synthesis. For example, poor regioselectivity in the reactions
of unsymmetrical substrates (Y * H, eq 1) precludes
effective use of the complementary reactivity patterns of the
otherwise versatile vinyl Sn and Si moieties, even when the
helical isomerization is frozen as in the bicyclic diene shown
in eq 2.3b Yet another limitation became apparent as we
sought application of the [Si-Sn]-mediated cyclization for
a general synthesis of dibenzocyclooctadienes (DBCOD)4
(Figure 1), an important class of compounds with wide-
ranging biological activities including inhibition of HIV
replication at microgram/milliliter levels.5
Figure 1. Biologically active dibenzocyclooctadienes.
DBCOD derivatives with dense functionality around the
C7∼C8 carbons, providing unprecedented opportunities for
the synthesis of a wide variety of these compounds, including
the more oxidized members such as the antileukemic agent
steganacin.
Exploratory studies of the Pd-catalyzed silyl-stannylation
cyclization of the model diynes 3 (R ) H, Ac, Bz, Bn,
OCH2OBn) under a variety of conditions gave only low to
moderate yields of the expected product(s) 4. Even though
4 is formed as a single stereoisomer, the reaction is
complicated by significant contamination from acyclic ad-
ducts 5 and 6.6 The protecting group on the C6-OH group
has an effect on the regioselectivity of these reactions.6 While
screening other similar [X-Y]-reagents, we found that the
diyne 3b undergoes highly regio- and stereoselective (atro-
pselective) cyclization upon reaction with Me3Sn-B-
[-N(Me)CH2CH2N(Me)]7 in the presence of PdCl2·(PPh3)2
to give a single product 8 (Scheme 2). The moisture-sensitive
bisazaborolidine was converted in situ into air-stable vinyl-
boronate 9 by treatment with pinacol in the presence of
catalytic amounts of a strong acid.8 Structures of the (ZZ)-
1,2-bisalkylidene dibenzocyclooctadienes 8 and 9 were
We reasoned that [Si-Sn]-mediated cyclization of 2,2′-
propargylbiphenyl derivatives (Scheme 1) would produce
(2) For recent reviews of multicomponent cyclizations, see: (a) Itoh,
K.; Matsuda, I.; Yamamoto, K. J. Synth. Org. Chem., Jpn. 1999, 57, 912.
(b) Suginome, M.; Ito, Y. Chem. ReV. 2000, 100, 3221. For other
representative examples involving acetylenes, see: (c) Tsuda, T.; Kiyoi, T.;
Miyane, T.; Saegusa, T. J. Am. Chem. Soc. 1988, 110, 8570. (d) Chatani,
N.; Fukumoto, Y.; Ida, T.; Murai, S. J. Am. Chem. Soc. 1993, 115, 11614.
(e) Kondo, T.; Suzuki, N.; Okada, T.; Mitsudo, T. J. Am. Chem. Soc. 1997,
119, 6187. (f) Ojima, I.; Zhu, J.; Vidal, E. S.; Kass, D. F. J. Am. Chem.
Soc. 1998, 120, 6690. (g) Madine, J. W.; Xiang Wang, X.; Widenhoefer,
R. A. Org. Lett. 2001, 3, 385. (h) Doung, H. A.; Cross, M. J.; Louie, J.
J. Am. Chem. Soc. 2004, 126, 11438. (i) Miura, T.; Shimada, M.; Murakami,
M. J. Am. Chem. Soc. 2005, 127, 1094. (j) Brummond, K. M.; You, L.
Tetrahedron 2005, 61, 6180. (k) Tsuchikama, K.; Kuwata, Y.; Shibata, T.
J. Am. Chem. Soc. 2006, 128, 13686. (l) Denmark, S. E.; Liu, H.-C. J. Am.
Chem. Soc. 2007, 129, 3737.
(3) (a) Apte, S.; Radetich, B.; Shin, S.; RajanBabu, T. V. Org. Lett.
2004, 6, 4053. (b) Shin, Ph. D. Thesis, The Ohio State University, 2004.
(4) (a) Ayers, D. D.; Loike, J. D. Lignans: Chemical, Biological and
Clinical Properties; Cambridge University Press: Cambridge, U. K., 1990.
(b) Chang, J.; Reiner, J.; Xie, J. Chem. ReV. 2005, 105, 4581. (c) Sefkow,
M. Top. Curr. Chem. 2005, 243, 185. (d) Ward, R. S. Nat. Prod. Rep. 1999,
16, 75. and previous biannual reports in this series.
Scheme 1
. Silyl-Stannylation Cyclization of a
2,2′-Propargylbiphenyl Derivative
(5) Representative references to the isolation and biological activities
of these classes of compounds: (a) Li, H.; Wang, L.; Yang, Z.; Kitanaka,
S. J. Nat. Prod. 2007, 70, 1999. (b) Chen, D.-F.; Zhang, S.-X.; Kozuka,
M.; Sun, Q.-Z.; Feng, J.; Wang, Q.; Mukainaka, T.; Nobukuni, Y.; Tokuda,
H.; Nishino, H.; Wang, H.-K.; Morris-Natschke, S. L.; Lee, K.-H. J. Nat.
Prod. 2002, 65, 1242. (c) Chen, D.-F.; Zhang, S.-X.; Xie, L.; Xie, J.-X.;
Chen, K.; Kashiwada, Y.; Zhou, B.-N.; Wang, P.; Cosentino, L. M.; Lee,
K.-H. Bioorg. Med. Chem. 1997, 5, 1715. (d) Kuo, Y.-H.; Wu, M.-D.; Hung,
C.-C.; Huang, R.-L.; Kuo, L.-M. Y.; Shen, Y.-C.; Ong, C.-W. Bioorg. Med.
Chem. 2005, 13, 1555. (e) Chen, D.-F.; Zhang, S.-X.; Chen, K.; Zhou, B.-
N.; Wang, P.; Cosentino, L. M.; Lee, K.-H. J. Nat. Prod. 1996, 59, 1066.
(f) Tan, R.; Li, L. N.; Fang, Q. Planta Med. 1984, 50, 414. (g) Ikeya, Y.;
Taguchi, H.; Yosioka, I. Chem. Pharm. Bull. 1982, 30, 3207. (h) Ikeya,
Y.; Taguchi, H.; Yosioka, I.; Kobayashi, H. Chem. Pharm. Bull. 1979, 27,
2695.
(6) See Supporting Information for details of the synthesis of axially
chiral diyne(s) 3 and a summary of the cyclization studies.
(7) (a) Onozawa, S.; Hatanaka, Y.; Choi, N.; Tanaka, M. Organome-
tallics 1997, 16, 5389. Preparation of the [B-Sn]-reagent: Niedenzu, K.;
Rothgery, E. F. Synth. Inorg. Met. Org. Chem. 1972, 2, 1.
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