A method for coupling of organoboron with electrophile involving ferric chloride

Abstract

This invention discloses a method for coupling organoboron with electrophilic reagents involving ferric chloride, belonging to the field of organic and polymer synthesis technology. Organic synthesis transformations involving or catalyzed by iron-containing compounds have always been an important research subject in green chemistry. Iron-containing compounds possess advantages such as low price, environmental friendliness, and abundant reserves; however, their application in organic chemical transformations often requires the introduction of activators and expensive ligands, greatly limiting their industrial application value. In this invention, the applicant utilizes ferric chloride as a deboronizing agent to successfully achieve the deboronization and iron conversion reaction of arylboronic acid pinacol esters without the aid of any ligands, activators, or other external additives. By introducing electrophilic reagents such as acyl chlorides, acid anhydrides, sulfonyl chlorides, and sulfinyl chlorides with intermediates, the corresponding coupled products are obtained. This invention technically provides a method for deboronization with ferric chloride and realizes its coupling with electrophilic reagents, which can be used for the synthesis of bulk chemical raw materials.

Description

Technical Field

[0001] This invention belongs to the field of organic and polymer synthesis technology, specifically relating to a method for the cleavage of CB bonds in organoboron involving ferric chloride and its coupling reaction with an electrophilic reagent. Background Technology

[0002] The organic synthesis transformation involving or catalyzed by iron-containing compounds has always been an important research focus in green chemistry. Iron-containing compounds generally have advantages such as low price, environmental friendliness, and abundant reserves, but their transformation in organic chemical transformations is hampered by unclear transformation mechanisms and the need for activators and expensive ligands, which greatly limits their industrial application value. In this invention, the applicant uses ferric chloride as a deboronizing agent to successfully achieve the deboronization to iron conversion of aryl boron without the aid of any ligands, activators, or other external additives. This reaction exhibits good functional group compatibility. Reacting the deboronization to iron conversion intermediate with electrophilic reagents revealed that it can couple with various types of electrophilic reagents to obtain coupling products. This method does not require the use of precious metal catalysts; it can achieve efficient transformation using only inexpensive ferric chloride, and has significant application value for the synthesis and preparation of known bulk chemical raw materials such as diaryl ketones, diaryl sulfones, and diaryl sulfoxides (Equation 1).

[0003] Summary of the Invention

[0004] The purpose of this invention is to provide a method for the deboronization and iron conversion of aryl boron promoted by ferric chloride and its coupling with an electrophilic reagent, the technical method of which is shown in Formula 2:

[0005]

[0006] The specific steps are as follows:

[0007] (1) Under a nitrogen atmosphere, add 0.2 mmol of pinacol arylboronic acid to a Schlenk tube, add 2 mL of solvent, stir, and add 2.0 equivalents of anhydrous ferric chloride to completely dissolve the substrate. The solvent is selected from one of dichloromethane, chloroform, toluene, 1,2-dichloroethane, chlorobenzene, and carbon tetrachloride.

[0008] (2) Stir the reaction solution at any temperature between 25°C and 100°C for 1 hour.

[0009] (3) Under nitrogen protection, the electrophilic reagent was added to the reaction solution and stirred for 4 hours. The electrophilic reagent was selected from aryl acyl chloride, alkyl acyl chloride, acetic anhydride, aryl sulfonyl chloride, sulfonyl chloride, and isocyanate.

[0010] (4) After the reaction is complete, the solid in the reaction solution is filtered, the filtrate is retained, and the solution is evaporated to dryness under reduced pressure. The crude product is separated by column chromatography with petroleum ether and ethyl acetate or dichloromethane as the eluent to obtain the pure coupling product. Attached Figure Description

[0011] Figure 1 The product in Example 1 1 H-NMR spectrum;

[0012] Figure 2 The product in Example 1 13 C-NMR spectrum;

[0013] Figure 3 The product in Example 2 1 H-NMR spectrum;

[0014] Figure 4 The product in Example 2 13 C-NMR spectrum;

[0015] Figure 5 The product in Example 3 1 H-NMR spectrum;

[0016] Figure 6 The product in Example 3 13 C-NMR spectrum;

[0017] Figure 7 The product in Example 4 1 H-NMR spectrum;

[0018] Figure 8 The product in Example 4 13 C-NMR spectrum;

[0019] Figure 9 The product in Example 5 1 H-NMR spectrum;

[0020] Figure 10 The product in Example 5 13 C-NMR spectrum;

[0021] Figure 11 The product in Example 6 1 H-NMR spectrum;

[0022] Figure 12 The product in Example 6 13 C-NMR spectrum;

[0023] Figure 13 The product in Example 7 1 H-NMR spectrum;

[0024] Figure 14 The product in Example 7 13 C-NMR spectrum;

[0025] Figure 15 The product in Example 8 1 H-NMR spectrum;

[0026] Figure 16 The product in Example 8 13 C-NMR spectrum; Detailed Implementation

[0027] The present invention is illustrated by way of examples. The specific material ratios, process conditions and results described in the examples are only for illustrating the present invention, and the present invention should not and will not be limited to the examples.

[0028] Example 1

[0029]

[0030] Take a dry 10mL Schlenk tube, weigh 0.4mmol (64.9mg) of anhydrous FeCl3 into the Schlenk tube, and under vacuum, blow the Schlenk tube with a hot air gun for about 3 minutes to remove a small amount of moisture. Then, evacuate the tube and introduce nitrogen gas. Repeat this process three times. Under nitrogen purging, 2 ml of anhydrous dichloromethane was added to the tube, followed by pinacol ester of p-methylphenylboronic acid (0.2 mmol, 43.6 mg). The mixture was stirred at room temperature for 1 hour. After complete deboron removal as confirmed by TLC, benzoyl chloride (0.2 mmol, 56.2 mg) was added, and the mixture was stirred at room temperature for 4 hours. The mixture was filtered to remove FeCl3, and the solvent was distilled off under reduced pressure. The crude product was separated by column chromatography using petroleum ether / dichloromethane (V petroleum ether:V dichloromethane = 6:4) as the eluent. After distillation under reduced pressure again, 20.0 mg of pure phenyl (p-tolyl) methyl ketone was finally obtained, with a yield of 51% and a purity >95% as determined by NMR.

[0031] Example 2

[0032]

[0033] Take a dry 10 mL Schlenk tube and weigh 0.4 mmol (64.9 mg) of anhydrous FeCl3 into it. Under vacuum, purge the Schlenk tube with a hot air gun for approximately 3 minutes to remove any remaining moisture. Then, evacuate again and purge with nitrogen gas, repeating this process three times. Under nitrogen purging, add 2 mL of anhydrous dichloromethane to the tube, followed by 0.2 mmol (46.4 mg) of pinacol 3,5-dimethylphenylboronic acid. Stir at room temperature for 1 hour. After complete deboron removal as confirmed by TLC, acetyl chloride (0.4 mmol, 31.4 mg) was added, and the mixture was stirred at room temperature for 4 hours. After filtration to remove FeCl3, the solvent was distilled off under reduced pressure to obtain the crude product. The crude product was then separated by column chromatography using petroleum ether / ethyl acetate (V petroleum ether:V ethyl acetate = 19:1) as the eluent. After distillation under reduced pressure again, 21.6 mg of pure 1-(2,4-dimethylphenyl)ethane-1-one was finally obtained, with a yield of 73% and a purity of >95% as determined by NMR.

[0034] Example 3

[0035]

[0036] Take a dry 10 mL Schlenk tube and weigh 0.4 mmol (64.9 mg) of anhydrous FeCl3 into it. Under vacuum, purge the Schlenk tube with a hot air gun for about 3 minutes to remove any remaining moisture. Then, evacuate the tube again and purge with nitrogen gas, repeating this process three times. Under nitrogen purging, add 2 mL of anhydrous dichloromethane to the tube, followed by 0.2 mmol (50.4 mg) of pinacol 3-fluoro-4-methoxyphenylboronic acid. Stir at room temperature for 1 hour. After complete deboron removal as confirmed by TLC, benzoyl chloride (0.4 mmol, 56.2 mg) was added, and the mixture was stirred at room temperature for 4 hours. After filtration to remove FeCl3, the solvent was distilled off under reduced pressure to obtain the crude product. The crude product was then separated by column chromatography using petroleum ether / ethyl acetate (V petroleum ether:V ethyl acetate = 4:1) as the eluent. After distillation under reduced pressure again, 29.0 mg of pure (3-fluoro-4-methoxyphenyl)(phenyl) methyl ketone was finally obtained, with a yield of 63% and a purity of >95% as determined by NMR.

[0037] Example 4

[0038]

[0039] Take a dry 10 mL Schlenk tube and weigh 0.4 mmol (64.9 mg) of anhydrous FeCl3 into it. Under vacuum, purge the Schlenk tube with a hot air gun for approximately 3 minutes to remove any remaining moisture. Then, evacuate again and purge with nitrogen gas, repeating this process three times. Under nitrogen purging, add 2 mL of anhydrous dichloromethane to the tube, followed by 0.2 mmol (52.4 mg) of pinacol 3,5-dimethyl-4-methoxyphenylboronic acid. Stir at room temperature for 1 hour. After complete deboron removal as confirmed by TLC, benzoyl chloride (0.4 mmol, 56.2 mg) was added, and the mixture was stirred at room temperature for 4 hours. After filtration to remove FeCl3, the solvent was distilled off under reduced pressure to obtain the crude product. The crude product was then separated by column chromatography using petroleum ether / ethyl acetate (V petroleum ether:V ethyl acetate = 9:1) as the eluent. After distillation under reduced pressure again, 41.3 mg of pure (4-methoxy-3,5-dimethylphenyl)(phenyl) methyl ketone was finally obtained, with a yield of 86% and a purity of >95% as determined by NMR.

[0040] Example 5

[0041]

[0042] Take a dry 10 mL Schlenk tube and weigh 0.4 mmol (64.9 mg) of anhydrous FeCl3 into it. Under vacuum, purge the Schlenk tube with a hot air gun for approximately 3 minutes to remove any remaining moisture. Then, evacuate again and purge with nitrogen gas, repeating this process three times. Under nitrogen purging, add 2 mL of anhydrous dichloromethane to the tube, followed by 0.2 mmol (46.8 mg) of 4-methoxyphenylboronic acid pinacol ester. Stir at room temperature for 1 hour. After complete deboron removal was confirmed by TLC, acetic anhydride (0.4 mmol, 40.8 mg) was added, and the mixture was stirred at room temperature for 4 hours. After filtration to remove FeCl3, the solvent was distilled off under reduced pressure to obtain the crude product. The crude product was then separated by column chromatography using petroleum ether / ethyl acetate (V petroleum ether:V ethyl acetate = 4:1) as the eluent. After distillation under reduced pressure again, 25.5 mg of pure 1-(4-methoxyphenyl)ethane-1-one was finally obtained, with a yield of 85% and a purity of >95% as determined by NMR.

[0043] Example 6

[0044]

[0045] Take a dry 10 mL Schlenk tube and weigh 0.4 mmol (64.9 mg) of anhydrous FeCl3 into it. Under vacuum, purge the Schlenk tube with a hot air gun for approximately 3 minutes to remove any remaining moisture. Then, evacuate again and purge with nitrogen gas, repeating this process three times. Under nitrogen purging, add 2 mL of anhydrous dichloromethane to the tube, followed by 0.2 mmol (46.8 mg) of 4-methoxyphenylboronic acid pinacol ester. Stir at room temperature for 1 hour. After complete deboron removal as confirmed by TLC, p-methoxybenzenesulfonyl chloride (0.4 mmol, 82.7 mg) was added, and the mixture was stirred at 60 °C for 2 hours. After filtration to remove FeCl3, the solvent was distilled off under reduced pressure to obtain the crude product. The crude product was then separated by column chromatography using petroleum ether / ethyl acetate (V petroleum ether:V ethyl acetate = 7:3) as the eluent. After distillation under reduced pressure again, 33.4 mg of pure 4,4′-sulfonylbis(methoxybenzene) was finally obtained, with a yield of 60% and a purity of >95% as determined by NMR.

[0046] Example 7

[0047]

[0048] Take a dry 10 mL Schlenk tube and weigh 0.4 mmol (64.9 mg) of anhydrous FeCl3 into it. Under vacuum, purge the Schlenk tube with a hot air gun for approximately 3 minutes to remove any remaining moisture. Then, evacuate again and purge with nitrogen gas, repeating this process three times. Under nitrogen purging, add 2 mL of anhydrous dichloromethane to the tube, followed by 0.2 mmol (46.8 mg) of 4-methoxyphenylboronic acid pinacol ester. Stir at room temperature for 1 hour. After complete deboron removal as confirmed by TLC, p-toluene isocyanate (0.4 mmol, 53.3 mg) was added, and the mixture was stirred at 40 °C for 5 hours. After filtration to remove FeCl3, the solvent was distilled off under reduced pressure to obtain the crude product. The crude product was then separated by column chromatography using petroleum ether / ethyl acetate (V petroleum ether:V ethyl acetate = 7:3) as the eluent. After distillation under reduced pressure again, 24.6 mg of pure 4-methoxy-N-(p-toluyl)benzamide was finally obtained, with a yield of 51% and a purity >95% as determined by NMR.

[0049] Example 8

[0050] Take a dry 10mL Schlenk tube, weigh 0.8mmol (129.8mg) of anhydrous FeCl3 into the Schlenk tube, and under vacuum, purge the Schlenk tube with a hot air gun for approximately 3 minutes.

[0051] To remove a small amount of moisture, the tube was evacuated and purged with nitrogen three times. Under nitrogen purging, 4 ml of anhydrous dichloromethane was added, followed by pinacol ester of 3,5-dimethylphenylboronic acid (0.4 mmol, 92.8 mg). The mixture was stirred at room temperature for 1 hour. After TLC confirmation of complete deboron removal, thionyl chloride (0.1 mmol, 11.9 mg) was added, and the mixture was stirred at room temperature for 1 hour. The mixture was filtered to remove FeCl3, and the solvent was distilled off under reduced pressure. The crude product was separated by column chromatography using petroleum ether / ethyl acetate (V petroleum ether:V ethyl acetate = 7:3) as the eluent. Distillation under reduced pressure was repeated to obtain 19.0 mg of pure 4,4′-sulfinylbis(1,3-dimethylbenzene), with a yield of 75% and a purity >95% as determined by NMR.

Claims

1. A method for coupling of organoboron with electrophile in the presence of ferric chloride, the reaction is shown as follows: R = methyl, methoxy, fluorine; Electrophile is selected from aryl acid chloride, alkyl acid chloride, acetic anhydride, aryl sulfonyl chloride, dichlorosulfoxide, isocyanate.

2. The method for coupling of organoboron with electrophile in the presence of ferric chloride according to claim 1, the steps are as follows: (1) under nitrogen atmosphere, add 0.2 mmol aryl boronic acid pinacol ester in a Schlenk tube, add 2 mL solvent, stir and add 2.0 equivalent of anhydrous ferric chloride, make the substrate completely dissolved, the solvent is selected from dichloromethane, chloroform, toluene, 1,2-dichloroethane, chlorobenzene, carbon tetrachloride, (2) stir the reaction solution at any temperature between 25℃ and 100℃ for 1-2 hours, (3) add electrophile to the reaction solution under nitrogen protection, continue to stir for 4 hours, (4) after the reaction is completed, filter the solid in the reaction solution, retain the filtrate, evaporate under reduced pressure, column chromatography is used to separate the crude product, eluent is petroleum ether and ethyl acetate or dichloromethane, to obtain pure coupling product. ​ ​ ​ ​ ​ ​

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