New pallada- and platinacycle complexes of phosphorus ylide: Synthesis, structural characterization, antioxidant capacity and catalytic behavior towards Mizoroki-Heck reactions

Article abstract of DOI:10.1016/j.poly.2017.06.043

The reactions of α-keto stabilized phosphorus ylide Ph₂P(CH₂)₂PPh₂C(H)C(O)C₆H₄-m-Br (Y) with [MCl₂(cod)] (M?=?Pd or Pt; cod?=?1,5-cyclooctadiene) in equimolar ratio using dichloromethane as a solvent are reported. These reactions led to the formation of new P, C-chelated pallada- and platinacycle complexes [MCl₂(Ph₂P(CH₂)₂PPh₂C(H)C(O)C₆H₄-m-Br)] (M?=?Pd (C1) and Pt (C2)). Characterization of the obtained compounds was performed by elemental analysis and IR, ¹H, ¹³C, and ³¹P NMR spectroscopic methods. Also, the unequivocal structures of these complexes were characterized crystallographically. Both structures consist of six-membered rings formed by coordination of the phosphorus ylide (Y) through the phosphine group and the ylidic carbon atom to the metal center. Furthermore, palladacycle C1 was employed as an efficient catalyst in the Mizoroki-Heck coupling reaction of several aryl chlorides and olefins. The coupled products of these reactions were obtained under aerobic conditions in high yields using aqueous DMF as a solvent. Additionally, the antioxidant capacity of the reported compounds with butylated hydroxytoluene (BHT) as standard was evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging method. Apparently, all synthesized compounds possess strong antioxidant capacity (IC₅₀; 0.584?±?0.009–0.751?±?0.003?mg/ml).

Full text of DOI:10.1016/j.poly.2017.06.043

Accepted Manuscript
New pallada- and platinacycle complexes of phosphorus ylide: synthesis, struc-
tural characterization, antioxidant capacity and catalytic behavior towards Miz-
oroki-Heck reactions
Seyyed Javad Sabounchei, Ali Hashemi, Abed Yousefi, Parviz Gohari
Derakhshandeh, Roya Karamian, Mostafa Asadbegy, Kristof Van Hecke
PII:
S0277-5387(17)30461-8
DOI:
http://dx.doi.org/10.1016/j.poly.2017.06.043
POLY 12724
Reference:
Polyhedron
To appear in:
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Accepted Date:
13 April 2017
24 June 2017
Please cite this article as: S. Javad Sabounchei, A. Hashemi, A. Yousefi, P. Gohari Derakhshandeh, R. Karamian,
M. Asadbegy, K. Van Hecke, New pallada- and platinacycle complexes of phosphorus ylide: synthesis, structural
characterization, antioxidant capacity and catalytic behavior towards Mizoroki-Heck reactions, Polyhedron (2017),
doi: http://dx.doi.org/10.1016/j.poly.2017.06.043
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New pallada- and platinacycle complexes of phosphorus ylide: synthesis,
structural characterization, antioxidant capacity and catalytic behavior
towards Mizoroki-Heck reactions
Seyyed Javad Sabouncheia*, Ali Hashemia, Abed Yousefia, Parviz Gohari
Derakhshandehb, Roya Karamianc, Mostafa Asadbegyc, Kristof Van Heckeb*
a Faculty of Chemistry, Bu-Ali Sina University, Hamedan, 65174, Iran
b XStruct, Department of Inorganic and Physical Chemistry, Ghent University,
Krijgslaan 281-S3, B-9000 Ghent, Belgium
c Department of Biology, Faculty of Science, Bu-Ali Sina University, P. O. Box
65175/4161, Hamedan - Iran
Abstract
The reactions of α-keto stabilized phosphorus ylide
Ph2P(CH2)2PPh2C(H)C(O)C6H4-m-Br (Y) with [MCl2(cod)] (M = Pd or Pt; cod =
1,5-cyclooctadiene) in equimolar ratio using dichloromethane as a solvent are
reported. These reactions led to the formation of new P, C-chelated pallada- and
platinacycle complexes [MCl2(Ph2P(CH2)2PPh2C(H)C(O)C6H4-m-Br)] (M = Pd
(C1) and Pt (C2)). Characterization of the obtained compounds was performed by
elemental analysis and IR, 1H, 13C, and 31P NMR spectroscopic methods. Also, the
*Corresponding author. E–mail address: jsabounchei@yahoo.co.uk; kristof.vanhecke@ugent.be.
1

unequivocal structures of these complexes were characterized crystallographically.
Both structures consist of six-membered rings formed by coordination of the
phosphorus ylide (Y) through the phosphine group and the ylidic carbon atom to
the metal center. Furthermore, palladacycle C1 was employed as an efficient
catalyst in the Mizoroki-Heck coupling reaction of several aryl chlorides and
olefins. The coupled products of these reactions were obtained under aerobic
conditions in high yields using aqueous DMF as a solvent. Additionally, the
antioxidant capacity of the reported compounds with butylated hydroxytoluene
(BHT) as standard was evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH)
free radical scavenging method. Apparently, all synthesized compounds possess
strong antioxidant capacity (IC50; 0.584 ± 0.009 to 0.751 ± 0.003 mg/ml).
Keywords: Pallada- and platinacycle; Phosphorus ylide; X-ray structure; Mizoroki-
Heck reaction; Antioxidant capacity.
1. Introduction
Stabilized phosphorus ylides are an important class of compounds that have
attracted considerable interest because of their value for a variety of industrial,
biological and chemical synthetic uses [1-4]. Unsymmetrical α-keto stabilized
ylides derived from diphosphines have shown more useful application in
organometallic chemistry due to their ambidentate character as ligands [5-9].
2

Furthermore, they are valuable key intermediates in metal-mediated organic
synthesis [10,11]. The coordination behavior of these compounds towards several
metal ions has been studied and it was found that phosphorus ylides can coordinate
to metal ions in three modes as depicted in Chart 1: monodentate (or unidentate),
bidentate (or chelating) and bridging (or bridging bidentate) modes.
Chart 1. Possible binding modes of phosphorus ylides to the metal M.
When a metal ion such as Hg(II) or Ag(I) interacts only with the free P atom of
the diphosphine group, the coordination structure is regarded as monodentate
[12,13]. If the coordination of ylide occurs through the Cα atom of the ylidic
group, it is categorized in the same above-mentioned coordination mode [14].
3

However, the ylides can also coordinate to the metal ions through the O atoms of
the carbonyl group. A few examples of O-coordinated ylides are known, some of
these complexes include a hard and very oxophilic metal center, such as Sn(IV)
[15] or group 4 metal ions with a high oxidation number e.g. Ti(IV), Zr(IV) or
Hf(IV) [16].
The bidentate (or chelating) coordination mode occurs when a metal ion (for
example Pd(II) or Cu(I)) interacts with two P and C atoms of the ylidic group to
give P, C-chelated complexes [17,18]. Although the P, O-chelated coordination
mode is also possible, it has to the best of our knowledge only been observed in the
Pd(II) complexes of mixed phosphine–β-ketophosphorus ylides [19]. Finally, the
bridging coordination mode is observed when a metal ion binds to one phosphorus
ylide through the P atom and another metal ion binds to the Cα or O atom [20].
The investigation of reactivity and coordination chemistry of carbonyl stabilized
ylides is an important research field of our group [12-14,17,18]. Recently, we have
reported the synthesis of palladium(II) complexes containing such phosphorus
ylides [17,21-23]. Now, we aim to expand the scope of these complexes to new
platinacycle complexes of bidentate phosphorus ylides.
As known from literature, palladium and platinum compounds might have
promising potential antioxidant applications [24-26]. Reactive oxygen or nitrogen
species (ROS or RNS), which are formed naturally in cells, have important roles in
4

for example cell signaling. However, high amounts of free radicals are hazardous
to the organisms and can damage major cell components, including DNA and
RNA, polypeptides chains and phospholipids that play an important role in the
development of diseases such as cancer and other disorders [27,28]. Antioxidants
such as ascorbic acid may prevent free radical damages in biological systems
[29,30]. In recent years, the syntheses of new compounds with antioxidant
properties have become very interesting [31-33]. So we devoted this study to
illuminate the potential of the reported compounds in free radical scavenging.
Additionally, Pd(II) complexes bearing phosphine groups have been extensively
applied as efficient catalysts in cross-coupling reactions [21-23,34-37].
Specifically, the Mizoroki-Heck reaction, which has emerged as the most
important and reliable method for construction of functionalized olefins, has been
catalyzed with the P, C-chelated Pd(II) complexes of such phosphorus ylides [38-
41]. Recently, a variety of catalytic systems for the Mizoroki-Heck coupling
reaction has been reported using aqueous media [41-44]. Application of
palladacycle complexes of phosphorus ylides as efficient catalysts in Mizoroki-
Heck coupling reactions of aryl chlorides under relatively mild experimental
conditions is one of the purposes of this work.
We have now focused our attention to the synthesis, spectroscopic (IR and
NMR) and X-ray structural characterization of these new pallada- and platinacycle
5

complexes of phosphorus ylide. Furthermore, the antioxidant capacity of these
complexes and also the palladium(II) catalyzed Mizoroki-Heck coupling reaction
of various aryl chlorides and olefins is reported.
2. Experimental
2.1. Materials and methods
Phosphorus ylide Ph2P(CH2)2PPh2C(H)C(O)C6H4-m-Br (Y) was prepared based
on literature methods [12]. Synthesis of Pd/Pt(II) complexes was carried out under
dry nitrogen using standard Schlenk techniques. [MCl2(cod)] (M = Pd or Pt)
complexes were prepared according to previously published procedures [45].
Dichloromethane was used as reagent grade and dried over P2O5. Elemental
analysis was performed on a Leco, CHNS-932 apparatus. The 1H, 13C and 31P
NMR spectra were recorded on BrukerAvance 500 MHz, 400 MHz and 250 MHz
and Jeol 90 MHz spectrometers in CDCl3 or DMSO-d6 as solvents at 25 °C. IR
spectra were recorded on KBr pellets using a Shimadzu 435-U04
spectrophotometer in the region of 4000-400 cm–1.
2.2. Crystallography
For the structures of C1 and C2, X-ray intensity data was collected at RT and
100 K, respectively, on a Rigaku Oxford Diffraction Supernova Dual Source (Cu
6

at zero) diffractometer equipped with an Atlas CCD detector using ω scans and
CuKα (λ = 1.54184 Å) radiation. The images were interpreted and integrated with
the program CrysAlisPro [46]. Using Olex2 [47], the structures were solved by
direct methods using the ShelXS [48] structure solution program and refined by
full matrix least-squares on F2 using the ShelXL [49] program package. Non-
hydrogen atoms were anisotropically refined and the hydrogen atoms in the riding
mode and isotropic temperature factors fixed at 1.2 times U(eq) of the parent
atoms.
2.3. Synthesis of complexes [MCl2(Ph2P(CH2)2PPh2C(H)C(O)C6H4-m-Br)]
(M = Pd or Pt)
General procedure: to a [MCl2(cod)] (M = Pd or Pt) (0.5 mmol)
dichloromethane solution (5 ml), a solution of ylide Y (0.5 mmol) (5 ml, CH2Cl2)
was added. The resulting solution was stirred for 2 h at room temperature and then
concentrated to ca. 2 ml under reduced pressure and treated with n-hexane (15 ml)
to afford the Pd(II) and Pt(II) complexes of phosphorus ylide.
2.3.1. Data for Pd(II) complex [PdCl2(Ph2P(CH2)2PPh2C(H)C(O)C6H4-m-Br)]
(C1). Yield: 0.323 g (81%). M.p. 208-210 °C (dec.). Anal. Calcd. for
C34H29BrCl2OP2Pd (%): C, 52.85; H, 3.78. Found: C, 52.93; H, 3.84. IR (KBr
7

Disk) ν(cm-1): 1625 (CO). 1H NMR (250.13 MHz, DMSO-d6) δH (ppm): 3.07–3.84
(br, CH2, 4H merged with residual H2O); 6.15 (br, CH); 7.03–8.39 (m, 24H, Ph).
31P NMR (36.26 MHz, DMSO-d6) δP (ppm): 22.74 (d, PPh2, 2JP-P = 21.76 Hz);
30.93 (bd, PCH, 2JP-P = 23.85 Hz). 13C NMR (62.90 MHz, DMSO-d6) δC (ppm):
20.25 (b, CH2); 121.84–140.18 (Ph); 194.58 (s, CO).
2.3.2. Data for Pt(II) complex [PtCl2(Ph2P(CH2)2PPh2C(H)C(O)C6H4-m-Br)]
(C2). Yield: 0.284 g (75%). M.p. 243-245 °C (dec.). Anal. Calcd. for
C34H29BrCl2OP2Pt (%): C, 45.76; H, 3.28. Found: C, 47.85; H, 3.38. IR (KBr Disk)
ν(cm-1): 1636 (CO). 1H NMR (89.60 MHz, DMSO-d6) δH (ppm): 3.01–3.78 (br,
CH2, 4H merged with residual H2O); 6.26 (br, CH); 7.30–8.41 (m, 24H, Ph). 31P
NMR (36.26 MHz, DMSO-d6) δP (ppm): 6.52 (dd, PPh2, 1JPt-P = 3952.% Hz, 2JP-P =
13.05 Hz); 20.75 (bdd, PCH, 2JPt-P = 130.17 Hz, 2JP-P = 23.85 Hz). 13C NMR (62.90
MHz, DMSO-d6) δC (ppm): 19.97 (b, CH2); 121.83–140.04 (Ph); 194.73 (s, CO).
2.4. Typical procedure for the Mizoroki-Heck coupling reaction
2.4.1. General procedure: palladacycle C1 (0.005 mmol), olefin (0.75 mmol),
aryl chloride (0.5 mmol), K2CO3 (1.0 mmol) and DMF/H2O (2 ml, 1:1) were added
to a small tube and the mixture was heated to 110 °C for 6 h in the presence of air.
The reactions were monitored by thin-layer chromatography (TLC). At the end of
8

the cross-coupling reactions, the mixture was cooled, extracted with n-
hexane:EtOAc (8:2), filtered and purified by recrystallization from ethanol and
water or purified by silica gel column chromatography (n-hexane:EtOAc, 8:2).
2.4.2. Data for Ph-CH=CH-Ph (3a). M.p. 122-124 °C. 1H NMR (500.13 MHz,
CDCl3) δH (ppm): 7.10-7.51 (m, 12H). 13C NMR (125.77 MHz, CDCl3) δC (ppm):
137.81, 129.16, 128.10, 127.00 [50].
2.4.3. Data for p-CH3O-Ph-CH=CH-Ph (3b). M.p. 132-134 °C. 1H NMR (400.61
MHz, CDCl3) δH (ppm): 3.75 (s, 3H, OCH3), 6.82-7.43 (m, 11H). 13C NMR
(100.62 MHz, CDCl3) δC (ppm): 159.32, 137.66, 130.16, 128.64, 128.22, 127.72,
127.21, 126.63, 126.25, 114.14, 55.34 (s, OCH3) [51].
2.4.4. Data for p-CH3OC-Ph-CH=CH-Ph (3c). M.p. 141-144 °C. 1H NMR
(89.60 MHz, CDCl3) δH (ppm): 2.58 (s, 3H), 6.81–8.53 (m, 7H). 13C NMR (125.77
MHz, CDCl3) δC (ppm): 196.99 (s,CO), 139.59,135.41, 130.98, 129.77, 129.04,
128.91, 128.82, 128.35, 126.92, 126.61, 27.50 (s, CH3) [51].
2.4.5. Data for Ph-CH=CHCOOEt (3d). 1H NMR (89.60 MHz, CDCl3) δH
(ppm): 7.06-8.05 (m, 6H), 6.35 (d, 1H, J = 15.03 Hz), 4.09 (q, 2H, J = 5.07 Hz),
1.15 (t, 3H, J = 5.11 Hz). 13C NMR (100.62 MHz, CDCl3) δC (ppm): 165.92 (s,
CO), 148.40, 141.51, 140.51, 128.52, 124.08, 122.52, 60.92 (s, CH2), 14.19 (s,
CH3) [52].
9

2.4.6. Data for p-CHO-Ph-CH=CHPh (3e). M.p. 112-114 °C. 1H NMR (500.13
MHz, CDCl3) δH (ppm): 7.13-8.03 (m, 11H), 10.06 (s, 1H). 13C NMR (127.77
MHz, CDCl3) δC (ppm): 192.71 (s, CO), 138.79, 137.26, 137.14, 132.73, 130.97,
129.79, 129.26, 129.21, 128.58, 127.61, 127.52, 127.12 [53].
The following compounds gave data consistent with those published: (E)-1-
methyl-4-styrylbenzene [54], (E)-ethyl-3-(4-formylphenyl)acrylate [55], (E)-ethyl-
3-(4-acetylphenyl)acrylate [52], (E)-ethyl-3-(4-methylphenyl)acrylate [56] and (E)-
ethyl-3-(4-methoxyphenyl)acrylate [56].
2.5. Antioxidant capacity
Antiradical capacity of the compounds was measured according to Mensor et al.
[57]. In order to obtain dilutions, different sample concentrations were prepared in
DMSO (0.2 to 1 mg/ml) and 2.5 ml of each concentration was added to 1 ml of a
DMSO solution of DPPH (0.3 mM). The samples were first kept in darkness at
room temperature for 30 min and then bleaching of DPPH was read at 517 nm. The
inhibition in percent for each concentration was calculated according to the
following formula:
Antioxidant capacity (%) = [1– (As – Ab)/Ac] × 100
10

Where, As contains 2.5 ml of samples + 1 ml of DPPH, Ab contains 2.5 ml of
samples + 1 ml DMSO and Ac contains 1 ml of DPPH + 2.5 ml DMSO. Tests were
carried out in triplicate and BHT was used as a positive control. The IC50 values,
which represent the concentration of the sample that caused 50% inhibition, were
calculated from the graph, plotting the inhibition percentage against sample
concentration.
3. Results and discussion
3.1. Synthesis
Reaction of ligand Y with [MCl2(cod)] (M = Pd or Pt) in equimolar ratio
yielded the new P, C-chelated pallada- and platinacycle complexes
[MCl2(Ph2P(CH2)2PPh2C(H)C(O)C6H4-m-Br)] (M = Pd (C1) and Pt (C2)) (Scheme
1). All complexes are moderately soluble in dichloromethane and insoluble in non-
polar solvents, such as n-hexane.
11

Scheme 1. Synthesis of pallada and platinacycle complexes C1 and C2.
3.2. Spectroscopy
The structure of the complexes was successfully characterized by 1H, 13C and
31P NMR spectroscopic methods and other conventional techniques such as IR and
elemental analysis. Table 1 shows a brief summary of these data.
Table 1. Spectroscopic data for compounds
Y
,
C1 and C2
IR; ν(CO)
cm-1
1H NMR;
δ(PCH) ppm
4.05
13C NMR;
δ(CO) ppm
183.35
31P NMR; δ(PCH)
and (PPh2) ppm
14.47, -15.63
30.93, 22.74
Compound
1571
1625
Y
1
6.15
194.58
1636
6.26
194.74
20.75, 6.52
2
Also, the exact structure of the complexes C1 and C2 at atomic resolution was
unequivocally determined by single crystal X-ray diffraction. The CHN elemental
analysis of the pallada- and platinacycle complexes indicated a 1:1 stoichiometry
between the MCl2 (M = Pd or Pt) and the phosphorus ylide.
Coordination of the ylide through the carbon atom (chelating mode) causes an
increase in the ν(CO) frequency, while for O-coordination a lower shift for this
frequency is expected [58]. The ν(CO), which is sensitive to complexation, occurs
at around 1570 cm-1 in the parent ylide, as in the case of other resonance stabilized
12

ylides [59]. The IR absorption bands around 1630 cm-1 show a significantly higher
frequency shift of ν(CO) than those of phosphorus ylide Y (see supplementary
data). Thus, the IR data obtained indicates that the chelation of the ylide to Pd(II)
and Pt(II) chlorides occurs through the ylidic carbon atom and PPh2 group [17,20].
The 31P chemical shift values for complexes C1 and C2 appear to be shifted
downfield with respect to the parent ylide, indicating that coordination of the ylide
occurred (Figure 1). The 31P NMR spectrum of complex C1 exhibits two doublets
around 23 and 31 ppm, which can be assigned to the PPh2 and PCH groups,
respectively. Whereas, the 31P NMR spectrum of C2 shows these peaks around 6
and 21 ppm along with two satellite peaks due to 195Pt-31P coupling.
13

Figure 1. 31P NMR spectra of Y, C1 and C2.
Also, the 1H NMR spectra show all the expected resonances of these complexes
(see supplementary data). The 1H chemical shift values for complexes C1 and C2
appear to be shifted downfield with respect to the parent ylide, as a consequence of
the P, C-coordination character of the ylide. Similar behavior was observed earlier
in the case of ylide complexes of copper(I) chlorides [18]. It must be noted that O-
coordination of the ylides generally leads to the formation of cis and trans isomers,
giving rise to two different signals in the 1H and 31P NMR spectra [60].
14

The most important aspect of 13C NMR spectra of these complexes is the
downfield shift of the signals due to the carbonyl group. The 13C NMR spectra of
complexes 1 and 2 show the characteristic peaks of the carbonyl group around 194
ppm, compared to 180 ppm for the same carbon in the parent free ylides, indicating
a much lower shielding of the carbon of the CO group in these complexes (see
supplementary data). This downfield shift has been previously observed in the
series of compounds [PdCl (η3-2-XC3H4) (C6H5)3PCHCOR] [X = H, CH3; R =
CH3, C6H5] and was attributed to a change in hybridization of the ylidic carbon
[61]. Thus, the spectral data clearly indicates the bidentate coordination of the
ylides through both the phosphine group and the ylidic carbon atom.
3.3. Crystallography
Crystals, suitable for single-crystal X-ray analysis, of complexes C1 and C2
were grown by vapor diffusion of methanol into a DMSO solution. The molecular
structures of these complexes are shown in Figure 2 and Figure 3. Relevant data
collection and refinement statistics are given in Table 2.
Table 2. Data collection and refinement statistics for C1 and C2
C1
C2
(C34H29BrCl2OP2Pd),
0.75(CH2Cl2)
(C34H29BrCl2OP2Pt
), (CH2Cl2)
946.34
Empirical formula
Formula weight (gmol- 836.41
15

1
)
T (K)
293(2)
100(2)
λ (Å)
1.54184
triclinic
P-1
1.54184
triclinic
P-1
Crystal system
Space group
a (Å)
b (Å)
c (Å)
11.3709(3)
17.1681(5)
19.4374(4)
99.055(2)
97.188(2)
105.918(2)
3546.50(16)
4
11.2414(3)
17.0630(4)
19.2633(4)
99.394(2)
97.003(2)
106.476(2)
3440.00(15)
4
α (°)
β (°)
γ (°)
V (Å3)
Z
ρcalc (gcm-3)
1.567
9.028
1.827
12.952
μ (mm-1)
F(000)
1670
1840
Crystal dimensions
0.12 x 0.09 x 0.08
0.17 x 0.12 x 0.09
(mm3)
2θmax (°)
150.80
67184
151.27
65323
Reflections collected
Independent
reflections
Observed reflections
[Io > 2σ (Io)]
Parameters refined
Final R indices [Io >
2σ (Io)]
14406
13983
9836
11768
739
766
R1 = 0.0590
R1 = 0.0509
ωR2 = 0.1473
R1 = 0.0886
ωR2 = 0.1700
ωR2 = 0.1271
R1 = 0.0621
ωR2 = 0.1376
1.028
R indices (all data)
Goodness-of-fit on F2 1.041
The asymmetric unit of the structure of C1 contains two palladacycle
[PdCl2(Ph2P(CH2)2PPh2C(H)C(O)C6H4-m-Br)] complexes (Figure 2). The two
complexes mainly differ in the conformation of the Ph2P(CH2)2PPh2 part and the
16

orientation of the C6H4-m-Br ring. In fact, the C6H4-m-Br ring is ∼180˚ flipped
when comparing these two complexes (see Supplementary Information for a fit of
the two complexes). The X-ray analysis unequivocally confirms the P-C chelating
mode of coordination of the ligand Ph2P(CH2)2PPh2C(H)C(O)C6H4-m-Br to the Pd
metal center. The Pd atom is four-coordinated by one P-atom of the phosphine
group, one ylidic C-atom and two chlorine atoms, showing a slightly distorted
square planar coordination environment. The P-Pd-C, P/C-Pd-Cl and Cl-Pd-Cl
angles are in the ranges of 87.75(15)-93.29(15)˚ and 87.29(16)-93.77(16)˚, for the
first and second complex, respectively, emphasizing the slightly distorted
coordination geometry.
Figure 2. Asymmetric unit of the structure of C1, showing thermal displacement
ellipsoids at the 30% probability level and labeling scheme of the hetero-atoms.
17

The Pd-Cl distances in the first complex (2.3824(18) vs 2.317(2) Å) and second
complex (2.3779(17) vs 2.334(2) Å) are significantly different, reflecting a
different trans effect of the phosphorus and ylidic carbon atoms [62]. The Pd-
C(ylide) bond lengths are 2.125(6) and 2.114(6) Å, which are similar to the ones
found in other Pd non-symmetric phosphorus ylides and Pd cyclic bis-ylides
[62,63]. The Pd-P bond lengths (2.2318(16) and 2.2391(17) Å) are also
comparable to analogous distances in dichloro-(1,2-
bis(diphenylphosphino)ethane)-Pd(II) complexes [64-66]. The C(1)-C(2) and
C(35)-C(36) bond lengths (1.479(10) and 1.480(10) Å) are significantly longer
than the corresponding distances in non-coordinating phosphanes, showing that the
stabilized resonance structure of the parent ylide is destroyed by the complex
formation [67].
The structure of C2 is isomorphous to that of C1 and hence the asymmetric unit
of the structure of C2 contains two platinacycle
[PtCl2(Ph2P(CH2)2PPh2C(H)C(O)C6H4-m-Br)] complexes (Figure 3). The structure
also shows the ∼180˚ flipped C6H4-m-Br ring, when comparing the two complexes
(see Supplementary Information for a fit of the two complexes).
18

The Pt atom is four-coordinated in a similar fashion as for C1, showing a slightly
distorted square planar coordination environment. Here, the P-Pt-C, P/C-Pt-Cl and
Cl-Pt-Cl angles are in the ranges of 86.99(18)-94.35(18)˚ and 86.59(17)-
94.29(17)˚, for the first and second complex, respectively.
Figure 3. Asymmetric unit of the structure of C2, showing thermal displacement
ellipsoids at the 50% probability level and labeling scheme of the hetero-atoms.
A similar trans effect of the phosphorus and ylidic carbon atoms is observed as in
C1, with the Pt-Cl distances of 2.3696(16) vs 2.3373(17) Å and 2.3779(16) vs
2.3262(18) Å, for the first and second complex, respectively. The Pt-C(ylide) bond
lengths (2.088(6) and 2.119(6) Å) and Pd-P bond lengths (2.2165(16) and
2.2048(15) Å) are somewhat shorter than the analogous distances with Pd in C1.
19

However, when searching the Cambridge Structural Database (CSD, version 5.38,
update Feb 2017), no P-C chelates of phosphorus ylides with Pt are found [68].
Analogous to C1, the stabilized resonance structure of the parent ylide is
destroyed by the complex formation, shown by C(1)-C(2) and C(35)-C(36) bond
lengths of 1.500(10) and 1.497(10) Å [67].
3.4. Mizoroki-Heck coupling reaction of aryl chlorides
The catalytic activity of palladacycle C1 in the Mizoroki-Heck coupling
reaction was then examined. Initially, we carried out a model reaction to optimize
the reaction conditions including base, solvent, temperature and catalyst loading
(Table 3). The reaction of styrene with chlorobenzene in DMF/H2O (1:1) at 110 °C
in the presence of K3PO4 (1 mmol) and 0.05 mmol of C1 as catalyst was chosen as
a model reaction, which led to formation of the coupled product in 69% yield
(Table 3, entry 1). Subsequently, a series of experiments was performed to find the
optimum conditions.
20

Table 3. Optimizations for the Mizoroki-Heck coupling
reactiona
Entry
Base
Solvent
Catalyst
loading
(mmol)
0.05
Temp.
(°C)
Yield
(%)b
1
K3PO4
K2CO3
NEt3
DMF/H2O
DMF/H2O
DMF/H2O
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
65
69
79
58
47
50
44
51
27
38
41
58
76
32
88
53
36
2
0.05
3
0.05
4
K3PO4
K2CO3
NEt3
Methanol/H2O 0.05
Methanol/H2O 0.05
Methanol/H2O 0.05
5
6
7
K3PO4
K2CO3
NEt3
Toluene/H2O
Toluene/H2O
Toluene/H2O
H2O
0.05
8
0.05
9
0.05
10
11
12
13
14
15
16
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
0.05
DMF
0.05
DMF/H2O
DMF/H2O
DMF/H2O
DMF/H2O
DMF/H2O
0.005
0.0005
0.1
0.005
0.005
25
a Reaction conditions for Mizoroki-Heck coupling reaction:
chlorobenzene (0.5 mmol), styrene (0.75 mmol), base (1 mmol), solvent
(2 ml), catalyst C1, in air.
b Isolated yield.
At the first stage of optimization, we studied the effect of base and solvent on
the reaction. Since the solubility and basicity of the base strongly depend on the
solvent used, these two parameters are closely connected. This optimization was
done with commonly used bases and solvents, including organic and inorganic
bases and aqueous protic and aprotic solvents. Coupling reactions carried out in the
presence of K2CO3 and K3PO4 give the desired coupling product in moderate to
21

high yields (Table 3, entries 2, 5 and 1, 4). However, the reactions in the presence
of NEt3 did not proceed efficiently even after prolonged stirring at reflux
temperature of the solvents, probably due to the low solubility of this organic base
in aqueous solvents (Table 3, entries 6 and 9). Among the tested aqueous solvents,
DMF/H2O gave higher yields of coupled product. Also, the reactions in water and
non-aqueous DMF led to lower yields, indicating the important role of the
solubility of the base in such catalytic systems (Table 3, entries 10 and 11).
Next, we investigated the effect of catalyst loading on the reaction. As
expected, varying the catalyst loading has a significant effect on the performance
of the catalyst. When the loading of palladacycle C1 decreased to 0.005 mmol, the
coupling reaction gave slightly lower product yield and the reaction resulted in
negligible yield of coupled product when the catalyst loading decreased to 0.0005
mmol (Table 3, entries 12 and 13). Also, an excessive amount of catalyst did not
increase the yield significantly (Table 3, entry 14). Therefore, with respect to the
economic aspect, 0.005 mmol of catalyst was chosen as the best catalyst loading.
Finally, the reactions were carried out at different temperatures. Decreasing the
temperature of the reactions led to a decrease of the yields and inherent increase of
the reaction time for completion of the reactions (Table 3, entries 15 and 16). Thus,
the optimum condition obtained for the Mizoroki-Heck coupling reaction consisted
22

of DMF/H2O as solvent, K2CO3 as base, 0.005 mmol of palladacycle C1 as catalyst
and reaction at reflux temperature (110 °C) for 6 h.
Using the optimized reaction conditions, palladacycle C1 was applied in the
reaction of various functionalized aryl chlorides bearing both electron-donating to
electron-withdrawing groups with styrene. Aryl chlorides were converted into the
corresponding coupled products in high yields (Table 4). Conversely, increasing
electron density on the aryl chlorides lowered the catalyst activity. That is, high
yields are achieved when styrene reacted with aryl chlorides bearing electron-
withdrawing substituent -CHO and -COCH3 (Table 4, entries 1 and 2). Deactivated
aryl chlorides 4-chlorotoluene and 4-chloroanisol gave lower yields indicating that
the reaction was sensitive to the electron density on the aryl chlorides (Table 4,
entries 4 and 5). The reaction of electronically neutral chlorobenzene with styrene
also produced good amounts of the product (Table 4, entry 3).
Table 4. Mizoroki-Heck coupling reaction of aryl chlorides catalyzed by
palladacycle C1a.
Entry
R
R'
Product
Yield
(%)b
85
1
2
3
CHO
Ph
p-OHC-Ph-CH=CHPh (3e)
p-CH3OC-Ph-CH=CHPh (3c)
Ph-CH=CHPh (3a)
COCH3 Ph
Ph
80
73
H
23

4
5
6
7
8
9
10
Me
OCH3
CHO
COCH3 EtOOC
H
Ph
Ph
EtOOC
p-Me-Ph-CH=CHPh
67
63
88
82
79
74
66
p-CH3O-Ph-CH=CHPh (3b)
p-OHC-Ph-CH=CHCOOEt
p-CH3OC-Ph-CH=CHCOOEt
Ph-CH=CHCOOEt (3d)
p-Me-Ph-CH=CHCOOEt
p-CH3O-Ph-CH=CHCOOEt
EtOOC
EtOOC
EtOOC
Me
OCH3
a Reaction conditions for Mizoroki-Heck coupling reaction: aryl chloride
(0.5 mmol), olefin (0.75 mmol), K2CO3 (1 mmol), DMF/H2O (2 ml),
catalyst C1 (0.005 mmol), in air.
b Isolated yield.
To extend the scope of our work, we next investigated the coupling reaction of
aryl chloride substrates with the more reactive olefin, ethyl acrylate. As expected,
an electron-withdrawing substituent on the olefin has an increasing effect on the
yield of the reaction (Table 4, entries 6-10). However, the coupling reaction of
deactivated aryl chlorides such as 4-chloroanisole gave the coupled acrylate
derivatives in lower yields (Table 4, entry 10).
To evaluate the homogeneous or heterogeneous nature of the active species, we
carried out the mercury drop test [69]. Since mercury leads to amalgamation of the
surface of a heterogeneous catalyst, and in contrast, Hg(0) is not expected to have a
poisoning effect on homogeneous palladium complexes, the results of this test can
aid in determining the nature of the active species [70]. Addition of a drop of
mercury to the reaction mixture at t = 0 did not affect the conversion of the
24

reaction, which suggests that amalgamation had not occurred and the catalysis was
homogeneous in nature.
As can be noticed in Table 4, by using aryl chlorides, good amounts of stilbene
and acrylate derivatives are yielded. The higher C–Cl bond dissociation energy
compared with C–Br and C–I bonds disfavors the oxidative addition step in
catalytic coupling reactions [71]. However, the ideal substrates for coupling
reactions are aryl chlorides, since they are cheaper and more widely available than
their bromide or iodide analogues. Table 5 shows a comparison between the
efficiency of this catalytic system in the Mizoroki-Heck coupling reaction of aryl
chlorides and the other catalytic systems. The results of this comparison showed
that the reported catalysts in literature need to be used in high loadings and showed
lower activity with aryl chloride substrates [72-75]. From an industrial point of
view, the low catalyst loading and short reaction time make this palladacycle an
ideal catalyst for the Mizoroki-Heck coupling reaction.
Table 5. Comparison of Mizoroki-Heck coupling reactions of chlorobenzene
and styrene using palladacycle C1 and other catalytic systems
Entr Pd source
y
Catalyst
loading
(mmol)
Condition
Yiel Ref.
d
(%)
25

1
2
imidazole-based
secondary phosphine
oxide ligated Pd(II)
0.02
K2CO3, DMF,
60 °C, 12 h
62
89
[57]
[58]
poly(N,N-dipyrid-2- 0.007
yl-endo-norborn-2-
ene-5-carbamide)
K2CO3,
DMAc/TBAB, 140
°C, 90 h
based Pd(II)
3
2,6-bis
(diphenylphosphino)
pyridine/Pd(II)
0.001
K2CO3,
DMAc/TBAB, 135
°C, 5 h
57
12
[59]
[60]
4
5
Polymer-Anchored
Schiff Base Pd(II)
0.005
0.005
K2CO3, DMF,
100 °C, 24 h
P, C-chelated
phosphorus ylide
Pd(II)
K2CO3, DMF/H2O, 73
110 °C, 6 h
This
wor
k
3.5. Antioxidant capacity
In the present study, the antioxidant capacity of the new compounds was
determined (Table 6 and Figure 4). Antioxidant enzymes and compounds act as a
health-protection factor in the human body and scientific evidence suggests that
these factors are very important due to their role in reducing the risk of diseases
such as cancer [27]. Our results showed that most of the synthesized compounds
showed good dose-dependent (0.2-1 mg/ml) antiradical properties (33.25 to
69.11%), (Table 6). Antioxidant capacity is reflected in a lower IC50 value. BHT as
a synthetic antioxidant represented a lower IC50 value (IC50; 0.199 ± 0.006 mg/ml)
26

than those of the two compounds studied here (IC50; 0.584 ± 0.009 to 0.751 ±
0.003 mg/ml), (Figure 4).
Table 6. DPPH radical scavenging capacity (%) of new compounds and
BHT as standard.
Conc.(mg/ml)
C1
C2
BHT
33.25 ± 0.9a
37.11 ± 2.0a
52.23 ± 1.3b
55.27 ± 0.6b
69.11 ± 2.3c
49.39
42.42 ± 2.1a
51.14 ± 0.6b
48.29 ± 1.4b
53.21 ± 0.6b
58.43 ± 2.5c
50.70
50.21 ± 1.3a
68.16 ± 1.2b
71.23 ± 2.2b
70.65 ± 0.7b
74.39 ± 2.3b
66.93
0.2
0.4
0.6
0.8
1
Average
Experiment was performed in triplicate and expressed as mean ± SD. Values
within column with different superscripts are significantly different (P <
0.05).
27

Figure 4. Comparison of DPPH radical scavenging ability (IC50 value) of the
studied cumarins and BHT as a positive control.
4. Conclusions
In summary, we report the synthesis and full characterization of new pallada-
and platinacycles C1 and C2. On the basis of the spectroscopic data, we propose
that ligand Y employed herein exhibits P, C-coordination behavior to the metal
centers. Furthermore, this coordination fashion has been confirmed by single
crystal X-ray diffraction experiments. The results show that chelation of ylide
through the ylidic carbon atom and phosphine group affords a six-membered ring.
Furthermore, the catalytic activity of palladacycle C1 towards the Mizoroki-Heck
coupling reaction was investigated. The results show that the coupling reactions of
various aryl chlorides with olefins proceed in high yields. Additionally, our study
28

clearly demonstrates that the new compounds exhibit biological properties (as
antioxidant agents) and could be useful in the development of novel therapeutic
agents.
Supplementary material
Physical measurements and selected 31P, 13C and 1H NMR spectra of some
compounds can be found in the online version.
CCDC 1514248-1514249 contain the supplementary crystallographic data for
complexes C1 and C2. These data can be obtained free of charge via
http://www.ccdc.cam.ac.uk/conts/retrieving.html, or from the Cambridge
Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax:
(+44) 1223-336-033; or e-mail: deposit@ccdc.cam.ac.uk).
Acknowledgements
Funding of our research from the Bu-Ali Sina University is gratefully
acknowledged. KVH thanks the Hercules foundation (project AUGE/11/029 “3D-
SPACE: 3D Structural Platform Aiming for Chemical Excellence”) and the
Research Foundation-Flanders (FWO) (project 1.5.216.15N) for funding.
29