J. S. Yadav et al. / Tetrahedron 61 (2005) 875–878
877
Scheme 2.
yield the b-keto esters in good yields. The reaction probably
proceeds through the activation of the aldehyde by
complexation with niobium(V) followed by nucleophilic
addition of EDA on the C]O group and subsequent 1,2-
hydride shift with loss of N resulting in the formation of
2
b-keto ester 3 (Scheme 2).
TLC, the reaction mixture was extracted with dichlo-
methane (3!10 mL). The combined organic extracts were
dried over anhydrous Na SO , concentrated in vacuum and
purified by column chromatography on silica gel (Merck,
100–200 mesh ethyl acetate–hexane, 1:9) to afford pure
b-keto esters.
2
4
The method is clean and the products are obtained in high
yields with high selectivity. No side products such as
glycidic esters were observed under the reaction conditions.
Other side products like diethyl maleate and/or fumarate
arising from carbene dimerization were not detected under
these conditions. To determine the efficiency of this
procedure, we have also performed the reactions with
various other Lewis acids such as InCl , CeCl $7H O,
2.1.1. Ethyl 3-oxo-3-(2-pyridyl) propanoate (3o). Pale
yellow liquid, IR (neat): n 3636, 3058, 2985, 2939, 1741,
K1
1703, 1644, 1582, 1327, 1197, 1032, 791, 746, 648 cm
.
1
H NMR (200 MHz, CDCl ): d 8.64 (d, JZ3.7 Hz, 1H),
3
8.04 (d, JZ8.1 Hz, 1H), 7.84 (t, JZ8.1 Hz, 1H), 7.47 (t, JZ
5.2 Hz, 1H), 4.16 (q, JZ7.4, 14.1 Hz, 2H), 4.12 (s, 2H),
C
1.24 (t, JZ7.4 Hz, 3H). EIMS: m/z (%): 193 (M , 10), 148
(30), 121 (80), 106 (50), 78 (100), 51 (40). Anal. Calcd for
3
3
2
TaCl and GdCl . Among these catalysts, NbCl was found
5
C H NO (193.201): C, 62.17; H, 5.74; N, 7.25. Found: C,
10 11
3
5
3
to be the most effective catalyst for this conversion. In the
absence of catalyst, no condensation was observed between
aldehyde and ethyl diazoacetate. As solvent, dichloro-
methane appears to give the best results. Ketones such as
acetophenone, cyclohexanone, and tetralone failed to
undergo condensation with EDA. This is due to the lower
reactivity of ketones in comparison with aldehydes. Other
diazoesters such as diethyl diazomalonate and ethyl
diazoacetoacetate did not yield any condensation product
under the reaction conditions. The scope of this method is
illustrated with respect to various aldehydes and ethyl
diazoacetate and the results are presented in Table 1.
62.10; H, 5.69; N, 7.31%.
2.1.2. Ethyl 3-(4-flourophenyl)-3-oxopropanoate (3p).
Brown oil, IR (neat) n 3548, 3076, 2985, 1740, 1688,
K1 1
1600, 1509, 1206, 1032, 845, 768, 569 cm . H NMR
(200 MHz, CDCl ): d 7.98–7.95 (m, 2H), 7.16–7.11 (m,
3
2H), 4.18 (q, JZ7.4, 14.1 Hz, 2H), 3.89 (s, 2H), 1.26 (t, JZ
7.4 Hz, 3H). EIMS: m/z (%): 210 (M , 10), 166 (5), 124
(100), 96 (20). Anal. Calcd for C H FO (210.203): C,
3
62.85; H, 5.27; F, 9.04. Found: C, 62.79; H, 5.32; F, 9.12%.
C
1
1
11
Acknowledgements
In summary, we describe a mild, convenient and efficient
protocol for the preparation of b-keto esters via the C–H
insertion of ethyl diazoacetate into aldehydes using NbCl5
as novel catalyst. This method provides improved yields of
b-keto esters including the less reactive aromatic substrates.
B. V. S. thanks CSIR, New Delhi for the award of
fellowship.
References and notes
2. Experimental
1
2
. Benetti, S.; Romagnoli, R. Chem. Rev. 1995, 95, 1065.
. (a) Hoffmann, R. W.; Helbig, W.; Ladner, W. Tetrahedron Lett.
Melting points were recorded on Buchi R-535 apparatus and
are uncorrected. IR spectra were recorded on a Perkin–
Elmer FT-IR 240-c spectrophotometer using KBr optics. H
1
982, 23, 3479. (b) Wang, C. L. J.; Salvino, J. M. Tetrahedron
1
Lett. 1984, 25, 5243. (c) Gilbert, J. C.; Kelly, T. A. Tetrahedron
Lett. 1989, 30, 4193. (d) Emmer, G. Tetrahedron 1992, 48,
7165.
NMR spectra were recorded on Gemini-200 spectrometer in
CDCl using TMS as internal standard. Mass spectra were
3
recorded on a Finning MAT 1020 mass spectrometer
operating at 70 eV.
3
4
. (a) Ishida, T.; Wada, K. Chem. Commun. 1975, 209. (b) Urban,
E.; Knuehl, G.; Helmchen, G. Tetrahedron 1995, 51, 13031. (c)
Magriotis, P. A.; Johnson, F. J. Org. Chem. 1984, 49, 1460. (d)
Ward, R. S. Synthesis 1992, 719.
2
.1. General procedure
. Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic
Methods for Organic Synthesis with Diazo Compounds; Wiley:
New York, 1998; p 551.
A mixture of aldehyde (1 mmol), ethyl diazoacetate
(1.2 mmol) and NbCl5 (5 mol%) in dichloromethane
(10 mL) was stirred at 27 8C for the appropriate time
(Table 1). After completion of the reaction, as indicated by
5. (a) Fernandez, V. H.; Herrera, L. F. J.; Perez, G. C. Carbohydr.
Res. 1983, 124, 333. (b) Holmquist, C. R.; Roskamp, E. J.