Method for synthesizing tetra-substituted alkenyl borate by catalyzing alkenyl sulfonate with iron
The synthesis of tetrasubstituted alkenylboronic esters by reacting an iron catalyst with alkenyl sulfonates solves the problem of difficult synthesis in existing technologies, realizes the synthesis of inexpensive and readily available tetrasubstituted alkenylboronic esters, and expands the synthesis strategy.
Patent Information
- Application Number
- CN202511435802.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-10-09
- Publication Date
- 2025-12-05
AI Technical Summary
The synthesis of tetrasubstituted alkenylboronic esters is difficult in the existing technology, especially since noble metal catalysis is the main method and the substrate range is limited, which restricts their application value in the field of synthesis.
Tetrasubstituted alkenylboronic acid esters were synthesized by using an iron catalyst and alkenyl sulfonate as starting materials, and by adding boron source reagent, alkali and sodium iodide and reacting at a specific temperature.
This study enables the synthesis of tetrasubstituted alkenylboronic esters using inexpensive and readily available iron catalysts, avoiding negative environmental impacts and providing a broader range of strategies for the synthesis of alkenylboronic esters.
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Abstract
Description
TECHNICAL FIELD
[0001] The application belongs to the technical field of organic chemistry, and particularly relates to a method for synthesizing tetra-substituted alkenyl borate by iron-catalyzed alkenyl sulfonate. BACKGROUND
[0002] Polysubstituted alkenes and their derivatives, as key structural units in organic synthesis, have special spatial configuration and electronic properties, which endow them with dual roles: (1) they exhibit significant biological activity in the field of medicinal chemistry; (2) they exhibit unique photoelectric response characteristics in the field of functional materials. Such molecules not only exist widely in natural products with pharmacological activity, but also have an irreplaceable role in the development of molecular devices (such as photoresponsive switches) and advanced materials due to their adjustable π-electron delocalization system. Polysubstituted alkenyl borate compounds have unique synthetic value, which can be directly used as pharmacophores for drug design, and can also be used as modification precursors to construct various carbon-carbon bonds and carbon hetero bonds through C-B bond conversion (such as Suzuki-Miyaura coupling reaction) to produce more valuable polysubstituted alkenes compounds. Therefore, it is of great significance to study the synthesis method of tetra-substituted alkenyl borate compounds.
[0003] In recent decades, researchers have developed various methods for preparing polysubstituted alkenyl boron compounds (alkyne boron hydride reaction, transition metal-catalyzed Miyaura boronation reaction, boron-Wittig alkenylation strategy). For example, the Nakamura team developed a new ligand-free iron catalytic system, which realized the double-boronization and boronization bifunctionalization of internal alkynes, and the method is suitable for various symmetrical and asymmetrical alkynes; for example, the Miyaurat team developed a palladium catalytic system, which realized the boronation reaction of polysubstituted alkenyl halides and halide-like compounds. It can be seen that the currently reported methods are mostly based on alkynes as starting materials, and polysubstituted alkenyl borate compounds are synthesized by the strategy of boronization bifunctionalization, but the abundance of alkynes in nature is low, the price is expensive, and the substrate range is narrow, which limits its application value in the field of synthesis; in addition, the method of pre-preparing polysubstituted alkenyl halides also has great limitations (such as the need to use noble metal catalysis, and the problem of limited substrate synthesis). Therefore, it is necessary to develop an economical, safe and efficient synthesis method. By using easily available compounds or easily prepared compounds as starting materials is an effective strategy to solve the above problems, and the P. Morken team reported a boron-Wittig alkenylation reaction strategy of carbonyl compounds, using bis[(pinacol)boron]methane as a reaction reagent, and polysubstituted alkenyl borate compounds were efficiently synthesized under basic conditions; the Jianbo Wang team reported a palladium-catalyzed carbene migration insertion strategy, which realized the oxidation boronation of hydrazine compounds to obtain various alkenyl boron compounds. Although such reactions have made some progress, there are still some shortcomings: ① mostly based on noble metal catalysis; ② it is difficult to synthesize tetra-substituted alkenyl borate; ③ the substitution of the synthesized tetra-substituted alkenyl boron is mostly the same. Therefore, it also limits its application value in the field of synthesis. SUMMARY
[0004] In view of the above prior art, the present application discloses a method for synthesizing tetra-substituted alkenyl borate by iron-catalyzed alkenyl sulfonate, to solve the technical problem of difficult synthesis of tetra-substituted alkenyl borate in the prior art.
[0005] In order to achieve the above purpose, the technical scheme adopted by the present application is to provide a method for synthesizing tetra-substituted alkenyl borate by iron-catalyzed alkenyl sulfonate, which comprises the following steps: dissolving compound 1 and compound 2 in a solvent, and adding an iron catalyst, a boron source reagent, a base and sodium iodide, and reacting at 70-90°C for 11-13h, then adding 2M HCl and continuing to react for 4-6h to obtain tetra-substituted alkenyl borate 3; the structural formula of compound 1, compound 2 and tetra-substituted alkenyl borate 3 is as follows: 、 、 ; wherein R1 is aryl or heteroaryl; R2 is aryl or alkyl; R3 is alkyl or heteroatom-containing cycloalkyl; the boron source reagent is B2pin2; and the base is MeONa.
[0006] On the basis of the above technical solution, the application can be further improved as follows.
[0007] Further, the iron catalyst is FeBr2; and the solvent is cyclohexane.
[0008] Further, the compound 1 is one of the compounds having the following structures: 、 、 ; The compound 2 is one of the compounds having the following structures: 、 .
[0009] Further, the ratio of the compound 1, the compound 2, the solvent, the iron catalyst, the boron source reagent, the base, sodium iodide and 2M HCl is 0.2mmol:0.4mmol:0.5mL:0.025mmol:0.7mmol:0.75mmol:0.4mmol:1mL.
[0010] The application has the following beneficial effects: 1. The iron catalyst in the reaction system of the application is cheap and easy to obtain, and can also avoid the negative impact of the reaction on the environment; through the synthesis method in the application, the target product with four different substituents can be successfully obtained, which provides an effective strategy for the synthesis of a wider range of alkenyl borate. DETAILED DESCRIPTION
[0011] The specific embodiments of the application will be described in detail below with reference to the examples.
[0012] Example 1 A method for synthesizing tetra-substituted alkenyl borate from alkenyl sulfonate through iron catalysis, and the synthesis route is as follows:
[0013] The synthesis method comprises the following steps: S1: Cut 3g of sodium metal into small pieces (50mg / piece) and place them in a 1L flask, add 500mL of cyclohexane, then reflux at 100℃ for 3h, collect the distilled cyclohexane and seal for storage; S2: The 8 mL reaction bottle with magnetic stirrer was dried in an oven for 4 h, and then placed in an argon-filled glove box. Then 0.025 mmol of ferrous bromide, 0.7 mmol of bis-pinacol borate, 0.75 mmol of sodium methoxide, 0.2 mmol of compound 1 and 0.4 mmol of sodium iodide were sequentially added to the reaction bottle, followed by the addition of 0.5 mL of distilled cyclohexane, and finally 0.4 mmol of compound 2. The reaction bottle was immediately taken out of the glove box after the bottle cap was tightened, and the reaction bottle was placed in a heating jacket at 80°C for 12 h. Then 2M HCl (1 mL) was added and the reaction was continued for 5 h. S3: After the reaction was completed, the reaction solution was cooled to room temperature, and then eluted by flash column chromatography (petroleum ether: ethyl acetate = 10:1) to obtain a white solid (product 1).
[0014] Example 2 A method for synthesizing tetra-substituted alkenyl borate ester from alkenyl sulfonate ester catalyzed by iron, and the synthetic route is as follows:
[0015] The synthesis method comprises the following steps: S1: 3 g of metallic sodium was cut into small pieces (50 mg / piece) and placed in a 1 L flask, 500 mL of cyclohexane was added, and then refluxed at 100°C for 3 h. The distilled cyclohexane was collected and stored in a sealed container. S2: The 8 mL reaction bottle with magnetic stirrer was dried in an oven for 4 h, and then placed in an argon-filled glove box. Then 0.025 mmol of ferrous bromide, 0.7 mmol of bis-pinacol borate, 0.75 mmol of sodium methoxide, 0.2 mmol of compound 1 and 0.4 mmol of sodium iodide were sequentially added to the reaction bottle, followed by the addition of 0.5 mL of distilled cyclohexane, and finally 0.4 mmol of compound 2. The reaction bottle was immediately taken out of the glove box after the bottle cap was tightened, and the reaction bottle was placed in a heating jacket at 70°C for 13 h. Then 2M HCl (1 mL) was added and the reaction was continued for 4 h. S3: After the reaction was completed, the reaction solution was cooled to room temperature, and then eluted by flash column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain a white solid (product 2).
[0016] Example 3 A method for synthesizing tetra-substituted alkenyl borate ester from alkenyl sulfonate ester catalyzed by iron, and the synthetic route is as follows:
[0017] S1: 3 g of metallic sodium was cut into small pieces (50 mg / piece) and placed in a 1 L flask, 500 mL of cyclohexane was added, and then refluxed at 100°C for 3 h. The distilled cyclohexane was collected and stored in a sealed container. S2: The 8 mL reaction bottle with magnetic stirrer was dried in an oven for 4 h, and then placed in an argon-filled glove box. Then 0.025 mmol of ferrous bromide, 0.7 mmol of bis(pinacolato)diboron, 0.75 mmol of sodium methoxide, 0.2 mmol of compound 1 and 0.4 mmol of sodium iodide were sequentially added to the reaction bottle, followed by the addition of 0.5 mL of distilled cyclohexane, and finally 0.4 mmol of compound 2 was added. After the reaction bottle cap was immediately tightened, the reaction bottle was taken out of the glove box and placed in a heating jacket at 90°C for 11 h. Then 2M HCl (1 mL) was added and the reaction was continued for 6 h; S3: After the reaction was completed, the reaction solution was cooled to room temperature, and then white solid (product 3) was obtained by fast column chromatography (petroleum ether: ethyl acetate = 10:1) elution.
[0018] Example 4 A method for synthesizing tetra-substituted alkenyl borate ester from alkenyl sulfonate ester catalyzed by iron, and the synthetic route is as follows:
[0019] S1: 3 g of sodium metal was cut into small pieces (50 mg / piece) and placed in a 1 L flask, 500 mL of cyclohexane was added, and then refluxed at 100°C for 3 h. The distilled cyclohexane was collected and stored in a sealed container; S2: The 8 mL reaction bottle with magnetic stirrer was dried in an oven for 4 h, and then placed in an argon-filled glove box. Then 0.025 mmol of ferrous bromide, 0.7 mmol of bis(pinacolato)diboron, 0.75 mmol of sodium methoxide, 0.2 mmol of compound 1 and 0.4 mmol of sodium iodide were sequentially added to the reaction bottle, followed by the addition of 0.5 mL of distilled cyclohexane, and finally 0.4 mmol of compound 2 was added. After the reaction bottle cap was immediately tightened, the reaction bottle was taken out of the glove box and placed in a heating jacket at 90°C for 11 h. Then 2M HCl (1 mL) was added and the reaction was continued for 6 h; S3: After the reaction was completed, the reaction solution was cooled to room temperature, and then white solid (product 3) was obtained by fast column chromatography (petroleum ether: ethyl acetate = 10:1) elution.
[0020] The structural characterization of product 1 in Example 1 is as follows: 1H NMR (400 MHz, CDC13) δ 7.05 (d, J = 8.5 Hz, 1.6 H), 7.05 (d, J = 8.5 Hz, 0.4 H), 6.83 (d, J = 8.5 Hz, 2 H), 3.79 (s, 3 H), 3.09-2.99 (m, 0.8 H), 2.84-2.74 (m, 0.2 H), 1.94 (s, 0.6 H), 1.83-1.75 (m, 2 H), 1.75-1.65 (m, 2 H), 1.60 (s, 2.4 H), 1.58-1.42 (m, 4 H), 1.25 (s, 12 H).
[0021] 13 C NMR (101 MHz, CDC13) δ 157.2, 151.1 (152.6), 134.5 (134.8), 129.9, 129.6 (128.0), 113.2, 83.1, 55.0, 48.0 (43.2), 31.3 (31.1), 26.1, 24.5, 14.6 (17.0).
[0022] HRMS (ESI-QTOF): Calcd for C 21 H 31 BO3, (M + Na) + : 365.2264; Found: 365.2268.
[0023] The structural characterization of product 2 in Example 2 is as follows: 1H NMR (400 MHz, CDC13) δ 7.01 (d, J = 8.6 Hz, 1.6 H), 6.96 (d, J = 8.6 Hz, 0.4 H), 6.82 (d, J = 8.5 Hz, 2.0 H), 4.06-4.01 (m, 1.6 H), 3.90-3.86 (m, 0.4 H), 3.81 (s, 0.6 H), 3.79 (s, 2.4 H), 3.48-3.38 (m, 1.6 H), 3.24-3.16 (m, 0.4 H), 2.92-2.82 (m, 0.8 H), 2.68-2.59 (m, 0.2 H), 1.94 (s, 0.6 H), 1.83-1.70 (m, 2 H), 1.60 (s, 2.4 H), 1.58-1.53 (m, 2 H), 1.26 (s, 10 H), 1.24 (s, 2 H).
[0024] 13 C NMR (101 MHz, CDC13) δ 157.5, 151.9, 134.2 (131.4), 130.0, 129.4 (128.5), 113.3, 83.2, 68.3 (67.8), 55.1, 43.9 (39.3), 31.3 (30.4), 24.6, 15.2 (17.7).
[0025] HRMS (ESI-QTOF): Calcd for C 21 H 31 BO4, (M+Na) + : 381.2213; Found: 381.2209.
[0026] The structural characterization of product 3 in Example 3 is as follows: 1 H NMR (400 MHz, CDC13) δ 7.17-7.05 (m, 3 H), 6.94 (d, J = 6.8 Hz, 2 H), 6.84 (d, J = 8.7 Hz, 2 H), 6.54 (d, J = 8.7 Hz, 2 H), 3.66 (s, 3 H), 3.09-3.00 (m, 1 H), 1.90-1.78 (m, 2 H), 1.53-1.47 (m, 4 H), 1.44-1.34 (m, 2 H), 1.32 (s, 12 H).
[0027] 13 C NMR (101 MHz, CDCl3) δ 157.0, 153.8, 140.1, 133.2, 127.2, 125.8,112.8, 83.6, 54.9, 48.9, 31.8, 24.9, 24.7.
[0028] The structure of product 4 in Example 4 is characterized as follows: 1 H NMR (400 MHz, CDCl3) δ 7.18 (d, J = 5.1 Hz, 1 H), 6.98-6.95 (m, 1H), 6.80 (d, J = 3.3 Hz, 0.8 H), 6.71 (d, J = 3.3 Hz, 0.2 H), 3.03-2.93 (m,0.8 H), 2.07-2.00 (m, 0.2 H), 1.94 (s, 0.7 H), 1.81 (s, 2.3 H), 1.80-1.74 (m,2 H), 1.72-1.66 (m, 2 H), 1.65-1.57 (m, 2 H), 1.54-1.45 (m, 2 H), 1.29 (s,9.4 H), 1.27 (s, 2.6 H).
[0029] 13 C NMR (101 MHz, CDCl3) δ 153.1, 143.7, 126.5 (126.7), 125.5, 124.8,123.7, 83.5, 48.6 (43.7), 31.6, 26.2, 24.6, 15.5 (17.4).
[0030] HRMS (ESI-QTOF): Calcd for C 18 H 27 BO2, (M+Na) + : 341.1723; Found: 341.1727.
[0031] The product yields of Examples 1-4 are shown in Table 1 below Table 1
[0032] Although the specific embodiments of the present application have been described in detail, it should be understood that the present patent is not limited to the details of the foregoing embodiments. Various modifications and changes can be made to the described embodiments without departing from the scope of the present patent.
Claims
1. A method for the iron-catalyzed synthesis of tetra-substituted alkenyl boronates from alkenyl sulfonates, characterized in that, The method comprises the following steps: dissolving compound 1 and compound 2 in a solvent, adding an iron catalyst, a boron source reagent, a base and sodium iodide, and reacting at 70-90 DEG C for 11-13 h, then adding 2M HCl to continue reacting for 4-6 h to obtain tetra-substituted alkenyl borate 3; the structural formulae of the compound 1, the compound 2 and the tetra-substituted alkenyl borate 3 are as follows: 、 、 ； Wherein R1 is aryl or heteroaryl; R2 is aryl or alkyl; R3 is alkyl or heteroatom-containing cycloalkyl; the boron source reagent is B2pin2; and the base is MeONa.
2. The process for iron-catalyzed synthesis of tetra-substituted alkenyl boronate ester from alkenyl sulfonic acid ester according to claim 1, characterized in that: The iron catalyst is FeBr2; and the solvent is cyclohexane.
3. The process for iron-catalyzed synthesis of tetra-substituted alkenyl boronate ester from alkenyl sulfonic acid ester according to claim 1, wherein, The compound 1 is one of the following compounds with the following structures: 、 、 ； The compound 2 is one of the following compounds with the following structures: 、 。 4. The iron-catalyzed synthesis of tetra-substituted alkenyl boronate esters from alkenyl sulfonic acid esters according to claim 3, characterized in that: The feed ratio of the compound 1, the compound 2, the solvent, the iron catalyst, the boron source reagent, the base, sodium iodide and 2M HCl is 0.2 mmol:0.4 mmol:0.5 mL:0.025 mmol:0.7 mmol:0.75 mmol:0.4 mmol:1 mL.