Stille coupling of alkynyl stannane and aryl iodide, a many-pathways reaction: The importance of isomerization

Article abstract of DOI:10.1021/om100978w

The kinetics of the Stille reaction between C₆Cl ₂F₃I and PhCCSnBu₃ have been studied for the whole catalytic system and for transmetalations as separate steps. The use of (trifluorodichlorophenyl)palladium derivatives slows down the reactions and allows for the observation of the intermediates cis-and trans-[Pd(C ₆Cl₂F₃)I(PPh₃)₂]. The first is formed in the oxidative addition step and isomerizes to the second. Both were studied as catalysts for the whole cycle. The kinetic study compares the relevance of the transmetalation step on each isomer. The competing transmetalations produce both cis-and trans-[Pd(C₆Cl ₂F₃)(PhCC)(PPh₃)₂]. The former undergoes very fast C-C coupling, while the second accumulates in solution due to extremely slow isomerization. Thus, the system is a case study of the effect of competing pathways in the Stille reaction and its consequences on the performance of the catalytic process.

Full text of DOI:10.1021/om100978w

Organometallics 2011, 30, 611–617 611
DOI: 10.1021/om100978w
Stille Coupling of Alkynyl Stannane and Aryl Iodide, a Many-Pathways
Reaction: The Importance of Isomerization
ꢀ
Monica H. Perez-Temprano, Ana M. Gallego, Juan A. Casares,* and Pablo Espinet*
ꢀ
´
ꢀ
IU CINQUIMA/Quımica Inorganica, Facultad de Ciencias, Universidad de Valladolid,
E-47071 Valladolid, Spain
Received October 13, 2010
The kinetics of the Stille reaction between C6Cl2F3I and PhCCSnBu3 have been studied for the
whole catalytic system and for transmetalations as separate steps. The use of (trifluorodichlorophenyl)-
palladium derivatives slows down the reactions and allows for the observation of the intermediates
cis- and trans-[Pd(C6Cl2F3)I(PPh3)2]. The first is formed in the oxidative addition step and isomerizes
to the second. Both were studied as catalysts for the whole cycle. The kinetic study compares the
relevance of the transmetalation step on each isomer. The competing transmetalations produce both
cis- and trans-[Pd(C6Cl2F3)(PhCC)(PPh3)2]. The former undergoes very fast C-C coupling, while the
second accumulates in solution due to extremely slow isomerization. Thus, the system is a case study
of the effect of competing pathways in the Stille reaction and its consequences on the performance of
the catalytic process.
Introduction
Obviously, the basic Scheme 1 needs to be adjusted to
include particular cases. For instance, coordinating solvents
can partially replace ligands in some reaction intermediates.5,15
If a chelating ligand is used, the thermodynamic products of
the oxidative addition and therefrom should be cis, rather
than the trans structures depicted in Scheme 1. Observation
of these chelated intermediates has been reported,4 and in
one case the process has been mechanistically studied using
NMR and UV/vis techniques.16,17 With bulky ligands most
intermediates will be tricoordinated instead of tetracoordi-
nated, as proposed recently by calculation and by some
experiments.18
Further variations to be considered, in the case of mono-
dentate ligands, are the stereochemistry of the initial oxida-
tive addition product and the cis to trans isomerization rate,
as compared to that of transmetalation (both rates will depend
on each particular case). The oxidative addition has been
thoroughly studied both theoretically and experimentally,
and two possible pathways are accepted: the three-center
mechanism that leads to cis-[PdRXL2]19 and an ionic me-
chanism that leads to trans-[PdRXL2].19a,b,20 When the cis to
trans isomerization reaction is comparatively fast, the fuga-
cious existence of the isomer cis-[PdRXL2] is irrelevant.
When this is not the case and cis-[PdRXL2] is produced
Among the mechanisms of palladium-catalyzed cross-
coupling processes, that of the Stille reaction is perhaps the
most studied experimentally.1,2 A comprehensive account of
mechanistic studies was published in 2004.3 The possible
general pathways for the process are summarized in Scheme 1.
The steps preceding the transmetalation have been experi-
mentally confirmed by observation or unambiguous kinetic
deduction of intermediates.4-6 Further studies,7-9 including
detailed theoretical (DFT) calculations10-12 and the obser-
vation of a post-transmetalation intermediate, [PdR1R2(AsPh3)-
(ISnBu3)],10 identified during the study of the retro-transme-
talation reaction on cis-[PdRf2(AsPh3)2] (R1 = R2 = Rf =
3,5-C6Cl2F3),13,14 have been published more recently.
*To whom correspondence should be addressed. E-mail: espinet@
qi.uva.es (P.E.).
(1) Stille, J. K. Angew. Chem. 1986, 98, 504-519; Angew. Chem., Int.
Ed. Engl. 1986, 25, 508-524.
(2) Milstein, D.; Stille, J. K. J. Am. Chem. Soc. 1978, 100, 3636–3638.
(3) Espinet, P.; Echavarren, A. M. Angew. Chem., Int. Ed. 2004, 43,
4704–4734.
(4) Casado, A. L.; Espinet, P.; Gallego, A. M.; Martınez-Ilarduya,
J. M. Chem. Commun 2001, 339–340.
(5) Casado, A. L.; Espinet, P.; Gallego, A. M. J. Am. Chem. Soc.
2000, 122, 11771–11782.
(6) Casado, A. L.; Espinet, P. J. Am. Chem. Soc. 1998, 120, 8978–
8985.
(7) Nilsson, P.; Puxty, G.; Wendt, O. F. Organometallics 2006, 25,
1285–1292.
(8) Ariafard, A.; Lin, Z.; Fairlamb, J. S. Organometallics 2006, 25,
5788–5794.
(9) Santos, L. S.; Rosso, G. B.; Pilli, R. A.; Eberlin, M. N. J. Org.
ꢀ
(13) Espinet, P.; Martınez-Ilarduya, J. M.; Perez-Briso, C.; Casado,
A.; Alonso, M. A. J. Organomet. Chem. 1998, 551, 9–20.
(14) For “retrotransmetalation” we mean the exchange of an R on
Pd for an X on Sn, the reverse of what happens in the so-called
transmetalation.
Chem. 2007, 72, 5809–5812.
(15) Casares, J. A.; Espinet, P.; Salas, G. Chem. Eur. J. 2002, 8 (21),
4844–4853.
(16) Crociani, B.; Antonaroli, S.; Beghetto, V.; Matteoli, U.; Scrivanti,
A. Dalton Trans. 2003, 2194–2202.
(10) Perez-Temprano, M. H.; Nova, A.; Casares, J. A.; Espinet, P.
J. Am. Chem. Soc. 2008, 130, 10518–10520.
(11) Nova, A.; Ujaque, G.; Maseras, F.; Lledos, A.; Espinet, P. J. Am.
Chem. Soc. 2006, 128, 14571–14588.
(17) Crociani, B.; Antonaroli, S.; Canovese, L.; Uguagliati, P.;
Visentin, F. Eur. J. Inorg. Chem. 2004, 4, 732–742.
(18) Ariafard, A.; Yates, B. F. J. Am. Chem. Soc. 2009, 131, 13981–
13991.
(12) (a) Alvarez, R.; Faza, O. N.; Lopez, C. S.; de Lera, A. R. Org.
Lett. 2006, 35. (b) Alvarez, R.; Faza, O. N.; de Lera, A. R.; Cardenas, D. J.
Adv. Synth. Catal. 2007, 349, 887–906.
r
2011 American Chemical Society
Published on Web 01/18/2011
pubs.acs.org/Organometallics

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Perez-Temprano et al.
612 Organometallics, Vol. 30, No. 3, 2011
Scheme 1
the transmetalation and the catalytic cycle starting on each
isomer 1 or 2. Additionally, the use of PhCtCSnBu3 pro-
vides a higher stability of the resulting alkynylpalladium
intermediates compared to their vinyl or aryl analogues22
and facilitates its observation.
The Pd-catalyzed reaction of RfI with (phenylethynyl)-
tributyltin in THF at 50 °C proceeds as expected for a Stille
process, affording the coupling product PhCtCRf (5) and
ISnBu3 (6) (eq 2). The reaction is very slow at this tempera-
ture and can be followed in the course of the first few hours
by NMR techniques, allowing for the observation of mech-
anistically informative intermediates, as well as some bypro-
ducts that are also analyzed below.
Scheme 2
Monitoring the Catalytic Reactions. As most of the com-
pounds involved in the catalysis studied contain C6F3Cl2, 19
F
NMR monitoring affords interesting information. The reac-
tion using trans-[PdRfI(PPh3)2] (1) as the initial catalyst, in
THF at 50 °C, showed that during the reaction compound 1
was partially replaced by two other palladium complexes
(Figure 1). One of them, cis-[PdRfI(PPh3)2] (2), is the kinetic
oxidative addition product of 3 to Pd(PPh3)n intermediates.
The other was identified as trans-[PdRf(CtCPh)(PPh3)2] (7), a
transmetalation product. For its unambiguous identification,
complex 7 was independently synthesized from PhCtCSnBu3
and trans-[PdRf(OTf)(PPh3)2]5 in THF at 0 °C, isolated, and
fully characterized.
upon oxidative addition, the transmetalation on cis- and
trans-[PdRXL2] intermediates needs to be considered. Then,
the transformations depicted in Scheme 2 have to be taken
into account. In this paper we study a case where this com-
petition of transmetalations on cis- and trans-[PdRXL2] com-
plexes is actually observed.
Throughout the catalysis depicted in Figure 1, the sum of
concentrations of the Pd(II) complexes (1 þ 2 þ 7) remained
constant,23 as no metallic palladium was detected for the first
hours of reaction, when there is still a large excess of the reagents.
The formation of some small but steadily increasing SnRfBu3 (8)
side product was also detected during the reactions. This side
product arises from undesired transmetalations.24 It is worth
noting that the amount of complex 7 continuously increased
during the reaction, and the evolution of the concentrations of 1
and 2 came, after about 2 h, to a quasi-equilibrium, after which
the ratio 1:2 remained almost constant,25 while their total
amount decreased steadily but slowly.
Results and Discussion
During preliminary experiments of a kinetic study, using
trans-[PdRfI(PPh3)2] (1) as catalyst, of the C-C coupling of
RfI (Rf = C6Cl2F3) (3) and PhCtCSnBu3 (4) we detected, at
variance with other studies on related systems, the presence
of cis-[PdRfI(PPh3)2] (2). This complex is an oxidative addi-
tion intermediate, assumed to occur but not detected in cat-
alytic conditions in our previous studies. Thermodynamically,
cis-[PdRfI(PPh3)2] is unstable and isomerizes completely to the
trans isomer (eq 1),21 but its detection under catalytic condi-
tions makes it kinetically and mechanistically significant for the
reaction. Since the complexes cis- and trans-[PdRfI(PPh3)2] can
both be isolated,21 this system offers a rare chance to study
The observation of cis-[PdRfI(PPh3)2] (2) during the
catalysis is remarkable and shows that, under the reaction
ꢀ
(22) (a) Espinet, P.; Fornies, J.; Martınez, F.; Sotes, M.; Lalinde, E.;
(19) For cases of oxidative addition to neutral Pd(0) complexes by a
concerted mechanism see: (a) Stille, J. K.; Lau, K. S. Y. Acc. Chem. Res.
1977, 10, 434–442. (b) Bickelhaupt, F. M.; Ziegler, T.; Schleyer, P. v. R.
Organometallics 1995, 14, 2288–2296. (c) Senn, H. M.; Ziegler, T. Orga-
nometallics 2004, 23, 2980–2988. (d) Ariafard, A.; Lin, Z. Organometallics
2006, 25, 4030–4033. (e) Lam, K. C.; Marder, T. B.; Lin, Z. Organometallics
2007, 26, 758–760. (f) Li, Z.; Fu, Y.; Guo, Q.-X.; Liu, L. Organometallics
2008, 27, 4043–4049. (g) Schoenebeck, F.; Houk, K. N. J. Am. Chem. Soc.
2010, 132, 2496–2497.
(20) For cases of oxidative addition to neutral Pd(0) complexes via
SN2 see: (a) Netherton, M. R.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41,
3910–3912. (b) Hills, I. D.; Netherton, M. R.; Fu, G. C. Angew. Chem., Int.
Ed. 2003, 42, 57495–752. (c) Rodríguez, N.; de Arellano, C. R.; Asensio, G.;
Medio-Simon, M. Chem. Eur. J. 2007, 13, 4223–4229. See also ref 19a,b.
(21) Casado, A. L.; Espinet, P. Organometallics 1998, 17, 954–959.
Moreno, M. T.; Ruiz, A.; Welch, A. J. J. Organomet. Chem. 1991, 403,
253–267. The preparation and characterization of trans- and cis-[Pd(C6F5)-
(CtCR)(PR3)2] complexes has been reported. Even the cis complexes do not
undergo alkynyl-aryl coupling under mild handling conditions, probably
due to the remarkable inertness of the Pd-C6F5 bond. (b) Osakada, K.;
Yamamoto, T. Coord. Chem. Rev. 2000, 198, 379–399.
(23) The metalated C6Cl2F3 groups can be observed easily, as their
19F chemical shifts are very different from those in organic molecules:
Casares, J. A.; Espinet, P.; Martın-Alvarez, J. M.; Martınez-Ilarduya,
J. M.; Salas, G. Eur. J. Inorg. Chem. 2005, 3825–3831.
ꢀ
(24) Fuentes, B.; Garcıa-Melchor, M.; Lledos, A.; Maseras, F.;
Casares, J. A.; Ujaque, G.; Espinet, P. Chem. Eur. J. 2010, 16, 8596–
8599.
(25) Strictly it is not a true equilibrium because of the continuous and
irreversible formation of complex 7.

Article
Organometallics, Vol. 30, No. 3, 2011 613
Figure 1. Concentration/time data for the reaction 3 þ 4, in
THF at 323 K, using 1 as catalyst. Starting conditions; [1] =
0.01 M; [3] = [4] = 0.20 M. Note that the disappearance of 3 is
not depicted and is far above the drawing limits. Solid lines
represent the best nonlinear fitting.
Figure 2. Concentration/time data for the reaction 3 þ 4, in
THF at 323.2 K, using 2 as catalyst. Starting conditions: [2] =
0.01 M; [3] = [4] = 0.20 M. Note that the disappearance of 3 is
not depicted and is out of the drawing limits. Solid lines repre-
sent the best nonlinear fitting.
Scheme 3
conditions, it is formed by oxidative addition more rapidly
than it disappears by isomerization to 1 (the trans complex is
the thermodynamic product) or by transmetalation. Thus, in
contrast with the reaction of 3 with Sn(vinyl)Bu3, previously
studied and reported,6 where only 1 was observed during the
catalysis, it is expected here that 2 might compete with 1 as
catalyst (that is, as the compound undergoing transmetalation).
Consequently, the coupling reaction was also studied and
monitored using 2 as the initial catalyst (Figure 2). Again, as
it happened starting from catalyst 1, the system converged
toward a quasi-equilibrium between complexes 1 and 2 while
the concentration of 7 steadily increased.
The observations made so far show that the choice of initial
catalyst 1 or 2 hardly affects the bulk result of the catalysis or the
nature and relative amount of the palladium complexes ob-
served, because a quasi-steady 1:2 ratio is reached soon in both
cases. In other words, the overall catalyzed reaction will take
place almost at the same rate and to the same extent, irrespective
of the isomer 1 or 2 chosen as starting catalyst.
The expected products of direct transmetalation on 1 or 2
are trans-[PdRf(CtCPh)(PPh3)2] (7) and cis-[PdRf(CtCPh)-
(PPh3)2] (9). The former is actually observed as a rather
persistent product in solution; the second is not observed
under the reaction conditions, suggesting that, when formed,
it immediately undergoes C-C coupling to give 5, as ob-
served before for a similar system.6 The synthesis of 9 was
attempted by different methods, but 9 was never detected:
even at low temperature (223 K) only the coupling product
was observed, supporting the ephemeral nature of the puta-
tive intermediate 9.
The reductive elimination of 7 was monitored by 19F
NMR in separate experiments. It couples quickly in solution,
when isolated, but the coupling is fairly efficiently quenched
in the presence of PhCtCSnBu3 or PPh3 in the reaction med-
ium (as under catalytic conditions) and becomes very slow.26
(26) For the concentration used in catalysis, about 90% of the
coupling product is formed in 3 h. The reaction has an induction time,
which suggests that probably the reaction is initiated only after some
phosphine oxidation favoring dissociation has occurred. This ligand
dissociation can be compensated in the presence of other external
coordinating species that exist under catalytic conditions (e.g., alkynyl
in large excess). Thus, under the conditions of Figures 1 and 2 the
coupling is less than 5% in 3 h.

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Perez-Temprano et al.
614 Organometallics, Vol. 30, No. 3, 2011
Figure 3. Concentration/time data for the transmetalation step obtained by 19F NMR, in THF. Starting conditions: (a) T = 323 K, [1]
= 0.01 M, [4] = 0.20 M; (b) T = 323 K, [2] = 0.01 M, [4] = 0.20 M; (c) T = 308 K, [1] = 0.01 M, [4] = 0.60 M; (d) T = 308 K, [1] = 0.01
M, [4] = 0.60 M. Solid lines in (a) and (b) correspond to the best nonlinear fitting (see text).
This indicates that the isomerization of complex 7 to 9 (and
its consequent coupling to 5 plus Pd0) is, comparatively, a
less important transformation during the catalyzed experi-
ments.
Monitoring the Transmetalation and Isomerization Reac-
tions. The possible participation of two different catalysts
(1 and 2) in the coupling studied gives rise to a kinetically
complicated system, where the catalytic pathways are not
only doubled but also interconnected (Scheme 3). For in-
stance, cis-[PdRfI(PPh3)2] (2) is being observed during the
catalysis, under continuous formation, by oxidative addition
of RfI and continuous consumption, either by its sponta-
neous isomerization to 1 followed by transmetalation or by
direct transmetalation. A kinetic study using data from the

Article
Organometallics, Vol. 30, No. 3, 2011 615
Scheme 4
Scheme 5
catalytic process is complicated, due to the fact that the
system is continuously being refueled with 2 by effect of the
oxidation of PdL2 with the electrophile 3. In order to simplify
the study, this refueling step can be disconnected by simply
frustrating the recycling at the oxidative addition step. This
means we need to study separately the noncyclic processes of
transmetalation plus coupling.
The absence or presence of RfI (3) in solution is not
expected to exert any influence on the rate constants of the
other steps of the cycle. Since both catalysts 1 and 2 (the
species on which the transmetalation takes place) are isol-
able, rate constants for Scheme 3 can be determined in the
studies starting at the transmetalation step, assuming that
the reductive elimination takes place on 9 and is very fast and
irreversible and the oxidative addition is faster than the
transmetalation step. Thus, it is assumed that the rate at
which the undetected 9 is formed corresponds to the rate at
which 5 is formed. These studies, starting from 1 or 2, are
shown in Figure 3 and were carried out under two different
conditions: (a) and (b) at 323 K, with catalyst:PhC2SnBu3 =
1:20 (as in the previous catalyses); and (c) and (d) at 308 K,
with catalyst:PhC2SnBu3 = 1:60.
The reaction profiles using 1 were very simple and showed
that the isomerization to give 2is negligible (only 1was observed),
as expected from the very different thermodynamic stabili-
ties of the complexes. Complexes 7 and 9 were formed
competitively at very similar rates, and the correspond-
ing rate constants (k4 = 6.6 ꢀ 10-5 M s-1 and k6 = 7.6 ꢀ
10-5 Ms-1) were obtained (Scheme 4).27 Since the isomerization
of 7 to 9 is very slow under the reaction conditions, all the
initial formation of 9 observed in Figure 3a,c can be correctly
assigned to direct transmetalation on 1. In other words, 7
and 9 are formed from 1 by transmetalation at very similar
rates.
The profile of the transmetalation on complex 2 was more
complicated (Figure 3 b,d). It can be seen at 323 K that 2
isomerizes to 1 quite rapidly. At the same time, 7 and 5 start
to be formed, and it is difficult to tell whether they are formed
in part from 2. At lower temperatures (308 K) the initial rate
of formation of 5 suggests that, in part, it proceeds from
transmetalation on 2. Hence, the conversions shown in
Scheme 5 need to be considered.
presence of 3.28 When this k2 value and the previously
determined k4 and k6 values were applied to the system in
Scheme 5, the values of k3 and k5 could be determined.29 The
fittings of the concentration/time experimental data of the
transmetalation/isomerization experiments were made using
a nonlinear least-squares fitting program, assuming that the
transmetalation is the rate-limiting step and taking into
account the isomerization of 2 to 1, as well as the unproduc-
tive transmetalation to give 7.30
The results are summarized in Table 1, which shows that
(i) the rates of transmetalation on 1 and 2 are very similar;
(ii) either complex leads to 7 and 9 at not very different
rates; (iii) however, each complex shows a small preference
toward retention of its configuration (k3 > k5 and k6 >
k4); (iv) k3 is comparable to k2 (k2/k3 = 2.73), meaning
that, under catalytic conditions with a large excess of the
organotin reagent, the two processes (transmetalation and
isomerization) will compete in rate. Furthermore, according
to these values, the cis complex 2 is somewhat more efficient
than the trans complex 1 in giving the cis product, thus
reducing the detrimental formation of 7. This effect is
more clearly observable when working at lower tempera-
ture and higher concentration of organotin (Figure 3c vs
Figure 3d).
The same model was used to fit the catalytic experiments,
affording the results in Table 2. The rate constants found are
somewhat higher than those obtained in the transmetalation
experiments. This is because in the catalytic experiments the
reductive elimination is immediately followed by oxidative
addition, which recycles the palladium and the phosphine
formed in the reductive elimination. In contrast, in the trans-
metalation experiments there is no oxidative addition after
the coupling, and the Pd(0) and free PPh3 released accu-
mulate, providing a changing concentration of free phos-
phine throughout the experiment and affecting pro-
gressively the observed rates. Since this effect could not
be corrected, the apparent rate constants calculated in
the transmetalation experiments (Table 1) are somewhat
A parallel experiment of isomerization of 2 to 1, under the
same conditions of solvent, concentration, and temperature,
but without organotin reagent, afforded a value for the
isomerization rate constant of k2 = 2.7 ꢀ 10-4 s-1, and it
could be seen that this rate did not change significantly in the
(28) The value obtained is slightly different from the reported data,
which has been attributed to the eventual presence of traces of ligand in
the slowest system or to the partial oxidation of phosphine in the fastest
reaction.21
(29) Alternatively, a multivariant experiment fixing only k2 allows us
to obtain the four constants k4, k6, k3, and k5 for the same experiments.
The values obtained are very similar (see the Supporting Information).
(30) The multivariable adjustment program Gepasi was used:
Mendes, P. Comput. Appl. Biosci. 1993, 9, 563–571. See the Supporting
Information for additional details.
(27) Small variations of the observed isomerization rate constant
depending on the conditions are due to self-dissociation of PPh3. See
ref 21 for mechanistic details.

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616 Organometallics, Vol. 30, No. 3, 2011
Table 1. Rate Constants (ꢀ105 M-1 s-1) for the Different
Reactions of the Proposed Mechanism in Schemes 4 and 5 in THF
at 323 K,a for the Data Obtained from the Transmetalation
Reactions
stated. The temperatures for the NMR probe were calibrated
using ethylene glycol as a temperature standard.32 In the 19F or
31P NMR spectra measured in nondeuterated solvents, a coaxial
2
tube containing acetone-d6 was used to maintain the lock H
signal. Combustion CHN analyses were made on a Perkin-
Elmer 2400 CHN microanalyzer. The compounds [Pd(PPh3)4],33
trans-[PdRf2(tht)2],34 [Pd2(C6Cl2F3)2(μ-Cl)2(tht)2],13 trans-[Pd-
(C6Cl2F3)Cl(PPh3)2],6 trans-[Pd(C6Cl2F3)I(PPh3)2] (1),6 cis-[Pd-
(C6Cl2F3)I(PPh3)2] (2),21 C6Cl2F3I (3),21 and trans-[Pd(C6Cl2F3)-
(OTf)(PPh3)2]5 were prepared by literature methods.
cat.
k3
k4
k5
k6
trans-[PdRfI(PPh3)2]
cis-[PdRfI(PPh3)2]
6.6 ( 0.1
7.6 ( 0.1
9.9 ( 0.4 6.6b
2.9 ( 0.4 7.6b
a The errors are given as standard deviations. b This rate constant has
been fixed for the nonlinear least-squares fitting.
Synthesis. C6Cl2F3CtCPh (5). To a stirred solution of [Pd-
(C6Cl2F2)I(AsPh3)2] (62.7 mg; 0.060 mmol) and C6Cl2F3I (3)
(392 mg; 1.20 mmol) in THF (6 mL) was added Sn(CtCPh)Bu3
(4) (420.6 mL; 1.20 mmol). The solution was heated under reflux
for 48 h. Then, the mixture was evaporated to dryness. The residue
was treated with diethyl ether (10 mL) and a saturated solution
of KF (10 mL). The mixture was stirred vigorously, and then
SnFBu3 was separated by filtration. The solution was dried over
MgSO4 and evaporated to crystallize the desired product (yield
217 mg, 60%). 13C{1H} NMR (CDCl3, 293 K): δ 157.4
(dm, 1JC-F = 255.3 Hz, o-CF), 155.0 (dm, 1JC-F = 254.1 Hz,
p-CF), 132.1 (s, o-CH), 129.8 (s, p-CH), 128.7 (s, m-CH), 121.9
(s, CPh), 107.7 (t, 2JC-F = 21.7 Hz, CC6Cl2F3), 101.2 (s, CtC),
73.8 (s, CtC). 19F NMR (CDCl3/THF 293 K): δ -108.86/
Table 2. Rate Constants (ꢀ104 M-1 s-1) for the Different
Reactions of the Proposed Mechanism in Scheme 3 in THF at
50 °C,a,b for the Data Obtained from the Catalytic Reactionsc
cat.
k3
k4
k5
k6
trans-[PdRfI(PPh3)2] 1.4 ( 0.9 5.5 ( 0.2 0.3 ( 0.9 2.7 ( 0.2
cis-[PdRfI(PPh3)2] 4.6 ( 0.2 4.6 ( 0.1 1.7 ( 0.2 1.6 ( 0.1
a See the Supporting Information for additional details. b Errors are
given as standard deviations. c k2 has been fixed to its known value. The
reductive elimination and the oxidative addition have been assumed to
be much faster than the transmetalation steps.
-109.55 (d, 4JF-F = 1.9 Hz, o-CF), -110.21/-110.72 (t, 4JF-F
=
underestimated, and those in Table 2, not affected by the
problem, are better.
1.9 Hz, p-CF). 1H NMR (CDCl3, 293 K): δ 7.62-7.57 (m, Ph),
7.43-7.39 (m, Ph). Anal. Calcd for C14H5Cl2F3 (mol wt
301.097): C, 55.85; H, 1.67. Found: C, 55.90; H, 1.92.
Conclusions
trans-[Pd(C6Cl2F3)(CtCPh)(PPh3)2 (7). trans-[Pd(C6Cl2F3)-
(OTf)(PPh3)2] (500 mg, 0.501 mmol) and PPh3 (272 mg, 1.04
mmol) were dissolved in THF (25 mL). The organotin com-
pound PhCtCSnBu3 was then added via syringe at 0 °C. The
solution was stirred until it turned deep brown (15 h). Then, the
mixture was evaporated to dryness. The residue was extracted in
THF/EtOH and evaporated again. The solid was washed with
EtOH and vacuum-dried. The solid residue was recrystallized
from CH2Cl2/EtOH at -28 °C (yield 230 mg, 39%). 19F NMR
(CDCl3/THF): δ -90.90/-90.02 (t), -122.40/-122.49 (s). 31P
NMR (THF): δ 28.03. Anal. Calcd for C50H35Cl2F3P2Pd: C,
64.43; H, 3.78. Found: C, 63.76; H, 3.61.
General Procedure for Kinetic Study. The kinetic experiments
were monitored by 19F NMR. In a standard experiment of
catalysis, an NMR tube graduated to 0.5 mL was charged with
the palladium complex 1 or 2 (5 ꢀ 10-3 mmol) and C6Cl2F3I (3)
(0.1 mmol) and dissolved under Ar or N2 at room temperature in
THF (∼0.3 mL). Then, the NMR tube was cooled to -78 °C,
PhCtCSnBu3 (4; 0.1 mmol) was added, and further THF was
added to reach the 0.50 mL mark. The NMR tube was charged
with an acetone-d6 capillary for NMR lock and placed into a
thermostated probe (323.0 ( 0.2 K).
In a standard experiment of transmetalation, an NMR tube
was charged with the palladium complex 1 or 2 (5 ꢀ 10-3 mmol)
and dissolved under Ar at room temperature in THF (∼0.3 mL).
Then, the NMR tube was cooled to -78 °C, PhCtCSnBu3 (4;
0.1 mmol) was added, and further THF was added to reach 0.50
mL final volume. The NMR tube was charged with an aceto-
ne-d6 capillary for NMR lock and placed into a thermostated
probe (323.0 ( 0.2 or 308 ( 0.2 K). The kinetic experiments were
monitored by 19F NMR, and concentration-time data were
acquired by integration of the 19F NMR signals. The fluorine
integrals of the 19F NMR were corrected to compensate the
different relaxation times of the nuclei in different substances.
This was done by measuring the integral of samples containing
mixtures of accurately weighed amounts of RfI or RfCCPh with
(fluoroaryl)palladium complexes and adjusting the value of the
integrals to the calculated (from their weight) values. The same
Real systems are far more complex than the simple image
of the metal-catalyzed cycles that is cursorily assumed.
Depending on the specific combination of reagents and
ligands, different alternative pathways can become accessi-
ble or dominant. In the case studied here, each of the two
products of the oxidative addition becomes the subject of the
transmetalation step. This happens because of the slow
isomerization of the initial cis-[PdRfI(PPh3)2] into the most
stable trans-[PdRfI(PPh3)2]. Later, cis-[PdRf(CtCPh)(PPh3)2]
and trans-[PdRf(CtCPh)(PPh3)2] are competitively formed
and, because of the very slow isomerization of the later into
cis-[PdRf(CtCPh)(PPh3)2] (which is the only gate to the
coupling product), the coupling reaction is partially fru-
strated by accumulating this relatively inert intermediate.
It is also worth noting that in the early stages of the studies
of the Stille reaction it was assumed that the transmetalation
step was rate-determining (rds).31 Later we could show that
also the oxidative addition or the reductive elimination can
happen to be the rds.6,4 Here we have found that the usually
ignored isomerization steps, which are hardly shown in the
cycles, are extremely important and can block or allow a
reaction pathway, which is decisive in the success or frustra-
tion of the chemical transformation pursued.
Experimental Section
General Methods. All reactions were carried out under N2 or
Ar in THF dried using a Solvent Purification System (SPS).
NMR spectra were recorded on Bruker ARX 300 and AV 400
instruments equipped with a VT-100 variable-temperature
probe. Chemical shifts are reported in ppm from tetramethylsi-
lane (1H), CCl3F (19F), and 85% H3PO4 (31P), with positive
shifts downfield, at ambient probe temperature unless otherwise
(31) Farina, V.; Krishnan, B. J. Am. Chem. Soc. 1991, 113, 9585–
9595.
(32) Amman, C.; Meier, P.; Merbach, A. E. J. Magn. Reson. 1982, 46,
319–321.
(33) Coulson, D. R. Inorg. Synth. 1972, 13, 121–123.
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(34) Uson, R.; Fornies, J.; Martınez, F.; Tomas, M. J. Chem. Soc.,
Dalton Trans. 1980, 888–893.

Article
Organometallics, Vol. 30, No. 3, 2011 617
ꢀ
from the Junta de Castilla y Leon (Grupos de Excelencia
GR169) is gratefully acknowledged.
ratio was used to multiply the integrals in the kinetic experi-
ments.
Acknowledgment. Financial support from the Spanish
MEC or MICINN (DGI, Grants CTQ2007-67411/BQU,
CTQ2010-18901, Consolider Ingenio 2010, Grant INTE-
CAT, CSD2006-0003; FPU fellowship to M.H.P-T.) and
Supporting Information Available: Text, figures, and tables
giving kinetic data and details of the kinetic analysis. This
material is available free of charge via the Internet at http://
pubs.acs.org.