C O MMU N I C A T I O N S
Scheme 2. Conversion of 14 to Furaquinocin E (5)a
Scheme 4. Synthesis of Analogue 27a
a
Conditions: (a) (i) n-BuLi, THF, -78 °C; (ii) 24, THF, -78 °C, 79%.
(
b) (i) PhCl, reflux; (ii) air, room temperature, 53%.
ligand 10. Using dimethylsquarate 24 for the construction of the
naphthoquinone gave 27.
The asymmetric palladium-catalyzed alkylation of phenols
combined with a reductive Heck reaction delivers an efficient
approach to the core structure of the furaquinocins. The use of a
protected squaric acid derivative allows the regioselective construc-
tion of the naphthoquinone. These reactions were highlighted in a
short asymmetric synthesis of furaquinocin E. The flexibility of
our approach should also allow for the synthesis of the other
furaquinocins, by changing the side-chain fragment, as well as of
analogues involving the quinone moiety. Efforts along this way
are currently pursued.
Acknowledgment. We acknowledge the National Science
Foundation and the National Institutes of Health (GM 33049) for
their generous support of our programs. O.R.T. thanks the Alex-
ander-von-Humboldt foundation for a postdoctoral fellowship. We
are grateful to A. Cole for solving the X-ray structure of 14. Mass
spectra were provided by the Mass Spectrometry Facility, University
of San Francisco, supported by the NIH Division of Research
Resources.
a
Conditions: (a) NaOMe, MeOH, room temperature, 94%. (b) TIPSOTf,
TEA, CH2Cl2, 96%. (c) NBS, THF, room temperature, 92%. (d) (i) DIBAL,
CH2Cl2, - 78 °C; (ii) 18, LHMDS, THF, 0 °C, 89% (two steps). (e) (i)
DIBAL, CH2Cl2, - 78 °C; (ii) TBDMSCl, imidazole, CH2Cl2, reflux, 89%
two steps). (f) (i) n-BuLi, THF, - 78 °C; (ii) 25, THF, -78 °C; (iii) oxalic
acid, THF/H2O, 50%. (g) (i) toluene, 110 °C; (ii) air, room temperature,
4%. (h) TBAF, THF, 0 °C, 65%.
(
6
Supporting Information Available: Characterization data for 5,
1
1, 13-17, 19-20, 22, 25-27 (PDF) and X-ray structure of 14 (CIF).
Scheme 3. Squaric Acid Derivativesa
This material is available free of charge via the Internet at http://
pubs.acs.org.
References
(
1) (a) Funayama, S.; Ishibashi, M.; Anraku, Y.; Komiyama, K.; Omura, S.
Tetrahedron Lett. 1989, 30, 7427. (b) Komiyama, K.; Funayama, S.;
Anraku, Y.; Ishibashi, M.; Takahashi, Y.; Omura, S. J. Antibiot. 1990,
a
Conditions: (a) (i) MeLi, THF, -100 °C; (ii) TFAA, -78 °C; (iii)
aniline, -78 °C to -15 °C (53%).
43, 247. (c) Funayama, S.; Ishibashi, M.; Komiyama, K.; Omura, S. J.
Org. Chem. 1990, 55, 1132. (d) Ishibashi, M.; Funayama, S.; Anraku,
Y.; Komiyama, K.; Omura, S. J. Antibiot. 1991, 44, 390.
ester to the alcohol, followed by TBDMS-protection, afforded the
advanced intermediate 20.
Squaric acid-based methodology is available for the construction
(2) (a) Smith, A. B., III; Sestelo, J. P.; Dormer, P. G. J. Am. Chem. Soc.
1
995, 117, 10755. (b) Smith, A. B., III; Sestelo, J. P.; Dormer, P. G.
Heterocycles 2000, 52, 1315.
(
3) (a) Saito, T.; Morimoto, M.; Akiyama, C.; Matsumoto, T.; Suzuki, K. J.
Am. Chem. Soc. 1995, 117, 10757. (b) Saito, T.; Suzuki, T.; Morimoto,
M.; Akiyama, C.; Ochiai, T.; Takeuchi, K.; Matsumoto, T.; Suzuki, K. J.
Am. Chem. Soc. 1998, 120, 11633.
7
of naphthoquinones. Use of the simple derivative 23 leads to
nucleophilic attack of a organometallic compound on the ketone
adjacent to the methoxy group (Scheme 3). After rearrangement
and oxidation, this would furnish a naphthoquinone which would
be regioisomeric to the furaquinocins concerning the substituents
on the quinone. To reverse the regioselectivity, a temporary
protection group was introduced.10 Imine 25 could be obtained in
(4) Trost, B. M.; Van Vranken, D. L.; Bingel, C. J. Am. Chem. Soc. 1992,
114, 9327. For a recent review: Trost, B. M. Chem. Pharm. Bull. 2002,
50, 1.
(
5) (a) Iwabuchi, Y.; Nakatami, M.; Yokoyama, N.; Hatekayama, S. J. Am.
Chem. Soc. 1999, 121, 10219. (b) Iwama, T.; Tsukiyama, S.; Kinoshita,
H.; Kanematsu, K.; Tsukurami, Y.; Iwamura, T.; Watanabe, S.; Kataoka,
T. Chem. Pharm. Bull. 1999, 47, 956. (c) Barrett, A. G. M.; Cook, A. S.;
Kamimura, A. Chem. Commun. 1998, 2553. (d) Hayase, T.; Shibata, T.;
Soai, K.; Wakalsuki, Y. Chem. Commun. 1998, 1271. (e) Marko, I. E.;
Giles, P. R.; Hindley, N. J. Tetrahedron 1997, 53, 1015. (f) Oishi, T.;
Oguri, H.; Hirama, M. Tetrahedron: Asymmetry 1995, 6, 1241. (g) For
use of a chiral auxiliary, see: Brzezinski, L. J.; Rafel, S.; Leahy, J. W. J.
Am. Chem. Soc. 1997, 119, 4317.
good yield, through a one-pot procedure.
Halogen-metal exchange on bromine 20 and addition of the
generated organolithium to imine 25, followed by hydrolysis of
the imine under mild acidic conditions, led to the addition product
2
1 in acceptable yield. All efforts to improve the yield, by using
(6) Trost, B. M.; Tsui, H.-C.; Toste, F. D. J. Am. Chem. Soc. 2000, 122,
534.
(
3
cerium- or magnesium-derived organometallics, failed. Thermal
rearrangement followed by oxidation in air delivers the desired
regioisomer of naphthoquinone 22. After deprotection of the silyl
ethers, furaquinocin E (5) is obtained. The spectroscopic data are
in full agreement with those published for the natural product.1d
To illustrate the flexibility of our strategy, an analogue was
prepared (Scheme 4). The intermediate 26 in the enantiomeric series
was obtained by the route described herein and by using the (S,S)-
7) (a) Moore, H. W.; Perri, S. T. J. Org. Chem. 1988, 53, 996. (b) Perri, S.
T.; Foland, S. D.; Decker, O. H. W.; Moore, H. W. J. Org. Chem. 1986,
5
1, 3067. (c) Liebeskind, L. S.; Iyer, S.; Jewell, C. F. J. Org. Chem. 1986,
1, 3065. (d) Liebeskind, L. S. Tetrahedron 1989, 45, 3053.
5
(8) (a) Schmidt, B.; Hoffmann, H. M. R. Tetrahedron 1991, 47, 9357. (b)
Also see: Trost, B. M.; Toste, F. D. J. Am. Chem. Soc. 1999, 121, 3543.
(
9) Evans, D. A.; Miller, S. J.; Ennis, S. D. J. Org. Chem. 1993, 58, 471.
(10) Winters, M. P.; Stranberg, M.; Moore, H. W. J. Org. Chem. 1994, 59,
572.
7
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J. AM. CHEM. SOC.
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