One-pot Tandem Heck alkynylation/cyclization reactions catalyzed by Bis(Pyrrolyl)pyridine based palladium pincer complexes

Article abstract of DOI:10.1016/j.tet.2020.131350

Ligand assisted palladium catalyzed one-pot tandem Heck alkynylation/cyclization reactions for the synthesis of benzofurans was reported in this paper. Well-defined palladium-pincer complexes exhibited excellent catalytic activities for the one-pot tandem Heck alkynylation/cyclization reactions yielding benzofuran derivatives using 0.1 molpercent catalyst. All the catalytic reactions are performed in air. The effects of variables such as solvents, the temperature on the catalytic activity are also reported. High product conversion was obtained for differently substituted 2-iodophenol at 120 °C in 10 h.

Full text of DOI:10.1016/j.tet.2020.131350

Journal Pre-proof
One-pot Tandem Heck alkynylation/cyclization reactions catalyzed by
Bis(Pyrrolyl)pyridine based palladium pincer complexes
Seema Yadav, Chandrakanta Dash
PII:
S0040-4020(20)30505-6
https://doi.org/10.1016/j.tet.2020.131350
TET 131350
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 23 February 2020
Revised Date: 15 June 2020
Accepted Date: 17 June 2020
Please cite this article as: Yadav S, Dash C, One-pot Tandem Heck alkynylation/cyclization reactions
catalyzed by Bis(Pyrrolyl)pyridine based palladium pincer complexes, Tetrahedron (2020), doi: https://
doi.org/10.1016/j.tet.2020.131350.
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Graphical Abstract:
Bis(pyrrolyl)pyridine based palladium-pincer complexes efficiently catalyzed the one-pot
tandem Heck alkynylation/cyclization reactions for the synthesis of benzofuran derivatives.
Pd-pincer
•
•
•
•
Well-defined catalyst system
Wide substrate scope (16 examples
Isolated yield up to 96%
)
DMSO
K3PO4
Reaction performed in air

One-Pot Tandem Heck Alkynylation/Cyclization Reactions Catalyzed by
Bis(Pyrrolyl)pyridine based Palladium Pincer Complexes
Seema Yadav, Chandrakanta Dash*
Department of Chemistry, School of Chemical Sciences and Pharmacy, Central University of
Rajasthan, Bandarsindri, Ajmer-305817, Rajasthan, India.
*Corresponding author:
Email: ckdash@curaj.ac.in
1

Abstract:
Ligand assisted palladium catalyzed one-pot tandem Heck alkynylation/cyclization reactions for
the synthesis of benzofurans was reported in this paper. Well-defined palladium-pincer
complexes exhibited excellent catalytic activities for the one-pot tandem Heck
alkynylation/cyclization reactions yielding benzofuran derivatives using 0.1 mol% catalyst. All
the catalytic reactions are performed in air. The effects of variables such as solvents, the
temperature on the catalytic activity are also reported. High product conversion was obtained for
differently substituted 2-iodophenol at 120 oC in 10 hours.
Keywords: Bis(pyrrolyl)pyridine, Palladium, Heck alkynylation, tandem reaction, Benzofurans
2

1. INTRODUCTION
Heterocyclic compounds are present in many natural products and medicinal chemistry.1 A large
number of oxygen containing heterocyclic compounds are known for their versatility and unique
properties in many chemotherapeutic agents and also exhibit excellent antibiotic activity.2
Benzofuran is the one of these heterocyclic compounds are found in many natural,
pharmaceutical products as well as in polymers.3 Many traditional methods are available for the
synthesis of benzofuran derivatives which involve multistep reactions with low functional group
tolerance.4 Tandem approach are becoming increasingly popular and beginning to get attention
due to environmentally benign and time improvement methodology.5 Tandem Heck
alkynylation/cyclization reaction (also known as domino Sonogashira coupling/cyclization)
catalyzed by transition metal catalysts has emerged as an efficient and powerful method.6
Tandem Heck alkynylation/cyclization reaction required combination of palladium and copper
catalysts. However, few examples of copper-free palladium catalyzed tandem Heck
alkynylation/cyclization reaction for the synthesis of benzofuran derivatives are reported in the
literature.7,8,9 Some of the palladium catalyzed tandem processes are also reported with high
catalyst loading. Therefore, a highly efficient, well-defined catalytic system is of considerable
importance.
Ligands play an important role in homogeneous transition metal-catalyzed reactions for the
efficient synthesis of biologically important scaffolds.10 The ligand framework in the transition
metal complexes regulates both the electronic and steric properties, which in turn significantly
affects their catalytic performance. Pincer ligands are an important class of ligands in metal-
based catalytic reactions for the synthesis of heterocycles in an efficient manner. Transition
3

metal complexes with 2,6-bis(pyrrolyl)pyridine ligand framework were not much studied in
homogeneous catalysis. The ligand framework has been used for the isolation of reaction
intermediate,11 LMCT photosensitizers,12 and in catalytic processes.12 Recently, we have
reported a series of bis(pyrrolyl)pyridine ligand-based palladium catalysts for Suzuki-Miyaura
cross-coupling reactions in aqueous medium.13 After we observed its potential in the catalytic
transformation, we became interested to utilize these classes of palladium pincer complexes (2a-
2b, Scheme 1) for the synthesis of benzofuran derivatives using tandem Heck alkynylation
reaction and intramolecular cyclization strategy. To our best of knowledge, this work is the first
successful application of 2,6-bis(pyrrolyl)pyridine pincer ligand based palladium catalysts for
one-pot tandem Heck alkynylation/cyclization reaction at low catalyst loading (Scheme 1).
Y
Y
I
Pd-Pincer
R
+
R
K3PO4, DMSO
O
OH
R'
R
R'
R
N
Pd-Pincer =
N
Pd
N
N
R'
R'
CH3
R = H, R' = Me (2a)
R = OMe, R' = C6H4-OMe (2b)
Scheme 1. Palladium-pincer complexes catalyzed one-pot tandem Heck alkynylation/cyclization
reactions
2. Results and Discussion
2.1. Synthesis and characterization of palladium complexes
4

The palladium complex 2a was synthesized from the reaction of corresponding ligand 1a and
Pd(OAc)2 in acetonitrile as shown in Scheme 2. The palladium complex 2a was characterized by
NMR spectroscopy, elemental analysis, and Mass spectrometry. The formation of 2a is
1
confirmed by H NMR spectroscopy through observing the disappearance of the pyrrole proton
signal at 9.59 ppm in ligand 1a,12 which indicates the formation of the Pd-Npyrrole bond. The HR-
MS data of the complex 2a exhibit the molecular ion peak m/z 535.1114 corresponding to the
molecular formula of the palladium complex. The palladium complex 2b was reported earlier
from our group.13
Scheme 2. Synthesis of palladium-pincer complex 2a.
2.2. One-pot tandem Heck alkynylation/cyclization reaction
In the first step of our catalytic studies, we selected the coupling of 2-iodophenol and
phenylacetylene as model substrates. To optimize the reaction conditions, various solvents
(entries 3-7) and bases (entries 1-3) were tested using 2b as a catalyst. Similar to earlier studies,
the base K3PO4 and solvent DMSO provided the best condition (entry 3) at 90° C for complete
conversion with 0.0005 mmol (0.1 mol %) catalyst loading in 10 hours in air. In some cases, the
cyclized product 3 was obtained along with a by-product 4 (Glaser coupling)14 as shown in Table
1. On comparison, the reaction in the presence of palladium precursor i.e. PdCl2(CH3CN)2 gave
5

48% conversion in the same reaction conditions (entry 9). Reactions performed without
palladium sources did not yield the expected benzofuran product (entry 10).
Table 1. Optimization of the reaction conditions for synthesis of 2-arylbenzofurana
Entry
Catalyst Loading
(mol %)
Solvent
Base
% Yieldb
3
4
1.
2.
3.
4.
5.
6.
7.
8.
9.
2b (0.1)
DMSO
DMSO
DMSO
DMF
Et3N
Cs2CO3
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
-
32
51
2b (0.1)
2b (0.1)
15
>99(96)c
86
7
-
2b (0.1)
0
2b (0.1)
1,4-Dioxane
EtOH
22
10
-
2b (0.1)
trace
29
2b (0.1)
toluene
DMSO
DMSO
DMSO
46
-
2b (0.1)
11
PdCl2(CH3CN)2 (0.1)
K3PO4
48
nrd
-
10.
-
K3PO4
nr
aReaction conditions: 2-Iodophenol (0.50 mmol), phenylacetylene (0.60 mmol), 0.1 mol %
b
(0.0005 mmol) of catalyst, base (1.00 mmol), and solvent (2 mL). The yields (%) were
c
determined by GC using 1,3,5-trimethoxybenzene as an internal standard. Isolated yield.
dWithout catalyst. nr = No reaction.
Considering the highest conversion of the product in DMSO using K3PO4 as a base (entry 3,
Table 1), several commercially available substituted 2-iodophenol and terminal alkynes (with
electron-withdrawing/donating group and amine group) have been tested in the same reaction
conditions. All the catalysis products were characterized by NMR, and compared with literature
data. The iodophenol based substrates such as 5-iodovanillin and 2-iodo-3-hydroxypyridine gave
o
low reaction yields (21-31%) using identical condition at 90 C. We observe the lowest yields,
up to 18% for the reaction of propargyl alcohol with and 2-iodophenol.
6

Table 2. One-pot tandem Heck alkynylation/cyclization reactions by 2a and 2b at 90 oC.a
S.No.
1.
Iodophenol
Alkyne
Product
Yield (%)b
2a
2b
89
96
2.
3.
88
90
81
79
65
82
73
84
69
86
4.
5.
6.
7.
NH2
39
26
46
31
O
8.
9.
25
28
10.
23
21
27
24
11.
aReaction conditions: 2-Iodophenol (0.50 mmol), alkyne (0.60 mmol), 0.1 mol % of 2a or 2b, K3PO4
(1.00 mmol), DMSO (2 mL), 90 oC, 10 hours. bIsolated yield.
7

The effect of temperature on the reaction rate was studied for one-pot tandem Heck
alkynylation/cyclization reactions. The reactions are performed using the substrates 5-
iodovanillin and 4-ethynyltoluene in the presence of catalyst 2b at five different temperatures
o
from 80-120 C (Figure 1). The reaction rate was increased exponentially on increasing the
reaction temperature from 80 oC to 120 oC. The reaction of 5-iodovanillin with 4-ethynyltoluene
at 80 oC gave only 26% product conversion, whereas, on raising the reaction temperature to 120
oC resulted in enhancement of product conversion up to 83% in same reaction time.
90
80
70
60
50
40
30
20
80
90
100
110
120
Temperature (oC)
Figure 1. Effect of temperature on reaction rate for one-pot tandem Heck
alkynylation/cyclization reaction (5-iodovanillin with 4-ethynyltoluene)
o
The yields of the benzofuran derivatives at temperature 120 C in 10 hours of reaction time are
shown in Table 3. The yields were increased up to 83% in the case of 5-iodovanillin, whereas 2-
iodo-3-hydroxypyridine substrate gave only up to 63%. When the catalyst loading was decreased
o
to 0.05 mol % at 120 C for the reaction of 2-iodophenol with phenylacetylene, only 62%
product conversion was observed after 10 hours.
8

Table 3. One-pot tandem Heck alkynylation/cyclization reactions by 2a and 2b at 120 oC.a
S.No.
12.
Iodophenol
Alkyne
Product
Yield (%)b
2a
2b
83
84
13.
14.
74
78
79
83
15.
70
58
78
63
16.
17.
18.
19.
52
51
53
58
56
62
20.
21.
56
85
53
86
aReaction conditions: 2-Iodophenol derivatives (0.50 mmol), alkyne (0.60 mmol), 0.1 mol % of 2a or 2b,
K3PO4 (1.00 mmol), DMSO (2 mL), 120 oC, 10 hours. bIsolated yield.
9

The comparison of the catalytic efficiencies of 2a and 2b complexes with other reported well-
defined palladium based catalysts for one-pot tandem Heck alkynylation/cyclization reactions
yielding benzofuran compounds is important (Table 4). Peris and co-workers reported initially
the one-pot tandem Heck alkynylation/cyclization reaction of 2-iodophenol with
phenylacetylene, yielding 2-phenylbenzofuran by using 1 mol % N-heterocyclic carbene based
palladium catalysts.9c Ghosh and co-workers reported the same catalytic transformation with 1
mol % of palladium catalyst supported by N-heterocyclic carbene and phosphine based ligands.9a
Recently, we have reported the same one-pot tandem Heck alkynylation/cyclization reactions
with 0.2 mol % of N-heterocyclic carbene-palladium catalysts.9b In addition to this, few well-
defined copper(II) complexes also catalyzed the tandem reaction of 2-iodophenol with various
terminal alkynes.6b,15 Concerning the examples from the in situ generated ligand assisted
catalysis systems with a phosphine based ligand (0.1 mol %) and palladium precursor [Pd(η3
-
C3H5)Cl]2 (0.05 mol %) catalyzed the reaction with excellent yield.8a Thus, in comparison to the
above reported well-defined catalysts, the palladium pincer complexes 2a−2b is efficient at 0.1
mol % catalyst loading and also has wide substrate scope (Table 4).
Based on our results and previous reports,8a,9a the possible reaction mechansim for the generation
of benzofuran derivatives was proposed in Scheme 3. The mechanism involves two catalytic
cycles, the Heck alkynylation cycle and an intramolecular cyclization reaction. Since our pincer
based catalysts are stable in catalytic reaction temperature,13 the first catalytic cycle may initiates
via Pd(II)/Pd(IV) catalytic reactions16 instead of Pd(0)/Pd(II) chemistry, the oxidative addition of
Pd(II) complexes with 2-iodophenol yields a Pd(IV) intermdediate (B). The coordination of
phenylacetylene to palladium by elimination solvent molecule yielded the intermediate C.
10

Table 4. Comparison with reported transition metal well-defined catalysts for one-pot tandem
Heck alkynylation/cyclization reaction of 2-iodophenol with phenylacetylene, giving 2-
phenylbenzofuran.
No.
catalyst
loading
(mol %)
time
(h)
base/
solvent
Temp. Yield ref.
(oC)
(%)
1.
9c
9a
1 mol %
(S/C = 50)
8
Cs2CO3/
DMSO
80
93
2.
3.
1 mol %
(S/C = 50)
4
Cs2CO3/
DMSO
80
81
9b
0.2 mol %
(S/C = 250)
16
10
K3PO4/
DMSO
90
90
>99
96
4.
5.
0.1 mol %
(S/C = 1000)
K3PO4/
DMSO
This
work
2a−2b
15
6b
0.15 mol %
(S/C = 300)
48
24
Cs2CO3/
dioxane
130
110
>99
92
6.
10 mol %
(S/C = 20)
Cs2CO3/
toluene
Deprotonation of palladium coordinated phenylacetylene moiety C affords an intermediate D,
which on further reductive elimination generates the palladium(II) species A and 2-
(phenylethynyl)phenol. The product 2-(phenylethynyl)phenol becomes the substrate for the next
catalytic cyclization step. On coordination with the palladium(II) species A giving the
intermediate E, which undergoes oxidative addition followed by intermolecular rearrangement
11

produces intermediate F. Finally, the reductive elimination of the intermediate F gives the
desired 2-phenylbenzofuran product along with the regeneration of initial palladium(II) species
A.
Scheme 3. Possible mechanism for the tandem Heck alkynylation/cyclization reaction.
3. Conclusions
In summary, we have shown that the palladium pincer complex supported by 2,6-
bis(pyrrolyl)pyridine ligand framework is an efficient catalytic system for one-pot tandem Heck
alkynylation/cyclization reaction. The temperature effect on the one-pot tandem Heck
alkynylation/cyclization reaction was studied. A variety of benzofuran derivatives were
o
quantitatively synthesized using 0.1 mol % catalysts loading at 120 C in 10 hours. These well-
defined catalytic systems exhibit high performance in terms of product conversion, broad
substrate scope, and high functional group tolerance. We believe that this catalytic process will
expand the scope of pincer ligand assisted transition metal-catalyzed reaction in organic
synthesis.
12

4. Experimental Sections:
4.1. General Methods and Materials.
All manipulations were carried out under an atmosphere of nitrogen or in air. NMR spectra were
recorded at 298 K on Bruker 500 MHz and JEOL 400 MHz NMR spectrometer. The chemical
shifts of proton and carbon are reported in ppm and referenced using residual proton (7.26 ppm)
and carbon signals (77.16 ppm) of CDCl3.17 NMR annotations used: br. = broad, d = doublet, m
= multiplet, s = singlet, t = triplet, sept = septet. Elemental analyses were performed using
Thermo Quest FLASH 2000 SERIES (CHNS) Elemental Analyzer. Mass data are collected from
Micromass Q-Tof spectrometer. All catalytic reactions were monitored on a Thermo Fisher
Trace 1300 series GC system by GC-FID with a TG-IMS column of 30 m length, 0.25 mm
diameter and 0.25 µm film thickness. Solvents were purchased from commercial suppliers and
used without further purification. Catalytic substrates (2-iodophenol, 5-iodovanillin, 2-Iodo-3-
hydroxypyridine, phenylacetylene, 4-ethynyltoluene, 3-ethynyltoluene, 4-ethylphenylacetylene,
4-tert-butylphenylacetylene, 4-ethynylanisole, 3-ethynylaniline), K3PO4 and Pd(OAc)2 were
purchased from Sigma-Aldrich and used as received without further purification. The ligands
1a,12 1b13 and palladium complex 2b13 were prepared by reported literature procedures.
4.2. Synthesis of Pd-Pincer complex (2a)
A solution of ligand 1a (0.115 g, 0.295 mmol) and Pd(OAc)2 (0.066 g, 0.295 mmol) in CH3CN
(ca. 25 mL) was heated at 90 °C under nitrogen for 24 hours. After cooling to room temperature,
the mixture was filtered through Celite and the filtrate was concentrated in a rotary evaporator.
The collected pale yellow solid compound was washed further using hexane (2x5 mL) and dried
under vacuum. The product 2a was obtained as pale yellow solid (0.131 g, 82 % yield). 1H NMR
13

(500 MHz, CDCl3): δ 7.44-7.42 (m, 4H), 7.36 (br s, 4H), 7.26 (br s, 2H), 6.93 (t, 1H, JHH = 7 Hz,
py), 6.52 (s, 2H), 5.89 (s, 2H, pyrrolide-H), 2.44-2.30 (m, 6H, CH3), 1.27 (s, 3H, CH3CN) ppm.
13C{1H} NMR (125 MHz, CDCl3): δ 154.9, 141.0, 138.0, 137.3, 135.0, 129.7, 129.3, 128.1,
126.2, 111.3, 109.4, 16.12, 1.03. Anal. Calcd for C29H24N4Pd: C, 65.11; H, 4.57; N, 10.47;
Found: C, 64.68; H, 4.58; N, 9.44 %. HRMS (ESI) calcd. for C29H25N4Pd+ [M+H]+ m/z
535.1114; Found 535.1114.
4.3. General Procedure for one-pot tandem Heck alkynylation/cyclization reaction
In a typical run, performed in air, a 25 mL of round bottom flask was charged with a mixture of
2-iodophenol (0.50 mmol), terminal alkyne (0.60 mmol), and K3PO4 (1.00 mmol). A palladium
complex (2a or 2b, 0.0005 mmol) was added to the mixture, followed by DMSO (ca. 2 mL) as a
solvent, and then the reaction mixture was heated (either at 90 oC or at 120 oC) for 10 hours. The
reaction mixture was cooled to room temperature, and water (ca. 20 mL) was added. The
resulting mixture was extracted with EtOAc (ca. 50 mL). The organic layer was further extracted
with EtOAc (ca. 2x20 mL). The organic layers were combined and vacuum dried to obtain a
crude product that was subsequently purified by column chromatography. The obtained
benzofuran derivatives (3aa−3ap) were characterized by NMR and Mass spectroscopy (See
Supporting Information Figures S4-S23).
1
2-Phenylbenzo[b]furan (3aa: Table 2, entry 1): H NMR (500 MHz, CDCl3): δ 7.90-7.89 (m,
2H), 7.62-7.60 (m, 1H), 7.56-7.54 (m, 1H), 7.49-7.46 (m, 2H), 7.38 (t, 1H, JHH = 7.0 Hz), 7.33-
7.24 (m, 2H), 7.05 (s, 1H) ppm.9b
14

1
2-(p-tolyl)benzofuran (3ab: Table 2, entry 2): H NMR (500 MHz, CDCl3): δ 7.84-7.82 (m,
2H), 7.64-7.58 (m, 2H), 7.34-7.30 (m, 4H), 7.03 (s, 1H), 2.46 (s, 3H) ppm.9b
2-m-Tolylbenzofuran (3ac: Table 2, entry 3): 1H NMR (500 MHz, CDCl3): δ 7.74 (s, 1H),
7.71-7.70 (m, 1H), 7.62-7.60 (m, 1H), 7.57-7.55 (m, 1H), 7.38-7.36 (m, 1H), 7.35-7.29 (m, 1H),
7.28-7.25 (m, 1H), 7.24-7.19 (m, 1H), 7.03 (s, 1H), 2.46 (s, 3H) ppm.9b
1
2-(4-Ethylphenyl)benzofuran (3ad: Table 2, entry 4): H NMR (500 MHz, CDCl3): δ 7.86 (d,
2H, JHH = 8.0 Hz), 7.63 (d, 1H, JHH = 8.0 Hz), 7.59 (d, 1H, JHH = 8.0 Hz), 7.35-7.34 (m, 3H),
7.33-7.28 (m, 1H), 7.03 (s, 1H), 2.75-2.71 (m, 2H), 1.34 (t, 3H, JHH = 8.0 Hz) ppm.9b
1
2-(4-tert-Butylphenyl)benzofuran (3ae: Table 2, entry 5): H NMR (500 MHz, CDCl3): δ 7.81
(d, 2H, JHH = 8.0 Hz), 7.58 (d, 1H, JHH = 8.0 Hz), 7.53 (d, 1H, JHH = 8.0 Hz), 7.48 (d, 2H, JHH
=
8.0 Hz), 7.29-7.22 (m, 2H), 6.99 (s, 1H), 1.37 (s, 9H) ppm.9b
1
2-(4-Methoxyphenyl)benzofuran (3af: Table 2, entry 6): H NMR (500 MHz, CDCl3): δ 7.83
(d, 2H, JHH = 8.0 Hz), 7.59 (d, 1H, JHH = 7.0 Hz), 7.53 (d, 1H, JHH = 8.0 Hz), 7.30-7.23 (m, 2H),
7.01 (d, 2H, JHH = 8.0 Hz), 6.92 (s, 1H), 3.89 (s, 3H) ppm.9b
3-(benzofuran-2-yl)aniline (3ag: Table 2-3, entry 7 & 12): 1H NMR (500 MHz, CDCl3): δ 7.60
(d, 1H, JHH = 8.0 Hz), 7.55 (d, 1H, JHH = 8.0 Hz), 7.32-7.27 (m, 2H), 7.26-7.23 (m, 3H), 7.00 (s,
1H), 6.70-6.69 (m, 1H), 3.68 (br s, 2H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ 156.1, 154.8,
146.8, 131.4, 129.8, 129.3, 124.2, 122.9, 120.9, 115.5, 115.5, 111.3, 111.2, 101.3 ppm.6e
15

1
7-Methoxy-2-(phenyl)benzofuran-5-carbaldehyde (3ah: Table 2-3, entry 8 & 13): H NMR
(500 MHz, CDCl3): δ 9.99 (s, 1H), 7.87(d, 2H, JHH = 7.5 Hz), 7.69 (s, 1H), 7.47-7.44 (m, 2H),
7.40-7.35 (m, 2H), 7.08 (s, 1H), 4.08 (s, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ 191.8,
157.8, 147.7, 146.1, 133.5, 130.8, 129.6, 129.2, 128.9, 125.2, 119.3, 104.6, 101.9, 56.2 ppm.18
1
7-Methoxy-2-(p-tolyl)benzofuran-5-carbaldehyde (3ai: Table 2-3, entry 9 & 14): H NMR
(500 MHz, CDCl3): δ 10.00 (s, 1H), 7.79 (d, 2H, JHH = 8.0 Hz), 7.71-7.70 (m, 1H), 7.36-7.35 (m,
1H), 7.28-7.26 (m, 2H), 7.04 (s, 1H), 4.09 (s, 3H), 2.41 (s, 3H) ppm. 13C{1H} NMR (100 MHz,
CDCl3): δ 191.9, 158.2, 147.6, 146.1, 139.5, 133.5, 131.1, 129.7, 126.9, 125.2, 119.3, 104.5,
101.2, 56.3, 21.5 ppm.18
7-methoxy-2-(4-methoxyphenyl)benzofuran-5-carbaldehyde (3aj: Table 2-3, entry 10 & 15):
1H NMR (500 MHz, CDCl3): δ 9.93 (s, 1H), 7.76 (d, 2H, JHH = 8.0 Hz), 7.61 (s, 1H), 7.28 (s,
1H), 6.92 (d, 2H, JHH = 8.0 Hz), 6.88 (s, 1H), 4.03 (s, 3H), 3.81 (s, 3H) ppm. 13C{1H} NMR (125
MHz, CDCl3): δ 192.1, 160.7, 158.2, 147.7, 146.2, 133.7, 131.4, 127.0, 122.6, 119.2, 114.6,
104.6, 100.5, 56.5, 55.6 ppm.19
1
2-phenylfuro[2,3-b]pyridine (3ak: Table 2-3, entry 11 & 16): H NMR (500 MHz, CDCl3): δ
8.52 (d, 1H, JHH = 8.0 Hz), 7.92-7.90 (m, 2H), 7.77 (d, 1H, JHH = 8.0 Hz), 7.50-7.47 (m, 2H),
7.43-7.40 (m, 1H), 7.23 (s, 1H), 7.22-7.19 (m, 1H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ
159.7, 149.1, 148.1, 146.1, 129.8, 129.6, 129.0, 125.4, 118.9, 117.9, 102.5 ppm.8a,20
16

1
2-(4-Tolyl)-furo[3,2-b]pyridine (3al: Table 3, entry 17): H NMR (500 MHz, CDCl3): δ 8.51-
8.50 (m, 1H), 7.80 (d, 2H, JHH = 8.0 Hz), 7.76-7.74 (m, 1H), 7.29 (d, 2H, JHH = 8.0 Hz), 7.20-
7.17 (m, 1H), 7.16 (s, 1H), 2.42 (s, 3H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ 160.0, 149.3,
148.0, 146.0, 139.9, 129.7, 127.1, 125.4, 118.6, 117.7, 101.8, 21.6 ppm.21
2-(4-ethylphenyl)furo[2,3-b]pyridine (3am: Table 3, entry 18): 1H NMR (500 MHz, CDCl3): δ
8.52-8.50 (m, 1H), 7.83-7.82 (m, 2H), 7.76-7.74 (m, 1H), 7.30 (d, 2H, JHH = 8.0 Hz), 7.20-7.18
(m, 1H), 7.17 (s, 1H), 2.71 (q, 2H, JHH = 7.5 Hz), 1.28 (t, 3H, JHH = 7.5 Hz) ppm. 13C{1H} NMR
(125 MHz, CDCl3): δ 160.0, 149.2, 147.9, 146.2, 145.9, 128.5, 127.2, 125.4, 118.6, 117.7, 101.7,
31.0, 15.3 ppm. HRMS (ESI) calcd. for C15H14NO+ [M+H]+ m/z 224.1075; Found 224.1075.
1
2-(4-Methoxyphenyl)-furo[3,2-b]pyridine (3an: Table 3, entry 19): H NMR (500 MHz,
CDCl3): δ 8.49-8.48 (m, 1H), 7.84 (d, 2H, JHH = 8.0 Hz), 7.73 (d, 1H, JHH = 8.0 Hz), 7.18-7.15
(m, 1H), 7.08 (s, 1H), 7.01-6.99 (m, 2H), 3.87 (s, 3H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ
160.9, 159.9, 149.5, 147.9, 145.9, 127.0, 122.6, 118.3, 117.5, 114.5, 100.8, 55.5 ppm.15,21
1
3-(Furo[2,3-b]pyridin-2-yl)aniline (3ao: Table 3, entry 20): H NMR (500 MHz, CDCl3): δ
8.54 (d, 1H, JHH = 8.0 Hz), 7.77 (d, 1H, JHH = 8.0 Hz), 7.33-7.30 (m, 1H), 7.29-7.7.28 (m, 1H),
7.25-7.21 (m, 1H), 7.20-7.19 (m, 2H), 6.77-6.75 (m, 1H), 3.35 (br.s, 2H) ppm. 13C{1H} NMR
(100 MHz, CDCl3): δ 207.2, 160.0, 149.1, 147.9, 147.0, 145.9, 130.6, 129.9, 117.8, 116.4, 115.8,
111.5, 102.3 ppm. HRMS (ESI) calcd. for C13H11N2O + [M+H]+ m/z 211.0871; Found 211.0871.
17

1
2-(4-Ethylphenyl)-7-methoxybenzofuran-5-carbaldehyde (3ap: Table 3, entry 21): H NMR
(500 MHz, CDCl3): δ 9.98 (s, 1H), 7.80 (d, 2H, JHH = 7.0 Hz), 7.67(s, 1H), 7.34 (s, 1H), 7.29-
7.28 (m, 2H), 7.01 (s, 1H), 4.08 (s, 3H), 2.70 (q, 2H, JHH = 7.5 Hz), 1.27 (t, 3H, JHH = 7.5 Hz)
ppm. 13C{1H} NMR (100 MHz, CDCl3): δ 191.8, 158.1, 147.6, 146.0, 145.7, 133.4, 131.0,
128.4, 127.0, 125.2, 119.2, 104.4, 101.2, 56.2, 28.8, 15.4 ppm. HRMS (ESI) calcd. for
+
C18H17O3 [M+H]+ m/z 281.1177; Found 281.1176.
Conflicts of interest
There are no conflicts to declare
Acknowledgments. This work was supported by the DST-SERB, New Delhi, Grant No.
YSS/2014/000054. SY thanks Central University of Rajasthan for research fellowship. Authors
are thankful to DST-FIST (Grant No. SR/FST/CSI-257/2014(c)) for providing instrumental
facilities. The authors thank Mr. Farsa Ram Soni and Ms. Isha Mishra for getting 13C NMR data.
Supplementary Data
Supplementary material related to this article can be found, in the online version, at DoI:
https://doi.org/10.1016/j.tet.2020.XXXXXX.
18

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Highlights:
•
•
•
Straightforward synthesis of [NNN] based palladium-pincer complexes as homogeneous
catalysts in cross-coupling reactions.
Excellent catalytic activity of bis(pyrrolyl)pyridine based palladium pincer complexes in
one-pot tandem Heck alkynylation/cyclization reactions.
The developed catalysts exhibit broad functional group compatibility and efficient
conversion of benzofuran derivatives.
1