CN109020864B - Application of metal hydride/palladium compound catalytic reduction system in reduction of alkenyl active methylene compound and reduction method - Google Patents

Application of metal hydride/palladium compound catalytic reduction system in reduction of alkenyl active methylene compound and reduction method Download PDF

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CN109020864B
CN109020864B CN201811064127.4A CN201811064127A CN109020864B CN 109020864 B CN109020864 B CN 109020864B CN 201811064127 A CN201811064127 A CN 201811064127A CN 109020864 B CN109020864 B CN 109020864B
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active methylene
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CN109020864A (en
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张士磊
毛玉健
刘晔
桂晶晶
陈韶华
胡延维
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Zhangjiagang Industrial Technology Research Institute Of Suzhou University
Suzhou University
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Abstract

The invention discloses an application of a metal hydride/palladium compound catalytic reduction system in reduction of an alkenyl active methylene compound and a reduction method. The reduction system of the invention is a simple method for reducing alkenyl active methylene compounds, the used hydride and palladium compound catalysts are all reagents which are easily obtained in a laboratory, and compared with a common hydrogen hydrogenation method and a reducing agent reduction method, the method is easier to operate, higher in safety, mild in condition, high in reaction yield, capable of performing two-step reaction in one pot, and high in atom economy and step economy.

Description

Application of metal hydride/palladium compound catalytic reduction system in reduction of alkenyl active methylene compound and reduction method
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to application of a metal hydride/palladium compound catalytic system in reduction and one-pot reaction of an alkenyl active methylene compound.
Background
Sodium hydride is a strong base which is frequently used in laboratories and industry, and for a long time, there are few reports on the use of sodium hydride as a reducing agent, and the existing reaction requires a large excess of reducing agent (3 equivalents) and at least 2 equivalents of sodium iodide as a promoter. The reduction of alkenyl-activated methylene compounds is a common chemical transformation to produce the corresponding monoalkyl-substituted activated methylene compounds; such reactions are typically reduced using hydrogen/palladium on carbon conditions; in addition, some hydrogen-negative agents, such as [ (Ph)3P)CuH]6 (Stryker reagent), R3SiH, Hantzsch esters, etc. can also accomplish this reduction of electron deficient double bonds. However, these reduction conditions are either hazardous, for exampleExplosive hydrogen; or the reagents are expensive, the reaction lacks atom economy and more waste needs to be disposed of after the reaction, such as [ (Ph)3P)CuH]6 (Stryker reagent), R3SiH, Hantzsch ester, etc., or some of them have limitations in industrial application because they require treatment of a large amount of wastewater after reaction.
Disclosure of Invention
The technical problem to be solved by the invention is to provide an application of a metal hydride/palladium compound catalytic reduction system, thereby providing a new method for reducing an alkenyl active methylene compound and an application of the method in a one-pot reaction.
The technical means of the invention for reducing the alkenyl active methylene compound is to take metal hydride as a reducing agent and palladium and salts thereof as catalysts to react in a solvent to obtain a double-bond reduced product. The specific technical scheme is as follows:
the application of a metal hydride/palladium compound catalytic reduction system in the reduction of alkenyl active methylene compounds.
The reduction method of the alkenyl active methylene compound comprises the steps of taking the alkenyl active methylene compound as a substrate, taking metal hydride as a reducing agent and taking a palladium compound as a catalyst, carrying out reduction reaction to obtain a reduction product, and finishing the reduction of the alkenyl active methylene compound.
In the technical scheme, after the reduction reaction, saturated ammonium chloride aqueous solution is added to stop the reaction, and then the reduction product is obtained through extraction, drying, rotary evaporation and column chromatography purification.
In the present invention, the chemical structural formula of the alkenyl activated methylene compound is as follows:
Figure DEST_PATH_IMAGE001
wherein R is1、R2Independently selected from hydrogen, alkyl, phenyl, substituted phenyl, naphthyl, pyridyl and quinolyl.
In the chemical structural formula of the alkenyl active methylene compound, alkyl can be methyl, and substituted phenyl can be halogen substituted phenyl or methoxy substituted phenyl.
In the present invention, the metal hydride includes sodium hydride, lithium hydride, potassium hydride, calcium hydride, preferably sodium hydride, lithium hydride, more preferably sodium hydride; the palladium compound comprises palladium chloride, palladium acetate, Pd (MeCN)2Cl2、[(η3-C3H5)PdCl]2、Pd(TFA)2、Pd(dppp)Cl2、Pd2(dba)3、Pd(C6H5CN)2Cl2、Pd(OH)2、Pd/C、Pd(PPh3)4、Pd(PPh3)2Cl2Palladium chloride and palladium acetate are preferred, and palladium chloride is more preferred.
In the invention, the molar ratio of the palladium compound, the metal hydride and the alkenyl active methylene compound is (0.01-1): (1-5): 1, preferably (0.03-0.1): (1-3): 1, more preferably 0.05: (1.5-2.5): 1, and most preferably 0.05: 2: 1.
In the invention, the reduction of the alkenyl active methylene compound is carried out in a solvent under the atmosphere of nitrogen; the solvent includes DMA (N, N-dimethylacetamide), DMF, THF, DME, or dioxane.
In the invention, the reduction temperature of the alkenyl active methylene compound is-50-120 ℃, preferably 0-50 ℃, and more preferably room temperature; the reduction time is 0.3 to 10 hours, preferably 0.4 to 5 hours, and more preferably 0.5 hour.
The sodium hydride/palladium reduced alkenyl active methylene compound has the following advantages: 1) compared with sodium borohydride, sodium hydride is cheaper (sodium borohydride is industrially prepared by taking sodium hydride as a raw material); compared with hydrogen/palladium carbon reduction, the sodium hydride method has higher safety; 2) the sodium hydride has small molecular weight, simple composition and small using amount in the reaction, so the method using the sodium hydride as the reducing agent is an atom economic method; the byproducts are harmless sodium salts, and no other waste is generated; 3) the product of the alkenyl active methylene compound reduced by sodium hydride is sodium salt before post-treatment, which is different from the prior reduction method, and the sodium salt with reactivity can continuously react with an electrophilic reagent to obtain a disubstituted product, thereby expanding the application of the alkenyl active methylene compound. In the one-pot reaction, the reducibility and the alkalinity of the sodium hydride are fully utilized, the atom economy and the step economy of the reaction are greatly improved, and the reaction cost is reduced.
The technical scheme of the invention can be specifically as follows: under the protection of nitrogen, suspending a palladium compound and a metal hydride in a solvent, stirring, adding a substrate alkenyl active methylene compound, reacting at-50 ℃ to 120 ℃ for 0.3-10 hours, adding a saturated ammonium chloride aqueous solution to stop the reaction, extracting with the solvent, evaporating to dryness, and purifying by column chromatography to obtain a product.
The reduction of alkenyl-activated methylene compounds is a chemical reaction often used in organic synthesis, and generally two types of methods are adopted: one is hydrogenation reduction using hydrogen/palladium carbon, in the process, the use of hydrogen is a potential hazard factor, and improper operation can cause fire and explosion; the other is reduction using a reducing agent, which is expensive and requires treatment of large amounts of wastewater. The invention has important significance in using the relatively safe and low-cost metal hydride to replace hydrogen and a reducing agent for the reduction of the alkenyl active methylene compound; and more importantly, the method fully utilizes the reducibility and alkalinity of the sodium hydride and can carry out one-pot reaction.
The reduction system of the invention is a simple method for reducing alkenyl active methylene compounds, the used hydride and palladium compound catalysts are all reagents which are easily obtained in a laboratory, and compared with a common hydrogen hydrogenation method and a reducing agent reduction method, the method is easier to operate, higher in safety, mild in condition, high in reaction yield, capable of performing two-step reaction in one pot, and high in atom economy and step economy.
Detailed Description
Example 1
Figure 47033DEST_PATH_IMAGE002
Palladium chloride (1.7 mg, 0.01 mmol, 5 mol%) and sodium hydride (60% in oil, 16 mg, 0.4 mmol, 2 equiv) were suspended in DMA (1.0 mL) under nitrogen, stirred at room temperature for 5 minutes, a solution of compound 1a (0.2 mmol) in DMA (0.5 mL) was added, then reacted at room temperature for 30 minutes, saturated aqueous ammonium chloride was added to quench the reaction, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, evaporated to dryness by rotary evaporation, and purified by column chromatography to give product 2a in 99% yield.1H NMR (400 MHz, CDCl3): δ 7.48 (t, J = 7.6 Hz, 2H), 7.38 (t, J = 7.3 Hz, 1H), 7.25-7.17 (m, 5H), 7.17-7.10 (m, 3H), 7.02-6.93 (m, 2H), 6.64 (d, J = 7.8 Hz, 1H), 3.95-3.88 (m, 1H), 3.52 (dd, J = 13.5, 4.2 Hz, 1H), 3.17 (dd, J= 13.5, 8.2 Hz, 1H). 13C NMR (151 MHz, CDCl3): δ 176.56, 144.51, 137.40, 134.57, 129.71, 128.31, 128.23, 128.18, 127.99, 126.83, 126.78, 124.83, 122.63, 47.36, 37.26. LR-MS (ESI): m/z 300.2 [M+H]+。
Figure DEST_PATH_IMAGE003
Under the protection of nitrogen, palladium chloride (1.7 mg, 0.01 mmol, 5 mol%) and sodium hydride (60% in oil, 16 mg, 0.4 mmol, 2 equiv) are suspended in DMA (1.0 mL), the mixture is stirred at room temperature for 5 minutes, a solution of the compound 1a (0.2 mmol) in the DMA (0.5 mL) is added, then the mixture is reacted at room temperature for 30 minutes, benzyl bromide (1.5 eq.) is added, the reaction is continuously stirred, after the reaction of the raw materials is finished, a saturated ammonium chloride aqueous solution is added to quench the reaction, the reaction is extracted by ethyl acetate, an organic phase is collected, a crude product is obtained by spin-drying a solvent, and column chromatography is carried out, so that the compound 3a is finally obtained, and the yield is 98%.1H NMR (400 MHz, CDCl3): δ 7.38-7.27 (m, 4H), 7.13-7.04 (m, 7H), 7.02-6.94 (m, 5H), 6.64 (d, J = 7.3 Hz, 2H), 6.21 (d, J = 7.7 Hz, 1H), 3.47 (d, J = 12.9 Hz, 2H), 3.25 (d, J = 12.9 Hz, 2H). 13C NMR (151 MHz, CDCl3): δ 177.80, 144.12, 136.08, 134.37, 130.26, 130.14, 129.49, 128.06, 127.85, 127.76, 126.81, 126.65, 124.42, 122.23, 108.88, 56.67, 43.83. LR-MS (ESI): m/z 390.3 [M+H]+。
Example 2
Figure 317608DEST_PATH_IMAGE004
Palladium acetate (2.2 mg, 0.01 mmol, 5 mol%) and lithium hydride (4.8 mg, 0.6 mmol, 3.0 equiv) were suspended in DMF (1.0 mL) under nitrogen, stirred at room temperature for 5 minutes, a solution of compound 1a (0.2 mmol) in DMF (0.5 mL) was added, then reacted at 120 ℃ for 0.5 hour, saturated aqueous ammonium chloride was added to stop the reaction, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, evaporated to dryness by rotary evaporation, and purified by column chromatography to give product 2a in 92% yield.
Example 3
Figure DEST_PATH_IMAGE005
Under the protection of nitrogen, Pd2(dba)3(1.8 mg, 0.002 mmol, 1 mol%) and potassium hydride (30% in oil, 133 mg, 1.0 mmol, 5 equiv) were suspended in THF (1.0 mL), stirred at room temperature for 5 minutes, a solution of compound 1a (0.2 mmol) in THF (0.5 mL) was added, followed by reaction at-50 ℃ for 10 hours, a saturated aqueous solution of ammonium chloride was added to terminate the reaction, extraction was performed with ethyl acetate, the combined extracts were dried over sodium sulfate, rotary evaporated to dryness, and purified by column chromatography to give product 2a in 71% yield.
Example 4
Figure 21995DEST_PATH_IMAGE006
Pd (TFA) under nitrogen protection2(67 mg, 0.2 mmol, 100 mol%) and calcium hydride (16 mg, 0.4 mmol, 2.0 equiv) were suspended in DME (1.0 mL), stirred at room temperature for 5 minutes, added with a solution of Compound 1a (0.2 mmol) in DME (0.5 mL), reacted at 90 ℃ for 0.5 hour, quenched with saturated aqueous ammonium chloride, extracted with ethyl acetate, combined extracts, and washed with sodium sulfateDrying, rotary evaporation and evaporation to dryness, and purifying by column chromatography to obtain the product 2a with the yield of 83%.
Example 5
Figure DEST_PATH_IMAGE007
Under the protection of nitrogen, [ (eta ]3-C3H5)PdCl]2(1.4 mg, 0.004 mmol, 2 mol%) and sodium hydride (60% in oil, 8 mg, 0.20 mmol, 1.0 equiv) were suspended in dioxane (1.0 mL), stirred at room temperature for 5 minutes, a solution of compound 1a (0.2 mmol) in dioxane (0.5 mL) was added, then reacted at 30 ℃ for 2 hours, a saturated aqueous ammonium chloride solution was added to stop the reaction, extracted with ethyl acetate, the extracts were combined, dried over sodium sulfate, rotary evaporated to dryness, and purified by column chromatography to give product 2a in 69% yield.
Example 6
Figure 719824DEST_PATH_IMAGE008
Pd/C (10%, 0.01 mmol, 5 mol%) and sodium hydride (60% in oil, 16 mg, 0.4 mmol, 2 equiv) were suspended in DMA (1.0 mL) under nitrogen, stirred at room temperature for 5 minutes, a solution of compound 1a (0.2 mmol) in DMA (0.5 mL) was added, then reacted at room temperature for 10 hours, saturated aqueous ammonium chloride was added to quench the reaction, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, rotary evaporated to dryness, purified by column chromatography to give product 2a in 8% yield.
Example 7
Figure DEST_PATH_IMAGE009
Pd (dppp) Cl under nitrogen protection2(6 mg, 0.01 mmol, 5 mol%) and sodium hydride (60% in oil, 16 mg, 0.4 mmol, 2 equiv) were suspended in DMA (1.0 mL), stirred at room temperature for 5 minutes, a solution of Compound 1a (0.2 mmol) in DMA (0.5 mL) was added, then reacted at room temperature for 1 hour, and saturated aqueous ammonium chloride was added to terminate the reactionExtracting with ethyl acetate, combining the extracts, drying with sodium sulfate, rotary-steaming to dryness, and purifying by column chromatography to obtain the product 2a with yield of 57%.
Example 8
Figure 596644DEST_PATH_IMAGE010
Pd (C) under nitrogen protection6H5CN)2Cl2(3.8 mg, 0.01 mmol, 5 mol%) and sodium hydride (60% in oil, 16 mg, 0.4 mmol, 2 equiv) were suspended in DMA (1.0 mL), stirred at room temperature for 5 minutes, a solution of compound 1a (0.2 mmol) in DMA (0.5 mL) was added, then reacted at room temperature for 1 hour, a saturated aqueous ammonium chloride solution was added to terminate the reaction, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, rotary evaporated to dryness, and purified by column chromatography to give product 2a in 62% yield.
Example 9
Figure DEST_PATH_IMAGE011
Under the protection of nitrogen, Pd (OH)2(1.4 mg, 0.01 mmol, 5 mol%) and sodium hydride (60% in oil, 16 mg, 0.4 mmol, 2 equiv) were suspended in DMA (1.0 mL), stirred at room temperature for 5 minutes, a solution of compound 1a (0.2 mmol) in DMA (0.5 mL) was added, followed by reaction at room temperature for 0.5 hour, saturated aqueous ammonium chloride solution was added to terminate the reaction, extraction was performed with ethyl acetate, the combined extracts were dried over sodium sulfate, rotary evaporated to dryness, and purified by column chromatography to give product 2a in 71% yield.
Example 10
Figure 467648DEST_PATH_IMAGE012
Palladium chloride (1.7 mg, 0.01 mmol, 5 mol%) and sodium hydride (60% in oil, 16 mg, 0.4 mmol, 2 equiv) were suspended in DMA (1.0 mL) under nitrogen, stirred at room temperature for 5 minutes, added with a solution of compound 1b (0.2 mmol) in DMA (0.5 mL), and then at room temperatureReacting for 30 minutes, adding saturated ammonium chloride aqueous solution to stop the reaction, extracting with ethyl acetate, combining extract liquor, drying with sodium sulfate, rotary-steaming to dryness, and purifying by column chromatography to obtain a product 2b with the yield of 98%.1H NMR (400 MHz, CDCl3): δ 7.49 (t, J = 7.6 Hz, 2H), 7.39 (t, J = 7.4 Hz, 1H), 7.22 (d, J = 7.6 Hz, 2H), 7.19-7.11 (m, 2H), 7.03-6.96 (m, 2H), 6.80-6.74 (m, 2H), 6.69-6.64 (m, 2H), 3.97-3.88 (m, 1H), 3.69 (s, 3H), 3.51 (dd, J= 13.5, 4.1 Hz, 1H), 3.13 (dd, J = 13.4, 8.4 Hz, 1H). 13C NMR (101 MHz, CDCl3): δ 176.56, 159.52, 144.52, 138.98, 134.57, 129.71, 129.30, 128.28, 128.19, 128.00, 126.78, 124.87, 122.64, 122.14, 114.69, 112.86, 109.34, 55.26, 47.28, 37.34. LR-MS (ESI): m/z 330.2 [M+H]+。
Example 11
Figure DEST_PATH_IMAGE013
Palladium chloride (1.7 mg, 0.01 mmol, 5 mol%) and sodium hydride (60% in oil, 16 mg, 0.4 mmol, 2 equiv) were suspended in DMA (1.0 mL) under nitrogen, stirred at room temperature for 5 minutes, a solution of compound 1c (0.2 mmol) in DMA (0.5 mL) was added, then reacted at room temperature for 30 minutes, saturated aqueous ammonium chloride was added to quench the reaction, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, evaporated to dryness by rotary evaporation, and purified by column chromatography to give product 2c in 98% yield.1H NMR (400 MHz, CDCl3): δ 7.49 (t, J = 7.5 Hz, 2H), 7.38 (t, J = 7.3 Hz, 1H), 7.31 (d, J = 7.7 Hz, 2H), 7.25-7.17 (m, 2H), 7.12 (t, J = 7.6 Hz, 1H), 7.08-6.91 (m, 3H), 6.89 (d, J = 7.2 Hz, 1H), 6.69 (d, J = 7.8 Hz, 1H), 3.98-3.90 (m, 1H), 3.60 (dd, J = 13.8, 5.0 Hz, 1H), 3.12 (dd, J = 13.7, 8.4 Hz, 1H). 13C NMR (101 MHz, CDCl3): δ 176.44, 161.37 (d, J = 246.0 Hz), 144.30, 134.59, 131.76 (d, J = 4.5 Hz), 129.72, 128.72 (d, J = 8.1 Hz), 128.18, 128.04, 127.94, 126.74, 125.07, 124.92, 124.02 (d, J = 3.6 Hz), 122.69, 115.47 (d, J = 22.2 Hz), 109.26, 46.05, 30.26. LR-MS (ESI): m/z 318.3 [M+H]+。
Example 12
Figure 743384DEST_PATH_IMAGE014
Palladium chloride (1.7 mg, 0.01 mmol, 5 mol%) and sodium hydride (60% in oil, 16 mg, 0.4 mmol, 2 equiv) were suspended in DMA (1.0 mL) under nitrogen, stirred at room temperature for 5 minutes, a solution of compound 1d (0.2 mmol) in DMA (0.5 mL) was added, then reacted at room temperature for 1 hour, saturated aqueous ammonium chloride was added to quench the reaction, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, evaporated to dryness by rotary evaporation, and purified by column chromatography to give product 2d in 97% yield.1H NMR (400 MHz, CDCl3): δ 7.84-7.77 (m, 1H), 7.77-7.70 (m, 2H), 7.62 (s, 1H), 7.49-7.41 (m, 4H), 7.40-7.31 (m, 2H), 7.20 (d, J = 7.5 Hz, 2H), 7.14-7.07 (m, 1H), 6.97-6.91 (m, 2H), 6.64 (d, J = 7.8 Hz, 1H), 4.02 (dd, J = 8.2, 4.4 Hz, 1H), 3.70 (dd, J = 13.6, 4.3 Hz, 1H), 3.32 (dd, J = 13.6, 8.4 Hz, 1H). 13C NMR (151 MHz, CDCl3): δ 176.60, 144.44, 135.12, 134.54, 133.44, 132.46, 129.68, 128.31, 128.20, 128.15, 128.01, 127.96, 127.87, 127.77, 127.71, 126.74, 126.09, 125.67, 124.88, 122.65, 109.36, 47.28, 37.41. LR-MS (ESI): m/z 350.2 [M+H]+。
Example 13
Figure DEST_PATH_IMAGE015
Palladium chloride (1.7 mg, 0.01 mmol, 5 mol%) and sodium hydride (60% in oil, 16 mg, 0.4 mmol, 2 equiv) were suspended in DMA (1.0 mL) under nitrogen, stirred at room temperature for 5 minutes, a solution of compound 1e (0.2 mmol) in DMA (0.5 mL) was added, then reacted at room temperature for 30 minutes, saturated aqueous ammonium chloride was added to stop the reaction, extracted with ethyl acetate, the extracts were combined, and sulfuric acid was used to prepare a solutionSodium drying, rotary evaporation to dryness, and column chromatography purification to obtain product 2e with 98% yield.1H NMR (400 MHz, CDCl3): δ 8.86 (d, J = 4.1 Hz, 1H), 8.27 (d, J = 8.3 Hz, 1H), 8.20 (d, J = 8.4 Hz, 1H), 7.76 (t, J = 7.5 Hz, 1H), 7.63 (t, J = 7.5 Hz, 1H), 7.53 (t, J = 7.6 Hz, 2H), 7.42 (t, J = 7.3 Hz, 1H), 7.35 (d, J = 7.7 Hz, 2H), 7.31 (d, J = 4.1 Hz, 1H), 7.16 (t, J = 7.7 Hz, 1H), 6.91 (t, J = 7.5 Hz, 1H), 6.77 (d, J = 7.9 Hz, 1H), 6.71 (d, J = 7.3 Hz, 1H), 4.16-4.02 (m, 2H), 3.36 (dd, J = 13.5, 9.5 Hz, 1H). 13C NMR (151 MHz, CDCl3): δ 176.17, 149.67, 148.34, 144.70, 144.23, 134.37, 130.28, 129.80, 129.74, 128.37, 128.35, 127.85, 127.44, 127.11, 126.65, 124.99, 123.76, 122.82, 122.47, 109.67 , 45.71, 34.03. LR-MS (ESI): m/z 351.1 [M+H]+。
Example 14
Figure 612114DEST_PATH_IMAGE016
Palladium chloride (1.7 mg, 0.01 mmol, 5 mol%) and sodium hydride (60% in oil, 16 mg, 0.4 mmol, 2 equiv) were suspended in DMA (1.0 mL) under nitrogen, stirred at room temperature for 5 minutes, a solution of compound 1f (0.2 mmol) in DMA (0.5 mL) was added, then reacted at room temperature for 30 minutes, saturated aqueous ammonium chloride was added to quench the reaction, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, evaporated to dryness by rotary evaporation, and purified by column chromatography to give product 2f (Diastereomer a/b = 58/42) in 96% yield. Diastereomer a: 1H NMR (400 MHz, CDCl3): δ 7.46 (t, J = 7.6 Hz, 2H), 7.36 (t, J = 7.4 Hz, 1H), 7.32-7.17 (m, 7H), 7.09 (t, J = 7.6 Hz, 1H), 6.89 (t, J = 7.4 Hz, 1H), 6.69-6.60 (m, 2H), 3.88-3.84 (m, 1H), 3.83-3.77 (m, 1H), 1.31 (d, J = 7.0 Hz, 3H). 13C NMR (151 MHz, CDCl3): δ 176.26, 144.85, 142.41, 134.63, 129.71, 128.34, 128.17, 128.06, 127.95, 126.85, 126.77, 126.66, 125.05, 122.46, 109.12, 52.58, 40.72, 14.32. Diastereomer b: 1H NMR (400 MHz, CDCl3): δ 7.40 (t, J = 7.4 Hz, 2H), 7.34 (d, J = 7.2 Hz, 2H), 7.18-7.09 (m, 4H), 7.05 (t, J = 7.4 Hz, 1H), 6.98 (d, J = 6.6 Hz, 2H), 6.92 (d, J = 7.5 Hz, 2H), 6.51 (d, J = 7.7 Hz, 1H), 3.79 (d, J = 4.4 Hz, 1H), 3.75-3.65 (m, 1H), 1.69 (d, J = 7.2 Hz, 3H). 13C NMR (151 MHz, CDCl3): δ 176.24, 144.97, 141.21, 134.45, 129.61, 128.25, 128.14, 128.11, 127.90, 127.03, 126.97, 126.85, 125.23, 122.37, 109.22, 52.49, 42.51, 19.22. LR-MS (ESI): m/z 314.2 [M+H]+。
example 15
Figure DEST_PATH_IMAGE017
Palladium chloride (1.7 mg, 0.01 mmol, 5 mol%) and sodium hydride (60% in oil, 16 mg, 0.4 mmol, 2 equiv) were suspended in DMA (1.0 mL) under nitrogen, stirred at room temperature for 5 minutes, a solution of compound 1g (0.2 mmol) in DMA (0.5 mL) was added, then reacted at room temperature for 30 minutes, saturated aqueous ammonium chloride was added to quench the reaction, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, evaporated to dryness by rotary evaporation, and purified by column chromatography to give 2g of product in 98% yield.1H NMR (400 MHz, CDCl3): δ 7.52 (t, J = 7.6 Hz, 2H), 7.44-7.31 (m, 4H), 7.20 (t, J = 7.7 Hz, 1H), 7.08 (t, J = 7.4 Hz, 1H), 6.79 (d, J = 7.8 Hz, 1H), 3.55 (d, J = 2.7 Hz, 1H), 2.66-2.54 (m, 1H), 1.18 (d, J = 7.0 Hz, 3H), 0.97 (d, J = 6.8 Hz, 3H). 13C NMR (151 MHz, CDCl3): δ 176.91, 144.85, 134.72, 129.70, 128.09, 127.81, 127.67, 126.77, 124.73, 122.64, 109.22, 51.76, 31.48, 19.90, 18.06. LR-MS (ESI): m/z 252.2 [M+H]+。

Claims (3)

1. The application of a metal hydride/palladium compound catalytic reduction system in the reduction of an alkenyl active methylene compound; the chemical structural formula of the alkenyl active methylene compound is as follows:
Figure DEST_PATH_IMAGE002
wherein R is1、R2Independently selected from hydrogen, alkyl, phenyl, substituted phenyl, naphthyl, pyridyl and quinolyl;
the metal hydride is sodium hydride, lithium hydride, potassium hydride or calcium hydride; the palladium compound is palladium chloride, palladium acetate, Pd (dppp) Cl2Or Pd (OH)2。
2. The use of claim 1, wherein the molar ratio of the palladium compound, the metal hydride and the alkenyl-active methylene compound is (0.01-1) to (1-5) to 1.
3. The use according to claim 1, wherein the reduction of the alkenyl-activated methylene compound is carried out in a solvent under a nitrogen atmosphere; the reduction temperature of the alkenyl active methylene compound is-50 ℃ to 120 ℃, and the reduction time is 0.3 to 10 hours.
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