E- Z Isomerization of Phosphine-Olefin (PEWO-F4) Ligands Revealed upon PdCl2 Capture: Facts and Mechanism

Article abstract of DOI:10.1021/acs.organomet.9b00679

The PEWO phosphines R₂P(o-C₆H₄CH-CHC(O)Ph), R₂P(o-C₆H₂F₂CH-CHC(O)Ph), and R₂P(o-C₆F₄CH-CHC(O)Ph) and their P-monodentate complexes trans-[PdCl₂(P-monodentate)₂] show, in solution and (when available) in the X-ray diffraction structures, an E configuration of the double bond. In contrast, the structures of [PdCl₂(P-chelate)] display E and Z configurations. The E/Z isomerization of the latter requires first decoordination of the double bond, which then allows for easy rotation about the electron-deficient double bond. Thus, the E/Z equilibria exist for the free and the P-monodentate complexes as well but are not observed because they are extremely displaced toward the E isomer. Their capture in the form of [PdCl₂(P-chelate)], with equilibrium constants on the order K_eq ≈ 1-3, allows the two configurations to be observed and isolated. Evaluation of their ability to couple Pf-Pf from cis-[PdPf₂(THF)₂] (Pf = C₆F₅) affords values of their ΔG^?(Pf-Pf)_Pd parameters confirming that higher substitution of H by F produces lower coupling barriers and a double bond that is more electron deficient when it is free and more electron withdrawing when it is coordinated.

Full text of DOI:10.1021/acs.organomet.9b00679

Article
pubs.acs.org/Organometallics
Cite This: Organometallics XXXX, XXX, XXX−XXX
E−Z Isomerization of Phosphine-Olefin (PEWO‑F4) Ligands Revealed
upon PdCl2 Capture: Facts and Mechanism
́
̃
Marconi N. Penas-Defrutos, Andrea Velez, Estefanía Gioria, and Pablo Espinet*
́
IU CINQUIMA/Química Inorganica, Facultad de Ciencias, Universidad de Valladolid, 47071 Valladolid, Spain
S
* Supporting Information
ABSTRACT: The PEWO phosphines R2P(o-C6H4CHCHC-
(O)Ph), R2P(o-C6H2F2CHCHC(O)Ph), and R2P(o-C6F4CH
CHC(O)Ph) and their P-monodentate complexes trans-[PdCl2(P-
monodentate)2] show, in solution and (when available) in the X-ray
diffraction structures, an E configuration of the double bond. In
contrast, the structures of [PdCl2(P-chelate)] display E and Z
configurations. The E/Z isomerization of the latter requires first
decoordination of the double bond, which then allows for easy
rotation about the electron-deficient double bond. Thus, the E/Z
equilibria exist for the free and the P-monodentate complexes as
well but are not observed because they are extremely displaced
toward the E isomer. Their capture in the form of [PdCl2(P-
chelate)], with equilibrium constants on the order Keq ≈ 1−3,
allows the two configurations to be observed and isolated. Evaluation of their ability to couple Pf−Pf from cis-[PdPf2(THF)2]
(Pf = C6F5) affords values of their ΔG⧧(Pf−Pf)Pd parameters confirming that higher substitution of H by F produces lower
coupling barriers and a double bond that is more electron deficient when it is free and more electron withdrawing when it is
coordinated.
INTRODUCTION
■
Since the recognition of Pd-catalyzed reactions with the Nobel
Prize to Heck, Suzuki, and Negishi in 2010, a main concern in
organic and organometallic chemistry has been the develop-
ment and control of new challenging C−E (E = C, N, O)
cross-coupling reactions. Ligand design is a crucial tool to
improve the performance of most catalytic transformations.
For example, hemilabile chelating ligands were studied because
of their useful versatility of creating or occupying coordinative
vacancies.1 Later on, the extraordinary performance of bulky
phosphines such as PtBu3 and PR2(biaryl) phosphines has led
Pd catalytic cycles to previously unforeseen efficiency.2
It is well-known that electron-withdrawing olefins (EWO)
are able to dramatically diminish in PdII complexes the
activation barrier to reductive elimination (RE), which in many
catalytic transformations constitutes the rate-limiting step.3
Figure 1. PEWO ligands.
Combining a phosphine with an electron-withdrawing olefin in
the same molecule produces PEWO ligands that facilitate
coordination of the EWO to Pd by the entropy-favored chelate
use of 19F NMR spectroscopy facilitated mechanistic studies
on the real origin of “reduction” product Ar−H instead of Ar−
alkyl, which is not β-H elimination from the alkyl as previously
believed.6
Ranking the relative ability of ligands to reduce the C−C
coupling barrier on PdII can be made by measuring ΔG⧧(Pf−
Pf)Pd upon addition of the desired ligand to cis-[PdPf2(THF)2]
effect. The good results reported by group of Lei and others
using the ligand PhPEWO-H4, shown in Figure 1A,4,5 for
Negishi catalysis led our group to explore the fluorinated
analogues RPEWO-F4 (Figure 1B), because the presence of
four F atoms should make the double bond more of an
electron attractor and consequently should further lower the
RE barrier in comparison to PhPEWO-H4. The palladium
complexes with PhPEWO-F4 turned out to be also excellent
catalysts in Negishi type aryl−alkyl couplings. Moreover, the
Received: October 11, 2019
© XXXX American Chemical Society
A
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(Pf = C6F5).7 Tetrafluorinated RPEWO-F4 ligands are able to
promote the difficult homocoupling of two cis C6F5 moieties
on Pd nearly as quickly as the extremely bulky ligand PtBu3 or
Scheme 2. Synthesis of Phosphines 2−4
8
t
some of the most used biaryl phosphines, such as BuXphos,
which are usually considered to behave as functionally three-
coordinate species.9 PhPEWO-H4 ligands do much worse than
all those previously mentioned.
The weak point of these PEWO ligands (which has been
explained in detail for related P-olefin hybrid ligands) is the
deep stabilization of the Pd0 species formed in the reductive
elimination.10 This increases the activation barrier of the
subsequent oxidative addition. Making the phosphine PR2
moiety a better donor should lead to a Pd0(RPEWO-F4)
center that is easier to oxidize, while the EWO-F4 moiety will
still keep on easing the reductive elimination. Alternatively,
diminishing the electron acceptor power of the EWO moiety
might provide a more convenient coupling/reoxidation
tradeoff. In order to test these ideas, we decided to prepare
the two new fluorinated PEWO ligands CyPEWO-F4 (1c) and
PhPEWO-H2F2 (3) (shown in Figure 1C) for evaluation of
their ΔG⧧(Pf−Pf)Pd parameters.
The electron-withdrawing olefins in Figure 1 are all drawn
with an E configuration, which is that observed for the free
PEWO phosphines of this work in chloroform or dichloro-
methane solution, and in their X-ray diffraction structures
reported here, but this configuration may not necessarily be
maintained in the different species along a catalytic cycle. In
fact, very little is known about this circumstance and its effect
on the energy of intermediates or transition states in the cycle.
The study of their complexes with PdCl2, which are in practice
synthesized in situ as precatalysts, allows us to achieve some
knowledge about E versus Z complexes.
H2F2 (3) have a high yield, and 3 was prepared with only
modest further yield loss. The major product of the first
reaction step with 1,2-dibromo-4,5-difluorobenzene is the
fluorinated phosphine 4, formed by an undesired C−C
coupling. Phosphines 2 and 4 can be efficiently separated
after the first reaction step using column chromatography.
Both are unreported in the literature (the nonfluorinated
homologue of 4 is commercially available).11 Phosphine 4 is
not used in this work except for its evaluation toward Pf−Pf
coupling induction in cis-[PdPf2(THF)2], but full details of its
characterization and its X-ray structure are given in the
Supporting Information.
The two new PEWO ligands, 1c and 3, have an E
configuration for the CC moiety in CDCl3 solution, as
supported by the values of the coupling constants observed in
1
their H NMR spectra (3JH−H ≈ 15 Hz). Moreover, the two
ligands also display an E configuration in their X-ray structures.
In fact, for all four free PEWO ligands used in this work (1a−c
1
and 3) only the E configuration is observed by 19F and H
NMR. In our previous works and here, the Z configuration has
never been detected when the olefin substituent is the group
C(O)Ph. During our work with P-olefin ligands, only on one
occasion (for the equivalent to 1a but with Me instead of
C(O)Ph) was an E/Z mixture obtained.6a In that case the two
configurational isomers could be separated chromatographi-
cally and did not interconvert in solution at 25 °C, suggesting
that their isomerization barrier as free olefins was reasonably
high.
RESULTS
■
Synthesis of New PEWO Ligands. Using the method-
ology previously developed in our group to obtain the
tetrafluorinated ligands PhPEWO-F4 (1a) and o-TolPEWO-
F4 (1b) from 1,2-Br2C6F4 in three steps (Scheme 1; see the
Determination of ΔG⧧(Pf−Pf)Pd for the new ligands.
Ligands 1c, 3, and 4 were submitted to the reported protocol
to determine their ΔG⧧(Pf−Pf)Pd values by measuring the rate
of formation of Pf−Pf upon addition of the ligand (2 equiv) to
cis-[PdPf2(THF)2] in toluene (Figure 2).7
Scheme 1. Synthesis of Phosphines 1a−c
Supporting Information for full details),6 the homologous
CyPEWO-F4 (1c) was prepared in 50% overall yield (Scheme
1). In spite of the presence of two alkyl groups in 1c, the wide
C−P−C angles they force and the fluorination of the aryl
substituent contribute to stabilizing the phosphorus atom
against oxidation, so that this phosphine, as 1a,b, is perfectly
stable to air and moisture for days.
Whereas the selective lithiation of one of the two C−Br
bonds and subsequent reaction with the corresponding ClPR2
is very efficient on o-C6Br2F4, with 1,2-dibromo-4,5-difluor-
obenzene different reaction conditions are needed (THF at
−90 °C) in order to obtain the bromo-PPh2 derivative 2
(Scheme 2). Even under these conditions, 2 is the minor
product of the reaction and is isolated in about 20% yield.
Luckily, the next two synthetic steps to produce PhPEWO-
Figure 2. Procedure for measuring ΔG⧧(Pf−Pf)Pd, illustrated for the
case of PEWO ligands. For an explanation of the PEWO acronyms in
the text see ref 12.
B
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The reaction of CyPEWO-F4 (1c) with cis-[PdPf2(THF)2]
in toluene is not simple. As in the case of 1a,b,7 1c also
produces a fast reaction at room temperature, which is better
monitored at 0 °C. In addition to the expected Pf−Pf (which is
formed in 30% yield) and PfH (in 3% yield), other products
are formed. The formation of Pf−Pf, which can be cleanly
monitored in the 19F NMR spectra to measure the initial rate
of formation, is accompanied by the appearance of an
unidentified product at higher rate and by other less defined
and less abundant products. The fact that the starting cis-
[PdPf2(THF)2] is being competitively consumed by other
processes affects negatively the rate of formation of Pf−Pf, so
that kobs is not a true rate constant. Since the other processes
are consuming competitively about two-thirds of the cis-
[PdPf2(THF)2], the real rate constant of the coupling induced
by 1c is in fact higher by a factor of almost 3 (see Figure S3
and comments in the Supporting Information). With all this
considered, a reasonable estimation for 1c would be ΔG⧧(Pf−
Pf)Pd ≤ 21.5 kcal mol−1.
(n = 2) to PdCl2.12 Our catalytic studies using PhPEWO-F4
(1a) suggest that, since the final reductive elimination occurs
from a [PdR1R2(PEWO-chel)] chelate complex, the ratio Pd:L
= 1:1 is convenient.6 This ratio can be achieved by preparing,
independently or in situ, the [PdCl2(PEWO-chel)] precatalyst
from PEWO and [PdCl2(NCMe)2] (6) in a 1:1 ratio. In the
case of 1a we had already reported the formation of the
complex via a trans-[PdCl2{E-(PhPEWO-F4)}2] (7a) inter-
mediate where the ligand is acting as a P-monodentate species
(Scheme 3),6a and the crystal structure of [PdCl2{Z-
(PhPEWO-F4-chel)}] (Z-8a) was solved.
Scheme 3. Synthesis of PEWO Chelating PdCl2 Complexes
The reaction with 4 at 25 °C did not induce coupling and
produced a cis-/trans-[PdPf2(4)2] mixture, as expected. In
contrast, ligand 3 induced efficient coupling (with only 3%
hydrolysis) at a rate slower than that previously reported for
1a,b, according to its higher ΔG⧧(Pf−Pf)Pd = 23.7 kcal mol−1
at 25 °C. The Pd0 complex [Pd(3-chel)2] (5), resulting from
Pf−Pf coupling, was isolated and fully identified. Its X-ray
structure is shown in Figure 3. The two ligands are coordinated
as P-olefin chelates, and the coordinated olefin clearly displays
the E configuration.
The reaction of 1a was revisited at 243 K for this paper
(Figure 4), and we could additionally detect intermediate E-8a
(not reported in our original paper) and confirm the sequence
E-7a/E-8a/Z-8a shown in Scheme 3.
Figure 3. X-ray structure of [Pd0(E-3-chel)2] (5). Bond distances in
Å.
On comparison of the ΔG⧧(Pf−Pf)Pd values for PEWO
ligands available so far, they decrease in the order PhPEWO-
H4 > PhPEWO-H2F2 > any PhPEWO-F4, confirming that the
ligand ability to accept back-donation toward the π* empty
orbital of the coordinated olefin, when the back-donation from
Pd increases as Pd evolves from PdII to Pd0, is critical to
facilitate a more accessible coupling barrier. In this respect the
high degree of fluorination of the aryl bearing the P atom and
the presence of the CO substituent at the other side of the
olefin play important roles in making the olefin strongly
electron withdrawing.
Figure 4. 19F and 31P spectra of a mixture in evolution from E-7a/E-
8a to Z-8a at 243 K in CD2Cl2 (the asterisks denote 7a).
For o-TolPEWO-F4 (1b), the corresponding intermediate
7b could not be observed. Perhaps it is not formed because of
the bulkiness of the o-Tol group in comparison to Ph in the
neighborhood of the coordination plane.13 The reaction led to
a mixture of the Z-8b and E-8b products at 298 K. Working in
a more controlled manner (details in the Supporting
Information) the kinetic product [PdCl2{E-(o-TolPEWO-
F4)}] (E-8b) was isolated. Complex E-8b evolves in chloro-
form or dichloromethane solution to reach an equilibrium of
the two isomers. The two configurational isomers could be
crystallized for X-ray diffraction studies, and Figure 5 collects
The protocol to measure ΔG⧧(Pf−Pf)Pd is not only able to
identify ligands efficient in producing fast coupling. Addition-
ally, as in the case of 1c, it is able to detect undesired
complications. Obviously, the use in catalysis of ligands
misbehaving at the coupling step should be made with caution.
Reaction of PEWO Ligands with [PdCl2(NCMe)2] (6).
Effect of Coordination of RPEWO-Fn 1a−c (n = 4) and 3
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Figure 5. X-ray structures of Z-8b (top) and E-8b (bottom)
respectively, with selected distances in Å. o-Tol and Ph groups are
shown as capped sticks. Crystallization solvent molecules and
hydrogen atoms (except olefinic hydrogens) are omitted for clarity.
their molecular structures. Both structures display a square-
planar geometry around the PdII atom, with the olefin bond
located roughly perpendicular to the coordination plane. The
Pd−Colefinic bond distances lay in a very short range: 2.184−
2.217 Å. Note that the C3−C4 distances are almost identical
for the two configurations.
Figure 6. Molecular structures of Z-9 (top) and E-10 (bottom), Bond
distances in Å. For E-10, only one of the two slightly different
molecules making part of the asymmetric unit is shown. Ph groups are
shown as capped sticks, and crystal solvent molecules have been
omitted for clarity.
expected, as olefin coordination is known to weaken the C−C
bond.
The evolution of the reaction of [PdCl2(NCMe)2] (6) and
CyPEWO-F4 (1c) seems to follow essentially the same steps as
for 1a, but with a faster rate. 19F and 31P NMR monitoring
reveals the presence of mixtures containing predominantly
[PdCl2{E-(CyPEWO-F4)}] (E-8c) and the formation of
[PdCl2{Z-(CyPEWO-F4)}] (Z-8c), which in turn evolves
very quickly in THF solution to unidentified products. The
total consumption of 8c was observed in 30 min at room
temperature, which prevented isolation for X-ray character-
ization of any of these two observed configurational isomers.
PhPEWO-H2F2 (3) shows interesting differences with the
tetrafluorinated analogues. The presence of trans-[PdCl2(3)2]
On comparison of the cases of PhPEWO-F4 (1a), PhPEWO-
H2F2 (3), and PhPEWO-H4 (L1), the strength of the olefin−
Pd interaction is progressively weaker as the the number of F
atoms in the 1,2-substituted aryl is lowered: PhPEWO-F4 (1a)
produces only the chelated complex with PdCl2, PhPEWO-H4
(L1) only the P-monodentate dimer, and PhPEWO-H2F2 (3) a
mixture of the two isomers in equilibrium.
DISCUSSION
■
The data discussed above show that all of the free PEWO
olefins display an E configuration. They initially P-coordinate
to PdCl2, also giving complexes with an E configuration.
Finally, we find E and Z configurations in the chelate
complexes of PdII and an E configuration in the Pd0 complex.
The E configuration is expected to be the most stable one for
the free olefins, as found for instance for the closely related
structures of chalcone derivatives and in most 1,2-substituted
olefins.14 It is indeed the only configuration observed in
solution. The P-bonded PdII complexes with the olefin
uncoordinated (7a,c) also display E configurations, supporting
that this is their more stable configuration. However, the lack
of observation of the Z configuration in these compounds does
not mean anything about their existence in very unequal
equilibria or their possible isomerization barrier.
1
as an intermediate could be confirmed by H, 19F, and 31P
NMR monitoring of the reaction. Attempts to obtain and
purify the putative complex [PdCl2{E-(PhPEWO-H2F2)}] (E-
9) were unsuccessful. The coordinated olefin shows a
dissociation equilibrium toward the formation of the less
soluble dimer (μ-Cl)2[PdCl{E-(PhPEWO-H2F2)}]2 (E-10). In
fact, crystallization for X-ray diffraction by slow evaporation of
a CHCl3 solution of the reaction solution produced a mixture
of yellow Z-9 and orange E-10 crystals in approximately a 1:2
ratio.
Figure 6 displays the X-ray structures of complexes Z-9 and
E-10. The configuration of the olefin and the length of the
C3−C4 bond differ in the two isomers. For the chelated Z-9,
the structure and relevant distances, including C3−C4, are very
similar to those of Z-8b, but in the P-monodentate E-10 dimer
the C3−C4 bond is considerably shorter (1.304 Å) than that
in Z-9 (1.381 Å) and almost identical with the value observed
in the structure of the free ligand 3 (Scheme 2). This was
It is only when the PEWO phosphines get coordinated to Pd
as chelate ligands that both E and/or Z configurations are
observed unambiguously. Since E-8b is available as an isolated
product, the evolution of one configuration or the other in
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CDCl3 or CD2Cl2 solution could be monitored. Starting from
E-8b the equilibrium with Z-8b in CDCl3 at 298 K is reached
in much less than 24 h. This is shown in Figure 7, which
fact that kinetically the isomerization rate is order 1 in Pd
concentration (Figure S7); hence, the evolution to the
isomerization transition states starts on a monomer. Moreover,
addition of a large overstoichiometric amount of MeCN
accelerates very significantly the isomerization rate (compare
k
obs values in Table 1), which now should be taking place at an
unobservable [PdCl2(P-monodentate)(NCMe)] (Ib) species,
also in undetectable concentration. These observations support
the configurational isomerization mechanism shown in Scheme
4 for the case of acetonitrile as additive, which requires
decoordination or (more likely) ligand substitution of the
coordinated double bond, followed by rotation around it.
Scheme 4. MeCN-Catalyzed E/Z Isomerization Mechanism
in Complexes 8b
1
Figure 7. H NMR monitoring of the isomerization of E-8b to Z-8b,
in CDCl3 at 298 K.
What we are proposing is that when this double bond is
noncoordinated, in a P-monocoordinate PEWO-F4 ligand, the
isomerization by rotation is feasible. We do not observe E and
Z isomers of 7a−c simply because the E isomer is much more
stable than the Z form, and the small concentration of the
latter in a very uneven equilibrium is unobservable. It is only
upon double bond coordination that the two chelate
complexes happen to have similar stability for the two
configurations and a more balanced equilibrium is reached.
Of course, if this happens to 7a−c there is little argument not
to accept that the same mechanism is operating also in the free
ligands.
displays the progressive appearance of the signals of the two
nonequivalent Me groups of the two o-Tol groups in Z-8b, at
the expense of the Me groups in E-8b. A similar behavior is
observed in CD2Cl2, obviously with a different equilibrium
constant. Note that the observation of isomerization in the
NMR tube on monitoring in the probe (that is in the dark)
excludes photomediation as the isomerization mechanism.
The NMR observation of the two sides of an established
equilibrium is only possible when the energy difference of the
species at the two sides (ΔG) is small enough. The equilibrium
constant in CDCl3, KE‑to‑Z = 3.35 corresponds to ΔG = 0.72
kcal mol−1, the Z isomer being more stable. In the somewhat
more polar CD2Cl2, KE‑to‑Z = 1.22 corresponds to ΔG = 0.12
kcal mol−1, the Z isomer again being more stable (Table 1).15
The experimental ΔG⧧
values at 298 K, in the
E‑to‑Z isom
absence of MeCN, are 23.5 kcal mol−1 in CD2Cl2, and 23.0
kcal mol−1 in CDCl3. The catalytic acceleration by addition of
MeCN requires a large MeCN:Pd ratio for the acceleration
reported as kobs in Table 1. This supports that the electron-
withdrawing olefin is not such a weak ligand when it is
involved in chelation: at least it is not easily displaced by
acetonitrile, since it requires 70 equiv just to form an still
unobservable amount of Ib in the ligand substitution
equilibrium. It is reasonable to presume that an appreciable
Table 1. Equilibrium Concentrations and Rate Constants
for Isomerization of E-8b to Z-8b
a
b
c
d
solvent
additive
E:Z
Keq
ΔG
kobs
CDCl3
CDCl3
CD2Cl2
CD2Cl2
23:77
3.35
−0.72
−0.12
8.0 × 10−5
2.2 × 10−4
3.5 × 10−5
2.2 × 10−4
MeCN
MeCN
deal of ΔG⧧
is invested in the release of the double
bond and only the rest pertains to the configurational
isomerization.
45:55
1.22
E‑to‑Z isom
a
b
Details in the Supporting Information. Polarity ET(30): 39.1 for
CHCl3; 40.7 for CH2Cl2.16 In kcal mol−1. In s−1.
c
d
In general the barrier to rotation in regular olefins is very
high, and different catalytic mechanisms have been proposed,18
but the aryl-EWO moiety in our phosphines is an α,β-
unsaturated chalcone type olefin. The double bond in
chalcones is electron deficient due to the polarization induced
by the CO group. This feature of chalcone derivatives is very
well documented.19 Chalcone itself shows ΔG⧧isom = 31.5 kcal
mol−1 in water, and activation energies of about 15 kcal mol−1
are common.19c Depending on the substituents on the aryls
These data were not determined for the other PEWO ligands,
but their experimental observations and the crystallization of
the two configurational isomers in more cases strongly suggest
that, although it is influenced by the R substituents of each
RPEWO and by the solvent, the energy difference between the
E and Z configurations in their chelated Pd complexes is small.
Examination of the X-ray diffraction structures supports that
the E/Z isomerization of the double bond cannot take place
unless previous decoordination of the double bond occurs,
which means that it takes place on an unobserved [PdCl2(P-
monodentate)(S)] complex.17 All of this is consistent with the
and the solvents used, experimental values as low as ΔG⧧
=
isom
9 kcal mol−1 have been found. In our RPEWO-F4 (1a−c)
ligands the double bond is submitted to an additional source of
electron polarization, due to the presence of the highly
electronegative F atoms (Scheme 5). The consequence is a
E
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very electron deficient double bond and a low activation
barrier to rotation.
Estefanía Gioria: 0000-0002-3258-7390
Pablo Espinet: 0000-0001-8649-239X
Notes
Scheme 5. Resonance Forms Contributing to High Electron
Deficiency of the Double Bond
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
́
The authors thank the Junta de Castilla y Leon (projects
VA051P17 and VA062G18) and the Spanish MINECO
(projects CTQ2016-80913-P and CTQ2017-89217-P) for
financial support. M.N.P.-D. gratefully acknowledges the
Spanish MECD for an FPU scholarship. Thanks are given to
́
Jonathan Martınez-Laguna for help in the syntheses of several
o-Tol derivatives.
CONCLUSIONS
■
REFERENCES
The progressive degree of H for F substitution in the sequence
of phosphines RPEWO-H4 < RPEWO-H2F2 < RPEWO-F4
produces increasing electron deficiency in the uncoordinated
double bond and, consequently, increasing electron-with-
drawing strength in the chelated complexes.
The uncoordinated ligands, the P-monodentate PdCl2
complexes, and the P-chelate complexes all have E/Z
conformational equilibria in solution with reasonably low
isomerization barriers, higher for the P-chelate complexes
because it requires releasing the double bond.
The two isomers in equilibrium are observed only in the
chelate complexes because the E and Z complexes have only
very small differences (<1 kcal mol−1). For the others, the E
isomer is observed.
These observations are interesting in the context of catalysis
because they suggest that the E/Z isomerizations can be
occurring quite efficiently between the main steps (e.g.,
coupling) along the catalytic cycle. They also point to
experimental differences in stability between configurational
isomers in the chelate Pd complexes that are lower than the
acceptable uncertainty in DFT calculations. This difficulty
should be taken into consideration when theoretical
calculations and experiments are combined in these kinds of
systems.
■
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(4) (a) Luo, X.; Zhang, H.; Duan, H.; Liu, Q.; Zhu, L.; Zhang, T.;
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(5) For hybrid phosphine-olefin ligands other than PEWO used in
Pd catalysis see, for example: (a) Cao, Z.; Liu, Y.; Liu, Z.; Feng, X.;
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Indoles and Pyrroles by Chiral Alkene-Phosphine Ligands. Org. Lett.
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(6) (a) Gioria, E.; Martínez-Ilarduya, J. M.; García-Cuadrado, D.;
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Electron-Withdrawing Olefins as Ligands for Efficient Pd-Catalyzed
Aryl-Alkyl Coupling. Organometallics 2013, 32, 4255−4261. (b) Gio-
ria, E.; Martínez-Ilarduya, J. M.; Espinet, P. Experimental Study of the
Mechanism of the Palladium-Catalyzed Aryl−Alkyl Negishi Coupling
Using Hybrid Phosphine−Electron-Withdrawing Olefin Ligands.
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(7) Gioria, E.; del Pozo, J.; Martínez-Ilarduya, J. M.; Espinet, P.
Promoting Difficult Carbon-Carbon Couplings: Which Ligand Does
Best? Angew. Chem., Int. Ed. 2016, 55, 13276−13280.
(8) See for example: (a) Cho, E. J.; Senecal, T. D.; Kinzel, T.; Zhang,
Y.; Watson, D. A.; Buchwald, S. L. The palladium-catalyzed
trifluoromethylation of aryl chlorides. Science 2010, 328, 1679−
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.organomet.9b00679.
■
S
Synthesis and characterization of the new phosphines
and complexes, X-ray diffraction structures, and kinetic
measurements (PDF)
Accession Codes
CCDC 1958367−1958375 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Author
*P.E.: fax, (+)34 983 423013; e-mail, espinet@qi.uva.es; web,
http://gircatalisishomogenea.blogs.uva.es.
■
ORCID
Marconi N. Pen
̃
as-Defrutos: 0000-0003-4804-8751
́
Andrea Velez: 0000-0003-1974-5507
F
DOI: 10.1021/acs.organomet.9b00679
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
(9) Functionally three-coordinate species refer to species where one
of the coordination positions either is free or is protected by a weak
interaction to some atom, whether intramolecular or intermolecular.
Examples are agostic interactions or weakly coordinating ligands.
These species can have lower coupling barriers, either because they
break that fourth interaction at a low energy cost or because the
coupling on the tetracoordinate species has a barrier lower than for
those with two strong ligands: Espinet, P.; Echavarren, A. M. The
mechanisms of the Stille reaction. Angew. Chem., Int. Ed. 2004, 43,
4704−4734.
(10) This has been explained in detail for related P-olefin hybrid
ligands: (a) Tuxworth, L. W.; Baiget, L.; Phanopoulos, A.; Metters, O.
J.; Batsanov, A. S.; Fox, M. A.; Howard, J. A. K.; Dyer, P. W.
Phosphine−alkene ligand-mediated alkyl−alkyl and alkyl−halide
elimination processes from palladium(II). Chem. Commun. 2012,
́
48, 10413−10415. (b) Estevez, L.; Tuxworth, L. W.; Sotiropoulos, J.
M.; Dyer, P. W.; Miqueu, K. Combined DFT and experimental
studies of C−C and C−X elimination reactions promoted by a
chelating phosphine−alkene ligand: the key role of penta-coordinate
PdII. Dalton Trans. 2014, 43, 11165−11179.
(11) It is commercially available under the CAS number 1088-00-2.
(12) The acronyms used for the ligands are easy to understand. For
instance, taking a complex case, [PdCl2{Z-(PhPEWO-F4-chel)}], this
is a PdCl2 complex with (by order) a Z ligand with two Ph groups in
the P atom and 4 F atoms in the aryl of the chalcone skeleton and is
coordinated as a chelate.
(13) The species [PdCl2{E-(PhPEWO-F4)}] (E-8a) and [PdCl2{E-
(CyPEWO-F4)}] (E-8c) could not be isolated in pure form, but they
were detected as intermediates mixed with the corresponding Z
isomers and the first formed trans-[PdCl2L2] (more details in
Supporting Information).
(14) This is a close reference because in fact the aryl-olefin
substituent of the P atom is a fluorinated chalcone (PhCH
CHC(O)Ph) radical.
(15) For comparison we calculated the difference in ΔG between E-
C6F5CHCHC(O)Ph and Z-C6F5CHCHC(O)Ph in CH2Cl2, and
the former is 3.0 kcal mol−1 more stable, which means that the Z
conformation in equilibrium would be undetectable by NMR (0.6%).
(16) (a) Reichardt, C. Solvatochromic Dyes as Solvent Polarity
́
Indicators. Chem. Rev. 1994, 94, 2319−2358. (b) Ceron-Carrasco, J.
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organic solvents. J. Phys. Org. Chem. 2014, 27, 512−518.
(17) S is extremely unlikely to be an empty coordination site and
could be instead weakly coordinated water present in the solvent, the
Cl bridge if dimerization to generate a small amount of an analogous
of E-10 occurs, or some other weak intramolecular interaction.
(18) Tan, E. H. P.; Lloyd-Jones, G. C.; Harvey, J. N.; Lennox, A. J. J.;
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pharmacological properties of chalcones. Res. Chem. Intermed. 2017,
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DOI: 10.1021/acs.organomet.9b00679
Organometallics XXXX, XXX, XXX−XXX