1830
H. Habib-Zahmani et al.
LETTER
successive washing with distilled water (2 20 mL) and
brine (20 mL) gave, after drying (MgSO4) and evaporation
of the solvent, the crude compounds which were purified by
flash chromatography on silica gel.
9336. (j) Tietze, L. F.; Hippe, T.; Steinmetz, A. Synlett 1996,
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Mañas, M.; Marquet, J.; Vallribera, A. Tetrahedron 1996,
52, 3377.
(9) For a comprehensive review on synthetic utilizations of -
ketoesters, see: Benetti, S.; Romagnoli, R.; De Risi, C.;
Spalluto, G.; Zanirato, V. Chem. Rev. 1995, 95, 1065.
(10) For a recent account, see: (a) Rodriguez, J. Synlett 1999,
505. (b) Lavoisier-Gallo, T.; Charonnet, E.; Pons, J. M.;
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(21) Filippini, M. H.; Rodriguez, J. Synth. Commun. 1995, 25,
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(23) All new compounds showed correct mass spectra or
elemental analyses (C, H, N); for example, 4d: yellow
crystals, mp 52–54 °C, Rf = 0.55 (Et2O/pentane, 30/70).
IR(neat): = 2923, 1734, 1706, 1617, 1430, 1265 cm–1. 1H
NMR (200 MHz, CDCl3): = 2.01 (m, 1 H), 2.54 (dd, broad,
J = 13.6, 7.1 Hz, 1 H), 2.64 (m, 1 H), 2.86 (dd, broad,
J = 13.6, 7.2 Hz, 1 H), 3.03 (m, 2 H), 3.74 (s, 3 H), 5.15 (m,
2 H), 5.73 (m, 1 H), 6.56 (dd, J = 3.4, 1.8 Hz, 1 H), 6.74 (d,
J = 3.4 Hz, 1 H), 7.28 (t, J = 3.2 Hz, 1 H), 7.62 (d, J = 1.4
Hz, 1 H). 13C NMR (100 MHz, CDCl3): = 26.7, 29.5, 39.0,
53.0, 60.9, 113.1, 117.3, 119.3, 121.5, 132.8, 133.6, 145.8,
152.5, 171.9, 172.2, 202.8. Anal. Calcd for C15H16O4: C,
69.22; H, 6.20. Found: C, 68.98; H, 6.21.
(24) For efficient preparations from the corresponding ketoesters,
see: (a) Cossy, J.; Thellend, A. Synthesis 1989, 753.
(b) Mottet, C.; Hamelin, O.; Garavel, G.; Deprés, J. P.;
Greene, A. E. J. Org. Chem. 1999, 64, 1380. (c) Ponde, D.
E.; Deshpande, V. H.; Bulbule, V. J.; Sudalai, A.; Gajare, A.
S. J. Org. Chem. 1998, 63, 1058.
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2439. (b) Evans, D. A.; Ennis, M. D.; Le, T. J. Am. Chem.
Soc. 1984, 106, 1154. (c) Hoffman, R. V.; Huizenga, D. J. J.
Org. Chem. 1991, 56, 6435.
(26) See inter alia: (a) Cossy, J.; Bouzide, A. Tetrahedron 1997,
53, 5775. (b) Moya, P.; Cantin, A.; Castillo, M.-A.; Primo,
J.; Miranda, M. A.; Primo-Yufera, E. J. Org. Chem. 1998,
63, 8530. (c) Nair, V.; Sheeba, V. J. Org. Chem. 1999, 64,
6898.
(11) Charonnet, E.; Filippini, M. H.; Rodriguez, J. Synthesis
2001, 788.
(12) For some important bioactive azaspiro compounds, see:
(a) Commins, D. L.; Zhang, Y. M.; Zheng, X. Chem.
Commun. 1998, 2509. (b) François, D.; Lallemand, M. C.;
Selkti, M.; Tomas, A.; Kunesh, M.; Husson, H. P. Angew.
Chem. Int. Ed. 1998, 37, 104. (c) Williams, G. M.;
Roughley, S. D.; Davies, J. E.; Holmes, A. B. J. Am. Chem.
Soc. 1999, 121, 4900. (d) Tsujimoto, T.; Ishihara, J.; Horie,
M.; Murai, A. Synlett 2002, 399. (e) Ishihara, J.; Horie, M.;
Shimada, Y.; Tojo, S.; Murai, A. Synlett 2002, 403.
(13) For selected references, see: (a) Abdulla, R. F.; Fuhr, K. F.
J. Org. Chem. 1978, 43, 4248. (b) Corey, E. J.; Mehrotra,
M. M. J. Am. Chem. Soc. 1984, 106, 3384. (c) Sasai, H.;
Shibasaki, M. Tetrahedron Lett. 1987, 28, 333. (d)Jung, M.
E.; Pan, Y. C.; Hart, M. W. Nat. Prod. Rep. 1988, 1.
(e) Iwasaki, G.; Sano, M.; Sodeoka, M.; Yoshida, K.;
Shibasaki, M. J. Org. Chem. 1988, 53, 4864.
(14) Deli, J.; Lorand, T.; Szabo, D.; Földesi, A. Pharmazie 1984,
39, 539.
(27) Babudri, F.; Ciminale, F.; Di Nunno, L.; Florio, S.
Tetrahedron 1982, 38, 557.
(15) (a) Tyndall, D. V.; Al Nakib, T.; Meegan, M. J. Tetrahedron
Lett. 1988, 29, 2703. (b) Huang, C.-Y.; Cabell, L. A.;
Anslyn, E. V. J. Am. Chem. Soc. 1994, 116, 2778.
(16) Sayed, H. H. Indian J. Chem., Sect. B 1998, 37, 1054.
(17) Popkov, S. V.; Kovalenko, L. V.; Tashchi, V. P.; Bogel’fer,
L. Y. Russ. Chem. Bull. 1994, 43, 1363; Izv. Akad. Nauk.,
Ser. Khim.; 1994, 8, 1439.
(28) (a) Snider, B. B.; Zhang, Q. Tetrahedron Lett. 1992, 33,
5921. (b) For our own recent contribution with cyclic
ketoamides, see: ref.11 (c) For related -functionalization of
chiral -ketoimides and their important synthetic
applications, see inter alia: Evans, D. A.; Kim, A. S.;
Metternich, R.; Novack, V. J. J. Am. Chem. Soc. 1998, 120,
5921; and references cited therein.
(29) Takada, N.; Umemura, N.; Suenaga, K.; Chou, T.; Nagatsu,
A.; Haino, T.; Yamada, K.; Uemura, D. Tetrahedron Lett.
2001, 42, 3491.
(18) Koch, K.; Smitrovich, J. H. Tetrahedron Lett. 1994, 35,
1137.
(19) Varma, R. S.; Kumar, D. Synthesis 1999, 1288.
(20) General Experimental Procedure: To a solution of 1,3-
dicarbonyl 1 (1 mmol) and DBU (3 mmol) in dry THF (8
mL) containing 10% dry MeOH in the case of -ketoesters
and MeOH alone (8 mL) in the case of -ketoamides was
added the corresponding aldehyde 2 (1 mmol) and halide 3
(2 mmol). The resulting solution was stirred under nitrogen
at r.t. or under reflux for the indicated time (Table 1). After
completion and evaporation of most of the solvent under
reduced pressure, water (50 mL) was added to the oily
residue. Extraction with Et2O (3 40 mL) followed by
(30) Takada, N.; Umemura, N.; Suenaga, K.; Uemura, D.
Tetrahedron Lett. 2001, 42, 3495.
(31) For other recent related RCM approaches to azaspiro
compounds, see inter alia: (a) Faure, S.; Piva-Leblanc, S.;
Piva, O. Tetrahedron Lett. 1999, 40, 6001. (b) Wallace, D.
J.; Goodman, J. M.; Kennedy, D. J.; Davies, A. J.; Cowden,
C. J.; Ashwood, M. S.; Cottrell, I. F.; Dolling, U. H.; Reider,
P. Org. Lett. 2001, 3, 671. (c) Hughes, R. C.; Dvorak, C. A.;
Meyers, A. I. J. Org. Chem. 2001, 66, 5545.
Synlett 2002, No. 11, 1827–1830 ISSN 0936-5214 © Thieme Stuttgart · New York