactions such as oxidation and nucleophilic substitution of the amino group in subsequent reactions, ensures the selectivity of the reaction, and enables subsequent reactions to proceed along the expected path. The protected N-Boc-3-aminopyridine has better stability under different reaction conditions and can withstand subsequent more stringent reaction conditions, thereby improving the feasibility of the entire synthetic route.
[0017] 4. This chiral precisely controlled synthesis process of 2,2'-[((1S,2S)-1,2-diphenyl-1,2-ethylene-bis(iminoethyl)]-bis[6-(1,1-dimethylethyl)]phenol, the introduction of chiral boron ligands provides a chiral environment for the chlorination reaction, can selectively introduce chlorine atoms at specific positions on the pyridine ring, and precisely control the formation of chiral centers, laying the foundation for the subsequent transmission of chiral structures and improving the reaction selectivity: the chiral boron ligands interact with the active intermediates in the reaction system, guide the selectivity of the chlorination reaction through steric hindrance and electronic effects, reduce the occurrence of side reactions, and improve the yield and purity of the target product.
[0018] 5. This chiral precise control 2,2'-[((1S,2S)-1,2-diphenyl-1,2-ethylene-bis(iminoethyl)]-bis[6-(1,1-dimethylethyl)]phenol synthesis process connects 2-chloro-3-aminopyridine and (1S,2S)-1,2-diphenyl-1,2-ethylenediamine through a nucleophilic substitution reaction to form the core skeleton structure of the target product, which determines the basic structure and stereochemical characteristics of the product. Based on the chiral matching principle, during the reaction process, the chiral information is accurately transferred from the chiral center induced by the chiral boron ligand to the newly formed chemical bond, ensuring the continuation and maintenance of the chiral structure and further improving the optical purity of the product.
[0019] 6. This chiral precise control process for the synthesis of 2,2'-[((1S,2S)-1,2-diphenyl-1,2-ethylene-bis(iminoethyl)]-bis[6-(1,1-dimethylethyl)]phenol introduces 6-tert-butylphenol into the existing molecular skeleton through a palladium-catalyzed coupling reaction, ultimately completing the synthesis of the target product and achieving the expected molecular structure construction. In this step of the reaction, the chiral environment induced by the chiral boron ligand continues to play a role, ensuring that the chiral structure does not change during the coupling process, maintaining the high optical purity of the product, and meeting the strict requirements of chirality for specific applications. DETAILED DESCRIPTION
[0020] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.
[0021] A chiral precisely controlled synthesis process for 2,2'-[((1S,2S)-1,2-diphenyl-1,2-ethylene-bis-iminoethyl)]-bis[6-(1,1-dimethylethyl)]phenol, using 3-aminopyridine as the starting material, introducing a chiral biboron ligand in the reaction step, utilizing the specific interaction between the chiral biboron ligand and the reactants and catalysts to precisely control the formation and configuration of the chiral center, and gradually constructing the complex structure of the target compound through a series of organic reactions, while ensuring the accurate transfer and maintenance of chirality throughout the synthesis process; Step 1: Protection of the amino group of 3-aminopyridine; the specific operation is: Dissolve 3-aminopyridine (10 g, 0.109 mol) in 100 mL of dry dichloromethane, add di-tert-butyl dicarbonate (24.7 g, 0.114 mol) and triethylamine (11.1 g, 0.109 mol), and stir at room temperature for 4 hours; After the reaction, the reaction solution was transferred to a separatory funnel and washed with 5% hydrochloric acid solution (2×50 mL), saturated sodium bicarbonate solution (2×50 mL) and saturated brine (50 mL) in sequence. The organic phase was separated and dried over anhydrous sodium sulfate. After filtration, the solvent was removed by distillation under reduced pressure to obtain N-Boc-3-aminopyridine, which provided a stable amino protection form for subsequent reactions.
[0022] Step 2: Chlorination reaction involving chiral biboron ligand; the specific operation is as follows: dissolve N-Boc-3-aminopyridine (15 g, 0.072 mol) in 120 mL of carbon tetrachloride, add chiral biboron ligand (0.5 g, the molar amount is determined according to the specific ligand), N-chlorosuccinimide (11 g, 0.082 mol) and azobisisobutyronitrile (AIBN, 0.1 g), and stir the reaction at 55 ° C for 10 hours under light conditions; After the reaction was completed, the mixture was cooled to room temperature, the insoluble matter was removed by filtration, the filtrate was distilled under reduced pressure to remove the solvent, and the obtained crude product was purified by column chromatography (petroleum ether: ethyl acetate = 4:1) to obtain N-Boc-2-chloro-3-aminopyridine, and its chiral purity was effectively controlled.
[0023] The chiral boron-linked ligand interacts with the active intermediate in the reaction system, and through steric hindrance and electronic effects, guides N-chlorosuccinimide to selectively chlorinate the pyridine ring, while inducing the formation of a chiral center and controlling its configuration.
[0024] Step 3, deprotection reaction of N-Boc-2-chloro-3-aminopyridine; the specific operation is: dissolve N-Boc-2-chloro-3-aminopyridine (12 g, 0.051 mol) in 80 mL of 4M hydrochloric acid in dioxane solution, and stir at room temperature for 3 hours; After the reaction is completed, dioxane and excess hydrochloric acid are distilled off under reduced pressure, the residue is dissolved in water, the pH is adjusted to 8-9 with saturated sodium carbonate solution, and then extracted with dichloromethane (3×50 mL), the organic phases are combined, dried over anhydrous sodium sulfate, filtered, and the solvent is distilled off under reduced pressure to obtain 2-chloro-3-aminopyridine.
[0025] Step 4: chiral matching condensation reaction with (1S,2S)-1,2-diphenyl-1,2-ethylenediamine; the specific operation is: add 2-chloro-3-aminopyridine (7 g, 0.05 mol), (1S,2S)-1,2-diphenyl-1,2-ethylenediamine (4.5 g, 0.023 mol) and potassium carbonate (13.8 g, 0.1 mol) to 100 mL of ethanol, and heat under reflux for 12 hours; After the reaction, the mixture was cooled to room temperature, the insoluble matter was removed by filtration, and the filtrate was distilled under reduced pressure to remove ethanol. Water (50 mL) was added to the residue, and the mixture was extracted with dichloromethane (3×50 mL). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was distilled under reduced pressure to obtain 2,2'-[((1S,2S)-1,2-diphenyl-1,2-ethylene-bis(iminoethyl)]-bipyridine dichloride.
[0026] Under alkaline conditions, the amino group of (1S,2S)-1,2-diphenyl-1,2-ethylenediamine undergoes nucleophilic substitution for the chlorine atom of 2-chloro-3-aminopyridine. Due to the chiral center introduced earlier and the chiral boron ligand-induced chiral environment, the reaction proceeds in a specific chiral matching manner, ensuring accurate chirality transfer.
[0027] Step 5: chiral coupling reaction with 6-tert-butylphenol, specifically: add 2,2'-[((1S,2S)-1,2-diphenyl-1,2-ethylene-bisiminoethyl)]-bipyridine dichloride (10 g, 0.018 mol), 6-tert-butylphenol (6 g, 0.036 mol), potassium carbonate (10 g, 0.072 mol), tetrakis(triphenylphosphine)palladium (Pd(PPh3)4, 0.6 g) and 150 mL of toluene into a reaction bottle, and heat under reflux for 24 hours under nitrogen protection; After the reaction is completed, the reaction mixture is cooled to room temperature, the insoluble matter is removed by filtration, the filtrate is washed with dilute hydrochloric acid (2×50 mL) and water (2×50 mL) in sequence, the organic phase is separated, and the mixture is dried over anhydrous sodium sulfate. After filtration, the solvent is removed by distillation under reduced pressure, and the mixture is purified by column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain high-purity and high-optical-purity 2,2'-[((1S,2S)-1,2-diphenyl-1,2-ethylene-bisiminoethyl)]-bis[6-(1,1-dimethylethyl)]phenol.
[0028] Under the action of palladium catalyst, the phenol oxide anion of 6-tert-butylphenol undergoes a coupling reaction with 2,2'-[((1S,2S)-1,2-diphenyl-1,2-ethylene-bis(iminoethyl)]-bipyridine dichloride. The chiral environment induced by the chiral boron ligand continues to play a role in this step, ensuring that the chirality does not change during the coupling process.
[0029] Comparison table of traditional synthesis methods and synthesis methods using chiral boron ligands Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.
Claims
1. A chiral precision-controlled synthesis process of 2,2'-[[(1S,2S)-1,2 - (-) - 1,2 - (-)]-bis[6-(1,1 - (-)]phenol, characterized in that: Using 3-aminopyridine as the starting material, a chiral boron-linked ligand is introduced into the reaction step. The specific interaction between the ligand and the reactants and catalysts is utilized to precisely control the formation and configuration of the chiral center. Through a series of organic reactions, the complex structure of the target compound is gradually constructed, while ensuring the accurate transfer and maintenance of chirality throughout the synthesis process. Step 1, protecting the amino group of 3-aminopyridine; Step 2: Chlorination reaction involving chiral boron-linked ligand; Step 3, deprotection reaction of N-Boc-2-chloro-3-aminopyridine; Step 4: chiral matching condensation reaction with (1S,2S)-1,2-diphenyl-1,2-ethylenediamine; Step 5: Chiral-maintaining coupling reaction with 6-tert-butylphenol.
2. The chiral precisely controlled synthesis process of 2,2'-[[(1S,2S)-1,2 - (-) - 1,2 - (-)]-bis[6-(1,1 - (-)]phenol according to claim 1, characterized in that: The specific operation of step one is: Dissolve 3-aminopyridine (10 g, 0.109 mol) in 100 mL of dry dichloromethane, add di-tert-butyl dicarbonate (24.7 g, 0.114 mol) and triethylamine (11.1 g, 0.109 mol), and stir at room temperature for 4 hours; After the reaction, the reaction solution was transferred to a separatory funnel and washed with 5% hydrochloric acid solution (2×50 mL), saturated sodium bicarbonate solution (2×50 mL) and saturated brine (50 mL) in sequence. The organic phase was separated and dried over anhydrous sodium sulfate. After filtration, the solvent was removed by distillation under reduced pressure to obtain N-Boc-3-aminopyridine, which provided a stable amino protection form for subsequent reactions.
3. The process for synthesizing 2,2'-[[(1S,2S)-1,2 - (-) - 1,2 - (-)]-bis[6-(1,1 - (-)]phenol with precise chirality control according to claim 1, characterized in that: The specific operation of the step 2 is as follows: dissolve N-Boc-3-aminopyridine (15 g, 0.072 mol) in 120 mL of carbon tetrachloride, add a chiral boron ligand (0.5 g), N-chlorosuccinimide (11 g, 0.082 mol) and azobisisobutyronitrile (0.1 g), and react at 55° C. under light conditions for 10 hours with stirring; After the reaction is completed, the mixture is cooled to room temperature, the insoluble matter is removed by filtration, the filtrate is distilled under reduced pressure to remove the solvent, and the obtained crude product is purified by column chromatography to obtain N-Boc-2-chloro-3-aminopyridine, the chiral purity of which is effectively controlled.
4. The chiral precisely controlled synthesis process of 2,2'-[[(1S,2S)-1,2 - (-) - 1,2 - (-)]-bis[6-(1,1 - (-)]phenol according to claim 3, characterized in that: In the step 2, the chiral boron-linked ligand interacts with the active intermediate in the reaction system, and guides N-chlorosuccinimide to selectively chlorinate the pyridine ring through steric hindrance and electronic effects, while inducing the formation of a chiral center and controlling its configuration.
5. The chiral precisely controlled synthesis process of 2,2'-[[(1S,2S)-1,2 - (-) - 1,2 - (-)]-bis[6-(1,1 - (-)]phenol according to claim 1, characterized in that: The specific operation of step 3 is: dissolving N-Boc-2-chloro-3-aminopyridine (12 g, 0.051 mol) in 80 mL of 4 M hydrochloric acid in dioxane solution, stirring at room temperature for 3 hours; After the reaction is completed, dioxane and excess hydrochloric acid are distilled off under reduced pressure, the residue is dissolved in water, the pH is adjusted to 8-9 with saturated sodium carbonate solution, and then extracted with dichloromethane (3×50 mL), the organic phases are combined, dried over anhydrous sodium sulfate, filtered, and the solvent is distilled off under reduced pressure to obtain 2-chloro-3-aminopyridine.
6. The chiral precisely controlled synthesis process of 2,2'-[[(1S,2S)-1,2 - (-) - 1,2 - (-)]-bis[6-(1,1 - (-)]phenol according to claim 1, characterized in that: The specific operation of step 4 is: add 2-chloro-3-aminopyridine (7 g, 0.05 mol), (1S, 2S)-1,2-diphenyl-1,2-ethylenediamine (4.5 g, 0.023 mol) and potassium carbonate (13.8 g, 0.1 mol) into 100 mL of ethanol, and heat under reflux for 12 hours; After the reaction, the mixture was cooled to room temperature, the insoluble matter was removed by filtration, and the filtrate was distilled under reduced pressure to remove ethanol. Water (50 mL) was added to the residue, and the mixture was extracted with dichloromethane (3×50 mL). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was distilled under reduced pressure to obtain 2,2'-[((1S,2S)-1,2-diphenyl-1,2-ethylene-bis(iminoethyl)]-bipyridine dichloride.
7. The chiral precisely controlled synthesis process of 2,2'-[[(1S,2S)-1,2 - (-) - 1,2 - (-)]-bis[6-(1,1 - (-)]phenol according to claim 6, characterized in that: In the step 4, under alkaline conditions, the amino group of (1S,2S)-1,2-diphenyl-1,2-ethylenediamine performs nucleophilic substitution on the chlorine atom of 2-chloro-3-aminopyridine. Due to the chiral center introduced in the early stage and the chiral boron ligand-induced chiral environment, the reaction proceeds in a specific chiral matching manner, ensuring accurate chirality transfer.
8. The chiral precisely controlled synthesis process of 2,2'-[[(1S,2S)-1,2 - (-) - 1,2 - (-)]-bis[6-(1,1 - (-)]phenol according to claim 1, characterized in that: The specific operation of step 5 is: add 2,2'-[((1S,2S)-1,2-diphenyl-1,2-ethylene-bisiminoethyl)]-bipyridine dichloride (10 g, 0.018 mol), 6-tert-butylphenol (6 g, 0.036 mol), potassium carbonate (10 g, 0.072 mol), tetrakis(triphenylphosphine)palladium (0.6 g) and 150 mL of toluene into a reaction bottle, and heat under reflux for 24 hours under nitrogen protection; After the reaction is completed, the mixture is cooled to room temperature, the insoluble matter is removed by filtration, the filtrate is washed with dilute hydrochloric acid (2×50 mL) and water (2×50 mL) in sequence, the organic phase is separated, and the mixture is dried over anhydrous sodium sulfate. After filtration, the solvent is removed by distillation under reduced pressure, and the mixture is purified by column chromatography to obtain high-purity and high-optical-purity 2,2'-[((1S,2S)-1,2-diphenyl-1,2-ethylene-bisiminoethyl)]-bis[6-(1,1-dimethylethyl)]phenol.
9. The process for synthesizing 2,2'-[[(1S,2S)-1,2 - (-) - 1,2 - (-)]-bis[6-(1,1 - (-)]phenol with precise chirality control according to claim 1, characterized in that: In the step 5, under the action of a palladium catalyst, the phenol oxide anion of 6-tert-butylphenol undergoes a coupling reaction with 2,2'-[((1S,2S)-1,2-diphenyl-1,2-ethylene-bis(iminoethyl)]-bipyridine dichloride, and the chiral environment induced by the chiral boron ligand continues to play a role in this step, ensuring that the chirality does not change during the coupling process.