C O MMU N I C A T I O N S
Table 1. Palladium-Catalyzed Suzuki-Miyaura Reactions
showed a difference in reactivity when compared to the in situ-
generated catalyst, it was found to be a more suitable precursor for
Suzuki and Heck coupling reactions. Work aimed at unveiling the
nature of catalytically active species in in situ-generated NHC-Pd
systems is ongoing.
Acknowledgment. We thank Francine Be´langer-Garie´py for the
X-ray crystal structure analysis. This work was supported by the
National Science and Engineering Research Council (NSERC) of
Canada, the Fond FCAR of Que´bec and the Universite´ de Montre´al.
S.P.N. acknowledges support from the National Science Foundation
for work performed at UNO.
entry
catalyst (2 mol %)
complex 1
complex 2
IMes‚HCl, Pd(OAc)2 (2:1)
IMes‚HCl, Pd(OAc)2 (1:1)
temp (°C)
yield (%)
1
2
3
4
80
80
80
80
<5
44
76
28
Supporting Information Available: Characterization data for new
compounds and experimental procedures (CIF/PDF). This material is
Table 2. Palladium-Catalyzed Heck Reactions
References
(1) For recent reviews: (a) Francis, M. B.; Jamison, T. F.; Jacobsen, E. N.
Curr. Opin. Chem. Biol. 1998, 2, 422-428. (b) Shimizu, K. D.; Snapper,
M. L.; Hoveyda, A. H. Chem. Eur. J. 1998, 4, 1885-1889. (c) Kuntz, K.
W.; Snapper, M. L.; Hoveyda, A. H. Curr. Opin. Chem. Biol. 1999, 3,
313-319. (d) Reetz, M. T. Angew. Chem., Int. Ed. 2001, 40, 284-310.
(e) Dahmen, S.; Brase, S. Synthesis 2001, 1431-1449. (f) Traverse, J.
F.; Snapper, M. L. Drug DiscoV. Today 2002, 7, 1002-1012. (g)
Berkowitz, D. B.; Bose, M.; Choi, S. Angew. Chem., Int. Edit. 2002, 41,
1603-1607. (h) de Vries, J. G.; de Vries, A. H. M. Eur. J. Org. Chem.
2003, 799-811.
entry
catalyst (2 mol %)
complex 1
complex 2
IMes‚HCl, Pd(OAc)2 (2:1)
IMes‚HCl, Pd(OAc)2 (1:1)
temp (°C)
yield (%)
1
2
3
4
120
120
120
120
<5
77
66
56
(2) (a) Grasa, G. A.; Moore, Z.; Martin, K. L.; Stevens, E. D.; Nolan, S. P.;
Paquet, V.; Lebel, H. J. Organomet. Chem. 2002, 658, 126-131. (b)
Charette, A. B.; Janes, M. K.; Lebel, H. Tetrahedron: Asymmetry 2003,
14, 867-872.
was formed together with (IMes)2Pd(OAc)2.8 Complex 1 was also
isolated in 68% from palladium (II) chloride, cesium carbonate,
and 2 equiv of IMes‚HCl (eq 2). The structure of complex 1 was
also unambiguously established by single-crystal X-ray analysis (see
Supporting Information). Attempts to convert complex 2 into the
C(2) isomer 1 in the presence of a base were unsuccessful.9
(3) (a) Huang, J.; Nolan, S. P. J. Am. Chem. Soc. 1999, 121, 9889-9890. (b)
Fu¨rstner, A.; Leitner, A. Synlett 2001, 290-292. (c) Herrmann, W. A.;
Bo¨hm, V. P. W.; Gsto¨ttmayr, C. W. K.; Grosche, M.; Reisinger, C. P.;
Weskamp, T. J. Organomet. Chem. 2001, 617, 616-628. (d) Grasa, G.
A.; Hillier, A. C.; Nolan, S. P. Org. Lett. 2001, 3, 1077-1080. (e) Viciu,
M. S.; Grasa, G. A.; Nolan, S. P. Organometallics 2001, 20, 3607-3612.
(f) Grasa, G. A.; Viciu, M. S.; Huang, J.; Zhang, C. M.; Trudell, M. L.;
Nolan, S. P. Organometallics 2002, 21, 2866-2873. (g) Hillier, A. C.;
Grasa, G. A.; Viciu, M. S.; Lee, H. M.; Yang, C. L.; Nolan, S. P. J.
Organomet. Chem. 2002, 653, 69-82. (h) Viciu, M. S.; Germaneau, R.
F.; Navarro-Fernandez, O.; Stevens, E. D.; Nolan, S. P. Organometallics
2002, 21, 5470-5472. (i) Pytkowicz, J.; Roland, S.; Mangeney, P.; Meyer,
G.; Jutand, A. J. Organomet. Chem. 2003, 678, 166-179. (j) Eckhardt,
M.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 13642-13643.
(4) Herrmann, W. A.; Elison, M.; Fischer, J.; Kocher, C.; Artus, G. R. J.
Angew. Chem., Int. Ed. Engl. 1995, 34, 2371-2374.
(5) For the only example of a C-5 IMes, see: (a) Gru¨ndemann, S.; Kovacevic,
A.; Albrecht, M.; Faller, J. W.; Crabtree, R. H. Chem. Commun. 2001,
2274-2275. (b) Gru¨ndemann, S.; Kovacevic, A.; Albrecht, M.; Faller, J.
W.; Crabtree, R. H. J. Am. Chem. Soc. 2002, 124, 10473-10481.
(6) For selected early examples of a C(2)-bound IMes, see: (a) Huang, J.;
Stevens, E. D.; Petersen, J. L.; Nolan, S. P. J. Am. Chem. Soc. 1999, 121,
2674-2678. (b) Huang, J.; Schanz, H.-J.; Stevens, E. D.; Nolan, S. P.
Organometallics 1999, 18, 2370-2375. (c) Jafarpour, L.; Huang, J.;
Stevens, E. D.; Nolan, S. P. Organometallics 1999, 18, 3760-3763.
(7) The related unusual C(2)-C(5) complex was also obtained with N,N′-
bis(2,6-diisopropylphenyl)imidazolium chloride (IPr‚HCl).
The reactivity of 1 and 2 was studied and compared with the in
situ-formed catalyst (from Pd(OAc)2 (1 equiv) and IMes‚HCl (2
equiv)) for the Suzuki-Miyaura (Table 1) and Heck reactions
(Table 2).
Complex 1 proved to be an inactive catalyst for both coupling
reactions, while complex 2 lead to the desired product. In Suzuki-
Miyaura reactions, complex 2 was not as efficient as the in situ-
formed catalyst.10 In sharp contrast, the highest isolated yield for
the Heck coupling reaction was obtained with 2.
In conclusion, these findings highlight the importance of the
procedure used for the generation of a catalytically active species
in cross-coupling reactions. It appears that the catalytically active
species precursor in cross-coupling reactions is not complex 1 in
both Suzuki and Heck coupling reactions. Although complex 2
(8) The normal C(2) complex 1 and (IMes)2Pd(OAc)2 were obtained as an
inseparable mixture.
(9) The mechanism for the formation of complex 2 has not been unambigu-
ously established. However, there are some indications that it proceeds
via the formation of a palladium-carbene complex that undergo a C-H
insertion into the C(5)-H bond of the second imidazolium salt. For
instance, the use of weaker base, such as dimethylaniline, led mainly to
formation of complex 2. Conversely, complex 2 could not be obtained
from palladium chloride, which suggest that palladium acetate acted as a
base for the formation of the carbene ligand. We thank a reviewer for
useful comments and suggestions regarding the mechanism for the
formation of 2.
(10) It should be noted that in Suzuki-Miyaura cross-coupling reactions, well-
defined complexes bearing only one NHC are better catalysts than those
bearing two. See ref 3f.
JA049759R
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J. AM. CHEM. SOC. VOL. 126, NO. 16, 2004 5047