D. Sarkar, R. V. Venkateswaran / Tetrahedron Letters 52 (2011) 3232–3233
3233
exposing the alkene to a stream of hydrogen in the presence of
Wilkinson catalyst to provide O-ethylbruguierol A (19)5 in quanti-
tative yield. Finally de-ethylation of 19 by treatment with sodium
ethylmercaptide in DMF afforded bruguierol A (1) in 78% yield as a
crystalline solid, whose mp and spectral characteristics fully
matched with those reported.3a,d Initial efforts at ring opening
and recyclisation of trans diene 17 to improve the yield of 18 have
not been encouraging and further studies will be needed.
In summary we have described an expedient synthesis of bru-
guierol A, encompassing a novel benzoxabicyclo[3.2.1]octane ring
system. The oxa-bridged tricyclic core was developed employing
ring closing metathesis as a key step. It is anticipated that, with
appropriate change in substitution in the aromatic ring, this meth-
odology can be extended for the synthesis of the related 2 and 3.
Acknowledgements
We thank the Department of Science and Technology, New Del-
hi, Govt. of India for the financial support. D.S. thanks the Council
of Scientific and Industrial Research, New Delhi for a Senior Re-
search fellowship.
References and notes
1. Han, L.; Huang, X.; Sattler, I.; Moellmann, U.; Fu, H.; Lin, W.; Grabley, S. Planta
Med. 2005, 71, 160–164.
2. (a) Onyeji, C. O.; Nicolaou, D. P.; Nightingale, C. H.; Bow, L. Int. J. Antimicrob.
Agents 1999, 11, 31–37; (b) Lefort, A.; Baptista, M.; Fantin, B.; Depardieu, F.;
Arthur, M.; Carbon, C.; Courvalin, P. Antimicrob. Agents Chemother. 1999, 43,
476–482.
Scheme 1.
3. (a) Ramana, C. V.; Salian, S. R.; Gonnade, R. G. Eur. J. Org. Chem. 2007, 5483–
5486; (b) Wu, J.-Z.; Zhen, Z. B.; Zhang, Y. H.; Wu, Y. K. Acta Chim. Sinica 2008, 66,
2138–2140; (c) Solorio, D. M.; Jennings, M. P. J. Org. Chem. 2007, 72, 6621–6623;
(d) Fananás, F. J.; Fernández, A.; Cevic, D.; Rodríguez, F. J. Org. Chem. 2009, 74,
932–934; (e) Hu, B.; Xing, S.; Ren, J.; Wang, Z. Tetrahedron 2010, 66, 5671–5674.
4. Sarkar, D.; Ghosh, S.; Venkateswaran, R. V. Tetrahedron Lett. 2009, 50, 1431–
1434.
5. All new compounds reported here gave analytical and spectral data consistent
with assigned structures. Selected spectral data: For 14: IR (KBr)
m ,
max 1690 cmÀ1
1720 cmÀ1 1H NMR (500 MHz, CDCl3) d 9.7 (s, 1H), 7.87 (d, J = 9 Hz, 1H), 6.85
.
(dd, J = 2.5 Hz, 9.2 Hz, 1H), 6.71 (d, J = 2.5 Hz, 1H), 4.09 (q, J = 7 Hz, 2H), 3.96 (s,
2H), 2.55 (s, 3H), 1.43 (t, J = 7 Hz, 3H). 13C NMR (125 MHz, CDCl3) d 198.95,
198.85, 162.2, 136.93, 133.52, 128.84, 119.53, 112.74, 63.95, 49.9, 28.39, 14.8.
HR-MS (EI) calcd for C12H14O3 207.0841, found 207.0839 [M+H]+. For 17: 1H
NMR (500 MHz, CDCl3) d 7.02 (d, J = 8.5 Hz, 1H), 6.76 (dd, J = 2 Hz, 8.5 Hz, 1H),
6.6 (d, J = 1.6 Hz, 1H), 5.97–6.04 (m, 2H), 5.35 (d, J = 17 Hz, 1H), 5.21 (d, J = 11 Hz,
1H), 5.15 (d, J = 11 Hz, 1H), 4.88 (d, J = 17.5 Hz, 1H), 4.29–4.27 (m, 1H), 4.03 (q,
J = 7 Hz, 2H), 2.85 (dd, J = 11 Hz, 16 Hz, 1H), 2.65 (dd, J = 16 Hz, 2.5 Hz, 1H), 1.58
(s, 3H), 1.41 (t, J = 7 Hz, 3H). 13C NMR (125 MHz, CDCl3) d 157.43, 144.03, 138.9,
135.19, 131.16, 128.6, 115.6, 115.2, 113.9, 112.8, 78.18, 69.88, 63.5, 35.2, 30.9,
15.03. HR-MS (EI) calcd for C16H20O2 245.1361, found 245.1367 [M+H]+. For 18:
1H NMR (300 MHz, CDCl3) d 6.95 (d, J = 8.4 Hz, 1H), 6.54 (d, J = 8.4 Hz, 1H), 6.52
(s, 1H), 6.13 (d, J = 5.7 Hz, 1H), 5.82 (dd, J = 1.5 Hz, 5.8 Hz, 1H), 5.01–5.03 (m,
1H), 3.90 (q, J = 6.9 Hz, 2H), 3.2 (dd, J = 6.04 Hz, 17.8 Hz, 1H), 2.36 (d, J = 17 Hz,
1H), 1.66 (s, 3H), 1.28 (t, J = 6.9 Hz, 3H). 13C NMR (125 MHz, CDCl3) d 158.58,
141.27, 135.22, 133.91, 127.21, 122.47, 116.75, 110.93, 83.65, 78.82, 63.51,
30.58, 19.86, 15.01. HR-MS (EI) calcd for C14H16O2 217.1048, found 217.1049
[M+H]+. For 19: 1H NMR (500 MHz, CDCl3) d 6.98 (d, J = 8.5 Hz, 1H), 6.6 (dd,
J = 2.0 Hz, 8.0 Hz, 1H), 6.53 (d, J = 2.5 Hz, 1H), 4.64 (t, J = 6 Hz, 1H), 3.92 (q,
J = 7 Hz, 2H), 3.26 (dd, J = 5.5 Hz, 16.2 Hz, 1H), 2.39 (d, J = 16.5 Hz, 1H), 2.17–2.18
(m, 1H), 2.16–2.17 (m, 1H), 1.89–1.94 (m, 1H), 1.73–1.78 (m, 1H), 1.63 (s, 3H),
1.31 (t, J = 7 Hz, 3H). 13C NMR (125 MHz, CDCl3) d 157.75, 136.53, 133.48,
123.89, 115.05, 112.2, 80.4, 74.4, 63.49, 43.1, 37.88, 29.8, 23.0, 15.0. HR-MS (EI)
calcd for C14H18O2 219.1205; found 219.1204 [M+H]+.
Scheme 2. Reagents and conditions: (a) K2CO3, acetone, MeI, reflux, 3 h, 92%; (b)
K2CO3, acetone, EtI, reflux, 3 h, 90%; (c) potassium tert-butoxide, methoxymethyl-
triphenyl phosphonium chloride, THF, À5 °C to rt, 1 h followed by 2 M HCl, THF, rt,
4 h, 80% (for two steps); (d) CH3COBr, AlBr3, DCM, 0 °C to rt, 2 h, 60%; (e)
vinylmagnesium bromide (2 equiv), THF, 0 °C to rt, 1 h; (f) 1 M H2SO4, THF, rt,
30 min, 60% (for two steps); (g) Grubbs’ 2nd generation (0.005 mol), DCM, rt, 7 h,
47%; (h) Rh(PPh3)3Cl, H2, rt, 11 h, 98%; (i) EtSNa, DMF, 110 °C,12 h, 86%.
was obtained in 47% yield and the structure of this tricyclic ring
system was adequately supported by spectral characteristics.5
Selective hydrogenation of the double bond was achieved by