Mechanism of the Stille reaction catalyzed by palladium ligated to arsine ligand: PhPdl(AsPh3)(DMF) is the species reacting with vinylstannane in DMF

Article abstract of DOI:10.1021/ja0204978

The kinetics of the reaction of PhPdI(AsPh₃)₂ (formed via the fast oxidative addition of Phl with Pd⁰(AsPh₃)₂) with a vinyl stannane CH₂=CH-Sn(n-Bu)₃ has been investigated in DMF. This reaction (usually called transmetalation step) is the prototype of the rate determining second step of the catalytic cycle of Stille reactions. It is established here that the transmetalation proceeds through PhPdI(AsPh₃)(DMF), generated by the dissociation of one ligand AsPh₃ from PhPdI(AsPh₃)₂. PhPdI(AsPh₃)(DMF) is the reactive species, which leads to styrene through its reaction with CH₂=CH-SnBu₃. Consequently, in DMF, the overall nucleophilic attack mainly proceeds via a mechanism involving PhPdI(AsPh₃)(DMF) as the central reactive complex and not PhPdI(AsPh₃)₂. The dimer [Ph₂Pd₂(μ²-I)₂ (AsPh₃)₂] has been independently synthesized and characterized by its X-ray structure. In DMF, this dimer dissociates quantitatively into PhPdI(AsPh₃)(DMF), which reacts with CH₂=CH-SnBu₃. The rate constant for the reaction of PhPdI-(AsPh₃)(DMF) with CH₂=CH-SnBu₃ has been determined in DMF for each situation and was found to be comparable.

Full text of DOI:10.1021/ja0204978

Published on Web 03/18/2003
Mechanism of the Stille Reaction Catalyzed by Palladium
Ligated to Arsine Ligand: PhPdI(AsPh3)(DMF) Is the Species
Reacting with Vinylstannane in DMF
Christian Amatore,*,† Ali A. Bahsoun,† Anny Jutand,*,† Gilbert Meyer,†
Alexandre Ndedi Ntepe,† and Louis Ricard‡
Contribution from the Ecole Normale Supe´rieure, De´partement de Chimie, UMR
CNRS-ENS-UPMC 8640, 24 Rue Lhomond, 75231 Paris Cedex 5, France, and Ecole
Polytechnique, DCPH, UMR CNRS 7653, 91128 Palaiseau, France
Received April 5, 2002
Abstract: The kinetics of the reaction of PhPdI(AsPh3)2 (formed via the fast oxidative addition of PhI with
Pd0(AsPh3)2) with a vinyl stannane CH2dCH-Sn(n-Bu)3 has been investigated in DMF. This reaction (usually
called transmetalation step) is the prototype of the rate determining second step of the catalytic cycle of
Stille reactions. It is established here that the transmetalation proceeds through PhPdI(AsPh3)(DMF),
generated by the dissociation of one ligand AsPh3 from PhPdI(AsPh3)2. PhPdI(AsPh3)(DMF) is the reactive
species, which leads to styrene through its reaction with CH2dCH-SnBu3. Consequently, in DMF, the
overall nucleophilic attack mainly proceeds via a mechanism involving PhPdI(AsPh3)(DMF) as the central
reactive complex and not PhPdI(AsPh3)2. The dimer [Ph2Pd2(µ2-I)2(AsPh3)2] has been independently
synthesized and characterized by its X-ray structure. In DMF, this dimer dissociates quantitatively into
PhPdI(AsPh3)(DMF), which reacts with CH2dCH-SnBu3. The rate constant for the reaction of PhPdI-
(AsPh3)(DMF) with CH2dCH-SnBu3 has been determined in DMF for each situation and was found to be
comparable.
Scheme 1. Initial Mechanism
Introduction
The mechanism of the Palladium-catalyzed Stille reaction1
(cross coupling of aryl halides and organostannanes derivatives,
eq 1) has been widely investigated.1-8 The original mechanism
proposed by Stille,1a in the case of monodentate ligand L,
included four steps: oxidative addition, transmetalation, trans-
cis isomerization and reductive elimination (Scheme 1), involv-
* Dedicated to Professor Marc Julia on the occasion of his 80th birthday.
† Ecole Normale Supe´rieure.
‡ Ecole Polytechnique.
(1) (a) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508-524. (b) Farina,
V.; Krishnamurthy, V.; Scott, W. J. The Stille Reaction in Organic
Reactions; Wiley: New York, 1997, Vol. 50, p 1.
(2) Louie, J.; Hartwig, J. F. J. Am. Chem. Soc. 1995, 117, 11 598-11 599.
(3) (a) Farina, V.; Krisnan, B. J. Am. Chem. Soc. 1991, 113, 9585-9595. (b)
Farina, V.; Roth, G. P. Recent AdVances in the Stille Reaction In AdV.
Metalorg. Chem. 1996, 5, 1-53.
ing saturated 16-electron aryl-PdII complexes, all ligated by two
phosphine ligands.
(4) (a) Casado, A. L.; Espinet, P. Organometallics 1998, 17, 7, 954-959. (b)
Casado, A. L.; Espinet, P. J. Am. Chem. Soc. 1998, 120, 8978-8985.
(5) For the mechanism of Stille reactions from aryl triflates, see ref 3 and (a)
Farina, V.; Krisnan, B.; Marshall, D. R.; Roth, G. P. J. Org. Chem. 1993,
58, 5434-5444. (b) Casado, A. L.; Espinet, P.; Gallego, A. J. Am. Chem.
Soc. 2000, 122, 11 771-11 782. (c) Casado, A. L.; Espinet P.; Gallego,
A. M.; Martinez-Ilarduya, J. M. J. Chem. Soc. Chem. Comm. 2001, 120,
339-340.
This initial mechanism has been progressively modified to
rationalize the effect of ligands (ex: AsPh3 vs PPh3) on the
efficiency of catalytic reactions.2-4 Much attention has been paid
to the transmetalation step, which was very early identified as
the rate determining step.2-4b Because this step is retarded by
excess ligand,2-4b aryl-PdII complexes, ligated by only one
(6) Ricci, A.; Angelucci, F.; Bassetti, M.; Lo Sterzo, C. J. Am. Chem. Soc.
2002, 124, 1060-1071.
(7) Mateo, C.; Ferna´ndez-Rivas, C.; Ca´rdenas, D. J.; Echavarren, A. M.
Organometallics 1998, 17, 7, 3661-3669.
(8) Amatore, C.; Bucaille, A.; Fuxa, A.; Jutand, A.; Meyer, G.; Ndedi Ntepe,
A. Chem. Eur. J. 2001, 2134-2142.
9
4212
J. AM. CHEM. SOC. 2003, 125, 4212-4222
10.1021/ja0204978 CCC: $25.00 © 2003 American Chemical Society

Mechanism of the Stille Reaction
A R T I C L E S
Scheme 2. Updated Mechanism (L ) AsPh3)3a,4b
(Scheme 3) upon following the original proposal of Farina in
THF3 (the structure of the complex in chloroform will be
discussed at the very end of this paper). In DMF, the equilibrium
constant KL ) [PhPdI(AsPh3)(DMF)][AsPh3]/[PhPdI(AsPh3)2]
was determined: KL ) 3.1 × 10-4 M at 25 °C,8 a value which
is not very different from that determined by Farina and
Krishnan (KL ) 8.6 × 10-4 M) on the basis of their investigation
of the kinetics of the catalytic reaction 2 in THF at 50 °C.3
We wish to report here new investigations on the kinetics of
the transmetalation step performed from PhPdI(AsPh3)2, which
establishes that PhPdI(AsPh3)(DMF) is the actual species which
reacts with CH2dCH-SnBu3 in DMF. A second approach of
the reactivity of PhPdI(AsPh3)(DMF) with CH2dCH-SnBu3
is also reported which involves a route initiated through the
dimer [Ph2Pd2(µ2-I)2(AsPh3)2], whose full and fast dissociation
in DMF generates PhPdI(AsPh3)(DMF) prior its reaction with
CH2dCH-SnBu3.
Scheme 3. Mechanism of the Oxidative Addition in DMF8
Results
Kinetics of the Transmetalation Step from PhPdI(AsPh3)2
in DMF: Principle of the Kinetic Method. Although the
complex PhPdI(AsPh3)2 had been isolated and fully character-
ized,8 we preferred to investigate the reactivity of CH2dCH-
SnBu3 with PhPdI(AsPh3)2 generated in situ by reacting 1 equiv
PhI with Pd0(dba)2 associated to 2 equivs AsPh3 in DMF (Eq
3,4),8 to mimic more closely the situation which occurs during
a real catalytic cycle.10
ligand L, have been proposed as key intermediates in the
transmetalation and henceforth in the reductive-elimination step
(Scheme 2).2,3,4b,9
In the course of our investigation on the effect of the arsine
ligand AsPh3 on the rate of the oxidative addition of PhI, which
is the first step of a catalytic reaction between PhI and the tri-
n-butyl(vinyl)tin in DMF (eq 2), we established that CH2dCH-
SnBu3 coordinates the active SPd0(AsPh3)2 complex prior to
its oxidative addition to PhI, thereby leading to the unreactive
(η2-CH2dCH-SnBu3)Pd0(AsPh3)2 species (Scheme 3).8
At the initial Pd0(dba)2 concentration of C0 ) 2 mM, the
oxidative addition (eq 4) was sufficiently fast (t1/2 ) 8 s at 25
°C) for the transmetalation step to be investigated without any
kinetic interference, once the oxidative addition was total.
The reaction of CH2dCH-SnBu3 was first monitored by 1H
NMR spectroscopy by reacting two equiv. CH2dCH-SnBu3
with PhPdI(AsPh3)2 in DMF-d7 at room temperature. This
reaction clearly produced styrene in quantitative yield (eq 5).
Due to this side route, which stores part of the catalytic charge
under an unreactive form, the oxidative addition of PhI is slower
when performed in the presence of the nucleophile, i.e., under
the conditions which prevail in a real catalytic reaction. The
complex PhPdI(AsPh3)2, formed after oxidative addition to
SPd0(AsPh3)2, was shown to dissociate one AsPh3 ligand in
chloroform and DMF.8 This decomplexation was observed to
proceed in appreciable extents in both solvents. This led to the
concomitant formation of a new PhPdII moiety ligated by only
one AsPh3, which was assigned to be PhPdI(AsPh3)(S) complex8
1
No intermediate complex(es) could be detected in the H
NMR spectrum. Moreover, 1H NMR spectroscopy did not
permit to monitor the kinetics of the transmetalation step with
sufficient time resolution. Conversely, we observed through
conductivity measurements that, in DMF, and over the whole
range of millimolar concentrations investigated here, ISnBu3
which is a product of the reaction, was completely dissociated
into I- and +SnBu3 (eq 5). Because ISnBu3 is generated
concomitantly with the coupling product, this observation
suggested a facile and very accurate way of monitoring the
kinetics of the reaction 5 in DMF with the required time
resolution.
(9) Louie and Hartwig have reported that stoichiometric reactions of orga-
nostannanes with 16-electron trans-ArPdXL2 (L ) PPh3) complexes proceed
in toluene via the reaction of 14-electron ArPdXL complexes formed by
dissociation of one ligand L (Scheme A).2 14-electron diorgano ArPdRL
complexes are then formed, which undergo a fast reductive elimination
(Scheme A).2
(10) Farina has used Pd02(dba)3 as precursor.3 We used Pd0(dba)2 because it
was used in our previous work8 to allow a comparison of the reactivity in
oxidative addition of Pd0 ligated to AsPh3 with that of Pd0 ligated to PPh3.
For a review on Pd0(dba)2 as precursor, see: Amatore, C.; Jutand, A. Coord.
Chem. ReV. 1998, 178-180, 511-528.
Scheme A. Mechanism of the transmetalation proceeding by prior dis-
sociation of one phosphine ligand L, followed by reductive elimination.2
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J. AM. CHEM. SOC. VOL. 125, NO. 14, 2003 4213

A R T I C L E S
Amatore et al.
Figure 2. Reaction of CH2dCH-SnBu3 with PhPdI(AsPh3)2 (2 mM) in
DMF at 25 °C. Determination of the reaction order in CH2dCH-SnBu3:
plot of kobs, determined as in Figure 1b, versus CH2dCH-SnBu3 concentra-
tion. PhPdI(AsPh3)2 was preformed in situ by the reaction of PhI (2 mM)
with Pd0(dba)2 (2 mM) and AsPh3 (4 mM).
-kobst. kobs varied linearly with the CH2dCH-SnBu3 concentra-
tion (Figure 2), thus establishing a reaction order of +1 in CH2d
CH-SnBu3.
The effect of AsPh3 concentration on the kinetics of the
transmetalation step was tested in the range 2-10 mM, by
addition of AsPh3 to PhPdI(AsPh3)2 (C0 ) 2 mM) prior to the
introduction of CH2dCH-SnBu3 (20 mM). PhPdI(AsPh3)2 was
generated in situ by reaction of PhI (2 mM) with Pd0(dba)2 (2
mM) associated to n equiv. AsPh3 (2 e n e 7). The reaction
proceeded slower and slower as the AsPh3 concentration was
made larger and larger (Figure 3a) suggesting a decomplexation
of one ligand AsPh3 from PhPdI(AsPh3)2 either before of after
reaction with CH2dCH-SnBu3.
Kinetics of the Transmetalation Step from [Ph2Pd2(µ2-
I)2(AsPh3)2] in DMF. Because the dimer [Ph2Pd2(µ2-I)2(As-
Ph3)2] 3 could be considered as a potential source of PhPdI-
(AsPh3)(DMF) 2 through the equilibrium in eq 6, the dimer 3
was synthesized by reacting PhI with Pd0(dba)2 and one equiv
AsPh3 in THF. THF was chosen as the solvent to facilitate the
workup by simple evaporation. Brown yellow crystals were
isolated and submitted to X-ray analysis, which revealed the
structure of the dimer trans-[Ph2Pd2(µ2-I)2(AsPh3)2] 3 (eq 7,
Figure 4, Table 1).12
Figure 1. (a) Kinetics of the reaction of CH2dCH-SnBu3 (30 mM) with
PhPdI(AsPh3)2 (2 mM) in DMF at 25 °C, as monitored by conductivity
measurements of I-
+
+SnBu3 (eq 5). PhPdI(AsPh3)2 was preformed in
situ by the reaction of PhI (2 mM) with Pd0(dba)2 (2 mM) and AsPh3 (4
mM). κexp: experimental conductivity at t, κ0: residual conductivity (3
µS.cm-1) measured before the addition of CH2dCH-SnBu3 (indicated by
the arrow) to the preformed PhPdI(AsPh3)2. (s): conductivity of an
authentic sample of ISnBu3 (2 mM) in DMF. (b) Plot of ln((κ∞-κ)/κ∞) )
lnx versus time (κ: conductivity of I-
ln((κ∞-κ)/κ∞) ) - kobst.
+
+SnBu3 at t, κ∞: final conductivity).
It was first checked that, in DMF, the conductivity of the
solution obtained after reaction of 15 equiv. of CH2dCH-SnBu3
with PhPdI(AsPh3)2 (2 mM) (Figure 1a) resulted identical (κ )
76 ( 5 µS.cm-1 at 25 °C) to that measured for an authentic
sample of ISnBu3 (2 mM) in DMF (κ ) 75 µS.cm-1 at 25 °C).
It has also been checked independently that CH2dCH-SnBu3
did not exhibit any conductivity in DMF. This ensured that the
presence of other reactants and products (eq 5) did not alter the
kinetic measurements when monitoring the progress of reaction
5 by conductivity measurements. Therefore, the kinetics of
reaction 5, i.e., of the overall transmetalation step could be
investigated extremely accurately through the measurement of
the rate of formation of I- + +SnBu3 by conductivity measure-
ments.
In the presence of an excess of CH2dCH-SnBu3, the
variation of lnx versus time, (x ) (κ∞-κ)/κ∞); κ: conductivity
of I- + +SnBu3 at t, κ∞: final conductivity determined in Figure
1a) which characterizes the advancement of the reaction, was
linear (Figure 1b). This establishes a reaction order of +1 for
the reactive Ph-PdII complex.11 The observed rate constant for
(11) Some deviation from the linearity was observed (Figure 1b). This is due
to a variation of the ligand concentration during the course of the reaction.
The exact kinetic law is given in eq 14 in the discussion part with n ) 2.
(12) For the synthesis of related dimer [Ph2Pd2(µ2-I)2(PPh3)2]: see: Grushin,
V. V.; Alper, H. Organometallics, 1993, 12, 1890-1901.
the formation of I-
+
+SnBu3, kobs (s-1) was then determined
from the slope of the regression line (Figure 1b), viz., lnx )
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Mechanism of the Stille Reaction
A R T I C L E S
Figure 4. X-ray structure of the dimeric complex [Ph2Pd2(µ2-I)2(AsPh3)2]
synthesized by reacting PhI with Pd0(dba)2 and AsPh3 (1 equiv).
Table 1. Crystallographic Data for [Ph2Pd2(µ2-I)2(AsPh3)2]
molecular formula: C96H80As4I4Pd4
molecular weight: 2466.48
crystal habit: brownish cube
crystal dimensions (mm): 0.18 × 0.18 × 0.18
crystal system: monoclinic
space group: C2/c
a(Å): 30.404(5)
b(Å): 15.008(5)
c(Å): 19.672(5)
â(°): 102.970(5)
V(Å3): 8747(4)
Z: 4
d(g-cm-3): 1.873
F000: 4736
µ(cm-1): 3.768
maximum θ: 30.03
HKL ranges: -42 42; -21 19; -27 27
reflections measured: 22625
independent reflections: 12753
rint: 0.0357
reflections used: 8922
criterion: > 2sigma(I)
refinement type: Fsqd
hydrogen atoms: riding
parameters refined: 487
reflections/parameter: 18
wR2: 0.1015
R1: 0.0402
weights a, b1: 0.0486; 0.0000
GoF: 1.014
Figure 3. Influence of AsPh3 concentration on the kinetics of the reaction
of CH2dCH-SnBu3 (20 mM) with PhPdI(AsPh3)2 (2 mM) in DMF at 25
°C. PhPdI(AsPh3)2 was preformed in situ by the reaction of PhI (2 mM)
with Pd0(dba)2 (2 mM) and n equivs AsPh3. (a) conductivity measured as
in Figure 1a, with n ) (s) 2; (- - -) 7. (b) Plot of (n - 1 + â/C0)lnx - x
+ 1 versus time (eq 14) with n ) (+) 3; (9) 4; (0) 5; (×) 6; (b) 7 (x )
difference peak/hole (e/Å3): 2.250(0.152)/-1.417(0.152)
Discussion
(κ∞-κ)/κ∞; κ: conductivity of I-
+
+SnBu3 at t; κ∞: final conductivity).
Transmetalation Step from PhPdI(AsPh3)(DMF) Gener-
ated from [Ph2Pd2(µ2-I)2(AsPh3)2] in DMF. From the kinetic
law shown in Figure 5: 1/x ) kappt + 1, one deduces that the
(c) (9) k4 values calculated from the slope of the straight lines obtained in
Figure 3b for each n value; (- - -) k4 value calculated for the reaction of
PhPdI(AsPh3)(DMF) (generated from the dimer [Ph2Pd2(µ2-I)2(AsPh3)2])
with CH2dCH-SnBu3 (Figure 5).
reaction order in PdII is clearly not /2, which should be the
1
case whenever the dimer 3 would be in rapid equilibrium with
its reactive monomeric species 2 PhPdI(AsPh3)(DMF) (eq 6).
Indeed, for a reaction of CH2dCH-SnBu3 with the monomeric
To determine whether CH2dCH-SnBu3 reacts with PhPdI-
(AsPh3)(DMF) or with [Ph2Pd2(µ2-I)2(AsPh3)2], the kinetics of
the reaction of [Ph2Pd2(µ2-I)2(AsPh3)2] 3 (1 mM) with 2 equivs
CH2dCH-SnBu3 in DMF was monitored by the conductivity
(13) At the end of the reaction, the final conductivity did not reach the value of
κ∞ ) 75 µS.cm-1 expected for a concentration of 2 mM of I-
+
+SnBu3,
but a lower value of 48 µS.cm-1, although the dimer was totally converted
into styrene. We rationalized this lower conductivity by remarking that
due to the lack of AsPh3 (only one AsPh3 per palladium is available) the
Pd0 formed in the reaction could be stabilized by complexation of the
released iodide ion to afford an ionic complex Pd0(AsPh3)I-.14 The intrinsic
conductance of this species is necessarily less than that of the free I- due
to the increased ionic radius. This should account for the observed smaller
value of the final conductivity. To test the effect of the complexation of
Pd0 by I- on the conductivity value, Pd0(dba)2 (2 mM) was added to a
measurements of I-
+
+SnBu3 generated during the reaction,
as for PhPdI(AsPh3)2 (vide supra).13 Plotting 1/x ) κ∞/(κ∞-κ)
versus time gave a straight line with an intercept equal to unity
(Figure 5) (κ: conductivity of I-
+
+SnBu3 at t, κ∞: final
solution of I-
of I-
+
+SnBu3 (2 mM) in DMF at 25 °C. The initial conductivity
conductivity): 1/x ) kappt + 1, attesting a kinetic rate law
corresponding to a 1:1 reaction between two reagents present
in stoichiometric amounts.
+
+SnBu3, κ ) 75 µS.cm-1 dropped to 63 µS.cm-1 when Pd0(dba)2
was added to the cell, evidencing the complexation of the low ligated Pd0-
(dba) generated in solution in DMF15 by I-, to form an anionic complex
Pd0(dba)I- more bulky than the free I-.
9
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A R T I C L E S
Amatore et al.
Scheme 4. Mechanism of the Reaction of [Ph2Pd2(µ2-I)2(AsPh3)2] and CH2)CH-SnBu3 in DMF
species 2 (rate constant k4) involved in such an equilibrium with
the dimer, the rate law would be: 1/x1/2 ) k4KC0t/2 + 1. The
rate law: 1/x ) kappt + 1 characterizes a rate determining step
involving a 1:1 reaction between two reagents present in
stoichiometric amounts. Consequently, in DMF the dimer 3
may: (i) dissociate upon dissolution to give PhPdI(AsPh3)-
(DMF), which reacts with CH2dCH-SnBu3 (rate constant k4
in Scheme 4) or (ii) be the reactive complex.
monobridged complex in which one PdII is ligated to CH2d
CH-SnBu3 as in: [PhPdL(η2-CH2dCH-SnBu3)(µ2-I)Pd(Ph)-
IL] 6 (L ) AsPh3) and then a fast reaction of the latter species
6 with a second CH2dCH-SnBu3 (rate constant k2) to form
two molecules of 4 (reaction order of 1 for CH2dCH-SnBu3
in each step). If k2 > k1 so that the steady-state approximation
may be applied to complex 6, the rate law is then 1/x ) k1C0(2
+ k1/k2)t + 1. This law is compatible with that found
experimentally (vide supra) with kapp ) k1(2 + k1/k2)C0. If we
consider now the route (i) (Scheme 4), the concentration of the
monomer 2 is twice that of the dimer, and the rate law is
Let us first discuss route (ii). At least two mechanisms may
be envisaged for the reaction of the dimer 3. On one hand, a
sequential reaction of the dimer with two molecules of CH2d
CH-SnBu3, the first one giving an equilibrium displaced by
the second one to form two molecules of 4 at once. This would
lead to a reaction order of 2 for CH2dCH-SnBu3. This
mechanism is ruled out because the corresponding rate law
evidently identical to that observed experimentally with kapp
2k4C0.
)
On the basis of the kinetic law, it is therefore impossible to
discriminate between the dimer 3 or the monomeric complex 2
as the reactive species involved in the reaction with CH2dCH-
SnBu3.
would be: 1/x2 ) 8kC0 t + 1. On the other hand, a sequential
2
reaction of the dimer 3 with one molecule of CH2dCH-SnBu3
reacting irreversibly (rate constant k1) to form a iodide-
To solve this conundrum, one needs therefore to assess if
upon dissolution in DMF, the dimer dissociates almost irrevers-
ibly or not. If it dissociates, then the rate law features the reaction
of the monomeric PhPdI(AsPh3)2(DMF) with kapp ) 2k4C0. If
it does not dissociate, the experimental rate law features a
sequential attack of the dimer with kapp ) k1(2 + k1/k2)C0.
Spectroscopic investigations were thus performed on solutions
of the dimer 3 in DMF, a coordinating solvent as well as in
noncoordinating solvents such as CHCl3 and CH2Cl2. The UV
spectra of the dimer [Ph2Pd2(µ2-I)2(AsPh3)2] 3 in CHCl3 or CH2-
Cl2 were similar (Figure 6a). However, in DMF, a different UV
spectrum was observed with a shift of the maximum of
absorbance of 40 nm to lower wavelengths, indicating that a
new species was generated. Moreover, the spectrum in DMF
was not concentration dependent. Consequently, in DMF, [Ph2-
Pd2(µ2-I)2(AsPh3)2] is fully dissociated to the monomeric spe-
cies PhPdI(AsPh3)(DMF) 2 (eq 8).16,17a This occurs by a fast
reaction irrespective of the fate of 2. In other words, in
chloroform the dimer 3 exists as such whereas in DMF, the
Figure 5. Kinetics of the reaction of CH2dCH-SnBu3 (2 mM) with [Ph2-
Pd2(µ2-I)2(AsPh3)2] (1 mM) in DMF at 25 °C, as monitored by conductivity
measurements of I-
+
+SnBu3 formed in the reaction. Plot of κ∞/(κ∞-κ)
) 1/x versus time (κ: conductivity of I-
conductivity). 1/x ) kC0t + 1.
+
+SnBu3 at t, κ∞: final
9
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Mechanism of the Stille Reaction
A R T I C L E S
Because the dimer [Ph2Pd2(µ2-I)2(AsPh3)2] does not exist in
solution in DMF (eq 8), the only equilibrium operating in DMF
when starting from PhPdI(AsPh3)2 involves PhPdI(AsPh3)(DMF)
(eq 9), as written in our previous paper (Scheme 3).8
This has been confirmed by the UV spectrum of PhPdI-
(AsPPh3)2 in DMF (Figure 6b) which exhibited the same
absorption band at 310 nm as that observed in Figure 6a in
DMF, characteristic of PhPdI(AsPh3)(DMF) generated from the
dimer 3 (eq 8).17b Consequently, in DMF, under these conditions
only two species are prone to react with CH2dCH-SnBu3:
PhPdI(AsPh3)(DMF) or PhPdI(AsPPh3)2.
According to Farina3a and Espinet,4b although their results
apply to THF, we need to consider two limiting mechanisms
for the transmetalation step: (i) reaction of CH2dCH-SnBu3
with PhPdI(AsPh3)2 14b via a pentacoordinated PdII transition
state [PhPdIL2(η2-CH2dCH-SnBu3)]‡4b (Scheme 5, route A in
which however complex 2 must be taken into account because
of the partial dissociation of complex 1 in eq 9 before reaction
of 1 with CH2dCH-SnBu3) or (ii) reaction of CH2dCH-
SnBu3 with PhPdI(AsPh3)(DMF) 2 formed from 1 by the prior
3a
decomplexation of one ligand AsPh3 (Scheme 5, route B).19
Because no intermediate complex(es) could be detected by
1H NMR spectroscopy during the course of the reaction up to
the styrene formation (vide supra), neither the intermediate
complex 4 nor 5 could accumulate in significant amount
(Scheme 5). Therefore, their concentration represents at most a
few percent of the palladium concentration and they behave as
transient species obeying steady-state kinetics. This establishes
Figure 6. UV spectroscopy in a 1 mm cell at 25 °C: (a) [Ph2Pd2(µ2-I)2-
(AsPh3)2]: (s - s) 0.69 mM in CH2Cl2; (- - -) 0.64 mM in CHCl3; (s)
0.62 mM in DMF at 25 °C. (b) PhPdI(AsPh3)2: (- - -) 2.2 mM in CHCl3;
(s) 2.2 mM in DMF.
dimer 3 does not exist in appreciable amount. Therefore, in DMF
one observes the reactivity of the monomeric complex 2
generated upon its dissociation (eq 8).
(17) (a) The 1H NMR spectrum of PhPdI(AsPh3)(DMF) complex generated from
the dimer [Ph2Pd2(µ2-I)2(AsPh3)2] (eq 8) exhibited two broad signals (Figure
7a and Experimental Section), which are assigned to the protons of the Ph
linked to the PdII in PhPdI(AsPh3)(DMF). In that case the p-H and m-H
could not be distinguished and no coupling detected. This may be due to
a fast exchange of the DMF ligand or to a fast isomerization of PhPdI-
(AsPh3)(DMF) complexes as suggested in eq A.
The complex in which the ligands Ph and AsPh3 would be in a trans position
on the PdII center is less probable because of the transphobia18 of Ph and
AsPh3 ligands. The reaction of both complexes 2 and 2a with CH2dCH-
SnBu3 will generate complexes of type 4, in which the ligands CH2dCH-
SnBu3 and iodide are in a cis position in favor of an easy elimination of
ISnBu3. (b) The 1H NMR signals of PhPdI(AsPh3)28 in the absence of excess
AsPh3 were not well resolved in DMF (Figure 7b, and the Experimental
Section). A broad signal was observed for the o-H and a unique broad
signal for the m-H and p-H of the Ph group linked to the PdII attesting the
existence of an equilibrium involving PhPdI(AsPh3)2. Upon addition of 6
equivs AsPh3 to PhPdI(AsPh3)2 in DMF-d7, a well resolved spectrum was
observed for PhPdI(AsPh3)2 similar to that observed in Figure 7c, showing
that the equilibrium relating PhPdI(AsPh3)2 to PhPdI(AsPh3)(DMF) and
AsPh3 (eq 9) was then completely shifted towards PhPdI(AsPh3)2. As
expected for the equilibrium in eq 9, the protons of the Ph group linked to
the PdII in PhPdI(AsPh3)2 in the absence of AsPh3 (Figure 7b) are located
between those of PhPdI(AsPh3)(DMF) (Figure 7a)17a and those of PhPdI-
(AsPh3)2 observed in the presence of excess AsPh3 (Figure 7c).
(18) Vivente, J.; Arcas, A.; Bautista, D.; Jones, P. G. Organometallics 1997,
16, 2127-2138.
Consequently, the kinetics observed in Figure 5 characterizes
the reactivity of PhPdI(AsPh3)(DMF) with CH2dCH-SnBu3
(Scheme 4). The rate constant k ) 15 M-1s-1, calculated from
the slope of the straight line (1/x ) kC0t + 1) is then: k ) 2k4
(Scheme 4). The intrinsic reactivity of PhPdI(AsPh3)(DMF) with
CH2dCH-SnBu3 can then be determined by this procedure.
This gives: k4 ) 7.5 ( 0.5 M-1s-1 (DMF, 25 °C).
Transmetalation Step from PhPdI(AsPh3)(DMF) Gener-
ated by Dissociation of AsPh3 from PhPdI(AsPh3)2 in DMF.
(14) It is well established that low ligated Pd0 complexes are stabilized by halide
ions to form anionic species Pd0L2X- (X ) Cl, Br, I.; L ) PPh3) with the
order of stabilization: I- > Br- > Cl-. See: Amatore, C.; Azzabi, M.;
Jutand, A. J. Am. Chem. Soc. 1991, 113, 8375-8384.
(15) Amatore, C.; Jutand, A.; Khalil, F.; M’Barki, M. A.; Mottier, L. Organo-
metallics 1993, 12, 3168-3178.
(16) Lo Sterzo et al. have reported the irreversible dissociation of a related dimer
into the corresponding monomer in DMF (as evidenced by the shift of 30
nm of the absorption band toward lower wavelengths explained by the
conversion of the dimer to the monomer upon switching from CH2Cl2 to
DMF).6
(19) Very recently, Lo Sterzo et al.6 established that the transmetalation of PhCt
C-SnBu3 in a Stille-type reaction in DMF may occur by the two
mechanisms postulated by Farina3a and Espinet,4b that is involving the prior
dissociation of the ligand L (L ) PPh3) or not. In the latter case, the related
pentacoordinated PdII complex postulated as a transition state by Casado
and Espinet4b has been characterized and demonstrated to be a true reaction
intermediate.6
9
J. AM. CHEM. SOC. VOL. 125, NO. 14, 2003 4217

A R T I C L E S
Amatore et al.
Scheme 5. Possible Mechanisms for the Formation of Styrene
from PhPdI(AsPh3)2 and CH2dCH-SnBu3 in DMF: Reaction of
CH2dCH-SnBu3 with Either PhPdI(AsPh3)2 1 (route A)4b or with
PhPdI(AsPh3)(DMF) 2 (route B)3 Formed by Dissociation of One
Ligand AsPh3 from 1
experiments, KL/L then varied from 0.15 to 0.03. Consequently,
eq 10 may simplify to eq 12 (K′4 ) k′+4/k′-4) at high L
concentration viz. for [L] > 6 mM.
Noteworthy, eq 11 (always true) and 12 (valid for [L] > 6
mM) have the same mathematical structure, so that routes A
and B could not be distinguished in the basis of the observed
rate law at high L concentrations. Both laws can be expressed
as in eq 13 with R ) k4KL and â ) KL for eq 11 and R ) k5K′4
and â ) k5/k′-4 for eq 12.
Due to the limiting solubility of AsPh3 in DMF (14 mM),
AsPh3 could not be added in larger excess. Therefore, the AsPh3
concentration could not be considered as being constant during
the reaction. Taking that into account, integration of eq 13
afforded eq 14 with x ) (κ∞-κ)/κ∞ and n being the initial equiv
of AsPh3 added to Pd0(dba)2 before the generation of PhPdI-
(AsPh3)2.
that the rate of appearance of the I-
+
+SnBu3 species is
identical to that of the generation of complexes 4 and 5. In other
words, the conductivity measurements reflect exactly the kinetics
of the transmetalation step. The fact that the rate of formation
of I- + +SnBu3 obeys a first-order reaction in CH2dCH-SnBu3
also confirms the hypothesis made just above, i.e., that reaction
7 in Scheme 5 is much faster than the formation of the
intermediate complex 4.
The kinetic law for the mechanism A (Scheme 5) is given
by eq 10, upon considering steady-state approximation for
complex 4 and taking into account the partial dissociation of
PhPdI(AsPPh3)2 to PhPdI(AsPPh3)(DMF) in eq 9 (L: AsPh3;
Sn: CH2dCH-SnBu3).20
A value of â ) 3.2 × 10-4 was determined so that all unified
plot of (n - 1 + â/C0)lnx - x + 1 versus time was linear
irrespective n (Figure 3b). These experimental kinetics thus
agree with eq 14. Furthermore, treating each series of experi-
ments corresponding to a single n value established also the
validity of eq 14, and afforded identical values for the individual
slopes (Figure 3b). Consequently, the experimental kinetics of
the transmetalation step is in agreement with the framework of
the mechanism B (Scheme 5) since eq 14 was shown to be valid
all over the range of AsPh3 concentration added to PhPdI-
(AsPh3)2 (2-10 mM). This would not be the case for the
mechanism A because eq 12 is valid only for high AsPh3
concentrations (>6 mM). Therefore, these kinetic results
disprove the mechanism A and sustain mechanism B. Conse-
quently, â ) 3.2 ( 0.1 × 10-4 M (DMF, 25 °C) affords a
second determination of KL in agreement with the value of KL
) 3.1 × 10-4 M (DMF, 25 °C) determined in our previous
work,8 because â ) KL for mechanism B (see above).
An average value of R can be calculated from the average
slope of the straight lines of Figure 3b or by averaging the slopes
obtained for each n values. Because R ) k4KL, then k4 ) 8.3 (
0.5 M-1s-1. This value of k4 is extremely close to that
determined from the kinetics of the transmetalation step (k4 )
7.5 M-1s-1), investigated upon starting from PhPdI(AsPh3)-
(DMF) generated by the fast dissociation of the dimer 3 (vide
supra and Figure 3c). Moreover, it is compatible with that
reported by Farina (k4 ) 108 M-1s-1 in THF at 50 °C)
considering the change of solvent and temperature.3
The factor ([L] + KL)/[L] represents the contribution of the
partial dissociation of PhPdI(AsPPh3)2 to PhPdI(AsPPh3)(DMF)
(eq 9), where KL ) 3.1 × 10-4 M in DMF (25 °C).8
The kinetic law for the mechanism B (Scheme 5) is given
by eq 11. Complex 2 cannot obey a steady state because we
observed previously that the AsPh3 dissociation occurred up to
ca. 32% in DMF (KL ) 3.1 × 10-4 mol L-1).8 The mechanism
B proceeds then through a Michaelis-Menton type kinetics20c
with the rate law given in eq 11.4b,20c
At this stage, we have thus shown experimentally that the
mechanism B in Scheme 5 is coherent with the kinetics of the
transmetalation step, whereas that in mechanism A is not
coherent except at large [L] values. The corresponding rate law
(eq 11, 14) is obeyed and the values of the coefficient KL and
The kinetics of the transmetalation step has been investigated
for added AsPh3 in the range 2-10 mM. In our series of
(20) (a) Gellene, G. I. J. Chem. Educ. 1995, 72, 196-199. (b) Andraos, J. J.
Chem. Educ. 1999, 76, 1578-1583. (c) Jencks W. P. Catalysis in Chemistry
and Enzymology; Dover, Ed., John Wiley & Sons: 1987; p 571.
9
4218 J. AM. CHEM. SOC. VOL. 125, NO. 14, 2003

Mechanism of the Stille Reaction
A R T I C L E S
k4 determined on the basis of this rate law are fully coherent
with the values of KL and k4 determined independently by two
different strategies applied to different series of experiments,
since PhPdI(AsPh3)(DMF) could be generated in DMF either
from the dimer [Ph2Pd2(µ2-I)2(AsPh3)2] (eq 8) or from PhPdI-
(AsPh3)2 (eq 9).8
in our previous paper)8 which was assigned to PhPdI(AsPh3)-
S.8 However, one referee of this work drawn our attention to a
work (still unpublished at that time) which reported that in
CDCl3, the species involving only one AsPh3 per PdII center
could not be PhPdI(AsPh3)S, due to the poor coordination
properties of chloroform, but the dimer 3 (eq 16).23 We therefore
checked (Figure 6a) that the dimer 3 exhibited the same UV
spectrum in CHCl3 and in CH2Cl2, which is an even less
coordinating solvent. The spectrum in DMF was different (vide
supra, Figure 6a) due to the irreversible formation of PhPdI-
(AsPh3)(DMF). Consequently, the dimer 3 most presumably
does not dissociate in chloroform. So that the complex formed
by the partial dissociation of PhPdI(AsPh3)2 in chloroform that
The same value of KL was determined: (i) from the
observation of the partial dissociation of PhPdI(AsPh3)2 to
PhPdI(AsPh3)(DMF) in DMF (eq 9, previous work)8 and (ii)
from the kinetics of the transmetalation step performed from
PhPdI(AsPh3)2 (this work). Similarly the same value of k4, which
characterizes the reactivity of PhPdI(AsPh3)(DMF) with CH2d
CH-SnBu3, has been determined (i) from the kinetics of the
reaction of CH2dCH-SnBu3 with PhPdI(AsPh3)(DMF) gener-
ated by the fast dissociation of the dimer 3 in DMF (this work)
and (ii) from the kinetics of the transmetalation step performed
from PhPdI(AsPh3)2 (this work). This definitively proves that,
mechanism B alone is able to sustain kinetically a rate equal to
the one determined experimentally in DMF. This evidences that
whenever mechanism A occurs in DMF, it may only accounts
for a minor contribution in parallel with the major route B. Such
a minor contribution may actually exist and be the explanation
why k4, as determined from PhPdI(AsPh3)2, viz. k4 ) 8.3
M-1s-1, is slightly larger (10%) than k4, as determined from
1
we observed by H NMR8 is most certainly the dimer 3 (Eq
16).
This was confirmed by the UV spectrum of PhPdI(AsPPh3)2
in chloroform (Figure 6b), which exhibited the same absorption
band at 350 nm as that of the dimer in chloroform (Figure 6a).
The equilibrium (16) is slow compared to the time scale of the
NMR, since thin well resolved signals were observed for the
protons of the Ph attached to the PdII centers in both complexes
2 and 3 (Figure 5a in our previous paper).8
On the basis of the spectroscopic data reported in this paper,
it appears that in chloroform PhPdI(AsPh3)2 dissociates to form
the dimer 3 (eq 16),24 whereas in DMF, it gives gives PhPdI-
(AsPh3)(DMF) (eq 9). Whatever the structure of the complex
in which the Ph-PdII is ligated by only one AsPh3, i.e.,
monomer in DMF or dimer in chloroform, this evidences that
PhPdI(AsPh3)2 easily releases one ligand AsPh3 in appreciable
amount in both solVents.
the dimer route, viz. k4 ) 7.5 M-1 -1
s . However, this participa-
tion may account at maximum for 10% of the reaction.21
Transmetalation from trans-PhPdI(PPh3)2 in DMF. The
reactivity of CH2dCH-SnBu3 (50 equiv) with trans-PhPdI-
(PPh3)2 generated in situ by the oxidative addition of PhI (1
equiv) with Pd0(dba)2 and PPh3 (2 equiv)15 in DMF has also
been monitored through the conductivity measurements of I-
+
+SnBu3 because those species are formed in the cross-
coupling reaction (eq 15).
The reaction was found to be 670 times slower than that with
PhPdI(AsPh3)2 at 25 °C. This confirms that the higher efficiency
of AsPh3 compared to that of PPh3 in the catalytic reaction in
DMF is due to the faster transmetalation step as initially
proposed by Farina in THF.3,22
The dissociation of one AsPh3 in chloroform has also been
observed for (p-Z-C6H4)PdI(AsPh3)2 complexes (Z ) Cl,
OMe), formed in situ by the oxidative addition of p-Z-C6H4-I
to Pd0(dba)2 and 2 equivs AsPh3 in CDCl3 (eq 17) and
1
characterized by H NMR spectroscopy (experimental part).
Equilibrium between [Ar2Pd2(µ2-I)2(AsPh3)2] and ArPdI-
(PPh3)2 in Chloroform. The dimer [Ph2Pd2(µ2-I)2(AsPh3)2] 3
1
exhibited in CDCl3 the same well resolved H NMR spectrum
(see the Experimental Section) as that of the complex generated
from PhPdI(AsPh3)2 after dissociation of one AsPh3 (Figure 5a
(21) This ratio (10%) has to be considered as the maximum relative participation
of mechanism A. Indeed, one may consider alternatively that the measure-
ments involving the dimer afforded a slightly lower value of k4 than the
true one, whenever the dimer dissociation was not irreversible enough to
afford instantly a concentration exactly double for the reactive monomer.
Thus, k ) 2(1 - ꢀ)k4, where ꢀ may not be exactly zero at initial time. This
would not be apparent in a plot such as that in Figure 5, provided ꢀ was
small (e10%) but may affect correspondingly the k4 value determined from
the measured k value.
(22) (a) To the best of our knowledge, the dissociation of one PPh3 from PhPdI-
(PPh3)2 has never been observed in chloroform, nor in DMF. However, in
DMF the partial ionization of PhPdI(PPh3)2 to trans-PhPd(PPh3)2(DMF)+
and I- has been observed.22b A conductivity of 10 µS was measured for
the solution of PhPdI(PPh3)2 (2 mM) in DMF, before the addition of CH2d
CH-SnBu3. Consequently, a reaction of CH2dCH-SnBu3 with the cationic
complex trans-PhPd(PPh3)2(DMF)+ is not excluded, leading to an inter-
mediate trans-PdPd(η2-CH2dCH-SnBu3)(PPh3)2+ complex. (b) Amatore,
C.; Carre´, E., Jutand, A. Acta Chem. Scand. 1998, 52, 100-106.
Besides the two major thin doublets of the aromatic protons
of p-Z-C6H4 of the saturated complex (p-Z-C6H4)PdI(AsPh3)2,
two minor thin doublets were detected and assigned to the
aromatic protons of p-Z-C6H4 in the dimer [(p-Z-C6H4)2Pd2I2-
(AsPh3)2] (eq 18). They disappeared when AsPh3 was added
into the NMR tube. Only the two doublets of complexes (p-
(23) This suggestion was further clarified through a personal communication
with Prof. P. Espinet (Poster at the ISCH 13 Meeting in Tarragona, Spain.
3-7 September 2002). Casares, J. A.; Espinet, P.; Salas, G. Chem. Eur. J.
2002, 8, 4844-4853.
9
J. AM. CHEM. SOC. VOL. 125, NO. 14, 2003 4219

A R T I C L E S
Amatore et al.
Scheme 6. Mechanism of the Stille Reaction in DMF: Cross-coupling of PhI with CH2dCH-SnBu3 Catalyzed by Pd0(dba)2 Associated to
AsPh3 (2 equiv.) (the steps indicated by the dashed arrows are too fast for their kinetics to be monitored here)
Conclusion
Z-C6H4)PdI(AsPh3)2 were then detected in agreement with
the shift of the equilibrium in Eq 18 toward its left-hand side.
The AsPh3 dissociation percentage did not depend significantly
on the substituent Z investigated here (16% for Z ) OMe and
18% for Z ) Cl). This is consistent with the fact that the aryl
ligand cannot exert any trans effect on the dissociation of the
AsPh3 ligand due to the trans structure of (p-Z-C6H4)PdI-
(AsPh3)2.
In DMF, at 25 °C, the transmetalation step of the Stille
reaction involving CH2dCH-SnBu3 as the nucleophile has been
found to proceed mainly via the 1:1 reaction of the tin derivative
with PhPdI(AsPh3)(DMF) formed by the dissociation of one
ligand AsPh3 from PhPdI(AsPh3)2. This is in agreement with
Farina’s conclusions for the same reactants and ligand, despite
the change of experimental conditions (THF, 50 °C). The
complex PhPdI(AsPh3)(DMF) is therefore the reactive species
which affords styrene following its reaction with the nucleophile
CH2dCH-SnBu3. The same complex PhPdI(AsPh3)(DMF) is
also generated in DMF from the dimeric complex [Ph2Pd2(µ2-I)2-
(AsPh3)2], which has been independently synthesized and
characterized by its X-ray structure. The intrinsic reactivity of
PhPdI(AsPh3)(DMF) with CH2dCH-SnBu3 in DMF has been
characterized through two different kinetic routes and led to
the determination of the same rate constant k4 ) 7.5 M-1s-1
(Scheme 6).
(24) The reactivity of the dimer [Ph2Pd2(µ2-I)2(AsPh3)2] has been investigated
in chloroform. Its reaction with 4 equivs CH2dCH-SnBu3 was first
monitored by 1H NMR in CDCl3 at room temperature. Styrene was formed
in a fast reaction, which thus excluded the possibility to detect any
intermediate complex(es). [Ph2Pd2(µ2-I)2(AsPh3)2] was totally converted in
that reaction. The kinetics of the reaction of [Ph2Pd2(µ2-I)2(AsPh3)2] (0.5
mM) with CH2dCH-SnBu3 (1 mM) in chloroform was then monitored
by UV spectroscopy at 290 nm. The plot of 1/x versus time was linear:
1/x ) kappt + 1 (x ) (D - D∞)/(D0 D∞); D0: initial absorbance, D∞:
-
final absorbance, D: absorbance at t) with kapp ) 0.005 s-1 at 25 °C. This
confirms that in chloroform, the dimer is not involved in an uphill
equilibrium with a monomer (equilibrium constant K) which would be the
reactive intermediate. Indeed, the rate law would then be: 1/x1/2 ) k4KC0t/2
+ 1 (vide supra). Consequently, the dimer 3 reacts directly with CH2d
CH-SnBu3 in chloroform. Again two mechanisms are possible as discussed
above for the reaction in DMF. The mechanism compatible with the kinetic
law is the one in which the dimer reacts first with one molecule of CH2d
CH-SnBu3 to form the transient complex [PhPdL(η2-CH2dCH-SnBu3)-
(µ2-I)Pd(Ph)IL] 6 (irreversible reaction with a rate constant k1), which then
reacts with a second molecule of CH2dCH-SnBu3 (rate constant k2) to
form two molecules of complex 4. The rate law is then 1/x ) k1C0(2 +
We established in a previous work that the role of AsPh3,
compared to PPh3, is to accelerate the oxidative addition by a
10-fold factor in DMF.8 However, this effect is partly canceled
out in the presence of the nucleophile CH2dCH-SnBu3, which
interferes in the catalytic cycle prior to the oxidative addition.
This results in a decelerating effect due to the partial complex-
ation of the reactive complex Pd0(AsPh3)2 by CH2dCH-SnBu3
to form the unreactive Pd0(η2-CH2dCH-SnBu3)(AsPh3)2.8,25
Consequently, in DMF at least the mechanism of the catalytic
Stille reaction is much more complex than classically reported
(Schemes 1 and 2). This is examplified in Scheme 6, where the
rate constants K1k3,8 k4 and the equilibrium constants K1K2,8
and KL,8 for the ligand dissociation, have been determined in
DMF.
k1/k2)t + 1 with kapp ) k1(2 + k1/k2)C0. Then k1(2 + k1/k2) ) 10 M-1s-1
.
If k2 . k1, as it is most presumable, then k1 ) 5 M-1s-1 (CHCl3, 25 °C).
This establishes that the dimer [Ph2Pd2(µ2-I)2(AsPh3)2] is the reactive species
in chloroform whereas PdPdI(AsPPh3)(DMF) is the reactive species in DMF
(vide supra). It is noteworthy that the value of the rate constant k1 is close
to that (k4 ) 7.5 M-1s-1) determined for PhPdI(AsPh3)(DMF) in DMF.
The followed route does not really stem from the intrinsic reactivity of
each species but rather from their relative concentration, which is imposed
in each solvent by the ability of the dimer to dissociate or not. The reaction
of PhPdI(AsPh3)2 with CH2dCH-SnBu3 was monitored by 1H NMR
spectroscopy in CDCl3. This reaction produced styrene in quantitative yield.
Because we have shown in this work that PhPdI(AsPh3)2 is involved in an
equilibrium with [Ph2Pd2(µ2-I)2(AsPh3)2] (eq 18), it could have been of
interest to determine whether CH2dCH-SnBu3 reacts with PhPdI(AsPh3)2
or with [Ph2Pd2(µ2-I)2(AsPh3)2] in chloroform. However, because Stille
reactions are never performed in chloroform, this investigation has not been
undertaken.
9
4220 J. AM. CHEM. SOC. VOL. 125, NO. 14, 2003

Mechanism of the Stille Reaction
A R T I C L E S
a KappaCCD diffractometer at 150.0(1)K with graphite mono-
chromated MoKR radiation (λ ) 0.71073 Å). Crystallographic
results are summarized in Table 1. Full details of the crystal-
lographic analysis are described in the Supporting Information.
Materials. Dimethylformamide was distilled from calcium
hydride under vacuum. Tetrahydrofuran was distilled from
sodium-benzophenone. Triphenylarsine, phenyl iodide, 1-chloro-
4-iodobenzene, 1-methoxy-4-iodobenzene, tri-n-butyl(vinyl)tin
and tri-n-butyltin iodide (Aldrich) were commercially available.
Pd0(dba)2 was prepared according to a described procedure.27
General Procedure for Conductivity Measurements. In a
cell thermostated at 25 °C containing 15 mL DMF was added
successively 17 mg (0.03 mmol) Pd0(dba)2, 18.4 mg (0.06
mmol) AsPh3 and 3.4 µL (0.03 mmol) PhI. The residual
conductivity κ0 (3 µS.cm-1) was measured. 87 µL (0.3 mmol)
CH2dCH-Sn(n-Bu)3 was then added and the conductivity
recorded versus time using a computerized homemade program,
until it reached a constant final value (Figure 1a).
[Ph2Pd2(µ2-I)2(AsPh3)2]. 100 mL of anhydrous THF was
added to 1 g (1.74 mmol) of Pd(dba)2, 0.532 g (1.74 mmol) of
AsPh3 and 0.39 mL (3.48 mmol) of PhI. After 2 h, THF was
evaporated. After addition of ethyl ether, brown yellow crystals
were collected 0.9 g (84% yield). Monocrystals were obtained
by vapor diffusion from CH2Cl2/Et2O. Anal. Calcd for C48H40-
As2I2Pd2: C, 46.7; H, 3.3. Found: C, 46.44; H, 3.35. 1H NMR
(250 MHz, CDCl3, TMS): δ 6.63 (t, 1H, J ) 7 Hz, p-H), 6.66
(t, 2H, J ) 7 Hz, m-H), 7.10 (dd, 2H, J ) 7 and 1.2 Hz, o-H),
7.26 (m, 6H, H of AsPh3), 7.31 (t, 9H, H of AsPh3) (addition
of AsPh3 into the NMR tube afforded the signals of PhPdI-
(AsPh3)2 already reported).8
Figure 7. 1H NMR (250 MHz, DMF-d7, ppm vs TMS): (a) PhPdI-
8
(AsPh3)(DMF) from [Ph2Pd2(µ2-I)2(AsPh3)2] (3 mM); (b) PhPdI(AsPh3)2
(4 mM); (c) [Ph2Pd2(µ2-I)2(AsPh3)2] (3 mM) and AsPh3 (5 equivs). The
8
spectrum observed upon addition of AsPh3 (6 equivs) to PhPdI(AsPh3)2
(3 mM), is identical to that in (c).
As established in this work, the greater efficiency of the Stille
reaction, when catalyzed by a Pd0 complex ligated by AsPh3
instead of PPh3, is thus due to an easier dissociation of AsPh3
from PhPdI(AsPh3)2 in THF and DMF. Therefore, besides
establishing the central involvement of PhPdI(AsPh3)(DMF) in
the Stille reaction in DMF, thereby confirming Farina’s proposal
in THF, this work demonstrates the essential kinetic role of such
species on the efficiency of Stille reactions performed with
AsPh3 ligated palladium catalysts. It is noteworthy that within
the range of AsPh3 concentrations investigated here, even if
PhPdI(AsPh3)(DMF) is no longer detected in the 1H NMR
spectrum in the presence of the highest excess of AsPh3 (Figure
7c), it remains the reactive complex, which is then present at a
lower concentration and is at the origin of the slower trans-
metalation step.26
[PhPdI(AsPh3)(DMF)] from [Ph2Pd2(µ2-I)2(AsPh3)2] (3 mM
in DMF-d7):1H NMR (250 MHz, DMF-d7, TMS): δ 6.62 (br
s, ∆ν1/2 ) 14 Hz, 3H, p-H and m-H), 6.99 (br s, ∆ν1/2 ) 18
Hz, 2H, o-H), 7.43 (m, 15H, H of AsPh3) (Figure 7a). Addition
of 4 equivs AsPh3 per dimer leads to the formation of pure
PhPdI(AsPh3)2 with a well-defined spectrum (vide infra and
Figure 7c).
However, when considering aryl iodides, which are highly
substituted by electron-withdrawing groups such as in C6Cl2F3-
I, Espinet et al. have established that ArPdI(AsPh3)2 complexes
are the reactive species in THF.4b This shows that the structure
of the reactive complex (ligated by one or two L ligands) is
highly dependent on the aryl group.
[PhPdI(AsPh3)2]8 (4 mM in DMF-d7) in the absence of
AsPh3: the signals of PhPdI(AsPh3)2 are not well resolved in
DMF-d7 due to its dynamic equilibrium with PhPdI(AsPh3)-
Experimental Section
1
All experiments were performed under a dry atmosphere of
Argon by following conventional Schlenk techniques. 1H NMR
spectra were recorded on a Bruker spectrometer (250 or 400
MHz). Conductivity was measured on a Radiometer Analytical
CDM210 conductivity meter (cell constant ) 1 cm-1). Crystal-
lographic data for [Ph2Pd2(µ2-I)2(AsPh3)2] were collected on
(DMF) and AsPh3. H NMR (250 MHz, DMF-d7, TMS): δ
6.47 (m, 3H, m-H and p-H), 6.83 (m, 2H, o-H), 7.43 (m, 30 H,
H of AsPh3) (Figure 7b).
[PhPdI(AsPh3)2]8 (3 mM) in the presence of 6 equivs AsPh3
or generated by addition of 5 equiv. AsPh3 to the dimer
[Ph2Pd2(µ2-I)2(AsPh3)2] in DMF-d7: 1H NMR (250 MHz,
DMF-d7): δ 6.37 (t, 2H, J ) 7 Hz, m-H), 6.46 (t, 1H, J ) 7
Hz, p-H), 6.78 (d, 2H, J ) 7 Hz, o-H), 7.42 (s, H of AsPh3)
(Figure 7c).
(25) In a real catalytic reaction where PhI is in large excess compared to the
palladium catalyst, the half-reaction time of the oxidative addition will be
considerably shorter than that (8 s) determined in the present work under
stoichiometric conditions ([Pd0] ) [PhI] ) 2 mM, vide supra). For example,
for [Pd0] ) 2mM and [PhI] ) 80 mM, t1/2 ) 0.2 s. However, in the presence
of CH2dCH-SnBu3 (80 mM) (the highest concentration investigated in
this work) the oxidative addition will be slower than that latter, with a
half-reaction time of ca. 1s, as estimated from our previous work.8
Nevertheless, this still corresponds to a very fast reaction in comparison to
the rate of the overall catalytic reaction. Indeed, the reaction of CH2d
CH-SnBu3 with PhPdI(AsPh3)2 (2 mM) investigated here was found to
be slower than the oxidative addition performed under the catalytic
conditions, i.e., in the presence of CH2dCH-SnBu3, since the fastest
transmetalation, observed with CH2dCH-SnBu3 (80 mM), exhibited a half-
reaction time of 9 s. These results confirm that the reaction of CH2dCH-
SnBu3 with PhPdI(AsPh3)2 via PhPdI(AsPh3)(DMF) is the rate determining
step of the catalytic cycle also in DMF, as previously established by Farina3
in THF, via the investigation of the kinetics of the catalytic reaction.
(26) This is an application of the steady-state approximation for a reactive moiety
involved in a fast equilibrium with a non reactive species.
[(p-MeO-C6H4)PdI(AsPh3)2]. 0.5 mL of CDCl3 was added
to 5.8 mg (0.01 mmol) of Pd(dba)2 and 6 mg (0.02 mmol) of
AsPh3 followed by 2.3 mg (0.01 mmol) of p-MeO-C6H4-I.
1H NMR (400 MHz, CDCl3): δ 2.19 (s, 3H, CH3), 6.07 (d,
2H, J ) 8.7 Hz), 6.52 (d, 2H, J ) 8.7 Hz), 7.30 (t, J ) 7.5 Hz,
m-H of AsPh3), 7.38 (m, p-H of AsPh3) 7.47 (m, o-H of AsPh3).
The 1H NMR spectrum also exhibited the signals of the dimer
[(p-MeO-C6H4)2Pd2I2(AsPh3)2] (16% dissociation): δ 2.23 (s,
(27) Takahashi, Y.; Ito, Ts.; Ishii, Y. J. Chem. Soc. Chem. Commun. 1970,
1065-1066.
9
J. AM. CHEM. SOC. VOL. 125, NO. 14, 2003 4221

A R T I C L E S
Amatore et al.
3H, CH3), 6.72 (d, 2H, J ) 9 Hz), 7.60 (d, 2H, J ) 9 Hz), 7.30
(t, J ) 7.5 Hz, m-H of AsPh3), 7.38 (m, p-H of AsPh3) 7.47
(m, o-H of AsPh3). The signals at 2.23, 6.72 and 7.60 ppm
disappeared upon addition of AsPh3 to afford only that of (p-
MeO-C6H4)PdI(AsPh3)2 described just above.
ppm disappeared upon addition of AsPh3 to afford only that of
(p-Cl-C6H4)PdI(AsPh3)2 described just above.
Acknowledgment. This work has been supported in part by
the Centre National de la Recherche Scientifique (CNRS, UMR
8640 and 7653), the Ministe`re de la Recherche (Ecole Normale
Supe´rieure) and the University Paris VI (UPMC). We thank
the editor, the referees and Professor P. Espinet for the
discussion about the existence of the dimer in chloroform. We
thank Johnson Matthey for a generous loan of sodium tetra-
chloropalladate.
[(p-Cl-C6H4)PdI(AsPh3)2]. 0.5 mL of CDCl3 was added to
5.8 mg (0.01 mmol) of Pd(dba)2 and 6 mg (0.02 mmol) of AsPh3
1
followed by 2.4 mg (0.01 mmol) of p-Cl-C6H4-I. H NMR
(250 MHz, CDCl3): δ 6.30 (d, 2H, J ) 8.4 Hz), 6.55 (d, 2H,
J ) 8.4 Hz), 7.30-7.38 (m, H of AsPh3), 7.40 (m, H of AsPh3).
The 1H NMR spectrum also exhibited the signals of the dimer
[(p-Cl-C6H4)2Pd2I2(AsPh3)2] (18% dissociation): δ 6.64 (d,
2H, J ) 8.4 Hz), 6.99 (d, 2H, J ) 8.4 Hz), 7.30-7.38 (m, H of
AsPh3), 7.40 (m, H of AsPh3). The signals at 6.64 and 6.99
Supporting Information Available: Full details of the
crystallographic analysis. This material is available free of
charge via the Internet at http://pubs.acs.org.
JA0204978
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4222 J. AM. CHEM. SOC. VOL. 125, NO. 14, 2003