Although the mechanism of the catalytic process described
above is not yet clear, several observations were made that
provide insight into the mode of action of Pd(phen)2(PF6)2.
The results of an intermolecular competitive reaction of
deuterium-labeled 6 (H/D = 1/1) with 2a gives a KIE value
of unity (eqn (2)). This finding clearly suggests that elimination
of hydrogen from the heteroarene is not involved in the
rate-limiting step. The results of a competitive reaction of 4
with an equimolar ratio of 2a and 2c demonstrate that the
electron deficient aryl halide 2a undergoes coupling faster than
its electron rich counterpart 2c (eqn (3)). This observation
suggests that either oxidative addition of the aryl iodide to
the Pd catalyst or electrophilic addition of the resulting Pd
complex to the heteroarene is rate-limiting provided that
the reaction is taking place via a conventional pathway.
Alternatively, the Pd(phen)2(PF6)2 catalyzed coupling reaction
might follow a radical mechanism. Recently, an Ir-catalyzed
reaction of anisole with iodobenzene was reported to give
three regioisomeric monoarylated products with an unusually
high ortho selectivity (o : m : p = 72 : 16 : 12). The intermediacy
of a phenyl radical in this process has been proposed.12
Interestingly, a similar ortho selectivity was observed in
Pd(phen)2(PF6)2 promoted arylation reaction of anisole with
2a (eqn (4)).
2004; (c) J.-P. Corbet and G. Mignani, Chem. Rev., 2006, 106,
2651; (d) I. J. S. Fairlamb, Chem. Soc. Rev., 2007, 36, 1036.
2 Selected examples of Pd catalysis: (a) T. Okazawa, T. Satoh,
M. Miura and M. Nomura, J. Am. Chem. Soc., 2002, 124, 5286;
(b) D. Kalyani, N. R. Deprez, L. V. Desai and M. S. Sanford,
J. Am. Chem. Soc., 2005, 127, 7330; (c) B. S. Lane, M. A. Brown
and D. Sames, J. Am. Chem. Soc., 2005, 127, 8050;
(d) L.-C. Campeau, M. Parisien, A. Jean and K. Fagnou, J. Am.
Chem. Soc., 2006, 128, 581; (e) N. R. Deprez, D. Kalyani,
A. Krause and M. S. Sanford, J. Am. Chem. Soc., 2006, 128,
4972; (f) M. Lafrance and K. Fagnou, J. Am. Chem. Soc., 2006,
128, 16496; (g) G. L. Turner, J. A. Morris and M. F. Greaney,
Angew. Chem., Int. Ed., 2007, 46, 7996; (h) X. Wang,
D. V. Gribkov and D. Sames, J. Org. Chem., 2007, 72, 1476;
(i) N. Lebrasseur and I. Larrosa, J. Am. Chem. Soc., 2008, 130,
2926; (j) L.-C. Campeau, M. Bertrand-Laperle, J.-P. Leclerc,
E. Villemure, S. Gorelsky and K. Fagnou, J. Am. Chem. Soc.,
2008, 130, 3276; (k) S. I. Gorelsky, D. Lapointe and K. Fagnou,
J. Am. Chem. Soc., 2008, 130, 10848; (l) I. Mori and A. Sugie, Bull.
Chem. Soc. Jpn., 2008, 81, 548; (m) L. Ackermann, A. Althammer
and S. Fenner, Angew. Chem., Int. Ed., 2009, 48, 201;
(n) S. Yanagisawa, K. Ueda, H. Sekizawa and K. Itami, J. Am.
Chem. Soc., 2009, 131, 14622.
3 Selected examples of Rh catalysis: (a) X. Wang, B. S. Lane and
D. Sames, J. Am. Chem. Soc., 2005, 127, 4996; (b) S. Yanagisawa,
T. Sudo, R. Noyori and K. Itami, J. Am. Chem. Soc., 2006, 128,
11748; (c) S. Proch and R. Kempe, Angew. Chem., Int. Ed., 2007,
46, 3135; (d) M. Nambo, R. Noyori and K. Itami, J. Am. Chem.
Soc., 2007, 129, 8080; (e) J. C. Lewis, A. M. Berman,
R. G. Bergman and J. A. Ellman, J. Am. Chem. Soc., 2008, 130,
2493; (f) A. M. Berman, J. C. Lewis, R. G. Bergman and
J. A. Ellman, J. Am. Chem. Soc., 2008, 130, 14926.
4 Selected examples of Ni catalysis: J. Canivet, J. Yamaguchi, I. Ban
and K. Itami, Org. Lett., 2009, 11, 1733.
5 (a) Selected examples of Ir catalysis: K. Fujita, M. Nonogawa and
R. Yamaguchi, Chem. Commun., 2004, 1926; (b) B. Join,
T. Yamamoto and K. Itami, Angew. Chem., Int. Ed., 2009, 48,
3644.
ð2Þ
6 Selected examples of Cu catalysis: (a) R. J. Phipps, N. P. Grimster
and M. J. Gaunt, J. Am. Chem. Soc., 2008, 130, 8172;
(b) H.-Q. Do, R. M. Kashif Khan and O. Daugulis, J. Am. Chem.
Soc., 2008, 130, 15185; (c) T. Yoshizumi, H. Tsurugi, T. Satoh and
M. Miura, Tetrahedron Lett., 2008, 49, 1598; (d) F. Besselievre,
S. Piguel, F. Mahuteau-Betzer and D. S. Grierson, Org. Lett.,
2008, 10, 4029.
7 Selected examples of Ru catalysis: (a) L. Ackermann, Org. Lett.,
C¸ etinkaya,
ð3Þ
ð4Þ
¨
2005, 7, 3123; (b) I. Ozdemir, S. Demir, B.
C. Gourlaouen, F. Maseras, C. Bruneau and P. H. Dixneuf,
J. Am. Chem. Soc., 2008, 130, 1156; (c) S. Oi, R. Funayama,
T. Hattori and Y. Inoue, Tetrahedron, 2008, 64, 6051.
8 (a) F. Shibahara, A. Kitagawa, E. Yamaguchi and T. Murai, Org.
Lett., 2006, 8, 5621; (b) F. Shibahara, A. Yoshida and T. Murai,
Chem. Lett., 2008, 37, 646; (c) F. Shibahara, E. Yamaguchi,
A. Kitagawa, A. Imai and T. Murai, Tetrahedron, 2009, 65,
5062; (d) F. Shibahara, R. Sugiura, A. Kitagawa, E. Yamaguchi
and T. J. Murai, J. Org. Chem., 2009, 74, 3566; (e) S. Tahara,
F. Shibahara, T. Maruyama and T. Murai, Chem. Commun., 2009,
7009.
In conclusion, the investigation described above has demon-
strated that the palladium complex bearing a nitrogen-based
ligand, Pd(phen)2(PF6)2, promotes efficient direct C–H bond
arylation reactions of heteroarenes. This catalytic system can
be used to carry out highly selective multiple arylation
reactions of unsubstituted heteroarenes. Further mechanistic
studies of this process and its application to the synthesis of
functional materials are currently underway.
9 [Pd(phen)2](PF6)2 has been used as a catalyst for copolymerization
of CO and olefins, see: (a) J. Durand, A. Scarel, B. Milani,
R. Seraglia, S. Gladiali, C. Carfagna and B. Binotti, Helv. Chim.
Acta, 2006, 89, 1752 and for reductive carbonylation of nitro-
arenes, see: (b) A. Bontempi, E. Alessio, G. Chanos and
G. Mestroni, J. Mol. Catal., 1987, 42, 67; (c) Y. Izumi, Y. Satoh,
H. Kondoh and K. Urabe, J. Mol. Catal., 1992, 72, 37.
10 The results are summarized in ESI.
This research was supported by a Grant-in-Aid for Scientific
Research from the MEXT and JSPS.
11 Diarylated thiophene 12 was coupled with another aryl iodide 2a
under identical conditions, but the reaction is very slow (33% yield
for 20 h).
Notes and references
12 A similar ortho-site selectivity is observed for uncatalyzed radical
aromatic substitution reactions reported by Davies, see
D. I. Davies, D. H. Hey and B. Summers, J. Chem. Soc. (C),
1971, 2681.
1 For recent reviews of cross-coupling reactions, see: (a) J. Hassan,
M. Sevignon, C. Gozzi, E. Schulz and M. Lemaire, Chem. Rev.,
´
2002, 102, 1359; (b) Metal-Catalyzed Cross-Coupling Reactions, ed.
A. de Meijere and F. Diederich, Wiley-VCH, Weinheim, 2nd edn,
ꢀc
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Chem. Commun., 2010, 46, 2471–2473 | 2473