Arylation and silylation methods of aryl cyclic ammonium salts

Abstract

The invention discloses an arylation and silylation method of an aryl cyclic ammonium salt, and the two types of reactions can respectively synthesize biphenyl and silyl-containing fatty amine compounds. Both systems use cyclic ammonium salts as electrophilic raw materials, nickel sources with different valence states as catalysts, and aryl magnesium bromide and silicon lithium reagents as nucleophilic reagents, respectively. In the presence of a ligand, the reaction is stirred at 80°C for 16 hours. Both types of reactions can obtain corresponding target products with a high yield, and the reaction has the advantages of mild conditions, excellent yield, good functional group tolerance, etc.

Description

Technical Field

[0001] The invention belongs to the technical field of synthesis and application of organic compounds, and particularly relates to a method for arylating and silylating an aryl cyclic ammonium salt. Background Art

[0002] Amine compounds are widely present in nature and can be used to synthesize many functional and drug molecules. Their synthesis and conversion are very important in the fields of industry and synthesis. The use of aryl cyclic ammonium salts as electrophilic reagents can achieve the synthesis of aliphatic amine compounds. Aryl cyclic ammonium salts have high reactivity and can exist stably in nature. 2 ) The breaking of the CN bond can realize different functional groups of itself and achieve 100% conversion of atoms. Arylation and silylation have always been important research topics in the field of synthesis. Arylation and silylation of aryl cyclic ammonium salts can synthesize fatty amine compounds containing biphenyl and silicon. Fatty amine compounds containing biphenyl are precursors of some industrial raw materials and can be widely used in industry, agriculture and dyes; and organosilicon compounds are also important synthetic intermediates and play an important role in the field of synthesis. Therefore, it is of great significance to develop two mild reaction systems to realize the arylation and silylation of aryl cyclic ammonium salts.

[0003] At present, there are many literature reports on the arylation methods of chain aryl ammonium salts. For example, as early as 1988, "Chemical Communications" (J. Chem. Soc. Chem. Commun. 1988, 975.) reported the cross-coupling reaction of aryl ammonium salts and aryl Grignard reagents. This method uses 10% equivalent triphenylphosphine palladium chloride as a catalyst, and no additional ligand is required. The system uses THF as a solvent and stirs at room temperature for 1 hour to obtain a high product yield. The reaction substrate has a wide range of applicability, the reaction is mild and rapid, and it has good practical value; in 2017, "German Angewandte Chemie" (Angew. Chem. Int. Ed. 2011, 50, 4901.) reported the cross-coupling reaction of aryl ammonium salts and aryl zinc reagents catalyzed by tricyclohexylphosphine nickel chloride. The reaction still does not require the addition of ligands. Only THF and NMP with a volume ratio of 1:1 are used as reaction solvents. The reaction is relatively mild and the substrate range is also very wide. Aryl ammonium salts with different electrical substituents and highly polar heterocyclic ammonium salts can obtain good yields. The system can also tolerate most active functional groups such as carbonyl, cyano, ester, etc., and has great practical value; in 2003, the Journal of the American Chemical Society (J.Am.Chem.Soc.2003,125,6046.) also reported Ni(cod) 2The combination of IMes·HCl and azacarbene catalyzes the cross-coupling reaction of aryl ammonium salts and phenylboronic acid. When weak base cesium fluoride is added to the reaction and dioxane is used as the reaction solvent, excellent product yields can be obtained. The substrate application range of the reaction is very wide. Aryl ammonium salts and aryl boronic acids with different electrical groups can achieve high yields. Alkenyl boronic acids can also react well in this system and have high practical value. However, the cleavage of the CN bond of these three types of chain aryl ammonium salts as electrophilic reagents in the coupling reaction will cause the departure of the amine group, resulting in low atom economy, and they cannot be used as nitrogen sources to synthesize amine compounds, which slightly reduces their practicality.

[0004] Aryl ammonium salts can also be used as electrophilic raw materials to participate in silylation reactions to synthesize silicon-containing fatty amine compounds. In 2021, Organic Letters (Org. Lett. 2021, 23, 5988.) reported a metal-free catalytic cross-coupling reaction of aryl ammonium salts and silyl borate esters. The reaction used lithium tert-butoxide as a base and THF as a solvent. The system reacted at 55°C for 12 hours to produce the target silylated product with medium to good yields. The system only showed medium yields for aryl ammonium salts without functional groups or neutral groups, but it showed good reactivity for aryl ammonium salts with charged substituents. Various functional groups such as methoxy, phenyl, trifluoromethyl, ester, and cyano groups can be tolerated in this system, providing an alternative for the silylation of aryl ammonium salts; in 2019, Chem. Sci. reported Ni(cod) 2 and IPr OMe · HCl catalyzes the cross-coupling reaction of aryl ammonium salts and triethylsilane. The reaction uses dioxane as solvent. At 40°C, the silylated product can be obtained in good yield. The substrate range of the reaction is also relatively wide. Aryl ammonium salts with different electrical substituents can achieve excellent yields. Aryl ammonium salts with heterocyclic groups such as pyridyl and pyrazolyl also have good yields. Most substituted aryl ammonium salts are not very effective for PhMe 2 SiH、BnMe 2 SiH can also be used to generate corresponding silylation products, and the reaction has certain practical value. However, similar to the above-mentioned arylation system of cyclic ammonium salts, the CN bond will also be broken in the silylation system, resulting in the departure of the amine group and the decrease in atomic utilization. In addition, the overall yield of the silylation system is low, and its practicality is greatly reduced.

[0005] In 2016, the Journal of the American Chemical Society (J.Am.Chem.Soc.2016,138,2985) reported a coupling reaction of cyclic ammonium salts, namely the reaction of N,N-dimethylindole ammonium salt with tetrahydroxydiboron, which achieved the construction of CB bonds and retained nitrogen-containing groups at the same time. This reaction is a photoreaction and does not require a transition metal catalyst. In the same year, the Journal of Organic Chemistry also reported the nickel-catalyzed coupling reaction of cyclic ammonium salts with PinBBPin, which also achieved the construction of CB bonds and retained the amino group at the same time, and can be used to synthesize boron-containing fatty amine compounds.

[0006] Therefore, we used aromatic cyclic ammonium salts as substrates and developed two simple and mild systems to achieve the arylation and silylation of aromatic cyclic ammonium salts. These two methods can also be used to synthesize fatty amine compounds containing biphenyl and silicon groups, which is of great significance. Summary of the invention

[0007] As mentioned above, there are many reports on the arylation of chain aryl ammonium salts. However, when chain aryl ammonium salts are used as electrophilic reagents, their (sp 2 )The breaking of the CN bond will cause the departure of the amine group, and its atom economy is low; and when the chain aryl ammonium salt is used as an electrophilic reagent, it is often accompanied by a demethylation reaction. Therefore, the present invention uses an aryl cyclic ammonium salt as an electrophilic raw material, uses cheap and readily available aryl Grignard reagents and silicon lithium reagents as nucleophilic reagents, and both systems use metal nickel as a system catalyst, tricyclohexylphosphine and diphenylcyclohexylphosphine are used as ligands, THF and toluene are used as solvents for the two types of reactions, and the system reacts at 80°C for 16 hours, and can harvest fatty amine compounds containing biphenyl and silicon groups with very good yields, which has important uses. In addition, the reaction conditions of these two types are mild, the system is simple, the functional group tolerance is good, and they have high practical value.

[0008] The arylation method of aryl cyclic ammonium salt of the present invention uses aryl magnesium bromide as a nucleophilic reagent, reacts at 80° C. for 16 hours in a solvent under anhydrous and oxygen-free conditions to obtain a fatty amine compound containing biphenyl.

[0009] The aryl cyclic ammonium salt is selected from the compounds of the following structures:

[0010]

[0011] In the above general formula, R 1 is selected from H, methoxy, methyl, fluorine, chlorine, etc.; R 2 Selected from H or methyl.

[0012] The aromatic cyclic ammonium salt is specifically selected from 6-methoxytetrahydroquinoline quaternary ammonium salt, 6-methyltetrahydroquinoline quaternary ammonium salt, 6-fluorotetrahydroquinoline quaternary ammonium salt, 6-chlorotetrahydroquinoline quaternary ammonium salt, 2-methyltetrahydroquinoline quaternary ammonium salt, tetrahydroindole quaternary ammonium salt and the like.

[0013] The catalyst is selected from Ni(cod) 2 、Ni(acac) 2 、NiCl 2 (PPh 3 ) 2 etc., the preferred catalyst for the arylation reaction is Ni(cod) 2 ; The ligand is PCy 3 .

[0014] The aryl magnesium bromide R 3 MgBr is selected from p-methoxyphenylmagnesium bromide, p-methylphenylmagnesium bromide, m-methylphenylmagnesium bromide, 3,5-dimethylphenylmagnesium bromide, p-dimethylaminophenylmagnesium bromide, 4-biphenylmagnesium bromide, 2-naphthylmagnesium bromide and the like.

[0015] The solvent is selected from THF, toluene, dioxane, etc., and the arylation reaction solvent is preferably THF.

[0016] The molar ratio of the aryl cyclic ammonium salt, aryl magnesium bromide, catalyst and ligand is 1.0:2.0-3.0:0.05:0.1, and the preferred molar ratio is 1.0:3.0:0.05:0.1.

[0017] The reaction route is as follows:

[0018]

[0019] R 3 It is p-methoxyphenyl, p-methylphenyl, m-methylphenyl, 3,5-dimethylphenyl, p-dimethylaminophenyl, 4-biphenyl, 2-naphthyl and the like.

[0020] The silylation method of aromatic cyclic ammonium salts of the present invention uses a silicolithium reagent as a nucleophilic reagent, reacts at 80° C. for 16 hours in a solvent under anhydrous and oxygen-free conditions to obtain a silicon-containing fatty amine compound.

[0021] The general structural formula of the aryl cyclic ammonium salt is shown below:

[0022]

[0023] In the above general formula, R 1 is selected from H, methoxy, methyl, fluorine, chlorine, etc.; R 2 Selected from H or methyl.

[0024] The aromatic cyclic ammonium salt is specifically selected from 6-methyltetrahydroquinoline quaternary ammonium salt, 6-fluorotetrahydroquinoline quaternary ammonium salt, 6-chlorotetrahydroquinoline quaternary ammonium salt, 2-methyltetrahydroquinoline quaternary ammonium salt and the like.

[0025] The catalyst is selected from Ni(cod) 2 、Ni(acac) 2 、NiCl 2 (PPh 3 ) 2 etc., the preferred catalyst for the silicidation reaction is NiCl 2 (dppe); the ligand is PPh 2 Cy.

[0026] The lithium silico reagent is selected from phenyl dimethyl lithium silico reagent and diphenyl methyl lithium silico reagent.

[0027] The solvent is selected from THF, toluene, dioxane, etc., and toluene is preferably used for the silylation reaction.

[0028] The molar ratio of the aromatic cyclic ammonium salt, the silicon lithium reagent, the catalyst and the ligand is 1.0:2.0-2.5:0.1:0.2, and the preferred molar ratio is 1.0:2.5:0.1:0.2.

[0029] The reaction route is as follows:

[0030]

[0031] In the present invention, the electrophilic raw material aryl cyclic ammonium salt is prepared by the methylation method of tetrahydroquinoline, that is, quinoline is first reduced to tetrahydroquinoline by tetrahydroxydiboron, and then tetrahydroquinoline is simply methylated in two steps under nitrogen protection to obtain a cyclic ammonium salt template product. Specifically, tetrahydroxydiborane (6.8 g, 75 mmol) is first added to a 250 mL round-bottom flask containing a stirrer, and then 50 mL of water and quinoline (2.0 g, 15 mmol) are added, and the mixture is stirred at 90° C. for 12 hours; after the reaction is completed, it is cooled to room temperature, ethyl acetate (25 mL) is added to the mixture, the organic phase is separated, the aqueous phase is extracted twice with ethyl acetate (2×20 mL), the organic extracts are combined and dried with anhydrous sodium sulfate and filtered, the filtrate is concentrated, and the residue is purified by column chromatography to obtain the product tetrahydroquinoline.

[0032] Weigh sodium hydride (1.0 g, 40 mmol) in a Schlenk bottle, add 10 mL of tetrahydrofuran and stir. Add tetrahydroquinoline (1.3 mL, 10 mmol) and 10 mL of tetrahydrofuran to another Schlenk bottle. After stirring for five minutes, slowly add the tetrahydrofuran solution of tetrahydroquinoline to the former Schlenk bottle at 0°C. After stirring for five minutes, slowly add iodomethane (1.9 mL, 30 mmol) at 0°C, and add 5 mL of tetrahydrofuran. Stir the mixture at room temperature for 12 hours, stop the reaction, add water dropwise to the mixture until no more bubbles are generated, then add ethyl acetate (25 mL), separate the organic layer, and extract the aqueous phase twice with ethyl acetate (2×20 mL). The combined organic extracts are dried over anhydrous sodium sulfate and filtered, the filtrate is concentrated, and the residue is purified by column chromatography to obtain the raw material precursor N-methyltetrahydroquinoline. Finally, the obtained N-methyltetrahydroquinoline (0.7 g, 5 mmol) was dissolved in anhydrous ether (10 mL), and MeOTf (0.7 mL, 6.5 mmol) was added dropwise at 0°C. After complete addition, the reaction mixture was stirred at room temperature for 4 hours. The filtrate was concentrated and washed with ether (2×15 mL), and vacuum dried to obtain the product.

[0033] Prepare arylmagnesium bromide and silicon lithium reagent and titrate their concentrations:

[0034] Weigh magnesium chips (0.30g, 12.5mmol) and add them to a Schlenk bottle with a stirrer. After evacuating and passing nitrogen three times, add 20mL of tetrahydrofuran, and then add a small amount of iodine. Use a syringe to extract an equal amount of bromobenzene (1.3mL, 12.5mmol) and add it to the reaction bottle. After stirring at room temperature for 4 hours, PhMgBr can be obtained. Its concentration is titrated with iodine under nitrogen conditions; under nitrogen conditions, add metallic lithium (0.14g, 20mmol) and 10mL of tetrahydrofuran to the Schlenk bottle with a stirrer. Place the system in an ice-water bath and stir. Slowly add phenyldimethylsilyl chloride (1.7mL, 10mmol), then place the reaction in an ice-water bath and ultrasonically treat for 1-1.5 hours. When the color turns reddish brown, transfer the reaction to a low-temperature cooling tank and continue stirring for 12 hours. After returning to room temperature, take out the clear liquid of the system under nitrogen conditions to obtain the required silicon-lithium reagent. According to the method of Kofron, the concentration of diphenylacetic acid can be obtained by titrating a THF solution with a silica lithium reagent.

[0035] In the present invention, both THF and toluene need to be dehydrated, degassed and purified, and the system needs to be placed in an anhydrous and oxygen-free nitrogen atmosphere for reaction.

[0036] The present invention provides a reaction method for arylating and silylating an aryl cyclic ammonium salt, and the specific preparation process is described as follows:

[0037] Arylation: Weigh N,N-dimethyltetrahydroquinoline quaternary ammonium salt (62.0 mg, 0.2 mmol) and Ni(cod) 2 (2.7 mg, 0.01 mmol) was added into a Schlenk bottle equipped with a magnet, and tricyclohexylphosphine (0.005 mmol) and arylmagnesium bromide (0.6 mmol) prepared in THF were added respectively. THF was added into the system until the solvent was about 2 mL in total. The system was stirred at 80 ° C for 16 hours, the reaction was stopped, water was added dropwise into the system until the Grignard reagent was completely consumed, extracted, and the organic phase was concentrated in vacuo, and then separated and purified by neutral alumina column chromatography and preparative thin layer chromatography (eluent: DCM / MeOH=10 / 1) to obtain the product.

[0038] Silylation: Cyclic ammonium salt (62.0 mg, 0.2 mmol), PCyPh 2 (10.8 mg, 0.04 mmol), NiCl 2 (dppe) (10.6 mg, 0.02 mmol) and 0.5 mL THF. Add silicon lithium reagent (0.5 mmol) dropwise under stirring, replace THF in the system with toluene (2 mL) under nitrogen protection, and finally stir the reaction at 80 ° C for 16 hours. After the reaction is completed, water is added dropwise to quench the excess silicon lithium reagent, and the subsequent treatment steps are the same as the above-mentioned arylation reaction. The obtained product is still a colorless liquid.

[0039] These two types of reactions can synthesize biphenyl-containing and silicon-containing fatty amine compounds, respectively. Biphenyl-containing fatty amine compounds are important industrial raw materials and can be widely used in medicine, pesticides, dyes and liquid crystal materials, while organosilicon compounds are important synthetic intermediates and are of great significance in the field of synthesis. The present invention can synthesize biphenyl-containing and silicon-containing fatty amine compounds with excellent yields, the conditions are relatively mild, the substrate range is wide, and it has high practicality.

[0040] The present invention has the following advantages:

[0041] 1. Mild reaction conditions; 2. Excellent yield; 3. Simple reaction operation; 4. Wide application range of substrates; 5. High atom utilization rate; 5. Ability to synthesize fatty amine compounds containing biphenyl and silicon groups. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] Figure 1 It is the product of the coupling reaction of tetrahydroquinoline quaternary ammonium salt and phenylmagnesium bromide. 1 H NMR spectrum.

[0043] Figure 2 It is the product of the coupling reaction of tetrahydroquinoline quaternary ammonium salt and phenylmagnesium bromide.13 C NMR spectrum.

[0044] Figure 3 It is the product of the coupling reaction of 6-methoxytetrahydroquinoline quaternary ammonium salt and phenylmagnesium bromide. 1 H NMR spectrum.

[0045] Figure 4 It is the product of the coupling reaction of 6-methoxytetrahydroquinoline quaternary ammonium salt and phenylmagnesium bromide. 13 C NMR spectrum.

[0046] Figure 5 It is the product of the coupling reaction of 6-methyltetrahydroquinoline quaternary ammonium salt and phenylmagnesium bromide. 1 H NMR spectrum.

[0047] Figure 6 It is the product of the coupling reaction of 6-methyltetrahydroquinoline quaternary ammonium salt and phenylmagnesium bromide. 13 C NMR spectrum.

[0048] Figure 7 It is the product of the coupling reaction of tetrahydroindole quaternary ammonium salt and phenylmagnesium bromide. 1 H NMR spectrum.

[0049] Figure 8 It is the product of the coupling reaction of tetrahydroindole quaternary ammonium salt and phenylmagnesium bromide. 13 C NMR spectrum.

[0050] Fig. 9 It is the product of the coupling reaction of tetrahydroquinoline quaternary ammonium salt and p-methylphenylmagnesium bromide. 1 H NMR spectrum.

[0051] Fig.10 It is the product of the coupling reaction of tetrahydroquinoline quaternary ammonium salt and p-methylphenylmagnesium bromide. 13 C NMR spectrum.

[0052] Fig.11 It is the product of the coupling reaction of tetrahydroquinoline quaternary ammonium salt and phenyldimethylsilyl lithium reagent. 1 H NMR spectrum.

[0053] Fig.12 It is the product of the coupling reaction of tetrahydroquinoline quaternary ammonium salt and phenyldimethylsilyl lithium reagent. 13 C NMR spectrum.

[0054] Fig.13 It is the product of the coupling reaction of 6-methyltetrahydroquinoline quaternary ammonium salt and phenyldimethylsilyl lithium reagent. 1 H NMR spectrum.

[0055] Fig.14It is the product of the coupling reaction of 6-methyltetrahydroquinoline quaternary ammonium salt and phenyldimethylsilyl lithium reagent. 13 C NMR spectrum. DETAILED DESCRIPTION

[0056] The technical solution of the present invention is further analyzed and explained below in conjunction with specific embodiments.

[0057] Embodiment 1:

[0058]

[0059] To a Schlenk bottle equipped with a magnet and filled with nitrogen, cyclic ammonium salt (62.0 mg, 0.2 mmol), Ni(cod) 2 (2.7 mg, 0.01 mmol), 0.02 mmol PCy prepared in THF 3 and 0.5mL THF. Add aryl Grignard reagent (0.6mmol) dropwise under stirring, then add THF dropwise to the system until the total reaction solvent is about 2mL, and stir the system at 80°C for 16 hours. After the reaction is completed, water is first added dropwise to the system to quench the excess Grignard reagent, then the mixture is extracted with ethyl acetate and dried, the resultant is concentrated and separated and purified by neutral alumina column chromatography and preparative thin layer chromatography to obtain the product (eluent: dichloromethane / methanol = 10 / 1), the product is a colorless liquid, and its yield is 90%.

[0060] 1 H NMR (400 MHz, CDCl 3 ): δ7.43–7.37(m,2H),7.37–7.28(m,5H),7.25–7.18(m,2H),2.64–2.56(t, 2H),2.18–2.13(t,2H),2.11(s,6H),1.57-1.65(m,J=9.1,7.8,5.8Hz,2H). 13 C NMR (101 MHz, CDCl 3 ): δ142.01(2C),139.90,130.22,129.40,129.34,128.20,127.55,126.93,125.87,59.59,45.39,31.12,29.42.HRMS(ESI):m / z 240.1831[M+H] + ,calcd.forC 17 H 22 N 240.1752.

[0061] The optimization process of the arylation reaction of cyclic ammonium salt in Example 1 is as follows:

[0062]

[0063] a Unless otherwise specified, the reactions were carried out under the conditions shown in the table sequence, and the reaction yields were detected by NMR, using 10.5 μL of 1,1,2,2-tetrachloroethane as an internal standard. b Isolated yield.

[0064] Embodiment 2:

[0065]

[0066] The experimental operation was carried out with reference to Example 1. The eluent was a DCM / MeOH mixed solvent with a volume ratio of 10 / 1. The product yield was 61%, and the product was a colorless liquid.

[0067] 1 H NMR (400 MHz, CDCl 3 ): δ7.29–7.27(m,2H),7.25–7.17(m,4H),6.97–6.91(m,2H),3.85(s,3H),2. 64–2.56(t,2H),2.23–2.17(t,2H),2.15(s,6H),1.60-1.66(m,J=7.8Hz,2H). 13 CNMR (101MHz, CDCl 3 ): δ158.61,141.57,139.84,134.33,130.38,130.31,129.31,127.29,125.87,113.59,59.40,55.36,45.17,31.04,29.05.HRMS(ESI):m / z 270.1963[M+H] + ,calcd.for C 18 H 24 NO 270.1858.

[0068] Embodiment 3:

[0069]

[0070] The experimental operation was carried out with reference to Example 1. The eluent was a DCM / MeOH mixed solvent with a volume ratio of 10 / 1. The product yield was 81%, and the product was a colorless liquid.

[0071] 1 H NMR (400 MHz, CDCl 3): δ 7.31–7.29 (m, 2H), 7.25–7.18 (m, 6H), 2.63 (t, 2H), 2.42 (s, 3H), 2.19 (t, 2H), 2.15 (s, 6H), 1.70–1.59 (m, 2H). 13 C NMR (101 MHz, CDCl 3 ): δ 141.91, 139.84, 139.02, 136.45, 130.27, 129.32, 129.15, 128.86, 127.33, 125.81, 59.51, 45.30, 31.05, 29.27, 21.18. HRMS (ESI): m / z 254.1909 [M+H] + , calcd. for C 18 H 24 N 254.2004.

[0072] Example 4:

[0073]

[0074] The experimental operation refers to Example 1. The eluent is a mixed solvent of DCM / MeOH with a volume ratio of 10 / 1. The product yield is 50%, and it is a colorless liquid.

[0075] 1 H NMR (500 MHz, CDCl 3 ): δ 7.66 (d, J = 7.3 Hz, 2H), 7.55 (s, 1H), 7.52–7.41 (m, 5H), 7.41–7.34 (m, 4H), 7.31 (d, J = 7.8 Hz, 1H), 2.71 (t, 2H), 2.23 (t, J = 7.5 Hz, 2H), 2.16 (s, 6H), 1.75–1.62 (m, 2H). 13 C NMR (126 MHz, CDCl 3 ): δ 141.62, 141.06, 141.01, 140.43, 140.19, 130.72, 129.34, 128.88, 128.27, 128.22, 127.38, 127.23, 127.01, 124.68, 59.47, 45.26, 31.24, 29.30. HRMS (ESI): m / z 316.2073 [M+H] + , calcd. for C 23 H 26 N 316.2065.

[0076] Example 5:

[0077]

[0078] The experimental operation was carried out with reference to Example 1. The eluent was a DCM / MeOH mixed solvent with a volume ratio of 10 / 1. The product yield was 63%, and the product was a colorless liquid.

[0079] 1 H NMR (500 MHz, CDCl 3 ): δ7.41(t,J=7.2Hz,2H),7.35(d,J=7.3Hz,1H),7.33–7.29(m,4H),7.26–7.20(m,2H),2.79(t,2H),2.40(t,2H),2.13(s,6H). 13 C NMR (126 MHz, CDCl 3 ): δ142.28,141.73,137.46,130.24,129.82,129.30,128.26,127.66,127.10,126.27,60.93.HRMS(ESI):m / z 226.1598[M+H] + ,calcd.for C 18 H 24 N 226.1596.

[0080] Embodiment 6:

[0081]

[0082] The experimental operation was carried out with reference to Example 1. The eluent was a DCM / MeOH mixed solvent with a volume ratio of 10 / 1. The product yield was 60%, and the product was a colorless liquid.

[0083] 1 H NMR (400 MHz, CDCl 3 ): δ7.44–7.38(m,2H),7.37–7.33(m,1H),7.33–7.27(m,4H),7.25–7.22(m,1H),7.22–7.18(m ,1H),2.61(t,2H),2.19(s,6H),2.16(d,J=7.1Hz,2H),1.53–1.44(m,2H),1.43–1.33(m,2H). 13 C NMR (101 MHz, CDCl 3): δ142.04,141.91,139.91,130.13,129.35,129.29,128.12,127.46,126.85,125.76,59.44,45.29,32.88,29.20,27.27.HRMS(ESI):m / z 254.1913[M+H] + ,calcd.for C 18 H 24 N 254.1909.

[0084] Embodiment 7:

[0085]

[0086] The experimental operation was carried out with reference to Example 1. The eluent was a DCM / MeOH mixed solvent with a volume ratio of 10 / 1. The product yield was 65%, and the product was a colorless liquid.

[0087] 1 H NMR (500 MHz, CDCl 3 ): δ7.31(t,J=7.2Hz,2H),7.25–7.19(m,4H),7.18–7.10(m,2H),2.52(t,2H),2.32 (td,2H),2.03(s,6H),1.65–1.47(m,1H),1.35–1.21(m,1H),0.74(d,J=6.5Hz,3H). 13 C NMR (126 MHz, CDCl 3 ): δ141.95(2C),140.20,130.16,129.49,129.33,128.16,127.56,126.91, 125.84,59.08,40.39,35.14,30.46,13.68.HRMS(ESI):m / z254.1912[M+H] + ,calcd.for C 18 H 24 N 254.1909.

[0088] Embodiment 8:

[0089]

[0090] The experimental operation was carried out with reference to Example 1. The eluent was a DCM / MeOH mixed solvent with a volume ratio of 10 / 1. The product yield was 70%, and it was a colorless liquid.

[0091] 1 H NMR (400 MHz, CDCl 3): δ7.30–7.25(m,2H),7.25–7.16(m,4H),6.94(d,2H),3.85(s,3H),2.60(t,J =9.2,6.8Hz,2H),2.18(t,J=8.5,6.6Hz,2H),2.14(s,6H),1.68–1.56(m,2H). 13 CNMR (101MHz, CDCl 3 ): δ158.61,139.84,134.33,130.38,130.31,129.31,127.30,125.87,113.59,59.40,55.36,45.17,31.04,29.05.HRMS(ESI):m / z 270.1866[M+H] + ,calcd.for C 18 H 24 NO 270.1858.

[0092] Embodiment 9:

[0093]

[0094] The experimental operation was carried out with reference to Example 1. The eluent was a DCM / MeOH mixed solvent with a volume ratio of 10 / 1. The product yield was 78%, and it was a colorless liquid.

[0095] 1 H NMR (400 MHz, CDCl 3 ; 13 C NMR (101 MHz, CDCl 3 ): δ149.59,142.15,140.14,130.51,130.20,130.02,129.27,126.88,125.81,112.33,59.65,45.42,40.79,31.17,29.40.HRMS(ESI):m / z 283.2257[M+H] + ,calcd.for C 19 H 27 N 2 283.2174.

[0096] Embodiment 10:

[0097]

[0098] The experimental operation was carried out with reference to Example 1. The eluent was a DCM / MeOH mixed solvent with a volume ratio of 10 / 1. The product yield was 72%, and the product was a colorless liquid.

[0099] 1 H NMR (400 MHz, CDCl 3 ): δ7.30–7.27(m,2H),7.25–7.21(m,1H),7.21–7.17(m,5H),2.60(t,2H),2.40(s,3H),2.18(t,2H),2.14(s,6H),1.68–1.55(m,2H). 13 C NMR (101 MHz, CDCl 3 ): δ141.91,139.84,139.02,136.45,130.27,129.29,129.15,128.86,127.33,125.81,59.51,45.30,31.05,29.27,21.25.HRMS(ESI):m / z 254.1905[M+H] + ,calcd.forC 18 H 24 N 254.1909.

[0100] Embodiment 11:

[0101]

[0102] The experimental operation was carried out with reference to Example 1. The eluent was a DCM / MeOH mixed solvent with a volume ratio of 10 / 1. The product yield was 74%, and the product was a colorless liquid.

[0103] 1 H NMR (400 MHz, CDCl 3 ): δ7.31–7.26(m,3H),7.25–7.20(m,1H),7.20–7.17(m,1H),7.15(d,J=8.1Hz,1H),7.10 (d,J=8.8Hz,2H),2.59(t,2H),2.39(s,3H),2.17(t,2H),2.13(s,6H),1.67–1.56(m,2H). 13 C NMR (101 MHz, CDCl 3): δ142.12,141.96,139.85,137.72,130.18,130.08,129.34,128.06,127.63,127.44,126.38,125.81,45.33,31.09,29.35.HRMS(ESI):m / z 254.1914[M+H] + ,calcd.for C 18 H 24 N 254.1909.

[0104] Embodiment 12:

[0105]

[0106] The experimental operation was carried out with reference to Example 1. The eluent was a DCM / MeOH mixed solvent with a volume ratio of 10 / 1. The product yield was 72%, and the product was a colorless liquid.

[0107] 1 H NMR (400 MHz, CDCl 3 ): δ7.30–7.27(m,2H),7.25–7.16(m,2H),6.98(s,1H),6.92(dt,J=1.5,0.7Hz ,2H),2.60(t,2H),2.35(s,6H),2.20(t,2H),2.16(s,6H),1.69–1.61(m,2H). 13 C NMR (101 MHz, CDCl 3 ): δ142.22,141.93,139.75,137.58,130.14,129.28,128.49,127.34,127.16,125.77,59.53,45.25,31.06,29.22,21.47.HRMS(ESI):m / z 268.2058[M+H] + ,calcd.for C 19 H 26 N268.2065.

[0108] Embodiment 13:

[0109]

[0110] The experimental operation was carried out with reference to Example 1. The eluent was a DCM / MeOH mixed solvent with a volume ratio of 10 / 1. The product yield was 50%, and it was a colorless liquid.

[0111] 1 H NMR (400 MHz, CDCl 3): δ7.69–7.60(m,4H),7.46(t,2H),7.41–7.34(m,3H),7.33–7.30(m,2H),7 .27–7.23(m,2H),2.65(t,2H),2.17(t,2H),2.11(s,6H),1.69–1.56(m,2H). 13 C NMR (101 MHz, CDCl 3 ): δ141.56,141.01,140.97,139.96,139.75,130.23,129.77,129.45,128.93,127 .62,127.41,127.19,126.92,125.93,59.57,45.37,31.15,29.46.HRMS(ESI):m / z 316.2065[M+H] + ,calcd.for C 23 H 26 N 316.2065.

[0112] Embodiment 14:

[0113]

[0114] The experimental operation was carried out with reference to Example 1. The eluent was a DCM / MeOH mixed solvent with a volume ratio of 10 / 1. The product yield was 82%, and the product was a colorless liquid.

[0115] 1 H NMR (400 MHz, CDCl 3 ): δ7.94–7.82(m,3H),7.77(s,1H),7.55–7.48(m,2H),7.46(dd,J=8.4,1.7Hz,1H),7.37–7.32(m ,2H),7.32–7.27(m,2H),2.65(t,2H),2.16(t,J=8.7,6.5Hz,2H),2.10(s,6H),1.71–1.61(m,2H). 13 C NMR (101 MHz, CDCl 3 ): δ141.86,139.61,139.48,133.37,132.40,130.48,129.41,128.10,127.90,127.85,127.81, 127.74(2C)(d,J=2.0Hz),126.37,126.07,126.03,59.18,44.93,30.99,28.75.HRMS(ESI):m / z 290.1909[M+H] +,calcd.for C 21 H 24 N 290.1909.

[0116] Embodiment 15:

[0117]

[0118] To a Schlenk bottle filled with nitrogen and equipped with a magnet, cyclic ammonium salt (62.0 mg, 0.2 mmol), PPh 2 Cy (10.8 mg, 0.04 mmol), NiCl (dppe) (10.6 mg, 0.02 mmol), and 0.5 mL THF. Add silicon lithium reagent (0.5 mmol) dropwise under stirring, replace THF in the system with toluene (2 mL) under nitrogen protection, and finally stir the reaction at 80 ° C for 16 hours. After the reaction is completed, water is added dropwise to quench the excess silicon lithium reagent. The subsequent treatment steps are the same as the above-mentioned arylation reaction treatment steps. The obtained product is still a colorless liquid with a yield of 91%.

[0119] 1 H NMR (400 MHz, CDCl 3 ): δ7.52(dd,J=7.7,1.5Hz,1H),7.50–7.46(m,2H),7.38–7.28(m,4H),7.24–7.1 7(m,2H),2.54(t,2H),2.14(s,6H),2.07(t,2H),1.59–1.47(m,2H),0.58(s,6H).

[0120] 13 C NMR (126 MHz, CDCl 3 ): δ148.28,139.54,135.96,135.62,134.11,129.89,129.09,128.81,127.9 7,125.36,59.16,45.04,33.88,29.52,-0.83.HRMS(ESI):m / z298.2381[M+H] + ,calcd.for C 19 H 28 NSi 298.1991.

[0121] The optimization process of the silylation reaction of the cyclic ammonium salt in Example 15 is as follows:

[0122]

[0123]

[0124] a Unless otherwise specified, the reactions were carried out under the conditions shown in the table sequence, and the reaction yields were detected by NMR, using 10.5 μL of 1,1,2,2-tetrachloroethane as an internal standard. b Isolated yield.

[0125] Embodiment 16:

[0126]

[0127] The experimental operation was carried out with reference to Example 15. The eluent was a DCM / MeOH mixed solvent with a volume ratio of 10 / 1. The product yield was 63%, and the product was a colorless liquid.

[0128] 1 H NMR (500 MHz, CDCl 3 ): δ7.43–7.37(m,2H),7.33(d,J=7.4Hz,1H),7.28–7.19(m,3H),6.98–6.92(m,2H), 2.43(t,2H),2.25(s,3H),2.05(s,6H),1.97(t,2H),1.50–1.39(m,2H),0.49(s,6H). 13 C NMR (126 MHz, CDCl 3 ): δ148.64,139.75,139.70,135.76,134.12,132.38,129.80,129.01,12 7.93,126.22,59.48,45.34,33.97,30.03,21.49,-0.73.HRMS(ESI):m / z 312.2150[M+H] + ,calcd.for C 20 H 30 NSi 312.2148.

[0129] Embodiment 17:

[0130]

[0131] The experimental operation was carried out with reference to Example 15. The eluent was a DCM / MeOH mixed solvent with a volume ratio of 10 / 1. The product yield was 28%, and the product was a colorless liquid.

[0132] 1 H NMR (400 MHz, CDCl 3): δ7.50–7.44(m,3H),7.37–7.30(m,3H),6.94–6.87(m,2H),2.53(t,2H),2.16(s,6H),2.06(t,2H),1.59–1.47(m,2H),0.57(s,6H). 13 C NMR (101 MHz, CDCl 3 ): δ164.38(d,J=248.5Hz),151.23(d,J=6.8Hz),139.26,137.51(d,J=7.6Hz),134.08,131.55,1 29.25,128.07,115.67(d,J=19.7Hz),112.45(d,J=19.5Hz),58.97,45.06,33.70,29.16,-0.81. 19 F NMR (376 MHz, CDCl 3 ):δ-111.99.HRMS(ESI):m / z 316.1890[M+H] + ,calcd.for C 19 H 27 FNSi 316.1897.

[0133] Embodiment 18:

[0134]

[0135] The experimental operation was carried out with reference to Example 15. The eluent was a DCM / MeOH mixed solvent with a volume ratio of 10 / 1. The product yield was 75%, and the product was a colorless liquid.

[0136] 1 H NMR (400 MHz, CDCl 3 ): δ7.41–7.35(m,2H),7.34(d,J=7.9Hz,1H),7.30–7.21(m,3H),7.10(t,2 H),2.43(t,2H),2.04(s,6H),1.95(t,2H),1.50–1.36(m,2H),0.49(s,6H). 13 CNMR (101MHz, CDCl 3 ): δ150.60,138.86,136.93,136.03,134.43,134.03,129.27,128.86,128.05,125.47,59.18,46.22,33.73,29.64,-0.90.HRMS(ESI):m / z 332.1597[M+H] +,calcd.for C 19 H 27 ClNSi332.1601.

[0137] Embodiment 19:

[0138]

[0139] The experimental operation was carried out with reference to Example 15. The eluent was a DCM / MeOH mixed solvent with a volume ratio of 10 / 1. The product yield was 30%, and the product was a colorless liquid.

[0140] 1 H NMR (500 MHz, CDCl 3 ): δ7.54(dd,J=7.7,1.5Hz,1H),7.51–7.45(m,2H),7.39–7.29(m,4H),7.24–7.20(m,2H),2.62–2.47(m ,3H),2.23(s,6H),1.74–1.63(m,1H),1.32–1.21(m,1H),0.85(d,J=6.6Hz,3H),0.58(d,J=4.1Hz,6H). 13 C NMR (126 MHz, CDCl 3 ): δ148.16,139.59,135.95,135.69,134.14,129.99,129.15,128.94,12 8.04,125.47,59.80,39.86,34.11,33.26,-0.70,-0.89.HRMS(ESI):m / z 312.2151[M+H] + ,calcd.for C 20 H 31 NSi312.2148.

[0141] Embodiment 20:

[0142]

[0143] The experimental operation was carried out with reference to Example 15. The eluent was a DCM / MeOH mixed solvent with a volume ratio of 10 / 1. The product yield was 64%, and the product was a colorless liquid.

[0144] 1 H NMR (400 MHz, CDCl 3):δ7.54–7.51(m,2H),7.51–7.49(m,2H),7.41–7.33(m,8H),7.27(d,J=7.9Hz,1H),7.16(td,J=7.4Hz,1H),2.53(t,2H),2.08(s,6H),1.92(t,2H),1.54–1.44(m,2H),0.89(s,3H). 13 C NMR(101MHz,CDCl 3 ):δ149.17,137.11,137.04,135.31,134.13,130.13,129.40,128.97,128.03,125.32,59.40,45.37,34.45,29.89,-1.48.HRMS(ESI):m / z 360.2151[M+H] + ,calcd.for C 24 H 31 NSi 360.2148。

Claims

1. Arylation method of aryl cyclic ammonium salts, Features: Using aryl magnesium bromide as a nucleophilic reagent, in the presence of a catalyst and a ligand combination, in a solvent, under anhydrous and oxygen-free conditions at 80° C., a fatty amine compound containing biphenyl can be obtained; The aryl cyclic ammonium salt is selected from the compounds of the following structures: ； In the above general formula, R 1 is selected from H, methoxy, methyl, fluorine, chlorine; R 2 Selected from H or methyl; The catalyst is selected from Ni(cod) 2 、Ni(acac) 2 、NiCl 2 (PPh 3 ) 2 , the ligand is PCy 3 ; The aryl magnesium bromide is selected from p-methoxyphenyl magnesium bromide, p-methylphenyl magnesium bromide, m-methylphenyl magnesium bromide, 3,5-dimethylphenyl magnesium bromide, p-dimethylaminophenyl magnesium bromide, 4-biphenyl magnesium bromide, and 2-naphthyl magnesium bromide.

2. The arylation method according to claim 1, Features: The catalyst is Ni(cod) 2 .

3. The arylation method according to claim 1, Features: The solvent is selected from THF, toluene and dioxane.

4. The arylation method according to claim 1, Features: The molar ratio of the aryl cyclic ammonium salt, aryl magnesium bromide, catalyst and ligand is 1.0: 2.0-3.0: 0.05:0.

1.

5. Silylation method of aryl cyclic ammonium salts, Features: Using a silicon-lithium reagent as a nucleophilic reagent, in the presence of a catalyst and a ligand combination, in a solvent, under anhydrous and oxygen-free conditions at 80°C, a silicon-containing fatty amine compound can be obtained; The general structural formula of the aryl cyclic ammonium salt is shown below: ； In the above general formula, R 1 is selected from H, methoxy, methyl, fluorine, chlorine; R 2 Selected from H or methyl; The catalyst is selected from Ni(cod) 2 、Ni(acac) 2 、NiCl 2 (PPh 3 ) 2 、NiCl 2 (dppe), the ligand is PPh 2 Cy.

6. The silicidation method according to claim 5, Features: The catalyst is NiCl 2 (dppe).

7. The silicidation method according to claim 5, Features: The solvent is selected from THF, toluene and dioxane.

8. The silicidation method according to claim 5, Features: The lithium silicon reagent is selected from phenyl dimethyl lithium silicon reagent and diphenyl methyl lithium silicon reagent.

9. The silicidation method according to claim 5, Features: The molar ratio of the aromatic cyclic ammonium salt, the silicon lithium reagent, the catalyst and the ligand is 1.0: 2.0-2.5: 0.1:0.2.

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