Synthesis, crystal structures and catalytic activities of new palladium(II)–bis(oxazoline) complexes

Article abstract of DOI:10.1007/s11243-016-0072-1

Palladium–bis(oxazoline) complexes (Pd-BOX-A and Pd-BOX-B) were synthesized and characterized by ¹H, ¹³C NMR, IR and elemental analysis. The molecular structures of the complexes were confirmed by single-crystal X-ray analysis. In both cases, the palladium center is coordinated by the nitrogen atoms of the two oxazoline rings and two chloride ligands in a distorted square planar geometry. Despite the fact that the bis(oxazoline) ligand is achiral, the asymmetrical substitution on the phenyl spacer and the rigid backbone of the complex Pd-BOX-A induce inherent chirality and the compound crystallizes as a racemic mixture. Both complexes were found to be highly effective catalysts for Suzuki–Miyaura, Mizoroki–Heck and Sonogashira cross-coupling reactions. They also show excellent catalytic activities toward carbonylative coupling reactions.

Full text of DOI:10.1007/s11243-016-0072-1

Transit Met Chem (2016) 41:739–749
DOI 10.1007/s11243-016-0072-1
Synthesis, crystal structures and catalytic activities of new
palladium(II)–bis(oxazoline) complexes
Mansur B. Ibrahim1 Imran Malik1 S. M. Shakil Hussain2 Atif Fazal3
•
•
•
•
Mohammed Fettouhi1 Bassam El Ali1
•
Received: 26 April 2016 / Accepted: 10 June 2016 / Published online: 29 July 2016
Ó Springer International Publishing Switzerland 2016
Abstract Palladium–bis(oxazoline) complexes (Pd-BOX-
A and Pd-BOX-B) were synthesized and characterized by
1H, 13C NMR, IR and elemental analysis. The molecular
structures of the complexes were confirmed by single-
crystal X-ray analysis. In both cases, the palladium center
is coordinated by the nitrogen atoms of the two oxazoline
rings and two chloride ligands in a distorted square planar
geometry. Despite the fact that the bis(oxazoline) ligand is
achiral, the asymmetrical substitution on the phenyl spacer
and the rigid backbone of the complex Pd-BOX-A induce
inherent chirality and the compound crystallizes as a
racemic mixture. Both complexes were found to be highly
effective catalysts for Suzuki–Miyaura, Mizoroki–Heck
and Sonogashira cross-coupling reactions. They also show
excellent catalytic activities toward carbonylative coupling
reactions.
enantioselective Diels–Alder reactions. Metal–bis(oxazo-
line) complexes have found wide application as catalysts in
organic synthesis. A variety of BOX ligands complexed
with different transition metals (Pd, Cu, Zn, Ni, Ru, Ir, Rh)
have been reported to possess excellent catalytic activities.
They have been employed in asymmetric transfer hydro-
genations of ketones [3], Diels–Alder [4] and epoxidation
reactions [5]. Recently, (BOX)zinc(II)alkyl compounds
grafted on inorganic supports were reported and their cat-
alytic activities for asymmetric hydrosilylation reactions
were examined [6]. Evans has also studied the catalytic
activities of bis(oxazoline) and pyridyl-bis(oxazoline)
Cu(II) and Zn(II) complexes in aldol and Diels–Alder
reactions [7]. In the last two decades, Cu(II)-BOX com-
plexes have been studied extensively. They have been used
as catalysts in enantioselective Diels–Alder reactions [8],
aminohydroxylation of olefins [9], olefin and furan cyclo-
propanation reactions [1], olefin aziridinations [10], Frie-
del–Craft alkylations [11], carbonyl-ene reactions [12],
Henry reactions [13] and enantioselective Claisen rear-
rangements [14]. Several reports on Pd(II)-(BOX) com-
plexes have demonstrated their utility in a number of
synthetic transformations. They show impressive catalytic
activities in enantioselective allylic alkylations [15], aero-
bic oxidation of benzylic alcohols [16], copolymerization
of olefins with CO [17], cyclopropanation [18], Wacker-
type cyclization [19], cyclization–carbonylation–cycliza-
tion (CCC) coupling [20] and cross-coupling reactions
[21].
Introduction
Bis(oxazoline) (BOX) ligands were first introduced in
catalysis by Evans [1] and Corey [2] in 1991, who reported
the asymmetric cyclopropanation of alkenes and
& Bassam El Ali
belali@kfupm.edu.sa
1
Chemistry Department, King Fahd University of Petroleum
and Minerals, Dhahran 31261, Saudi Arabia
Recently, we have reported the synthesis of bis(oxazo-
line)–palladium complexes and their catalytic activities in
cross-coupling reactions [22–25]. Herein, we report on the
synthesis and characterization of two new palladium(II)–
bis(oxazoline) complexes. These were found to possess
high catalytic activities in Suzuki–Miyaura, Mizoroki–
2
Center for Integrative Petroleum Research, King Fahd
University of Petroleum and Minerals, Dhahran 31261,
Saudi Arabia
3
Center of Research Excellence in Petroleum Refining and
Petrochemicals, King Fahd University of Petroleum and
Minerals, Dhahran 31261, Saudi Arabia
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Transit Met Chem (2016) 41:739–749
Heck and copper-free Sonogashira coupling reactions and
also in carbonylative coupling reactions.
130.0 (C-5 arom), 130.5 (C-6 arom), 140.3 (C-4 arom),
162.1 (C-40), 162.4 (C-10); IR (CH2Cl2) t (cm-1) 2930,
1655, 1460, 1354, 1266, 1085, 969, 830, 735; GC-MS m/
z 287 (M?1). Anal. Calcd. for C17H22N2O2 (%): C, 71.30;
H, 7.75; N, 9.81. Found: C, 71.27; H, 7.67; N, 9.83 %.
Experimental
Materials and instruments
R,R-2,20-benzene-1,2-diylbis(4-ethyl-4,5-dihydro-
1,3-oxazole) (BOX-B)
Chemicals were purchased from Sigma-Aldrich and used
as received. All solvents used in the synthesis were distilled
before use. The products were purified using flash column
chromatography packed with 60 F silica gel purchased
from Fluka Chemie AG (Buchs, Switzerland).
1H and 13C NMR spectra were obtained using a JEOL
1500–500 MHz NMR spectrometer. Chemical shifts are
reported in ppm using tetramethylsilane (TMS) as refer-
ence and CDCl3 as solvent. IR spectra (cm-1) were
recorded with a FTIR spectrometer (Perkin-Elmer 16F
model). Elemental analyses were obtained on a Perkin-
Elmer Series 11 (CHNS/O) Analyzer 2400. Merck 60 F254
silica gel plates (250 lm layer thickness) were used for
TLC analyses. A Varian Saturn 2000 GC-MS machine was
used for product analysis.
Yellow oil; isolated yield (87 %); 1H NMR (500 MHz,
CDCl3) d (ppm): 7.72–7.69 (m, 2H, CH-4,5 arom),
7.45–7.43 (m, 2H, CH-3, 6 arom), 4.43–4.39 (m, 2H),
4.21–4.18 (m, 2H), 4.00–3.96 (m, 2H), 1.77–1.71 (m, 2H),
1.63–1.57 (m, 1H), 0.99 (t, J = 7.35, 6H, (NCHCH2CH3 9
2)); 13C NMR (125 MHz, CDCl3) d (ppm); 10.08
(NCHCH2CH3 9 2), 28.37 (NCHCH2CH3 9 2), 68.30
(NC(CH2CH3)2 9 2), 72.56 (OCH2 9 2), 128.45 (C-1,2
arom), 129.72 (C-3,6 arom), 130.27 (C-4,5 arom), 163.75
(OC=N) IR t (cm-1) 2967, 1661, 1256, 1192; GC-MS m/
z 273 (M?1) Anal. Calc. for C16H20N2O2 (%): C, 70.56; H,
7.40; N, 10.29. Found: C, 70.54; H, 7.33; N, 10.31 %.
Synthesis of the complexes
Synthesis of the bis(oxazolines)
A solution of bis(benzonitrile)–palladium(II) chloride
(0.50 mmol) in DMF (8 mL) plus the required BOX ligand
(0.50 mmol) was stirred under nitrogen at room tempera-
ture for 6 h. The progress of the reaction was monitored by
TLC until no free BOX was observed. The solvent was
separated by rotary evaporation. Crude product was
recrystallized from DMF. The crystals were separated and
A solution of the required phthalonitrile derivative
(4.0 mmol) and zinc triflate (5.0 mol%, 0.20 mmol) in dry
chlorobenzene (30 mL) was stirred at room temperature for
15 min, and then a solution of the appropriate amino
alcohol (8.0 mmol) in dry chlorobenzene (5 mL) was
slowly added. The temperature was raised to 135 °C, and
the reaction mixture was refluxed for 24 h. The product of
the reaction was dissolved in 30 mL of dichloromethane
and extracted twice with distilled water (2 9 20 mL). The
aqueous layer was then separated, and the combined
organic layers were dried with anhydrous sodium sulfate.
The dichloromethane was removed using a rotary evapo-
rator to obtain the crude product, which was purified using
silica gel column chromatography with dichloromethane/
ether (4/1) as eluent.
1
washed with ether and then characterized by H and 13C
NMR, elemental analysis, IR spectroscopy and single-
crystal X-ray crystallography [26].
Dichlorido[2,20-(4-methylbenzene-1,2-diyl)bis(4,4-
dimethyl-4,5-dihydro-1,3-oxazole)-N,N0]
palladium(II) (Pd-BOX-A)
1
Pale yellow solid; H NMR (500 MHz, CDCl3) d (ppm):
7.70 (d, J = 7.9 Hz, 1H, C-5 arom), 7.61 (s, 1H, C-3
arom), 7.54 (d, J = 7.9 Hz, 1H, C-6 arom), 4.32–4.23 (m,
4H, OCH2 9 2), 2.51 (s, 3H, CH3 on arom), 1.75 (s, 6H,
NC(CH3)2), 1.62 (s, 3H, NC(CH3), 1.59 (s, 3H, NC(CH3);
13C NMR (125 MHz, CDCl3) d (ppm); 21.5 (CH3 on
arom), 28.2 (NC(CH3), 28.3 (NC(CH3), 28.8 (NC(CH3),
28.9 (NC(CH3), 71.1 (NC(CH3)2), 71.2 (NC(CH3)2), 80.8
(OCH2), 80.9 (OCH2), 123.1, (C-2 arom), 125.9 (C-1
arom), 129.0 (C-3 arom), 130.8 (C-5 arom), 132.0 (C-6
arom), 143.7 (C-4 arom), 164.2 (C-40), 164.3 (C-10); IR t
(cm-1): 2973, 1637, 1457, 1374, 1122, 1068, 958, 829,
730; Anal. Calc. for C18H25Cl2N2O2Pd, (478.73): C, 45.16;
H, 5.26; N, 5.85; Found: C, 45.51; H, 5.21; N, 5.89 %.
2,20-(4-methylbenzene-1,2-diyl)bis(4,4-dimethyl-4,5-
dihydro-1,3-oxazole) (BOX-A)
Yellow oil; isolated yield (87 %); 1H NMR (500 MHz,
CDCl3) d (ppm): 7.50 (d, J = 7.93 Hz, 1H, 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, OCH2 9 2), 2.24 (s, 3H, CH3 on arom),
1.25 (s, 12H, NC(CH3)2 9 2); 13C NMR (125 MHz,
CDCl3) d (ppm); 20.8 (CH3 on arom), 27.8 (NC(CH3)2 9
2), 67.5 (NC(CH3)2 9 2), 79.1 (OCH2), 79.2 (OCH2),
125.4, (C-2 arom), 128.2 (C-1 arom), 129.4 (C-3 arom),
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Dichlorido(R,R-2,20-benzene-1,2-diylbis[4-ethyl-4,5-
dihydro-1,3-oxazole)-N,N0] palladium(II)
(Pd-BOX-B)
The characterization data of the compounds were in
entire agreement with those reported in the literature [22].
General procedure for Sonogashira coupling
1
Yellow solid; isolated yield (90 %); H NMR (500 MHz,
CDCl3) d (ppm): 7.87–7.85 (m, 2H, CH arom), 7.76–7.74
(m, 3H, CH arom), 4.80–4.66 (m, 2H), 4.34–4.28 (m, 2H),
4.17–4.14 (m, 1H), 2.75–2.70 (m, 1H), 2.65–2.60 (m, 1H),
2.25–2.19 (m, 1H), 2.02–1.96 (m, 1H), 1.87–1.81 (m, 1H),
1.10–1.02 (m, 6H, NCHCH2CH3 9 2); 13C NMR
(125 MHz, CDCl3) d (ppm); 8.97 (NCHCH2CH3), 10.10
(NCHCH2CH3), 26.70 (NCHCH2CH3) 27.56 (NCHCH2-
CH3), 66.32 [NC(CH2CH3)], 70.30 [NC(CH2CH3)], 73.07
(OCH2), 74.50 (OCH2), 124.42 (C-arom), 124.96 (C-
arom), 125.64 (C-arom), 130.57 (C-arom), 131.55 (C-
arom), 132.94 (C-arom), 164.36 (OC=N), 165.90 (OC=N);
IR t (cm-1): 2960, 2873, 1645, 1589, 1458, 1385, 1340,
1301, 1246, 1133, 944, 781; Anal. Calc. for C16H20Cl2-
N2O2Pd, (447.99): C, 42.74; H, 4.48; N, 6.23. Found: C,
42.63; H, 4.69; N, 6.61 %.
In a 10-mL round-bottom flask, the appropriate palladium
complex (0.010 mmol) was dissolved in acetonitrile
(4 mL). Aryl halide (1.0 mmol), alkyne (1.2 mmol), KOH
(2.0 mmol) and distilled water (4 mL) were added. The
mixture was stirred at room temperature (or 60 °C) for the
required time. After completion of the reaction, the product
was extracted 3 times with EtOAc (5 mL). The combined
organic layer was dried over Na2SO4, and the product was
analyzed with GC and GC-MS. The product was further
purified using column chromatography with hexane-EtOAc
as eluent. The characterization data were in entire agree-
ment with the previously reported literature [23].
General procedure for carbonylation
of aminoalcolcols
A 45-mL glass-lined autoclave was charged with iodoben-
zene (1.0 mmol), the required aminoalcohol (2.2 mmol),
Pd-BOX-A (0.010 mmol), K2CO3 (3.0 mmol), CH3CN
(5 mL). The autoclave was purged three times with CO and
pressurized with 100 psi of CO and then heated at 120 °C
for 3–12 h. After completion of the reaction, the autoclave
was cooled to room temperature and the excess CO was
released carefully. The reaction mixture was diluted with
EtOAc and filtered, then concentrated by rotary evaporation
and purified by chromatography using EtOAc as eluent to
afford the product. The characterization data were in entire
agreement with the previously reported literature [27].
General procedure for Suzuki–Miyaura coupling
The required palladium complex (0.20 mol%, 0.0020 mmol),
aryl halide (1.0 mmol), aryl boronic acid (1.5 mmol),
potassium carbonate (2.0 mmol), DMF (4 mL) and dis-
tilled water (4 mL) were placed in a 250-mL round-bottom
flask. The mixture was stirred at room temperature under
air. The progress of the reaction was monitored by gas
chromatography. After completion of the reaction, the
product was extracted 3 times with 5 mL of EtOAc and the
combined organic extract was dried over MgSO4. The
solvent was then removed under reduced pressure using a
rotary evaporator. The product was purified by column
chromatography using hexane-EtOAc (8:2).
2-benzamido-2-methylpropyl benzoate (10b)
1
White solid; isolated yield (78 %); H-NMR (500 MHz,
The characterization data of the compounds were in
entire agreement with those reported in the literature [22].
CDCl3) d (ppm): 8.01 (d, J = 7.0, 2H), 7.71 (d, J = 7.30,
2H), 7.53 (t, J = 7.31, 1H), 7.43–7.35 (m, 5H), 6.54 (s, 1H),
4.52 (s, 2H), 1.55 (s, 6H) 13C-NMR (125 MHz, CDCl3) d
(ppm); 167.1, 166.7, 135.2, 133.1, 131.2, 129.7, 129.5,
128.4, 128.3, 126.7, 70.1, 54.2, 23.9; IR v (cm-1) 3261, 3062,
1709, 1635, 1538, 1391, 1366, 1317, 1281, 1160; GC-MS m/
z 297 (M?); Anal. Calc. for C18H19NO3, (297.34): C, 72.71;
H, 6.44; N, 4.71. Found: C, 72.56; H, 6.36; N, 4.52 %.
General procedure for Mizoroki–Heck coupling
The required palladium complex (0.010 mmol), aryl halide
(1.0 mmol), styrene (1.5 mmol), KOH (2.0 mmol), DMF
(3 mL) and distilled water (1 mL) were placed in a 15-mL
round-bottom flask. A condenser was attached, and the mix-
ture was stirred at 90 °C. The progress of the reaction was
monitored by the gas chromatography. After completion of
the reaction, the product was extracted 3 times with 5 mL of
EtOAc. The combined organic extract was dried over MgSO4.
The solvent was then removed under reduced pressure using a
rotary evaporator. The product was purified by column chro-
matography using hexane-EtOAc (7:3) as eluent.
(S)-2-benzamido-3,3-dimethylbutyl benzoate (10c)
Light brown solid; isolated yield (82 %); [a]2D0 = ?3.57°
(c = 0.28 in CH2Cl2); 1H-NMR (500 MHz, CDCl3) d
(ppm): 7.97 (d, J = 7.31, 2H), 7.70 (d, J = 7.30, 2H), 7.51
(t, J = 7.35, 1H), 7.46 (t, J = 7.31, 1H 7.41–7.37 (m, 4H),
6.17 (d, J = 8.85, 1H), 4.57 (t, J = 10.65, 1H), 4.50–4.45
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Table 1 Crystallographic data
for Pd-BOX-A and Pd-BOX-B
Parameters
Pd-BOX-A
Pd-BOX-B
Chemical formula
Formula weight
Crystal system
Space group
C17 H22 Cl2 N2 O2 Pd
C16 H20 Cl2 N2 O2 Pd
449.64
463.67
Monoclinic
P21/n
Orthorhombic
P212121
Temperature (K)
Radiation
296
296
˚
MoKa(k = 0.71073 A)
qcalc (g cm-3
)
1.582
1.683
˚
a (A)
8.0861(4)
7.3897(18)
˚
b (A)
23.7532(13)
10.408(3)
˚
c (A)
10.4338(6)
23.068(6)
b (°)
V (A )
103.6820(10)
90
3
˚
1947.16(18)
1774.3(7)
Z
4
4
Refl. collect./Uniq.
Refl. obser. [I [ 2r (I)]
R (int)
26395/4845
20361/4419
4140
3272
0.0272
0.0845
Data/restr/parameter.
Goodness of fit on F2
R indices [I [ 2r (I)]
R indices (all data)
Largest diff. peak,
4845/0/222
4419/106/237
1.027
0.987
R1 = 0.0259; wR2 = 0.0594
R1 = 0.0336; wR2 = 0.0630
0.430
R1 = 0.0503; wR2 = 0.0576
R1 = 0.0809; wR2 = 0.0601
0.680
-3
˚
Hole (e A
)
-0.257
-0.371
Table 2 Selected bond lengths
°
Pd-BOX-A
Pd-BOX-B
˚
(A) and bond angles ( ) for Pd-
BOX-A and Pd-BOX-B
Bond lengths
Bond angles
Bond lengths
Bond angles
Pd1–N1 2.0315(17) N1–Pd1–N2
87.35(7)
91.84(5)
Pd1–N1 2.012(4)
N1–Pd1–N2
86.69(15)
Pd1–N2 2.0477(18) N1–Pd1–Cl1
Pd1–N2 2.016(4)
N1–Pd1–Cl2 176.89(12)
Pd1–Cl1 2.2751(6)
Pd1–Cl2 2.2924(6)
N2–Pd1–Cl1 178.56(6)
N1–Pd1–Cl2 177.04(5)
Pd1–Cl1 2.2894(14) N2–Pd1–Cl2
Pd1–Cl2 2.2744(15) N1–Pd1–Cl1
90.30(11)
92.52(11)
N1–C1
N1–C2
1.277(3)
1.508(3)
N2–Pd1–Cl2
Cl1–Pd1–Cl2
C1–N1–C2
92.37(5)
88.38(2)
N1–C3
N1–C5
1.511(7)
1.279(6)
N2–Pd1–Cl1 176.50(12)
Cl2–Pd1–Cl1
C3–N1–Pd1
C5–N1–Pd1
C5–N1–C3
90.53(6)
129.0(4)
123.8(3)
106.8(4)
N2–C13 1.278(3)
N2–C15 1.511(3)
107.34(18) N2–C12 1.274(5)
122.01(14) N2–C14 1.464(6)
C1–N1–Pd1
C2–N1–Pd1
O1–C1
O1–C5
1.339(3)
1.465(3)
130.65(14) O1–C4
1.470(6)
1.354(6)
C13–N2–C15 108.42(19) O1–C5
C12–N2–C14 109.4(4)
C12–N2–Pd1 125.3(3)
C14–N2–Pd1 125.2(3)
O2–C13 1.349(3)
O2–C14 1.447(4)
C13–N2–Pd1 123.72(16) O2–C12 1.341(5)
C15–N2–Pd1 127.81(16) O2–C13 1.453(6)
C1–O1–C5
104.05(18)
C5–O1–C4
106.2(4)
C13–O2–C14 105.9(2)
C12–O2–C13 106.3(4)
(m, 2H), 1.09 (s, 9H) 13C-NMR (125 MHz, CDCl3) d
(ppm); 167.7, 166.9, 134.8, 133.1, 131.3, 129.7, 129.6,
X-Ray structure analysis
128.5, 128.4, 126.7, 64.2, 56.3, 34.2, 26.8; IR v (cm-1
)
X-Ray intensity data for Pd-BOX-A and Pd-BOX-B were
collected on a Bruker-AXS Smart Apex system equipped
with graphite monochromatized MoKa radiation
3260, 2960, 1721, 1639, 1548, 1450, 1351, 1314, 1269,
1118; GC-MS m/z 325 (M?); Anal. Calc. for C20H23NO3,
(325.40): C, 73.82; H, 7.12; N, 4.30. Found: C, 73.94; H,
6.89; N, 4.37 %.
˚
(k = 0.71073 A). The data were collected using SMART,
and the integration was performed using SAINT [28]. An
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Transit Met Chem (2016) 41:739–749
743
Scheme 1 Synthesis of new
palladium–bis(oxazoline)
complexes. BOX-A
R1=R2=R3=CH3; BOX-B
R1=R2=H, R3=CH2CH3
1
R
1
R
HO
NH
2
Zn(OTf)2
+
2
O
O
reflux, 24h
3
2
R
R
N
N
CN
CN
R
3
R
2
2
3
R
R
R
1
R
1
O
DMF
O
3
+ PdCl (PhCN)
2
2
O
O
N
N
RT, 6h
N
N
Pd
3
R
2
R
2
R
Cl
R
Cl
3
R
2
2
3
R
R
R
[30]. All non-hydrogen atoms were refined anisotropically.
Hydrogen atoms were placed at calculated positions using
a riding model. For Pd-BOX-B, atoms C1 (C1A), C2
(C2A) and C3 (C3A) were constrained to partial site
occupancies, which refined to values of 0.76(1) and
0.24(1). The parameters of atoms involved in disorder were
restrained with the SIMU, RIGU and SADI commands.
Molecular graphics were generated using ORTEP-3 [31].
Crystal data and details of the data collection are summa-
rized in Tables 1 and 2.
Results and discussion
The bis(oxazoline) pro-ligands BOX-A and BOX-B were
prepared by reacting the substituted phthalonitrile with two
equivalents of 2-aminoalcohol, catalyzed by zinc triflate
Zn(OTf)2 (Scheme 1). BOX-A and BOX-B were then
treated with bis(benzonitrile)dichloridopalladium(II) in
DMF at room temperature to produce the two complexes,
Pd-BOX-A and Pd-BOX-B. Both complexes were char-
1
acterized by H and 13C NMR, IR, elemental analysis and
Fig. 1 ORTEP diagram of Pd-BOX-A showing the atomic labeling
scheme. Thermal ellipsoids have been drawn at the 30 % probability
level
X-ray crystallography.
empirical absorption correction was carried out using
SADABS [29]. The structures were solved by direct
methods with SHELXS-97 and refined by full-matrix least-
squares procedures on F2 using the program SHELXL-97
Properties and structure of Pd-BOX-A
The palladium complex Pd-BOX-A was recrystallized
from dichloromethane by the addition of hexane. A single
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Transit Met Chem (2016) 41:739–749
Fig. 2 Hydrogen bonding interactions in Pd-BOX-A. Symmetry codes: (i) -x, -y, 1-z; (ii) -1 ? x, y, z; and (iii) -1/2 ? x, 1/2-y, -1/2 ? z
Table 3 Hydrogen bonding
geometries for Pd-BOX-A and
D—HÁÁÁA (o)
˚
˚
˚
D—HÁÁÁA
D—H (A)
HÁÁÁA (A)
DÁÁÁA (A)
Pd-BOX-B
Pd-BOX-A
C5-H5BÁÁÁCl2(i)
C5-H5AÁÁÁO1(ii)
Pd-BOX-B
0.97
0.97
2.82
2.78
3.794(3)
3.690(3)
179.4
156.2
C2-H2AÁÁÁCl2(iii)
C3-H3ÁÁÁCl1(iv)
C13-H13AÁÁÁCl2(iv)
C13-H13BÁÁÁCl2(v)
C15-H15BÁÁÁCl2(iv)
0.97
0.98
0.97
0.97
0.97
2.79
2.98
2.75
2.78
2.93
3.704(6)
3.704(6)
3.530(4)
3.547(4)
3.723(4)
157.4
131.6
138.0
136.2
139.7
Symmetry codes: (i) -1?x, y, z; (ii) -x, -y, 1-z; (iii) 2-x, y-0.5, 0.5-z; (iv) x-1, y, z; (v) x-0.5,
0.5-y, -z
crystal suitable for X-ray crystallography was grown from
DMF solution. The complex was obtained as needle-
shaped crystals. The complex was also characterized by 1H
and 13C NMR spectroscopy. All of the proton and carbon
resonances in the spectra of the complex are shifted to
some extent compared to their positions in the spectra of
the free pro-ligand. For example, in the spectrum of BOX-
A, the methyl groups attached to the oxazoline rings were
observed as a singlet at 1.25 ppm. In the spectrum of Pd-
BOX-A, four distinct singlets were observed at 1.75, 1.62,
1.59 and 1.56 ppm, integrating for three protons each.
Similar trends were observed in the 13C spectrum. The
splitting of a single peak into four peaks, together with
changes in chemical shifts, confirms the formation of Pd-
BOX-A from BOX-A. Furthermore, from the FTIR data,
the C=N band shifted from 1655 to 1637 cm-1 due to
complexation.
The molecular structure of Pd-BOX-A is shown in
Fig. 1. The complex crystallizes in the P2(1)/n space group
with one molecule in the asymmetric unit. The palladium
center is coordinated by the two oxazoline nitrogens of the
bidentate ligand and two chloride ligands in a distorted
square planar geometry. The cis-bond angles are in the
range: 87.35(7)°–92.37(5)° (Table 1), and the Pd-N and
Pd-Cl bond distances are similar to those found in other
bis(oxazoline)–palladium complexes [32–34]. The mole-
cule resembles a chair, with the [PdN2Cl2] moiety being
the seat and the benzene ring spacer being the back. The
dihedral angle between the phenyl spacer and the [PdN2-
Cl2] mean plane is 85.9(1)°. Coordination to the metal
requires twisting of the two oxazoline rings, such that the
dihedral angles formed by the two oxazoline CNO planes
and the phenyl spacer are 44.5(1)° and 57.3(2)°. The two
oxazoline rings adopt an envelope conformation with the
123

Transit Met Chem (2016) 41:739–749
745
phenyl and the rigid backbone curvature of the metal
complex induce inherent chirality and the compound
crystallizes as a racemate [22].
Properties and structure of Pd-BOX-B
The palladium complex Pd-BOX-B was recrystallized
from dichloromethane by adding hexane. A single crystal
suitable for X-ray was grown from DMF solution. The
complex was obtained in form of yellow, needle-shaped air
1
stable crystals. As with Pd-BOX-A, the H and 13C NMR
spectra of Pd-BOX-B showed shifts in the positions of all
the proton and carbon resonances compared to the free pro-
1
ligand. For example, in the H NMR spectrum of BOX-B,
the CH3 groups were observed as a triplet at 0.99 ppm. In
the 1H NMR spectrum of the Pd-BOX-B complex, the
equivalent signal took the form of a multiplet with a
chemical shift range of 1.10–1.02 ppm. In the FTIR spec-
tra, a shift in the position of C=N band from 1661 cm-1 in
the spectrum of free BOX-B to 1645 cm-1 in the spectrum
of Pd-BOX-B is an indication that the ligand is coordi-
nated to the palladium.
The molecular structure of Pd-BOX-B is depicted in
Fig. 3. This complex crystallizes in the space group
P212121 with one molecule in the asymmetric unit, and the
coordination sphere is similar to that of Pd-BOX-A, with a
distorted square planar geometry. The cis-bond angles are
in the range of 86.69(15)°–92.52(11)°. The dihedral angle
between the phenyl spacer and the [PdN2Cl2] mean plane is
78.7(1)°, and the dihedral angles of the two oxazoline CNO
planes with the phenyl spacer are 42.2(1)° and 44.1(1)°,
respectively. One oxazoline ring is essentially planar, while
Fig. 3 ORTEP diagram of Pd-BOX-B showing the atomic labeling
scheme. Thermal ellipsoids have been drawn at the 30 % probability
level
flap atom being displaced out of the mean plane of the
˚
˚
other four atoms by 0.432(4) A (C5) and 0.292(6) A (C14),
respectively. The ring conformation is partly supported by
non-classical hydrogen bonding interactions C–HÁÁÁ(Cl, O)
(Fig. 2; Table 3). Despite the fact that the bis(oxazoline)
ligand is achiral, the asymmetrical substitution on the
Fig. 4 Hydrogen bonding
interactions in Pd-BOX-B.
Symmetry codes: (i) 2-x, y-1/
2, 1/2-z; (ii) x-1/2, 1/2-y,
-z; (iii) x-1, y, z
123

746
Transit Met Chem (2016) 41:739–749
Scheme 2 Suzuki–Miyaura
coupling of aryl halides with
various aryl boronic acids
2
R
X
B(OH)
2
Pd-BOX-A
K CO
+
2
3
1
2
R
R
DMF / H O
2
1
R
3
1
2
Table 4 Suzuki–Miyaura
coupling of aryl halides with
various aryl boronic acids
Entry
Aryl halide (1)
R1
X
Aryl boronic acid (2)
R2
Time
(h)
Coupling product (3)
yield (%)a
1
H
I
CH3
1.5
1.5
0.5
0.5
1
95
91
95
94
96
95
95
89
85
90
94
93
87
2
OCH3
NO2
COCH3
COCH3
CN
I
H
3
I
H
4
I
CH3
5
Br
Br
Br
Cl
Cl
Cl
I
H
6
H
1
7
OCH3
H
H
2
8b
9b
10b
11c
12c
13b,c
CH3
OCH2CH3
H
12
12
12
1.5
1
H
CHO
H
CH3
H
OCH3
H
Br
Cl
CH3
12
Reaction conditions: Pd-BOX-A (0.0020 mmol), aryl halide (1.0 mmol), aryl boronic acid (1.5 mmol),
K2CO3 (2.0 mmol), DMF-H2O (1:1) (8 mL), room temperature
a
Isolated yield
b
Reaction carried out at 110 °C
Pd-BOX-B (0.0020 mmol) was used as a catalyst
c
Catalytic coupling reactions
the other adopts an envelope conformation with the flap
atom being displaced out of the mean plane of the other
˚
four atoms by 0.402(8) A (C3). Non-classical hydrogen
The Pd-BOX-A complex was tested as a catalyst in
Suzuki–Miyaura cross-coupling reactions of both activated
and deactivated aryl halides with various phenylboronic
acids (Scheme 1; Table 4). Aryl iodides bearing electron-
withdrawing substituents showed excellent reactivity, giv-
ing high product yields in short reaction times (Table 4,
entries 3, 4). However, a long reaction time was required
for electron-rich substrates (Table 4, entry 2). The reac-
tivity of aryl bromides was lower than that of aryl iodides.
Complete conversion and excellent yields were observed
bonding interactions C–HÁÁÁCl are also observed for this
complex (Fig. 4; Table 3). One oxazoline moiety was
found to have its C(oxazoline)HCH2CH3 (C3–C2–C1)
group disordered over two sites. The occupancies of the
major and minor components refined to 0.76(1) and
0.24(1), respectively (Fig. 3). The structure is consistent
with a co-crystal of diastereomeric complexes (R,R-
BOX)PdCl2 and (R,S-BOX)PdCl2 with
0.76(1):0.24(1).
a
ratio
Scheme 3 Sonogashira
I
coupling reaction of aryl iodides
with different alkynes catalyzed
by Pd-BOX-A
Pd-BOX-A
3
1
3
R
R
R
+
KOH
1
R
CH3CN-H2O
5
4
1
123

Transit Met Chem (2016) 41:739–749
747
Table 5 Sonogashira coupling reaction of aryl iodides with different
alkynes catalyzed by Pd-BOX-A
Table 6 Mizoroki–Heck coupling of aryl iodides with different
styrene derivatives
Entry Aryl Iodide (1) Alkyne
R1
Time Coupling
(h)
Entry
Aryl Iodide
(1)
R1
Styrene derivative
(6)
R3
Coupling product
(7)
yield (%)a
(4)
R3
product
(5)
yield (%)a
1
H
H
94
96
96
91
95
94
1
H
Ph
2
3
3
1
1
3
4
4
4
3
2
4
96
90
95
97
96
90
84
91
89
90
94
85
2
OCH3
COCH3
H
H
2
H
4-CF3C6H4
4-NH2 C6H4
Ph
3
H
3
H
4
Cl
4
NO2
CN
OCH3
H
5
6b
H
OCH3
H
5
Ph
OCH3
6
Ph
Reaction conditions: Pd-BOX-A (0.010 mmol), aryl iodide (1.0
mmol), styrene derivative (1.5 mmol), KOH (2.0 mmol), DMF-H2O
(3:1) (8 mL), 90 °C, 2 h
7b
8b
9b
10b
11c
12c
n-C4H9
ClCH2CH2CH2
NCCH2CH2CH2
n-C4H9
Ph
H
a
H
Isolated yield
b
CN
H
Pd-BOX-B (0.010 mmol) was used as a catalyst
H
n-C4H9
Reaction condition: Pd-BOX-A (0.010 mmol), aryl iodide (1.0
mmol), alkyne (1.5 mmol), KOH (2 mmol), CH3CN-H2O (1:1) (8
mL), room temperature
alkynes to give the coupling products in excellent yields
(Table 5). The coupling of iodobenzene with pheny-
lacetylene gave the internal alkyne in excellent yield
(96 %) in 2 h (Table 5, entry 1). The reactions of deacti-
vated aryl iodides with phenylacetylene were complete in
shorter times (Table 5, entries 4, 5). Longer reaction times
were required with activated aryl iodides (Table 5, entry
6). The catalyst was also highly active in coupling reac-
tions of aryl iodides with aliphatic alkynes, giving the
coupling products in good yields at 60 °C after 3–4 h
(Table 5, entries 7–10).
a
Isolated yield
b
Reaction carried out at 60 °C
Pd-BOX-B (0.010 mmol) was used as a catalyst
c
after 1 h with electron-deficient substituents on the aryl
halides (Table 4, entries 5, 6), while the reaction was
complete after 2 h when bromobenzene with an electron-
rich substituent was used (Table 4, entry 7). Aryl chlorides
were again less reactive, such that the coupling reactions
required higher temperature (110 °C) and longer time
(12 h) (Table 4, entries 8–10) (Scheme 2).
The Pd-BOX-B complex showed very similar catalytic
activity as Pd-BOX-A in the Sonogashira cross-coupling
reaction of iodobenzene with phenylacetylene and with
1-hexyne (Table 5, entries 11-12).
The Pd-BOX-B complex showed similar catalytic
activity to Pd-BOX-A in the Suzuki–Miyaura cross-cou-
pling reaction of aryl halides with aryl boronic acids
(Table 4, entries 11–13).
Pd-BOX-A was also evaluated as a catalyst in Mizor-
oki–Heck coupling of aryl iodides with styrene derivatives
(Scheme 4). Both activated and deactivated aryl iodides
reacted with styrene derivatives to give the desired prod-
ucts in excellent yields (Table 6, entries 1–3). Both elec-
tron-rich or electron-deficient substituents on styrene also
provided coupling products in quantitative yields (Table 6,
entries 4, 5). Other palladium catalysts, such as Pd–phos-
phine or nitrogen catalysts used in the Heck reaction,
generally require high temperature and longer times for the
To further investigate catalytic applications of Pd-BOX-
A in coupling reactions, the Sonogashira coupling reaction
was also studied. A variety of terminal acetylenes were
employed with different aryl iodides, under copper-free,
phosphine-free and aerobic conditions (Scheme 3). Acti-
vated and deactivated aryl iodides reacted smoothly with
Scheme 4 Mizoroki–Heck
coupling of aryl iodides with
different styrene derivatives
4
R
I
Pd-BOX-A
+
1
KOH; DMF-H2O
1
R
4
R
R
R.T.
7
1
6
123

748
Transit Met Chem (2016) 41:739–749
Scheme 5 8a: R1=R2=H; 8b:
R1=R2=CH3; R1=H,
R2=C(CH3)3
2
O
2
1
O
1
R
R
R
R
1
2
Pd-BOX-A
R
O
Ph
OH
Ph-I
1
HO
+
+
CO
+
Ph
O
N
H
Ph
N
R
2
K2CO3; CH3CN
100 psi; 120oC
3-12 h
H
NH
8a-c
O
10
9
2
O
1
R
R
Ph
Ph
N
H
+
O
O
11
in the Mizoroki–Heck coupling reaction of aryl iodide with
styrene (Table 5, entry 6).
Table 7 Aminocarbonylation of iodobenzene with aminoalcohols
Entry Aminoalcohol
8
Amide
9a-c
Amidoester Ketoamidoester
10a-c
11a-c
yield (%)a
yield (%)a yield (%)a
Catalytic applications of Pd-BOX-A
in carbonylative coupling reactions
R1
R2
1b
2
H
H
0
10a
50
10a
50
0
The carbonylation of iodobenzene with aminoalcohols was
studied using Pd-BOX-A as a catalyst (Scheme 5;
Table 7). Pd-BOX-A showed high efficiency for the
alkoxycarbonylation and aminocarbonylation of different
aminoalcohols with iodobenzene. The selective aminocar-
bonylation of idobenzene with aminoalcohols (8a, b) was
achieved with excellent yields in short reaction times (3 h),
giving the corresponding amides 9 (Table 7, entries 2 and
4). Also, amino- and alkoxycarbonylation were accom-
plished to selectively produce the new amidoesters 10 in
high yields with two equivalents of iodobenzene and a
longer reaction time (12 h) (Table 7, entries 3 and 5). It is
worth noting that a new optically active amidoester 10c
was obtained by the carbonylation of the optically active
aminoalcohol (Table 7, entry 5). As expected, Pd-BOX-B
showed high catalytic activity, similar to Pd-BOX-A, in
the carbonylative coupling of iodobenzene, 1, with the
aminoalcohol, 8b (Table 7, entries 6 and 7).
CH3 CH3
CH3 CH3
9b
81
0
10b
9
3c
4
10b
78
0
0
0
0
0
H
H
C(CH3)3 9c
85
10c
12
5c
6d
7c,d
C(CH3)3
0
10c
82
CH3 CH3
CH3 CH3
9b
79
0
10b
11
10b
76
Reaction condition: Pd-BOX-A (0.010 mmol), iodobenzene (1.0
mmol), aminoalcohol (1.1 mmol), K2CO3 (1.5 mmol), CH3CN (5
mL), 120 °C, 3 h
a
Isolated yield
b
6 h
Some amidothioester derivatives have been prepared by
the reaction of benzoylfluoride with disulfide, using a
rhodium catalyst [36]. To the best of our knowledge, metal-
catalyzed carbonylation reactions of aryliodide with cys-
teamine have not previously been studied. Pd-BOX-A was
employed as catalyst for carbonylation of iodobenzene
with cysteamine under a CO atmosphere, giving diben-
zoylcysteamine 13 in excellent yield (Scheme 6).
c
Iodobenzene (2.2 mmol), 12 h
d
Pd-BOX-B (0.010 mmol) was used as a catalyst
complete conversion into product [35, 36], while Pd-BOX-
A required lower temperature and shorter times (2 h).
Similarly, Pd-BOX-B showed excellent catalytic activity
O
Pd-BOX-A
0.010 mmol
S
I
SH
N
H
H N
2
+
CO
+
O
K2CO3 (1.5 mmol)
CH3CN (5 mL)
100 psi;120 oC
3-12 h
13
99%
12 (1.1 mmol)
1 (1.0 mmol)
Scheme 6 Pd-BOX-A-catalyzed the carbonylation of iodobenzene with cysteamine
123

Transit Met Chem (2016) 41:739–749
749
8. Evans DA, Miller SJ, Lectka T, Matt PV (1999) J Am Chem Soc
121:7559
Conclusion
9. Michaelis DJ, Williamson KS, Yoon TP (2009) Tetrahedron
65:5118
10. Evans DA, Faul MM, Bilodeau MT (1994) J Am Chem Soc
116:2742
11. Singh PK, Bisai A, Singh VK (2007) Tetrahedron Lett 48:1127
12. McDonagh C, OLeary P (2009) Tetrahedron Lett 50:979
13. Evans DA, Seidel D, Reuping M, Lam HW, Shaw JT, Downey
CW (2003) J Am Chem Soc 125:12692
14. Abraham L, Korner M, Schwab P, Hiersemann M (2004) Adv
Synth Catal 346:1281
15. Cattoen X, Pericas MA (2009) Tetrahedron 65:8199
16. Hara K, Tayama S, Kano H, Masuda T, Takakusagi S, Kondo T,
Uosaki K, Sawamura M (2007) Chem. Commun 41:4280
17. Sirbu D, Consiglio G, Milani B, Kumar PGA, Pregosin PS,
Gischig S (2005) J Organomet Chem 690:2254
18. Denmark SE, Stavenger RA, Faucher AM, Edward JP (1997) J
Org Chem 62:3375
We have described the synthesis, characterization and
crystal structures of two new palladium–bis(oxazoline)
complexes. Both complexes show excellent catalytic
activities in Suzuki–Miyaura, Sonogashira, Mizoroki–Heck
and carbonylation reactions. A variety of biaryls, internal
alkenes, internal alkynes, amides, amidoesters and an
amidothioester were prepared in high yields using Pd-
BOX-A as catalyst. Pd-BOX-B showed almost the same
catalytic activity as Pd-BOX-A for all investigated
reactions.
Supplementary data
19. Uozumi Y, Kato K, Hayashi T (1998) J Org Chem 63:5071
20. Jiang Y, Kusakabe T, Takahashi K, Kato K (2014) Org Biomol
Chem 12:3380
21. Takemoto T, Iwasa S, Hamada H, Shibatomi K, Kameyama M,
Motoyama Y, Nishiyama H (2007) Tetrahedron Lett 48:3397
22. Hussain SMS, Ibrahim MB, Fazal A, Suleiman R, Fettouhi M, El
Ali B (2014) Polyhedron 70:39
23. Ibrahim MB, El Ali B, Fettouhi M, Ouahab L (2015) Appl
Organomet Chem 29:400
24. Ibrahim MB, Hussain SMS, Fazal A, Fettouhi M, El Ali B (2015)
J Coord Chem 68:432
Crystallographic data for the structural analysis of com-
plexes have been deposited in the Cambridge Crystallo-
graphic Data Center, CCDC Nos. 1033026 and 1040966 for
Pd-BOX-A and B, respectively. This material can be
obtained free of charge via http://www.ccdc.cam.ac.uk/ or
from the Director, CCDC, 12, Union Road, Cambridge, CB2,
1EZ, UK (Fax: ?441223336033; E-mail: deposit@ccdc.
cam.ac.uk.
25. Ibrahim MB, El Ali B, Malik I, Fettouhi M (2016) Tetrahedron
Lett 57:554
26. Ruiyun G, Portscheller JL, Day VW, Malinakova HC (2007)
Organometallics 26:3874
27. Boukattya F, Stanovych A, Setzer P, Abid S, Ammar H (2012)
Chem Commun 48:8655
Acknowledgments We gratefully acknowledge financial support by
King Abdulaziz City for Science and Technology (KACST) through
the science and technology unit at King Fahd University of Petroleum
and Minerals (KFUPM), the Kingdom of Saudi Arabia, award number
(11-PET1665-04).
28. Bruker SMART and SAINT Bruker AXS Inc (2008) Madison WI
29. Shedldrick GM (1996) SADABS program for empirical absorp-
tion correction of area detector data. University of Gottingen,
References
¨
Gottingen
30. Sheldrick GM (2008) Acta Crystallogr Sect A Found Crystallogr
64:112
1. Evans DA, Woerpel KA, Hinman MM, Faul MM (1991) J Am
Chem Soc 113:726
2. Corey EJ, Imai N, Zhang HY (1991) J Am Chem Soc 113:728
3. Debono N, Besson M, Pinel C, Djakovitch L (2007) Tetrahedron
Lett 45:2235
4. Davies DL, Fawcett J, Garratt SA, Russell DR (2002) J Orga-
nomet Chem 662:43
5. Serrano I, Lopez MI, Ferrer I, Poater A, Parella T, Fontrodona X,
Sola M, Llobet A, Rodriguez M, Romero I (2011) Inorg Chem
50:6044
31. Farrugia LJ (2012) J Appl Cryst 45:849
32. El Hatimi A, Gomez M, Jansat S, Muller G, Font-Bardia M,
Solans X (1998) J Chem Soc Dalton Trans 4229
33. Gottumukkala AL, Matcha K, Lutz M, de Vries JG, Minnaard AJ
(2012) Chem Eur J 18:6907
34. Abu-Surrah AS, Kettunen M, Lappalainen K, Piironen U, Klinga
M, Leskela M (2002) Polyhedron 21:27
35. Wang A-E, Xie J-H, Wang L-X, Zhou Q-L (2005) Tetrahedron
61:259
6. Roux EL, Mallmann AD, Merle N, Toufik M, Anwander R
(2015) Organometallics 34:5146
36. Jung E, Park K, Kim J, Jung H-T, Oh I-K, Lee S (2010) Inorg
Chem Commun 13:1329
7. Evans DA, Kozlowski MC, Tedrow JS (1996) Tetrahedron Lett
37:7481
123