ORGANIC
LETTERS
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Vol. XX, No. XX
000–000
Regioselective Synthesis of Multisubstituted
Benzenes by Palladium-Catalyzed
Intermolecular Reaction of
β‑Iodo-β-silylstyrenes with Alkynes
Hidenori Kinoshita, Hirotoshi Takahashi, and Katsukiyo Miura*
Department of Applied Chemistry, Graduate School of Science and Engineering,
Saitama University, 255 Shimo-ohkubo, Sakura-ku, Saitama 338-8570, Japan
Received April 19, 2013
ABSTRACT
The Pd-catalyzed reaction between β-iodo-β-silylstyrenes and terminal alkynes in i-Pr2NEt gave 1,2,3,5-tetrasubstituted benzenes with complete
regioselection. The use of certain silylacetylenes as alkynes enabled efficient synthesis of 1,3,5-trissilyl-2-arylbenzenes, which could be
transformed into other multisubstituted benzenes by displacement of the silyl groups.
Multisubstituted benzenes are quite ubiquitous building
blocks of various compounds ranging from biologically
active natural products to functional materials. Therefore,
a number of methods for constructing multisubstituted
benzenes have so far been developed.1,2 In particular,
transition-metal-catalyzed reactions among three two-
carbon units provide easy access to the structural motifs.
Cyclotrimerization of alkynes is a well-known example
of these reactions.3,4 As another intriguing example, the
Pd-catalyzed cascade reaction of 2-bromoalkenediynes is
useful for thesynthesisof tricyclic compounds containing a
benzene ring (Scheme 1).5 In contrast to the successful intra-
molecular process, to the best of our knowledge, its inter-
molecular version using independent haloalkenes and
alkynes has not been applied to the efficient synthesis of
(4) For selective examples of intermolecular [2 þ 2 þ 2] cyclotrimer-
ization, see: (a) Ozerov, O. V.; Ladipo, F. T.; Patrick, B. O. J. Am. Chem.
Soc. 1999, 121, 7941. (b) Li, J.; Jiang, H.; Chen, M. J. Org. Chem. 2001,
66, 3627. (c) Tanaka, K.; Shirasaka, K. Org. Lett. 2003, 5, 4697. (d)
Takeuchi, R.; Nakaya, Y. Org. Lett. 2003, 5, 3659. (e) Yamamoto, Y.;
Ishii, J.; Nishiyama, H.; Itoh, K. J. Am. Chem. Soc. 2004, 126, 3712. (f)
Yamamoto, Y.; Ishii, J.; Nishiyama, H.; Itoh, K. J. Am. Chem. Soc.
2005, 127, 9625. (g) Tanaka, K.; Nishida, G.; Ogino, M.; Noguchi, K.
Org. Lett. 2005, 7, 3119. (h) Tanaka, K.; Toyoda, K.; Wada, A.;
Shirasaka, K.; Hirano, M. Chem.;Eur. J. 2005, 11, 1145. (i) Hilt, G.;
Volger, T.; Hess, W.; Galbiati, F. Chem. Commun. 2005, 1474. (j) Hilt,
G.; Hess, W.; Volger, T.; Hengst, C. J. Organomet. Chem. 2005, 690,
5170. (k) Saino, N.; Amemiya, F.; Tanabe, E.; Kase, K.; Okamoto, S.
Org. Lett. 2006, 8, 1439. (l) Goswami, A.; Ito, T.; Okamoto, S. Adv.
Synth. Catal. 2007, 349, 2368. (m) Hilt, G.; Hengst, C.; Hess, W. Eur. J.
Org. Chem. 2008, 2293. (n) Xu, Y.-L.; Pan, Y.-M.; Wu, Q.; Wang, H.-S.;
Liu, P.-Z. J. Org. Chem. 2011, 76, 8472.
(1) For selective examples using transition metal catalysis, see: (a)
Rubina, M.; Conley, M.; Gevorgyan, V. J. Am. Chem. Soc. 2006, 128,
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Tsuji, H.; Yamagata, K.; Fujimoto, T.; Nakamura, E. J. Am. Chem. Soc.
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Lett. 2008, 10, 3009. (e) Izawa, Y.; Pun, D.; Stahl, S. S. Science 2011, 333,
209.
(2) For selective examples of nontransition-metal-mediated reac-
tions, see: (a) Crone, B.; Krisch, S. F.; Umland, K.-D. Angew. Chem.,
Int. Ed. 2010, 49, 4661. (b) Yang, F.; Qiu, Y.-F.; Ji, K.-G.; Niu, Y.-N.;
Ali, S.; Liang, Y.-M. J. Org. Chem. 2012, 77, 9029. (c) Diallo, A.; Zhao,
Y.-L.; Wang, H.; Li, S.-S.; Ren, C.-Q.; Liu, Q. Org. Lett. 2012, 14, 5776.
(3) (a) Vollhardt, K. P. C. Angew. Chem., Int. Ed. Engl. 1984, 23, 539.
(b) Schore, N. E. In Comprehensive Organic Synthesis; Trost, B. M.,
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Lautens, M.; Klute, W.; Tam, W. Chem. Rev. 1996, 96, 49. (d) Saito, S.;
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E.; Lahiri, K. Eur. J. Org. Chem. 2005, 4741. (f) Yamamoto, Y. Curr.
Org. Chem 2005, 9, 503. (g) Gandon, V.; Aubert, C.; Malacria, M. Chem.
Commun. 2006, 2209.
(5) (a) Meyer, F. E.; de Meijere, A. Synlett 1991, 777. (b) Negishi, E.;
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10.1021/ol4010883
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