Chiral tetraaryl substituted methane and preparation method thereof

Abstract

The invention belongs to the technical field of synthetic chemistry and particularly relates to chiral tetraaryl substituted methane and a preparation method thereof. The general structural formula ofchiral tetraaryl substituted methane is represented as formula I in the description, and Ar<1>, Ar<2>, Ar<3> and Ar<4> in the general structural formula represented as formula I are independently selected from any one of aryl, heteroaryl, substituted aryl and substituted heteroaryl and are different from one another. Chiral tetraaryl substituted methane has specific molecular shape and spatial configuration, thereby having special pharmaceutical nature and great prospects in the aspect of development of new drugs; with the adoption of the preparation method, the problem that a chiral tetraaryl quaternary carbon center, namely, the chiral tetraaryl methane structure cannot be constructed by direct catalysis in the field of chemical and pharmaceutical synthesis is solved, meanwhile, the preparation method is simple to operate, practical and has high yield, and the preparation process has the characteristics of being green, economical and environmentally friendly and facilitating industrialization.

Description

technical field

[0001] The invention belongs to the technical field of synthetic chemistry, and in particular relates to a chiral tetraaryl-substituted methane and a preparation method thereof. Background technique

[0002] Aryl-substituted methane has attracted extensive attention in the fields of organic materials, life sciences, and supramolecular chemistry due to its applications in optical devices, functional material frameworks, drug release, and protein translocation detection. However, the current limited synthesis methods of arylmethanes also greatly restrict their application development in the fields of synthesis and drug development. Contents of the invention

[0003] The object of the present invention is to provide a chiral tetraaryl-substituted methane and its preparation method, aiming to solve the technical problem of limited types and synthesis of the existing aryl methane.

[0004] For realizing above-mentioned purpose of the invention, the technical sc...

Examples

preparation example Construction

[0023] On the other hand, the embodiment of the present invention also provides a preparation method of chiral tetraaryl-substituted methane, comprising the following steps:

[0024] dissolving the compound represented by formula II and the compound represented by formula III in a solvent, and performing a synthesis reaction under the condition of a chiral phosphoric acid catalyst to obtain the compound represented by formula I;

[0025]

[0026] Among them, in the above compounds, Ar 1 、Ar 2 、Ar 3 and Ar 4 are independently selected from any one of aryl, heteroaryl, substituted aryl and substituted heteroaryl, and Ar 1 、Ar 2 、Ar 3 and Ar 4 different from each other.

[0027] In the above-mentioned preparation method provided by the embodiment of the present invention, the compound shown in formula II, that is, triaryl-substituted methanol and the compound shown in formula III, that is, aryl nucleophile are used to react under the condition of chiral phosphoric acid ...

Embodiment 1

[0039]

[0040] Using Ar 1 For 4-hydroxyphenyl, Ar 2 is 2-methoxyphenyl, Ar 3 The phenyl triaryl carbinol and 2-methylpyrrole are used as reaction raw materials, and the reaction is carried out with a chiral phosphoric acid catalyst. The specific implementation process is as follows:

[0041] Dissolve triarylmethanol (61.2mg, 0.2mmol) and 2-methylpyrrole (32.4mg, 0.4mmol) in 1,2-dichloroethane (3.6mL), and cool the mixture to 0°C, slowly drop A solution of chiral phosphoric acid (14.9 mg, 0.015 mmol) in 1,2-dichloroethane (0.4 mL) was added. After that, it was placed at 0°C and stirred for 48 hours. Its reaction equation is as follows:

[0042]

[0043] The reaction solution was directly applied to silica gel column chromatography to obtain 71.7 mg of the target product Ia as a pale yellow foamy solid, with a calculated yield of 97%.

[0044] After the preparation of this step is completed, in order to further verify that the purified compound is indeed the target ...

Embodiment 2

[0053]

[0054] Using Ar 1 For 4-hydroxyphenyl, Ar 2 For 2-benzo[1,3]-dioxolanyl, Ar 3 The phenyl triaryl carbinol and 2-methylpyrrole are used as reaction raw materials, and the reaction is carried out with a chiral phosphoric acid catalyst. The specific implementation process is as follows:

[0055] Dissolve triarylmethanol (64.0mg, 0.2mmol) and 2-methylpyrrole (32.4mg, 0.4mmol) in 1,2-dichloroethane (3.6mL), and cool the mixture to 0°C, slowly drop A solution of chiral phosphoric acid (14.9 mg, 0.015 mmol) in 1,2-dichloroethane (0.4 mL) was added. After that, it was placed at 0°C and stirred for 48 hours.

[0056] The reaction solution was directly applied to silica gel column chromatography to obtain 72.1 mg of the target product Ib as a pale yellow foamy solid, with a calculated yield of 94%.

[0057] After the preparation of this step is completed, in order to further verify that the purified compound is indeed the target product to be prepared in this example, t...

technical field

[0001] The invention belongs to the technical field of synthetic chemistry, and in particular relates to a chiral tetraaryl-substituted methane and a preparation method thereof. Background technique

[0002] Aryl-substituted methane has attracted extensive attention in the fields of organic materials, life sciences, and supramolecular chemistry due to its applications in optical devices, functional material frameworks, drug release, and protein translocation detection. However, the current limited synthesis methods of arylmethanes also greatly restrict their application development in the fields of synthesis and drug development. Contents of the invention

[0003] The object of the present invention is to provide a chiral tetraaryl-substituted methane and its preparation method, aiming to solve the technical problem of limited types and synthesis of the existing aryl methane.

[0004] For realizing above-mentioned purpose of the invention, the technical sc...

Examples

preparation example Construction

[0023] On the other hand, the embodiment of the present invention also provides a preparation method of chiral tetraaryl-substituted methane, comprising the following steps:

[0024] dissolving the compound represented by formula II and the compound represented by formula III in a solvent, and performing a synthesis reaction under the condition of a chiral phosphoric acid catalyst to obtain the compound represented by formula I;

[0025]

[0026] Among them, in the above compounds, Ar 1 、Ar 2 、Ar 3 and Ar 4 are independently selected from any one of aryl, heteroaryl, substituted aryl and substituted heteroaryl, and Ar 1 、Ar 2 、Ar 3 and Ar 4 different from each other.

[0027] In the above-mentioned preparation method provided by the embodiment of the present invention, the compound shown in formula II, that is, triaryl-substituted methanol and the compound shown in formula III, that is, aryl nucleophile are used to react under the condition of chiral phosphoric acid ...

Embodiment 1

[0039]

[0040] Using Ar 1 For 4-hydroxyphenyl, Ar 2 is 2-methoxyphenyl, Ar 3 The phenyl triaryl carbinol and 2-methylpyrrole are used as reaction raw materials, and the reaction is carried out with a chiral phosphoric acid catalyst. The specific implementation process is as follows:

[0041] Dissolve triarylmethanol (61.2mg, 0.2mmol) and 2-methylpyrrole (32.4mg, 0.4mmol) in 1,2-dichloroethane (3.6mL), and cool the mixture to 0°C, slowly drop A solution of chiral phosphoric acid (14.9 mg, 0.015 mmol) in 1,2-dichloroethane (0.4 mL) was added. After that, it was placed at 0°C and stirred for 48 hours. Its reaction equation is as follows:

[0042]

[0043] The reaction solution was directly applied to silica gel column chromatography to obtain 71.7 mg of the target product Ia as a pale yellow foamy solid, with a calculated yield of 97%.

[0044] After the preparation of this step is completed, in order to further verify that the purified compound is indeed the target ...

Embodiment 2

[0053]

[0054] Using Ar 1 For 4-hydroxyphenyl, Ar 2 For 2-benzo[1,3]-dioxolanyl, Ar 3 The phenyl triaryl carbinol and 2-methylpyrrole are used as reaction raw materials, and the reaction is carried out with a chiral phosphoric acid catalyst. The specific implementation process is as follows:

[0055] Dissolve triarylmethanol (64.0mg, 0.2mmol) and 2-methylpyrrole (32.4mg, 0.4mmol) in 1,2-dichloroethane (3.6mL), and cool the mixture to 0°C, slowly drop A solution of chiral phosphoric acid (14.9 mg, 0.015 mmol) in 1,2-dichloroethane (0.4 mL) was added. After that, it was placed at 0°C and stirred for 48 hours.

[0056] The reaction solution was directly applied to silica gel column chromatography to obtain 72.1 mg of the target product Ib as a pale yellow foamy solid, with a calculated yield of 94%.

[0057] After the preparation of this step is completed, in order to further verify that the purified compound is indeed the target product to be prepared in this example, t...

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