CN112812064B - Chiral dibenzo [ e, g ] [1,4] diazocine ligand and preparation method thereof - Google Patents

Chiral dibenzo [ e, g ] [1,4] diazocine ligand and preparation method thereof Download PDF

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CN112812064B
CN112812064B CN202110022559.4A CN202110022559A CN112812064B CN 112812064 B CN112812064 B CN 112812064B CN 202110022559 A CN202110022559 A CN 202110022559A CN 112812064 B CN112812064 B CN 112812064B
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CN112812064A (en
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朱强
罗宇
罗爽
王希龙
彭燕
王潮琴
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Guangzhou Institute of Biomedicine and Health of CAS
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
    • C07F9/6503—Five-membered rings
    • C07F9/6506—Five-membered rings having the nitrogen atoms in positions 1 and 3
    • C07F9/65068—Five-membered rings having the nitrogen atoms in positions 1 and 3 condensed with carbocyclic rings or carbocyclic ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6571—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms
    • C07F9/657154—Cyclic esteramides of oxyacids of phosphorus
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6571—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms
    • C07F9/6574—Esters of oxyacids of phosphorus
    • C07F9/65744—Esters of oxyacids of phosphorus condensed with carbocyclic or heterocyclic rings or ring systems

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Abstract

The application belongs to the technical field of organic molecules, and particularly relates to an organic compound and a preparation method thereof. The organic compound comprises chiral dibenzo [ e, g][1,4]The diazacyclooctatetraene skeleton has a structural general formula shown in formula I or formula II:R 1 、R 2 、R 3 、R 4 、R 5 and R is 6 Each independently selected from: at least one of hydrogen, hydroxy, amino, alkyl, methoxy, aryl, heteroaryl, alkenyl, alkynyl, alkylphosphorus, arylsilyl, phosphoxy, arylphosphoxy, halogen, thiourea; r is R 0 Selected from: at least one of aryl phosphorus group, alkyl phosphorus group, phosphoramidite group, phosphate group, dithiophosphate group, phosphoramide group, cyclopentadienyl group and quaternary ammonium salt. The organic compound has good structural stability, high derivative selectivity and flexible application, and can select substituents in a framework according to actual requirements to obtain a series of chiral ligands and catalysts.

Description

Chiral dibenzo [ e, g ] [1,4] diazocine ligand and preparation method thereof
Technical Field
The application belongs to the technical field of organic molecules, and particularly relates to an organic compound and a preparation method thereof.
Background
The existing classical axis chiral ligand frameworks are as follows: 1,1' -binaphthol (I), spiro-diphenol (II), 5', 6', 7', 8' -octahydro- [1,1' -binaphthyl ] -2,2' -diphenol (III), 2,2', 6' -substituted biphenyls (IV) and the like, and ether chains (V), biphenols of carbon chains (VI) and the like, have the following structural formula:
however, in the synthesis process of different asymmetric ligand skeleton catalysts, the ligand and substrate action modes are often unique and subtle, and little change of the ligand and the substrate can lead to abrupt change of product reactivity and selectivity, so that development and application of chiral ligand skeleton catalysts are limited.
Disclosure of Invention
The invention aims to provide an organic compound containing chiral dibenzo [ e, g ] [1,4] diazocine skeleton and a preparation method thereof, which aim to solve the technical problems that the existing chiral ligand skeleton has poor universality, the reactivity and selectivity of a product change suddenly due to a little change of a ligand and a substrate, and the chiral compound skeleton type is less.
In order to achieve the purposes of the application, the technical scheme adopted by the application is as follows:
in a first aspect, the present application provides an organic compound comprising a chiral dibenzo [ e, g ] [1,4] diazocine backbone, the organic compound having the general structural formula shown in formula I or formula II:
wherein R is 1 、R 2 、R 3 、R 4 、R 5 And R is 6 Each independently selected from: at least one of hydrogen, hydroxy, amino, alkyl, methoxy, aryl, heteroaryl, alkenyl, alkynyl, alkylphosphorus, arylsilyl, phosphoxy, arylphosphoxy, halogen, thiourea; r is R 0 Selected from: at least one of aryl phosphorus group, alkyl phosphorus group, phosphoramidite group, phosphate group, dithiophosphate group, phosphoramide group, cyclopentadienyl group and quaternary ammonium salt.
In a second aspect, the present application provides a method for preparing an organic compound, comprising the steps of:
dissolving a 1,1 '-biphenyl-2, 2' -diamine derivative, an benzil derivative and a chiral phosphoric acid catalyst in an organic solvent for catalytic reaction to obtain an organic compound containing a chiral dibenzo [ e, g ] [1,4] diazocine skeleton;
wherein the organic matter isThe structural general formula of the compound is shown in formula I or formula II: wherein R is 1 、R 2 、R 3 、R 4 、R 5 And R is 6 Each independently selected from: at least one of hydrogen, hydroxy, amino, alkyl, methoxy, aryl, heteroaryl, alkenyl, alkynyl, alkylphosphorus, arylsilyl, phosphoxy, arylphosphoxy, halogen, thiourea; r is R 0 Selected from: at least one of aryl phosphorus group, alkyl phosphorus group, phosphoramidite group, phosphate group, dithiophosphate group, phosphoramide group, cyclopentadienyl group and quaternary ammonium salt.
The organic compound provided in the first aspect of the present application comprises chiral dibenzo [ e, g][1,4]Diazacyclooctatetraene skeleton, and substituent R attached to the skeleton structure 0 、R 1 、R 2 、R 3 、R 4 、R 5 And R is 6 The skeleton is of a dibenzodiazocine structure, has good skeleton structure stability, high derivative selectivity and flexible application, and can be used for preparing R in a compound according to actual application requirements 0 、R 1 、R 2 、R 3 、R 4 、R 5 And R is 6 The substituents in the positions are selected to obtain a range of chiral ligands or catalysts having catalytic activity, such as: chiral phosphorus ligand, chiral phosphoramidite ligand, chiral phosphoric acid, chiral diene ligand, chiral phase transfer catalyst, chiral thiourea catalyst and the like, and the ligand and the catalyst compound are applied to different asymmetric synthesis reactions and all show excellent catalytic performance. In addition, the present application includes chiral dibenzo [ e, g][1,4]Organic compounds of the diazacyclooctatetraene backbone may also be applied to the synthesis of Metal Organic Framework (MOF) materials.
According to the preparation method of the organic compound, 1 '-biphenyl-2, 2' -diamine derivative and benzil derivative are dissolved in an organic solvent and reacted under the catalysis of a chiral phosphoric acid catalyst, so that the organic compound containing chiral dibenzo [ e, g ] [1,4] diazocine skeleton can be obtained. The preparation method of the organic compound containing chiral dibenzo [ e, g ] [1,4] diazocine skeleton has simple process and mild condition, and is suitable for large-scale production and application. And the prepared organic compound containing chiral dibenzo [ e, g ] [1,4] diazocine skeleton has good structural stability, high catalytic activity and wide application range.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present application, the following description will briefly introduce the drawings that are needed in the embodiments or the description of the prior art, it is obvious that the drawings in the following description are only some embodiments of the present application, and that other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of a compound (R) -3 provided in the examples of the present application;
FIG. 2 is a nuclear magnetic resonance hydrogen spectrum of compound A provided in the examples of the present application;
FIG. 3 is a nuclear magnetic resonance hydrogen spectrum of compound B provided in the examples of the present application;
FIG. 4 is a nuclear magnetic resonance hydrogen spectrum of Compound C provided in the examples of the present application
FIG. 5 is a nuclear magnetic resonance hydrogen spectrum of compound D provided in the examples of the present application;
FIG. 6 is a nuclear magnetic resonance hydrogen spectrum of compound E provided in the examples of the present application;
FIG. 7 is a nuclear magnetic resonance hydrogen spectrum of compound F provided in the examples of the present application;
FIG. 8 is a nuclear magnetic resonance hydrogen spectrum of compound G provided in the examples of the present application;
FIG. 9 is a nuclear magnetic resonance hydrogen spectrum of compound H provided in the examples of the present application;
FIG. 10 is a nuclear magnetic resonance hydrogen spectrum of compound I provided in the examples of the present application;
fig. 11 is a nuclear magnetic resonance hydrogen spectrum of compound J provided in the examples of the present application.
Detailed Description
In order to make the technical problems, technical schemes and beneficial effects to be solved by the present application more clear, the present application is further described in detail below with reference to the embodiments. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the present application.
In the present invention, the term "and/or" describes an association relationship of an association object, which means that three relationships may exist, for example, a and/or B may mean: a alone, a and B together, and B alone. Wherein A, B may be singular or plural. The character "/" generally indicates that the context-dependent object is an "or" relationship.
In the present invention, "at least one" means one or more, and "a plurality" means two or more. "at least one of" or the like means any combination of these items, including any combination of single item(s) or plural items(s). For example, "at least one (individual) of a, b, or c," or "at least one (individual) of a, b, and c" may each represent: a, b, c, a-b (i.e., a and b), a-c, b-c, or a-b-c, wherein a, b, c may be single or multiple, respectively.
It should be understood that, in various embodiments of the present invention, the sequence number of each process described above does not mean that the execution sequence of some or all of the steps may be executed in parallel or executed sequentially, and the execution sequence of each process should be determined by its functions and internal logic, and should not constitute any limitation on the implementation process of the embodiments of the present invention.
The terminology used in the embodiments of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used in this application and the appended claims, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise.
The weights of the relevant components mentioned in the description of the embodiments of the present invention may refer not only to the specific contents of the components, but also to the proportional relationship between the weights of the components, so long as the contents of the relevant components in the description of the embodiments of the present invention are scaled up or down within the scope of the disclosure of the embodiments of the present invention. Specifically, the mass in the specification of the embodiment of the invention can be a mass unit which is known in the chemical industry field such as mu g, mg, g, kg.
The terms "first" and "second" are used for descriptive purposes only and are not to be construed as indicating or implying a relative importance or implicitly indicating the number of technical features indicated for distinguishing between objects such as substances from each other. For example, a first XX may also be referred to as a second XX, and similarly, a second XX may also be referred to as a first XX, without departing from the scope of embodiments of the invention. Thus, a feature defining "a first" or "a second" may explicitly or implicitly include one or more such feature.
In a first aspect, an embodiment of the present application provides an organic compound, where the organic compound includes a chiral dibenzo [ e, g ] [1,4] diazocine skeleton, and the structural general formula of the organic compound is shown in formula I or formula II below:
wherein R is 1 、R 2 、R 3 、R 4 、R 5 And R is 6 Each independently selected from: at least one of hydrogen, hydroxy, amino, alkyl, methoxy, aryl, heteroaryl, alkenyl, alkynyl, alkylphosphorus, arylsilyl, phosphoxy, arylphosphoxy, halogen, thiourea; r is R 0 Selected from: at least one of aryl phosphorus group, alkyl phosphorus group, phosphoramidite group, phosphate group, dithiophosphate group, phosphoramide group, cyclopentadienyl group and quaternary ammonium salt.
The organic compound provided in the first aspect of the embodiments of the present application comprises chiral dibenzo [ e, g][1,4]Diazacyclooctatetraene skeleton, and substituent R attached to the skeleton structure 0 、R 1 、R 2 、R 3 、R 4 、R 5 And R is 6 The method comprisesThe framework is of a dibenzodiazocine structure, the stability of the framework structure is good, the selectivity of the derivative is high, the application is flexible, and R in the compound can be determined according to the actual application requirement 0 、R 1 、R 2 、R 3 、R 4 、R 5 And R is 6 The substituents in the positions are selected to obtain a range of chiral ligands or catalysts having catalytic activity, such as: chiral phosphorus ligand, chiral phosphoramidite ligand, chiral phosphoric acid, chiral diene ligand, chiral phase transfer catalyst, chiral thiourea catalyst and the like, and the ligand compounds are applied to different asymmetric synthesis reactions and all show excellent catalytic performance. In addition, the present application includes chiral dibenzo [ e, g][1,4]Organic compounds of the diazacyclooctatetraene backbone may also be applied to the synthesis of Metal Organic Framework (MOF) materials.
In some embodiments, embodiments of the present application comprise organic compounds of chiral dibenzo [ e, g ] [1,4] diazocine backbones, including derivative compounds of:
wherein R and R' are each independently selected from: at least one of alkyl, aryl and heteroaryl, and other substituent groups can be selected from the following specific examples. In some embodiments, embodiments of the present application include organic compounds comprising chiral dibenzo [ e, g ] [1,4] diazocine backbones, R and R' are phenyl, including derivative compounds of:
at least one of them. Wherein R is 7 And R is 8 Each independently selected from: at least one of methyl, ethyl, isopropyl, (R) -1-phenethyl; r is R 9 、R 10 、R 11 And R is 12 Each independently selected from: hydrogen, methyl, methoxy, O i Pr, OTIPS, OTBDPS; ar (Ar) 1 、Ar 2 、Ar 3 、Ar 4 、Ar 5 、Ar 6 、Ar 7 、Ar 8 、Ar 9 、Ar 10 、Ar 11 、Ar 12 、Ar 13 、Ar 14 、Ar 15 、Ar 16 、Ar 17 Each independently selected from: 4-CH 3 C 6 H 4 Radical, 4-OCH 3 C 6 H 4 Radical, 3-CH 3 C 6 H 4 Radical, 2-CH 3 C 6 H 4 Radical, 3,5- (CH) 3 ) 2 C 6 H 3 Basic, 3,5- t Bu) 2 C 6 H 3 Radical, 3,4,5- (OMe) 3 C 6 H 2 Radical, 4-FC 6 H 4 Radical, 3,4,5-F 3 C 6 H 2 Radical, 4-ClC 6 H 4 Group, 1-naphthyl, 2-naphthyl, phenyl, 4-tBuC 6 H 4 Radical, 4-NO 2 C 6 H 4 Radical, 3,5- (CF) 3 ) 2 C 6 H 3 Basic, 3,5- t Bu) 2 -4-OMeC 6 H 2 Radicals, 9-phenanthryl, 9-anthracyl, 1-pyrenyl, C 6 F 5 Radical, 2,4,6- (Me) 3 C 6 H 2 Basic, 2,4,6- i Pr) 3 C 6 H 2 Base, 2,4,6- (Cy) 3 C 6 H 2 At least one of the groups. The chiral ligand and the catalyst compound can be applied to different asymmetric synthesis reactions, and have excellent catalytic performance.
The derivative compound containing chiral dibenzo [ e, g ] [1,4] diazocine skeleton provided by the embodiment of the application can be prepared by the following method.
A second aspect of embodiments of the present application provides a method for preparing an organic compound, including the steps of:
dissolving a 1,1 '-biphenyl-2, 2' -diamine derivative, an benzil derivative and a chiral phosphoric acid catalyst in an organic solvent for catalytic reaction to obtain an organic compound containing a chiral dibenzo [ e, g ] [1,4] diazocine skeleton;
wherein the structural formula of the 1,1 '-biphenyl-2, 2' -diamine derivative is as follows:the structural formula of the benzil derivative is as follows: />The structural general formula of the organic compound is shown in formula I or formula II: />Formula (I);wherein R is 1 、R 2 、R 3 、R 4 、R 5 And R is 6 Each independently selected from: at least one of hydrogen, hydroxy, amino, alkyl, methoxy, aryl, heteroaryl, alkenyl, alkynyl, alkylphosphorus, arylsilyl, phosphoxy, arylphosphoxy, halogen, thiourea; r is R 0 Selected from: at least one of aryl phosphorus group, alkyl phosphorus group, phosphoramidite group, phosphate group, dithiophosphate group, phosphoramide group, cyclopentadienyl group and quaternary ammonium salt.
In some embodiments, the 1,1 '-biphenyl-2, 2' -diamine derivative, the benzil derivative, and the chiral phosphoric acid catalyst are dissolved in an organic solvent such as tetrahydrofuran, and the organic compound containing a chiral dibenzo [ e, g ] [1,4] diazocine skeleton is obtained by catalytic reaction at a temperature of 60-80 ℃ for 12-48 hours.
In some embodiments, the synthetic route is as follows:
according to the preparation method of the organic compound provided by the second aspect of the embodiment of the application, the 1,1 '-biphenyl-2, 2' -diamine derivative and the benzil derivative are dissolved in an organic solvent and reacted under the catalysis of a chiral phosphoric acid catalyst, so that the organic compound containing the chiral dibenzo [ e, g ] [1,4] diazocine skeleton can be obtained. The preparation method of the organic compound containing chiral dibenzo [ e, g ] [1,4] diazocine skeleton is simple in process, mild in condition and suitable for large-scale production and application. And the prepared organic compound containing chiral dibenzo [ e, g ] [1,4] diazocine skeleton has good structural stability, high catalytic activity and wide application range.
In some embodiments, the 1,1' -biphenyl-2, 2' -diamine derivative is selected from chiral or racemic 6,6' -dimethoxy- [1,1' -biphenyl ] -2,2' -diamine; the benzil derivative is selected from benzil; the preparation of the organic compound comprises the following steps:
s10, dissolving chiral or racemized 6,6' -dimethoxy- [1,1' -biphenyl ] -2,2' -diamine, benzil and chiral phosphoric acid catalyst in a first organic solvent, and carrying out condensation reaction to obtain a compound (R) -3;
s20, converting one or two methoxy groups in the compound (R) -3 into hydroxyl groups to respectively obtain a compound A,and compound B, < >>
The examples of the present application use chiral or racemic 6,6 '-dimethoxy- [1,1' -biphenyl]2,2' -diamine and benzil are used as raw materials, and are subjected to dehydration condensation reaction under the catalysis of chiral phosphoric acid catalyst to obtain R 2 、R 3 A compound (R) -3 with methoxy attached at the position; then one or two methoxy groups in the compound (R) -3 are converted into hydroxyl groups, and thenAnd obtaining a compound A and a compound B respectively. The derivative compounds A and B synthesized in the examples of the present application can be used as chiral bisphenol ligands and Ti (O) i Pr) 4 And the like to jointly catalyze the asymmetric addition reaction of aldehyde. In addition, compounds a and B, as important precursor compounds, can also be derivatized to various chiral ligands and catalysts.
In some embodiments, in step S10, the equivalent ratio of chiral 6,6' -dimethoxy- [1,1' -biphenyl ] -2,2' -diamine (R) -1 to benzil 2 is 1: (1-1.3), dissolving the diphenyl phosphate proton acid catalyst (Diphenyl phosphate) and 20mol percent of diphenyl phosphate proton acid catalyst in a first organic solvent such as Tetrahydrofuran (THF), dioxane, ethylene glycol dimethyl ether, toluene and the like, and then carrying out dehydration condensation reaction for 12-36 hours under the heating condition of 60-80 ℃ to obtain the compound (R) -3 by separation.
In other embodiments, in step S10, the equivalent ratio of racemic 6,6' -dimethoxy- [1,1' -biphenyl ] -2,2' -diamine (rac) -1 to benzil 2 is 1: (2-2.3), dissolving the two and 10mol percent of chiral phosphoric acid (S) -CPA serving as a catalyst in a first organic solvent such as Tetrahydrofuran (THF) and the like, carrying out asymmetric condensation reaction for 1-3 days at the room temperature of 20-38 ℃, and separating to obtain the compound (R) -3.
In some embodiments, in step S20, the step of converting one or both methoxy groups in compound (R) -3 to hydroxyl groups comprises: mixing compound (R) -3, tris (pentafluorophenyl) boron, triethylsilane and a second organic solvent, adding potassium fluoride and ethanol for reaction, and separating to obtain compound A and compound B. Specifically, under the condition of room temperature, the compound (R) -3, the tris (pentafluorophenyl) boron and the triethylsilane solvent are stirred for 4 to 8 hours in a second organic solvent such as Dichloromethane (DCM), chloroform, toluene and the like, the tris (pentafluorophenyl) boron is taken as a catalyst to remove methyl groups of one or two methoxy groups in the compound (R) -3, the triethylsilicon group (TES protecting group) is connected, then potassium fluoride and ethanol are added and stirred for 12 to 24 hours, the TES protecting group is replaced by hydroxyl groups, the compound A is obtained by separation,and compound B, < >>Preferably, in the reaction system, the molar concentration of tris (pentafluorophenyl) boron is 30 mole% and the equivalent ratio of compound (R) -3 to triethylsilane is 1: (4-6).
In other embodiments, the step of converting one or both methoxy groups in compound (R) -3 to hydroxyl groups comprises: adding BBr dropwise to a solution of compound (R) -3 (solvent such as dichloromethane, chloroform, etc.) at a temperature of 0deg.C or less 3 And (3) reacting for several hours, removing one or two methoxy groups in the compound (R) -3, and connecting hydroxyl groups to obtain the compound A and the compound B.
In some embodiments, compounds a and B are synthesized as follows:
in some embodiments, the method further comprises the step of: dissolving the compound A and hexamethylphosphoric triamide in a third organic solvent, reacting to obtain a compound C,specifically, the equivalent ratio of compound a to hexamethylphosphoric triamide (HMPT) is 1: (1-2), dissolving the two in a third organic solvent such as toluene, tetrahydrofuran, dioxane, ethylene glycol dimethyl ether and the like, reacting for 4-8 hours under the inert atmosphere condition of 100-120 ℃, and separating to obtain the compound C.
In some embodiments, the method further comprises the step of: dissolving the compound A and hexaethylphosphoramidite in a fourth organic solvent, reacting to obtain a compound D,specifically, the equivalent ratio of compound a to Hexaethylphosphoramidite (HEPT) is 1: (1-2) dissolving both in a fourth organic solvent such as toluene, and an inert atmosphere at 100-120deg.CReacting for 4-8 hours under the condition, and separating to obtain the compound D.
In some embodiments, the method further comprises the step of: dropwise adding diisopropylamine into a mixed solution of phosphorus trichloride and triethylamine at the temperature of not higher than 0 ℃ and then reacting at room temperature; then adding the mixed solution of the compound A and triethylamine, reacting to obtain a compound E,specifically, the equivalent ratio of phosphorus trichloride to triethylamine is 1: (5-6), dissolving the two in an organic solvent such as dichloromethane, and then placing the mixture in an ice bath at 0 ℃; dropwise adding diisopropylamine 5 (wherein the equivalent ratio of diisopropylamine to phosphorus trichloride is 1:1), and slowly heating to room temperature for reacting for 5-10 hours; and adding a dichloromethane mixed solution of the compound A and triethylamine, wherein the equivalent ratio of the compound A to the triethylamine to the phosphorus trichloride is 1: (2-3): (2-3), reacting for 12-36 hours at room temperature, and separating to obtain the compound E. Diisopropylamine is added dropwise at the temperature of not higher than 0 ℃ in the first stage of the application, and PCl is attacked by reactant amine in a nucleophilic manner 3 The P atom of (C) falls one molecule of HCl and amine is linked, the reaction is very active, and the low-temperature condition can effectively avoid the occurrence of multiple substitution. In the second reaction stage, two phenolic hydroxyl oxygen on A nucleophilic attack P, 2 molecules of HCl are removed, and a final product E or F is generated; in order to ensure an excessive amount of base, HCl produced can be neutralized, and therefore, a mixed solution of compound a and triethylamine is added.
In some embodiments, the method further comprises the step of: at a temperature of not higher than 0deg.C, subjecting (+) -bis [ (R) -1-phenethyl group]Dropwise adding amine into a mixed solution of phosphorus trichloride and triethylamine, and reacting at room temperature; then adding the mixed solution of the compound A and triethylamine, reacting to obtain a compound F,specifically, the equivalent ratio of phosphorus trichloride to triethylamine is 1: (5-6), dissolving the two in an organic solvent such as dichloromethane, and then placing the mixture in an ice bath at 0 ℃; dropwise adding (+) -di [ (R) -1-phenethyl]Amine Compound 6 (wherein diisopropylamine and TriThe equivalent ratio of the phosphorus chloride is 1:1), and then the reaction is carried out for 5 to 10 hours after the temperature is slowly raised to the room temperature; and adding a dichloromethane mixed solution of the compound A and triethylamine, wherein the equivalent ratio of the compound A to the triethylamine to the phosphorus trichloride is 1: (2-3): (2-3), reacting for 12-36 hours at room temperature, and separating to obtain the compound F.
In some embodiments, the method further comprises the step of: mixing the compound A with pyridine and phosphorus oxychloride, reacting at 70-90 ℃, adding water, and reacting at 40-60 ℃; then adding hydrochloric acid, reacting at 90-120 ℃, separating to obtain a compound G,specifically, the equivalent ratio of the compound A to phosphorus oxychloride is 1: (2-3), adding 1mL of compound A and pyridine into a dry reaction vessel, adding phosphorus oxychloride which is evaporated, and reacting for 3-7 hours at 70-100 ℃ to react phosphorus oxychloride with two phenolic hydroxyl groups to generate phosphoryl chloride; then adding 0.2mL of water, reacting for 10-15 hours at the temperature of 40-60 ℃, and hydrolyzing phosphoryl chloride to generate phosphoric acid; after the reaction is finished, 6N HCl (6 mL) is added to react for 20 to 60 minutes at the temperature of between 90 and 110 ℃, wherein the process is an acidification process, and because the reaction system is provided with pyridine base, hydrochloric acid is added to fully acidify in order to completely free the phosphoric acid group, so that the phosphoric acid group is prevented from reacting with pyridine to exist in a salt form. After the reaction, ethyl acetate and water (preferably with the volume ratio of 1:1) are used for extraction, an ethyl acetate phase is collected, then reduced pressure rotary evaporation is carried out, the residue is recrystallized by ethyl acetate and petroleum ether, and a solid is collected, namely the compound G.
In some embodiments, compounds C, D, E, F and G were synthesized as follows:
in some embodiments, the method further comprises the step of: compound B was reacted with trifluoromethanesulfonic anhydride (Tf 2 O) and pyridine (C) 5 H 5 N) dissolving in a fifth organic solvent such as dichloromethane, and reacting to obtainCompound (R) -7. Preferably, the equivalent ratio of compound B to triflic anhydride and pyridine is 1:2: (3-5), the reaction conditions are as follows: the reaction is carried out for 12 to 36 hours at room temperature.
And dissolving the compound (R) -7 with a first palladium catalyst such as palladium acetate, 1, 3-bis (diphenylphosphine) propane, N-diisopropylethylamine and diphenylphosphines in a sixth organic solvent such as dimethyl sulfoxide, and reacting to obtain the compound (R) -8. Preferably, the molar concentration of the first palladium catalyst in the reaction system is 10 to 15mol% and the molar concentration of 1, 3-bis (diphenylphosphine) propane is 23 to 28mol%. Preferably, the equivalent ratio of the compound (R) -7 to N, N-diisopropylethylamine and diphenylphosphines is 1 (3-5): (1-2). Preferably, the reaction conditions are: reacting for 12-36 hours under the heating condition of 90-110 ℃.
Dissolving (R) -8, trichlorosilane and N, N-dimethylaniline in a seventh organic solvent such as toluene and the like, reacting to obtain a compound H,preferably, the equivalent ratio of (R) -8 to trichlorosilane is 1: (30-40). Preferably, the reaction conditions are: reacting for 12-36 hours under the heating condition of 90-110 ℃.
In some embodiments, compound H is synthesized as follows:
in some embodiments, the method further comprises the step of: and dissolving the compound A, trifluoromethanesulfonic anhydride and pyridine in an eighth organic solvent such as dichloromethane and the like, and reacting to obtain the compound (R) -9. Preferably, the equivalent ratio of compound a to triflic anhydride and pyridine is 1: (4-6): (9-11). Preferably, the reaction conditions are: the reaction is carried out for 24 to 36 hours at room temperature.
Dissolving the compound (R) -9 and a second palladium catalyst such as palladium acetate, 1, 4-bis (diphenylphosphine) butane, N-Diisopropylethylamine (DIPEA) and diphenylphosphine in a ninth organic solvent such as dimethyl sulfoxide, reacting to obtain a compound I,preferably, the molar concentration of the second palladium catalyst in the reaction system is 20 to 30mol% and the molar concentration of 1, 4-bis (diphenylphosphine) butane is 40 to 60mol%. Preferably, the equivalent ratio of the compound (R) -9 to N, N-diisopropylethylamine and diphenylphosphines is 1 (3-5): (5-7). Preferably, the reaction conditions are: reacting for 12-36 hours under the heating condition of 110-150 ℃.
In some embodiments, the method further comprises the step of: the compound (R) -9 is dissolved in a tenth organic solvent such as methylene dichloride and the like to react with a third palladium catalyst such as palladium acetate, 1, 3-bis (diphenylphosphine) propane, N-Diisopropylethylamine (DIPEA) and diphenylphosphino to obtain the compound (R) -10. Preferably, in the reaction system, the molar concentration of the third palladium catalyst is 20 to 30mol% and the molar concentration of 1, 3-bis (diphenylphosphine) propane is 40 to 60mol%. Preferably, the equivalent ratio of the compound (R) -9 to N, N-diisopropylethylamine and diphenylphosphines is 1 (7-9): (2-5). Preferably, the reaction conditions are: reacting for 12-36 hours under the heating condition of 90-110 ℃.
The compound (R) -10, trichlorosilane and N, N-dimethylaniline are dissolved in eleventh organic solvents such as toluene and the like to react to obtain the compound (R) -11. Preferably, the equivalent ratio of compound (R) -10 to trichlorosilane is 1: (65-75). Preferably, the reaction conditions are: reacting for 12-36 hours under the heating condition of 90-110 ℃.
Dissolving a compound (R) -11 and a fourth palladium catalyst such as palladium acetate, 1, 4-bis (diphenylphosphine) butane, N-Diisopropylethylamine (DIPEA) and diphenylphosphino into a twelfth organic solvent such as dimethyl sulfoxide, reacting to obtain a compound J,preferably, in the reaction system, the molar concentration of the fourth palladium catalyst is 15 to 25mol% and the molar concentration of the 1, 4-bis (diphenylphosphine) butane is 40 to 60mol%. Preferably, the equivalent ratio of the compound (R) -11 to N, N-diisopropylethylamine and diphenylphosphines is 1 (7-9): (2-5). Preferably, the method comprises the steps of,the reaction conditions are as follows: reacting for 12-24 hours under the heating condition of 90-110 ℃.
In some embodiments, the method further comprises the step of: dissolving a compound (R) -11 and a fifth palladium catalyst such as palladium acetate, 1, 4-bis (diphenylphosphine) butane, N-diisopropylethylamine and diphenylphosphino into a thirteenth organic solvent such as dimethyl sulfoxide, reacting to obtain a compound K,preferably, in the reaction system, the molar concentration of the fifth palladium catalyst is 15 to 25mol% and the molar concentration of 1, 4-bis (diphenylphosphine) butane is 40 to 60mol%. Preferably, the equivalent ratio of the compound (R) -11 to N, N-diisopropylethylamine and diphenylphosphines is 1 (7-9): (2-5). Preferably, the reaction conditions are: reacting for 24-48 hours under the heating condition of 90-110 ℃.
In some embodiments, compounds I, J and K were synthesized as follows:
the derivative compounds C-F containing chiral dibenzo [ e, g ] [1,4] diazocine skeleton, which are synthesized in the embodiment, can be used as chiral phosphoramidite ligands, and compared with other chiral phosphine ligands, the chiral phosphine ligands have the advantages of stable skeleton structure, simple synthesis, easy modification and the like, so that the chiral phosphine ligands can be widely applied to various asymmetric catalytic reactions, such as: the asymmetric hydrogenation reaction, the asymmetric conjugate addition reaction, the asymmetric allylation reaction, the asymmetric Heck reaction, the asymmetric cycloaddition reaction, the asymmetric coupling reaction and the like can all show excellent catalytic performance and have stable catalytic effect.
The derivative compound G containing chiral dibenzo [ e, G ] [1,4] diazocine skeleton, which is synthesized in the embodiment, can be used as a chiral phosphoric acid catalyst and is applied to asymmetric reaction catalyzed by protonic acid, and the application is very wide.
The derivative compound H containing chiral dibenzo [ e, g ] [1,4] diazocine skeleton synthesized in the embodiment can be used as chiral monophosphorus ligand to catalyze the asymmetric hydrosilylation reaction of olefin together with palladium.
The derivative compound I-K containing chiral dibenzo [ e, g ] [1,4] diazocine skeleton synthesized in the embodiment can be used as chiral biphosphine ligand and various metals such as Ru, pd, ag, rh, ir, au and the like to catalyze various asymmetric reactions, such as: tsuji-Trost Allylation reaction, asymmetric conjugate addition reaction, buchwald-Hartwig reaction, asymmetric Michelal addition reaction, asymmetric cycloaddition reaction, asymmetric Aldol reaction, asymmetric Heck reaction, asymmetric nucleophilic addition reaction and the like can all show excellent catalytic performance and stable catalytic effect.
In order that the implementation details and operations described above can be clearly understood by those skilled in the art, and that the embodiments of the present application include an organic compound having a chiral dibenzo [ e, g ] [1,4] diazocine skeleton and a preparation method thereof, the technical solutions described above are exemplified by a plurality of embodiments below.
Example 1
Derivative compounds a and B comprising a chiral 6, 7-diphenyl dibenzo [ e, g ] [1,4] diazocine backbone comprising the following preparation steps:
the method comprises the following steps: chiral 6,6' -dimethoxy- [1,1' -biphenyl ] -2,2' -diamine (R) -1 and benzil 2 (1.1 eq.) were taken and added to THF, and reacted at 70℃for 24 hours with 20mol% diphenyl phosphate as catalyst to obtain (R) -3 in 95% yield.
The second method is as follows: the despin 6,6' -dimethoxy- [1,1' -biphenyl ] -2,2' -diamine (rac) -1 and benzil 2 (2 eq.) were added to THF and reacted at 35 ℃ for 48 hours with 10mol% chiral phosphoric acid (S) -CPA as catalyst to give (R) -3 in 48% yield, 68% ee, which was obtained as 99% ee after one-step in situ precipitation and phase separation.
(R) -3 and tris (pentafluorophenyl) boron (30 mol.) triethylsilane (5.0 eq.) was stirred in DCM at room temperature for 5 hours and then potassium fluoride and ethanol were added and stirred at room temperature for 12 hours. Compounds A and B were obtained in 72% and 16% yields, respectively.
The synthetic route is as follows:
example 2
A derivative compound C comprising a chiral 6, 7-diphenyl dibenzo [ e, g ] [1,4] diazocine backbone comprising the steps of: compound a was reacted with hexamethylphosphoric triamide (HMPT, 1.5 eq.) in toluene solution at 115 ℃ for 6 hours to give compound C in 63% yield.
Example 3
A derivative compound D comprising a chiral 6, 7-diphenyl dibenzo [ e, g ] [1,4] diazocine backbone comprising the steps of: compound a was reacted with hexaethylphosphoramidite (HEPT, 1.5 eq.) in toluene solution at 115 ℃ for 6 hours to give compound D in 72% yield.
Example 4
A derivative compound E comprising a chiral 6, 7-diphenyl dibenzo [ E, g ] [1,4] diazocine backbone comprising the steps of: taking a dry Schlenk tube, adding DCM, phosphorus trichloride (2 eq.) and triethylamine (10 eq.) into the tube, then placing the tube at 0 ℃, dropwise adding diisopropylamine 5 into the tube, and slowly heating the tube to room temperature for reaction for 7 hours; an additional solution of compound a (1 eq.) and triethylamine (2 eq.) in DCM was added and reacted at room temperature for 18 hours to give compound E in 65% yield.
Example 5
A derivative compound F comprising a chiral 6, 7-diphenyl dibenzo [ e, g ] [1,4] diazocine backbone comprising the steps of: taking a dry Schlenk tube, adding DCM, phosphorus trichloride (2 eq.) and triethylamine (10 eq.) into the tube, then placing the tube at 0 ℃, dropwise adding compound 6 (2 eq.) into the tube, and slowly heating the tube to room temperature for reaction for 7 hours; an additional solution of compound a (1 eq.) and triethylamine (2 eq.) in DCM was added and reacted at room temperature for 18 hours to give compound F in 56% yield.
Example 6
A derivative compound G comprising a chiral 6, 7-diphenyl dibenzo [ e, G ] [1,4] diazocine backbone comprising the steps of: taking a dry Schlenk tube, adding 1mL of compound A and pyridine, adding phosphorus oxychloride (2 eq.) which is evaporated now, reacting for 5 hours at 80 ℃, adding 0.2mL of water, reacting for 12 hours at 50 ℃, adding 6N HCl (6 mL) after the reaction is finished, reacting for 30 minutes at 100 ℃, extracting with ethyl acetate and water (1:1) after the reaction is finished, collecting an ethyl acetate phase, performing rotary evaporation under reduced pressure, recrystallizing residues with ethyl acetate and petroleum ether, collecting solids, and obtaining the compound G in 45% yield.
The synthetic routes for examples 2-6 are as follows:
example 7
A derivative compound H comprising a chiral 6, 7-diphenyl dibenzo [ e, g ] [1,4] diazocine backbone comprising the steps of:
compound B was taken and reacted with trifluoromethanesulfonic anhydride (2 eq.) and pyridine (4 eq.) in DCM solution for 24 hours at room temperature to give compound (R) -7 in 78% yield;
(R) -7 was reacted with palladium acetate (12.5 mol%), 1, 3-bis (diphenylphosphine) propane (25 mol%), N-diisopropylethylamine (4 eq.) and diphenylphosphine oxide (1.5 eq.) in dimethyl sulfoxide solution at 100℃for 24 hours to give compound (R) -8 in 89% yield;
(R) -8 was reacted with trichlorosilane (35 eq.) N, N-dimethylaniline in toluene solution at 100℃for 24 hours to give Compound H in 74% yield.
The synthetic route is as follows:
example 8
A derivative compound I comprising a chiral 6, 7-diphenyl dibenzo [ e, g ] [1,4] diazocine backbone comprising the steps of:
compound a and trifluoromethanesulfonic anhydride (5 eq.) pyridine (10 eq.) were reacted in DCM solution at room temperature for 24 hours to give compound (R) -9 in 95% yield;
(R) -9 was reacted with palladium acetate (25 mol%), 1, 4-bis (diphenylphosphine) butane (50 mol%), N-diisopropylethylamine and diphenylphosphine (6 eq.) in dimethyl sulfoxide solution at 125℃for 24 hours to give compound I in 36% yield.
Example 9
A derivative compound J comprising a chiral 6, 7-diphenyl dibenzo [ e, g ] [1,4] diazocine backbone comprising the steps of:
(R) -9 was reacted with palladium acetate (25 mol%), 1, 3-bis (diphenylphosphine) propane (50 mol%), N-diisopropylethylamine (8 eq.) and diphenylphosphine oxide (3 eq.) at 100℃for 24 hours to give compound (R) -10 in 78% yield;
(R) -10 was reacted with trichlorosilane (70 eq.) and N, N-dimethylaniline in toluene solution at 100℃for 24 hours to give Compound (R) -11 in 86% yield;
(R) -11 was reacted with palladium acetate (20 mol%), 1, 4-bis (diphenylphosphine) butane (50 mol%), N-diisopropylethylamine and diphenylphosphine oxide (3 eq.) in dimethyl sulfoxide solution at 100℃for 12 hours to give compound J in 50% yield.
Example 10
A derivative compound K comprising a chiral 6, 7-diphenyl dibenzo [ e, g ] [1,4] diazocine backbone comprising the steps of:
(R) -11 was reacted with palladium acetate (20 mol%), 1, 4-bis (diphenylphosphine) butane (50 mol%), N-diisopropylethylamine and diphenylphosphine oxide (3 eq.) in dimethyl sulfoxide solution at 100℃for 36 hours to give compound K in 60% yield.
The synthetic routes for examples 8-10 are as follows:
further, the present application carried out the nuclear magnetic resonance qualitative analysis on chiral 6, 7-diphenyl dibenzo [ e, g ] [1,4] diazocine skeleton derivative compounds synthesized in examples 1 to 10, respectively, and the nuclear magnetic resonance data of the compounds A to K in examples 1 to 10 are as follows:
(R)-3
1H NMR(500MHz,CDCl3)δ7.78(d,J＝7.5Hz,4H),7.38(t,J＝6.7Hz,2H),7.32(t,J＝7.4Hz,4H),7.23(t,J＝8.1Hz,2H),6.79(d,J＝7.9Hz,2H),6.67(d,J＝8.2Hz,2H),3.70(s,6H).13C NMR(125MHz,CDCl3)δ167.11,158.00,152.29,134.01,131.73,129.06,128.74,128.28,114.63,112.88,107.49,55.93.
compound A
1 H NMR(500MHz,DMSO)δ9.21(s,2H),7.64(d,J＝7.4Hz,4H),7.45–7.42(m,2H),7.39(t,J＝7.3Hz,4H),7.04(t,J＝7.9Hz,2H),6.55(t,J＝8.3Hz,4H). 13 C NMR(125MHz,DMSO)δ165.88,155.79,153.45,134.13,131.66,129.11,128.46,127.53,113.03,111.35,110.31.
Compound B
1 H NMR(500MHz,CDCl 3 )δ7.73(d,J＝7.0Hz,4H),7.38(t,J＝7.2Hz,2H),7.32–7.26(m,5H),7.16(t,J＝7.4Hz,1H),6.78(d,J＝7.9Hz,1H),6.71(d,J＝8.1Hz,2H),6.67(d,J＝7.9Hz,1H),5.17(s,1H),3.77(s,3H). 13 C NMR(125MHz,CDCl 3 )δ167.37,166.77,156.67,154.77,153.92,153.22,134.46,134.34,131.51,131.38,129.99,129.38,128.69,127.99,127.90,113.69,112.37,112.24,112.16,111.90,107.16,56.09.
Compound C
1 H NMR(500MHz,CDCl 3 )δ7.77(t,J＝8.5Hz,4H),7.45–7.38(m,2H),7.38–7.32(m,4H),7.29(t,J＝8.0Hz,1H),7.21(t,J＝7.9Hz,1H),6.94(d,J＝8.1Hz,1H),6.91(d,J＝7.9Hz,1H),6.86(d,J＝7.8Hz,1H),6.81(d,J＝7.9Hz,1H),2.59(s,3H),2.57(s,3H). 13 C NMR(125MHz,CDCl 3 )δ167.26,166.75,152.55,152.35,151.92(d,J＝5.2Hz),151.47,134.37(d,J＝6.3Hz),131.63(d,J＝6.2),129.69,129.60,128.80(d,J＝8.5Hz),127.92(d,J＝6.4Hz),118.71,117.96,117.56,117.39,116.26,36.01,35.85. 31 P NMR(202MHz,CDCl 3 )δ146.30.
Compound D
1 H NMR(500MHz,CDCl 3 )δ7.78(t,J＝8.7Hz,4H),7.43–7.32(m,6H),7.29(d,J＝7.6Hz,1H),7.21(t,J＝8.0Hz,1H),6.94(d,J＝8.0Hz,1H),6.91(d,J＝7.8Hz,1H),6.86(d,J＝7.6Hz,1H),6.80(d,J＝7.9Hz,1H),3.11–3.05(m,2H),2.90–2.83(m,2H),1.04(t,J＝6.4Hz,6H). 13 C NMR(125MHz,CDCl 3 )δ167.25,166.64,152.49,152.28,151.86(d,J＝5.4Hz),151.72,134.40(d,J＝8.0Hz),131.59(d,J＝6.9Hz),129.62,129.41,128.79(d,J＝10.6Hz),127.91(d,J＝8.8Hz),118.78,117.78(d,J＝1.7Hz),117.71(d,J＝1.8Hz),117.32(d,J＝3.5Hz),116.09,38.28(d,J＝21.7Hz),14.70(d,J＝2.1Hz). 31 P NMR(202MHz,CDCl 3 )δ147.66.
Compound E
1 H NMR(500MHz,CDCl 3 )δ7.77(t,J＝8.3Hz,4H),7.43–7.32(m,6H),7.28(d,J＝8.0Hz,1H),7.21(t,J＝7.9Hz,1H),6.94(d,J＝7.9Hz,1H),6.89(d,J＝8.0Hz,1H),6.86(d,J＝8.0Hz,1H),6.82(d,J＝7.9Hz,1H),3.48–3.33(m,2H),1.18(t,J＝7.3Hz,12H). 13 C NMR(125MHz,CDCl 3 )δ167.22,166.60,152.40,152.36,152.18,152.06(d,J＝6.9Hz),134.42(d,J＝5.3Hz),131.56(d,J＝7.4Hz),129.58,129.02,128.79(d,J＝11.8Hz),127.90(d,J＝10.8Hz),118.86(d,J＝4.2Hz),117.89(d,J＝1.9Hz),117.64,117.30,117.17,115.68,44.68(d,J＝12.7Hz),24.47(d,J＝8.9Hz). 31 P NMR(202MHz,CDCl 3 )δ150.49.
Compound F
1 H NMR(500MHz,CDCl 3 )δ7.76(t,J＝9.1Hz,4H),7.42–7.30(m,7H),7.16(s,9H),7.06(s,1H),7.03(t,J＝8.0Hz,2H),6.89(d,J＝7.9Hz,1H),6.76–6.71(m,2H),4.49–4.39(m,2H),1.67(d,J＝6.6Hz,6H). 13 C NMR(125MHz,CDCl 3 )δ167.11,166.76,152.59,152.33,152.10,152.02,151.88,143.19,134.33(d,J＝9.7Hz),131.61(d,J＝4.6Hz),129.74,129.20,128.80(d,J＝12.2Hz),128.00(d,J＝2.8Hz),127.92(d,J＝11.6Hz),127.70,126.58,118.92(d,J＝4.8Hz),117.98(d,J＝2.5Hz),117.85,117.27,116.60(d,J＝2.0Hz),115.44,54.46(d,J＝10.9Hz),23.05(d,J＝12.4Hz). 31 P NMR(202MHz,CDCl 3 )δ149.35.
Compound G
1 H NMR(500MHz,DMSO)δ7.75(d,J＝7.6Hz,4H),7.52(t,J＝7.2Hz,2H),7.53–7.40(m,6H),7.03(d,J＝7.9Hz,2H),6.96(d,J＝8.0Hz,2H),4.05(s,OH). 13 C NMR(125MHz,DMSO)δ166.68,152.31,149.64,133.45,132.34,130.43,129.31,127.68,117.40,117.32,116.07. 31 P NMR(202MHz,DMSO)δ0.26.
Compound H
1 H NMR(500MHz,CDCl 3 )δ7.73(d,J＝7.9Hz,2H),7.66(d,J＝7.9Hz,2H),7.39–7.34(m,2H),7.35–7.28(m,9H),7.24(d,J＝7.4Hz,1H),7.18(t,J＝6.6Hz,3H),7.14(t,J＝7.8Hz,1H),7.06(d,J＝7.9Hz,1H),6.97(t,J＝7.4Hz,2H),6.82(d,J＝4.3Hz,1H),6.59(t,J＝9.2Hz,2H),3.48(s,3H). 13 C NMR(125MHz,CDCl 3 )δ167.45,166.38,157.07(d,J＝1.4Hz,),153.78,152.83,152.77,139.46(d,J＝12.3Hz),138.20(d,J＝13.3Hz),138.06(d,J＝14.4Hz),134.66(d,J＝25.2Hz),133.52(d,J＝19.6Hz),133.30(d,J＝20.0Hz),131.28,131.18,130.92,130.63,129.26,128.58(d,J＝13.8Hz),128.18(d,J＝6.0Hz),127.97(d,J＝6.0Hz),127.91(d,J＝3.7Hz),120.60,116.72,116.67,112.32,106.41,55.05). 31 PNMR(202MHz,CDCl 3 )δ-9.58.
Compound I
1 H NMR(500MHz,CDCl 3 )δ7.55(d,J＝7.0Hz,4H),7.46(s,4H),7.36–7.28(m,11H),7.27–7.18(m,7H),7.04(t,J＝7.2Hz,2H),6.97(s,4H),6.74(d,J＝7.4Hz,2H),6.69(d,J＝6.7Hz,2H). 13 C NMR(125MHz,CDCl 3 )δ166.74,153.49(t,J＝3.7Hz),139.46(t,J＝3.3Hz),138.37(t,J＝8.2Hz),135.90(t,J＝4.7Hz),134.57,134.38(t,J＝10.9Hz),133.57(t,J＝10.8Hz),131.72(t,J＝15.9Hz),131.34,129.47,128.46,128.37(t,J＝4.6Hz),128.32(d,J＝2.6Hz),128.16,127.92,127.85(t,J＝3.6Hz),120.03,112.69. 31 P NMR(202MHz,CDCl 3 )δ-8.93.
Compound J
1 H NMR(500MHz,CDCl 3 )δ7.82–7.75(m,2H),7.63(d,J＝7.5Hz,2H),7.51(t,J＝6.7Hz,2H),7.45–7.34(m,9H),7.31–7.27(m,8H),7.23–7.21(m,3H),7.17–7.12(m,4H),6.94(d,J＝6.1Hz,1H),6.85(t,J＝6.3Hz,3H),6.64(d,J＝6.7Hz,1H),6.46(d,J＝7.7Hz,1H). 13 C NMR(125MHz,CDCl 3 )δ166.83,166.51,154.20,154.11,152.45,152.40,141.80(d,J＝13.4Hz),138.48(d,J＝16.5Hz),136.44(d,J＝13.6Hz),134.73(d,J＝22.0Hz),134.48,134.42,134.03,133.79(d,J＝17.4Hz),133.59,132.77(d,J＝4.8Hz),132.25(d,J＝9.0Hz),131.95,131.66(d,J＝7.7Hz),131.60(d,J＝7.6Hz),131.43,131.30(d,J＝9.7Hz),131.15(d,J＝1.9Hz),130.67(d,J＝2.3Hz),130.44(d,J＝12.1Hz),130.31(d,J＝3.9Hz),130.07(d,J＝3.9Hz),128.58,128.40,128.29,128.13(d,J＝8.0Hz),128.03,128.00(d,J＝3.0Hz),127.82(d,J＝1.5Hz),127.74,127.65,127.60,123.36,119.20. 31 P NMR(202MHz,CDCl 3 )δ25.78,-10.94.
The foregoing description of the preferred embodiments of the present application is not intended to be limiting, but is intended to cover any and all modifications, equivalents, and alternatives falling within the spirit and principles of the present application.

Claims (1)

1. Chiral dibenzo [ e, g][1,4]A process for the synthesis of diazocine ligands, characterized in that racemic 6,6 '-dimethoxy- [1,1' -biphenyl]Dissolving 2,2' -diamine, benzil and chiral phosphoric acid catalyst in a first organic solvent, carrying out dehydration condensation reaction to obtain a compound (R) -3,wherein, the structural formula of the chiral phosphoric acid catalyst is as follows: />
Converting one or two methoxy groups in the compound (R) -3 into hydroxyl groups to respectively obtain a compound A,and compound B, < >>
The first organic solvent is THF;
the step of converting one or two methoxy groups in said compound (R) -3 to hydroxyl groups comprises: mixing the compound (R) -3, tris (pentafluorophenyl) boron, triethylsilane and a second organic solvent, adding potassium fluoride and ethanol for reaction, and separating to obtain a compound A and a compound B; alternatively, BBr is added dropwise to the solution of said compound (R) -3 at a temperature of not higher than 0 ℃to obtain a solution of said compound (R) -3 3 Obtaining a compound A and a compound B through reaction;
dissolving the compound A and tris (dimethylamino) phosphine in a third organic solvent, reacting to obtain a compound C,
and/or dissolving the compound A and the tri (diethylamino) phosphine in a fourth organic solvent, reacting to obtain a compound D,
dropwise adding diisopropylamine into a mixed solution of phosphorus trichloride and triethylamine at the temperature of not higher than 0 ℃ and then reacting at room temperature; then adding the mixed solution of the compound A and triethylamine, reacting to obtain a compound E,
and/or, under the condition of not higher than 0 ℃, carrying out (+) -di [ (R) -1-phenethyl]Dropwise adding amine into a mixed solution of phosphorus trichloride and triethylamine, and reacting at room temperature; then adding the mixed solution of the compound A and triethylamine, reacting to obtain a compound F,
mixing the compound A with pyridine and phosphorus oxychloride, reacting at 70-90 ℃, adding water, and reacting at 40-60 ℃;then adding hydrochloric acid, reacting at 90-120 ℃, separating to obtain a compound G,
dissolving the compound B, trifluoromethanesulfonic anhydride and pyridine in a fifth organic solvent, reacting to obtain a compound (R) -7,
dissolving the compound (R) -7, a first palladium catalyst, 1, 3-bis (diphenylphosphine) propane, N-diisopropylethylamine and diphenylphosphine oxide in a sixth organic solvent, reacting to obtain a compound (R) -8,
dissolving the (R) -8, trichlorosilane and N, N-dimethylaniline in a seventh organic solvent, reacting to obtain a compound H,
dissolving the compound A, trifluoromethanesulfonic anhydride and pyridine in an eighth organic solvent, reacting to obtain a compound (R) -9,
dissolving the compound (R) -9, a second palladium catalyst, 1, 4-bis (diphenylphosphine) butane, N-diisopropylethylamine and diphenylphosphine in a ninth organic solvent, reacting to obtain a compound I,
dissolving the compound (R) -9, a third palladium catalyst, 1, 3-bis (diphenylphosphine) propane, N-diisopropylethylamine and diphenylphosphine oxide in a tenth organic solvent, reacting to obtain a compound (R) -10,
dissolving the compound (R) -10, trichlorosilane and N, N-dimethylaniline in an eleventh organic solvent, reacting to obtain the compound (R) -11,
dissolving the compound (R) -11, a fourth palladium catalyst, 1, 4-bis (diphenylphosphine) butane, N-diisopropylethylamine and diphenylphosphine oxide in a twelfth organic solvent, reacting to obtain a compound J,and the compound (A) is a compound (B),
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