Synthesis and characterization of novel chiral NHC-palladium complexes and their application in copper-free Sonogashira reactions

Article abstract of DOI:10.1039/c2dt12391f

A new series of chiral N-heterocyclic carbene (NHC) palladium complexes were synthesized from a relatively inexpensive amino acid, l-phenylalanine. All these compounds were fully characterized by ¹H-NMR, ¹³C-NMR and elemental analysis. The X-ray molecular structures of two of the complexes were reported. The catalytic activity of the four palladium complexes was successfully tested in the Sonogashira reaction under copper free conditions in air. The palladium complex 3a provided good activity in the Sonogashira coupling reaction. The Royal Society of Chemistry 2012.

Full text of DOI:10.1039/c2dt12391f

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PAPER
Synthesis and characterization of novel chiral NHC–palladium complexes and
their application in copper-free Sonogashira reactions†
a
a
a
a
a
b
b
Longguang Yang, Pei Guan, Pan He, Qian Chen, Changsheng Cao,* Yu Peng, Zhan Shi,
b
a,c
Guangsheng Pang and Yanhui Shi*
Received 12th December 2011, Accepted 12th February 2012
DOI: 10.1039/c2dt12391f
A new series of chiral N-heterocyclic carbene (NHC) palladium complexes were synthesized from a
relatively inexpensive amino acid, L-phenylalanine. All these compounds were fully characterized by
1
13
H-NMR, C-NMR and elemental analysis. The X-ray molecular structures of two of the complexes
were reported. The catalytic activity of the four palladium complexes was successfully tested in the
Sonogashira reaction under copper free conditions in air. The palladium complex 3a provided good
activity in the Sonogashira coupling reaction.
8
Introduction
the high catalyst loadings, and the use of unstable, expensive
5
and toxic phosphine ligands. Consequently, it is necessary to
The Sonogashira cross-coupling reaction has become one of the
most important methods in the synthesis of aryl alkynes from
aryl halides or triflates. Compounds bearing carbon–carbon
triple bonds are often encountered in natural products, pharma-
ceuticals, and biologically important molecules, as well as in
molecules with materials related applications. In a typical Sono-
develop air-stable, robust and well-defined Pd-complexes with
inexpensive ligands. We have developed an interest in exploring
the utility of N/O-functionlized N-heterocyclic carbenes in
chemical catalysis, with special emphasis on developing inex-
pensive, user-friendly, and highly efficient precatalysts for C–C
1
2
9
cross-coupling reactions. To explore new efficient catalysts for
gashira procedure, the reaction is conducted using a phosphane-
including palladium complex with a catalytic amount of copper
Sonogashira coupling reactions, we prepared a series of novel
chiral NHC–palladium complexes from the relatively inexpen-
sive L-phenylalanine and reported on the use of these complexes
to catalyze the copper-free Sonogashira coupling reaction under
aerobic conditions.
(
I) salt as catalyst in the presence of an amine. Although copper
would greatly increase the reaction rate, it induces unwanted
homo-coupled products of terminal alkynes through a Hay–
Glaser-type reaction. Moreover, Cu-acetylide generated in situ
3
is extremely sensitive to air and moisture, so inert atmospheric
conditions are required. A solution to this problem is to elimin-
4
Results and discussion
ate copper in the reaction. In the last few decades, more and
Imidazolium salts
more efficient palladium catalysts containing hindered phos-
5
6
phane and NHC ligands have been developed working in the
The optically pure imidazoline 1 was prepared by a 5-step
absence of Cu. Although the N-heterocyclic carbenes have been
used widely in organometallic chemistry and catalysis, Sonoga-
sequence starting from L-phenylalanine according to the litera-
ture procedure (Scheme 1). Although all five steps provided
7
10
shira coupling based on N-heterocyclic carbenes is relatively
rarer compared to phosphine based precatalysts. Most of the
copper-free Sonogashira reactions suffer from problems due to
from moderate to good yield in the formation of all the reaction
intermediates, the overall yield in the formation of 1 was ca.
30%. The imidazolium bromides 2 were synthesized by direct
substitution reaction of imidazoline 1 with the readily available
corresponding alkyl bromides in good yield. The reaction for
compound 2a was performed in toluene at 65 °C for 5 h,
whereas the reactions for 2(b–d) were conducted in acetonitrile
at 110 °C for 10 h.
a
School of Chemistry and Chemical Engineering and Jiangsu Key
Laboratory of Green Synthetic Chemistry for Functional Materials,
Xuzhou Normal University, Xuzhou, Jiangsu 221116, PR China. E-mail:
yhshi_2000@126.com; Fax: +86-516-83500349; Tel: +86-516-
8
3500349
b
State Key Laboratory of Inorganic Synthesis and Preparative
Chemistry, College of Chemistry, Jilin University, Changchun, Jilin
Synthesis of NHC–palladium complexes
1
30012, PR China
c
State Key Laboratory of Coordination Chemistry, Nanjing University,
Nanjing, Jiangsu 210093, PR China
The synthesis of NHC–palladium complexes 3(a–d) was
achieved by the procedure shown in Scheme 2. The reaction of 2
†
CCDC reference numbers 858709 and 858710 for 3a and 3c, respect-
with one equiv. of PdCl in pyridine in the presence of K CO
3
ively. For crystallographic data in CIF or other electronic format see
DOI: 10.1039/c2dt12391f
2
2
as a base and NaBr as the provider of bromide ion afforded
5020 | Dalton Trans., 2012, 41, 5020–5025
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Fig. 1 The ORTEP structure of complex 3a showing 30% probability
ellipsoids; hydrogen atoms are omitted for clarity. Selected bond lengths
Scheme 1 Synthesis of compounds 2.
(Å) and bond angles (°): Pd1–C1 1.965(4), Pd1–Br1 2.4309(67), Pd1–
Br2 2.4339(7), Pd1–N3 2.114(4), C1–N1 1.328(5), C1–N2 1.349(5),
C1–Pd1–Br1 85.64(3), C1–Pd1–Br2 91.93(13), Br1–Pd1–N3 91.73(10),
Br2–Pd1–N3 90.81(10), N1–C1–N2 109.2(4).
Scheme 2 Synthesis of complexes 3.
complexes 3 in moderate to good yield. All of these complexes
were characterized by NMR spectroscopy and gave satisfactory
elemental analyses. The complexes are air and moisture stable
and can be stored in an air atmosphere in the solid state for more
than 6 months without any noticeable decomposition.
The proton signal of NCHN from the imidazolium bromides 2
(
9.99 ppm for 2a; 9.18 ppm for 2b; 8.76 ppm for 2c; 9.73 ppm
1
for 2d) was absent in the H NMR of the palladium complexes,
confirming carbene generation. In addition, the formation of the
metal complexes was evident from the distinctive Pd–Ccarbene
peak (182.8 ppm for 3a, 182.7 ppm for 3b, 182.6 ppm for 3c
and 182.1 ppm for 3d), which significantly shifted downfield
relative to that of the imidazolinium NCHN peak of the starting
ligand precursor (158.6 ppm for 2a, 157.3 ppm for 2b,
Fig. 2 The ORTEP structure of complex 3c showing 30% probability
ellipsoids; hydrogen atoms are omitted for clarity. Selected bond lengths
(Å) and bond angles (°): Pd1–C1 1.967(8), Pd1–Br1 2.4311(12), Pd1–
Br2 2.4256(12), Pd1–N3 2.111(7), C1–N1 1.332(9), C1–N2 1.333(10),
C1–Pd1–Br1 91.1(2), C1–Pd1–Br2 87.4(2), Br1–Pd1–N3 90.4(2), Br2–
Pd1–N3 90.7(2), N1–C1–N2 109.8(7).
1
59.1 ppm for 2c, 158.7 ppm for 2d).
Single crystals for the solid-state structure determination of 3a
and 3c could be obtained by slow diffusion of diethyl ether into
a saturated DCM solution. The molecular structures of 3a and 3c
were determined by means of X-ray diffraction studies. The mol-
ecular diagrams of 3a and 3c are shown in Figs 1 and 2 and
selected crystallographic data are shown in Table 1. Two com-
plexes show slightly distorted square-planar geometries around
palladium center, which are surrounded by imidazolylidene, two
bromo ligands in a trans configuration, and a pyridine. The Pd–
Ccarbene distance is 1.965(45) Å for 3a and 1.967(8) Å for 3c,
similar to those shown by other palladium-related species, i.e.
As optically pure L-phenylalanine was used as a starting
material, we suggested that all of these palladium complexes
were chiral because the chiral center would survive in all the
experimental processes. The X-ray structure of 3a and 3c
confirmed there is a stereogenic center with S configuration in
the back bone of imidazoline ring. The specific rotation of these
Pd complexes in DCM is 6.3° for 3a; 104.8° for 3b; 78.9° for 3c
and 72.4° for 3d.
(
1-(mesityl)-3-(pyrimidine)imidazole-2-ylidend)PdCl [1.964(3)
2
Sonogashira coupling reaction
11
Å]. The Pd–Npyridine distance in complex 3a [2.114(4) Å], 3c
2.111(7) Å] is comparable to that observed in other related pal-
[
To evaluate the catalytic activity of 3a–3d in the Cu-free Sono-
gashira coupling reactions under aerobic conditions, we per-
formed the reaction of 1-iodo-2-methoxybenzene with
9
ladium carbene analogues. All other distances and angles lie in
the expected range.
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Table 1 Crystal data and structure refinement details for 3a and 3c
Table 2 Coupling reactions under different reactions
Complex
3a
3c
Formula
C
34
H
39Br
2
N
3
Pd
29 2 3
C H37Br N OPd
709.84
298(2)
Formula weight
Temperature of
measurement (K)
Crystal system
Space group
a (Å)
b (Å)
c (Å)
α (°)
β (°)
755.90
298(2)
a
b
Entry
Pd cat.
Solvent
Yield (%)
Triclinic
P1ˉ
Monoclinic
P2(1)/n
10.4260(11)
17.3900(18)
16.7852(15)
90.00
95.8990(10)
90.00
3027.2(5)
4
1
2
3
4
5
6
7
8
9
3a
3b
3c
3d
3a
3a
3a
3a
3a
DMSO
DMSO
DMSO
DMSO
DMF : H
DMF
THF
Toluene
Dioxane
69
36
49
31
45
23
0
10.6900(10)
11.0661(11)
14.7279(15)
109.010(2)
90.6700(10)
96.2090(10)
1635.5(3)
2
2
O = 3 : 1
γ (°)
Volume (Å )
Z
3
0
0
Crystal size
F(000)
Theta range for data
collection (°)
Goodness-of-fit on F
0.45 × 0.43 × 0.38
760
2.576–27.954
0.43 × 0.40 × 0.30
1424
2.287–24.529
a
Reaction conditions: 0.5 mmol of aryl iodides,
1
mmol
b
phenylacetylene and 1 mmol of K
two runs with dodecane as an internal standard.
2
CO
3
in 2 mL solvents. Average of
2
1.038
1.079
Final R indices [I > 2σ(I)]
R
1
= 0.0400
wR = 0.0964
= 0.0686
wR = 0.1103
R
1
= 0.0630
wR = 0.1253
= 0.0894
wR = 0.1334
2
2
R indices (all data)
R
1
R
1
naphthalen-1-ylboronic acid (1.2 mmol) catalyzed by 0.5 mol%
of 3a was investigated. The reaction was carried out in dioxane
with KOH (3 mmol) as base at 100 °C for 24 h. The product
was isolated in 99% yield, unfortunately, with only 5% ee. We
are currently optimizing the conditions to further improve the
catalytic results. Further reactivity studies of these and related
catalyst systems in various reactions are on going in our labora-
tories and we hope to discover an efficient universal catalyst
system.
2
2
phenylacetylene in DMSO in the presence of K CO as base at
2
3
1
00 °C for 1 h, using 1 mol% catalyst loading. As can be seen
from the results shown in Table 2 (entries 1–4), complex 3a is
the one that provides the best activity (69% yield), whereas the
other complexes (3b–3d) do not show good activity, especially
3
d, leading to only 31% yield.
The solvent is normally a very important parameter determin-
Conclusion
ing cross-coupling efficiency, so we tested the reaction catalyzed
by 3a in different solvents (Table 2, entries 1 and 5–9). The
results showed that DMSO is the best solvent tested, and a rela-
tively low yield was observed in DMF or a mixed solvent of
DMF with water (3 : 1). No product was even observed in THF,
toluene or dioxane as solvent at all. Therefore, solvent does play
a very important role in this catalytic reaction.
To probe the substrate scope of the reaction, more aryl iodides
and bromides were chosen to react with phenylacetylene using
mol% catalyst 3a with 2 equiv. K CO in DMSO (2 mL) in air
2 3
In summary, we have designed and synthesized a series of novel
N-heterocyclic carbene (NHC) palladium complexes from a rela-
tively inexpensive amino acid. They are highly stable to air and
moisture. Complex 3a appears to have good activity in the Sono-
gashira cross-coupling reaction under the much desired copper
free and phosphine free conditions in air. The yields of the Sono-
gashira reactions catalyzed by 3a ranging from 55–91%. The
reaction can be completed in a short time (ca. 1 h) with low cata-
lyst loading (1 mol%).
1
(Table 3). The results showed that 3a could not only catalyze the
cross-coupling reaction of phenylacetylene with more reactive
aryl iodides, but also could catalyze the reaction in good to mod-
erate yield (55%–86%) with less reactive aryl bromides in the
absence of copper co-catalysis. Unfortunately, the catalyst was
not effective for aryl chloride (entry 12). The higher yield was
obtained for aryl bromides with a strong electron-withdrawing
group compared to those with a weaker electron-withdrawing
group (like entry 1 vs. entry 5). The aryl bromides with para-
substitution led to lower yields than the bromides with substi-
tution at the ortho- or meta-position (entry 5 vs. entry 6; entry 7
vs. entry 9). Furthermore, the reaction went well with aliphatic
alkyne as well (entries 13–18), for example the reaction of 1-
hexyne with para-nitrobromobenzene gave 91% yield. All of the
reactions were very fast, and they can be completed within 1 h.
As all the Pd complexes are chiral complexes, it is
interesting to test them in an asymmetric reaction. Initially, asym-
metric Suzuki reaction of 1-bromonaphthalene (1 mmol) with
Experimental
General procedures
The chiral imidazolinium bromides were prepared according to
10
our previous procedure. Pyridine was distilled from calcium
hydride under an argon atmosphere. Potassium carbonate was
ground to a fine powder prior to use. All other reagents were
commercially available and were used without further purifi-
1
13
cation. H and C NMR spectra were recorded on a Bruker
DPX 400 MHz spectrometer at room temperature and referenced
to the residual signals of the solvent. Elemental analyses were
performed on a EuroVektor Euro EA-300 elemental analyzer.
GC-MS was performed on an Agilent 6890-5973N system with
electron ionization (EI) mass spectrometry. Optical rotation was
measured with Autopol IV automatic polarimeter in DCM sol-
ution. X-ray crystallography was conducted on a Rigaku
5022 | Dalton Trans., 2012, 41, 5020–5025
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Table 3 Sonogashira coupling reactions of phenylacetylene with aryl halides
a
b
Entry
Aryl halides
Alkyne
Product
Yield (%)
1
84
78
76
2
3
4
5
6
71
79
84
7
8
9
60
59
55
61
63
1
0
11
1
1
1
1
1
1
2
3
4
5
6
7
0
91
90
77
88
95
1
8
72
a
b
2 3
Reaction conducted with 1 mmol of aryl halides, 2 mmol of alkyne and 2 mmol of K CO in 2 mL of DMSO. Isolated yield on average of two
runs.
mercury CCD device with graphite-monochromated Mo Kα
radiation (λ = 0.71073 Å). The crystal data collection and refine-
ment parameters are summarized in Table 1. Absorption correc-
tion was performed by SADABS program. The structure was
solved by direct methods using the SHELXS-97 program and
Hz, 1H), 3.77–3.82 (m, 1H), 3.27 (dd, J = 12.0 Hz, J = 4.0 Hz,
1H), 3.13–3.18 (m, 1H), 2.69–2.76 (m, 1H), 2.26–2.31 (m, 1H),
1.31 (d, J = 4.0 Hz, 3H), 1.17 (t, J = 8.0 Hz, 6H), 1.11 (d, J =
13
8.0 Hz, 3H). C NMR (CDCl , 100 MHz): 158.6, 146.3, 146.0,
3
133.5, 132.9, 130.9, 129.7, 129.5, 129.3, 129.1, 128.9, 127.8,
2
refined by full-matrix least squares techniques on F .
124.7, 60.2, 56.8, 49.7, 36.5, 28.8, 28.3, 25.2, 25.1, 23.8, 23.7.
1
2
b Yield: 55%. H NMR (CDCl , 400 MHz): δ 9.18 (s, 1H),
3
7
2
.31–7.38 (m, 4H), 7.25 (d, J = 8.0 Hz, 2H), 7.16 (t, J = 8.0 Hz,
H), 5.22–5.30 (m, 1H), 4.44–4.47 (m, 1H), 4.24 (t, J = 12.0
Data for product 2
1
2
7
6
a Yield: 94%. H NMR (CDCl , 400 MHz): δ 9.99 (s, 1H),
Hz, 1H), 3.77–3.82 (m, 1H), 3.48 (dd, J = 12.0 Hz, J = 12.0 Hz,
1H), 3.09–3.15 (m, 1H), 2.81 (br, 1H), 2.41 (br, 1H), 1.68 (d, J
= 8.0 Hz, 3H), 1.61 (d, J = 4.0 Hz, 3H), 1.26 (d, J = 4.0 Hz,
3
.56 (d, J = 4.0 Hz, 2H), 7.34–7.46 (m, 7H), 7.13–7.18 (m, 4H),
.13 (d, J = 12.0 Hz, 1H), 4.64–4.75 (m, 2H), 3.95 (t, J = 12.0
This journal is © The Royal Society of Chemistry 2012
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1
3
25
1
3
H), 1.22 (d, J = 8.0 Hz, 3H), 1.15–1.18 (m, 6H). C NMR
(0.13 g, 59%). [α]D = 104.8°; H NMR (CDCl , 400 MHz): δ
3
(
1
2
CDCl , 100 MHz): 157.3, 146.4, 146.2, 133.9, 131.0, 129.9,
29.7, 129.3, 127.8, 124.9, 124.7, 61.3, 57.2, 50.0, 38.2, 28.8,
8.72 (d, J = 8.0 Hz, 2H), 7.61 (t, J = 8.0 Hz, 1H), 7.36 (t, J =
8.0 Hz, 1H), 7.32–7.16 (m, 9H), 6.17–6.10 (m, 1H), 4.48–4.40
(m, 1H), 3.81 (t, J = 8.0 Hz, 1H), 3.62–3.56 (m, 2H), 3.50 (dd, J
= 12.0 Hz, J = 4.0 Hz, 1H), 3.44–3.38 (m, 1H), 2.84 (t, J = 12.0
Hz, 1H), 1.76 (d, J = 8.0 Hz, 3H), 1.62 (d, J = 4.0 Hz, 3H), 1.50
(d, J = 8.0 Hz, 3H), 1.42 (d, J = 8.0 Hz, 3H), 1.20 (d, J = 4.0
3
8.5, 25.1, 25.0, 24.2, 24.1, 22.9, 21.9.
1
2
c Yield: 90%. H NMR (CDCl , 400 MHz): δ 8.76 (s, 1H),
3
7
.35–7.42 (m, 4H), 7.20 (d, J = 8.0 Hz, 3H), 7.10 (d, J = 8.0
Hz, 1H), 5.18–5.26 (m, 1H), 5.03–5.06 (m, 1H), 4.51–4.59 (m,
H), 4.27 (t, J = 12.0 Hz, 1H), 3.92–4.06 (m, 2H), 3.79–3.84
m, 1H), 3.69–3.73 (m, 1H), 3.08–3.24 (m, 3H), 1.97–2.03 (m,
13
1
(
1
Hz, 3H), 1.04 (d, J = 8.0 Hz, 3H). C NMR (CDCl3,
100 MHz): 182.7, 152.4, 148.4, 148.3, 137.5, 136.2, 134.3,
129.5, 129.0, 127.2, 124.6, 124.5, 124.3, 59.0, 58.3, 53.1, 41.2,
28.5, 27.5, 27.1, 24.7, 24.3, 23.7, 20.3. Anal. Calc. for
1
3
H), 1.23–1.27 (m, 6H), 1.04 (t, J = 8.0 Hz, 6H). C NMR
(CDCl , 100 MHz): 159.1, 147.1, 146.1, 133.6, 131.0, 129.8,
3
−1
1
2
29.4, 129.3, 127.8, 125.0, 124.5, 60.5, 57.0, 56.5, 48.0, 36.5,
C H Br N Pd (707.88 g mol ): C, 50.90; H, 5.58; N, 5.94.
30 39 2 3
8.4, 28.2, 25.2, 25.0, 24.0.
Found: C, 50.55; H, 5.47; N, 6.12%.
1
2
d Yield: 91%. H NMR (CDCl , 400 MHz): δ 9.73 (s, 1H),
3
7.34–7.39 (m, 4H), 7.21 (d, J = 4.0 Hz, 2H), 7.15 (t, J = 8.0 Hz,
2H), 4.90 (s, br, 1H), 4.72 (br, 1H), 4.07 (t, J = 12.0 Hz, 1H),
3.78–3.82 (m, 1H), 3.66–3.73 (m, 1H), 3.29 (dd, J = 12.0 Hz, J
Synthesis of complex 3c
To an oven-dried 50 mL r.b.f. containing 2c (0.133 g,
=
4.0 Hz, 1H), 3.08–3.13 (m, 1H), 2.78 (s, br, 1H), 2.28 (s, br,
0.3 mmol), PdCl2 (0.053 g, 0.3 mmol), K CO3 (0.415 g,
2
1
H), 1.77–1.82 (m, 2H), 1.65–1.71 (m, 2H), 1.27–1.29 (m, 3H),
.18–1.23 (m, 6H), 1.09–1.11 (m, 3H), 1.01 (t, J = 8.0 Hz, 3H).
3 mmol) and NaBr (0.155 g, 1.5 mmol) with a septum, was
injected pyridine (5 mL) under argon. The reaction mixture was
stirred at 80 °C for 12 h. After cooling to room temperature, the
mixture was filtered through a plug of Celite and washed with
DCM. After the volatile was removed under vacuum, the solid
was recrystallized by DCM–ether to give 3c as a yellow solid
1
1
3
C NMR (CDCl , 100 MHz): 158.7, 146.5, 146.3, 133.6,
3
1
2
30.9, 129.8, 129.6, 129.3, 127.8, 124.7, 60.4, 56.6, 45.7, 36.6,
9.4, 28.8, 28.3, 25.2, 25.1, 24.0, 23.9, 19.4, 13.6.
25
1
(
0.16 g, 73%). [α] = 78.9°; H NMR (CDCl , 400 MHz): δ
D 3
Synthesis of complex 3a
8
.68 (d, J = 8.0 Hz, 2H), 7.64 (t, J = 8.0 Hz, 1H), 7.38 (t, J =
To an oven-dried 50 mL r.b.f. containing 2a (0.147 g,
8.0 Hz, 1H), 7.33–7.18 (m, 9H), 5.36–5.29 (m, 1H), 4.55–4.47
(m, 1H), 4.36–4.22 (m, 2H), 3.97–3.89 (m, 2H), 3.64–3.55 (m,
2H), 3.41–3.29 (m, 2H), 2.99–2.96 (m, 1H), 2.86–2.80 (m, 1H),
1.48 (d, J = 4.0 Hz, 3H), 1.42 (d, J = 4.0 Hz, 3H), 1.16 (d, J =
0
.3 mmol), PdCl2 (0.053 g, 0.3 mmol), K CO (0.415 g,
2 3
3
mmol) and NaBr (0.155 g, 1.5 mmol) with a septum, was
injected pyridine (5 mL) under argon. The reaction mixture was
stirred at 80 °C for 12 h, then 90 °C for 6 h. After cooling to
room temperature, the mixture was filtered through a plug of
Celite and washed with DCM. After the volatile was removed
under vacuum, the solid was recrystallized by DCM–ether to
13
8.0 Hz, 3H), 1.07 (d, J = 8.0 Hz, 3H). C NMR (CDCl3,
100 MHz): 182.6, 152.3, 148.3, 148.2, 137.7, 135.8, 134.0,
129.7, 129.3, 129.0, 127.2, 124.6, 124.4, 60.9, 59.8, 58.5, 50.4,
38.5, 28.5, 28.4, 27.3, 27.2, 24.4. Anal. Calc. for
2
5
1
−1
give 3a as a yellow solid (0.19 g, 85%). [α]D = 6.3°; H NMR
CDCl , 400 MHz): δ 8.74 (d, J = 4.0 Hz, 2H), 7.68 (d, J = 4.0
C H Br N OPd (709.85 g mol ): C, 49.07; H, 5.25; N, 5.92.
29
37
2 3
(
Found: C, 48.76; H, 5.06; N, 6.12%.
3
Hz, 2H), 7.62 (t, J = 8.0 Hz, 1H), 7.47 (t, J = 8.0 Hz, 2H), 7.40
t, J = 8.0 Hz, 2H), 7.31 (d, J = 8.0 Hz, 1H), 7.25–7.17 (m, 6H),
(
Synthesis of complex 3d
6.98 (d, J = 8.0 Hz, 2H), 6.72 (d, J = 12.0 Hz, 1H), 4.82 (d, J =
2.0 Hz, 1H), 4.02–3.95 (m, 1H), 3.89–3.77 (m, 2H), 3.54 (dd,
1
To an oven-dried 50 mL r.b.f. containing 2d (0.137 g,
J = 12.0 Hz, J = 4.0 Hz, 1H), 3.38–3.27 (m, 2H), 2.79–2.73 (m,
H), 1.53 (d, J = 8.0 Hz, 3H), 1.48 (d, J = 8.0 Hz, 3H), 1.21 (d,
J = 8.0 Hz, 3H), 1.07 (d, J = 8.0 Hz, 3H). C NMR (CDCl3,
0.3 mmol), PdCl2 (0.053 g, 0.3 mmol), K CO3 (0.415 g,
2
1
3 mmol) and NaBr (0.155 g, 1.5 mmol) with a septum, was
injected pyridine (5 mL) under argon. The reaction mixture was
stirred at 80 °C for 12 h. After cooling to room temperature, the
mixture was filtered through a plug of Celite and washed with
DCM. After the volatile was removed under vacuum, the solids
was recrystallized by DCM–ether to give 3d as a yellow solid
1
3
1
1
1
00 MHz): 182.8, 152.3, 148.3, 148.2, 137.5, 135.9, 135.3,
34.1, 129.6, 129.2, 129.1, 128.9, 128.2, 127.0, 124.6, 124.5,
24.3, 59.1, 58.5, 53.7, 37.9, 28.6, 28.3, 27.2, 27.1, 24.6, 24.4.
−1
Anal. Calc. for C H Br N Pd (756.93 g mol ): C, 53.95; H,
34
39
2 3
25
1
5
.33; N, 5.55. Found: C, 53.56; H, 5.21; N, 5.72%.
(0.18 g, 82%). [α] = 72.4°; H NMR (CDCl , 400 MHz): δ
D 3
8.72 (d, J = 8.0 Hz, 2H), 7.62 (t, J = 8.0 Hz, 1H), 7.39–7.27 (m,
4H), 7.24–7.17 (m, 6H), 5.19–5.11 (m, 1H), 4.39–4.32 (m, 1H),
3.89 (t, J = 8.0 Hz, 1H), 3.79–3.72 (m, 1H), 3.69–3.62 (m,
Synthesis of complex 3b
To an oven-dried 50 mL r.b.f. containing 2b (0.133 g,
1H), 3.60–3.55 (m, 1H), 3.37–3.26 (m, 2H), 2.84–2.78 (m, 1H),
2.06–1.91 (m, 2H), 1.58–1.52 (m, 2H), 1.48 (d, J = 8.0 Hz, 3H),
1.43 (d, J = 4.0 Hz, 3H), 1.16 (d, J = 8.0 Hz, 3H), 1.07 (t, J =
0
.3 mmol), PdCl2 (0.053 g, 0.3 mmol), K CO (0.415 g,
2 3
3
mmol) and NaBr (0.155 g, 1.5 mmol) with a septum, was
13
injected pyridine (5 mL) under argon. The reaction mixture was
stirred at 80 °C for 12 h. After cooling to room temperature, the
mixture was filtered through a plug of Celite and washed with
DCM. After the volatile was removed under vacuum, the solid
was recrystallized by DCM–ether to give 3b as a yellow solid
8.0 Hz, 6H). C NMR (CDCl , 100 MHz): 182.1, 152.3, 148.3,
3
137.5, 135.9, 134.2, 129.5, 129.2, 129.0, 127.1, 124.5, 124.3,
59.9, 58.3, 49.0, 38.2, 30.0, 28.5, 28.3, 27.2, 24.5, 24.4, 20.3,
−1
14.1. Anal. Calc. for C H Br N Pd (721.07 g mol ): C,
31
41
2 3
51.58; H, 5.72; N, 5.82. Found: C, 51.33; H, 5.54; N, 6.03%.
5024 | Dalton Trans., 2012, 41, 5020–5025
This journal is © The Royal Society of Chemistry 2012

View Article Online
General procedure for the Sonogashira coupling reaction
3 G. Evano, N. Blanchard and M. Toumi, Chem. Rev., 2008, 108, 3054–
3
131.
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4
5
In a typical run, a 5 mL vial equipped with a magnetic bar was
charged with a mixture of aryl halide (1 mmol), alkyne
2
(
2 mmol), Pd catalyst (0.01 mmol), K CO (2 mmol) and 2 mL
2 3
of DMSO in air. The reaction was heated at 100 °C for 1 h, after
which time the mixture was cooled to room temperature and
brine was added to it. The resulting mixture was extracted with
ethyl acetate 3 times, and the crude oil was obtained by remov-
ing the volatile. The product was purified by flash column
chromatography on silica gel.
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Graduate Foundation of Jiangsu Education Committee
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(
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1172188 and 21104064), PAPD and the State Key Laboratory
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This journal is © The Royal Society of Chemistry 2012
Dalton Trans., 2012, 41, 5020–5025 | 5025