Method for preparing 1,3-dicarbonyl compound based on metal hydride/palladium compound system

Abstract

Disclosed is a method for preparing a 1,3-dicarbonyl compound based on a metal hydride/palladium compound system. The method includes the following steps: suspending a palladium compound and a metal hydride in a solvent under the protection of nitrogen, then adding an electron-deficient olefin compound, reacting same at 0° C.-100° C. for 0.3 to 10 hours, then adding a saturated ammonium chloride aqueous solution to stop the reaction, and then subjecting same to extraction, evaporation until dryness, and column chromatography purification to obtain the 1,3-dicarbonyl compound. The hydride and palladium compound catalysts used by the present invention are reagents easily obtained in a laboratory. Compared to a common hydrogen hydrogenation method, the method is easier to operate, and has a higher safety, mild conditions, and a high reaction yield.

Claims

1. A method of preparing a 1,3-dicarbonyl compound comprising: under the protection of nitrogen, suspending a palladium compound and a metal hydride in a solvent to form a mixture; adding an electron-deficient olefinic compound to the mixture; stirring the mixture at 0° C. to 100° C. for 0.3 to 10 hours to obtain the 1,3-dicarbonyl compound.

2. The method according to claim 1, wherein the metal hydride is sodium hydride, lithium hydride, potassium hydride, or calcium hydride; and the palladium compound is palladium chloride, palladium acetate, Pd.sub.2(dba).sub.3, Pd(TFA).sub.2, [(η.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.

3. The method according to claim 2, wherein the metal hydride is sodium hydride or lithium hydride; and the palladium compound is palladium chloride or palladium acetate.

4. The method according to claim 3, wherein the metal hydride is sodium hydride; and the palladium compound is palladium chloride.

5. The method according to claim 1, wherein the electron-deficient olefin compound has the following structure: ##STR00014## R is an aryl, an alkyl, an alkoxy, or an amino group.

6. The method according to 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.

7. The method according to claim 6, 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.

8. The method according to claim 1, further comprising: adding a saturated ammonium chloride aqueous solution to the mixture to quench reaction; and conducting extraction, drying, rotary evaporation, and column chromatography to obtain the 1,3-dicarbonyl compound.

9. The method according to claim 1, wherein the solvent is DMA (dimethylacetamide), DMF (dimethylformamide), THF (tetrahydrofuran), DME (dimethoxyethane), or dioxane.

10. The method according to claim 1, wherein the mixture is stirred at 25 to 60° C. for 0.3 to 2 h.

Description

EMBODIMENTS OF THE INVENTION

Example 1

(1) ##STR00003##

(2) 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.1H NMR (400 MHz, CDCl.sub.3): δ 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): δ 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

(3) ##STR00004##

(4) 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

(5) ##STR00005##

(6) 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 1a (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

(7) ##STR00006##

(8) 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 1a (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

(9) ##STR00007##

(10) Under the protection of nitrogen, [(η.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 1a (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

(11) ##STR00008##

(12) 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 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 63%.

Example 7

(13) ##STR00009##

(14) 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 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 77%.

Example 8

(15) ##STR00010##

(16) 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

(17) ##STR00011##

(18) 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): δ 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): δ 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

(19) ##STR00012##

(20) 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): δ 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, CDCl3): δ 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

(21) ##STR00013##

(22) 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 NMR (400 MHz, CDCl.sub.3): δ 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): δ 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]+.