LETTER
Synthesis of Benzofused Bisoxepin and Bisoxocin Derivatives
2213
(15) (a) Kong, Z.-L.; Tzeng, S.-C.; Liu, Y.-C. Bioorg. Med.
Chem. Lett. 2005, 15, 163. (b) Pearson, D. P. G.; Leigh, S.
J.; Sutherland, I. O. J. Chem. Soc., Perkin Trans. 1 1979,
3113. (c) Sorrell, T. N.; Ellis, D. J. J. Org. Chem. 1985, 50,
5765.
(16) Ithart, A.; Plubrukarn, A.; Kongsaeree, P.; Bui, T.;
Keawpradub, N.; Houghton, P. J. Org. Lett. 2003, 5, 2879.
(17) Takahasi, I.; Nomura, A.; Kitajama, H. Synth. Commun.
1990, 20, 1569.
We therefore wondered whether the methodology could
be utilized to access oxepin-fused anthraquinone deriva-
tives. During attempted monorearrangement of 1,5-di-
allyloxyanthraquinone (32), the biphenol 33 was
obtained18 in 26% yield as a by-product. We have
observed that the yield of the latter could be raised to 65%
if the reaction was conducted under identical conditions
but for 5 hours instead of 2.5 hours as reported. The latter
was then subjected to the same sequence of reactions, viz.
double allylation19 leading to the bisdiene 34 followed by
its TDRCM20 smoothly led to the bisoxepin derivative 35
in good yield.21
(18) Cambie, R. C.; Howe, T. A.; Pausler, M. G.; Rutledge, P. S.;
Woodgate, P. D. Aust. J. Chem. 1987, 40, 1063.
(19) General Procedure for the Synthesis of the Bisdienes.
A heterogeneous mixture of the appropriate biphenol (1.0
mmol), allyl bromide (or 4-bromobutene; 4.0 mmol), anhyd
K2CO3 (8.0 mmol) and dry acetone (10 mL) was refluxed
under stirring under nitrogen atmosphere for 18 h. It was
then filtered and the filter cake was washed with acetone
(2 × 10 mL). The combined acetone solution was then
concentrated in vacuo and the residual mass was
In short, we have demonstrated that sequential double
Claisen rearrangement and TDRCM provides direct ac-
cess to a range of hitherto unknown benzofused bisoxepin
and bisoxocin derivatives in good yield. The compounds
prepared may prove to be of biological interest.
chromatographed over silica gel.
Data for compound 3: 1H NMR (300 MHz, CDCl3): d = 6.84
(s, 1 H), 6.13–5.91 (m, 4 H), 5.45 (dd, 2 H, J = 17.1, 1.2 Hz),
5.27 (d, 2 H, J = 9.4 Hz), 5.08 (overlapping doublets, 4 H),
4.28 (d, 4 H, J = 5.4 Hz), 3.36 (d, 4 H, J = 6.5 Hz), 2.22 (s,
3 H). 13C NMR (75 MHz, CDCl3): d = 153.9 (s), 137.2 (d),
129.4 (d), 128.7 (d), 125.0 (s), 115.8 (t), 111.4 (s), 75.1 (t),
34.1 (t), 10.7 (q). Anal. Calcd for C19H24O2: C, 80.24; H,
8.51. Found: C, 80.48; H, 8.39.
Acknowledgment
Financial assistance from DST, New Delhi (Grant No. SR/S1/OC-
51/2005) is gratefully acknowledged. T.B. is thankful to CSIR, New
Delhi, for a fellowship.
Compound 10: 1H NMR (300 MHz, CDCl3): d = 6.67 (s, 2
H), 6.04–5.96 (m, 4 H), 5.42 (dd, 2 H, J = 17.2, 1.4 Hz), 5.22
(dd, 2 H, J = 10.4, 1.1 Hz), 5.04–5.01 (m, 4 H), 4.48 (d, 4 H,
J = 1.2 Hz), 3.37 (d, 4 H, J = 6.3 Hz). 13C NMR (75 MHz,
CDCl3): d = 150.3 (s), 137.1 (d), 133.8 (d), 127.5 (s), 116.8
(t), 115.4 (t), 114.5 (d), 69.8 (t), 34.2 (t). Anal. Calcd for
C18H22O2: C, 79.96; H, 8.20. Found: C, 80.07; H, 8.23.
Compound 16: mp 82 °C. 1H NMR (300 MHz, CDCl3):
d = 7.40–7.34 (m, 4 H), 6.88 (d, 2 H, J = 9.1 Hz), 6.15–5.98
(m, 4 H), 5.45 (d, 2 H, J = 17.4 Hz), 5.29 (d, 2 H, J = 9.6 Hz),
5.14–5.05 (m, 4 H), 4.58 (d, 4 H, J = 4.8 Hz), 3.48 (d, 4 H,
J = 6.5 Hz). 13C NMR (75 MHz, CDCl3): d = 155.3 (s),
136.9 (d), 133.5 (d), 133.4 (d), 129.0 (s), 128.3 (s), 125.3 (d),
116.8 (t), 115.4 (t), 111.8 (d), 68.8 (t), 34.5 (t).
References and Notes
(1) Stefinovic, M.; Snieckus, V. J. Org. Chem. 1998, 63, 2808.
(2) (a) Kishuku, H.; Shindo, M.; Shishido, K. Chem. Commun.
2003, 350. (b) Sabui, S. K.; Venkateswaran, R. V.
Tetrahedron Lett. 2004, 45, 983. (c) Lecornue, F.; Ollivier,
J. Synlett 2004, 1613. (d) Vyvyan, J. R.; Oaksmith, J. M.;
Parks, B. W.; Peterson, E. M. Tetrahedron Lett. 2005, 46,
2457.
(3) Huang, S.; Kuo, H.; Chen, C. Tetrahedron Lett. 2001, 42,
7473.
(4) Satoh, Y.; Libby, A. H.; Powers, C.; Kowalski, T.; White, D.
H.; Kimble, E. F. Bioorg. Med. Chem. Lett. 1994, 4, 549.
(5) Kiyama, R.; Honma, T.; Hayashi, K.; Ogawa, M.; Hara, M.;
Fujimoto, M.; Fujishita, T. J. Med. Chem. 1995, 38, 2728.
(6) Carl, K.; Joseph, L. US 4,073,912; Chem. Abstr. 1978, 89,
24156.
(7) For a review, see: Yet, L. Chem. Rev. 2000, 100, 2963.
(8) For some recent applications of RCM reaction in medium
ring heterocycle formation, see: (a) Barberis, M.; Losada, P.
G.; Pleite, S.; Rodriguez, J. R.; Soriano, J. F.; Mendiola, J.
Tetrahedron Lett. 2005, 46, 4847. (b) Gracias, V.; Gasiecki,
A. F.; Djuric, S. W. Org. Lett. 2005, 7, 3183. (c) Kim, Y. J.;
Lee, D. Org. Lett. 2004, 6, 4351. (d) Lane, C.; Snieckus, V.
Synlett 2000, 1294.
(9) (a) Chattopadhyay, S. K.; Maity, S.; Panja, S. Tetrahedron
Lett. 2002, 43, 7781. (b) Chattopadhyay, S. K.; Dey, R.;
Biswas, S. Synthesis 2005, 403.
(10) Kotha, S.; Mandal, K. Tetrahedron Lett. 2004, 45, 1391.
(11) Pain, C.; Celanire, S.; Guillaunet, G.; Joseph, B. Synlett
2003, 2089.
Compound 28: 1H NMR (300 MHz, CDCl3): d = 7.82 (d, 2
H, J = 8.4 Hz), 7.32 (d, 2 H, J = 8.5 Hz), 6.26–6.15 (m, 2 H),
6.08–5.99 (m, 2 H), 5.51 (dd, 2 H, J = 17.4, 1.4 Hz), 5.32
(dd, 2 H, J = 11.2, 1.0 Hz), 5.13–5.07 (m, 4 H), 4.49 (d, 4 H,
J = 5.4 Hz), 3.59 (d, 4 H, J = 6.3 Hz). 13C NMR (75 MHz,
CDCl3): d = 152.5 (s), 137.2 (d), 133.9 (d), 128.9 (s), 128.3
(d), 128.0 (s), 118.3 (d), 117.3 (t), 115.9 (t), 75.3 (t), 33.9 (t).
Anal. Calcd for C22H24O2: C, 82.46; H, 7.55. Found: C,
82.57; H, 7.64.
Compound 34: mp 98 °C. IR (KBr,): 1669, 1258, 1073, 993
cm–1. 1H NMR (300 MHz, CDCl3): d = 8.04 (d, 2 H, J = 7.9
Hz), 7.60 (d, 2 H, J = 7.9 Hz), 6.27–6.16 (m, 2 H), 6.02–5.94
(m, 2 H), 5.44 (dd, 2 H, J = 17.2, 1.0 Hz), 5.32 (d, 2 H,
J = 10.1 Hz), 5.16–5.09 (m, 4 H), 4.54 (d, 4 H, J = 5.6 Hz),
3.55 (d, 4 H, J = 6.4 Hz). 13C NMR (75 MHz, CDCl3):
d = 180.5 (s), 156.7 (s), 141.6 (s), 135.7 (d), 135.5 (s), 133.7
(d), 125.3 (s), 123.4 (d), 118.0 (t), 117.0 (t), 75.2 (t), 34.2 (t).
Anal. Calcd for C26H24O4: C, 77.98; H, 6.04. Found: C,
78.11; H, 6.20.
(12) (a) Wallace, D. J. Tetrahedron Lett. 2005, 46, 591.
(b) Clark, J. S.; Hamelin, O. Angew. Chem. Int. Ed. 2000, 39,
372. (c) Bassindale, M. J.; Hamley, P.; Leituer, A.; Harrity,
J. P. A. Tetrahedron Lett. 1999, 40, 3247. (d) Fang, Z.;
Hong, J. H. Org. Lett. 2004, 6, 993. (e) Ahmed, A.; Ohler,
E.; Mulzer, J. Synthesis 2001, 2007.
(20) General Procedure for TDRCM.
To a solution of the appropriate bisdiene (0.2 mmol) in dry,
degassed CH2Cl2 (25 mL) was added Grubbs’ catalyst (5, 15
mg, 10 mol%) under argon atmosphere and the resulting
solution was stirred at r.t. for the time indicated in Table 1.
(13) Chattopadhyay, S. K.; Paul, B. K.; Maity, S. Chem. Lett.
2003, 32, 1190.
(14) Schlosser, M.; Michel, D.; Croft, S. L. Synthesis 1996, 591.
Synlett 2006, No. 14, 2211–2214 © Thieme Stuttgart · New York