Ethyl pentanoate Ethyl 3-oxo-2-propylheptanoate

We found that the reaction led to the corresponding products 2a–2l in excellent isolated yields with all substrates. The reaction appears to be quite tolerant to differences in the position, number and electronic contribution of the substituent on the benzene ring. For example, the reactions of 3-oxo-N-phenylbutanamide, N-(4-methoxyphenyl)-3-oxobutanamide, N-(2-methoxyphenyl)-3-oxobutanamide, N-(2,5-dichlorophenyl)-3-oxobutanamide, N-(2,4-dimethoxyphenyl)-3-oxobutanamide as well as N-(4-chloro-2,5-dimethoxyphenyl)-3-oxobutanamide all lead to the corresponding products (2a, 2e, 2f, 2g, 2j, and 2k, respectively) in excellent isolated yield. Similarly, the reactions of other N-(alkylsubstituted)-3-oxobutanamides were investigated, such as that of N-methyl-3-oxobutanamide (1l), which led to 1-(methylcarbamoyl)-2-oxopropyl acetate in 89% yield. Furthermore, we applied this method to non-carbamoyl 1,3-dicarbonyl compounds. These substrates, namely 1-phenylbutane-1,3-dione, 1,3-diphenylpropane-1,3-dione and ethyl 3-oxo-3-phenylpropanoate, all produced products in moderate isolated yields (2m, 2n, 2o).

Ethyl 3-oxo-2- phenylpropanoate

Diethyl 2-oxo-3- phenylbutanedioate
Photo provided by


An oven-dried Schlenk flask was evacuated, filled with nitrogen, and thencharged with pentane-2,4-dione (1.00 g, 10 mmol),ethyl-3-bromo-3-phenylpropanoate (2.82 g, 11 mmol), tributylamine (3 ml),PPh3 (52.5 mg, 0.2 mmol), Pd(OAc)2 (24 mg, 0.1 mmol), and DMF (10 ml) togive a yellow solution. The reaction mixture was heated at 373 K withstirring. The reaction mixture was cooled to room temperature after 22 h andthe resulting yellow-orange mixture was diluted with Et2O (10 ml). Themixture was washed with H2O (15 ml) and the aqueous layer was extracted withEt2O (20 ml). The combined organic layers were dried (MgSO4), filtered,and concentrated in vacuo. The crude material was purified by flashcolumn chromatography on silica gel (petroleum ether:EtOAc, 9:1) andrecrystallized from EtOAc, yield 2.27 g (82%). Colorless crystals suitable forX-ray diffraction were obtained by recrystallization from a solution of thetitle compound from ethyl acetate, over a period of one week.

2-Methyl-1,3- cyclopentanedione

Palladium-catalyzed coupling reactions have become an important tool in modernorganic synthesis chemistry (Hu et al. 2008). They have made awidevariety of active pharmaceutical ingredients, natural substances and othercomplex organic molecules economically accessible (Hu & Yu et al.,2009; Hu, Ouyang et al., 2009). The pentane-2,4-dionederivatives,which have physiological activity, are effective intermediates in thesynthesis of many complex natural products (Vijaikumar & Pitchumani,2010).We have reported some novel palladium-catalyzed intermolecular andintramolecular reactions of aryl halides with the olefins and diynes (Hu, Linet al., 2010; Hu, Ren et al., 2010). The reactionof ethyl3-bromo-3-phenylpropanoate with pentane-2,4-dione, in the presence ofpalladium(II) acetate and triphenylphosphine, in DMF at 373 K for 22 h, gavethe unexpected title product.

Ethyl 3-oxobutanoate(ethyl acetoacetate) Ethanol
Photo provided by

Conjugate base of ethyl 3-oxobutanoate (stronger base)

H atoms were positioned geometrically and refined using a riding model(including free rotation about the methyl C—C bond), with C—H = 0.93–0.97 Å and with Uiso(H) = 1.2 (1.5 for methyl groups) timesUeq(carrier C).

Diethyl carbonate CH3CH2OCOCH2CH3

Ethyl 2-isopropyl-5-methyl- 3-oxohexanoate