Abnormal N-heterocyclic carbene palladium complex: Living catalyst for activation of aryl chlorides in Suzuki-Miyaura cross coupling

Article abstract of DOI:10.1039/c1cc15732a

Palladium complexes bearing abnormal N-heterocyclic carbene were used as catalysts in Suzuki-Miyaura cross coupling of aryl chlorides at 25 °C. The catalyst remained active for 10 successive catalytic runs and can activate 4-chlorotoluene at 25 °C with 0.01 mol% catalyst loading resulting in a TON of 9500 within 6 h.

Full text of DOI:10.1039/c1cc15732a

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Abnormal N-heterocyclic carbene palladium complex: living catalyst for
activation of aryl chlorides in Suzuki–Miyaura cross couplingw
Samaresh Chandra Sau, Subhankar Santra, Tamal K. Sen, Swadhin K. Mandal* and
Debasis Koley
Received 16th September 2011, Accepted 24th October 2011
DOI: 10.1039/c1cc15732a
Palladium complexes bearing abnormal N-heterocyclic carbene were
used as catalysts in Suzuki–Miyaura cross coupling of aryl chlorides
at 25 8C. The catalyst remained active for 10 successive catalytic
runs and can activate 4-chlorotoluene at 25 8C with 0.01 mol%
catalyst loading resulting in a TON of 9500 within 6 h.
activity as compared to their normal NHC counterpart (nNHC).
For example, in 2004, Lebel and co-workers demonstrated the
catalytic activity of the aNHC based palladium complex towards
Suzuki–Miyaura cross coupling using aryl chlorides at 80 1C
whereas the corresponding nNHC analog remained inactive under
identical conditions.8 This report prompted us to test the catalytic
activity of palladium complexes prepared from the newly
reported6 1,3-bis(2,6-diisopropylphenyl)-2,4-diphenyl-imidazolium
salts IA and IB for Suzuki–Miyaura cross coupling of aryl
chlorides. It is noteworthy that the ready availability and low
cost of aryl chlorides relative to aryl bromides or iodides in
Suzuki–Miyaura cross coupling has been economically attractive.
However, the activation of aryl chloride substrates in Suzuki–
Miyaura cross coupling has been limited as compared to the
activation of aryl bromide and aryl iodide substrates because
of the strength of the CꢀCl bond in comparison to the CꢀBr
or CꢀI bond. Since the reports of activation of aryl chloride
substrates during the late 1990’s9 there are now few studies
available in the literature for Suzuki–Miyaura cross coupling
of aryl chlorides.10,11 However, the Suzuki–Miyaura cross
coupling of aryl chlorides at room temperature has remained
one of the great challenges in this area specifically at very low
catalyst loading.
The isolation of heteroatom stabilized carbenes [normal
N-heterocyclic carbenes (nNHCs)] by Arduengo et al.1 has
led to numerous catalytic applications in organometallic
chemistry. The N-heterocyclic carbenes also have been used
as nucleophiles for organocatalytic reactions.2 The nNHCs
bind to a metal center through the C-2 center generating a normal
mode of metal binding (refer to Scheme 1 for numbering).
Crabtree, Faller and co-workers first demonstrated in 2001 that
2-pyridylmethylimidazolium salts react with IrH5(PPh3)2 in
which an abnormal mode of metal binding of the NHCs was
observed through the C-4 center.3 Later on, a few other
complexes featuring the so-called abnormal mode of binding
was reported.4 The abnormal mode of bonding increases the
electron density at the metal center substantially, and now a
number of imidazole based carbene salts specifically designed
for abnormal mode of binding have been reported.5
However, it took a while to isolate the abnormal N-heterocyclic
carbenes (aNHCs).6 Metal coordinated aNHCs have proven to
be excellent catalysts resulting in the activation of un-reactive
bonds such as C–H and H–H7 and in some cases the aNHC
coordinated metal complexes have outperformed the catalytic
Herein we report the synthesis of halobridged CꢀH activated
palladium dimers 1 and 2 using 1,3-bis(2,6-diisopropylphenyl)-
2,4-diphenyl-imidazolium salts IA and IB, respectively. Both
1 and 2 were tested for their efficacy in Suzuki–Miyaura cross
coupling of aryl chlorides. The preliminary results indicate that
the aryl chlorides can be activated under Suzuki–Miyaura cross
coupling conditions at room temperature leading to nearly
quantitative yield of the corresponding biphenyls. The catalyst
remained active for 10 successive catalytic cycles without loss
of any activity. The catalyst 1 successfully activated 4-chloro-
toluene under a low catalyst loading of 0.01 mol% at room
temperature with TON value of 9500 within 6 h.
Two imidazolium salts, IA and IB (Scheme 1), are employed for
the current study as aNHC precursors to prepare palladium
complexes. The addition of IA or IB to a dry 1,4-dioxane solution
of Pd(OAc)2 in 1 : 1 ratio resulted in the change of color from
yellow to deep brown with the formation of a halobridged C–H
activated palladium dimer 1 or 2 (Scheme 1). Previously Herrmann
and co-workers have reported the synthesis of phosphorus
coordinated C–H activated halobridged palladacycle dimers.12
Scheme 1 Synthesis of compounds 1 and 2.
Department of Chemical Sciences, Indian Institute of Science
Education and Research-Kolkata, Mohanpur-741252, India.
E-mail: swadhin.mandal@iiserkol.ac.in
w Electronic supplementary information (ESI) available: Experimental
and theoretical details including all analytical data. CCDC 843993 (1)
and 843992 (2). For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c1cc15732a
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 555–557 555

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Table 1 Suzuki–Miyaura cross coupling reactions of aryl chlorides at
room temperaturea
Entry Substrate
1
Cat. Time/h Product
Yieldb (%)
98
1
2
1
2
1
2
1
2
1
4
4
8
7
3
3
2
2
2
2
3
4
5
6
7
8
9
97
98
98
97
98
98
98
98
Fig. 1 Perspective ORTEP views of the molecular structure of 1.
Thermal ellipsoids are drawn with 50% probability. Hydrogen atoms
and solvent molecules (diethyl ether and dichloromethane) have been
omitted for the sake of clarity.
The compounds 1 and 2 were isolated by column chromatography
using dichloromethane and recrystallized as yellow crystals
from CH2Cl2/Et2O in nearly 80% yield. The complexes were
characterized by elemental analysis, NMR spectroscopy, and
X-ray crystallography. The molecular structures of 1 and 2
were determined by X-ray crystallographic studies establishing
the abnormal mode of binding of the carbene. The X-ray
measurements (see ESIw) revealed that compounds 1 and 2 are
isostructural. The solid state structures (Fig. 1 and also see
ESIw for molecular structure of 2) displayed that the ortho aryl
CꢀH bond activation has taken place during the reaction. The
geometry around palladium is square planar where each
palladium center is bonded to the C-5 center of the carbene
displaying an abnormal mode of binding, CꢀH activated
ortho aryl carbon, and two chlorides. The PdꢀC bond lengths
revealed that PdꢀC(carbene) bond distances (1.989(4) A in
1 and 1.980(3) A in 2) are shorter than that observed for PdꢀC
(aryl) bond distances (2.017(4) A in 1 and 2.031(1) A in 2).
The PdꢀC(carbene) bond distances are comparable to that
observed in earlier studies.8 As a part of our interest to develop
an efficient palladium catalyst for the CꢀC coupling reaction13
we checked the efficiency of these palladium complexes (1 and 2)
for the Suzuki–Miyaura coupling reaction. The study begins
with an optimization of the operating conditions on a model
reaction involving 4-chlorotoluene and phenylboronic acid
(see ESIw for details). It was observed that 1,4-dioxane/NaOMe
and 1,4-dioxane/Cs2CO3 are the most effective combination for
this particular catalytic system to carry out the Suzuki–Miyaura
reaction. We tested these combinations for a number of aryl
chloride substrates successfully at room temperature leading to
nearly quantitative isolated yield of the biphenyl (Table 1).
Chlorobenzene as well as chlorobenzene attached with electron
donating groups at the para-position furnished the corresponding
biaryl products (entries 1–6, Table 1) utilizing a strong base
(NaOMe) while chlorobenzenes bearing electron withdrawing
groups at the para-position gave the corresponding biaryls
(entries 7–10, Table 1) upon applying a milder base (Cs2CO3).
The catalytic reactions were performed with 0.73 mol% loading
of the catalysts (1 and 2). The result revealed that activation of
aryl chlorides having electron donating groups is more difficult
compared to those having electron withdrawing groups at the
same position. The progress of the reaction was monitored with
1H NMR spectroscopy using 4-chlorotoluene and catalyst 1 at
defined time intervals revealing that within the first 75 minutes,
10
2
2
98
a
Reaction conditions: 0.73 mol% catalyst (1 or 2), aryl chloride
(1 mmol), phenylboronic acid (1.5 mmol) and base (2 mmol, NaOMe
for entries 1–6 and Cs2CO3 for entries 7–10), 5 mL dry 1,4-dioxane.
b
Isolated yield after chromatography.
the reaction reaches near completion resulting in 95%
conversion (see ESIw).
One of the major problems in homogeneous catalysis is
catalyst’s recycling inability as they are inseparable from the
reaction mixture. Herein, we assessed the longevity of catalyst 1
by performing several catalytic runs into the same reaction pot to
check whether the catalyst remains active for several catalytic
cycles.13a We have carried out 10 successive catalytic runs by
using 0.73 mol% of catalyst. After every 4 h interval we add a
fresh batch of substrates (4-chlorotoluene and phenylboronic
acid) and base without adding any additional catalyst into the
reaction vessel. After each 4 h interval, we checked the substrate
consumption by recording the 1H NMR spectrum of the reaction
mixture after initial workup. The 1H NMR spectrum indicates a
complete consumption of substrates within 4 h time at 25 1C for
10 successive catalytic runs (see ESIw) indicating no loss of
catalytic activity. After 10 catalytic cycles the overall isolated
yield of 4-methylbiphenyl is 95%. This result clearly demonstrates
that the catalyst stays active for 10 consecutive catalytic runs. This
result further prompted us to check the catalyst’s ability to
execute the Suzuki–Miyaura reaction of 4-chlorotoluene with
phenylboronic acid under lower catalyst loading at room
temperature. The results indicate that the catalyst 1 is almost
equally active for coupling of 4-chlorotoluene with 0.01 mol%
catalyst resulting in a nearly quantitative yield of the product
at room temperature with a TON value of 9500 within 6 h
(Table 2). Further lowering the catalyst loading to 0.005 mol%
leads to 65% yield at room temperature in longer time (26 h).
We carried out DFT calculations in order to have insight into the
Pd–carbene bonding. The DFT optimized (BP86/6-31G(d) level)
c
556 Chem. Commun., 2012, 48, 555–557
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Table 2 Suzuki–Miyaura coupling reaction of 4-chlorotoluene at
different catalyst (1) loadinga
0.005 mol% at room temperature. The catalyst remained active
for 10 successive catalytic runs without any loss of its activity which
is in line with the DFT calculation describing the Pd–carbene
bond as a strong one preventing from any palladium leaching
in solution.
Entry
Catalyst (mol%)
Time/h
Yieldb (%)
TON
272
692
1371
9500
1
2
3
4
5
0.36
0.14
0.07
0.01
0.005
4
4
5
6
26
98
97
96
95
65
Financial support from the Department of Science and
Technology (DST), India (Grant No. SR/FT/CS-020/2008),
is highly acknowledged. SCS is thankful to UGC, SS and TKS
are thankful to CSIR for their research fellowships. SKM and
DK thank Prof. S. Dattagupta for support and constant
encouragement.
13 000
a
Reaction conditions: catalyst 1, 4-chlorotoluene (1 mmol), phenyl-
boronic acid (1.5 mmol), NaOMe (2 mmol), 5 mL dry 1,4-dioxane.
b
Isolated yield after column chromatography.
References
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Fig. 2 Natural bond orbitals of 1m showing (a) PdꢀC(carbene) and
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Color code: C grey, Cl green, N blue and Pd pink.
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 555–557 557