with previously reported approaches, the present metho-
dology reported also allows us to synthesize taiwaniaquinoids
which present an A/B trans-configuration. Thus, phenol 10 is a
suitable intermediate for synthesizing a wide range of taiwania-
quinoids. Utilizing this, the first synthesis of (À)-taiwaniaquinone
G (3) starting from commercial (+)-sclareolide (17) (14 steps,
25% overall yield) has been achieved.
The authors thank the Spanish Ministry of Science and
Technology (Project CTQ2006-12697) and the Junta de
Andalucia (PAI FQM-348) for financial support.
Notes and references
1 (a) W. Lin, J. Fang and Y. Chang, Phytochemistry, 1995, 40, 871;
(b) W. Lin, J. Fang and Y. Cheng, Phytochemistry, 1996, 42, 1657;
(c) C. Chang, S. Chien, S. Lee and Y. Kuo, Chem. Pharm., 2003,
51, 1420; (d) C.-I. Chang, J.-Y. Chang, C.-C. Kuo, W.-Y. Pan and
Y.-H. Kuo, Planta Med., 2005, 71, 72.
2 H. Ohtsu, M. Iwamoto, U. Ohishi, S. Matsunaga and R. Tanaka,
Tetrahedron Lett., 1999, 40, 6419.
3 K. Kawazoe, M. Yamamoto, Y. Takaishi, G. Honda, T. Fujita
and E. Sezik, Phytochemistry, 1999, 50, 493.
4 (a) M. Iwamoto, H. Ohtsu, H. Tokuda, H. Nishino, S. Matsunaga
and R. Tanaka, Bioorg. Med. Chem., 2001, 9, 1911; (b) T. Minami,
M. Iwamoto, H. Ohtsu, H. Ohishi, R. Tanaka and A. Yoshitake,
Planta Med., 2002, 68, 742; (c) J. Hanson, Nat. Prod. Rep., 2004,
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5 R. M. Mc Fadden and B. M. Stoltz, J. Am. Chem. Soc., 2006, 128,
7738.
6 E. Fillion and D. Fishlock, J. Am. Chem. Soc., 2005, 127, 13144.
7 S. Li and P. Chiu, Tetrahedron Lett., 2008, 49, 1741.
8 G. Liang, Y. Xu, I. B. Sciple and D. Trauner, J. Am. Chem. Soc.,
2006, 126, 11022.
Scheme 4 Synthesis of (À)-taiwaniaquinone G (3) from phenol 10.
hydroxyphenol 22 ([a]2D5: À17.41; c 0.8, CHCl3) by treatment
with MeMgBr (4 equiv.). Treatment of this compound with
Et3SiH and CF3COOH gave the desired phenol 10 ([a]2D5:
À19.41; c 1.1, CHCl3).
Finally, the functionalization of the aromatic C ring was
addressed. After considering the previously reported taiwania-
quinoids, we focused on taiwaniaquinone G (3), the most
immediate terpenoid possessing an A/B trans-configuration
which has not yet been synthesized. At this point, it should be
emphasized that intermediate 10 possesses a different substitution
pattern from that of the phenolic precursors utilized in previously
reported syntheses, which forced us to investigate new strategies
to achieve the target quinone. Most preceding authors utilized
1,3-6,8 or 3,4-dihydroxy10 derivatives, instead of the 1-hydroxy
substituted compound 10 reported here; those were transformed
into the final compound after a 2- or 3-step sequence in 45–52%
yield. Stoltz5 and She11 used a 3-hydroxy precursor, which
afforded quinone 9 in a 3-step sequence (35% overall yield).
Starting from phenol 10, we have developed a very efficient
synthesis of taiwaniaquinone G (3) (Scheme 4).
9 L. Planas, M. Mogi, H. Takita, T. Ajimoto and M. Node, J. Org.
Chem., 2006, 71, 2896.
10 M. Banerjee, R. Mukhopadhyay, B. Achari and A. K. Banerjee,
Org. Lett., 2003, 5, 3931; M. Banerjee, R. Mukhopadhyay,
B. Achari and A. K. Banerjee, J. Org. Chem., 2006, 71, 2787.
11 S. Tang, Y. Xu, J. He, J. Zheng, X. Pan and X. She, Org. Lett.,
2008, 10, 1855.
12 E. J. Alvarez-Manzaneda, R. Chahboun, E. Cabrera Torres,
E. Alvarez, R. Alvarez-Manzaneda, A. Haidour and J. M.
Ramos, Tetrahedron Lett., 2004, 45, 4453 and references cited
therein.
Quinone 23 ([a]2D5: À26.31; c 0.9, CHCl3) was smoothly ob-
tained by treating phenol 10 with Fremy’s salt. All our attempts
to directly transform compound 23 into methoxy derivative 3,
utilizing diverse previously reported conditions, e.g. HgCl2, I2,
MeOH16 or Fe2(SO4)3, MeOH,17 were unsuccessful. This goal
was finally achieved after treatment of bromoquinone 24 ([a]2D5:
À23.61; c 1.1, CHCl3) with MeONa in MeOH.
13 H. Tanimoto and T. Oritani, Tetrahedron: Asymmetry, 1996, 7,
1695.
14 Synthesis of compound 14 has also been reported by Hagiwara
et al. These authors prepared this homoallylic iodide from a
Wieland–Miescher ketone analogue, after an 11-step sequence
(21% overall yield). See: (a) H. Hagiwara, F. Takeuchi,
M. Nozawa, T. Hoshi and T. Suzuki, Tetrahedron, 2004, 60,
1983; (b) H. Hagiwara, H. Nagatomo, S. Kazayama, H. Sakai,
T. Hoshi, T. Suzuki and M. Ando, J. Chem. Soc., Perkin Trans. 1,
1999, 457; (c) H. Hagiwara and H. Uda, J. Org. Chem., 1988, 53,
2308.
15 Ozonolysis of compound 14 to give diketone 18 has also been
accomplished by Hagiwara’s group (ref. 14a). However, these
authors reported low yields for this transformation, probably
due to the small quantity of starting material they utilized.
16 G. A. Kraus and I. Kim, J. Org. Chem., 2003, 68, 4517.
17 G. A. Kraus and N. Zhang, Tetrahedron Lett., 2002, 43, 9597.
In this way, phenol 10 was transformed into taiwaniaquinone
G (3) in a 3-step sequence in 81% overall yield. The optical
rotation of synthetic taiwaniaquinone G (3) ([a]2D5: À91.41; c 1.1,
CHCl3) was similar to that reported for the natural product
([a]2D2: À120.81; c 0.29, CHCl3); the spectroscopic properties were
identical to those previously described.1d
In summary, a new synthetic strategy towards taiwaniaquinoids,
based on a thermal 6p electrocyclization, is described. In contrast
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This journal is The Royal Society of Chemistry 2009
594 | Chem. Commun., 2009, 592–594