1018
U. Albrecht et al. / Tetrahedron Letters 46 (2005) 1017–1019
2. Bach, P.; Bols, M. Tetrahedron Lett. 1999, 40, 3460.
Table 1. Productsand yields
a
3. Miyashita, M.; Awen, B. Z. E.; Yoshikoshi, A. Tetrahe-
dron 1990, 46, 7569.
3
R
%
a
b
c
d
e
f
Ph
30
81
73
36
72
33
44
42
4. For a review, see: (a) Gilchrist, T. L. J. Chem. Soc., Chem.
Rev. 1983, 12, 53; see also: (b) Gilchrist, T. L.; Roberts, T.
G. J. Chem. Soc., Chem. Commun. 1978, 847; (c) Zimmer,
R.; Reißig, H. U. Liebigs Ann. Chem. 1991, 553; (d) Yoon,
S. C.; Kim, K.; Park, Y. J. J. Org. Chem. 2001, 66, 7334;
(e) Naruse, M.; Aoyagi, S.; Kibayashi, C. Tetrahedron
Lett. 1994, 35, 595.
5. (a) Bowman, W. R.; Davies, R. V.; Slawin, A. M. Z.;
Sohal, G. S.; Titman, R. B.; Wilkins, D. J. J. Chem. Soc.,
Perkin Trans. 1 1997, 155; (b) Dondas, H. A.; Grigg, R.;
Hadjisoteriou, M.; Markandu, J.; Kennewell, P.; Thorn-
son-Pett, M. Tetrahedron 2001, 57, 1119.
6. (a) Tiecco, M.; Testaferri, L.; Tingoli, M.; Bagnoli, L.;
Marini, F. J. Chem. Soc., Perkin Trans. 1 1993, 1989; (b)
Grigg, R.; Hadjisoteriou, M.; Kennewell, P.; Markandu,
J. J. Chem. Soc., Chem. Commun. 1992, 1537.
7. Bishop, R.; Hawkins, S. C.; Quibuyen, T. A. O.; Brooks,
P. R. Tetrahedron Lett. 1988, 29, 6805.
4-MeC6H5
4-(MeO)C6H5
3-MeC6H5
3-(MeO)C6H5
2-MeC6H5
1-Naphthyl
2-Naphthyl
g
h
a Yields of isolated products.
OH
N
O
N
OH
i
O
+
Br
()n
1i-l
()n
3i-l
2
8. Armesto, D.; Austin, M. A.; Griffiths, O. J.; Horspool, W.
M.; Carpintero, M. J. Chem. Soc., Chem. Commun. 1996,
2715.
9. (a) Kaiser, A.; Mayer, K. K.; Sellmer, A.; Wiegrebe, W.
Monatsh. Chem. 2003, 3, 343; (b) Ellames, G. J.; Hewkin,
C. T.; Jackson, R. F. W.; Smith, D. I.; Standen, S. P.
Tetrahedron Lett. 1989, 26, 3471.
10. Saiki, H.; Mukai, T. Chem. Lett. 1981, 1561.
11. Lathbury, D.; Gallagher, T. J. Chem. Soc., Chem. Com-
mun. 1986, 1017.
12. Castin, V.; Rentzea, C. N. Angew. Chem. 1980, 92, 195.
13. Boberg, F.; Ruhr, M.; Garburg, K. H.; Garming, A.
J. Heterocycl. Chem. 1986, 23, 759.
14. For reviews of dianions including oxime 1,4-dianions, see:
(a) Kaiser, E. M.; Petty, J. D.; Knutson, P. L. A. Synthesis
1977, 509; (b) Thompson, C. M.; Green, D. Tetrahedron
1991, 47, 4223.
15. For a review of cyclization reactions of dianions, see:
Langer, P.; Freiberg, W. Chem. Rev. 2004, 104,
4125.
Scheme 2. Synthesis of bicyclic oxazines. Reagents and conditions: (i)
(1) n-BuLi (2.5 equiv), 1 h, ꢀ78 ꢁC; (2) 10 min, 20 ꢁC; (3) 2,
ꢀ78 ! 20 ꢁC, 16 h.
Table 2. Productsand yields
a
%
3
n
i
1
2
3
7
38
51
49
52
j
k
l
a Yields of isolated products.
OH
N
O
N
OH
2
i
16. For the synthesis of isoxazoles by reaction of dilithiated
oximes with esters, see: (a) Beam, C. F.; Dyer, M. C. D.;
Schwarz, R. A.; Hauser, C. R. J. Org. Chem. 1970, 35,
1806; for the synthesis of isoxazolin-5-ones from oximes
and carbon dioxide, see: (b) Griffiths, J. S.; Beam, C. F.;
Hauser, C. R. J. Chem. Soc. C 1971, 974.
1m
3m (48%)
Scheme 3. Synthesis of 1,2-oxazine 3m. Reagentsand condition:s (i)
(1) n-BuLi (2.5 equiv), 1 h, ꢀ78 ꢁC; (2) 10 min, 20 ꢁC; (3) 2,
ꢀ78 ! 20 ꢁC, 16 h.
17. For reactionsof silyl enol etherswith a-chloroximes, see:
(a) Reissig, H.-U.; Hippeli, C.; Arnold, T. Chem. Ber.
The cyclization of 2 with oximes 1i–l, prepared from
cycloalkanones, afforded the corresponding 6,6-, 6,7-,
6,8- and 6,12-bicyclic 1,2-oxazines 3i–l (Scheme 2, Table
2). The cyclization of tetralone-derived oxime 1m with 2
afforded the tricyclic 1,2-oxazine 3m (Scheme 3). All
products 3i–m were formed as1:1 mixturesof
diastereomers.
1990, 123, 2403; for reactionsof allylislaneswith
chloroximes, see: (b) Hippeli, C.; Reissig, H.-U. Synthesis
a-
1987, 77.
18. For other cyclization reactionsof epibromohydrin from
our laboratory, see: (a) Langer, P.; Freifeld, I. Chem. Eur.
J. 2001, 7, 565; (b) Albrecht, U.; Langer, P. Synlett 2004,
2200.
19. Typical procedure for the preparation of dihydrooxazines 3:
to a THF solution (10 ml) of oxime 1b (0.298 g, 2.0 mmol)
wasadded n-butyllithium (5.0 mmol, 2.5 M) at ꢀ78 ꢁC.
After stirring for 1 h at ꢀ78 ꢁC, the mixture waswarmed
to 20 ꢁC and stirred for 10 min. Subsequently, epi-
bromohydrin (300 mg, 2.2 mmol) wasadded at ꢀ78 ꢁC.
After warming of the mixture to 20 ꢁC for 16 h, a
saturated aqueous solution of NH4Cl (20 ml) wasadded.
The organic and the aqueouslayer were separated and the
latter wasextracted with ethyl acetate (3 · 30 ml). The
combined organic layerswere dried (Na 2SO4), filtered and
the solvent of the filtrate was removed in vacuo. The
residue was purified by chromatography (silica gel, n-
Acknowledgements
Financial support from the Deutsche Forschungsge-
meinschaft is gratefully acknowledged.
References and notes
1. (a) Streith, J.; Defoin, A. Synlett 1996, 189; (b) Defoin, A.;
Sarazin, H.; Streith, J. Tetrahedron 1997, 53, 13769.