J. H. Rigby, M. Aasuml / Tetrahedron Letters 44 (2003) 5029–5031
5031
(3)
Equations (2) and (3) depict reactions in which the aryl
ring moiety possesses either a methoxy or thiomethoxy
substituent. Not surprisingly the methoxy methyl group
is severed during the conversion of 107 into 117 whereas
the thiomethyl group survives the corresponding trans-
formation of 137 into 14.7
2. For recent entries into the benzoxepin system, see: (a)
Sugita, Y.; Yokoe, I. Heterocycles 2000, 53, 1251; (b)
Satoh, T.; Kurihara, T. Tetrahedron Lett. 1998, 39,
9215; (c) Fu¨rstner, A.; Thiel, O. R. J. Org. Chem. 2000,
65, 2204; (d) Rayabarapu, D. K.; Cheng, C.-H. J. Am.
Chem. Soc 2002, 124, 5630.
3. Murray, R. D. H.; Robinson, J. A. In Progress in the
Chemistry of Organic Natural Products; Herz, W.; et al.,
Eds.; Springer-Verlag, 1991; Vol. 58, p. 204.
4. Couture, P.; Terlouw, J. K.; Warkentin, J. J. Am. Chem.
Soc. 1996, 118, 4214.
5. (a) Rigby, J. H. Synlett 2000, 1; (b) Rigby, J. H.; Lau-
rent, S.; Dong, W.; Danca, M. D. Tetrahedron 2000, 56,
10101; (c) Rigby, J. H.; Wang, Z. Org. Lett. 2002, 4,
4289; (d) Rigby, J. H.; Wang, Z. Org. Lett. 2003, 5, 263.
6. (a) Hofmann, R. H.; Luthhardt, H. J. Chem. Ben. 1968,
101, 3861; (b) Bekhazi, M.; Smith, P. J.; Warkentin, J.
Can. J. Chem. 1984, 62, 1646; (c) Sharma, P. K.;
Warkentin, J. Tetrahedron Lett. 1995, 36, 7591; (d)
Lown, J. W.; Matsumoto, K. Can. J. Chem. 1971, 49,
3443; (e) Bekhazi, M.; Warkentin, J. Can. J. Chem.
1983, 61, 619.
Several other examples of this novel ring forming pro-
cess are collected in Table 1. It is noteworthy that a
nitro substituent seems to survive the reaction condi-
tions more or less intact, although the yield of the
resultant benzoxepin is modest. It is possible that the
powerful electron withdrawing character of this sub-
stituent has a deleterious influence on the course of the
rearrangement process. Entry 4 reveals that this reac-
tion sequence can be extended to a dihydrofuran
exhibiting a naphthalene substituent.
Further work is currently underway in our laboratory
to clarify certain aspects of the mechanistic pathway for
the conversion of the dihydrofurans into benzoxepins.
7. This compound exhibits spectral (1H, 13C NMR, IR)
and analytical (HRMS and/or combustion analysis) data
fully consistent with the assigned structure.
8. Typical cycloaddition procedure: A mixture of the oxa-
diazoline (1 equiv.) and DMAD (2 equiv.) was heated in
benzene at reflux for 16–24 h. The products were
purified by flash column chromatography.
Acknowledgements
The authors wish to thank the National Science Foun-
dation for their generous support of this research.
References
9. Typical rearrangement procedure: To a solution of the
dihydrofuran (1 equiv.) in CH2Cl2 at 0°C was added
BBr3 (4 equiv.). The resultant mixture was stirred at
room temperature for 48 h at which time it was
quenched with H2O and extracted into CH2Cl2. The
products were purified by flash column chromatography.
10. The identity of compound 8 was unambiguously estab-
lished by single-crystal X-ray analysis.
1. (a) Engler, A.; Anke, T.; Sterner, O. J. Antibiot. 1997,
50, 330; (b) Ishikawa, N. K.; Yamaji, K.; Tahara, S.;
Fukushi, Y.; Takahasio, K. Phytochemistry 2000, 54,
777; (c) Marriott, K.-S.; Anderson, M.; Jackson, Y. A.
Heterocycles 2001, 55, 91; (d) Tersawa, K.; Hosoya, H.;
Sugita, Y.; Yokoe, I.; Sakagami, H. Anticancer Res.
2000, 20, 2951.