Pd/Indanone-Based Ligands: An Efficient Catalyst System for Ullmann-Type, Suzuki-Miyaura, and Mizoroki-Heck Cross-Coupling Reactions with Aryl Tosylates and Aryl Halides

Article abstract of DOI:10.1055/s-0036-1589058

2-Hydroxyindan-1-ones have been efficiently synthesized and successfully applied as ligands in Pd-catalyzed Ullmann type, Suzuki-Miyaura, and Mizoroki-Heck cross-coupling reactions with aryl tosylates and aryl halides. The ligands are air- and moisture-stable and have shown high catalytic activity with Pd(OAc) ₂ in these cross-coupling reactions. The system tolerates a variety of functional groups in the product and can be re-used at least three times with maximum efficiency..

Full text of DOI:10.1055/s-0036-1589058

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–K
paper
A
en
M. Waheed, N. Ahmed
Paper
Synthesis
Pd/Indanone-Based Ligands: An Efficient Catalyst System for
Ullmann-Type, Suzuki–Miyaura, and Mizoroki–Heck Cross-Cou-
pling Reactions with Aryl Tosylates and Aryl Halides
Mohammed Waheed*
Naseem Ahmed*
0
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0-
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3
2-
2
6
9
9-
6
3
6
Pd(OAc)2, L1, K3PO4
O
Ullmann Products
X
dioxane, r.t. or 80 °C
OH
Department of Chemistry, Indian Institute of Technology
Roorkee, Roorkee 247 667, India
nasemfcy@iitr.ac.in
Pd(OAc)2, L1
Suzuki Products
Heck Products
Y
EtOH, K2CO3, reflux/r.t.
O
OH
R
Pd(OAc)2, L1, K3PO4
X, Y = Cl, Br, I, OTs
R = H, CHO, CN, Ac
OH, NH2, OMe
L1
dioxane, 80 °C
Received: 24.03.2017
Accepted after revision: 22.05.2017
Published online: 31.07.2017
mations (Figure 1). Considering these properties, a range of
methods have been reported for the synthesis of coumarins
and their derivatives.16–20
DOI: 10.1055/s-0036-1589058; Art ID: ss-2017-t0191-op
Abstract 2-Hydroxyindan-1-ones have been efficiently synthesized
and successfully applied as ligands in Pd-catalyzed Ullmann type, Suzu-
ki–Miyaura, and Mizoroki–Heck cross-coupling reactions with aryl to-
sylates and aryl halides. The ligands are air- and moisture-stable and
have shown high catalytic activity with Pd(OAc)2 in these cross-cou-
pling reactions. The system tolerates a variety of functional groups in
the product and can be re-used at least three times with maximum effi-
ciency.
O
OH
HO
O
H
N
OH
O
H2N
N
H
O
O
N
O
O
OH
NH2
O
O
Vipirinin (HIV-1Vpr inhibitor)
Biphenomycin B (antibiotic)
Key words palladium acetate, Ullmann coupling, Suzuki coupling,
Heck coupling, catalyst recycling
O
O
O
Transition-metal-catalyzed cross-coupling reactions
have become an extremely versatile tool in modern organic
synthesis for the formation of new carbon–carbon and car-
bon–heteroatom bonds.1 Among these reactions, Pd-cata-
lyzed Ullmann type, Suzuki–Miyaura and Mizoroki–Heck
cross-couplings are powerful synthetic tools for the synthe-
sis of ethers, symmetric/unsymmetric biaryls and alkenes
associated with low cost, relatively low toxicity, commercial
availability of a large number of phenols, boronic acids and
alkenes.2,3 These methods are widely used in the synthesis
of biologically active natural products, fine chemicals, her-
bicides, and pharmaceuticals.4–10
The aryl–O, aryl–C, and aryl–N bonds as well as the bi-
aryl moiety are important structural motifs in organic and
bioorganic chemistry, and they are found in numerous cos-
metics, natural products, and pharmaceuticals.11 They are
prevalent in many compounds that are of materials and
pharmaceutical interest.12 The natural product Biphenomy-
cin B,13 the agrochemical Boscalid,14 and liquid crystals for
LCD screens15 are examples of immensely economically
valuable biaryls that involve C–C, C–N, and C–O bond for-
O
Geiparvarin (anticancer activity)
NC
C7H15
C8H17O
NCB, 807 (liquid crystal)
Figure 1 Structures of some biologically active coumarin and biaryl
core-containing molecules
Aryl tosylates are inexpensive compared with the corre-
sponding triflates and nonaflates and are therefore desir-
able alternative precursors for cross-coupling reactions.
Moreover, aryl tosylates are more convenient to use be-
cause they are more stable toward hydrolysis than the cor-
responding triflates.21
Based on a literature survey,22,23 herein we report air-
and moisture-stable, inexpensive and easily prepared oxy-
gen-based ligands in Ullmann type, Suzuki–Miyaura, and
Mizoroki–Heck cross-coupling reactions for aryl halides
and aryl tosylates. A full report on the effect of bases, sol-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–K

B
M. Waheed, N. Ahmed
Paper
Synthesis
vents, and catalyst loading on coupling reaction of aryl ha-
lides and aryl tosylates with arylboronic acid, alkenes and
phenols is also provided.
Air- and moisture-stable indanone based ligands L1–L4
were synthesized from chalcone epoxides using SnCl4 cata-
lyst in CH2Cl2 at 0 °C by following the reported method and
used as ligands in the Ullmann type coupling reaction
(Scheme 1).24 Indanone-based ligands have two donor at-
oms at adjacent carbons, which can be use for ligation with
metal ions. Similar to benzoin (α-hydroxyketone) as a li-
gand for different metal ions,25 indanone-based ligands L1–
L4 have two donor atoms at a suitable distance to form a
complex with the Pd ion.
Figure 3 Interaction of L1 with 1 equiv of Pd ions, emission spectra in
MeOH
O
O
SnCl4 (10 mol%)
OH
O
not obtain single crystals of the complex, but we have char-
acterized the metal complex by elemental analysis, IR, and
melting point. Elemental analysis shows that only one li-
gand combines with Pd(OAc)2 and one acetate group re-
mains. The presence of one acetate group meant that one
site is very labile for the combination of aryl tosylates/ha-
lides leading to coupling products.
CH2Cl2, 0 °C, 2–3 min
L1 = Me
L2 = Cl
L3 = Br
L4 = NO2
X
X = Cl, Br, NO2, Me
X
85–92%
Scheme 1 Synthesis of indan-1-one ligands
Optimization of reaction conditions was undertaken by
using the coupling of 4-tosyloxycoumarin and p-cresol as a
model reaction in the Ullmann type coupling reaction (Ta-
ble 1). Herein, we studied a range of bases, ligands, solvents,
temperatures, and stoichiometries. The best results were
obtained for the reaction in dioxane in the presence of 0.3
mol% of Pd(OAc)2/L1, and potassium phosphate (2 equiv), at
80 °C for two hours; the results are summarized in Table 1.
We first evaluated the catalytic efficiency of these li-
gands for Ullmann type coupling reaction (Table 1). These
ligands showed moderate to excellent yield for the synthe-
sis of compound 3. We observed that all ligands are very ef-
fective in Ullmann type coupling reaction and gave good
yields in short reaction time. We found that ligands L1 and
L3 show higher catalytic efficiency than L2 and L4, and re-
actions were complete within two hours (entries 1–3). A
lower yield (80%) than obtained with any of the other li-
gands was achieved when L4 was used as a ligand in diox-
ane at 80 °C (entry 4). Ligand L1 displayed the best catalytic
efficiency, which gave the product in excellent yield up to
90% within two hours (entry 1), although ligands L2–L4
gave good yields in 2–4 hours. Therefore, L1 was chosen as
the optimal ligand for cross-coupling reaction between 4-
tosyloxycoumarin and p-cresol (entries 2–4).
The interaction of L1 with the Pd ion was shown by ab-
sorption-emission spectra (Figure 2 and Figure 3), in which
L1 showed a weak and broad shoulder at 224 nm with a
highly intense band at 244 nm and an intense emission
band at 312 nm (λmax 240 nm).
Figure 2 Interaction of L1 with 1 equiv of Pd ions, absorption spectra
in MeOH
Upon addition of one equiv of Pd, the band at 224 nm
increased and shifted to 244 nm in the absorption spectra.
Similarly, in the emission spectra, fluorescence quenching
occurred; this can be ascribed to the deprotonation of the
OH group, which subsequently affects the electronic prop-
erties of L1 (Figure 2 and Figure 3).
Attempts to synthesize and isolate a Pd–L1 complex led
to isolation of a material that could not be characterized by
using NMR spectroscopic techniques. Unfortunately, we did
For optimization of the base, we selected a series of bas-
es for inclusion in the coupling reaction between 4-tosyl-
oxycoumarin and p-cresol. We used carbonate and bicar-
bonate bases, phosphate base as well as some hydroxide
bases for the Ullmann type coupling reaction. We started
optimization by keeping K3PO4 as base and changed the sol-
vents. Good to excellent yields were observed when K3PO4
was used as base and the reaction reached completion
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–K

C
M. Waheed, N. Ahmed
Paper
Synthesis
Table 1 Optimization of Ligand, Base and Solventa
Having optimized the reaction conditions, we applied
the protocol for a diverse range of phenol derivatives with
4-tosyloxycoumarin as well as 4-bromocoumarin. Both
electron-deficient and electron-rich phenol derivatives
were used for the Ullmann type cross-coupling reactions.
Notably, the reactions with 4-bromocoumarin could reach
completion at room temperature within 2–3 hours.
OTs
O
O
OH
Pd(OAc)2, L
base, solvent, reflux
O
O
O
1a
3
The scope of the protocol was probed for various sub-
strate phenols with 4-tosyloxycoumarin/4-bromocouma-
rin. We used activated electron-rich phenols such as p-
cresol, o-cresol and 2-methoxy phenol and deactivated
electron-poor phenols such as 3-hydroxyacetophenone,
Entry
Ligand
Base
K3PO4
Solvent
Time (h)
Yield (%)
1
2
L1
L2
L3
L4
L1
L1
L1
L1
L1
L1
L1
L1
–
dioxane
dioxane
dioxane
dioxane
DMF
2
3
90b
84
88
80
85
73
66
70
68
62
60
56
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
Na2CO3
K2CO3
K2CO3
Et3N
3
2
R
4
4
X
OH
5
2.5
8
Pd(OAc)2, L1
O
+
6
MeCN
K3PO4, dioxane
r.t./80 °C, 1–2 h
R
O
OH
7
EtOH
12
12
6
R = H, Me, Cl, OMe,
Ac, CN, CHO, NO2
O
O
1a X = OTs
1b X = Br
8
MeOH
DMSO
dioxane
dioxane
DMSO
dioxane
dioxane
2–13
9
10
11
12
13
14
10
12
12
24
24
O
O
O
O
NaOH
KOH
O
O
O
c
O
O
K3PO4
K3PO4
–
2, 86% (OTs)
90% (Br)
3, 90% (OTs)
94% (Br)
4, 87% (OTs)
91% (Br)
d
L1
–
a Reaction conditions: 4-tosyloxycoumarin (1.0 mmol), phenol (1.2 mmol),
Cl
OHC
O
O
O
O
base (2.0 mmol), solvent (5 mL), Pd(OAc)2/L (0.3 mol%).
b At 80 °C.
O
O
c Without ligand.
d Without Pd(OAc)2.
O
O
O
O
O
7, 84% (OTs)
88% (Br)
6, 86% (OTs)
90% (Br)
5, 90% (OTs)
93% (Br)
within 2–3 hours (Table 1, entries 1–5). We then replaced
phosphate base K3PO4 with carbonate bases K2CO3 and Na2-
CO3 and obtained good yields within 6–12 hours (entries 7–
9).
CN
O
Cl
O
O2N
O
O
We also used hydroxide bases NaOH and KOH, which
gave moderate yields within 12 h (Table 1, entries 11 and
12). We then tried reactions without using Pd(OAc)2 and li-
gand, and we found that no cross-coupling products were
observed after 24 hours (entries 13 and 14). We optimized
the solvent further by assessing aprotic polar solvent such
as DMF, DMSO, which gave moderate to good yields within
2–6 hours (entries 1–5, and 9). Aprotic polar solvent diox-
ane delivered excellent yields within 2–4 hours at room
temperature (entries 1 and 4). The use of protic polar sol-
vent such as ethanol and methanol delivered moderate
yields (entries 7 and 8). Similarly, acetonitrile gave a moder-
ate yield in 8 hours (entry 6). Herein, we noted that de-
creasing the amount of catalyst mixture (Pd(OAc)2/L1),
base, or temperature led to reduced yields, whereas increas-
ing the amount of catalyst mixture (Pd(OAc)2/L1), base, or
temperature failed to improve the yields.
O
O
O
O
O
8, 82% (OTs)
86% (Br)
9, 80% (OTs)
84% (Br)
10, 75% (OTs)
78% (Br)
O
O
OHC
O
O
O
O
O
O
O
O
O
13, 78% (OTs)
12, 75% (OTs)
11, 77% (OTs)
82% (Br)
80% (Br)
83% (Br)
Scheme 2 Ullmann type coupling reaction between 4-tosyloxycouma-
rin/4-bromocoumarin and phenols. Reagents and conditions: 4-tosyloxy-
coumarin or 4-bromocoumarin (1.0 mmol), phenol (1.2 mmol), K3PO4
(2.0 mmol), dioxane (5 mL), Pd(OAc)2/L1 (0.3 mol%).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–K

D
M. Waheed, N. Ahmed
Paper
Synthesis
4-hydroxyacetophenone, 4-hydroxybenzaldehyde, 2-cy-
anophenol and 4-nitrophenol. We also studied the coupling
of hindered phenols with 4-tosyloxycoumarin/4-bromo-
coumarin, for example o-cresol, 2-methoxyphenol, 4-hy-
droxy-3-methoxybenzaldehyde, o-chlorophenol and 2-cy-
anophenol coupled with 4-tosyloxycoumarin/4-bromocou-
marin to give the corresponding coupled products in good
to excellent yields (Scheme 2, compounds 4–6, 8, and 9).
Excellent yield was obtained when activated electron-rich
phenols such as p-cresol and 2-methoxyphenol were cou-
pled with 4-tosyloxycoumarin/4-bromocoumarin in diox-
ane at 80 °C/room temperature (Scheme 2, compounds 3,
5). Good yields were obtained when deactivated electron-
poor phenols such as 3-hydroxyacetophenone, 4-hydroxy-
acetophenone, 4-hydroxy-3-methoxybenzaldehyde, 2-cy-
anophenol and 4-nitrophenol were coupled with 4-tosy-
loxycoumarin/4-bromocoumarin in dioxane at 80 °C/room
temperature (Scheme 2, compounds 6, 9–13).
Table 2 Optimization of Base and Solventa
O
O
B(OH)2
H
Pd(OAc)2, L1
H
+
base, solvent, reflux
TsO
16c
Entry
Base
Solvent
Time (h)
Yield (%)
1
2
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
K3PO4
K3PO4
Et3N
MeOH
EtOH
2
2
87
92
84
76
70
82
85
60
50
55
3
i-PrOH
DMF
2.5
3
4
5
DMSO
MeOH
EtOH
3
6
2.5
2.5
7
7
8
EtOH
9
KOH
dioxane
EtOH
7
With successful completion of the Ullmann type cou-
pling reaction, we applied the indanone-based ligands to
Suzuki–Miyaura coupling reaction under reflux conditions.
As a model reaction for optimization of the reaction
conditions, we applied 4-tosyloxybenzaldehyde and phen-
ylboronic acid in the Suzuki–Miyaura cross-coupling reac-
tion (Table 2). A range of solvents, temperatures, and bases
were assessed in varying quantities. The best results were
obtained for the reaction in dioxane in the presence of 0.1
mol% of Pd(OAc)2/L1 and two equivalents of potassium car-
bonate at 80 °C for two hours. The results are summarized
in Table 2. Decreasing the amount of catalyst or base, or re-
ducing the temperature, led to reduced yield, whereas in-
creasing the amount of catalyst or base, or raising the tem-
perature, failed to improve the yield. We also examined
other solvents, and bases in the model reaction but these
attempts did not improve the yield. Performing the reaction
at room temperature did not afford the desired product.
When the reaction was performed without either ligand or
Pd(OAc)2 and we found that no coupling products were ob-
served after 12 h (entries 11 and 12).
10
11
12
NaOH
K2CO3
K2CO3
7
b
EtOH
12
12
–
c
EtOH
–
a Reaction conditions: 4-tosyloxybenzaldehyde (1.0 mmol), phenylboronic
acid (1.2 mmol), base (2.0 mmol), solvent (5 mL), Pd(OAc)2/L1 (0.1 mol%).
b Without ligand.
c Without Pd(OAc)2.
used them directly for the coupling reactions. A moderate
yield was obtained with deactivated electron-rich aryl
halides/tosylates such as 4-bromophenol/4-chlorophenol,
Table 3 Optimization of Base and Solventa
O
O
H
Pd(OAc)2, L1
H
+
base, solvent,
TsO
reflux
Entry
Base
K2CO3
Solvent
Time (h)
Yield (%)
Under optimized reaction conditions, we then per-
formed the reactions with a range of substrates and phenyl-
boronic acid (Scheme 3).
1
2
EtOH
MeOH
i-PrOH
DMF
24
24
24
12
12
8
50
60
45
80
70
90b
83
87
K2CO3
Na2CO3
K2CO3
Et3N
3
Generally, it was observed that aryl tosylates/halides
having electron-withdrawing groups were more reactive in
the Suzuki–Miyaura cross-coupling reaction with arylbo-
ronic acid than aryl tosylates/halides having electron-do-
nating groups. Herein, we used aryl tosylates as well as aryl
halides for Suzuki–Miyaura cross-coupling reaction. Nota-
bly, for both aryl bromide and aryl iodide, room tempera-
ture conditions were used instead of reflux conditions in
ethanol. The scope of the protocol was applied for various
substrates of aryl chlorides, aryl bromides, aryl iodides and
aryl tosylates with arylboronic acid. Notably, we synthe-
sized aryl tosylates by following a reported procedure26 and
4
5
DMF
6
K3PO4
K3PO4
K3PO4
K3PO4
–
dioxane
DMF
7
10
10
24
24
8
DMSO
DMF
c
9
–
d
10
DMF
–
a Reaction conditions: 4-tosyloxybenzaldehyde (1.0 mmol), styrene (1.5
mmol), base (2.0 mmol), solvent (5 mL), 0.3 mol% of Pd(OAc)2/L1.
b At 80 °C.
c Without ligand.
d Without base.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–K

E
M. Waheed, N. Ahmed
Paper
Synthesis
excellent yield was obtained when activated electron-poor
aryl halides/tosylates such as 4-bromobenzaldehyde/4-
tosyloxybenzaldehyde, 4-bromoacetophenone/4-tosyloxy-
acetophenone, and 4-bromocoumarin/4-tosyloxycoumarin
reacted with phenylboronic acid in ethanol at room tem-
perature/reflux conditions (Scheme 2, compounds 15, 16,
24).
With successful completion of the Suzuki–Miyaura
cross-coupling reaction for aryl halide, we also used these
indanone-based ligands for Mizoroki–Heck cross-coupling
at 80 °C. The reaction of 4-tosyloxybenzaldehyde and sty-
rene was selected as a model reaction to optimize the reac-
tion conditions (Table 3).
The use of common bases such as Na2CO3 and K2CO3 was
found to be effective, affording good yield of product and
completion within 12–24 hours under reflux conditions
(Table 3, entries 1–4). Excellent yields were obtained within
eight hours when K3PO4 was used as base (entries 6–8). Hy-
droxide bases (NaOH and KOH) gave moderate to poor
yields. We observed that the use of protic polar solvents
such as isopropanol, ethanol and methanol gave poorer
yields (45–60% in 24 h; entries 1–3). Good yields were ob-
tained in DMSO and DMF (entries 7 and 8), but an excellent
yield was achieved when dioxane was used at 80 °C (entry
6).
Pd(OAc)2, L1
B(OH)2
X
R
+
Z
Z
EtOH, K2CO3
r.t./80 °C, 1–2 h
R = aryl, coumarin
Z = H, CHO, Ac, OH, chalcone
X = Br, I, Cl, OTs
O
O
H
14, 88% (Br)
15, 90% (Br)
16, 92% (Br)
88% (OTs)
82% (Cl)
88% (OTs)
86% (Cl)
90% (OTs)
O
O
CN
O
Ph
OH
19, 90% (Br)
17, 80% (Br)
18, 80% (Br)
OH
O
NH2
21, 68% (Br)
72% (I)
22, 70% (Br)
76% (I)
20, 70% (Br)
73% (I)
65% (Cl)
60% (Cl)
62% (Cl)
23, 80% (Br)
75% (Cl)
O
O
84% (OTs)
24, 92% (Br)
90% (OTs)
We then used a range of deactivated electron-rich aryl
tosylates/halides as well as activated electron-poor aryl to-
sylates/halides for the coupling between alkenes and aryl
tosylates/halides (Scheme 4). It was observed that aryl to-
sylates/halides with electron-withdrawing groups were
more reactive than those with electron-donating groups in
the Mizoroki–Heck coupling reactions. Herein, we observed
that electron-withdrawing groups gave better yields than
Scheme 3 Suzuki–Miyaura reaction of aryl halides/tosylate with aryl
boronic acid. Reagents and conditions: aryl tosylate/halide (1.0 mmol),
phenylboronic acid (1.2 mmol), base (2.0 mmol), EtOH (5 mL),
r.t./80 °C, 0.1 mol% of Pd(OAc)2/L1.
4-bromoaniline/4-chloroaniline, 4-bromotoluene/4-tosyl-
oxytoluene, and 4-bromoanisole/4-tosyloxyanisole coupled
with phenylboronic acid (Scheme 3, compounds 20–23). An
R1
Pd(OAc)2, L1, K3PO4
X
R1
+
R
Z
dioxane, 80 °C, 8–10 h
Z
R1 = Ph, CO2Me
R = aryl, coumarin
Z = H, CHO, Ac, OH, chalcone
X = Br, I, OTs
O
O
O
O
O
MeO
O
MeO
OH
OH
25, 86% (OTs)
26, 87% (OTs)
O
27, 83% (Br)
28, 88% (Br)
92% (Br)
92% (Br)
O
MeO
H
OH
OH
MeO
O
30, 80% (Br)
29, 78% (Br)
31, 88% (OTs)
O
O
83% (I)
80% (I)
90% (Br)
O
O
32, 88% (OTs)
33, 90% (OTs)
90% (Br)
92% (Br)
Scheme 4 Mizoroki–Heck reaction of aryl tosylates/halides with alkenes. Reagents and conditions: aryl tosylates/halides (1.0 mmol), alkene (1.5 mmol),
K3PO4 (2.0 mmol), dioxane (5 mL), 0.3 mol% of Pd(OAc)2/L1.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–K

F
M. Waheed, N. Ahmed
Paper
Synthesis
electron-donating groups (Scheme 4, compounds 25–26,
31). Deactivated electron-rich aryl halides such as 4-bro-
mophenol/4-iodophenol and 2-hydroxyacetophenone gave
moderate yields and the reaction required longer to reach
completion (Scheme 4, compounds 27–30).
In conclusion, we have developed efficient air- and
moisture-stable indanone-based ligands and successfully
applied them to Ullmann type, Suzuki–Miyaura, and Mizo-
roki–Heck cross-coupling reactions with aryl tosylate and
aryl halides. Our protocol can be used to couple various aryl
tosylates and aryl halides with a range of coupling partners
in high yields under mild conditions.
GC-MS: m/z (%) = 238 [M+, C16H14O2], 239, 238, 160, 132, 105 (100),
77.
3-(4-Chlorophenyl)-2-hydroxy-2,3-dihydroindan-1-one (L2)24
Yield: 232 mg (90%); yellow solid; mp 132–134 °C.
IR (KBr): 3383, 3068, 1677, 1591, 1488, 1402 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.92 (d, J = 7.4 Hz, 2 H), 7.69 (t, J =
7.4 Hz, 1 H), 7.56 (t, J = 7.7 Hz, 1 H), 7.49 (d, J = 8.7 Hz, 2 H), 7.35 (d, J =
8.4 Hz, 2 H), 5.36 (dd, J = 7.2, 1.9 Hz, 1 H), 5.21 (d, J = 2.1 Hz, 1 H), 4.15
(d, J = 7.9 Hz, 1 H).
13C NMR (101 MHz, CDCl3): δ = 197.4, 136.6, 134.7, 134.4, 133.4,
129.4, 129.2, 128.7, 128.5, 75.8, 62.9.
GC-MS: m/z (%) = 258 [M+, C15H11ClO2], 260, 258, 125, 105 (100), 89,
77, 51.
Chemicals were purchased from commercial sources and used with-
out further purification. All reactions were monitored by TLC using
pre-coated silica gel aluminum plates. Visualization of TLC plates was
accomplished with a UV lamp. Column chromatography was per-
formed using silica gel 60–120 mesh size with EtOAc–hexane as elu-
ent. All products were characterized by NMR, IR and GC-MS. 1H and
13C NMR spectra were recorded in deuterated chloroform (CDCl3)
with a 400/500 MHz and 101 MHz spectrometer, respectively. Chemi-
cal shifts are reported in parts per million (ppm, δ) downfield from
tetramethylsilane. Proton coupling patterns are described as singlet
(s), doublet (d), triplet (t), quartet (q), multiplet (m), and broad (br).
3-(4-Bromophenyl)-2-hydroxy-2,3-dihydroindan-1-one (L3)24
Yield: 266 mg (88%); yellow solid; mp 134–136 °C.
IR (KBr): 3386, 3065, 1677, 1592, 1485, 1400 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.91 (d, J = 8.4 Hz, 2 H), 7.69 (t, J =
7.5 Hz, 1 H), 7.56 (t, J = 7.6 Hz, 1 H), 7.50 (d, J = 8.6 Hz, 2 H), 7.43 (d, J =
8.4 Hz, 2 H), 5.35 (d, J = 7.3 Hz, 1 H), 5.19 (s, 1 H), 4.16 (d, J = 7.3 Hz,
1 H).
13C NMR (101 MHz, CDCl3): δ = 197.4, 137.0, 134.4, 133.4, 131.7,
129.7, 129.2, 128.5, 122.9, 75.8, 62.9.
GC-MS: m/z (%) = 302 [M+, C15H11BrO2], 305, 302, 196, 169, 105 (85),
89 (100), 76, 63, 51.
Typical Procedure for Synthesis of the Complex
A mixture of Pd(OAc)2 (0.2 mmol) and ligand L1 (0.2 mmol) in CH2Cl2
(3 mL) were stirred at r.t. for 5 h. The solvent was removed under re-
duced pressure and the collected red-brown precipitate was filtered
and washed several times with EtOH to remove traces of unreacted
materials. The purity of the complex was confirmed by elemental
analysis and by TLC.
3-(4-Nitrophenyl)-2-hydroxy-2,3-dihydroindan-1-one (L4)24
Yield: 237 mg (88%); yellow solid; mp 152–154 °C.
IR (KBr): 3453, 2923, 1690, 1599, 1519, 1448, 1345, 1264 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.26 (d, J = 8.8 Hz, 2 H), 8.01 (d, J =
7.9 Hz, 2 H), 7.65 (t, J = 7.4 Hz, 1 H), 7.57–7.49 (m, 3 H), 4.28 (d, J =
1.8 Hz, 1 H), 4.20 (d, J = 1.7 Hz, 1 H), 3.48 (s, 1 H).
Yield: 71 mg (88%); brown solid; mp >250 °C.
IR (KBr): 3014, 1610, 1563, 1410, 1345 cm–1
.
13C NMR (101 MHz, CDCl3): δ = 192.0, 148.3, 142.7, 135.2, 134.4,
Anal. Calcd for C18H16O4Pd: C, 53.68; H, 4.00. Found: C, 53.55; H, 4.10.
129.0, 128.4, 126.6, 124.0, 60.8, 58.0.
GC-MS: m/z (%) = 269 [M+, C15H11NO4], 269, 241, 176, 165, 136, 105
(100), 89, 77, 63, 51.
General Procedure for Synthesis of Indan-1-one Derivatives L1–L4
SnCl4 (10 mol%) was added to a stirred solution of chalcone epoxide (1
mmol) in CH2Cl2 (5 mL) at 0 °C. Upon completion of the reaction, the
mixture was poured in a 10% aqueous Na2CO3 solution and extracted
with CH2Cl2 (3 × 10 mL). The combined organic layer was dried with
anhydrous Na2SO4 and the solvent was evaporated in vacuum to ob-
tain a solid. The residue was purified by silica gel column chromatog-
raphy (hexane–EtOAc) to afford the corresponding pure products L1–
L4 in 85–92% yield.
General Procedure for Ullmann Type Cross-Coupling Reactions (2–
13)
A mixture of 4-tosyloxycoumarin/4-bromocoumarin (1.0 mmol),
phenols (1.2 mmol), K3PO4 (2.0 mmol), ligand (0.3 mol%), and
Pd(OAc)2 (0.3 mol%) in dioxane (5 mL) was stirred at r.t./80 °C. After
the completion of the reaction (monitored by TLC) solvent was re-
moved under reduced pressure. Water (10 mL) was added to the reac-
tion mixture and extracted with EtOAc (3 × 10 mL). The combined or-
ganic layer was dried with anhydrous Na2SO4 and the solvent was
concentrated in vacuum to obtain a light pink-white solid. The resi-
due was purified by silica gel column chromatography (EtOAc–hex-
ane, 5–10%) to afford the corresponding pure products.
2-Hydroxy-3-p-tolyl-2,3-dihydroindan-1-one (L1)24
Yield: 202 mg (85%); yellow solid; mp 115–117 °C.
IR (KBr): 3413, 3059, 1674, 1597, 1448, 1402 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.94 (d, J = 7.9 Hz, 2 H), 7.71–7.64 (m,
1 H), 7.56 (t, J = 7.6 Hz, 1 H), 7.46 (d, J = 7.6 Hz, 2 H), 7.19 (d, J = 7.6 Hz,
2 H), 5.40 (d, J = 5.5 Hz, 1 H), 5.24 (d, J = 5.5 Hz, 1 H), 4.15 (s, 1 H), 2.36
(s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 197.8, 138.7, 135.1, 134.2, 133.6,
129.2, 129.0, 128.5, 127.8, 76.0, 63.7, 21.1.
4-Phenoxy-2H-chromen-2-one (2)27
Yield: 272 mg (86% for -OTs); 201 mg (90% for -Br); white solid; 132–
134 °C.
IR (KBr): 1713, 1626, 1485, 1390, 1221, 1190 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–K

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M. Waheed, N. Ahmed
Paper
Synthesis
1H NMR (400 MHz, CDCl3): δ = 8.04 (d, J = 7.8 Hz, 1 H), 7.62 (t, J =
7.7 Hz, 1 H), 7.49 (t, J = 7.5 Hz, 2 H), 7.37 (t, J = 7.8 Hz, 2 H), 7.18 (d, J =
7.5 Hz, 2 H), 6.85 (d, J = 7.5 Hz, 1 H), 5.42 (s, 2 H).
13C NMR (101 MHz, CDCl3): δ = 166.4, 162.7, 153.6, 152.3, 132.8,
130.4, 126.8, 124.1, 123.1, 121.3, 116.8, 115.4, 93.5.
4-(4-Chlorophenoxy)-2H-chromen-2-one (7)27
Yield: 265 mg (84% for -OTs); 201 mg (88% for -Br); white solid; mp
124–126 °C.
IR (KBr): 3099, 1721, 1624, 1567, 1482, 1390, 1233, 1174 cm–1
1H NMR (400 MHz, CDCl3): δ = 8.00 (d, J = 7.8 Hz, 1 H), 7.63 (t, J =
7.8 Hz, 1 H), 7.46 (d, J = 8.8 Hz, 2 H), 7.38–7.34 (m, 2 H), 7.14 (d, J =
8.8 Hz, 2 H), 5.41 (s, 1 H).
.
HRMS: m/z [M + Na]+ calcd for C15H10NaO3: 261.0528; found:
261.0521.
13C NMR (101 MHz, CDCl3): δ = 166.0, 162.3, 153.6, 150.8, 133.0,
132.4, 130.6, 124.2, 123.0, 122.7, 116.9, 115.2, 93.7.
4-(p-Tolyloxy)-2H-chromen-2-one (3)27
Yield: 284 mg (90% for -OTs); 210 mg (94% for -Br); white solid; mp
131–133 °C.
HRMS: m/z [M + Na]+ calcd for C15H9ClNaO3: 295.0138; found:
295.0129.
IR (KBr): 1714, 1621, 1496, 1391, 1231, 1173 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.03 (d, J = 7.9 Hz, 1 H), 7.61 (t, J =
7.8 Hz, 1 H), 7.37–7.33 (m, 2 H), 7.28–7.26 (m, 2 H), 7.05 (d, J = 7.8 Hz,
2 H), 5.42 (s, 1 H), 2.40 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 166.6, 162.75, 153.6, 150.1, 136.6,
132.7, 130.9, 124.0, 123.0, 120.9, 116.8, 115.5, 93.4, 20.9.
4-(2-Chlorophenoxy)-2H-chromen-2-one (8)27
Yield: 259 mg (82% for -OTs); 192 mg (86% for -Br); light-yellow solid;
150–152 °C.
IR (KBr): 1714, 1621, 1496, 1391, 1231, 1173 cm–1
1H NMR (400 MHz, CDCl3): δ = 8.06 (d, J = 7.9 Hz, 1 H), 7.63 (t, J =
7.8 Hz, 1 H), 7.54 (d, J = 7.9 Hz, 1 H), 7.41–7.35 (m, 3 H), 7.33–7.25 (m,
2 H), 5.31 (s, 1 H).
.
HRMS: m/z [M + Na]+ calcd for C16H12NaO3: 275.0684; found:
275.0675.
13C NMR (101 MHz, CDCl3): δ = 165.0, 162.3, 153.6, 148.2, 132.9,
131.3, 128.6, 128.0, 126.9, 124.2, 123.2, 123.0, 116.8, 114.9, 93.5.
4-(o-Tolyloxy)-2H-chromen-2-one (4)27
Yield: 275 mg (87% for -OTs); 201 mg (91% for -Br); light-pink solid;
mp 124–126 °C.
HRMS: m/z [M + Na]+ calcd for C15H9ClNaO3: 295.0138; found:
295.0124.
IR (KBr): 2924, 1711, 1626, 1486, 1393, 1226, 1176 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.06 (d, J = 7.8 Hz, 1 H), 7.62 (t, J =
7.8 Hz, 1 H), 7.38 (d, J = 8.3 Hz, 2 H), 7.34–7.22 (m, 3 H), 7.09 (d, J =
7.7 Hz, 1 H), 5.30 (s, 1 H), 2.19 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 165.5, 162.6, 153.6, 150.5, 132.7,
132.0, 130.1, 127.8, 126.9, 124.1, 122.9, 121.3, 116.8, 115.2, 92.9, 15.6.
2-[(2-Oxo-2H-chromen-4-yl)oxy]benzonitrile (9)27
Yield: 253 mg (80% for -OTs); 188 mg (84% for -Br); light-yellow solid;
mp 200–202 °C.
IR (KBr): 3099, 2235, 1724, 1618, 1567, 1482, 1385, 1229, 1165 cm–1
1H NMR (400 MHz, CDCl3): δ = 8.05 (d, J = 7.7 Hz, 1 H), 7.8 (d, J =
7.7 Hz, 1 H), 7.75 (t, J = 7.9 Hz, 1 H), 7.65 (t, J = 7.9 Hz, 1 H), 7.48 (t, J =
7.6 Hz, 1 H), 7.38 (t, J = 8.5 Hz, 3 H), 5.38 (s, 1 H).
.
GC-MS: m/z (%) = 252 [M+, C16H12O3], 253, 252 (100), 223, 211, 181,
145, 121, 89, 65, 63.
13C NMR (101 MHz, CDCl3): δ = 165.1, 161.8, 153.7, 153.6, 134.9,
134.4, 133.30, 127.3, 124.4, 123.0, 122.5, 116.9, 114.6, 114.2, 107.1,
94.2.
GC-MS: m/z (%) = 263 [M+, C16H9NO3], 264, 263, 222, 145, 121 (100),
89, 63.
4-(2-Methoxyphenoxy)-2H-chromen-2-one (5)27
Yield: 284 mg (90% for -OTs); 208 mg (93% for -Br); light-pink solid;
mp 150–152 °C.
IR (KBr): 1719, 1624, 1568, 1497, 1391, 1265, 1184 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.06 (d, J = 7.8 Hz, 1 H), 7.60 (t, J =
7.8 Hz, 1 H), 7.37–7.28 (m, 3 H), 7.15 (d, J = 7.8 Hz, 1 H), 7.03 (q, J =
7.7 Hz, 2 H), 5.33 (s, 1 H), 3.8 (s, 3 H).
4-(4-Nitrophenoxy)-2H-chromen-2-one (10)27
Yield: 237 mg (75% for -OTs); 174 mg (78% for -Br); light-yellow solid;
mp 158–160 °C.
13C NMR (101 MHz, CDCl3): δ = 165.8, 163.0, 153.6, 151.0, 140.7,
IR (KBr): 3085, 1720, 1621, 1522, 1484, 1384, 1230, 1174 cm–1
1H NMR (400 MHz, CDCl3): δ = 8.40 (d, J = 9.1 Hz, 2 H), 7.98 (d, J =
7.9 Hz, 1 H), 7.66 (t, J = 7.9 Hz, 1 H), 7.41–7.36 (m, 4 H), 5.47 (s, 1 H).
.
132.5, 127.8, 124.0, 123.2, 122.6, 121.3, 116.7, 115.3, 113.0, 92.8, 55.7.
HRMS: m/z [M + Na]+ calcd for C16H12NaO4: 291.0633; found:
291.0655.
13C NMR (101 MHz, CDCl3): δ = 165.1, 161.8, 157.2, 153.7, 145.9,
133.3, 126.3, 124.4, 122.9, 122.1, 117.0, 114.8, 94.8.
3-Methoxy-4-[(2-oxo-2H-chromen-4-yl)oxy]benzaldehyde (6)27
Yield: 272 mg (86% for -OTs); 201 mg (90% for -Br); light-yellow solid;
mp 188–190 °C.
GC-MS: m/z (%) = 283 [M+, C15H9NO5], 284, 256, 196, 145, 121 (100),
89, 63.
IR (KBr): 1713, 1629, 1494, 1392, 1269, 1138 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 10.00 (s, 1 H), 8.02 (d, J = 8.0 Hz, 1 H),
4-(3-Acetylphenoxy)-2H-chromen-2-one (11)27
7.63–7.55 (m, 3 H), 7.37–7.34 (m, 3 H), 5.30 (s, 1 H), 3.87 (s, 4 H).
Yield: 243 mg (77% for -OTs); 186 mg (83% for -Br); white solid; mp
138–140 °C.
13C NMR (101 MHz, CDCl3): δ = 190.62, 165, 162.3, 153.5, 151.9,
145.5, 135.8, 132.8, 124.9, 124.1, 123.1, 123.1, 116.8, 114.9, 111.5,
93.2, 56.1.
HRMS: m/z [M + Na]+ calcd for C17H12NaO5: 319.0582; found:
319.0549.
IR (KBr): 3090, 1718, 1619, 1568, 1493, 1392, 1264, 1180 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.02 (d, J = 7.9 Hz, 1 H), 7.93 (d, J =
7.8 Hz, 1 H), 7.78 (s, 1 H), 7.62 (q, J = 8.9 Hz, 2 H), 7.38 (q, J = 7.8 Hz,
3 H), 5.36 (s, 1 H), 2.63 (s, 3 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–K

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M. Waheed, N. Ahmed
Paper
Synthesis
GC-MS: m/z (%) = 280 [M+, C17H12O4], 280, 279 (100), 265, 261, 237,
145, 121, 89, 63.
1H NMR (500 MHz, CDCl3): δ = 8.04 (d, J = 8.3 Hz, 2 H), 7.69 (d, J =
8.3 Hz, 2 H), 7.63 (d, J = 7.8 Hz, 2 H), 7.47 (t, J = 7.6 Hz, 2 H), 7.40 (t, J =
7.3 Hz, 1 H), 2.64 (s, 3 H).
4-(4-Acetylphenoxy)-2H-chromen-2-one (12)27
13C NMR (101 MHz, CDCl3): δ = 197.7, 145.7, 139.7, 135.7, 128.9,
128.8, 128.1, 127.2, 127.1, 26.6.
GC-MS: m/z (%) = 196 [M+, C14H12O], 197, 196, 182, 150 (100), 126, 76,
63.
Yield: 246 mg (75% for -OTs); 184 mg (80% for -Br); light-yellow solid;
mp 162–163 °C.
IR (KBr): 3069, 1716, 1682, 1565, 1488, 1391, 1270, 1183 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.10 (d, J = 8.6 Hz, 2 H), 8.01 (d, J =
7.8 Hz, 1 H), 7.63 (t, J = 7.8 Hz, 1 H), 7.37 (t, J = 8.6 Hz, 2 H), 7.28 (d, J =
8.6 Hz, 2 H), 5.43 (s, 1 H), 2.65 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 2.65 (s, 3 H), 196.5, 165.6, 162.2,
156.0, 153.6, 135.5, 133.1, 130.9, 124.3, 123.0, 121.4, 116.9, 115.0,
94.1, 26.6.
Biphenyl-4-carbaldehyde (16)28a
Yield: 169 mg (92% for -Br); 120 mg (86% for -Cl); 248 mg (90% for -
OTs); white solid; mp 58–60 °C.
IR (KBr): 3025, 2836, 2745, 1690, 1601, 1396, 1214, 1170, 833,
761 cm–1
.
GC-MS: m/z (%) = 280 [M+, C17H12O4], 281, 280, 265, 145 (100), 121,
89, 63.
1H NMR (500 MHz, CDCl3): δ = 10.06 (s, 1 H), 7.96 (d, J = 8.2 Hz, 2 H),
7.76 (d, J = 8.2 Hz, 2 H), 7.64 (d, J = 7.5 Hz, 2 H), 7.48 (t, J = 7.3 Hz, 2 H),
7.42 (t, J = 7.4 Hz, 1 H).
4-[(2-Oxo-2H-chromen-4-yl)oxy]benzaldehyde (13)27
13C NMR (101 MHz, CDCl3): δ = 191.9, 147.1, 139.6, 135.0, 130.2,
128.9, 128.4, 127.6, 127.3.
GC-MS: m/z (%) = 182 [M+, C13H10O], 183, 182, 151 (100), 126, 75, 63.
Yield: 246 mg (78% for -OTs); 184 mg (82% for -Br); white solid; mp
168–170 °C.
IR (KBr): 3065, 2952, 2861, 1712, 1623, 1491, 1390, 1237, 1181 cm–1
.
2-Hydroxy-1-acetobiphenyl (17)28b
1H NMR (400 MHz, CDCl3): δ = 10.06 (s, 1 H), 8.04 (d, J = 8.3 Hz, 2 H),
8.00 (d, J = 7.9 Hz, 1 H), 7.65 (t, J = 7.9 Hz, 1 H), 7.40–7.35 (m, 4 H),
5.46 (s, 1 H).
13C NMR (101 MHz, CDCl3): δ = 190.4, 165.4, 162.1, 157.1, 153.7,
134.7, 133.2, 132.1, 124.3, 123.0, 122.0, 116.9, 115.0, 94.4.
Yield: 171 mg (80% for -Br); white solid; mp 120–122 °C.
IR (KBr): 3431, 1675, 1639, 1399, 1260, 1075 cm–1
1H NMR (500 MHz, CDCl3): δ = 12.32 (s, 1 H), 7.92 (s, 1 H), 7.71 (d, J =
8.6 Hz, 1 H), 7.56 (d, J = 7.5 Hz, 2 H), 7.47 (t, J = 7.7 Hz, 2 H), 7.38 (t, J =
7.2 Hz, 1 H), 7.08 (d, J = 8.6 Hz, 1 H), 2.69 (s, 3 H).
.
GC-MS: m/z (%) = 266 [M+, C16H10O4], 267, 266, 238, 197, 145, 121
(100), 89, 63.
HRMS: m/z [M + H]+ calcd for C14H13O2: 213.0916; found: 213.0905.
General Procedure for Suzuki–Miyaura Cross-Coupling Reactions
(14–24)
3-Cyano-4-methoxybiphenyl (18)28c
Yield: 169 mg (80% for -Br); white solid; mp 109–110 °C.
A mixture of aryl halide/tosylate (1.0 mmol), phenylboronic acid (1.2
mmol), K2CO3 (2.0 mmol), ligand (0.1 mol%) and Pd(OAc)2 (0.1 mol%)
in EtOH (5 mL) was stirred at r.t. The progress of the reaction was
monitored by TLC. Upon completion of the reaction, solvent was re-
moved under reduced pressure. Water (10 mL) was added to the reac-
tion mixture and extracted with EtOAc (3 × 10 mL). The combined or-
ganic layer was dried with anhydrous Na2SO4 and the solvent was
concentrated in vacuum to obtain a light yellow-white solid. The resi-
due was purified by silica gel column chromatography (EtOAc–hex-
ane, 5–10%) to afford the corresponding pure products.
IR (KBr): 3123, 2227, 1609, 1512, 1480, 1398, 1287, 1185, 1125, 1016,
834, 771, 670 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.78–7.74 (m, 2 H), 7.50 (d, J = 7.7 Hz,
2 H), 7.44 (t, J = 7.6 Hz, 2 H), 7.36 (t, J = 7.3 Hz, 1 H), 7.05 (d, J = 8.6 Hz,
1 H), 3.98 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 160.4, 138.5, 134.1, 132.9, 132.0,
128.9, 127.6, 126.5, 116.4, 111.6, 102.0, 56.1.
GC-MS: m/z (%) = 209 [M+, C14H11NO], 209 (100), 194, 166, 140, 115,
76, 63.
Biphenyl (14)28a
(2E)-3-Biphenyl-1-phenyl-prop-2-en-1-one (19)28b
Yield: 137 mg (88% for -Br); 218 mg (88% for -OTs); colorless needles;
mp 64–66 °C.
IR (KBr): 1630, 1398, 820, 749 cm–1
1H NMR (500 MHz, CDCl3): δ = 7.60 (d, J = 7.8 Hz, 4 H), 7.45 (t, J =
7.6 Hz, 4 H), 7.35 (t, J = 7.6 Hz, 2 H).
13C NMR (101 MHz, CDCl3): δ = 141.2, 128.7, 127.2, 127.1.
GC-MS: m/z (%) = 154 [M+, C12H10], 155, 154 (100), 128, 76.
Yield: 257 mg (90% for -Br); pale-yellow solid; mp 120–122 °C.
IR (KBr): 1648, 1611, 1400, 1124, 1070 cm–1
.
.
1H NMR (500 MHz, CDCl3): δ = 8.10 (d, J = 8.3 Hz, 2 H), 7.83 (d, J =
15.7 Hz, 1 H), 7.73 (d, J = 8.3 Hz, 2 H), 7.66 (d, J = 7.5 Hz, 2 H), 7.58–
7.53 (m, 3 H), 7.50–7.47 (m, 2 H), 7.42–7.39 (m, 1 H), 7.24 (d, J =
7.8 Hz, 2 H), 2.40 (s, 3 H).
HRMS: m/z [M + H]+ calcd for C21H17O: 285.1279; found: 285.1268.
4-Acetylbiphenyl (15)28a
4-Aminobiphenyl (20)28f
Yield: 178 mg (90% for -Br); 142 mg (82% for -Cl); 255 mg (88% for -
OTs); white solid; mp 118–120 °C.
Yield: 120 mg (70% for -Br); 160 mg (73% for -I); 79 mg (62% for -Cl);
light-yellow solid; mp 162–164 °C.
IR (KBr): 2993, 1677, 1602, 1399, 1261, 1071, 765 cm–1
.
IR (KBr): 3463, 3240, 1630, 1482, 1400, 1077 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.58 (d, J = 7.5 Hz, 2 H), 7.47–7.42 (m,
4 H), 7.31 (t, J = 7.5 Hz, 1 H), 6.78 (d, J = 8.4 Hz, 2 H), 3.78 (s, 2 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–K

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M. Waheed, N. Ahmed
Paper
Synthesis
13C NMR (101 MHz, CDCl3): δ = 145.7, 141.0, 131.4, 129.5, 128.6,
127.9, 126.3, 126.1, 115.3.
GC-MS: m/z (%) = 169 [M+, C12H11N], 169, 144, 139, 113, 125, 77, 62
(100), 52.
monitored by TLC. Upon completion of the reaction, the mixture was
cooled to r.t., and solvent was removed under reduced pressure. Water
(10 mL) was added to the mixture, and extracted with EtOAc (3 × 10
mL). The combined organic layer was dried with anhydrous Na2SO4
and the solvent was concentrated in vacuum to obtain a solid. The
residue was purified by silica gel column chromatography (EtOAc–
hexane, 5–10%) to afford the corresponding pure products.
4-Hydroxybiphenyl (21)28a
Yield: 117 mg (68% for -Br); 158 mg (72% for -I); 83 mg (65% for -Cl);
white solid; mp 163–165 °C.
(E)-4-Acetylstilbene (25)28d
IR (KBr): 3451, 1636, 1566, 1422, 1172 cm–1
.
Yield: 249 mg (86% for -OTs); 182 mg (92% for -Br); white solid; mp
140–142 °C.
1H NMR (500 MHz, CDCl3): δ = 7.54 (d, J = 7.4 Hz, 2 H), 7.48 (d, J =
8.6 Hz, 2 H), 7.41 (t, J = 7.7 Hz, 2 H), 7.30 (t, J = 7.4 Hz, 1 H), 6.91 (d, J =
8.6 Hz, 2 H), 4.81 (s, 1 H).
13C NMR (101 MHz, CDCl3): δ = 154.9, 140.7, 138.4, 133.9, 132.4,
128.7, 128.3, 126.6, 117.7, 115.6.
IR (KBr): 1676, 1637, 1403, 1265, 1178, 1071, 936 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.95 (d, J = 8.3 Hz, 2 H), 7.58 (d, J =
8.3 Hz, 2 H), 7.54 (d, J = 7.7 Hz, 2 H), 7.38 (t, J = 7.5 Hz, 2 H), 7.30 (t, J =
7.4 Hz, 1 H), 7.23 (d, J = 16.3 Hz, 1 H), 7.13 (d, J = 16.3 Hz, 1 H), 2.60 (s,
3 H).
GC-MS: m/z (%) = 170 [M+, C12H10O], 171, 170 (100), 152, 141, 115, 85,
76, 63.
13C NMR (101 MHz, CDCl3): δ = 197.4, 141.9, 136.6, 135.9, 131.4,
128.8, 128.7, 128.2, 127.4, 126.7, 126.4, 26.5.
GC-MS: m/z (%) = 222 [M+, C16H14O], 222, 207 (100), 178, 152, 103, 89,
76.
4-Methoxybiphenyl (22)28a
Yield: 130 mg (70% for -Br); 178 mg (76% for -I); 85 mg (60% for -Cl);
white solid; mp 87–88 °C.
IR (KBr): 1642, 1610, 1522, 1485, 1401, 1284, 1197, 1037 cm–1
.
(E)-3-(4-Acetylphenyl)acrylic Acid Methyl Ester (26)28g
1H NMR (400 MHz, CDCl3): δ = 7.55 (t, J = 8.4 Hz, 4 H), 7.42 (t, J =
7.3 Hz, 2 H), 7.31 (t, J = 7.3 Hz, 1 H), 6.99 (d, J = 8.4 Hz, 2 H), 3.86 (s,
3 H).
Yield: 252 mg (87% for -OTs); 182 mg (92% for -Br); white solid; mp
104–105 °C.
IR (KBr): 3011, 1712, 1678, 1637, 1403, 1323, 1266, 1206, 1079, 992,
13C NMR (101 MHz, CDCl3): δ = 159.0, 140.8, 133.7, 128.7, 128.2,
827 cm–1
.
128.1, 126.7, 114.1, 55.3.
GC-MS: m/z (%) = 184 [M+, C13H12O], 184 (100), 169, 141, 115, 76, 63.
1H NMR (500 MHz, CDCl3): δ = 7.96 (d, J = 8.2 Hz, 2 H), 7.69 (d, J =
16.0 Hz, 1 H), 7.59 (d, J = 8.2 Hz, 2 H), 6.51 (d, J = 16.0 Hz, 1 H), 3.81 (s,
3 H), 2.60 (s, 3 H).
4-Methylbiphenyl (23)28a
HRMS: m/z [M + Na]+ calcd for C12H12NaO3: 227.0684; found:
Yield: 146 mg (80% for -Br); 94 mg (75% for -Cl); 220 mg (65% for -
OTs); white solid; 46–48 °C.
227.0683.
(E)-2-Hydroxyl-4-acetylstilbene (27)28g
IR (KBr): 1634, 1400, 823, 753 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.63 (d, J = 7.5 Hz, 2 H), 7.55 (d, J =
8.1 Hz, 2 H), 7.48 (t, J = 7.5 Hz, 2 H), 7.37 (t, J = 7.7 Hz, 1 H), 7.30 (d, J =
7.8 Hz, 2 H), 2.45 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 141.2, 138.3, 137.0, 129.6, 129.4,
129.3, 128.7, 126.9, 21.0.
Yield: 177 mg (83%); white solid; mp 216–218 °C.
IR (KBr): 1606, 1444, 1344, 1306, 1182, 1089, 698 cm–1
1H NMR (500 MHz, CDCl3): δ = 12.30 (s, 1 H), 7.80 (d, J = 1.9 Hz, 1 H),
7.71 (dd, J = 8.7, 1.9 Hz, 1 H), 7.50 (d, J = 7.6 Hz, 2 H), 7.36 (t, J = 7.6 Hz,
2 H), 7.28 (d, J = 7.4 Hz, 1 H), 7.06 (d, J = 16.3 Hz, 1 H), 7.00–6.97 (m,
2 H), 2.70 (s, 3 H).
.
HRMS: m/z [M + H]+ calcd for C13H13: 169.1017; found: 169.1011.
13C NMR (101 MHz, CDCl3): δ = 204.4, 162.0, 137.1, 139.8, 128.9,
128.7, 128.6, 127.6, 127.1, 126.3, 119.6, 118.9, 29.6.
4-Phenyl-2H-chromen-2-one (24)28e
Yield: 206 mg (92% for -Br); 284 mg (90% for -OTs); white solid; mp
92–94 °C.
HRMS: m/z [M + H]+ calcd for C16H15O2: 239.1072; found: 239.1060.
(E)-2-Hydroxyl-3-(4-acetylphenyl)acrylic Acid Methyl Ester (28)28g
Yield: 188 mg (88%); yellow solid; mp 111–113 °C.
IR (KBr): 3072, 1732, 1609, 1440, 1400, 1363, 1250, 1184, 940 cm–1
1H NMR (400 MHz, CDCl3): δ = 7.56–7.47 (m, 5 H), 7.45–7.43 (m, 2 H),
7.40 (d, J = 8.3 Hz, 1 H), 7.22 (t, J = 7.6 Hz, 1 H), 6.37 (s, 1 H).
.
IR (KBr): 3444, 2961, 1702, 1638, 1478, 1434, 1372, 1272, 1183, 1032,
809 cm–1
.
13C NMR (101 MHz, CDCl3): δ = 160.7, 155.6, 154.1, 135.1, 131.8,
1H NMR (500 MHz, CDCl3): δ = 12.48 (s, 1 H), 7.85 (d, J = 1.9 Hz, 1 H),
7.68 (dd, J = 8.7, 1.9 Hz, 1 H), 7.65 (d, J = 16.0 Hz, 1 H), 7.01 (d, J =
8.7 Hz, 1 H), 6.34 (d, J = 16.0 Hz, 1 H), 3.81 (s, 3 H), 2.67 (s, 3 H).
129.6, 128.8, 128.3, 126.9, 124.1, 118.9, 117.2, 115.1.
HRMS: m/z [M + Na]+ calcd for C15H10NaO2: 245.0578; found:
245.0556.
13C NMR (101 MHz, CDCl3): δ = 204.2, 167.3, 164.0, 143.3, 134.8,
131.4, 125.5, 119.6, 119.3, 116.3, 51.7, 26.5.
HRMS: m/z [M + Na]+ calcd for C12H12NaO4: 243.0633; found:
General Procedure for Mizoroki–Heck Cross-Coupling Reactions
(25–33)
A mixture of aryl halides/tosylates (1.0 mmol), alkenes (1.5 mmol),
K3PO4 (2.0 mmol), ligand (0.3 mol%) and Pd(OAc)2 (0.3 mol%) was
heated in dioxane (5 mL) at 80 °C. The progress of the reaction was
243.0634.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–K

J
M. Waheed, N. Ahmed
Paper
Synthesis
(E)-4-Hydroxystilbene (29)28a
HRMS: m/z [M + Na]+ calcd for C17H12NaO2: 271.0735; found:
271.0728.
Yield: 134 mg (78% for -Br); 176 mg (80% for -I); white solid; mp 166–
168 °C.
IR (KBr): 3426, 3014, 1639, 1602, 1510, 1445, 1400, 1235, 961,
Acknowledgment
819 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.49 (d, J = 7.5 Hz, 2 H), 7.41 (d, J =
8.3 Hz, 2 H), 7.35 (t, J = 7.5 Hz, 2 H), 7.23 (m, 1 H), 7.06 (d, J = 16.3 Hz,
1 H), 6.97 (d, J = 16.3 Hz, 1 H), 6.83 (d, J = 8.3 Hz, 2 H), 4.86 (s, 1 H).
We are grateful to the University Grant commission (UGC), New Delhi
for a junior research fellowship (JRF) for M.W. and to the Editor for
useful comments.
13C NMR (101 MHz, CDCl3): δ = 155.2, 137.5, 130.3, 128.6, 128.1,
127.9, 127.3, 126.7, 126.2, 115.6.
GC-MS: m/z (%) = 196 [M+, C14H12O], 197, 196 (100), 177, 165, 152,
Supporting Information
115, 97, 89, 82, 76, 63.
Supporting information for this article is available online at
https://doi.org /10.1055/s-0036-1589058.
S
u
p
p
o
nrtogI
f
rmoaitn
S
u
p
p
ortiInfogrmoaitn
(E)-3-(4-Hydroxyphenyl)acrylic Acid Methyl Ester (30)28g
Yield: 135 mg (80% for -Br); 182 mg (83% for -I); white solid; mp 120–
122 °C.
References
IR (KBr): 3451, 1636, 1566, 1422, 1290, 1172 cm–1
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mp 108–110 °C.
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.
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164–166 °C.
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.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–K

K
M. Waheed, N. Ahmed
Paper
Synthesis
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–K