Polyhedron 70 (2014) 39–46

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Polyhedron

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

0277-5387/$ - see front matter � 2013 Elsevier Ltd. All rights reserved.http://dx.doi.org/10.1016/j.poly.2013.12.023

⇑ Corresponding author. Tel.: +966 13 860 4491; fax: +966 13 860 4277.E-mail address: belali@kfupm.edu.sa (B. El Ali).

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 Arabiab Center for Petroleum and Minerals, King Fahd University of Petroleum & Minerals, Dhahran 31261, Saudi Arabiac Center of Research Excellence in Petroleum Refining and Petrochemicals, King Fahd University of Petroleum & Minerals, Dhahran 31261, Saudi Arabiad 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:Received 4 October 2013Accepted 22 December 2013Available online 30 December 2013

Keywords:PalladiumBis(oxazoline)Inherent chiralityCoupling reactions

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 thetwo heterocycles of the bidentate ligand and two chloride ions in a distorted square planar geometry. Thecoordination to the palladium ion allows these non C2-symmetric bis(oxazoline) ligand-based complexesto 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 showedhigh catalytic activities towards numerous C–C coupling reactions with various aryl halides, aryl boronicacids, alkenes and alkynes. The reactions were optimized for the most suitable temperature, solvent, andbase system.

� 2013 Elsevier Ltd. All rights reserved.

1. Introduction

Palladium-catalyzed C–C bond coupling reactions have beenestablished as a powerful tool for the production of monomersfor polymers, agrochemicals, pharmaceuticals, flavors and fra-grances [1]. During the last decades, the Suzuki–Miyaura [2],Mizoroki–Heck [3], and Sonogashira [4] coupling reactions havebeen playing key roles in organometallic chemistry and recent or-ganic synthesis. Particularly, these reactions are involved in themajority of methods used to construct biaryl compounds [5] forthe total synthesis of natural products, material science and supra-molecular chemistry [6]. Recently the scope and practical use ofsuch coupling reactions have significantly enhanced and the designand synthesis of new ligands to facilitate these coupling reactionshave great contributions to this progress [7]. A good number of re-ports deal with catalytic species based on transition metals andphosphine 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,

phosphine ligands are in general air and moisture sensitive. Thus,rather than the catalytic species generated in situ, the developmentof new catalysts that are well defined, efficient, inexpensive, insen-sitive to air and moisture, and less toxic is highly desirable. Analternative would be nitrogen-based ligands which are generallynon-toxic, stable to air/moisture, modular, and less expensive thanphosphine ligands [9]. Therefore, the current research is more fo-cused on the synthesis of ligands containing nitrogen as a donoratom 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] andparticularly 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 ofpalladium-bis(oxazoline) complexes in C–C bond coupling reac-tions have been reported so far [18]. In this paper, we report onthe 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 catalyticapplications to C–C bond cross coupling reactions such asSuzuki–Miyaura, Mizoroki–Heck, and Sonogashira reactions arepresented.

40 S.M. Shakil Hussain et al. / Polyhedron 70 (2014) 39–46

2. Experimental

2.1. Materials and instrumentation

2.1.1. MaterialsStarting material for the synthesis of ligands and complexes

was purchased from Sigma Aldrich and used without further puri-fication. Chlorobenzene (anhydrous) was purchased from SigmaAldrich and used as received. Other solvents used in the synthesiswere 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 fromFluka Chemie AG (Buchs, Switzerland). Palladium compounds werepurchased from Strem Company.

2.1.2. Instrumentation1H and 13C NMR spectra were recorded on 500 MHz Joel 1500

NMR machine. Chemical shifts (d) were reported in ppm relativeto tetramethyl silane (TMS) using CDCl3. IR spectra were recordedon Perkin-Elmer 16F PC FT-IR spectrometer and reported in wavenumbers (cm�1), or by Nicolet™ 6700 FT-IR spectrometer. Gaschromatography (GC) analyses were realized on Agilent GC 6890.The products of the reactions were also analyzed on GC–MS VarianSaturn 2000 equipped with 30 m capillary column (HP-5). Thin-layer chromatography (TLC) analyses were performed on silicagel Merck 60 F254 plates (250 lm layer thickness).

2.2. Synthesis of the ligands 1 and 2

We have adopted a synthetic route by analogy to otherbis(oxazoline) ligands [19,20]. A 100-mL two-necked round bot-tom flask fixed with a reflux condenser was charged substituteddicyanobenzene (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 for5 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 wasremoved under reduced pressure to give an oily residue whichwas dissolved in 25 mL of dichloromethane. The solution was ex-tracted twice with 15 mL of water and the aqueous phase waswashed with 15.0 mL of dichloromethane. The combined organiclayers were dried with sodium sulfate and the solvent was re-moved under vacuum to give the crude oil. Further purificationof the ligands was done by silica gel column chromatography(ether/dichloromethane 1/4).

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, 156.0,158.8, 161.6, 161.7; IR m (cm�1) 2969, 1656, 1488, 1354, 1233,1078, 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%.

2.2.2. 2,20-(4-Phenoxy-1,2-phenylene)bis(4-isopropyl-4,5-dihydrooxazole) (2)

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

� 2), 4.00–4.08 (m, 4H, OCH2 � 2), 1.84 (m, 2H, isopropyl CH� 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 (isopropylCH), 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, 130.6,131.6, 131.7, 156.0, 158.9, 163.0, 163.1; IR m (cm�1) 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 chargedwith Bis(benzonitrile)palladium(II) chloride (0.400 mmol, 0.153 g)and 1 (0.400 mmol) in CH2Cl2 (5.0 mL) at room temperature andstirred for 4 h. The reaction was monitored by TLC until no free 1was observed. The organic phase was separated and filtered andthe solvent was removed under reduced pressure. The resulting so-lid was dissolved in a minimum amount of CH2Cl2 and layered withhexane. After 24 h, the crystals started to develop. The crystalswere 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 diffractionanalysis.

2.3.1. Dichlorido(2,20-(4-phenoxy-1,2-phenylene)bis(4,4-dimethyl-4,5-dihydrooxazole)-N,N’)palladium(II) (A)

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, 120.7,125.7, 127.8, 130.5, 132.6, 154.3, 161.5, 163.7, 164.0; IR m (cm�1)2972, 1637, 1582, 1486, 1372, 1236, 1063, 961, 729; UV–Vis spec-trum (CH2Cl2) kmax, 301 nm (e = 1003 M�1 cm�1); Anal. Calc. forC22H24Cl2N2O3Pd (541.77): C, 48.77; H, 4.47; N, 5.17. Found: C,48.83; H, 4.66; N, 5.29%.

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, 133.1,134.6, 154.2, 161.7, 164.5, 164.8; IR m (cm�1) 3063, 2963, 1640,1585, 1484, 1380, 1228, 1064, 692; UV–Vis spectrum (CH2Cl2) kmax,299 nm (e = 2157 M�1 cm�1); Anal. Calc. for C24H28Cl2N2O3Pd(569.82): C, 50.59; H, 4.95; N, 4.92. Found: C, 50.28; H, 4.88; N,5.11%.

2.4. General procedure for the Suzuki–Miyaura coupling reaction

The reaction was conducted in a 15 mL round bottom flask. Arylhalide (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 for6 h at 70 �C under argon. After completion of the reaction, themixture was cooled down to room temperature, filtered and

Table 2Selected bond lengths (Å) and bond angles (o) for compounds A and B.

Bond lengths Bond angles

Compound APd1–N1 2.031(5) N1–Pd1–N2 87.6(2)Pd1–N2 2.056(5) N1–Pd1–Cl2 176.3(2)Pd1–Cl1 2.295(2) N2–Pd1–Cl2 91.7(2)Pd1–Cl2 2.280(2) N1–Pd1–Cl1 91.5(1)N1–C5 1.273(7) N2–Pd1–Cl1 174.0(1)N2–C12 1.264(7) Cl2–Pd1–Cl1 88.81(7)Compound BPd1–N1 2.018(4) N1–Pd1–N2 88.5(2)Pd1–N2 2.041(4) N1–Pd1–Cl1 88.3(1)Pd1–Cl1 2.285(2) N2–Pd1–Cl1 176.7(1)Pd1–Cl2 2.286(2) N1–Pd1–Cl2 178.3(1)N1–C1 1.274(6) N2–Pd1–Cl2 91.3(1)N2–C7 1.273(6) Cl1–Pd1–Cl2 91.97(8)

S.M. Shakil Hussain et al. / Polyhedron 70 (2014) 39–46 41

immediately analyzed by GC and GC–MS. The GC yield was deter-mined based on the amount of aryl halide. The reaction mixturewas washed with H2O and EtOAc and the organic layer was driedusing MgSO4. The solvent was removed under reduced pressureand the product was separated by column chromatography usinghexane–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 agreementwith those observed in literature.

2.5. General procedure for Mizoroki–Heck coupling reaction

The reaction was conducted in a 15 mL round bottom flask. Arylhalide (0.50 mmol), alkene (0.75 mmol), Pd–BOX complex(0.010 mmol), K2CO3 (2.0 mmol), DMF (5.0 mL) was stirred for12 h at 70 �C under argon. After completion of the reaction, themixture was cooled down, filtered and immediately analyzed byGC and GC–MS. The GC yield was determined based on the amountof aryl halide. The reaction mixture was washed with H2O andEtOAc and the organic layer was dried using MgSO4. The solventwas 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 ofthe compounds 8a [31], 8b [31], 8e [31], 8c [32], 8d [33] and 8f[34] were in total agreement with those observed in literature.

2.6. General procedure for Sonogashira coupling reaction

The reaction was conducted in a 15 mL round bottom flask. Arylhalide (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 thencooled down, filtered and immediately analyzed by GC andGC–MS. The GC yield was determined based on the amount of arylhalide. The reaction mixture was washed with H2O and EtOAc andthe organic layer was dried using MgSO4. The solvent was removedunder reduced pressure and the product was separated by columnchromatography using hexane–EtOAc (97:3) solvent system to

Table 1Crystallographic data for A and B.

Compound A B

Chemical formula C22H24Cl2N2O3Pd�0.25H2O C24H28Cl2N2O3PdFormula weight 546.24 569.78Crystal system triclinic triclinicSpace group P�1 P�1T (K) 120 296Radiation Mo Ka (k = 0.71073 Å)qcalc (g cm�3) 1.619 1.521a (Å) 9.639(1) 9.9207(6)b (Å) 13.045(2) 12.2824(7)c (Å) 18.610(3) 12.3884(7)a (�) 84.220(2) 108.988(1)b (�) 85.894(2) 110.775(1)c (�) 74.488(2) 101.803(1)V (Å3) 2240.9(5) 1244.1(1)Z 4 2Refl. collect./Uniq. 30241/11093 17140/6173Refl. obser. [I > 2r(I)] 8638 4690Rint 0.0453 0.0201Data/restr./parameter 11093/4/650 6173/0/330Goodness-of-fit (GOF) on F2 1.094 1.034R indices [I > 2r(I)] R1 = 0.0712. wR2 = 0.1869 R1 = 0.0561.

wR2 = 0.1630R indices (all data) R1 = 0.0906. wR2 = 0.1980 R1 = 0.0711.

wR2 = 0.1756Largest difference in peak,

hole (e �3)3.978, �2.539 1.746, �0.392

give the pure products. The characterization data of the compound10 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 SmartApex system equipped with a graphite monochromatized Mo Karadiation (k = 0.71073 Å). The data were collected using SMARTand the integration was performed using SAINT [21]. An empiricalabsorption correction was carried out using SADABS [22]. The struc-tures were solved by direct methods with SHELXS-97 and refinedby full-matrix least squares procedures on F2 using the programSHELXL-97 [23]. All non-hydrogen atoms were refined anisotropi-cally except disordered carbon atoms: C40A, C40B, C40C, C40Dand C50 in compound A, were isotropically refined. Hydrogenatoms on un-disordered carbon atoms were placed at calculatedpositions using a riding model. The phenoxy-group atoms in bothcompounds were constrained to double site partial occupancieswhich were refined to 0.685(9) and 0.759(9) values respectivelyfor the two molecules of the asymmetric unit of compound Aand 0.658(8) for compound B. Crystal data and details of the datacollection are summarized in Table 1. Selected bond lengths andbond angles are given in Table 2.

3. Results and discussion

3.1. Synthesis of ligands and corresponding Pd(II)-complexes

The ligands 1 and 2 were synthesized by treating substitutedphthalonitrile with 2-achiral amino alcohol in the presence ofZn(OTf)2 as depicted in Scheme 1. The treatment of ligands 1 and2 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 fullycharacterized by elemental and spectroscopic techniques and themolecular structures were determined on the basis of X-raycrystallography.

3.2. Molecular structures of compounds A and B

Complex A crystallizes in the P�1 space group with two mole-cules in the asymmetric unit. The palladium ion is bound to thenitrogen atoms of the two oxazoline heterocycles of the bidentateligand 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 thePd–N and Pd–Cl bond distances are similar to those found in otherbis(oxazoline) palladium complexes [20,24,25]. The dihedral

+HO NH2

R1

Zn(OTf)2reflux. 24 h N ONO

PhO

R1R

PhO

CNNC

N ONO

PhO

R1R

+ Pd(PhCN)2Cl2CH2Cl2RT, 4h N ONO

PhO

Pd

ClClR1RComplex A, R = R1 = methyl

Complex B, R = H, R1 = isopropyl

RR1

R

RR1RR1

Ligand 1, R = R1 = methylLigand 2, R = H, R1 = isopropyl

Scheme 1. Synthesis of the ligands and the palladium-bis(oxazoline) complexes.

N+

OON+

Pd2-

Cl Cl

O

N+

OON+

Pd2-

Cl Cl

O

Fig. 2. Inherent chirality in palladium bis(oxazoline) complexes.

42 S.M. Shakil Hussain et al. / Polyhedron 70 (2014) 39–46

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, thecoordination to the palladium ion allows this non C2-symmetricbis(oxazoline) ligand-based complex to acquire a rigid backbonecurvature and the molecule resembles a chair with the [PdN2Cl2]moiety being the seat and the benzene ring spacer being the backof the chair. The dihedral angle between the mean planes of thetwo moieties is 87.4(2)� and 85.7(2)� for the two molecules respec-tively (Fig. 1). This rigid curvature generates an inherent chiralityin the complex and the two mirror images are not superimposable(Fig. 2). The complex crystallizes as a pseudoracemate and thepacking 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 coplanaritywith the benzene ring spacer with a torsion angle of 83(1)� and85(1)� for the two molecules respectively.

Compound B crystallizes also in the P�1 space group and theasymmetric unit contains a single molecule with a distorted square

Fig. 1. Molecular structure of compound A.

planar geometry similarly to A (Fig. 3). The cis-bond angles aroundthe palladium ion are in the range 88.3(1)–91.97(8)� and the Pd–Nand Pd–Cl bonds lengths are in normal ranges. The dihedral angles,between each of two oxazoline heterocycles and the benzene ringspacer mean plane are 40.0(3)� and 42.2(3)� respectively. Similarlyto A, the complex presents a rigid curvature in a chair-like mode.The dihedral angle between the mean planes of [PdN2Cl2] moietyand the benzene ring spacer is 78.4(1)�. The complex crystallizesas 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 thesymmetry of the ligand. The phenyl ring of the phenoxy pendantarm is not coplanar with the benzene ring spacer showing a torsionangle of 83(1)�.

3.3. Suzuki–Miyaura coupling reaction of iodobenzene withphenylboronic acid catalyzed by Pd–BOX (A or B)

3.3.1. Effect of solvents and bases in Suzuki–Miyaura coupling reactionof iodobenzene with phenylboronic acid

The new palladium-bis(oxazoline) complexes A and B were ap-plied in catalytic studies of the Suzuki–Miyaura, Mizoroki–Heckand Sonogashira coupling reactions. The catalytic studies were

Fig. 3. Molecular structure of compound B.

Table 3Effect of Solvent and base in Suzuki–Miyaura coupling reaction between iodobenzeneand phenylboronic acid in the presence of Pd–BOX Aa (and Bb).

Entry Solvent Base Yield (%)c

1 DMF K2CO3 1002 CH2Cl2 K2CO3 273 Acetonitrile K2CO3 734 DME K2CO3 545 Toluene K2CO3 636 Dioxane K2CO3 527 DMSO K2CO3 998 DMF Et3N 519 DMF Na2CO3 84

10 DMF K-OH 9811 DMF K3PO4 8012 DMF K2HPO4 7613 DMF KH2PO4 12

a Reaction conditions: Pd–BOX A (0.0100 mmol), Iodobenzene (0.500 mmol),phenylboronic acid (0.600 mmol), base (2.00 mmol, solvent (5.0 mL), 70 �C, 6 h.

b 99% GC yield with complex B under the conditions of entry 1.c Determined by GC.

S.M. Shakil Hussain et al. / Polyhedron 70 (2014) 39–46 43

initiated on Suzuki–Miyaura coupling reactions by adopting iodo-benzene and phenylboronic acid model substrates in the presenceof Pd–BOX complex A as catalyst at 70 �C for 6 h (Eq. (1)). Differentsolvents and bases were screened and the results are summarizedin Table 3. It was interesting to observe in all experiments that theexpected biphenyl was formed as the sole product of the reactions.A complete conversion of iodobenzene was observed in 6 h usingK2CO3 as a base and DMF as a solvent (Table 3, entry 1). However,the use of polar aprotic solvent having low boiling point such asCH2Cl2 led to poor conversion of iodobenzene (Table 3, entry 2).The conversion was improved with polar aprotic solvents that havehigher boiling point such as acetonitrile and DME (Table 3, entries

I BHO

HO+ palladium catalyst

K2CO3, DMF70 oC, 6 h3a 4a 5a

ð3Þ

3 and 4). It is important to note that the non-polar solvents such astoluene and dioxane gave relatively low conversions (Table 3, en-tries 5 and 6), which are similar to those observed in literatureusing other Pd–BOX complexes. The results obtained in Suzukireaction with the complexes A and B are superior to those observedby Takemoto and co-workers [18]. The excellent conversion wasalso 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. Anorganic base, such as Et3N, decreased the conversion (Table 3, entry8). However, excellent conversion was obtained by using inorganicbases such as Na2CO3 and KOH (Table 3, entries 9 and 10), whichare consistent with those observed in such kind of transformation[26]. We have further studied the effects of various other basessuch as potassium phosphate (mono-, di-, and tri-basic). Di- andtri-potassium phosphate led to very good conversions (Table 3, en-tries 11 and 12). However, mono-potassium phosphate gave verylow conversion (Table 3, entry 13).

I BHO

HO+ Complex A

base, solvent70 oC, 6 h3a 4a 5a

ð1Þ

3.3.2. Effect of activated and deactivated aryl halides with arylboronicacids in Suzuki–Miyaura coupling reaction using complex A

We further extended the study of the catalytic activity of thenew Pd–BOX complex A. We have examined the effect of variousaryl halides with different arylboronic acids (Eq. (2)) and the re-sults are summarized in Table 4. The Suzuki coupling reactions ofdifferent aryl halides containing electron rich and electron with-drawing substituents reacted smoothly with phenylboronic acidto give the biaryl compounds as sole products in high conversions(Table 4, entries 1–3). Similarly, the Suzuki coupling reactions ofvarious arylboronic acids with iodobenzene underwent almostquantitatively to give only the targeted coupling products. Theseresults indicate that electron rich and electron withdrawingsubstituents on the phenyl ring of aryl boronic acids have no majoreffect on such kind of transformation (Table 4, entries 4–6).

Ar-I + Ar-B(OH) 2Complex A

K2CO3, DMF70°C, 6 h

Ar-Ar

3a-d 4a-d 5b-gð2Þ

3.3.3. Effect of the type of palladium catalysts in Suzuki–Miyauracoupling reaction of iodobenzene with phenylboronic acid

We have compared the catalytic activity of the new Pd–BOXcomplex 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–BOXA > Pd(OAc)2 > PdCl2(PhCN)2 > PdSO4. This result clearly indicatesthat the palladium catalyst with effective ligands play a key roleto improve the conversion of these reactions [26].

3.4. Mizoroki–Heck coupling reactions of aryl iodides with olefinscatalyzed by Pd–BOX complex A or B

We next examined the catalytic activities of the new complexesin Mizoroki–Heck coupling reaction of different aryl iodides withmethyl acrylate and with styrene (Eq. (4)). We have observed thatactivated and deactivated aryl iodides reacted successfully withthe electron-deficient alkenes such as methyl acrylate to give onlythe desired coupling products in quantitative yield (Table 6, entries1–5). However, the treatment of iodobenzene with styrene at 70 �Cafforded 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 activityin the coupling reaction of iodobenzene with methyl acrylate andafforded only the coupling product with excellent conversion ofiodobenzene (Table 6, entry 8).

OMe

O

6Ar-I + Complex AK2CO3,DMF70 oC,12h

Product

3a-e8a-f

7

or ð4Þ

Table 4Effect of various aryl halides and arylboronic acids in Suzuki–Miyaura coupling reaction using Pd–BOX (A) as catalysta.

Entry Aryl halides 3 Aryl boronic acids 4 Coupling product 5 Yield %b

1IO2N

3bB

OH

OH4a

O2N

5b

89

2IH3COC

3cB

OH

OH4a

H3COC5c

86

3IH2N

3dB

OH

OH4a

H2N5d

81

4I

3a B

Cl

Cl

OH

OH4b

Cl

Cl5e

87

5I

3aB

OH

OH4c

F3C F3C5f

95

6I

3aB

OH

OH4d

H3C H3C5g

94

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.b Isolated yield.

Table 5Relative activities of different palladium catalysts in Suzuki–Miyaura couplingreaction of iodobenzene with phenylboronic acid.a

Entry Palladium catalysts Yield (%)b

1 Pd–BOX (A) 1002 Pd(OAc)2 933 PdCl2(PhCN)2 884 PdSO4 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 6Mizoroki–Heck coupling reactions of aryl iodides with olefins catalyzed by Pd–BOX comp

Entry Aryl halides 3 Olefins 6 or 7

1I

3a OMe

O

62

IO2N3b OMe

O

63

IH3COC3c OMe

O

64

IH2N3d OMe

O

65 3d

IMeO3e

OMe

O

6

44 S.M. Shakil Hussain et al. / Polyhedron 70 (2014) 39–46

3.5. Sonogashira coupling reaction of iodobenzene withphenylacetylene catalyzed by the Pd–BOX complex A or B

Similarly, we have investigated the catalytic activity of the newPd–BOX complexes (A) and (B) in Sonogashira coupling reaction(Eq. (5)). We have studied the coupling reaction of iodobenzenewith phenylacetylene with Pd–BOX (A) or (B) as catalyst and inthe 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).

lex A.a

Products 8 Yield %b

CO2Me

8a

96

CO2Me

8bO2N

97

CO2Me

8cH3COC

96

CO2Me

8dH2N

94

CO2Me

8eMeO

94

Table 7Sonogashira coupling reaction of iodobenzene with phenylacetylene catalyzed by Pd–BOX complex (A) or (B).a

No. Palladium complex Yield (%)b

1 Complex A 752 Complex B 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.

Table 6 (continued)

Entry Aryl halides 3 Olefins 6 or 7 Products 8 Yield %b

6I

3a 78f

65

7I

3a 78f

92c

8I

3a OMe

O

6

CO2Me

8a

95d

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.b Isolated yield.c Temperature was 110 �C.d Pd–BOX (B) was used.

I + HC CPd-BOX A / B

CuI, Et3N, DMF70 oC, 12h

C C ð5Þ

S.M. Shakil Hussain et al. / Polyhedron 70 (2014) 39–46 45

4. Conclusion

We have described in this study the synthesis and characteriza-tion of two new non C2-symmetric bis(oxazoline) ligands and theirdichloride palladium complexes for which the X-ray structureswere determined. The coordination to the palladium ion allowsthese bis(oxazoline) ligand-based complexes to acquire a rigidbackbone curvature and an inherent chirality. The complexes werefound to be highly active and versatile catalysts in Suzuki–Miya-ura, Mizoroki–Heck and Sonogashira coupling reactions of elec-tron-deficient and electron rich substrates with no majordifferences in their activities. Further research is in progress to im-prove the catalytic performance of these catalysts especially inSonogashira coupling reactions.

Acknowledgements

The authors would like to acknowledge the support provided byKing Abdulaziz City for Science and Technology (KACST) throughthe Science & Technology Unit at King Fahd University of Petro-leum & Minerals (KFUPM) for funding this work through projectNo. 11-PET1665-04. as part of the National Science, Technologyand Innovation Plan.

Appendix A. Supplementary data

CCDC 955503 and 929604 contains the supplementary crystal-lographic data for A and B. These data can be obtained free ofcharge via http://www.ccdc.cam.ac.uk/conts/retrieving.html, orfrom 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 thisarticle can be found, in the online version, at http://dx.doi.org/10.1016/j.poly.2013.12.023.

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