Palladium-bis(oxazoline) complexes with inherent chirality: Synthesis, crystal structures and applications in Suzuki, Heck and Sonogashira coupling reactions

Article abstract of DOI:10.1016/j.poly.2013.12.023

New palladium-bis(oxazoline) (Pd-BOX) complexes were synthesized and characterized. The X-ray crystal structures of the two complexes showed that the palladium ion is bound to the nitrogen atoms of the two heterocycles of the bidentate ligand and two chloride ions in a distorted square planar geometry. The coordination to the palladium ion allows these non C₂-symmetric bis(oxazoline) ligand-based complexes to acquire a rigid backbone curvature generating an inherent chirality. The catalytic activities were evaluated in Suzuki-Miyaura, Mizoroki-Heck and Sonogashira coupling reactions. The complexes showed high catalytic activities towards numerous C-C coupling reactions with various aryl halides, aryl boronic acids, alkenes and alkynes. The reactions were optimized for the most suitable temperature, solvent, and base system.

Full text of DOI:10.1016/j.poly.2013.12.023

Polyhedron 70 (2014) 39–46
Contents lists available at ScienceDirect
Polyhedron
journal homepage: www.elsevier.com/locate/poly
Palladium–bis(oxazoline) complexes with inherent chirality: Synthesis,
crystal structures and applications in Suzuki, Heck and Sonogashira
coupling reactions
S.M. Shakil Hussain b, Mansur B. Ibrahim a, Atif Fazal c, Rami Suleiman d, Mohammed Fettouhi a,
Bassam El Ali a,
⇑
a Chemistry Department, King Fahd University of Petroleum & Minerals, Dhahran 31261, Saudi Arabia
b Center for Petroleum and Minerals, King Fahd University of Petroleum & Minerals, Dhahran 31261, Saudi Arabia
c Center of Research Excellence in Petroleum Refining and Petrochemicals, King Fahd University of Petroleum & Minerals, Dhahran 31261, Saudi Arabia
d Center of Research Excellence in Corrosion, King Fahd University of Petroleum & Minerals, Dhahran 31261, Saudi Arabia
a r t i c l e i n f o
a b s t r a c t
Article history:
New palladium–bis(oxazoline) (Pd–BOX) complexes were synthesized and characterized. The X-ray crys-
tal structures of the two complexes showed that the palladium ion is bound to the nitrogen atoms of the
two heterocycles of the bidentate ligand and two chloride ions in a distorted square planar geometry. The
coordination to the palladium ion allows these non C2-symmetric bis(oxazoline) ligand-based complexes
to acquire a rigid backbone curvature generating an inherent chirality. The catalytic activities were eval-
uated in Suzuki–Miyaura, Mizoroki–Heck and Sonogashira coupling reactions. The complexes showed
high catalytic activities towards numerous C–C coupling reactions with various aryl halides, aryl boronic
acids, alkenes and alkynes. The reactions were optimized for the most suitable temperature, solvent, and
base system.
Received 4 October 2013
Accepted 22 December 2013
Available online 30 December 2013
Keywords:
Palladium
Bis(oxazoline)
Inherent chirality
Coupling reactions
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
phosphine ligands are in general air and moisture sensitive. Thus,
rather than the catalytic species generated in situ, the development
Palladium-catalyzed C–C bond coupling reactions have been
established as a powerful tool for the production of monomers
for polymers, agrochemicals, pharmaceuticals, flavors and fra-
grances [1]. During the last decades, the Suzuki–Miyaura [2],
Mizoroki–Heck [3], and Sonogashira [4] coupling reactions have
been playing key roles in organometallic chemistry and recent or-
ganic synthesis. Particularly, these reactions are involved in the
majority of methods used to construct biaryl compounds [5] for
the total synthesis of natural products, material science and supra-
molecular chemistry [6]. Recently the scope and practical use of
such coupling reactions have significantly enhanced and the design
and synthesis of new ligands to facilitate these coupling reactions
have great contributions to this progress [7]. A good number of re-
ports deal with catalytic species based on transition metals and
phosphine ligands to catalyze the coupling reactions [8]. However,
there are limited number of reports that describes the use of nitro-
gen as a donor atom with palladium complexes [7,9]. In addition,
of new catalysts that are well defined, efficient, inexpensive, insen-
sitive to air and moisture, and less toxic is highly desirable. An
alternative would be nitrogen-based ligands which are generally
non-toxic, stable to air/moisture, modular, and less expensive than
phosphine ligands [9]. Therefore, the current research is more fo-
cused on the synthesis of ligands containing nitrogen as a donor
atom such as oxime-based palladacycle [10], amine [11], bis N-het-
erocyclic carbene [12], and N-heterocyclic carbene-oxazoline [13].
In this context, dinitrogenated bis(oxazoline) ligands [14–16] and
particularly their C2-symmetric chiral molecules have been exten-
sively used with different metal ions in asymmetric catalysis [17].
However, only few examples that describe the applications of
palladium-bis(oxazoline) complexes in C–C bond coupling reac-
tions have been reported so far [18]. In this paper, we report on
the synthesis and characterization of two new bis(oxazoline)
(BOX) ligands and their corresponding chloridobis(oxazoline)palla-
dium(II) (Pd–BOX) complexes. The results of the catalytic
applications to C–C bond cross coupling reactions such as
Suzuki–Miyaura, Mizoroki–Heck, and Sonogashira reactions are
presented.
⇑
Corresponding author. Tel.: +966 13 860 4491; fax: +966 13 860 4277.
E-mail address: belali@kfupm.edu.sa (B. El Ali).
0277-5387/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.poly.2013.12.023

40
S.M. Shakil Hussain et al. / Polyhedron 70 (2014) 39–46
ꢁ 2), 4.00–4.08 (m, 4H, OCH2 ꢁ 2), 1.84 (m, 2H, isopropyl CH
2. Experimental
ꢁ 2), 1.01 (d, J = 6.1 Hz, 6H, isopropyl CH3 ꢁ 2), 0.92 (d, J = 6.7 Hz,
6H, isopropyl CH3 ꢁ 2); 13C NMR (125 MHz, CDCl3) d (ppm): 18.1
(isopropyl CH3 ꢁ 2), 19.0 (isopropyl CH3 ꢁ 2), 32.5 (isopropyl
CH), 32.6 (isopropyl CH), 70.4 (OCH2), 70.6 (OCH2), 72.9 (NCH),
73.0 (NCH), 119.4, 119.5, 119.6, 122.9, 124.0, 129.9, 130.5, 130.6,
2.1. Materials and instrumentation
2.1.1. Materials
Starting material for the synthesis of ligands and complexes
was purchased from Sigma Aldrich and used without further puri-
fication. Chlorobenzene (anhydrous) was purchased from Sigma
Aldrich and used as received. Other solvents used in the synthesis
were of reagent grade (Merck) and were distilled before use. Puri-
fication of the products was carried out using flash column chro-
matography. The column was packed with Silica gel 60 F from
Fluka Chemie AG (Buchs, Switzerland). Palladium compounds were
purchased from Strem Company.
131.6, 131.7, 156.0, 158.9, 163.0, 163.1; IR
m
(cmꢀ1) 2959, 2926,
1653, 1589, 1489, 1355, 1224, 1090, 736; GC–MS m/z 393 (M+1);
Anal. Calc. for C24H28N2O3 (392.50): C, 73.44; H, 7.19; N, 7.14.
Found: C, 73.54; H, 7.04; N, 7.37%.
2.3. Synthesis of the palladium-bis(oxazoline) complexes A and B
A 25-mL round-bottom flask flushed with argon was charged
with Bis(benzonitrile)palladium(II) chloride (0.400 mmol, 0.153 g)
and 1 (0.400 mmol) in CH2Cl2 (5.0 mL) at room temperature and
stirred for 4 h. The reaction was monitored by TLC until no free 1
was observed. The organic phase was separated and filtered and
the solvent was removed under reduced pressure. The resulting so-
lid was dissolved in a minimum amount of CH2Cl2 and layered with
hexane. After 24 h, the crystals started to develop. The crystals
were separated and washed with Et2O and characterized with dif-
ferent spectroscopic techniques including 1H NMR, 13C NMR, FT-IR,
elemental analysis in addition to X-ray single-crystal diffraction
analysis.
2.1.2. Instrumentation
1H and 13C NMR spectra were recorded on 500 MHz Joel 1500
NMR machine. Chemical shifts (d) were reported in ppm relative
to tetramethyl silane (TMS) using CDCl3. IR spectra were recorded
on Perkin-Elmer 16F PC FT-IR spectrometer and reported in wave
numbers (cmꢀ1), or by Nicolet™ 6700 FT-IR spectrometer. Gas
chromatography (GC) analyses were realized on Agilent GC 6890.
The products of the reactions were also analyzed on GC–MS Varian
Saturn 2000 equipped with 30 m capillary column (HP-5). Thin-
layer chromatography (TLC) analyses were performed on silica
gel Merck 60 F254 plates (250 lm layer thickness).
2.3.1. Dichlorido(2,20-(4-phenoxy-1,2-phenylene)bis(4,4-dimethyl-
4,5-dihydrooxazole)-N,N’)palladium(II) (A)
2.2. Synthesis of the ligands 1 and 2
Yellow solid; mp 242–243 °C; 1H NMR (500 MHz, CDCl3) d
(ppm): 7.74 (d, J = 8.8 Hz, 1H), 7.46 (t, J = 8.2 Hz, 2H), 7.30 (d,
J = 2.4 Hz, 1H), 7.27 (t, J = 7.6 Hz, 1H), 7.22 (d, J = 2.4 Hz, 1H), 7.15
(d, J = 7.6 Hz, 2H), 4.30–4.19 (m, 4H, OCH2 ꢁ 2), 1.75 (s, 3H,
NC(CH3), 1.73 (s, 3H, NC(CH3), 1.61 (s, 3H, NC(CH3), 1.58 (s, 3H,
NC(CH3); 13C NMR (125 MHz, CDCl3) d (ppm); 28.2 (NC(CH3),
28.3 (NC(CH3), 29.0 (NC(CH3), 29.1 (NC(CH3), 71.2 (NC(CH3)2),
71.5 (NC(CH3)2), 80.8 (OCH2), 80.9 (OCH2), 118.7, 119.2, 120.7,
We have adopted a synthetic route by analogy to other
bis(oxazoline) ligands [19,20]. A 100-mL two-necked round bot-
tom flask fixed with a reflux condenser was charged substituted
dicyanobenzene (500 mg, 3.50 mmol), zinc triflate (5 mol%,
0.18 mmol, 0.060 g), and dry chlorobenzene (20.0 mL) under free-
oxygen and free-water conditions. The mixture was stirred for
5 min and then a solution of achiral 2-aminoalcohol (8.80 mmol)
in dry chlorobenzene (5.0 mL) was added slowly. The reaction mix-
ture was heated and refluxed at 135 °C for 24 h. The solvent was
removed under reduced pressure to give an oily residue which
was dissolved in 25 mL of dichloromethane. The solution was ex-
tracted twice with 15 mL of water and the aqueous phase was
washed with 15.0 mL of dichloromethane. The combined organic
layers were dried with sodium sulfate and the solvent was re-
moved under vacuum to give the crude oil. Further purification
of the ligands was done by silica gel column chromatography
(ether/dichloromethane 1/4).
125.7, 127.8, 130.5, 132.6, 154.3, 161.5, 163.7, 164.0; IR
2972, 1637, 1582, 1486, 1372, 1236, 1063, 961, 729; UV–Vis spec-
trum (CH2Cl2) kmax, 301 nm (
= 1003 Mꢀ1 cmꢀ1); Anal. Calc. for
22H24Cl2N2O3Pd (541.77): C, 48.77; H, 4.47; N, 5.17. Found: C,
48.83; H, 4.66; N, 5.29%.
m )
(cmꢀ1
e
C
2.3.2. Dichlorido(2,20-(4-phenoxy-1,2-phenylene)bis(4-isopropyl-4,5-
dihydrooxazole)-N,N0)palladium(II) (B)
Orange solid; mp 235–236 °C; 1H NMR (500 MHz, CDCl3) d
(ppm): 7.90 (d, J = 8.6 Hz, 1H), 7.50–7.45 (m, 3H), 7.31–7.27 (m,
2H), 7.18–7.14 (m, 2H), 4.96–4.92 (m, 2H, NCH ꢁ 2), 4.62–4.54
(m, 2H, OCH2 ꢁ 2), 4.42–4.35 (m, 2H, OCH2 ꢁ 2), 2.69 (m, 2H, iso-
propyl CH ꢁ 2), 1.31 (d, J = 7.0 Hz, 6H, isopropyl CH3 ꢁ 2), 0.91 (d,
J = 6.7 Hz, 6H, isopropyl CH3 ꢁ 2); 13C NMR (125 MHz, CDCl3) d
(ppm): 16.1 (isopropyl CH3 ꢁ 2), 20.3 (isopropyl CH3 ꢁ 2), 30.7
(isopropyl CH ꢁ 2), 69.4 (OCH2 x 2), 71.0 (NCH), 71.3 (NCH),
117.7, 120.4, 120.5, 120.7, 121.0, 125.6, 126.4, 130.5, 133.1,
2.2.1. 2,20-(4-Phenoxy-1,2-phenylene)bis(4,4-dimethyl-4,5-
dihydrooxazole) (1)
Greenish oil; isolated yield = 94%; 1H NMR (500 MHz, CDCl3) d
(ppm): 7.64 (d, J = 8.5 Hz, 1H), 7.28–7.24 (m, 3H), 7.06 (t,
J = 7.9 Hz, 1H), 6.98–6.92 (m, 3H), 3.97 (s, 4H, OCH2 ꢁ 2), 1.29 (s,
12H, NC(CH3)2 ꢁ 2); 13C NMR (125 MHz, CDCl3) d (ppm); 28.0
(NC(CH3)2 ꢁ 2), 67.7 (NC(CH3)2), 67.9 (NC(CH3)2), 79.3 (OCH2),
79.4 (OCH2), 119.4, 119.6, 123.0, 124.0, 129.8, 130.6, 131.5, 156.0,
134.6, 154.2, 161.7, 164.5, 164.8; IR
1585, 1484, 1380, 1228, 1064, 692; UV–Vis spectrum (CH2Cl2) kmax
299 nm
= 2157 Mꢀ1 cmꢀ1); Anal. Calc. for C24H28Cl2N2O3Pd
m
(cmꢀ1) 3063, 2963, 1640,
,
(
e
158.8, 161.6, 161.7; IR
m
(cmꢀ1) 2969, 1656, 1488, 1354, 1233,
(569.82): C, 50.59; H, 4.95; N, 4.92. Found: C, 50.28; H, 4.88; N,
5.11%.
1078, 974, 737; GC–MS m/z 365 (M+1); Anal. Calc. for C22H24N2O3
(364.44): C, 72.51; H, 6.64; N, 7.69. Found: C, 72.44; H, 6.52; N,
7.87%.
2.4. General procedure for the Suzuki–Miyaura coupling reaction
2.2.2. 2,20-(4-Phenoxy-1,2-phenylene)bis(4-isopropyl-4,5-
dihydrooxazole) (2)
The reaction was conducted in a 15 mL round bottom flask. Aryl
halide (0.50 mmol), phenylboronic acid (0.60 mmol), Pd–BOX com-
plex (0.010 mmol), K2CO3 (2.0 mmol), DMF (5.0 mL) was stirred for
6 h at 70 °C under argon. After completion of the reaction, the
mixture was cooled down to room temperature, filtered and
Colorless oil; isolated yield = 86%; 1H NMR (500 MHz, CDCl3) d
(ppm): 7.71 (d, J = 8.9 Hz, 1H), 7.30–7.34 (m, 3H), 7.13 (t,
J = 7.3 Hz, 1H), 6.08–7.04 (m, 3H), 4.35 (t, J = 17.3 Hz, 2H, NCH

S.M. Shakil Hussain et al. / Polyhedron 70 (2014) 39–46
41
Table 2
immediately analyzed by GC and GC–MS. The GC yield was deter-
Selected bond lengths (Å) and bond angles (o) for compounds A and B.
mined based on the amount of aryl halide. The reaction mixture
was washed with H2O and EtOAc and the organic layer was dried
using MgSO4. The solvent was removed under reduced pressure
and the product was separated by column chromatography using
hexane–EtOAc (90:10) solvent system to give the pure products.
The characterization data of the compounds 5a [27], 5d [27], 5f
[27], 5g [27], 5b [28], 5c [29] and 5e [30] were in total agreement
with those observed in literature.
Bond lengths
Bond angles
Compound A
Pd1–N1
Pd1–N2
Pd1–Cl1
Pd1–Cl2
N1–C5
N2–C12
Compound B
Pd1–N1
Pd1–N2
Pd1–Cl1
Pd1–Cl2
N1–C1
2.031(5)
2.056(5)
2.295(2)
2.280(2)
1.273(7)
1.264(7)
N1–Pd1–N2
N1–Pd1–Cl2
N2–Pd1–Cl2
N1–Pd1–Cl1
N2–Pd1–Cl1
Cl2–Pd1–Cl1
87.6(2)
176.3(2)
91.7(2)
91.5(1)
174.0(1)
88.81(7)
2.018(4)
2.041(4)
2.285(2)
2.286(2)
1.274(6)
1.273(6)
N1–Pd1–N2
N1–Pd1–Cl1
N2–Pd1–Cl1
N1–Pd1–Cl2
N2–Pd1–Cl2
Cl1–Pd1–Cl2
88.5(2)
88.3(1)
176.7(1)
178.3(1)
91.3(1)
91.97(8)
2.5. General procedure for Mizoroki–Heck coupling reaction
The reaction was conducted in a 15 mL round bottom flask. Aryl
halide (0.50 mmol), alkene (0.75 mmol), Pd–BOX complex
(0.010 mmol), K2CO3 (2.0 mmol), DMF (5.0 mL) was stirred for
12 h at 70 °C under argon. After completion of the reaction, the
mixture was cooled down, filtered and immediately analyzed by
GC and GC–MS. The GC yield was determined based on the amount
of aryl halide. The reaction mixture was washed with H2O and
EtOAc and the organic layer was dried using MgSO4. The solvent
was removed under reduced pressure and the product was sepa-
rated by column chromatography using hexane–EtOAc (90:10) sol-
vent system to give the pure products. The characterization data of
the compounds 8a [31], 8b [31], 8e [31], 8c [32], 8d [33] and 8f
[34] were in total agreement with those observed in literature.
N2–C7
give the pure products. The characterization data of the compound
10 were in total agreement with those observed in literature [35].
2.7. X-ray crystallography
Single crystal data collection for complexes A and B was per-
formed at 120 K and 296 K respectively, on a Bruker-Axs Smart
Apex system equipped with a graphite monochromatized Mo K
a
radiation (k = 0.71073 Å). The data were collected using SMART
and the integration was performed using SAINT [21]. An empirical
absorption correction was carried out using SADABS [22]. The struc-
tures were solved by direct methods with SHELXS-97 and refined
by full-matrix least squares procedures on F2 using the program
SHELXL-97 [23]. All non-hydrogen atoms were refined anisotropi-
cally except disordered carbon atoms: C40A, C40B, C40C, C40D
and C50 in compound A, were isotropically refined. Hydrogen
atoms on un-disordered carbon atoms were placed at calculated
positions using a riding model. The phenoxy-group atoms in both
compounds were constrained to double site partial occupancies
which were refined to 0.685(9) and 0.759(9) values respectively
for the two molecules of the asymmetric unit of compound A
and 0.658(8) for compound B. Crystal data and details of the data
collection are summarized in Table 1. Selected bond lengths and
bond angles are given in Table 2.
2.6. General procedure for Sonogashira coupling reaction
The reaction was conducted in a 15 mL round bottom flask. Aryl
halide (0.50 mmol), Et3N (0.50 mmol), Alkyne (0.75 mmol),
Pd–BOX complex (0.010 mmol), CuI (0.020 mmol), DMF (5.0 mL)
was stirred for 12 h at 70 °C under argon. The mixture was then
cooled down, filtered and immediately analyzed by GC and
GC–MS. The GC yield was determined based on the amount of aryl
halide. The reaction mixture was washed with H2O and EtOAc and
the organic layer was dried using MgSO4. The solvent was removed
under reduced pressure and the product was separated by column
chromatography using hexane–EtOAc (97:3) solvent system to
Table 1
Crystallographic data for A and B.
Compound
A
B
3. Results and discussion
Chemical formula
Formula weight
Crystal system
Space group
T (K)
C
22H24Cl2N2O3Pdꢂ0.25H2O C24H28Cl2N2O3Pd
546.24
569.78
3.1. Synthesis of ligands and corresponding Pd(II)-complexes
triclinic
triclinic
ꢀ
ꢀ
P1
P1
The ligands 1 and 2 were synthesized by treating substituted
phthalonitrile with 2-achiral amino alcohol in the presence of
Zn(OTf)2 as depicted in Scheme 1. The treatment of ligands 1 and
2 with palladium dichlorodibenzonitrile, PdCl2(PhCN)2, in CH2Cl2
at room temperature afford the corresponding palladium com-
plexes A and B, respectively. Both Pd–BOX complexes were fully
characterized by elemental and spectroscopic techniques and the
molecular structures were determined on the basis of X-ray
crystallography.
120
Mo K
1.619
296
Radiation
a (k = 0.71073 Å)
qcalc (g cmꢀ3
a (Å)
)
1.521
9.639(1)
13.045(2)
18.610(3)
84.220(2)
85.894(2)
74.488(2)
2240.9(5)
4
9.9207(6)
12.2824(7)
12.3884(7)
108.988(1)
110.775(1)
101.803(1)
1244.1(1)
2
b (Å)
c (Å)
a
(°)
b (°)
c
(°)
V (Å3)
Z
Refl. collect./Uniq.
Refl. obser. [I > 2r(I)]
30241/11093
8638
17140/6173
4690
3.2. Molecular structures of compounds A and B
Rint
0.0453
0.0201
Data/restr./parameter
11093/4/650
6173/0/330
1.034
ꢀ
Goodness-of-fit (GOF) on F2 1.094
Complex A crystallizes in the P1 space group with two mole-
R indices [I > 2
r
(I)]
R1 = 0.0712. wR2 = 0.1869
R1 = 0.0906. wR2 = 0.1980
3.978, ꢀ2.539
R1 = 0.0561.
wR2 = 0.1630
R1 = 0.0711.
wR2 = 0.1756
1.746, ꢀ0.392
cules in the asymmetric unit. The palladium ion is bound to the
nitrogen atoms of the two oxazoline heterocycles of the bidentate
ligand and two chloride ions in a distorted square planar geometry.
The cis-bond angles are in the range: 87.6(2)–91.7(2)° and the
Pd–N and Pd–Cl bond distances are similar to those found in other
bis(oxazoline) palladium complexes [20,24,25]. The dihedral
R indices (all data)
Largest difference in peak,
hole (e Åꢀ3
)

42
S.M. Shakil Hussain et al. / Polyhedron 70 (2014) 39–46
PhO
PhO
NC
HO
NH2
R1
Zn(OTf)2
reflux. 24 h
+
O
R
O
N
N
O
O
R
CN
R1
Ligand 1, R = R1 = methyl
R1
R
Ligand , R = H, R1 = isopropyl
2
PhO
PhO
O
O
O
O
N+
Pd2-
N+
Pd2-
N+
N+
CH2Cl2
RT, 4h
+
Pd(PhCN)2Cl2
O
O
O
O
N
N
R
N
N
Cl
Cl
Cl
Cl
Pd
R1
R1
R
R
R1
Complex A, R = R1 = methyl
R1
R
Cl Cl
Complex , R = H, R1 = isopropyl
Fig. 2. Inherent chirality in palladium bis(oxazoline) complexes.
B
Scheme 1. Synthesis of the ligands and the palladium-bis(oxazoline) complexes.
planar geometry similarly to A (Fig. 3). The cis-bond angles around
the palladium ion are in the range 88.3(1)–91.97(8)° and the Pd–N
and Pd–Cl bonds lengths are in normal ranges. The dihedral angles,
between each of two oxazoline heterocycles and the benzene ring
spacer mean plane are 40.0(3)° and 42.2(3)° respectively. Similarly
to A, the complex presents a rigid curvature in a chair-like mode.
The dihedral angle between the mean planes of [PdN2Cl2] moiety
and the benzene ring spacer is 78.4(1)°. The complex crystallizes
as a pseudoracemate. The packing disorder of the two enantiomers
(R, S) and (S, R) in the crystal structure was modeled using a two-
site occupancy for the phenoxy group substituent lowering the
symmetry of the ligand. The phenyl ring of the phenoxy pendant
arm is not coplanar with the benzene ring spacer showing a torsion
angle of 83(1)°.
angles, between each of two oxazoline heterocycles and the ben-
zene ring spacer mean planes are (41.5(2)°, 42.7(3)°) and
(44.9(3)°, 47.5(2)°) for the two molecules respectively.
Interestingly and despite the fact that the ligand is achiral, the
coordination to the palladium ion allows this non C2-symmetric
bis(oxazoline) ligand-based complex to acquire a rigid backbone
curvature and the molecule resembles a chair with the [PdN2Cl2]
moiety being the seat and the benzene ring spacer being the back
of the chair. The dihedral angle between the mean planes of the
two moieties is 87.4(2)° and 85.7(2)° for the two molecules respec-
tively (Fig. 1). This rigid curvature generates an inherent chirality
in the complex and the two mirror images are not superimposable
(Fig. 2). The complex crystallizes as a pseudoracemate and the
packing disorder of the two enantiomers in the structure was mod-
eled using a two-site occupancy for the phenoxy group substituent.
The phenyl ring of the phenoxy group is twisted from coplanarity
with the benzene ring spacer with a torsion angle of 83(1)° and
85(1)° for the two molecules respectively.
3.3. Suzuki–Miyaura coupling reaction of iodobenzene with
phenylboronic acid catalyzed by Pd–BOX (A or B)
3.3.1. Effect of solvents and bases in Suzuki–Miyaura coupling reaction
of iodobenzene with phenylboronic acid
The new palladium-bis(oxazoline) complexes A and B were ap-
plied in catalytic studies of the Suzuki–Miyaura, Mizoroki–Heck
and Sonogashira coupling reactions. The catalytic studies were
ꢀ
Compound B crystallizes also in the P1 space group and the
asymmetric unit contains a single molecule with a distorted square
Fig. 1. Molecular structure of compound A.
Fig. 3. Molecular structure of compound B.

S.M. Shakil Hussain et al. / Polyhedron 70 (2014) 39–46
43
Table 3
3.3.2. Effect of activated and deactivated aryl halides with arylboronic
acids in Suzuki–Miyaura coupling reaction using complex A
Effect of Solvent and base in Suzuki–Miyaura coupling reaction between iodobenzene
and phenylboronic acid in the presence of Pd–BOX Aa (and Bb).
We further extended the study of the catalytic activity of the
new Pd–BOX complex A. We have examined the effect of various
aryl halides with different arylboronic acids (Eq. (2)) and the re-
sults are summarized in Table 4. The Suzuki coupling reactions of
different aryl halides containing electron rich and electron with-
drawing substituents reacted smoothly with phenylboronic acid
to give the biaryl compounds as sole products in high conversions
(Table 4, entries 1–3). Similarly, the Suzuki coupling reactions of
various arylboronic acids with iodobenzene underwent almost
quantitatively to give only the targeted coupling products. These
results indicate that electron rich and electron withdrawing
substituents on the phenyl ring of aryl boronic acids have no major
effect on such kind of transformation (Table 4, entries 4–6).
Entry
Solvent
Base
Yield (%)c
1
2
3
4
5
6
7
8
9
10
11
12
13
DMF
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Et3N
Na2CO3
K-OH
K3PO4
K2HPO4
KH2PO4
100
27
73
54
63
52
99
51
84
98
80
76
12
CH2Cl2
Acetonitrile
DME
Toluene
Dioxane
DMSO
DMF
DMF
DMF
DMF
DMF
DMF
a
Reaction conditions: Pd–BOX
A (0.0100 mmol), Iodobenzene (0.500 mmol),
Complex A
phenylboronic acid (0.600 mmol), base (2.00 mmol, solvent (5.0 mL), 70 °C, 6 h.
Ar-I
+
Ar-B(OH) 2
Ar-Ar
b
99% GC yield with complex B under the conditions of entry 1.
K2CO3, DMF
70°C, 6 h
ð2Þ
c
Determined by GC.
3a-d
4a-d
5b-g
initiated on Suzuki–Miyaura coupling reactions by adopting iodo-
benzene and phenylboronic acid model substrates in the presence
of Pd–BOX complex A as catalyst at 70 °C for 6 h (Eq. (1)). Different
solvents and bases were screened and the results are summarized
in Table 3. It was interesting to observe in all experiments that the
expected biphenyl was formed as the sole product of the reactions.
A complete conversion of iodobenzene was observed in 6 h using
K2CO3 as a base and DMF as a solvent (Table 3, entry 1). However,
the use of polar aprotic solvent having low boiling point such as
CH2Cl2 led to poor conversion of iodobenzene (Table 3, entry 2).
The conversion was improved with polar aprotic solvents that have
higher boiling point such as acetonitrile and DME (Table 3, entries
3.3.3. Effect of the type of palladium catalysts in Suzuki–Miyaura
coupling reaction of iodobenzene with phenylboronic acid
We have compared the catalytic activity of the new Pd–BOX
complex A with other commercially available palladium com-
plexes such as Pd(OAc)2, PdCl2(PhCN)2 and PdSO4 in the Suzuki–
Miyaura coupling reaction of iodobenzene with phenylboronic acid
(Eq. (3)). The results are shown in Table 5.
The order of relative catalytic activities of these three catalysts,
based on the conversion of iodobenzene, is: Pd–BOX
A > Pd(OAc)2 > PdCl2(PhCN)2 > PdSO4. This result clearly indicates
that the palladium catalyst with effective ligands play a key role
to improve the conversion of these reactions [26].
HO
palladium catalyst
I
+
B
ð3Þ
HO
K2CO3, DMF
70 oC, 6 h
5a
4a
3a
3 and 4). It is important to note that the non-polar solvents such as
toluene and dioxane gave relatively low conversions (Table 3, en-
tries 5 and 6), which are similar to those observed in literature
using other Pd–BOX complexes. The results obtained in Suzuki
reaction with the complexes A and B are superior to those observed
by Takemoto and co-workers [18]. The excellent conversion was
also achieved with the use of other polar aprotic solvent with high-
er boiling point such as DMSO (Table 1, entry 7). Similarly, the ef-
fect of different bases was studied using DMF as a solvent. An
organic base, such as Et3N, decreased the conversion (Table 3, entry
8). However, excellent conversion was obtained by using inorganic
bases such as Na2CO3 and KOH (Table 3, entries 9 and 10), which
are consistent with those observed in such kind of transformation
[26]. We have further studied the effects of various other bases
such as potassium phosphate (mono-, di-, and tri-basic). Di- and
tri-potassium phosphate led to very good conversions (Table 3, en-
tries 11 and 12). However, mono-potassium phosphate gave very
low conversion (Table 3, entry 13).
3.4. Mizoroki–Heck coupling reactions of aryl iodides with olefins
catalyzed by Pd–BOX complex A or B
We next examined the catalytic activities of the new complexes
in Mizoroki–Heck coupling reaction of different aryl iodides with
methyl acrylate and with styrene (Eq. (4)). We have observed that
activated and deactivated aryl iodides reacted successfully with
the electron-deficient alkenes such as methyl acrylate to give only
the desired coupling products in quantitative yield (Table 6, entries
1–5). However, the treatment of iodobenzene with styrene at 70 °C
afforded lown2b conversion and the reaction required higher reac-
tion temperature for complete conversion (Table 6, entry 6 and 7).
The palladium complex B showed also very high catalytic activity
in the coupling reaction of iodobenzene with methyl acrylate and
afforded only the coupling product with excellent conversion of
iodobenzene (Table 6, entry 8).
O
OMe
Complex A
6
HO
Ar-I
Product
8a-f
+
or
Complex A
ð4Þ
I
+
B
K2CO3,DMF
ð1Þ
HO
base, solvent
70oC,12h
3a-e
70 oC, 6 h
5a
4a
3a
7

44
S.M. Shakil Hussain et al. / Polyhedron 70 (2014) 39–46
Table 4
Effect of various aryl halides and arylboronic acids in Suzuki–Miyaura coupling reaction using Pd–BOX (A) as catalysta.
Entry
1
Aryl halides 3
Aryl boronic acids 4
Coupling product 5
Yield %b
89
OH
B
O2N
I
O2N
OH
5b
3b
4a
2
3
4
86
81
87
OH
B
H3COC
H3COC
H2N
I
5c
OH
3c
4a
OH
B
OH
I
H2N
Cl
5d
3d
4a
Cl
I
OH
B
3a
OH
5e
4b
Cl
Cl
5
6
95
94
OH
OH
OH
OH
I
F3C
F3C
B
B
5f
3a
4c
I
H3C
H3C
3a
5g
4d
a
Reaction conditions: Pd–BOX A (0.0100 mmol), aryl halide (0.500 mmol), arylboronic acid (0.600 mmol), K2CO3 (2.00 mmol), DMF (5.0 mL), 70 °C, 6 h.
Isolated yield.
b
3.5. Sonogashira coupling reaction of iodobenzene with
phenylacetylene catalyzed by the Pd–BOX complex A or B
Table 5
Relative activities of different palladium catalysts in Suzuki–Miyaura coupling
reaction of iodobenzene with phenylboronic acid.a
Similarly, we have investigated the catalytic activity of the new
Pd–BOX complexes (A) and (B) in Sonogashira coupling reaction
(Eq. (5)). We have studied the coupling reaction of iodobenzene
with phenylacetylene with Pd–BOX (A) or (B) as catalyst and in
the presence of CuI as a cocatalyst and Et3N as a base at 70 °C.
The results, summarized in Table 7, showed good conversion
(77%) with Pd–BOX (A) and slightly lower conversion of iodoben-
zene (57%) with Pd–BOX (B), affording the corresponding diphen-
ylacetylene as the sole product (Table 7, entries 1–2).
Entry
Palladium catalysts
Yield (%)b
1
2
3
4
Pd–BOX (A)
Pd(OAc)2
PdCl2(PhCN)2
PdSO4
100
93
88
85
a
Reaction conditions: Palladium catalyst (0.0100 mmol), iodobenzene
(0.500 mmol), phenylboronic acid (0.600 mmol), K2CO3 (2.00 mmol), DMF (5.0 mL),
70 °C, 6 h.
b
Determined by GC.
Table 6
Mizoroki–Heck coupling reactions of aryl iodides with olefins catalyzed by Pd–BOX complex A.a
Entry
1
Aryl halides 3
Olefins 6 or 7
Products 8
Yield %b
96
O
CO2Me
I
8a
OMe
3a
6
2
3
4
5
97
96
94
94
O
CO2Me
O2N
I
8b
OMe
OMe
OMe
OMe
3b
3d
O2N
6
O
CO2Me
H3COC
H2N
I
8c
CO2Me
H3COC
3c
6
O
I
8d
H2N
6
O
3d
CO2Me
8e
MeO
I
MeO
6
3e

S.M. Shakil Hussain et al. / Polyhedron 70 (2014) 39–46
45
Table 6 (continued)
Entry
6
Aryl halides 3
Olefins 6 or 7
Products 8
Yield %b
65
I
3a
7
8f
7
92c
95d
I
3a
7
8f
8
O
CO2Me
I
8a
OMe
3a
6
a
Reaction conditions: Pd–BOX A or B (0.0100 mmol), aryl halide (0.500 mmol), olefin (0.750 mmol), K2CO3 (2.00 mmol), DMF (5.0 mL), 70 °C, 12 h.
Isolated yield.
Temperature was 110 °C.
Pd–BOX (B) was used.
b
c
d
Appendix A. Supplementary data
Table 7
Sonogashira coupling reaction of iodobenzene with phenylacetylene catalyzed by Pd–
BOX complex (A) or (B).a
CCDC 955503 and 929604 contains the supplementary crystal-
lographic data for A and B. These data can be obtained free of
charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html, or
from the Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: (+44) 1223-336-033; or e-mail: de-
posit@ccdc.cam.ac.uk. Supplementary data associated with this
article can be found, in the online version, at http://dx.doi.org/
10.1016/j.poly.2013.12.023.
No.
Palladium complex
Yield (%)b
1
2
Complex A
Complex B
75
52
a
Reaction Conditions: Palladium complex A/B (0.0100 mmol), iodobenzene
(0.500 mmol), phenylacetylene (0.750 mmol), CuI (0.0200 mmol), Et3N
(0.600 mmol), DMF (5.0 mL), 70 °C, 12 h.
b
Isolated yield.
Pd-BOX A / B
I
+ HC
C
C C
ð5Þ
CuI, Et N, DMF
3
o
70 C, 12h
4. Conclusion
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