Methyl ketone compound deoxidation reduction alkenylation method

Abstract

The invention discloses a method for deoxidation reduction alkenylation of a methyl ketone compound, which is characterized by comprising the following steps: mixing the methyl ketone compound, a reducing agent and a solvent under the action of a protective gas and a catalyst, and then heating for reaction to obtain an alkenylation product, the structural formula of the methyl ketone compound is # imgabs0 #; the structural formula of the alkenylation product is # imgabs 1 #. The preparation method has the beneficial effects that (1) the raw materials are wide in source, easy to obtain and low in cost, and part of the raw materials are simple and efficient to synthesize; the preparation method is simple to operate and mild in reaction condition; (2) no toxic or harmful gas is generated after the reaction, the influence on the atmosphere is small, and the health of operators is also guaranteed; (3) the method has wide universality and high yield; (4) methyl ketone is directly deoxidized and reduced into corresponding olefin, no metal reagent participates in, the cost is lower, the compatibility of functional groups is good, the chemical selectivity and conversion rate are higher, and the universality is good.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and particularly relates to a method for deoxygenative reductive alkenylation of methyl ketone compounds. Background Art

[0002] Carbonyl compounds are important natural resources, and their catalytic reduction reaction is a hot topic in the field of organic synthesis. In particular, the reduction and deoxygenation of aromatic ketones to obtain the corresponding alkanes or alkenes is a powerful tool for synthesizing biofuels from biomass raw materials. In 1969, Shapiro proposed an effective strategy for converting ketones to alkenes, that is, the reaction of ketones with (p-toluenesulfonyl)hydrazine to obtain the corresponding hydrazone, and the reaction of hydrazone with a strong base (such as n-butyllithium) to obtain alkenes. Subsequently, Carney and Hiegel improved the Clemmensen reduction process and also obtained a method for reducing aryl ketones to aryl alkenes. Although traditional methods have been widely used, the substrate scope is limited and metal waste will be generated. Developing a widely applicable and simple alkenylation reaction is a very meaningful topic. In recent years, methods for directly deoxygenating ketones to prepare alkenes catalyzed by rhenium (ChemCatChem, 2015, 7(7): 1177-83), molybdenum, rhodium (Green Chemistry, 2016, 18(9): 2675-81) and nickel (JACS Au, 2022, 2(8): 1929-34) complexes have been developed, opening up new ways for the green and efficient synthesis of alkenes, but still facing problems such as unstable metal reagents and limited substrate scope. And metal-free catalytic conditions often have problems such as the need for high temperature and high pressure (Angew.Chem. Int. Ed., 2015, 54(29): 8511-4) or the addition of strong acids or excessive bases, as well as complex catalysts and the need for stepwise reactions. Therefore, it is particularly important to develop a metal-free and mild catalytic system to deoxygenate and reduce ketone compounds to alkenes. Summary of the Invention

[0003] Aiming at the deficiencies of the existing technology, the purpose of the present invention is to provide a method for deoxygenative reductive alkenylation of methyl ketone compounds.

[0004] To achieve the above purpose, the present invention provides the following technical solutions: A method for deoxygenative reductive alkenylation of methyl ketone compounds, comprising the following steps: Under the action of a protective gas and a catalyst, mix a methyl ketone compound, a reducing agent, and a solvent, and then heat up the reaction to obtain an alkenylation product; The structural formula of the methyl ketone compound is: ; The structural formula of the alkenylation product is: 。

[0005] As a further improvement of the present invention, the methyl ketone compound is 4-biphenylacetone or 4-chlorobiphenylacetone or 2-phenylacetophenone or 2-naphthylacetone or 4-tert-butylacetophenone or 4-bromoacetophenone or 4-iodoacetophenone or 3-chloroacetophenone or 2-benzofuranylacetone.

[0006] As a further improvement of the present invention, the catalyst is tris(pentafluorophenyl)borane.

[0007] As a further improvement of the present invention, the reducing agent is pinacolborane.

[0008] As a further improvement of the present invention, the reaction temperature is 60 - 100 °C.

[0009] As a further improvement of the present invention, the reaction time is 10 - 15 h.

[0010] As a further improvement of the present invention, the solvent is n-hexane.

[0011] As a further improvement of the present invention, the molar ratio of the methyl ketone compound, the catalyst and the reducing agent is 0.5 - 1.5:0.03 - 0.08:1.5 - 2.

[0012] As a further improvement of the present invention, the molar ratio of the methyl ketone compound, the catalyst and the reducing agent is 1.0:0.05:1.8.

[0013] As a further improvement of the present invention, the protective gas is nitrogen.

[0014] The reaction equation of the present invention is:

[0015] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) The raw materials of the present invention are widely sourced and easily obtainable, with low costs, and some raw materials can be synthesized simply and efficiently; the preparation method is easy to operate, the reaction conditions are mild, energy consumption is reduced, and the reaction selectivity is strong, enabling direct synthesis of the target product with a maximum yield of up to 95%; (2) The present invention does not generate toxic and harmful gases after the reaction, has little impact on the atmosphere, and also ensures the health of the operators; (3) The present invention has broad universality and high yield. It is an important supplement to the synthetic method of deoxygenating and reducing methyl ketones to olefins, providing important ideas for the synthesis of dyes and pharmaceutical molecules from biomass raw materials and so on.

[0016] (4) In the present invention, methyl ketones are directly deoxygenated and reduced to the corresponding olefins without the participation of metal reagents. This not only has a relatively low cost and good functional group compatibility, but also has high chemoselectivity and conversion rate, and good universality. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 It is a schematic diagram of the reaction principle of Example 1 of the present invention; Figure 2 It is a schematic diagram of the reaction principle of the prior art. DETAILED DESCRIPTION OF THE INVENTION Example 1

[0018] Preparation of 4 - biphenylylstyrene, the structural formula is as follows:

[0019] Under a nitrogen atmosphere, 0.5 mmol of the raw material 4 - biphenylylacetone, 0.025 mmol of the catalyst tris(pentafluorophenyl)borane, 0.9 mmol of pinacol borane, and 1.0 mL of n - hexane as the solvent were added, and the reaction was carried out at 80 °C for 12 hours. The product was separated by column chromatography with a yield of 92%. 1H NMR (400 MHz, CDCl3) δ 7.65 (dd, J = 11.7, 8.3 Hz, 4H), 7.59 – 7.44 (m, 4H), 7.41 (d, J = 7.3 Hz, 1H), 6.82 (dd, J = 17.6, 10.9 Hz, 1H), 5.86 (d, J = 17.6 Hz, 1H), 5.34 (d, J = 10.9 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 140.8, 140.6, 136.7, 136.7, 128.8, 127.3, 127.2, 127.0, 126.7, 113.9. Example 2

[0020] Preparation of 4 - chlorophenylstyrene, the structural formula is as follows:

[0021] Under a nitrogen atmosphere, 0.5 mmol of the raw material 4-chlorobiphenylacetophenone, 0.025 mmol of the catalyst tris(pentafluorophenyl)borane, 0.9 mmol of pinacolborane, and 1.0 mL of n-hexane as the solvent were added. The reaction was carried out at 80 °C for 12 hours, and the product was separated by column chromatography with a yield of 87%. 1H NMR (400 MHz, CDCl3) δ 7.48 (dd, J = 16.5, 7.9 Hz, 7H), 7.38 (d, J = 8.3 Hz, 2H), 6.74 (dd, J = 17.6, 10.9 Hz, 1H), 5.78 (d, J = 17.6 Hz, 1H), 5.28 (d, J = 10.8 Hz, 1H). 13C NMR (126 MHz, CDCl3) 139.4, 139.3, 137.1, 136.4, 133.5, 129.1, 128.3, 127.2, 126.9, 114.3. Example 3

[0022] Preparation of 2-biphenylethene, the structural formula is as follows:

[0023] Under a nitrogen atmosphere, 0.5 mmol of the raw material 2-biphenylacetophenone, 0.025 mmol of the catalyst tris(pentafluorophenyl)borane, 0.9 mmol of pinacolborane, and 1.0 mL of n-hexane as the solvent were added. The reaction was carried out at 80 °C for 12 hours, and the product was separated by column chromatography with a yield of 75%. 1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 5.0 Hz, 1H), 7.52 – 7.28 (m, 8H), 6.78 (dd, J = 17.5, 11.0 Hz, 1H), 5.76 (d, J = 17.5 Hz, 1H), 5.24 (d, J = 10.6 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 141.0, 136.1, 135.9, 130.2, 129.9, 128.1, 127.8, 127.6, 127.1, 125.8, 114.8. Example 4

[0024] Preparation of 2-naphthylethene, the structural formula is as follows:

[0025] Under a nitrogen atmosphere, 0.5 mmol of starting material 2-acetonaphthone, 0.025 mmol of catalyst tris(pentafluorophenyl)borane, 0.9 mmol of pinacolborane, and 1.0 mL of n-hexane as the solvent were added, and the reaction was carried out at 80 °C for 12 hours. The product was separated by column chromatography with a yield of 74%. 1H NMR (400 MHz, CDCl3) δ 7.82 – 7.76 (m, 3H), 7.74 (s, 1H), 7.63 (d, J = 8.5 Hz, 1H), 7.48 – 7.40 (m, 2H), 6.87 (dd, J = 17.6, 10.9 Hz, 1H), 5.86 (d, J = 17.6 Hz, 1H), 5.33 (d, J = 10.9 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 137.0, 135.1, 133.6, 133.2, 128.2, 128.1, 127.7, 126.4, 126.3, 126.0, 123.2, 114.2. Example 5

[0026] Preparation of 4-tert-butylstyrene, the structural formula is as follows:

[0027] Under a nitrogen atmosphere, 0.5 mmol of starting material 4-tert-butylacetophenone, 0.025 mmol of catalyst tris(pentafluorophenyl)borane, 0.9 mmol of pinacolborane, and 1.0 mL of n-hexane as the solvent were added, and the reaction was carried out at 80 °C for 12 hours. The product was separated by column chromatography with a yield of 82%. 1H NMR (400 MHz, CDCl3) δ 7.45 (d, J = 0.8 Hz, 4H), 6.80 (ddd, J = 17.6, 10.9, 0.7 Hz, 1H), 5.81 (d, J = 17.6 Hz, 1H), 5.29 (d, J = 10.9 Hz, 1H), 1.42 (s, 9H). 13C NMR (126 MHz,) δ 151.0, 136.7, 135.0, 126.1, 125.6, 113.1, 34.7, 31.4. Example 6

[0028] Preparation of 4-bromostyrene, the structural formula is as follows:

[0029] Under a nitrogen atmosphere, 0.5 mmol of the raw material 4-bromoacetophenone, 0.025 mmol of the catalyst tris(pentafluorophenyl)borane, 0.9 mmol of pinacolborane, and 1.0 mL of n-hexane as the solvent were added, and the reaction was carried out at 80 °C for 12 hours. The yield of the product obtained by column chromatography separation was 91%. 1H NMR (400 MHz, CDCl3) δ 7.50 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 6.70 (dd, J = 17.6, 10.9 Hz, 1H), 5.79 (dd, J = 17.6, 0.5 Hz, 1H), 5.33 (d, J = 10.9 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 136.6, 135.9, 131.8, 127.9, 121.7, 114.7. Example 7

[0030] Preparation of 4-iodostyrene, the structural formula is as follows:

[0031] Under a nitrogen atmosphere, 0.5 mmol of the raw material 4-iodoacetophenone, 0.025 mmol of the catalyst tris(pentafluorophenyl)borane, 0.9 mmol of pinacolborane, and 1.0 mL of n-hexane as the solvent were added, and the reaction was carried out at 80 °C for 12 hours. The yield of the product obtained by column chromatography separation was 83%. 1H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 8.2 Hz, 2H), 7.26 (s, 1H), 7.14 (d, J = 8.2 Hz, 2H), 6.63 (dd, J = 17.6, 10.9 Hz, 1H), 5.75 (d, J = 17.6 Hz, 1H), 5.27 (d, J = 10.9 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 137.6, 137.1, 135.9, 128.0, 114.8, 93.1. Example 8

[0032] Preparation of 3-chlorostyrene, the structural formula is as follows:

[0033] Under a nitrogen atmosphere, 0.5 mmol of the raw material 3-chloroacetophenone, 0.025 mmol of the catalyst tris(pentafluorophenyl)borane, 0.9 mmol of pinacolborane, and 1.0 mL of n-hexane as the solvent were added, and the reaction was carried out at 80 °C for 12 hours. The product was separated by column chromatography with a yield of 95%. 1H NMR (400 MHz, CDCl3) δ 7.44 (s, 1H), 7.35 – 7.29 (m, 2H), 7.29 – 7.18 (m, 2H), 7.12 (d, J = 7.2 Hz, 1H), 5.81 (d, J = 17.6 Hz, 1H), 5.35 (d, J = 10.9 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 139.6, 135.8, 129.9, 127.9, 126.3, 124.6, 115.5, 29.9. Example 9

[0034] Preparation of 2-vinylbenzofuran, the structural formula is as follows:

[0035] Under a nitrogen atmosphere, 0.5 mmol of the raw material 2-benzofuranylacetone, 0.025 mmol of the catalyst tris(pentafluorophenyl)borane, 0.9 mmol of pinacolborane, and 1.0 mL of n-hexane as the solvent were added, and the reaction was carried out at 80 °C for 12 hours. The product was separated by column chromatography with a yield of 47%. 1H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 7.6 Hz, 1H), 7.50 (d, J = 8.3 Hz, 1H), 7.31 (d, J = 5.1 Hz, 1H), 7.25 (d, J = 7.3 Hz, 1H), 6.64 (s, 2H), 6.01 (d, J = 17.5 Hz, 1H), 5.43 (d, J = 11.2 Hz, 1H). 13C NMR (126 MHz, )δ 154.9, 154.8, 128.8, 125.3, 124.7, 122.8, 121.0, 115.8, 111.0, 104.8. Raw material table: Name Manufacturer 4-Biphenylacetone Energy Chemical 4-Chlorobiphenylacetone Energy Chemical 2-Biphenylphenylacetone Energy Chemical 2-Naphthylacetone Energy Chemical 4-tert-Butylacetophenone Energy Chemical 4-Bromoacetophenone Energy Chemical 4-Iodoacetophenone Energy Chemical 3-Chloroacetophenone Energy Chemical 2-Benzofuranylacetone Energy Chemical Tris(pentafluorophenyl)borane Alfa Aesar Pinacolborane J&K Scientific n-Hexane Sinopharm In the prior art, the patent number is 202411165213.X, and the patent name is "A Method for Keto-Deoxygenation Reduction", which discloses a method for keto-deoxygenation reduction. The method includes: mixing a ketone compound, a composite catalyst, a reducing agent and an organic solvent to obtain a mixed raw material; performing a reduction reaction on the mixed raw material under an inert gas atmosphere to obtain a reaction product; performing column chromatography separation on the reaction product to obtain an alkane compound. Among them, the composite catalyst includes lutetium chloride and tris(pentafluorophenyl)borane, and the amount of substance n1 of the lutetium chloride and the amount of substance n2 of the tris(pentafluorophenyl)borane satisfy the relationship: n1:n2 = 2:1. Through the synergistic catalytic effect of lutetium chloride and tris(pentafluorophenyl)borane, this method can achieve the deoxygenation reduction process of different ketone compounds under mild conditions to obtain alkane compounds with diverse structures, thereby reducing the difficulty of deoxygenation reduction of ketone compounds.

[0036] However, the prior art mainly reduces ketone compounds to olefin compounds and cannot reduce them to olefin compounds, that is, double bonds cannot be formed.

[0037] Compared with the prior art, referring to Figure 1 , taking Example 1 as an example, the reaction principle of the present invention is specifically as follows: First, tris(pentafluorophenyl)borane B(C6F5)3 activates pinacol borane HBpin to form intermediate B. Biphenyl acetone undergoes hydroboration reaction with intermediate A to form intermediate B, and at the same time, tris(pentafluorophenyl)borane B(C6F5)3 is regenerated. Intermediate B further coordinates with intermediate A to form intermediate C, intermediate C continues to undergo boration reaction to form intermediate D and intermediate E, then intermediate E undergoes C-O bond cleavage to remove one molecule of (OBpin)2 to form a carbocation intermediate F, and finally intermediate F eliminates H+ to form the product biphenyl ethylene.

[0038] The patent reaction principle of the prior art, referring to Figure 2 , is specifically as follows: First, tris(pentafluorophenyl)borane B(C6F5)3 activates pinacol borane HBpin to form intermediate B. Acetophenone coordinates with LuCl3 to generate intermediate A. Intermediate A undergoes hydroboration reaction with intermediate B to form intermediate C, and at the same time, tris(pentafluorophenyl)borane B(C6F5)3 and LuCl3 are regenerated. Intermediate C further undergoes addition with intermediate B to form intermediate D, intermediate D continues to undergo boration reaction to form intermediate F and intermediate E, then intermediate F undergoes C-O bond cleavage to remove one molecule of (OBpin)2 to form a carbocation intermediate G, and finally intermediate G is attacked by H- ions to form ethylbenzene, and tris(pentafluorophenyl)borane B(C6F5)3 is regenerated to complete the whole cycle.

[0039] The reaction mechanisms of the two are different, and the reaction temperature, the equivalent amount of pinacol borane used, the catalyst selection, and the solvent selection are completely different. The most obvious difference lies in the action principle of the catalyst and the step of the final carbocation intermediate. In this application, the carbocation undergoes dehydrogenation to obtain an alkene. In the prior art patents, the carbocation combines with an H anion to obtain an alkane, and lutetium chloride activates the substrate ketone. Moreover, the reaction temperature, solvent, and the amount of HBpin used will all affect the entire mechanism process.

[0040] A carbocation is an intermediate in organic reactions, and there are carbocation intermediates and HBpin in both reaction systems. The hydride ion of HBpin can act as a nucleophile and attack the carbocation, thus obtaining the alkane product of the patented application. By avoiding the nucleophilic attack of the hydride ion on the carbocation and choosing the deprotonation of the carbocation, the alkene product of the current patent application can be obtained. This selective control is closely related not only to the catalyst but also to the temperature, solvent, and the amount of pinacol borane used. The influence of the solvent on the carbocation: In the 1,4-dioxane solvent, the carbocation will be stabilized due to the coordination of oxygen, enabling it to react with the excess pinacol borane to obtain an alkane. This step of the reaction is relatively easy and does not require heating and cannot be heated because an increase in temperature will cause the carbocation to undergo deprotonation to obtain an alkene. The influence of temperature on the activity of the carbocation: An increase in temperature is conducive to the deprotonation of the carbocation intermediate to form an alkene. However, it is also affected by the solvent and the amount of pinacol borane. The non-polar solvent hexane does not coordinate and stabilize the carbocation, making the carbocation highly active. Moreover, if an excessive amount of pinacol borane is added to the reaction system, obvious by-products such as alcohols and alkanes will also be generated. The influence of pinacol borane on the reaction: If an alkene product is expected, the amount of pinacol borane cannot be too excessive or too small. This 1.8 equivalent is obtained through repeated exploratory experiments. If it is more than this amount, by-products such as alcohols and alkanes will be obtained. If it is less than this amount, alcohol by-products will also be obtained. Moreover, for 1.8 equivalents of pinacol borane, if the solvent is changed, such as 1,4-dioxane, by-products will also be generated, and it is impossible to obtain our alkene product with high yield. Therefore, selectively obtaining an alkene is achieved through the synergistic action of the solvent, temperature, and the amount of pinacol borane used.

[0041] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) The raw materials of the present invention are widely sourced and easy to obtain, with low costs, and some raw materials are synthesized simply and efficiently; the preparation method is easy to operate, the reaction conditions are mild, the energy consumption is reduced, and the reaction selectivity is strong, and the target product can be directly synthesized, with the highest yield reaching 95%; (2) The present invention does not generate toxic and harmful gases after the reaction, has little impact on the atmosphere, and at the same time ensures the health of the operators; (3) The present invention has broad universality and high yield. The present invention is an important supplement to the synthetic method of deoxygenating and reducing methyl ketone to olefin, providing important ideas for the synthesis of dyes and drug molecules from biomass raw materials and so on.

[0042] (4) In the present invention, methyl ketone is directly deoxygenated and reduced to the corresponding olefin without the participation of metal reagents. It not only has a relatively low cost, good functional group compatibility, but also has high chemoselectivity and conversion rate, and good universality.

[0043] The above are only the preferred embodiments of the present invention, and the protection scope of the present invention is not limited to the above embodiments. All technical solutions falling within the idea of the present invention belong to the protection scope of the present invention. It should be pointed out that for those of ordinary skill in the art, several improvements and refinements made without departing from the principle of the present invention should also be regarded as within the protection scope of the present invention.

Claims

1. A method for deoxygenative reductive alkenylation of methyl ketone compounds, characterized in that: It includes the following steps: Under the action of a protective gas and a catalyst, mix the methyl ketone compound, a reducing agent, and a solvent, and then raise the temperature for reaction to obtain an alkenylation product; The structural formula of the methyl ketone compound is as follows: ; The structural formula of the alkenylation product is as follows: .

2. The method for deoxygenative reductive alkenylation of methyl ketone compounds according to claim 1, characterized in that: The methyl ketone compound is 4-biphenylacetone or 4-chlorobiphenylacetone or 2-biphenylacetophenone or 2-naphthylacetone or 4-tert-butylacetophenone or 4-bromoacetophenone or 4-iodoacetophenone or 3-chloroacetophenone or 2-benzofuranylacetone.

3. The method for deoxygenative reductive alkenylation of methyl ketone compounds according to claim 1, characterized in that: The catalyst is tris(pentafluorophenyl)borane.

4. The method for deoxygenative reductive alkenylation of methyl ketone compounds according to claim 1, characterized in that: The reducing agent is pinacol borane.

5. The method for deoxygenative reductive alkenylation of methyl ketone compounds according to claim 1, characterized in that: The reaction temperature is 60 - 100 °C.

6. The method for deoxygenative reductive alkenylation of methyl ketone compounds according to claim 1, characterized in that: The reaction time is 10 - 15 h.

7. The method for deoxygenative reductive alkenylation of methyl ketone compounds according to claim 1, characterized in that: The solvent is n-hexane.

8. The method for deoxygenative reductive alkenylation of methyl ketone compounds according to claim 1, characterized in that: The molar ratio of the methyl ketone compound, the catalyst, and the reducing agent is 0.5 - 1.5: 0.03 - 0.08: 1.5 - 2.

9. The method for deoxygenative reductive alkenylation of methyl ketone compounds according to claim 1, characterized in that: The molar ratio of the methyl ketone compound, the catalyst, and the reducing agent is 1.0: 0.05: 1.

8.

10. The method for deoxygenative reductive alkenylation of methyl ketone compounds according to claim 1, characterized in that: The protective gas is nitrogen.

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