阅读说明：本技术 一种具有轴手性联萘骨架的Trost配体及其制备方法 (Trost ligand with axial chiral binaphthyl skeleton and preparation method thereof ) 是由 陆海华 王亚辉 高卫 于 2020-05-18 设计创作，主要内容包括：本发明公开一种新型光学纯联萘Trost配体及其制备方法,通过(S)-2’-(二芳基膦)-[1,1’-联萘]-2-羧酸与手性二胺发生缩合反应得到具有轴手性联萘骨架的Trost配体。本发明开创性的研究了新型Trost配体的制备方法,在传统的的Trost配体中引入轴手性联萘骨架,同时增加了分子的刚性和立体控制能力,有效促进了手性双膦配体在不对称催化反应中的应用。<Image he="220" wi="700" file="DDA0002497196920000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>(The invention discloses a novel optical pure binaphthyl Trost ligand and a preparation method thereof, which is prepared by (S) -2 '- (diarylphosphine) - [1, 1' -binaphthyl]And (3) carrying out condensation reaction on the-2-carboxylic acid and chiral diamine to obtain the Trost ligand with an axial chiral binaphthyl skeleton. The invention creatively researches a preparation method of a novel Trost ligand, introduces an axial chiral binaphthyl skeleton into the traditional Trost ligand, increases the rigidity and the stereo control capability of molecules, and effectively promotes the application of chiral diphosphine ligand in asymmetric catalytic reaction.)

1. A Trost ligand with an axial chiral binaphthyl skeleton is characterized in that the structure is shown as a formula (I), and the isomer is shown as a formula (II):

wherein:

Ar₂is one of phenyl, p-methylphenyl, p-phenylphenyl, p-fluorophenyl, 3, 5-dimethylphenyl or 2-naphthyl;

is chiral diamine, and has the following specific structure:

in the formulae (Ib) and (IIb) the aryl Ar is a phenyl ring or 2, 4, 6- (CH)₃)₃-C₆H₂-。

2. A method for preparing a Trost ligand having an axial chiral binaphthyl skeleton according to claim 1, comprising the steps of:

(1) preparing (S) -2 '- (diarylphosphine) - [1, 1' -binaphthyl ] -2-carboxylic acid, adding the successfully prepared (S) -2 '- (diarylphosphine) - [1, 1' -binaphthyl ] -2-carboxylic acid and chiral diamine into a reactor according to the molar ratio of 2-4: 1, simultaneously adding a condensing agent, a first acid-binding agent and a first solvent, stirring and reacting for 10-12 h at 20-30 ℃, adding a first quenching agent after the reaction is finished, extracting, and performing column chromatography separation by using n-hexane/ethyl acetate to obtain the novel optical pure binaphthyl Trost ligand shown in the formula (I);

the specific equation is as follows:

3. the method for preparing a Trost ligand having an axial chiral binaphthyl skeleton according to claim 2, wherein: in the step (1), the first solvent is 1, 2-dichloroethane, the condensing agent is 2-chloro-1-methylpyridine iodide, the first acid-binding agent is N, N-diisopropylethylamine, and the first quenching agent is 1M hydrochloric acid aqueous solution.

4. The method for preparing a Trost ligand having an axial chiral binaphthyl skeleton according to claim 2, wherein: the preparation method of the (S) -2 '- (diarylphosphine) - [1, 1' -binaphthyl ] -2-carboxylic acid specifically comprises the following steps:

(21) condensation reaction: adding a mixture of 1: 2-3 of (S) -BINOL (1, 1' -bi-2-naphthol) and trifluoromethanesulfonic anhydride, adding a second acid-binding agent and a second solvent, reacting at 25 ℃ for 3 hours, adding a second quenching agent after the reaction is finished, extracting, drying, removing the solvent, and performing column chromatography separation by using n-hexane and ethyl acetate to obtain a first intermediate shown in formula (V);

(22) monocarbonylation reaction: adding a first composite catalyst, N' -diisopropylethylamine, a carbonylation reagent and a third solvent into the first intermediate, reacting for 24 hours at 80-100 ℃, cooling to room temperature, adding a third quenching agent, removing the solvent after extraction, and performing column chromatography separation by using N-hexane and ethyl acetate to obtain a second intermediate shown in formula (VI);

(23) phosphine oxidation: adding a second composite catalyst, N' -diisopropylethylamine, diphenylphosphine oxide and a fourth solvent into the second intermediate, reacting for 30 hours at 110-130 ℃, cooling to room temperature, adding a fourth quenching agent, removing the solvent after extraction, and performing column chromatography separation by using N-hexane and ethyl acetate to obtain a third intermediate as shown in a formula (VII);

(24) reduction reaction: adding a fifth solvent into the third intermediate, adding composite reducing agents trichlorosilane and N, N' -diisopropylethylamine at the temperature of 0 ℃, heating to 110-120 ℃, reacting for 4 hours, adding a fifth quenching agent after the reaction is finished, drying and removing the solvent after extraction, and performing column chromatography separation by using normal hexane and ethyl acetate to obtain a fourth intermediate, wherein the formula is shown in formula (VIII);

(25) and (3) hydrolysis reaction: adding a hydrolyzing agent and methanol into the fourth intermediate, and reacting at 90-100 ℃ for 12h to obtain a final product, wherein the final product is shown as a formula (III);

the specific reaction process equation is as follows:

5. the method for preparing a Trost ligand having an axial chiral binaphthyl skeleton according to claim 4, wherein: in the step (21), the second acid-binding agent is pyridine, the second solvent is toluene, and the second quenching agent is saturated sodium bicarbonate.

6. The method for preparing a Trost ligand having an axial chiral binaphthyl skeleton according to claim 4, wherein: the first composite catalyst in the step (22) is Pd (OAc)₂/1,3-(PPh₂)₂-C₃H₆The carbonylation reagent is CO, the third solvent is a mixed solvent of dimethyl sulfoxide and methanol according to the volume ratio of 3:2, and the third quenching agent is saturated ammonium chloride.

7. The method for preparing a Trost ligand having an axial chiral binaphthyl skeleton according to claim 4, wherein: the second composite catalyst in the step (23) is Pd (OAc)₂/1,4-(PPh₂)₂-C₄H₈The fourth solvent is dimethyl sulfoxide, and the fourth quenching agent is saturated ammonium chloride.

8. The method for preparing a Trost ligand having an axial chiral binaphthyl skeleton according to claim 4, wherein: in the step (24), the fifth solvent is toluene, and the fifth quenching agent is methanol.

9. The method for preparing a Trost ligand having an axial chiral binaphthyl skeleton according to claim 4, wherein: in the step (25), the hydrolytic agent is a potassium hydroxide aqueous solution.

Technical Field

The invention belongs to the technical field of chemical preparation, and particularly relates to a Trost ligand with an axial chiral binaphthyl skeleton and a preparation method thereof.

Background

Chirality is an asymmetry of a substance that is ubiquitous in nature. The chirality of many drugs is closely related to their potency and activity. Asymmetric catalysis is an important method for obtaining chiral drugs or chiral compounds, and mainly comprises organic small molecule catalysis and metal catalysis. In the study of asymmetric reaction catalyzed by metal, chiral ligand is a key factor influencing the stereoselectivity of reaction, so that the chiral ligand with simple structure, convenient synthesis and high catalytic selectivity is a subject which is always concerned by organic chemists in the field of asymmetric synthesis. WhereinC₂The symmetric chiral ligand has high stereoselectivity and catalytic effect in asymmetric catalytic reaction, and thus, the chiral ligand is widely applied by people. In a plurality of C₂Among symmetric ligands, Trost ligands are N and P ligands which have simple synthesis methods and good stereoselectivity, and are widely applied to various asymmetric catalytic reactions by scientists in various countries in recent years. However, modification and improvement of the chiral carbon skeleton in the Trost ligand are limited, and further development is needed.

On the other hand, the chiral biaryl compounds are a class of compounds also having C₂Axial chiral compounds of the axis of symmetry. Different from a common central chiral compound, biaryl molecules are hindered from rotating around a biphenyl axis to generate an axial chiral isomer, and the unique stereo structure determines that the molecules have a larger rigid structure and high stereo control capability. Therefore, a series of novel compounds derived by taking chiral biaryl as a carbon skeleton are paid attention to by virtue of excellent chiral control capability, and therefore, the introduction of the chiral biaryl into a chiral ligand structure to develop a novel ligand for application in asymmetric catalytic reaction has important significance.

Disclosure of Invention

The purpose of the invention is as follows: the invention aims to provide a Trost ligand with an axial chiral binaphthyl skeleton and a preparation method thereof aiming at the defects of the prior art.

The technical scheme is as follows: the structure of the Trost ligand with the axial chiral binaphthyl skeleton is shown as a formula (I), and the isomer is shown as a formula (II):

wherein:

Ar₂is one of phenyl, p-methylphenyl, p-phenylphenyl, p-fluorophenyl, 3, 5-dimethylphenyl or 2-naphthyl;

is chiral diamine, and has the following specific structure:

the chiral diamine with another configuration has the following specific structure:

in the formulae (Ib) and (IIb) the aryl Ar is a phenyl ring or 2, 4, 6- (CH)₃)₃-C₆H₂-。

The invention also provides a preparation method of the Trost ligand with the axial chiral binaphthyl skeleton, which comprises the following steps:

(1) preparing (S) -2 '- (diarylphosphine) - [1, 1' -binaphthyl ] -2-carboxylic acid, adding the successfully prepared (S) -2 '- (diarylphosphine) - [1, 1' -binaphthyl ] -2-carboxylic acid and chiral diamine into a reactor according to the molar ratio of 2-4: 1, simultaneously adding a condensing agent, a first acid-binding agent and a first solvent, stirring and reacting for 10-12 h at 20-30 ℃, adding a first quenching agent after the reaction is finished, extracting, and performing column chromatography separation by using n-hexane/ethyl acetate to obtain the novel optical pure binaphthyl Trost ligand shown in the formula (I);

the specific equation is as follows:

further, in the step (1), the first solvent is 1, 2-dichloroethane, the condensing agent is 2-chloro-1-methylpyridine iodide, the first acid-binding agent is N, N-diisopropylethylamine, and the first quenching agent is 1M hydrochloric acid aqueous solution.

Further, the preparation method of the raw material (S) -2 '- (diarylphosphine) - [1, 1' -binaphthyl ] -2-carboxylic acid specifically comprises the following steps:

(21) condensation reaction: adding a mixture of 1: 2-3 of (S) -BINOL (1, 1' -bi-2-naphthol) and trifluoromethanesulfonic anhydride, adding a second acid-binding agent and a second solvent, reacting at 25 ℃ for 3 hours, adding a second quenching agent after the reaction is finished, extracting, drying, removing the solvent, and performing column chromatography separation by using n-hexane and ethyl acetate to obtain a first intermediate shown in formula (V);

(22) monocarbonylation reaction: adding a first composite catalyst, N' -diisopropylethylamine, a carbonylation reagent and a third solvent into the first intermediate, reacting for 24 hours at 80-100 ℃, cooling to room temperature, adding a third quenching agent, removing the solvent after extraction, and performing column chromatography separation by using N-hexane and ethyl acetate to obtain a second intermediate shown in formula (VI);

(23) phosphine oxidation: adding a second composite catalyst Pd (OAc) to the second intermediate₂/1,4-(PPh₂)₂-C₄H₈Reacting N, N' -diisopropylethylamine, diphenylphosphine oxide and a fourth solvent at 110-130 ℃ for 30h, cooling to room temperature, adding a fourth quenching agent, extracting, removing the solvent, and performing column chromatography separation by using N-hexane and ethyl acetate to obtain a third intermediate as shown in a formula (VII);

(24) reduction reaction: adding a fifth solvent into the third intermediate, adding composite reducing agents trichlorosilane and N, N' -diisopropylethylamine at the temperature of 0 ℃, heating to 110-120 ℃, reacting for 4 hours, adding a fifth quenching agent after the reaction is finished, drying and removing the solvent after extraction, and performing column chromatography separation by using normal hexane and ethyl acetate to obtain a fourth intermediate, wherein the formula is shown in formula (VIII);

(25) and (3) hydrolysis reaction: adding a hydrolyzing agent and methanol into the fourth intermediate, and reacting at 90-100 ℃ for 12h to obtain a final product, wherein the final product is shown as a formula (III);

the specific reaction process equation is as follows:

further, in the step (21), the second acid-binding agent is pyridine, the second solvent is toluene, and the second quenching agent is saturated sodium bicarbonate.

Further, the method can be used for preparing a novel materialIn step (22), the first composite catalyst is Pd (OAc)₂/1,3-(PPh₂)₂-C₃H₆The carbonylation reagent is CO, the third solvent is a mixed solvent of dimethyl sulfoxide and methanol according to the volume ratio of 3:2, and the third quenching agent is saturated ammonium chloride.

Further, in the step (23), the second composite catalyst is Pd (OAc)₂/1,4-(PPh₂)₂-C₄H₈The fourth solvent is dimethyl sulfoxide, and the fourth quenching agent is saturated ammonium chloride.

Further, in the step (24), the fifth solvent is toluene, and the fifth quenching agent is methanol.

Further, in the step (25), the hydrolytic agent is a potassium hydroxide aqueous solution.

Has the advantages that: (1) the invention pioneers and synthesizes 2 '- (diarylphosphine) - [1, 1' -binaphthyl ] with S configuration]2-carboxylic acid, and 2 '- (diarylphosphine) - [1, 1' -binaphthyl ] adopting the S configuration]The research of-2-carboxylic acid synthesizes Trost ligand with axial chiral binaphthyl skeleton, and the successful introduction of chiral biaryl into chiral ligand structure has important significance in developing novel ligand for asymmetric catalytic reaction, and enriches C₂The chiral carbon skeleton of the symmetric ligand effectively promotes the further development of the Trost ligand in the field of catalysis asymmetry; in the invention, through the research of the inventor on the characteristics of the raw materials, a condensation agent, an acid binding agent and a corresponding solvent are selected and added in a targeted manner, so that the smooth proceeding of the reaction process is ensured, and the yield and the purity of the product are improved.

Drawings

FIG. 1 shows the preparation of a compound of formula (III)¹H NMR spectrum;

FIG. 2 shows the preparation of a compound of formula (III)¹³C NMR spectrum;

FIG. 3 shows the preparation of a compound of formula (III)³¹A P NM spectrogram;

FIG. 4 shows the compound of formula (I) of the product of the present invention¹H NMR spectrum;

FIG. 5 shows the compound of formula (I) of the present invention¹³C NMR spectraA drawing;

FIG. 6 shows the preparation of the compound of formula (I)³¹A P NM spectrogram;

FIG. 7 shows the preparation of a compound of formula (II)¹H NMR spectrum;

FIG. 8 shows the preparation of a compound of formula (II)¹³C NMR spectrum;

FIG. 9 shows the preparation of a compound of formula (II)³¹P NM spectrum.

Detailed Description

The technical solution of the present invention is described in detail below with reference to the accompanying drawings, but the scope of the present invention is not limited to the embodiments.