Angewandte
Chemie
leads quantitatively to phenylpyrazole, which confirms the
presence of one pyrazole ring at the copper center (path B).
It is noteworthy that no change occurs in the 31P NMR
spectra (solution and precipitate) if PhBr is first added to 5.
The further addition of pyrazole and base are required for
the reaction to take place, again quantitatively. A similar
general behavior is observed in the case of phenols.
We can thus propose a pathway involving precoordina-
tion of the nucleophile at the copper center as the first step
(Scheme 3). The corresponding anionic complex 6a could
then undergo oxidative addition of PhBr with release of CsI
Scheme 2. Copper-catalyzed arylation of pyrazole as determined by
31P NMR spectroscopic analysis of the reaction.
better understood than those catalyzed be copper, for which
comparatively few studies have been performed.[5c,11] Eluci-
dating the mechanism thus constitutes one of the most
exciting challenges in Ullmann reactions. By following the
reactions by 31P NMR spectroscopy, we found a standard
coupling between PhBr and pyrazole (or phenol) when using
one equivalent of copper precatalyst.
Scheme 3. Possible catalytic cycle with a first ligand/pyrazolate
exchange followed by oxidative addition on an anionic or neutral CuI
intermediate (S=CH3CN).
(path C). Alternatively, CsI could also be released from the
complex 6a as a consequence of a stabilizing intervention of
the solvent before oxidative addition occurs on the neutral
CuI complex 6b (path D). This latter pathway could contrib-
ute to an explanation of the crucial role of the solvent in
copper-catalyzed reactions.[11] In both pathways, the resulting
intermediate would be probably a copper(III) complex
([PyrCuLPhBr], undetermined structure) from which the
cross-coupling product is expelled and the catalytically active
species reformed by reductive elimination.
In conclusion, we have reported the first known applica-
tion of a butadienylphosphine as a ligand in a catalytic
reaction. Phosphine 4, available on a large scale from a
recently developed general synthetic method, was found to be
a very efficient ligand in Ullmann-type copper-catalyzed
arylation reactions. This ligand also provided us with some
insight into this reaction, whose mechanism has been little
studied until now. Work is now in progress to explore
potential fields of application of these ligands in catalysis
and also as dienes in Diels–Alder reactions.
In the first step, the addition of CuI to two equivalents of
(Z)-4 ligand results in the quantitative formation of complex 5
as a white precipitate (no phosphorus product is present in
solution). The further addition of pyrazole (1 equiv) does not
induce any change in either the precipitate or filtrate
(31P NMR). In contrast, the subsequent introduction of base
(Cs2CO3, 2 equiv) provokes the release of one equivalent of
butadienylphosphine (Z)-4 (d = À27 ppm in CH3CN) into the
solution, in which pyrazole could no longer be detected.[12]
Therefore, one equivalent of ligand (Z)-4 at the copper center
has likely been substituted by one pyrazolate group. The
corresponding green precipitate 6 might thus be a copper
complex in which the metal atom is bound to one pyrazole
and one butadienylphosphine group. 13C NMR spectroscopic
analysis of the precipitate confirmed this proposal since the
signal for C5 of the pyrazole ring appears as a doublet (3JCP
=
10.25 Hz). Moreover, the 31P NMR spectrum indicates the
presence of one compound (CDCl3, d = À25 ppm) which is
different from 5 (CDCl3, d = À21 ppm) and from (Z)-4
(CDCl3, d = À28.08 ppm). Finally, according to the NMR
spectra, the complex does not involve coordinated acetoni-
trile. However, these data do not allow us to determine the
exact structure of complex 6, for which an X-ray structure
would be very helpful. If in a final step one equivalent of PhBr
is added to the mixture, the expected coupling product is
obtained in 100% yield (path A). Even more interestingly,
the addition of PhBr (1 equiv) to isolated precipitate 6 also
Received: February 11, 2008
Revised: July 18, 2008
Published online: November 28, 2008
Publication delayed on authorsꢀ request.
Keywords: arylation · copper · homogeneous catalysis ·
.
P ligands · reaction mechanisms
Angew. Chem. Int. Ed. 2009, 48, 333 –336
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
335