Direct arylation of 2-methylthiophene with isolated [PdAr(μ-O 2CR)(PPh3)]n complexes: Kinetics and mechanism

Article abstract of DOI:10.1021/om300367k

The palladium-catalyzed direct arylation of aromatic compounds with aryl halides has been proposed to involve an arylpalladium carboxylate intermediate. However, isolated arylpalladium complexes, which undergo C-H bond cleavage of aromatic substrates without the aid of additional activators or promoters, have been scarcely documented. This paper reports that [PdAr(μ-O ₂CR)(PPh₃)]_n complexes (1: Ar = Ph, 2-MeC ₆H₄, 2,6-Me₂C₆H₃; R = Me, ^tBu) successfully react with 2-methylthiophene (2) in the absence of additives to afford 5-aryl-2-methylthiophenes (3) in high yields. The reactivity increases with increasing bulkiness of the Ar group, whereas the bulky pivalate ligand (R = ^tBu) reduces the reactivity as compared with the acetate ligand (R = Me). Complex 1 is in equilibrium with the monomeric species [PdAr(O₂CR-κ²O)(PPh₃)] (5) in solution, as confirmed by IR spectroscopy. Kinetic examinations have suggested that the direct arylation proceeds via 5, which undergoes C-H bond cleavage of 2. Complex 1 serves as a good catalyst for direct arylation of 2 with aryl bromides.

Full text of DOI:10.1021/om300367k

Article
pubs.acs.org/Organometallics
Direct Arylation of 2-Methylthiophene with Isolated [PdAr(μ-O2CR)
(PPh3)]n Complexes: Kinetics and Mechanism
Masayuki Wakioka, Yuki Nakamura, Qifeng Wang, and Fumiyuki Ozawa*
International Research Center for Elements Science (IRCELS), Institute for Chemical Research, Kyoto University, Uji, Kyoto
611-0011, Japan
S
* Supporting Information
ABSTRACT: The palladium-catalyzed direct arylation of
aromatic compounds with aryl halides has been proposed to
involve an arylpalladium carboxylate intermediate. However,
isolated arylpalladium complexes, which undergo C−H bond
cleavage of aromatic substrates without the aid of additional
activators or promoters, have been scarcely documented. This
paper reports that [PdAr(μ-O2CR)(PPh3)]n complexes (1: Ar
= Ph, 2-MeC6H4, 2,6-Me2C6H3; R = Me, tBu) successfully react with 2-methylthiophene (2) in the absence of additives to afford
5-aryl-2-methylthiophenes (3) in high yields. The reactivity increases with increasing bulkiness of the Ar group, whereas the
bulky pivalate ligand (R = tBu) reduces the reactivity as compared with the acetate ligand (R = Me). Complex 1 is in equilibrium
with the monomeric species [PdAr(O2CR-κ2O)(PPh3)] (5) in solution, as confirmed by IR spectroscopy. Kinetic examinations
have suggested that the direct arylation proceeds via 5, which undergoes C−H bond cleavage of 2. Complex 1 serves as a good
catalyst for direct arylation of 2 with aryl bromides.
Recent theoretical studies have suggested the intermediacy of
an arylpalladium carboxylate, which undergoes C−H bond
cleavage of aromatic substrates, typically via a concerted
metalation−deprotonation (CMD) pathway.4,5 However, iso-
lated aryl complexes that undergo C−H bond cleavage of
aromatic compounds have been extremely limited.6−9 Mori and
co-workers reported that [PdAr(X)(bipy)] (X = I, Br, Cl)
reacted with thiophenes to afford the corresponding arylth-
iophenes in good to high yields, where the addition of AgNO3
and KF to the system was essential for the reaction to proceed.6
More recently, Hartwig and co-workers carried out detailed
kinetic examinations using [PdAr(O2CMe-κ2O)(PtBu3)].8 They
found that the arylpalladium acetate itself is poorly reactive, but
it coupled with pyridine N-oxide via a cooperative C−H
functionalization process with the aid of a cyclometalated
complex.8b Thus, although theoretical studies have suggested a
simple reaction process for the conversion of A to B, isolated
arylpalladium complexes, which are reactive to aromatic
compounds without the aid of additional activators or
promoters, have been scarcely documented.
INTRODUCTION
■
Dehydrohalogenative coupling of aromatic compounds with
aryl halides catalyzed by palladium complexes (so-called direct
arylation) has attracted a great deal of attention.1 It has been
recognized that direct arylation is advantageous over traditional
cross-coupling reactions in terms of reduced waste generation
and fewer reaction steps. Moreover, direct arylation that does
not need organometallic reagents has excellent functional group
tolerance. In this context, a number of studies have been carried
out to improve the catalytic activity and to expand the substrate
scope.2 Recently, direct arylation has been applied to
polycondensation reactions giving π-conjugated polymers.3
Scheme 1 outlines a generally accepted catalytic cycle for
Pd(0)-catalyzed direct arylation, which is basically similar to
Scheme 1. Plausible Catalytic Cycle for Direct Arylation
Herein, we disclose that arylpalladium complexes of the
formula [PdAr(μ-O2CR)(PPh3)]n (1, eq 1) react with 2-
methylthiophene (2) to afford 5-aryl-2-methylthiophenes (3)
as direct arylation products in high yields. The reactions
successfully proceed without the use of additives. Kinetic and
structural examinations have suggested that 1 is interconverted
with the monomeric species [PdAr(O2CR-κ2O)(PPh3)] (5) in
solution, and 5 reacts with 2 to afford 3.
that for cross-coupling reactions.1 A distinct difference between
the two catalytic cycles exists in the conversion of
monoarylpalladium A into diarylpalladium B (step b). Cross-
coupling involves the transmetalation of A with organometallic
reagents, whereas direct arylation requires C−H bond cleavage
of aromatic substrates on A, and this step is often assumed as
the turnover limit in the catalytic cycle.2f
Received: May 1, 2012
Published: June 14, 2012
© 2012 American Chemical Society
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RESULTS AND DISCUSSION
■
Figure 1. Time course of the formation of 3a and PhPh in the reaction
of 1a (18 mM) with 2 (0.72 M) in 1,4-dioxane at 90 °C, followed by
HPLC using C6Me6 as an internal standard.
Synthesis and Reactions of 1. Complexes 1a−e having
three kinds of aryl and carboxylate ligands were prepared by the
treatment of the corresponding μ-hydroxy complexes with
carboxylic acids, according to the synthetic procedure for 1a
(eq 1).10 X-ray diffraction analysis revealed that 2-methylphenyl
(1b) and phenyl (1d) complexes adopt a dimeric structure with
μ-carboxylate ligands, similarly to 1a,11 whereas 2,6-dimethyl-
phenyl complex 1c is a tetramer of the [Pd(2,6-Me2C6H3)(μ-
O2CMe)(PPh3)] units in the crystal (vide infra).
Treatment of 1a (10 μmol, 18 mM) with 2-methylthiophene
(2, 0.40 mmol, 40 equiv/1a) in 1,4-dioxane at 90 °C for 3 h
afforded 5-phenyl-2-methylthiophene (3a, 9.6 μmol, 96%/1a)
and [PdPh(O2CMe)(PPh3)2] (4a), along with deposition of
Pd-black and a small amount of biphenyl (0.4 μmol, 4%/1a)
(Scheme 2). The formation of 3a and biphenyl was confirmed
Figure 2. (a) First-order plot for the formation of 3a in the reaction of
1a (18 mM) with 2 (0.72 M) in 1,4-dioxane at 90 °C. (b) Plot of first-
order rate constants (kobsd) against the concentrations of 2 in 1,4-
dioxane at 90 °C.
Scheme 2. Reaction of 1a with 2-Methylthiophene (2)
the following rate equation: d[3a]/dt = k2[1a][2] (k2 = 3.5(2)
× 10−4 s−1 M−1).
In the above experiments, we noticed that the amounts of
biphenyl varied with experimental procedures. The reaction in
Scheme 2 was examined in a gastight NMR sample tube,
degassed through freeze−pump−thaw cycles, where 4%/1a of
biphenyl was formed. On the other hand, the kinetic runs given
in Figures 1 and 2 were carried out using standard Schlenk
techniques under a nitrogen atmosphere to perform repeated
sampling for HPLC analysis, where 12−16%/1a of biphenyl
was formed. Since the contamination with air could be a reason
for the increasing amounts of biphenyl, further experiments
were conducted in a gastight NMR sample tube. In this case,
the reaction progress was followed by NMR spectroscopy, and
organic products were analyzed by HPLC at 100% conversion
of the starting complex 1.
by HPLC using C6Me6 as an internal standard. The reaction
solution was evaporated, dissolved in CD2Cl2, and examined by
NMR spectroscopy, showing the absence of 1a and the
formation of 4a (9.5 μmol, 95%/1a). These observations
indicate that one-half of 1a is converted to 2 and Pd-black, and
the other half is converted to 4a, while the biphenyl formation
takes place in a small quantity as well.
The reaction was particularly smooth in dimethylacetamide
(DMA) as a polar solvent.12 The bis-PPh3 complex 4a was
clearly less reactive than the mono-PPh3 complex 1a.13
Moreover, the iodide [PdPh(μ-I)(PPh3)]2 and hydroxy [PdPh-
(μ-OH)(PPh3)]2 complexes did not react with 2.
Table 1 summarizes the effects of acetic acid (AcOH), pivalic
i
acid (PivOH), and Pr2NEt on the reaction of 1a with 2. The
i
Table 1. Effects of Carboxylic Acids and Pr2NEt on the
a
Reaction of 1a with 2 in 1,4-Dioxane at 90 °C
Kinetic Studies. Figure 1 shows the time course of the
formation of 3a and biphenyl in the reaction of 1a with 2 (40
equiv) in 1,4-dioxane at 90 °C. Both compounds were
simultaneously produced in the system. Their formation
continued at a slower rate after the total yield reached 100%/
1a, due to the slow conversion of 4a.13 As a result, the first-
order plot gradually deviated from a straight line (Figure 2a),
but the formation rate of 3a could be estimated from the early
stage of the plot. The rate constants observed at five different
concentrations of 2 exhibited a good linear correlation with the
[2]0 values (Figure 2b). The kinetic data were consistent with
b
entry
additive (mM)
t1/2 (min)
product ratio 3a:PhPh
1
2
3
4
5
6
7
none
46
66
96:4
83:17
81:19
95:5
95:5
98:2
AcOH (20)
AcOH (39)
PivOH (20)
PivOH (39)
iPr2NEt (20)
iPr2NEt (39)
139
131
231
53
56
98:2
a
b
Reaction conditions: [1a]0 = 18 mM, [2]0 = 0.72 M. Half-lives of 1a
estimated by 31P{1H} NMR spectroscopy.
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addition of AcOH and PivOH caused a notable drop in the
reactivity (entries 1−5). On the other hand, the effect of
iPr2NEt was relatively small, while the selectivity for 3a was
slightly improved (entries 6, 7).
Table 2 compares the reactions of 1a−e with 2 in THF at 65
°C. Interestingly, the reactivity of acetate complexes 1a−c
Table 3. IR Data for 1a−d in KBr and CH2Cl2 (cm−1)
a
Table 2. Effects of Ar and RCO2 Ligands on the Reactions of
1a−e with 2 in THF at 65 °C
solution (CH2Cl2)
a
a
b
complex
solid (KBr)
bridging (1)
bidentate (5) ratio 1:5
c
b
1a
1b
1c
1d
1578, 1415
1581, 1417
1548, 1413
1577, 1415
1578, 1419
1581, 1416
1551, 1413
1577, 1415
−
100:0
84:16
57:43
100:0
entry
Ar
R
t1/2 (min) product ratio 3:ArAr
1517, 1450
1
2
3
4
5
Ph
Me
Me
Me
tBu
CF3
(1a)
(1b)
(1c)
(1d)
(1e)
176
89
91:9
100:0
100:0
93:7
1516, 1450
c
2-MeC6H4
2,6-Me2C6H3
Ph
−
57
a
Wavenumbers of νCO2asym and νCO2sym absorptions in KBr or CH2Cl2
559
550
b
asym
([Pd] = 20 mM). Ratio of the νCO2
and bidentate (5) complexes. Not observed.
absorptions of bridging (1)
Ph
45:55
c
a
Reaction conditions: [1]0 = 18 mM except for 1c (9 mM), [2]0 =
b
0.72 M. Half-lives of 1 estimated by 31P{1H} NMR spectroscopy.
the data for 1c. Unlike 1c, complexes 1a, 1b, and 1d adopt
dimeric structures bridged by two μ-acetate ligands in the solid
increased with increasing bulkiness of Ar groups: 1a < 1b < 1c
(entries 1−3). Since the selectivity for direct arylation products
3 (5-aryl-2-methylthiophenes) was also improved, it was
considered that a bulky Ar group enhanced the reactivity
toward 2. Pivalate (1d) and trifluoroacetate (1e) complexes
were clearly less reactive than the acetate complexes, and 1e
formed biphenyl as the major product (entries 4, 5).
Structural Examinations. The reactivity difference be-
tween 1a−d was correlated with their solution structures.
Figure 3 shows the IR spectra of 1c in a solid (KBr) and a
asym
sym
state, showing the νCO2
and νCO2 bands at around 1580
and 1415 cm−1, respectively (ΔνCO2 ≈ 165 cm−1). In CH2Cl2,
1b exhibited small absorptions arising from the monomeric
species [Pd(2-MeC6H4)(O2CMe-κ2O)(PPh3)] (5b) (1517 and
1450 cm−1; ΔνCO2 = 67 cm−1), in addition to the absorptions of
the parent dimer 1b. In contrast, 1a and 1d showed no notable
absorptions assignable to monomeric species. With consid-
asym
eration of the absorbance values of νCO2
bands, it was
concluded that the amount of monomeric species generated
from the parent dimer or tetramer in solution increases in the
order 1d ≈ 1a < 1b < 1c. This order is in accordance with the
increasing reactivity order of these complexes toward 2-
methylthiophene (2).
Figure 4 shows the crystal structure of μ-pivalate complex 1d,
which adopts a folded structure of two square-planar units,
connected by two μ-pivalate ligands. The phenyl ligand on one
of the square-planar units is located close to the PPh3 ligand on
the other square-planar unit, and they undergo steric repulsion
from each other. On the other hand, the tBu groups of pivalate
Figure 3. IR spectra of 1c in KBr and CH2Cl2 ([Pd] = 20 mM).
solution (CH2Cl2). This complex has a tetrameric form of the
[Pd(2,6-Me2C6H3)(μ-O2CMe)(PPh3)] units in the solid state
asym
sym
(Figure S2), showing the νCO2
and νCO2 bands at 1548
and 1413 cm−1, respectively. The difference between the two
absorptions (ΔνCO2 = 135 cm−1) is consistent with the bridging
coordination of acetate ligands.14
On the other hand, 1c dissolved in CH2Cl2 ([1c]0 = 5 mM;
[Pd] = 20 mM) exhibited two sets of νCO2 bands. The
absorptions at 1551 and 1413 cm−1 are due to the tetrameric
complex 1c with bridging acetates, whereas those observed at
1516 and 1450 cm−1 (ΔνCO2 = 66 cm−1) are assignable to the
monomeric complex [Pd(2,6-Me2C6H3)(O2CMe-κ2O)(PPh3)]
(5c), having a bidentate acetate ligand.15 Since the 31P{1H}
NMR spectrum was significantly broadened at room temper-
ature, it was concluded that the tetrameric and monomeric
complexes are rapidly interconverted with each other in
solution (eq 2).
Figure 4. Crystal structure of 1d·CH2Cl2 with 30% probability
ellipsoids. Hydrogen atoms and a CH2Cl2 molecule are omitted for
clarity. Selected bond distances (Å) and angles (deg): Pd−C1 =
1.987(3), Pd−P1 = 2.2368(7), Pd−O1 = 2.111(2), Pd−O2 =
2.118(2), C1−Pd−P1 = 89.83(8), O1−Pd−O2 = 88.22(8).
The structures of 1a, 1b, and 1d were similarly examined by
IR spectroscopy. Table 3 summarizes the results, together with
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ligands are extruded outside the molecule and, thus, are much
less sterically demanding for the molecular structure. Dimeric
complexes 1a11 and 1b (Figure S1) displayed similar crystal
structures.
Reflecting these structural features, the folding angle between
two coordination planes was almost the same for μ-acetate (1a,
49.1°) and μ-pivalate (1d, 48.9°) complexes (Table S1). In
contrast, the folding angle of 1b, having a bulky 2-methylphenyl
ligand (57.4°), was clearly wider than that of phenyl complexes
(49.0 0.1°). Thus, it is likely that the dimeric form of 1b is
unstable for steric reasons and prone to dissociate to the
monomeric form 5b in solution. Although the steric condition
of tetrameric 1c could not be simply compared with that of the
dimeric analogues, it seems reasonable that the bulky 2,6-
dimethylphenyl ligand in 1c leads to a marked propensity to
form the monomeric complex 5c in solution.
Figure 5. Catalytic direct arylation of 2-methylthiophene (2, 1.0
mmol) with PhBr (0.5 mmol) and 2,6-Me2C6H3Br (0.5 mmol) in
DMA (1.0 mL) in the presence of 1a (0.010 mmol) and K2CO3 (1.0
mmol) at 90 °C.
Reaction Mechanism. Accordingly, the formation process
of 3 from 1 and 2 would be described as shown in Scheme 3.
content of 5 tends to provide the higher reactivity toward 2, it
is reasonable that 5 reacts with 2 to give 3. These observations
are consistent with the CMD pathway, which has been
proposed by theoretical studies,4,5 but so far scarcely
reproduced by experimental studies using isolated arylpalla-
dium complexes.
Scheme 3. Proposed Mechanism for Reaction of 1 and 2
EXPERIMENTAL SECTION
■
General Considerations. All manipulations were carried out
under a nitrogen atmosphere using standard Schlenk techniques.
Nitrogen was dried by passing through P2O5 (Merck, SICAPENT).
NMR spectra were recorded on a Bruker Avance 400 spectrometer
(1H NMR 400.13 MHz, 13C NMR 100.62 MHz, 19F NMR 376.46
MHz, and 31P NMR 161.97 MHz). Chemical shifts are reported in δ
(ppm), referenced to 1H (residual) and 13C signals of deuterated
solvents as internal standards or to the 19F signal of C6F6 (δ −163.0)
and the 31P signal of 85% H3PO4 (δ 0.0) as external standards.
Elemental analysis was performed by ICR Analytical Laboratory,
Kyoto University. IR spectra were recorded on a JASCO FT/IR-410 or
FT/IR-4100 spectrometer in a KBr pellet or a NaCl cell (path length =
0.1 cm). Analytical HPLC was carried out on a JASCO HPLC
assembly consisting of a PU-2080 Plus pump, a model RI-1530
refractive index detector, and an Intersil ODS-P column (CH3CN/
H2O = 3:2 v/v). GLC analysis was performed on a Shimadzu GC-
2025 instrument equipped with a FID detector and a CBP-1 capillary
column (25 m × 0.25 mm). Mass spectra were measured on a
Shimadzu GC-MS QP2010 spectrometer (EI, 70 eV).
Toluene (Kanto, dehydrated), and CH2Cl2, Et2O, and THF (Wako,
dehydrated) were used as received. 1,4-Dioxane and DMA were dried
over Na/Ph2CO and CaH2, respectively, distilled, and stored over
activated MS4A. 2-Methylthiophene and bromoarenes were distilled
after passing through a short pad of activated alumina. K2CO3 was
dried overnight at 120 °C under vacuum and handled in a glovebox.
[PdCl2(PPh3)2],16 [PdPh(μ-OH)(PPh3)]2,17 [Pd(2-MeC6H4)(μ-
OH)(PPh3)]2,18 [PdPh(μ-O2CMe)(PPh3)]2 (1a),10 [PdPh(O2CMe)-
(PPh3)2] (4a),19 [PdPh(μ-I)(PPh3)]2,17 and 5-phenyl-2-methylthio-
phene (3a)20 were prepared according to the literature. All other
chemicals were obtained from commercial suppliers and used without
further purification.
Although complex 1 exists as a dimer or tetramer of the
[PdAr(μ-O2CR)(PPh3)] units in the solid state, they are in
equilibrium with the monomeric complex 5 in solution. Since
the reactivity of 1 is clearly enhanced by increasing the amount
of 5, it is reasonable that product 3 is formed from 5.
Coordination of 2 to 5, followed by C−H bond cleavage of the
thiophene ligand on C, forms an aryl−thienyl intermediate D,
which reductively eliminates 3, along with the formation of
[Pd(PPh3)] and AcOH. Probably, the highly coordinatively
unsaturated Pd(0) species thus generated rapidly decomposes
under the reaction conditions to provide free PPh3 and Pd-
black. The free PPh3 then combines with a part of 1 to form
[PdAr(O2CR)(PPh3)2] (4).
Catalytic Properties of 1. Complex 1a served as a good
catalyst for direct arylation of 2-methylthiophene (2) with aryl
bromides. Figure 5 demonstrates the competitive formation of
3a and 3c in the catalytic reaction of 2 with PhBr and 2,6-
Me2C6H3Br. It is seen that PhBr is evidently more reactive than
2,6-Me2C6H3Br in the catalytic system. This reactivity order is
opposite of that observed in stoichiometric systems (entries 1
and 3 in Table 2), indicating that the rate of catalytic reaction is
controlled by an elementary process other than step b in
Scheme 1: presumably the oxidative addition step a.
Synthesis of [Pd(2,6-Me2C6H3)(μ-OH)(PPh3)]2. This complex
was prepared according to the procedure for [PdPh(μ-OH)-
(PPh3)]2.17 A mixture of [PdCl2(PPh3)2] (1.43 g, 2.0 mmol), 2,6-
dimethyliodobenzene (500 μL, 3.4 mmol), a 25 M aqueous solution of
KOH (2 mL), and benzene (40 mL) was stirred under reflux for 6
days. After water (50 mL) and benzene (50 mL) were added to the
hot heterogeneous solution, the organic layer was separated, and the
aqueous phase was washed with benzene (3 × 60 mL). The combined
benzene solution was filtered through a Celite pad, and the filtrate was
concentrated to afford a yellow oil, which was sonicated in acetone (40
mL) to afford a white solid. The solid was collected by filtration,
washed with acetone, and dried under vacuum to afford a mixture of
CONCLUSION
■
It has been found that the complexes [PdAr(μ-O2CR)(PPh3)]n
(1), bearing PPh3 and μ-carboxylate ligands, are sufficiently
reactive toward 2-methylthiophene (2), affording the corre-
sponding direct arylation products 3 in high yields. Although
complexes 1 adopt a dimeric or tetrameric structure in the solid
state, they are interconverted with the monomeric species
[PdAr(O2CR-κ2O)(PPh3)] (5) in solution. Since the higher
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[Pd(2,6-Me2C6H3)(μ-OH)(PPh3)]2 (56%) and [Pd(2,6-Me2C6H3)(μ-
I)(PPh3)]2 (4%) (600 mg, 60% in total), which was employed for the
synthesis of 1c without separation. The identification data for [Pd(2,6-
Me2C6H3)(μ-OH)(PPh3)]2 are as follows. 1H NMR (CD2Cl2): δ
−1.82 (d, J = 2.8 Hz, 2H, OH), 2.61 (s, 12H, CH3), 6.43 (d, J = 7.6
Hz, 4H, H3,5 of C6H3), 6.57 (t, J = 7.6 Hz, 2H, H4 of C6H3), 7.21 (dt, J
= 7.6, 2.0 Hz, 12H, H2,6 of Ph), 7.31−7.39 (m, 18H, H3,4,5 of Ph).
31P{1H} NMR (CD2Cl2): δ 31.0 (s). 13C{1H} NMR (CD2Cl2): δ 26.8
(d, J = 4 Hz, CH3), 124.1 (s, C4 of C6H3), 125.6 (s, C3,5 of C6H3),
128.6 (d, J = 11 Hz, C3,5 of Ph), 130.8 (d, J = 1 Hz, C4 of Ph), 131.9
(d, J = 48 Hz, C1 of Ph), 134.6 (d, J = 12 Hz, C2,6 of Ph), 142.0 (d, J =
2 Hz, C2,6 of C6H3), 153.0 (d, J = 6 Hz, C1 of C6H3). Anal. Calcd for
0.93C52H50O2P2Pd2·0.07C52H48I2P2Pd2: C, 62.63; H, 5.05. Found: C,
62.82; H, 5.10.
Reaction of [PdPh(μ-O2CMe)(PPh3)]2 (1a) with 2-Methylthio-
phene (2) (Scheme 2 and Table 1). A typical procedure for the
experiments in Scheme 1 and Table 1 is as follows. Complex 1a (10.1
mg, 0.010 mmol) and C6Me6 (4.1 mg, 0.025 mmol; internal standard)
were placed in an NMR sample tube equipped with a Teflon screw
valve, and 1,4-dioxane (0.50 mL) and 2-methylthiophene (2; 39 μL,
0.40 mmol) were added at room temperature. The solution was
degassed three times by freeze−pump−thaw cycles. The sample tube
was placed in an oil bath controlled to 90 °C. The reaction was
followed at intervals by 31P{1H} NMR spectroscopy using the
following marker signals: 1a (δ 30.7), [PdPh(O2CMe)(PPh3)2] (4a;
δ 21.9). After complete consumption of 1a, the coupling product (3a)
and biphenyl were analyzed by GC-MS and HPLC. The solution was
concentrated to dryness, dissolved in CD2Cl2 (0.5 mL), and analyzed
by 1H and 31P{1H} NMR spectroscopy. The amount of 4a was
determined by 1H NMR spectroscopy using the following marker
signals: C6Me6 (δ 2.20), 4a (δ 6.56). The NMR data of 4a were
identical to those reported.18 1H NMR (CD2Cl2): δ 0.87 (s, 3H, CH3),
6.31 (virtual triplet, J = 7.2 Hz, 2H, H3,5 of PdPh), 6.52 (d, 1H, J = 7.2
Hz, H4 of PdPh), 6.56 (d, 2H, J = 7.6 Hz, H2,6 of PdPh), 7.28 (virtual
triplet, J = 7.6 Hz, 12H, H2,6 of PPh), 7.36 (d, 6H, J = 7.2 Hz, H4 of
PPh), 7.40 (br, 12H, H3,5 of PPh). 31P{1H} NMR (CD2Cl2): δ 23.2
(s).
Kinetic Examinations for the Reaction of [PdPh(μ-O2CMe)-
(PPh3)]2 (1a) with 2-Methylthiophene (2) (Figures 1 and 2). A
typical procedure is as follows. To a 10 mL Schlenk tube containing
complex 1a (40.4 mg, 0.040 mmol) and C6Me6 (16.3 mg, 0.10 mmol;
internal standard) were added successively 1,4-dioxane (2.0 mL) and 2
(155 μL, 1.60 mmol). The resulting solution (total volume = 2.2 mL)
was degassed three times by freeze−pump−thaw cycles. The solution
was stirred at 90 °C under a nitrogen atmosphere. The amounts of 5-
phenyl-2-methylthiophene (3a) and biphenyl produced at intervals
were followed by HPLC.
Synthesis of [PdPh(μ-O2CtBu)(PPh3)]2 (1d). This complex was
prepared according to the procedure for [PdPh(μ-O2CMe)(PPh3)]2.10
A mixture of [PdPh(μ-OH)(PPh3)]2 (90.3 mg, 0.10 mmol), pivalic
acid (38.1 mg, 0.37 mmol), and benzene (5 mL) was stirred at room
temperature for 10 min to afford a pale yellow solution. The solvent
was removed, and the residue was dissolved in CH2Cl2 (5 mL), diluted
with hexane (20 mL), and allowed to stand at −20 °C to afford pale
yellow crystals of 1d, which were collected by filtration, washed with
cold Et2O, and dried under vacuum (35.6 mg, 32%). The complexes
[Pd(2-MeC6H4)(μ-O2CMe)(PPh3)]2 (1b) and [Pd(2,6-Me2C6H3)(μ-
O2CMe)(PPh3)]4 (1c) were similarly prepared using [Pd(2-MeC6H4)-
(μ-OH)(PPh3)]2 and [Pd(2,6-Me2C6H3)(μ-OH)(PPh3)]2 instead of
[PdPh(μ-OH)(PPh3)]2, and acetic acid instead of pivalic acid,
respectively.
1
1b: 61% yield. H NMR (CD2Cl2): δ 1.80 (br, 6H, O2CCH3),
2.10−2.72 (brm, 6H, CH3C6H4), 6.30−6.60, 6.61−6.88, 6.90−7.52
(brm, 38H in total, Ph and C6H4). 31P{1H} NMR (CD2Cl2): δ 32.0
(br), 29.6 (br). IR (CH2Cl2): 1581, 1517, 1450, 1416 cm−1 (νCO2). IR
(KBr): 1581, 1417 cm− 1 (νC O 2 ). Anal. Calcd for
C54H50O4P2Pd2·0.5H2O; C, 61.96; H, 4.91. Found: C, 61.82; H, 4.86.
1c: 47% yield. 1H NMR (CD2Cl2): δ 1.90 (br, 12H, O2CCH3), 2.41
(br, 24H, (CH3)2C6H3), 6.44 (d, J = 7.3 Hz, 8H, H3,5 of C6H3), 6.65
(t, J = 7.3 Hz, 4H, H4 of C6H3), 7.23−7.31, 7.36−7.45 (m, 60H in
total, Ph). 31P{1H} NMR (CD2Cl2): δ 31.2 (br). 13C{1H} NMR
(CD2Cl2): δ 24.8 (brs, O2CCH3), 25.7 (brs, (CH3)2C6H3), 125.0 (s,
C4 of C6H3), 126.4 (s, C3,5 of C6H3), 128.9 (d, J = 11 Hz, C3,5 of Ph),
130.8 (d, J = 52 Hz, C1 of Ph), 131.3 (s, C4 of Ph), 134.8 (d, J = 12
Hz, C2,6 of Ph), 140.9 (s, C2,6 of C6H3), 150.0 (s, C1 of C6H3). IR
(CH2Cl2): 1550, 1515, 1449, 1413 cm−1 (νCO2). IR (KBr): 1547, 1412
cm−1 (νCO2). Anal. Calcd for C112H108O8P4Pd4: C, 63.11; H, 5.10.
Found: C, 62.82; H, 5.10.
Reactions of [PdAr(μ-O2CR)(PPh3)]n (1) with 2-Methylthio-
phene (2) (Table 2). A typical procedure is as follows (entry 1).
Complex 1a (8.1 mg, 0.0080 mmol) and C6Me6 (3.2 mg, 0.020 mmol;
internal standard) were placed in an NMR sample tube equipped with
a Teflon screw valve, and THF (0.40 mL) and 2-methylthiophene (2;
31 μL, 0.32 mmol) were added at room temperature. The mixture was
degassed three times by freeze−pump−thaw cycles and heated at 40
°C to dissolve 1a. A capillary containing a solution of PPh2(C6H4-2-
OMe) (40 mM) in toluene-d8 was loaded into the NMR sample tube
as an internal standard. The system was again degassed three times by
freeze−pump−thaw cycles and placed in an NMR sample probe
controlled to 65.0 0.1 °C. The reaction was examined at intervals by
31P{1H} NMR spectroscopy using the following marker signals: 1a (δ
1d: 1H NMR (CD2Cl2): δ 0.62 (s, 15.3H, C(CH3)3), 1.17 (s, 2.7H,
C(CH3)3), 6.67−6.74, 6.77−6.84, 6.91−6.96 (m, 10H in total, PdPh),
7.02−7.10, 7.20−7.31, 7.33−7.40, 7.43−7.51 (m, 30H in total, PPh).
31P{1H} NMR (CD2Cl2): δ 30.7 (s, 1.7P), 32.2 (s, 0.30P). IR
(CH2Cl2): 1577, 1415 cm−1 (νCO2). IR (KBr): 1577, 1414 cm−1
(νCO2). Anal. Calcd for C58H58O4P2Pd2·CH2Cl2: C, 60.11: H, 5.13.
Found: C, 60.34; H, 5.36.
Synthesis of [PdPh(μ-O2CCF3)(PPh3)]2 (1e). To a suspension of
[PdPh(μ-OH)(PPh3)]2 (92.2 mg, 0.10 mmol) in toluene (4 mL) at
−78 °C was added trifluoroacetic acid (23 μL, 0.30 mmol). After
stirring the mixture for a few minutes, Et2O (15 mL) was added at the
same temperature to precipitate a white solid, which was collected by
filtration, washed with cold Et2O, and dried under vacuum (37.5 mg,
34%). 1H NMR (CD2Cl2): δ 6.74−6.80 (m, 6H, H2,4,6 of PdPh), 6.94
(t, J = 7.2 Hz, 4H, H3,5 of PdPh), 7.11−7.17, 7.18−7.27, 7.33−7.40
(m, 60H in total, PPh). 31P{1H} NMR (CD2Cl2): δ 31.1 (s). 19F NMR
(CD2Cl2): δ −75.3 (s). 13C{1H} NMR (CD2Cl2): δ 116.5 (q, J = 287
Hz, CF3), 124.9 (s, C4 of PdPh), 128.1 (d, J = 3 Hz, C3,5 of PdPh),
128.9 (d, J = 11 Hz, C3,5 of PPh), 129.3 (d, J = 54 Hz, C1 of PPh),
131.3 (d, J = 2 Hz, C4 of PPh), 135.0 (d, J = 12 Hz, C2,6 of PPh), 137.3
(d, J = 3 Hz, C2,6 of PdPh), 145.9 (s, C1 of PdPh), 164.3 (q, J = 38 Hz,
CO2). IR (CH2Cl2): 1563, 1434 cm−1 (νCO2). IR (KBr): 1562, 1434
cm−1 (νCO2). Anal. Calcd for C52H40F6O4P2Pd2: C, 55.88; H 3.61.
Found: C, 55.98; H, 3.87.
30.7), 4a (δ 22.0), PPh2(C6H4-2-OMe) (δ −13.9). After complete
consumption of 1a, organic products formed in the system (3a and
biphenyl) were analyzed by GC-MS and HPLC.
Catalytic Direct Arylation of 2-Methylthiophene (2) with
Aryl Bromides. To a 10 mL Schlenk tube containing complex 1a
(10.1 mg, 0.010 mmol), K2CO3 (138 mg, 1.0 mmol), and C6Me6 (8.1
mg, 0.050 mmol; internal standard) were added successively DMA
(0.50 mL), 2 (97 μL, 1.0 mmol), bromobenzene (53 μL, 0.50 mmol),
and 2,6-dimethylbromobenzene (67 μL, 0.50 mmol). The solution was
degassed three times by freeze−pump−thaw cycles. The mixture was
stirred at 90 °C, and the amounts of the 5-phenyl-2-methylthiophene
(3a) and 2-methyl-5-(2,6-dimethylphenyl)thiophene (3c) produced at
intervals were followed by GLC.
X-ray Structural Analysis. Single crystals of 1b−d suitable for X-
ray diffraction study were grown by slow diffusion of pentane (1b) or
hexane (1c, 1d) into CH2Cl2 solutions at −20 °C. The intensity data
were collected on a Rigaku Mercury CCD diffractometer with
graphite-monochromated Mo Kα radiation (λ = 0.71070 Å). The
intensity data were collected at 173 K and corrected for Lorentz and
polarization effects and for absorption. The structures were solved by
heavy atom Patterson methods (PATTY), expanded using Fourier
techniques (DIRDIF99),21 and refined on F2 for all reflections
(SHELXL-97).22 Non-hydrogen atoms, except for the oxygen atom of
crystal water in 1b, were refined anisotropically. Hydrogen atoms were
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Organometallics
Article
placed at calculated positions using AFIX instructions. The molecular
structures are given in Figure 4 (1d) and Figure S1 (1b) and Figure S2
(1c) in Supporting Information. Selected bond distances and angles
are listed in Table S1. The crystal data and the summary of data
collection and refinement are listed in Table S2.
(c) Lu, W.; Kuwabara, J.; Kanbara, T. Macromolecules 2011, 44, 1252.
(d) Fujitani, Y.; Kuwabara, J.; Lu, W.; Kanbara, T. ACS Macro Lett.
2012, 1, 67. (e) Berrouard, P.; Najari, A.; Pron, A.; Gendron, D.;
Morin, P.-O.; Pouliot, J.-R.; Veilleux, J.; Leclerc, M. Angew. Chem., Int.
Ed. 2012, 51, 2068. (f) Schipper, D. J.; Fagnou, K. Chem. Mater. 2011,
23, 1594. (g) Kowalski, S.; Allard, S.; Scherf, U. ACS Macro Lett. 2012,
1, 465. (h) Hassan, J.; Schulz, E.; Gozzi, C.; Lemaire, M. J. Mol. Catal.
A: Chem. 2003, 195, 125.
(4) (a) Lafrance, M.; Rowley, C. N.; Woo, T. K.; Fagnou, K. J. Am.
Chem. Soc. 2006, 128, 8754. (b) Gorelsky, S. I.; Lapointe, D.; Fagnou,
K. J. Am. Chem. Soc. 2008, 130, 10848. (c) Gorelsky, S. I.; Lapointe,
D.; Fagnou, K. J. Org. Chem. 2012, 77, 658. (d) Ishikawa, A.; Nakao,
DFT Calculations for IR Assignments. Geometry optimization
for model compounds were carried out for 1a (1a′: [PdPh(μ-
O2CMe)(PH3)]2), 5a (5a′: [PdPh(O2CMe-κ2O)(PH3)]), 1c (1c′:
[Pd(2,6-Me2C6H3)(μ-O2CMe)(PH3)]4), and 5c (5c′: [Pd(2,6-
Me2C6H3)(O2CMe-κ2O)(PH3)]). All calculations were performed
without any symmetry constraints using the B3LYP level of density
functional theory.23 The Gaussian 03 program package was used for all
calculations.24 The Pd atom was described using the LANL2DZ basis
set including a double-ζ basis set with the Hay and Wadt effective core
potential.25 The 6-31G(d) basis set was used for other atoms.26 The
optimized geometry of 1a′, 5a′, and 5c′ exhibited no imaginary
frequency, while the optimized geometry of 1c′ exhibited one small
imaginary frequency (−15.44i cm−1). The calculated vibrational
frequencies were scaled by 0.9613, which is customary for the
B3LYP method.27 Calculated vibrational wavenumbers are summar-
ized in Table S3. The calculated data are consistent with the
experimental values given in Table 3. The Cartesian coordinates of
model compounds are reported in Tables S4−S7.
́
Y.; Sato, H.; Sakaki, S. Dalton Trans. 2010, 39, 3279. (e) Guihaume, J.;
Clot, E.; Eisenstein, O.; Perutz, R. N. Dalton Trans. 2010, 39, 10510.
(f) Biswas, B.; Sumitomo, M.; Sakaki, S. Organometallics 2000, 19,
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Chem. Soc. 2005, 127, 13754.
(5) For reviews on the mechanism of C−H bond cleavage, see:
(a) Boutadla, Y.; Davies, D. L.; Macgregor, S. A.; Poblador-
Bahamonde, A. I. Dalton Trans. 2009, 5820. (b) Balcells, D.; Clot,
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(6) (a) Sugie, A.; Kobayashi, K.; Suzaki, Y.; Osakada, K.; Mori, A.
Chem. Lett. 2006, 35, 1100. (b) Mori, A.; Sugie, A.; Furukawa, H.;
Suzaki, Y.; Osakada, K.; Akita, M. Chem. Lett. 2008, 37, 542. (c) Sugie,
A.; Furukawa, H.; Suzaki, Y.; Osakada, K.; Akita, M.; Monguchi, D.;
Mori, A. Bull. Chem. Soc. Jpn. 2009, 82, 555.
ASSOCIATED CONTENT
* Supporting Information
Crystallographic and computational details and crystallographic
data (CIF files). This material is available free of charge via the
Internet at http://pubs.acs.org.
■
S
(7) Sun, H.-Y.; Gorelsky, S. I.; Stuart, D. R.; Campeau, L.-C.; Fagnou,
K. J. Org. Chem. 2010, 75, 8180.
(8) (a) Tan, Y.; Hartwig, J. F. J. Am. Chem. Soc. 2011, 133, 3308.
(b) Tan, Y.; Barrios-Landeros, F.; Hartwig, J. F. J. Am. Chem. Soc.
2012, 134, 3783.
(9) A related mechanistic study on Ru(II)-catalyzed direct arylation
has been reported: Ackermann, L.; Vicente, R.; Potukuchi, H. K.;
Pirovano, V. Org. Lett. 2010, 12, 5032.
(10) Grushin, V. V.; Bensimon, C.; Alper, H. Organometallics 1995,
14, 3259.
(11) Hursthouse, M. B.; Solan, O. D.; Thornton, P.; Walker, N. P. C.
Polyhedron 1986, 5, 1475.
AUTHOR INFORMATION
Corresponding Author
*E-mail: ozawa@scl.kyoto-u.ac.jp.
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to Dr. Y. Nakajima (Kyoto Univ.) for X-ray
crystallographic assistance. This work was supported by
KAKENHI (23350042, 24750088) from Japan Society for the
Promotion of Science.
(12) The yields of 3a at 65 °C for 2 h in four different solvents: 90%
(DMA) > 28% (THF) > 13% (1,4-dioxane) > trace (toluene).
(13) The reaction of 4a with 2 (40 equiv) in 1,4-dioxane at 90 °C for
3 h gave 3a (32%/4a) and biphenyl (3%/4a).
(14) Nakamoto, K. Infrared and Raman Spectra of Inorganic and
Coordination Compounds; John Wiley & Sons: New York, 1978.
(15) The IR assignments were confirmed by DFT calculations.
(16) Noskowska, M.; Sliwinska, E.; Ducamal, W. Transition Met.
́
Chem. 2003, 28, 756.
(17) Grushin, V. V.; Alper, H. Organometallics 1993, 12, 1890.
(18) Joannna, P. W.; Hartwig, J. F. Angew. Chem., Int. Ed. 2002, 41,
4289.
(19) Negishi, E.; Takahashi, T.; Baba, S.; Van Horn, E. D.; Okukado,
N. J. Am. Chem. Soc. 1987, 109, 2393.
DEDICATION
■
This paper is dedicated to Prof. Robert H. Grubbs (Caltech) on
the occasion of his 70th birthday.
́
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