Ligandless, anionic, arylpalladium halide intermediates in the heck reaction

Article abstract of DOI:10.1021/ja909306f

(Chemical Equation Presented) We report the isolation and reactivity of a series of "ligandless," anionic arylpalladium complexes of the general structure [Pd(Ar)Br₂]₂²- by the reaction of (tBu₃P)Pd(Ar)(Br) and bromide. These anionic complexes insert olefins at room temperature, and these fast insertions indicate that the anionic complexes are kinetically competent to be intermediates in Heck-Mizoroki reactions conducted under "ligandless" conditions (lacking added dative ligand). Kinetic studies showed that the anionic complexes insert olefins much faster than the corresponding neutral, P(t-Bu)₃-ligated complexes. Addition of halide to the reaction of the neutral complex (tBu ₃P)Pd(Ar)(Br) and styrene led to a significant rate acceleration, suggesting that the anionic complex forms rapidly and reversibly in situ from the neutral species prior to migratory insertion. These data, along with studies on the regioselectivity for reaction of aryl halides with butyl vinyl ether in the presence of the different starting catalysts, are consistent with the intermediacy of the same anionic, arylpalladium intermediates in Heck reactions catalyzed by palladium complexes containing bulky trialkylphosphine ligands as in reactions conducted under ligandless conditions.

Full text of DOI:10.1021/ja909306f

Published on Web 12/16/2009
Ligandless, Anionic, Arylpalladium Halide Intermediates in the Heck Reaction
Brad P. Carrow and John. F. Hartwig*
Department of Chemistry, UniVersity of Illinois, 600 South Mathews AVenue, Urbana, Illinois 61801
Received November 2, 2009; E-mail: jhartwig@uiuc.edu
Palladium-catalyzed coupling reactions conducted without added
dative ligand are run on both small and industrial scales, despite
the development of modern phosphine and carbene ligands. Studies
to reveal the mechanism of reactions under these “ligandless”
conditions are more challenging than those of systems known to
react through discrete complexes containing supporting ligands.
Studies of “ligandless” systems have identified the presence of
1H NMR spectrum of 1 contained a doublet at 5.49 ppm for the
proton of the phosphonium salt, in addition to the resonances for
the palladium-bound aryl group and the tert-butyl groups on
31
1
phosphorus. The P{ H} NMR spectrum consisted of a signal with
t
3
a chemical shift similar to that of [HP Bu ]Br.
Scheme 1
1
-3
colloidal palladium in such reactions,
and molecular species
generated from these nanoparticles are proposed as the active
3
catalyst in solution. However, conclusions about the structures of
such species have been largely speculative. The anionic species
-
-
[
(Ar)PdX
2 3
] and [PdX ] lacking dative ligands have been detected
2,3
by mass spectrometry and EXAFS, and complexes of the formula
A more general synthesis of dimeric, dianionic arylpalladium halide
complexes is shown in Scheme 1. Phenyl and 4-fluorophenyl com-
plexes 2-4 were prepared from the reaction of trialkylphosphonium
2
-
[
(Ar)PdX
2
]
2
containing perhalogenated aryl groups have been
4
isolated. However, ligandless arylpalladium halide complexes
lacking the stability imparted by a perhaloaryl group have never
been isolated, and the reactions of discrete, “ligandless” anionic
t
12
and tetraalkylammonium halides with ( Bu
ucts were obtained directly from a nonpolar reaction solvent in
8-86% yield. Complexes 1-4 are air-stable, crystalline solids. Single-
3
P)Pd(Ar)(Br). The prod-
5
arylpalladium halide complexes have not been described.
3
crystal X-ray diffraction indicates that they are dimeric complexes
containing two µ-halide ligands in the solid state (see Supporting
Information for X-ray data). Conductivity measurements indicate that
the complexes remain dimeric in solution. The conductivity of a 1
mM solution of 3 in nitrobenzene was 49 ohm- cm mol . This
1
2
-1
“
Jeffery conditions” involving simple palladium salts, inorganic
6
13
base, and tetraalkylammonium salts are classic conditions for the Heck
reaction (eq 1). Depending on the identity of the halogen and the
alkene, the oxidative addition or the olefin insertion steps of the
value falls in the range of conductivities of 2:1 electrolytes, and a
7,8
2:1 electrolyte is consistent with a dianionic, dimeric structure.
9
catalytic cycle can be turnover limiting. In either case, migratory
insertion of the alkene into an arylpalladium complex forms the
carbon-carbon bond in the product and controls the selectivity for
formation of one isomer over another. Thus, to understand and affect
the yields of the Heck reaction, the arylpalladium intermediate and
the pathway by which it reacts with alkenes under conditions
commonly used for the Heck reaction must be identified.
The combination of an ammonium bromide salt and a neutral,
P(t-Bu) -ligated arylpalladium halide complex equilibrates with the
3
Here, we report the synthesis, isolation, structural characteriza-
tion, and reactivity of anionic arylpalladium halide complexes
combination of the anionic complex and free phosphine. Exchange of
halide for phosphine occurred immediately upon mixing the neutral
2-
[(Ar)PdBr ]
2 2
lacking a dative ligand. Mechanistic data imply that
4
complex 5 with NR Br (eq 3). The equilibrium constant determined
19
31
-1
14
these complexes are intermediates in Heck reactions catalyzed by
ligandless palladium. Moreover, we provide data that imply that
that such “ligandless” species are also intermediates in reactions
catalyzed by complexes of some of the most commonly used
phosphines, including those catalyzed by the combination of
palladium and a bulky trialkylphosphine.
by F and P NMR spectroscopy at 20 °C was 11 ( 1 mol L.
Anionic complexes 2 and 3 react with alkenes and vinylarenes
under mild conditions (Scheme 2). Complex 2 reacted with styrene
in a mixture of acetonitrile and toluene with added MeCy N to
2
form trans-stilbene in high yield within 10 min at 25 °C. Reactions
occurred in the absence of base; however, higher yields of the
vinylarenes (by ca. 10%) were obtained in the presence of added
amine, presumably because the consumption of the H-Pd-X
product prevents unproductive consumption of the starting complex.
These reactions of the anionic complexes with olefins typically
0
resulted in precipitation of a black solid (presumably Pd ) during
We first observed the formation of anionic arylpalladium
the reaction. In the case of the reaction of phosphonium salt 2 with
complexes lacking dative ligands from the combination of 2-bro-
styrene (Scheme 2), the soluble palladium products were quantified
t
31
mobenzotrifluoride and the Pd(II) complex ( Bu
3
P)
2
Pd(H)(Br) (eq
by P NMR spectroscopy. The only species observed in solution
1
0,11
t
2
).
This reaction formed the anionic 2-trifluoromethyl-phenyl
was Pd(P Bu
3
)
2
(25%). The remaining palladium product is likely
complex 1 lacking any neutral, L-type, ligands in high yield. The
the precipitated species.
10.1021/ja909306f  2010 American Chemical Society
J. AM. CHEM. SOC. 2010, 132, 79–81 9 79

C O M M U N I C A T I O N S
To assess whether the phosphonium cation generates a phosphine
ligand and the reaction occurs through this phosphine complex, we
studied the reactions of alkenes and vinylarenes with complex 3
containing an ammonium, rather than a phosphonium, ion. Acrylates
and styrene reacted with 3 to give the cinnamate and stilbene products
in high yield. Even 3,3-dimethyl-1-butene reacted to form a vinylarene
product at room temperature. 1,2-Disubstituted alkenes react more
slowly than less substituted alkenes in the Heck arylation, but the
anionic complex 3 reacted with trans-methyl cinnamate to afford
the trisubstituted olefin product in good yield at only 50 °C.
Presumably the phosphonium cation in 2 releases free P(t-Bu)
3
in the
18
presence of amine base and forms a highly active P(t-Bu)
3
-ligated
19
Pd(0) species for oxidative addition of this aryl bromide. Thus, these
reactions of the anionic species with alkenes imply that the isolated
complexes are competent to be intermediates in the Heck reactions of
iodo- and bromoarenes with terminal and disubstituted olefins.
Further studies implied that these ligandless complexes are also
intermediates in Heck reactions conducted under some of the mildest
20
conditions developed recently. Because “ligandless” complexes 2-4
were prepared from arylpalladium complexes ligated by P(t-Bu)
ligandless, anionic complexes would be formed reversibly in a catalytic
system involving P(t-Bu) -ligated palladium complexes. If the anionic
3
,
Scheme 2
3
complexes were more reactive than the neutral species, then the
products would actually result from reaction of the alkene with the
species lacking any dative ligand. Thus, we conducted experiments to
compare the rates of reactions of the anionic arylpalladium complexes
to those of neutral P(t-Bu)
revealed the unexpected result that the anionic complexes react faster
than the neutral analogues ligated by P(t-Bu)
Comparisons of the rates of reactions of styrene with ligandless and
P(t-Bu) -ligated arylpalladium halide complexes 4 and 5 are shown in
Figure 1. Reaction of anionic 4 with styrene and MeCy N in a mixture of
acetonitrile and toluene (4:1) at 20 °C occurred with a kobs value of 2.9 ×
s . This value was much faster than that of the analogous reaction
of the neutral, three-coordinate 5 with the same quantity of styrene in the
3
-ligated analogues. These experiments
3
.
3
2
-
3 -1
10
a
Based on GC analysis with n-C14H30 as internal standard.
21
t
2 3
presence of MeCy N (0.05 M) and P Bu (0.17 M).
Scheme 3
The rate of decay of the neutral, three-coordinate species in the
presence of added halide (Figure 1) was measured to test the potential
that the anionic species are intermediates in reactions of phosphine-
t
ligated complexes. Reaction of ( Bu
3 6 4
P)Pd(C H -p-F)(Br) (5) with
styrene in the presence of N(heptyl)
yield (92% yield as determined by F NMR spectroscopy) and to
4
Br (0.68 M) occurred in good
19
-5
-1
9
0% conversion after 7 h (kobs ) 8.9 × 10 s ), while the same
reaction conducted in the absence of added bromide proceeded to only
2
2
13% conversion over the same time.
a
b
Isolated yield. DMG ) N,N-dimethylglycine.
2
-
These results show that the anionic complex [(Ar)PdX
2
]
2
is
competent to be an intermediate in Heck reactions catalyzed by
ligandless palladium systems that typically occur over several hours
1
5
at elevated temperature. Moreover, these results show that the
anionic arylpalladium complexes are more reactive than neutral
16,17
analogues ligated by PPh
3
.
The faster reactions of alkenes with
these anionic complexes than with related neutral complexes run
counter to the typically faster insertions of alkenes into the M-C
bonds of more electrophilic complexes.
t
Figure 1. Decay of 5 (0.034 M) in the presence of styrene (0.17 M), P Bu
3
21
(
0.17 M), N(heptyl)
and toluene (4:1) at 20 °C, and decay of 4 (0.017 M) in the presence of
styrene (0.17 M) and MeCy N (0.05 M) in acetonitrile and toluene (4:1) at
4
2
Br (0-0.68 M), and MeCy N (0.05 M) in acetonitrile
To gain additional data on the competence of 2-4 to be intermedi-
ates in the Heck reaction, we conducted reactions of aryl halides with
olefins catalyzed by 2-4 under three common sets of reaction
conditions (Scheme 3). The reaction of iodobenzene with methyl
acrylate catalyzed by the parent phenyl complex 3 at 30 °C gave trans-
methyl cinnamate in 96% yield. Similarly, the reaction of 4-bromo-
benzotrifluoride with styrene catalyzed by p-fluorophenyl complex 4
at 130 °C gave the substituted stilbene in high yield. Finally, the
reaction of the deactivated aryl bromide 4-bromo-N,N-dimethylaniline
with methyl methacrylate occurred in the presence of 2 to give the
substituted cinnamate product in high yield at room temperature.
2
1
9
20 °C as monitored by F NMR spectroscopy.
3
To test further the potential that the ligandless and P(t-Bu) -
ligated complexes react with olefins through a common intermedi-
ate, we evaluated the ratios of products formed from the isolated
anionic complexes and from reactions conducted with common
catalysts for the Heck reaction. Because prior studies have
indicated that the distribution of isomers formed from the Heck
reaction varies with the steric and electronic properties of the
electrophile, olefin, and catalyst, we considered that this selectivity
2
3
80
J. AM. CHEM. SOC. 9 VOL. 132, NO. 1, 2010

C O M M U N I C A T I O N S
could be used to probe for an intermediate that is common to
reactions initiated with different catalyst precursors.
ancillary ligands to control selectiVity should focus on dative ligands
more tightly bound than P(t-Bu) or on anionic additives. Future studies
3
In particular, Heck reactions of vinyl ethers form different ratios of
will test this hypothesis and explore the role of these species in other
palladium-catalyzed processes.
23
isomeric products with different catalysts, and we measured the isomeric
ratios of products of the reactions catalyzed by palladium complexes of
triphenylphosphine, 1,3-bis-(diphenyl-phosphino)propane (dppp), and P(t-
Acknowledgment. We thank the NIH (NIGMS, GM 58108) for
support of this work and Johnson-Matthey for a gift of PdCl . We
2
thank Dr. Per Ryberg for helpful discussions on the insertions of vinyl
ethers and Dale Pahls for DFT calculations of the νCO values.
Bu)
reaction of bromobenzene or iodobenzene with butyl vinyl ether catalyzed
by Pd(PPh or the combination of Pd(OAc) and PPh as well as that
from the reaction of phenyl triflate and butyl vinyl ether catalyzed by
Pd(OAc) and dppp (Scheme 4) were much different from that obtained
from reaction of Pd dba and P(t-Bu) . Thus, we concluded that this
3
under the same conditions. The distribution of products from the
3
)
4
2
3
Supporting Information Available: Crystallographic data for 1 and
2
2
, experimental procedures and characterization of palladium com-
2
3
3
plexes. This material is available free of charge via the Internet at http://
pubs.acs.org.
selectivity would be a valid probe for a common intermediate.
Scheme 4
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The studies reported here reveal some basic principles about the
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of catalysts for reactions occurring by alkene insertion. First, these
studies show that alkene insertion can be fast, even for complexes
lacking a positive charge or electron-poor dative ligands. The faster
reactions of the anionic complex versus those of the neutral species
contrast the typical trend of faster insertions of alkenes into the
(
(
21) In the absence of added halide, rate acceleration by the palladium product
t
(
Bu
3
P)
2
Pd(H)(Br) was observed and addition of MeCy
2
N was necessary
to scavenge HBr. The resulting salt (MeCy
2
N · HBr) subsequently crystal-
lized from solution during the course of the reaction.
2
4
(22) No intermediates were observed, and the olefin product was formed with
metal-carbon bonds of complexes that are more electrophilic,
a rate constant that was similar to that of the decay of starting complex 5
25
-5 -1
including cationic organopalladium complexes. The anionic com-
(kobs ) 7.4 × 10
s ).
(
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5
7, 3558. (b) Cabri, W.; Candiani, I.; Bedeschi, A.; Penco, S.; Santi, R. J.
26
frequencies, and therefore, we suggest that the anionic complexes
in this work are more reactive than neutral, phosphine-ligated analogues
because they are less hindered.
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3
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species. At the same time, these studies show that efforts to use
(
26) DFT calculations of CO stretching frequencies for neutral and anionic Pd
complexes suggest that the anionic complex contains a more electron-rich
metal center (see Supporting Information).
JA909306F
J. AM. CHEM. SOC. 9 VOL. 132, NO. 1, 2010 81