Accessing a Biologically Relevant Benzofuran Skeleton by a One-Pot Tandem Heck Alkynylation/Cyclization Reaction Using Well-Defined Palladium N-Heterocyclic Carbene Complexes

Article abstract of DOI:10.1021/acs.inorgchem.5b02727

Well-defined palladium N-heterocyclic carbene (NHC) complexes were employed in the one-pot tandem Heck alkynylation/cyclization sequence for preparing biologically relevant benzofuran compounds under copper-free conditions in a time-efficient step-reduced

Full text of DOI:10.1021/acs.inorgchem.5b02727

Article
pubs.acs.org/IC
Accessing a Biologically Relevant Benzofuran Skeleton by a One-Pot
Tandem Heck Alkynylation/Cyclization Reaction Using Well-Defined
Palladium N‑Heterocyclic Carbene Complexes
Anuj Kumar, Manoj Kumar Gangwar, A. P. Prakasham, Darshan Mhatre, Alok Ch. Kalita,
and Prasenjit Ghosh*,†
†Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400 076, India
S
* Supporting Information
ABSTRACT: Well-defined palladium N-heterocyclic carbene
(NHC) complexes were employed in the one-pot tandem Heck
alkynylation/cyclization sequence for preparing biologically relevant
benzofuran compounds under copper-free conditions in a time-
efficient step-reduced fashion. In particular, a series of binuclear
palladium complexes, 1b−1e and 2b−2e, of the alkyl-bridged NHC
ligands, namely, {1,1′-di-R1-4,4′-R2-di-1,2,4-triazoline-5,5′-diylid-2-
ene] (R1 = i-Pr; R2 = −(CH2)2−, −(CH2)3−), and their mononuclear
analogues, trans-(NHC)PdBr2(pyridine) (3b) and cis-(NHC)-
PdBr2(PPh3) (3c), successfully catalyzed the one-pot tandem Heck
alkynylation/cyclization reaction of 2-iodophenol with a variety of
terminal alkyne substrates, yielding 2-substituted benzofuran deriva-
tives. The mononuclear complexes 3b and 3c were nearly half as
active as the representative dinuclear analogue 1c under analogous reaction conditions, thereby implying that, at the same mole
percent of the palladium loading, the monometallic 3b and 3c and the bimetallic 1c complexes were equally effective as catalysts.
The two sites of the bimetallic complex 1c performed as two separate independent catalytic sites, displaying no cooperativity
effect in the catalysis. Finally, the practical utility of the aforementioned catalysts was demonstrated for a representative catalyst
1c through the convenient synthesis of a key intermediate, 3-[2-(benzo[d][1,3]dioxol-5-yl)-7-methoxybenzofuran-5-yl]propan-1-
ol, in a total-synthesis protocol of the natural product Egonol.
(which also is popularly referred to as Heck alkynylation)19−23
INTRODUCTION
■
as part of a broader study on a variety of C−C20,24−26,27−31 C−
Benzofurans constitute an important motif ubiquitous in many
N,31−33 and C−B34 bond-forming reactions and founded on
which we chose to undertake the next logical extension of
targeting more complex transformations like that of the one-pot
tandem Heck alkynylation/cyclization reaction under similar
copper-free conditions for obvious reasons. In particular, we
decided to explore the utility of the monometallic and
bimetallic palladium NHC (Pd-NHC) complexes for the one-
pot tandem Heck alkynylation/cyclization reaction. Further-
more, as a bimetallic palladium catalyst was reported to be
more efficient than its monometallic counterparts,11 and we
decided to verify the same for the monometallic and bimetallic
palladium complexes of our NHC ligands. Lastly, we decided to
focus on the 1,2,4-triazole-derived NHC ligands primarily
because of (i) a prior report of the 1,2,4-triazole-derived NHC-
based palladium catalysts outperforming the imidazole-based
analogues for the same one-pot tandem Heck alkynylation/
cyclization reaction yielding benzofuran compounds11 and (ii)
bioactive compounds like BNC105,1 amiodarone,2 cytotoxic
flavonoids,3 and the natural products Daphnodorin A and B,4
Egonol,5,6 and Moracin O and P.7,8 Hence, an efficient
synthesis of benzofuran compounds is of considerable interest.
In this context, the one-pot tandem reaction involving
sequential Heck alkynylation reaction and intramolecular
cyclization provides a step-efficient time-improved approach
for construction of the benzofuran framework. Because only a
handful of examples of the use of well-defined catalysts
exist,9−11 with the majority being under ligand-assisted catalysis
(LAC) conditions,12−15 we became interested in developing
well-defined homogeneous catalytic systems for the one-pot
tandem Heck alkynylation/cyclization reaction for accessing the
benzofuran compounds.
With one of our objectives being furthering the scope of the
transition-metal complexes of the N-heterocyclic carbenes
(NHCs) in homogeneous catalysis16,17 and in biomedical
applications,18 we became interested in exploring the potential
of these complexes in more challenging tandem reactions. The
motivation for the current work came from our earlier successes
with the Sonogashira coupling under copper-free conditions
Received: November 24, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.inorgchem.5b02727
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
the fact that the 1,2,4-triazole-derived NHCs are less explored
than their imidazole-based counterparts.35,36
of the binuclear PEPPSI-themed complexes 1b and 2b with
PPh3, the corresponding mixed-NHC/phosphine complexes 1c
and 2c were obtained in 38−84% yield. Finally, reactions of
both the PEPPSI-themed 1b and 2b complexes and mixed-
NHC/phosphine-derived 1c and 2c complexes with AgO-
COCF3 yielded the trifluoroacetate derivatives 1d and 2d and
also 1e and 2e, respectively, in 72−96% yield. It is worth noting
that, among the 1b−1e and 2b−2e complexes, only the 2e
complex showed two sets of resonances in an approximate 1:4
ratio in its 1H NMR spectrum at room temperature, suggesting
an exchange between two conformers. The variable-temper-
Here, in this contribution, we report a series of Pd-NHC
complexes, 1b−1e, 2b−2e, 3b, and 3c, of the 1,2,4-triazole-
derived NHC ligands that efficiently carried out the one-pot
tandem Heck alkynylation/cyclization reaction under copper-
free conditions, giving various benzofuran compounds (Figure
1). A comparison of the catalytic efficiencies of the
1
ature H NMR experiment (Supporting Information, Figures
S140−S143) indicated a faster exchange at a higher temper-
ature, with the ratio decreasing to ca. 1:1.08 at 100 °C
(Supporting Information, Figures S140−S143). The possibility
of a cis−trans isomerism was ruled out based on the 31P{1H}
NMR results that showed the corresponding phosphorus
resonances appearing at 25.7 and 25.3 ppm in concurrence
with a cis structure of the 2e complex.25 Subsequent structural
characterization by the single-crystal X-ray diffraction study
gave the molecular structure of the major conformer (Figure 2
and the Supporting Information, Figure S3).
Quite expectedly, the Pd−NCN resonance of the 1b−1e and
2b−2e complexes appeared at ca. 148.9−167.0 ppm in the
13C{1H} NMR spectrum in concurrence with the range
observed for related complexes.20,37 Likewise, the Pd−PPh3
resonance for the 1c, 2c, 1e, and 2e complexes appeared at ca.
25.3−27.3 ppm in the 31P{1H} NMR spectrum, indicating cis
disposition of the PPh3 ligand with respect to the NHC ligand
in these cis-(NHC)Pd(PPh3)X2-type complexes.25,38−40
The molecular structure of the PEPPSI-themed complexes
1b and 2b, the mixed-NHC/phosphine complexes 1c and 2c,
and the trifluoroacetate analogues 1d, 1e, and 2e, as determined
by X-ray diffraction studies, revealed the binuclear structure of
these complexes with two palladium atoms bound to two
carbene centers in each of the alkyl-bridged NHC ligands
(Figures 3−6 and the Supporting Information, Figures S1−S3
and Table S1). However, in no instance was chelation of two
carbene centers of an alkyl-bridged NHC ligand to one
palladium atom observed. This is an outcome of the longer
bridging ethyl and propyl linkers present between the two
carbene centers of the NHC ligands, as opposed to a shorter
methylene linker, for which chelation of both carbene centers
to a single palladium center was seen.41−43
Figure 1. Palladium complexes of 1,2,4-triazole-derived NHC ligands.
monometallic and bimetallic Pd-NHC complexes was under-
taken to probe the cooperativity effect, if any, present in the
tandem catalysis. As a proof of concept, we further demonstrate
the practical utility of these catalysts for a representative
catalyst, 1c, by synthesizing a benzofuran intermediate, namely,
3-(2-(benzo[d][1,3]dioxol-5-yl)-7-methoxybenzofuran-5-yl)-
propan-1-ol, of a total-synthesis pathway to the bioactive
natural product Egonol (Scheme 3).
Consistent with a d8 configuration, the palladium center was
found to be in square-planar geometry in all of the 1b−1e, 2b,
2c, and 2e complexes. The Pd−Ccarbene bond distances in 1b
[1.964(6) and 1.945(6) Å], 2b [1.972(7) and 1.956(7) Å], 1c
[1.982(3) Å], 2c [1.980(5) and 1.978(5) Å], 1d [1.97(3) Å] 1e
[1.954(3) Å], and 2e [1.964(5) and 1.971(5) Å] are slightly
smaller than the sum of the individual covalent radii of the
palladium and carbon atoms (2.12 Å).44 The Pd−Npyridine bond
distances in 1b [2.083(5) and 2.084(5) Å], 2b [2.090(6) and
2.070(6) Å], and 1d [2.02(3) Å] are comparable to the sum of
the covalent individual radii of the palladium and nitrogen
atoms (2.10 Å).44 Quite expectedly, owing to a large covalent
radius of phosphorus (1.07 Å)44 over nitrogen (0.71 Å),44 the
Pd−PPh3 bond distances in 1c [2.2560(8) Å], 2c [2.2727(13)
and 2.2629(14) Å], 1e [2.2547(7) Å], and 2e [2.2397(11) and
2.2448(11) Å] are longer than the Pd−Npyridine bond distances
found in 1b [2.083(5) and 2.084(5) Å], 2b [2.090(6) and
2.070(6) Å], and 1d [2.02(3) Å].
RESULTS AND DISCUSSION
■
A series of binuclear palladium complexes, 1b−1e and 2b−2e,
were synthesized with the view of their application in one-pot
tandem Heck alkynylation/cyclization reactions for accessing
the 2-substituted benzofuran-type frameworks in more
convenient and fewer reaction sequences. With the intent of
undertaking a comparative structure−activity-correlation study,
several related variants of Pd-NHC complexes were thus
synthesized (Figure 1). The binuclear PEPPSI (pyridine-
enhanced precatalyst preparation, stabilization, and initiation)-
themed complexes 1b and 2b were obtained by direct reaction
of the corresponding dicationic triazolium dibromide salts 1a
and 2a with 2 equiv of PdBr2 in pyridine in the presence of
K2CO3 as a base in 90−91% yield (Scheme 1). Upon treatment
B
DOI: 10.1021/acs.inorgchem.5b02727
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
Scheme 1. Synthesis of the Palladium Complexes of Various Alkyl-Bridged Bis(1,2,4-triazole)-Derived NHC Ligands
Figure 2. Conformational exchange observed in the solution 1H NMR
spectrum of complex 2e.
Notable is the molecular structure of 1d showing a cis
Figure 3. ORTEP diagram of 1b with thermal ellipsoids shown at the
50% probability level. Selected bond lengths (Å) and angles (deg):
Pd1−C1 1.964(6), Pd1−Br1 2.4256(11), Pd1−Br2 2.4244(10), Pd1−
N7 2.083(5), Pd2−C8 1.945(6), Pd2−Br3 2.4261(11), Pd2−Br4
2.4258(11), Pd2−N8 2.084(5); C1−Pd1−Br1 89.4(2), Br1−Pd1−Br2
175.42(3), C1−Pd1−Br2 88.6(2), C1−Pd1−N7 177.3(2), N7−Pd1−
Br1 90.37(17), C8−Pd2−Br3 88.3(2), Br3−Pd2−Br4 175.08(3), C8−
Pd2−Br4 86.8(2), C8−Pd2−N8 175.7(3), N8−Pd2−Br4 91.89(18).
disposition of the pyridine ligand relative to the NHC ligand,
which, to our knowledge, is the only structurally characterized
example of a cis-(NHC)PdX2(pyridine)-type complex (X = an
anionic ligand) ever reported in the literature (Figure 5).45 In
contrast, numerous structurally characterized examples of the
trans-(NHC)PdX2(pyridine)-type complexes (X = an anionic
ligand), having a pyridine ligand bound trans to the NHC
ligand, are known in the literature.45,46
The syntheses of the monometallic analogues 3b and 3c were
undertaken in order to probe the cooperativity effect in catalysis
in these bimetallic Pd-NHC complexes, 1b−1e and 2b−2e, and
were thus obtained by analogous synthetic procedures
described earlier for the bimetallic Pd-NHC counterparts
(Scheme 2). The molecular structures of the monometallic
analogues 3b and 3c were similar to those of the their dinuclear
counterparts 1b, 2b, 1c, and 2c (Supporting Information,
Figures S4 and S5 and Table S2). The tandem Heck
alkynylation/cyclization reaction between two representative
2-iodophenol and phenylacetylene substrates as catalyzed by
the palladium complexes 1b−1e and 2b−2e of various alkyl-
bridged bis(1,2,4-triazole)-derived NHC ligands is given in eq
1.
C
DOI: 10.1021/acs.inorgchem.5b02727
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
Figure 6. ORTEP diagram of 1e with thermal ellipsoids shown at the
50% probability level. Selected bond lengths (Å) and angles (deg):
Pd1−C1 1.954(2), Pd1−O3 2.0728(17), Pd1−O1 2.0790(17), Pd1−
P1 2.2547(7); C1−Pd1−O3 94.50(8), O1−Pd1−O3 83.81(7), C1−
Pd1−O1 177.17(8), C1−Pd1−P1 90.90(7), P1−Pd1−O3 168.95(5).
Figure 4. ORTEP diagram of 1c with thermal ellipsoids shown at the
50% probability level. Selected bond lengths (Å) and angles (deg):
Pd1−C1 1.982(3), Pd1−Br1 2.4958(8), Pd1−Br2 2.4608(4), Pd1−P1
2.2560(8); C1−Pd1−Br1 87.12(8), Br1−Pd1−Br2 93.164(14), C1−
Pd1−Br2 178.48(9), C1−Pd1−P1 91.18(8), P1−Pd1−Br1 177.85(3),
P1−Pd1−Br2 88.50(2).
PdI2(PPh3) complex [a-NHC = 1-benzyl-3-R1-4-R2-1,2,3-
triazol-5-ylidene, where R1 = Me and R2 = Ph] over its
PEPPSI-themed analogues trans-(a-NHC)PdI2(pyridine) [a-
NHC = 1-benzyl-3-R1-4-R2-1,2,3-triazol-5-ylidene, where R1 =
Me and R2 = Ph] and the mixed-NHC/phosphine complexes
trans-(a-NHC)PdI2(PPh3) [a-NHC = 1-benzyl-3-R1-4-R2-1,2,3-
triazol-5-ylidene, where R1 = Me, Et and R2 = C6H10OH)]-type
complexes in the Hiyama coupling of aryl iodide and
PhSi(OMe)3 substrates.25 The time-dependent mercury drop
experiment, in which mercury additions were performed at
different time intervals, showed no change within significant
errors in the product yields, varying from 81% in the absence of
mercury to 84% in the presence of mercury from the start of
the reaction (Supporting Information, Table S3) and is
indicative of the homogeneous nature of the catalysis.
A comparison of the activity of the monometallic and
bimetallic complexes revealed that, at 1 mol % catalyst loading,
the monometallic analogues 3b and 3c produced reaction yields
of nearly half that of a representative bimetallic Pd-NHC
complex, 1c, and only at double the catalyst loading of 2 mol %
did the monometallic analogues 3b and 3c match up with the
reaction yield of 1 mol % of a representative bimetallic Pd-
NHC complex, 1c, under analogous reaction conditions (entry
1 of Table 2 and the Supporting Information, Table S4). This
observation implied that, at the same mole percent of the
palladium loading, the monometallic complexes 3b and 3c and
the bimetallic complex 1c were equally active, thus ruling out
the possibility of the presence of a cooperativity effect in the
catalysis. The two sites of the bimetallic complex, 1c, behaved
independently of each other as two separate catalytic sites.
A substrate scope study was undertaken for the most active
complex 1c with the aim of exploring the catalyst versatility.
Substrates ranging from electron-donating terminal aryl
alkynes, namely, 4-ethynyl-1,2-dimethoxybenzene, 1-ethynyl-4-
methoxybenzene, 4-ethynyl-N,N-dimethylaniline, and 5-
ethynylbenzo[d][1,3]dioxole (Table 2, entries 2−5), to an
electron-withdrawing one, namely, 1-ethynyl-4-fluorobenzene
(Table 2, entry 6), to even aliphatic analogues, namely, 1-
ethynylcyclohexan-1-ol, but-3-yn-1-ol, and propargyl alcohol
(Table 2, entries 7−9), were reacted with 2-iodophenol in the
presence of the catalyst 1c, giving the corresponding
substituted benzofuran derivatives 5−12 in moderate-to-good
isolated yield (47−84%). The electron-rich terminal aryl
Figure 5. ORTEP diagram of 1d with thermal ellipsoids shown at the
50% probability level. Selected bond lengths (Å) and angles (deg):
Pd1−C1 1.97(3), Pd1−O3 2.07(2), Pd1−O1 2.02(2), Pd1−N4
2.02(3); C1−Pd1−O3 177.6(10), O1−Pd1−O3 87.9(9), C1−Pd1−
O1 90.3(12), C1−Pd1−N4 92.0(712), N4−Pd1−O3 89.7(10), N4−
Pd1−O1 177.1(9).
Significantly enough, all of the 1b−1e and 2b−2e complexes
effectively catalyzed the one-pot tandem Heck alkynylation/
cyclization reaction between o-iodophenol substrates with
terminal alkynes, giving the desired benzofuran compounds
(eq 1). In particular, the tandem reaction was performed at 1
mol % catalyst loading (1b−1e and 2b−2e) for the two
representative substrates, 2-iodophenol and phenylacetylene, in
the presence of Cs2CO3 as the base at 80 °C in dimethyl
sulfoxide (DMSO), yielding the desired 2-phenylbenzofuran
product in 58−81% isolated yield (Table 1). The benzofuran
product was purified by column chromatography in silica gel by
elution with petroleum ether. More interestingly, the ethyl-
bridged 1b−1e complexes exhibited higher yields (72−81%)
than the propyl analogues 2b−2e (58−70%). Furthermore,
among the ethyl-bridged 1b−1e complexes, the cis-mixed-
NHC/phosphine complex 1c displayed the maximum yield of
81%. In this context, it is worth noting that we had earlier
observed similar higher activity of a related cis-(a-NHC)-
D
DOI: 10.1021/acs.inorgchem.5b02727
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
Scheme 2. Synthesis of the Monometallic Palladium Complexes of a 1,2,4-Triazole-Derived NHC Ligand
Table 1. Tandem Heck Alkynylation/Cyclization Reaction between Two Representative 2-Iodophenol and Phenylacetylene
Substrates As Catalyzed by the Palladium Complexes 1b−1e and 2b−2e of Various Alkyl-Bridged Bis(1,2,4-triazole)-Derived
b
NHC Ligands
a
b
Isolated yields. Reaction conditions: 2-iodophenol (0.110 g, 0.500 mmol), phenylacetylene (0.078 g, 0.760 mmol), and Cs2CO3 (0.489 g, 1.50
mmol) in the presence of 1 mol % catalyst and in 3 mL of DMSO. Reaction time = 4 h; temperature = 80 °C.
alkynes were more reactive, yielding the desired products 5−8
in 47−70% yield in 4 h of reaction time (Table 2, entries 2−5),
while the electron-deficient terminal aryl alkyne 1-ethynyl-4-
fluorobenzene reacted slowly over a reaction time of 24 h,
producing the benzofuran product 9 in 53% yield (Table 2,
entry 6). The aliphatic ones 1-ethynylcyclohexan-1-ol and but-
3-yn-1-ol (Table 2, entries 7 and 8) also reacted in 24 h of
reaction time, giving the corresponding products 10 and 11 in
79% and 62% yield, respectively. The propargyl alcohol was the
least reactive one, producing 84% yield of the product 12 in 48
h of reaction time (Table 2, entry 9). Overall, the terminal aryl
alkynes were more reactive than the aliphatic alkynes for the
one-pot tandem Heck alkynylation/cyclization reaction. The
catalyst 1c proved to be ineffective for a terminal alkyne bearing
ester functionality, as observed for the representative ethyl
propiolate substrate. Along the same lines, the o-bromophenol
and o-chlorophenol substrates yielded no product under
analogous reaction conditions.
The comparison of the catalytic activities of the 1b−1e and
2b−2e complexes with the other reported catalysts for the one-
pot tandem Heck alkynylation/cyclization reaction yielding
benzofuran compounds is important. We are aware of only one
prior report of the use of well-defined PEPPSI-themed
(NHC)PdCl2(pyridine)-type catalysts11 analogous to that of
our 1b−1e and 2b−2e complexes for the tandem reaction and
of a few other reports of the in situ generated palladium
phosphine complexes under LAC conditions.12−15 In particular,
several PEPPSI-themed (NHC)PdCl2(pyridine) (NHC =
1,2,4-trimethyltriazolyldiylidene, 1,3-dimethylimidazolylidene,
and 1,4-dimethyltriazolylidene) type complexes performed the
one-pot tandem Heck alkynylation/cyclization reaction of 2-
iodophenol with phenylacetylene, giving 2-phenylbenzofuran at
1 mol % catalyst loading in DMSO in the presence of Cs2CO3
as the base in 16−93% yield.11 Furthermore, among these
catalysts, the bimetallic (NHC)Pd2Cl4(pyridine)2 (NHC =
1,2,4-trimethyltriazolyldiylidene) catalyst was the most active,
exhibiting 93% of the product yield in 8 h of reaction time,
while the monometallic 1,2,4-triazole-derived (NHC)-
PdCl2(pyridine) (NHC = 1,4-dimethyltriazolylidene) displayed
88% of the product yield after 16 h of reaction time for the
reaction of 2-iodophenol with phenylacetylene. The imidazole-
derived (NHC)PdCl2(pyridine) (NHC = 1,3-dimethylimida-
zolylidene) catalyst was the least active one, exhibiting only
16% of the product yield after a longer reaction time of 20 h for
the reaction of 2-iodophenol with phenylacetylene.11 As for the
non-NHC-based catalysts, a well-defined copper pincer
complex, namely, dichloro{2-[(1H-pyrazol-1-yl-kN2)methyl]-
6-(1H-pyrazol-1-yl-kN2)pyridine-kN}copper(II), catalyzed the
reaction of various halophenol and terminal alkyne substrates at
a low catalyst loading of 0.15 mol %, giving the desired
benzofuran products in good-to-excellent yield but a relatively
higher temperature of 130 °C.9
With regard to the examples from the in situ generated LAC-
based systems, a tetraphosphine ligand, namely, N2,N2,N6,N6-
tetrakis[(diphenylphosphanyl)methyl]pyridine-2,6-diamine
(0.1 mol %), and [Pd(η3-C3H5)Cl]2 (0.05 mol %) catalyzed the
one-pot tandem Heck alkynylation/cyclization reaction of a
variety of halophenol and alkynes, giving the benzofuran
E
DOI: 10.1021/acs.inorgchem.5b02727
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
Table 2. Selected Results for the Tandem Heck Alkynylation/Cyclization Reaction of Iodophenol and Various and Terminal
b
Alkyne Substrates As Catalyzed by 1c
a
b
Isolated yields. Reaction conditions: 2-iodophenol (0.500 mmol), terminal alkyne (0.750 mmol), and Cs2CO3 (1.50 mmol) in the presence of 1c
(1 mol %) and in 3 mL of DMSO. Temperature = 80 °C.
Scheme 3. Synthesis of a Benzofuran Intermediate (13) in a Total-Synthesis Sequence of the Natural Product Egonol by the
One-Pot Tandem Heck Alkynylation/Cyclization Reaction As Catalyzed by 1c
products in poor-to-excellent yield (17−99%) and also at a very
high temperature of 130 °C.12 The reactions of iodoresorcinol
and various alkynes were catalyzed by Pd(PPh3)Cl2 (5 mol %)
in the presence of CuI (5 mol %) as a cocatalyst, giving the
corresponding benzofuran product in 68−93% yield.47 Thus,
against this backdrop, the catalyst 1c not only is efficient at 1
mol % catalyst loading and operates at a significantly lower
reaction temperature of 80 °C but also is versatile with regard
to exhibiting broad substrate scope in establishing its generality
of usage as a catalyst for the one-pot tandem Heck
alkynylation/cyclization reaction between 2-iodophenol with
nine different terminal alkyne substrates for yielding the 2-
substituted benzofuran compounds.
intermediate in the total-synthesis sequence of the bioactive
natural product Egonol (Scheme 3).5,6 In particular, one-pot
tandem Heck alkynylation/cyclization reaction between 4-
hydroxy-3-iodo-5-methoxybenzaldehyde (iodovanillin) and 5-
ethynylbenzo[d][1,3]dioxole was catalyzed by 1c, yielding the
corresponding biologically relevant benzofuran intermediate 13
in DMSO in 36% yield in 4 h of reaction time at 80 °C.
A proposed mechanism based on simplified mononuclear cis/
trans-(NHC)PdX2(L) (X = Br, OCOCF3 and L = PPh3,
pyridine) type complexes suggests the presence of two catalytic
cycles involving the Heck alkynylation cycle, followed by an
intramolecular cyclization reaction, leading to the benzofuran
product formation (Scheme 4). The first catalytic cycle initiates
with the reduction of the palladium(II) complexes 1b−1e and
2b−2e to a palladium(0) species (A), which upon oxidative
Finally, the catalyst 1c, as demonstrated through a simple
practical synthesis of a benzofuran compound (13), is an
F
DOI: 10.1021/acs.inorgchem.5b02727
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
Scheme 4. Proposed Mechanism for the Tandem Heck Alkynylation/Cyclization Reaction between Two Representative 2-
Iodophenol and Phenylacetylene Substrates As Catalyzed by a Simplified Mononuclear (NHC)PdX2(L) (X = Br, OCOCF3 and
L = PPh3, py) Type Complex
addition with 2-iodophenol yields an intermediate (B). The
coordination of phenylacetylene to palladium yielded the
species C, which yielded the intermediate D upon deprotona-
tion of the palladium-coordinated terminal acetylene moiety.
The completion of the Heck alkynylation cycle is accompanied
by the reductive elimination of 2-(phenylethynyl)phenol from
the intermediate D. The product of the first catalytic cycle, 2-
(phenylethynyl)phenol, becomes the substrate for the next
catalytic cycle. It enters the intramolecular cyclization catalytic
cycle by undergoing oxidative addition to the palladium(0)
species A, giving intermediate E, which upon intermolecular
rearrangement produces intermediate F. Finally, the reductive
elimination from the intermediate F gives the desired 2-
phenylbenzofuran (4) along with regeneration of the
palladium(0) species A.
observed in the representative binuclear catalyst 1c compared
with their mononuclear analogues 3b and 3c.
EXPERIMENTAL SECTION
■
General Procedures. All manipulations were carried out using
standard Schlenk techniques. Palladium bromide, phenylacetylene, 1-
ethynyl-4-fluorobenzene, 1-ethynyl-4-methoxybenzene, 4-ethynyl-
N,N-dimethylaniline, 1-ethynylcyclohexanol, but-3-yn-1-ol, and silver
trifluoroacetate were purchased from Sigma-Aldrich. The ligand
precursors 1,1′-diisopropyl-4,4′-ethylenedi-1,2,4-triazolium dibromide
(1a), 1,1′-diisopropyl-4,4′-propylenedi-1,2,4-triazolium dibromide
(2a), and 1-isopropyl-4-ethyl-1,2,4-triazolium bromide (3a) were
synthesized according to modified literature procedures.48 The alkynes
4-ethynyl-1,2-dimethoxybenzene and 5-ethynylbenzo[d][1,3]dioxole
were prepared according to modified literature procedures.49 1H,
13C{1H}, 19F{1H}, and 31P{1H} NMR spectra were recorded on
Bruker 400 MHz and Bruker 500 MHz NMR spectrometers. 1H NMR
peaks are labeled as singlet (s), doublet (d), triplet (t), broad (br),
triplet of triplets (tt), doublet of doublets (dd), multiplet (m), and
septet (sept). IR spectra were recorded on a PerkinElmer Spectrum
One Fourier transform infrared spectrometer. Mass spectrometry
(MS) measurements were done on a Micromass Q-Tof and Bruker
Maxis Impact spectrometers. Elemental analysis was carried out on a
Thermo Finnigan Flash EA 1112 series (CHNS) elemental analyzer.
X-ray diffraction data for compounds 1b−1e, 2b, 2c, 2e, 3b, and 3c
were collected on a Rigaku Hg 724+ diffractometer. Crystal data
collection and refinement parameters are summarized in the
Supporting Information, Tables S1 and S2. The structures were
solved using direct methods and standard difference map techniques
and refined by full-matrix least-squares procedures on F2.50,51 CCDC
927582 (1b), 939419 (2b), 954478 (1c), 941939 (2c), 1004371 (1d),
999451 (1e), 1011414 (2e), 1451364 (3b), and 1451354 (3c) contain
the supplementary crystallographic data for this paper (Supporting
Information). These data can be obtained free of charge from the
Cambridge Crystallographic Data center via www.ccdc.cam.ac.uk/
data_request/cif.
CONCLUSION
■
In summary, a series of binuclear palladium complexes, namely,
1b−1e and 2b−1e, of ethyl- and propyl-bridged NHC ligands
effectively catalyzed the one-pot tandem Heck alkynylation/
cyclization reaction of 2-iodophenol with terminal alkynes,
yielding the 2-substituted benzofuran compounds, and of these,
the mixed-NHC/phosphine catalyst 1c was the most active.
The utility of the representative catalyst 1c was demonstrated
through the synthesis of a key benzofuran intermediate
required in a total-synthesis sequence of the natural product
Egonol, thereby projecting the potential of these catalysts in
these types of one-pot tandem Heck alkynylation/cyclization
reactions. Because the current study is among the first for the
NHC-based catalysts, it throws open exciting new opportunities
for further developments, not only for one-pot tandem Heck
alkynylation/cyclization reactions for producing benzofuran-
type frameworks in an efficient manner in reduced numbers of
reaction steps but also for a parallel utility in other related
tandem reactions. No evidence for cooperative catalysis was
Synthesis of [1,1′-Diisopropyl-4,4′-ethylenedi-1,2,4-triazo-
line-5,5′-diylidene]Pd2Br4(pyridine)2 (1b). A mixture of 1a (0.192
g, 0.470 mmol), PdBr2 (0.250 g, 0.940 mmol), and K2CO3 (0.259 g,
G
DOI: 10.1021/acs.inorgchem.5b02727
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
1.88 mmol) was refluxed in pyridine (5 mL, 63 mmol) for 16 h. The
reaction mixture was cooled to room temperature, diluted with ethyl
acetate (ca. 150 mL), and then washed with an aqueous CuSO4
solution (ca. 3 × 60 mL) and water (ca. 50 mL). The organic layer was
separated, dried over Na2SO4, and finally vacuum-dried to give the
as a stationary phase and eluting with a mixed medium of CH2Cl2/
MeOH (98:2, v/v) to give product 1e as a colorless solid (0.105 g,
1
72%). H NMR (CDCl3, 500 MHz, 25 °C): δ 8.98 (s, 2H, NC(3)
HN), 7.54−7.51 (m, 6H, C6H5), 7.44−7.39 (m, 24H, C6H5), 5.36
(sept, 2H, 3JHH = 7 Hz, CH(CH3)2), 4.58−4.56 (m, 2H, CH2), 4.39−
1
3
product 1b as a yellow solid (0.396 g, 90%). H NMR (CDCl3, 400
4.35 (m, 2H, CH2), 1.43 (d, 6H, JHH = 7 Hz, CH(CH3)2), 1.01 (d,
3
3
6H, JHH = 7 Hz, CH(CH3)2). 13C{1H} NMR (CDCl3, 125 MHz, 25
MHz, 25 °C): δ 9.04 (d, 4H, JHH = 6 Hz, C5H5N), 8.28 (s, 2H,
3
3
2
NC(3)HN), 7.83 (t, 2H, JHH = 6 Hz, C5H5N), 7.41 (t, 4H, JHH = 6
°C): δ 161.9 (br, OCOCF3), 159.2 (d, JCP = 8 Hz, PdNCN), 145.2
3
(2C, NC(3)HN), 133.6 (d, 3JCP = 10 Hz, C6H5), 132.7 (d, 4JCP = 4 Hz,
C6H5), 129.6 (d, 2JCP = 11 Hz, C6H5), 126.0 (d, 1JCP = 58 Hz, C6H5),
Hz, C5H5N), 5.74 (sept, 2H, JHH = 7 Hz, CH(CH3)2), 5.52 (br, 4H,
CH2), 1.59 (d, 12H, JHH = 7 Hz, CH(CH3)2). 13C{1H} NMR
3
2
(CDCl3, 100 MHz, 25 °C): δ 153.3 (PdNCN), 153.0 (C5H5N), 144.3
(NC(3)HN), 138.4 (C5H5N), 124.9 (C5H5N), 56.0 (CH(CH3)2), 47.7
(CH2), 21.9 (CH(CH3)2). IR data (KBr pellet): 3459 (m), 3120 (w),
3049 (w), 2983 (w), 2924 (w), 2851 (w), 1740 (m), 1605 (w), 1538
(w), 1448 (s), 1369 (m), 1253 (w), 1208 (m), 1071 (w), 1048 (w),
1017 (w), 990 (w), 855 (w), 759 (m), 735 (w), 692 (m), 663 (w)
cm−1. HRMS (ES): m/z 858.8186 ([M − Br]+). Calcd: m/z 854.8210.
Anal. Calcd for C22H30Pd2N8Br4: C, 28.14; H, 3.22; N, 11.93. Found:
C, 28.50; H, 2.88; N, 11.66.
114.2 (d, JCF = 289 Hz, OCOCF3), 56.1 (CH(CH3)2) 56.0
(CH(CH3)2) 47.4 (CH2), 23.0 (CH(CH3)2), 20.9 (CH(CH3)2).
31P{1H} NMR (CDCl3, 202 MHz, 25 °C): δ 25.5 (PdPPh3). 19F{1H}
NMR (CDCl3, 470 MHz, 25 °C): δ −75.1 (PdOCOCF3). IR data
(KBr pellet): 3435 (w), 3119 (w), 3058 (w), 2993 (w), 2923 (w),
2851 (w), 1693 (s), 1584 (w), 1536 (w), 1484 (w), 1438 (w), 1407
(w), 1315 (w), 1197 (s), 1144 (m), 1099 (m), 998 (w), 908 (w), 843
(m), 791 (w), 727 (m), 713 (m), 694 (m), 537 (m), 511 (m), 497
(m) cm−1. LRMS (ES): m/z 1064.2 ([M + H − OCOCF3 − PPh3]+).
Calcd: m/z 1062.0. Anal. Calcd for C56H50F12N6O8P2Pd2: C, 46.78; H,
3.51; N, 5.85. Found: C, 45.91; H, 3.21; N, 6.34.
Synthesis of [1,1′-Diisopropyl-4,4′-ethylenedi-1,2,4-triazo-
line-5,5′-diylidene]Pd2Br4(PPh3)2 (1c). A mixture of 1b (0.300 g,
0.320 mmol) and PPh3 (0.193 g, 0.736 mmol) was stirred in CH2Cl2
(ca. 20 mL) at room temperature for 6 h. The solvent was removed
under vacuum to give the crude product as a yellow solid. The crude
product was recrystallized from CH3CN to give the product 1c as a
Synthesis of [1,1′-Diisopropyl-4,4′-propylenedi-1,2,4-triazo-
line-5,5′-diylidene]Pd2Br4(pyridine)2 (2b). A mixture of 2a (0.199
g, 0.470 mmol), PdBr2 (0.250 g, 0.940 mmol) and K2CO3 (0.259 g,
1.88 mmol) was refluxed in pyridine (5 mL, 63 mmol) for 16 h. The
reaction mixture was cooled to room temperature, diluted with ethyl
acetate (ca. 150 mL), and then washed with an aqueous CuSO4
solution (ca. 3 × 60 mL) and water (ca. 50 mL). The organic layer was
separated, dried over Na2SO4, and finally vacuum-dried to give the
1
yellow solid (0.351 g, 84%). H NMR (CDCl3, 400 MHz, 25 °C): δ
7.81 (s, 2H, NC(3)HN), 7.76−7.39 (br, 30H, C6H5), 5.25 (sept, 2H,
3JHH = 7 Hz, CH(CH3)2), 4.95 (d, 2H, 2JHH = 10 Hz, CH2CH2), 4.06
2
3
(d, 2H, JHH = 10 Hz, CH2CH2), 1.45 (d, 6H, JHH = 7 Hz,
CH(CH3)2), 0.92 (d, 6H, JHH = 7 Hz, CH(CH3)2). 13C{1H} NMR
3
1
product 2b as a yellow solid (0.410 g, 91%). H NMR (CDCl3, 400
(CDCl3, 100 MHz, 25 °C): δ 167.0 (PdNCN), 143.6 (NC(3)HN),
3
MHz, 25 °C): δ 9.04 (d, 4H, JHH = 5 Hz, C5H5N), 8.39 (s, 2H,
1
134.1 (d, JCP = 44 Hz, C6H5), 132.0 (C6H5), 129.1 (C6H5), 129.0
3
3
NC(3)HN), 7.81 (t, 2H, JHH = 7 Hz, C5H5N), 7.39 (t, 4H, JHH = 7
(C6H5), 55.9 (CH(CH3)2), 46.2 (CH2), 22.5 (CH(CH3)2), 20.4
(CH(CH3)2). 31P{1H} NMR (CDCl3, 162 MHz, 25 °C): δ 27.3
(PdPPh3). IR data (KBr pellet): 3444 (m), 3104 (w), 3049 (w), 2982
(w), 2925 (w), 2851 (w), 1682 (w), 1538 (w), 1480 (m), 1435 (s),
1369 (m), 1246 (w), 1215 (w), 1163 (w), 1095 (s), 998 (w), 982 (w),
746 (m), 694 (s), 666 (w), 616 (w), 531 (s), 511 (s), 493 (m) cm−1.
HRMS (ES): m/z 1224.9174 ([M − Br]+). Calcd: m/z 1220.9195.
Anal. Calcd for C48H50Pd2N6P2Br4: C, 44.17; H, 3.86; N, 6.44. Found:
C, 44.37; H, 3.60; N, 6.29.
3
Hz, C5H5N), 5.74 (sept, 2H, JHH = 7 Hz, CH(CH3)2), 4.71 (t, 4H,
3JHH = 7 Hz, CH2), 3.34 (quint, 2H, 3JHH = 7 Hz, CH2), 1.59 (d, 12H,
3JHH = 7 Hz, CH(CH3)2). 13C{1H} NMR (CDCl3, 100 MHz, 25 °C):
δ 152.9 (C5H5N), 152.7 (Pd−NCN), 143.6 (NC(3)H−N), 138.4
(C5H5N), 124.9 (C5H5N), 55.8 (CH(CH3)2), 46.9 (CH2), 29.1 (CH2),
22.0 (CH(CH3)2). IR data (KBr pellet): 3445 (w), 3114 (m), 3042
(w), 2981 (m), 2933 (w), 2869 (w), 1735 (w), 1603 (m), 1531 (m),
1471 (m), 1446 (s), 1381 (m), 1350 (w), 1297 (w), 1258 (w), 1214
(w), 1194 (m), 1069 (m), 1048 (w), 1016, (w), 989, (w), 870, (w),
798 (w), 756 (s), 693 (s), 667 (m), 644 (m) cm−1. HRMS (ES): m/z
872.8345 ([M − Br]+). Calcd: m/z 868.8367. Anal. Calcd for
C23H32Pd2N8Br4: C, 28.99; H, 3.38; N, 11.76. Found: C, 28.94; H,
2.84; N, 12.37.
Synthesis of [1,1′-Diisopropyl-4,4′-ethylenedi-1,2,4-triazo-
line-5,5′-diylidene]Pd2(OCOCF3)4(pyridine)2 (1d). A mixture of
1b (0.134 g, 0.143 mmol) and AgOCOCF3 (0.157 g, 0.713 mmol) was
stirred in CH2Cl2 (ca. 20 mL) at room temperature for 4 h. The
reaction mixture was filtered over Celite, and the filtrate was finally
dried under vacuum to give the product 1d as a colorless solid (0.131
Synthesis of [1,1′-Diisopropyl-4,4′-propylenedi-1,2,4-triazo-
line-5,5′-diylidene]Pd2Br4(PPh3)2 (2c). A mixture of 2b (0.392 g,
0.411 mmol) and PPh3 (0.270 g, 1.02 mmol) in CH2Cl2 (ca. 40 mL)
was stirred at room temperature for 6 h. The solvent was removed
under vacuum to give the crude product as a yellow solid. The crude
product was purified by column chromatography using silica gel as a
stationary phase and eluting it with a mixed medium of CHCl3/MeOH
(98:2, v/v) and finally crystallized overnight from CH3CN to give
product 2c as a yellow crystalline solid (0.201 g, 38%). 1H NMR
(CDCl3, 400 MHz, 25 °C): δ 8.44 (s, 2H, NC(3)HN), 7.48−7.30 (br,
30H, C6H5), 5.32 (sept, 2H, 3JHH = 7 Hz, CH(CH3)2), 3.79−3.74 (m,
2H, CH2), 3.47−3.37 (m, 2H, CH2), 2.44−2.40 (m, 2H, CH2), 1.57
1
g, 85%). H NMR (CDCl3, 400 MHz, 25 °C): δ 8.56−8.54 (m, 4H,
C5H5N), 8.07 (s, 2H, NC(3)HN), 7.95 (tt, 2H, 3JHH = 8 Hz, 4JHH = 2
Hz, C5H5N), 7.54 (t, 4H, 3JHH = 8 Hz, C5H5N), 5.73 (sept, 2H, 3JHH
=
3
7 Hz, CH(CH3)2), 5.48 (s, 4H, CH2), 1.58 (d, 12H, JHH = 7 Hz,
CH(CH3)2). 13C{1H} NMR (CDCl3, 125 MHz, 25 °C): δ 162.3 (q,
3JCF = 36 Hz, OCOCF3), 149.8 (PdNCN), 148.7 (C5H5N), 144.6
2
(NC(3)HN), 139.7 (C5H5N), 125.5 (C5H5N), 114.2 (q, JCF = 289
Hz, OCOCF3), 55.9 (CH(CH3)2), 47.6 (CH2), 22.2 (CH(CH3)2).
19F{1H} NMR (CDCl3, 470 MHz, 25 °C): δ −74.03 (PdOCOCF3).
IR data (KBr pellet): 3434 (w), 3128 (w), 2984 (w), 1680 (s), 1609
(w), 1542 (w), 1453 (m), 1421 (w), 1407 (w), 1384 (w), 1234 (w),
1188 (s), 1137 (m), 1074 (w), 1053 (w), 990 (w), 845 (m), 789 (w),
761 (w), 728 (m), 696 (w), 522 (w) cm−1. HRMS (ES): m/z
959.0262 ([M − OCOCF3]+). Calcd: m/z 959.0226. Anal. Calcd for
C30H30F12N8O8Pd2: C, 33.63; H, 2.83; N, 10.46. Found: C, 33.45; H,
2.49; N, 11.06.
3
3
(d, 6H, JHH = 7 Hz, CH(CH3)2), 0.94 (d, 6H, JHH = 7 Hz,
CH(CH3)2). 13C{1H} NMR (CDCl3, 100 MHz, 25 °C): δ 165.6
(PdNCN), 144.0 (NC(3)HN), 134.1 (d, JCP = 40 Hz, C6H5), 131.7
(C6H5), 129.0 (C6H5), 129.0 (C6H5), 55.9 (CH(CH3)2), 45.0 (CH2),
29.3 (CH2), 22.5 (CH(CH3)2), 20.6 (CH(CH3)2). 31P{1H} NMR
(CDCl3, 162 MHz, 25 °C): δ 26.8 (PdPPh3). IR data (KBr pellet):
3504 (w), 3051 (w), 2983 (w), 2936 (w), 1619 (w), 1535 (w), 1480
(m), 1635 (s), 1368 (w), 1331 (w), 1291 (w), 1218 (w), 1131 (w),
1095 (s), 1050 (w), 998 (w), 988 (w), 880 (w), 748 (s), 695, (s), 667,
(m), 530, (s), 511 (s), 495 (m) cm−1. LRMS (ES): m/z 1078.2 ([M −
PPh3 + Na]+). Calcd: m/z 1074.8. Anal. Calcd for C49H52Pd2N6P2Br4:
C, 44.61; H, 3.97; N, 6.37. Found: C, 44.70; H, 3.77; N, 6.36.
Synthesis of [1,1′-Diisopropyl-4,4′-ethylenedi-1,2,4-triazo-
line-5,5′-diylidene]Pd2(OCOCF3)4(PPh3)2 (1e). A mixture of 1c
(0.134 g, 0.103 mmol) and AgOCOCF3 (0.135 g, 0.614 mmol) was
stirred in CH2Cl2 (ca. 30 mL) at room temperature for 4 h. The
reaction mixture was filtered over Celite, and the filtrate was dried
under vacuum to give the crude product as a colorless solid. The crude
product was finally purified by column chromatography using silica gel
H
DOI: 10.1021/acs.inorgchem.5b02727
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
Synthesis of [1,1′-Diisopropyl-4,4′-propylenedi-1,2,4-triazo-
line-5,5′-diylidene]Pd2(OCOCF3)4(pyridine)2 (2d). A mixture of
2b (0.153 g, 0.161 mmol) and AgOCOCF3 (0.177 g, 0.803 mmol) was
stirred in CH2Cl2 (ca. 30 mL) at room temperature for 4 h. The
reaction mixture was filtered over Celite, and the filtrate was finally
dried under vacuum to give the product 2d as a light-yellow solid
(0.171 g, 96%). 1H NMR (CDCl3, 500 MHz, 25 °C): δ 8.47−8.46 (m,
4H, C5H5N), 8.37 (s, 2H, NC(3)HN), 7.92−7.88 (m, 2H, C5H5N),
7.50−7.46 (m, 4H, C5H5N), 5.80 (sept, 2H, 3JHH = 7 Hz, CH(CH3)2),
MHz, 25 °C): δ 9.03 (br, 2H, C5H5N), 8.02 (s, 1H, NC(3)HN), 7.78
(t, 1H, 3JHH = 6 Hz, C5H5N), 7.37−7.34 (m, 2H, C5H5N), 5.74 (sept,
3
3
1H, JHH = 7 Hz, CH(CH3)2), 4.59 (q, 2H, JHH = 6 Hz, CH2CH3),
3
3
1.69 (t, 3H, JHH = 7 Hz, CH2CH3), 1.60 (d, 6H, JHH = 7 Hz,
CH(CH3)2). 13C{1H} NMR (CDCl3, 100 MHz, 25 °C): δ 152.8
(PdNCN), 152.8 (C5H5N), 142.3 (NC(3)HN), 138.2 (C5H5N), 124.8
(C5H5N), 55.5 (CH(CH3)2), 44.3 (CH2CH3), 22.0 (CH(CH3)2), 15.6
(CH2CH3). IR data (KBr pellet): 3459 (m), 3119 (w), 2976 (w), 2932
(w), 2924 (w), 1634 (w), 1605 (w), 1540 (w), 1471 (w), 1448 (s),
1369 (w), 1274 (m), 1208 (m), 1125 (w), 1071 (m), 1046 (m), 1017
(m), 993 (m), 853 (w), 758 (m), 735 (w), 695 (m), 665 (w) cm−1.
Anal. Calcd for C12H18Br2N4Pd: C, 29.75; H, 3.74; N, 11.56. Found:
C, 30.24; H, 4.51; N, 11.29.
3
4.77 (t, 4H, JHH = 7 Hz, CH2), 3.17 (t, 2H, 3JHH = 7 Hz, CH2), 1.57
(d, 12H, 3JHH = 7 Hz, CH(CH3)2). 13C{1H} NMR (CDCl3, 125 MHz,
25 °C): δ 162.3 (q, 3JCF = 38 Hz, OCOCF3), 149.7 (Pd−NCN), 148.9
(C5H5N), 143.5 (NC(3)HN), 139.6 (C5H5N), 125.5 (C5H5N), 114.2
2
(q, JCF = 288 Hz, OCOCF3), 55.7 (CH(CH3)2) 45.9 (CH2), 30.9
Synthesis of cis-[1-Isopropyl-4-ethyl-1,2,4-triazol-5-ylidene]-
PdBr2(PPh3) (3c). A mixture of 3b (0.500 g, 1.03 mmol) and PPh3
(0.325 g, 1.24 mmol) was stirred in CH2Cl2 (ca. 60 mL) at room
temperature for 6 h. The solvent was removed under vacuum to give
the crude product as a yellow solid. The crude product was purified by
column chromatography using silica gel as a stationary phase and
eluting it with a mixed medium of CHCl3/MeOH (98:2, v/v) to give
(CH2), 22.1 (CH(CH3)2). 19F{1H} NMR (CDCl3, 470 MHz, 25 °C):
δ −74.2 (PdOCOCF3). IR data (KBr pellet): 3440 (w), 3115 (w),
2983 (w), 2928 (w), 2851 (w), 1682 (s), 1537 (w), 1448 (w), 1371
(w), 1300 (w), 1210 (m), 1129 (m), 1071 (w), 838 (w), 804 (w), 759
(w), 724 (w) 694 (w), 518 (w) cm−1. Anal. Calcd for
C31H32F12Pd2N8O8: C, 34.30; H, 2.97; N, 10.32. Found: C, 34.08;
H, 2.84; N, 9.79.
1
product 3c as a yellow solid (0.445 g, 65%). H NMR (CDCl3, 500
Synthesis of [1,1′-Diisopropyl-4,4′-propylenedi-1,2,4-triazo-
line-5,5′-diylidene]Pd2(OCOCF3)4(PPh3)2 (2e). A mixture of 2c
(0.168 g, 0.127 mmol) and AgOCOCF3 (0.168 g, 0.764 mmol) was
stirred in CH2Cl2 (ca. 30 mL) at room temperature for 4 h. The
reaction mixture was filtered over Celite, and the filtrate was dried
under vacuum to give the product 2e as a colorless solid (0.121 g,
65%). Both the 1H and 13C NMR spectra showed the presence of two
MHz, 25 °C): δ 7.73 (s, 1H, NC(3)HN), 7.56−7.47 (m, 9H, C6H5),
3
7.39−7.36 (m, 6H, C6H5), 5.29 (sept, 1H, JHH = 7 Hz, CH(CH3)2),
2
3
4.27 (qd, 1H, JHH = 14 Hz, JHH = 7 Hz, CH2CH3), 3.48 (qd, 1H,
2JHH = 14 Hz, JHH = 7 Hz, CH2CH2), 1.51 (d, 3H, JHH = 7 Hz,
3
3
CH(CH3)2), 1.32 (t, 3H, 3JHH = 7 Hz, CH2CH3), 0.95 (d, 6H, 3JHH
=
7 Hz, CH(CH3)2). 13C{1H} NMR (CDCl3, 125 MHz, 25 °C): δ 166.6
1
(PdNCN), 141.8 (NC(3)HN), 134.4 (d, JCP = 11 Hz, C6H5), 131.5
1
isomers. The major-to-minor isomer ratio was 4:1. H NMR (CDCl3,
(C6H5), 128.8 (C6H5), 128.7 (C6H5), 55.7 (CH(CH3)2), 44.0
(CH2CH3), 20.7 (CH(CH3)2), 20.6 (CH(CH3)2), 14.7 (CH2CH3).
31P{1H} NMR (CDCl3, 202 MHz, 25 °C): δ 26.5 (PdPPh3). IR data
(KBr pellet): 2969 (w), 2925 (w), 2850 (w), 1646 (w), 1479 (w),
1435 (w), 1373 (w), 1268 (w), 1093 (s), 1027 (s), 798 (w), 746 (w),
694 (m), 531 (w) cm−1. HRMS (ES): m/z 588.0227 ([M − Br]+).
Calcd: m/z 586.0237. Anal. Calcd for C25H28Br2N3PPd: C, 44.97; H,
4.23; N, 6.29. Found: C, 45.37; H, 4.19; N, 6.28.
400 MHz, 25 °C): (major) δ 8.55 (s, 2H, NC(3)HN), 7.55−7.52 (m,
3
6H, C6H5), 7.48−7.34 (m, 24H, C6H5), 5.43 (sept, 2H, JHH = 7 Hz,
CH(CH3)2), 3.95 (br, 2H, CH2), 3.37 (br, 2H, CH2), 2.30 (br, 2H,
3
3
CH2), 1.45 (d, 6H, JHH = 7 Hz, CH(CH3)2), 0.97 (d, 6H, JHH = 7
Hz, CH(CH3)2). 13C{1H} NMR (CDCl3, 125 MHz, 25 °C): δ 161.6
(br, 4C, OCOCF3), 157.6 (PdNCN), 157.6 (PdNCN), 146.0 (2C,
NC(3)HN), 133.8 (C6H5), 133.7 (C6H5), 132.7 (C6H5), 132.6
(C6H5), 129.5 (C6H5), 129.4 (C6H5), 126.5 (C6H5), 126.0 (C6H5),
General Procedure for the Heck Alkynylation/Cyclization
Reaction of Iodophenols. In a typical catalysis run, performed in air,
a 10 mL vial was charged with a mixture of the 2-iodophenol, a
terminal alkyne substrate, and Cs2CO3 in a molar ratio of 1:1.5:3. A
palladium complex (1b−1e and 2b−2e; 1 mol %) was added to the
mixture, followed by DMSO (ca. 3 mL) solvent, and then the reaction
mixture was heated at 80 °C for a time period of t hours. The reaction
mixture was cooled to room temperature, and water (ca. 12 mL) was
added. The resulting mixture was extracted with EtOAc (ca. 50 mL).
The aqueous layer was further extracted with EtOAc (ca. 3 × 20 mL).
The organic layers were combined and vacuum-dried to obtain a crude
product that was subsequently purified by column chromatography
using silica gel as a stationary phase and eluting it with a mixed
medium of petroleum ether/EtOAc to give the desired product (4−
12).
2
114.5 (q, 4C, JCF = 289 Hz, OCOCF3), 56.1 (2C, CH(CH3)2), 45.7
(2C, CH2), 30.3 (2C, CH2), 23.1 (2C, CH(CH3)2), 20.8 (2C,
CH(CH3)2). 31P{1H} NMR (CDCl3, 202 MHz, 25 °C): δ 25.7
(PdPPh3). 19F{1H} NMR (CDCl3, 470 MHz, 25 °C): δ −75.0
1
(PdOCOCF3). H NMR (CDCl3, 400 MHz, 25 °C): (minor) δ 8.02
(s, 2H, NC(3)HN), 7.55−7.52 (m, 6H, C6H5), 7.48−7.34 (m, 24H,
C6H5), 5.40 (sept, 2H, 3JHH = 7 Hz, CH(CH3)2), 4.34 (br, 2H, CH2),
3
3.60 (br, 2H, CH2), 2.75 (br, 2H, CH2), 1.35 (d, 6H, JHH = 7 Hz,
3
CH(CH3)2), 0.89 (d, 6H, JHH = 7 Hz, CH(CH3)2). 13C{1H} NMR
(CDCl3, 125 MHz, 25 °C): δ 161.6 (br, 4C, OCOCF3), 157.6
(PdNCN), 157.6 (PdNCN), 144.1 (2C, NC(3)HN), 132.7 (C6H5),
132.6 (C6H5), 132.3 (C6H5), 132.2 (C6H5), 128.9 (C6H5), 128.7
2
(C6H5), 126.7 (C6H5), 126.0 (C6H5), 114.5 (q, 4C, JCF = 289 Hz,
OCOCF3), 56.1 (2C, CH(CH3)2), 46.2 (2C, CH2), 29.9 (2C, CH2),
22.7 (2C, CH(CH3)2), 20.6 (2C, CH(CH3)2). 31P{1H} NMR (CDCl3,
202 MHz, 25 °C): δ 25.3 (PdPPh3). 19F{1H} NMR (CDCl3, 470
MHz, 25 °C): δ −74.0 (PdOCOCF3). IR data (KBr pellet): 3520 (w),
3112 (w), 3060 (w), 2991 (w), 2942 (w), 2675 (w), 2576 (w), 2329
(w), 1980 (w), 1682 (s), 1585 (w), 1538 (w), 1483 (w), 1437 (s),
1314 (w), 1195 (s), 1098 (s), 1027 (w), 998 (w), 890 (w), 842 (m),
790 (w), 747 (m), 726 (s), 694 (s), 536 (s), 512 (s), 497 (m) cm−1.
LRMS (ES): m/z 1339.1 ([M − OCOCF3]+). Calcd: m/z 1337.1.
Anal. Calcd for C57H52O8F12N6P2Pd2: C, 47.16; H, 3.61; N, 5.79.
Found: C, 47.00; H, 3.22; N, 6.59.
2-Phenylbenzofuran.12
1
Yield: 0.079 g, 81%. H NMR (CDCl33, 400 MHz, 25 °C): δ 7.88 (d,
3
2H, JHH = 8 Hz, C6H5), 7.59 (d, 1H, JHH = 8 Hz, C8H5O), 7.54 (d,
1H, 3JHH = 8 Hz, C8H5O), 7.47 (t, 2H, 3JHH = 8 Hz, C8H5O), 7.37 (t,
3
1H, JHH = 8 Hz, C6H5), 7.31−7.21 (m, 2H, C6H5), 7.04 (s, 1H,
C8H5O). 13C{1H} NMR (CDCl3, 100 MHz, 25 °C): δ 156.1
(C8H5O), 155.1 (C8H5O), 130.7 (C8H5O), 129.4 (C6H5), 129.0
(C6H5), 128.7 (C8H5O), 125.1 (C6H5), 124.4 (C8H5O), 123.1
(C8H5O), 121.1 (C6H5), 111.4 (C8H5O), 101.5 (C8H5O).
2-(3,4-Dimethoxyphenyl)benzofuran.52
Synthesis of trans-[1-Isopropyl-4-ethyl-1,2,4-triazol-5-
ylidene]PdBr2(pyridine) (3b). A mixture of 3a (0.471 g, 2.14
mmol), PdBr2 (0.569 g, 0. 2.14 mmol), and K2CO3 (0.443 g, 3.21
mmol) was refluxed in pyridine (5 mL, 63 mmol) for 16 h. The
reaction mixture was cooled to room temperature, diluted with ethyl
acetate (ca. 100 mL), and then washed with an aqueous CuSO4
solution (ca. 3 × 60 mL) and water (ca. 50 mL). The organic layer was
separated, dried over Na2SO4, and finally vacuum dried to give the
1
product 3b as a yellow solid (0.818 g, 79%). H NMR (CDCl3, 400
I
DOI: 10.1021/acs.inorgchem.5b02727
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
1
Yield: 0.089 g, 70%. H NMR (CDCl3, 500 MHz, 25 °C): δ 7.57 (d,
1-Benzofuran-2-ylcyclohexan-1-ol.12
3
3
1H, JHH = 8 Hz, C8H5O), 7.52 (d, 1H, JHH = 8 Hz, C8H5O), 7.44
(dd, 1H, 3JHH = 8 Hz, 4JHH = 2 Hz, C8H9O2), 7.38 (d, 1H, 4JHH = 2 Hz,
3
C8H9O2), 7.29−7.20 (m, 2H, C8H5O), 6.94 (d, 1H, JHH = 8 Hz,
C8H9O2), 6.91 (s, 1H, C8H5O), 6.78 (d, 2H, JHH = 8 Hz, C8H9O2),
3
1
4.00 (s, 3H, CH3 of C8H9O2) 3.94 (s, 3H, CH3 of C8H9O2). 13C{1H}
NMR (CDCl3, 100 MHz, 25 °C): δ 156.1 (C8H5O), 154.9 (C8H5O),
149.7 (C8H9O2), 149.3 (C8H9O2), 129.6 (C8H5O), 124.0 (C8H5O),
123.7 (C8H9O2), 123.0 (C8H5O), 120.8 (C8H9O2), 118.1 (C8H5O),
111.5 (C8H9O2), 111.2 (C8H9O2), 108.2 (C8H5O), 100.2 (C8H5O),
56.2 (CH3 of C8H9O2), 56.1 (CH3 of C8H9O2).
Yield: 0.085 g, 79%. H NMR (CDCl3, 500 MHz, 25 °C): δ 7.52 (d,
3
3
1H, JHH = 8 Hz, C8H5O), 7.44 (d, 1H, JHH = 8 Hz, C8H5O), 7.26−
7.18 (m, 2H, C8H5O), 6.59 (s, 1H, C8H5O), 2.09−2.04 (m, 3H,
C6H11O), 1.93−1.90 (m, 2H, C6H11O), 1.80−1.73 (m, 2H, C6H11O),
1.62−1.54 (m, 3H, C6H11O), 1.43−1.36 (m, 1H, C6H11O). 13C{1H}
NMR (CDCl3, 125 MHz, 25 °C): δ 163.0 (C8H5O), 154.7 (C8H5O),
128.5 (C8H5O), 124.1 (C8H5O), 122.8 (C8H5O), 122.1 (C8H5O),
111.4 (C8H5O), 101.3 (C8H5O), 70.8 (C6H11O), 36.3 (C6H11O), 25.6
(C6H11O), 22.2 (C6H11O).
2-(4-Methoxyphenyl)benzofuran.12
2-Benzofuran-2-ylethan-1-ol.12
1
Yield: 0.075 g, 67%. H NMR (CDCl3, 500 MHz, 25 °C): δ 7.80 (d,
2H, 3JHH = 8 Hz, C7H7O), 7.56 (d, 1H, 3JHH = 8 Hz, C8H5O), 7.50 (d,
3
1H, JHH = 8 Hz, C8H5O), 7.25−7.20 (m, 2H, C8H5O), 6.98 (d, 2H,
1
3JHH = 8 Hz, C7H7O), 6.89 (s, 1H, C8H5O), 3.86 (s, 3H, CH3 of
C7H7O). 13C{1H} NMR (CDCl3, 100 MHz, 25 °C): δ 160.1
(C7H7O), 156.1 (C8H5O), 154.9 (C8H5O), 129.7 (C8H5O), 126.6
(C7H7O), 123.9 (C8H5O), 123.5 (C7H7O), 123.0 (C8H5O), 120.8
(C8H5O), 114.4 (C7H7O), 111.2 (C8H5O), 99.6 (C8H5O), 55.6 (CH3
of C7H7O).
Yield: 0.052 g, 62%. H NMR (CDCl3, 500 MHz, 25 °C): δ 7.49 (d,
3
3
1H, JHH = 8 Hz, C8H5O), 7.42 (d, 1H, JHH = 8 Hz, C8H5O), 7.25−
7.17 (m, 2H, C8H5O), 6.50 (s, 1H, C8H5O), 3.98 (t, 2H, 3JHH = 7 Hz,
3
CH2), 3.04 (t, 2H, JHH = 7 Hz, CH2), 1.84 (br, 1H, CH2OH).
13C{1H} NMR (CDCl3, 100 MHz, 25 °C): δ 156.1 (C8H5O), 155.0
(C8H5O), 128.8 (C8H5O), 123.7 (C8H5O), 122.8 (C8H5O), 120.6
(C8H5O), 111.0 (C8H5O), 103.9 (C8H5O), 60.9 (CH2), 32.2 (CH2).
Benzofuran-2-ylmethanol.54
4-Benzofuran-2-yl-N,N-dimethylaniline.53
1
Yield:0.056 g, 47%. H NMR (CDCl3, 500 MHz, 25 °C): δ 7.74 (d,
1
2H, 3JHH = 8 Hz, C8H10N), 7.50 (d, 1H, 3JHH = 8 Hz, C8H5O), 7.48 (d,
Yield: 0.063 g, 84%. H NMR (CDCl3, 500 MHz, 25 °C): δ 7.54 (d,
3
3
3
1H, JHH = 8 Hz, C8H5O), 7.46 (d, 1H, JHH = 8 Hz, C8H5O), 7.30−
7.20 (m, 2H, C8H5O), 6.66 (s, 1H, C8H5O), 4.77 (s, 2H, CH2), 2.05
(br, 1H, CH2OH). 13C{1H} NMR (CDCl3, 100 MHz, 25 °C): δ 156.6
(C8H5O), 155.3 (C8H5O), 128.3 (C8H5O), 124.6 (C8H5O), 123.0
(C8H5O), 121.3 (C8H5O), 111.4 (C8H5O), 104.3 (C8H5O), 58.4
(CH2).
1H, JHH = 8 Hz, C8H5O), 7.26−7.18 (m, 2H, C8H5O), 6.81 (s, 1H,
3
C8H5O), 6.78 (d, 2H, JHH = 8 Hz, C8H10N), 3.03 (s, 6H, CH3 of
C8H10N). 13C{1H} NMR (CDCl3, 125 MHz, 25 °C): δ 157.2
(C8H5O), 154.7(C8H5O), 129.4 (C8H10N), 130.0 (C8H5O), 126.3
(C8H10N), 123.2 (C8H5O), 122.8 (C8H10N), 120.3 (C8H5O), 118.8
(C8H5O), 112.3 (C8H10N), 110.9 (C8H5O), 98.2 (C8H5O), 40.5 (CH3
of C8H10N).
2-Benzo[d][1,3]dioxol-5-yl-7-methoxybenzofuran-5-carbal-
dehyde.6
5-Benzofuran-2-ylbenzo[d][1,3]dioxole.52
1
1
Yield: 0.074 g, 62%. H NMR (CDCl3, 500 MHz, 25 °C): δ 7.55 (d,
Yield: 0.053 g, 36%. H NMR (CDCl3, 400 MHz, 25 °C): δ 10.0 (s,
3
3
1H, CHO of C10H7O3), 7.69 (s, 1H, C10H7O3), 7.43 (dd, 1H, 3JHH = 8
Hz, JHH = 2 Hz, C7H5O2), 7.35 (s, 1H, C10H7O3), 7.34 (s, 1H,
1H, JHH = 8 Hz, C8H5O), 7.49 (d, 1H, JHH = 8 Hz, C8H5O), 7.44
(dd, 1H, 3JHH = 8 Hz, 4JHH = 2 Hz, C7H5O2), 7.38 (d, 1H, 4JHH = 2 Hz,
4
3
C7H5O2), 6.96 (s, 1H, C10H7O3), 6.89 (d, 1H, 3JHH = 8 Hz, C7H5O2),
6.03 (s, 2H, C7H5O2), 4.09 (s, 3H, OCH3 of C10H7O3). 13C{1H}
NMR (CDCl3, 125 MHz, 25 °C): δ 192.0 (CHO of C10H7O3), 157.9
(C10H7O3), 148.3 (C7H5O2), 148.2 (C7H5O2), 147.6 (C10H7O3), 146.1
(C10H7O3), 133.6 (C10H7O3), 131.2 (C10H7O3), 124.0 (C7H5O2),
119.8 (C7H5O2), 119.2 (C10H7O3), 108.9 (C7H5O2), 105.7 (C7H5O2),
104.7 (C10H7O3), 101.7 (C10H7O3), 100.4 (C7H5O2), 56.4 (OCH3 of
C10H7O3). HRMS (ES): m/z 296.0683 ([M]+). Calcd: m/z 296.0679.
Mercury Drop Experiment Performed at Varying Time
Intervals. 1. Mercury Addition at the Start of the Reaction. A 10
mL vial was charged with a mixture of 2-iodophenol, phenylacetylene,
and Cs2CO3 in a molar ratio of 1:1.5:3, and mercury (0.121 g, 0.603
mmol) was added subsequently. The palladium complex 1c (1 mol %)
was added to the mixture, followed by DMSO (ca. 3 mL) solvent, and
then the reaction mixture was heated at 80 °C for 4 h. The reaction
mixture was cooled to room temperature, and water (ca. 12 mL) was
added. The resulting mixture was extracted with EtOAc (ca. 50 mL).
The water layer was further extracted with EtOAc (ca. 3 × 20 mL).
The organic layers were combined and vacuum-dried to give crude
product as a brown solid, which was purified by column
chromatography using silica gel as a stationary phase and eluting it
C7H5O2), 7.27−7.20 (m, 2H, C8H5O), 6.88 (d, 1H, JHH = 8 Hz,
C7H5O2), 6.86 (s, 1H, C8H5O), 6.01 (s, 2H, C7H5O2). 13C{1H} NMR
(CDCl3, 125 MHz, 25 °C): δ 156.0 (C8H5O), 154.8 (C8H5O), 148.3
(C7H5O2), 148.2 (C7H5O2), 129.5 (C8H5O), 125.0 (C8H5O), 124.1
(C7H5O2), 123.1 (C8H5O), 120.8 (C7H5O2), 119.3 (C8H5O), 111.2
(C7H5O2), 108.9 (C8H5O), 105.7 (C7H5O2), 101.5 (C8H5O), 100.4
(C7H5O2).
2-(4-Fluorophenyl)benzofuran.12
Yield: 0.057 g, 53%. 1H NMR (CDCl3, 500 MHz, 25 °C): δ 7.86−7.83
(m, 2H, C6H4F), 7.58 (d, 1H, 3JHH = 8 Hz, C8H5O), 7.52 (d, 1H, 3JHH
= 8 Hz, C8H5O), 7.30−7.22 (m, 2H, C8H5O), 7.16−7.12 (m, 2H,
C6H4F), 6.96 (s, 1H, C8H5O). 13C{1H} NMR (CDCl32, 125 MHz, 25
°C): δ 164.1 (C8H5O), 162.1 (C8H5O), 155.1 (d, JCF = 21 Hz,
4
C6H4F), 134.7 (d, JCF = 9 Hz, C6H4F), 129.4 (C8H5O), 127.1
4
(C6H4F), 127.0 (d, JCF = 9 Hz, C6H4F), 124.5 (C8H5O), 123.2
(C8H5O), 121.8 (C8H5O), 116.2 (C6H4F), 116.0 (C6H4F), 111.3
(C8H5O), 101.2 (C8H5O).
J
DOI: 10.1021/acs.inorgchem.5b02727
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
with neat petroleum ether to give product 4 as a white solid (0.082 g,
84%).
(7) Xia, Y.; Jin, Y.; Kaur, N.; Choi, Y.; Lee, K. Eur. J. Med. Chem.
2011, 46, 2386−2396.
2. Mercury Addition after 1 h of Reaction Time. A 10 mL vial was
charged with a mixture of 2-iodophenol, phenylacetylene, and Cs2CO3
in a molar ratio of 1:1.25:3. The palladium complex 1c (1 mol %) was
added to the mixture, followed by DMSO (ca. 3 mL) solvent, and then
the reaction mixture was heated at 80 °C for 1 h. Mercury (0.126 g,
0.628 mmol) was added, and the reaction mixture was further heated
at 80 °C for 3 h. The reaction mixture was cooled to room
temperature, and water (ca. 12 mL) was added. The resulting mixture
was extracted with EtOAc (ca. 50 mL). The water layer was further
extracted with EtOAc (ca. 3 × 20 mL). The organic layers were
combined and vacuum-dried to give crude product as a brown solid,
which was purified by column chromatography using silica gel as a
stationary phase and eluting it with neat petroleum ether to give
product 4 as a white solid (0.070 g, 72%).
(8) Kaur, N.; Xia, Y.; Jin, Y.; Dat, N. T.; Gajulapati, K.; Choi, Y.;
Hong, Y.-S.; Lee, J. J.; Lee, K. Chem. Commun. (Cambridge, U. K.)
2009, 1879−1881.
(9) Moure, M. J.; SanMartin, R.; Dominguez, E. Adv. Synth. Catal.
2014, 356, 2070−2080.
(10) Anga, S.; Kottalanka, R. K.; Pal, T.; Panda, T. K. J. Mol. Struct.
2013, 1040, 129−138.
(11) Zanardi, A.; Mata, J. A.; Peris, E. Organometallics 2009, 28,
4335−4339.
(12) Zhou, R.; Wang, W.; Jiang, Z.-J.; Wang, K.; Zheng, X.-l.; Fu, H.-
Y.; Chen, H.; Li, R.-X. Chem. Commun. (Cambridge, U. K.) 2014, 50,
6023−6026.
(13) Konno, T.; Chae, J.; Ishihara, T.; Yamanaka, H. Tetrahedron
2004, 60, 11695−11700.
(14) Arcadi, A.; Blesi, F.; Cacchi, S.; Fabrizi, G.; Goggiamani, A.;
Marinelli, F. Tetrahedron 2013, 69, 1857−1871.
(15) Sarkar, S.; Pal, R.; Chatterjee, N.; Dutta, S.; Naskar, S.; Sen, A.
K. Tetrahedron Lett. 2013, 54, 3805−3809.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.inorg-
chem.5b02727.
■
S
(16) Kumar, A.; Ghosh, P. Eur. J. Inorg. Chem. 2012, 2012, 3955−
3969.
(17) Prakasham, A. P.; Ghosh, P. Inorg. Chim. Acta 2015, 431, 61−
100.
NMR, IR, mass, and elemental analysis data of the
palladium complexes 1b−1e, 2b−2e, 3b, and 3c, an X-
ray metrical data comparison table, ORTEP plots of 2b,
2c, 2e, 3b, and 3c, and mercury(0) drop test results
(PDF)
(18) John, A.; Ghosh, P. Dalton Trans. 2010, 39, 7183−7206.
(19) John, A.; Modak, S.; Madasu, M.; Katari, M.; Ghosh, P.
Polyhedron 2013, 64, 20−29.
(20) Dash, C.; Shaikh, M. M.; Ghosh, P. Eur. J. Inorg. Chem. 2009,
2009, 1608−1618.
X-ray crystallographic data in CIF format (CIF)
(21) John, A.; Shaikh, M. M.; Ghosh, P. Dalton Trans. 2009, 10581−
10591.
(22) Ray, L.; Barman, S.; Shaikh, M. M.; Ghosh, P. Chem. - Eur. J.
AUTHOR INFORMATION
Corresponding Author
*E-mail: pghosh@chem.iitb.ac.in. Fax: +91-22-2572-3480.
Notes
■
2008, 14, 6646−6655.
(23) Samantaray, M. K.; Shaikh, M. M.; Ghosh, P. J. Organomet.
Chem. 2009, 694, 3477−3486.
(24) Samantaray, M. K.; Dash, C.; Shaikh, M. M.; Pang, K.; Butcher,
R. J.; Ghosh, P. Inorg. Chem. 2011, 50, 1840−1848.
(25) Modak, S.; Gangwar, M. K.; Nageswar Rao, M.; Madasu, M.;
Kalita, A. C.; Dorcet, V.; Shejale, M. A.; Butcher, R. J.; Ghosh, P.
Dalton Trans. 2015, 44, 17617−17628.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the Department of Science and Technology (EMR/
2014/000254), New Delhi, India, for financial support of this
research. We gratefully acknowledge Professor R. Murugavel for
the use of his Single Crystal X-ray Diffraction Facility
established through a DAE-SRC Outstanding Investigator
Award along with the Single Crystal X-ray Diffraction Facility,
Department of Chemistry, IIT Bombay, Mumbai, India, for the
crystallographic characterization data. Computational facilities
from the IIT Bombay Computer Center are gratefully
acknowledged. A.K., M.K.G., and A.P.P. thank CSIR, New
Delhi, India, for research fellowships.
(26) Rao, M. N.; Haridas, M.; Gangwar, M. K.; Rajakannu, P.; Kalita,
A. C.; Ghosh, P. Eur. J. Inorg. Chem. 2015, 2015, 1604−1615.
(27) Katari, M.; Rajaraman, G.; Ghosh, P. J. Organomet. Chem. 2015,
775, 109−116.
(28) Samantaray, M. K.; Shaikh, M. M.; Ghosh, P. Organometallics
2009, 28, 2267−2275.
(29) Ray, S.; Shaikh, M. M.; Ghosh, P. Eur. J. Inorg. Chem. 2009,
2009, 1932−1941.
(30) Ray, L.; Shaikh, M. M.; Ghosh, P. Dalton Trans. 2007, 4546−
4555.
(31) Ray, L.; Shaikh, M. M.; Ghosh, P. Organometallics 2007, 26,
958−964.
(32) Dash, C.; Shaikh, M. M.; Butcher, R. J.; Ghosh, P. Inorg. Chem.
2010, 49, 4972−4983.
REFERENCES
■
(33) Dash, C.; Shaikh, M. M.; Butcher, R. J.; Ghosh, P. Dalton Trans.
2010, 39, 2515−2524.
(1) Flynn, B. L.; Gill, G. S.; Grobelny, D. W.; Chaplin, J. H.; Paul, D.;
Leske, A. F.; Lavranos, T. C.; Chalmers, D. K.; Charman, S. A.;
Kostewicz, E.; Shackleford, D. M.; Morizzi, J.; Hamel, E.; Jung, M. K.;
Kremmidiotis, G. J. Med. Chem. 2011, 54, 6014−6027.
(2) Singh, S. N.; Fletcher, R. D.; Fisher, S. G.; Singh, B. N.; Lewis, H.
D.; Deedwania, P. C.; Massie, B. M.; Colling, C.; Lazzeri, D. N. Engl. J.
Med. 1995, 333, 77−82.
(3) Shi, Y.-Q.; Fukai, T.; Sakagami, H.; Chang, W.-J.; Yang, P.-Q.;
Wang, F.-P.; Nomura, T. J. Nat. Prod. 2001, 64, 181−188.
(4) Yuan, H.; Bi, K. J.; Li, B.; Yue, R. C.; Ye, J.; Shen, Y. H.; Shan, L.;
Jin, H. Z.; Sun, Q. Y.; Zhang, W. D. Org. Lett. 2013, 15, 4742−4745.
(5) Naveen, M.; Reddy, C. U.; Hussain, M. M.; Chaitanya, M.;
Narayanaswamy, G. J. Heterocycl. Chem. 2013, 50, 1064−1066.
(6) Choi, D. H.; Hwang, J. W.; Lee, H. S.; Yang, D. M.; Jun, J.-G.
Bull. Korean Chem. Soc. 2008, 29, 1594−1596.
(34) Kumar, A.; Bheeter, L. P.; Gangwar, M. K.; Sortais, J.-B.; Darcel,
C.; Ghosh, P. J. Organomet. Chem. 2015, 786, 63−70.
(35) Ros, A.; Alcarazo, M.; Iglesias-Siguenza, J.; Diez, E.; Alvarez, E.;
Fernandez, R.; Lassaletta, J. M. Organometallics 2008, 27, 4555−4564.
(36) Gnanamgari, D.; Moores, A.; Rajaseelan, E.; Crabtree, R. H.
Organometallics 2007, 26, 1226−1230.
(37) Chan, K.-T.; Tsai, Y.-H.; Lin, W.-S.; Wu, J.-R.; Chen, S.-J.; Liao,
F.-X.; Hu, C.-H.; Lee, H. M. Organometallics 2010, 29, 463−472.
(38) Gierz, V.; Seyboldt, A.; Maichle-Moessmer, C.; Froehlich, R.;
Rominger, F.; Kunz, D. Eur. J. Inorg. Chem. 2012, 2012, 1423−1429.
(39) Schneider, S. K.; Herrmann, W. A.; Herdtweck, E. J. Mol. Catal.
A: Chem. 2006, 245, 248−254.
(40) Guo, S.; Huynh, H. V. Organometallics 2014, 33, 2004−2011.
K
DOI: 10.1021/acs.inorgchem.5b02727
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
(41) Albrecht, M.; Crabtree, R. H.; Mata, J.; Peris, E. Chem. Commun.
(Cambridge, U. K.) 2002, 32−33.
(42) Unger, Y.; Meyer, D.; Strassner, T. Dalton Trans. 2010, 39,
4295−4301.
(43) Mercs, L.; Labat, G.; Neels, A.; Ehlers, A.; Albrecht, M.
Organometallics 2006, 25, 5648−5656.
(44) Cordero, B.; Gomez, V.; Platero-Prats, A. E.; Reves, M.;
Echeverria, J.; Cremades, E.; Barragan, F.; Alvarez, S. Dalton Trans.
2008, 2832−2838.
(45) Cambridge Structural Database, version 5.36; Cambridge
Crystallographic Data Centre: Cambridge, U.K., 2014.
(46) Valente, C.; Calimsiz, S.; Hoi, K. H.; Mallik, D.; Sayah, M.;
Organ, M. G. Angew. Chem., Int. Ed. 2012, 51, 3314−3332.
(47) Berliner, M. A.; Cordi, E. M.; Dunetz, J. R.; Price, K. E. Org.
Process Res. Dev. 2010, 14, 180−187.
(48) Riederer, S. U.; Gigler, P.; Hoegerl, M.; Herdtweck, E.; Bechlars,
B.; Herrmann, W. A.; Kuehn, F. E. Organometallics 2010, 29, 5681−
5692.
(49) Ueda, H.; Yamaguchi, M.; Kameya, H.; Sugimoto, K.;
Tokuyama, H. Org. Lett. 2014, 16, 4948−4951.
(50) Sheldrick, G. M. SHELXL-97, Program for refinement of crystal
structures; University of Gottingen: Gottingen, Germany, 1997.
(51) Sheldrick, G. M. SHELXS-97, Program for solution of crystal
structures; University of Gottingen: Gottingen, Germany, 1997.
(52) Liao, L.-Y.; Shen, G.; Zhang, X.; Duan, X.-F. Green Chem. 2012,
14, 695−701.
(53) Cano, R.; Yus, M.; Ramon, D. J. Tetrahedron 2012, 68, 1393−
1400.
(54) Gabriele, B.; Mancuso, R.; Salerno, G. J. Org. Chem. 2008, 73,
7336−7341.
NOTE ADDED AFTER ASAP PUBLICATION
■
This paper was published on the Web on February 29, 2016,
with a minor error in the the Abstract. The corrected version
was reposted on March 1, 2016.
L
DOI: 10.1021/acs.inorgchem.5b02727
Inorg. Chem. XXXX, XXX, XXX−XXX