APPLICATION OF METAL HYDRIDE/PALLADIUM COMPOUND SYSTEM IN PREPARATION OF 1,3-DICARBONYL COMPOUND IN CASCADE REACTION OF ELECTRON-DEFICIENT ALKENE COMPOUND

Abstract

Provided is an application of a metal hydride/palladium compound system in the preparation of a 1,3-dicarbonyl compound in a cascade reaction of an electron-deficient alkene compound, said reaction comprising the following steps: under the protection of nitrogen, a palladium compound and a metal hydride are suspended and stirred in a solvent, then an electron-deficient alkene compound is added; the mixture reacts at 0 C. to 100 C. for 0.3 to 10 hours; a saturated ammonium chloride aqueous solution is added to stop the reaction, and then extraction, drying by evaporation and purification by column chromatography are performed to obtain the product of 1,3-dicarbonyl compound. The hydride and palladium compound catalysts used in the method are reagents easily obtained in a laboratory; compared with the commonly used methods of hydrogenation with hydrogen gas, the method can be easily operated, and has high safety, mild conditions and high reaction yield.

Claims

1. A method of preparing a 1,3-dicarbonyl compound comprising: reducing an electron-deficient olefinic compound with a metal hydride in the presence of a palladium compound in an organic solvent to obtain the 1,3-dicarbonyl compound, wherein the electron-deficient olefinic compound has the following structure: ##STR00014## R is an aryl, an alkyl, an alkoxy, or an amino group; wherein the 1,3-dicarbonyl compound has the following structure: ##STR00015## wherein the metal hydride is sodium hydride, lithium hydride, potassium hydride, or calcium hydride; wherein the palladium compound is palladium chloride, palladium acetate, Pd.sub.2(dba).sub.3, Pd(TFA).sub.2, [(.sup.3-C.sub.3H.sub.5)PdCl].sub.2, Pd(dppp)Cl.sub.2, Pd(C.sub.6H.sub.5CN).sub.2Cl.sub.2, or Pd(OH).sub.2; and wherein the organic solvent is DMA (dimethylacetamide), DMF (dimethylformamide), THF (tetrahydrofuran), DME (dimethoxyethane), or dioxane.

2. The method of claim 1, wherein a molar ratio of the palladium compound:the metal hydride:the electron-deficient olefin compound is (0.01 to 1):(1 to 5):1.

3. The method of claim 2, wherein the molar ratio of the palladium compound:the metal hydride:the electron-deficient olefin compound is (0.05 to 0.15):(1 to 3):1.

4. The method of claim 3, wherein the molar ratio of the palladium compound:the metal hydride:the electron-deficient olefin compound is 0.1:2:1.

5. The method of claim 1, wherein the reduction of the electron-deficient olefinic compound is conducted under the protection of nitrogen atmosphere, at 0 C. to 100 C., for 0.3 to 10 hours.

6. The method of claim 5, wherein the reduction of the electron-deficient olefinic compound is conducted at 25 to 60 C., for 0.3 to 2 hours.

Description

EMBODIMENTS OF THE INVENTION

EXAMPLE 1

[0023] ##STR00003##

[0024] Under the protection of nitrogen, palladium chloride (5.3 mg, 0.03 mmol, 10 mol %) and sodium hydride (60% in oil, 24 mg, 0.6 mmol, 2 equiv) were stirred and suspended in DMA (1.5 mL) for 5 min at 25 C., and then the compound 1a (0.3 mmol) in DMA (0.5 mL) was added. The reaction was conducted at 25 C. for 2 h. The reaction was quenched by adding a saturated aqueous ammonium chloride solution. The product was subjected to extraction with ethyl acetate, combining the extract, drying with sodium sulphate, rotary evaporation, and column chromatography to obtain the product 3a with a yield is >99%. The mixture of enol and keto form, enol/keto=16/84. .sup.1 NMR (400 MHz, CDCl.sub.3): 10.37 (br, 1H, enol), 7.78 (d, J=7.6 Hz, 1H), 7.63 (t, J=7.2 Hz, 1H), 7.53-7.35 (m, 2H), 3.86 (s, 3H, enol), 3.79 (s, 3H, keto), 3.74 (dd, J=8.1, 3.9 Hz, 1H, keto), 3.57 (dd, J=17.3, 3.4 Hz, 1H, keto), 3.52 (s, 2H, enol), 3.38 (dd, J=17.2, 8.2 Hz, 1H, keto). 13C NMR (151 MHz, CDCl3): 199.58, 169.68, 153.73, 143.33 (enol), 135.61, 135.32 (enol), 129.54 (enol), 127.97, 126.97 (enol), 126.68, 124.86, 120.89, 102.30 (enol), 53.27, 52.95, 51.39 (enol), 32.65 (enol), 30.40. LR-MS (ESI): m/z 191.2 [M+H]+.

EXAMPLE 2

[0025] ##STR00004##

[0026] Under the protection of nitrogen, palladium acetate (2.7 mg, 0.015 mmol, 5 mol %) and lithium hydride (7.2 mg, 0.9 mmol, 3.0 equiv) were stirred and suspended in DMF (1.5 mL) for 5 min at 25 C., and then the compound 1a (0.3 mmol) in DMF (0.5 mL) was added. The reaction was conducted at 100 C. for 0.3 h. The reaction was quenched by adding a saturated aqueous ammonium chloride solution. The product was subjected to extraction with ethyl acetate, combining the extract, drying with sodium sulphate, rotary evaporation, and column chromatography to obtain the product 3a with a yield is 91%.

EXAMPLE 3

[0027] ##STR00005##

[0028] Under the protection of nitrogen, Pd.sub.2(dba).sub.3 (2.7 mg, 0.003 mmol, 1 mol %) and potassium hydride (30% in oil, 200 mg, 1.5 mmol, 5 equiv) were stirred and suspended in THF (1.5 mL) for 5 min at 25 C., and then the compound la (0.3 mmol) in THF (0.5 mL) was added. The reaction was conducted at 0 C. for 10 h. The reaction was quenched by adding a saturated aqueous ammonium chloride solution. The product was subjected to extraction with ethyl acetate, combining the extract, drying with sodium sulphate, rotary evaporation, and column chromatography to obtain the product 3a with a yield is 82%.

EXAMPLE 4

[0029] ##STR00006##

[0030] Under the protection of nitrogen, Pd(TFA).sub.2 (100 mg, 0.3 mmol, 100 mol %) and calcium hydride (24 mg, 0.6 mmol, 2.0 equiv) were stirred and suspended in DME (1.5 mL) for 5 min at 25 C., and then the compound la (0.3 mmol) in DME (0.5 mL) was added. The reaction was conducted at 90 C. for 0.3 h. The reaction was quenched by adding a saturated aqueous ammonium chloride solution. The product was subjected to extraction with ethyl acetate, combining the extract, drying with sodium sulphate, rotary evaporation, and column chromatography to obtain the product 3a with a yield of 83%.

EXAMPLE 5

[0031] ##STR00007##

[0032] Under the protection of nitrogen, [(.sup.3-C.sub.3H.sub.5)PdCl].sub.2 (2.1 mg, 0.006 mmol, 2 mol %) and sodium hydride (60% in oil, 12 mg, 0.30 mmol, 1.0 equiv) were stirred and suspended in dioxane (1.5 mL) for 5 min at 25 C., and then the compound la (0.3 mmol) in dioxane (0.5 mL) was added. The reaction was conducted at 30 C. for 2 h. The reaction was quenched by adding a saturated aqueous ammonium chloride solution. The product was subjected to extraction with ethyl acetate, combining the extract, drying with sodium sulphate, rotary evaporation, and column chromatography to obtain the product 3a with a yield of 65%.

EXAMPLE 6

[0033] ##STR00008##

[0034] Under the protection of nitrogen, Pd(dppp)Cl.sub.2 (18 mg, 0.03 mmol, 10 mol %) and sodium hydride (60% in oil, 24 mg, 0.6 mmol, 2 equiv) were stirred and suspended in DMA (1.5 mL) for 5 min at 25 C., and then the compound la (0.3 mmol) in DMA (0.5 mL) was added. The reaction was conducted at 25 C. for 2 h. The reaction was quenched by adding a saturated aqueous ammonium chloride solution. The product was subjected to extraction with ethyl acetate, combining the extract, drying with sodium sulphate, rotary evaporation, and column chromatography to obtain the product 3a with a yield of 63%.

EXAMPLE 7

[0035] ##STR00009##

[0036] Under the protection of nitrogen, Pd(C.sub.6H.sub.5CN).sub.2Cl.sub.2 (11.4 mg, 0.03 mmol, 10 mol %) and sodium hydride (60% in oil, 24 mg, 0.6 mmol, 2 equiv) were stirred and suspended in DMA (1.5 mL) for 5 min at 25 C., and then the compound la (0.3 mmol) in DMA (0.5 mL) was added. The reaction was conducted at 25 C. for 2 h. The reaction was quenched by adding a saturated aqueous ammonium chloride solution. The product was subjected to extraction with ethyl acetate, combining the extract, drying with sodium sulphate, rotary evaporation, and column chromatography to obtain the product 3a with a yield of 77%.

EXAMPLE 8

[0037] ##STR00010##

[0038] Under the protection of nitrogen, Pd(OH).sub.2 (4.2 mg, 0.03 mmol, 10 mol %) and sodium hydride (60% in oil, 24 mg, 0.6 mmol, 2 equiv) were stirred and suspended in DMA (1.5 mL) for 5 min at 25 C., and then the compound 1a (0.3 mmol) in DMA (0.5 mL) was added. The reaction was conducted at 25 C. for 2 h. The reaction was quenched by adding a saturated aqueous ammonium chloride solution. The product was subjected to extraction with ethyl acetate, combining the extract, drying with sodium sulphate, rotary evaporation, and column chromatography to obtain the product 3a with a yield of 69%.

EXAMPLE 9

[0039] ##STR00011##

[0040] Under the protection of nitrogen, palladium chloride (5.3 mg, 0.03 mmol, 10 mol %) and sodium hydride (60% in oil, 24 mg, 0.6 mmol, 2 equiv) were stirred and suspended in DMA (1.5 mL) for 5 min at 25 C., and then the compound 1b (0.3 mmol) in DMA (0.5 mL) was added. The reaction was conducted at 25 C. for 2 h. The reaction was quenched by adding a saturated aqueous ammonium chloride solution. The product was subjected to extraction with ethyl acetate, combining the extract, drying with sodium sulphate, rotary evaporation, and column chromatography to obtain the product 3b with a yield of 98%. .sup.1H NMR (400 MHz, CDCl.sub.3): 7.69 (d, J=7.6 Hz, 1H), 7.59-7.40 (m, 6H), 7.38-7.29 (m, 2H), 3.74 (dd, J=8.0, 4.3 Hz, 1H), 3.56 (dd, J=16.9, 3.9 Hz, 1H), 3.37 (s, 3H), 3.13 (dd, J=16.8, 8.1 Hz, 1H). .sup.13C NMR (151 MHz, CDCl.sub.3): 202.19, 169.67, 154.41, 143.94, 135.80, 135.10, 129.94, 128.24, 127.95, 127.61, 126.46, 124.42, 51.10, 37.92, 31.80. LR-MS (ESI): m/z 266.1 [M+H]+.

EXAMPLE 10

[0041] ##STR00012##

[0042] Under the protection of nitrogen, palladium chloride (5.3 mg, 0.03 mmol, 10 mol %) and sodium hydride (60% in oil, 24 mg, 0.6 mmol, 2 equiv) were stirred and suspended in DMA (1.5 mL) for 5 min at 25 C., and then the compound 1c (0.3 mmol) in DMA (0.5 mL) was added. The reaction was conducted at 25 C. for 2 h. The reaction was quenched by adding a saturated aqueous ammonium chloride solution. The product was subjected to extraction with ethyl acetate, combining the extract, drying with sodium sulphate, rotary evaporation, and column chromatography to obtain the product 3c with a yield of 98%. The mixture of enol and keto form, enol/keto=84/16. .sup.1H NMR (400 MHz, CDCl.sub.3): 7.81 (d, J=7.6 Hz, 1H, enol), 7.72 (d, J=7.6 Hz, 1H, keto), 7.63-7.46 (m, 2H, enol and keto), 7.44-7.33 (m, 1H, enol and keto), 4.11-3.92 (m, 1H, keto), 3.77-3.68 (m, 1H, keto), 3.58 (s, 2H, enol), 3.12 (dd, J=17.4, 7.7 Hz, 1H, keto), 2.49 (s, 3H, keto), 2.17 (s, 3H, enol). .sup.13C NMR (151 MHz, CDCl.sub.3): 201.52 (keto), 199.85 (keto), 191.56, 177.60, 154.24 (keto), 147.63, 138.31, 135.52 (keto), 135.14 (keto), 132.88, 127.76 (keto), 127.43, 126.73 (keto), 125.85, 124.61 (keto), 123.28, 110.56, 62.07 (keto), 30.38, 29.82 (keto), 28.00 (keto), 21.18. LR-MS (ESI): m/z 175.1 [M+H]+.

EXAMPLE 11

[0043] ##STR00013##

[0044] Under the protection of nitrogen, palladium chloride (5.3 mg, 0.03 mmol, 10 mol %) and sodium hydride (60% in oil, 24 mg, 0.6 mmol, 2 equiv) were stirred and suspended in DMA (1.5 mL) for 5 min at 25 C., and then the compound 1d (0.3 mmol) in DMA (0.5 mL) was added. The reaction was conducted at 25 C. for 2 h. The reaction was quenched by adding a saturated aqueous ammonium chloride solution. The product was subjected to extraction with ethyl acetate, combining the extract, drying with sodium sulphate, rotary evaporation, and column chromatography to obtain the product 3d with a yield of 99%. The mixture of enol and keto form, enol/keto=87/13. .sup.1H NMIR (400 MHz, CDCl.sub.3): 15.08 (br, 1H, enol), 8.14 (d, J=7.6 Hz, 2H, keto), 8.00-7.92 (m, 2H, enol), 7.89 (d, J=7.6 Hz, 1H, enol), 7.73 (d, J=7.6 Hz, 1H, keto), 7.62-7.48 (m, 5H, enol and keto), 7.44 (t, J=7.2 Hz, 1H, enol), 7.40-7.35 (m, 1H, keto), 4.87 (dd, J=7.4, 2.6 Hz, 1H, keto), 3.94 (s, 2H, enol), 3.90-3.75 (m, 1H, keto), 3.34 (dd, J=17.1, 7.7 Hz, 1H, keto). .sup.13C NMR (151 MHz, CDCl3): 200.12 (keto), 195.95, 194.40 (keto), 170.91, 154.47 (keto), 148.70, 145.81 (keto), 138.03, 136.43 (keto), 135.41 (keto), 134.94 (keto), 133.68 (keto), 133.47, 131.40, 129.96, 128.74, 128.25, 127.83 (keto), 127.59, 126.65 (keto), 125.73, 124.77(keto), 123.57, 109.58, 56.69 (keto), 32.37, 30.20 (keto). LR-MS (ESI): m/z 237.0 [M+H]+.