2-(1-benzotriazolyl)pyridine: A robust bidentate ligand for the palladium-catalyzed C-C (Suzuki, Heck, Fujiwara-Moritani, Sonogashira), C-N and C-S coupling reactions

Article abstract of DOI:10.1002/adsc.201200583

A new class of bidentate ligand, 1-(pyridine-2-yl)-1H-benzo[d][1,2,3] triazole has been designed and employed for the palladium-catalyzed C-C (Suzuki, Heck, Fujiwara-Moritani, and Sonogashira), C-N and C-S coupling reactions. The ligand was found to be inexpensive, thermally stable, easy to synthesize from easily accessible starting materials on a multigram scale, show simplicity in use, and robustness in application, making this ligand effective for different coupling reactions. Suitably, the donor ability of the N=N bond of the benzotriazole ring and lone pair of electrons on the N of the pyridine ring enhance the bidentate ability of the ligand.

Full text of DOI:10.1002/adsc.201200583

FULL PAPERS
DOI: 10.1002/adsc.201200583
2-(1-Benzotriazolyl)pyridine: A Robust Bidentate Ligand for the
À
Palladium-Catalyzed C C (Suzuki, Heck, Fujiwara–Moritani,
À
À
Sonogashira), C N and C S Coupling Reactions
Akhilesh K. Verma,a,* Rajeev R. Jha,a Ritu Chaudhary,a Rakesh K. Tiwari,b
and Abhinandan K. Danodiaa
a
Department of Chemistry, University of Delhi, Delhi – 110007, India
E-mail: averma@acbr.du.ac.in
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston,
b
Rhode Island, RI 02881, USA
Received: July 4, 2012; Revised: October 15, 2012; Published online: February 1, 2013
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200583.
Abstract: A new class of bidentate ligand, 1-(pyri- for different coupling reactions. Suitably, the donor
dine-2-yl)-1H-benzo[d]
signed and employed for the palladium-catalyzed C
C (Suzuki, Heck, Fujiwara–Moritani, and Sonoga- ring enhance the bidentate ability of the ligand.
ACHTUNGTNER[NUNG 1,2,3]triazole has been de- ability of the N=N bond of the benzotriazole ring
À
and lone pair of electrons on the N of the pyridine
À
À
shira), C N and C S coupling reactions. The ligand
was found to be inexpensive, thermally stable, easy
to synthesize from easily accessible starting materials Keywords: benzotriazoles; Fujiwara–Moritani reac-
on a multigram scale, show simplicity in use, and ro- tion; Heck reaction; N-arylation; S-arylation; Sono-
bustness in application, making this ligand effective gashira coupling; Suzuki coupling
Introduction
drawbacks, e.g., various phosphine ligands are expen-
sive, air sensitive,[7] and prone to degrade at high tem-
Transition metal-catalyzed carbon-carbon, carbon-ni- peratures. Many other phosphine-free palladium com-
trogen, and carbon-sulfur bond formating reactions plexes like N-heterocyclic carbenes,[8–11] carbocyclic
are among the most important processes in chemistry, carbenes,[12] imines,[13] ureas,[14] thioureas[15] and sele-
because they provide key steps in the construction of nides[16] have emerged as an alternative for these cou-
various organic substrates, complex bioactive mole- pling reactions. To the best of our knowledge, the so
cules, agrochemicals, natural products and pharma- far known ligands reported in the literatureare limited
ceutically viable molecules.[1] In 2010, the Nobel Prize for a few coupling reactions. Thus, the development
in Chemistry awarded to Heck, Negishi, and Suzuki of an inexpensive, broadly applicable and robust cata-
À
for their work on cross-coupling reactions emphasized lytic system to generate a variety of CACTHUNGTRENNNUG
the importance of palladium in organic synthesis.[2]
C
N
ACHTUNGTRENNUNG
À
À
cally distinct partners to sustain synthetic transforma- tions offer significant advantages over traditional
À
tions like C H functionalization, alkylation, alkynyla- methods, which require either activated molecules or
tion, alkenylation, benzylation and a variety of aryla- harsh reaction conditions. Recently, significant devel-
tion reactions efficiently.[4]
opments in the Suzuki coupling reaction[17] and N-ary-
Up to the 1990s, triphenylphosphine was used as lation of aryl halides, have been reported by Buch-
a ligand[5] in most of the palladium-catalyzed reac- wald[18] and Hartwig.[19] The stereoelectronic effects
tions, and thereafter wide varieties of ligands have and the bite angle[20] of the N,N bidentate ligands are
been designed to carry out these reactions efficiently significant factors for the coupling reactions. Designed
under mild reaction conditions.[6] In spite of the tre- benzotriazole-based ligands are easy to prepare and
mendous utility of these ligands in palladium-cata- are thermally and air stable. Suitably, the donor abili-
lyzed organic synthesis, they suffered from several ty of the N=N bond of the benzotriazole ring and
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Akhilesh K. Verma et al.
FULL PAPERS
lone pair of electrons on the N of the pyridine ring Results and Discussion
enhance the bidentate ability of the ligand.
Katritzky’s group has extensively explored benzo- The Suzuki coupling reaction represents one of the
triazole as a synthetic auxiliary due to its incredible most synthetically valuable methods for the synthesis
properties.[21] The designed ligand L4 was suppose to of biaryl derivatives.[17] This reaction has been success-
_
provide a compelling variation to the theme of NN bi- fully applied for the synthesis of complex and biologi-
dentate ligand,[22] since benzotriazole and pyridine cally important natural and synthetic compounds.[26]
can provide electrons for the formation of a complex A search of the literature revealed that the coupling
with metals. Benzotriazole possesses, both electron- of hindered substrates has been less studied and
donor as well as electron-acceptor properties with re- needs to be explored.[27] Thus, we initiated our study
spect to the group attached to it.[21] In view of the with the sterically hindered 2,4,6-trimethoxyphenyl-
above facts, and our recent success on the coupling boronic acid (2a). To identify the optimal reaction
reactions using benzotriazole as a ligand[23,24] we were conditions for the reaction, we examined the reaction
motivated for the design of a more efficient and prac- of 4-bromotoluene (1a) with boronic acid 2a, using
tical ligand for the palladium-catalyzed coupling reac- 3 mol% of Pd
ACHTUNGRTEN(NUNG OAc)2, 6 mol% of ligand L1 and
tions (Scheme 1). Herein for the first time, we are re- 2.0 equiv. of K2CO3 in 2.0 mL of DMF/H2O (4:1) at
porting
1-(pyridine-2-yl)-1H-benzo[d]ACTHNGUTERNN[UG 1,2,3]triazole 258C. Using above reaction conditions, product 3a
(L4)[25] as a robust, phosphine-free, inexpensive and was obtained in only 8% yield (Table 1, entry 1). In-
air stable bidentate ligand for the palladium-catalyzed creasing the catalyst loading from 3 to 5 mol% and
Suzuki, Heck, Fujiwara–Moritani, Sonogashira, Buch- ligand L1 from 5 to 10 mol% afoorded the desired
À
À
wald–Hartwig (C N), and C S coupling reactions coupling product 3a in 42% yield (entry 2). The yield
(Scheme 2). The designed ligand L4 could be synthe- of the product remained the same after 12 h (entry 3).
sized on a multigram scale by the reaction of inexpen- Reaction with ligands L2 and L3 provided the cou-
sive and readily available benzotriazole and 2-bromo- pling product 3a in 50 and 58% yields, respectively,
pyridine under copper catalysis in 96% yield.[21,23,24b] It after 12 h (entries 4 and 5). Fortunately, when ligand
is essential to note that the ligand is air stable and L4 was used, it afforded the desired coupling product
thermally stable up to 274.78C.[36,25]
3a in 93% yield (entry 6). With a selective ligand in
hand, other parameters like time, base and solvent
were investigated.
The progress of the reaction was monitored at dif-
ferent time intervals at room temperature. After 1 h,
coupling product 3a was obtained in 75% yield
(entry 7), and similarly we observed that the reaction
was completed after 2 h (entry 8). Decreasing the cat-
alyst loading from 5 to 2 mol% and then to 1 mol%,
did not affect the yield of the coupling product 3a
(entries 9 and 10). However, further decreasing the
catalyst loading from 1 mol% to 0.8 and then
0.5 mol%, afforded the coupling product in 63 and
52% yields, respectively (entries 11 and 12). Decreas-
Scheme 1. Ligands L1–L4, designed for various palladium-
catalyzed coupling reactions.
Scheme 2. The applications of ligand L4 in various coupling reactions.
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2-(1-Benzotriazolyl)pyridine: A Robust Bidentate Ligand
Table 1. Optimization of the reaction conditions for the
by utilizing variety of aryl halides 1a–h and boronic
acids 2a–k (Table 2). The reaction tolerates various
functional groups attached at different positions of
the boronic acids 2a–k that could be useful for later
modifications (Table 2, entries 1–14). The reaction of
5-bromoindole 1b with boronic acids 2b and 2c af-
forded the coupling products 3b and 3c in 71 and
73% yields, respectively (entries 2 and 3). Reactions
with a less hindered substituent on the boronic acid
afforded the coupling products 3d–f in higher yields
(entries 4–6). Coupling of aryl halide 1c with 4-vinyl-
phenylboronic acid (2f), afforded the product 3g che-
moselectively in 92% yield, no Heck coupling product
was observed in this reaction (entry 7). Reaction of
1,4-dibromo-2,5-diiodobenzene (1d) with p-tolylbor-
onic acid (2g) provided the coupling products 3h se-
lectively in 83% yield (entry 8). It was observed that
the reaction of hindered 1,2,3,4-tetrabromothiophene
(1e) with 4.5 equiv. of 2h furnished the tetrasubstitut-
ed coupling product 3i in 80% yield (entry 9). The re-
action conditions were also found to be compatible
with sterically hindered heteroarenes with the core
nucleus present either in many alkaloids or having
a wide range of biological activities.[28] The 4-
Suzuki coupling.[a]
Entry Pd. cat. (mol%) L [mol%] Time [h] Yield [%][b]
1
2
3
4
5
6
7
8
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
N
L1 (6)
L1 (10)
L1 (10)
L2 (5)
L3 (5)
L4 (5)
L4 (5)
L4 (5)
L4 (2)
L4 (1)
02
02
12
12
12
12
01
02
02
02
02
02
02
02
02
02
02
02
02
02
02
06
8
42
42
50
58
93
75
93
93
93
63
52
9
10
11
12
13
14
15
16
17
18
19
20
21
22
Pd
N
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
L4 (1)
L4 (1)
L4 (1)
L4 (1)
L4 (1)
L4 (1)
L4 (1)
L4 (1)
L4 (2)
–
70[c]
78[d]
80[e]
79[f (])
73 g]
78 h]
85
60
93
05
iodopyrano
G
(1f)
and
4-(4-
bromophenyl)pyrroloAHCTUNTGRENNUNG
tion with boronic acids 2i, 2h and 2j provided the cor-
responding coupling products 3j–l in 79, 83 and 88%
yields, respectively (entries 10–12). Fortunately we
were pleased to see that one of the most influential
phase-II anticancer drugs, 9-bromonoscapine[29] 1h, on
coupling with boronic acids 2k and 2g afforded the
products 3m and 3n in 65 and 72% yields, respectively
(entries 13 and 14).
CHTUNGTRENNUNG
PdCl2 (1)
Pd
Pd
[a]
Unless otherwise specified, all reactions were performed
with 1a (1.0 mmol), 2a (1.2 equiv.), and base K2CO3
(2.0 equiv.) in solvent (2.0 mL).
Isolated yields.
Using 1.5 equiv. K2CO3.
Using 2.0 equiv. Na2CO3.
Using 2.0 equiv. Cs2CO3.
Using toluene:H2O (9:1).
Using DME:H2O (4:1).
Using DMSO: H2O (9:1).
[b]
[c]
[d]
[e]
[f]
The Heck reaction is another synthetically valuable
À
C C bond forming reaction used for the synthesis of
a wide variety of natural products and biologically
active compounds.[30] With the success of designed
ligand L4 in a wide variety of Suzuki coupling reac-
tion, we next optimized suitable conditions for the
Heck reaction.[25]
[g]
[h]
The coupling of 1.0 mmol of 4-bromoanisole (1i)
ing the amount of base from 2.0 to 1.5 equiv. afforded with 1.5 equiv. of n-butyl acrylate (4a), by using
the product 3a in lower yield (entry 13). Other bases 3 mol% Pd(OAc)2, 3 mol% ligand L4, and 2.0 equiv.
AHCTUNGTRENNUNG
like Na2CO3 and Cs2CO3 were found to be inferior of K2CO3 in 2.0 mL of DMF at 1208C for 10 h, afford-
for the reaction (entries 14 and 15). Amongst the dif- ed the desired product 5a in 94% yield (Table 3,
ferent solvent systems, DMF/H2O (4:1) was found to entry 1). To establish the scope of the ligand, various
be most efficient (entries 10, 16–18). Other palladium olefins and substituted aryl halides were used. Reac-
sources like PdCl2, Pd2ACHTNUGRTENUNG(dba)3 were found to be less ef- tions of acrylates 4a, 4c, 4d, acrylonitrile 4f, styrene
fective (entries 19 and 20). On changing the catalyst 4b and alkenes 4e, 4g with a variety of aryl halides af-
system by increasing the ligand from 1 mol% to forded the corresponding coupling products 5a–j in
2 mol%, the yield of the product remained the same good to excellent yields (entries 1–10). Aryl halide 1j
(entry 21). In the control experiment, a trace amount provided the coupling product 5b in 90% yield
of coupling product was obtained in the absence of (entry 2). The ortho-substituted aryl halide 1k provid-
ligand (entry 22).
Under the optimized conditions (Table 1, entry 10), reaction conditions were also found to be compatible
we examined the scope and generality of the reaction with base sensitive, 4-iodopyrano[4,3-b]quinoline 1l,
ed the desired product 5c in 82% yield (entry 3). The
AHCTUNGTRENNUNG
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Akhilesh K. Verma et al.
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Table 2. Suzuki-coupling of aryl/heteroaryl halides with boronic acids using ligand L4.[a]
Entry
1
ArX
Boronic acid
Product
Yield [%][b]
93/83[c]
2
71[d]
3
4
5
1b
1a
73[d]
89
2d
91/86[c]
6
7
1a
1c
90
92
8
83[e]
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2-(1-Benzotriazolyl)pyridine: A Robust Bidentate Ligand
Table 2. (Continued)
Entry
9
ArX
Boronic acid
Product
Yield [%][b]
80[e]
10
79[d]
11
2h
83[d]
12
1g
88[d]
13
65[f]
14
1h
2g
72[f]
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Akhilesh K. Verma et al.
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[a]
Unless otherwise specified, all reactions were performed with aryl halide 1 (1.0 mmol), boronic acids 2 (1.2 equiv.),
Pd(OAc)2 (1.0 mol%), L4 (1 mol%), and K2CO3 (2.0 equiv.) in DMF/H2O at 258C for 2–4 h.
Isolated yields.
ACHTUNGTRENNUNG
[b]
[c]
[d]
[e]
[f]
Using 5 mol% of Pd
At 258C for 6 h.
ACHTNUGTNERN(UNG OAc)2, 10 mol% of L1, and 2 equiv. K2CO3 in DMF/water (4:1) at 808C for 2 h.
Using 2.2 equiv. of 2g and 4.5 equiv. of 2h for 6 h.
Using 5 mol% of Pd(OAc)2, 5 mol% of L4, and 2 equiv. Cs2CO3 in DME/water (1:1) at 808C for 6 h.
AHCTUNGTRENNUNG
Table 3. Heck reaction aryl/heteroaryl halides with alkenes/acrylates using ligand L4.[a]
Entry
1
ArX
Alkene
Product
Yield [%][b]
94
2
3
4a
90
82
4
5
77
1g
1g
85[c]
6
7
4c
4a
84[c]
91
8
9
1a
1i
68[d]
89
10
1a
76
[a]
Unless otherwise specified, all reactions were performed with aryl halide 1 (1.0 mmol), olefin 4 (1.5 equiv.), Pd
(3.0 mol%), L4 (3.0 mol%), K2CO3 (2.0 equiv.) in 3.0 mL of DMF at 1208C for 8–10 h.
Isolated yields.
ACHTUNGTRENNUNG(OAc)2
[b]
[c]
[d]
Using 5 mol% Pd
ACHTUGNTERN(NUNG OAc)2, 5 mol% ligand L4, and 2 equiv. of K3PO4.
Using 3 equiv. of KF.
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2-(1-Benzotriazolyl)pyridine: A Robust Bidentate Ligand
Table 4. Fujiwara–Moritani reaction of indoles with alkene/
acrylates using ligand L4.[a]
and furnished the coupling product 5d in 77% yield
(entry 4). Quinoxaline derivative 1g on reaction with
acrylates 4d and 4c using K3PO4 afforded the corre-
sponding coupling product 5e and 5f in 85% and 84%
yields, respectively (entries 5 and 6). Reaction of aryl
halide 1m bearing an electron-withdrawing keto
group with acrylate 4a, afforded the alkenylated prod-
uct 5g in 91% yield (entry 7). Coupling of 1a with 2-
cyclopenten-1-one (4e) was also found to be compati-
ble, and afforded the desired product 5h in 68% yield
(entry 8). The reaction of 1i with acrylonitrile (4f) af-
forded the desired product 5i in 89% yield (entry 9).
Interestingly, coupling of aryl halide 1a with 4,5-dihy-
dro-1,3-dioxepine (4g) provided the desired coupling
product 5j in 76% yield (entry 10).
Entry Indole
Alkene Product
Yield
[%][b]
1
4a
80
70
2
3
4
5
1b
4c
4a
4a
The efficacy of ligand L4 was further extended for
the oxidative-Heck (Fujiwara–Moritani)[25,31] coupling
reaction between indoles and alkenes. Reaction of
substituted indoles (6a, 6b and 1b) with 1.5 equiv. of
76
72
alkene 4a, 4b, 4c, using 2 mol% Pd
ACHTUNGRTEN(NUNG OAc)2, 2 mol% of
ligand L4, and 2.0 equiv. Cu(OAc)2 as oxidant in
AHCTUNGTRENNUNG
2.0 mL of DMF:DMSO (4:1) at 1208C for 12 h af-
forded the alkenylated products 7a–f regioselectively
at the 3-position of the indole in 70–80% yields
(Table 4, entries 1–6). It is interesting to note that the
reaction of 5-bromoindole (1b) with alkene 4c afford-
ed the Fujiwara–Moritani coupling product 7b regio-
selectively at the 3-position of the indole in 70%
yield, no Heck coupling product was observed at the
5-position of indole (entry 2).
During the last decade, the Sonogashira reaction
has become one of the most widely used methods for
the incorporation of an alkyne functionality into or-
ganic compounds.[32] A wide variety of natural prod-
ucts, pharmaceuticals, agriculture chemicals, organic
materials was synthesized by using the Sonogashira
coupling reaction. After attaining successful results in
Suzuki, Heck and Fujiwara–Moritani coupling reac-
tions, we next checked the efficacy and versatility of
the ligand L4 in the Sonogashira coupling reaction.[4b]
The coupling of aryl bromide 1i with alkyne 8a was
used as a test reaction. After exploring a wide range
1b
6b
6a
4b
4b
77
75
6
[a]
All the reactions were performed using an N-heterocycle
(1.0 mmol) and olefin (1.5 equiv.), Pd(OAc)2
(2 mol%), Cu(OAc)2 (2 equiv.) and L4 (2 mol%) in
6
4
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
2.0 mL of DMF:DMSO (4:1) at 1208C for 12 h.
Isolated yield.
[b]
of conditions,[25] we found that coupling product 9a metal-catalyzed tandem reactions[23a,b] and Bergman
was obtained in 90% yield using 2 mol% Pd
(OAc)2, cyclizations.[33]
2 mol% L4, and 2 equiv. K2CO3 in 2 mL of DMF at
AHCTUNGTRENNUNG
The obtained successful results in various palladi-
À
1008C for 1 h without any homocoupling of the um-catalyzed C C coupling reactions (Suzuki, Heck,
alkyne (Table 5, entry 1). Reactions proceeded well Fujiwara–Moritani and Sonogashira), encouraged us
with ortho-substituted halide 1k (entry 2). Alkyne 8c to expand the applicability of the ligand L4 for other
[23c,d,34]
[23e,34]
À
À
bearing an electron-rich thiophene ring, proved fa- important class of C N
and C S
coupling
vourable for the reaction (entries 3 and 4). 1,4-Dibro- reactions. Coupling of N-heterocycle 6a with aryl hal-
mo-2,5-diiodobenzene 1d, and 2,3,4,5-tetrabromothio- ides 1k and 1n under optimized reaction conditions[25]
phene 1e afforded the coupling products 9e and 9f se- provided the desired cross-coupling products 10a and
lectively in 73% and 80% yields (entries 5 and 6). 10b in 78 and 67% yields, respectively (Table 6, en-
Thiophene halide 1e, on coupling with 8c, afforded tries 1 and 2). Electron-rich 3-methylindole (6c), 2-
the tetra-alkynylated coupling product 9g in 60% methylindole (6d) and pyrrole (6e) on reaction with
yields (entry 7). Compounds 9e, 9f and 9g are useful halides 1a, 1p and 1i afforded the N-arylated products
synthetic intermediate and can be further used for 10c–f in 73–77% yields (entries 3–6). Reaction of 4-
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Akhilesh K. Verma et al.
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Table 5. Sonogashira coupling using ligand L4.[a]
Entry
ArX
Alkyne
Product
Yield [%][b]
90
1
1i
2
3
1k
77
81
4
8c
75
5
6
1d
1e
73[c]
8d
8c
80[c]
7
1e
60[d]
[a]
Unless otherwise specified, all reactions were carried out using aryl halide 1 (1.0 mmol), alkyne 8 (1.2 equiv.), Pd
(2.0 mol%), L4 (2.0 mol%), K2CO3 (2.0 equiv.) in DMF (2.0 mL) at 1008C for 1–2 h.
Isolated yield.
ACHTUNGTRENNUNG(OAc)2
[b]
[c]
[d]
Using alkyne (2 equiv.), K2CO3 (4 equiv.), Pd
ACHTUNGRTEN(NUNG OAc)2 (2 mol%), and L4 (2 mol%).
Using 8c (4 equiv.), K2CO3 (8 equiv.), Pd(OAc)2 (5 mol%), and L4 (5 mol%).
AHCTUNGTRENNUNG
methoxyaniline (6f) afforded the coupling product in and 1r with an ortho-substituted electron-donating
53% yield using 10 mol% L4 and 10 mol% PdACTHUNGTRENNNUG
(entry 7).
We next investigated the application of ligand L4 in mothiophene 1e provided the tetra-S-arylated and
the coupling of aryl thiols with aryl bromides. The highly crowded product 2,3,4,5-[tetrakis(4-methoxy-
coupling of aryl bromide 1i with thiophenol 11a was phenyl)thio]thiophene 12d in 83% yield (entry 4).
used as a test reaction. After screening a wide range Aryl halide 1k on reaction with 2-methylbenzenethiol
of conditions,[25] we found that coupling product 12a (11d) afforded the product 12e in 87% yield (entry 5).
was obtained in 94% yield using 1 mol% PdACHTNUTRGNE(NUG OAc)2, Coupling of octanethiol (11e) with electron-rich aryl
1 mol% L4, 1.4 equiv. KO-t-Bu in 2.0 mL of DMSO halide 1i provided the desired couple product 12f in
at 1008C for 12 h (Table 7, entry 1). Aryl halides 1q 67% yield (entry 6).
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2-(1-Benzotriazolyl)pyridine: A Robust Bidentate Ligand
Table 6. N-Arylation of indoles, pyrrole and aniline with aryl halides using ligand L4.[a]
Entry
N-Heterocycle
ArX
Product
Yield [%][b]
1
1k
78
2
6a
1n
1a
67
3
4
77
74
6c
5
6
1i
73
74
1p
7
1i
53[c]
[a]
All the reactions were performed with an N-heterocycle 6 (1.0 mmol), aryl or heteroaryl halide 1 (1.2 equiv.), Pd
(5.0 mol%), L4 (5.0 mol%), and KO-t-Bu (2.0 equiv.), in DMSO (2.0 mL) at 1208C for 24 h.
Isolated yields.
ACHTUNGTRENNUNG(OAc)2
[b]
[c]
Using PdACHTUNGTRENNUNG(OAc)2 (10.0 mol%), L4 (10.0 mol%).
Conclusions
cles as well as in material science. Furthermore, stud-
ies on the practical applications of such cross-coupling
In conclusion, we have designed an affordable and reactions are in progress within the group.
robust N,N-type bidentate ligand 1-(pyridine-2-yl)-
1H-benzo[d]ACHTUNGTRENNUNG[1,2,3]triazole (L4) for the palladium-cat-
alyzed coupling reactions. Developed ligand L4 effi-
ciently catalyzed the C C (Suzuki, Heck, Fujiwara–
Experimental Section
À
À
À
Moritani, and Sonogashira), C N and C S coupling
reaction. Noteworthy is the efficacy of ligand L4 to
tolerate a variety of functional groups attached to re-
actants as well as simplicity, low cost and ready acces-
sibility of ligand on a multigram scale. This ligand is
expected to find applications in organic synthesis in
General Methods
All the reactions were performed in oven-dried Schlenks
flask under an argon atmosphere. Column chromatography
was performed using silica gel (100–200 mesh). Thin layer
chromatography (TLC) was performed on silica gel GF254
1
plates. H and 13C NMR spectra were recorded at 300 and
general and in the synthesis of a variety of heterocy- 75 MHz or 400 and 100 MHz, respectively. Thin-layer chro-
Adv. Synth. Catal. 2013, 355, 421 – 438
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asc.wiley-vch.de
429

Akhilesh K. Verma et al.
FULL PAPERS
Table 7. S-Arylation of thiols with aryl halides using ligand L4.[a]
Entry
ArX
Thiol
Product
Yield [%][b]
94
1
1i
2
3
93
11a
92[c]
4
1e
83[d]
5
1k
1i
87
67
6
[a]
Unless otherwise specified, all reactions were performed using arenethiol 11 (1.2 equiv.), aryl halide 1 (1.0 mmol), KO-t-
Bu (1.4 equiv.), Pd(OAc)2 (1.0 mol%) and L4 (1.0 mol%) in DMSO (1.0 mL) at 1008C for 8–12 h.
Isolated yields.[c] At 808C.
AHCTUNGTRENNUNG
[b]
[d]
Using thiol 11c (4.0 equiv.), KO-t-Bu (5.0 equiv.), PdACTHNUTRGENNG(U OAc)2 (2.0 mol%) and L4 (2.0 mol%) in DMSO (4.0 mL) at 1008C
matography was performed using commercially prepared 60
F254 silica gel plates and visualization was effected with short
wavelength UV light (254 nm) and staining over an I2 cham-
ber. All melting points are uncorrected. High resolution
mass spectra were recorded on a double focusing magnetic
sector mass spectrometer.
raphy (hexane/ethyl acetate) to afford the desired product
in excellent yields.
4-(4-Bromophenyl)pyrroloACHTNUGRTNEUNG
[1,2-a]quinoxaline (1g):[37] The
product was obtained as white needles (DCM/ether); yield:
308.9 mg (96%); mp 104–1068C; 1H NMR (400 MHz,
CDCl3): d=8.00–7.90 (m, 2H), 7.90–7.80 (m, 3H), 7.70–7.60
(m, 2H), 7.50 (td, J=8.7 and 1.5 Hz, 1H), 7.50 (td, J=8.0
and 1.4 Hz, 1H), 6.94 (t, J=3.0 Hz, 1H), 6.93 (t, J=2.9 Hz,
1H); 13C (100 MHz, CDCl3): d=153.0, 137.2, 136.0, 131.7,
130.2, 127.7, 127.0, 125.3, 124.9, 124.1, 114.8, 114.1, 113.6,
108.5; IR (KBr): n=3139, 3110, 3079, 3043, 2919, 1612,
Procedure for the Synthesis of Pyrroloquinoxalines
(1g)
1587, 1531, 1473, 1420, 1391, 1369, 1097, 823, 749, 710 cmÀ1
;
To
a well-stirred solution of 4-bromobenzaldehyde 5
HR-MS (ESI): m/z=322.0106, calcd. for C17H11BrN2 (M+
(1.2 equiv.), benzotriazole (1.0 equiv.) and 10 mol% AlCl3 in
THF, 1-(2-aminophenyl)pyrrole (1.0 mmol) was added. The
reaction mixture was stirred at room temperature for 8–
10 h. After the completion of the reaction, the mixture was
extracted with ethyl acetate and water. The organic phases
were washed with NaOH brine and dried with Na2SO4. The
solvent was evaporated under vacuum and the obtained
crude reaction mixture was purified by column chromatog-
H+): 322.0106.
Procedure for the Synthesis of Ligand (BtCH2Bt) L3
A
flask was charged with CuI (10 mol%), BtCH2Cl
(1.0 mmol) and benzotriazole (1.0 equiv.) in DMF (5 mL).
The reaction mixture was then heated at 1008C in the pres-
430
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Adv. Synth. Catal. 2013, 355, 421 – 438

2-(1-Benzotriazolyl)pyridine: A Robust Bidentate Ligand
ence of base K2CO3 (2.0 equiv.) for 5–6 h. After the comple-
tion of reaction, reaction mixture was allowed to come to
room temperature. To the reaction mixture was added ethyl
acetate, and the resulting suspension was filtered. The fil-
trate was concentrated, and the residue was purified by
column chromatography on silica gel to provide the desired
product.
(s, 2H), 7.54–7.44 (m, 4H), 7.25–7.22 (m, 2H), 6.61 (s, 2H);
13C NMR (75 MHz, CDCl3): d=134.9, 134.8, 128.4, 124.6,
122.5, 119.3, 111.0, 102.9; HR-MS (ESI): m/z=232.1001,
calcd. for C16H12N2 (M+H+): 232.1000.
4-(1H-Indol-5-yl)-N,N-dimethylaniline (3c):[41] The prod-
uct was obtained as white needles (DCM/ether); yield:
172.2 mg (73%); mp 134–1368C; 1H NMR (300 MHz,
CDCl3): d=8.07 (brs, 1H), 7.80 (s, 1H), 7.54 (d, J=8.7 Hz,
2H), 7.41 (dd, J=8.7 and 2.7 Hz, 2H), 7.23–7.17 (m, 1H),
6.82 (d, J=8.7 Hz, 2H), 6.57 (s, 1H), 2.98 (s, 6H); 13C NMR
(75 MHz, CDCl3): d=149.5, 134.8, 133.6, 131.1, 128.4, 127.9,
124.6, 121.6, 118.3, 113.1, 111.1, 102.9, 40.8; IR (KBr): n=
3003, 2955, 2899, 2834, 1606, 1511, 1495, 1242, 1175, 1029,
832 cmÀ1; HR-MS: m/z=236.1316, calcd. for C16H16N2 (M+
H+): 236.1313.
DiACHTUNGTRENNUNG(1H-benzo[d]ACHTUNGTRENNUNG
[1,2,3]triazol-1-yl)methane (L3):[38] The
product was obtained as white needles (DCM/ether); yield:
0.225 g (90%); mp 78–808C; 1H NMR (300 MHz, CDCl3):
d=8.06 (d, J=8.4 Hz, 1H), 7.95 (d, J=8.4 Hz, 1H), 7.87–
7.83 (m, 2H), 7.56 (dt, J=6.3 and 0.9 Hz, 1H), 7.42–7.36 (m,
5H); 13C NMR (75 MHz, CDCl3): d=146.3, 145.0, 132.6,
128.6, 127.5, 124.6, 120.2, 118.5, 109.9, 64.8; HR-MS (ESI):
m/z=250.0965, calcd. for C13H10N6 (M+H+): 250.0967.
2-(4-Methylphenyl)-biphenyl (3d):[39] The product was ob-
1
Procedure for the Synthesis of Ligand (BtPy) L4[24b]
tained as a colourless oil; yield: 217.3 mg (89%): H NMR
(300 MHz, CDCl3): d=7.33–7.25 (m, 4H), 7.23–7.18 (m,
1H), 7.13–7.07 (m, 4H), 6.95–6.89 (m, 3H), 6.54 (d, J=
7.2 Hz, 1H), 2.29 (s, 3H); 13C NMR (75 MHz, CDCl3): d=
141.7, 140.5, 138.5, 137.1, 131.7, 130.6, 129.8, 129.7, 128.6,
127.8, 127.4, 127.2, 127.0, 126.4, 21.1; HR-MS (ESI): m/z=
244.1252, calcd. for C19H16 (M+H+): 244.1252.
To a solution of DMSO (3.0 mL), CuI (5.0 mol%), KO-t-Bu
(1.4 equiv.), benzotriazole (1.0 mmol) and 1.1 equiv. of 2-
bromopyridine was added. The reaction mixture was al-
lowed to stirred at 1208C for 12 h. After the completion, of
reaction, the resulting solution was filtered, and the reaction
mixture was extracted with ethyl acetate and water. The or-
ganic layer was evaporated under reduced pressure. The
crude reaction mixture was purified by column chromatog-
raphy using ethyl acetate/hexane as the eluent.
2-(3-Nitrophenyl)-biphenyl (3e):[39] The product was ob-
tained as white needles (DCM/ether); yield: 249.1 mg
1
(91%); mp: 60–628C: H NMR (300 MHz, CDCl3): d=8.00–
7.96 (m, 2H), 7.39 (s, 4H), 7.32–7.22 (m, 2H), 7.14 (s, 3H),
7.04–7.03 (m, 2H); 13C NMR (75 MHz, CDCl3) d=148.1,
143.3, 141.0, 140.5, 138.0, 136.1, 130.8, 130.3, 129.9, 128.7,
128.6, 128.2, 127.9, 127.0, 124.6, 121.5; IR (KBr): n=2960,
2923, 2851, 1532, 1466, 1453, 1437, 1347, 1085, 875, 766, 748,
1-(Pyridine-2-yl)-1H-benzo[d]ACHTUNGTRNEUNG
[1,2,3]triazole (L4):[24b] The
product was obtained as white needles (DCM/ether); yield:
1
0.182 g (96%); mp 109–1118C; H NMR (300 MHz, CDCl3):
d=8.67–8.61 (m, 2H), 8.30 (d, J=8.4 Hz, 1H), 8.13(d,
J=8.1 Hz, 1H), 7.94 (td, J=7.5 and 8.1 Hz, 1H), 7.61 (td,
J=7.5 and 7.8 Hz, 1H), 7.46 (td, J=7.8 and 7.5 Hz, 1H),
7.47–7.27 (m, 1H); 13C NMR (75 MHz, CDCl3): d=151.6,
148.3, 146.7, 138.8, 131.5, 128.7, 124.9, 122.2, 119.7, 114.8,
114.4; IR (KBr): n=3112, 3065, 1595, 1475, 1287, 1073,
1061, 784, 752, 735 cmÀ1; HR-MS (ESI): m/z=196.0750,
calcd. for C11H8N4 (M+H+): 196.0749.
701 cmÀ1
;
HR-MS (ESI): m/z=275.0945, calcd. for
C18H13NO2 (M+H+): 275.0946.
4’-(4-Flurobenzyloxy)-4-methylbiphenyl (3f):[39] The prod-
uct was obtained as white needles (DCM/ether); yield:
262.9 mg (90%); mp 100–1058C; 1H NMR (300 MHz,
CDCl3): d=7.44–7.31 (m, 6H), 7.15 (d, J=7.8, 2H), 7.02–
6.91 (m, 4H), 4.96 (s, 2H), 2.29 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=164.1, 160.9, 157.9, 137.8, 136.4, 134.1, 132.7,
129.4, 129.3, 129.2, 127.9, 126.6, 115.6, 115.3, 115.0, 69.4,
21.0; IR (KBr): n=2916, 2863, 1497, 1236, 806 cmÀ1; HR-
MS (ESI): m/z=292.1263, calcd. for C20H17FO (M+H+):
292.1263.
General Procedure for the Suzuki Reaction (3a–n)
To
a mixture of DMF/water (4:1; 2 mL), PdACTHNUTGENRUGN(OAc)2
(1.0 mol%), ligand L4 (1.0 mol%) were added aryl halide
(0.5 mmol), arylboronic acid (1.2 equiv.) and K2CO3
(2.0 equiv.). The reaction mixture was then flushed with ni-
trogen and stirred at room temperature until the aryl halide
was consumed, as determined by TLC. The reaction mixture
was extracted with ethyl acetate and water. Organic layer
was evaporated under reduced pressure. The crude reaction
mixture was purified using silica gel column chromatography
using ethyl acetate/hexane as the eluent.
3-Nitro-4’-vinylbiphenyl (3g):[39] The product was obtained
as white needles (DCM/ether); yield: 206.1 mg (92%); mp
1
68–708C; H NMR (300 MHz, CDCl3): d=8.36 (s, 1H), 8.11
(d, J=7.2 Hz, 1H), 7.84 (d, J=7.1 Hz, 1H), 7.54–7.37 (m,
5H), 6.73 (q, J=10.8 Hz, 1H), 5.78 (d, J=17.7 Hz, 1H),
5.26 (d, J=10.8 Hz, 1H); 13C NMR (75 MHz, CDCl3): d=
148.7, 142.3, 137.8, 136.3, 135.9, 132.7, 129.7, 127.2, 126.9,
126.6, 121.9, 121.6, 114.8; IR (KBr): n=3082, 2960, 2925,
2851, 1668, 1625, 1527, 1511, 1344, 902, 843.1, 805.9,
2,4,6-Trimethoxy-4’-methylbiphenyl (3a):[39] The product
was obtained as a white needles (DCM/ether); yield:
730.4 cmÀ1
;
HR-MS (ESI): m/z=225.0790, calcd. for
1
240.0 mg (93%), mp 48–508C; H NMR (300 MHz, CDCl3):
C14H11NO2 (M+H+): 225.0790.
d=7.45 (d, J=7.8 Hz, 2H), 7.23 (d, J=7.8 Hz, 2H), 6.76 (s,
2H), 3.91 (s, 6H), 3.88 (s, 3H), 2.39 (s, 3H); 13C NMR
(75 MHz, CDCl3): d=153.5, 138.5, 137.4, 137.2, 137.1, 129.5,
126.9, 104.2, 60.9, 56.2, 21.1; IR (KBr): n=2933, 2834, 1588,
1500, 1458, 1420, 1237, 1131, 809, 767 cmÀ1; HR-MS (ESI):
m/z=258.1259, calcd. for C16H18O3 (M+H+): 258.1256.
1H,1’H-5,5’-Biindole (3b):[40] The product was obtained as
white needles (DCM/ether); yield: 116.9 mg (71%); mp 80–
2’,5’-Dibromo-4,4’’-dimethyl-1,1’:4’,1’’-terphenyl (3h): The
product was obtained as white needles (DCM/ether); yield:
343.1 mg (83%); mp 162–1648C; 1H NMR (400 MHz,
CDCl3): d=7.60 (s, 2H), 7.32 (d, J=8.0 Hz, 4H), 7.24 (d,
J=6.4 Hz, 4H), 2.4 (s, 6H); 13C NMR (100 MHz, CDCl3):
d=142.6, 137.9, 136.6, 135.2, 129.1, 128.8, 121.4, 21.3; HR-
MS (ESI): m/z=413.9621, calcd. for C20H16Br2 (M+H+):
413.9619.
1
858C; H NMR (300 MHz, CDCl3): d=8.13 (brs, 2H), 7.89
Adv. Synth. Catal. 2013, 355, 421 – 438
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Akhilesh K. Verma et al.
FULL PAPERS
2,3,4,5-Tetrakis(4-methoxyphenyl)thiophene (3i):[42] The
product was obtained as yellow needles (DCM/ether); yield:
406.4 mg (80%); mp 178–1808C; 1H NMR (400 MHz,
CDCl3): d=7.13(d, J=8.8 Hz, 4H), 6.84 (d, J=8.8 Hz, 4H),
6.74 (d, J=8.8 Hz, 4H), 6.65 (d, J=8.8 Hz, 4H), 3.75 (s,
6H), 3.72 (s, 6H); 13C NMR (100 MHz, CDCl3): d=158.6,
158.0, 138.3, 137.2, 131.9, 130.3, 129.1, 127.0, 113.7, 113.3,
55.2, 55.0; HR-MS (ESI): m/z=508.1705, calcd. for
C32H28O4S (M+H+): 508.1708.
1(3H)-one (3n):[44] The product was obtained as white nee-
dles (DCM/ether); yield: 361.5 mg (72%); mp 210–2128C;
1H NMR (300 MHz, CDCl3): d=7.26–7.22 (m, 2H), 7.13 (d,
J=7.8 Hz, 2H), 7.09 (d, J=8.1 Hz, 1H), 6.12 (d, J=8.1 Hz,
1H), 5.97 (s, 1H), 5.91 (s, 1H), 5.56 (d, J=4.2 Hz, 1H), 4.50
(d, J=4.2 Hz, 1H), 4.11 (d, J=5.4 Hz, 6H), 3.90 (s, 3H),
2.56 (s, 3H), 2.38 (s, 3H), 2.27–2.18 (m, 1H), 2.14–2.13 (m,
2H), 1.69–1.62 (m 1H); 13C NMR (75 MHz, CDCl3): d=
168.1, 152.3, 147.6, 146.0, 140.9, 139.5, 137.3, 133.7, 131.1,
130.9, 130.0, 129.8, 129.0, 120.6, 117.9, 117.8, 117.7, 116.5,
115.1, 100.8, 82.1, 62.4, 61.1, 59.6, 50.9, 46.8, 27.1, 21.3; IR
(KBr): n=2936, 2903, 2853, 2806, 1758, 1497, 1467, 1458,
4-(4-Ethylphenyl)-1-methoxy-3-phenyl-1H-pyranoACHTUNTRGNEUNG[4,3-
b]quinoline (3j):[43] The product was obtained as orange nee-
dles (DCM/ether); yield: 310.0 mg (79%); mp 92–948C;
1H NMR (300 MHz, CDCl3): d=8.05 (s, 1H), 7.97 (d, J=
8.4 Hz, 1H), 7.77 (d, J=8.1 Hz, 1H), 7.60 (td, J=6.9 and
1.2 Hz, 1H), 7.42 (t, J=8.1 Hz, 1H), 7.35–7.31 (m, 4H),
7.23–7.13 (m, 5H), 6.29 (s, 1H), 3.74 (s, 3H), 2.67 (q, J=
7.5 Hz, 2H), 1.26 (t, J=7.8 Hz, 3H); 13C NMR (75 MHz,
CDCl3): d=153.2, 150.0, 148.8, 143.7, 135.5, 132.7, 132.3,
132.2, 129.9, 129.5, 128.7, 128.4, 128.0, 127.6, 127.3, 126.8,
126.4, 125.7, 122.6, 117.5, 100.0, 56.1, 28.6, 15.4; HR-MS
(ESI): m/z=393.1729, calcd. for C27H23NO2 (M+H+):
393.1729.
1438, 1422, 1377, 1270, 1084, 1056, 1032, 1010, 819, 715 cmÀ1
;
HR-MS (ESI): m/z=503.1942, calcd. for C29H29NO7 (M+
H+): 503.1944.
General Procedure for the Heck Reaction (5a–j)
A mixture of aryl halide (1.0 mmol), PdACTHNUTRGENUG(N OAc)2 (3.0 mol%),
L4 (3.0 mol%) and K2CO3 (2.0 equiv.) in 3.0 mL of DMF
was flushed with nitrogen with the addition of alkene
(1.5 equiv.) and the reaction mixture was stirred at 1208C
with the progress of reaction being monitored by TLC.
After completion of the reaction, the mixture was diluted
with ethyl acetate and water. The organic layer was washed
with brine, dried over Na2SO4, and concentrated under re-
duced pressure. The residue was purified by silica gel chro-
matography using ethyl acetate/hexane as eluent.
4-(4’-Methoxybiphenyl-4-yl)pyrroloACTHNUTRGNEUNG[1,2-a]quinoxaline
(3k):[37] The product was obtained as white needles (DCM/
ether); yield: 290.6 mg (83%); mp 187–1908C; 1H NMR
(300 MHz, CDCl3): d=8.06 (d, J=7.5 Hz, 4H), 7.90 (d, J=
8.1 Hz, 1H), 7.73 (d, J=7.8 Hz, 2H), 7.60 (d, J=8.4 Hz,
2H), 7.50–7.40 (m, 2H), 7.07–7.01 (m, 3H), 6.90 (s, 1H),
3.90 (s, 3H); 13C NMR (75 MHz, CDCl3): d=159.3, 154.0,
142.2, 136.7, 136.2, 133.0, 130.1, 129.0, 128.2, 127.0, 126.8,
125.3, 125.2, 114.6, 114.3, 114.0, 113.6, 108.6, 55.3; HR-MS
(ESI): m/z=350.1418, calcd. for C24H18N2O (M+H+):
350.1419.
(E)-Butyl 3-(4-methoxyphenyl)acrylate (5a):[45] The prod-
uct was obtained as a viscous colourless oil; yield: 219.9 mg
1
(94%); H NMR (300 MHz, CDCl3): d=7.64 (d, J=15.9 Hz,
1H), 7.46 (d, J=8.7 Hz, 2H), 6.90 (d, J=8.7 Hz, 2H), 6.32
(d, J=15.9, Hz, 1H), 4.19 (t, J=6.9 Hz, 2H), 3.82 (s, 3H),
1.73–1.64 (m, 2H), 1.44 (q, J=7.5 Hz, 2H), 0.96 (t, J=
7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=167.4, 161.3,
144.2, 130.8, 127.2, 115.7, 113.3, 64.2, 55.3, 30.7, 19.2, 10.9;
HR-MS (ESI): m/z=234.1256, calcd. for C14H18O3 (M+H+):
234.1256.
4-[4’-(Methylthio)biphenyl-4-yl]pyrroloACTHNUTRGNE[NUG 1,2-a]quinoxaline
(3l):[37] The product was obtained as white needles (DCM/
ether); yield: 322.2 mg (88%); mp 173–1758C; 1H NMR
(400 MHz, CDCl3): d=8.10–8.00 (m, 3H), 7.99–7.98 (m,
1H), 7.88–7.86 (m, 1H), 7.73 (d, J=8.0 Hz, 2H), 7.60 (d, J=
8.0 Hz, 2H), 7.51–7.45 (m, 2H), 7.34 (d, J=8.8 Hz, 2H),
7.04 (m, 1H), 6.90 (t, J=3.3 Hz, 1H), 2.53 (s, 3H);
13C NMR (100 MHz, CDCl3): d=153.8, 141.8, 138.1, 137.2,
136.2, 130.2, 129.1, 127.4, 127.1, 127.0, 126.9, 126.8, 125.2,
114.6, 113.9, 113.6, 108.5, 15.7; IR (KBr): n=2919, 1458,
1475, 1423, 1369, 1318, 1098, 816, 761, 742, 721 cmÀ1; HR-
MS (ESI): m/z=366.1190, calcd. for C24H18N2S (M+H+):
366.1191.
(E)-Butyl 3-phenylacrylate (5b):[46] The product was ob-
1
tained as a colourless oil; yield: 182.5 mg (90%); H NMR
(300 MHz, CDCl3): d=7.61 (d, J=16.2 Hz, 1H), 7.45 (dd,
J=3.6 and 1.5 Hz, 2H), 7.39–7.30 (m, 3H), 6.34 (d, J=
15.9 Hz, 1H), 4.16 (t, J=6.9 Hz, 2H), 1.64–1.59 (m, 2H),
1.40–1.32 (m, 2H), 0.96 (t, J=7.2 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d=167.1, 144.5, 134.5, 130.4, 129.3, 128.8,
127.5, 118.2, 64.4, 31.6, 19.2, 13.7; HR-MS (ESI): m/z=
204.1150, calcd. for C13H16O2 (M+H+): 204.1150.
6,7-Dimethoxy-3-(4-methoxy-6-methyl-9-phenyl-5,6,7,8-
tetrahydroACHTUNGTRENNUNG[1,3]dioxoloACHTUNTGREN[NUGN 4,5-g]isoquinolin-5-yl)isobenzofuran-
(E)-1-Methoxy-2-styrylbenzene (5c):[47] The product was
obtained as a viscous colourless oil; yield: 171.3 mg (82%):
1H NMR (400 MHz, CDCl3): d=7.52 (d, J=8.0 Hz, 1H),
7.45 (t, J=8.1 Hz, 3H), 7.26 (t, J=7.3 Hz, 2H), 7.18–7.14
(m, 2H), 7.03 (d, J=16.1 Hz, 1H), 6.89 (t, J=7.4 Hz, 1H),
6.82 (d, J=8.0 Hz, 1H), 3.80 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=156.9, 137.9, 129.1, 128.6, 128.5, 127.3, 126.5,
123.4, 120.7, 110.9, 55.5; IR (KBr): n=2925, 1592, 1486,
1480, 1242, 1105, 1029, 964, 752, 689 cmÀ1; HR-MS (ESI): m/
z=210.1046, calcd. for C15H14O (M+H+): 210.1045.
1(3H)-one (3m): The product was obtained as white needles
(DCM/ether); yield: 317.2 mg (65%); mp 189–1918C;
1H NMR (300 MHz, CDCl3): d=7.37–7.24 (m, 3H), 7.18 (d,
J=6.9 Hz, 3H), 6.98 (d, J=8.1 Hz, 1H), 5.90 (s, 1H), 5.84
(s, 1H), 5.57 (s, 1H), 4.49 (s, 1H), 4.07–3.96 (m, 6H), 3.83
(s, 3H), 2.51 (s, 3H), 2.21–2.16 (m, 2H), 1.32–1.06 (m, 2H);
13C NMR (75 MHz, CDCl3): d=167.9, 152.4, 147.7, 146.2,
140.8, 139.6, 133.7, 129.9, 128.3, 127.5, 118.0, 117.9, 116.6,
100.9, 62.3, 61.3, 59.5, 56.9, 29.7; IR (KBr): n=2942, 2856,
2795, 1752, 1492, 1439, 1376, 1262, 1276, 1059, 1077, 1014,
1034, 706 cmÀ1; HR-MS (ESI): m/z=489.1785, calcd. for
C28H27NO7 (M+H+): 489.1788.
(E)-Methyl3-(1-methoxy-3-(p-tolyl)-1H-pyranoACTHNUTRGENUG[N 4,3-b]qui-
nolin-4-yl)acrylate (5d):[43] The product was obtained as
a pale yellow needles (DCM/ether); yield: 298.0 mg (77%);
1
6,7-Dimethoxy-3-(4-methoxy-6-methyl-9-p-tolyl-5,6,7,8-
mp 149–1508C; H NMR (300 MHz, CDCl3): d=8.24 (d, J=
tetrahydro
G
G
8.8 Hz, 1H), 8.19 (s, 1H), 7.82–7.79 (m, 3H), 7.73 (t, J=
432
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Adv. Synth. Catal. 2013, 355, 421 – 438

2-(1-Benzotriazolyl)pyridine: A Robust Bidentate Ligand
5.8 Hz, 1H), 7.54–7.51 (m, 3H), 7.28 (d, J=8.08 Hz, 2H),
6.21 (s, 1H), 3.77 (s, 3H), 3.74 (s, 3H), 2.41 (s, 3H);
13C NMR (75 MHz, CDCl3): d=169.0, 162.6, 148.9, 148.2,
141.1, 139.5, 132.9, 13o.8, 130.5, 130.2, 129.4, 129.2, 127.6,
126.5, 126.3, 122.7, 119.2, 110.9, 100.7, 56.7, 51.3, 21.5; HR-
MS (ESI): m/z=387.1471, calcd. for C24H21NO4 (M+H+):
387.1471.
(dd, J=2.2 and 7.3 Hz, 1H), 5.10 (d, J=7.3 Hz, 1H), 4.84
(dd, J=3.6 and 7.3 Hz, 1H), 4.75 (d, J=7.32 Hz, 1H), 3.90–
3.86 (m, 1H), 3.71–3.68 (m, 1H), 3.37- 3.32 (m, 1H), 2.25 (s,
3H); 13C NMR (100 MHz, CDCl3): d=145.9, 137.8, 136.6,
129.3, 127.8, 112.3, 98.1, 47.9, 21.0; HR-MS (ESI): m/z=
190.0995 calcd. for C12H14O2 (M+H+): 190.0994.
(E)-Ethyl 3-{4-(pyrrolo
ACHTUNGTRENN[UNG 1,2-a]quinoxalin-4 yl)phenyl}acry-
late (5e):[37]: The product was obtained as white needles
General Procedure for the Fujiwara–Moritani
(DCM/ether); yield: 290.8 mg (85%); mp 89–918C; Reaction (7a–f)
1H NMR (400 MHz, CDCl3): d=8.05–8.01 (m, 4H), 7.90 (d,
PdACTHNUTRGEN(UGN OAc)2 (2.0 mol%) and L4 (2.0 mol%) were added to
J=8.0 Hz, 1H), 7.80 (d, J=16.1 Hz, 1H), 7.70 (d, J=8.0 Hz,
2H), 7.50 (t, J=8.0 Hz, 1H), 7.49 (t, J=9.5 Hz, 1H), 7.01–
6.99 (m, 1H), 6.90 (t, J=3.0 Hz, 1H), 6.53 (d, J=16.1 Hz,
1H), 4.29 (q, J=8.0 Hz, 2H), 1.35 (t, J=7.3 Hz, 3H); 13C
(100 MHz, CDCl3): d=166.8, 153.3, 143.8, 140.0, 136.1,
135.7, 130.2, 129.1, 128.2, 127.7, 127.1, 125.3, 125.1, 119.1,
114.7, 114.1, 113.6, 108.4, 60.6, 14.3; IR (KBr): n=2926,
1718, 1627, 1437, 1370, 1320, 1172, 986, 831, 750, 742,
a mixture of the alkene (1.5 equiv.), copper(II) acetate
(2.0 equiv.) and the N-heterocycle (1.0 mmol) in
DMF:DMSO (4:1, 2.0 mL). The reaction mixture was then
flushed with nitrogen and heated at 1208C for 12 h. After
completion of the reaction, the mixture was cooled to room
temperature, then filtered and washed with saturated aque-
ous NaCl solution. The resultant solution was extracted with
ethyl acetate. The combined organic fractions were dried
over anhydrous Na2SO4 and concentrated under vacuum to
yield the crude product. The crude product was purified by
column chromatography (ethyl acetate/hexane).
712 cmÀ1
C22H18N2O2 (M+H+): 342.1368.
(E)-Methyl 3-{4-(pyrrolo[1,2-a]quinoxalin-4-yl)phenyl}-
;
HR-MS (ESI): m/z=342.1365, calcd. for
AHCTUNGTRENNUNG
acrylate (5f):[37] The product was obtained as pale yellow
needles (DCM/ether); yield: 275.6 mg (84%); 102–1048C;
1H NMR (300 MHz, CDCl3): d=8.04 (d, J=7.8 Hz, 4H),
7.90 (d, J=7.8 Hz, 1H), 7.80–7.70 (m, 3H), 7.50–7.40 (m,
2H), 7.03 (d, J=18.3 Hz, 2H), 6.50 (d, J=15.9 Hz, 1H),
3.80 (s, 3H); 13C (75 MHz, CDCl3): d=167.3, 153.3, 144.2,
140.2, 136.1, 135.7, 130.3, 129.2, 128.3, 127.8, 127.2, 125.4,
125.1, 119.7, 114.8, 114.1, 113.7, 108.5, 51.8; HR-MS (ESI):
m/z=328.1212, calcd. for C21H16N2O2 (M+H+): 328.1212.
(E)-Butyl 3-(4-acetylphenyl)acrylate (5g):[48] The product
was obtained as a colourless oil; yield: 222.8 mg (91%);
1H NMR (300 MHz, CDCl3): d=7.97 (d, J=8.3 Hz, 2H),
7.69 (d, J=16.1 Hz, 1H), 7.61 (d, J=8.3 Hz, 2H), 6.53 (d,
J=16.0 Hz, 1H), 4.23 (t, J=6.6 Hz, 2H), 1.73–1.65 (m, 2H),
2.61 (s, 3H), 1.48–1.41 (m, 2H), 0.97 (t, J=7.3 Hz, 3H);
13C NMR (75 MHz, CDCl3): d=197.1, 166.5, 142.9, 138.8,
138.0, 128.8, 128.1, 120.8, 64.6, 30.7, 26.6, 19.2, 13.7; HR-MS
(ESI): m/z=246.1253, calcd. for C15H18O3 (M+H+):
246.1256.
(E)-Butyl 3-(1H-indol-3-yl)acrylate (7a):[50] The product
was obtained as yellow needles (DCM/ether); yield:
1
194.4 mg (80%); mp 81–858C; H NMR (300 MHz, CDCl3):
d=8.60 (s, 1H), 7.87–7.82 (m, 2H), 7.40 (d, J=1.8, Hz, 1H),
7.33 (d, J=7.2 Hz, 1H), 7.22–7.15 (m, 2H), 6.40 (d, J=
15.9 Hz, 1H), 4.15 (t, J=6.6 Hz, 2H), 1.68–1.58 (m, 2H),
1.39 (q, J=7.5 Hz, 2H), 0.90 (t, J=7.5 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d=167.4, 161.3, 144.2, 130.8, 127.2, 115.7,
113.3, 64.2, 30.7, 19.2, 10.9; IR (KBr): n=3271, 2959, 2929,
2868, 1682, 1572, 1616, 1433, 1272, 1227, 1181, 1115, 1085,
970, 819, 724 cmÀ1; HR-MS (ESI): m/z=243.1259, calcd. for
C15H17NO2 (M+H+): 243.1259.
(E)-Methyl 3-(5-bromo-1H-indol-3-yl)acrylate (7b): The
product was obtained as white needles (DCM/ether); yield:
195.3 mg (70%); mp 128–1308C; 1H NMR (400 MHz,
CDCl3): d=8.67 (brs, 1H), 7.95–7.94 (m, 1H), 7.78 (d, J=
16.1 Hz, 1H), 7.40–7.39 (m, 1H), 7.30–7.27 (m, 1H), 7.19 (d,
J=5.9 Hz, 1H), 6.32 (d, J=16.1 Hz, 1H), 3.75 (s, 3H);
13C NMR (100 MHz, CDCl3): d=168.5, 137.7, 135.6, 129.5,
126.9, 126.2, 123.0, 114.8, 113.5, 113.1, 113.1, 51.5; HR-MS
(ESI): m/z=278.9895, calcd. for C12H10BrNO2 (M+H+):
278.9895.
3-p-Tolylcyclopent-2-enone (5h): The product was ob-
tained as white needles (DCM/ether); yield: 117.0 mg
(68%); mp 136–1388C; 1H NMR (300 MHz, CDCl3): d=
7.56 (d, J=8.1 Hz, 2H), 7.26 (d, J=7.8 Hz, 2H), 6.54 (s,
(E)-Butyl 3-(5-methoxy-1H-indol-3-yl)acrylate (7c): The
product was obtained as white needles (DCM/ether); yield:
207.4 mg (76%); mp 160–1628C; 1H NMR (400 MHz,
CDCl3): d=8.44 (brs, 1H), 7.83 (d, J=16.1 Hz, 1H), 7.38 (d,
J=2.9 Hz, 1H), 7.25–7.24 (m, 1H), 7.21–7.18 (m, 1H), 6.85
(dd, J=2.2 and 8.8 Hz, 1H), 6.30 (d, J=15.4 Hz, 1H), 4.15
(t, J=6.2 Hz, 2H), 3.82 (s, 3H), 1.65–1.60 (m, 2H), 1.41–
1.35 (m, 2H), 0.90 (t, J=7.3 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=168.6, 155.4, 138.3, 132.0, 129.2, 125.9, 113.3,
113.2, 112.6, 112.4, 102.5, 64.1, 55.9, 30.9, 19.2, 13.8; HR-MS
(ESI): m/z=273.1365, Calcd for C16H19NO3 (M+H+):
273.1365.
1H), 3.02–3.05 (m, 2H), 2.56–2.59 (m, 2H), 2.41ACTHNUGRTNEUNG(s, 3H);
13C NMR (75 MHz, CDCl3): d=209.4, 174.1, 141.9, 131.3,
129.6, 126.8, 126.6, 35.3, 29.7, 21.6; HR-MS (ESI): m/z=
172.0888, calcd. for C12H12O (M+H+): 172.0888.
(E)-3-(4-Methoxyphenyl)acrylonitrile (5i):[49] The product
was obtained as a colourless liquid; yield: 140.8 mg (89%);
1H NMR (400 MHz, CDCl3): d=7.69 (d, J=8.8 Hz, 1H),
7.29 (d, J=8.1 Hz, 1H), 7.20 (d, J=16.1 Hz, 1H), 6.85–6.80
(m, 2H), 5.60 (d, J=16.1 Hz, 1H), 3.74 (s, 3H); 13C NMR
(100 MHz, CDCl3): d=161.9, 149.9, 130.8, 128.9, 126.1,
118.6, 114.3, 114.1, 93.1, 55.3; IR (KBr): n=2962, 2933,
2840, 2212, 1628, 1603, 1573, 1252, 1174, 802, 768 cmÀ1; HR-
MS (ESI): m/z=159.0680, calcd. for C10H9NO (M+H+):
159.0684.
(E)-Butyl 3-(5-bromo-1H-indol-3-yl)acrylate (7d):[51] The
product was obtained as white needles (DCM/ether); yield:
231.2 mg (72%); mp 143–1458C; 1H NMR (400 MHz,
CDCl3): d=8.68 (brs, 1H), 8.01 (s, 1H), 7.82 (d, J=16.1 Hz,
1H), 7.45–7.44 (m, 1H), 7.35–7.32 (m, 1H), 7.27–7.24 (m,
1H), 6.38 (d, J=16.1 Hz, 1H), 4.20 (t, J=6.6 Hz, 2H), 1.72–
6-(p-Tolyl)-4,5-dihydro-1,3-dioxepine (5j): The product
was obtained as a colourless liquid; yield: 144.4 mg (76%);
1H NMR (400 MHz, CDCl3): d=7.08–7.04 (m, 4H), 6.37
Adv. Synth. Catal. 2013, 355, 421 – 438
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433

Akhilesh K. Verma et al.
FULL PAPERS
1.65 (m, 2H), 1.46–1.39 (m, 2H), 0.95 (t, J=7.3 Hz, 3H);
13C NMR (100 MHz, CDCl3): d=168.4, 137.5, 135.7, 129.6,
126.9, 126.2, 123.0, 114.8, 113.8, 113.0, 64.3, 30.8, 19.2, 13.7;
IR (KBr): n=3199, 3171, 2955, 2899, 1660, 1622, 1452, 1389,
1288, 1259, 1234, 1063, 970, 841, 795 cmÀ1; HR-MS (ESI):
m/z=321.0364, calcd. for C15H16BrNO2 (M+H+): 321.0364.
(E)-5-Methoxy-3-styryl-1H-indole (7e): The product was
obtained as yellow needles (DCM/ether); yield: 191.7 mg
(77%); mp 110–1128C; 1H NMR (300 MHz, CDCl3): d=
8.09 (brs, 1H), 7.52 (d, J=7.2 Hz, 2H), 7.41–7.19 (m, 7H),
7.05 (d, J=16.5 Hz, 1H), 6.92 (dd, J=6.6 and 2.1 Hz, 1H),
3.92 (s, 3H); 13C NMR (75 MHz, CDCl3): d=154.7, 138.5,
131.9, 128.6, 126.6, 126.1, 125.8, 125.2, 124.3, 121.6, 115.4,
112.6, 112.1, 102.4, 56.1; HR-MS (ESI): m/z=249.1155,
calcd. for C17H15NO (M+H+): 249.1154.
7.23–7.21 (m, 1H), 7.19–7.17 (m, 1H), 7.01–6.98 (m, 1H);
13C NMR (100 MHz, CDCl3): d=147.6, 143.0, 139.2, 130.2,
129.3, 125.1, 122.9, 122.8, 120.4, 88.7, 86.5; IR (KBr): n=
3045, 3105, 2925, 2849, 2212, 1565, 1461, 1438, 1399, 1020,
783, 749, 624 cmÀ1; HR-MS: m/z=262. 9404, calcd. for
C11H6BrNS (M+H+): 262.9404.
3-Methyl-1-(2-(thiophen-3-ylethynyl)phenyl)-1H-indole
(9d):[24] The product was obtained as a yellow oil; yield:
1
234.8 mg (75%); H NMR (300 MHz, CDCl3): d=7.70–7.66
(m, 2H), 7.49–7.44 (m, 2H), 7.39–7.35 (m, 2H), 7.27 (d, J=
5.0 Hz, 2H), 7.23–7.21 (m, 1H), 7.19 (dd, J=2.0 and 3.2 Hz,
1H), 7.11 (d, J=3.2 Hz, 1H), 6.79 (d, J=5.2 Hz, 1H), 2.44
(s, 3H); 13C NMR (75 MHz, CDCl3): d=141.1, 136.8, 133.3,
129.7, 129.5, 129.2, 129.0, 126.9, 126.8, 126.7, 125.3, 122.1,
120.6, 119.7, 119.1, 111.3, 111.1, 90.0, 86.3, 9.9; IR (KBr): n=
3103, 2931, 2851, 1594, 1489, 1459, 1360, 867, 777 cmÀ1; HR-
MS: m/z=313.0928, calcd. for C21H15NS (M+H+): 313.0925.
4,4’-(2,5-Dibromo-1,4-phenylene)bis(ethyne-2,1-diyl)bis-
(ethylbenzene) (9e): The product was obtained as white nee-
dles (DCM/ether); yield: 357.2 mg (73%); mp: 176–1788C;
1H NMR (300 MHz, CDCl3): d=7.75 (s, 2H), 7.49 (d, J=
8.1 Hz, 4H), 7.20 (d, J=8.1 Hz, 4H), 2.67 (q, J=7.5 Hz,
4H), 1.24 (t, J=7.5 Hz, 6H); 13C NMR (75 MHz, CDCl3):
d=145.7, 136.5, 135.9, 135.2, 132.3, 131.7, 129.7, 128.0, 127.3,
125.5, 125.3, 123.8, 122.5, 120.0, 119.6, 119.3, 119.0, 114.2,
111.7, 95.7, 86.5, 28.9, 28.7, 15.4, 15.3; IR (KBr): n=3042,
3029, 2959, 2924, 2864, 2214, 1509, 1448, 1420, 1371, 1052,
880, 827, 750, 710 cmÀ1; HR-MS: m/z=489.9934, calcd. for
C26H20Br2 (M+H+): 489.9932.
(E)-3-Styryl-1H-indole (7f):[51] The product was obtained
as pale yellow needles (DCM/ether); yield: 164.2 mg (75%);
1
mp 100–1028C; H NMR (300 MHz, CDCl3): d=8.22 (brs,
1H), 8.11 (s, 1H), 7.53 (d, J=7.2 Hz, 2H), 7.39–7.32 (m,
5H), 7.28–7.13 (m, 3H), 7.06 (d, J=16.5 Hz, 1H); 13C NMR
(75 MHz, CDCl3): d=138.2, 135.4, 128.7, 126.3, 125.8, 125.6,
124.5, 122.8, 120.8, 115.3, 113.8, 112.8; IR (KBr): n=3056,
3021, 2960, 2923, 2853, 1624, 1598, 1455, 1337, 1315, 950,
738 cmÀ1; HR-MS (ESI): m/z=219.1049, calcd. for C16H13N
(M+H+): 219.1048.
General Procedure for the Sonogashira Reaction (9a–
g)
3,4-Dibromo-2,5-bis[(4-ethylphenyl)ethynyl]thiophene
(9f): The product was obtained as yellow needles (DCM/
ether); yield: 396.1 mg (80%); mp 115–1178C; 1H NMR
(400 MHz, CDCl3): d=7.41 (d, J=8.2 Hz, 4H), 7.13 (d, J=
8.2 Hz, 4H), 2.60 (q, J=7.7 Hz, 4H), 1.17 (t, J=7.7 Hz,
6H); 13C NMR (100 MHz, CDCl3): d=145.9, 131.7, 128.0,
121.3, 119.0, 118.6, 98.9, 80.4, 28.9, 15.3; HR-MS: m/z=
495.9499, calcd. for C24H18Br2S (M+H+): 495.9496.
3,3’,3’’,3’’’-[Thiophene-2,3,4,5-tetrayltetrakis(ethyne-2,1-
diyl)]tetrathiophene (9g): The product was obtained as light
yellow needles (DCM/ether); yield: 304.2 mg (60%); mp
115–1178C; 1H NMR (400 MHz, CDCl3): d=7.62–7.59 (m,
4H), 7.33–7.30 (m, 4H), 7.25–7.20 (m, 4H); 13C NMR
(100 MHz, CDCl3): d=130.1, 130.0, 129.9, 129.7, 127.8,
125.8, 125.5, 121.6, 121.2, 121.1 (2C), 121.0, 120.5, 118.1,
94.4, 93.2, 91.4, 82.1, 80.9, 80.4, 80.3; IR (KBr): n=3103,
2955, 2925, 2851, 2207, 1660, 1622, 1407, 1354, 872, 775,
683 cmÀ1; HR-MS: m/z=507.9543, calcd. for C28H12S5 (M+
H+): 507.9543.
A
flask was charged with PdACTHUGNTERNNU(G OAc)2 (2.0 mol%), L4
(2.0 mol%), K2CO3 (2.0 equiv.) and 1.0 mmol of aryl halide
in 2.0 mL of DMF under a nitrogen atmosphere. After stir-
ring at room temperature for 15 min, the terminal alkyne
(1.2 equiv.), was added to the flask, and the reaction mixture
stirred at the 1008C for 1–2 h. After the completion of reac-
tion, the mixture was cooled to room temperature, diluted
with ethyl acetate and the resulting suspension was filtered.
The filtrate was concentrated, and the residue was purified
by column chromatography on silica gel to provide the de-
sired product (ethyl acetate/hexane).
1-Methoxy-4-(p-tolylethynyl)benzene (9a):[52] The product
was obtained as white needles (DCM/ether); yield: 199.9 mg
(90%); mp: 120–1228C; 1H NMR (400 MHz, CDCl3): d=
7.44 (d, J=8.8 Hz, 2H), 7.39 (d, J=8.0 Hz, 2H), 7.13 (d, J=
8.0 Hz, 2H), 6.85 (d, J=8.8 Hz, 2H), 3.80 (s, 3H), 2.34 (s,
3H); 13C NMR (100 MHz, CDCl3): d=159.4, 138.0, 132.9,
131.3, 129.0, 128.9, 120.4, 115.5, 113.9, 88.6, 88.1, 55.2, 21.5;
HR-MS (ESI): m/z=222.1046, calcd. for C16H14O (M+H+):
222.1045.
1-Methoxy-2-(phenylethynyl)benzene (9b):[53] The product
was obtained as a pale yellow oil; yield: 160.8 mg (77%);
1H NMR (300 MHz, CDCl3): d=7.57–7.49 (m, 4H), 7.33–
7.28 (m, 3H), 6.96 (m, 2H), 3.91 (s, 3H); 13C NMR
(75 MHz, CDCl3): d=159.9, 133.5, 131.6, 129.7, 128.3, 128.2,
126.5, 123.5, 120.5, 112.4, 110.7, 93.4, 85.7, 55.8; IR (KBr):
n=3057, 3020, 2959, 2938, 2215, 1593, 1497, 1275, 1245, 751,
690 cmÀ1; HR-MS (ESI): m/z=208.0889, calcd. for C15H12O
(M+H+): 208.0888.
3-Bromo-2-(thiophen-3-ylethynyl)pyridine (9c): The prod-
uct was obtained as a yellow oil; yield: 213.1 mg (81%);
1H NMR (400 MHz, CDCl3): d=8.42 (dd, J=1.4 and 4.6 Hz,
1H), 7.79 (dd, J=1.4 and 8.2 Hz, 1H), 7.60–7.59 (m, 1H),
General Procedure for the N-arylation Reaction
(10a–g)
To a solution of DMSO (2.0 mL), PdACTHNUTRGNENUG(OAc)2 (5.0 mol%), L4
(5.0 mol%), KO-t-Bu (2.0 equiv.), 1.0 mmol of the N-hetero-
cycle and 1.2 equiv. of heteroaryl halide were added. The
mixture was then heated at 1208C under a nitrogen atmos-
phere until the aryl halide was consumed, as determined by
TLC. The reaction mixture was washed with ethyl acetate
and water. The organic layer was then washed with brine
and dried over Na2SO4. The solvent was removed under
vacuum, and the crude residue was purified by column chro-
434
asc.wiley-vch.de
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 421 – 438

2-(1-Benzotriazolyl)pyridine: A Robust Bidentate Ligand
matography on silica gel using hexanes or a mixture of
hexane and ethyl acetate as eluent.
7.52 (brs, 1H), 6.90 (d, J=8.1 Hz, 4H), 6.81–6.78 (m, 4H),
3.67 (S, 6H); 13C NMR (100 MHz, DMSO-d6): d=152.8,
138.0, 118.1, 114.5, 55.2; IR (KBr): n=3421, 2958, 2937,
1-(2-Methoxyphenyl)-1H-indole (10a):[54] The product was
obtained as white needles (DCM/ether); yield: 173.9 mg
2914, 2839, 1510, 1298, 1240, 1221, 1180, 829, 816, 762 cmÀ1
;
HR-MS: m/z=229.1108, calcd. for C14H15NO2 (M+H+):
1
(78%); mp 68–708C; H NMR (300 MHz, CDCl3): d=7.77–
229.1103.
7.73 (m, 1H), 7.51–7.34 (m, 4H), 7.33–7.12 (m, 3H), 6.72 (d,
J=3.0 Hz, 1H), 6.59 (d, J=3.3 Hz, 1H), 3.85 (s, 3H);
13C NMR (75 MHz, CDCl3): d=158.2, 136.3, 132.8, 128.9,
128.3, 125.9, 122.1, 121.0, 120.0, 114.7, 110.3, 102.8, 55.6; IR
General Procedure for the S-Arylation Reaction
(KBr): n=2927, 2854, 1596, 1474, 1455, 1275, 1246, 1093, (12a–f)
1021, 744 cmÀ1
;
HR-MS: m/z=223.0998, calcd. for
To a round-bottomed flask containing 1.0 mmol of ArX 1,
1.4 mmol of KO-t-Bu, 1.0 mol% of Pd(OAc)2 and 1.0 mol%
C15H13NO (M+H+): 223.0997.
AHCTUNGTRENNUNG
1-(3-Bromo-pyridin-2-yl)-1H-indole (10b):[23c] The product
was obtained as a colorless oil; yield: 182.1 mg (67%);
1H NMR (300 MHz, CDCl3): d=8.48 (d, J=3.6 Hz, 1H),
8.03 (dd, J=1.6 and 6.3 Hz, 1H), 7.59 (dd, J=1.3 and
5.4 Hz, 1H), 7.43 (d, J=3.3 Hz, 1H), 7.35 (d, J=8.1 Hz,
1H), 7.28–7.08 (m, 3H), 6.63 (d, J=3.0 Hz, 1H); 13C NMR
(75 MHz, CDCl3): d=150.2, 147.8, 143.3, 135.9, 129.0, 127.7,
123.4, 122.6, 121.7, 120.9, 115.7, 111.9, 104.4; IR (KBr): n=
3055, 2924, 2853, 1567, 1474, 1458, 1330, 1210, 1022, 742,
614 cmÀ1; HR-MS: m/z=271.9949, calcd. for C13H9BrN2
(M+H+): 271.9949.
of L4, 2.0 mL of solvent were added under a nitrogen at-
mosphere. After that thiophenol (11) 1.0 equiv. was added
in the reaction mixture, which was stirred vigorously for
12 h at 1008C. After the completion of reaction, ethyl ace-
tate was added to the reaction mixture and the whole
washed with water. The organic layer was collected, dried
over Na2SO4, evaporated under vacuum, and the residue
was purified by column chromatography to afford the de-
sired product (ethyl acetate/hexane).
(4-Methoxyphenyl)ACTHNUTRGNEUNG
(p-tolyl)sulfane (12a):[59] The product
was obtained as a colourless oil; yield: 215.1 mg (94%);
1H NMR (300 MHz, CDCl3): d=7.29–7.24 (m, 4H), 6.87–
6.83 (m, 4H), 3.78 (s, 3H), 2.44 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=158.1, 130.1, 128.7, 114.6, 55.3, 18.0; IR (KBr):
n=3003, 2936, 2835, 1590, 1491, 1475, 1288, 1247, 1172,
1030, 825, 636, 622 cmÀ1; HR-MS: m/z=230.0765, calcd. for
C14H14OS (M+H+): 230.0765.
3-Methyl-1-p-tolyl-1H-indole (10c):[55] The product was
obtained as
a colourless oil; yield: 170.2 mg (77%);
1H NMR (300 MHz, CDCl3): d=7.65–7.52 (m, 2H), 7.37 (d,
J=8.1 Hz, 1H), 7.32–7.12 (m, 6H), 2.43 (s, 3H), 2.40 (s,
3H); 13C NMR (75 MHz, CDCl3): d=136.1, 131.0, 129.6,
129.1, 128.1, 125.3, 123.1, 121.3, 119.6, 113.8, 111.4, 30.1,
20.6; IR (KBr): n=2925, 2962, 2857, 1616, 1512, 793,
756 cmÀ1; HR-MS: m/z=221.1204, calcd. for C16H15N (M+
H+): 221.1204.
Phenyl
colourless oil; yield: 86.1 mg (93%); 1H NMR
(o-tolyl)sulfane (12b):[60] The product was obtained
ACHTUNGTRENNUNG
as
a
(300 MHz, CDCl3): d=7.51–7.48 (m, 2H), 7.32–7.27 (m,
5H), 7.26–7.22 (m, 1H), 7.19–7.11 (m, 1H), 2.48 (s, 3H);
13C NMR (75 MHz, CDCl3): d=137.5, 137.0, 132.2, 131.2,
130.0, 129.7, 128.9, 126.3, 21.0; HR-MS: m/z=200.0661,
calcd. for C13H12S (M+H+): 200.0660.
1-(2-Bromophenyl)-3-methyl-1H-indole (10d):[23c] The
product was obtained as a colourless oil; yield: 210.8 mg
1
(74%); H NMR (300 MHz, CDCl3): d=7.79 (d, J=8.0 Hz,
1H), 7.68–7.66 (m, 1H), 7.45 (q, J=8.0 Hz, 2H), 7.34–7.32
(m, 1H), 7.23–7.21 (m, 2H), 7.13–7.11 (m, 1H), 7.06 (s, 1H),
2.44 (s, 3H); 13C NMR (75 MHz, CDCl3): d=138.9, 137.1,
134.1, 129.9, 129.3, 129.1, 128.4, 126.4, 122.4, 121.9, 119.8,
119.2, 112.5, 110.7, 9.9; IR (KBr): n=3053, 2919, 2855, 1615,
1591, 1454, 737 cmÀ1; HR-MS: m/z=285.0153, calcd. for
C15H12NBr (M+H+): 285.0153.
2-(p-Tolylthio)pyridine (12c):[61] The product was obtained
as
a
colourless oil; yield: 185.0 mg (92%); 1H NMR
(300 MHz, CDCl3): d=8.41 (dd, J=2.4 and 3.6 Hz, 1H),
7.51–7.47 (m, 2H), 7.42 (dt, J=5.7 and 1.8 Hz, 1H), 7.26–
7.23 (m, 2H), 6.99–6.94 (m, 1H), 6.83 (d, J=6.0 Hz, 1H),
2.39 (s, 3H); 13C NMR (75 MHz, CDCl3): d=162.2, 149.5,
139.4, 136.6, 135.2, 130.4, 127.2, 120.8, 119.6, 21.3; HR-MS:
m/z=201.0612, calcd. for C12H11NS (M+H+): 201.0612.
1-(4-Methoxyphenyl)-2-methyl-1H-indole (10e):[56] The
product was obtained as white needles; (DCM/ether); yield:
172.9 mg (73%); mp 63–658C; H NMR (300 MHz, CDCl3):
1
2,3,4,5-Tetrakis(4-methoxyphenylthio)thiophene
(12d):
d=7.58–7.54 (m, 1H), 7.28–7.23 (m, 2H), 7.12–7.05 (m,
4H), 7.02 (d, J=2.1 Hz, 1H), 6.37 (s, 1H), 3.89 (s, 3H), 2.27
(s, 3H); 13C NMR (75 MHz, CDCl3): d=159.0, 138.5, 137.4,
130.6, 129.2, 128.0, 120.8, 119.8, 119.5, 114.6, 110.0, 100.7,
55.5, 13.3; HR-MS: m/z=237.1154, calcd. for C16H15NO
(M+H+): 237.1154.
The product was obtained as colourless oil; yield:
a
1
527.9 mg (83%); H NMR (400 MHz, CDCl3): d=7.40–7.37
(m, 3H), 7.29–7.25 (m, 5H), 6.85–6.79 (m, 8H), 3.78 (s, 3H),
3.75 (s, 9H); 13C NMR (100 MHz, CDCl3): d=160.5, 159.6,
158.7, 148.6, 136.0, 135.3, 132.7, 131.1, 129.3, 125.8, 124.9,
123.9, 122.8, 115.1, 114.8, 114.5, 55.3 (2C), 55.2 (2C); IR
(KBr): n=3001, 2936, 2834, 1590, 1572, 1492, 1461, 1289,
1247, 1172, 1030, 825, 798 cmÀ1; HR-MS: m/z=636.0589,
calcd. for C32H28O4S5 (M+H+): 636.0591.
1-(2-Bromophenyl)-1H-pyrrole (10f):[57] The product was
obtained as
a colourless oil; yield: 163.5 mg (74%);
1H NMR (400 MHz, CDCl3): d=7.71 (dd, J=1.0 and 6.9 Hz,
1H), 7.42–7.34 (m, 2H), 7.25 (dd, J=2.0 and 6.0 Hz, 1H),
6.90 (t, J=2.0 Hz, 2H), 6.37 (t, J=2.0 Hz, 2H); 13C NMR
(100 MHz, CDCl3): d=140.5, 133.9, 128.9, 128.4, 128.3,
122.4, 120.0, 109.3; HR-MS: m/z=220.9840, calcd. for
C10H8BrN (M+H+): 220.9840.
(2-Methoxyphenyl)ACTHNUTRGNEUNG
(o-tolyl)sulfane (12e):[62] The product
was obtained as a colourless oil; yield: 199.1 mg (87%);
1H NMR (300 MHz, CDCl3): d=7.34 (d, J=7.2 Hz, 1H),
7.27–7.13 (m, 4H), 6.78–6.72 (m, 3H), 3.74 (s, 3H), 2.38 (s,
3H); 13C NMR (75 MHz, CDCl3): d=160.0, 140.3, 137.6,
133.4, 133.2, 130.6, 129.9, 128.1, 126.7, 121.5, 114.8, 111.9,
55.2, 20.6; HR-MS: m/z=230.0765, calcd. for C14H14OS
(M+H+): 230.0765.
Bis(4-methoxyphenyl)amine (10g):[58] The product was ob-
tained as colourless needles (ether/hexane); yield: 121.4 mg
(53%); mp 97–988C; 1H NMR (400 MHz, DMSO-d6): d=
Adv. Synth. Catal. 2013, 355, 421 – 438
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
435

Akhilesh K. Verma et al.
FULL PAPERS
(4-Methoxyphenyl)
(octyl)sulfane
E
[4] a) C. Johansson, T. J. Colacot, Angew. Chem. 2010, 122,
686–718; Angew. Chem. Int. Ed. 2010, 49, 676–707;
b) H. Doucet, J. C. Hierso application, Angew. Chem.
2007, 119, 850–888; Angew. Chem. Int. Ed. 2007, 46,
834–871; c) M. Nakanishi, D. Katayev, C. Besnard, E. P.
Kundig, Angew. Chem. 2011, 123, 7576–7579; Angew.
Chem. Int. Ed. 2011, 50, 7438–7441; d) Z. Wang, K. Li,
D. Zhao, J. Lan, J. You, Angew. Chem. 2011, 123, 5477–
5481; Angew. Chem. Int. Ed. 2011, 50, 5365–5369.
[5] a) A. Zapf, M. Beller, Chem. Commun. 2005, 431–440,
and references cited therein; b) D. S. Surryand, S. L.
Buchwald, Angew. Chem. 2008, 120, 6438–6461; Angew.
Chem. Int. Ed. 2008, 47, 6338–6361.
1
obtained as a yellow oil; yield: 168.9 mg (67%); H NMR
(400 MHz, CDCl3): d=7.34 (dd, J=6.6 and 2.2 Hz, 2H),
6.77 (dd, J=6.6 and 2.2 Hz, 2H), 3.72 (s, 3H), 2.74 (t, J=
7.3 Hz, 2H), 2.43–2.41 (m, 2H), 1.55–1.46 (m, 6H), 1.32–
1.28 (m, 2H), 1.21–1.18 (m, 2H), 0.82–0.78 (m, 3H);
13C NMR (100 MHz, CDCl3): d=158.7, 132.9, 126.9, 114.4,
55.3, 35.8, 34.3, 31.8, 29.1, 28.8, 22.6, 15.5, 14.1; IR (KBr):
n=2954, 2925, 2854, 1593, 1493, 1463, 1284, 1245, 1035, 826,
638 cmÀ1; HR-MS: m/z=252.1550, calcd. for C15H24OS (M+
H+): 252.1548.
[6] a) A. F. Littke, C. Dai, G. C. Fu, J. Am. Chem. Soc.
2000, 122, 4020–4028; b) A . Zapf, A. Ehrentraut, M.
Beller, Angew. Chem. 2000, 112, 4315–4317; Angew.
Chem. Int. Ed. 2000, 39, 4153–4155; c) J. P. Stambuli, R.
Kuwano, J. F. Hartwig, Angew. Chem. 2002, 114, 4940–
4942; Angew. Chem. Int. Ed. 2002, 41, 4746–4748;
d) C. A. Fleckenstein, H. Plenio, Chem. Eur. J. 2007,
13, 2701–2716; e) C. A. Fleckenstein, H. Plenio, J. Org.
Chem. 2008, 73, 3236–3244; f) N. Kataoka, Q. Shelby,
J. P. Stambuli, J. F. Hartwig, J. Org. Chem. 2002, 67,
5553–5566; g) A . S. Guram, A. O. King, J. G. Allen, X.
Wang, L. B. Schenkel, J. Chan, E. E. Bunel, M. M. Faul,
R. D. Larsen, M. J. Martinelli, P. J. Reider, Org. Lett.
2006, 8, 1787–1789; h) T. Hoshi, T. Nakazawa, I. Saitoh,
A. Mori, T. Suzuki, J. Sakai, H. Hagiwara, Org. Lett.
2008, 10, 2063–2066; i) K. L. Billingsley, K. W. Ander-
son, S. L. Buchwald, Angew. Chem. 2006, 118, 3564–
3568; Angew. Chem. Int. Ed. 2006, 45, 3484–3488; j) K.
Billingsley, S. L. Buchwald, J. Am. Chem. Soc. 2007,
129, 3358–3366; k) C. M. So, C. P. Lau, F. Y. Kwong,
Angew. Chem. 2008, 120, 8179–8183; Angew. Chem.
Int. Ed. 2008, 47, 8059–8063; l) B. Bhayana, B. P. Fors,
S. L. Buchwald, Org. Lett. 2009, 11, 3954–3957.
Acknowledgements
We thank DST, UGC, University of Delhi (DU-DST
PURSE) for financial support, USIC for instrumentation fa-
cilities. R.R.J, R.C, and A.D are greatful to CSIR, RGNF and
DST for the Fellowships.
References
[1] Reviews on transition metal-catalyzed reactions, see:
a) J. Magano, J. R. Dunetz, Chem. Rev. 2011, 111,
2177–2250, and references cited therein; b) X. Chen,
K. M. Engle, D. Wang, J. Q. Yu, Angew. Chem. 2009,
121, 5196–5217; Angew. Chem. Int. Ed. 2009, 48, 5094–
5115; c) L. Ackermann, R. Vicente, A. R. Kapdi,
Angew. Chem. 2009, 121, 9976–10011; Angew. Chem.
Int. Ed. 2009, 48, 9792–9826; d) I. Nakamura, Y. Yama-
moto, Chem. Rev. 2004, 104, 2127–2198; e) J. A. Gla-
dysz, Chem. Rev. 2011, 111, 1167–1169; f) H. Li,
C. C. C. J. Seechurn, T. J. Colacot, ACS Catal. 2012, 2,
1147–1164; g) T. M. Shaikh, C.-M. Weng, F.-E. Hong,
Coord. Chem. Rev. 2012, 256, 771–803; h) C. C. C. J.
Seechurn, M. O. Kitching, T. J. Colacot, V. Snieckus,
Angew. Chem. 2012, 124, 5150–5174; Angew. Chem.
Int. Ed. 2012, 51, 5062–5085; i) G. Cahiez, A. Moyeux,
Chem. Rev. 2010, 110, 1435–1462; j) A. Roglans, A. P.
-Quintana, M. Moreno-Manas, Chem. Rev. 2006, 106,
4622–4643; k) J. Hassan, M. Sevignon, C. Gozzi, E.
Schulz, M. Lemaire, Chem. Rev. 2002, 102, 1359–1469.
[2] a) A. Suzuki, Angew. Chem. 2011, 123, 6854–6869;
Angew. Chem. Int. Ed. 2011, 50, 6722–6737; b) E. I. Ne-
gishi, Angew. Chem. 2011, 123, 6870–6897; Angew.
Chem. Int. Ed. 2011, 50, 6738–6764; c) X. F. Wu, P. An-
barasan, H. Neumann, M. Beller, Angew. Chem. 2010,
122, 9231–9234; Angew. Chem. Int. Ed. 2010, 49, 9047–
9050; d) M. J. Niphakis, G. I. Georg, Org. Lett. 2011,
13, 196–199; e) H. A. Ioannidou, C. Kizas, P. A. Kou-
tentis, Org. Lett. 2011, 13, 3466–3469; f) F. Proutiere, F.
Schoenebeck, Angew. Chem. 2011, 123, 8342–8345;
Angew. Chem. Int. Ed. 2011, 50, 8192–8195.
[7] a) L. Ackermann, H. K. Potukuchi, A. Althammer, R.
Born, P. Mayer, Org. Lett. 2010, 12, 1004–1007; b) L.
Ackermann, R. Vicente, N. Hofmann, Org. Lett. 2009,
11, 4274–4276; c) L. Ackermann, Synthesis 2006, 1557–
1571.
[8] a) C. W. K. Gstttmayr, V. P. W. Bhm, E. Herdtweck, M.
Grosche, W. A. Herrmann, Angew. Chem. 2002, 114,
1421–1423; Angew. Chem. Int. Ed. 2002, 41, 1363–1365;
b) G. Altenhoff, R. Goddard, C. W. Lehmann, F. Glo-
rius, Angew. Chem. 2003, 115, 3818–3821; Angew.
Chem. Int. Ed. 2003, 42, 3690–3193; c) C. Song, Y. Ma,
Q. Chai, C. Ma, W. Jiang, M. B. Andrus, Tetrahedron
2005, 61, 7438–7446; d) N. Marion, O. Navarro, J. Mei,
E. D. Stevens, N. M. Scott, S. P. Nolan, J. Am. Chem.
Soc. 2006, 128, 4101–4111; e) M . G. Organ, S. Calimsiz,
M. Sayah, K. H. Hoi, A. J. Lough, Angew. Chem. 2009,
121, 2419–2423; Angew. Chem. Int. Ed. 2009, 48, 2383–
2387.
[9] a) W. A. Herrmann, K. Ofele, S. K. Schneider, E.
Herdtweck, S. D. Hoffmann, Angew. Chem. 2006, 118,
3943–3947; Angew. Chem. Int. Ed. 2006, 45, 3859–3862;
b) Q. Dai, W. Gao, D. Liu, L. M. Kapes, X. Zhang, J.
Org. Chem. 2006, 71, 3928–3934.
[10] a) D. Bianchi, R. Bortolo, R. D’Aloisio, M. K. Ricci,
Angew. Chem. 1999, 111, 734–736; Angew. Chem. Int.
Ed. 1999, 38, 706–708; b) C. Yang, S. P. Nolan, Synlett
[3] a) R. Martin, S. L. Buchwald, Acc. Chem. Res. 2008, 41,
1461–1473; b) G. C. Fu, Acc. Chem. Res. 2008, 41,
1555–1564; c) R. Chinchilla, C. Njera, Chem. Rev. 2007,
107, 874–922; d) A. Molnar, Chem. Rev. 2011, 111,
2251–2320; e) S. M. Islam, P. Mondal, K. Tuhinab, A. S.
Roya, J. Chem. Technol. Biotechnol. 2010, 85, 999–
1010, and references cited therein.
436
asc.wiley-vch.de
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 421 – 438

2-(1-Benzotriazolyl)pyridine: A Robust Bidentate Ligand
2001, 10, 1539–1542; c) M. J. Dai, B. Liang, C. H. Wang,
Z. J. You, J. Xiang, G. B. Dong, J. H. Chen, Z. Yang,
Adv. Synth. Catal. 2004, 346, 1669–1673.
Lett. 2007, 48, 4207–4210; e) A. K. Verma, J. Singh, R.
Chaudhary, Tetrahedron Lett. 2007, 48, 7199–7202.
[24] a) A. K. Verma, S. P. Shukla, J. Singh, V. Rustagi, J.
Org. Chem. 2011, 76, 5670–5684; b) A. R. Katritzky, J.
wu, Synthesis 1994, 597–600.
[11] a) M. R. Buchmeiser, K. Wurst, J. Am. Chem. Soc.
1999, 121, 11101–11107; b) T. Kawano, T. Shinomaru, I.
Ueda, Org. Lett. 2002, 4,
[25] See the Supporting Information.
2545–2547; c) C. Najera, J. Gil-Moito, S. Karlstrum,
L. R. Falvello, Org. Lett. 2003, 5, 1451–1454.
[26] a) A. G. Myers, N. J. Tom, M. E. Fraley, s. B. Cohen,
D. J. Madar, J. Am. Chem. Soc. 1997, 119, 6702–6710;
b) N. K. Garg, D. D. Caspi, B. M. Stoltz, J. Am. Chem.
Soc. 2004, 126, 9552–9553; c) G. Bringmann, R. Gotz,
P. A. Keller, R. Walter, M. R. Boyd, F. Lang, A. Gara-
cia, J. J. Walsh, L. Tellitu, K. V. Bhaskar, T. R. Kelly, J.
Org. Chem. 1998, 63, 1090–1097.
[27] a) T. Hoshi, I. Saitoh, T. Nakazawa, T. Suzuki, J. Sakai,
H. Hagiwara, J. Org. Chem. 2009, 74, 4013–4016;
b) K. R. J. Thomas, P. Tyagi, J. Org. Chem. 2010, 75,
8100–8111, and references cited therein; c) O. Navarro,
R. A. Kelly, E. D. Stevens, S. P. Nolan, J. Am. Chem.
Soc. 2003, 125, 16194–16195; d) G. Altenhoff, G.; R.
Goddard, C. W. Lehmann, F. Glorius, J. Am. Chem.
Soc. 2004, 126, 15195–15201.
[12] a) D. Bourissou, O. Guerret, F. P. Gabai, G. Betrand,
Chem. Rev. 2000, 100, 39–92; b) D.-H. Lee, M.-J. Jin,
Org. Lett. 2011, 13, 252–255; c) G. A. Molander, B.
Canturk, Angew. Chem. 2009, 121, 9404–9425; Angew.
Chem. Int. Ed. 2009, 48, 9240–9261; d) D. F. Wass, M. F.
Haddow, T. W. Hey, A. Guy Orpen, C. A. Russell,
R. L. Wingad, M. Green, Chem. Commun. 2007, 2704–
2706; e) Q. Yao, M. Zabawa, J. Woo, C. Zheng, J. Am.
Chem. Soc. 2007, 129, 3088–3089.
[13] D. A. Alonso, C. Najera, M. C. Pacheco, Org. Lett.
2000, 2, 1823–1826.
[14] X. Cui, Y. Zhou, N. Wang, L. Liu, Q. Guo, Tetrahedron
Lett. 2007, 48, 163–167.
[15] a) D. Yang, Y. C. Chen, N. Y. Zhu, Org. Lett. 2004, 6,
1577–1580; b) W. Chen, R. Li, B. Han, B. J. Li, Y. C.
Chen, Y. Wu, L. S. Ding, D. Yang, Eur. J. Org. Chem.
2006, 1177–1184.
[16] Q. Yao, E. P. Kinney, C. Zheng, Org. Lett. 2004, 6,
2997–2999.
[28] a) M. J. Niphakis, G. I. Georg, Org. Lett. 2011, 13, 196–
199; b) M. Anniyappan, D. Muralidharan, P. T. Peru-
mal, Tetrahedron Lett. 2003, 44, 3653–3657; c) L. H.
Singer, N. P. Kong, J. Am. Chem. Soc. 1966, 88, 5213–
5219; d) N. Ravindranath, C. Ramesh, M. R. Reddy, B.
Das, Chem. Lett. 2003, 3, 222–223; e) R. A Smits, H. D.
Lim, A. Hanzer, J. Med. Chem. 2008, 51, 2457–2467.
[29] a) A. K. Verma, S. Bansal, J. Singh, R. K. Tiwari, V. K.
Sankar, V. Tandon, R. Chandra, Bioorg. Med. Chem,
2006, 14, 6733–6736, and references cited therein;
b) J. W. Landen, V. Hau, M. Wang, T. Davis, B. Ciliax,
B. H. Wainer, E. G. V. Meir, J. D. Glass, H. C. Joshi,
D. R. Archer, Clin. Cancer Res. 2004,10, 5187–5201;
c) R. C. Mishra, P. Karna, S. R. Gundala, V. Pannu,
R. A. Stanton, K. K. Gupta, M. H. Robinson, M.
Lopus, L. Wilson, M. Henary, R. Aneja, Biochem.
Pharmacol. 2011, 82, 110–121; d) R. A. Stanton, K. M.
Gernert, J. H. Nettles, R. Aneja, Med. Res. Rev. 2011,
31, 443–481; e) R. Aneja, T. Miyagi, P. Karna, T. Ezell,
D. Shukla, M. V. Gupta, C. Yates, S. R. Chinni, H.
Zhau, L. W. Chung, H. C. Joshi, Eur. J. Cancer 2010,
46, 1668–1678; f) K. Ye, Y. Ke, N. Keshava, J. Shanks,
J. A. Kapp, R. R. Tekmal, J. Petros, H. C. Joshi, Proc.
Natl. Acad. Sci. USA 1998, 95, 1601–1606.
[17] For recent reviews, see: a) N. Miyaura, A. Suzuki,
Chem. Rev. 1995, 95, 2457–2483; b) A. Suzuki, J. Orga-
nomet. Chem. 1999, 576, 147–168; c) M. Lamblin, L. N.
Hardy, J. C. Hierso, E. Fouquet, F. X. Felpinb, Adv.
Synth. Catal. 2010, 352, 33–79.
[18] a) J. P. Wolfe, S. Wagaw, S. L. Buchwald, J. Am. Chem.
Soc. 1996, 118, 7215–7215; b) J. P. Wolfe, S. L. Buch-
wald, J. Org. Soc., 1997, 62, 1264–1267; c) J. F. Mar-
coux, S. Wagaw, S. L. Buchwald, J. Org. Soc., 1997, 62,
1568–1569; d) D. W. Old, J. P. Wolfe, S. L. Buchwald, J.
Am. Chem. Soc. 1998, 120, 9722–9723; e) J. P. Wolfe,
S. L. Buchwald, Angew. Chem. 1999, 111, 2570–2573;
Angew. Chem. Int. Ed. 1999, 38, 2413–2416; f) J. P.
Wolfe, R. A. Singer, B. H. Yang, S. L. Buchwald, J. Am.
Chem. Soc. 1999, 121, 9550–9561.
[19] For aminations see: a) J. F. Hartwig, Synlett 1997, 329–
340; b) G. Mann, J. F. Hartwig, M. S. Driver, C. F.
Rivas, J. Am. Chem. Soc. 1998, 120, 827–828.
[20] B. C. Hamann, J. F. Hartwig, J. Am. Chem. Soc. 1998,
120, 3694–3703.
[21] a) A. R. Katritzky, X. Lan, J. Z. Yang, O. V. Denisko.
Chem. Rev. 1998, 98, 409–548; b) C. Richardson, P. J.
Steel, Dalton Trans. 2003, 992–1000.
[22] a) C. A. Bessel, J. A. Margarucci, J. H. Acquaye, R. S.
Rubmo, J. Crandai, A. J. Jircitano, K. J. Takeuchi, J.
Inorg. Chem. 1993, 32, 5779–5784; b) J. P. Collman, M.
Zhong, C. Zhang, S. Costanzo, J. Org. Chem. 2001, 66,
7892–7897.
[23] a) A. K. Verma, T. Kesharwani, J. Singh, V. Tandon,
R. C. Larock, Angew. Chem. 2009, 121, 1150—1163;
Angew. Chem. Int. Ed. 2009, 48, 1138–1143; b) A. K.
Verma, M. Joshi, V. P. Singh, Org. Lett. 2011, 13, 1630–
1633; c) A. K. Verma, J. Singh, R. C. Larock, Tetrahe-
dron 2009, 65, 8434–8439; d) A. K. Verma, J. Singh,
V. K. Sankar, R. Chaudhary, R. Chandra, Tetrahedron
[30] a) R. F. Heck, J. P. Nolley Jr, J. Org. Chem. 1972, 37,
2320–2322; b) J. L. Bras, J. Muzart, Chem. Rev. 2011,
111, 1170–1214, and references cited therein; c) S. J.
Danishefsky, J. J. Masters, W. B. Young, J. T. Link, L. B.
Snyder, T. V. Magee, D. K. Jung, R. C. A. Isaacs, W. G.
Bornmann, C. A. Alaimo, C. A. Coburn, M. J. Di Gran-
di, J. Am. Chem. Soc. 1996, 118, 2843–2859; d) C. Y.
Hong, N. Kado, L. E. Overman, J. Am. Chem. Soc.
1993, 115, 11028–11029; e) V. H. Rawal, S. Iwasa, J.
Org. Chem. 1994, 59, 2685–2686; f) L. E. Overman,
D. J. Ricca, V. D. Tran, J. Am. Chem. Soc. 1993, 115,
2042–2044; g) D. J. Kucera, S. J. OꢁConnor, L. E. Over-
man, J. Org. Chem. 1993, 58, 5304–5306.
[31] a) N. P. Grimster, C. Gauntlett, C. R. A. Godfrey, M. J.
Gaunt, Angew. Chem. 2005, 117, 3185–3189; Angew.
Chem. Int. Ed. 2005, 44, 3125–3129; b) L. Djakovitch,
P. Rouge, J. Mol. Catal. A 2007, 273, 230–239; c) I.
Adv. Synth. Catal. 2013, 355, 421 – 438
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
437

Akhilesh K. Verma et al.
FULL PAPERS
Moritani, Y. Fujiwara, Tetrahedron Lett. 1967, 8, 1119–
1122.
[44] C. Acuff, D. Kalman, PCT Int. Appl. 2010030582, 2010.
[45] G. Xie, P. Chellan, J. Mao, K. Chibale, G. S. Smith,
Adv. Synth. Catal. 2010, 352, 1641–1647.
[46] A. V. Mekhaev, A. V. Pestov, P. A. Slepukhin, Yu. G.
Yatluk, M. G. Pervova, M. A. Samorukova, O. N. Chu-
pakhin, Russian. J. Org. Chem. 2011, 47, 1366–1369.
[47] S. Proch, Y. Mei, J. M. R. Villanueva, Y. Lu, A. Karpov,
M. Ballauff, R. Kempe, Adv. Synth. Catal. 2008, 350,
493–500.
[32] a) D.-S. Kim, J. Ham, Org. Lett. 2010, 12, 1092–1095
and references cited therein; b) S. S. Bag, R. Kundu, M.
Das, J. Org. Chem. 2011, 76, 2332–2337; c) O. Vechor-
kin, D. Barmaz, V. Proust, X. Hu, J. Am. Chem. Soc.
2009, 131, 12078–12079 and references cited therein.
[33] a) K. K. Wang, Chem. Rev. 1996, 96, 207–222; b) A.
Basak, S. Mandal, S. S. Bag, Chem. Rev. 2003, 103,
4077–4094.
[34] a) E.-I. Negishi, S. Baba, J. Chem. Soc. Chem.
Commun. 1976, 596–597; b) S. Baba, E.-I. Negishi, J.
Am. Chem. Soc. 1976, 98, 6729–6731; c) M. Carril, R. S.
Martin, E. Dominguez, Chem. Soc. Rev. 2008, 37, 639–
647; d) Z. Huang, E.-I. Negishi, J. Am. Chem. Soc.
2007, 129, 14788–14792.
[48] J. Ye, X. Zhang, W. Chen, S. Shimada, Organometallics
2008, 27, 4166–4172.
[49] A. K. Gupta, C. H. Song, C. H. Oh, Tetrahedron Lett.
2004, 45, 4113–4116.
[50] R. Alvarez, C. Martinez, Y. Madich, J. Denis, J. M. Aur-
recoechea, A. R. de Lera, Chem. Eur. J. 2010, 16,
12746–12753.
[35] a) S. Schroter, C. Stock, T. Bach, Tetrahedron 2005, 61,
2245–2267; b) S.-W. Cheng, M.-C. Tseng, K.-H. Lii, C.-
R. Leec, S.-G. Shyu, Chem. Commun. 2011, 47, 5599–
5601; c) I. P. Beletskaya, V. P. Ananikov, Chem. Rev.
2011, 111, 1596–1636; d) P. H. Lee, Y. Park, S. Park, E.
Lee, S. Kim, J. Org. Chem. 2011, 76, 760–765;
e) D. J. C. Prasad, G. Sekar, Org. Lett. 2011, 13, 1008–
1011.
[51] N. P. Grimster, C. Gauntlett, C. R. A. Godfrey, M. J.
Gaunt, Angew. Chem. 2005, 117, 3185–3189; Angew.
Chem. Int. Ed. 2005, 44, 3125–3129.
[52] T. Li, X. Qu, G. Xie, J. Mao, Chem. Asian J. 2011, 6,
1325–1330.
[53] T. Li, X. Qu, Y. Zhu, P. Sun, H. Yang, Y. Shan, H.
Zhang, D. Liu, X. Zhang, J. Mao, Adv. Synth. Catal.
2011, 353, 2731–2738.
[36] I. Novak, T. Abu-Izneid, J. Phys. Chem. A: 2009, 113,
9751–9756.
[54] A. Klapars, J. C. Antilla, X. Huang, S. L. Buchwald, J.
Am. Chem. Soc. 2001, 123, 7727–7729.
[37] A. K. Verma, R. R. Jha, V. K. Sankar, T. Aggarwal,
R. P. Singh, R. Chandra, Eur. J. Org. Chem. 2011, 11,
6998–7010.
[38] A. R. Katritzky, C. V. Hughes, S. Rachwal, J. Hetero-
cycl. Chem. 1989, 26, 1579–1588.
[55] S. Haneda, Y. Adachi, M. Hayashi, Tetrahedron 2009,
65, 10459–10462.
[56] H. Zhang, Q. Cai, D. Ma, J. Org. Chem. 2005, 70, 5164–
5173.
[57] R. Zhu, L. Xing, X. Wang, C. Cheng, D. Su, Y. Hu,
Adv. Synth. Catal. 2008, 350, 1253–1257.
[58] F. A. Neugebauer, H. Fischer, Chem. Ber. 1971, 104,
886–894.
[59] Y. Feng, H. Wang, F. Sun, Y. Li, X. Fu, K. Jin, Tetrahe-
dron 2009, 65, 9737–9741.
[39] R. R. Jha, R. Chaudhary, R. Chandra, A. K. Verma, J.
Indian Chem. Soc. 2011, 88, 1187–1194.
[40] K. Billingsley, S. L. Buchwald, J. Am. Chem. Soc. 2007,
129, 3358–3366.
[41] Y.-Y. Peng, J. Liu, X. Lei, Z. Yin, Green Chem. 2010,
12, 1072–1075.
[60] X.-Y. Zhang, X.-Y. Zhang, S.-R. Guo, J. Sulfur Chem.
[42] D. T. Tung, D. T. Tuan, N. Rasool, A. Villinger, H.
Reinke, C. Fischer, P. Langera, Adv. Synth. Catal. 2009,
351, 1595–1609.
2011, 32, 23–35.
[61] D. J. C. Prasad, G. Sekar, Org. Lett. 2011, 13, 1008–
1011.
[43] T. Aggarwal, M. Imam, N. K. Kaushik, V. S. Chauhan,
A. K. Verma, ACS Comb. Sci. 2011, 13, 530–536.
[62] W. Deng, Y. Zou, Y.-F. Wang, L. Liu, Q.-X. Guo Synlett
2004, 1254–1258.
438
asc.wiley-vch.de
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 421 – 438