Method for preparing β-arylamine compound and analog thereof

Abstract

The present application provides a method for preparing a β-arylamine compound and an analog thereof, comprising the following step: mixing a rhodium catalyst, a base, a compound represented by formula (1), a compound represented by formula (2), and a compound represented by formula (3), and then reacting the mixture in an inert atmosphere to obtain a compound represented by formula (A). By means of the reaction of a compound represented by formula (1), a compound represented by formula (2), and a compound represented by formula (3), which are used as starting materials, in an inert atmosphere under the action of a rhodium catalyst and a base, a β-arylamine compound represented by formula (A) and an analog thereof can be prepared in one step; thus, the present application significantly reduces the number of synthesis steps and the synthesis time, features a simple addition manner, employs readily available starting materials, and has relatively high yield and purity.

Description

Process for preparing beta-arylamines and analogs thereof TECHNICAL FIELD

[0001] The present application relates to the technical field of chemical synthesis, and particularly relates to a process for preparing beta-arylamines and analogs thereof. BACKGROUND

[0002] Beta-arylamines are an important class of chemical products or synthetic intermediates, and the benzylamine structure thereof has an important role in medicine and other aspects. For example, Agomelatine shown in formula (I) is a new type of antidepressant drug, and is mainly used for treating adult depression. The Agomelatine has a standard beta-arylamines structure: Formula (I).

[0003] For another example, the compound shown in formula (A-2) is also proved to have an antidepressant effect, and also has a standard beta-arylamines structure: Formula (A-2).

[0004] The prior art discloses various routes for synthesizing beta-arylamines, but generally has the defects of multiple and complicated reaction steps and low yield. SUMMARY

[0005] Therefore, the purpose of the present application is to provide a process for preparing beta-arylamines and analogs thereof. The process provided by the present application can prepare beta-arylamines and analogs thereof in one step, and has a short reaction route and high yield.

[0006] The present application provides a process for preparing beta-arylamines and analogs thereof, comprising the following steps: mixing a rhodium catalyst, a base, a compound shown in formula (1), a compound shown in formula (2) and a compound shown in formula (3), and then reacting under an inert atmosphere to obtain a compound shown in formula (A);

[0007] Formula (1) Ar-M; Formula (2); Formula (3); Formula (A);

[0008] wherein Ar is selected from an aromatic group optionally substituted by one or more substituents or a heteroaromatic group optionally substituted by one or more substituents; and M is a boron-containing substituent, and the B atom of the boron-containing substituent is connected to the Ar group;

[0009] X is halogen;

[0010] R6, R7, R8, R9are each independently selected from one of hydrogen, halogen, alkyl optionally substituted with one or more substituents, alkenyl optionally substituted with one or more substituents, alkynyl optionally substituted with one or more substituents, alkoxy optionally substituted with one or more substituents, cyano, amido optionally substituted with one or more substituents, ester optionally substituted with one or more substituents, ketone optionally substituted with one or more substituents, phenyl optionally substituted with one or more substituents, naphthyl optionally substituted with one or more substituents, nitrogen-containing heterocycle optionally substituted with one or more substituents, oxygen-containing heterocycle optionally substituted with one or more substituents, sulfur-containing heterocycle optionally substituted with one or more substituents;

[0011] the substituents are selected from alkyl, haloalkyl, alkoxy, haloalkoxy, cyano, halogen, alkenyl, haloalkenyl, alkenyloxy, alkylthio, haloalkylthio, alkyl-substituted boronate, alkanoate, benzyloxy, or aryl.

[0012] In some specific implementations, R6, R7, R8are each independently selected from hydrogen or alkyl optionally substituted with one or more substituents.

[0013] R9is selected from phenyl optionally substituted with one or more substituents or ketone optionally substituted with one or more substituents.

[0014] the substituents are selected from alkoxy or alkyl.

[0015] In some specific implementations, the molar ratio of the compound represented by formula (1), the compound represented by formula (2), and the compound represented by formula (3) is 0.2-1:0.8-4.0:0.2-3.0.

[0016] In some specific implementations, the molar ratio of the compound represented by formula (1) to the base is 0.2-1:1-3.

[0017] The molar percentage of the rhodium catalyst in the compound represented by formula (1) is 1%-100%.

[0018] In some specific implementations, the temperature of the reaction is 0 ℃-200 ℃, and the time is 20 min-36 hours.

[0019] In some embodiments, the rhodium catalyst is selected from one or more of acetylacetone bis(ethylene)rhodium(I), dicarbonyl acetylacetone rhodium(I), (1,5- cyclooctadiene)chloro rhodium(I) dimer, bis(1,5-cyclooctadiene)-trifluoromethanesulfonic acid rhodium, bis(1,5-cyclooctadiene)tetrafluoroborate rhodium, tris(triphenylphosphine)rhodium(I) bromide, bis[(1,5-cyclooctadiene)(methoxy)rhodium], (1,5- cyclooctadiene)2,4-pentanedione rhodium(I), chloro bis(ethylene)rhodium(I) dimer, dimeric hydroxy(1,5-cyclooctadiene)rhodium(I), 1,2-bis[(2S,5S)-2,5- diphenylphosphino]ethane(1,5-cyclooctadiene)tetrafluoroborate rhodium(I), carbonylbis(triphenylphosphine)rhodium(I) chloride, bis(1,5-cyclooctadiene)rhodium(I) antimony hexafluoride, tris(triphenylphosphine)carbonylhydrido rhodium(I), (R)-(-)-t- butylmethyl(di-t-butylphosphinomethyl)phosphino(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate.

[0020] In some embodiments, the base is selected from one or more of lithium trimethylsilanolate, sodium trimethylsilanolate, potassium trimethylsilanolate, lithium tert-butoxide, potassium tert-butoxide, sodium tert-butoxide, lithium methoxide, potassium methoxide, sodium methoxide, lithium carbonate, sodium bicarbonate, sodium carbonate, potassium carbonate, sodium thiosulfate, cesium carbonate, lithium hydroxide, potassium hydroxide, sodium hydroxide, calcium hydroxide, magnesium hydroxide, barium hydroxide, sodium sulfate, potassium dihydrogen phosphate, potassium sulfate, potassium trihydrogen phosphate, calcium hydrogen phosphate, potassium tetrahydrogen phosphate, calcium dihydrogen phosphate, calcium tetrahydrogen phosphate, calcium trihydrogen phosphate, sodium phosphate, sodium trihydrogen phosphate, sodium dihydrogen phosphate, sodium tetrahydrogen phosphate, magnesium dihydrogen phosphate, magnesium phosphate, magnesium trihydrogen phosphate, aluminum dihydrogen phosphate, aluminum tetrahydrogen magnesium phosphate, aluminum trihydrogen phosphate, copper phosphate, aluminum tetrahydrogen phosphate, copper dihydrogen phosphate, copper trihydrogen phosphate, and copper tetrahydrogen phosphate.

[0021] In some embodiments, the solvent used for the reaction is selected from one or more of water, deuterium water, ethanol, methanol, isopropanol, n-hexane, n-pentane, cyclopentane, dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, methyl tert-butyl ether, diethyl ether, acetone, benzene, deuterated benzene, toluene, deuterated toluene, p-xylene, o-xylene, m-xylene, ethylbenzene, chlorobenzene, dichloromethane, deuterated dichloromethane, chloroform, deuterated chloroform, tetrahydrofuran, and 1,4-dioxane.

[0022] In some embodiments, the compound of Formula (1) is selected from one or more of aryl boronic acid, (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) aryl compound, aryl potassium trifluoroborate, aryl boronic acid neopentyl glycol ester, 2-aryl-1,3,2-benzene dithiol borane.

[0023] In some specific implementations, the compound shown in formula (2) is selected from bromoethylene.

[0024] The present application uses the compound shown in formula (1), the compound shown in formula (2) and the compound shown in formula (3) as raw materials, and reacts under the action of a rhodium catalyst and a base in an inert atmosphere to obtain the β-arylamine compound shown in formula (A) and its analogues in one step, greatly shortening the synthesis steps and time, and the feeding mode is simple, the raw materials are easy to obtain, and the yield and purity are high.

[0025] BRIEF DESCRIPTION OF DRAWINGS

[0026] Fig. 1 is a hydrogen spectrum of the β-arylamine compound provided in Example 1 of the present application;

[0027] Fig. 2 is a carbon spectrum of the β-arylamine compound provided in Example 1 of the present application;

[0028] Fig. 3 is a hydrogen spectrum of the β-arylamine compound provided in Example 2 of the present application;

[0029] Fig. 4 is a carbon spectrum of the β-arylamine compound provided in Example 2 of the present application;

[0030] Fig. 5 is a hydrogen spectrum of the β-arylamine compound provided in Example 3 of the present application;

[0031] Fig. 6 is a carbon spectrum of the β-arylamine compound provided in Example 3 of the present application;

[0032] Fig. 7 is a hydrogen spectrum of the β-arylamine compound provided in Example 4 of the present application;

[0033] Fig. 8 is a carbon spectrum of the β-arylamine compound provided in Example 4 of the present application;

[0034] Fig. 9 is a hydrogen spectrum of the β-arylamine compound provided in Example 5 of the present application;

[0035] Fig. 10 is a carbon spectrum of the β-arylamine compound provided in Example 5 of the present application;

[0036] Fig. 11 is a hydrogen spectrum of the β-arylamine compound provided in Example 6 of the present application;

[0037] Fig. 12 is a carbon spectrum of the β-arylamine compound provided in Example 6 of the present application. DETAILED DESCRIPTION

[0038] It should be understood that the expression "one or more of' individually includes each of the recited objects and various combinations of two or more of the recited objects, unless otherwise specifically stated in the context and use of the expression. The expression "and / or" in conjunction with two or more recited objects should be understood to have the same meaning, unless otherwise specifically stated in the context.

[0039] The use of the terms "including," "comprising," or "having" and variations thereof, as used in this document, are intended to be open and permissive, and thus do not exclude additional, unrecited elements or steps. The terms "substantially," "essentially," "virtually," and the like, are used in the sense of "largely but not perfectly" or "ultimately small but not zero," as understood by one of ordinary skill in the art.

[0040] It should be understood that the order of steps or order for performing certain actions is immaterial so long as the application remains operable. Moreover, two or more steps or actions can be conducted simultaneously.

[0041] The use of any and all examples, or exemplary language herein, is intended merely to better illuminate the application and does not pose a limitation on the scope of the application unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the application.

[0042] Further, the numerical ranges and parameters setting forth the broadest scope of the application are approximations, and are merely intended to convey general information as to the scope of the application. Consistent with the application as claimed, consi stent with good practice, the numerical values are approximations. Therefore, unless otherwise indicated, it is intended that the numbers set forth in the specific examples are approximate but intended to be within standard experimental error. It will be apparent to one of ordinary skill in the art, however, that available methods of the art can not be used, for example, to determine certain quantities to an absolute level of precision. Where particular values are provided, unless otherwise stated the exact mechanism of measurement or derivation from original data is not to be believed to be a requirement for a claim. Moreover, it is intended that all ranges provided herein are "open" ranges in that the recited maximum and minimum values are not included in the ranges, unless the context clearly dictates otherwise. Thus, for example, a range of "1 to 10" is intended to include all sub-ranges between (and including) the recited minimum and maximum values, i.e., the range of 1 to 8. Also, it should be understood that all ranges provided herein are "open" ranges in that the recited maximum and minimum values are not included in the ranges, unless the context clearly dictates otherwise. Thus, for example, a range of "1 to 10" is intended to include all sub-ranges between (and including) the recited minimum and maximum values, i.e., the range of 1 to 8.

[0043] The term "halogen" represents fluorine, chlorine, bromine and iodine;

[0044] The term "alkyl" represents a saturated straight chain or branched chain hydrocarbon group having from 1 to 6 carbon atoms, such as methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylethyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, and 1-ethyl-2-methylpropyl;

[0045] The term "alkenyl" represents an unsaturated straight-chain or branched-chain hydrocarbon group having 2 or 3 to 6 carbon atoms and one double bond in any desired position, for example, C2-C6-alkenyl such as ethenyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-1-butenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1,1-dimethyl-2-propenyl, 1,2-dimethyl-1-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-1-propenyl, 1-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl, 2-methyl-1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1-pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1,1-dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl, 1,2-dimethyl-1-butenyl, 1,2-dimethyl-2-butenyl, 1,2-dimethyl-3-butenyl, 1,3-dimethyl-1-butenyl, 1,3-dimethyl-2-butenyl, 1,3-dimethyl-3-butenyl, 2,2-dimethyl-3-butenyl, 2,3-dimethyl-1-butenyl, 2,3-dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 3,3-dimethyl-1-butenyl, 3,3-dimethyl-2-butenyl, 1-ethyl-1-butenyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 2-ethyl-1-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1,1,2-trimethyl-2-propenyl, 1-ethyl-1-methyl-2-propenyl, 1-ethyl-2-methyl-1-propenyl or 1-ethyl-2-methyl-2-propenyl;

[0046] The term "alkynyl" represents a straight or branched chain hydrocarbon group having from 2 to 6 carbon atoms and one triple bond in any desired position, such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl, 1,1-dimethyl-2-propynyl, 1-ethyl-2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 1-methyl-4-pentynyl, 2-methyl-3-pentynyl, 2-methyl-4-pentynyl, 3-methyl-1-pentynyl, 3-methyl-4-pentynyl, 4-methyl-1-pentynyl, 4-methyl-2-pentynyl, 1,1-dimethyl-2-butynyl, 1,1-dimethyl-3-butynyl, 1,2-dimethyl-3-butynyl, 2,2-dimethyl-3-butynyl, 3,3-dimethyl-1-butynyl, 1-ethyl-2-butynyl, 1-ethyl-3-butynyl, 2-ethyl-3-butynyl, and 1-ethyl-1-methyl-2-propynyl;

[0047] The term "alkoxy" represents a straight or branched chain alkyl group having from 1 to 6 carbon atoms, as described above, bonded to the main structure through an -O- linkage;

[0048] The term "amido" represents a straight or branched chain alkyl group having from 1 to 6 carbon atoms, as described above, bonded to the main structure through an -NH-CO- linkage;

[0049] The term "ester" represents a straight or branched chain alkyl group having from 1 to 6 carbon atoms, as described above, bonded to the main structure through a -COO- linkage;

[0050] The term "keto" represents a straight or branched chain alkyl group having from 1 to 6 carbon atoms, as described above, bonded to the main structure through a -CO- linkage;

[0051] The term "aryl" represents an unsaturated aromatic hydrocarbon group having from 6 to 20 carbon atoms, such as phenyl, o-tolyl, 1-naphthyl (or α-naphthyl), or 2-naphthyl, and the like;

[0052] The term "heteroaryl" represents an aryl group as described above wherein at least one carbon atom is replaced by a heteroatom, such as N, O, or S;

[0053] The term "nitrogen-containing heterocyclic group" represents a heterocyclic group containing nitrogen, which is bonded to the main structure through -N-, and can further contain, as ring members, in addition to C and N, a group of heteroatoms consisting of oxygen, sulfur, for example, can be a 5-membered nitrogen-containing heterocyclic group containing one to four nitrogen atoms or one to three nitrogen atoms and one sulfur or oxygen atom; the nitrogen-containing heterocyclic group can be a nitrogen-containing six-membered heterocyclic group containing carbon atoms and one to five nitrogen atoms, and can further contain, as ring members, a sulfur atom or an oxygen atom, and the like;

[0054] The term "oxygen-containing heterocyclic group" represents a heterocyclic group containing oxygen, which is bonded to the main structure through -O-, and can further contain, as ring members, in addition to C and O, a group of heteroatoms consisting of nitrogen, sulfur, for example, can be a 5-membered oxygen-containing heterocyclic group containing one to four oxygen atoms or one to three oxygen atoms and one sulfur or nitrogen atom; the oxygen-containing heterocyclic group can be an oxygen-containing six-membered heterocyclic group containing carbon atoms and one to five oxygen atoms, and can further contain, as ring members, a sulfur atom or a nitrogen atom, and the like;

[0055] The term "sulfur-containing heterocyclic group" represents a heterocyclic group containing sulfur, which is bonded to the main structure through -S-, and can further contain, as ring members, in addition to C and S, a group of heteroatoms consisting of oxygen, nitrogen, for example, can be a 5-membered nitrogen-containing heterocyclic group containing one to four sulfur atoms or one to three sulfur atoms and one nitrogen or oxygen atom; the sulfur-containing heterocyclic group can be a sulfur-containing six-membered heterocyclic group containing carbon atoms and one to five sulfur atoms, and can further contain, as ring members, a sulfur atom or a nitrogen atom, and the like;

[0056] The term "boronate group" represents a boronate group (BO3-) bonded to the main structure.

[0057] The present application provides a preparation method of a β-aryl amine compound and its analogues, comprising the following steps:

[0058] Rhodium catalyst, base, compound represented by formula (1), compound represented by formula (2) and compound represented by formula (3) are mixed and reacted under inert atmosphere to obtain compound represented by formula (A);

[0059] Formula (1) Ar-M; Formula (2); Formula (3); Formula (A);

[0060] Wherein, Ar is selected from aryl group optionally substituted by one or more substituents or heteroaryl group optionally substituted by one or more substituents; M is boron-containing substituent, the B atom of the boron-containing substituent is connected with Ar group;

[0061] X is halogen;

[0062] R6, R7, R8, R9are each independently selected from one of hydrogen, halogen, alkyl optionally substituted with one or more substituents, alkenyl optionally substituted with one or more substituents, alkynyl optionally substituted with one or more substituents, alkoxy optionally substituted with one or more substituents, cyano, amido optionally substituted with one or more substituents, ester optionally substituted with one or more substituents, ketone optionally substituted with one or more substituents, phenyl optionally substituted with one or more substituents, naphthyl optionally substituted with one or more substituents, nitrogen-containing heterocycle optionally substituted with one or more substituents, oxygen-containing heterocycle optionally substituted with one or more substituents, sulfur-containing heterocycle optionally substituted with one or more substituents;

[0063] said substituents are selected from alkyl, haloalkyl, alkoxy, haloalkoxy, cyano, halogen, alkenyl, haloalkenyl, alkenyloxy, alkylthio, haloalkylthio, alkyl-substituted boronate, alkanoate, benzyloxy, or aryl.

[0064] The present application uses the compound shown in formula (1), the compound shown in formula (2) and the compound shown in formula (3) as raw materials, and carries out reaction in an inert atmosphere under the action of rhodium catalyst and base, to prepare the β-aryl amine compound shown in formula (A) and its analogues in one step, greatly shortens the synthesis steps and time, the feeding mode is simple, the raw materials are easy to obtain, and the yield and purity are high.

[0065] The present application uses the compound shown in formula (1) as raw material:

[0066] Ar-M formula (1);

[0067] wherein M is a boron-containing substituent, the B atom of the boron-containing substituent is connected with the Ar group, for example, it can be a boronic acid residue losing at least one hydroxyl group, a boronic ester residue losing at least one hydroxyl group or a borate residue losing at least one hydroxyl group, optionally, the boronic ester or borate can be substituted by halogen. In the present application, the M group acts as a leaving group, as long as the B atom is connected with the Ar group, it can be removed under the action of catalyst and base, so that the Ar group reacts with the double bond of the compound shown in formula (2), therefore, the present application does not have special restriction on the boron-containing group.

[0068] In formula (1), Ar is selected from aryl optionally substituted with one or more substituents or heteroaryl optionally substituted with one or more substituents, preferably selected from phenyl optionally substituted with one or more substituents, biphenyl optionally substituted with one or more substituents, naphthyl optionally substituted with one or more substituents, indolyl optionally substituted with one or more substituents, furanyl optionally substituted with one or more substituents, or pyridyl optionally substituted with one or more substituents, more preferably biphenyl optionally substituted with one or more substituents, naphthyl optionally substituted with one or more substituents, or indolyl optionally substituted with one or more substituents.

[0069] In some specific implementations, examples of the substituents are as follows: examples of alkyl include methyl, ethyl, propyl, butyl, pentyl, hexyl, and isomers thereof and cycloalkyl. Examples of alkenyl include ethenyl, propenyl, butenyl, pentenyl, hexenyl, and isomers thereof and cycloalkenyl. Examples of alkynyl include ethynyl, propynyl, butynyl, pentynyl, hexynyl, and isomers thereof. Alkoxy refers to a group formed by connecting an alkyl group described above with an oxygen atom, such as methoxy, ethoxy, and the like. Haloalkyl refers to a group formed by substituting an alkyl group described above with one or more halogens, such as trifluoromethyl. Haloalkoxy refers to a group formed by connecting a haloalkyl group described above with an oxygen atom, such as trifluoromethoxy, and the like. Halogen refers to fluorine, chlorine, bromine, iodine. Haloalkenyl refers to a group formed by substituting an alkenyl group described above with one or more halogens, such as difluoroethenyl. Alkenyloxy refers to a group formed by connecting an alkenyl group described above with an oxygen atom, such as ethenyloxy, propenyloxy, and the like. Examples of alkylthio include methylthio, ethylthio, propylthio, butylthio, pentylthio, hexylthio, and isomers thereof and cycloalkylthio. Haloalkylthio refers to a group formed by substituting an alkylthio group described above with one or more halogens, such as trifluoromethylthio. Examples of alkyl-substituted boronate groups include 3,4-tetramethyldioxolylboronate, and the like. Alkylcarboxy refers to a group formed by substituting an alkyl group described above with one or more carboxy groups. Examples of alkyl alkanoate groups include methyl formate, and the like. Examples of aryl include naphthalene, biphenyl, and the like.

[0070] In some specific implementations, the substituents can be 1, 2, or 3, and the substituents are preferably alkyl, haloalkyl, halogen, alkenyl, and the like.

[0071] In some specific implementations, the compound of formula (1) includes, but is not limited to, aryl boronic acid, (4,4,5,5-tetramethyl-1,3,2-dioxaborinan-2-yl) aryl compound, aryl potassium trifluoroborate, aryl boronic acid neopentyl glycol ester, 2-aryl-1,3,2-benzodiol borane, such as phenyl boronic acid, (4,4,5,5-tetramethyl-1,3,2-dioxaborinan-2-yl) phenyl compound, phenyl potassium trifluoroborate, 4-biphenyl potassium trifluoroborate, phenyl boronic acid neopentyl glycol ester, 2-phenyl-1,3,2-benzodiol borane, 2-naphthalene boronic acid pinacol ester, N-methyl indole-5-boronic acid, etc.

[0072] The present application uses a halogenated olefin of formula (2) as a raw material: Formula (2);

[0073] In the formula, X is halogen, preferably bromine.

[0074] R6, R7, R8 are each independently selected from one of hydrogen, halogen, alkyl optionally substituted with one or more substituents, alkenyl optionally substituted with one or more substituents, alkynyl optionally substituted with one or more substituents, alkoxy optionally substituted with one or more substituents, cyano, amido optionally substituted with one or more substituents, ester optionally substituted with one or more substituents, ketone optionally substituted with one or more substituents, phenyl optionally substituted with one or more substituents, naphthyl optionally substituted with one or more substituents, nitrogen-containing heterocycle optionally substituted with one or more substituents, oxygen-containing heterocycle optionally substituted with one or more substituents, sulfur-containing heterocycle optionally substituted with one or more substituents, preferably independently selected from hydrogen or alkyl optionally substituted with one or more substituents. Each substituent has the definition as described above, which is not repeated here, and is preferably alkyl or alkoxy.

[0075] In some specific implementations, the compound of formula (2) includes, but is not limited to, bromoethylene, chloroethylene, iodoethylene, and fluoroethylene.

[0076] The present application uses a compound of formula (3) as a raw material, which has the following structural formula: .

[0077] R9is selected from one of hydrogen, halogen, alkyl optionally substituted with one or more substituents, alkenyl optionally substituted with one or more substituents, alkynyl optionally substituted with one or more substituents, alkoxy optionally substituted with one or more substituents, cyano, amido optionally substituted with one or more substituents, ester optionally substituted with one or more substituents, ketone optionally substituted with one or more substituents, phenyl optionally substituted with one or more substituents, naphthyl optionally substituted with one or more substituents, nitrogen-containing heterocycle optionally substituted with one or more substituents, oxygen-containing heterocycle optionally substituted with one or more substituents, sulfur-containing heterocycle optionally substituted with one or more substituents, preferably from one of phenyl optionally substituted with one or more substituents or ketone optionally substituted with one or more substituents. Each substituent has the definition as described above, which is not repeated herein, preferably alkyl or alkoxy.

[0078] In some specific implementations, the compound of formula (3) includes, but is not limited to, acetamide, p-methoxyaniline, 5-amino furan-2-carboxylic acid methyl ester, 4-(furan-2-yl)aniline, 3-amino furan-2-carboxylic acid methyl ester, 2-naphthylamine.

[0079] In the preparation method provided by the application, the solvent used for the reaction includes, but is not limited to, one or more of water, deuterium water, ethanol, methanol, isopropanol, n-hexane, n-pentane, cyclopentane, dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, methyl tert-butyl ether, diethyl ether, acetone, benzene, deuterated benzene, toluene, deuterated toluene, p-xylene, o-xylene, m-xylene, ethylbenzene, chlorobenzene, dichloromethane, deuterated dichloromethane, chloroform, deuterated chloroform, tetrahydrofuran and 1,4-dioxane, preferably p-xylene, tetrahydrofuran, 1,4-dioxane or dimethyl sulfoxide.

[0080] The present application uses a rhodium-containing compound as a catalyst, and in some specific implementations, the rhodium catalyst includes, but is not limited to, one or more of acetylacetonebis(ethylene)rhodium(I), dicarbonylacetone rhodium(I), (1,5-cyclooctadiene)chlororhodium(I) dimer, bis(1,5-cyclooctadiene)-trifluoromethanesulfonic acid rhodium, bis(1,5-cyclooctadiene)tetrafluoroboric acid rhodium, tris(triphenylphosphine)rhodium(I) bromide, bis[(1,5-cyclooctadiene)(methoxy)rhodium], (1,5-cyclooctadiene)2,4-pentanedione rhodium(I), chlorobis(ethylene)rhodium(I) dimer, dimeric hydroxy(1,5-cyclooctadiene)rhodium(I), 1,2-bis[(2S,5S)-2,5-diphenylphosphino]ethane(1,5-cyclooctadiene)tetrafluoroboric acid rhodium(I), carbonylbis(triphenylphosphine)rhodium(I) chloride, bis(1,5-cyclooctadiene)rhodium(I) hexafluoroantimonate, tris(triphenylphosphine)carbonylhydrido rhodium(I), (R)-(-)-t-butylmethyl(di-t-butylphosphinomethyl)phosphino(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate, preferably bis(1,5-cyclooctadiene)tetrafluoroboric acid rhodium, chlorobis(ethylene)rhodium(I) dimer, acetylacetonebis(ethylene)rhodium(I), or tris(triphenylphosphine)rhodium(I) bromide.

[0081] The present application also includes a base in the preparation method, and the base includes, but is not limited to, one or more of lithium trimethylsilanolate, sodium trimethylsilanolate, potassium trimethylsilanolate, lithium tert-butoxide, potassium tert-butoxide, sodium tert-butoxide, lithium methoxide, potassium methoxide, sodium methoxide, lithium carbonate, sodium bicarbonate, sodium carbonate, potassium carbonate, sodium thiosulfate, cesium carbonate, lithium hydroxide, potassium hydroxide, sodium hydroxide, calcium hydroxide, magnesium hydroxide, barium hydroxide, sodium sulfate, potassium dihydrogen phosphate, potassium sulfate, potassium trihydrogen phosphate, calcium hydrogen phosphate, potassium tetrahydrogen phosphate, calcium dihydrogen phosphate, calcium tetrahydrogen phosphate, calcium trihydrogen phosphate, sodium phosphate, sodium trihydrogen phosphate, sodium dihydrogen phosphate, sodium tetrahydrogen phosphate, magnesium dihydrogen phosphate, magnesium phosphate, magnesium trihydrogen phosphate, aluminum dihydrogen phosphate, magnesium tetrahydrogen phosphate aluminum phosphate, aluminum trihydrogen phosphate, copper phosphate, aluminum tetrahydrogen phosphate, copper dihydrogen phosphate, copper trihydrogen phosphate, and copper tetrahydrogen phosphate, preferably sodium carbonate, lithium tert-butoxide, or cesium carbonate.

[0082] In the present application, the molar ratio of the compound represented by formula (1), the compound represented by formula (2) and the compound represented by formula (3) is 0.2-1:0.8-4.0:0.2-3.0, preferably 0.5-0.8:1-3.5:1-3. In some specific embodiments, the molar ratio of the compound represented by formula (1) to the base is 0.2-1:1-3, preferably 0.5-0.8:1.5-3. In some specific embodiments, the molar percentage of the rhodium catalyst in the compound represented by formula (1) is 1%-100%, preferably 2%-50%, more preferably 3%-15%. In some specific embodiments, the molar volume ratio of the compound represented by formula (1) to the reaction medium is 0.2 mmol-1 mmol:0.5 mL-10 mL, preferably 0.3 mmol:2 mL-6 mL.

[0083] In the present application, the compound represented by formula (1), the compound represented by formula (2) and the compound represented by formula (3), the rhodium catalyst and the base are mixed uniformly in a reaction medium, and then reacted to obtain the β-arylamine compound represented by formula (A) and its analogs, and the reaction process is as follows:

[0084] In some specific embodiments, the reaction temperature is 0 ℃-200 ℃, preferably 40 ℃-150 ℃, more preferably 60 ℃-120 ℃, more preferably 70 ℃-100 ℃; the reaction time is 20 min-36 h, preferably 5 h-30 h, more preferably 6 h-24 h. In some specific embodiments, the reaction is preferably carried out in an oil bath.

[0085] After the reaction is completed, the reaction medium, i.e., the solvent, is removed, and the obtained residue is eluted by silica gel column chromatography to obtain the β-arylamine compound represented by formula (A) and its analogs.

[0086] In the present application, the compound represented by formula (1), the compound represented by formula (2) and the compound represented by formula (3) are used as raw materials, and the reaction is carried out in an inert atmosphere under the action of a rhodium catalyst and a base to obtain the β-arylamine compound represented by formula (A) and its analogs in one step, which greatly shortens the synthesis steps and time, has a simple feeding mode, and has raw materials that are easy to obtain, high yield and high purity.

[0087] The synthesis method of the β-arylamine compound and its analogs provided in the present application is further described below in combination with examples. Example 1

[0088] Under the protection of inert atmosphere, 0.3 mmol of potassium 4-biphenyltrifluoroborate, 1 mmol of bromoethylene, 1.1 mmol of p-methoxyaniline, 0.03 mmol of tris(triphenylphosphine)rhodium(I) bromide and 1.5 mmol of sodium carbonate were mixed and 6 mL of p-xylene was added, and the reaction was stirred in a 100 ℃ oil bath for 20 h. After the reaction was completed, the solvent was removed, the residue was eluted by silica gel column chromatography, and the product was collected to obtain a β-arylamine compound and its analogs with a purity of 96% and a yield of 60%.

[0089] The β-arylamine compound and its analogs were subjected to nuclear magnetic analysis, and the results are shown in FIG. 1 and FIG. 2. FIG. 1 is the hydrogen spectrum of the β-arylamine compound and its analogs provided in Example 1 of the present application, and FIG. 2 is the carbon spectrum of the β-arylamine compound and its analogs provided in Example 1 of the present application. The nuclear magnetic data are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.63-7.56 (m, 2H), 7.58-7.52 (m, 2H), 7.49-7.40 (m, 2H), 7.39- 7.30 (m, 1H), 7.30 (d, J = 8.14 Hz, 2H), 6.88 – 6.78 (m, 2H), 6.73-6.63 (m, 2H), 3.76 (s, 3H), 3.41 (t, J = 7.03 Hz, 2H), 2.97 (t, J = 7.03 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 152.4, 141.9, 140.9, 139.4, 138.4, 129.3, 128.8, 127.4, 127.2, 127.1, 115.0, 114.7, 55.8, 46.2, 35.2. HRMS (EI) m / z: [(M)+] Calcd for C 21 H 21 NO + 303.1623; Found 303.1619.

[0090] It has the structure of formula (A-1) and the chemical name is N-(2-([1,1'-biphenyl]-4-yl)ethyl)-4-methoxyaniline, N-(2-([1,1'-biphenyl]-4-yl)ethyl)-4-methoxyaniline: Formula (A-1). Example 2

[0091] Under the protection of inert atmosphere, 0.3 mmol of 2-naphthalene boronic acid pinacol ester, 1 mmol of bromoethylene, 1.1 mmol of cyclobutyl formamide, 0.03 mmol of bis(1,5-cyclooctadiene)-rhodium trifluoromethanesulfonate and 1.5 mmol of sodium methoxide were mixed and 6 mL of dioxane was added, and the reaction was stirred in 100 ℃ oil bath for 20 h. After the reaction was completed, the solvent was removed, the residue was eluted by silica gel column chromatography, and the product was collected to obtain the β-aryl amine compound and its analogs with a purity of 93% and a yield of 51%.

[0092] The β-aryl amine compound and its analogs were subjected to nuclear magnetic analysis, and the results are shown in FIG. 3 and FIG. 4. FIG. 3 is the hydrogen spectrum of the β-aryl amine compound and its analogs provided in Example 2 of the present application, and FIG. 4 is the carbon spectrum of the β-aryl amine compound and its analogs provided in Example 2 of the present application. The nuclear magnetic data is as follows: 1 H NMR (500 MHz, Chloroform-d) δ 8.12 (d, J = 8.48 Hz, 1H), 7.86 (dd, J = 8.06, 1.49 Hz, 1H), 7.75 (d, J = 8.21 Hz, 1H), 7.57-7.50 (m, 1H), 7.52-7.46 (m, 1H), 7.44-7.37 (m, 1H), 7.31 (d, J = 6.84 Hz, 1H), 5.50 (s, 1H), 3.72-3.51 (m, 2H), 3.29 (t, J = 7.09 Hz, 2H), 2.91 (p, J = 8.58 Hz, 1H), 2.33-2.18 (m, 2H), 2.16-2.02 (m, 2H), 1.99-1.87 (m, 1H), 1.89-1.78 (m, 1H). 13 C NMR (126 MHz, Chloroform-d) δ 175.2, 135.2, 133.9, 132.0, 128.8, 127.4, 126.8, 126.2, 125.8, 125.5, 123.8, 40.2, 40.0, 32.9, 25.4, 18.1. HRMS (EI) m / z: [(M)+] Calcd for C 17 H 19 NO + 253.1467; Found 253.1462.

[0093] It has a structure of formula (A-2), and its chemical name is N-(2-(naphthalen-2-yl)ethyl)cyclobutanecarboxamide: Formula (A-2).

[0094] Example 3

[0095] Under the protection of an inert atmosphere, 0.3 mmol of N-methylindole-5-boronic acid, 1 mmol of bromoethylene, 1.1 mmol of p-methoxyaniline, 0.03 mmol of chlorobis(ethylene)rhodium(I) dimer, and 1.5 mmol of cesium carbonate were mixed and 6 mL of tetrahydrofuran was added, and the reaction was stirred in a 100 ℃ oil bath for 20 h. After the reaction was completed, the solvent was removed, the residue was eluted by silica gel column chromatography, and the product was collected to obtain a β-arylamines compound and its analogs with a purity of 91% and a yield of 53%.

[0096] The β-arylamines compound and its analogs were subjected to nuclear magnetic analysis, and the results are shown in FIG. 5 and FIG. 6. FIG. 5 is the hydrogen spectrum of the β-arylamines compound and its analogs provided in Example 3 of the present application, and FIG. 6 is the carbon spectrum of the β-arylamines compound and its analogs provided in Example 3 of the present application. The nuclear magnetic data is as follows: 1 H NMR (500 MHz, Chloroform-d) δ 7.46 (d, J = 1.57 Hz, 1H), 7.27 (d, J = 8.41 Hz, 1H), 7.09 (dd, J = 8.41, 1.57 Hz, 1H), 7.05 (d, J = 3.09 Hz, 1H), 6.84-6.75 (m, 2H), 6.67-6.57 (m, 2H), 6.43 (d, J = 3.09 Hz, 1H), 3.79 (s, 3H), 3.75 (s, 3H), 3.39 (t, J = 7.00 Hz, 2H), 3.02 (t, J = 7.00 Hz, 2H). 13 C NMR (126 MHz, Chloroform-d) δ 152.4, 141.9, 135.7, 129.85, 129.2, 128.7, 122.6, 120.7, 114.9, 109.4, 100.5, 55.8, 47.0, 35.4, 32.9. HRMS (EI) m / z: [(M)+] Calcd for C 18 H 20N2O + 280.1576; Found 280.1574.

[0097] which has the structure of formula (A-3), and the chemical name of 4-methoxy-N-(2-(1-methyl-1H-indol-5-yl)ethyl)aniline: formula (A-3).

[0098] Example 4

[0099] Under the protection of an inert atmosphere, 0.3 mmol of [1,1'-biphenyl]-4-ylboronic acid, 1 mmol of bromoethylene, 1.1 mmol of 4-(furan-2-yl)aniline, 0.03 mmol of bis(1,5-cyclooctadiene)rhodium(I) hexafluoroantimonate and 1.5 mmol of potassium carbonate were mixed, 6 mL of m-xylene was added, and the reaction was stirred in a 100 ℃ oil bath for 20 h. After the reaction was completed, the solvent was removed, the residue was eluted by silica gel column chromatography, and the product was collected to obtain the β-arylamines and analogs thereof with a purity of 97% and a yield of 60%.

[0100] The β-arylamines and analogs thereof were subjected to nuclear magnetic analysis, and the results are shown in FIGS. 7 and 8. FIG. 7 is the hydrogen spectrum of the β-arylamines and analogs thereof provided in Example 4 of the present application, and FIG. 8 is the carbon spectrum of the β-arylamines and analogs thereof provided in Example 4 of the present application. The nuclear magnetic data thereof are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.64 – 7.50 (m, 3H), 7.50 – 7.41 (m, 1H), 7.43 – 7.38 (m, 1H), 7.40 – 7.32 (m, 0H), 7.35 – 7.28 (m, 1H), 6.74 – 6.65 (m, 1H), 6.52 – 6.39 (m, 1H), 3.48 (t, J = 7.0 Hz, 1H), 2.99 (t, J = 7.0 Hz, 1H). 13C NMR (101 MHz, Chloroform-d) δ 154.7, 147.0, 140.9, 140.8, 139.5, 138.2, 129.3, 128.8, 127.4, 127.2, 127.1, 125.3, 121.3, 113.3, 111.5, 102.2, 45.2, 35.0. HRMS (EI) m / z: [(M)+] Calcd for C 24 H 21 NO + 339.1623; Found 339.1620.

[0101] It has the structure of formula (A-4), and its chemical name is N-(2-([1,1'-biphenyl]-4-yl)ethyl)-4-(furan-2-yl)aniline, N-(2-([1,1'-biphenyl]-4-yl)ethyl)-4-(furan-2-yl)aniline: Formula (A-4).

[0102] Example 5

[0103] Under the protection of an inert atmosphere, 0.3 mmol of [1,1'-biphenyl]-4-ylboronic acid, 1 mmol of bromoethylene, 1.1 mmol of 3-aminofuran-2-carboxylic acid methyl ester, 0.03 mmol of chlorobis(ethylene)rhodium(I) dimer and 1.5 mmol of potassium tert-butoxide were mixed and 6 mL of n-hexane was added, and the reaction was stirred in a 100 ℃ oil bath for 20 h. After the reaction was completed, the solvent was removed, the residue was eluted by silica gel column chromatography, and the product was collected to obtain the β-arylamines and analogs thereof with a purity of 94% and a yield of 52%.

[0104] The β-arylamines and analogs thereof were subjected to nuclear magnetic analysis, and the results are shown in FIGS. 9 and 10. FIG. 9 is a hydrogen spectrum of the β-arylamines and analogs thereof provided in Example 5 of the present application, and FIG. 10 is a carbon spectrum of the β-arylamines and analogs thereof provided in Example 5 of the present application. The nuclear magnetic data thereof are as follows: 1H NMR (400 MHz, Chloroform-d) δ 7.61 - 7.51 (m, 4H), 7.50 - 7.38 (m, 3H), 7.38 - 7.27 (m, 1H), 7.30 - 7.26 (m, 2H), 6.19 (d, J = 2.1 Hz, 1H), 3.84 (s, 3H), 3.46 (t, J = 7.2 Hz, 2H), 2.93 (t, J = 7.2 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 160.8, 146.5, 140.9, 139.6, 137.8, 129.2, 128.8, 128.4, 127.4, 127.2, 127.0, 115.7, 102.3, 51.0, 46.7, 36.3. HRMS (EI) m / z: [(M) + ] Calcd for C 20 H 19 NO3 + 321.1365; Found 321.1361.

[0105] which has the structure of Formula (A-5), chemical name methyl 3-((2-([1,1'-biphenyl]-4-yl)ethyl)amino)furan-2-carboxylate: Formula (A-5).

[0106] Example 6

[0107] Under the protection of inert atmosphere, 0.3 mmol of 1-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole, 1 mmol of vinyl bromide, 1.1 mmol of p-methoxyaniline, 0.03 mmol of tris(triphenylphosphine)rhodium(I) bromide and 1.5 mmol of sodium phosphate were mixed and 6 mL of acetone was added, and the reaction was stirred in a 100 °C oil bath for 20 h. After the reaction was completed, the solvent was removed, the residue was eluted by silica gel column chromatography, and the product was collected to obtain the β-arylamine compound and its analogs with a purity of 92% and a yield of 48%.

[0108] The β-arylamines and analogs thereof were subjected to nuclear magnetic analysis, and the results are shown in FIG. 11 and FIG. 12. FIG. 11 is a hydrogen spectrum of the β-arylamines and analogs thereof provided in Example 6, and FIG. 12 is a carbon spectrum of the β-arylamines and analogs thereof provided in Example 6. The nuclear magnetic data are as follows: 1 H NMR (500 MHz, Chloroform-d) δ 6.83 – 6.76 (m, 2H), 6.63 – 6.59 (m, 2H), 6.57 (dd, J = 2.7, 1.8 Hz, 1H), 6.08 (dd, J = 3.5, 2.7 Hz, 1H), 5.97 (dd, J = 3.5, 1.8 Hz, 1H), 3.75 (s, 3H), 3.54 (s, 3H), 3.35 (t, J = 6.9 Hz, 2H), 2.87 (t, J = 6.9 Hz, 2H). 13 C NMR (126 MHz, Chloroform-d) δ 152.3, 142.1, 130.1, 121.8, 115.0, 114.5, 106.9, 106.5, 55.8, 44.0, 33.7, 26.2. HRMS (EI) m / z: [(M)+] Calcd for C 14 H 18 N2O + 230.1419; Found 230.1416.

[0109] which has the structure of formula (A-6) and the chemical name 4-methoxy-N-(2-(1-methyl-1H-pyrrol-2-yl)ethyl)aniline: formula (A-6).

[0110] The above only describes the preferred embodiments of the present application, and it should be noted that for those skilled in the art, without departing from the principles of the present application, a number of improvements and refinements can be made, and these improvements and refinements should also be considered as the protection scope of the present application.

Claims

1. A method for preparing a β-arylamines compound and its analogues, comprising the following steps: mixing a rhodium catalyst, a base, a compound represented by formula (1), a compound represented by formula (2) and a compound represented by formula (3) and then reacting under an inert atmosphere to obtain a compound represented by formula (A); formula (A); wherein Ar is selected from an aromatic group optionally substituted by one or more substituents or a heteroaromatic group optionally substituted by one or more substituents; M is a boron-containing substituent, the B atom of the boron-containing substituent being connected to the Ar group; X is halogen; R 6, R 7, R 8, R 9 are each independently selected from one of hydrogen, halogen, alkyl optionally substituted by one or more substituents, alkenyl optionally substituted by one or more substituents, alkynyl optionally substituted by one or more substituents, alkoxy optionally substituted by one or more substituents, cyano, amido optionally substituted by one or more substituents, ester optionally substituted by one or more substituents, ketone optionally substituted by one or more substituents, phenyl optionally substituted by one or more substituents, naphthyl optionally substituted by one or more substituents, nitrogen-containing heterocycle optionally substituted by one or more substituents, oxygen-containing heterocycle optionally substituted by one or more substituents, sulfur-containing heterocycle optionally substituted by one or more substituents; the substituents are selected from alkyl, haloalkyl, alkoxy, haloalkoxy, cyano, halogen, alkenyl, haloalkenyl, alkenyloxy, alkylthio, haloalkylthio, alkyl-substituted boronic acid ester, alkanoate, benzyloxy or aromatic group; R 6, R 7, R 8 are each independently selected from hydrogen or alkyl optionally substituted by one or more substituents; R 9 is selected from phenyl optionally substituted by one or more substituents or ketone optionally substituted by one or more substituents; the substituents are selected from alkoxy or alkyl; the molar ratio of the compound represented by formula (1), the compound represented by formula (2) and the compound represented by formula (3) is 0.2-1:0.8-4.0:0.2-3.0; the molar ratio of the compound represented by formula (1) to the base is 0.2-1:1-3; the rhodium catalyst accounts for 1%-100% of the molar percentage of the compound represented by formula (1); the reaction temperature is 0 ℃-200 ℃ and the reaction time is 20 min-36 hours. ​ Ar-M formula (1); formula (2); formula (3); ​ ​ ​ ​ ​ 2. The production method according to claim 1, characterized by, ​ ​ ​ 3. The production method according to claim 1 or 2, characterized by, ​ 4. The production method according to claim 1 or 2, characterized by, ​ ​ 5. The production method according to claim 1 or 2, characterized by, ​ 6. The production method according to claim 1 or 2, characterized by, The rhodium catalyst is selected from one or more of acetylacetone bis(ethylene)rhodium(I), dicarbonyl acetylacetone rhodium(I), (1,5-cyclooctadiene)chloro rhodium(I) dimer, bis(1,5-cyclooctadiene)-trifluoromethanesulfonic acid rhodium, bis(1,5-cyclooctadiene)tetrafluoroborate rhodium, tris(triphenylphosphine)rhodium(I) bromide, bis[(1,5-cyclooctadiene)(methoxy)rhodium], (1,5-cyclooctadiene)2,4-pentanedione rhodium(I), chloro bis(ethylene)rhodium(I) dimer, dimeric hydroxy(1,5-cyclooctadiene)rhodium(I), 1,2-bis[(2S,5S)-2,5-diphenylphosphino]ethane(1,5-cyclooctadiene)tetrafluoroborate rhodium(I), carbonylbis(triphenylphosphine)chlororhodium(I), bis(1,5-cyclooctadiene)rhodium(I) hexafluoroantimonate, tris(triphenylphosphine)carbonylhydrido rhodium(I), (R)-(-)-t- butylmethyl(di-t-butylphosphinomethyl)phosphino(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate.

7. The production method according to claim 1 or 2, characterized by, The base is selected from one or more of lithium trimethylsilanolate, sodium trimethylsilanolate, potassium trimethylsilanolate, lithium t-butoxide, potassium t-butoxide, sodium t-butoxide, lithium methoxide, potassium methoxide, sodium methoxide, lithium carbonate, sodium bicarbonate, sodium carbonate, potassium carbonate, sodium thiosulfate, cesium carbonate, lithium hydroxide, potassium hydroxide, sodium hydroxide, calcium hydroxide, magnesium hydroxide, barium hydroxide, sodium sulfate, potassium dihydrogen phosphate, potassium sulfate, potassium trihydrogen phosphate, calcium hydrogen phosphate, potassium tetrahydrogen phosphate, calcium dihydrogen phosphate, calcium tetrahydrogen phosphate, calcium trihydrogen phosphate, sodium phosphate, sodium trihydrogen phosphate, sodium dihydrogen phosphate, sodium tetrahydrogen phosphate, magnesium dihydrogen phosphate, magnesium phosphate, magnesium trihydrogen phosphate, aluminum dihydrogen phosphate, aluminum tetrahydrogen phosphate, aluminum trihydrogen phosphate, copper phosphate, aluminum tetrahydrogen phosphate, copper dihydrogen phosphate, copper trihydrogen phosphate, and copper tetrahydrogen phosphate.

8. The production method according to claim 1 or 2, characterized by, The solvent used for the reaction is selected from one or more of water, furan, 2-methyltetrahydrofuran, acetonitrile, dimethylsulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, methyl t-butyl ether, diethyl ether, acetone, benzene, deuterated benzene, toluene, deuterated toluene, p-xylene, o-xylene, m-xylene, ethylbenzene, chlorobenzene, dichloromethane, deuterated dichloromethane, chloroform, deuterated chloroform, tetrahydrofuran, and 1,4-dioxane.

9. The production method according to claim 1 or 2, characterized by, The compound of Formula (1) is selected from one or more of aryl boronic acid, (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) aryl compound, aryl potassium trifluoroborate, aryl boronic acid neopentyl glycol ester, and 2-aryl-1,3,2-benzodiol borane.

10. The production method according to claim 1 or 2, characterized by, The compound of Formula (2) is selected from bromoethene.

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