Palladium-tetraphosphine complex: an efficient catalyst for the
coupling of aryl halides with alkynes
Marie Feuerstein, Florian Berthiol, Henri Doucet* and Maurice Santelli*
Laboratoire de Synthèse Organique associé au CNRS, Faculté des Sciences de Saint Jérôme,
Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France.
E-mail: henri.doucet@univ.u-3mrs.fr; m.santelli@univ.u-3mrs.fr; Fax: 04 91 98 38 65; Tel: 04 91
28 84 16
Received 6th June 2003, Accepted 6th June 2003
First published as an Advance Article on the web 11th June 2003
The cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)-
cyclopentane–[PdCl(η3–C3H5)]2 system catalyses the coup-
ling of aryl halides with alkynes with very high ratios
of substrates–catalyst in good yields; a turnover number of
2600000 can be obtained for the reaction of 4-trifluoro-
methylbromobenzene with phenylacetylene in the presence
of this catalyst.
specifically bound to the same face of the cyclopentane ring.
The presence of four phosphines close to the metal centre seems
to increase the stability of the catalyst. A very high efficiency
has been observed for allylic substitution,9a,9b and for Suzuki
cross-coupling using tedicyp as the ligand.9c We have also
reported recently the first results obtained for Heck reactions.9d
In this paper, we wish to report on the efficiency of this ligand
for the reaction of aryl halides with terminal alkynes.
The coupling reaction of terminal alkynes with aryl halides
provides an efficient method for the preparation of arylalkynes
(Scheme 1). The classical method used to perform this reaction
is to employ a palladium catalyst in the presence of a catalytic
amount of copper iodide.1,2 These palladium complexes are
generally associated with the triphenylphosphine ligand.3 Even
if the catalyst formed by association of this ligand with
palladium complexes is quite efficient in terms of yield of
adduct, the efficiency in terms of ratio of substrate–catalyst is
generally low, and 1–10% of the catalyst must be used. Recently
a few more efficient catalysts have been successfully used for
this reaction. For example, Herrmann et al. have reported that
the palladacycle [Pd(o-tol)(OAc)]2 is efficient for the reaction
of 4-bromoacetophenone with phenylacetylene.4a An oxime
palladacycle in the presence of tetrabutylammonium acetate
also led to coupling products with high turnover numbers
(TONs).4b Two of the most active catalytic systems uses
palladium associated to bulky monodentate phosphine
ligands.5 Carbene ligands also lead to the formation of
palladium catalysts which are more efficient than those of
triphenylphosphine for this reaction.6 Finally, a very efficient
catalyst for this reaction has been prepared with a bis-
pyrimidine ligand. With this ligand a TON of 22300 has been
obtained for the reaction of iodobenzene with phenylacetyl-
ene.7 If carbenes, pyrimidines or monophosphine ligands have
been successfully used for this reaction, to our knowledge,
the efficiency of tetraphosphine ligands has not yet been
demonstrated.
In the literature, many reaction conditions have been
employed, so our first objective was to determine the most
suitable reaction conditions with our tetraphosphine ligand.
We observed that the reaction of 4-bromoacetophenone with
phenyl acetylene in the presence of triethylamine and the
catalytic system [PdCl(η3–C3H5)]2–tedicyp in DMF at room
temperature does not proceed (Table 1, entry 1). The reaction
performed at 50 and 80 ЊC using similar conditions led to the
coupling product in reasonable yields, however in all cases an
important amount of the dimer of phenylacetylene was
observed (entries 2–4). The reaction performed at 140 ЊC with
piperidine as base led to higher reaction rates, but the dimer of
phenylacetylene was still observed (entries 6 and 7). A much
cleaner and faster reaction was observed using K2CO3 as base
(entry 8). With this base, only traces of dimerisation product
were observed.
Next we tried to evaluate the importance of the presence of
phosphine ligands on the complex using these conditions. So we
performed the reaction with [PdCl(η3–C3H5)]2 as catalyst in
the absence of ligand. We observed that 4-bromoanisole with
phenylacetylene in the presence of 0.1% catalyst was recovered
unreacted (Table 1, entry 9). Then, we studied the difference of
efficiency between mono, di and polydentate ligands bearing
diphenylphosphino groups for this reaction. For this we
compared the rate of the reaction in the presence of mono-
phosphines, a diphosphine and with our tetraphosphine. The
reaction performed in the presence of 0.1% catalyst, led to
the addition product in 5 and 3% conversion when PPh3 and
P(o-Tol)3 were used as ligands (Table 1, entries 10 and 11) and
50% conversion with dppb (entry 12). With the tetradentate
ligand Tedicyp conversions of 100% and 38% in the presence
of 0.1 and 0.01% catalyst were obtained (entries 13 and 14).
Then, we tried to evaluate the scope and limitations of the
Tedicyp–palladium complex for this reaction. A survey of
catalytic coupling of aryl halides with alkynes is provided
in Table 2. A wide variety of functional groups on the aryl
bromide are tolerated. In the presence of activating groups
high reaction rates are observed. For example, the coupling
of 4-fluorobromobenzene, 4-trifluoromethylbromobenzene, 4-
bromoacetophenone, 4-bromobenzophenone, 4-bromobenzo-
nitrile and 4-bromobenzaldehyde with phenylacetylene in the
presence of 0.0001% of the Tedicyp–palladium complex (ratio
substrate–catalyst: 1000000) led to the coupling products
in 70–100% yields (Table 2, entries 3, 5, 13, 15, 18 and 19).
A turnover number of 2800000 has been obtained for the
Scheme 1
The nature of phosphine ligands on complexes has an
important influence on the rate of catalysed reactions. In order
to find more efficient palladium catalysts we have prepared
a new tetrapodal8 phosphine ligand, cis,cis,cis-1,2,3,4-tetrakis-
(diphenylphosphinomethyl)cyclopentane or Tedicyp 19a (Fig.
1) in which the four diphenylphosphino groups are stereo-
Fig. 1
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 3
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 2 3 5 – 2 2 3 7
2235
Feuerstein, Marie
