LETTER
Synthesis of 4,5-Dihydroisoxazoles
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(5) (a) Mukaiyama, T.; Hoshino, T. J. Am. Chem. Soc. 1960, 82,
5339. (b) Vigalok, I. V.; Moisak, I. E.; Svetlakov, N. V.
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(f) Basel, Y.; Hassner, A. Synthesis 1997, 309.
inexpensive procedure rests on water elimination without
need of a dehydrating agent. Since furoxans have never
been observed in these experiments,10 we believe that
nitrile oxides are not reaction intermediates and water is
released from the nitro compound after reaction with the
dipolarophile.11
Further investigation presently in progress in our labora-
tory is aimed at improving the catalytic system, extending
the scope and elucidating the mechanism of the process.
(g) Maugein, N.; Wagner, A.; Mioskowsi, C. Tetrahedron
Lett. 1997, 38, 1547. (h) Giacomelli, G.; De Luca, L.;
Porcheddu, A. Tetrahedron 2003, 59, 5437.
(6) (a) Cecchi, L.; De Sarlo, F.; Machetti, F. Tetrahedron Lett.
2005, 46, 7877. (b) Cecchi, L.; De Sarlo, F.; Faggi, C.;
Machetti, F. Eur. J. Org. Chem. 2006, 3016. (c) Cecchi, L.;
De Sarlo, F.; Machetti, F. Eur. J. Org. Chem. 2006, 4852.
(d) Machetti, F.; Cecchi, L.; Trogu, E.; De Sarlo, F. Eur. J.
Org. Chem. 2007, 4352.
(7) Snider, B. B.; Che, Q. Tetrahedron 2002, 58, 7821.
(8) Warsinsky, R.; Steckhan, E. J. Chem. Soc., Perkin Trans. 1
1994, 2027.
Acknowledgment
Authors thank the Ministero dell’Università e Ricerca (MiUR,
Italy, project COFIN-PRIN 2005 – prot. 2005038048) for financial
support. L.C. thanks Università di Firenze for Doctoral Fellowship.
Financial support by the Ente Cassa di Risparmio di Firenze for the
purchase of the 400 MHz NMR instrument is gratefully acknowl-
edged.
(9) Typical Procedure for the Catalysed Condensation of 1-
Nitropentane and Methyl Acrylate
References and Notes
Copper(II) acetate (3.9 mg, 0.021 mmol) was treated with a
solution of nitropentane (124 mg, 1.06 mmol), methyl
acrylate (37 mg, 0.42 mmol), and 1-methylpiperidine (21
mg, 0.21 mmol) in CHCl3 (1.4 mL) and the mixture
magnetically stirred in a sealed vessel (Schlenk) at 60 °C.
After 40 h the reaction mixture was concentrated and the
residue dissolved in EtOAc (15 mL) and washed with 5%
HCl (3 × 15 mL portions), sat. Na2CO3 (3 × 15 mL
portions), and brine (3 × 15 mL portions). The organic layer
was dried (Na2SO4), filtered, and concentrated. The residue
was purified by chromatography on silica gel eluting first
with hexane and then with hexane–Et2O (4:3). The
isoxazoline [Rf (hexane–Et2O) = 0.22, 71 mg] was obtained
as a clear oil in 90% yield.
(1) (a) Kozikowski, A. P. Acc. Chem. Res. 1984, 17, 410.
(b) Baraldi, P. G.; Barco, A.; Benetti, S.; Pollini, G. P.;
Simoni, D. Synthesis 1987, 857. (c) Litvinovskaya, R. P.;
Khripach, V. A. Russ. Chem. Rev. (Engl. Transl.) 2001, 70,
405. (d) Kotyatkina, A. I.; Zhabinsky, V. N.; Khripach, V.
A. Russ. Chem. Rev. (Engl. Transl.) 2001, 70, 641.
(2) For selected recent examples, see: (a) Itoh, T.; Watanabe,
M.; Fukuyama, T. Synlett 2002, 1323. (b) Lemaire, M.;
Veny, N.; Gefflaut, T.; Gallienne, E.; Chênevert, R.; Bolte,
J. Synlett 2002, 1359. (c) Li, S.; Donaldson, W. A. Synthesis
2003, 2064. (d) Fuller, A. A.; Chen, B.; Minter, A. R.;
Mapp, A. K. Synlett 2004, 1409. (e) Sewald, N. Angew.
Chem. Int. Ed. 2003, 42, 5794. (f) Muri, D.; Lohse-Fraefel,
N.; Carreira, E. M. Angew. Chem. Int. Ed. 2005, 44, 4036.
(g) Zimmermann, P. J.; Lee, J. Y.; Hlobilova (née
Analytical Data
1H NMR (400 MHz, CDCl3): d = 0.91 (t, J = 7.6 Hz, 3 H,
CH3), 1.29–1.41 (m, 2 H, CH2CH3), 1.48–1.59 (m, 2 H,
CH2CH2C-3), 2.35 (t, J = 8.0 Hz, 2 H, CH2C-3), 3.19 (d,
J = 9.0 Hz, 2 H, 4-H), 3.76 (s, 3 H, OCH3), 4.96 (t, J = 9.0
Hz, 1 H, 5-H) ppm. 13C NMR (100.58 MHz, CDCl3):
d = 13.6 (q, CH3), 22.2 (t, CH2CH3), 26.8 (t, CH2C-3), 28.3
(t, CH2CH2CH3), 40.8 (t, C-4), 52.6 (q, OCH3), 76.8 (d, C-
5), 158.4 (s, C-3), 171.0 (s, C=O) ppm. MS (EI, 70 eV):
m/z (%) = 185 (<1) [M]+, 143 (23), 126 (12) [M – CO2Me]+,
98 (20), 57 (100). IR (CDCl3): 1739 (C=O), 1622 (C=N)
cm–1. Anal. Calcd for C9H15NO3 (185.22): C, 58.36; H, 8.16;
N, 7.56. Found: C, 58.19; H, 8.43; N, 7.89.
Blanarikova), I.; Endermann, R.; Häbich, D.; Jäger, V. Eur.
J. Org. Chem. 2005, 3450. (h) Fleming, K. N.; Taylor, R. E.
Angew. Chem. Int. Ed. 2004, 43, 1728.
(3) (a) Antczak, C.; Bauvois, B.; Monneret, C.; Florent, J.-C.
Bioorg. Med. Chem. 2001, 9, 2843. (b) Olson, R. E.;
Sielecki, T. M.; Wityak, J.; Pinto, D. J.; Batt, D. G.; Frietze,
W. E.; Liu, J.; Tobin, A. E.; Orwat, M. J.; Di Meo, S. V.;
Houghton, G. C.; Lalka, G. K.; Mousa, S. A.; Racanelli, A.
L.; Hausner, E. A.; Kapil, R. P.; Rabel, S. R.; Thoolen, M. J.;
Reilly, T. M.; Anderson, P. S.; Wexler, R. R. J. Med. Chem.
1999, 42, 1178. (c) Alcázar, J.; Alonso, J. M.; Andrés, J. I.;
Bartolomé, J. M.; Fernández, J. Synlett 2005, 3139.
(4) Arai, M. A.; Kuraishi, M.; Arai, T.; Sasai, H. J. Am. Chem.
Soc. 2001, 123, 2907.
(10) Torssell, K. B. G. Nitrile Oxides, Nitrones, Nitronates in
Organic Synthesis; VCH Publishers: New York, 1988, 55.
(11) McKillop, A.; Kobylecki, R. J. Tetrahedron 1974, 30, 1365.
Synlett 2007, No. 15, 2451–2453 © Thieme Stuttgart · New York