Palladium complexes catalyzed regioselective arylation of 2-oxindole via in situ C(sp2)?OH activation mediated by PyBroP

Article abstract of DOI:10.1016/j.jorganchem.2016.09.026

Pd(II) complexes appended with ONO pincer type ligand were synthesized, structurally characterized and successfully applied as catalysts for regieoselective C?2 arylation of 2-oxindole via in situ C (sp²)?OH activation in aqueous-organic media

Full text of DOI:10.1016/j.jorganchem.2016.09.026

Journal of Organometallic Chemistry 824 (2016) 7e14
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Palladium complexes catalyzed regioselective arylation of 2-oxindole
via in situ C(sp2)ꢀOH activation mediated by PyBroP
,
*
A. Vignesh a, Werner Kaminsky b, N. Dharmaraj a
a Inorganic & Nanomaterials Research Laboratory, Department of Chemistry, Bharathiar University, Coimbatore 641 046, India
b Department of Chemistry, University of Washington, Seattle, WA 98195, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 July 2016
Received in revised form
1 September 2016
Accepted 29 September 2016
Available online 30 September 2016
Pd(II) complexes appended with ONO pincer type ligand were synthesized, structurally characterized
and successfully applied as catalysts for regieoselective Cꢀ2 arylation of 2-oxindole via in situ C (sp2)ꢀOH
activation in aqueous-organic media under an open atmosphere at room-temperature. This catalyst was
reused up to four cycles. Favourably, the present protocol doesn't require the addition of any external
oxidant, additives or phase transfer agents.
© 2016 Elsevier B.V. All rights reserved.
Keywords:
Pd(II) complexes
C(sp2)ꢀOH activation
Aqueous-organic media
Room-temperature
1. Introduction
noticed that aromatic Csp2eOH activation is profoundly difficult
when compared to activating Csp3eOH bonds because of a higher
Tautomerizable heterocycles are most suitable synthons in
molecular engineering [1] and have been used as substrates for Pd-
catalyzed cross-couplings via in situ CeOH activation in the pres-
ence of phosphonium salts. In this context, Kang et al. [2] reported
direct arylation of tautomerizable heterocycles utilizing boronic
acids as coupling accomplice. Herein, we demonstrate bromo-tris-
pyrrolidino-phosphonium hexafluorophpsphate (PyBroP) medi-
ated CeOH activation methodology [3] for arylation of 2-oxindole
in the presence of palladium pincer type complex. Indole and its
derivatives present as one of the main constituents of many natural
and synthetic compounds exhibit medicinal [4] as well as material
properties applicable to organic photovoltaics [5], OLED [6], sensors
[7], nanomaterials [8], and forming useful coordination complexes
[9].
energy barrier and aromatic ring stability [11]. This CeOH activa-
tion methodology creates CeO electrophiles are considered a
suitable alternative to aryl halides in CeC bond formation reactions
[12].
For this reason, a series of aryl CeO electrophiles like acetates
[13], carbamates [14], esters [15], ethers [16], pivalates [17], phos-
phoramides [18], phosphonates [19], triflates [19], sulfamates [20],
carbonates [21], and tosylates [22] were introduced as coupling
partners in metal-catalyzed cross-coupling reactions. Very recently,
PyBroP mediated CeOH activation in the presence of metal cata-
lysts has attracted the attention of several researchers. So far,
PyBroP mediated CeOH activation was reported for urea [11],
phenol [23], 1-naphthol [24], 2-quinoxalinone [2], 2-methyl-1H-
pyridazine-3,6-dione
[25],
2-hydroxypyridine
[26],
2-
Known synthetic routes so far developed to synthesize, for
example, C-2 arylated indole derivatives exclude CeOH activation
[10]. In addition, those methods require high catalyst loading,
elevated temperature, prolonged reaction time, additives, oxidants,
and usually require to work in a nitrogen atmosphere. It should be
oxoquninoline [27], and 2(1H)-pyrazinones [28] in the literature.
Palladium based pincer complexes are widely utilized as catalysts
for various organic reactions including CeH activation and they
undoubtedly play a vital role in the continuous search for the
development of new and efficient protocols to form CeC bonds
[29]. Some of these complexes are workable in aqueous or aqueous-
organic media [30]. We already examined palladium pincer type
complexes as catalysts for organic reactions [31]. We herein report
the synthesis and spectral characterization of three new palladium
(II) complexes (1e3) bearing ONO pincer type ligands including X-
* Corresponding author.
E-mail address: dharmaraj@buc.edu.in (N. Dharmaraj).
URL: http://ndharmaraj.wix.com/inrl
http://dx.doi.org/10.1016/j.jorganchem.2016.09.026
0022-328X/© 2016 Elsevier B.V. All rights reserved.

8
A. Vignesh et al. / Journal of Organometallic Chemistry 824 (2016) 7e14
ray structures, and studies of their catalytic activity towards C-2
arylation of 2-oxindole using substituted aryl boronic acids in H2O/
EtOH media under open-flask conditions.
C, 61.59; H, 3.73; N, 5.99. Found (%) C, 61.58; H, 3.74; N, 5.98.
UVevisible (solvent: DMSO, nm): 302, 323, 344, 369. Selected IR
bands (KBr, n
in cmꢀ1): 1590 (CeN]NeC), 1526 (C]N), 1477 (NO2),
1433 (PPh3), 1249 (imidolate eN]CeO), 1186 (naphtholate CeO).
2. Experimental procedure
1H NMR (CDCl3,
d
ppm): H1 NMR: 9.65 (s, 1H), 9.55 (d, J ¼ 16.0 Hz,
2H), 7.62 (d, J ¼ 6.4 Hz, 3H), 7.52 (t, J ¼ 7.4 Hz, 3H), 7.46 (t, J ¼ 7.4 Hz,
2.1. General information
5H), 7.40 (d, J ¼ 6.8 Hz, 2H), 7.25e7.30 (m, 5H), 6.94 (t, J ¼ 3.8 Hz,
2H), 6.44 (d, J ¼ 16 Hz, 3H). 13C NMR (CDCl3,
d ppm) 185.6, 155.8,
Elemental analyses (C, H, and N) were performed on a Vario EL
154.7, 138.1, 135.6, 130.7, 130.3, 129.2, 128.9, 128.8, 128.7, 127.8,
125.7, 124.5, 124.4, 121.8, 117.1, 113.3.
III Elemental analyzer instrument. IR spectra (4000e400 cmꢀ1
)
were recorded on a Nicolet Avatar Model FT-IR spectrophotometer.
Melting points were determined with a Lab India instrument. 1H
and 13C NMR spectra were recorded in deuterated CHCl3 as solvent
on BRUKER 400 and 100 MHZ instruments, respectively. All reagent
grade chemicals were used without further purification unless
otherwise specifically mentioned. Solvents were purified and dried
according to standard procedures [32].
2.4. Single-crystal X-ray diffraction studies
Suitable crystals of complexes 1e3 with approximate di-
mensions of 0.24
ꢂ
0.15
x
0.10, 0.30
ꢂ
0.10 x 0.03 and
0.17 ꢂ 0.15 ꢂ 0.05 mm3 were mounted on a loop with oil. The data
collection were performed by using Bruker APEX II single crystal X-
ray diffractometer. All the data were collected using graphite
2.2. Synthesis of ligands H2L1e H2L3
monochromated Mo K
a
radiation (
l
¼ 0.71073 Å) from a fine focus
sealed tube X-ray source. The collected data were integrated and
scaled using hkl-SCALEPACK [34] (for complex 1) and SAINT,
SADABS within the APEX2 software package by Bruker [35] (for
complex 2, and 3). While using hkl-SCALEPACK program applies a
multiplicative correction factor (S) to the observed intensities (I)
and has the following form:
The pincer type ligands H2L1eH2L3 were synthesized from
equimolar quantity of o-hydroxynaphthaldehyde with appropriate
hydrazides such as benzhydrazide (H2L1), p-chlorobenzhydrazide
(H2L2), and p-nitrobenzhydrazide (H2L3) in ethanol according to a
literature method [33]. The reaction mixture was then refluxed on a
water-bath for 6 h and poured into crushed ice. The corresponding
pincer type hydrazones formed as colorless solid were filtered,
washed repeatedly with distilled water and recrystallized from
ethanol with 80e90% yield. The purity of the ligands were checked
by various analytical techniques and is in accordance with litera-
ture report [33].
ꢁ
ꢀ
ꢂ.
2
q
Þ
l2
S ¼ eꢀ2B sin
scale
ð
S is calculated from the scale and the B factor determined for
each frame and is then applied to I to give the corrected intensity
(Icorr). Solution by direct methods (SHELXS, SIR97) [36] produced a
complete heavy atom phasing models consistent with the proposed
structures. The structure was completed by difference Fourier
synthesis with SHELXL97 [37,38]. The scattering factors are from
Waasmair and Kirfel [39] Hydrogen atoms were placed in
geometrically idealized positions and constrained to ride on their
parent atoms with CeH distances in the range 0.95e1.00 Å.
Isotropic thermal parameters Ueq were fixed such that they were
1.2 Ueq of their parent atom Ueq for CH's and 1.5 Ueq of their parent
atom Ueq in case of methyl groups. All non-hydrogen atoms were
refined anisotropically by full-matrix least-squares.
2.3. General method for the synthesis of the palladium complexes
To a warm methanolic solution (20e30 mL) of appropriate li-
gands (H2L1eH2L3) (1 equiv.) was added a chloroform solution of
[PdCl2(PPh3)2] (1 equiv.) followed by two drops of triethylamine.
Then the reaction mixture was refluxed for 8e10 h and kept at
room temperature for crystallization. Needle like reddish brown
crystals suitable for X-ray studies were obtained on slow evapo-
ration over 45e60 days.
[Pd(L1) (PPh3)] (complex 1) Yield: 85% (112 mg). M. p.
232e234 ꢁC. Elemental analysis (%) calculated for C36H27N2O2PPd;
C, 65.81; H, 4.14; N, 4.26. Found (%) C, 65.82; H, 4.15; N, 4.27.
UVevisible (solvent: DMSO, nm): 303, 325, 341, 354. Selected IR
2.5. General procedure for catalytic reaction and reusability
n
in cmꢀ1): 1581 (CeN]NeC), 1528 (C]N), 1433
To a mixture of H2OeEtOH (70:30%), 2-oxindole (3.0 mmol),
NEt3 (6.0 equiv) and PyBroP (1.2 equiv.) were added and stirred for
10 min. To this reaction mixture, complex 3 (0.01 mol) was added
and stirred for 30 min at room-temperature followed by the
addition of KOH (5 mmol) and phenylboronic acid (4.0 mmol). The
progress of the reaction was monitored by thin layer chromatog-
raphy (TLC). After the completion of the reaction the product
mixture was cooled to room temperature; the catalyst was
precipitated by the addition of ethyl acetate separated by centri-
fugation and washed thoroughly with water (to remove inorganic
salts). The identity of the products was confirmed by 1H and 13C
NMR techniques. The recovered catalyst was dried and utilized for
next cycle under same reaction conditions. The stability of recov-
ered catalyst was identified by 1H, 31P NMR spectra, melting point
data and Rf value of TLC.
bands (KBr,
(PPh3), 1260 (imidolate eN]CeO), 1185 (naphtholate CeO). 1H
NMR (CDCl3,
ppm) 9.86 (s, 1H), 9.30 (d, J ¼ 8 Hz, 4H), 7.81 (s, 2H),
d
7.55 (d, J ¼ 7.6 Hz, 2H), 7.23e7.36 (m, 10H), 7.15 (t, J ¼ 5.8 Hz, 6H),
6.44 (d, J ¼ 15.6 Hz, 2H); 13C NMR (CDCl3,
d ppm) 183.5, 167.5, 145.2,
142.2, 138.5, 134.7, 129.4, 128.3, 127.0, 124.4, 123.9, 120.7, 119.3,
118.4, 112.0.
[Pd(L2) (PPh3)] (complex 2) Yield: 80% (111 mg). M. p.
239e242
36H26ClN2O2PPd; C, 62.53; H, 3.79; N, 4.05. Found (%) C, 62.52; H,
3.78; N, 4.05. UVevisible (solvent: DMSO, nm): 306, 329, 342, 353.
Selected IR bands (KBr,
in cmꢀ1): 1591(CeN]NeC), 1526 (C]N),
1429 (PPh3), 1267 (imidolate eN]CeO), 1184 (naphtholate CeO),
745 (CeCl). 1H NMR (CDCl3, ppm): H1 NMR: 9.86 (s, 1H), 9.16 (d,
ꢁC.
Elemental
analysis
(%)
calculated
for
C
n
d
J ¼ 12.0 Hz, 2), 7.73 (s, 2H), 7.65 (s, 2H), 7.48 (s, 2H), 7.38 (t,
J ¼ 6.0 Hz, 9H), 7.18 (t, J ¼ 3.8 Hz, 6H), 6.43 (d, J ¼ 16.0 Hz, 2H); 13
C
NMR (CDCl3,
d
ppm) 183.2, 167.0, 143.7, 142.2, 139.5, 134.2, 131.1,
3. Results and discussion
129.4, 128.7, 127.3, 123.9, 123.3, 120.1, 119.7, 117.7, 114.6.
[Pd(L3) (PPh3)] (complex 3) Yield: 88% (124 mg). M. p.
Palladium complexes of the composition [Pd (L1eL3) (PPh3)]
were synthesized by reacting equimolar quantity of [PdCl2(PPh3)2]
246e248 ꢁC. Elemental analysis (%) calculated for C36H26N3O4PPd;

A. Vignesh et al. / Journal of Organometallic Chemistry 824 (2016) 7e14
9
and respective aryl hydrazones (H2L1eH2L3) via metal introduction
route as depicted in Scheme 1. The chosen hydrazones are suitable
to provide three donor atoms i.e. two oxygen atoms and a nitrogen
atom to form pincer type palladium complexes.
FT-IR spectra of free ligands H2L1- H2L3 displayed medium
bands at 3410, 3412 and 3430 cmꢀ1 respectively, due to the pres-
ence of OeH group in naphthalene ring. A strong band observed at
3052, 3098 and 3110 cmꢀ1 confirmed the presence of NeH func-
tional group in the free ligands. The absorption due to C]O
stretching was observed at 1632, 1631 and 1642 cmꢀ1. IR spectra of
the palladium complexes 1e3 did not show any bands due to NeH
and C]O functional groups. Absence of these bands indicates that
the ligands underwent tautomerization followed by deprotonation
prior to coordination of the imidolate oxygen to palladium (II) ion.
Further, the new bands appeared in the regions of 1181e1186 cmꢀ1
and 1590-1610 cmꢀ1 were attributed to the CeO and CeN]NeC
fragments of the coordinated ligand. The spectra of complexes 1e3
showed a strong band at 1482, 1431 and 1477 cmꢀ1 to reveal the
presence of PPh3. From the above discussions, the coordination of
pincer type hydrazone ligands via naphtholate oxygen, azomethine
nitrogen, and imidolate oxygen to palladium ion were identified
[40].
Fig. 1. ORTEP diagram of complex 1 with thermal ellipsoids at the 50% probability
level.
The proton NMR spectra of complexes 1e3 registered a down-
field resonance of sharp singlets at
d 9.86, 9.86, and 9.65 respec-
tively due to azomethine proton. All the aromatic protons of the
complexes 1e3 displayed their resonances in the region of
the palladium ion, while the fourth coordination site is occupied by
a triphenylphosphine molecule. The geometry around the Pd(II)
centre in complexes 1e3 is best described as distorted square-
planar. ORTEP representations of complexes 1e3 are shown in
Figs. 1e3. The observed bond lengths and bond angles are in good
agreement with reported data on related palladium (II) complexes
[43]. Crystal data, structure refinement selected bond distances and
bond angles of the complexe 1e3, were gathered in Tables 1e4.
To establish the feasibility of direct arylation of 2-oxindole in a
regioselective manner, we applied Kang et al. [2], conditions using
2-oxindole and phenylboronic acid as model substrates in presence
of PyBroP and complex 2 as catalyst. As expected, the reaction
proceeded but to afford only 17% of the desired product. In order to
increase the yield of desired product, we examined diverse sol-
vents, bases and catalysts. Initially, we tried this reaction in water
wherein no reaction was observed owing to the insoluble nature of
the catalyst (Table 5, entry 1). Hence, we conducted the same
experiment by including some organic solvents to dissolve the
catalyst. To identify a most suitable solvent for this catalytic pro-
cess, combinations of MeOH, THF, EtOAc, DMF, CH3CN, DMSO,
EtOH, toluene, benzene, CHCl3 and DCM solvents with water were
d
6.42e9.55 ppm. It's important to note here that we didn't observe
any signal due to NeH proton which indicated that the enolization
of carbonyl oxygen followed by its coordination to palladium ion in
the imidolate form. Also, the non-existence of a resonance attrib-
utable to the OeH group attached to naphthalene ring revealed that
there occurred a deprotonation prior to its coordination to palla-
dium ion in the complexes 1e3 [41]. The 13C NMR spectra of all the
Pd(II) complexes showed a downfield shift in the position of azo-
methine carbon (C]N) compared to free ligands and appeared at
d
183.5, 183.2 and 185.6 ppm. The signals corresponding to imi-
dolate carbon atom (N]CeO) appeared at 167.5, 167.0 and 155.8.
In addition, the 13C NMR spectra of all the Pd(II) complexes dis-
played signals in the region of 111.3e149.1 ppm due to various
d
d
aromatic carbon atoms of both hydrazone and triphenyl phosphine
moieties [42].
Single-crystal XRD of complexes 1e3 show that pincer type li-
gands (H2L1e H2L3) adopt to the palladium ion in a binegative
tridentate manner. The naphtholate oxygen, azomethine nitrogen
and the deprotonated imidol oxygen act as three donor atoms and
each forma five membered and a six membered chelate ring with
Scheme 1. Synthesis of ONO pincer type ligands and their Pd(II) Complexes.

10
A. Vignesh et al. / Journal of Organometallic Chemistry 824 (2016) 7e14
Table 1
Selected bond lengths (Å) and angles (ꢁ) for the complex 1.
Complex
1
N (1)ePd (1)
O (1)ePd (1)
O (2)ePd (1)
P (1)ePd (1)
C (11)eN (1)
C (12)eN (2)
C (12)eO (1)
C (1)eO (2)
1.9680 (3)
1.9890 (2)
1.9680 (2)
2.2922 (10)
1.2980 (4)
1.3040 (5)
1.3200 (4)
1.3180 (4)
1.4000 (4)
1.4360 (5)
1.4050 (5)
80.10 (11)
93.75 (11)
173.77 (10)
177.91 (9)
98.42 (8)
N (1)eN (2)
C (10)eC (11)
C (1)eC (10)
N (1) e Pd (1) e O (1)
O (2) e Pd (1) e N (1)
O (1) e Pd (1) e O (2)
N (1) e Pd (1) e P (1)
O (1) e Pd (1) e P (1)
O (2) e Pd (1) e P (1)
C (11) e N (1) e Pd (1)
N (2) e C (12) e O (2)
N (2) e N (1) e Pd (1)
87.76 (8)
125.90 (2)
125.10 (3)
115.30 (2)
Fig. 2. ORTEP diagram of complex 2 with thermal ellipsoids at the 50% probability
level.
Table 2
Selected bond lengths (Å) and angles (ꢁ) for the complex 2.
Complex
2
tested. Next, we studied the role of various bases such as KOH,
K2CO3, NaOH, Na2CO3, Et3N and pyridine. The outcome of the above
trials regarding the choice of solvent and base suggested that uti-
lizing KOH as a base with a H2O/EtOH solvent mixture produced
84% of the arylated indole while any other combination of solvents
gave less product (Table 5). The comparison of catalytic potential of
the complexes 1, 2 and 3 were examined as well. Among those,
complex 3 exhibited the best performance for the reaction to afford
94% isolated yield (Table 5, entry 26). The presence of an electron
withdrawing eNO2 in the pincer type ligand coordinated to Pd ion
in complex 3 may be the reason for the excellent performance of
this complex [44]. Thus, the following conditions were utilized: 2-
oxindole (3 mmol), aryl boronic acid (4 mmol) KOH (5, mmol), Et3N
(6 eqv.), PyBroP (1.2 eqv.), H2O/EtOH (70:30%), and complex 3 as
catalyst (0.01 mol %); all at room-temperature.
N (1)ePd (1)
O (1)ePd (1)
O (2)ePd (1)
P (1)ePd (1)
C (8)eN (1)
C (1)eN (2)
C (1)eO (2)
C (18)eO (1)
1.976 (5)
1.952 (4)
2.001 (4)
2.2936 (18)
1.284 (6)
1.312 (7)
1.328 (7)
1.320 (7)
1.402 (6)
1.412 (8)
1.424 (9)
92.9 (2)
N (1)eN (2)
C (8)eC (9)
C (9)eC (18)
N (1) e Pd (1) e O (1)
O (2) e Pd (1) e N (1)
O (1) e Pd (1) e O (2)
N (1) e Pd (1) e P (1)
O (1) e Pd (1) e P (1)
O (2) e Pd (1) e P (1)
C (8) e N (1) e Pd (1)
N (2) e C (1) e O (2)
N (2) e N (1) e Pd (1)
81.2 (2)
174.04 (19)
174.70 (15)
92.31 (13)
93.62 (15)
126.5 (4)
125.1 (6)
113.9 (4)
The scope of catalytic activity was examined at above optimized
conditions on a series of aryl boronic acids decorated by both,
electron-rich or electron-deficient groups (Table 6). Within the
Table 3
Selected bond lengths (Å) and angles (ꢁ) for the complex 3.
Complex
3
N (1)ePd (1)
O (1)ePd (1)
O (2)ePd (1)
P (1)ePd (1)
C (11)eN (1)
C (12)eN (2)
C (1)eO (1)
C (12)eO (2)
1.974 (3)
1.961 (3)
1.981 (2)
2.2825 (9)
1.2940 (5)
1.3040 (5)
1.308 (4)
1.321 (4)
1.400 (4)
1.424 (6)
1.420 (5)
93.61 (11)
80.34 (11)
173.91 (9)
176.27 (9)
88.71 (8)
97.37 (7)
126.2 (3)
125.9 (4)
115.1 (2)
N (1)eN (2)
C (10)eC (11)
C (1)eC (10)
N (1) e Pd (1) e O (1)
O (2) e Pd (1) e N (1)
O (1) e Pd (1) e O (2)
N (1) e Pd (1) e P (1)
O (1) e Pd (1) e P (1)
O (2) e Pd (1) e P (1)
C (11) e N (1) e Pd (1)
N (2) e C (12) e O (2)
N (2) e N (1) e Pd (1)
Fig. 3. ORTEP diagram of complex 3 with thermal ellipsoids at the 50% probability
level.

A. Vignesh et al. / Journal of Organometallic Chemistry 824 (2016) 7e14
11
Table 4
Crystal data and structure refinement for complexes 1, 2 and 3.
Complex
1 (R ¼ H)
2 (R ¼ Cl)
3 (R ¼ NO2)
CCDC number
Empirical formula
Formula weight
Temperature (K)
Wavelength (Å)
Crystal system
Space group
Unit cell dimensions
a (Å)
1022416
C36 H27 N2 O2 P Pd
657.02
130 (2)
0.71073
1022419
C36 H26 Cl N2 O2 P Pd
691.41
292 (2)
0.71073
1022417
C36 H26 N3 O4 P Pd
701.97
100 (2)
0.71073
Triclinic
P ꢀ1
Monoclinic
P 21/n
Monoclinic
P 21/c
15.7562 (5)
8.8280 (3)
20.6955 (8)
90
97.0600 (10)
90
2856.83 (17)
8.9410 (15)
23.823 (4)
30.581 (6)
90
93.790 (4)
90
6500 (2)
8
8.8556 (4)
14.9323 (11)
15.0168 (7)
60.333 (3)
80.889 (3)
78.713 (5)
1687.66 (17)
2
b (Å)
c (Å)
a
b
g
(ꢁ)
(ꢁ)
(ꢁ)
Volume (Å3)
Z
4
Density (calculated) (Mg mꢀ3
)
)
1.528 Mg/m3
0.743
1.413
0.736
2800
1.381
0.639
712
Absorption coefficient (mmꢀ1
F (000)
1336
Crystal size (mm3)
0.24 ꢂ 0.15 x 0.10
0.30 ꢂ 0.10 x 0.03
0.17 ꢂ 0.15 x 0.05
Reflections collected
Independent reflections
Max. and min. transmission
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
11566
54110
86402
6731 [R (int) ¼ 0.0647]
0.9294 and 0.8419
Full-matrix least-squares on F2
6731/0/382
16017 [R (int) ¼ 0.1415]
0.9782 and 0.8093
Full-matrix least-squares on F2
16017/0/775
8389 [R (int) ¼ 0.0613]
0.9688 and 0.8992
Full-matrix least-squares on F2
8389/0/406
0.983
0.781
1.052
Final R indices [I > 2
s
(I)]
R1 ¼ 0.0500, wR2 ¼ 0.1225
R1 ¼ 0.0767, wR2 ¼ 0.1367
1.491 and ꢀ1.304
R1 ¼ 0.0655, wR2 ¼ 0.0990
R1 ¼ 0.2165, wR2 ¼ 0.1303
0.563 and ꢀ0.469
R1 ¼ 0.0547, wR2 ¼ 0.1215
R1 ¼ 0.0818, wR2 ¼ 0.1299
0.572 and ꢀ1.051
R indices (all data)
Largest diff. peak and hole (e.Åꢀ3
)
Table 5
Optimization of cross-coupling Conditionsa
selected compounds, aryl boronic acids featuring strongly acti-
vating groups such as eOCH3, and eOH gave significant yields
(Table 6, entries 6e, 6f, and 6i). Remarkably, a boronic acid with high
steric hindrance i.e., 2, 6-dimethoxyphenylboronic acid utilized in
the reaction gave 70% of the desired product (Table 6, entry 6 g).
Successfully, naphthyl and biphenyl boronic acids were also
smoothly converted into desired arylated indoles (Table 6, entries
6j and 6k). Likewise, aryl boronic acids possessing mꢀCl, peBr, and
peN(CH3)2 groups underwent the reaction smoothly to afford the
expected products in good yields (Table 6, entries 6l, 6 m, and 6n). It
is significant to note that the presence of halogens (bromo/chloro)
in the arylated indoles possess an additional advantage (Table 6,
entries 6l and 6 m) as they are suitable for further functionalization
through cross coupling. However, aryl boronic acids bearing alkyl
groups like p et-butyl, and eCH3 group at either ortho or para as
well as at both ortho and meta positions gave 82, 90, 92, and 89%
yields, respectively (Table 6, entries 6h, 6b, 6c, and 6d).
Moderately deactivating groups like acetyl or formyl, occupying
the meta and para position of phenylboronic acids, were well
tolerated under the reaction conditions to afford the desired
coupling product (Table 6, entries 6ꢁ, 6p and 6q). Moreover, a
phenylboronic acid with deactivating eCF3 group in the para po-
sition also reacted smoothly to give the corresponding arylated
product (Table 6, entry 6r). Based on the above observations,
reacting indoles with electron-rich aryl boronic acids is more
feasible than with others.
Entry
Catalyst
Base
Solvent
Yield (%)b
1
2
3
4
5
6
7
8
Complex 2
Complex 2
Complex 2
Complex 2
Complex 2
Complex 2
Complex 2
Complex 2
Complex 2
Complex 2
Complex 2
Complex 2
Complex 2
Complex 2
Complex 2
Complex 2
Complex 2
Complex 2
Complex 2
Complex 2
Complex 2
Complex 2
Complex 2
Complex 2
Complex 1
Complex 3
No base
No base
KOH
K2CO3
NaOH
Na2CO3
Et3N
Pyridine
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
H2O
NRc
12
76
69
66
60
37
32
52
49
56
44
51
76
84
55
53
45
32
68
72
84
76
70
79
94
H2O/MeOH
H2O/MeOH
H2O/MeOH
H2O/MeOH
H2O/MeOH
H2O/MeOH
H2O/MeOH
H2O/THF
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
H2O/EtOAc
H2O/DMF
H2O/CH3CN
H2O/DMSO
H2O/MeOH
H2O/EtOH
H2O/toluene
H2O/benzene
H2O/CHCl3
H2O/DCM
H2O/EtOH (10%)
H2O/EtOH (20%)
H2O/EtOH (30%)
H2O/EtOH (40%)
H2O/EtOH (50%)
H2O/EtOH (30%)
H2O/EtOH (30%)
In order to prove the efficacy of this catalytic methodology for
industrial application, we tested the gram scale synthesis of 2-
phenyl-3-H-indole (6a) as a representative example wherein
(Scheme 2) 82% yield of the product was realized.
To screen the reusability, the selected catalyst 3 was utilized
under parallel reaction conditions. The first cycle afforded 94% of
the corresponding coupled product followed by 88% in the next
run. However, third and fourth cycles gave 80% and 69% of the
coupled product. The lower yield observed after the fourth cycle
Bold implies the optimization of the reaction conditions.
a
Reaction conditions: 2-oxindole (3 mmol), phenylboronic acid (4 mmol), base
(5, mmol), Et3N (6 eqv.), PyBroP (1.2 eqv.) solvent (80:20%) and catalyst (0.01 mol %)
stirred at room temperature for 4e6 h.
b
Isolated yield.
No reaction.
c

12
A. Vignesh et al. / Journal of Organometallic Chemistry 824 (2016) 7e14
Table 6
Cross-coupling of 2-oxindole and various aryl boronic acids (6ae6r) under optimized reaction conditions.a
may be due to decomposition of the catalyst to leach out palladium.
The overall result of the reusability experiment is summarized in
Fig. 4. The stability of recovered catalyst was identified by 1H NMR
spectra, melting point data and Rf value of TLC. The detailed re-
covery process is provided in experimental section. The 1H NMR
spectrum of the used catalyst recovered from the first catalytic
cycle confirmed that the pincer structure of complex 3 remained
intact.
Based on previous reports [2,31,45e47], a plausible mechanism
for CeOH activation is proposed in Scheme 3. Initially, Pd(0)L (I)
Scheme 2. Gram scale synthesis of 2-phenyl-3-H-indole (6a).

A. Vignesh et al. / Journal of Organometallic Chemistry 824 (2016) 7e14
13
formed through a two-electron reduction of the starting palladium
(II) complex in presence of a base [45]. The phosphonium salt in-
termediate I obtained by the activation of indol-2-ol with PyBroP
enters into the Pd (0)L catalytic cycle via oxidative addition to give
intermediate II. Addition of KOH to intermediate II gave an inter-
mediate III through metathetic process. Transmetalation of inter-
mediate III with phenylboronic acid provides intermediate IV,
which undergoes reductive elimination to afford 2-phenylindole
with regeneration of the Pd (0)L. Finally, oxidation of active spe-
cies Pd(0) L by O2 led to the catalyst Pd(II)L [46,47].
4. Conclusions
First report on the arylation of 2-oxindole with aryl boronic
acids via PyBroP mediated in situ C (sp2)ꢀOH activation catalyzed
by Pd(II) pincer type complexes in H2O/EtOH mixture at room-
temperature. All the palladium complexes were characterized by
IR, 1H, 13C NMR and single-crystal X-ray diffraction. The current
strategy afforded 94% of the coupled product in a highly region-
selective manner with the catalyst the reusable up to four cycles.
Fig. 4. Reusability of catalyst 3.
Scheme 3. Proposed mechanism for arylation of 2-oxindole.

14
A. Vignesh et al. / Journal of Organometallic Chemistry 824 (2016) 7e14
[19] H. Firouzabadi, N. Iranpoor, M. Gholinejad, A. Samadi, J. Mol. Catal. A Chem.
377 (2013) 190.
[20] G.J. Chen, F.S. Han, Eur. J. Org. Chem. (2012) 3575.
[21] K.W. Quasdorf, M. Riener, K.V. Petrova, N.K. Garg, J. Am. Chem. Soc. 131 (2009)
17748.
Hence, the present palladium catalyzed methodology could be
considered as an attractive route to synthesize a series of biologi-
cally active 2-arylindoles in excellent yield.
[22] H. Gao, Y. Li, Y.G. Zhou, F.S. Han, Y.J. Lin, Adv. Synth. Catal. 353 (2011) 309.
[23] N. Iranpoor, F. Panahi, Org. Lett. 17 (2015) 214.
Acknowledgements
[24] G.J. Chen, J. Huang, L.X. Gao, F.S. Han, F.S. Chem, Eur. J. 17 (2011) 4038.
[25] A. Sharma, D. Vachhani, E.V. Eycken, Org. Lett. 14 (2012) 1854.
[26] S.M. Li, J. Huang, G.J. Chena, F.S. Han, Chem. Commun. 47 (2011) 12840.
[27] S.Y. Kumar, C. Dasarathan, K. Prabakaran, F.R.N. Khan, E.D. Jeong, E.H. Chung,
H.G. Kim, RSC Adv. 4 (2014) 40259.
Mr. A. Vignesh thanks the University Grants Commission (UGC),
New Delhi, India. for the award of Senior Research Fellowship (SRF)
under UGC-BSR RFSMS.
[28] V.P. Mehata, S.G. Modha, E.V.V. Eycken, J. Org. Chem. 75 (2010) 976.
[29] a) D.B. Garagorri, K. Kirchner, Acc. Chem. Res. 41 (2008) 201;
b) N. Selander, K.J. Szabo, Chem. Rev. 111 (2011) 2048;
c) J.L. Niu, X.Q. Hao, J.F. Gong, M.P. Song, Dalton Trans. 40 (2011) 5135.
[30] a) A.K. Crawford, A.H. Cowley, S.M. Humphrey, Catal. Sci. Technol. 4 (2014)
1456;
b) W. Susanto, C.Y. Chu, W.J. Ang, T.C. Chou, L.C. Lo, Y. Lam, J. Org. Chem. 77
(2012) 2729;
c) H.D. Velazquezd, F. Verpoort, Chem. Soc. Rev. 41 (2012) 7032.
[31] a) A. Vignesh, W. Kaminsky, N.S.P. Bhuvanesh, N. Dharamraj, RSC Adv. 5
(2015) 59428;
Appendix A. Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.jorganchem.2016.09.026.
References
[1] The Merck Index, An Encyclopedia of Chemicals, Drugs and Biologicals, 3th
ed., Merck & Co., Inc., Whitehouse Station, NJ, 2001.
[2] a) F.A. Kang, Z. Sui, W.V. Murray, J. Am. Chem. Soc. 130 (2008) 11300;
b) F.A. Kang, C. James, J.C. Lanter, C. Cai, Z. Sui, W.V. Murray, Chem. Commun.
46 (2010) 1347.
b) A. Vignesh, W. Kaminsky, N. Dharmaraj, RSC Adv. 5 (2015) 77948;
c) A. Vignesh, W. Kaminsky, N. Dharmaraj, Green Chem. 18 (2016) 3295;
(d) A. Vignesh, W. Kaminsky, N. Dharmaraj, ChemCatChem (2016), http://
dx.doi.org/10.1002/cctc.201600717.
[32] A.I. Vogel, Text Book of Practical Organic Chemistry, 5th ed., Longman, London,
1989.
[3] a) G. Tan, T. Szilvasi, S. Inoue, B. Blom, M. Driess, J. Am. Chem. Soc. 136 (2014)
9732.
[33] P. Sathyadevi, P. Krishnamoorthy, R.R. Butorac, A.H. Cowley, N.S.P. Bhuvanesh,
N. Dharmaraj, Dalton Trans. 40 (2011) 9690.
[34] Z. Otwinowsky, W. Minor, Methods in Enzymology, in: C.W. Carter,
R.M. Sweet (Eds.) vol. 276, Academic Press, New York, 1997, p. 307.
[35] Bruker, APEX2 (Version 2.1-4), SAINT (Version 7.34A), SADABS (Version 2007/
4), BrukerAXS Inc, Madison, Wisconsin, USA, 2007.
[36] (a) A. Altomare, C. Burla, M. Camalli, G.L. Cascarano, C. Giacovazzo,
A. Guagliardi, A.G.G. Moliterni, G. Polidori, R. Spagna, J. Appl. Cryst. 32 (1999)
115;
[4] V. Sharma, P. Kumar, D. Pathak, J. Heterocycl. Chem. 47 (2010) 491.
[5] Z.K. Owczarczyk, W.A. Braunecker, A. Garcia, R. Larsen, A.M. Nardes,
N. Kopidakis, D.S. Ginley, D.C. Olson, Macromolecules 46 (2013) 1350.
[6] M.S. Park, D.H. Choi, B.S. Lee, J.Y. Lee, J. Mater. Chem. 22 (2012) 3099.
[7] P.A. Gale, Chem. Commun. (2008) 4525.
[8] J. Nanda, A. Biswas, B. Adhikari, A. Banerjee, Angew. Chem. Int. 52 (2013)
5041.
ꢀ
ꢀ
[9] A. Gonzalez, J. Granell, C. Lopez, R. Bosque, L.J. Rodríguez, J. Organomet. Chem.
726 (2013) 21.
(b) A. Altomare, G.L. Cascarano, C. Giacovazzo, A. Guagliardi, J. Appl. Cryst. 26
(1993) 343.
[10] a) S.B. Lane, D. Sames, Org. Lett. 6 (2004) 2897;
b) Z. Liang, B. Yao, Y. Zhang, Org. Lett. (2010) 3185;
[37] G.M. Sheldrick, SHELXL-97, Program for the Refinement of Crystal Structures,
c) S.B. Lane, A.M. Brown, D. Sames, J. Am. Chem. Soc. 127 (2005) 8050;
d) C. Sollert, K. Devaraj, A. Orthaber, P.J. Gates, L.T. Pilarski, Chem. Eur. J. 21
(2015) 1;
€
University of Gottingen, Germany, 1997.
[38] S. Mackay, C. Edwards, A. Henderson, C. Gilmore, N. Stewart, K. Shankland,
A. Donald, MaXus: a Computer Program for the Solution and Refinement of
Crystal Structures from Diffraction Data, University of Glasgow, Scotland,
1997.
[39] D. Waasmaier, A. Kirfel, Acta Cryst. A 51 (1995) 416.
[40] D. Pandiarajan, R. Ramesh, Y. Liu, R. Suresh, Inorg. Chem. Commun. 33 (2013)
33.
[41] M.M. Tamizh, B.F.T. Cooper, C.L.B. Macdonald, R. Karvembu, Inorg. Chim. Acta
394 (2013) 393.
[42] S.K. Gupta, P.B. Hitchcock, Y.S. Kushwah, G.S. Argal, Inorg. Chim. Acta 360
(2007) 2145.
[43] S. Das, S. Pal, J. Organomet. Chem. 691 (2006) 2575.
[44] X.W. Liu, J.L. Shi, J.B. Wei, C. Yang, J.X. Yan, K. Peng, L. Dai, C.G. Li, B.Q. Wang,
Z.J. Shi, Chem. Commun. 51 (2015) 4599.
[45] J. Dutta, M.G. Richmond, S. Bhattacharya, Dalton Trans. 44 (2015) 13615.
[46] P.B. White, J.N. Jaworski, C.G. Fry, B.S. Dolinar, I.A. Guzei, S.S. Stahl, J. Am.
Chem. Soc. 138 (2016) 4869.
e) G.S. Modha, F.M. Greaney, J. Am. Chem. Soc. 137 (2015) 1416;
f) S. Cacchi, G. Fabrizi, L.M. Parisi, Org. Lett. 5 (2003) 3843.
[11] J.P. Dalvadi, K.P. Patel, H.K. Chikhalia, Tetrahedron 70 (2014) 9394.
[12] (a) B.M. Rosen, K.W. Quasdorf, D.A. Wilson, N. Zhang, A.M. Resmerita,
N.K. Garg, V. Percec, Chem. Rev. 111 (2011) 1346;
b) J. Yamaguchi, K. Muto, K. Itami, Eur. J. Org. Chem. 19 (2013);
(c) D.G. Yu, B.J. Li, Z.J. Shi, Acc. Chem. Res. 43 (2010) 1486.
[13] B.T. Guan, Y. Wang, B.J. Li, D.G. Yu, Z.J. Shi, J. Am. Chem. Soc. 130 (2008) 14468.
[14] a) M. Baghbanzadeh, C. Pilger, C.O. Kappe, J. Org. Chem. 76 (2011) 1507;
b) K.W. Quasdorf, M. Riener, K.V. Petrova, N.K. Garg, J. Am. Chem. Soc. 131
(2009) 17748;
c) K.W. Quasdorf, A.A. Finch, P. Liu, A.L. Silberstein, A. Komaromi, T. Blackburn,
S.D. Ramgren, K.N. Houk, V. Snieckus, N.K. Garg, J. Am. Chem. Soc. 133 (2011)
6352.
[15] P. Leowanawat, N. Zhang, V. Percec, J. Org. Chem. 77 (2012) 1018.
[16] M. Tobisu, T. Shimasaki, N. Chatani, Angew. Chem. Int. 47 (2008) 4866.
[17] K.W. Quasdorf, X. Tian, N.K. Garg, J. Am. Chem. Soc. 130 (2008) 14422.
[18] Y.L. Zhao, Y. Li, L.X. Gao, F.S. Han, Chem. Eur. J. 16 (2010) 4991.
[47] J. Yu, J. Liu, G. Shi, C. Shao, Y. Zhang, Angew. Chem. Int. 127 (2015) 4151.