1,1′-methylene-3,3′-bis[(N -(tert -butyl)imidazol-2-ylidene] and Its effect in palladium-catalyzed C-C coupling

Article abstract of DOI:10.1055/s-0034-1379954

A catalytic system utilizing a chelate carbene ligand containing bulk tert-butyl groups is described for palladium-catalyzed Heck and Suzuki coupling reactions. The Heck reaction focused on the coupling of different aryl bromides with mono- and 1,1-disubstituted olefins while the Suzuki reaction involved the coupling of aryl bromides and phenylboronic acid to afford the corresponding biphenyls. The catalyst system performs well with low Pd(OAc)₂ levels (0.025 mol% Pd). In all cases with monosubstituted olefins, the trans-configured products were obtained, while the results of Heck reaction of 1,1-disubstituted olefins exhibited a high selectivity favoring the terminal product.

Full text of DOI:10.1055/s-0034-1379954

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1,1′-Methylene-3,3′-bis[(N-(tert-butyl)imidazol-2-ylidene] and Its
Effect in Palladium-Catalyzed C–C Coupling
Shirin Nadria
Ezzat Rafieea
Sirous Jamalib
Mohammad Joshaghani*a
a Faculty of Chemistry, Razi University, Kermanshah 67149, Iran
mjoshaghani@razi.ac.ir
b Chemistry Department, Sharif University Technology, P.O. Box
11155-3615, Tehran, Iran
Received: 10.10.2014
Accepted after revision: 27.11.2014
Published online: 14.01.2015
DOI: 10.1055/s-0034-1379954; Art ID: st-2014-d0853-l
R
N
N
N
N
N
N
M
Abstract A catalytic system utilizing a chelate carbene ligand contain-
ing bulk tert-butyl groups is described for palladium-catalyzed Heck
and Suzuki coupling reactions. The Heck reaction focused on the cou-
pling of different aryl bromides with mono- and 1,1-disubstituted ole-
fins while the Suzuki reaction involved the coupling of aryl bromides
and phenylboronic acid to afford the corresponding biphenyls. The cat-
alyst system performs well with low Pd(OAc)2 levels (0.025 mol% Pd). In
all cases with monosubstituted olefins, the trans-configured products
were obtained, while the results of Heck reaction of 1,1-disubstituted
olefins exhibited a high selectivity favoring the terminal product.
M
N
N
N
N
R
N
R
M
R
R
R
M = metal
Figure 1 Examples of monodentate, chelating, and pincer-type carbe-
ne ligands
lating bis-NHC ligands. Applications of both aliphatic and
aromatic linkers have been reported in the literature.6,8 Ad-
ditionally, the effect of the nature of the N-substituent
groups R in the NHC backbone on structure and catalytic
activity has been investigated by several research groups.
For example, studies from Organ’s group have shown that
NHC-based ligands bearing isopentylphenyl N-substituents
are more reactive in amination reactions than the isopro-
pylphenyl one and reported that this difference in activity
can be rationalized in terms of the difference in amine co-
ordination and/or deprotonation.9,10 The catalytic activity
for a family of complexes of general formula (NHC)-Pd(al-
lyl)Cl in aryl amination has been investigated by Nolan’s
group, and this relative reactivity trend is attributed to the
steric nature of the N-substituent groups.11,12
Key words palladium, carbene Ligand, C–C coupling, Heck reaction,
Suzuki reaction
Whilst the benefits of phosphine ligands are obvious in
a variety of transition-metal-catalyzed reactions, there is
growing interest in the search for the design of new organo-
metallic catalysts with carbene ligands, particularly with N-
heterocyclic carbene (NHC) ligands.1–3 The interest is due to
a combination of factors, including strong σ-donor property
concomitant with a negligible π-accepting ability, and high
stability toward heat, air, and moisture. Thus, carbene li-
gands are useful as a mimic of phosphines in catalysis. Im-
idazole–carbene ligands display different coordination
modes. They have been found to act as monodentate li-
gands where the imidazolium ring is coordinated to the
metal center at the C(2) position on the ring,4,5 but mainly
act as bidentatechelating6,7 or pincer-type ligands8 (Figure
1).
We previously reported the synthesis and structural
characterization of bis-NHC platinum complex 2,
[PtMe2(bis-NHC)], in which bis-NHC, 1,1′-methylene-3,3′-
bis[(N-(tert-butyl)imidazol-2-ylidene] (1) acts as a chelat-
ing ligand (Scheme 1).13 The chelating complex 2 demon-
strated the ability to fix aerial CO2.
The N-substituent group and nature of the linker that
connects the pair of NHC rings are two important factors
which influence the coordination mode and activity of che-
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S. Nadri et al.
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was achieved after one hour without the need for any
tetraalkylammonium salt as additive (Table 1, entry 1).
Since the yield of the coupling product was satisfactory, fur-
ther optimization of reaction conditions was not carried
out. We then checked the generality and scope of the cata-
lyst with a wide range of substrates with different electron-
ic and steric effects. As shown in Table 1,Pd(OAc)2/NHC li-
gand 1 was found to be tolerant towards different function-
al groups on the aryl bromides. The reaction of 4-
bromotoluene proceeded well to give the desired product
in 93% yield (Table 1, entry 2). When the substitution posi-
tion of the methyl group on the aryl bromide changed from
para to meta (Table 1, entry 3), the activity remained un-
changed, which seems to suggest that the steric hindrance
of meta substituent on the aryl ring does not affect the yield
and reaction time. For the electron-rich aryl bromide, 4-
bromoanisole, the catalyst was efficient and conversion ap-
proached nearly 80% within three hours (Table 1, entry 4).
In the cases of 1-bromo-4-nitrobenzene and 4-bromobenz-
aldehyde the maximum yield of Heck products were 79%
and 62%, respectively (Table 1, entries 5 and 6), because
such substrates are prone to suffer a competing dehaloge-
nation process, which is more likely to take place with aryl
halides bearing electron-withdrawing groups.22 Further-
more, as reported by Svennebring et al. the competing re-
ductive amination is another side reaction that can occur
on formyl-functionalized compounds, albeit at very high
temperature conditions.23
t-Bu
N
N
N
N
Me
Me
N
N
1) Ag2O (4 equiv), CH2Cl2 90 min
Pt
t-Bu
N
N
2) [Pt2Me4(m-SMe2)2]
t-Bu
2
t-Bu
Br2
1
Scheme 1 The synthesis route of bis-NHC platinum complex 2
Because of its similarity to platinum, we envisaged that
palladium may also be able to behave in a similar fashion,
and
1,1′-methylene-3,3′-bis[(N-(tert-butyl)imidazol-2-
ylidene] (1), could be an effective ligand in palladium-cata-
lyzed coupling reactions, owing to its chelating coordina-
tion mode as well as its electronically rich and sterically
hindered tert-butyl groups. In this direction, to understand
the utility of NHC ligand 1 in palladium-catalyzed coupling
reactions and based on our experience in cross-coupling re-
actions,14–20 we have chosen the Heck and Suzuki reactions
as test cases. In this paper we present our results in detail.
Our initial experiments focused on Heck coupling be-
tween bromobenzene and butyl acrylate as the vinylic sub-
strate.21 Using NHC ligand 1, a preliminary experiment in
N,N-dimethylformamide (DMF) at 135 °C with potassium
carbonate (K2CO3) as the base and 0.025 mol% of Pd(OAc)2
was successful, and about 97% yield of coupling product
Table 1 Heck Reaction of Various Aryl Bromides with Monosubstituted Olefinsa
R1
R1
Pd(OAc)2, NHC-ligand 1
R1
R2
R2
+
+
R1
Br
+
R2
K2CO3, DMF, 135 °C
R2
gem
R2 = CO2n-Bu or Ph
trans
cis
Entry
1
Aryl bromide
Olefin
Time (h)
trans (%)
TONb
3880
Br
n-butyl acrylate
n-butyl acrylate
1
1
97
94
2
3
3760
3800
Me
Me
Br
n-butyl acrylate
1
95
Br
Br
Br
4
n-butyl acrylate
n-butyl acrylate
2
4
80
79
3200
3160
MeO
O2N
5c
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Table 1 (continued)
Entry
Aryl bromide
Olefin
Time (h)
5
trans (%)
TONb
2480
6
n-butyl acrylate
n-butyl acrylate
62
OHC
NC
Br
Br
7c
8
2
2
90
81
3600
3240
Br
n-butyl acrylate
9
10
11
12
n-butyl acrylate
n-butyl acrylate
styrene
7
2
2
2
20
84
92
88
800
3360
3680
3520
Br
Br
S
Br
styrene
Br
13
14
styrene
styrene
2
2
90
51
3600
2040
Br
MeO
Br
Br
15
16
styrene
styrene
4
3
73
83
2920
3320
Br
S
a Reaction conditions: aryl bromide (4 mmol), olefin (4 mmol), K2CO3 (4 mmol), Pd(OAc)2 (0.025 mol%), ligand 1 (0.05 mol%), DMF (3 mL).
b TON = turnover number (mol product/mol catalyst).
c N-(Butyl)3 was used as the base.
4-Bromobenzonitrile led to an excellent yield (Table 1,
entry 7). This observation was of interest since, in our pre-
vious work,20 this substrate was completely unreactive
when 2,6-bis(diphenylphosphino)pyridine was employed
as the ligand; probably due to steric effects exerted by com-
petitive coordination of the cynao group to the palladium
center, as reported by Hong’s group.24 Here it seems that
the chelating coordination mode of NHC ligand 1 effectively
prevents the cyano group from the coordinating to the pal-
ladium center. While fused aromatic bromides such as 1-
bromonaphthalene reacted cleanly to give the correspond-
ing Heck product (Table 1, entry 8), 4-bromobiphenyl was
unreactive and only gave the coupled product in 20% yield
after seven hours (Table 1, entry 9). The reason for this in-
complete conversion is not clear for us at this time. Apart
from the above substrates, we found that the Pd(OAc)2/NHC
ligand 1 combination could also catalyze the Heck reaction
of heterocyclic substrates such as 3-bromothiophene (Table
1, entry 10). The reaction of aryl bromides with styrene was
also tested under our conditions (Table 1, entries 11–16). A
similar catalytic activity of the Pd(OAc)2/NHC ligand 1 sys-
tem has been observed in the Heck reaction with styrene;
though, the yield of products were slightly lower than for
the reaction of butyl acrylate.
It has already been reported that addition of silver(I) ox-
ide (Ag2O) facilitates formation of the Pd–NHC complex by
transmetalation of the NHC ligand from the corresponding
Ag–NHC compound to the palladium center.25–27 Recently,
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we had successfully demonstrated this strategy,13 where
treatment of the silver carbene complex, [Ag2(bis-NHC-
1)Br2], generated in situ from the corresponding bis(imidaz-
olium) dibromide salt and Ag2O with [Pt2Me4(μ-SMe2)2], al-
lowed the isolation of bis(carbene)platinum complex
[Pt(Me)2(bis-NHC-1)] (2). We should mention here that, in
contrast to earlier works, we found that the addition of
Ag2O is not necessary to achieve successful Heck coupling
catalyzed by Pd(OAc)2/NHC ligand 1. This observation
means that the complexation of NHC ligand 1 to the palla-
dium center proved to be accessible by the standard syn-
thetic routes such as in situ deprotonation and reaction
with Pd(OAc)2 or direct metalation by reaction with palla-
dium species.
The efficiency of Pd(OAc)2/NHC ligand 1 system may be
partly due to chelating coordination mode of NHC ligand 1
that affects the binding properties of the substrates around
the metal center, and partly due to appreciate the role of
bulky substituents such as tert-butyl in the ligand back-
bone in regard to basicity and steric hindrance, which
would affect the efficiency of some of the steps in a catalyt-
ic cycle. In other words, chelation of NHC ligand 1 and the
existence of tert-butyl groups led to a synergistic effect
which gave rise to the activity and stability of the derived
palladium catalyst. It should be noted that the catalytic sys-
tem was nonsensitive to oxygen, and the coupling reactions
could be performed under air effectively. Other thing to be
considered is that all reactions were found to be completely
regio- and stereoselective, giving only trans-configured
products on the less substituted carbon with lower electron
density of the olefin double bond, regardless of the stereo-
electronic properties of the aryl bromides.
Given our success with the Pd(OAc)2/NHC ligand 1 com-
bination for the coupling of monosubstituted olefins, we
felt that it might also be quite effective for the coupling of
1,1-disubstituted olefins which are known to be hard sub-
strates because of steric reasons. As illustrated in Scheme 2
from the intermediate A that is formed after olefin migra-
tory insertion step, there are two possible pathways for pal-
ladium β-hydride elimination to occur. Intermediate A can
H
H
H
H
H
H
H
H
H
H
α
H
β
H
H
β
H
H
[Pd]
R
H
R
R
R
E or Z internal isomer
terminal isomer
R = CO2Bu or Ph
A
double arylated
3
4
5
Scheme 2 The possible direction of β-hydride elimination in Heck reaction of 1,1-disubstituted olefins
Table 2 Heck Coupling Reaction of 1,1-Disubstituted Olefinsa
R
R
R
R
Pd(OAc)2, NHC ligand 1
Ar
Ar
Ar
ArHBr
R = CO2n-Bu or Ph
+
+
+
K2CO3, DMF, 135 °C
Ar
internal
terminal
double arylated
Entry
1
Aryl bromide
Olefin
Time (h)
Internal (%)
16
Terminal (%)
81
Double arylated (%) TONb
Br
n-butyl methacrylate
3
3
5
3
0
0
0
0
3240
2880
3400
3160
Me
2
3
4
n-butyl methacrylate
α-methylstyrene
α-methylstyrene
0
15
10
72
85
79
Br
Br
Me
Br
a Reaction conditions: aryl bromide (4 mmol), olefin (4 mmol), K2CO3 (4 mmol), Pd(OAc)2 (0.025 mol%), ligand 1 (0.05 mol%), DMF (3 mL).
b TON = turnover number (mol product/mol catalyst).
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Table 3 Suzuki Reaction of Aryl Bromides with Phenylboronic Acida
Pd(OAc)2, NHC ligand 1
R
Br
(HO)2B
+
R
K2CO3, DMF, H2O, 135 °C
Entry
1
Aryl bromide
Time (h)
1
Yield (%)
96
TONb
3840
Br
2
3
1
5
94
73
4760
2920
Me
Br
OHC
Br
Br
4
3
82
3280
a Reaction conditions: aryl bromide (4 mmol), phenylboronic acid (4 mmol), K2CO3 (4 mmol), Pd(OAc)2 (0.025 mol%), ligand 1 (0.05 mol%), DMF (3 mL), H2O
(1 mL).
b TON= turnover number (mol product/mol catalyst).
eliminate Hβ on the methyl group and eventually generates
the Heck product 3 with an internal double bond, the ste-
reochemistry of which can be E or Z. The other pathway in-
volves elimination of Hβ from the benzylic methylene group
which would afford compound 4 bearing a disubstituted
double bond, which is susceptible to further arylation to
give 5.
Beller has reported that regioselectivity and product
distribution is base-dependent, as inorganic bases such as
sodium acetate gave a mixture of the two regioisomers
with the terminal olefin as the major product; whereas the
internal olefin was favored by organic bases such Bu3N or
diisopropylethylamine (DIPEA) and proposed that a direct
proton abstraction by the amine takes place toward the
most acidic benzylic protons.28 In contrast, Morales ob-
tained the internal olefin as the major product, irrespective
of the nature of the base.29
Thus, it remained to be seen whether the combination of
Pd(OAc)2/NHC ligand 1 could be also effective in Suzuki re-
actions (Table 3).
Preliminary testing for Suzuki reaction was carried out
by treating bromobenzene with phenylboronic acid in DMF
and K2CO3.30 A minimal amount of water was added to the
reaction to help dissolve the phenylboronic acid. The reac-
tion proceeded well to afford biphenyl in 94% yield after
one hour (Table 3, entry 1). We next examined the coupling
of several other representative aryl bromides with phenyl-
boronic acid with the results listed in Table 3. With respect
to the electron-rich, electron-neutral, and electron-poor
aryl bromides as well as sterically hindered substrates, all
reacted with phenylboronic acid smoothly to provide the
corresponding biaryl products in good to high yields.
In conclusion, the catalytic system generated in situ
from Pd(OAc)2 and NHC ligand 1 can be useful for both Heck
and Suzuki coupling reactions with a number of substrates
under an air atmosphere. It is worth noting that addition of
Ag2O, which is sometimes required for fast coordination of
carbene ligands to metal centers, was not necessary.
As shown in Table 121 the reactivity of 1,1-disubstituted
olefins is reduced compared to monosubstituted ones. The
results indicate that, under our reaction conditions, the
elimination of methyl hydrogen is much faster than that of
benzylic hydrogen and both n-butyl methacrylate and α-
methylstyrene gave terminal olefins as the major coupling
products, and only a small amount of internal olefins were
formed (Table 2). This may be because the methyl group
has three hydrogens increasing the chances of elimination.
Biaryls are an important class of ‘building blocks’ that
are widely employed in organic synthesis and pharmaceuti-
cal or agrochemical areas making the Suzuki coupling reac-
tion one of the most important modern synthetic methods.
Acknowledgment
The authors thank Razi University Research Council for support of
this work.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1379954.
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References and Notes
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(21) Typical Experimental Procedure for the Heck Arylation
A reaction tube was charged with aryl bromide (4 mmol), olefin
(4 mmol), and K2CO3(4 mmol) under air. A solution of Pd(OAc)2
(0.025 mol% in 1 mL of DMF) followed by a solution of NHC
ligand 1 (0.05 mol% in 2 mL of DMF) was added through a
rubber septum, and the resulting mixture was heated at 135 °C
for the appropriate time. Upon completion of the reaction, the
reaction mixture was cooled to r.t. and quenched with H2O.
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layers were dried over MgSO4, filtered, the solvent was evapo-
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(30) General Procedure for the Suzuki Coupling
A reaction tube was charged with PhB(OH)2 (4 mmol), aryl
bromide (4 mmol), and K2CO3(4 mmol) under an air atmo-
sphere. A solution of Pd(OAc)2 (0.025 mol% in 1 mL of DMF)
along with a solution of NHC ligand 1 (0.05 mol% in 2 mL of
DMF) was added through a rubber septum. After addition of
H2O (1 mL), the resulting mixture was heated at 135 °C for the
appropriate time. After extraction with Et2O, the organic phase
was dried over MgSO4, filtered, the solvent evaporated, and the
crude product was characterized by NMR spectroscopy.
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