Angewandte
Chemie
DOI: 10.1002/anie.200905953
Coupling Reactions
Decarboxylative Cross-Coupling of Aryl Tosylates with Aromatic
Carboxylate Salts**
Lukas J. Gooßen,* Nuria Rodrꢀguez, Paul P. Lange, and Christophe Linder
In memory of Keith Fagnou
Metal-catalyzed coupling reactions are effective synthetic
tive couplings hinges on a broad substrate scope, the use of
inexpensive and readily available carbon electrophiles, and
mild reaction conditions. The early protocols allowed the
coupling of diversely functionalized ortho-substituted ben-
zoates, heterocyclic arenecarboxylates, and a-oxocarboxy-
lates with a wide variety of aryl and heteroaryl halides.[5,8,9]
However, the strongly coordinating halide ions that were
formed in the process were found to impede the decarbox-
ylation of other arenecarboxylates.[5b] A decisive extension of
the substrate scope covering the full range of substitution
patterns including meta- and para-substituted arenecarbox-
ylates was achieved by new catalysts that allowed the use of
aryl triflates as carbon electrophiles.[10] The coupling of these
substrates releases only noncoordinating anions that do not
hinder the decarboxylation at the copper center.[5b] Unfortu-
nately, the practical utility of this protocol is limited by the
expense and the sensitivity of aryl triflates.
À
tools for the formation of C C bonds between nucleophilic
and electrophilic substrates at positions predefined by leaving
groups.[1] Recently, decarboxylative coupling reactions have
À
emerged as powerful alternatives for regioselective C C bond
formation,[2] thus providing new protocols for Heck-type
reactions,[3] oxidative arylations,[4] redox-neutral cross-cou-
pling reactions,[5] and allylations.[6]
The redox-neutral decarboxylative coupling reactions that
have been developed in our research group[5a] aim at replacing
sensitive and costly organometallic reagents, which are tradi-
tionally used as nucleophilic coupling partners, with stable,
inexpensive and widely available carboxylate salts.[5,7] In this
type of reaction, a copper(I) or silver(I) catalyst mediates the
extrusion of CO2 from the carboxylates while a palladium
complex catalyzes the coupling of the resulting carbon
nucleophiles with carbon electrophiles (Scheme 1).
In view of the high performance level of traditional cross-
couplings, a widespread practical application of decarboxyla-
The use of the inexpensive and more robust aryl p-
toluenesulfonates (tosylates) is of profound interest for all
types of cross-coupling reactions, and substantial effort has
been devoted to the development of catalyst systems capable
of activating them.[11] In earlier protocols, nickel complexes
were mostly used as catalysts,[12] until a new class of bulky,
electron-rich phosphines was discovered that strongly facili-
tates the oxidative addition of aryl tosylates to palladium
catalysts.[13] In recent years, aryl tosylates have successfully
been employed as substrates in, for example, Stille,[14]
Suzuki,[15] and Kumada coupling reactions,[16] aminations,[17]
and ortho-arylations.[18]
The use of aryl tosylates as substrates in decarboxylative
coupling reactions should have an even higher synthetic
impact, when considering that a low coordinating ability of
the leaving group is an essential prerequisite for accessing the
full range of carboxylic acid substrates.
Scheme 1. Cu/Pd-catalyzed decarboxylative cross-coupling. M=Ag,
Cu; R=(hetero)aryl, vinyl, acyl; R’=(hetero)aryl; X=I, Br, Cl, OTf.
Tf =trifluoromethanesulfonyl.
We started the development of the catalyst for the desired
decarboxylative cross-coupling (see Scheme in Table 1) with a
series of protodecarboxylation reactions in the presence of
phosphine ligands to identify phosphines that would not
interfere with the decarboxylation step.[19] Fortunately, the
conversion of 3-nitrobenzoic acid into nitrobenzene using
Cu2O/1,10-phenanthroline (phen) catalysts was not affected
by the electron-rich, sterically demanding phosphines that are
known to activate unreactive leaving groups (Scheme 2).
We next investigated the performance of palladium
complexes with such ligands as catalysts in the decarboxyla-
tive coupling of potassium 2-nitrobenzoate (1a) with 4-tolyl
tosylate (2a) in combination with a Cu2O/phen co-catalyst
(Table 1).
[*] Prof. Dr. L. J. Gooßen, Dr. N. Rodrꢀguez, P. P. Lange, C. Linder
FB Chemie–Organische Chemie, TU Kaiserslautern
Erwin-Schrꢁdinger-Strasse Geb. 54
67663 Kaiserslautern (Germany)
Fax: (+49)631-205-3921
E-mail: goossen@chemie.uni-kl.de
[**] We thank the Deutsche Forschungsgemeinschaft, Saltigo GmbH,
and NanoKat for funding, as well as the A. v. Humboldt Foundation
for a scholarship to N.R.
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2010, 49, 1111 –1114
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1111