1744
S. Li, P. Chiu / Tetrahedron Letters 49 (2008) 1741–1744
OH
OMe
established under the University Grants Committee of
the Hong Kong Special Administrative Region, China
(Project No. AoE/P-10/01).
OH
O
O
O
H
H
b
a
MeO
MeO
MeO
OMe
OMe
OH
14
2
Taiwaniaquinol B(1)
Supplementary data
OMe
O
H
Detailed experimental procedures for the synthesis and
characterization of compounds 2, 3, 6–8. Supplementary
data associated with this article can be found, in the online
refs. 9, 11
MeO
15
Scheme 4. Synthesis of Taiwaniaquinol B (1) Reaction conditions: (a)
BCl3, 1 M in CH2Cl2, 0 °C, 20 min, 98%; (b) (i) PhI(OAc)2, CH3CN/H2O
(2:1), rt, 0.5 h, (ii) Na2S2O3, rt, 2 h, 85%.
References and notes
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Pharm. Bull. 2003, 51, 1420; (d) Chang, C. I.; Chang, J.-Y.; Kuo,
C.-C.; Pan, W.-Y.; Kuo, Y.-H. Planta Med. 2005, 71, 72.
2. Kawazoe, K.; Yamamoto, M.; Takaishi, Y.; Honda, G.; Fujita, T.;
Sezik, E.; Yesilada, E. Phytochemistry 1999, 50, 493.
3. Ohtsu, H.; Iwamoto, M.; Ohishi, H.; Matsunaga, S.; Tanaka, R.
Tetrahedron Lett. 1999, 40, 6419.
4. Iwamoto, M.; Ohtsu, H.; Tokuda, H.; Nishino, H.; Matsunaga, S.;
Tanaka, R. Bioorg. Med. Chem. 2001, 9, 1911.
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reaction, following both pathways a and b (Table 1, entry
6). The fact that using TMSOTf as a Lewis acid led to the
generation of some 2 could be due to the promotion of the
reaction by TMSOTf by pathway b, then due to small
amounts of TfOH in the reaction, further resulted in
tricycle 2 (Table 1, entry 9). The presence of TfOH is also
implicated in the substantial yield of 7 in this reaction.
Since compound 2 is a key intermediate in Banerjee’s
total synthesis8 of ( )-taiwaniaquinol B and ( )-taiwani-
aquinone D, this synthetic route already constitutes a short
formal total synthesis of these two natural products.
However, we found that the application of an alternative
three-step protocol, slightly modified from that reported
by Fillion11 and by Trauner,9 resulted in a superior yield
of taiwaniaquinol B (Scheme 4). The selective and quanti-
tative demethylation of 2 by boron trichloride to give 14,
followed by a mild PhI(OAc)2 oxidation,20 and a sodium
thiosulfate reduction21 in one-pot afforded ( )-taiwani-
aquinol B. Using a less oxidized aromatic precursor 15
(Scheme 4), the final functionalizations to generate 1 by
Fillion and Trauner proceeded in 47% and 48% yields,
respectively, compared to 83% from 2 in this work.
In conclusion, we have developed an efficient route for
the synthesis of the hydrofluorenone carboskeleton by
sequential cationic cyclizations promoted by acid. From
trienone 3, cyclization to form ring C is promoted by Lewis
acid, while cyclization to give ring B is induced by Brønsted
acid. A one-pot domino bis-cyclization to generate the
rings B and C is possible through the use of TMSOTf,
albeit in low yield. The direct treatment of trienone 3 with
Brønsted acid results instead in the formation of a bicyclic
enol ether. This route is applicable to the synthesis of other
taiwaniaquinoid natural products and analogues with sim-
ilar skeletons. Efforts to optimize the domino cyclization
and establish asymmetric versions of this synthesis are in
progress.
13. (a) Sutherland, J. K. In Comprehensive Organic Synthesis; Trost, B.
M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 3, p 341; (b)
Brunoldi, E.; Luparia, M.; Porta, A.; Zanoni, G.; Viari, G. Curr. Org.
Chem. 2006, 10, 2259.
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121, 7443; (b) Tius, M. A. Eur. J. Org. Chem. 2005, 2193.
15. Carreno, M. C.; Ruano, J. L. G.; Toledo, M. A.; Urbano, A.
˜
Tetrahedron: Asymmetry 1997, 8, 913.
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¨
Stetter, H.; Hillboll, G.; Skobel, S. Chem. Ber. 1986, 119, 1689.
17. Cyclization of geranic acid occurred in the presence of both protic and
Lewis acids: (a) Bernhauer, K.; Forster, R. J. Prakt. Chem. 1936, 147,
199; (b) Stork, G.; Burgstahler, A. W. J. Am. Chem. Soc. 1955, 77,
5068.
18. Pseudodamascone cyclizes to give a-damascone under both protic and
Lewis acidic conditions: Schulte-Elte, K. H.; Strickler, H.; Firtz, G.;
Pickenhagen, W.; Gadola, M.; Limacher, J.; Mueller, B. L.; Wuffli,
F.; Ohloff, G. Liebigs Ann. Chem. 1975, 484.
19. Suzuki, T.; Ohwada, T.; Shudo, K. J. Am. Chem. Soc. 1997, 119,
6774.
20. Pelter, A.; Elgendy, S. Tetrahedron Lett. 1988, 29, 677.
21. Vincent, G.; Williams, R. M. Angew. Chem., Int. Ed. 2007, 46,
1517.
Acknowledgments
This research was supported by the University of Hong
Kong, the Research Grants Council of Hong Kong SAR
(HKU 7017/04P), and the Areas of Excellence Scheme