Copper(I) iodide polyphosphine adducts at low loading for sonogashira alkynylation of demanding halide substrates: Ligand exchange study between copper and palladium

Article abstract of DOI:10.1021/om1003336

The prestabilization of copper iodide with a multidentate ferrocenyl phosphine ligand promotes the palladium-catalyzed cross-coupling of demanding halides with phenylacetylene in a selective way. Novel CuI-triphosphine adducts are described in the solid s

Full text of DOI:10.1021/om1003336

Organometallics 2010, 29, 2815–2822 2815
DOI: 10.1021/om1003336
Copper(I) Iodide Polyphosphine Adducts at Low Loading for Sonogashira
Alkynylation of Demanding Halide Substrates: Ligand Exchange Study
between Copper and Palladium
ꢀ ꢀ ꢁ
Matthieu Beauperin, Andre Job, Helene Cattey, Sylviane Royer, Philippe Meunier, and
Jean-Cyrille Hierso*
ꢀ
ꢀ
Institut de Chimie Moleculaire de l’Universite de Bourgogne (ICMUB-UMR CNRS 5260),
ꢀ
Universite de Bourgogne, 9 Avenue Alain Savary, 21078 Dijon, France
Received April 22, 2010
The prestabilization of copper iodide with a multidentate ferrocenyl phosphine ligand promotes the
palladium-catalyzed cross-coupling of demanding halides with phenylacetylene in a selective way. Novel
CuI-triphosphine adducts are described in the solid state and in solution. Their use allowed the introduc-
tion of the copper iodide cocatalyst in unprecedented low amounts (0.4 to 0.1 mol %) in systems also em-
ploying low amounts of “ligand-free” [PdII(η3-allyl)Cl]2 precursor (0.2 to 0.05 mol %). The scope of
substrates is reported, and electronically or sterically deactivated bromides were efficiently coupled.
Concerning aryl chlorides, electron-poor activated substrates were also coupled using this innovative low-
metal-content catalytic system. Some rarely tackled mechanistic aspects are discussed herein. In particular,
the transfer of ligand from copper to palladium monitored by NMR was found to be different depending
on the polyphosphine ligand. The inhibition of diyne formation was also an interesting feature provided
by the prestabilized copper species used in low amount, contrary to the employment of 5 mol % CuI with
palladium. Notably, the copper(I) iodide phosphine adduct 6, formed from 1,2-bis(diphenylphosphino)-
10-(diisopropylphosphino)-4-tert-butylferrocene, also allowed under copper-only conditions the “palladium-
free” coupling of the electron-rich deactivated 4-iodotoluene to phenylacetylene.
Introduction
bromides) is the so-called Sonogashira reaction, which is based
on the tandem catalytic use of a palladium complex with a cop-
per salt (Scheme 1, left).3 Recent reports often focus on water
solvent, copper-free, or aerobic conditions.4 Nevertheless, the
cross-coupling of terminal alkynes to other organic fragments
(aryls, amides, azides, etc.) catalyzed by palladium and/or cop-
per often suffers from oxidative homocoupling of the terminal
alkynes (Scheme 1, side reactions on the right).5-7 This acetyl-
enic coupling, when intended, is a powerful tool in molecular
construction.8 However, it could be significantly detrimental
as a side-reaction,5b especially since it can be promoted by
both copper(I) salts8,9 and palladium(II) complexes.10,11
Metal-catalyzed reactions to selectively yield valuable (aryl)-
alkynes are mainly dependent on palladium chemistry for the
alkynylation of demanding aryl halides by employing terminal
alkynes.1,2 One of the leading methods used to activate these
appealing but demanding compounds (i.e., most aryl chloride
substrates and sterically and/or electronically deactivated
*Corresponding author. Fax: 33 3 8039 3682. Tel: 33 3 8039 6106.
E-mail: jean-cyrille.hierso@u-bourgogne.fr.
(1) (a) Doucet, H.; Hierso, J.-C. Angew. Chem., Int. Ed. 2007, 46, 834.
ꢀ
(b) Chinchilla, R.; Najera, C. Chem. Rev. 2007, 107, 874.
(2) Negishi, E. I.; Anastasia, L. Chem. Rev. 2003, 103, 1979.
(3) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett.
1975, 4467.
(5) For recently reported examples, see: (a) Elangovan, A.; Wang,
Y. H.; Ho, T. I. Org. Lett. 2003, 5, 1841. (b) Gelman, D.; Buchwald, S. L.
Angew. Chem., Int. Ed. 2003, 42, 5993. (c) Wolf, C.; Lerebours, R. Org.
Biomol. Chem. 2004, 2, 2161. (d) Rao Volla, C. M.; Vogel, P. Tetrahedron
Lett. 2008, 49, 5961.
(6) Hamada, T.; Ye, X.; Stahl, S. S. J. Am. Chem. Soc. 2008, 130, 833.
(7) Katayama, T.; Kamata, K.; Yamaguchi, K.; Mizuno, N. Chem-
SusChem 2009, 2, 59.
(4) (a) For a review on pure water conditions, see: Lamblin, M.; Nassar-
Hardy, L.; Hierso, J.-C.; Fouquet, E.; Felpin, F. X. Adv. Synth. Catal. 2010,
352, 33. (b) Under strictly deaerated copper-free water/alcohol conditions:
Fleckenstein, C. A.; Plenio, H. Green Chem. 2008, 10, 563. (c) In neat water:
Gu, S.; Chen, W. Organometallics 2009, 28, 909. (d) Under atmospheric
conditions: Ray, L.; Barman, S.; Shaikh, M. M.; Ghosh, P. Chem.;Eur. J.
2008, 14, 6646. (e) Under copper-free atmospheric and aqueous conditions:
Samantaray, M. K.; Shaikh, M. M.; Ghosh, P. J. Organomet. Chem. 2009, 694,
3477. In the conditions reported in (c), (d), and (e) mostly organic iodides are
coupled and only a few activated bromides are used (nonhindered, electron-poor).
Iodides are facile substrates, their industrial use is detrimental due to their mass,
and their price can be 50 times higher than bromides. For instance, 2-iodopyridine
(98%) is found around 45.5 ꢀ 102 h/mol and 2-bromopyridine (99%) at 0.9 ꢀ
102 h/mol from small-scale commercial sources (Sigma-Aldrich, 2009 lowest
prices). (f) Ionic liquid conditions can also be useful and possibly better nontoxic
alternatives; see: (g) Saleh, S.; Picquet, M.; Meunier, P.; Hierso, J.-C. Tetrahedron
2009, 65, 7146. (h) Hierso, J.-C.; Boudon, J.; Picquet, M.; Meunier, P. Eur. J. Org.
Chem. 2007, 583.
(8) For an excellent review, see: Siemsen, P.; Livingston, R. C.;
Diederich, F. Angew. Chem., Int. Ed. 2003, 39, 2632.
€
(9) (a) Bohlmann, F.; Schonowsky, H.; Inhoffen, E.; Grau, G. Chem.
Ber. 1964, 97, 794. (b) Fomina, L.; Vazquez, B.; Tkatchouk, E.; Fomine, S.
Tetrahedron 2002, 58, 6741. (c) Kamata, K.; Yamaguchi, S.; Kotani, M.;
Yamaguchi, K.; Mizuno, N. Angew. Chem., Int. Ed. 2008, 47, 2407.
(10) (a) Liu, Q.; Burton, D. J. Tetrahedron Lett. 1997, 38, 4371.
(b) Alper, H.; Saldana-Maldonado, M. Organometallics 1989, 8, 1124.
(11) Batsanov, A. S.; Collings, J. C.; Fairlamb, I. J. S.; Holland, J. P.;
Howard, J. A. K.; Lin, Z.; Marder, T. B.; Parsons, A. C.; Ward, R. M.;
Zhu, J. J. Org. Chem. 2005, 70, 703.
r
2010 American Chemical Society
Published on Web 05/27/2010
pubs.acs.org/Organometallics

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Beauperin et al.
2816 Organometallics, Vol. 29, No. 12, 2010
Scheme 1. Sonogashira Reaction and Alkyne Homocoupling
Side-Reactions
Scheme 3. Synthesis of Copper(I) Iodide Triphosphine Adducts
4 and 6
Sonogashira alkynylation by initial ligand complexation to
copper instead of palladium. With regard to the many environ-
mental challenges attached to contemporary chemistry, the
development of selective catalytic reactions under significantly
lower metal contents is of high interest. Therefore, we decided to
explore whether other benefits could be obtained from new CuI
adducts in the alkynylation of organic halides.
Scheme 2. Synthesis of the Copper(I) Iodide Tetraphosphine
Adduct 2
Herein, synthesis of the first copper(I) iodide ferrocenyl
triphosphine adducts is described together with their charac-
terization in the solid state by single-crystal X-ray diffraction
(XRD) and in solution by NMR. The catalytic performances
reported focus on the alkynylation of deactivated aryl sub-
strates (bromides and chlorides) since ligand-less systems
are efficient with iodides or some activated aryl bromides
(electron-poor).1,13 Our efforts were also devoted to the
minimization of metal content. Finally, a better mechanistic
understanding was sought through the monitoring of ligand
Typically, the Sonogashira reactionrequires inertand oxygen-
free conditions to restrain oxidative homocoupling of
alkynes. On the other hand, more convenient handling condi-
tions, for instance without the need of a glovebox or of deoxy-
genating the reagents (especially the liquid participants), are
preferred for large-scale industrial applications.
1
transfer from copper to palladium by H and 31P NMR at
variable temperatures from 183 to 353 K.
We initiated a program aiming to develop air-stable, moist-
ure- and temperature-resistant polydentate auxiliaries, which
could allow efficient catalytic reactions in the presence of low
amounts of metals (less than 1 mol %). For environmental and
economical reasons the minimization of metal amounts in
metal-catalyzed reactions is a crucial objective, and novel strate-
gies to shore up this goal are highly desirable. In the course of
this program, the first examples of copper(I)-ferrocenyltetra-
phosphine complexes have been reported (Scheme 2).12
Our investigations showed that 1 mol % of adduct 2 com-
bined with 1 mol % of a “ligand-free” palladium(II) precursor
was much more efficient and selective for Sonogashira coupling
than the system combining the palladium complex coordinated
to the same tetraphosphine metallo-ligand 1 in the presence of 5
mol % of CuI.12 This was evidenced by the selective coupling of
the deactivated 4-bromoanisole to phenylacetylene. The CuILn/
PdII precursor system avoided the concurrent and deleterious
consumption of phenylacetylene by formation of diyne or eny-
nes. Additionally, the use of adduct 2 offered practical advan-
tages since it was efficient in only 1 mol % amount and its
stability to air allowed much easier storage and handling com-
pared to anhydrous CuI. To the best of our knowledge, this was
the first time that such high selectivity had been induced in
Results and Discussion
Copper(I) Iodide-Triphosphine Adducts Characterization. In
order to obtain a better knowledge of ferrocenyl polyphos-
phine coordination behavior toward copper salts, two new
triphosphine adducts, 4 and 6, were synthesized quantita-
tively from the triphosphines 3 and 5 (Scheme 3).
In the solid state, XRD studies confirmed the expected
tridentate coordination of the ligand 3 or 5 to one copper
iodide (Figures 1 and 2). The distorted tetrahedral environ-
ment for the copper center is analogous in 4 and 6 to the one
found for the adduct 2,12 the main general difference being
the uncoordinated phosphorus donor atom in the tetraphos-
phine adduct 2.
A comparison of atom distances and angles is given in Table 1.
A correlation is found between the ligand rigidity and the
greater difference found within the three Cu-P bond distances
in the complexes. Due to the total number of substituents on
the ferrocene backbone, 2 is more hindered than 4, which is
in turn more hindered than 6. For the most rigid adduct, 2,
(13) (a) Urgaonkar, S.; Verkade, J. G. J. Org. Chem. 2004, 69, 5752.
(b) Li, J.-H; Hu, X.-C.; Liang, Y.; Xie, Y. X. Tetrahedron 2006, 62, 31.
(c) Thathagar, M. B.; Rothenberg, G. Org. Biomol. Chem. 2006, 4, 111.
(d) Mori, S.; Yanase, T.; Aoyagi, S.; Monguchi, Y.; Maegawa, T.; Sajiki, H.
Chem.;Eur. J. 2008, 14, 6994.
ꢀ
(12) Beauperin, M.; Fayad, E.; Amardeil, R.; Cattey, H.; Richard, P.;
ꢁ
Brandes, S.; Meunier, P.; Hierso, J.-C. Organometallics 2008, 27, 1506.

Article
Organometallics, Vol. 29, No. 12, 2010 2817
Figure 3. Molecular structure of 6 viewed from above.
to the case of tetraphosphine adduct 2, the broadness of signals
is not related to the fluxional behavior of the CuI moiety in
dynamic exchange between the phosphorus atoms.12 This is
shown at low temperature by NMR measurements conducted
between 298 and 182 K, where the appearance of signals, as well
as their chemical shifts, is unchanged.14 In contrast, for adduct 2
above 213 K the mutual location of phosphorus donors toward
the copper atom is exchanged at a high rate, leading at 298 K to
one averaged signal for the three bonded phosphorus atoms.12,14
For 4 at 182 K the 1H NMR signals corresponding to the five
protons of the cyclopentadienyl rings are clearly distinguished at
4.61, 4.48, 4.24, 4.22, and 3.55 ppm. The chemical shift for the
methyl protons of the two tert-butyl groups are also significantly
different at 1.25 and 0.77 ppm.
Figure 1. X-ray molecular structure of CuI-triphosphine
adduct 4.
The 31P NMR spectrum of triphosphine adduct 6 also dis-
plays two broad signals, centered at -0.65 ppm (phosphorus
atom holding isopropyl groups) and -28.0 ppm. Similarly to
adduct 4, upon cooling to 182 K, no changes in the NMR
patterns were detected. In the 1H NMR of 6 at 182 K three
signals are observed for the six protons of the cyclopenta-
dienyl rings at 4.83, 4.36, and 4.04 ppm, and the methyl
protons of the tert-butyl group are observed at 1.32 ppm.
The characterization of the triphosphine adducts 4 and 6 has
confirmed the preferred tridentate coordination adopted to
stabilize copper(I) iodide. Spectroscopic studies have also
revealed that the fluxional behavior evidenced from variable-
temperature NMR measurements for adduct 2 is not observed
in the case of 4 and 6. With regard to the structural differences
between the three compounds, dynamic exchange previously
detected for 2 seems to be a direct consequence of the presence
of four phosphorus donors. The distinction in structure and
solution dynamic behavior between the polyphosphine ad-
ducts 2, 4, and 6 led us to test their performances in C(sp)-
C(sp2) bond coupling processes with metal catalysis.
Figure 2. X-ray molecular structure of CuI-triphosphine
adduct 6.
Table 1. Structural Parameter Comparison for Copper Adducts 2,
4, and 6a
2 (CH3CN)2 4 (MeC6H5)1.5 6 (MeC6H5)1.5
3
3
3
˚
˚
˚
d P(1)-Cu (A)
2.273(2)
2.355(2)
2.310(3)
103.8
106.9
85.9
2.321(4)
2.289(1)
2.274(1)
109.8
99.2
86.2
2.281(1)
2.296(4)
2.296(8)
101.4
108.1
87.3
d P(2)-Cu (A)
d P(3)-Cu (A)
P(1)-Cu-P(2) (deg)
P(1)-Cu-P(3) (deg)
P(2)-Cu-P(3) (deg)
a Crystal data for 2 are reported in ref 12.
˚
a difference in the Cu-P bond distances of 0.037 to 0.082 A is
observed, which is reduced to 0.015 to 0.047 A for 4 and is
˚
Catalytic Performances in Sonogashira Alkynylation Reac-
tions. The influence of the copper(I) iodide triphosphine
adducts 4 and 6 in Sonogashira alkynylation of deactivated
aryl halide substrates was investigated in light of the pre-
viously reported results obtained by employing 2.12 Table 2
summarizes the screening of catalytic performances in the
coupling of the deactivated electron-rich 4-bromoanisole
with phenylacetylene from various systems incorporating
the copper iodide polyphosphine adducts.
˚
even smaller for 6 (0.015 A difference or less).
The molecular crystal structures obtained for 2, 4, and 6
have in common three substantially different P-Cu-P
angles, each roughly lying within the same range of values:
85.9° to 87.3° (chelating homoannular phosphorus), 99.2° to
108.1°, and 101.4 to 109.8°. As shown in Figure 3, the mole-
cular structure of 6 virtually displays a plane of symmetry,
which is absent in the structures of 2 and 4. The ferrocene
backbone is orientated following a staggered conformation
of the cyclopentadienyl rings.
In the absence of palladium, the systems incorporating only
either CuI or the adduct 2 were inefficient (Table 2, entries 1 and
2). As known from the literature,1,2 in the absence of ligand the
In CD2Cl2 solution at 298 K, the 31P NMR spectrum of 4
exhibits two broad signals at -22.8 and -30.9 ppm of respective
intensity 2:1. The signal at lower field is thus attributed to the
chelating pair of homoannular phosphorus atoms. In contrast
(14) See the NMR spectra in the Supporting Information.

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Beauperin et al.
2818 Organometallics, Vol. 29, No. 12, 2010
Table 2. Screening of Phenylacetylene Coupling to 4-Bromoanisolea
palladium/ligand
catalytic system
alkynylation
productb
alkyne
dimerization
entry
copper source
1
2
3
4
5
6
7
8
5 mol % CuI
1 mol % 2
5 mol % CuI
0
no
no
0
25%
20%
10 to 30%
40 to 65%
80 to 90%
85%
99%
96%
83%
0.5% [Pd(allyl)Cl]2
0.5% [Pd(allyl)Cl]2/ 1
0.5% [Pd(allyl)Cl]2/ 1
0.5% [Pd(allyl)Cl]2/ 5
0.5% [Pd(allyl)Cl]2
0.5% [Pd(allyl)Cl]2
0.5% [Pd(allyl)Cl]2
0.2% [Pd(allyl)Cl]2
0.05% [Pd(allyl)Cl]2
moderate (40%c)
no
5 mol % CuI
5 mol % CuI
1 mol % 2
1 mol % 4
1 mol % 6
high (>60%c)
substantial (50%c)
low (<10%c)
traces
no
traces
traces
9
10
11
0.4 mol % 6
0.1 mol % 6
a Reaction conditions: 4-bromoanisole (3.38 ꢀ 10-3 mol), phenylacetylene (2 equiv), K2CO3 (2 equiv), and the catalytic system stirred at 120 °C over
20 h in 10 mL of DMF under argon. b GC yields average of two consistent runs or more. c Based on phenylacetylene consumption, determined by GC.
coupling of 4-bromoanisole is difficult (entry 3). In our case
substantial amounts of alkyne dimerization were concurrently
obtained. In the absence of a copper source, a low 20% yield of
coupling was obtained from Pd/1 with, however, no diyne or
enyne formation (entry 4).15 The use of copper adducts 2and 6in
the presence of [Pd(allyl)Cl]2 was more efficient in this coupling
than a direct mixture of palladium with polyphosphine 1or 5and
5% CuI (entries 7 and 9 compared to 5 and 6), result-
ing in a significant inhibition of diyne formation. The use of
the copper adducts 4 and 6 confirmed that the prestabilization of
copper iodide with a multidentate ferrocenyl phosphine ligand
promotes the palladium cross-coupling of demanding halides
with phenylacetylene in a selective way (entries 8 and 9).
The near-quantitative conversion to (4-methoxyphenyl)phe-
nylacetylene obtained from the system employing the adduct 6
(1 mol %) with 1 mol % Pd (entry 9) led us to focus our screen-
ing on the minimization of metal compounds employed in the
catalytic reactions. A very high conversion of 96% to (4-methoxy-
phenyl)phenylacetylene was obtained in the presence of 0.4 mol
% of copper and palladium (entry 10). From 0.1 mol % of the
metals the conversion decreased to a still satisfactory 83% yield
(entry 11). While the decrease of the quantity of palladium
is rather common in cross-coupling reactions,16 most of the
Sonogashira reactions are reported with CuI amounts ranging
between 5 and 10 mol %. In the experiments reported in Table 2,
the use of 5 mol % CuI is always correlated to the formation of
substantial amounts of alkyne dimerization products. In the
recent rebirth of copper-catalyzed coupling reactions, attempts
to formulate processes with lower loadings of copper catalysts
are a desirable general goal.17 Therefore, the use of 0.4 mol % of
CuI (25 to 10 times less than common conditions) for coupling
of demanding substrates would be a valuable achievement.
The scope of this system was further examined under low-
metal-content conditions. Table 3 shows the performances ob-
tained for the coupling of phenylacetylene with a variety of
halide substrates. By employing 0.4 mol % of 6 and the palla-
dium source, the electron-rich 4- and 3-bromoanisole were
efficiently coupled in yields of over 90% (96% and 92%, respec-
tively, Table 3 entries 1 and 2). Other deactivated electron-
donating substituted aryl halides were tested, showing that
the system tolerates either para-, meta-, or ortho-substitution.
However, 2-bromotoluene gave only 80% conversion (entry 4)
compared to the less hindered 3-bromotoluene, for which 96%
conversion was obtained (entry 3). The sterically hindered
ortho-substituted 2-bromonaphthalene was almost quantita-
tively converted into the desired product (entry 5). We were
also pleased to see that a highly efficient bis-alkynylation was
possible on 1,2-dibromobenzene (entry 6). The resulting pro-
duct is of particular interest for further activation of the internal
triple bonds toward fused-ring formation (through hydroami-
nation, for instance). Under the successful conditions estab-
lished for electronically or sterically demanding aryl bromides,
the catalytic system was tested on aryl chlorides. The coupling of
the deactivated 4-chloroanisole was ineffective (entry 7). How-
ever, electron-poor 4-chloroacetophenone and 4-chlorobenzo-
nitrile were activated to yield moderate to good conversion to
alkynylated aryls (entries 8-11). Using as low as 0.1 mol % of
copper and palladium, 27% yield of coupling product was
obtained (entry 8), and 46% in the presence of 0.4 mol % of
catalysts (entry 9). Under the same catalytic conditions 4-chloro-
acetophenone was coupled in 36% yield (entry 11). By employ-
ing 2 mol % of copper adduct and palladium the yield with
4-chlorobenzonitrile increased above 65% (entry 10). The
attempts to expand the scope of the system to C(sp)-C(sp3)
bond coupling with bromocyclohexane and bromooctane un-
fortunately failed (entries 12 and 13). To date, only few very
catalytic systems exist to promote these couplings, all devel-
oped under glovebox conditions.18 Finally, we were glad to see
that copper adduct 6 in the absence of palladium promotes the
coupling of electron-rich 4-iodotoluene to phenylacetylene in
almost quantitative conversion. This performance matches
some relevant “palladium-free” copper-based systems reported
using nitrogen- or oxygen-containing ligands.19
In general, when the conversions of expected product were
low, we observed that the triphosphine system was produc-
ing more alkyne dimerization than the tetraphosphine sys-
tem. Having established some synthetic and practical ad-
vantages of using molecularly well-defined CuI-stabilized
adducts in Sonogashira reactions (less metal involved, CuI
adducts as air- and moisture-insensitive reagents for storage
and handling), we were interested in obtaining more infor-
mation on the interactions in solution between the polyphos-
phine ligands and the copper and the palladium centers. In
(15) The sometimes deleterious effect of copper by nonproductive
consumption of the alkynes has been noted by many authors; see for
instance ref 5b.
(18) (a) Vechorkin, O.; Barmaz, D.; Proust, V.; Hu, X. J. Am. Chem.
Soc. 2009, 31, 12078. (b) Eckhardt, M.; Fu, G. C. J. Am. Chem. Soc. 2003,
125, 13642. (c) Altenhoff, G.; Wurtz, S.; Glorius, F. Tetrahedron Lett. 2006,
47, 2925.
ꢀ
(16) For reviews, see: (a) Hierso, J.-C.; Beauperin, M.; Meunier, P.
Eur. J. Inorg. Chem. 2007, 3767. (b) Hierso, J.-C.; Smaliy, R.; Amardeil, R.;
Meunier, P. Chem. Soc. Rev. 2007, 36, 1754.
(19) See for instance: Monnier, F.; Turtaut, F.; Duroure, L.;
(17) Monnier, F.; Taillefer, M. Angew. Chem., Int. Ed. 2008, 47, 3096.
Taillefer, M. Org. Lett. 2008, 10, 3203, and references therein.

Article
Organometallics, Vol. 29, No. 12, 2010 2819
Table 3. Scope of [Pd/6] Catalytic Performances at Low
Metal Loadingsa
a Reaction conditions: aryl halide (3.38 ꢀ 10-3 mol), phenylacetylene (2 equiv), K2CO3 (2 equiv), and the catalytic system stirred at 120 °C over 20 h in
10 mL of DMF under argon. b GC yields average of 2 runs or more; isolated yields range between 90% and 95% of these values.
particular, important questions arise concerning the ad-
ducts’ stability and the possibility of ligand transfer from
one metal to the other in the course of the tandem catalytic
reaction.
to allyl decoordination.14 Upon heating at 353 K (80 °C) for 2 h,
the presence of a phosphine bonded to copper is still detectable
but in a very low concentration and is difficult to quantify.14
These experiments were checked several times and in different
solvents, and we were very surprised to observe that in CDCl3
instead of CD2Cl2 the equilibrium between 6 and 7 is immedi-
ately and totally shifted toward 7at rt.14 This is a clear indication
that in such intricate bimetallic systems the influence of solvent
on the species formed and their equilibrium is of high impor-
tance.
The same kind of experiments were conducted with the tri-
phosphine Cu adduct 4 in CD2Cl2. Analogous behavior was
observed with this triphosphine, showing a partial transfer of
ligand from copper to palladium. The 1H NMR indicates after
10 min a ratio 80:20 in favor of palladium complexes.14 How-
ever, the coordination to palladium is more complex in this case
(Figure 5). Apparently the three phosphorus atoms are bonded to
palladium (sharp signals as AB spin system at 35.9 and 34.1 ppm
corresponding to a cis chelation and a singlet at 14.2 ppm
corresponding to a monodentate trans P-bonding to Pd20).
In addition a broader signal indicative of dynamic exchange is
Interactions of Copper(I) Adducts with Palladium(II). We
investigated by 31P and 1H NMR experiments the interaction
of copper adducts 2, 4, and 6 with palladium allyl chloride in
various solvent (CDCl3, CD2Cl2, DMF, toluene) at tempera-
tures between 183 K (-90 °C) and 353 K (80 °C). We were
particularly interested in evaluating the lifetime of copper
interaction with phosphorus in the presence of palladium.
Upon mixing the triphosphine Cu adduct 6 in CD2Cl2 with
0.5 equiv of the dimeric palladium chloride at rt, a portion of the
triphosphine ligand 5 is transferred to palladium, giving rise to
the palladium complex 7, clearly characterized in the 31P NMR
by two sharp singlets at 37.3 ppm (bonded -PPh2) and 2.1 ppm
(uncoordinated -P(i-Pr)2) of respective intensity of about 2:1
(Figure 4). According to the subsequent 1H NMR,14 an equi-
librium around 50:50 is obtained between copper adduct 6 and
Pd complex 7. This equilibrium is immediately obtained and
was found to be stable after 30 min. Upon heating the mixture
for 1 h at 323 K (50 °C), the equilibrium is almost not modified;
however a novel palladium species is obtained, presumably due
ꢀ
(20) Roger, J.; Mom, S.; Beauperin, M.; Royer, S.; Meunier, P.;
Ivanov, V. V.; Doucet, H.; Hierso, J.-C. ChemCatChem 2010, 2, 296.

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Beauperin et al.
2820 Organometallics, Vol. 29, No. 12, 2010
Figure 4. 31P NMR of a 1:1 mixture of 6 to PdII in CD2Cl2 at 298 K.
Figure 6. 31P NMR of a 1:1 mixture of 2 with PdII in CDCl3 at
298 K.
phosphine area and might correspond to a bimetallic species
where the tricoordination of CuI is conserved and a fluxional
monodentate cis-P bonding for the ligand appears (Figure 6).
The exact attribution of the two other phosphorus signals
at 34.6 and 34.9 ppm in the area corresponding to palla-
dium coordination is more delicate but should correspond to
palladium allyl species stabilized by phosphorus.21 These signals
after 24 h at 277 K are altered for a series of several super-
imposed multiplets probably due to allylic decoordination. Upon
heating the mixture of adduct 2 to palladium chloride in CDCl3/
toluene (1:1) for 1 h at 353 K, it appears that mostly the
palladium-phosphine area is changed (formation of bimetallic
1 Pd2Cl4 and possibly monometallic 1 PdCl2), while copper-
phosphine species are still detectable around -25.0 ppm. These
results were similar in CD2Cl2/toluene (1:1),13 showing that the
Pd/2 system is less sensitive to solvent than Pd/6.
In summary, CuI adducts stabilized by tridentate or tetra-
dentate ligands lead to very different species when simply
mixed with a palladium precursor at rt. Clearly, the CuI phos-
phine adduct 2 formed with the tetraphosphine 1 is more
resistant to ligand transfer and higher temperatures. Concern-
ing the triphosphine adducts the ligand transfer can be very
fast, leading to palladium monometallic species from 6 and
Figure 5. 31P NMR of a 1:1 mixture of 4 with PdII in CD2Cl2 at
283 K.
observed at 36 ppm, possibly due to a monodentate cis P-bond-
ing to Pd. The presence of copper-phosphine-stabilized species
is easier to detect at lower temperature (283 K) from broad
signals centered at -10, -23, and -32 ppm. However, the
nature of these species is unclear, and their chemical shifts are
clearly different from those of adduct 4 (possibly clusters or di-
meric species of Bohlmann type are formed,8 due to the shortage
of ligand after transfer to Pd). Upon heating to 353 K in CD2-
Cl2/toluene (1:1) for 2 h, both Pd and Cu species remain
detectable in 31P NMR.
3
3
The mixture of the Cu-tetraphosphine adduct 2 with 0.5
equiv of the dimeric palladium chloride at rt in CDCl3
immediately reaches an equilibrium, which is conserved after
24 h at 277 K (Figure 6).
The presence of copper adduct 2 in more than 70% was esti-
mated from 1H NMR.13 VT-31P NMR at 190 K clearly ascer-
tained that the two broad signals observed at -25.5 and -26.4
ppm relate to 2. In addition, palladium-containing species are
formed with the appearance of several peaks around 35 ppm.
Interestingly, two broad signals of weaker intensity are found at
-23.5 and -24.0 ppm, which seems to indicate the formation of
other copper-phosphine species. Because of their deshielding
and apparently 1:2 mutual intensity, they might be correlated to
the broad signal found at 36.5 ppm in the palladium-bonded
(21) Possibly bis-(P-chelating) bimetallic species [1 Pd2Cl2(allyl)2]
3
are formed; however doublets or multiplets are expected in this case.
See ref 22a.

Article
Organometallics, Vol. 29, No. 12, 2010 2821
multimetallic from 4. In general the equilibrium obtained bet-
ween palladium and copper species at rt is conserved at 50 °C
but slowly modified at 80 °C. To establish a rationale for the
general catalytic behavior observed for the three species would
be rather speculative at this stage; however the best results
obtained from the system incorporating Pd/6 might be related
to the rather exclusive formation of 7 without variety of addi-
tional mononuclear or multinuclear phosphorus-stabilized
metallic species. From the system incorporating Pd/6, when
the conversion of coupling products was low, we observed that
this triphosphine system was producing more alkyne dimeriza-
tion than the tetraphosphine Pd/2 system. Thus, better results
were obtained concerning the inhibition of diyne formation
over systems incorporating Pd/2, which might be related to the
greater lifetime of copper adduct 2. Further studies of interest
would certainly concern the competitive kinetic studies be-
tween diyne formation and aryl/alkyne coupling. Nevertheless,
the use of 0.4 mol % CuI adduct clearly led to much slower
diyne formation than the use of 5 mol % CuI.
Synthesis of 1,10,2-Tris(diphenylphosphino)-30,4-di-tert-butyl-
ferrocene, 3. To a suspension of FeCl2 (0.5 g, 3.93 mmol) in THF
(50 mL) was added dropwise at -40 °C a solution of 1-diphe-
nylphosphino-3-tert-butylcyclopentadienyllithium (1.08 g, 3.45
mmol) in THF (15 mL). The mixture was stirred for 2 h after
reaching room temperature. A solution of 1,2-bis(diphenylphos-
phino)-4-tert-butylcyclopentadienyllithium (1.71 g, 3.45 mmol) in
THF (15 mL) was dropwise added at -40 °C. After removal of
THF under vacuum, toluene (100 mL) was added. The mixture was
then refluxed for 15 h. After filtration, the resulting filtrate was
concentrated to yield ferrocenes (2 g), which were separated first by
chromatography on silica gel (toluene/hexane, 1:1) and then puri-
fied by thin-layer chromatography (ethyl acetate/hexane, 5:95) to
yield pure 3 (880 mg, 32%). 1H NMR (CDCl3, 300 MHz, 298 K): δ
7.72-6.78 (m, 30H, Ph), 4.62 (s, 1H, Cp), 4.39 (s, 1H, Cp), 4.31 (s,
2H, Cp), 3.63 (s, 1H, Cp), 0.93 (s, 9H, t-Bu), 0.71 (s, 9H, t-Bu). 31P
NMR (CDCl3, 121.4 MHz, 298 K): δ -20.6 (s, 1P), -25.4 (AB q,
2P). 13C (CDCl3, 75 MHz, 298 K): δ 127.1-142.8 (m, 36C, Ph),
107.4 (s, 1C, 4-Fc), 107.0 (s, 1C, 30-Fc), 82.1 (d, 1C, 1JCP = 20 Hz,
1-Fc,), 80.1 (d, 1C, 1JCP = 15 Hz, 2-Fc,), 76.7 (d, 1C, 1JCP = 13.5
Hz, 10-Fc,), 75.9 (dd, 1C, 2JCP = 28 Hz, 3JCP = 4.5 Hz, 3-Fc,), 72.5
2
(s, 1C, 50-Fc), 70.9 (s, 1C, 40-Fc), 70.3 (dd, 1C, JCP = 4.5 Hz,
Conclusions
3JCP e 1 Hz, 5-Fc,), 68.5 (d, 1C, 2JCP = 4.5 Hz, 20-Fc,), 31.9, 31.7
(s, 3C each, t-BuCH3), 30.4, 30.0 (s, 1C, each, t-BuCCH3). Anal.
Found for C54H53FeP3 (MW 850.78): C 75.80; H 6.82. Calcd: C
76.25, H 6.28 (fractional amount of solvent is retained). Exact mass
(ESI): m/z 850.27040 (Mþ), σ = 0.043, err[ppm] = 2.61.
Several unprecedented CuI-polyphosphine adducts were
quantitatively synthesized and are fully described in the solid
state and in solution. We found that the prestabilization of cop-
per iodide with a multidentate ferrocenylphosphine ligand
promotes “ligand-free” palladium Sonogashira cross-coupling
of deactivated aryl bromides and electron-poor chlorides. The
system has some practical and economical advantages: (i) its
efficient inhibition of alkyne oxidative homocoupling, (ii) the
easiness of weighing and storing the CuI adducts, and (iii) the
outstandingly low amount of copper needed (0.4 to 0.1 mol %)
with also noticeable low amounts of palladium. The coordina-
tion behavior of polydentate ligands toward palladium and cop-
per and, in particular, the transfer from one metal to the other
are reported. These studies show that copper-ligand inter-
actions might be very likely in traditional tandem Pd/Cu cross-
coupling reactions, thus opening the way to new perspectives in
mechanistic understanding.
Copper-Triphosphine Adduct 4. To a solution of triphosphine
3 (190 mg, 2.22 ꢀ 10-4 mmol) in CH3CN (15 mL) was added
anhydrous CuI (42 mg, 2.21 ꢀ 10-4 mmol). The mixture was
refluxed for 3 h. After cooling, the orange solution was evapo-
rated under reduced pressure to give complex {P,P0,P00-[1,10,2-
tris(diphenylphosphino)-3,40-di-tert-butylferrocene]iodocopper-
(I)}, 4 (230mg, 99% yield). 1H NMR(CD2Cl2, 600MHz, 298 K):
δ 8.22-6.80 (m, 30H, Ph), 4.60 (s, 1H, Cp), 4.56 (s, 1H, Cp), 4.24
(s, 2H, Cp), 3.70 (s, 1H, Cp), 1.35 (s, 9H, t-Bu), 0.95 (s, 9H, t-Bu).
31P NMR (CD2Cl2, 242.9 MHz, 298 K): δ -22.77 (s, br, 2P),
-30.93 (s, br, 1P). 13C NMR (CD2Cl2, 125.75 MHz, 298 K): δ
138.5, 134.6, 133.9 (m, 2C each, ipso-C6H5), 134.0-127.0 (m, 30C,
C6H5), 111.6 (s, 1C, 4-Fc), 106.5 (s, 1C, 30-Fc), 84.9 (d, 1C, 1JCP
=
32.5 Hz, 1-Fc), 79,3 (d, 1C, 1JCP=21.25 Hz, 2-Fc,), 76.7 (s, 1C, 10-
Fc), 73.1 (d, 1C, 2JCP=10 Hz, 50-Fc), 72.1 (s, 1C, 40-Fc), 68.5 (s, 1C,
5-Fc), 67.7 (s, 1C, 20-Fc), 66.3 (s, 1C, 3-Fc) 30.9, 30.3 (s, 3C each,
t-BuCH3), 30.2, 29.4 (s, 1C each, t-BuCCH3). Anal. Found
for C54H53CuFeIP3 (MW 1041.23): C 61.74; H 5.39. Calcd:
C 62.29, H 5.13. Exact mass (ESI): m/z 913.20001 (M - Iþ),
σ=0.030, err[ppm]=2.68.
Experimental Section
General Procedures. The reactions were carried out in oven-
dried (115 °C) glassware under an argon atmosphere using
Schlenk and vacuum-line techniques. The solvents were distilled
over appropriate drying and deoxygenating agents prior to use,
except for acetonitrile, which was deoxygenated by several nitro-
Copper-Triphosphine Adduct 6. To a solution of 1,2-bis-
(diphenylphosphino)-10-(diisopropylphosphino)-4-tert-butyl-
ferrocene, 5 (99 mg, 1.08 ꢀ 10-4 mmol), in CH3CN (10 mL) was
added anhydrous CuI (20.5 mg, 1.08 ꢀ 10-4 mmol). The mixture
was refluxed for 3 h. After cooling, the orange solution was
evaporated under reduced pressure to give complex {P,P0,
P00-[1,2-bis(diphenylphosphino)-10-(diisopropylphosphino)-4-
1
gen freezing/vacuum cycles. H, 31P, and 13C NMR, including
variable-temperature NMR experiments, were performed on a
600 MHz Bruker Avance II and a 300 MHz Bruker Avance.
Elemental analyses and electrospray mass spectrometry (on a
Bruker microOTOF-Q instrument) were performed at the
1
tert-butylferrocene]iodocopper(I)}, 6 (100 mg, 99% yield). H
NMR (CD2Cl2, 600 MHz, 298 K): δ 8.00-6.80 (m, 20H, Ph),
4.88, 4.38, 4.12 (s, 2H each, Cp), 2.02 (s, 2H, CH i-Pr), 1.44-1.41
(m, 6H, CH3 i-Pr), 1.40 (s, 9H, t-Bu), 1.20-1.09 (m, 6H, CH3
i-Pr). 31P NMR (CD2Cl2, 242.9 MHz, 298 K): δ -0.65 (s, br, 1P),
-28.05 (s, br, 2P). 13C NMR (CD2Cl2, 125.75 MHz, 298 K): δ
135.9 (s, 4C, ipso-C6H5), 134.0-128.0 (m, 20C, C6H5), 110.2 (s,
1C, 4-Fc), 82.9 (s, 1C, 10-Fc), 80.3 (s, 2C, 1, 2-Fc), 74.4 (s, 2C, 20,
50-Fc), 71.8 (s, 2C, 3, 5-Fc), 69.8 (s, 2C, 30, 40-Fc), 31.8 (s, 3C,
t-BuCH3), 31.5 (s, 1C, t-BuCCH3), 28.1 (s, 2C, CH i-Pr), 21.3,
20.0 (s, 2C each, CH3 i-Pr). Anal. Found for C44H49CuFeIP3
(MW 917.09): C 56.38; H 5.64. Calcd: C 57.63, H 5.39 (fractional
amount of solvent is retained). Exact mass (ESI): m/z 789.16871
(M - Iþ), σ=0.033, err[ppm]=2.22.
ꢀ
PACSMUB of the “Institut de Chimie Moleculaire de l’Uni-
versite de Bourgogne” (ICMUB-UMR CNRS 5260). GC and
GC-MS analysis were done on a Supelco equity-5 capillary
column on a Shimadzu GC-2014 for GC or from a hp-5 capillary
column (30 m) for GC-MS. The synthesis and characterization
of compounds 1, 2, and 5 were reported elsewhere.22,12,23
ꢀ
(22) (a) Hierso, J.-C.; Fihri, A.; Amardeil, R.; Meunier, P.; Doucet,
H.; Santelli, M.; Donnadieu, B. Organometallics 2003, 22, 4490. (b)
Broussier, R.; Bentabet, E.; Amardeil, R.; Richard, P.; Meunier, P.; Kalck, P.;
Gautheron, B. J. Organomet. Chem. 2001, 637-639, 126.
(23) (a) Hierso, J.-C.; Ivanov, V. V.; Amardeil, R.; Richard, P.;
Meunier, P. Chem. Lett. 2004, 33 (10), 1296. (b) Hierso, J.-C.; Fihri,
A.; Amardeil, R.; Meunier, P.; Doucet, H.; Santelli, M.; Ivanov, V. V.
Org. Lett. 2004, 6, 3473.
Sonogashira Catalytic Reactions. The reaction of aryl halide
(3.38 ꢀ 10-3 mol), phenylacetylene (0.75 mL, 6.76 ꢀ 10-3 mol,

ꢀ
Beauperin et al.
2822 Organometallics, Vol. 29, No. 12, 2010
2 equiv), and K2CO3 (0.935 g, 6.76 ꢀ 10-3 mol, 2 equiv) with
0.4 mol % of copper adduct 6 (13.5 μmol, 12.4 mg) in the
presence of 0.2 mol % [PdCl(η3-C3H5)]2 (6.8 μmol, 2.5 mg), at
120 °C over 20 h in DMF (10 mL), under argon, affords the
coupling products. Pure products were obtained after addition
of water, extraction with organic solvents, separation, drying,
concentration, and chromatography on silica gel.
the CNRS for a grant. The ANR program “Chimie Pour
ꢀ
le Developpement Durable” is sincerely acknowledged
for supporting this research via the project ANR-09-
CP2D-03 CAMELOT.
Supporting Information Available: Crystal data and structure
refinement for 4 and 6, exact-mass data, 1H, 31P, and 13C NMR
spectra for 3, 4, and 6, organic product characterization, and
details of catalytic experiments. This material is available free of
charge via the Internet at http://pubs.acs.org.
Acknowledgment. This work was supported by the
ꢀ
“Conseil Regional de Bourgogne”. M.B. and A.J. thank