ORGANIC
LETTERS
2010
Vol. 12, No. 21
4728-4731
Gold-Catalyzed Oxidative Coupling
Reactions with Aryltrimethylsilanes
William E. Brenzovich, Jr., Jean-Franc¸ois Brazeau, and F. Dean Toste*
Department of Chemistry, UniVersity of California, Berkeley, California 94720,
United States
Received September 13, 2010
ABSTRACT
During continuing studies with a novel oxidative gold oxyarylation reaction, arylsilanes were found to be competent coupling partners, providing
further evidence for an intramolecular electrophilic aromatic substitution mechanism. While providing yields complementary to those of the
previously described boronic acid methods, the use of trimethylsilanes reduces the observation of homocoupling byproducts and allows for
facile intramolecular coupling reactions.
With the development of transition metal-catalyzed cross-
coupling reactions, significant effort has been expended in
the development of inexpensive and reliable organometallic
reagents as coupling partners.1 In this context, organosilanes
present an attractive solution; however, there have been
relatively few reports of transition-metal-catalyzed reactions
with the readily accessible aryltrimethylsilanes. Moreover,
a stoichiometric additive such as fluoride or hydroxide is
typically employed to activate the relatively unreactive silicon
center for transmetalation.2 Alternatively, a variety of reactive
silicon reagents have been designed and utilized in transition
metal-catalyzed cross-coupling reactions on milder condi-
tions.3 During our recent examination of the Selectfluor-
mediated gold-catalyzed amino- and oxyarylation of terminal
olefins with boronic acids,4 mechanistic experimentation and
computational analysis provided evidence against transmeta-
lation to the gold center. Instead, studies suggested a
bimolecular reductive elimination reminiscent of an elec-
trophilic aromatic substitution. While unactivated trimethy-
larylsilanes do not typically directly engage in cross-
couplings,5 they can readily react as nucleophiles in aromatic
(3) Selected silicon-based cross-coupling reactions: (a) Hatanaka, Y.;
Hiyama, T. J. Org. Chem. 1988, 53, 920. (b) Hatanaka, Y.; Fukushima, S.;
Hiyama, T. Chem. Lett. 1989, 1711. (c) Mowery, M. E.; DeShong, P. J. Am.
Chem. Soc. 1999, 64, 1684. (d) Mowery, M. E.; DeShong, P. Org. Lett.
1999, 2137. (e) Hirabayashi, K.; Mori, A.; Kawashima, J.; Suguro, M.;
Nishihara, Y.; Hiyama, T. J. Org. Chem. 2000, 65, 5342. (f) Murata, M.;
Shimazaki, R.; Watanabe, S.; Masuda, Y. Synthesis 2001, 2231. (g)
Denmark, S. E.; Sweis, R. F. J. Am. Chem. Soc. 2001, 123, 6439. (h) Lee,
J.-Y.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 5616. (i) Nakao, Y.; Takeda,
M.; Matsumoto, T.; Hiyama, T. Angew. Chem., Int. Ed. 2010, 49, 4447.
(4) For Au-catalyzed amino- and oxyarylation of alkenes: (a) Zhang,
G.; Cui, L.; Wang, Y.; Zhang, L. J. Am. Chem. Soc. 2010, 132, 1474. (b)
Brenzovich, W. E., Jr.; Benitez, D.; Lackner, A. D.; Shunatona, H. P.;
Tkatchouk, E.; Goddard, W. A., III; Toste, F. D. Angew. Chem., Int. Ed.
2010, 49, 5519. (c) Melhado, A. D.; Brenzovich, W. E., Jr.; Lackner, A. D.;
Toste, F. D. J. Am. Chem. Soc. 2010, 132, 8885. For other oxidative gold-
catalyzed reactions, see: (d) Kar, A.; Mangu, N.; Kaiser, H. M.; Beller,
M.; Tse, M. K. Chem. Commun. 2008, 3, 386. (e) Hashmi, A. S. K.;
Ramamurthi, T. D.; Rominger, F. J. Organomet. Chem. 2009, 694, 592. (f)
Zhang, G.; Peng, Y.; Cui, L.; Zhang, L. Angew. Chem., Int. Ed. 2009, 48,
3112. (i) Iglesias, A.; Mun˜iz, K. Chem.sEur. J. 2009, 15, 10563. (j) Ye,
L.; Cui, L.; Zhang, G.; Zhang, L. J. Am. Chem. Soc. 2010, 132, 3258. (k)
Hopkinson, M. N.; Tessier, A.; Salisbury, A.; Giuffredi, G. T.; Combettes,
L. E.; Gee, A. D.; Gouverneur, V. Chem.sEur. J. 2010, 16, 4739.
(1) (a) Metal-Catalyzed Cross-Coupling Reactions, 2nd ed.; de Meijere,
A., Diederich, F., Eds.; Wiley-VCH: Weinheim, Germany, 2004; Vols. 1
and 2. (b) Handbook of Organopalladium Chemistry for Organic Synthesis;
Negishi, E.-i., Ed.; Wiley-Interscience: New York, 2002.
(2) For recent reviews on cross-coupling with silicon reagents, see ref
1 and. (a) Denmark, S. E.; Butler, C. R. Chem. Commun. 2009, 20. (b)
Denmark, S. E.; Regens, C. S. Acc. Chem. Res. 2008, 41, 1486. (bb)
Denmark, S. E.; Baird, J. D. Chem.sEur. J. 2006, 12, 4954. (c) Nakoa,
Y.; Sahoo, A. K.; Imanaka, H.; Yada, A.; Hiyama, T. Pure Appl. Chem.
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W. M.; DeShong, P. Tetrahedron 2005, 61, 12201. (e) Spivey, A. C.;
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10.1021/ol102194c 2010 American Chemical Society
Published on Web 09/29/2010