ORGANIC
LETTERS
2005
Vol. 7, No. 9
1857-1860
High-Yielding Intramolecular Direct
Arylation Reactions with Aryl Chlorides
Louis-Charles Campeau, Praew Thansandote, and Keith Fagnou*
Department of Chemistry, UniVersity of Ottawa, 10 Marie Curie,
Ottawa, Canada K1N 6N5
Received March 8, 2005
ABSTRACT
An N-heterocyclic carbene palladium catalyst system is used to promote direct arylation of a broad range of aryl chlorides to form six- and
five-membered ring biaryls. An influence of the halide on the palladium precatalyst on catalyst activation has been revealed, as has a beneficial
effect of NHC salts that allows the turnover numbers to be increased by simple addition of imidazolium salts to the reaction mixture.
N-Heterocyclic carbene (NHC) ligands have become increas-
ingly employed in transition metal catalysis.1,2 The 1:1
NHC-metal complexes typically exhibit enhanced reactivity
compared to analogous 2:1 species,3 and these observations
have prompted the development of several methods to
prepare NHC metal complexes with a well defined 1:1
ligand-to-metal ratio.4 Despite the impressive reactivity of
these catalysts, they can be prone to decomposition after
insertion of the aryl halide.5 Cavell, Caddick, and Grushin
have shown that in the absence of a good nucleophile, NHC
aryl palladium(II) species are unstable and undergo facile
aryl-NHC reductive elimination to give the arylimidazolium
salts and catalyst death.6
Direct arylation processes are an important class of C-H
functionalization reaction that uses a simple arene in place
of the organometallic component.7,8 At present, direct ary-
lation processes commonly require the use of aryl iodides
or bromides, with near complete exclusion of aryl chlo-
rides.9,10 The study of NHC catalysts in the context of direct
arylation reactions could therefore not only enable the general
use of aryl chlorides in these reactions but also provide an
opportunity to circumvent NHC catalyst decomposition since
these reactions must be able to occur in the absence of a
strong nucleophile. Herein, we describe a generally applicable
catalyst system for the efficient intramolecular direct aryla-
(1) Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1290.
(2) Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G. In
Principles and Applications of Organotransition Metal Chemistry; Univer-
sity Science: Mill Valley, CA, 1987.
(3) For example see: (a) Hillier, A. C.; Grasa, G. A.; Viciu, M. S.; Lee,
H. M.; Yang, C.; Nolan, S. P. J. Organomet. Chem. 2002, 653, 69. (b)
Huang, J.; Nolan, S. P. J. Am. Chem. Soc. 1999, 121, 9889. (c) Huang, J.;
Grasa, G. A.; Nolan, S. P. Org. Lett. 1999, 1, 1307. (d) Lee, H. M.; Nolan,
S. P. Org. Lett. 2000, 2, 119. (e) Grasa, G. A.; Viciu, M. S.; Huang, J.;
Nolan, S. P. J. Org. Chem 2001, 66, 7729. (f) Grasa, G. A.; Viciu, M. S.;
Huang, J.; Zhang, C.; Trudell, M. L.; Nolan, S. P. Organometallics 2002,
21, 2866. (g) Viciu, M. S.; Kissling, R. M.; Stevens, E. D.; Nolan S. P.
Org. Lett. 2002, 4, 2229. (h) Viciu, M. S.; Germaneau, R. F.; Navarro-
Fernandez, O.; Stevens E. D.; Nolan, S. P. Organometallics 2002, 21, 5740.
(4) (a) Viciu, M. S.; Navarro, O.; Germaneau, R. F.; Kelly, R. A., III;
Sommer, W.; Marion, N.; Stevens, E. D.; Cavallo, L.; Nolan, S. P.
Organometallics 2004, 23, 1629. (b) Jensen, D. R.; Schultz, M. J.; Mueller,
J. A.; Sigman, M. S. Angew. Chem., Int. Ed. 2003, 42, 3810. (c) Frisch, A.
C.; Rataboul, F.; Zapf, A.; Beller, M. J. Organomet. Chem. 2003, 687,
403. (d) Viciu, M. S.; Stevens, E. D.; Petersen, J. L.; Nolan, S. P.
Organometallics 2004, 23, 3752.
(5) For a review, see: Crudden, C. M.; Allen, A. P. Coord. Chem. ReV.
2004, 248, 2247.
(6) (a) Marshall, W. J.; Grushin, V. V. Organometallics 2003, 22, 1591.
(b) McGuinness, D. S.; Green, M. J.; Cavell, K. J.; Skeleton, B. W.; White,
A. H. J. Organomet. Chem. 1998, 565, 165. (c) McGuinness, D. S.; Cavell,
K. J.; Skeleton, B. W.; White, A. H. Organometallics 1999, 18, 1596. (d)
Caddick, S.; Cloke, F. G. N.; Hitchcock, P. B.; Leonard, J.; Lewis, A. K.;
McKerrecher, D.; Titcomb, L. R. Organometallics 2002, 21, 4318.
10.1021/ol050501v CCC: $30.25
© 2005 American Chemical Society
Published on Web 04/07/2005