Palladium complexes with abnormal N-heterocyclic carbene ligands derived from 1,2,3-triazolium ions and their application in Suzuki coupling

Article abstract of DOI:10.1016/j.tetlet.2009.08.002

Chiral and achiral pincer type palladium complexes bearing abnormal N-heterocyclic carbene ligands derived from 1,2,3-triazole are reported. Both complexes are effective as catalysts for non-asymmetric Suzuki coupling reaction for the synthesis of bipheny

Full text of DOI:10.1016/j.tetlet.2009.08.002

Tetrahedron Letters 50 (2009) 5834–5837
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Tetrahedron Letters
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Palladium complexes with abnormal N-heterocyclic carbene ligands derived
from 1,2,3-triazolium ions and their application in Suzuki coupling
*
Thandavamurthy Karthikeyan, Sethuraman Sankararaman
Department of Chemistry, Indian Institute of Technology Madras, Chennai 600 036, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Chiral and achiral pincer type palladium complexes bearing abnormal N-heterocyclic carbene ligands
derived from 1,2,3-triazole are reported. Both complexes are effective as catalysts for non-asymmetric
Suzuki coupling reaction for the synthesis of biphenyl derivatives. However, both the complexes failed
to catalyze the formation of binaphthyl derivatives, by the asymmetric Suzuki coupling in case of the chi-
ral complex and the non-asymmetric version in case of the achiral pincer complex. Instead deboronation
of arylboronic acid occurred very efficiently leaving the aryl bromide intact.
Received 15 July 2009
Revised 30 July 2009
Accepted 5 August 2009
Available online 9 August 2009
Ó 2009 Elsevier Ltd. All rights reserved.
In 1968 Wanzlick and Ofele almost simultaneously and indepen-
dently reported the potential of imidazolium-derived N-heterocy-
clic carbenes (NHC) as ligands for transition metals.1 Although the
ability of NHCs to act as efficient ligands by coordination through
C2 carbon of the imidazolidene has been well established, isolation
and structural characterization of free NHCs were reported only in
the early 90s with the discovery of the Arduengo carbenes.2 Re-
cently, NHCs derived from deprotonation of imidazolium ions at
the C4 position have been reported.3 Unlike the Wanzlick–Ofele–
Arduengo carbenes in this class of NHCs, the carbene center (C4)
is not flanked by heteroatoms on both sides and their structures
can only be represented as zwitter ions and not in the neutral
canonical form (Scheme 1). Such carbenes are termed as abnormal
NHCs. Metallation via C4-H activation results in the formation of
C4-bound metal carbene complexes (Scheme 1).
gand, both based on 1,2,3-triazolylidene, and their utility in
Suzuki coupling reactions.
Reaction of chiral triazole derivative 15 with methyl iodide
yielded the corresponding quaternary ammonium iodide 2 in
quantitative yield (Scheme 2). In an attempt to synthesize the cor-
responding chiral quaternary ammonium hydroxide (3), quater-
nary ammonium iodide 2 was treated with silver oxide. 1H NMR
spectrum of the crude product revealed the absence of triazole ring
proton that appeared at 9.47 ppm for 2. The crude product was
identified as the silver complex (4) of the abnormal NHC formed
from 2 (Scheme 2). This observation is consistent with the report
of Albrecht.6 The silver carbene complex (4) was unstable under
ambient conditions and also decomposed upon exposure to light.
Nevertheless it was characterized by 1H NMR, ESI-MS, and HRMS.
The molecular ion corresponding to the cation part of 4 showed
A handful of abnormal NHCs from other heterocycles such as
pyrazolylidene, isothiozolylidene, pyridylidene, and 1,2,3-triazoly-
lidene have been reported.4 Recently, we have reported pyrroli-
dine-1,2,3-triazole conjugates as organocatalysts for the
asymmetric Michael addition reaction with excellent diastereo
and enantioselectivities.5 During our attempts to prepare the cor-
responding chiral quaternary ammonium hydroxide of 1, we stum-
bled upon formation of the silver complex of abnormal NHC
derived from 2 (Scheme 2). During the course of our investigation
Albrecht6 has reported the synthesis and structural characteriza-
tion of late transition metal complexes with abnormal NHC ligands
derived from 1,2,3-triazolylidenes. Herein we report the first chiral
palladium complex bearing abnormal NHC ligand and the first pal-
ladium pincer complex bearing abnormal bis-NHC chelating li-
R
N
R
N
R
N
H
base
M
H
M
N
R
N
R
NHC
N
R
C2 bound metal
carbene complex
base
R
N
R
N
R
N
R
N
M
M
N
R
N
R
N
R
N
R
C4 bound metal
abnormal NHC
carbene complex
* Corresponding author. Tel.: +91 4422574210; fax: +91 4422570545.
E-mail address: sanka@iitm.ac.in (S. Sankararaman).
Scheme 1. Metal complexes derived from normal (C2) and abnormal (C4) NHCs
from imidazolium ion.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.08.002

T. Karthikeyan, S. Sankararaman / Tetrahedron Letters 50 (2009) 5834–5837
5835
out Pd(0), the reaction of phenylboronic acid with 4-cyanobromo-
benzene was carried out in the presence of mercury. Though the
reaction took longer time for completion (9 vs 14 h), the coupling
product was obtained in 98% yield, indicating that the reaction
was catalyzed by 5. Attempted coupling of 1,4-phenylenediboronic
acid with 4-methoxybromobenzene using 5 did not proceed and
only starting materials were recovered under the conditions given
in Table 1. The more reactive 2-bromo-5-tert-butylisophthalalde-
hyde (Table 1, entry 4, ArBr) also failed to react with 1,4-phenyl-
enediboronic acid.
Me
Ph
Ph
Ph
N
N
N
I-
N
N
MeI
N
CH3CN
70 ºC
N
Boc
N
Boc
100%
1
2
Me
N
Ag2O
Ag2O
Me
HO-
N
As stated earlier, complex 5 is chiral and it is potentially useful
for the asymmetric C–C cross-coupling reactions. We focused our
attention on the asymmetric Suzuki coupling for the synthesis of
chiral binaphthalene derivatives. Although palladium catalysts
bearing other NHC ligands have been successfully used in non-
asymmetric Suzuki coupling,8,9 to this date there has been no re-
port on the asymmetric version of Suzuki coupling using NHC li-
gand based catalysts, especially of the sterically hindered
substrates. Therefore, we wanted to study the utility of complex
5 for the asymmetric synthesis of chiral binaphthalene derivatives.
Accordingly, 1-bromo-2-methoxynaphthalene (6) was treated with
2-methoxy-1-naphthylboronic acid (7) in the presence of K2CO3
and 10 mol % of 5 in THF. To our dismay only deboronation of 7
to yield 2-methoxynaphthalene (8) was observed and 6 remained
intact. The same deboronation was observed when 2-benzyloxy-
1-bromonaphthalene (9) was reacted with 2-benzyloxy-1-naph-
thylboronic acid (10) to yield 2-benzyloxynaphthalene (11) and 9
was recovered. Also reaction of 1-iodo-2-naphthol with 7 led to
only deboronation, and 2-methoxynaphthalene (8) and 1-iodo-2-
naphthol were recovered from the reaction mixture. Attempted
coupling of 1-naphthylboronic acid with 6 yielded 1,1-binaphthyl-
ene as the product and 6 was recovered back from the reaction. It is
well documented that sterically demanding boronic acids with two
ortho substituents are prone to deboronation during Suzuki cou-
pling reaction.10 Nevertheless, some successful coupling of steri-
cally hindered boronic acids has been reported under rigorously
anhydrous conditions. Our attempts to carry out asymmetric Suzu-
ki coupling using rigorously dried THF and DME under various con-
ditions failed to yield the desired binaphthalene derivatives. Only
deboronated products were obtained in nearly quantitative yields
in all the reactions (Table 2). Deboronation in Suzuki coupling of
sterically hindered substrates is explained on the basis of forma-
tion of trans-diarylpalladium(0) intermediate in which C–C cou-
pling is disfavored compared to cis-diarylpalladium(0)
intermediate. As a result of the formation of trans isomer, the cat-
alytic cycle is stagnated and the reaction does not proceed further
to the reductive elimination step to complete the catalytic cycle.
Under these conditions, the boronic acid undergoes deboronation
in the presence of the base and often due to the presence of adven-
titious water in the reaction. This problem can be addressed by
using a chelating ligand for the palladium complex which prevents
the conversion of the cis-diarylpalladium(0) intermediate to the
trans isomer. Alternatively, the transmetallation of the boronic
acid could be a slow step, especially in sterically demanding sub-
strates, leading to deboronation reaction. To rule out the formation
of the trans-diarylpalladium(0) intermediate, we proceeded to syn-
thesize an achiral version of a pincer type palladium complex.
Methylation of the bis-triazole derivative 12 (obtained by the addi-
tion of benzyl azide to 1,3-diethynylbenzene) gave the bis-quater-
nary ammonium iodide 13 in 95% yield. It was further treated with
silver oxide followed by PdCl2(CH3CN)2 to afford complex 15
(Scheme 4). The intermediate silver carbene complex 14 was
unstable for isolation and complete characterization. Nevertheless,
it was characterized by ESI-MS, and HRMS data which corre-
sponded to C26H24N6Ag, the cationic part of the silver carbene com-
plex 14. Complex 15 was characterized by IR, NMR, ESI-MS and
N
Me
Ph Ph
Ag
N
N
N
Boc
N
N
3
N
N
[AgI2] -
N
Boc
N
Boc
4
Scheme 2. Synthesis of silver complex of abnormal NHC derived from 2.
the isotope peaks that matched with the calculated spectrum. In
view of the instability of the silver complex, it was decided to pre-
pare the palladium complex of the abnormal carbene derived from
2. The NHC complexes of palladium have been shown to be useful
in cross-coupling reactions.7 Attempted synthesis of the corre-
sponding palladium complex by treatment of 2 with Pd(OAc)2 in
DMSO, following the procedure reported by Albrecht,6 yielded a
mixture of intractable material. Therefore transmetallation of in
situ-generated silver carbene complex 4 was carried out.
Treatment of 2 with silver oxide followed by [Pd(Cl)2(CH3CN)2]
in dichloromethane afforded the corresponding palladium com-
plex 5 (Scheme 3) in 67% yield as an air stable pale yellow solid.
It was purified by chromatography over silica gel and characterized
by IR, 1H and 13C NMR, ESI-MS, and HRMS data.
Attempts to grow single crystals of 5 yielded only a microcrys-
talline solid that was unsuitable for X-ray crystallographic analysis.
Palladium catalysts bearing NHC ligands have been used for cross-
coupling reactions, in particular Suzuki and Heck coupling reac-
tions.7 NHC ligands are good alternative to the conventional phos-
phine ligands, and catalysts bearing NHC ligands react with a high
degree of efficiency in C–C bond forming reactions compared to
ligandless catalysts. Although complex 5 is chiral it was first tested
for its catalytic activity in simple non-asymmetric Suzuki reactions
for the synthesis of substituted biphenyls. Various substituted aryl
bromides were treated with phenylboronic acid and 4-meth-
oxyphenylboronic acid in THF in the presence of catalytic amounts
of 5. The catalyst loading varied from 2 to 20 mol % depending
upon the substrates. The coupling products were obtained in good
yields and the results are summarized in Table 1. In Table 1, entries
3, 7, and 8 are noteworthy because methoxy-substituted deriva-
tives are generally less reactive in Suzuki coupling and using the
catalyst 5, high yields of the coupling products were obtained. To
rule out the possibility of the reaction being catalyzed by leached
Me
Me
Ph
Boc N
Cl
N
Ph
N
I-
N
N
1. Ag2O, CH2Cl2, rt
N
Pd
N
N
N
2.PdCl2(CH3CN)2
rt, 67%
N
Cl
N Boc
N
Ph
Boc
Me
2
5
Scheme 3. Synthesis of palladium complex 5 from 2 via in situ-generated silver
complex.

5836
T. Karthikeyan, S. Sankararaman / Tetrahedron Letters 50 (2009) 5834–5837
Table 1
Synthesis of biphenyls by Suzuki coupling using complex 5a
5 (2 to 20 mol%)
K2CO3, 70- 75 ºC
ArBr + Ar'B(OH)2
Ar-Ar'
Entry
ArBr
Ar0B(OH)2
Ar–Ar0
5 (mol %)
Time (h)
Yield (%)
1b
2
3
1-Bromonaphthalene
1,2-Dibromobenzene
1-Bromo-2-methoxynaphthalene
PhB(OH)2
PhB(OH)2
PhB(OH)2
1-Phenylnaphthalene
o-Terphenyl
2-Methoxy-1-phenylnaphthalene
20
20
10
16
18
12
73
60
93
Ph
Br
OHC
CHO
OHC
CHO
4
PhB(OH)2
5
7
84
Bu-
t
Bu-t
5
1-Bromo-4-nitrobenzene
4-Bromobenzonitrile
1-Bromo-4-methoxybenzene
1-Bromo-4-methylbenzene
PhB(OH)2
PhB(OH)2
4-Methoxy-phenylboronic acid
4-Methoxy-phenylboronic acid
4-Nitrobiphenyl
4-Cyanobiphenyl
4,40-Dimethoxybiphenyl
4-Methoxy-40-methylbiphenyl
5
5
2
2
8
9
40
40
90
90
79
96
6
7c
8c
a
Entries 1–6, 0.35 mmol scale, 1 equiv ArBr, 2 equiv PhB(OH)2, 3 equiv K2CO3, entries 7–8, 0.88 mmol scale, 1 equiv ArBr, 1.2 equiv 4-methoxyphenylboronic acid, 3 equiv
K2CO3.
b
CsF as base.
c
Yield based on 37% conversion for entry 7 and 30% conversion for entry 8.
Table 2
MeI, CH3CN
75 ºC, 15 h
95%
Me
Me
Attempted asymmetric Suzuki coupling for the synthesis of binaphthalene
derivativesa
N
N
N
N
N
N
N
N
N
N
2I-
13
N
N
Br
B(OH)2
R
Br
Bn
Bn
Bn
12
Bn
R
R
+
R
5
+
75 ºC
Ag2O, 8h
rt, CH2Cl2
R = OMe 6
R = OBn
7
10
6
9
8
11
9
Me
Me
N
N
N
Me
N
Me
Entry
ArBr
ArB(OH)2
5 (mol %)
Base/solvent
Product
PdCl2(CH3CN)2
rt, 12 h, 18%
N
N
N
1
2
3
4
6
9
6
9
6
6
7
10
7
10
10
10
20
20
10
10
K2CO3/THF
K2CO3/THF
KOBu-t/DME
KOBu-t/DME
Cs2CO3/DME
K2CO3/THF
8
11
8
11
N
Bn
N
N
Ag
[AgI2] -
Bn
N
N
Pd
Cl Cl
15
Bn
Bn
14
5
7
8
6b
1-NpB(OH)2
Np–Np
a
Scheme 4. Synthesis of pincer palladium complex 15.
1 equiv of ArBr, 2 equiv of ArB(OH)2 and 3 equiv of base.
1-NpB(OH)2 = 1-naphthylboronic acid and Np–Np = 1,1-binaphthylene.
b
alysts might be due to slow transmetallation of the sterically
demanding boronic acids, leading to deboronation reaction.
In conclusion, we report the first example of a chiral palladium
complex (5) bearing an abnormal NHC ligand based on 1,2,3-triaz-
olylidene precursor and the first example of the corresponding pin-
cer complex (15) derived from bis-1,2,3-triazolylidene precursor.
We have demonstrated that both the complexes are useful as cat-
alysts for the non-asymmetric Suzuki coupling reaction for the
synthesis of biphenyl derivatives. However, both the complexes
failed to catalyze the formation of binaphthyl derivatives, the
asymmetric version of Suzuki coupling in the case of 5 and the or-
dinary version in the case of 15. Under the reaction conditions deb-
oronation of arylboronic acid occurred very efficiently leaving the
aryl bromide intact in the reaction.
HRMS. The absence of triazolium ring proton resonance at
9.47 ppm in the 1H NMR spectrum indicated that both the rings
had undergone deprotonation resulting in the formation of the cor-
responding biscarbene leading to the formation of 15 via 14. The
molecular ion peak in MS corresponded to C26H25N6Cl2Pd, [M+1]
ion, and showed the isotope distribution pattern expected for this
formula, based on the calculated spectrum. Complex 15 was tested
for its catalytic activity in Suzuki coupling. Coupling of 4-bromoni-
trobenzene and 4-bromobenzonitrile with phenylboronic acid
yielded 4-nitro- and 4-cyanobiphenyl, respectively, in >90% yields.
However, attempted coupling of 1-bromo-2-methoxynaphthalene
(6) and 2-methoxynaphthalen-1-ylboronic acid (7) using 15 and
Cs2CO3 in DME resulted only in deboronation of 7 to yield 2-meth-
oxynaphthylene (8) and 6 remained intact in the reaction. To our
disappointment, even the use of the pincer complex 15 as catalyst
in the Suzuki reaction did not result in the formation of the desired
binaphthyl derivative. We speculate that the failure of the Suzuki
coupling to yield binaphthyl derivatives using 5 and 15 as pre-cat-
Acknowledgments
We thank DST, New Delhi, for financial support, Department of
Chemistry and SAIF, IIT Madras for spectral data and IIT Madras for
a fellowship to T.K.

T. Karthikeyan, S. Sankararaman / Tetrahedron Letters 50 (2009) 5834–5837
5837
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Supplementary data
Supplementary data (detailed experimental procedure, copies
of 1H NMR, 13C NMR, mass spectrum of palladium complexes, char-
acterization data for the Suzuki products are available in supple-
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References and notes
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Ofele, K. J. Organomet. Chem. 1968, 12, P42–P43.
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