Mechanism of the stille reaction. 2. Couplings of aryl triflates with vinyltributyltin. Observation of intermediates. A more comprehensive scheme

Article abstract of DOI:10.1021/ja001511o

The mechanism of the [PdL₄]-catalyzed couplings between R-OTf (R = pentahalophenyl; L = PPh₃, AsPh₃) and Sn(CH = CH₂)Bu₃ has been studied. The addition of LiCl favors the coupling for L = AsPh₃ in THF but retards it for L = PPh₃. Separate experiments show that for L = AsPh₃, LiCl accelerates the otherwise very slow and rate-determining oxidative addition of the aryl triflate to [PdL₄], leading to trans-[PdRClL₂]. Therefore, the overall process is accelerated. For L = PPh₃, the rate-determining step is the transmetalation. Complex trans-[PdRXL₂], with X = Cl, is formed in the presence of LiCl, whereas an equilibrium mixture mainly involving species with X = TfO, L, or S (S = solvent) is established in the absence of LiCl. Since the transmetalation is slower for X = Cl than for the other complexes, the overall process is retarded by addition of LiCl. The transmetalation in complexes trans-[PdRXL₂], with X = Cl, follows the S(E)2(cyclic) mechanism proposed in Part 1 (Casado, A. L.; Espinet, P. J. Am. Chem. Soc. 1998, 120, 8978-8985), giving the coupling product R-CH=CH₂'directly. For X = TfO or L, rather stable intermediates trans-[PdR(CH=CH₂)L₂] are detected, supporting an S(E)2(open) mechanism. The key intermediates undergoing transmetalation in the conditions and solvents most commonly used in the literature have been identified. The operation of S(E)2(cyclic) and S(E)2(open) pathways emphasizes common aspects of the Stille reaction with the Hiyama reaction where, using R²SiF₃ that is chiral at the α-carbon of R², retention or inversion at the transmetalated chiral carbon can be induced. This helps us to understand the contradictory stereochemical outcomes in the literature for Stille couplings using R²SnR₃ derivatives that are chiral at the α-carbon of R² and suggests that stereocontrol of the Stille reaction might be achieved.

Full text of DOI:10.1021/ja001511o

J. Am. Chem. Soc. 2000, 122, 11771-11782
11771
Mechanism of the Stille Reaction. 2. Couplings of Aryl Triflates with
Vinyltributyltin. Observation of Intermediates. A More
Comprehensive Scheme
Arturo L. Casado, Pablo Espinet,* and Ana M. Gallego
Contribution from the Departamento de Qu´ımica Inorga´nica, Facultad de Ciencias,
UniVersidad de Valladolid, E-47005 Valladolid, Spain
ReceiVed May 1, 2000
Abstract: The mechanism of the [PdL4]-catalyzed couplings between R-OTf (R ) pentahalophenyl; L )
PPh3, AsPh3) and Sn(CHdCH2)Bu3 has been studied. The addition of LiCl favors the coupling for L ) AsPh3
in THF but retards it for L ) PPh3. Separate experiments show that for L ) AsPh3, LiCl accelerates the
otherwise very slow and rate-determining oxidative addition of the aryl triflate to [PdL4], leading to trans-
[PdRClL2]. Therefore, the overall process is accelerated. For L ) PPh3, the rate-determining step is the
transmetalation. Complex trans-[PdRXL2], with X ) Cl, is formed in the presence of LiCl, whereas an
equilibrium mixture mainly involving species with X ) TfO, L, or S (S ) solvent) is established in the absence
of LiCl. Since the transmetalation is slower for X ) Cl than for the other complexes, the overall process is
retarded by addition of LiCl. The transmetalation in complexes trans-[PdRXL2], with X ) Cl, follows the
SE2(cyclic) mechanism proposed in Part 1 (Casado, A. L.; Espinet, P. J. Am. Chem. Soc. 1998, 120, 8978-
8985), giving the coupling product RsCHdCH2 directly. For X ) TfO or L, rather stable intermediates trans-
[PdR(CHdCH2)L2] are detected, supporting an SE2(open) mechanism. The key intermediates undergoing
transmetalation in the conditions and solvents most commonly used in the literature have been identified. The
operation of SE2(cyclic) and SE2(open) pathways emphasizes common aspects of the Stille reaction with the
Hiyama reaction where, using R2SiF3 that is chiral at the R-carbon of R2, retention or inversion at the
transmetalated chiral carbon can be induced. This helps us to understand the contradictory stereochemical
outcomes in the literature for Stille couplings using R2SnR3 derivatives that are chiral at the R-carbon of R2
and suggests that stereocontrol of the Stille reaction might be achieved.
Introduction
Scheme 1
Recently, we have proposed a new mechanism for the Stille
couplings of R1I with R2SnBu3 (Scheme 1; X ) I, R1 ) aryl,
R2 ) vinyl or aryl).1 The proposed transmetalation step consists
of an associative L-for-R2 substitution on the catalyst trans-
[PdR1IL2]. The two most remarkable features in this new
mechanism are (i) the role of X as a bridging group which assists
the R2 transfer between the two metal atoms via an “SE2(cyclic)”
mechanism (activated complex framed in the center of Scheme
1) and (ii) the immediate cis configuration and three coordination
of the bis(organo)palladium(II) intermediate, which rapidly
eliminates the coupling product R1-R2.2
The most commonly used electrophiles in Stille couplings
are organic iodides, bromides, and triflates (trifluoromethyl
sulfonates).3 We restricted our proposal of an SE2(cyclic)
transmetalation to X ) halide; i.e., the catalytic cycle in Scheme
1 would hold for organic iodides and bromides (for chlorides,
although the transmetalation step works perfectly as an isolated
reaction, the oxidative addition step is difficult, this often
precluding the operation of the catalysis; see, however, recent
advances in the activation of chlorides).4 Moreover, we warned
that other mechanisms could operate under different conditions,
such as coordinating solvents or lack of halide in the system.
In fact, couplings of triflates (X ) OTf) show several distinct
experimental features that cannot be understood within the frame
of Scheme 1. One of the most striking aspects is the effect of
the addition of LiCl. Stille et al. found the addition of
stoichiometric LiCl necessary to achieve couplings of organic
* To whom correspondence should be addressed. E-mail: espinet@
qi.uva.es.
(1) Part 1: Casado, A. L.; Espinet, P. J. Am. Chem. Soc. 1998, 120,
8978-8985. A brief review on Stille couplings is given therein.
(2) For this nomenclature, see: Hatanaka, Y.; Hiyama, T. J. Am. Chem.
Soc. 1990, 112, 7794-7796.
(3) A comprehensive review of the synthetic applications of this reaction
has appeared recently. See: Farina, V.; Krishnamurthy, V.; Scott, W. J.
The Stille Reaction; Wiley: New York, 1998.
(4) (a) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 1999, 38, 2411-
2413. (b) Sturmer, R. Angew. Chem., Int. Ed. 1999, 38, 3307-3308.
10.1021/ja001511o CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/17/2000

11772 J. Am. Chem. Soc., Vol. 122, No. 48, 2000
Casado et al.
Scheme 2
Chart 1
All these valuable studies showed clearly that the Stille
reaction is a complex matter and its mechanism cannot be
limited to just one pathway. Moreover, the importance of using
neutral ligands of lower donicity toward Pd(II), which could
decoordinate easily, was stressed and led to important synthetic
improvements. However, the studies suffered from some limita-
tions. The most important was that, since the different steps of
the cycle were not studied separately, the kinetic measurements
had to assume first-order kinetics overall for this multistep
reaction; in other words, it was assumed that the transmetalation
was rate-determining in all the experiments, regardless of the
neutral ligand or the electrophile (triflate or halide) used.7b
Another important drawback was that systems studied usually
restricted the evidence on intermediates to 31P NMR spectros-
copy (if any evidence at all was available). Consequently, details
on the true nature of the intermediates (e.g., stereochemistry at
Pd) could not be conveniently assessed. This aspect, as we
discuss later, is of some importance.
Thus, in the currently accepted mechanistic proposals (Scheme
2), it is assumed that all the transmetalation reactions involve
Cl-for-R2 or S-for-R2 exchange (S ) solvent or “empty site”).
It is also assumed that the nucleophile should always attack a
highly electrophilic reactive intermediate bearing an “empty”
coordination site, such as trans-[PdR1(S)L2]+ or cis-[PdR1(S)-
ClL], while neutral triflate complexes trans-[PdR1(OTf)L2] or
cationic complexes [PdR1L3]+ are disregarded. The transmeta-
lation mechanism (Scheme 2, transition states were not speci-
fied) leads to intermediates trans-[PdR1R2L2] in all cases,
regardless of the configuration of the reactive intermediates. It
can be remarked also that intermediates trans-[PdR1R2L2] have
not previously been observed in any Stille coupling. The direct
formation of the coupling product R1-R2 from the latter is not
straightforward but requires the dissociation of L and subsequent
isomerization to the cis form.11 In spite of this, it has been taken
for granted that the elimination process is a fast step in all cases.
A further point that needs to be discussed is the nature of
the transmetalation transition states and the stereochemical
implications on the transmetalated chiral carbons. This latter
aspect of the Stille reaction has been rarely considered. In a
seminal paper, Labadie and Stille found g65% inversion for
the coupling of a chiral benzylic stannane and an acyl chloride.12
They considered the dichotomy between cyclic and open
transition states for the electrophilic cleavage of carbon-tin
bonds and proposed the open transition state in Chart 1
(involving Cl-for-R substitution on a Pd complex which has
previously dissociated an L ligand). They pointed out that the
behavior they were observing (inversion via SE2 open mecha-
nism) might be due to the high polarity of the solvent used.
Some years later, Falck et al. found ca. 98% retention of
configuration in the coupling of chiral R-alkoxystannanes with
acyl chlorides and remarked, “This is in stark contrast with
triflates.5 It was assumed that the role of the chloride ions was
to replace the triflate in the coordination plane of an eventual
triflatopalladium(II) species (formed upon oxidative addition of
the organic triflate), leading to a chloropalladium(II) complex.
The transmetalation should supposedly take place more readily
on the latter than on the triflatopalladium(II) complex. Soon it
became apparent that the requirement of LiCl is not general,
and many exceptions have been reported. In fact, Piers et al.
have reported cases where addition of LiCl retards the coupling.6
Farina et al. have extensively studied this LiCl effect and have
found it to be both accelerating and retarding, depending on
the solvent (THF, or NMP ) 1-methyl-2-pyrrolidinone), the
organic triflate (R1 ) aryl or vinyl), and the neutral ancillary
ligand (L ) AsPh3 or PPh3).7 From their own experiments and
from other studies in the literature on related Pt systems,8 they
have proposed the existence of “at least two mechanistically
distinct pathways for the transmetalation reaction”,9 summarized
7a,3
in Scheme 2,
“a faster one proceeding via cationic species
B and (with L ) PPh3) a slower one proceeding via ligand
dissociation (through D)”.3 In THF solvent, LiCl would be
necessary to induce coupling because the initial oxidative
addition product A “is catalytically incompetent, whereas ligand
substitution with chloride leads to the reactive species C”.3 It
was suggested that “in the absence of Cl intermediates A and/
or B may be too unstable to complete a catalytic cycle”.9 In
highly polar solvents, like NMP, LiCl is often unnecessary and
can be even an inhibitor of the coupling. Chen and He, who
isolated the oxidative addition product [Pd(C6H4Cl-p)(OSO2RF)-
(PPh3)2] (RF = HCF2CF2OCF2CF3), also proposed a catalytic
cycle through C.10
(5) (a) Scott, W. J.; Stille, J. K. J. Am. Chem. Soc. 1986, 108, 3033-
3040. (b) Echavarren, A. M.; Stille, J. K. J. Am. Chem. Soc. 1987, 109,
5478-5486. (c) Stille, J. K.; Echavarren, A. M.; Williams, R. M.; Hendrix,
J. A. Org. Synth. 1993, 71, 97-106.
(6) Piers, E.; Friesen, R. W.; Keay, B. A. J. Chem. Soc., Chem. Commun.
1985, 809-810. (b) Piers, E.; Friesen, R. W. J. Org. Chem. 1986, 51, 3405-
3406.
(7) (a) Farina, V.; Roth, G. P. In AdVances in Metal-Organic Chemistry;
Liebeskind, L. S., Ed.; JAI Press: Greenwich, CT, 1995; Vol. 5, pp 1-53.
(b) Farina, V.; Krishnan, B. J. Am. Chem. Soc. 1991, 113, 9585-9595.
(8) Stang, P. J.; Kowalski, M. H.; Schiavelli, M. D.; Longford, D. J.
Am. Chem. Soc. 1989, 111, 3347-3356.
(9) Farina, V.; Krishnan, B.; Marshall, D. R.; Roth, G. P. J. Org. Chem.
1993, 58, 5434-5444.
(10) Chen, Q.-Y.; He, Y.-B. Chin. J. Chem. 1990, 451-468.
(11) Tatsumi, K.; Hoffmann, R.; Yamamoto, A.; Stille, J. K. Bull. Chem.
Soc. Jpn. 1981, 54, 1857-1867.
(12) Labadie, J. W.; Stille, J. K. J. Am. Chem. Soc. 1983, 105, 6129-
6137.

Mechanism of the Stille Reaction
J. Am. Chem. Soc., Vol. 122, No. 48, 2000 11773
Table 1. Coupling Reactions between C6F5-OTf (1) and
Sn(CHdCH2)Bu3 (2) Catalyzed by [PdL4]: Conversion to
C6F5sCHdCH2 (3a)a
couplings between tetraalkylstannanes and benzoyl chloride
where inversion of configuration has been demonstrated. The
origins of this phenomenon and the potential involvement of
the R-heteroatom warrant further investigation.” 13 In a different
context, the possible involvement of cyclic and open transition
states in the Stille reaction was also considered in studies on
the possible intramolecular nucleophilic assistance at some
organotins bearing potentially coordinating arms.14 By assuming
as “plausible” either closed or open transition states in different
solvents (depending on the solvent polarity), many overall rates
observed for catalytic processes could be explained if the nucleo-
philic assistance was able to stabilize only “closed” transition
states, but other rates did not fit this suggestion.14c These scarce
precedents are intriguing and interesting and stress the need for
a better evaluation of the likeliness of different plausible inter-
mediates and transition states in different reaction conditions.
In this paper, we undertake the study of the Pd-catalyzed
couplings between C6F5-OTf (1) and Sn(CHdCH2)Bu3 (2),15
which has allowed us to achieve a number of interesting
results: (a) The three steps (oxidative addition, transmetalation,
and reductive elimination) of the same Stille cycle are studied
separately. (b) The role of LiCl (whether accelerating, retarding,
or neutral) in solvents of moderate polarity (THF, PhCl, CH2-
Cl2) is demonstrated by measuring its effect on the different
steps involved in the cycle. (c) The organopalladium(II)
intermediates formed upon oxidative addition of 1 to Pd(PPh3)4
are fully characterized, and their behavior toward transmetalation
is kinetically studied. (d) A transmetalation intermediate, trans-
[PdRR′L2], is detected and fully identified. (e) The key role of
the coordination stereochemistry at Pd is revealed, a detailed
view of the exchange at the transmetalation (which-for-which)
is proposed, and an analysis of the consequences, including its
stereochemical implications, is offered. These results, along with
those in Part 1, afford a more complete picture of the Stille
reaction using monodentate ligands.
conversion (%)
entry
L
solvent
additiveb
10 h
24 h
1
2
3
4
5
6
7
8
PPh3
PhCl
PhCl
THF
THF
PhCl
PhCl
THF
THF
none
LiCl
none
LiCl
none
LiCl
none
LiCl
86
92
65
0
96
100
100
6
7
7
PPh3
PPh3
PPh3
AsPh3
AsPh3
AsPh3
AsPh3
6
5
13
79
14
87
a At 50 °C; [1] ) [2] ) 0.2 mol L-1, [PdL4] ) 0.01 mol L-1
) 0.2 mol L-1
.
b [LiCl]
.
Table 2. Organopalladium(II) Species Formed upon the Oxidative
Addition of C6F5-OTf (1) to [PdL4]a
entry
1
L
solvent
PhCl
additiveb
complex(es)c
PPh3
none
trans-[PdR(OTf)L2]
[PdRL3]+
2
PPh3
PhCl
LiCl
none
trans-[PdR(OTf)L2]
[PdRL3]+
trans-[PdRClL2]
trans-[PdR(THF)L2]+
[PdRL3]+
3
PPh3
THF
4
5
6
7
8
PPh3
THF
PhCl
PhCl
THF
THF
LiCl
none
LiCl
none
LiCl
trans-[PdRClL2]
none
none
none
trans-[PdRClL2]
AsPh3
AsPh3
AsPh3
AsPh3
a After 30 min at 20 °C; [1] ) 0.2 mol L-1, [PdL4] ) 0.01 mol L-1
b [LiCl] ) 0.2 mol L-1 c R ) C6F5.
.
.
(entries 1-3 vs 5-7). (3) The use of LiCl affects the rate of
coupling in THF: the reaction catalyzed by [Pd(PPh3)4] is
strongly retarded (entry 3 vs 4), whereas that catalyzed by [Pd-
(AsPh3)4] is accelerated (entry 7 vs 8). To understand the origin
of these differences, the oxidative additions of 1 to [PdL4], and
the transmetalations of the resulting organopalladium(II) inter-
mediates with 2, were studied separately.
Results
Coupling of C6F5-OTf with Sn(CHdCH2)Bu3 Catalyzed
by [PdL4] (L ) PPh3, AsPh3). The rate of reaction between
C6F5-OTf (1) and Sn(CHdCH2)Bu3 (2) catalyzed by [PdL4]
(eq 1) depends strongly on the neutral ligand L (PPh3 or AsPh3),
the solvent, and whether LiCl is added. The conversion into
Oxidative Addition of C6F5-OTf to [PdL4]. The reactions
of C6F5-OTf (1) and [PdL4] (L ) PPh3, AsPh3) in a 20:1 mol
ratio (similar to that used in the catalytic reactions) were carried
out with and without LiCl, and the resulting organopalladium-
(II) species (Table 2) were identified by 19F and 31P{1H} NMR.
The oxidative addition of C6F5-OTf (1) to [Pd(PPh3)4] was
very fast either in PhCl or in THF (Scheme 3). In PhCl, it led
to trans-[Pd(C6F5)(OTf)(PPh3)2] (4a) as the major organopal-
ladium(II) product, but [Pd(C6F5)(PPh3)3]+ (5a+) was also
formed in a smaller amount. In THF, trans-[Pd(C6F5)(THF)-
(PPh3)2]+ (7a+), 4a, and 5a+ were formed (4a, 5a‚(TfO), and
7a‚(TfO) are involved in dynamic equilibria, analyzed later for
the corresponding C6Cl2F3 complexes). When the reaction was
carried out in the presence of LiCl, the final products depended
on the solvent. In THF, trans-[Pd(C6F5)Cl(PPh3)2] (6a) was the
only product detected. These results are in agreement with those
found by Jutand and Mosleh for other aryl triflates in DMF
(dimethylformamide), except that in that case [PdAr(PPh3)3]+
species were not detected.16 In PhCl, the main products were
4a and 5a+, and only a small amount of 6a was formed. In
separate experiments, complex 6a was quantitatively formed
by treatment of 4a with LiCl in THF at ambient temperature,
whereas no reaction was observed in PhCl. All the compounds
were identified by comparison with original samples prepared
separately.
the coupling product C6F5-CHdCH2 (3a) was studied by 19F
NMR under different conditions, and the results are summarized
in Table 1.
These results show the following: (1) The addition of LiCl
scarcely affects the coupling rates in PhCl (entries 1 vs 2, and
5 vs 6), probably because of its low solubility or low dissociation
in this solvent. (2) [Pd(PPh3)4] is a more efficient catalyst than
[Pd(AsPh3)4] in PhCl, and also in THF in the absence of LiCl
(13) Ye, J.; Bath, R. K.; Falck, J. R. J. Am. Chem. Soc. 1994, 116, 1-5.
(14) (a) Vedejs, E.; Haight, A. R.; Moss, W. O. J. Am. Chem. Soc. 1992,
114, 6556-6558. (b) Brown, J. M.; Pearson, M.; Jastrzebsky, J. T. B. H.;
van Koten, G. J. Chem. Soc., Chem. Commun. 1992, 1440-1441. (c) Farina,
V. Pure Appl. Chem. 1996, 68, 73-78.
(15) 1 was used because of the advantages provided by fluorophenyl
derivatives in mechanistic studies involving Pd(II) derivatives. Some
previous examples are given by Casado and Espinet (Casado, A. L.; Espinet,
P. Organometallics 1998, 17, 3677-3683), as well as in refs 1, 17, 22, and
32.
In contrast, the oxidative addition of 1 to [Pd(AsPh3)4] was
very slow. No reaction was observed in THF or PhCl after 30

11774 J. Am. Chem. Soc., Vol. 122, No. 48, 2000
Casado et al.
Scheme 3
Table 3. Transmetalation Reactions between trans-[Pd(C6F5)XL2]
and Sn(CHdCH2)Bu3 (2): Conversion to C6F5sCHdCH2 (3a)a
Figure 1. (a) 19F NMR spectrum (282 MHz, PhCl, room temperature,
triflate and Fortho signals) of trans-[Pd(C6Cl2F3)(OTf)(PPh3)2] (4c). (b)
Spectrum after addition of free PPh3 (Pd:PPh3 ) 1:8).
conversion (%)
entry
X
L
solvent
additiveb
2 h
10 h
1
2
Cl
PPh3
PhCl
PhCl
PhCl
PhCl
THF
THF
THF
THF
PhCl
PhCl
PhCl
PhCl
THF
THF
THF
THF
none
PPh3
none
PPh3
none
PPh3
none
PPh3
none
AsPh3
none
AsPh3
none
AsPh3
none
AsPh3
0
0
20
0
8
0
81
1
15
4
28
23
92
36
100
100
0
0
94
2
65
0
100
9
39
12
51
46
100
100
100
100
[PdR(THF)(PPh3)2]+ (in THF) are formed upon oxidative
addition of R-OTf to [PdL4] (L ) PPh3). To facilitate the study
of these equilibria by 19F and 31P NMR techniques, we prepared
the corresponding complexes with R ) 3,5-C6Cl2F3, which
behave similarly to those with R ) C6F5 but show simpler and
more informative NMR spectra.17
The complex trans-[Pd(C6Cl2F3)(OTf)(PPh3)2] (4c) is stable
in noncoordinating solvents (CDCl3, CH2Cl2, or PhCl), and the
coordinated triflate gives sharp 19F NMR resonances (singlet,
Figure 1a). The addition of PPh3 gave rise to new signals
corresponding to [Pd(C6Cl2F3)(PPh3)3](TfO) (5c‚(TfO)) in equi-
librium with 4c (eq 2 and Figure 1b). The Fpara (not shown in
Cl
PPh3
3
TfO
TfO
Cl
PPh3
4
PPh3
5
PPh3
6
Cl
PPh3
7
TfO
TfO
Cl
PPh3
8
PPh3
9
AsPh3
AsPh3
AsPh3
AsPh3
AsPh3
AsPh3
AsPh3
AsPh3
10
11
12
13
14
15
16
Cl
TfO
TfO
Cl
Cl
TfO
TfO
a At 23 °C; [2] ) 0.2 mol L-1, [Pd] ) 0.01 mol L-1
0.02 mol L-1
.
b [Additive] )
.
min at ambient temperature. The addition of LiCl did not
produce any perceptible effect in PhCl, but it accelerated very
efficiently the reaction in THF, yielding trans-[Pd(C6F5)Cl-
(AsPh3)2] (6b).
Figure 1) and triflate signals are singlets, but the multiplicity
of the Fortho signals changes from a triplet in 4c (4JF(ortho)-P(cis)
) 7.7 Hz) to a doublet of triplets in 5c+ (4JF(ortho)-P(trans) ) 10.5
The results presented in Table 3 and discussed later show
that, in THF, the transmetalation step is always faster for triflates
than for halides. Hence, it can be concluded that the low yields
found in couplings between 1 and 2 catalyzed by [Pd(AsPh3)4]
in the absence of solubilized LiCl are due to the slowness of
the oxidative addition step (note the correspondence between
Tables 1 and 2, entries 5-7). In other words, although the Stille
coupling rate is often controlled by the transmetalation step, in
the case of aryl triflates in THF, the oxidatiVe addition is Very
slow and becomes rate-determining.
4
Hz; JF(ortho)-P(cis) ) 4.5 Hz).
In THF (a solvent similar in polarity to PhCl, but more
coordinating), the spectra of trans-[Pd(C6Cl2F3)(OTf)(PPh3)2]
(4c) show a strong temperature dependence, since 4c is involved
in a slow equilibrium with trans-[Pd(C6Cl2F3)(THF)(PPh3)2]-
(TfO) (7c‚(TfO), eq 3). At low temperatures 4c is very
Equilibria between trans-[PdR(OTf)L2] or trans-[PdRIL2]
and Cationic Complexes in Solution. As shown in Table 2,
equilibrium mixtures of trans-[PdR(OTf)L2], [PdRL3]+, and
(16) Jutand, A.; Mosleh, A. Organometallics 1995, 14, 1810-1817. We
disagree, however, in the formulation of the neutral compound as an ionic
pair [PdAr(PPh3)2]+‚TfO- involving a 14-e cation. In our case, the IR spectra
in Nujol clearly show coordinated triflate for 4a-d. Our formulation is in
agreement with the result reported in ref 10. We believe that the observation
of anionic triflate, reported by Jutand and Mosleh to support the ionic
formulation, might be due to the following reaction in the preparation of
the KBr pellet (the IR spectra are reported in KBr): [PdAr(OTf)(PPh3)2]
+ KBr f [PdArBr(PPh3)2] + K(TfO).
predominant, but above room temperature it has almost disap-
peared (Figure 2), so it can be considered that at 50 °C the
(17) Espinet, P.; Mart´ınez-Ilarduya, J. M.; Pe´rez-Briso, C.; Casado, A.
L.; Alonso, M. A. J. Organomet. Chem. 1998, 551, 9-20. In fact, the only
reason 3,5-C6Cl2F3 was not used for the whole study was the commercial
availability of C6F5OH, which facilitated the preparation of the correspond-
ing triflate 1.

Mechanism of the Stille Reaction
J. Am. Chem. Soc., Vol. 122, No. 48, 2000 11775
Scheme 4
Figure 2. Temperature dependence of equilibrium (3) in THF. Only
the Fortho signals of the C6Cl2F3 group are shown. Simultaneous
conversion between signals for covalent and ionic triflate is observed.
equilibrium is fully displaced to the right, toward 7c+. In the
presence of PPh3, an equilibrium of 7c‚(TfO) with [Pd(C6Cl2F3)-
(PPh3)3](TfO) (5c‚(TfO)) is established (eq 4).
catalytic proportions) of trans-[Pd(C6Cl2F3)X(PPh3)2] (X ) Cl,
I, or OTf) with PPh3 and must be assigned to trans-[Pd(C6-
Cl2F3)(HMPA)(PPh3)2]X formed quantitatively in situ. In the
absence of free PPh3, trans-[Pd(C6Cl2F3)Cl(PPh3)2] gave only
62.5% of trans-[Pd(C6Cl2F3)(HMPA)(PPh3)2]Cl, and the cor-
responding triplet was flanked by two doublet signals (20% for
the one at lower field of the triplet, 17.5% for that at higher
field). In a 1:2:20 mixture trans-[Pd(C6Cl2F3)Cl(PPh3)2]:PPh3:
LiCl, only the triplet (53%) and the low-field doublet (47%)
were observed. These observations suggest that the complex
giving rise to the low-field doublet contains one phosphine and
one chloride, while that producing the high-field doublet
contains one phosphine but no chloride; accordingly, the
assignments shown in Scheme 4 are proposed. In NMP, the
results were somewhat different: the triplet observed for trans-
[Pd(C6Cl2F3)I(PPh3)2] (8) moved 1.7 ppm downfield upon
addition of AgBF4 to force the formation of [Pd(C6Cl2F3)(NMP)-
(PPh3)2]BF4; this suggests that 8 stays as the neutral complex
in NMP solution. However, [Pd(C6Cl2F3)(OTf)(PPh3)2] was fully
converted to [Pd(C6Cl2F3)(NMP)(PPh3)2](TfO) upon being
dissolved in NMP, and their signals were unaffected by addition
of free PPh3 (to make Pd:PPh3 ) 1:4). Thus, NMP as solvent
(probably coordinating as a ketone) is less coordinating than
HMPA and is able to displace triflate and PPh3 trans to R, but
cannot displace halides trans to R, or phosphine cis to R.20
The existence of similar dissociation equilibria for [PdPhX-
(PPh3)2] (X ) Cl, Br, I, OAc) in DMF (dimethylformamide)
has been demonstrated recently, and the corresponding dis-
sociation constants have been determined by chronoamperom-
etry. They follow the order Cl < Br < I < OAc.21
Substitution of PPh3 for I- in [PdR(PPh3)3]+ and in trans-
[PdR(THF)(PPh3)2]+. The last step in the Stille cycle is the
reductive coupling producing R1R2, which requires a cis
arrangement of R1 and R2 in the Pd complex undergoing
reductive elimination.11 The cyclic mechanism in Scheme 1
necessarily leads to a cis arrangement of R1 and R2 followed
by fast coupling. However, in cases when a cyclic mechanism
cannot operate due to the inability of the Pd complex to make
an extra Pd-X-Sn bridge (for instance, with [PdR1(PPh3)3]+),
the transmetalation becomes (as viewed from the metal) a simple
associative substitution reaction with the R carbon of R2 acting
Some equilibrium constants at 50 °C were obtained by NMR
analysis (see Experimental Section),18 from which it is possible
to calculate the extent of these equilibria in the catalytic mixtures
(where the Pd:free L ratio is 1:2). For eq 2 in PhCl, K ) 3.4 ×
10-3 affords 4c/5c+ ) 92/8 under catalytic conditions. In CH2-
Cl2, a more polar noncoordinating solvent, the equilibrium
constant is much bigger than that in PhCl (K ) 1.0; 4c/5c+
)
34/66 under catalytic conditions), suggesting that the ionic
complex 5c‚(TfO) is noticeably stabilized by solvation. In fact,
the equilibrium in PhCl can be shifted to the right by increasing
the ionic strength of the solvent medium upon addition of [NBu4]-
[ClO4]. In THF at 50 °C, 4c is fully transformed into 7c+; for
eq 4, K ) 2.13 L mol-1 affords 7c+/5c+) 96/4 for a solution
10-2 M in Pd.
The cationic complexes 5c+ and 7c+ were synthesized
-
separately and fully characterized as their BF4 salts. Their
behavior in CDCl3 or PhCl was studied by NMR techniques
(see Experimental Section). No coordination of tetrafluoroborate
was observed, showing that, differently from triflate, BF4- does
not compete with L or THF for the coordination site. The PPh3
ligand trans to the aryl group is rather weakly coordinated, and
equilibrium (4) is established in THF solution (eq 4), as observed
for 4c at 50 °C.19
Furthermore, we checked the behavior of trans-[Pd(C6-
Cl2F3)X(PPh3)2] (X ) Cl, I, or OTf) and [Pd(C6Cl2F3)(PPh3)3]-
BF4 in some solvents commonly used in Stille couplings at 50
°C. In HMPA (hexamethylphosphoramide), a solvent used by
Stille in ref 12, the Fortho signals of a 1:1 mixture of [Pd(C6-
Cl2F3)(PPh3)3]BF4 and PPh3 showed only a triplet. This same
triplet was also the only signal observed in 1:2 mixtures (usual
(18) Note that, for simplicity, these adimensional constants are defined
as K ) [cation][TfO-]/[4c][L] regardless of the solvent, although in some
solvents ionic pairs are formed. This means that the constants are valid
only in the conditions specified in the text.
(19) The 19F NMR spectra of 5c+ in wet CDCl3 showed additional signals
due to trans-[Pd(C6Cl2F3)(OH2)(PPh3)2]+. The “unexpected” competence
for the trans coordination site of the weak but hard THF (or OH2) versus
the strong but soft PPh3 is associated with the trans influence of the ligands
involved (Hartley, F. R. Chem. Soc. ReV. 1973, 2, 163-179). The well-
known destabilizing effect of two mutually trans soft ligands attached to a
soft metal center has been named the “antisymbiotic effect” (Pearson, R.
G. Inorg. Chem. 1973, 12, 712-713), and more recently “transphobia”
(Vicente, J.; Arcas, A.; Bautista, D.; Jones, P. G. Organometallics 1997,
16, 2127-2138. Vicente, J.; Abad, J. A.; Frankland, A. D.; Ram´ırez de
Arellano, M. C. Chem. Eur. J. 1999, 5, 3067-3076).
(20) Many complexes with O-donor HMPA or with DMF are known.
See: Goggin, P. L. Sulfoxides, Amides, Amine Oxides and Related Ligands.
In ComprehensiVe Coordination Chemistry; Wilkinson, G., Gillard, R. D.,
McCleverty, J. A., Eds; Pergamon Press: Oxford, 1987; Vol. 2, pp 487-
503.
(21) Amatore, C.; Carre´, E.; Jutand, A. Acta Chem. Scand. 1998, 52,
100-106.

11776 J. Am. Chem. Soc., Vol. 122, No. 48, 2000
Casado et al.
as the entering ligand. R2 can then go trans or cis to R1, or
competitively to both sites, depending on the trans effects of
R1 and the other ligands. A cis to R1 substitution leads to cis
R1-R2 arrangement and fast coupling (at least with monodentate
ligands), whereas a trans substitution leads to trans R1-R2
arrangement and slower coupling (topomerization is needed,
which can be slow). This means that we are more likely to
observe a trans-R1R2Pd intermediate (if formed) than a cis-
R1R2Pd. In other words, we should not expect necessarily to
see both intermediates, even if substitution at both sites was
taking place: we could detect only a trans intermediate, and
still a cis substitution could be taking place in addition to the
trans substitution. For this reason, to check the cis or trans
stereoselectivity of a simple associative substitution of PPh3 on
[Pd(C6Cl2F3)(PPh3)3]+ (5c+), I- was chosen as a model nu-
cleophile. Complex 5c‚(BF4) was reacted with (NBu4)I in CH2-
Cl2. After 5 min at room temperature, trans-[Pd(C6Cl2F3)I-
(PPh3)2] (8) and cis-[Pd(C6Cl2F3)I(PPh3)2] (9) had formed in a
ca. 1:5 ratio (eq 5). Since the rate of isomerization of 9 to 8 is
Figure 3. Reaction profiles of the transmetalation reactions between
Sn(CHdCH2)Bu3 (2) and the following complexes: (a) [Pd(C6Cl2F3)-
(PPh3)3]BF4 (5c‚(BF4)); (b) 5c‚(BF4) + 2PPh3; (c) trans-[Pd(C6Cl2F3)-
(OTf)(PPh3)2] (4c); (d) 4c + 2PPh3. [Pd] ) 0.01 mol L-1, [Sn] ) 0.2
mol L-1 in CH2Cl2 at 50 °C. Byproduct: C6Cl2F3-SnBu3 (11).
to that used in the catalytic reactions. The results are summarized
in Table 3. An exact interpretation of each result is difficult
because of the many factors involved, as will be discussed later,
but it is clear that in all cases the triflato complexes reacted
faster than their corresponding chloro complexes. In the
couplings catalyzed by [Pd(PPh3)4] in THF (Table 1, entry 4),
where the oxidative addition is fast, the transmetalation is rate-
determining.24 Since the presence of Cl- conVerts the triflato
complex in the corresponding chloro complex, the net effect
upon addition of LiCl is retardation.
We have seen that, under catalytic conditions, the species
trans-[PdR(OTf)L2] can be in equilibrium with [PdRL3]+, [PdR-
(THF)L2]+, or both. To gain some knowledge of the transmeta-
lation step, the reactions of trans-[Pd(C6Cl2F3)(OTf)(PPh3)2] (4c)
and [Pd(C6Cl2F3)(PPh3)3]BF4 (5c‚BF4) with 2 were monitored
by 19F NMR in CH2Cl2.25 Some profiles are shown in Figure
3.
negligible under these conditions,22 the observed ratio corre-
sponds to the kinetic outcome of the substitution reaction.
Although the PPh3 trans to the aryl group is substituted faster,
the substitution of the PPh3 in the cis position occurs also at a
noticeable rate (1/5), suggesting that the trans effects for C6-
Cl2F3 and PPh3 differ by less than 1 order of magnitude.23 This
suggests that, in an open transmetalation using stannane, cis
and trans ligand substitutions by the entering R2 group will be
probably competitive, both occurring with detectable rates. As
discussed later, this is, in fact, the case.
On the other hand, when the same model substitution reaction
with I- was carried out on either trans-[Pd(C6Cl2F3)(OTf)-
(PPh3)2] (4c) or trans-[Pd(C6Cl2F3)(THF)(PPh3)2]BF4 (7c.(BF4))
in THF (both complexes give the cation trans-[Pd(C6Cl2F3)-
(THF)(PPh3)2]+ (7c+) in THF), the only product observed was
trans-[Pd(C6Cl2F3)I(PPh3)2] (8), showing that the substitution
of the THF ligand was very favorable kinetically in this case
(eq 6).
The most remarkable finding was the formation of trans-
[Pd(C6Cl2F3)(CHdCH2)(PPh3)2] (10) as an observable inter-
mediate, which slowly decomposes to the coupling product
C6Cl2F3-CHdCH2 (3b). Because of this decomposition, com-
plex 10 could not be isolated as a pure compound, but it was
unambiguously characterized by NMR studies on crude samples
containing about 70% of 10 (see Experimental Section).26 Its
1H NMR spectrum shows three resonances for the vinyl protons,
coupled to each other (1H COSY) and also coupled to the two
equivalent 31P nuclei of the PPh3 ligands (1H-31P HMQC).27
1
This latter coupling was evidenced by it suppression in a H-
Transmetalation on Organopalladium(II) Complexes
Formed after the Oxidative Addition. The transmetalation
reactions between either trans-[Pd(C6F5)(OTf)L2] (L ) PPh3
(4a), AsPh3 (4b)) or trans-[Pd(C6F5)ClL2] (L ) PPh3 (6a),
AsPh3 (6b)) and Sn(CHdCH2)Bu3 (2) to give the coupling
product C6F5sCHdCH2 (3a) were studied in PhCl and THF
by 19F NMR (eq 7). The Pd:Sn stoichiometry was 1:20, similar
(23) This seems to be in agreement with the trans effect data for
comparable groups reported in the following: Tobe, M. L. Substitution
Reactions. In ComprehensiVe Coordination Chemistry; Wilkinson, G.,
Gillard, R. D., McCleverty, J. A., Eds.; Pergamon Press: Oxford, 1987;
Vol. 2, pp 281-329.
(24) It could be argued that the formation of the coupling product involves
transmetalation plus coupling, and the latter could also be the rate-
determining step. However, as we report later in this section, transmetalated
intermediates (such as 10) are not observed in either PhCl or THF,
supporting that the coupling in these solvents is much faster than the
transmetalation. Under these circumstances, the rates observed can be taken
as transmetalation rates.
(25) Dichloromethane is noncoordinating and avoids solvolysis processes
in the complexes occurring during the experiments. This comparative study
was not be performed in PhCl because of the low solubility of [Pd(C6-
Cl2F3)(PPh3)3]BF4 (5c+‚BF4-).
(26) An alternative attempt to synthesize 10, the treatment of 4c with
vinylmagnesium chloride in cold toluene, led to a mixture of 10, trans-
[Pd(C6Cl2F3)Cl(PPh3)2] (6c), and unreacted 4c.
(22) Casado, A. L.; Espinet, P. Organometallics 1998, 17, 954-959.

Mechanism of the Stille Reaction
J. Am. Chem. Soc., Vol. 122, No. 48, 2000 11777
Scheme 5
The compound trans-[Pd(C6Cl2F3)(THF)(PPh3)2](BF4) (7c‚
(BF4)) also led to 10 upon treatment with 2 in CH2Cl2, at a rate
similar to that found for 4c. Again, a small amount of byproduct
11 was detected. The possible formation of 10 in other solvents
used in the catalytic couplings was also checked. Complex [Pd-
(C6Cl2F3)(OTf)(PPh3)2] (4c) did not produce 10 in PhCl or THF.
Compound 5c‚(BF4) yielded 10 in both solvents, THF and PhCl.
Compound 7c‚(BF4) yielded some 10 in PhCl, but not in THF.
Finally, trans-[Pd(C6Cl2F3)Cl(PPh3)2] (6c) did not produce 10
in any of the three solvents.
1
Figure 4. 1H (upper) and H{31P} (lower) NMR (300 MHz, CDCl3,
room temperature) spectra of the vinyl resonances in a sample of trans-
[Pd(C6Cl2F3)(CHdCH2)(PPh3)2] (10).
{31P} NMR spectrum (Figure 4). The trans arrangement of the
molecule was confirmed in its 31P{1H} NMR spectrum, which
shows only one signal (triplet of doublets because of 19F-31P
couplings). The 19F NMR spectrum showed a triplet for the Fortho
and a triplet for the Fpara atoms. This multiplicity arises from
19F-31P couplings, which were clearly observable in a 19F-
31P HMQC experiment. To the best of our knowledge, this is
the first time that an intermediate between the transmetalation
and the coupling steps in a Stille cycle is observed and
unambiguously characterized.
Discussion
The origin of the complex behavior of the Stille coupling
resides in the variety of factors controlling the overall outcome
of the reaction. First, these determine which step is the slowest
in the catalytic cycle, which can be either the oxidative addition,
the transmetalation, or even the reductive elimination,29 depend-
ing on the systems involved and the conditions used. Further-
more, the transmetalation step can be occurring at different rates
on one or more different organopalladium(II) intermediates,
which in turn are conditioned by the organic electrophile used,
the solvent, the addition or not of LiCl, and the ancillary ligands.
Which Step Is Rate Determining in the Catalytic Cycle?
Role of LiCl in the Stille Coupling Using Aryl Triflates. The
low rates found in the [PdL4]-catalyzed couplings of C6F5-
OTf (1) and Sn(CHdCH2)Bu3 (2) in THF or PhCl (Table 2)
for L ) AsPh3 are clearly due to the slowness of the oxidative
addition of 1 to a [Pd(AsPh3)n] species, so that this step becomes
rate-determining. Amatore et al.,30 and Jutand and Mosleh,16
have shown recently that, in the presence of chloride ions,
species of the type [PdL2Cl]- are formed and undergo oxidative
addition of aryl triflates to give trans-[PdR1ClL2]. According
to this, it seems clear that the addition of LiCl in THF accelerates
the oxidative addition step (rate-determining for L ) AsPh3)
because it induces the formation of more nucleophilic species
The analysis of the profiles in Figure 3 reveals some
interesting kinetic features: (i) Although complex 10 is an
intermediate between 5c+ and 3b (upper part of Scheme 5),
the profile for the formation of 3b (Figure 3a,b) shows that it
is being formed at a considerable rate at early stages of the
reaction, when the concentration of intermediate 10 is still very
low. Thus, a more direct transformation from 5c+ to 3b must
be occurring simultaneously (lower part of Scheme 5). This
contribution is also clear in the transmetalation on 4c (Figure
3c). The direct transformation of 4c into 3b, contributing from
the beginning, is responsible for the additional curvature of the
profile of 3b until 4c disappears (initial 50 min). Once all the
starting material has been consumed, the formation of 3b via
10 becomes dominant. Indeed, crude samples of 10 decomposed
in solution, giving 3b quantitatively. (ii) In all cases, the addition
of free PPh3 retards the formation of both 10 and the final
product 3b (this was also observed in the decomposition of crude
samples of 10). This L-retardation effect is not as pronounced
in CH2Cl2 as in other solvents (see Table 3). (iii) In the case of
4c, the addition of free PPh3 caused fast formation of 5c+ (Figure
3d), in agreement with eq 3. (iv) A byproduct, C6Cl2F3-SnBu3
(11), was formed from 10 when the concentration of the latter
was very high (Figure 3c). The addition of PPh3 inhibited the
formation of 11 (Figure 3d). Compound 11 is apparently formed
from 10 by anionic-ligand exchange (eq 8), which is strongly
retarded by free L.28 Note that the formation of these byproducts
[PdCln(AsPh3)4-n]
n- (eq 9). A similar proposal has been made
by Reetz et al. in order to explain the beneficial role of a
phosphonium chloride in the oxidative addition of aryl chlorides
to palladium(0) complexes.31
(29) For examples of Stille couplings frustrated at the reductive elimina-
tion step, see: (a) Ca´rdenas, D. J.; Mateo, C.; Echavarren, A. M. Angew.
Chem., Int. Ed. Engl. 1994, 33, 2445-2447. (b) Mateo, C.; Ca´rdenas, D.
J.; Ferna´ndez-Rivas, C.; Echavarren, A. M. Chem. Eur. J. 1996, 2, 1596-
1606. See also: (c) Mateo, C.; Ferna´ndez-Rivas, C.; Echavarren, A. M.;
Ca´rdenas, D. J. Organometallics 1997, 16, 1997-1999. (d) Mateo, C.;
Ferna´ndez-Rivas, C.; Ca´rdenas, D. J.; Echavarren, A. M. Organometallics
1998, 17, 3661-3669.
could eventually give rise to homocoupling products in ligand-
free or ligand-poor catalytic process, while this complication
should be inhibited in ligand-rich catalysis.
(27) Braun, S.; Kalinowski, H.-O.; Berger, S. 100 and More Basic NMR
Experiments; VCH: New York, 1996.
(28) A similar exchange process takes place between [Pd(C6Cl2F3)2-
(AsPh3)2] and SnXBu3 (X ) Cl, Br, I) and is retarded by free AsPh3. Casado,
A. L. Doctoral Thesis, Universidad de Valladolid, March 1998.
(30) Amatore, C.; Jutand, A.; Sua´rez, A. J. Am. Chem. Soc. 1993, 115,
9531-9541 and references therein.
(31) Reetz, M. T.; Lohmer, G.; Schwickardi, R. Angew. Chem., Int. Ed.
1998, 37, 481-483.

11778 J. Am. Chem. Soc., Vol. 122, No. 48, 2000
Casado et al.
In contrast, the couplings catalyzed by [Pd(PPh3)4] in THF
are retarded by LiCl. In this case, the oxidative addition of the
aryl triflate 1 to [Pd(PPh3)4] is fast, regardless of whether LiCl
is added. In the absence of LiCl, the oxidative addition gives
complexes trans-[Pd(C6F5)X(PPh3)2] (X ) TfO (4a), PPh3
(5a+), or THF (7a+)), but in the presence of LiCl, the product
is trans-[Pd(C6F5)Cl(PPh3)2] (6a). The transmetalation on any
of them is slower than the oxidative addition and is rate-
determining. Since the transmetalation is slower on 6a than on
either 4a, 5a+, or 7a+ (Table 3), the presence of LiCl produces
a net retarding effect on the catalytic coupling.
Scheme 6
In summary, the addition of LiCl produces overall accelera-
tion only when the oxidative addition is slow and rate-
determining, which can happen when [PdL4] is not very
nucleophilic (poor donor L). Otherwise, a retardation is pro-
duced, at least in solvents of moderate polarity. In this respect,
it is interesting to note that the oxidative addition to not very
nucleophilic [PdL4] species can become fast in very polar
solvents, as shown by some results of Farina et al. on
[Pd(AsPh3)4].9 This is probably due to stabilization of a polar
transition state in the oxidative addition. In such a case, no
beneficial effect should be expected upon LiCl addition.
Mechanism of the Transmetalation Step in the Stille
Coupling with Triflates. In the presence of LiCl, and in
solvents of moderate polarity and that are not highly coordinat-
ing, the transmetalation step occurs on intermediates trans-
[PdR1ClL2], following the associative “SE2(cyclic)” mechanism
outlined in Scheme 1, which was discussed in detail in Part 1
of this work.1 It is characterized by an R2-for-L exchange leading
directly to a cis arrangement of R1 and R2 around the Pd center.
The formation of the cross-coupling product after the trans-
metalation is immediate, and this avoids the detection by NMR
at room temperature of any transmetalation product prior to the
coupling product. An important retarding effect upon addition
of free neutral ligand L is found experimentally.
In the absence of LiCl and using PhCl, THF, or CH2Cl2 as
solvent, the transmetalation can occur on trans-[PdR1(OTf)L2],
[PdR1L3]+, or trans-[PdR1(THF)L2]+. Our experiments show
that, under certain conditions, important amounts of the
intermediate trans-[PdR1(CHdCH2)L2] (10) are produced. This
observable intermediate has a noticeable stability, as is to be
expected since it should isomerize to a cis arrangement prior
to reductive elimination of 3b. This behavior is in contrast with
the nondetection of intermediates in the “SE2(cyclic)” mecha-
nism, where a cis arrangement for R1 and R2 is necessarily
produced.
Chart 2
unable or less able to coordinate (such as benzyl or phenyl), a
direct coordination of the R carbon should be proposed for the
associative substitution of L, S, or TfO-. Regardless of the initial
stages of interaction, eventually the transition state has to involve
coordination of the R carbon, as shown in Chart 2 (2.I for
substitution trans to R1; 2.II for substitution cis to R1). A slower
transmetalation is to be expected for less nucleophilic stannanes,
as observed, and this supports the contention that the substitution
follows an associative mechanism. This mechanism is exactly
an SE2 electrophilic cleavage, with the Pd complex acting as
the electrophile. Solvent molecules or TfO- could assist the
elimination of the leaving group SnR3
+
.
In the reactions monitored in CH2Cl2, the coupling product
is being formed at a rate higher than could be expected from
the decomposition of 10 only. This proves that, besides the trans-
to-R1 substitution, there is also a cis-to-R1 substitution. Since
this competing cis and trans substitution is observed in cases
where the ligands lack bridging ability (as in [Pd(C6Cl2F3)-
(PPh3)3]+ (5a+)), this means that two “SE2(open)” mechanisms
are operating (as observed for I- as nucleophile in eq 5), which
bring the entering group either cis or trans to R1. We label them
“SE2(open-cis)” and “SE2(open-trans)”, respectively.
Cyclic and open pathways might operate in the transmeta-
lation on trans-[Pd(C6Cl2F3)(OTf)(PPh3)2] (4c), due to the
potential bridging ability of triflate. In the polar CH2Cl2, the
reaction profile in Figure 3c reveals two parallel pathways
producing 3b: the fast formation of 10 indicates the dominance
of an SE2(open-trans) pathway (ca. 80%), probably due to the
easy displacement of the poorly coordinating anionic triflate
group. The other smaller contribution, following a cis substitu-
tion, can be assigned to either an SE2(cyclic) or an SE2(open-
cis) transfer. In the less polar (and also noncoordinating) PhCl,
4c did not produce 10, showing that the reaction occurs almost
exclusively by substitution of the cis PPh3 ligand. Moreover, a
sharp retarding effect upon addition of PPh3 was noticed here
(Table 3). This suggests that, in that case, the cis transmetalation
follows an SE2(cyclic) rather than an SE2(open-cis) pathway.
Interestingly, when the reaction was carried out using a solution
of NBu4ClO4 in PhCl, the formation of 10 was again detected,
showing that the increase produced in the polarity of the solvent
accelerates the SE2(open-trans) pathway. These results stress
The experiments using [NBu4]I as the nucleophile (eq 5 and
related experiments) show that, in an open mechanism, the
entering nucleophile can either display high preference for the
trans position or produce competing substitution of the ligands
cis and trans to R1, depending on the complex on which the
substitution occurs. Similarly, in an open transmetalation using
vinyl stannane as the nucleophile, the possible pathways for
the formation and the fate of the transmetalation products are
those summarized in Scheme 6 (L1 ) L or S). The formation
of the coupling product from 12 requires only dissociation,
whereas that from 10 requires also topomerization;11 the later
can be slow, making 10 observable.32
Initial approach of the vinyl stannane acting as a π-ligand
seems very plausible,33 as it would be for alkynyl stannanes
also. For the most general case of stannanes with R2 groups
(32) We have shown in a closely related [PdR2L2] system that the main
barrier to cis-trans isomerization was not the dissociation of L, but the
cis-trans topomerization in the three-coordinate species: Casado, A. L.;
Casares, J. A.; Espinet, P. Inorg. Chem. 1998, 37, 4154-4156.
(33) Cationic palladium complexes with coordinated styrene derivatives
have been characterized unambiguously: Rix, F. C.; Brookhart, M.; White,
P. S. J. Am. Chem. Soc. 1996, 118, 2436-2448.

Mechanism of the Stille Reaction
J. Am. Chem. Soc., Vol. 122, No. 48, 2000 11779
the importance of the nature of the ligand being replaced and
the solvent: the ease of displacement of anionic ligands (TfO-)
from neutral complexes should be accelerated in polar solvents,
where the polar transition state (Chart 2, 2.I, L1 ) OTf, X)
should be stabilized, decreasing the activation energy toward
its substitution. Much less an effect should be expected for the
replacement of neutral ligands, whether from neutral or from
cationic species. In THF, trans-[Pd(C6Cl2F3)(THF)(PPh3)2]+ is
formed almost quantitatively in solution, and the transmetalation
in this case led selectively to cis substitution, suggesting that
THF is inducing an “SE2(cyclic)” transmetalation. This is sup-
ported by the fact that trans-[Pd(C6Cl2F3)(THF)(PPh3)2][BF4]
does not produce 10 in THF. In PhCl the displacement of
coordinated THF is easier and a noticeable amount of 10 is
formed.
Chart 3
PPh3. In the presence of LiCl, however, the only intermediate
observed is trans-[PdR1XL2].
The existence of two transmetalation pathways in the Stille
reaction, SE2(cyclic) and SE2(open), has important stereochem-
ical consequences.34 The steps following transmetalation in the
cycle (isomerization and reductive elimination) are known to
occur with retention of configuration at sp3 carbons. Hence, the
transmetalation step determines the stereochemical outcome of
the overall coupling reaction with chiral organotins. This step
has to bring about retention of configuration for an SE2(cyclic)
pathway. For an SE2(open) mechanism, the studies on bromi-
nation of stannanes show that the bromination occurs predomi-
nantly with retention of configuration, but it switches to
inversion under the influence of steric requirements, such as in
sec-butyltrineopentyltin.34
In fact, the contradictory stereochemical outcomes reported
in the literature can be nicely reconciled on this basis and add
further support to our mechanistic analysis of the transmetalation
step.12,13 Thus, the 98% retention of configuration reported by
Falck et al. in the coupling of chiral R-alkoxystannanes with
acyl chlorides in toluene (these conditions should favor strongly
the SE2(cyclic) pathway because they favor [Pd(acyl)ClL2] over
other species) suggests that this pathway can be very sterose-
lective and leads to retention. On the other hand, Labadie and
Stille found inversion (g65%) in the coupling of a chiral
benzylic stannane to an acyl chloride in HMPA. Here, our results
suggest that the transmetalation must be occurring on [Pd-
(COPh)(HMPA)(PPh3)2]Cl (Chart 3), rather than on [Pd(COPh)-
Cl(PPh3)2] (Chart 1), as assumed in the original paper. Since
the bridging ability of HMPA is very poor, we should expect
an SE2(open) mechanism. The stereoselectivity reported by Stille
is perfectly compatible with an open mechanism leading to
inversion, which might be favored by the steric requirement of
the metal complex.
A More Comprehensive Catalytic Cycle for the Stille
Reaction. The studies presented in this paper suggest that the
Pd-catalyzed coupling of organotin reagents and organic elec-
trophiles can follow any of two paths which differ in the
transmetalation step (which could be competing depending on
the conditions). These are represented together in Scheme 7,
which shows also the structures proposed for the corresponding
activated complexes.
One of the paths (upper part of Scheme 7) involves an SE-
(cyclic) transmetalation step. It requires an X ligand able to act
as bridging group, implies an L-for-R2 replacement at the Pd
center, and leads directly to a cis arrangement followed by
immediate coupling. This pathway is strongly retarded by free
L. This mechanism should be very favored in nonpolar solvents
and in the presence of good bridging groups (halides).
A Generalization of the Mechanism of the Transmetala-
tion Step and Stereochemical Implications in the Stille
Coupling. In a general case, the transmetalation has to occur
on trans-[PdR1XL2] (X ) halide), trans-[PdR1L3]+, trans-[PdR1-
(S)L2]+ (S ) solvent), trans-[PdR1(OTf)L2], [PdR1(S)2L]+, or
trans-[PdR1X(S)L], which are the species observed in this work.
They are exchanging in solution, and their ratios depend on
factors such as the concentration of free L, the nature of L, the
solvent polarity, the solvent coordinating ability, the nature of
R1, and the temperature. Thus, the situation is complex and can
change dramatically depending on the factors mentioned. Each
case needs to be studied separately since the actual mechanism
will depend on the species existing and undergoing fast
transmetalation in those reaction conditions. It is interesting that,
in contrast to previous assumptions (Scheme 2), the transmeta-
lation does not necessarily occur on a poorly coordinated
complex, nor involve S substitution, nor afford a trans complex.
The studies in this paper led us to propose intermediates
which are different from those proposed in the literature so far.
The most common reaction conditions used in catalysis are T
g 50 °C, Pd:L ) 1:2, L ) PPh3, absence of LiCl for RX (X )
halide), addition of LiCl for R-OTf. According to our observa-
tions, under these conditions the last three species listed in the
previous paragraph are never observed. Thus, intermediates
proposed in the literature such as D (see Scheme 2) look very
unlikely in any solvent.
When highly coordinating polar solvents, such as HMPA,
are used, they are able to displace any halide, triflate, or L trans
to R1, to give trans-[PdR1(HMPA)L2]+ on which the trans-
metalation occurs. Hence, in HMPA, intermediates such as C
and D in Scheme 2 are also highly improbable. Moreover, the
intermediate actually observed in solution in our work, trans-
[PdR1(HMPA)L2]+, would not lead to the transition state
proposed in the literature (Chart 1), and for this reason that
transition state is very improbable (note that, although some D
seems to be formed in the presence of very large amounts of
LiCl in HMPA, LiCl was not added in the study by Labadie
and Stille, which will be discussed later).12
NMP displaces OTf or PPh3 but cannot displace halides;
hence, the transmetalation should occur on trans-[PdR1(NMP)-
L2]+ in the absence of LiCl but on [PdR1ClL2] when LiCl has
been added to help the oxidative addition. In other words, in
the presence of LiCl, the intermediates B and D proposed in
the literature (Scheme 2) are both unlikely.
(34) These two limiting mechanisms have been proposed for the
electrophilic cleavage of Sn-R bonds with X2 (X ) Br, I) in the
following: Rahm, A.; Pereyre, M. J. Am. Chem. Soc. 1977, 99, 1672-
1673. Although the Pd-Sn transmetalation can be formally regarded as a
similar reaction, the behavior of the organopalladium(II) intermediates
cannot be immediately deduced from that of X2 electrophiles, since the
structure of the Pd(II) complexes intermediates (ligands and geometry)
determines the transmetalation pathway.
In THF at 50 °C, the triflate is displaced, and in the presence
of PPh3, trans-[PdR1L3]+ and trans-[PdR1(THF)L2]+ (7c+/5c+
) 96/4 for a solution 10-2 M in Pd) are the intermediates
available for transmetalation, but this mixture can be modified
as a function of temperature, concentration, and proportion of

11780 J. Am. Chem. Soc., Vol. 122, No. 48, 2000
Casado et al.
one solvent, the solvents and the chemical shifts are indicated separated
by bars. In nondeuterated solvents, a capillary of acetone-d6 was used
for the lock; the chemical shifts given result from setting the following
absolute (SF) frequencies for zero: 282.407650 MHz for 19F and
121.496145 for 31P. The fine structure descriptions given (including
coupling constants J, in Hz) correspond to CDCl3.
Scheme 7
C6F5OH, Tf2O, and C6F5sCHdCH2 (3a, 19F NMR (PhCl/THF) δ
3
-139.95/-141.08 (m, o-CF), -152.92/-154.40 (t, JFF ) 20.8 Hz,
p-CF), -159.63/-161.20 (m, m-CF)) were used as purchased (Aldrich).
LiCl was flame vacuum-dried and stored under N2 prior to use. Sn-
(CHdCH2)Bu3 (2),1 [Pd(PPh3)4],35 [Pd(AsPh3)4],36 C6Cl2F3-CHdCH2
(3b),1 [Pd2(C6F5)2(µ-Cl)2(tht)2],37 trans-[Pd(C6Cl2F3)Cl(PPh3)2] (6c),17
trans-[Pd(C6Cl2F3)Cl(AsPh3)2] (6d),1 cis-[Pd(C6Cl2F3)I(PPh3)2] (9),17 and
trans-[Pd(C6Cl2F3)I(PPh3)2] (8)17 were prepared as reported.
C6F5-OTf (1). To solution of C6F5OH (2.00 g, 10.9 mmol) in CH2-
Cl2 (15 mL) at -78 °C was added NEt3 (4.0 mL, 28.0 mmol). Tf2O
(2.0 mL, 11.9 mmol) was then added dropwise via syringe. The mixture
was stirred for 10 min into the cold bath and then for 30 min at ambient
temperature. The resulting red solution was quenched with aqueous
NaHCO3 and sequentially washed with 10% hydrochloric acid (30 mL),
brine (30 mL), and water (30 mL). The organic layer was separated,
dried over MgSO4, and evaporated. The residual yellow oil was vacuum-
distilled (40 °C/0.5 mmHg), giving 1 as a colorless liquid (2.25 g,
73%): d ) 1.60. IR (liquid on NaCl): 1520 (s), 1146 (s), 1231 (s),
1134 (s), 1000 (s), 799 (m), 758 (m), 612 (m). 13C{1H} (CDCl3): δ
143.0 (m, CF), 139.7 (m, CF), 139.4 (m, C), 136.3 (m, CF), 118.4 (q,
1JCF ) 321 Hz, CF3). 19F NMR (CDCl3/PhCl/THF): δ -73.27/-
69.45/-69.98 (t, 6JFF ) 6.8 Hz, CF3), -150.98/-147.35/-149.03 (m,
o-CF), -153.11/-148.82/-151.00 (t, 3JFF ) 22.3, p-CF), -160.22/-
156.02/-158.08 (m, m-CF). MS m/z (relative intensity): 316 (0.3)
[M+], 183 (3), 155 (8), 69 (100) [CF3+]. HRMS: calcd for C7F8SO3,
m/z 315.9440; found, m/z 315.9441.
trans-[PdR(OTf)L2] (R ) C6F5, L ) PPh3, 4a; L ) AsPh3, 4b; R
) C6Cl2F3, L ) PPh3, 4c; L ) AsPh3, 4d). The corresponding complex
6a-d (0.105 mmol) was added to a stirred solution of AgOTf (26.9
mg, 0.105 mmol) in acetone/CH2Cl2 (3/3 mL) shielded from the light.
The mixture was stirred for 30 min. The AgCl formed was carefully
filtered out, and the solution was evaporated to dryness, affording white
solids 4a-d which were washed with n-pentane (2 × 1 mL) and
vacuum-dried.
The second pathway (lower part of Scheme 7) follows an
SE(open) transmetalation mechanism. It is the only possible path
in the absence of bridging ligands but can also operate in their
presence, under appropriate conditions, when they are displaced
from the coordination sphere. It implies X-for-R2 or L-for-R2
replacement at the Pd center, leads competitively to cis and trans
arrangements, and seems to be less retarded by added L. This
mechanism should be favored by the use of (1) polar, coordinat-
ing solvents that lack bridging ability and (2) easily leaving,
poorly coordinating anionic ligands that lack bridging ability.
Note that if the solvent is able to act as a bridging ligand, [PdR1-
(S)L2]+ could induce a cyclic mechanism (upper part of Scheme
7, with S playing the role of X).
The geometry of the transmetalation product, cis- or trans-
[PdR1R2L2], although mechanistically very relevant, can be less
important from a synthetic viewpoint, since the isomerization
step is fast under the usual catalytic conditions. However, it
could become important if very efficient catalyzed cross
couplings running at lower temperatures are developed. More-
over, the stability of trans-[PdR1R2L2] can eventually give rise
to some homocoupling side products.
Finally, it is worth noting that the double pathway found for
the Stille reaction emphasizes its common aspects with the
Hiyama reaction where, using R2SiF3 that is chiral at the
R-carbon of R2, retention or inversion at the transmetalated chiral
carbon can be induced.2 It seems reasonable that controlling
the reaction conditions of the Stille coupling in order to favor
either the cyclic or the open pathway, stereocontrol of the Stille
reaction might also be achieved. A more detailed investigation
of these aspects is in progress.
4a (88%). IR (KBr): 1505 (vs), 1468 (vs), 1436 (vs), 1313 (s),
1232 (vs), 1212 (vs), 1180 (s), 1097 (s), 1022 (vs), 958 (vs), 743 (s),
1
694 (vs), 633 (s), 523 (vs), 510 (vs), 497 (m). H NMR (CDCl3): δ
7.7-7.5 (m, 2 CH), 7.5-7.3 (m, 3 CH). 19F NMR (CDCl3/PhCl/
THF): δ -79.21/-74.88/-75.5 (s, CF3), -117.76/-113.15/-113.76
3
(m, o-CF), -161.30/-157.25/-158.9 (t, JFF ) 18.9 Hz, p-CF),
-162.07/-157.51/-158.96 (m, m-CF). 31P{1H} NMR (CDCl3/PhCl/
4
6
THF): δ 23.50/27.83/27.95 (td, JFP ) 7.9 Hz, JFP ) 2.9 Hz). Anal.
Calcd for C43H30F8O3P2PdS: C, 54.53; H, 3.19. Found: C, 54.33; H,
3.21.
4b (90%). IR (KBr): 1505 (vs), 1465 (vs), 1438 (vs), 1324 (s),
1233 (vs), 1216 (vs), 1027 (vs), 956 (vs), 742 (vs), 692 (vs), 631 (s),
467 (m). 1H NMR (CDCl3): δ 7.5-7.3 (m, 3 CH), 7.2-7.0 (m, 2 CH).
19F NMR (CDCl3/PhCl/THF): δ -78.46/-74.16/-74.83 (s, CF3),
-117.12/-112.64/-113.22 (m, o-CF), -160.23/-156.18/-157.82 (t,
3JFF ) 20.1 Hz, p-CF), -161.75/-157.26/-158.76 (m, m-CF). Anal.
Calcd for C43H30As2F8O3PdS: C, 49.90; H, 2.92. Found: C, 49.55; H,
2.82.
Experimental Section
4c (60%). IR (KBr): 1483 (s), 1436 (vs), 1409 (vs), 1326 (vs), 1234
(vs), 1208 (vs), 1099 (s), 1023 (s), 779 (m), 774 (m), 693 (vs), 632
All reactions were carried out under N2. Solvents were distilled from
sodium/benzophenone (THF, diethyl ether) or CaH2 (PhCl, CH2Cl2,
1
CHCl3, HMPA, NMP) and stored under N2. Infrared spectra (in cm-1
)
(m), 523 (vs), 511 (s). IR (THF): 1299 (vs), 1284 (vs), 1270 (s). H
(CDCl3): δ 7.65-7.59 (m, 2 CH), 7.5-7.3 (m, 3 CH). 19F NMR
(CDCl3/PhCl/THF): δ -79.23/-74.88/-75.54 (s, CF3), -91.55/-
87.07/-87.29 (t, 4JFP ) 7.7 Hz, o-CF), -119.59/-115.21/-116.21 (s,
p-CF). 31P{1H} NMR (CDCl3/PhCl/THF): δ 23.37/27.64/27.8 (td, 4JFP
were recorded on a Perkin-Elmer FT-IR 1720 X spectrometer. Combus-
tion analyses were done on a Perkin-Elmer 2400 CHN microanalyzer.
Mass spectra were taken on a Hewlett-Packard 5980 spectrometer (70
eV, EI). High-resolution spectra were taken on a HRMS VG Autospec
M spectrometer (70 eV, EI). 1H, 1H{31P}, 1H COSY, 1H-31P HMQC,
13C{1H}, 19F, 19F-31P HMQC, 31P{1H}, and 119Sn{1H} NMR experi-
ments were run on a Bruker ARX-300 spectrometer equipped with a
VT-100 variable-temperature probe. Chemical shifts are reported in
ppm from SiMe4 (1H, 13C), CCl3F (19F) in CDCl3, 85% H3PO4 (31P), or
net SnMe4 (119Sn) at room temperature. When recorded in more than
6
) 7.7 Hz, JFP ) 2.9 Hz). Anal. Calcd for C43H30Cl2F6O3P2PdS: C,
52.70; H, 3.09. Found: C, 52.57; H, 3.08.
(35) Coulson, D. R. Inorg. Synth. 1972, 13, 121-123.
(36) [Pd(AsPh3)4] was prepared as described in ref 35 for [Pd(PPh3)4].
(37) Uso´n, R.; Fornie´s, J.; Mart´ınez, F.; Toma´s, M. J. Chem. Soc., Dalton
Trans. 1980, 888-893.

Mechanism of the Stille Reaction
J. Am. Chem. Soc., Vol. 122, No. 48, 2000 11781
4d (76%). IR (KBr): 1437 (vs), 1412 (vs), 1316 (vs), 1232 (vs),
mL) at -78 °C. The mixture was stirred for 16 h, allowing the bath to
reach room temperature. The resulting white suspension was quenched
with aqueous NaHCO3. The organic phase was separated, washed with
water (2 × 50 mL), and then dried over MgSO4. The solvent was
evaporated, and the residue was flash-chromatographed (silicagel/n-
hexane), giving 11 as a colorless liquid (5.56 g, 89%). d ) 1.23 g/mL.
IR (liq on NaCl): 2959 (vs), 2922 (vs), 1407 (vs), 1059 (vs), 1046 (s),
781 (s), 667 (m). 1H NMR δ (CDCl3): 1.53 (m, CH2), 1.34 (m, CH2),
1.21 (m, CH2), 0.93 (m, CH3). 13C{1H} NMR δ (CDCl3): 160.23 (ddd,
1JCF ) 238.3 Hz, 3JCF ) 22.5 Hz, 3JCF ) 5.1 Hz, o-CF), 155.4 (dt, 1JCF
1211 (vs), 1186 (vs), 1022 (vs), 781 (s), 738 (vs), 693 (vs), 634 (s),
1
466 (s). H (CDCl3): δ 7.6-7.5 (m, 2 CH), 7.5-7.4 (m, 3 CH). 19F
NMR (CDCl3/PhCl/THF): δ -78.46/-74.11/-74.78 (s, CF3), -90.97/-
86.58/-86.75 (s, o-CF), -118.64/-114.26/-115.44 (s, p-CF). Anal.
Calcd for C43H30As2Cl2F6O3PdS: C, 48.36; H, 2.83. Found: C, 48.17;
H, 2.80.
[PdR(PPh3)3](BF4) (R ) C6F5, 5a.(BF4); R ) C6Cl2F3, 5c.(BF4)).
The corresponding complex 6a,c (0.157 mmol) was added to a stirred
solution of AgBF4 (30.5 mg, 0.157 mmol) in acetone/CH2Cl2 (3/3 mL)
shielded from the light. The mixture was stirred for 30 min. The AgCl
formed was carefully filtered off, and PPh3 (41.1 mg, 0.157 mmol)
was added to the solution. The mixture was stirred for 30 min and
evaporated to dryness, affording 5a,c‚[BF4] as white solids which were
washed with diethyl ether (2 × 1 mL) and vacuum-dried.
5a‚[BF4] (91%). IR (KBr): 1481 (m), 1435 (vs), 1403 (s), 1097
(vs), 1051 (vs), 777 (m), 746 (s), 700 (vs), 523 (vs), 511 (s), 493 (m).
3
2
4
) 250.4 Hz, JCF ) 5.5 Hz, p-CF), 110.5 (dt, JCF ) 54.1 Hz, JCF
)
3.5 Hz, CSn), 106.2 (ddd, 2JCF ) 29.8 Hz, 2JCF ) 20.6 Hz, 4JCF ) 5.8
Hz, CCl), 28.7 (s, sat 3JCSn ) 20.8 Hz, CH2Me), 27.1 (s, sat 2JC
)
119
Sn
64.1 Hz, sat 2JC Sn ) 62.9 Hz, CH2), 13.5 (s, sat 4JHSn ) 2.8 Hz, CH3),
117
4
1
1
119
117
11.4 (t, JCF ) 2.0 Hz, sat JC
) 358.8 Hz, sat JC
) 343.0,
Sn
Sn
SnCH2). 19F NMR (CDCl3/THF): δ -95.05/-91.21 (d, 4JFF ) 2.4 Hz,
3
4
sat JFSn ) 5.9 Hz, o-CF), -110.99/-107.94 (t, JFF ) 2.4 Hz, sat
5JFSn ) 3.4 Hz, p-CF). 119Sn{1H} NMR (CDCl3) δ -21.47 (td, 3JFSn
)
-
1H (CDCl3): δ 7.5-7.0 (m, CH). 19F NMR (CDCl3/PhCl):
δ
5
5.9 Hz, JFSn ) 3.4 Hz). EM m/z (relative intensity): 433 (7) [M+
-113.16/-108.28 (m, o-CF), -154.29/-146.20 (s, 9BF4-), -154.34/-
C4H9], 377 (18) [M+ - 2C4H9], 321 (26) [M+ - 3C4H9], 139 (42), 41
(100). Anal. Calcd for C18H27Cl2F3Sn: C, 44.22; H, 5.55. Found: C,
44.43; H, 5.27.
146.25 (s, 10BF4-), -158.50/-154.70 (t, JFF ) 20.1 Hz, p-CF),
3
-158.96/-154.77 (m, m-CF). 31P{1H} NMR (CDCl3/PhCl): δ 23.18/
2
26.99 (d, JPP ) 26.5 Hz, 2 P), 18.67/22.53 (m, P). Anal. Calcd for
Signals Observed for Complexes Dissolved in Solvents Com-
monly Used in Stille Couplings in Different Conditions. [Pd-
C60H45BF9P3Pd: C, 62.82; H, 3.95. Found: C, 62.71; H, 4.06.
5c‚[BF4] (82%). IR (KBr): 1435 (vs), 1403 (vs), 1097 (vs), 1051
(vs), 777 (m), 746 (s), 700 (vs), 523 (vs), 511 (vs), 493 (m). 1H
(CDCl3): δ 7.4-7.2 (m, 3 CH), 7.1-7.0 (m, 2 CH). 19F NMR (CDCl3/
4
(C6Cl2F3)Cl(PPh3)2]. 19F NMR (HMPA): δ -85.78 (d, JFP ) 10.84
Hz, o-CF), -86.87 (t, 4JFP ) 6.7 Hz, o-CF), -88.05 (d, 4JFP ) 9.6 Hz,
o-CF), -117.35 (s, p-CF), -117.59 (s, p-CF), -121.01 (s, p-CF).
[Pd(C6Cl2F3)Cl(PPh3)2]:PPh3:LiCl (1:2:20). 19F NMR (HMPA):
4,trans
4,cis
THF/PhCl): δ -87.73/-82.66/-82.98 (dt,
J
) 10.5 Hz,
J
FP
FP
) 4.5 Hz, o-CF), -154.58/-148.34/-146.43 (s, 10BF4-), -154.64/-
148.39/-146.49 (s, 11BF4-), -116.75/-114.11/-112.83 (s, p-CF). 31P-
4
4
δ -86.87 (t, JFP ) 6.7 Hz, o-CF), -88.05 (d, JFP ) 9.6 Hz, o-CF),
-117.59 (s, p-CF), -121.01 (s, p-CF).
{1H} NMR (CDCl3/THF/PhCl): δ 22.93/26.6/26.83 (dtd, JPP ) 26.9
2
[Pd(C6Cl2F3)X(PPh3)2] (X
)
Cl, I):PPh3 (1:2). 19F NMR
Hz, 4,cisJFP ) 4.5 Hz, 6,cisJFP ) 29 Hz, 2 P), 18.31/22.55/22.03 (tt, 2JPP
) 26.9 Hz, 4,transJFP ) 10.5 Hz, P). Anal. Calcd for C60H45P3BCl2F7Pd:
C, 61.07; H, 3.84. Found: C, 61.18; H, 4.22.
4
(HMPA): δ -86.87 (t, JFP ) 6.5 Hz, o-CF), -117.59 (s, p-CF).
[Pd(C6Cl2F3)(OTf)(PPh3)2]:PPh3 (1:2). 19F NMR (HMPA):
δ
-74.12 (s, CF3), -86.86 (t, 4JFP ) 6.5 Hz, o-CF), -117.58 (s, p-CF).
trans-[Pd(C6F5)ClL2] (L ) PPh3, 6a; AsPh3, 6b). L (3.88 mmol)
was added to a stirred suspension of [Pd2(C6F5)2(µ-Cl)2(tht)2] (700 mg,
0.882 mmol), yielding a white precipitate. The mixture was stirred for
1 h and evaporated to dryness. The solid was washed with diethyl ether
and recrystallized at -28 °C from CH2Cl2.
[Pd(C6Cl2F3)(PPh3)3](BF4):PPh3 (1:1). 19F NMR (HMPA):
δ
4
-86.85 (t, JFP ) 6.5 Hz, o-CF), -117.58 (s, p-CF), -147.59 (s,
10BF4-), -147.64 (s, 11BF4-).
[Pd(C6Cl2F3)I(PPh3)2]. 19F NMR (NMP): δ -88.07 (t, JFP ) 6.5
4
6a (98%). IR (KBr): 1502 (s), 1458 (vs), 1433 (vs), 1098 (s), 952
(vs), 744 (s), 693 (vs), 523 (vs), 513 (s), 498 (m). 1H (CDCl3): δ 7.7-
7.6 (m, 2 CH), 7.45-7.3 (m, 3 CH). 19F NMR (CDCl3/PhCl/THF): δ
-117.40/-112.59/-113.34 (m, o-CF), -162.82/-158.53/-160.12 (t,
3JFF ) 20.1 Hz, p-CF), -163.16/-158.61/-160.43 (m, m-CF). 31P-
Hz, o-CF), -117.65 (s, p-CF). After addition of 1 equiv of AgBF4:
4
-86.35 (t, JFP ) 7.1 Hz, o-CF), -115.62 (s, p-CF).
[Pd(C6Cl2F3)(OTf)(PPh3)2]. 19F NMR (NMP): δ -74.56 (s, CF3),
4
-86.37 (t, JFP ) 7.6 Hz, o-CF), -115.64 (s, p-CF).
Catalytic and Stoichiometric Experiments. These were carried out
4
{1H} NMR (CDCl3/PhCl/THF): δ 24.93/29.36/29.31 (td, JFP ) 7.3
in NMR tubes (5 mm) similarly as reported before.1
6
Hz, JFP ) 2.4 Hz). Anal. Calcd for C42H30ClF5P2Pd: C, 60.52; H,
Determination of Equilibria in Equations 2 and 3. NMR tubes
(5 mm) were charged with 4c (5.9 ( 0.1 mg) and an excess of PPh3.
The samples were dissolved under N2 in THF, PhCl, or CH2Cl2 and
taken to a volume of 600 ( 5 µL, giving a concentration of (10.0 (
0.2) × 10-2 mol L-1 in Pd. An acetone-d6 capillary was introduced
(for NMR lock), and the tubes were placed into a thermostated probe
at 323.2 ( 0.2 K (the temperature was checked by an ethylene glycol
standard method). After several minutes, 19F and 31P{1H} spectra were
carefully acquired using relaxation times long enough for meaningful
integration of signals of the complexes 4c, 5c+, or 7c+, and free PPh3.
Numerical analysis leads to the K values reported for eqs 2 and 3.
NMR Characterization of trans-[Pd(C6Cl2F3)(CHdCH2)(PPh3)2]
(10). A crude sample of 10 was obtained as follows. Complex 4c (300
mg, 0.306 mmol) was dissolved in CH2Cl2 (30 mL) and heated at 50
°C in a septum-capped tube. Organotin 2 (1.80 mL, 6.12 mmol) was
then added via syringe, whereupon the solution suddenly turned deep
brown. After 30 min, the mixture was cooled in an ice bath and
evaporated to dryness. The residue was washed with cold n-hexane (2
× 10 mL) to remove the excess of 2 and then extracted in diethyl
ether (3 × 10 mL). Evaporation of the ethereal solution at 0 °C afforded
a greenish powder which contained about 70% of 10. This degree of
purity sufficed for unambiguous NMR characterization. 1H NMR
(CDCl3): δ 7.5-7.3 (m, arom-CH), 6.32 (ddt, transJHH ) 18.3 Hz, cisJHH
3.63. Found: C, 60.76; H, 3.77.
6b (95%). IR (KBr): 1057 (vs), 1045 (vs), 780 (vs), 702 (vs). H
1
(CDCl3): δ 7.62 (m, 2 CH), 7.45-7.30 (m, 3 CH). 19F NMR (CDCl3/
PhCl/THF): δ -116.46/-111.82/-112.51 (m, o-CF), -161.77/-
157.59/-159.33 (t, 3JFF ) 20.3 Hz, p-CF), -163.00/-158.44/-160.02
(m, m-CF). Anal. Calcd for C42H30As2ClF5Pd: C, 54.75; H, 3.28.
Found: C, 54.53; H, 3.44.
trans-[Pd(C6Cl2F3)(THF)(PPh3)2](BF4) (7c‚(BF4)). Complex 6c
(0.136 g, 0.157 mmol) was added to a stirred solution of AgBF4 (30.5
mg, 0.157 mmol) in THF (6 mL) shielded from the light. The mixture
was stirred for 30 min. The AgCl formed was carefully filtered off,
and the solution was evaporated to dryness. The white residue was
dissolved in CH2CH2 (2 mL) and THF (one drop), layered with
n-hexane (3 mL), and kept at -28 °C. Separated microcrystalline 7c‚
[BF4] was collected and dried with N2 (55%). IR (KBr): 1634 (m),
1482 (m), 1435 (vs), 1410 (vs), 1098 (vs), 1084 (s), 1053 (s), 998 (m),
1
779 (m), 744 (m), 707 (m), 693 (vs), 523 (vs), 511 (s), 495 (m). H
NMR (CDCl3): δ 7.6-7.4 (m, 30 H, CH), 3.72 (m, 4 H, OCH2), 1.84
(m, 4 H, CCH2). 19F NMR (CDCl3/PhCl/THF): δ -91.87/-87.36/-
4
6
87.40 (t, JFP ) 7.6 Hz, o-CF), -118.58/-114.52/-116.18 (t, JFP
)
2.9 Hz, p-CF), -154.71/-145.04/-154.21 (s, BF4-). 31P{1H} NMR
(CDCl3/PhCl/THF): δ 23.44/27.46/27.50 (td, JFP ) 7.5 Hz, JFP
4
6
)
3
cis
3.0 Hz). Anal. Calcd for C46H38BCl2F7OP2Pd: C, 55.82; H, 3.87.
Found: C, 55.77; H, 3.68.
Sn(C6Cl2F3)Bu3 (11). SnClBu3 (3.48 mL, 12.8 mmol) was slowly
added to a solution of [Li(C6Cl2F3)] (14.02 mmol) in diethyl ether (60
) 11.3 Hz, JHP ) 9.0 Hz, CHPd), 5.16 (broad d,
J
) 11.3 Hz,
HH
4
4JHP < 3 Hz, CCH), 4.14 (broad d,
J
) 18.3 Hz, JHP < 3 Hz,
trans
HH
CCH). 19F NMR (CDCl3/PhCl/THF/CH2Cl2): δ -90.85/-85.79/-
86.10/-86.67 (t, 4JFP ) 3.1 Hz, o-CF), -123.13/-118.22/-119.46/-

11782 J. Am. Chem. Soc., Vol. 122, No. 48, 2000
Casado et al.
6
119.51 (t, JFP ) 2.0 Hz, p-CF). 31P{1H} NMR (CDCl3/PhCl/THF/
VA80-99), and fellowships to A.L.C. and A.M.G. from the
Ministerio de Educacio´n y Cultura are very gratefully acknowl-
edged. We are indebted to the technical services of the
Universidad de Vigo for the high-resolution mass spectrum of
C6F5-OTf.
4
6
CH2Cl2): δ 28.38/32.72/32.7/32.0 (td, JFP ) 3.1 Hz, JFP ) 2.0 Hz).
Acknowledgment. Financial support by the Direccio´n
General de Investigacio´n Cient´ıfica y Te´cnica (Project No.
PB96-0363) and the Junta de Castilla y Leo´n (Project No.
JA001511O