Palladium-bisimidazol-2-ylidene complexes as catalysts for general and efficient Suzuki cross-coupling reactions of aryl chlorides with arylboronic acids

Article abstract of DOI:10.1016/S0040-4039(99)02133-4

A series of bisimidazolium salts 1-6 were synthesized and evaluated as precursors to bisimidazol-2-ylidene ligands in palladium-catalyzed Suzuki cross-coupling reactions with aryl chlorides and arylboronic acids. The bisimidazolium salt 6 was found to be superior over imidazolium and other bisimidazolium salts affording high yields of biaryl products employing a wide variety of substrates. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(99)02133-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 595–598
Palladium-bisimidazol-2-ylidene complexes as catalysts for
general and efficient Suzuki cross-coupling reactions of aryl
chlorides with arylboronic acids
Chunming Zhang and Mark L. Trudell ∗
Department of Chemistry, University of New Orleans, New Orleans, Louisiana 70148, USA
Received 19 October 1999; revised 9 November 1999; accepted 12 November 1999
Abstract
A series of bisimidazolium salts 1–6 were synthesized and evaluated as precursors to bisimidazol-2-ylidene
ligands in palladium-catalyzed Suzuki cross-coupling reactions with aryl chlorides and arylboronic acids. The
bisimidazolium salt 6 was found to be superior over imidazolium and other bisimidazolium salts affording high
yields of biaryl products employing a wide variety of substrates. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: Suzuki reactions; carbenes; imidazolylidene; palladium; aryl chlorides; arylboronic acids.
The palladium-catalyzed Suzuki cross-coupling reactions of aryl halides and triflates with arylboronic
acids provide a general and efficient synthetic route to biaryl compounds and have found widespread
use in many areas of organic synthesis.1 Routinely these procedures employ phosphine-based catalyst
systems and arylbromide, aryl iodide or aryl triflate substrates. The use of aryl chlorides as chemical
feedstock in coupling chemistry has proven difficult but would economically benefit a number of
industrial procedures.2,3 Significant advances have been recently reported by Buchwald,4 Fu5 and
Guram,6 which used modified-phosphine palladium systems.
Nucleophilic N-heterocyclic carbenes, especially the imidazol-2-ylidenes have attracted consider-
able attention as possible alternatives for widely used phosphine ligands in homogeneous catalysis.7
We recently reported on the Suzuki cross-coupling reactions of aryl chlorides and arylboronic acids
employing a Pd2(dba)3/IMes·HCl catalyst system.8 As part of an ongoing investigation aimed at the
development of novel imidazol-2-ylidenes as ligands for transition metal catalysis, we wish to report the
efficient Suzuki coupling reactions of aryl chlorides with aryl boronic acids using palladium-bisimidazol-
2-ylidene (Pd–L) catalyst systems preformed from Pd(OAc)2 and bisimidazolium salts (L·2HX).
∗
Corresponding author. Tel: (504) 280-7337; fax (504) 280-6860; e-mail: mtrudell@uno.edu (M. L. Trudell)
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02133-4
tetl 16061

596
The bisimidazolium salts 1–6 (Fig. 1) were prepared by heating the corresponding dibromides or
dichlorides and 2 equivalents of a 1-aryl-imidazole in xylene. As an example, a mixture of dibromo-
methane (1.0 mmol) and N-(3,5-dimethylphenyl)imidazole (2.0 mmol) was heated in xylene (5 mL)
at 140°C for 2 days. This afforded the salt 2 in 70% yield. Alternatively, a mixture of 1,3-di(α-
chloromethyl)-2,4,6-trimethylbenzene (1.0 mmol) and N-(2,4,6-trimethylphenyl)imidazole (2.0 mmol)
was heated in xylene (5 mL) at 120°C for 48 h and furnished 6 in 85% yield.
Fig. 1. Bisimidazolium salts
The Pd(OAc)2/L·2HX catalyzed reaction of 4-chlorotoluene and phenylboronic acid was selected as
a model reaction for investigating the efficiencies of these bisimidazolylidene (L) ligand precursors. As
shown in Table 1, the bisimidazolium salts (±)-5 and 6 were found to be effective substrates and afforded
the desired biaryl product in high yields. The salt 4 provided a moderate yield of the biaryl compound
while the salts 1, 2, and 3, which possessed considerably less steric hindrance, were found to be less
efficient and exhibited very low conversion.
The utility of the Pd(OAc)2/bisimidazolium salt 6 catalyst system for general Suzuki cross-coupling
reactions of aryl chlorides was further investigated to determine the scope and limitations of reaction
(Table 2). The Pd(OAc)2/6 catalyst system was found to be generally efficient in catalyzing the cross-
coupling reactions of a variety of aryl chlorides and arylboronic acids. Electron-donating and electron-
withdrawing substituents were both well tolerated by the catalytic system and provided the corresponding
biaryl products in excellent yields. Moreover, the ancillary bisimidazol-2-ylidene ligand generated from
6 was found to exhibit higher efficiency than that of imidazol-2-ylidene ligand generated from IMes·HCl
(comparison of entry 1 and entry 2 in Table 2).
In summary, the novel bisimidazolium salts were prepared as bisimidazol-2-ylidene ligand precursors
for Pd-catalyzed Suzuki coupling reactions of aryl chlorides with arylboronic acids. The Pd(OAc)2/6
catalyst system has been shown to be generally very efficient for high yielding cross-coupling reactions
of aryl chlorides and arylboronic acids. The catalytic system involving air stable components Pd(OAc)2

597
Table 1
Ligand effects in Pd(OAc)2/L·2HX-catalyzed Suzuki reaction of 4-chlorotoluene and phenylboronic
acid9
Table 2
Pd(OAc)2/6-catalyzed Suzuki cross-coupling reactions of aryl chlordes with arylboronic acids9
and bisimidazolium salt 6, should be amenable for large scale synthesis. Further investigations of this
catalytic system and other transition metal-catalyzed organic transformations are ongoing.10
Acknowledgements
We are grateful to the National Institute on Drug Abuse for financial support of this research.

598
References
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Weiheim, Germany, 1998; Chapter 2. (c) Suzuki, A. J. Organomet. Chem. 1999, 576, 147–168.
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9. All reactions were conducted by heating Pd(OAc)2 (0.025 mmol) and a bisimidazolium salt (0.025 mmol) and Cs2CO3 (2.0
mmol) in dry dioxane (3 mL) at 80°C under argon for a 30 min catalyst activation period, followed by the addition of the
aryl chloride (1.0 mmol) and the arylboronic acid (1.5 mmol).
10. Huang, J.; Zhang, C.; Trudell, M. L.; Nolan, S. P. Unpublished results.