C-C reductive elimination in palladium complexes, and the role of coupling additives. A DFT study supported by experiment

Article abstract of DOI:10.1021/ja808036j

A DFT study of R-R reductive elimination (R = Me, Ph, vinyl) in plausible intermediates of Pd-catalyzed processes is reported. These include the square-planar tetracoordinated systems cis- [PdR₂ (PMe ₃)₂] themselves, possi

Full text of DOI:10.1021/ja808036j

Published on Web 02/20/2009
C-C Reductive Elimination in Palladium Complexes, and the
Role of Coupling Additives. A DFT Study Supported by
Experiment
Mart´ın Pe´rez-Rodr´ıguez,† Ataualpa A. C. Braga,| Max Garcia-Melchor,‡
Mo´nica H. Pe´rez-Temprano,§ Juan A. Casares,§ Gregori Ujaque,‡ Angel R. de
†
,†
Lera, Rosana Alvarez,* Feliu Maseras,*,‡,| and Pablo Espinet*,§
´
Departamento de Qu´ımica Orga´nica, Facultad de Qu´ımica, UniVersidade de Vigo,
Lagoas-Marcosende s/n, 36310 Vigo, Galicia, Spain, Institute of Chemical Research of Catalonia
(ICIQ), AV. Pa¨ısos Catalans, 16, 43007 Tarragona, Catalonia, Spain, Unitat de Qu´ımica F´ısica,
Edifici Cn, UniVersitat Auto`noma de Barcelona, 08193 Bellaterra, Catalonia, Spain, and
IUCINQUIMA/Qu´ımica Inorga´nica, Facultad de Ciencias, UniVersidad de Valladolid,
47071 Valladolid, Castilla y Leo´n, Spain
Received October 11, 2008; E-mail: rar@uvigo.es; fmaseras@iciq.es; espinet@qi.uva.es
Abstract: A DFT study of R-R reductive elimination (R ) Me, Ph, vinyl) in plausible intermediates of
Pd-catalyzed processes is reported. These include the square-planar tetracoordinated systems cis-
[PdR2(PMe3)2] themselves, possible intermediates cis-[PdR2(PMe3)L] formed in solution or upon addition
of coupling promoters (L ) acetonitrile, ethylene, maleic anhydride (ma)), and tricoordinated intermediates
cis-[PdR2(PMe3)] (represented as L ) empty). The activation energy ranges from 0.6 to 28.6 kcal/mol in
the gas phase, increasing in the order vinyl-vinyl < Ph-Ph < Me-Me, depending on R, and ma < “empty”
< ethylene < PMe3 ≈ MeCN, depending on L. The effect of added olefins was studied for a series of
olefins, providing the following order of activation energy: p-benzoquinone < ma < trans-1,2-dicyanoethylene
< 3,5-dimethylcyclopent-1-ene < 2,5-dihydrofuran < ethylene < trans-2-butene. Comparison of the
calculated energies with experimental data for the coupling of cis-[PdMe2(PPh3)2] in the presence of additives
(PPh3, p-benzoquinone, ma, trans-1,2-dicyanoethylene, 2,5-dihydrofuran, and 1-hexene) reveals that: (1)
There is no universal coupling mechanism. (2) The coupling mechanism calculated for cis-[PdMe2(PMe3)2]
is direct, but PPh3 retards the coupling for cis-[PdMe2(PPh3)2], and DFT calculations support a switch of
the coupling mechanism to dissociative for PPh3. (3) Additives that would provide intermediates with coupling
activation energies higher than a dissociative mechanism (e.g., common olefins) produce no effect on
coupling. (4) Olefins with electron-withdrawing substituents facilitate the coupling through cis-
[PdMe2(PR3)(olefin)] intermediates with much lower activation energies than the starting complex or a
tricoordinated intermediate. Practical consequences are discussed.
Introduction
cumulated in the past decade or so and discussed the role of
each partner (reactive ligands and ancillary ligands, electronic,
The field of transition metal-catalyzed C-C and C-Het
coupling processes1-3 has witnessed an explosion of empirical
research aimed at the promotion of otherwise difficult reactions.
Notable among those are the C-C coupling of aryl chlorides
with a variety of organometallic partners (B, Sn, Mg, or Zn
nucleophiles),4,5 and the formation of C-Het (N, O, S) bonds.6,7
Hartwig has nicely summarized the experimental results ac-
and steric effects) on the coupling rate and efficiency.8 One
interesting conclusion is that C-C and C-Het couplings can
be discussed under very similar schemes. Novel bulky
phosphines9,10 and carbene ligands11 have been instrumental to
facilitate these processes. The role of solvents and additives has
been investigated.4 Kinetic analysis of the processes, isolation
of reaction intermediates, monitoring of the evolution of these
species,4,12,13 and computational studies14-17 have corroborated
or modified mechanistic proposals, or suggested stimulating
† Universidade de Vigo.
| ICIQ.
‡ Universitat Auto`noma de Barcelona.
§ Universidad de Valladolid.
(4) Espinet, P.; Echavarren, A. M. Angew. Chem., Int. Ed. 2004, 43, 4704–
4734.
(1) Brown, J. M.; Cooley, N. A. Chem. ReV. 1988, 88, 1031–1046.
(2) Ozawa, F. Reductive Elimination. In Fundamentals of Molecular
Catalysis; Kurosawa, H., Yamamoto, A., Eds.; Elsevier: New York,
2003; Vol. 3, pp 479-511.
(3) (a) de Meijere, A.; Diederich, F.; Metal Catalyzed Cross-Coupling
Reactions, 2nd ed.; John Wiley & Sons: New York, 2004. (b) Tamao,
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3650 J. AM. CHEM. SOC. 2009, 131, 3650–3657
10.1021/ja808036j CCC: $40.75
2009 American Chemical Society

C-C Reductive Elimination in Palladium Complexes
A R T I C L E S
Scheme 1
alternative mechanistic views. Nowadays, the excessively
schematic mechanisms of metal-catalyzed cross-coupling reac-
tions are being revisited, and more detailed and complex views
are replacing the traditional beliefs.
Recent results show that each of the main steps in the catalytic
cycle of Pd-catalyzed coupling reactions (oxidative addition,
transmetalation, isomerization, and reductive elimination) can be
rate determining, depending on the reagents, the ligands, the solvent,
and the additives.4 Often taken for granted, the final C-C or C-Het
coupling is critical for the success of the reaction, as the other steps
are frequently reversible,13 and it is the irreversible reductive
elimination that must pull the catalytic cycle forward. Since the
early theoretical works of Tatsumi, Hoffmann, Yamamoto and
Stille,18 and Low and Goddard,19 the reductive elimination step
had received scant attention, but recently Ananikov, Musaev, and
Morokuma carried out extensive studies on the C-C reductive
elimination, in the gas phase, of the most common types of coupling
partners in square-planar cis-[MRR′(PH3)2] complexes (R or R′ )
methyl, vinyl, phenyl, alkynyl; M ) Pd, Pt).20 Moreover, Bo et
al. studied the effect of the bite angle of chelating diphosphines
on the formation of C-C and C-O bonds.21 The feasibility of
Ar-F elimination from Pd(II) has been theoretically assessed and
then experimentally addressed.22 Finally, during the development
of the present study, Ananikov, Musaev, and Morokuma published
a theoretical investigation of the reductive elimination from square
planar and T-shaped Pd species with phosphines of different
bulkiness.23 Despite these recent contributions, the theoretical
description of the reductive elimination step is still rather incom-
plete. For instance, the role of additives, solvents, or other ligands
present in solution is not well understood, and the feasibility under
experimental circumstances of the species proposed in-silico has
not been experimentally tested. This article reports theoretical
results on cis-[PdMe2(PMe3)L] systems that model some C-C
coupling conditions, which are then compared to experimental
results on cis-[PdMe2(PPh3)2] + L systems.
intermediates formed in the presence of solvents, ligands, or
coupling additives. The ancillary ligand PMe3 was chosen as a more
realistic phosphine model than PH3. Nonsymmetrical complexes
(PdRR′L2) were spared because it has been shown that their
computed activation energies are roughly the average between those
of their symmetrical counterparts;20 note, however, that experi-
mental evidence shows that coupling rates are faster for PdRR′L2
than for PdR2L2 or PdR′2L2.8 The following L ligands were used:
(i) L ) PMe3 gives square-planar tetracoordinated complexes cis-
[MR2(PMe3)2]; (ii) L ) MeCN models σ-donor coordinating
solvents of moderate donating ability; (iii) L ) ethylene represents
π-coordinating molecules present in solution in cross-coupling
reactions involving vinyl, allyl, and other CdC containing moi-
eties,24 for example, the starting electrophile or the coupling
product; (iv) L ) ma (maleic anhydride, an electron-withdrawing
olefin) was included due to reports showing that electron-withdraw-
ing olefins are additives that promote the reductive elimination
step;25 and (v) finally, L ) “empty position” represents tricoordi-
nated T-shaped cis-[PdR2(PR3)] complexes with only one ancillary
phosphine ligand, suggested by kinetic studies to be coupling
intermediates in some cases.10,18,26 Evidence for the formation of
monophosphine complexes with one bulky phosphine as the only
ancillary ligand includes crystal structures of apparently tricoordi-
nated complexes, in which Pd turns out to be stabilized by weak
agostic interactions,27,28 and also true T-shaped complexes.28
A
theoretical study of the factors making T-shaped palladium
complexes more accessible has appeared very recently.29
As this work was progressing, the experimental tests in parallel
to the initial calculations pushed us to extend the models to gain
insight on the effect of olefins. On the other hand, a study dealing
with case (v) appeared, which covered some aspects pursued in
this chapter of our study.23 Our data on case (v) are still needed in
the context of our discussion, but, for the sake of page economy,
only the novel aspects of tricoordinated intermediates will be dealt
with in the text, while more information is given in the Supporting
Information.
Computational Models
The models chosen, cis-[PdRR(PMe3)(L)] (R ) Me, vinyl, and
Ph) complexes, represent, depending on L, plausible coupling
(12) Casares, J. A.; Espinet, P.; Fuentes, B.; Salas, G. J. Am. Chem. Soc.
2007, 129, 3508–3509.
Results and Discussion
(13) Pe´rez-Temprano, M. H.; Nova, A.; Casares, J. A.; Espinet, P. J. Am.
Chem. Soc. 2008, 130, 10518–10520.
Overall Reaction Profile. The reductive elimination process
shows four significant stages in the reaction profile (Scheme
1):19-21,23 (i) the cis reactant species, 1; (ii) the transition state
TS1-2; (iii) an intermediate adduct, 2, with the R-R coupling
product weakly bound to the metal center; and (iv) the coupling
product already separated from the Pd(0) complex (stage 3).
Each stage was computed for all R and L combinations (R )
(14) Niu, S.; Hall, M. B. Chem. ReV. 2000, 100, 353–405.
(15) Goossen, L. J.; Koley, D.; Hermann, H. L.; Thiel, W. J. Am. Chem.
Soc. 2005, 127, 11102–11114.
(16) (a) Braga, A. A. C.; Morgon, N. H.; Ujaque, G.; Maseras, F. J. Am.
Chem. Soc. 2005, 127, 9298–9307. (b) Nova, A.; Ujaque, G.; Maseras,
F.; Lledos, A.; Espinet, P. J. Am. Chem. Soc. 2006, 128, 14571–14578.
(c) Braga, A. A. C.; Ujaque, G.; Maseras, F. Organometallics 2006,
25, 3647–3658.
(17) (a) Alvarez, R.; Faza, O. N.; López, C. S.; de Lera, A. R. Org. Lett.
´
2006, 8, 35–38. (b) Alvarez, R.; Faza, O. N.; de Lera, A. R.; Ca´rdenas,
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D. J. AdV. Synth. Catal. 2007, 349, 887. (c) Alvarez, R.; Pe´rez, M.;
(24) Albe´niz, A. C.; Espinet, P.; Mart´ın-Ruiz, B. Chem.-Eur. J. 2001, 7,
2481–2489.
Faza, O. N.; de Lera, A. R. Organometallics 2008, 27, 3378–3389.
(18) Tatsumi, K.; Hoffmann, R.; Yamamoto, A.; Stille, J. K. Bull. Chem.
Soc. Jpn. 1981, 54, 1857–1867.
(25) (a) Goliaszewski, A.; Schwartz, J. J. Am. Chem. Soc. 1984, 106, 5028–
5030. (b) Goliaszewski, A.; Schwartz, J. Tetrahedron Lett. 1985, 26,
5779–5789. (c) Kluwer, A. M.; Elsevier, C. J.; Bu¨hl, M.; Lutz, M.;
Spek, A. L. Angew. Chem., Int. Ed. 2003, 42, 3501–3504. (d)
Sustmann, R.; Lau, J. Chem. Ber. 1986, 119, 2531–2541.
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(27) (a) Stambuli, J. P.; Buhl, M.; Hartwig, J. F. J. Am. Chem. Soc. 2002,
124, 9346–9347. (b) Stambuli, J. P.; Incarvito, C. D.; Buhl, M.;
Hartwig, J. F. J. Am. Chem. Soc. 2004, 126, 1184–1194.
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(20) Ananikov, V. P.; Musaev, D. G.; Morokuma, K. Organometallics 2005,
24, 715–723.
(21) Zuidema, E.; Van Leeuwen, P. W. N. M.; Bo, C. Organometallics
2005, 24, 3703–3710.
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(23) Ananikov, V. P.; Musaev, D. G.; Morokuma, K. Eur. J. Inorg. Chem.
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A R T I C L E S
Pe´rez-Rodr´ıguez et al.
Table 1. Thermodynamic Data (∆Gq in kcal/mol, Relative to
Reactant 1) for the Reductive Elimination of R-R Starting from the
cis-[PdR2(PMe3)(L)] Complexes
a
R
L
TS1-2
2a
3a
Me
ma
8.6
13.2
21.7
27.0b
28.6
2.9
-43.0
-19.9
-34.8
-32.9
-35.0
-46.4
-33.3
-30.9
-31.2
-33.9
-56.2
-39.9
-43.0
-32.6
-36.1
-49.3
-25.6
-43.7
-37.8
-43.1
-50.7
-27.2
-43.7
-36.1
-41.9
-51.9
-24.9
-43.3
-35.6
-40.1
empty
CH2CH2
MeCN
PMe3
Ph
ma
empty
CH2CH2
MeCN
PMe3
4.9
11.3
13.2
12.8
0.6
4.9
8.9
vinyl
ma
empty
CH2CH2
MeCN
PMe3
11.9
11.5
a In gas phase. Values in acetonitrile including solvation energies
using a continuum model are given in the Supporting Information.
b This value corresponds to the overall energy barrier for the stepwise
mechanism (see text).
from cis-[PdR2(PMe3)L]. The trend of computed barriers is
Csp3-Csp3 > CAr-CAr > Csp2-Csp2 for any series with an
identical L ligand (occasional exceptions within the error of
calculation are found for very similar values of CAr-CAr and
Csp2-Csp2 data). This and the trends in bond angles and lengths
(Supporting Information) are in coincidence with the sequences
reported for cis-[PdR2(PH3)2] complexes.20
In general, the structures where Me-Me elimination occurs
deviate from planarity, and the corresponding transition states
TS1-2 show distorted tetrahedral structures around the metal.
In contrast, the complexes with Ph or vinyl groups feature almost
planar TS1-2 structures. The higher directionality of the
M-C(sp3) bond, its weaker M-C bond dissociation energy,
and a larger influence of steric effects have been deemed
responsible for these structural differences.20 Whereas the
activation energies reported for PH3 complexes are about 4 times
lower for the Csp2-Csp2 relative to the Csp3-Csp3 bond
formation,20 the differences calculated for the bulkier PMe3
ligand are significantly smaller (2.5-fold at most). This could
be due to a destabilization of the reactants 1 for R ) Me, arising
from the higher crowding with PMe3 as compared to PH3, which
could attenuate the differences in energy for higher absolute
values. All of the coupling processes are strongly exothermic,
which makes the C-C coupling irreversible. Values differing
by as much as 25 kcal/mol are computed for eliminations
starting from tricoordinated Pd versus tetracoordinated Pd
complexes. For the latter, the more exothermic reductive
eliminations for each R are those with ma as auxiliary ligand,
followed by those with ethylene, phosphine, and acetonitrile.
The significance of these thermodynamic results should not be
overemphasized, however, as its connection to the experimental
conditions is not straightforward. Considering, for instance, a
catalytic process in the presence of excess PMe3 as auxiliary
ligand and with ma as coupling promoter, the most likely
Pd(II) species in solution preceding the coupling will be
[PdR2(PMe3)2], in equilibrium with minute amounts of a
[PdR2(PMe3)(ma)] intermediate, due to the fact that PMe3 is a
much better ligand toward Pd(II) than is ma. On the other hand,
coordination of the strongly acceptor ma is much better in the
Figure 1. Optimized geometry of the reactant 1 and the transition state
TS1-2 for the reductive elimination of ethane. (A) L ) PMe3; (B) L )
MeCN; (C) L ) empty; (D) L ) CH2CH2; (E) L ) ma. Relevant selected
distances (Å) are shown.
Me, Ph, vinyl; L ) empty position, ethylene, PMe3, ma, MeCN).
Details of the 60 computed geometries, tables of selected
geometrical parameters, and a discussion of the geometrical
changes along the reductive elimination are given as Supporting
Information.
The structures of the reactants and the transition states are
shown in Figure 1 for R ) Me (for the other R groups the
coordination geometries are similar). Fairly symmetrical con-
comitant shortening of the C-C distance and elongation of the
Pd-C distances is observed as the reactants evolve to their
transition states. For L ) empty, the coupling is direct. For L
* empty, the calculation predicts also direct coupling, now in
the tricoordinated complex. As an exception (not found in any
of the published studies), for R ) Me and L ) MeCN a stepwise
mechanism is predicted, initiated by MeCN dissociation and
followed by coupling in the resulting tricoordinated complex.
It makes sense that the case of a dissociative coupling is found
in the calculation for the combination of the strongest R σ-donor
(Me) with MeCN, which is a weak donor, non π-acceptor ligand.
Influence of the R Group on the Energy Barrier. Table 1
gathers ∆Gq data calculated for the 15 reductive eliminations
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C-C Reductive Elimination in Palladium Complexes
A R T I C L E S
Scheme 2
reduced Pd(0) complex [Pd(PMe3)2(ma)].30 Consequently, the
thermodynamic balance for the experimental reductive elimina-
tion might well correspond to a process going from PdR2(PMe3)2
+ ma to Pd(PMe3)2(ma) + R-R, rather than any of the direct
coupling models studied here.
Figure 2. Key orbital interactions in the transition state for reductive
elimination from tricoordinated complexes (left) and tetracoordinated
complexes (right).
addition is the result of a side-on coordination of the single
bond to the metal; σ-donation from the R-R σ bonding orbital
plus back-donation from the metal to the R-R σ* antibonding
orbital will eventually break the R-R bond. In fact, the
geometries observed for the transition states TS1-2, which are
very symmetric for R ) phenyl and vinyl, and less so but still
fairly symmetric for R ) Me, support this mechanism.
The Ts1-2 values in Table 1 indicate that, for each R group
considered, the activation energy for different L ligands
decreases in the order MeCN ≈ PMe3 > CH2CH2 > “empty” >
ma. The range of energy values is large, and larger for the
complexes with R ) Me reflecting the higher absolute values
involved in the reductive elimination of this group. Synthetic
interest is usually to favor the coupling, and we will discuss in
the following sections the reasons why the cases of L ) empty
and L ) ma are particularly favorable.
The geometry of the C-Pd-C triangle is relatively similar
for all of the computed tetracoordinated transition states, but
the reductive elimination from tricoordinated complexes (the
case L ) empty) is different from the others, as this is the only
case where the bond is formed in a position trans to the
phosphine ligand (Figure 1). The qualitative difference in
reductive elimination from tetracoordinated or from tricoordi-
nated complexes has been previously noted and analyzed using
simple extended Hu¨ckel descriptions,18,32 and by DFT calcula-
tions in a recent study.23 Those computational studies and ours
show that the reductive elimination is easier for the tricoordi-
nated systems. This lower reductive elimination barrier in
tricoordinated systems (L ) “empty”) can be explained con-
sidering the orbital interactions shown in Figure 2. The key
factor is the different occupation of the σM orbital for 3-coor-
dinated and 4-coordinated d8 complexes in the corresponding
symmetry.33 Whereas for both types of complex the interactions
roughly corresponding to π-symmetry are bonding, those
roughly corresponding to σ-symmetry are repulsive for the two
interacting full orbitals in the 4-coordinated system, but bonding
for the empty-full interaction in the 3-coordinated system. This
orbital diagram also explains the fact that the forming C-C
bond is placed trans to the phosphine in the tricoordinated
system. It follows as well from this diagram that any external
The activation barriers calculated are much higher for R )
Me than for R ) Ph or vinyl, both in vacuum and in continuum
MeCN solution. The values for the coupling of Csp3 centers
are so high in some cases (e.g., ca. 28.6 kcal/mol when L )
PMe3) that this step becomes a likely candidate to be rate
determining in a cycle. In other words, failures in coupling alkyl
organometallics with alkyl halides or pseudohalides should not
be attributed cursorily to the oxidative addition or the trans-
metalation step. For R ) Ph and vinyl, the activation barriers
are smaller and likely less critical for synthetic purposes. It is
worth mentioning that a continuum solvent correction (see
Supporting Information) increases more the calculated barriers
for R ) vinyl, making vinyl and phenyl barriers similar.
Very interestingly, Table 1 reveals that the influence of R is
not necessarily prevailing over other factors, and can be
overcome if different L ligands are used to couple different R
groups (i.e., cis-[PdR2(PMe3)L] versus cis-[PdR′2(PMe3)L′]). In
other words, the nature of L is extremely important.
Influence of the L Group on the Coupling Barrier. This factor
has not been theoretically considered in the literature. In an
experimental reaction using phosphines as the initial ligands,
the model complexes studied here could be interconnected by
ligand-substitution or ligand-dissociation equilibria (Scheme
2).31 The reductive elimination would take place from tetraco-
ordinated (pathways 1 and 2) or tricoordinated (pathway 3)
complexes and should be the microscopic reverse of the
oxidative addition of a nonpolar C-C bond. The latter is
believed to follow a concerted mechanism,2 where the oxidative
(30) Espinet, P.; Albe´niz, A. C. In ComprehensiVe Organometallic Chem-
istry; Mingos, D. M. P., Crabtree, R. H., Canty, A., Eds.; Elsevier:
Oxford, 2007; Vol. 8, pp 317-332.
(31) In principle, these equilibria could be analyzed theoretically from the
computed ligand dissociation energies, collected in Table SI4 of the
Supporting Information, but estimation of these specific equilibrium
constants with the computational methods applied is troublesome. In
fact, the two magnitudes reported, potential energy and free energy,
present sharply different values, with differences around 16 kcal/mol.
This discrepancy proves the importance of entropic corrections in these
bimolecular processes. Unfortunately, in our computational approach,
these particular terms are estimated through assumption of ideal gas
behavior of the molecules, which is obviously not the optimal choice
for systems in solution. Moreover, experimental reactions can be
carried out in solvents of very different polarity. Thus, rather than
focusing on the intrinsically inaccurate estimation of these equilibrium
constants, we decided to analyze the trends in the computed activation
barriers associated with the different ligands, where entropic contribu-
tions are less critical.
(32) Tatsumi, K.; Nakamura, A.; Komiya, S.; Yamamoto, A.; Yamamoto,
T. J. Am. Chem. Soc. 1984, 16, 8181–8188.
(33) Jean, Y. Molecular Orbitals of Transition Metal Complexes; Oxford
University Press: London, 2005.
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Pe´rez-Rodr´ıguez et al.
factor withdrawing density from the σM orbital in a 4-coordi-
nated molecule will lower the barrier for reductive elimination
in tetracoordinated compounds.
The low barrier associated with the tricoordinated system has
important mechanistic implications. If there is a weak ligand,
or if the crowding in the tetracoordinated complex is high,
tricoordination will be more easily accessible,29 and it may be
energetically more efficient for the system to release one ligand
and undergo reductive elimination from the tricoordinated
species (pathway 3 in Scheme 2). In fact, this is what we find
in our calculations for cis-[PdMe2(PMe3)(NCMe)], and in our
experiments for cis-[PdMe2(PPh3)2] (see later). Dissociative
coupling might be fairly general for reasonably hindered
compounds.
For the cases found to couple directly in cis-[PdMe2(PMe3)L],
the trend PMe3 > CH2CH2 > ma confirms that the barrier
decreases with the π-acceptor ability of L. As discussed above,
the more π-acceptor the ligand, the lower should be the coupling
barrier because they draw electron density away from the σM
and this orbital is antibonding in the transition state. Consis-
tently, ethylene is a better π-acceptor than is PMe3 and produces
a lower coupling barrier. The barrier for ma is even lower
because it is a much stronger π-acceptor,34,35 to the point that
the coupling is calculated to be easier for the tetracoordinated
complex with ma than for the tricoordinated species (for R )
Me, ∆Gq is 21.7 for L ) ethylene, 13.2 kcal/mol for the
tricoordinated species, and 8.6 kcal/mol for L ) ma).
Electronic and Structural Factors in Olefins. The structures
of the reactant 1 and the transition state TS1-2, for ethylene
and ma (Figure 1), show that for ethylene the olefin rotates from
a perpendicular to an “in-plane” coordination during the reaction,
whereas ma is coordinated in-plane already in the reactant. The
olefin orientation is defined by the Pd-P-X-Colefin dihedral
angle, where X is the midpoint of the CdC bond. In the reactant,
the dihedral angle is 89.0° for ethylene, but only 9.0° for MA.
In the transition state, however, the double bond is practically
in the metal plane in both cases (dihedral values of 0.1° for
CH2CH2, and 6.5° for ma). To examine this matter, additional
systems with the ligands trans-2-butene, fumaronitrile (trans-
1,2-dicyanoethylene), 3,5-dimethylcyclopent-1-ene, and 2,5-
dihydrofuran were studied. Fumaronitrile was chosen as a strong
π-accepting olefin with no hindrance to perpendicular coordina-
tion; 3,5-dimethylcyclopent-1-ene is a conjugated cyclic olefin
with expectedly medium π-acceptor properties; 2,5-dihydrofuran
is a cyclic olefin structurally very similar to ma, but without
electron-withdrawing substituents; and trans-2-butene is steri-
cally similar to trans-1,2-dicyanoethylene, but lacks strong
electron-withdrawing substituents. Only the reactant and the
transition state with R ) Me were computed for these systems.
The key results are summarized in Figure 3 for the geometries,
and in Table 2 for the computed energy barriers.
Figure 3. Optimized geometry of the reactant 1 and the transition state
TS1-2 for additional olefins with different steric and electronic features.
(F) L ) trans-2-butene; (G) L ) trans-1,2-dicyanoethylene; (H) 2,5-
dihydrofuran; (I) L ) 3,5-dimethylencyclopent-1-ene; (J) L ) p-benzo-
quinone. Relevant selected distances (in Å) are shown.
Table 2. Computed Energy Barrier (∆Gq, kcal/mol) and Orientation
(deg) of Olefin for the Reductive Elimination of Me-Me Starting
from the cis-[PdMe2(PMe3)(L)] Complexes
P-Pd-X-
Colef (1)
P-Pd-X-
Colef (TS1-2)
entry
L
∆Gq
1
2
3
4
5
6
7
8
trans-2-butene
ethylene
23.0
21.7
19.8
15.9
10.0
8.6
65.1
89.0
88.3
13.5
71.7
9.0
4.2
0.1
-0.4
-0.4
6.0
6.5
-2.4
2,5-dihydrofuran
3,5-dimethylcyclopent-1-ene
trans-1,2-dicyanoethylene
maleic anhydride
p-benzoquinone
empty
The computed geometries show that, for the transition state,
the torsion angle is always close to 0°, regardless of the structure
aspect of the olefin. The in-plane arrangement observed for
TS1-2 is also observed in the final Pd(0) product (stage 3) and
5.9
13.2
10.9
(34) Albe´niz, A. C.; Espinet, P.; Pe´rez-Mateo, A.; Nova, A.; Ujaque, G.
Organometallics 2006, 25, 1293–1297.
in the structures found experimentally for [PdL2(olefin)] com-
plexes.30 Along with an incipient Me-Me bond (compare C-C
distances of about 2.8 Å in the Pd(II) reactants 1 with 2.1-2.2
Å in TS1-2 and 1.54 Å for a C-C single bond), the transition
states show a clear elongation (about 0.03-0.04 Å) of the
coordinated CdC double bond, reflecting the increased electron
(35) The ma ligand is a very strong π-acceptor, to the point that the
oxidation level of its formally Pd(0) complexes must be relatively
high. This is shown, for instance, by the fact that these complexes are
air stable and difficult to oxidize (see refs 30 and 33). It looks
reasonable that, as the reductive elimination progresses, the overall
π-acceptance will increase more steeply for ma than for other poorer
π-acceptors, making this lowering of the barrier particularly effective.
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3654 J. AM. CHEM. SOC. VOL. 131, NO. 10, 2009

C-C Reductive Elimination in Palladium Complexes
A R T I C L E S
back-donation to the olefin π* orbitals. This supports the
qualitative orbital diagram proposed in Figure 2, which predicts
strong electronic preference for the in-plane arrangement in
TS1-2
.
There is no general preferred arrangement of the olefin for
the reactants 1. Angles spanning the whole range 0-90° are
found, apparently not related to the π-acceptor strength of the
olefin. Typically, simple olefins coordinate to Pd(II) with the
double bond roughly perpendicular to the coordination
plane (entry 2), or making a somewhat smaller angle to minimize
interligand repulsion (entries 1 and 5). It would appear that for
cyclic-planar olefins the in-plane coordination is favored (entries
4, 6, and 7), but this is not the case of 2,5-dihydrofuran (entry
3). Inspection of the calculated structures suggests that often
there are only minor differences (1-3 kcal/mol) for alternative
arrangements and in many cases the minimum might be dictated
by subtle steric repulsions. Hence, although one could wonder
whether the in-plane coordination of the double bond “prepares”
the reactant for reductive elimination, in fact there is no
conclusive support for this (nor against) in Table 2.36
There is, however, a clear relationship with the electronic
effect of the olefin substituents. Comparing for instance entries
1, 2, and 5, the substituents have only a small effect on the
structure, which should hardly affect the energy barrier, and
the sequence of ∆Gq observed (trans-2-butene > CH2CH2 >
trans-1,2-dicyanoethylene) corresponds to the increase of
electron withdrawal (or decrease of electron donation) of the
substituents. This electronic effect is expected to be smaller for
the reactant, where the π back-donation ability of Pd(II) is
modest,37 than for the transition state, which is very much
stabilized by electron withdrawal from the antibonding orbital
σM (Figure 2). Replacement of H by Me (entry 1 vs 2) brings
about only a minor increase in activation barrier of 1.3 kcal/
mol, while the inclusion of strong π-acceptor substituents (Ct N
or CdO) produces a substantial lowering of the barrier. The
differences of 13 kcal/mol between trans-2-butene and fuma-
ronitrile (entries 1 and 5), and 11.2 kcal/mol between 2,5-
dihydrofuran and maleic anhydride (entries 3 and 6), clearly
reflect the enormous importance of the π-acceptor ability of L
on the reductive elimination process. Dimethylcyclopent-1-ene
(entry 4), a less strong acceptor olefin, produces intermediate
values. The optimal effects are achieved for maleic anhydride
and p-benzoquinone (entries 6 and 7), which appear very good
choices as coupling additives. Very interestingly, these and the
fumaronitrile (entries 5-7) provide a lower coupling barrier on
the tetracoordinated complex than the barrier for the tricoordi-
nated (entry 8).
Figure 4. Coupling conversion of [PdMe2(PPh3)2] (4) in acetone-d6 in the
presence of additives. Upper plot is at 250.7 K, for the fast reactions; for
the rest, no conversion is observed at this temperature. Lower plot is at
301.3 K, for the fast reactions; the conversion for fumaronitrile or
p-benzoquinone at this temperature is 100% in the first measurement and
is not plotted.
Experimental Studies on the System cis-[PdMe2(PPh3)2] +
Additive. The computational results above indicate clearly which
features in L should favor the reductive elimination in complexes
cis-[PdR2(PR′3)L]. It is difficult, however, to find in the literature
quantitative experimental support for these predictions, as in
operational catalytic systems the cis-[PdR2(PR′3)L] intermediates
should be non observable. We decided to study the systems
cis-[PdMe2(PPh3)2] (4) + additive (additive ) PPh3, ma,
p-benzoquinone, fumaronitrile, dihydrofuran, 1-hexene) in acetone-
d6.38 Three circumstances in the real system differ from the
theoretical conditions. First, the experimental phosphine used
is somewhat bulkier and less basic. Second, in the experimental
system, the corresponding complexes 1, where the calculation
starts, must be formed in solution (except for L ) PPh3) by
dissociation (for L ) empty) or by ligand substitution (Scheme
2), which means that not only the TS1-2 but also the preequi-
librium constant that determines the concentration of 1 will
influence the coupling rate observed. Finally, the experimental
reactions are studied in acetone-d6, which is a hard coordinating
solvent. In other words, the experimental study deals with a
related but not identical process, shown on top of Figure 4.
(36) An additional set of calculations we carried out to check whether the
energy barrier to olefin rotation could be relevant to the overall kinetics.
In these calculations, collected in the Supporting Information (Figure
SI5), we found two local minima for cis-[PdMe2(PMe3)(H2CdCH2)].
The most stable one is the out-of-plane species reported in the text; a
secondary in-plane species is 4.7 kcal/mol higher in energy. The
transition state between these two minima is only 1.2 kcal/mol above
the least stable minimum, indicative of a fast process at room
temperature.
(37) The filled d orbitals in square-planar Pd(II) complexes are very stable,
and this reduces their involvement in back donation. This can be noted,
for instance, in the fact that Pd(II)–carbene bonds show typical single
bond distances. See some X-ray structures in: (a) Albe´niz, A. C.;
Espinet, P.; Manrique, R.; Pe´rez-Mateo, A. Angew. Chem., Int. Ed.
2002, 41, 2363–2366. (b) Albe´niz, A. C.; Espinet, P.; Manrique, R.;
Pe´rez-Mateo, A. Chem.-Eur. J. 2005, 11, 1565–1573. (c) Albe´niz,
A. C.; Espinet, P.; Pe´rez-Mateo, A. Organometallics 2006, 25, 1293–
1297.
The experiments with maleic anhydride revealed the forma-
tion of ethane and methane, the latter associated with Pd-Me
acidolysis by maleic acid produced by the water contamination
of the acetone-d6 (Scheme 3). At low temperature, the formation
of the corresponding Pd(0) and Pd(II) products was confirmed.
Thus, although ma induces very fast coupling (comparable to
(38) PPh3 was used instead of the PMe3 used for calculations, due to its
much easier handling. The choice turned out to be fortunate, and PPh3
produced a range of coupling rates that could be monitored by 1H
NMR. Moreover, it contributed to reveal the importance of the steric
effect of the phosphine.
9
J. AM. CHEM. SOC. VOL. 131, NO. 10, 2009 3655

A R T I C L E S
Pe´rez-Rodr´ıguez et al.
[PdMe2(PPh2Me)2] upon addition of PPh2Me,18,41 in DMF or
THF, whereas coupling in tetracoordinated complexes was
calculated for complexes with PH3.20 On the other hand, a
dissociative mechanism was calculated here for cis-
[PdMe2(PMe3)(NCMe)]. Thus, the interpretation of the rest of
our calculated (with PMe3) and experimental (with PPh3) data
has to be made in the light of this propensity to dissociation
observed for the complexes with bulkier phosphines or with
weaker L ligands.
Scheme 3
Whereas the values in Table 2 predict a graduation of
coupling activation energy from cis-[PdMe2(PMe3)(olefin)] for
common olefins (entries 1-3), the experiments show no
difference for the coupling of cis-[PdMe2(PPh3)2] upon addition
of olefin, whether linear (1-hexene) or cyclic (dihydrofuran).
In these cases, the formation of small amounts in equilibrium
of a putative cis-[PdMe2(PPh3)(olefin)] is kinetically insignifi-
cant,42 and the coupling occurs via dissociation to the tricoor-
dinated [PdMe2(PPh3)] (path 3 in Scheme 2). As the replacement
of PMe3 by an olefin is even less favorable than that of PPh3,
it can be extrapolated that the addition of common olefins to
promote the coupling in cis-[PdMe2(PMe3)2] should also be
ineffective, regardless of the theoretical prediction that a cis-
[PdMe2(PMe3)(olefin)] intermediate would couple more easily
than cis-[PdMe2(PMe3)2], because that intermediate is not
expected to form in kinetically significant amounts.
Table 3. Experiments at ca. 300 K
additive
concentration/10-3 mmol
temperature/K
[4]o/10-3 mmol
none
PPh3
fumaronitrile
p-benzoquinone
maleic anhydride
2,5-dihydrofuran
1-hexene
301.6
301.6
301.0
301.3
301.3
301.3
301.1
1.06
1.06
1.06
1.06
1.06
1.06
1.06
1.02
3.28
3.40
3.12
3.10
3.12
Table 4. Experiments at ca. 250 K
additive
concentration/10-3 mmol
temperature/K
[4]o/10-4 mmol
fumaronitrile
p-benzoquinone
maleic anhydride
3.14
3.09
3.11
250.7
250.7
250.7
5.90
5.90
5.90
In contrast, the dramatic activating effect observed experi-
mentally for π-acceptor olefins (Figure 4) indicates that, in these
cases of considerably lower coupling barrier, the formation of
a small proportion of intermediate cis-[PdMe2(PPh3)(acceptor
olefin)] becomes kinetically decisive, and these olefins drive
the reaction through pathway 2 in Scheme 2. In this respect, it
is interesting to note that the recent use of chelating ligands
providing P and electron-deficient olefin coordinating ends,
P(acceptor olefin)R2, has led to a dramatic improvement in
efficiency of C(sp3)-C(sp3) and C(sp3)-C(sp2) couplings in
Suzuki and Negishi reactions.43 Obviously, the chelate effect
helps to increase the stability and concentration of a coupling
active intermediate cis-[PdR′R′′(P(acceptor olefin)R2)], and
likely that of the corresponding transition state.
p-benzoquinone), the actual rate could not be properly quanti-
fied. In a practical sense, ma looks to be a problematic coupling
additive in reactions where complete dryness cannot be
guaranteed.
For the other additives, the experimental results show a clear
division. The strongly π-acceptor olefins produce a dramatic
acceleration of the coupling, somewhat larger for the cyclic
olefin p-benzoquinone. The common olefins do not produce any
significant effect (the differences are within experimental error)
on the coupling rate shown by cis-[PdMe2(PPh3)2] alone. Finally,
the addition of PPh3 brings about retardation of the coupling,
which is an indication of prior dissociation of phosphine before
coupling takes place on a tricoordinated complex. This latter
result is in contrast with our calculation for cis-[PdMe2(PMe3)2],
where coupling occurs in the tetracoordinated complex. Hence,
the electronic and steric differences between PPh3 and PMe3
turn out to be mechanistically decisive, as dissociation becomes
more accessible for the bulkier phosphine. In fact, DFT
calculations for the dissociation process of cis-[PdMe2(PR3)2]
into cis-[PdMe2(PR3)] and PR3 afford markedly different values:
∆E 12.1 kcal mol for R ) Ph, versus 21.7 kcal mol for R )
Me, which makes a considerable difference of 9.6 kcal mol,
and clearly supports easier dissociation for R ) Ph.39 The
entropic contributions, difficult to compute accurately, would
further weigh in favor of a dissociative mechanism.40 Experi-
mental retardation of coupling had been reported for cis-
Conclusions
The C-C coupling in cis-[PdR2(PR′3)2] complexes can occur
directly, or on tetracoordinated intermediates cis-[PdR2(PR′3)L]
formed upon addition of an additive L, or on tricoordinated
intermediate [PdR2(PR′3)] formed by phosphine dissociation.
The size and nature of the R group and the phosphine, as well
as the coordinating features of L, have a determinant influence
on the coupling mechanism. The ancillary ligands used in
catalysis can be critical to the feasibility of a catalytic cycle.
In difficult couplings, the addition of olefins with electron-
withdrawing substituents as coupling promoters can be decisive
for the success of the coupling, as the formation of a coupling
(39) See also refs 23 and 29.
(41) Guillie, A.; Stille, J. K. J. Am. Chem. Soc. 1980, 102, 4933–4941.
(42) There are two reasons for this: (a) Assuming that the order of activation
energy found for PMe3 complexes is maintained for PPh3 complexes,
coupling is faster in the tricoordinated intermediate formed by PPh3
dissociation than in the tetracoordinated complex formed with a
common olefin (roughly speaking, ligands in entries 1-4 of Table 2).
(b) In energetically limiting cases, it would help to lack of effect that
the amount of a putative tetracoordinated intermediate with coordinated
olefin is probably insignificant.
(40) Calculated free energy values are ∆G )-6.4 kcal mol for R ) Ph
versus 5.5 kcal mol for R ) Me. The trend in computed free energies
thus confirms the easier dissociation for PPh3. The absolute free energy
values should not be taken, however, as quantitatively correct. In fact,
if these values were quantitatively correct, the complex with PPh3
should be observed as fully dissociated. Even if dissociation was only
1%, the dissociated species should be detected (by NMR at 250 K).
This is not the case, suggesting that cis-[PdMe2(PPh3)2]:[PdMe2(PPh3)]
g 100:1, wherefrom ∆Geq.dis. (250 K) g 2.3 kcal mol for R ) Ph. It
is well known that entropic contributions for bimolecular processes
are overestimated in this type of calculations.
(43) (a) Williams, D. B. G.; Shaw, M. L. Tetrahedron 2007, 63, 1624–
1629. (b) Luo, X.; Zhang, H.; Duan, H.; Liu, Q.; Zhu, L.; Zhang, T.;
Lei, A. Org. Lett. 2007, 9, 4571–4574.
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3656 J. AM. CHEM. SOC. VOL. 131, NO. 10, 2009

C-C Reductive Elimination in Palladium Complexes
A R T I C L E S
were cooled at -78 °C, and a solution of cis-[PdMe2(PPh3)2]45 (4)
in acetone-d6 was added (0.7 mL). The tubes were placed into a
thermostated probe. Concentration-time data were then acquired
intermediate cis-[PdMe2(PR3)(acceptor olefin)] can reduce the
coupling barrier up to 15 kcal/mol (higher concentration of this
kind of active intermediate can be favored using phosphine-
olefin chelating ligands). It should be noted, however, that
olefins with electron-withdrawing substituents disfavor the
subsequent oxidative addition and could render this step rate
determining in the cycle.44 Hence, a tradeoff between the two
effects of acceptor olefins should be reached in each case.
Bulkier phosphines help to access to lower energy dissociative
couplings. Because coupling on a tricoordinated complex has
lower activation energy than most couplings on a tetracoordi-
nated complex, the use of bulky phosphines that facilitate ligand
dissociation favors a faster coupling. Furthermore, when the
coupling takes place on tricoordinated intermediates, the more
difficult alkyl-alkyl couplings come closer in activation energy
to the easier phenyl-phenyl or vinyl-vinyl couplings. Hence,
the positive effect of bulky ancillary ligands is particularly
important for the case of alkyl-alkyl coupling.
Interestingly, the calculations suggest and the experiment
shows that in cases where a low coupling barrier is operating
via a tricoordinated intermediate (e.g., with bulky phosphines),
the addition of small electron-deficient olefins able to coordinate
can still help very noticeably to further accelerate the coupling
rate (e.g., 7.3 kcal/mol reduction of the coupling barrier is
observed in Table 2 comparing entries 8 and 7), forming a cis-
[PdR2(bulky phosphine)(acceptor olefin)] intermediate with even
lower activation energy. In summary, this study explains the
effect of potentially coordinating additives on the reductive
elimination and opens the path for the experimental design of
more efficient catalytic systems.
1
from H integration of signals of 4. The experimental data are
collected in Tables 3 and 4. The exact temperature was calibrated
with an ethylene glycol standard for Table 3, and with a methanol
standard for Table 4.
Acknowledgment. We thank the Spanish Ministerio de
Educacio´n y Ciencia (INTECAT Consolider Ingenio-2010
(CSD2006-0003), and Consolider Ingenio 2010 (CSD2007-
00006); SAF07-63880, FEDER; CTQ2005-09000-CO2-01;
CTQ2005-09000-CO2-02; CTQ2007-67411/BQU; CTQ2008-
06647-C02-01/BQU; “Juan de la Cierva” contract to A.A.C.B.;
studentship to M.H.P-T.); the Xunta de Galicia (Parga Pondal
Contract to M.P.-R.); the Catalan DURSI through project
2005SGR00715; the Junta de Castilla y Leo´n (Projects VA044A07
and GR169); the UAB for a PIF studentship to M.G-M.; and
the ICIQ foundation for financial support. We also thank CESGA
and CESCA for generous allocation of computational resources.
Supporting Information Available: Computational methods.
Complete computational data and discussion for the complexes
with R ) Me, Ph, and vinyl and L ) PMe3, MeCN, empty,
CH2CH2, ma. Computational data for the complexes with R )
Me and L ) trans-2-butene, 2,5-dihydrofuran, 3,5-dimethyl-
cyclopent-1-ene, trans-1,2-dicyanoethylene, p-benzoquinone.
Data for the ligand dissociation from cis-[PdMe2(PPh3)2] and
cis-[PdMe2(PMe3)L], and for the olefin rotation in cis-
[PdMe2(PMe3)(H2CdCH2)]. This material is available free of
charge via the Internet at http://pubs.acs.org.
Experimental Section
Kinetic Study of the Reductive Elimination. The kinetic
experiments were monitored by 1H NMR at 400 MHz. NMR tubes
(5 mm) were charged with the corresponding olefin. Next, the tubes
JA808036J
(44) Fairlamb, I. J. S.; Kapdi, A. R.; Lee, A. F.; McGlacken, G. P.;
Weissburger, F.; de Vries, A. H. M.; Schmieder-van de Vondervoort,
L. Chem.-Eur. J. 2006, 12, 8750–8761, and references therein.
(45) Byers, P. K.; Canty, A. J.; Jin, H.; Kruis, D.; Markies, B. A.; Boersma,
J.; van Koten, G. Inorg. Synth. 1998, 32, 170.
9
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