in the Ullmann reaction prevented the applications in the
synthesis of functionalized biaryls.
Palladium-Catalyzed Homocoupling and
Cross-Coupling Reactions of Aryl Halides in
Poly(ethylene glycol)
Recently, the selective palladium-catalyzed coupling of aryl
halides under mild conditions has been developed.9 The reaction
is usually conducted in the presence of the reducing agents,
such as formate salt,9b,c hydrogen gas,9d amines,9e alcohols,9f,g
and zinc.9h-k These reducing agents, however, diminish the
selectivity in some cases due to the competitive chemisorption
and hydride forming ability, which lead to the parallel reduction
reaction. For example, undesired reductions of carbonyl and
nitro group as well as the hydrodehalogenation are often
observed when metal was employed as the reductants. Although
organic reductants show some advantages over inorganic
reductants in solubility and selectivity, the hydrodehalogenation
of aryl halides is still problematic in many cases. On the other
hand, the synthesis of unsymmetrical biaryls via palladium-
catalyzed cross-coupling reaction of aryl halides is a relatively
unexplored area.10
Liang Wang, Yuhong Zhang,* Leifang Liu, and
Yanguang Wang*
Department of Chemistry, Zhejiang UniVersity,
Hangzhou 310027, P. R. China
ReceiVed NoVember 6, 2005
The preliminary studies of others and our group have revealed
that PEG can be used as a reaction medium for selective
reactions with easy recyclability of solvent and catalysts.11
Unlike several of the “neoteric solvents” such as ionic liquids
(ILs) where toxicity and environmental burden data are for the
The direct coupling of aryl halides to prepare symmetrical
and unsymmetrical biaryls were performed successfully in
poly(ethylene glycol) (PEG) using Pd(OAc)2 as the catalyst
in the absence of other additives or reductants. The selectivity
toward biaryl depended on the amount of PEG used.
Excessive PEGs induce the increase of hydrodehalogenation
product, and the best selectivity to biaryl is obtained when
the concentration of the hydroxyl group in PEG achieves
100 mol % relative to aryl halides. The catalyst system could
be recycled and reused up to five times with no loss of
catalytic activity.
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Biaryls are important building blocks of numerous agro-
chemicals, pharmaceucals, natural products, conducting materi-
als, and asymmetric catalysts.1 Due to their widespread appli-
cations, the development of straightforward and environmentally-
friendly methods for the preparation of biaryls has aroused many
attentions.2 The cross coupling of aryl halides with arylmetals
mediated by palladium is one of the effective methodologies
for the synthesis of biaryls. Many different arylmetals, including
arylboronic acids,3 arylstannanes,4 arylzinc,5 aryl Grignard
regents,6 and so on,7 have been thoroughly investigated.
However, these methods require more than one equimolar
amount of arylmetal regents. The direct dimerization of aryl
halides without the preparation step of arylmetal is considered
to be a more convenient and straightforward method for the
synthesis of biaryls. For example, the Ullmann reaction has long
been employed to generate the C-C bond from aryl halides
directly.8 Unfortunately, the relatively harsh conditions required
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* To whom correspondence should be addressed. Tel: +86-571-87953253.
Fax: +86-571-87951895.
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10.1021/jo052300a CCC: $33.50 © 2006 American Chemical Society
Published on Web 01/10/2006
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J. Org. Chem. 2006, 71, 1284-1287