ORGANIC
LETTERS
Pyridine Ligands as Promoters in PdII/0-
2012
Vol. 14, No. 7
1760–1763
Catalyzed CÀH Olefination Reactions
Asako Kubota, Marion H. Emmert, and Melanie S. Sanford*
University of Michigan, Department of Chemistry, 930 North University Avenue, Ann
Arbor, Michigan 48109-1055, United States
Received February 14, 2012
ABSTRACT
Commercially available pyridine ligands can significantly enhance the rate, yield, substrate scope, and site selectivity of arene CÀH olefination
(FujiwaraÀMoritani) reactions. The use of a 1:1 ratio of Pd/pyridine proved critical to maximize reaction rates and yields.
The Pd-mediated CÀH olefination of benzene was first
reported in 1967 by Fujiwara and Moritani.1 Since this
initial publication, numerous catalytic versions of this
transformation have been developed. The vast majority of
these catalytic protocols proceed under “ligandless” condi-
tions (with PdII salts such as Pd(OAc)2 as catalysts) and use
oxidants such as peroxides, peroxyesters, dioxygen, poly-
oxometalates, CuII, or AgI to achieve catalytic turnover.2
A variety of aromatic compounds can be employed as arene
substrates,2 and high levels of site selectivity are possible
using substrates that contain directing groups.2À5
Despite the above illustrated advances, several signifi-
cant problems remain unsolved.6,7 First, the substrate
scope for simple aromatics that do not contain directing
groups remains primarily limited to electron-rich and
-neutral derivatives; in general, electron-deficient arenes
exhibit sluggish reactivity.7e,h Second, most substituted
aromatic substrates react to afford mixtures of isomeric
products.6,7e While there has been some success in the use
of solvent and/or oxidant to control site selectivity in the
CÀH olefination of heterocycles (e.g., indole, pyrrole),8
catalyst controlled selectivity remains challenging for most
other classes of arene substrates. Third, the vast majority
of catalytic FujiwaraÀMoritani (FÀM) reactions require
(1) Moritani, I.; Fujiwara, Y. Tetrahedron Lett. 1967, 1119.
(2) (a) Moritani, I.; Fujiwara, Y. Synthesis 1973, 524. (b) Karimi, B.;
Behzadnia, H.; Elhamifar, D.; Akhavan, P. F.; Esfahani, F. K.; Zamani,
A. Synthesis 2010, 1399. (c) Le Bras, J.; Muzart, J. Chem. Rev. 2011, 111,
1170.
(3) For recent examples of substrate-directed CÀH olefination, see: (a)
Wang, D. H.; Engle, K. M.; Shi, B. F.; Yu, J.-Q. Science 2010, 327, 315.
(b) Lu, Y.; Wang, D. H.; Engle, K. M.; Yu, J.-Q. J. Am. Chem. Soc. 2010,
132, 5916. (c) Garcia-Rubia, A.; Urones, B.; Arrayas, R. G.; Carretero,
J. C. Angew. Chem., Int. Ed. 2011, 50, 10927. (d) Garcia-Rubia, A.;
Fernandez-Ibanez, M. A.; Arrayas, R. G.; Carretero, J. C. Chem.;Eur.
J. 2011, 17, 3567. (e) Dai, H. X.; Stepan, A. F.; Plummer, M. S.; Zhang,
Y. H.; Yu, J.-Q. J. Am. Chem. Soc. 2011, 133, 7222. (f) Zhu, C.; Falck,
J. R. Org. Lett. 2011, 13, 1214. (g) Wang, L.; Liu, S.; Li, Z.; Yu, Y. Org.
Lett. 2011, 13, 6137.
(6) (a) Jia, C.; Lu, W.; Kitamura, T.; Fujiwara, Y. Org. Lett. 1999, 1,
2097. (b) Dams, M.; De Vos, D. E.; Celen, S.; Jacobs, P. A. Angew.
Chem., Int. Ed. 2003, 42, 3512. (c) Obora, Y.; Okabe, Y.; Ishii, Y. Org.
Biomol. Chem. 2010, 8, 4071.
(7) (a) Fujiwara, Y.; Moritani, I.; Matsuda, M.; Teranishi, S.
Tetrahedron Lett. 1968, 3863. (b) Fujiwara, Y.; Moritani, I.; Danno,
S.; Asano, R.; Teranishi, S. J. Am. Chem. Soc. 1969, 91, 7166. (c) Shue,
R. S. J. Chem. Soc. D 1971, 1510. (d) Shue, R. S. J. Catal. 1972, 26, 112.
(e) Fujiwara, Y.; Asano, R.; Moritani, I.; Teranishi, S. J. Org. Chem.
1976, 41, 1681. (f) Zhang, X.; Fan, S.; He, C. Y.; Wan, X.; Min, Q. Q.;
Yang, J.; Jiang, Z. X. J. Am. Chem. Soc. 2010, 132, 4506. (g) Li, Z.;
Zhang, Y.; Liu, Z. Q. Org. Lett. 2012, 14, 74. (h) Zhang, Y.; Li, Z.; Liu,
Z. Q. Org. Lett. 2012, 14, 226.
(8) (a) Grimster, N. P.; Gauntlett, C.; Godfrey, C. R. A.; Gaunt, M. J.
Angew. Chem., Int. Ed. 2005, 44, 3125. (b) Beck, E. M.; Grimster, N. P.;
Hatley, R.; Gaunt, M. J. J. Am. Chem. Soc. 2006, 128, 2528. (c) Beck,
E. M.; Hatley, R.; Gaunt, M. J. Angew. Chem., Int. Ed. 2008, 47, 3004.
(d) Potavathri, S.; Dumas, A. S.; Dwight, T. A.; Naumiec, G. R.;
Hammann, J. M.; DeBoef, B. Tetrahedron Lett. 2008, 49, 4050.
(4) For sp3-CÀH olefination, see: (a) Zhang, Y. H.; Shi, B. F.; Yu,
J.-Q. J. Am. Chem. Soc. 2009, 131, 5072. (b) Stowers, K. J.; Fortner,
K. C.; Sanford, M. S. J. Am. Chem. Soc. 2011, 133, 6541. (c) Wang, C.;
Ge, H. Synthesis 2011, 2590.
(5) (a) Miura, M.; Tsuda, T.; Satoh, T.; Pivsa-Art, S.; Nomura, M.
J. Org. Chem. 1998, 63, 5211. (b) Boele, M. D. K.; van Strijdonck, G. P. F.;
de Vries, A. H. M.; Kamer, P. C. J.; de Vries, J. G.; van Leeuwen, P. W.
N. M. J. Am. Chem. Soc. 2002, 124, 7904. (c) Zaitsev, V. G.; Daugulis, O.
J. Am. Chem. Soc. 2005, 127, 4156. (d) Cai, G.; Fu, Y.; Li, Y.; Wan, X.;
Shi, Z. J. Am. Chem. Soc. 2007, 129, 7666. (e) Wang, J. R.; Yang, C. T.;
Liu, L.; Guo, Q. X. Tetrahedron Lett. 2007, 48, 5449. (f) Li, J. J.; Mei, T. S.;
Yu, J.-Q. Angew. Chem., Int. Ed. 2008, 47, 6452.
r
10.1021/ol300281p
Published on Web 03/12/2012
2012 American Chemical Society