Pd(η3-1-PhC3H4)(η5- C5H5), an unusually effective catalyst precursor for Suzuki-Miyaura cross-coupling reactions catalyzed by bis-phosphine palladium(0) compounds

Article abstract of DOI:10.1021/om300154m

It has previously been shown that the easily handled, heat- and air-stable compound Pd(η³-1-PhC₃H₄)(η⁵- C₅H₅) (Vb) reacts rapidly with a wide variety of tertiary phosphines L to produce near-quantitative yields of the corresponding Pd(0) compounds PdL₂, which are widely believed to be the active species in many often-used cross-coupling catalyst systems based on Pd(PPh ₃)₄ (I), Pd₂(dba)₃ (II), PdCl ₂ (III), and Pd(OAc)₂ (IV). However, catalyst precursors I-IV are in fact known to preferentially generate sterically hindered, three-coordinate Pd(0) species rather than two-coordinate PdL₂, and thus Vb is hypothetically expected to be a better catalyst precursor for e.g. Suzuki-Miyaura cross-coupling reactions. Utilizing the conventional Suzuki-Miyaura cross-coupling reaction of phenylboronic acid with bromoanisole, comparisons are made of the efficacies of catalyst systems based on Vb with those based on compounds I-IV (L = the representative phosphines PPh ₃, PCy₃, PBu^t₃). As anticipated, catalysts generated from Vb are significantly more competent and, as a bonus, Vb makes palladium(0) complexes PdL₂ available under rigorously anhydrous conditions.

Full text of DOI:10.1021/om300154m

Article
pubs.acs.org/Organometallics
3
5
Pd(η -1-PhC H )(η -C H ), an Unusually Effective Catalyst Precursor
3
4
5 5
for Suzuki−Miyaura Cross-Coupling Reactions Catalyzed by Bis-
Phosphine Palladium(0) Compounds
Andrew W. Fraser, Jessica E. Besaw, Laura E. Hull, and Michael C. Baird*
Department of Chemistry, Queen’s University, Kingston, Ontario K7L 3N6, Canada
ABSTRACT: It has previously been shown that the easily handled, heat- and
3
5
air-stable compound Pd(η -1-PhC H )(η -C H ) (Vb) reacts rapidly with a
3
4
5
5
wide variety of tertiary phosphines L to produce near-quantitative yields of the
corresponding Pd(0) compounds PdL , which are widely believed to be the
2
active species in many often-used cross-coupling catalyst systems based on
Pd(PPh ) (I), Pd (dba) (II), PdCl (III), and Pd(OAc) (IV). However, catalyst precursors I−IV are in fact known to
3
4
2
3
2
2
preferentially generate sterically hindered, three-coordinate Pd(0) species rather than two-coordinate PdL , and thus Vb is
2
hypothetically expected to be a better catalyst precursor for e.g. Suzuki−Miyaura cross-coupling reactions. Utilizing the
conventional Suzuki−Miyaura cross-coupling reaction of phenylboronic acid with bromoanisole, comparisons are made of the
efficacies of catalyst systems based on Vb with those based on compounds I−IV (L = the representative phosphines PPh , PCy ,
3
3
t
PBu ). As anticipated, catalysts generated from Vb are significantly more competent and, as a bonus, Vb makes palladium(0)
3
complexes PdL available under rigorously anhydrous conditions.
2
wide variety of palladium-catalyzed carbon−carbon bond
the vast majority of palladium-catalyzed cross-coupling studies
utilize the much more easily manipulated, commercially
available catalyst precursors Pd(PPh ) (I), Pd (dba) (II;
A
forming methodologies are available through reactions
catalyzed by Pd(0) compounds believed to be of the type PdL
2
3 4
2
3
1
(
L = phosphine ligand), with Suzuki−Miyaura cross-coupling
dba = PhCHCHCOCHCHPh), PdCl (III), and/or
2
5
reactions having particular significance in the synthesis of biaryl
Pd(OAc) (IV), the last three in association with added L.
2
1a,h
derivatives. In the general case, the aryl halide ArX (X = C−l,
Unfortunately, while I and II contain the metal already in the 0
oxidation state, I exists in solution primarily as the tris-
Br, I) reacts catalytically with the arylborate species [Ar′BY3]
6
(
Y = halide, alkoxide, etc.) to form the coupled product Ar−Ar′.
The most widely accepted catalytic cycle (Scheme 1) typically
phosphine complex Pd(PPh ) while II reacts with phosphines
3
3
7
to form species of the type Pd(dba)L . In neither case are the
2
desired PdL species formed, but rather sterically hindered, less
active three-coordinate complexes and thus optimal catalytic
2
Scheme 1
activities may not be achieved.
Impetus for widespread use of the Pd(II) catalyst precursors
5
III and IV is found in seminal research by Amatore and
8
Jutand, who have shown that treatment of e.g. IV with 3 equiv
of triarylphosphines L results in the formation of catalytically
−
active Pd(0) complexes [Pd(OAc)L ] in addition to oxidized
2
phosphorus byproducts. Similarly, reduction of the analogous
halo compounds PdX L (X = Cl, Br, I) results in formation of
2
2
−
8d
the Pd(0) complexes [PdXL ] . Therefore, as with catalyst
2
precursors I and II, the major palladium species derived from
reduction of Pd(II) precursors are not the often presumed
catalytically active compounds PdL2 but, again, three-
coordinate species. Complicating the issue, there is to our
knowledge no evidence that reductions of Pd(II) precursors are
involves oxidative addition of ArX to a bis-phosphine
palladium(0) compound PdL2 (L = tertiary phosphines)
followed by transmetalation and reductive elimination steps, a
8k
ever effected either rapidly or completely in the majority of
2
process which has been studied both experimentally and
1,9a,b
catalyst systems employed in cross-coupling studies.
It is
3
computationally.
also not generally known if “poor” phosphine-based catalyst
systems are intrinsically inferior (in the context of the catalytic
cycle, as is frequently assumed) or, trivially, because the
Although specific catalytically active compounds such as
t
4a
Pd(PCy ) and Pd(PBu ) have long been available and a
3
2
3 2
general route to compounds of this type has recently been
4
b
reported, Pd(0) compounds are in fact air-sensitive and
Received: February 24, 2012
Published: March 15, 2012
5
preformed catalysts of the type PdL are rarely used. Instead,
2
©
2012 American Chemical Society
2470
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Organometallics
Article
phosphines involved are just poor reducing agents for Pd(II)
salts.
I−IV for a representative Suzuki−Miyuara cross-coupling
reaction. To this end we utilized as a basis of comparison the
representative reaction of phenylboronic acid with 4-
bromoanisole (eq 2), the 4-bromoanisole chosen to distinguish
The intrinsic complexities involved in cross-coupling
chemistry and arising from these problems have long been
recognized, and the relevant mechanistic literature has been
referred to as a “morass, with an endless list of hypothesized or
1i
claimed true catalytic species”. Other authors call attention to
more practical problems arising from the aforementioned
uncertainties, such as the extensive screening and optimization
procedures which are found to be necessary in many of the
between the desired product 4-methoxybiphenyl and the
homocoupling coupling product biphenyl. In addition,
bromoanisole is a more difficult coupling partner than is the
analogous bromobenzene and should better distinguish subtle
differences in efficacies of the various precursors.
10
studies reported in the literature.
In this vein, and assuming also that the two-coordinate
species PdL are generally more active than are the sterically
2
hindered three-coordinate derivatives, it seems quite possible
that a significant number of cross-coupling studies have not
made optimal use of the palladium added. The result could be
unnecessarily high reaction temperatures, unnecessarily long
reaction times, and/or yields lower than would be possible if
Shown in Figure 1 are reaction profiles for the formation of
4-methoxy-1,1′-biphenyl using various catalyst precursors with
specifically PdL were used. Also, of course, where reduction of
2
Pd(II) by a phosphine actually does occur to some extent,
utilization of one-third of an expensive and/or difficult to
prepare phosphine as a reducing agent is clearly wasteful and
undesirable.
To make possible the more effective use of both palladium
and phosphine in the generation of catalysts PdL , we and
2
3
others have described the use of the compounds Pd(η -
5
C H )(η -C H ) (Va, R = H), which react rapidly and
3
5
5
5
quantitatively with phosphines L to form the compounds
4
a
PdL as in eq 1.
2
Figure 1. Yield of 4-methoxy-1,1′-biphenyl from the cross-coupling of
phenylboronic acid and 4-bromoanisole catalyzed by 5 mol % Pd
catalyst systems utilizing (a) Vb + 2PPh , (b) Pd(PPh ) , and (c)
3
3 4
Pd(OAc) + 3PPh , all in dioxane containing 1 equiv of Cs CO at 50
2
3
2
3
°
C.
Unfortunately, Va decomposes on storage at room temper-
4
a
PPh as ligand L. Each reaction was carried out several times
3
ature and therefore, in spite of its potential advantages, is not
4c
under the conditions shown with periodic sampling and
monitoring by GC of both the 4-methoxy-1,1′-biphenyl and
the bromoanisole starting material. In general, there was good
mass balance between reactant and product.
a practical catalyst precursor. As an alternative, we have
shown that the easily synthesized air- and heat-stable analogue
3
5
Pd(η -1-PhC H )(η -C H ) (Vb, R = Ph) also reacts readily
3
4
5
5
with phosphines L as in eq 1 (L = a variety of mono- and
As can be seen, the Pd(OAc) -based catalyst system was
2
bidentate phosphines), forming the compounds PdL quickly
2
1
1
clearly very ineffective, possibly because of sluggish reduction of
Pd(II) under these conditions; we note that reports of
applications of this commonly used catalyst precursor generally
and efficiently. Compound Vb should therefore be a very
useful catalyst precursor for the generation of PdL and appears
2
to be a potentially very useful cross-coupling catalyst precursor
because it makes rapid, quantitative, and economical use of
both the palladium and the phosphine.
12
involve higher temperatures and longer reaction times. Water
1
is also frequently added to reaction mixtures, in the apparent
To test the hypothesis that Vb might be significantly superior
belief that it is required for reduction to occur, although it has
been shown that the rate-determining step in the formation of
to I−IV in its ability to form PdL and hence generate
2
catalytically active species, we have carried out an investigation
in which we compare Vb with compounds I−IV as catalyst
precursors for a representative, conventional Suzuki−Miyaura
cross-coupling reaction. We now report our findings, noting that
our intention has not been to develop new catalysts per se but rather
to investigate the potentially greater competence of Vb relative to I−
IV, the catalyst precursors most commonly utilized. We ultimately
come to the conclusion that Vb is to be preferred over the
alternatives because it generates the desired catalytically active
Pd(0) species from e.g. Pd(OAc)
(PPh ) is an inner-sphere
2 3 2
reduction and that the role of water is to convert the oxidized
8
b,c,e,f,h
phosphorus species to OPPh .
Nonetheless, we
3
repeated the reaction shown in Figure 1c, utilizing 20%
aqueous dioxane; as anticipated on the basis of the
8b,c,e,f,h
literature,
we obtained a reaction profile essentially
identical with that shown in Figure 1c. Thus, the intrinsic
efficacy of the IVb/PPh system was not underestimated when
3
working under anhydrous conditions.
species PdL quickly and more efficiently.
2
The other frequently used catalyst precursor, Pd(PPh ) ,
3
4
exhibited somewhat greater activity, but Vb was clearly the
most effective of the three, exhibiting a higher initial rate and
producing a higher yield of product over the course of the
experiment. The observation that the reaction rate leveled off
RESULTS AND DISCUSSION
■
We report herein an investigation of the effectiveness of Vb
compared with those of the commonly used catalyst precursors
2
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Organometallics
Article
well before 100% conversion will be discussed below. Note that
use of Vb alone, without added phosphine, was ineffective.
Figure 2 shows the reaction profile of the same coupling
reaction, but with PPh substituted by the bulkier PCy , which
3
3
Figure 3. Yield of 4-methoxy-1,1′-biphenyl from the cross-coupling of
phenylboronic acid and 4-bromoanisole catalyzed by 5 mol % Pd
t
t
catalyst systems utilizing (a) Vb + 2PBu , (b) Pd (dba) + 4PBu , (c)
3
2
3
3
3
t
t
[
PdCl(η -C H )] + 4PBu , (d) PdCl + 3PBu , and (e) Pd(OAc) +
PBu , all in dioxane containing 1 equiv of Cs CO at 50 °C.
3 2 3
3
5
2
3
2
3
2
t
3
Figure 2. Yield of 4-methoxy-1,1′-biphenyl from the cross-coupling of
t
4a
phenylboronic acid and 4-bromoanisole catalyzed by 5 mol % Pd
51.7 (w), possibly indicating the presence of free PBu
and
3
1
t
catalyst systems utilizing (a) Vb + 2PCy , (b) / Pd (dba) + 2PCy ,
3
2
2
3
3
[Pd(C H OMe)(μ-Br)(PBu )] , the product of oxidative
6 4 3 2
and (c) Pd(OAc) + 3PCy , all in dioxane containing 1 equiv of
t
13g
2
3
addition of bromoanisole to Pd(PBu ) ;
there was no
3
2
Cs CO at 50 °C.
t
4a
2
3
evidence for Pd(PBu ) (δ 84.7).
3
2
3
The catalyst systems based on [PdCl(η -C H )] and
3
5
2
has been shown elsewhere to be an effective ligand for Suzuki−
13
Pd (dba) exhibited somewhat better activities, but the use of
2 3
Miyaura coupling reactions.
We found, as is shown, that the PCy /Pd(OAc) system gave
Vb resulted clearly in a higher initial rate of coupling and higher
conversions over all time periods. Near-quantitative conversion
to 4-methoxybiphenyl was achieved within 1 h using Vb.
Reason for Decreases in Rates: Catalyst Deactivation?
As indicated in Figures 1−3, the profiles of those reactions
which were not essentially completed within 1 h tended to level
off after about 1 h. In an effort to determine whether this
behavior was a result of catalyst deactivation or of side reactions
involving the phenylboronic acid, we carried out an experiment
3
2
only trace amounts of product, suggesting that PCy is a poor
3
reducing agent under these conditions. As with catalysts based
on PPh , water is frequently (but not always) added to PCy -
3
3
1
3
based catalysts, although the possible role(s) of water with
ligands L other than triarylphosphines have not been
ascertained with certainty. Water has been reported to be
necessary for the reduction of Pd(OAc) by the bidentate
2
14a
phosphine binap, but a subsequent investigation involving
reduction by another bidentate phosphine, dppp, revealed that
intramolecular reduction by coordinated dppp occurs, as with
involving the Vb/PPh catalyst system, analogous to that shown
3
in Figure 1. After about 2 h, at which point cross-coupling had
definitely ceased, an additional 1 equiv of phenylboronic acid
was added to the reaction mixture. As is shown in Figure 4,
cross-coupling began anew and thus the problem clearly did not
involve catalyst deactivation.
Interestingly, however, addition of a 2- or 3-fold molar excess
of phenylboronic acid at the beginning of a reaction of the type
shown in Figure 4 resulted in essentially quantitative yield of
cross-coupling product within 1 h. This finding is rather
PPh , but that the redox reaction is reversible. The water serves
3
8g
merely to shift the equilibrated reaction to completion. Water
is apparently not required in reactions involving Pd(OAc)
2
n
14b,c
8c
8c
activation by PBu ,
PMe Ph, and PMePh2, but we
3
2
nonetheless carried out a cross-coupling reaction as in Figure 2c
but utilizing 20% aqueous dioxane. Only a 4% yield of coupled
product was obtained, and thus again the added water had no
effect on the yield of the cross-coupling reaction.
surprising, as it means that the Vb/PPh catalyst system may be
3
Catalyst precursors Pd (dba) and Vb resulted ultimately in
2
3
higher, comparable conversions, but use of the latter resulted in
a higher initial rate of coupling and is certainly more effective at
short reaction times. As with the PPh system, the reactions did
3
not go to completion.
We next employed the sterically demanding, normally very
t
13a−d,g
effective PBu (Figure 3),
to further our comparison of
3
Vb with conventional palladium catalyst precursors.
As was found with the Pd(OAc) /PPh and Pd(OAc) /PCy
2
3
2
3
systems, the palladium(II)-based catalyst systems Pd(OAc) /
2
t
t
PBu and PdCl /PBu exhibited low efficacies, although in this
3
2
3
case the use of aqueous dioxane with Pd(OAc) resulted in a
2
higher conversion (48%) after 2.5 h (not shown). Interestingly,
31
t
a
P NMR investigation of the Pd(OAc) /PBu reaction
2 3
Figure 4. Yield of 4-methoxy-1,1′-biphenyl from the cross-coupling of
phenylboronic acid and 4-bromoanisole catalyzed by 5 mol % Vb and
mixture indicated that one of the major palladium species in
solution was a cyclometalated complex of the type reported
previously (δ −9.04) and discussed above. The P NMR
spectrum also exhibited resonances at δ 65.5 (s), 62.2 (s), and
2
3
equiv of PPh ; another 1 equiv of phenylboronic acid was added after
h.
9c
31
3
2
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Article
t
1
comparable in activity to the Vb/PBu catalyst system if one of
the reactants is present in excess.
way, and we obtained H NMR spectra of a typical reaction
mixture containing phenylboronic acid and cesium carbonate in
dioxane. Although phenyboronic acid and phenylboroxine were
present in the expected proportions in a freshly prepared
3
In any case, these results indicate that the originally added
phenylboronic acid was for some reason no longer available for
cross-coupling after about 1 h and we briefly investigated
possible mode(s) of deterioration to less active species.
1
solution, addition of cesium carbonate resulted in the H
resonances of both being quickly replaced by resonances of at
least six new phenyl-containing compounds (o-H doublets at δ
7.47, 7.67, 7.73, 7.83, 7.89, 7.98). Brief heating to 50 °C
followed by cooling to 25 °C revealed the presence of
additional unidentifiable resonances, and we terminated the
investigation, since it seemed very unlikely that we would be
able to identify many of the new compounds.
Moreno-Man
̃
as et al. have identified several side reactions of
phenylboronic acid which can occur during Suzuki−Miyaura
15a
cross-coupling reactions,
including protodeboronation to
give benzene, homocoupling to give biphenyl, hydroxylation to
give phenol, and dehydration on heating to give phenyl-
boroxine (Scheme 2).
SUMMARY AND CONCLUSIONS
Scheme 2
■
Our results clearly confirm our hypothesis that combinations of
Vb with various representative phosphines would generate
catalyst solutions which are much more active than catalyst
systems obtained using combinations of catalyst precursors I−
IV with the same phosphines. The reason almost certainly lies
in the fact that Vb generates catalytically active species PdL2
quickly and quantitatively while the others do not, in part at
least for the reasons discussed above. A second advantage of the
In general, our GC studies did not reveal the presence of
benzene as a byproduct and yields of biphenyl and phenol were
too low (∼5%) to account for the discrepancies. Phenyl-
boroxine has been reported to exhibit relatively low cross-
coupling activity in other systems,
indeed much less effective than is phenylboronic acid in its
ability to cross-couple with bromoanisole. Phenylboroxine is
also likely to be formed at the temperature used in our cross-
coupling experiments, and at one point we considered the
possibility that dehydration of the phenylboronic acid was the
reason for the lowering of activity. This hypothesis was
dispelled, of course, when we found (see above) that water has
no effect on the efficacy of the Pd(OAc) /PPh system. Thus,
use of Vb is that the Pd(0) products PdL are formed under
2
rigorously anhydrous conditions. The potential benefits of
carrying out cross-coupling chemistry in the absence of water
1
6,17a
and we found that it is
20
have been noted previously.
The potential problems associated with use of catalyst
precursors I−IV are discussed above and have been recognized
by others but there seems previously to have been little
recognition of this fact and I−IV all continue to be used
15b
5
frequently. However, while our study shows that Pd (dba)
2
3
21
can be effective for Suzuki−Miyaura cross-coupling reactions,
catalyst systems based on reduction of palladium(II) are
unreliable and, in the absence of experiments explicitly
demonstrating the actual formation in high yields of the
anticipated palladium(0) compounds, should not be utilized
when comparing e.g. the effectiveness of various phosphine
ligands in cross-coupling reactions involving boronic acids.
Our results have also provided the first evidence available, to
our knowledge, for the negative consequences of phenylboronic
acid degradation during the course of Suzuki−Miyaura cross-
coupling reactions. Our reaction profiles also provide
information on the time scale over which this side reaction is
a factor affecting yields of cross-coupled products. Most
publications in the area of catalytic cross-coupling reactions
report isolated yields, obtained on termination of reactions after
2
3
added water enhances neither the reduction of Pd(OAc) nor
the concentration of active phenyl-boron species.
2
However, we note that there is a strong sense in the literature
that unexpectedly facile dehydration of phenylboronic acid can
result in the presence of phenylboroxine impurities, presumed
to decrease reactivity; water is therefore frequently added to
commercial phenylboronic acid reaction mixtures in an attempt
1
8
17
to convert any phenylboroxine present to phenylboronic acid.
To the contrary, however, Tokunaga et al. have provided an
alternative scenario. They find that the exchange process shown
in Scheme 2 occurs sufficiently slowly on the NMR time scale
1
that the H chemical shifts of phenyboronic acid and
19a
phenylboroxine are readily distinguishable. Using the NMR
data, K for the equilibrium shown was determined in CDCl3
and found to be such that a solution of phenyboronic acid over
a range of temperatures actually contains about 75% or more of
the phenyl-boron moieties present as phenylboroxine. There-
1
arbitrary periods of time. In such studies, little distinction can
be made between catalytic reactions which are still proceeding
at the point of termination and those whose rates have
decreased to zero before the point of termination. Indeed, the
advantages of reactions which are completed within a relatively
short time span, well before the point of termination, likewise
remain unappreciated. Thus use of isolated yields in
comparisons of various ligand systems can also be misleading.
1
9b
fore, and as we have confirmed,
examination of a high-
1
quality sample of phenylboronic acid by H NMR spectroscopy
in an anhydrous NMR solvent reveals the presence of a very
large proportion of phenylboroxine, suggesting incorrectly that
the sample is badly contaminated (and probably leading to the
aforementioned attempts to suppress dehydration of phenyl-
boronic acid by adding water). Added water is not required to
EXPERIMENTAL SECTION
■
General Procedures. All syntheses were carried out under a dry,
deoxygenated argon or nitrogen atmosphere with standard Schlenk
line techniques. Argon was deoxygenated by passage through a heated
column of BASF copper catalyst and then dried by passing through a
column of 4 A molecular sieves. Solvents were dried by the procedure
“restore” the dehydrated phenylboronic acid, as the equilibrium
of Scheme 2 shifts to the left as phenylboronic acid is
consumed via e.g. transmetalation.
That said, it seemed clear that the phenylboronic acid
present in our reaction mixtures must be deteriorating in some
2
2
described in the literature. The authors state that H O levels of <5
2
ppm can be obtained for drying THF over appropriately activated
2
473
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Organometallics
Article
molecular sieves for 72 h. Although we are using 1,4-dioxane as a
solvent, one can assume similar levels of dryness are achieved.
Phosphines were purchased from Strem Chemicals and all other
compounds from Aldrich. Handling and storage of air-sensitive
stirred at 50 °C for 3 h. Aliquots of 0.5 mL were removed at specified
intervals, diluted with ∼10 mL of ethyl ether, filtered through a pad of
Celite with 10−20 mL of ethyl ether, concentrated in vacuo to a solid,
dissolved in 20 mL of toluene/hexadecane (0.0034 M), and analyzed
t
compounds (PBu , PCy ) were carried out in an MBraun Labmaster
by GC.
Utilizing [PdCl(η -C
3
3
3
glovebox. NMR spectra were recorded on Bruker 400 or 600 MHz
H
3
)]
5
2
. Under an atmosphere of argon, a
1
spectrometers, with H NMR data being referenced to TMS via the
solution of 4-bromoanisole (0.935 g, 5.0 mmol) and phosphine (0.5
t
residual proton signals of the deuterated solvents, and GC experiments
were carried out using a Varian 3900 GC equipped with a CP 8400
autosampler, a 0.32 mm Varian fused silica column, and an FID. The
injector temperature was set at 250 °C, the initial column temperature
at 140 °C, and the detector temperature at 250 °C. Hexadecane was
added as an internal standard, and GraphPad Software Prism Version
mmol of PBu
3
) in 5 mL of dioxane was added to a mixture of
)] (0.0458 g, 0.125 mmol), phenylboronic acid (0.610
g, 5.0 mmol), and Cs CO (3.258 g, 10 mmol) in 5 mL of dioxane,
3
[PdCl(η -C
H
3
5
2
2
3
and the mixture was stirred at 50 °C for 3 h. Aliquots of 0.5 mL were
removed at specified intervals, diluted with ∼10 mL of ethyl ether,
filtered through a pad of Celite with 10−20 mL of ethyl ether,
concentrated in vacuo to a solid, dissolved in 20 mL of toluene/
hexadecane (0.0034 M), and analyzed by GC.
3
.02 was used for curve fitting.
3
5
23
Synthesis of Pd(η -1-PhC H )(η -C H ) (Vb). THF was dried
3
4
5 5
by passage through a column of activated alumina and was stored over
Utilizing PdCl
bromoanisole (0.935 g, 5.0 mmol) and phosphine (0.5 mmol of PBu
in 5 mL of dioxane was added to a mixture of PdCl (0.0443 g, 0.25
mmol), phenylboronic acid (0.610 g, 5.0 mmol), and Cs CO (3.258
2
. Under an atmosphere of argon, a solution of 4-
t
4
1
Å molecular sieves. A solution of NaCp in THF (2.0 M, Aldrich;
)
3
.45 mL, 2.90 mmol of NaCp) was diluted by THF (20 mL) in a
2
3
dropping funnel and added dropwise to a solution of [Pd(η -1-
PhC H )Cl] (0.601 g, 1.16 mmol) in THF (20 mL) at −78 °C. The
2
3
g, 10 mmol) in 5 mL of dioxane, and the mixture was stirred at 50 °C
for 3 h. Aliquots of 0.5 mL were removed at specified intervals, diluted
with ∼10 mL of ethyl ether, filtered through a pad of Celite with 10−
3
4
2
resulting deep purple solution was stirred for 5 min, warmed to room
temperature, and then placed in an ice bath. The solvent was removed
from the cooled solution under reduced pressure, and the product was
extracted using three 20 mL portions of hexanes. The filtrate was
reduced under vacuum, yielding an oily purple solid. The solid was
dissolved in a minimum of hexanes, and purple-red crystals were
collected at −40 °C. Beautiful purple-red crystals can also be obtained
2
0 mL of ethyl ether, concentrated in vacuo to a solid, dissolved in 20
mL of toluene/hexadecane (0.0034 M), and analyzed by GC.
AUTHOR INFORMATION
■
1
Notes
by sublimation, but with some loss. Yield: 0.565 g, 84%. H NMR
The authors declare no competing financial interest.
(
C D , 600 MHz): δ 2.16 (d, J = 10.5 Hz, 1H, H(3a)), 3.36 (d, J = 6.1
7 8
Hz, 1H, H(3s)), 3.84 (d, J = 9.8 Hz, 1H, H(1)), 5.14 (ddd, J = 10.5,
9
7
.8, 6.1 Hz, 1H, H(2)), 5.63 (s, 5H, C H ), 6.98−7.03 (m, 3H), 7.24−
ACKNOWLEDGMENTS
5
5
■
.27 (m, 2H)).
General Experimental Methodologies for Determining
Reaction Profiles: Formation of 4-Methoxy-1,1′-biphenyl.
We are grateful to Johnson-Matthey for a generous loan of
PdCl and acknowledge financial support from the Natural
2
3
5
Utilizing Pd(η -1-PhC H )(η -C H ) (Vb). Under an atmosphere of
argon, Vb (0.072 g, 0.25 mmol) and a phosphine (0.5 mmol;
PPh , PCy , PBu ) were combined in 5 mL of dioxane and
stirred at 25 °C for h. The resulting brown solution was added
to a mixture of 4-bromoanisole (0.935 g, 5.0 mmol),
phenylboronic acid (0.610 g, 5.0 mmol), and Cs CO (3.258
Sciences and Engineering Research Council of Canada
(Discovery Grant to M.C.B., Undergraduate Summer Award
to J.E.B.) and Queen’s University (MacLaughlin Scholarship to
A.W.F.).
3
4
5 5
t
3
3
3
2
3
REFERENCES
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Utilizing Pd(PPh ) . Under an atmosphere of argon, a solution of 4-
3
4
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(
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2 3
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t
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3
3
2
(
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2
3
stirred at 50 °C for 3 h. Aliquots of 0.5 mL were removed at specified
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2
3
bromoanisole (0.935 g, 5.0 mmol) and phosphine (0.5 mmol; PPh ,
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3
t
PCy , PBu ) in 5 mL of dioxane was added to a mixture of Pd (dba)
3
3
2
3
(
0.114 g, 0.125 mmol), phenylboronic acid (0.610 g, 5.0 mmol), and
Cs CO (3.258 g, 10 mmol) in 5 mL of dioxane, and the mixture was
2
3
2
474
dx.doi.org/10.1021/om300154m | Organometallics 2012, 31, 2470−2475

Organometallics
Article
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(
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t
preformed catalyst, Pd(PBu ) . Of the remaining hits, 26 (52%)
3
2
(
16) See, for example: Antoft-Finch, A.; Blackburn, T.; Snieckus, V. J.
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3
4
2
3
Pd(OAc) , and 21 (42%) utilized preformed PdCl L or a
2
2 2
(
combination of PdCl and L. Note that PdCl reacts readily with
2
2
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(
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3
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(
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(
1
1
́
(
19) (a) Tokunaga, Y.; Ueno, H.; Shimomura, Y.; Seo, T. Heterocycles
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́
2
3
(
9
8.8% pure as the crystalline solid and phenylboroxine prepared as in
1
15b
1
the literature.
H NMR of phenylboronic acid: in CDCl , δ 7.74 (d,
3
(
o-H), 7.41 (t, m-H), 7.61 (t, p-H); in dioxane, δ 7.67 (d, o-H), 7.24 (t,
3
m-H), 7.30 (t, p-H); in D O, δ 7.77 (d, o-H), 7.46 (t, m-H), 7.53 (t, p-
2
S.; Shaik, S. J. Organomet. Chem. 2004, 689, 3728. (i) Amatore, C.;
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1
H). H NMR of phenylboroxine: in CDCl , δ 8.25 (d, o-H), 7.51 (t,
3
m-H), 7.60 (t, p-H); in dioxane, δ 8.16 (d, o-H), 7.40 (t, m-H), 7.48 (t,
p-H).
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stoichiometric (3:1) ratios.
t
3
(
9) Indeed, reaction of IV with PBu , generally regarded as one of
the more effective phosphines in palladium(0)-catalyzed cross-
1
coupling reactions, results in significant cyclometalation of the
t
3
PBu to give complexes of relatively low catalytic activity. (a) Wu, L.;
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(
21) Complicating the issue, however, we find that Pd (dba) -based
2 3
catalyst systems are relatively ineffective for Sonogashira coupling
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preparation.
2
011, 30, 5038. (c) Thus, a 31P NMR spectrum run at 25 °C after the
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attributable to a metalated product, in addition to resonances at δ 62.2
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t
t
3
5
and 65.5, attributable to free PBu and a complex of PBu ,
(23) Note that Pd(η -1-PhC H )(η -C H ) (Vb) is now available
3
3
3 4 5 5
4a,9a
respectively.
10) (a) Biscoe, M. R.; Fors, B. P.; Buchwald, S. L. J. Am. Chem. Soc.
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2
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(
2
2
Konakahara, T. Org. Lett. 2010, 12, 1300. (e) Shang, R.; Xu, Q.; Jiang,
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4
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̈
́
2
1
2
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dx.doi.org/10.1021/om300154m | Organometallics 2012, 31, 2470−2475