8920
M. Ebisawa et al. / Tetrahedron Letters 48 (2007) 8918–8921
OMe
OBn
those reported for naturally occurring dictyomedins A
and B.
4
EtOOC
EtOOC
OMe
OBn
HO
t-Bu-P4 base (10 mol%)
O
F
In conclusion, the first syntheses of dyctyomedins A, B
have been accomplished using phosphazene catalyzed
diarylether formation and palladium catalyzed intramo-
lecular biaryl formation as key steps and the structures
of natural dictyomedins were unambiguously confirmed.
Further study for the analog synthesis of dyctyomedins
using our methodology for biological evaluation is
underway.
3
TMS-NEt2 (2 eq.), DMF
rt, 3 h, 94%
Br
Br
12
O
EtOOC
OMe
OBn
X
B
O
5a: X=OMe
5b: X=H
O
BnO
PdCl2(dppf) (3 mol%)
2M Na2CO3, Dioxane
100 oC, 24 h
13a: X= OMe 98%
13b: X= H 94%
X
OBn
Scheme 1. Biaryl ether synthesis and Suzuki coupling.
Acknowledgments
This work was partly supported by the Grant-in-Aid for
Scientific Research on Priority Areas ‘Advanced Mole-
cular Transformations of Carbon Resources’ (No.
19020005) and ‘Synergistic Effects for Creation of Func-
tional Molecules’ (No. 19027008) and other Research
Grants (No. 19390002 and No. 18659001) from the
Ministry of Education, Science, Sports and Culture,
Japan, and a grant from Yamada Science Foundation.
We thank Dr. Haruhisa Kikuchi for the generous supply
of valuable data of dictyomedins and for kind
discussions.
ined the halogenation of 13a,b. Judging from the electron
density of aromatic ring carbons, the halogenation is
expected to proceed at the position adjacent to biaryl
ether oxygen at B ring. So the diaryl ethers 13a,b were
treated with NBS in DMF at room temperature and
the desired mono brominated products 14a,b were
obtained in 94%, 91% yields, respectively. Then, palla-
dium catalyzed intramolecular biaryl formation11 was
investigated and 14a,b were treated with Pd(OAc)2 and
PCy3 in the presence of K2CO3 at 100 °C for 1 h under
microwave irradiation. Conventional oilbath heating
gave the product in low yield with the formation of many
side products. The use of microwave dramatically accel-
erated the cyclization and the irradiation was critical to
obtain the products in high yields in a shorter reaction
time (Scheme 2).
Supplementary data
Experimental procedures and spectral data of synthe-
sized compounds. Supplementary data associated with
this article can be found, in the online version, at
The final deprotection of benzyl groups was carried
out by H2, 10% Pd/C and the consequent hydrolysis
of the ethoxycarbonyl group afforded dictyomedins A
and B in 98% and 86% yields, respectively. (Scheme 3,
1a and 1b). The spectroscopic properties of both
synthetic dyctyomedins A and B were identical with
References and notes
1. (a) Takaya, Y.; Kikuchi, H.; Komiya, J.; Maeda, Y.; Ito,
A.; Oshima, Y. Tetrahedron Lett. 2001, 42, 61; (b)
Kaniwa, K.; Ohtsuki, T.; Yamamoto, Y.; Ishibashi, M.
Tetrahedron Lett. 2006, 47, 1505.
2. (a) Sawyer, J. S. Tetrahedron 2000, 56, 5045; (b) Lee, M.;
Bernardo, M. M.; Meroueh, S. O.; Brown, S.; Fridman,
R.; Mobashery, S. Org. Lett. 2005, 7, 4463; (c) Nicolaou,
K. C.; Cho, S. Y.; Hughes, R.; Winssinger, N.; Smethurst,
C.; Labischinski, H.; Endermann, R. Chem. Eur. J. 2001,
7, 3798; (d) Boger, D. L.; Yohannes, D.; Zhou, J.; Patane,
M. A. J. Am. Chem. Soc. 1993, 115, 3420.
3. (a) Chen, Y.-J.; Chen, H.-H. Org. Lett. 2006, 8, 5609; (b)
Gujadhur, R. K.; Bates, C. G.; Venkataraman, D. Org.
Lett. 2001, 3, 4315.
4. Burgos, C. H.; Barder, T. E.; Huang, X.; Buchwald, S. L.
Angew. Chem., Int. Ed. 2006, 45, 4321.
EtOOC
OMe
OBn
EtOOC
Br
OMe
OBn
O
O
NBS (1 eq.)
DMF, rt, 6 h
13a: X=OMe
13b: X=H
X
X
14a: X= OMe 94%
14b: X= H 91%
OBn
OBn
O
EtOOC
OMe
OBn
Pd(OAc)2 (10 mol%)
PCy3 (20 mol%)
K2CO3 (2eq.), DMF
MW 100 oC, 1 h
X
15a: X= OMe 99%
15b: X= H 99%
OBn
Scheme 2. Dibenzofuran formation.
5. (a) Smith, M. B.; March, J. Advanced Organic Chemistry,
5th ed.; Wiley-Interscience: New York, 2001, Chapter 13,
pp 850; (b) Paradisi, C. In Trost, B. M., Ed.; Comprehen-
sive Organic Synthesis; Pergamon Press: Oxford, 1991;
Vol. 4, p 423; (c) Buncel, E.; Dust, J. M.; Terrier, F. Chem.
Rev. 1995, 59, 33.
HOOC
OMe
EtOOC
OMe
OBn
1) 10% Pd-C, H2 (1 atm)
EtOAc-MeOH (1:1)
rt, 24 h
O
OH
O
6. (a) Imahori, T.; Kondo, Y. J. Am. Chem. Soc. 2003, 125,
8082; (b) Imahori, T.; Hori, C.; Kondo, Y. Adv. Synth.
Catal. 2004, 346, 1090; (c) Kobayashi, K.; Ueno, M.;
Kondo, Y. Chem Commun. 2006, 3128; (d) Ueno, M.;
Wheatley, A. E. H.; Kondo, Y. Chem. Commun. 2006,
2) 1M NaOH, THF
rt, 3h
X
X
15a: X= OMe
15b: X= H
1a: X= OMe 98%
1b: X= H 86%
OH
OBn
Scheme 3. Deprotection to dictyomedins.