Effective palladium(II)-bis(oxazoline) catalysts: Synthesis, crystal structure, and catalytic coupling reactions

Article abstract of DOI:10.1080/00958972.2014.995100

New bis(oxazoline) ligands and their palladium complexes were synthesized and characterized. X-ray crystal structures of the two new complexes showed distorted square planar geometry with the palladium ion bonded to nitrogens of two bidentate heterocycles in addition to two bromides and two acetate ions for Pd-BOX-1 and Pd-BOX-2, respectively. The complexes adopt a chair structure with a rigid curvature inducing an inherent chirality. The complexes were effective catalysts for Suzuki-Miyaura, Mizoroki-Heck, and copper-free Sonogashira coupling reactions in aqueous dimethylformamide and under aerobic conditions. The reaction conditions were optimized for best solvent, base, and temperature. The substrate scope of the new catalytic system was evaluated for coupling reactions of a variety of aryl halides with aryl boronic acids, alkenes, and alkynes.

Full text of DOI:10.1080/00958972.2014.995100

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Effective palladium(II)-bis(oxazoline)
catalysts: synthesis, crystal structure,
and catalytic coupling reactions
a
b
c
Mansur B. Ibrahim , S.M. Shakil Hussain , Atif Fazal , Mohammed
a
a
Fettouhi & Bassam El Ali
a
Chemistry Department, King Fahd University of Petroleum &
Minerals, Dhahran, Saudi Arabia
b
Center for Petroleum and Minerals, King Fahd University of
Petroleum & Minerals, Dhahran, Saudi Arabia
c
Center of Research Excellence in Petroleum Refining, and
Petrochemicals Research Institute, King Fahd University of
Petroleum and Minerals, Dhahran, Saudi Arabia
Accepted author version posted online: 08 Dec 2014.Published
online: 09 Jan 2015.
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To cite this article: Mansur B. Ibrahim, S.M. Shakil Hussain, Atif Fazal, Mohammed Fettouhi &
Bassam El Ali (2015) Effective palladium(II)-bis(oxazoline) catalysts: synthesis, crystal structure,
and catalytic coupling reactions, Journal of Coordination Chemistry, 68:3, 432-448, DOI:
10.1080/00958972.2014.995100
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Journal of Coordination Chemistry, 2015
Vol. 68, No. 3, 432–448, http://dx.doi.org/10.1080/00958972.2014.995100
Effective palladium(II)-bis(oxazoline) catalysts: synthesis,
crystal structure, and catalytic coupling reactions
MANSUR B. IBRAHIM†, S.M. SHAKIL HUSSAIN‡, ATIF FAZAL§,
MOHAMMED FETTOUHI† and BASSAM EL ALI*†
†Chemistry Department, King Fahd University of Petroleum & Minerals, Dhahran, Saudi Arabia
‡Center for Petroleum and Minerals, King Fahd University of Petroleum & Minerals, Dhahran, Saudi
Arabia
§Center of Research Excellence in Petroleum Refining, and Petrochemicals Research Institute,
King Fahd University of Petroleum and Minerals, Dhahran, Saudi Arabia
(
Received 7 September 2014; accepted 10 November 2014)
New bis(oxazoline) ligands and their palladium complexes were synthesized and characterized. X-
ray crystal structures of the two new complexes showed distorted square planar geometry with the
palladium ion bonded to nitrogens of two bidentate heterocycles in addition to two bromides and
two acetate ions for Pd-BOX-1 and Pd-BOX-2, respectively. The complexes adopt a chair structure
with a rigid curvature inducing an inherent chirality. The complexes were effective catalysts for
Suzuki–Miyaura, Mizoroki–Heck, and copper-free Sonogashira coupling reactions in aqueous
dimethylformamide and under aerobic conditions. The reaction conditions were optimized for best
solvent, base, and temperature. The substrate scope of the new catalytic system was evaluated for
coupling reactions of a variety of aryl halides with aryl boronic acids, alkenes, and alkynes.
Keywords: Bis(oxazoline); Palladium; Crystal structure; Suzuki–Miyaura; Mizoroki–Heck;
Sonogashira
1. Introduction
The synthetic utility of coupling reactions is illustrated by a wide variety of molecules
produced and utilized either as starting materials, intermediates, or as final products [1].
*
Corresponding author. Email: belali@kfupm.edu.sa
This article was originally published with errors. This version has been corrected. Please see Erratum (http:dx.doi.
org/10.1080/00958972.2015.1009258).
©
2015 Taylor & Francis

Palladium(II)-bis(oxazoline)
433
Coupling reactions have been extensively employed in the synthesis of important industrial
raw materials [2], pharmaceuticals, and biologically active molecules [3]. Palladium com-
plexes are primary catalysts for coupling reactions. They are particularly attractive due to
their tolerance and compatibility with the reaction conditions and with a broad range of
functional groups [4]. Most palladium-catalyzed coupling reactions are conventionally car-
ried out in the presence of phosphine ligands and under rigorously dried organic solvents [5
(
a)–(g)]. Methods have been reported using nitrogen-based ligands in palladium-catalyzed
coupling in aqueous and organic solvents [6]. Although, some phosphine ligands have been
reported to show stability toward air and moisture, the difficulty associated with their syn-
thesis, the high production cost, and extreme toxicity restricted their applications [7–9].
Nitrogen ligands have been found to be easily accessible, air- and moisture-stable, modular,
and less expensive [10].
In this article, we have developed new catalytic systems based on palladium-bis(oxazo-
line) (Pd-BOX) complexes. These catalytic systems have shown high catalytic activities in
Suzuki–Miyaura [11], Mizoroki–Heck [12], and copper-free Sonogashira [13] coupling reac-
tions using aqueous organic solvents and under aerobic conditions. The structure of BOX
ligands allows formation of structurally constrained metal chelates with substituents on oxaz-
oline rings in close proximity with the donor nitrogen, hence, providing strong directing
effect and high activity in the reaction being catalyzed [14, 15]. The newly synthesized
complexes were fully characterized using spectroscopic techniques and their molecular
structures were established using X-ray structure analysis.
2
2
. Experimental
.1. Materials and instrumentation
Materials for synthesis of ligands and complexes were purchased from Sigma-Aldrich and
used as received. All solvents (reagent grade) used in the synthesis were distilled before
use. The products were purified using flash column chromatography packed with 60 F Sil-
ica gel from Fluka Chemie AG (Buchs, Switzerland).
1
13
H and C NMR spectral data were obtained using a 500 MHz NMR instrument (Jeol
500 model). Chemical shifts were recorded in ppm using tetramethylsilane (TMS) as
1
−
1
reference and CDCl as solvent. IR spectra were recorded in wave numbers (cm ) using a
3
FT-IR spectrometer (Perkin-Elmer 16F model). Elemental analyses were performed on a
Perkin Elmer Series 11 (CHNS/O) Analyzer 2400. Merck 60 F254 silica gel plates (250 μm
layer thickness) were used for thin-layer chromatography (TLC) analyses. A Varian Saturn
2
000 GC–MS (30 m capillary column) was used to analyze the products. Agilent 6890 Gas
chromatography (GC) was used to monitor the reactions and analyze the products.
2
.2. Synthesis of bis(oxazoline) ligands (BOX-1 and BOX-2)
A 50 mL round bottom flask equipped with a reflux condenser was charged with the appro-
priate amount of the substituted phthalonitrile (4.0 mM), zinc triflate (5.0 M%, 0.20 mM),
and chlorobenzene (30 mL) under argon. The mixture was stirred to dissolve the phthalonit-
rile and then 2-aminoalcohol (8.0 mM), dissolved in dry chlorobenzene, was slowly added.
The temperature was raised to 135 °C and the reaction mixture was refluxed for 24 h. The

4
34
M.B. Ibrahim et al.
product of the reaction, which was obtained as an oily residue, was dissolved in 30 mL of
dichloromethane and then extracted twice with distilled water (20 mL). The aqueous layer
was separated and washed with dichloromethane. The separated organic layers were dried
using anhydrous sodium sulfate. The dichloromethane was removed under vacuum on a
rotary evaporator to give the crude product, which was then purified using silica gel column
chromatography with dichloromethane/ether (4/1) as eluent [14, 16, 17].
2
.2.1. 2,2′-(4-Methyl-1,2-phenylene)bis(4,4-dimethyl-4,5-dihydrooxazole) (BOX-1). Yel-
1
low oil, isolated yield 92%; H NMR (500 MHz, CDCl ) δ (ppm): 7.50 (d, J = 7.93 Hz,
3
1
H, C-5 arom), 7.41 (s, 1H, C-3 arom), 7.12 (d, J = 7.93 Hz, 1H, C-6 arom), 3.92 (s, 4H,
1
3
OCH2 x 2), 2.24 (s, 3H, CH3 on arom), 1.25 (s, 12H, NC(CH3)2 x 2); C NMR
(
125 MHz, CDCl ) δ (ppm); 20.8 (CH on arom), 27.8 (NC(CH ) x 2), 67.5 (NC(CH ) x
3 3 3 2 3 2
2
1
), 79.1 (OCH ), 79.2 (OCH ), 125.4, (C-2 arom), 128.2 (C-1 arom), 129.4 (C-3 arom),
2 2
30.0 (C-5 arom), 130.5 (C-6 arom), 140.3 (C-4 arom), 162.1 (C-4′), 162.4 (C-1′); IR
−
1
(CH Cl ) ν (cm ) 2930, 1655, 1460, 1354, 1266, 1085, 969, 830, 735; GC–MS m/z 287
2 2
(
M + 1). Anal. Calcd for C H N O (%): C, 71.3; H, 7.7; N, 9.8. Found: C, 71.0; H, 7.7;
17 22 2 2
N, 9.9.
2
.2.2. 2,2′-(4-Nitro-1,2-phenylene)bis(4,4-dimethyl-4,5-dihydrooxazole) (BOX-2). Green
1
solid, isolated yield 91%; H NMR (500 MHz, CDCl ) δ (ppm): 8.56 (s, 1H, C-3 arom),
3
8
.28 (d, J = 6.1 Hz, 1H, C-5 arom), 7.89 (d, J = 8.5 Hz, 1H, C-6 arom), 4.09 (s, 4H, OCH
2
1
3
x 2), 1.38 (s, 12H, NC(CH ) x 2); C NMR (125 MHz, CDCl ) δ (ppm); 28.0 (NC(CH )
3 2
3
2
3
x 2), 68.5 (NC(CH ) x 2), 80.0 (OCH x 2), 124.7 (C-3 arom), 124.9 (C-5 arom), 130.4
3
2
2
(
(
C-2 arom), 131.1 (C-6 arom), 134.5 (C-1 arom), 148.5 (C-4 arom), 160.1 (C-4′), 160.5
-1
C-1′); IR (CH Cl ) ν (cm ) 2932, 1659, 1530, 1352, 1266, 1185, 1043, 968, 736; GC–MS
2
2
m/z 318 (M + 1). Anal. Calcd for C H N O (%): C, 60.5; H, 6.0; N, 13.2. Found: C,
1
6 19 3 4
6
0.6; H, 6.0; N, 13.3.
2
.3. Synthesis of palladium bis(oxazoline) complexes (Pd-BOX-1 and Pd-BOX-2)
In a 25 mL round bottom flask flushed with nitrogen was charged 0.5 mM of the appropri-
ate palladium(II) salt (in 8 mL DMF) and 0.5 mM of BOX ligand. PdBr was used with
2
BOX-1 to prepare Pd-BOX-1, and Pd(OAc) was used with BOX-2 for preparation of
2
Pd-BOX-2. The reaction mixture was stirred at room temperature for 6 h. The progress of
the reaction was monitored by TLC. After completion of the reaction, the solvent was
removed using a rotary evaporator. The crude product was dissolved in CH Cl and layered
2
2
with hexane to obtain pure crystals. The crystals were separated and washed with ether and
1
13
characterized with different spectroscopic techniques including H and C NMR, elemental
analysis, IR spectroscopy, and single-crystal X-ray diffraction [14].
2
.3.1. Dibromido(2,2′-(4-methyl-1,2-phenylene)bis(4,4-dimethyl-4,5-dihydrooxazole)-N,
1
N′)palladium(II) (Pd-BOX-1). Brown solid; isolated yield 89%, m.p. 232 °C; H NMR
500 MHz, CDCl ) δ (ppm): 7.69 (d, J = 7.9 Hz, 1H, C-5 arom), 7.59 (s, 1H, C-3 arom),
(
3
7
.52 (d, J = 7.9 Hz, 1H, C-6 arom), 4.31–4.23 (m, 4H, OCH x 2), 2.49 (s, 3H, CH on
2 3
1
3
arom), 1.77 (s, 6H, NC(CH ) ), 1.58 (s, 3H, NC(CH ), 1.55 (s, 3H, NC(CH ); C NMR
3
2
3
3

Palladium(II)-bis(oxazoline)
435
(
125 MHz, CDCl ) δ (ppm); 21.5 (CH on arom), 28.9 (NC(CH ), 29.0 (NC(CH x 2),
3
3
3
3
2
2
9.1 (NC(CH ), 71.1 (NC(CH ) ), 71.2 (NC(CH ) ), 80.9 (OCH ), 81.0 (OCH ), 123.1 (C-
3 3 2 3 2 2 2
arom), 125.9 (C-1 arom), 130.1 (C-3 arom), 130.6 (C-5 arom), 133.3 (C-6 arom), 143.7
−
1
(C-4 arom), 164.0 (C-4′), 164.1 (C-1′); IR (KBr) ν (cm ) 2969, 2920, 1630, 1457, 1374,
1
327, 1207, 1122, 1067, 961, 830, 722. Anal. Calcd for C H Br N O Pd (%): C, 36.9;
1
7
22
2 2 2
H, 4.0; N, 5.1. Found: C, 37.0; H, 4.0; N, 5.0; UV–vis: λ (CH Cl )/nm: 383; ε/
max
2
2
−
1
−1
LM cm : 12,650.
2
.3.2. Diacetato(2,2′-(4-nitro-1,2-phenylene)bis(4,4-dimethyl-4,5-dihydrooxazole)-N,N′)
1
palladium(II) (Pd-BOX-2). Green solid; isolated yield 92%, m.p. 149 °C; H NMR
500 MHz, CDCl ) δ (ppm): 8.72 (s, 1H, C-3 arom), 8.52 (d, J = 8.8 Hz, 1H, C-5 arom),
(
3
8
.10 (d, J = 8.5 Hz, 1H, C-6 arom), 4.38–4.27 (m, 4H, OCH x 2), 1.74 (s, 3H, NC(CH ),
2 3
1
.73 (s, 3H, NC(CH ), 1.63 (s, 3H, NC(CH ), 1.61 (s, 3H, NC(CH ), 1.42 (s, 3H,
3
3
3
1
3
OCOCH ), 1.41 (s, 3H, OCOCH ); C NMR (125 MHz, CDCl ) δ (ppm); 22.8 (OCOCH
3
3
3
3
x 2), 26.2 (NC(CH ), 26.3 (NC(CH ), 29.2 (NC(CH x 2), 70.3 (NC(CH ) x 2), 80.9
3
3
3
3 2
(
OCH x 2), 125.5 (C-3 arom), 126.0 (C-5 arom), 127.8 (C-2 arom), 131.5 (C-1 arom),
2
1
32.1 (C-6 arom), 149.5 (C-4 arom), 162.8 (C-4′), 163.1 (C-1′), 177.9 (OCOCH ), 178.0
3
−1
(OCOCH ). IR (KBr) ν (cm ): 2980, 1651, 1605, 1533, 1500, 1376, 1329, 1222, 1172,
3
1
129, 1063, 951, 713. Anal. Calcd for C H N O Pd (%): C, 44.3; H, 4.6; N, 7.8. Found:
20 25 3 8
−
1
−1
C, 44.3; H, 4.7; N, 7.7; UV–vis: λmax(CH Cl )/nm: 360; ε/LM cm : 5926.
2
2
2
.4. General procedure for Suzuki–Miyaura coupling reaction
In a 25 mL round bottom flask, palladium complex (0.0020 mM) was dissolved in DMF
4 mL). Aryl halide (1.0 mM), aryl boronic acid (1.5 mM), potassium carbonate (2.0 mM),
(
and distilled water (4.0 mL) were added. The mixture was stirred at room temperature for
the required time. After complete reaction, the product was extracted three times with ethyl
acetate (5 mL). The combined organic extract was dried with anhydrous sodium sulfate.
The volume was reduced to 4 mL using a rotary evaporator. The product was analyzed by
GC and GC–MS. The product was further purified using column chromatography with hex-
ane-EtOAc (8 : 2) as eluent. The characterization data of 3a–3e [14, 18] were in agreement
with those observed in the literature.
2
.5. General procedure for Mizoroki–Heck coupling reaction
In a 15 mL round bottom flask, palladium complex (0.010 mM) was dissolved in DMF
(
(
2 mL). Aryl halide (1.0 mM), styrene (1.50 mM), KOH (2.0 mM), and distilled water
2 mL) were added. A condenser was attached and the mixture was stirred at 90 °C for the
required time. After completion of the reaction, the product was extracted three times with
ethyl acetate (5 mL). The combined organic extract was dried with anhydrous sodium sul-
fate. The volume was reduced to 4 mL using a rotary evaporator and the product was ana-
lyzed by GC and GC–MS. The product was further purified using column chromatography
with hexane-EtOAc (7 : 3) as eluent. The characterization data of 5a–5e [14, 18] were in
agreement with those observed in the literature.

4
36
M.B. Ibrahim et al.
2.6. General procedure for Sonogashira coupling reaction
In a 15 mL round bottom flask, palladium complex (0.010 mM) was dissolved in DMF
(
(
2 mL). Aryl halide (1.0 mM), alkyne (1.5 mM), KOH (2.00 mM), and distilled water
2 mL) were added. A condenser was attached and the mixture was stirred at 70 °C for the
required time. After completion of the reaction, the product was extracted three times with
ethyl acetate (5 mL). The combined organic layer was dried with anhydrous sodium sulfate.
The volume was reduced to 4 mL using a rotary evaporator. The product was analyzed by
GC and GC–MS. The product was further purified using column chromatography with
hexane-EtOAc (7 : 3) as eluent. The characterization data of 7a–7g [14, 18, 19] were in
agreement with those observed in the literature.
2
.7. X-ray structure determination
Single-crystal data collection for 1 and 2 was performed at 120 and 296 K, respectively, on
a Bruker-AXS Smart Apex system equipped with graphite monochromated Mo Kα radia-
tion (λ = 0.71073 Å). The data were collected using SMART and the integration was per-
formed using SAINT [20]. An empirical absorption correction was carried out using
SADABS [21] The structures were solved by direct methods with SHELXS-97 and refined
.
2
by full-matrix least squares on F using SHELXL-97 [22]. All nonhydrogen atoms were
refined anisotropically. Hydrogens were placed at calculated positions using a riding model.
Crystal data and details of the data collection are summarized in table 1. Selected bond
lengths and angles are given in table 2.
Table 1. Crystallographic data for 1 and 2.
Pd-BOX
1
2
Chemical formula
Formula weight
Crystal system
Space group
C
17
H
22Br
2
N
2
O
2
Pd
C
21 2 3 8
H27Cl N O Pd
552.59
Monoclinic
P2 /n
120
626.76
Monoclinic
P2 /c
296
1
1
Temperature (K)
Radiation
Mo Kα (λ = 0.71073 Å)
−
3
ρ
Calcd (g cm
)
1.872
1.551
a (Å)
b (Å)
c (Å)
β (°)
V (Å )
Z
9.881(2)
17.233(3)
11.612(2)
97.273(3)
1961.2(6)
4
11.0974(7)
18.991(1)
12.7396(8)
91.926(1)
2683.3(3)
4
3
Refl. collected/unique
Refl. observed [I >2 σ(I)]
R(int)
25,922/4904
4004
0.0449
36,216/6665
4502
0.0750
Data/restraints/parameters
Goodness-of-fit on F
4904/0/222
1.123
6665/0/322
1.111
2
R indices [I >2 σ(I)]
R indices (all data)
Largest diff. peak/hole (e Å
R
R
1
= 0.0371; wR
= 0.0518; wR
2
= 0.0776
= 0.0820
R
R
1
= 0.0536; wR
= 0.0799; wR
2
= 0.1109
= 0.1270
1
2
1
2
–3
)
1.289/−0.810
0.894/−0.802

Palladium(II)-bis(oxazoline)
437
Table 2. Selected bond lengths (Å) and angles (°) for 1 and 2.
Bond lengths
Bond angles
Pd-BOX-1
Pd1–N1
Pd1–N2
Pd1–Br1
Pd1–Br2
2.063(3)
2.045(3)
2.4158(7)
2.4162(7)
N2–Pd1–N1
86.9(1)
175.70(9)
91.69(9)
92.02(9)
173.1(1)
88.85(2)
N2–Pd1–Br1
N1–Pd1–Br1
N2–Pd1–Br2
N1–Pd1–Br2
Br1–Pd1–Br2
Pd-BOX-2
Pd1–N1
Pd1–N2
Pd1–O1
Pd1–O4
2.020(3)
2.022(3)
2.001(2)
1.996(2)
N1–Pd1–N2
O1–Pd1–N1
O1–Pd1–N2
O4–Pd1–O1
O4–Pd1–N1
O4–Pd1–N2
88.0(1)
92.9(1)
177.6(1)
87.2(1)
172.9(1)
91.6(1)
3. Results and discussion
Our interest includes development of nonoptically active palladium bis(oxazoline) com-
plexes and exploring their application as catalysts in coupling reactions. Although, a pleth-
ora of chiral metal–bis(oxazoline) complexes have been reported to be used efficiently in
asymmetric catalysis [23], the use of nonoptically active palladium bis(oxazoline)
complexes in coupling reactions is generally an underexplored area of research [24].
3
.1. Synthesis of BOX ligands and corresponding Pd(II)-BOX complexes
Treatment of phthalonitrile derivative with two equivalents of 2-amino alcohol in the pres-
ence of Zn(OTf) afforded the corresponding bis(oxazoline) ligands BOX-1 and BOX-2
2
(scheme 1). The complexes Pd-BOX-1 and Pd-BOX-2 were obtained by reacting PdBr2
and Pd(OAc) with BOX-1 and BOX-2 in DMF, respectively [14]. The Pd-BOX complexes
2
were fully characterized using spectroscopic techniques and the molecular structures were
determined using X-ray diffraction analysis.
3
.2. Molecular structures of Pd-BOX-1 and Pd-BOX-2
Pd-BOX-1 crystallizes in the P2 /n space group. The palladium bonds to nitrogens of two
1
oxazoline heterocycles in addition to two bromides with a distorted square planar geometry.
The corresponding cis-angles are 86.94(12)°–92.02(9)° (figure 1). The Pd–N and Pd–Br
bond distances (table 2) are similar to those reported for other bis(oxazoline)palladium com-
plexes [14, 25] and dibromido(diimine)palladium(II) complexes [26, 27], respectively.
Bonding to the metal ion results in tilting of the two oxazoline heterocycle planes from the
benzene ring spacer. The dihedral angles between the mean planes of each of the two oxaz-
oline heterocycles and the benzene ring spacer mean plane are 38.0(3)° and 48.1(2)°. The
metal complex structure is reminiscent of a chair with the [PdN Br ] moiety being the seat
2
2
and the benzene ring spacer being the back of the chair (figure 1). The dihedral angle
between the two moieties is 88.1(1)°. Despite the achirality of the ligand, this rigid chair
curvature, together with the unsymmetrical substitution of the benzene spacer, generates an

4
38
M.B. Ibrahim et al.
Scheme 1. Synthesis of bis(oxazoline) ligands and their corresponding palladium complexes.
inherent chirality in the molecule and the complex crystallizes as racemic. We previously
reported similar cases of inherent chirality in metal complexes of achiral bisoxazolines [14].
Pd-BOX-2 crystallizes in the P2 /c space group. Similarly to Pd-BOX-1, the geometry
1
around the palladium ion is distorted square planar with cis-angles of 87.22(10)°–92.94(11)°
(
figure 2). The Pd–N and Pd–O bond lengths are similar to those reported for bis(oxazoline)
Figure 1. Molecular structure of Pd-BOX-1.

Palladium(II)-bis(oxazoline)
439
Figure 2. Molecular structure of Pd-BOX-2 (Dichloromethane has been omitted for clarity).
bis(trifluoroacetato)palladium(II) complexes [28] and the Pd–N bond lengths are significantly
shorter than those of Pd-BOX-1 (table 2), likely due to the difference in σ and π donor effects
of the acetate and bromide. As expected by steric effect, the two acetato acyl groups lie on
opposite sides of the [PdN O ] plane. The complex adopts a similar chair structure to
2
2
Pd-BOX-1 with a rigid curvature inducing inherent chirality and the compound crystallizes
as a racemic dichloromethane solvate.
3.3. Evaluation of the synthesized palladium-bis(oxazoline) complexes as catalysts in
coupling reactions
We have investigated the use of Pd-BOX-1 and Pd-BOX-2 as catalysts for carbon–carbon
bond formation, typically Suzuki–Miyaura [11], Mizoroki–Heck [12], and Sonogashira [13]
coupling reactions in DMF–H O and under aerobic conditions.
2
3
.3.1. Suzuki–Miyaura coupling reaction of phenylboronic acid and aryl halides using
Pd-BOX-1 as a catalyst. The palladium-catalyzed Suzuki–Miyaura coupling reaction of
aryl boronic acids and aryl halides is a versatile method for synthesis of biaryls. We previ-
ously reported formation of biaryls at high temperature and for longer reaction time. How-
ever, we are delighted to achieve the formation of biaryls at room temperature with
extremely short time using Pd-BOX-1 in aqueous organic media as a new catalytic system
(table 3).

4
40
M.B. Ibrahim et al.
Table 3. Suzuki–Miyaura coupling reactions of 4-iodoacetophenone with phenyl boronic
a
acid.
b
Entry
Pd complex
Solvent
Base
Yield (%)
1
2
Pd-BOX-1
Pd-BOX-1
Neat DMF
K
K
2
2
CO
CO
3
20
98
DMF–H
1 : 1)
Neat H
Dioxane–H
1 : 1)
CH CN–H
1 : 1)
DMF–H
1 : 1)
DMF–H
1 : 1)
DMF–H
1 : 1)
DMF–H
1 : 1)
DMF–H
1 : 1)
DMF–H
1 : 1)
DMF–H
1 : 1)
DMF–H
1 : 1)
DMF–H
1 : 1)
2
O
3
(
3
4
Pd-BOX-1
Pd-BOX-1
2
O
K
K
2
2
CO
CO
3
16
38
2
O
3
(
5
6
7
8
9
Pd-BOX-1
Pd-BOX-1
Pd-BOX-1
Pd-BOX-1
Pd-BOX-1
Pd-BOX-2
Pd-BOX-3
Pd-BOX-4
3
2
O
K
2
CO
3
28
20
(
2
2
2
2
2
2
2
2
2
O
Et
KOH
KH PO
PO
3
N
(
O
O
O
O
O
O
O
O
51
(
2
4
06
(
K
K
K
K
K
K
3
2
2
2
2
2
4
95
(
10
CO
CO
CO
CO
CO
3
3
3
3
3
95
(
11
98
(
12
13
14
97
(
PdCl
2
2
-Bpy
Traces
40
(
PdCl
-Phen
(
a
Reaction conditions: [Pd] (0.0020 mM), phenylboronic acid (1.5 mM), 4-iodoacetophenone (1.0 mM),
b
base (2.0 mM), solvent (8 mL), 20 min, r.t.; Isolated yield.
(1)
PhO
PhO
O
O
O
O
N
N
N
N
N
N
N
N
Pd
Pd
Pd
Pd
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Pd-BOX-3
Pd-BOX-4
PdCl -Bpy
PdCl -Phen
2
2
Figure 3. Palladium complexes having bidentate nitrogen donating ligands.

Palladium(II)-bis(oxazoline)
441
In order to determine the best conditions, a series of reactions were performed at room
temperature and under aerobic conditions using 4-iodoacetophenone and phenyl boronic acid
as model substrates. The effect of solvent was carefully investigated and the results are
presented in table 3. Low conversion (20%) was observed when neat DMF was used as a sol-
vent (table 3, entry 1). However, addition of water increases the yield of the coupling product.
A full conversion was obtained with a ratio of 1 : 1 of DMF–water (table 3, entry 2); the reac-
tion in neat water decreases significantly the yield of the product to 16% (table 3, entry 3).
Other solvent systems such as dioxane–water and acetonitrile–water gave yields of 38 and
2
8%, respectively (table 3, entries 4 and 5).
We further screened various bases using the optimized solvent system. The use of trieth-
ylamine resulted in poor yield of coupling product (20%) (table 3, entry 6). However, potas-
sium hydroxide gave moderate yield (50%) of the product (table 3, entry 7). The dibasic
potassium hydrogen phosphate (table 3, entry 8) gave only traces of product, whereas excel-
lent result (95%) was obtained with the tribasic potassium hydrogen phosphate (table 3,
entry 9).
We further compare Pd-BOX-1 and Pd-BOX-2 with other palladium complexes (figure 3)
[
14, 19]. The palladium complexes were evaluated in the coupling reaction of 4-iodoaceto-
phenone with phenylboronic acid, as model substrates, under the optimized reaction
conditions (table 3). Pd-BOX-2, Pd-BOX-3, and Pd-BOX-4 gave isolated yields of 95, 98,
and 97%, respectively (table 3, entries 10–12). Surprisingly, the reaction did not take
place using PdCl -Bpy (table 3, entry 13); however, PdCl -Phen led to low yield of product
2
2
(40%) (table 3, entry 14).
To explore the activity and versatility of the new catalysts, the optimized catalytic system
was applied to various substrates. Aryl iodides having electron withdrawing groups such as
COCH and NO and electron donating groups such as OCH and NH coupled smoothly
3
2,
3
2
with the phenylboronic acids (table 4, entries 1–5) to give the corresponding coupling prod-
ucts in excellent yields (>90%). Despite the high activity of the new catalysts, the reaction
rate depends on the type of substitution on the benzene ring. Aryl iodides having electron
withdrawing groups (table 4, entries 1 and 2) reacted faster and full conversions were
obtained within 20 min. Aryl iodides with electron donating substituents (table 4, entries 4
and 5) took 90 min to attain almost complete conversions. An aryl bromide and an aryl
chloride as less activated halides were also considered in the Suzuki–Miyaura coupling
reactions with phenyl boronic acid (table 4, entries 6 and 7). The reaction of the aryl bro-
mide gave excellent yield (99%) of the coupling product but a longer reaction time (1 h)
was required. The aryl chloride was less reactive at room temperature and a yield (90%)
was obtained at 110 °C after 90 min of reaction.
The air- and moisture-stable Pd-BOX catalysts showed advantages in terms of the cata-
lytic activity, the diversity of the substrates, the reaction temperature, or the reaction time as
compared to catalysts based on palladium(II) complexes in the presence of phosphine
ligands [5(a)–(c)] or nitrogen-based ligands [6].
(2)

4
42
M.B. Ibrahim et al.
Table 4.a Suzuki–Miyaura coupling reactions of various aryl iodides with aryl boronic acids using Pd-BOX-1 as a
catalyst.
Iodobenzene
Arylboronic acid
Coupling product
b
Entry
1
1a–g
2a–b
3a–g
Time (min)
20
Yield (%)
97
1a
2a
3a
2
20
95
1
b
2a
2b
2a
3b
3c
3d
3
4
5
90
90
90
96
93
94
1
c
1d
1e
2a
3e
6
60
90
96
90
1
f
2a
2a
3f
c
7
1g
3g
a
2 3
Reaction conditions: Pd-BOX-1 (0.0020 mM), aryl boronic acid (1.5 mM), aryl halide (1.0 mM), K CO (2.0 mM), DMF
b
c
(
2
4.0 mL), H O (4.0 mL), r.t.; Isolated yield; 110 °C.
3.3.2. Mizoroki–Heck coupling reactions of styrene derivatives with aryl iodides cata-
lyzed by Pd-BOX-1. The cross-coupling reactions of aryl halides with olefins, known as
Mizoroki–Heck coupling, is a well-known and widely used methodology for the regioselec-
tive synthesis of various unsaturated compounds [12, 29]. The palladium bis(oxazoline)
complexes were evaluated as catalysts in Mizoroki–Heck coupling reactions of styrene with
different aryl iodides (equation 3). The reaction conditions were optimized as presented in
table 5.

Palladium(II)-bis(oxazoline)
443
a
Table 5. Mizoroki–Heck coupling reactions of iodobenzene with styrene.
b
Entry
Pd complex
Solvent
Base
Yield (%)
1
2
Pd-BOX-1
Pd-BOX-1
Neat DMF
KOH
KOH
48
99
DMF–H
3 : 1)
2
O
(
3
4
Pd-BOX-1
Pd-BOX-1
Neat water
Dioxane–H
KOH
KOH
9
20
2
O
(
3 : 1)
DMF–H
3 : 1)
DMF–H
3 : 1)
DMF–H
3 : 1)
DMF–H
3 : 1)
DMF–H
3 : 1)
DMF–H
5
6
7
8
9
Pd-BOX-1
Pd-BOX-1
Pd-BOX-2
Pd-BOX-3
Pd-BOX-4
2
2
2
2
2
2
O
O
O
O
O
O
K
2
CO
3
84
64
97
98
96
70
56
(
3
Et N
(
KOH
KOH
KOH
KOH
KOH
(
(
(
10
2
PdCl -Bpy
(
3 : 1 mL)
DMF–H
3 : 1)
11
2
PdCl -Phen
2
O
(
a
Reaction conditions: [Pd] (0.01 mM), iodobenzene (1.00 mM), styrene (1.5 mM), KOH (2.0 mM),
b
solvent (4 mL), 90 °C, 2 h; Isolated yield.
(3)
In the absence of water (neat DMF, table 5, entry 1), only moderate yield (50%) was
achieved. However, in a mixture of DMF–water (3 : 1 mL) (table 5, entry 2), the coupling
product was obtained in quantitative yield. The yield of product decreased sharply to traces
in neat water (table 5, entry 3).
We have also evaluated other palladium bis(oxazoline) complexes and other commer-
cially available palladium complexes of bidentate nitrogen donor ligands such as 2,2′ bipyr-
idine and 1,10-phenanthroline [19]. Pd-BOX-2, Pd-BOX-3, and Pd-BOX-4 yielded full
conversions (entries 7, 8 and 9). PdCl -Bpy and PdCl -Phen gave lower isolated yields
2
2
(70 and 56%, respectively) (entries 10 and 11).
The optimized catalytic system was then applied to substrates having either activating or
deactivating substituents (table 6). As expected, the time required for completion of reac-
tions depends on the type of substituent attached to the benzene ring on either the aryl
halide and/or the styrene. However, some interesting results were observed (table 6, entries
2
and 3). An activating methoxy group attached to the styrene (table 6, entry 2) led to a full
conversion in 1.5 h. However, when the same activating methoxy group is attached to the
aryl halide (table 6, entry 3), a decrease in reaction rate was observed and full conversion
was achieved in 2.5 h. Catalytic activities of the new Pd-BOX catalysts are higher in the
Mizoroki–Heck coupling reactions at relatively milder conditions of temperature and reac-
tion time as compared to palladium–phosphine [5(d) and (e)] or palladium–nitrogen catalyst

4
44
M.B. Ibrahim et al.
Table 6.a Mizoroki–Heck coupling reactions of styrene derivatives with aryl iodides using Pd-BOX-1 as a
catalyst.
Aryl iodide
Styrene derivative
Coupling product
b
Entry
1
1a–d
4a–c
5a–e
Time (h)
2
Yield (%)
99
1
1
c
c
4a
4b
4a
5a
5b
5b
2
3
4
1.5
2.5
2
95
94
97
1d
1
1
a
c
4a
4c
5c
5d
5
6
a
2
1
96
98
1
a
4a
5e
Reaction conditions: Pd-BOX-1 (0.010 mM), aryl iodide (1.0 mM), styrene derivative (1.50 mM), KOH (2.0 mM), DMF (3 mL),
H O (1 mL), 90 °C; Isolated yield.
2
b
systems [6, 33], where higher temperatures (120–140 °C) and longer reaction times
6–24 h) are sometimes applied to obtain high yields of coupling products.
(
(4)

Palladium(II)-bis(oxazoline)
445
a
Table 7. Sonagashira coupling reaction of phenylacetylene with iodobenzene.
b
Entry
Pd complex
Solvent
Base
Yield 7a (%)
1
2
Pd-BOX-1
Pd-BOX-1
DMF
DMF–H
KOH
KOH
52
96
2
O
(
3 : 1)
3
4
Pd-BOX-1
Pd-BOX-1
Water
DMF–H
KOH
NaOH
20
94
2
2
2
2
O
O
O
O
(
3 : 1)
DMF–H
3 : 1)
DMF–H
3 : 1)
DMF–H
5
6
7
8
9
Pd-BOX-1
Pd-BOX-1
Pd-BOX-2
Pd-BOX-3
Pd-BOX-4
K
2
CO
3
82
85
93
94
96
86
64
(
3
Et N
(
KOH
KOH
KOH
KOH
KOH
(
3–1 mL)
DMF–H
3 : 1)
DMF–H
3 : 1)
DMF–H
3 : 1)
DMF–H
3 : 1)
2
2
2
2
O
O
O
O
(
(
1
0
2
PdCl -Bpy
(
11
2
PdCl -Phen
(
a
Reaction conditions: [Pd] (0.010 mM), iodobenzene (1.0 mM), phenylacetylene (1.5 mM), base
b
(
2.0 mM), solvent (4 mL), 70 °C, 1 h; Isolated yield.
3.3.3. Sonogashira coupling reactions of phenylacetylene with aryl iodides catalyzed
by Pd-BOX-1. An important method for the synthesis of alkyne derivatives is the
Sonogashira cross-coupling reaction. Traditionally, the Sonogashira coupling reactions are
catalyzed by palladium complexes in the presence of copper salt. Recently, active catalytic
systems are being developed that make this reaction possible in the absence of copper
[
30–32]. In our research, the new Pd bis(oxazolines) complexes were also applied to cop-
per-free Sonogashira coupling of aryl iodides with terminal alkynes in aqueous DMF and
under aerobic conditions. The reaction conditions were also optimized and the results are
summarized in table 7. Similar to the Heck reaction, the best solvent system was
DMF–H O (3 : 1 mL) (table 7, entry 2), and KOH was the most suitable base for the
2
Sonogashira coupling reaction.
We have further evaluated the ligand effect by considering additional palladium-BOX
complexes such as Pd-BOX-2, Pd-BOX-3, and Pd-BOX-4 [14], and two commercially
available palladium complexes, PdCl -Bpy and PdCl -Phen. The palladium-BOX com-
2
2
plexes synthesized in our laboratories (Pd-BOX-1, Pd-BOX-2, Pd-BOX-3, and Pd-BOX-4)
were better than the commercially available palladium complexes (PdCl -Bpy and PdCl -
2
2
Phen) (table 7, entries 6–11).
(5)
The excellent results encouraged us to extend our studies to a range of activated and deacti-
vated substrates. The results are summarized in table 8. Most of the substrates studied

4
46
M.B. Ibrahim et al.
a
Table 8. Sonogashira coupling reactions of different aryl iodides with aryl alkynes.
Aryl iodide
Aryl alkyne
Coupling product
b
Entry
1
1a–f
6a–b
7a–g
Time (h)
2
Yield 7a–g (%)
94
1
1
c
a
6a
7a
2
1
98
6a
6a
7b
7c
3
4
1
1
96
97
1b
1
f
6a
6b
7d
7e
5
6
1
99
1a
3
2
91
93
1
d
6a
6b
7f
7
1
c
7g
a
Reaction conditions: Pd-BOX-1 (0.010 mM), aryl halide (1.0 mM), alkyne (1.5 mM), KOH (2.0 mM), DMF (3 mL), H
0 °C; Isolated yield.
2
O (1 mL),
b
7
yielded excellent results. The reaction time depends on the type of substituent attached to
the aryl iodide.

Palladium(II)-bis(oxazoline)
447
Again, Pd-BOX catalyst showed high catalytic activity in Sonogashira cross-coupling
reactions at lower temperature (70 °C) and shorter reaction time (1–3 h) compared to
reported palladium catalyst systems [5].
(6)
4. Conclusion
The synthesis, characterization, crystal structure, and catalytic activities of new palladium-
bis(oxazoline) complexes (Pd-BOX) have been described. The X-ray crystal structure
reveals a square planar geometry and an inherent chirality in both new complexes. Highly
active catalytic systems based on the new Pd-BOX complexes have been developed for
Suzuki–Miyaura, Mizoroki–Heck, and copper-free Sonogashira coupling reactions in
aqueous DMF and under aerobic conditions. Excellent catalytic activities were observed
with Pd-BOX as compared to previously reported palladium–phosphine and palladium–
dinitrogen catalysts applied for the same coupling reactions. In addition, the fact that
Pd-BOX complexes are more active catalysts than other palladium(II)–dinitrogen complexes
was confirmed from the results obtained with other palladium complexes having bidentate
nitrogen donor ligands, such as PdCl -Bpy and PdCl -Phen, in the same catalytic coupling
2
2
reactions. Almost complete conversions were observed with all palladium-bis(oxazoline)
complexes. The observed increase in rate of the coupling reactions due to addition of water
could be attributed to the possible formation of hydroxypalladium complexes [PdL (OH) ],
2
2
which are known to possess higher catalytic activity than their corresponding halopalladium
complexes [6].
Supplementary material
Crystallographic data have been deposited with the Cambridge Crystallographic Data Cen-
ter, CCDC No. 902796 and 929605 for 1 and 2, respectively. Copies of this information
may be obtained free of charge from the Director, CCDC, 12 Union Road, Cambridge,
CB2 1EZ, UK (Fax: +44 1223 336033; E-mail: deposit@ccdc.cam.ac.uk or http://www.
ccdc.cam.ac.uk).
Acknowledgements
The authors would like to acknowledge the support provided by King Abdulaziz City for
Science and Technology (KACST) through the Science & Technology Unit at King Fahd
University of Petroleum & Minerals (KFUPM) for funding this work through project No.
11-PET1665-04, as part of the National Science, Technology, and Innovation Plan.

4
48
M.B. Ibrahim et al.
References
[
[
[
[
[
1] M.A. Oberli, S.L. Buchwald. Org. Lett., 14, 4606 (2012).
2] M. Toyota, C. Komori, M.J. Ihara. Org. Chem., 65, 7110 (2000).
3] G. Amiet, H.M. Hügel, F. Nurlawis. Synlett, 3, 495 (2002).
4] T.W. Lyons, M.S. Sanford. Chem. Rev., 110, 1147 (2010).
5] (a) Q. Dai, W. Gao, D. Liu, L.M. Kapes, X. Zhang. J. Org. Chem., 71, 3928 (2006); (b) S.J. Sabounchei, M.
Ahmadi, Z. Nasri. J. Coord. Chem., 66, 411 (2013); (c) K. Wang, Q. Fu, R. Zhou, X. Zheng, H. Fu, H. Chen,
R. Li. Appl. Organomet. Chem., 27, 232 (2013); (d) A.-E. Wang, J.-H. Xie, L.-X. Wang, Q.-L. Zhou. Tetrahe-
dron, 61, 259 (2005); (e) E. Jung, K. Park, J. Kim, H.-T. Jung, I.-K. Oh, S. Lee. Inorg. Chem. Commun., 13,
1
329 (2010); (f) K. Saikia, B. Deb, B.J. Borah, P.P. Sarmah, D.K. Dutta. J. Organomet. Chem., 696, 4293
2012); (g) J.T. Guan, T.Q. Weng, G. Yu, S.H. Liu. Tetrahedron Lett., 48, 7129 (2007).
6] S. Akkoc, Y. Gok. J. Coord. Chem., 66, 1396 (2013); A. Aktas, S. Akkoc, Y. Gok. J. Coord. Chem., 66, 2901
2013).
(
[
(
[
[
[
7] A.N. Marziale, S.H. Faul, T. Reiner, S. Schneider, J. Eppinger. Green Chem., 12, 35 (2010).
8] P. Conelly-Espinosa, D. Morales-Morales. Inorg. Chim. Acta, 363, 1311 (2010).
9] S.M. Islam, P.A. Mondal, S. Roy, S. Mondal, D. Hossain. Tetrahedron Lett., 51, 206 (2010).
[
[
[
[
10] B. Banik, A. Tairai, N. Shahnaz, P. Das. Tetrahedron Lett., 53, 5627 (2012).
11] M.A. Selepe, F.R. Van Heerden. Molecules, 18, 4739 (2013).
12] Y. Diao, R. Hao, J. Kou, M. Teng, G. Huang, Y. Chen. Appl. Organomet. Chem., 27, 546 (2013).
13] R. Chinchilla, C. Nájera. Chem. Soc. Rev., 40, 5084 (2011); C. Liu, Q. Ni, F. Bao, J. Qiu. Green Chem., 13,
1
260 (2011).
14] S.M. Shakil Hussain, M.B. Ibrahim, A. Fazal, R. Suleiman, M. Fettouhi, B. El Ali. Polyhedron, 70, 39
2014).
[
(
[
[
[
[
15] J.K. Whitesell. Chem. Rev., 89, 1581 (1989).
16] G. Desimoni, G. Faita, K.A. Jorgensen. Chem. Rev., 111, 284 (2011).
17] D.A. Evans, K.A. Woerpel, M.M. Hinman, M.M. Faul. J. Am. Chem. Soc., 113, 726 (1991).
18] K. Srinivas, P. Srinivas, P.S. Prathima, K. Balaswamy, B. Sridhar, M.M. Rao. Catal. Sci. Technol., 2, 1180
(
2012).
[19] B. Lin, S. Huang, W. Wu, C. Mou, F. Tsai. Molecules, 15, 1957 (2010).
[20] Bruker. SMART and SAINT, Bruker AXS Inc., Madison, WI (2008).
[21] G.M. Sheldrick. SADABS. Program for Empirical Absorption Correction of Area Detector Data, University
of Gottingen, Göttingen (1996).
[22] G.M. Sheldrick. Acta Crystallogr., Sect. A: Found. Crystallogr., 64, 112 (2008).
[23] A.K. Ghosh, P. Mathivanan, J. Cappiello. Tetrahedron: Asymmetry, 9, 1 (1998).
[24] T. Takemoto, S. Iwasa, H. Hamada, K. Shibatomi, M. Kameyama, Y. Motoyama, H. Nishiyama. Tetrahedron
Lett., 48, 3397 (2007).
[25] A.S. Abu-Surrah, M. Kettunen, K. Lappalainen, U. Piironen, M. Klinga, M. Leskelä. Polyhedron, 21, 27
(
2002).
[
[
26] R. Guo, J.L. Portscheller, V.W. Day, H.C. Malinakova. Organometallics, 26, 3874 (2007).
27] R. Hage, R.A.G. de Graaff, J.G. Haasnoot, K. Kieler, J. Reedijk. Acta Crystallogr., Sect. C: Cryst. Struct.
Commun., 46, 2349 (1990).
[28] K. Kato, C. Matsuba, T. Kusakabe, H. Takayama, S. Yamamura, T. Mochida, H. Akita, T.A. Peganova, N.V.
Vologdin, O.V. Gusev. Tetrahedron, 62, 9988 (2006).
[
[
[
[
[
29] V.V. Grushin, H. Alper. Organometallics, 12, 1890 (1993).
30] H. Zhong, J. Wang, L. Li, R. Wang. Dalton Trans., 43, 2098 (2014).
31] A. Komaromi, Z. Novak. Chem. Commun., 4968 (2008).
32] B. Liang, M. Dai, J. Chen, Z. Yang. J. Org. Chem., 70, 391 (2005).
33] C.-H. Ying, S.-B. Yan, W.-L. Duan. Org. Lett., 16, 500 (2014).