A Solvent-free and one-pot strategy for ecocompatible synthesis of substituted benzofurans from various salicylaldehydes, secondary amines, and nonactivated alkynes catalyzed by copper(I) oxide nanoparticles

Article abstract of DOI:10.1055/s-0034-1378206

Copper(I) oxide nanoparticles (CONPs) catalyze multicomponent coupling/cycloisomerization reactions between various 2-hydroxybenzaldehydes, secondary amines, and nonactivated alkynes to give 2,3-disubstituted 1-benzofurans. All reactions are carried out u

Full text of DOI:10.1055/s-0034-1378206

PAPER
▌2489
pAapeSr olvent-Free and One-Pot Strategy for Ecocompatible Synthesis of
Substituted Benzofurans from Various Salicylaldehydes, Secondary Amines,
and Nonactivated Alkynes Catalyzed by Copper(I) Oxide Nanoparticles
2
2
,3-Disubstituted 1-Benzofurans Using Cu O Nanoparticles
Hashem Sharghi,* Pezhman Shiri, Mahdi Aberi
Department of Chemistry, Shiraz University, Shiraz, 71454, Iran
Fax +98(711)2280926; E-mail: shashem@chem.susc.ac.ir
Received: 03.03.2014; Accepted after revision: 12.05.2014
alization, a few examples are: cross-coupling of sodium
benzofuran-2-yl)dimethylsilanolate with aryl bromides
Abstract: Copper(I) oxide nanoparticles (CONPs) catalyze multi-
component coupling/cycloisomerization reactions between various
(
9
a
or aryl chlorides using (t-Bu P) Pd, the addition of phe-
2-hydroxybenzaldehydes, secondary amines, and nonactivated
3
2
alkynes to give 2,3-disubstituted 1-benzofurans. All reactions are nols to bromoalkynes and intramolecular cyclization of
9
b
carried out under solvent- and ligand-free conditions at 100 °C in (Z)-2-bromovinyl phenyl ethers, copper(I) bromide cat-
air. The combination of copper-catalyzed C–H activation and an O-
alyzed coupling of N-tosylhydrazones and terminal
annulation process is essential for this transformation. This method-
ology provides rapid access to substituted 1-benzofurans in good to
excellent yields with high atom economy and high catalytic effi-
ciency. This procedure eliminates the need for propargylamine de-
rivatives, uncyclized intermediates that make purification difficult.
9c
alkynes, palladium-catalyzed one-pot synthesis of 1-
benzofurans from 2-chlorophenols and terminal
9
d
alkynes, synthesis of either C2- or C3-substituted 1-ben-
9
e
zofurans from 2-chloro-1-(2-hydroxyphenyl)ethanones,
The CONPs and tetrabutylammonium bromide were reused suc- transformation of O-arylated products into substituted
9f
cessfully for up to five times.
benzofurans, synthesis of 2,3-disubstituted benzofurans
by platinum–olefin-catalyzed carboalkoxylation of O-
Key words: 1-benzofurans, copper(I) oxide nanoparticles, one-pot
cascade reaction, solvent-free conditions, morpholine
9
g
alkynylphenyl acetals, palladium-catalyzed synthesis of
9
h
benzofurans from 2-chloroaryl alkynes and a host of
9
i–n
other methods.
The benzofuran scaffold has played a critical role in the While these methods enriched the approaches to 1-benzo-
1
discovery of bioactive molecules. Structural and substi- furan derivatives, their utility and applicability are often
tution modifications on this oxygen heterocyclic building compromised by the loss of catalyst, their use of expen-
block often lead to the identification of compounds with a sive metals and ligands, the utilization of harsh reaction
2
wide variety of biological activity, such as anticancer,
anti-oxidative, and anti-inflammatory properties.
conditions, and their adverse environmental impact due to
the use of volatile and toxic organic solvents.
3
4
Over the past few years, transition-metal-catalyzed Mannich In this respect, a newly emerged one-pot multicomponent
base cycloisomerization reactions have proved to be a reaction of a salicylaldehyde, activated or nonactivated
very simple and efficient route for the synthesis of com- alkynes, and a secondary amine is a reliable pathway to-
plex nitrogen/oxygen heterocyclic buildings.5 However, wards 1-benzofurans. Initially, Li and Nguyen reported
there are a few reports of the one-pot multicomponent that [Cu]- or [Ag]-catalyzed coupling of salicylaldehydes,
synthesis of 1-benzofurans using copper-catalyzed cou- amines, and alkynes containing a heteroatom afforded
,6
6a
6
pling/annulation reaction. Thus in recent years, the de- 2,3-disubstituted 1-benzofurans with good efficiency.
6
b
velopment of methods for the synthesis of 1-benzofurans Then, Sakai and co-workers reported that this cou-
in a sustainable manner has been an active research topic pling/cycloisomerization reaction could be realized via
in both academic and pharmaceutical research. One-pot Cu(I) and Cu(II) as a two metal catalytic system in the
and multicomponent conditions have emerged as power- presence of 4-(dimethylamino)pyridine as the base. How-
ful techniques to enhance the reaction rates of a variety of ever, the alkynes employed therein were limited to those
chemical transformations,7 while reactions catalyzed by activated alkynes bearing a Csp–Si bond. Recently, Zhang
,8
6
c
green catalysts such as copper are attractive in the grow- and co-workers also presented an improved, more gen-
ing field of green chemistry. Furthermore, this chemistry eral procedure starting from nonactivated terminal
represents a rare example of a copper-catalyzed cou- alkynes in the presence of CuI/[bmim]OAc and
pling/cycloisomerization reaction. The prominence of 1- [bmim]PF . However, these methods are still associated
6
benzofurans as a basic framework in biologically active with one or more restrictions such as low reaction rate,
compounds and natural products has promoted extensive utilization of harsh reaction conditions, non-reusability of
experimental studies toward their synthesis and function- the catalyst, the use of toxic and expensive solvents, and
limited substrate scope. Herein, we report a novel modifi-
cation of the work developed by Li and Nguyen and later
by Sasaki and co-workers for the one-pot multicomponent
synthesis of highly regioselective 2,3-disubstituted 1-ben-
SYNTHESIS 2014, 46, 2489–2498
Advanced online publication: 25.06.2014
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1
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DOI: 10.1055/s-0034-1378206; Art ID: ss-2014-z0156-op
Georg Thieme Verlag Stuttgart · New York
©

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H. Sharghi et al.
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zofurans using copper(I) oxide nanoparticles (CONPs)10 in 2-hydroxybenzaldehyde. Thus, potassium carbonate as
as a reusable and efficient catalyst under solvent-free con- a base and tetrabutylammonium bromide as an additive
ditions. Moreover, the catalyst and tetrabutylammonium were added to the reaction mixture. It was found that the
bromide can be used for five reaction cycles.
propargylic amine derivative 4 could be smoothly cy-
clized to afford 4-(2-benzyl-1-benzofuran-3-yl)morpho-
line (5a) as the desired product (Scheme 1).
As part of our continuing interest in the development of
greener catalysts and cleaner procedures for organic reac-
1
1
tions used in the laboratory and industry, herein we de- These results prompted us to investigate the further appli-
veloped a new method for the synthesis of 2,3- cability of this reaction (Table 1). In order to establish the
disubstituted 1-benzofuran derivatives via a tandem al- optimum reaction conditions, the three component reac-
kyne–aldehyde–amine (A3) coupling followed by cycli- tion between salicylaldehyde, morpholine, and phenyl-
zation under mild conditions, very high reaction rate, and acetylene (1:1.1:1) was studied varying the parameters
using an inexpensive and reusable catalyst.
such as the copper catalyst, solvent, and base.
In an attempt to carry out the multicomponent cou- Initially, the use of a series of copper sources [including
pling/cycloisomerization reaction between 2-hydroxy- Cu(OAc) , CuBr , CuSO , CuO powder, Cu O, CONPs]
2
2
4
2
benzaldehyde, morpholine, and phenylacetylene with was examined in this reaction (Table 1, entries 1–5 and
CONPs as catalyst under solvent-free conditions at 100 °C, 12). Copper(I) oxide nanoparticles (CONPs) were found
2-[1-(morpholin-4-yl)-3-phenylprop-2-ynyl]phenol (4) to be the most effective catalyst in terms of stability, reac-
was formed and the cyclization failed to take place. This tion rate, and isolated yield of the product.
may be due to the low nucleophilicity of the oxygen atom
Table 1 Copper-Catalyzed Coupling/Cycloaddition Reaction of 2-Hydroxybenzaldehyde, Morpholine, and Phenylacetylene under Various
a
Conditions
b
c
Entry
Catalyst (mol%)
Base
Solvent
Temp (°C)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
Cu(OAc) ·H O (25)
K CO
–d
100
100
100
100
100
100
100
reflux
130
100
reflux
100
100
100
100
100
100
100
100
100
100
100
1.75
1.75
1.75
1.75
1.75
1.75
1.75
1.75
1.75
1.75
1.75
1.25
1.75
1.75
1.75
1.75
3.00
1.75
4.00
4.00
4.00
3.00
70
71
75
62
83
89
87
23
13
0
2
2
2
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
CuSO (25)
K CO
–d
4
2
CuBr (25)
K CO
–d
2
2
CuO powder (15)
K CO
–d
2
Cu O (20)
K CO
–d
2
2
CONPs (15)
CONPs (15)
CONPs (15)
CONPs (15)
CONPs (15)
CONPs (15)
CONPs (15)
CONPs (10)
CONPs (5)
K CO
toluene
1,4-dioxane
MeCN
PEG-300
2
K CO
2
K CO
2
K CO
2
1
1
1
1
1
1
1
1
1
1
2
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
K CO
H O
2
2
K CO
EtOH
–d
0
2
K CO
90
83
75
91
90
25
77
0
2
K CO
–d
2
K CO
–d
2
CONPs (20)
CONPs (25)
CONPs (20)
CONPs (15)
CONPs (15)
CONPs (15)
CONPs (15)
CONPs (15)
K CO
–d
2
K CO
–d
2
Et N
–d
3
Cs CO
–d
2
3
K PO
–d
3
4
NaOAc
–d
49
57
0
i-Pr N
–d
3
–
–d
a
b
c
d
All reactions were carried out in the present of TBAB.
CONPs = copper(I) oxide nanoparticles
Isolated yield.
Solvent-free reaction.
Synthesis 2014, 46, 2489–2498
© Georg Thieme Verlag Stuttgart · New York

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2,3-Disubstituted 1-Benzofurans Using Cu O Nanoparticles
2491
2
O
O
O
N
O
N
H
CONPs, base, TBAB
100 °C
+
+
+
N
H
OH
O
1a
3a
OH
2a
4
5
a
Scheme 1 The reaction between 2-hydroxybenzaldehyde, morpholine, and phenylacetylene as a model reaction
Recently, the acceleration of copper-catalyzed organic re- assisted O-annulation reaction (entries 6 and 7). Lower
actions by using ligated copper halides as the catalyst has yields were observed for 5a when using other solvents,
attracted much attention, however because of the use of such as acetonitrile and PEG-300 (entries 8 and 9). How-
expensive and challenging synthetic routes to the ligands, ever, no desired product was detected when the reaction
these methods are not acceptable. Due to their inexpen- was performed in ethanol and water (entries 10 and 11).
sive, simple preparation, and low sensitivity to light and The absence of solvent increased the concentration of the
air, CONPs were chosen for the further exploration of the reactants and was beneficial in accelerating the cou-
scope and limitations of this three-component coupling pling/cycloisomerization reaction. As well, avoiding the
reaction of salicylaldehydes, secondary amines, and non- use of toxic chemicals and reducing environmental pollu-
activated alkynes.12
tion, all one-pot three-component reactions were per-
formed under solvent-free conditions (entry 12 and Table
In the next step, we found that the loading levels of the
CONPs also have an effect on the yield. According to Ta-
ble 1, entries 12–16, the optimal catalyst loading in the
synthesis of 5a is at a concentration of 15 mol%. When the
amount of CONPs was reduced, the yield of 5a decreased,
2
). In the next step, the effect of various inorganic and or-
ganic bases was screened via this one-pot cascade reaction
and the results showed that potassium carbonate was still
the best choice (entries 12 and 17–22).
whereas raising CONPs concentration did not lead to an The scope and generality of this Mannich base O-annula-
appreciable increase in the yield. During our optimization tion reaction catalyzed by CONPs was explored using a
studies, the effect of solvents was examined and among variety of substrates. In all cases, one-pot and three-com-
the solvents tested in Table 1, toluene and 1,4-dioxane ponent reactions proceeded well and afforded the desired
were the most suitable reaction media for three-compo- products 5a–n in excellent yields and high regioselectivi-
nent coupling reactions of salicylaldehydes, secondary ties (Table 2).
amines, and nonactivated alkynes followed by base-
Table 2 Solvent-Free and One-Pot Three-Component Synthesis of 2,3-Disubstituted 1-Benzofuransa
b
Entry
Aldehyde
Amine
Alkyne
Product
Time (h)
1.25
Yield (%)
O
O
O
N
H
1
90 (79c)
N
H
Ph
OH
3
a
O
Ph
2a
1
a
5
5
a
N
2
3
1a
1a
N
H
3a
3a
1.25
1.25
90 (75c)
O
Ph
2b
b
Ph
Ph
N
N
N
87
N
H
O
Ph
2c
5
c
©
Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 2489–2498

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H. Sharghi et al.
PAPER
a
Table 2 Solvent-Free and One-Pot Three-Component Synthesis of 2,3-Disubstituted 1-Benzofurans (continued)
b
Entry
Aldehyde
Amine
Alkyne
Product
Time (h)
1.25
Yield (%)
Ph
Ph
N
4
1a
N
3a
89
85
88
H
O
Ph
2d
5
5
d
e
N
N
5
6
1a
1a
3a
3a
1.50
1.50
H
O
Ph
2e5
Ph
N
Ph
Ph
Ph
N
H
O
Ph
2f
5
f
O
N
O
7
8
9
1a
2a
2c
2a
1.25
1.25
6.50
89
85
79
3
b
5
g
Ph
N
N
O
1a
3b
5
h
O
O
N
H
OH
3a
O
Ph
N
N
O
O
1
b
5
i
Synthesis 2014, 46, 2489–2498
© Georg Thieme Verlag Stuttgart · New York

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2,3-Disubstituted 1-Benzofurans Using Cu O Nanoparticles
2493
2
a
Table 2 Solvent-Free and One-Pot Three-Component Synthesis of 2,3-Disubstituted 1-Benzofurans (continued)
b
Entry
Aldehyde
Amine
Alkyne
Product
Time (h)
1.50
Yield (%)
O
O
N
N
H
1
0
1
2a
3a
88
O
N
OH
O
O
Ph
1
c
5
j
N
1
1c
2b
3a
3a
N
1.50
1.50
89
89
O
O
Ph
5
k
Ph
N
N
12
1c
2c
N
O
O
Ph
5
l
Ph
O
H
N
O
O
OH
N
N
13
2a
3a
3.25
80
N
H
N
O
N
HO
O
O
Ph
1
d
5
m
NH2
1
4
1a
1a
3a
3a
–
1.50
1.50
0
0
2g
NH2
Cl
15
–
2h
a
Conditions: salicylaldehyde (1.0 mmol), secondary amine (1.1 mmol), nonactivated alkyne (1.0 mmol), CONPs (15 mol%), TBAB (1.0
mmol), K CO (1.0 mmol).
2
3
b
c
Isolated yield.
Reaction was performed on a 10-mmol scale.
©
Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 2489–2498

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Various cyclic and noncyclic secondary amines also re- Table 3 Reusability of Copper(I) Oxide Nanoparticles and Tetrabu-
tylammonium Bromide in the Synthesis of 2,3-Disubstituted 1-Ben-
zofurans
acted with salicylaldehyde and phenylacetylene to afford
the desired products in good to excellent yields (Table 2).
Unfortunately, aromatic amines, such as aniline and 4-
chloroaniline, gave no reaction (entries 15 and 16).
a
Reaction run
Time (h)
Yield (%)
1
2
3
4
5
1.25
1.25
1.25
1.25
1.25
90
88
85
85
82
Due to their wide range of pharmacological and biological
activity, the synthesis of compounds bearing
morpholine13 is a current target. Working on the envis-
aged strategy, we discovered that we could successfully
accomplish the synthesis of the desired 1-benzofurans
containing morpholin-4-ylmethyl using a copper-cata-
lyzed coupling/cycloisomerization process involving C–
H activation without elaborate reaction conditions (entries
a
Isolated yield.
9–12). In addition, this methodology could then be ex-
tended to the synthesis of a bis(1-benzofuran) by the suc-
cessive multicomponent coupling/cycloisomerization
reactions in good yield (entry 13).
Finally, to check the feasibility of this procedure on a pre-
parative scale, we performed the coupling/cycloisomer-
ization of salicylaldehyde, morpholine or piperidine and
phenylacetylene on a 10-mmol scale in the present of the
catalyst. As expected, the reaction proceeded similarly to
the experiment on a smaller scale, except that a slightly
longer reaction time was required (Table 2, entries 1 and
Considering that the literature focuses on the reusability
of CONPs especially those methods that use CONPs and
tetrabutylammonium bromide together, they were reused
1
0
for five cycles of the reaction (Table 3). After comple-
tion of the reaction, the mixture was extracted with diethyl
ether. In order to reuse copper(I) oxide nanoparticles and
tetrabutylammonium bromide together, they were solidi-
fied, evaporated in vacuo, cooled, and then subjected to a
second run by charging with the same substrates (salicyl-
aldehyde derivative, secondary amine, phenylacetylene,
2).
Herein, we proposed a mechanism for the CONPs cata-
lyzed preparation of 2,3-disubstituted 1-benzofurans
(
Scheme 2), which is in analogy to the established mech-
14
anism as reported in the literature.
and K CO ). The copper content in the product was deter- We believe that the synthesis of 2,3-disubstituted 1-ben-
2
3
mined through ICP. Results indicate that 7% of the copper zofurans under these conditions follows through an imin-
content was leached during the five reaction cycles.
ium ion A by the reaction of salicylaldehyde and
R1
R2
+
N
O
R1
+
H2O
R1
H2N
H
+
R2
+ H2N
R3
R2
OH
OH
B
A
R3
H
R1
R2
N
R1
R3
H
HN
R2
O
H
CONPs
C
base
base
R1
R1
R2
R2
N
H
N
aromatization
R3
O
R3
O
D
Scheme 2 Proposed mechanism for the synthesis of 2,3-disubstituted 1-benzofurans in the presence of CONPs
Synthesis 2014, 46, 2489–2498 © Georg Thieme Verlag Stuttgart · New York

PAPER
2,3-Disubstituted 1-Benzofurans Using Cu O Nanoparticles
2495
2
secondary amine in the presence of catalyst by the elimi- 13C NMR (CDCl
nation of a water molecule. The CONPs probably facili-
): δ = 32.29, 52.61, 67.72, 111.72, 119.93, 122.11,
23.49, 126.09, 126.49, 128.56, 128.76, 138.19, 150.25, 153.50.
3
1
+
+
+
tates the formation of A by increasing the electrophilicity MS: m/z (%) = 296 (M + 3, 3.0), 295 (M + 2, 18.7), 294 (M + 1,
+
7
1
9.2), 293 (M , 100.0), 234 (79.4), 218 (16.1), 178 (12.3), 158 (0.1),
21 (62.3), 91 (46.8), 73 (31.9), 57 (53.4).
of the carbonyl group. The Cu–acetylide intermediate B
generated in situ results in the activation of the C–H bond
due to the reaction of acetylene and catalyst. Then B re-
acts with A to provide corresponding amine as intermedi-
ate C. At this stage, the potassium carbonate plays its role
Anal. Calcd for C H NO (293.364): C, 77.79; H, 6.53; N, 10.91.
Found: C, 77.83; H, 6.55; N, 10.90.
19 19
2
1
-(2-Benzyl-1-benzofuran-3-yl)piperidine (5b)
as a base to increase the nucleophilicity of the oxygen Brown solid; yield: 262 mg (90%); mp 74–75 °C.
atom on the aryl ring to give intermediate D. It was ex-
IR (KBr): 663 (w), 702 (w), 756 (s), 856 (w), 979 (w), 1026 (w),
pected that under the reaction conditions, a subsequent 1149 (w), 1218 (m), 1288 (w), 1380 (w), 1458 (m), 1612 (m), 1720
–1
isomerization of D into the desired product would occur (w), 1797 (w), 2854 (w), 2939 (m), 3024 cm (w).
1
(
Scheme 2).
H NMR (CDCl ): δ = 1.35–1.43 (m, 2 H), 1.49–1.52 (m, 4 H),
.91–2.96 (m, 4 H), 3.96 (s, 2 H), 6.94–7.16 (m, 8 H), 7.42–7.47 (m,
H).
3
2
1
In summary, we have developed and implemented a sim-
ple, green, efficient, and highly selective methodology for
the one-pot and three-component tandem reaction of sali-
cylaldehydes, secondary amines, and nonactivated al-
kynes under solvent-free conditions using CONPs as a
catalyst. This procedure has several unique advantages,
such as large-scale synthesis, high conversions, cleaner
reaction profile, and cost efficiency. These advantages
make it a green process for the highly regioselective syn-
13
C NMR (CDCl ): δ = 24.31, 26.79, 32.48, 53.80, 111.51, 120.16,
3
1
1
21.80, 123.22, 126.34, 128.49, 128.59, 134.43, 138.54, 148.92,
53.45.
+
+
+
MS: m/z (%) = 293 (M + 2, 0.5), 292 (M + 1, 2.0), 291 (M , 3.3),
38 (10.5), 216 (14.4), 121 (100.0), 91 (66.0), 65 (25.3).
2
Anal. Calcd for C H NO (291.392): C, 82.44; H, 7.26; N, 4.81.
Found: C, 82.46; H, 7.29; N, 7.22.
2
0
21
thesis of 2,3-disubstituted 1-benzofurans from a wide 1-(2-Benzyl-1-benzofuran-3-yl)-4-phenylpiperazine (5c)
Brown solid; yield: 320 mg (87%); mp 115–120 °C.
range of substrates. Hence, we believe that it will find
wide application in organic synthesis as well as in indus- IR (KBr): 694 (s), 756 (s), 933 (w), 1026 (s), 1126 (s), 1226 (s),
1
326 (w), 1380 (w), 1450 (s), 1496 (s), 1596 (s), 1720 (w), 2831
try.
–
1
(
w), 2917 (w), 3055 cm (w).
1
H NMR (CDCl ): δ = 3.12 (s, 8 H), 3.97 (s, 2 H), 6.65–7.18 (m, 13
3
All chemicals and solvents were obtained from Fluka, Aldrich, and
Merck and used without further purification. The determination of
purity of the substrates and reaction monitoring were accomplished
by TLC on silica gel PolyGram SILG/UV 254 plates. Column chro-
matography was carried out using a short glass column of silica gel
H), 7.46–7.49 (m, 1 H).
13
C NMR (CDCl ): δ = 32.38, 50.26, 52.37, 111.68, 116.44, 120.03,
3
1
1
22.09, 123.46, 126.23, 126.47, 128.51, 128.58, 128.82, 128.89,
29.20, 138.26, 150.01, 151.48, 153.49.
+
+
+
6
0 (70–230 mesh). NMR spectra were recorded on a Bruker Avance
MS: m/z (%) = 370 (M + 2, 1.1), 369 (M + 1, 3.1), 368 (M , 6.0),
35 (22.1), 292 (100.0), 223 (13.3), 194 (10.1), 165 (12.6), 121
24.0), 91 (48.6), 57 (18.8).
1
13
DPX-250 ( H NMR at 250 MHz and C NMR at 62.9 MHz) spec-
trometer using TMS as an internal standard in pure deuterated sol-
vents. Mass spectra were determined on a Shimadzu GCMS-QP
3
(
Anal. Calcd for C H N O (368.477): C, 81.49; H, 6.56; N, 7.60.
2
5
24
2
1000 EX instruments at 70 or 20 eV. IR spectra were obtained using
Found: C, 81.51; H, 6.55; N, 7.57.
a Shimadzu FT-IR 8300 spectrophotometer. Melting points were
determined on a Buchi Melting Point B-545 electrical melting point
N,2-Dibenzyl-N-ethyl-1-benzofuran-3-amine (5d)
apparatus. Cu O nanoparticles were prepared according to a previ-
2
Brown oil; yield: 303 mg (89%).
15
ously reported procedure.
IR (KBr): 663 (w), 756 (s), 833 (w), 1026 (w), 1118 (m), 1218 (m),
1365 (w), 1458 (s), 1612 (s), 1720 (m), 2862 (w), 2962 cm–1 (s).
Copper-Catalyzed Coupling/Cycloisomerization Reaction;
General Procedure
CONPs (15 mol%) were added to a mixture of salicylaldehyde de-
rivative (1.0 mmol), secondary amine (1.1 mmol), phenylacetylene
1
H NMR (CDCl ): δ = 1.05 (t, J = 7.25 Hz, 3 H), 3.21 (q, J = 7.25
3
Hz, 2 H), 4.05 (s, 2 H), 4.32 (s, 2 H), 7.14–7.41 (m, 13 H), 7.69–
7.73 (m, 1 H).
(
1.0 mmol), TBAB (1.0 mmol), and K CO (1.0 mmol) at 100 °C,
2 3
13
C NMR (CDCl ): δ = 14.05, 31.78, 48.42, 59.82, 111.72, 120.05,
and the mixture was stirred for the time shown in Table 2 (TLC
3
1
1
21.90, 123.22, 124.10, 124.83, 126.29, 126.99, 128.20, 128.39,
28.70, 128.84, 137.99, 139.47, 152.75, 153.68.
monitoring). After completion of the reaction, Et O was added to
2
the mixture and the mixture was filtered and the solution was
washed with water. The solvent was concentrated to afford the
crude product, which after chromatography (silica gel 60, 70–230
mesh, hexane–EtOAc) gave the corresponding 2,3-disubstituted 1-
benzofurans.
+
+
+
MS: m/z (%) = 343 (M + 2, 1.1), 342 (M + 1, 4.2), 341 (M , 4.4),
66 (9.3), 250 (3.9), 148 (3.9), 121 (32.2), 91 (100.0), 65 (13.2).
2
Anal. Calcd for C H NO (341.451): C, 84.42; H, 6.76; N, 4.10.
2
4
23
Found: C, 84.43; H, 6.74; N, 4.09.
4
-(2-Benzyl-1-benzofuran-3-yl)morpholine (5a)
2
-Benzyl-N,N-diisobutyl-1-benzofuran-3-amine (5e)
Light yellow solid; yield: 264 mg (90%); mp 105–108 °C.
Brown oil; yield: 284 mg (85%).
IR (KBr): 540 (w), 748 (s), 840 (w), 902 (w), 1033 (m), 1110 (s),
IR (KBr): 663 (w), 756 (s), 833 (w), 1026 (w), 1118 (m), 1218 (m),
1365 (w), 1458 (s), 1612 (s), 1720 (m), 2862 (w), 2962 cm–1 (s).
1211 (s), 1257 (s), 1380 (m), 1450 (s), 1496 (m), 2846 (w), 2962
–1
cm (m).
1H NMR (CDCl
H), 2.90 (d, J = 7.25 Hz, 4 H), 4.22 (s, 2 H), 7.15–7.41 (m, 8 H),
.64–7.69 (m, 1 H).
): δ = 0.95 (d, J = 6.5 Hz, 12 H), 1.61–1.77 (m, 2
1
3
H NMR (CDCl ): δ = 3.18 (t, J = 4.75 Hz, 4 H), 3.86 (t, J = 4.75
3
Hz, 4 H), 4.17 (s, 2 H), 7.14–7.40 (m, 8 H), 7.66–7.69 (m, 1 H).
7
©
Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 2489–2498

2496
H. Sharghi et al.
PAPER
1
3
C NMR (CDCl ): δ = 20.88, 27.35, 32.05, 64.59, 111.72, 120.29,
IR (KBr): 702 (w), 756 (w), 856 (w), 910 (w), 1110 (s), 1203 (s),
1265 (w), 1450 (m), 1643 (m), 2846 (w), 2954 cm (w).
3
–
1
1
21.82, 123.24, 126.40, 126.52, 128.44, 128.74, 138.02, 151.74,
1
53.86.
1
H NMR (CDCl ): δ = 2.41 (t, J = 4.5 Hz, 4 H), 3.09 (t, J = 4.5 Hz,
3
+
+
+
MS: m/z (%) = 337 (M + 2, 8.0), 336 (M + 1, 11.1), 335 (M ,
6.7), 292 (100.0), 260 (26.3), 236 (12.1), 207 (23.5), 121 (49.6), 86
38.2), 57 (62.4).
4 H), 3.60 (t, J = 4.5 Hz, 4 H), 3.73 (s, 2 H), 3.77 (t, J = 4.5 Hz, 4
H), 4.10 (s, 2 H), 7.04–7.21 (m, 7 H), 7.50 (dd, J = 7.5 Hz, J = 1.25
Hz, 1 H).
1
(
1
2
13
Anal. Calcd for C H NO (335.488): C, 82.34; H, 8.71; N, 4.18.
C NMR (CDCl ): δ = 32.31, 52.55, 53.24, 56.09, 66.90, 67.69,
3
23
29
Found: C, 82.36; H, 8.72; N, 4.15.
118.95, 120.81, 122.10, 124.77, 125.93, 126.43, 128.47, 128.53,
1
28.82, 138.23, 150.03, 152.38.
N,2-Dibenzyl-N-(2-phenylethyl)-1-benzofuran-3-amine (5f)
Brown solid; yield: 367 mg (88%); mp 57–59 °C.
+
+
+
MS: m/z (%) = 394 (M + 2, 29.7), 393 (M + 1, 70.5), 392 (M ,
73.1), 307 (100.0), 276 (12.0), 249 (14.7), 221 (24.7), 149 (14.5),
IR (KBr): 702 (s), 748 (s), 843 (w), 1026 (m), 918 (w), 1072 (w),
1
33 (41.3), 105 (21.6), 86 (89.9), 57 (84.1).
1
126 (m), 1257 (m), 1365 (m), 1450 (s), 1496 (s), 1604 (m), 1797
–
1
Anal. Calcd for C H N O (392.496): C, 73.44; H, 7.19; N, 7.14.
24 28 2 3
Found: C, 73.47; H, 7.22; N, 7.17.
(m), 1728 (s), 2846 (m), 2923 (m), 3031 cm (s).
1
H NMR (CDCl ): δ = 2.79 (t, J = 8 Hz, 2 H), 3.47 (t, J = 8 Hz, 2
3
H), 3.98 (s, 2 H), 4.35 (s, 2 H), 7.05–7.30 (m, 17 H), 7.41–7.45 (m,
4-[2-Benzyl-5-(morpholin-4-ylmethyl)-1-benzofuran-3-yl]mor-
pholine (5j)
White solid; yield: 348 mg (88%); mp 98–100 °C.
1
H), 7.70–7.73 (m, 1 H).
13
C NMR (CDCl ): δ = 31.84, 35.31, 55.79, 60.19, 111.82, 120.01,
3
1
1
1
22.10, 123.39, 126.00, 126.36, 126.58, 126.65, 127.16, 128.28,
28.46, 128.72, 128.78, 128.98, 137.94, 139.11, 140.03, 152.65,
53.74.
IR (KBr): 540 (w), 609 (w), 702 (m), 763 (w), 918 (w), 1033 (w),
1110 (s), 1203 (m), 1257 (m), 1326 (w), 1373 (w), 1458 (m), 2815
–
1
(m), 2962 cm (w).
1H NMR (CDCl
): δ = 2.46–2.48 (m, 4 H), 3.16–3.20 (m, 4 H), 3.56
(s, 2 H), 3.70–3.73 (m, 4 H), 3.84–3.88 (m, 4 H), 3.16 (s, 2 H), 7.18–
.33 (m, 7 H), 7.59 (s, 1 H).
13C NMR (CDCl
): δ = 32.35, 52.58, 53.62, 63.58, 67.04, 67.70,
11.33, 120.39, 124.87, 126.01, 126.48, 128.56, 128.67, 131.70,
138.18, 150.61, 152.90.
+
+
+
MS: m/z (%) = 419 (M + 2, 1.2), 418 (M + 1, 3.1), 417 (M , 5.1),
26 (39.8), 234 (5.9), 121 (33.0), 91 (100.0).
3
3
7
Anal. Calcd for C H NO (417.549): C, 86.30; H, 6.52; N, 3.35.
Found: C, 86.27; H, 6.55; N, 3.39.
30
27
3
1
4
-[2-(4-tert-Butylbenzyl)-1-benzofuran-3-yl]morpholine (5g)
Brown solid; yield: 310 mg (89%); mp 68–70 °C.
+
+
+
MS: m/z (%) = 394 (M + 2, 32.8), 393 (M + 1, 66.3), 392 (M ,
1.2), 307 (95.8), 276 (11.3), 249 (21.8), 221 (29.0), 178 (10.6), 149
17.9), 133 (43.3), 105 (24.5), 86 (100.0), 57 (95.3).
IR (KBr): 563 (w), 709 (w), 748 (s), 840 (w), 918 (w), 1026 (w),
8
(
1
1
1
110 (s), 1203 (s), 1257 (s), 1365 (w), 1450 (s), 1512 (m), 1612 (s),
728 (s), 2854 (w), 2965 cm (s).
–
1
Anal. Calcd for C H N O (392.496): C, 73.44; H, 7.19; N, 7.14.
24
28
2
3
H NMR (CDCl ): δ = 1.22 (s, 9 H), 3.11 (t, J = 4.5 Hz, 4 H), 3.78
3
Found: C, 73.47; H, 7.15; N, 7.11.
(t, J = 4.5 Hz, 4 H), 4.06 (s, 2 H), 7.06–7.32 (m, 7 H), 7.55–7.61 (m,
1
H).
4-{[2-Benzyl-3-(piperidin-1-yl)-1-benzofuran-5-yl]methyl}mor-
pholine (5k)
13
C NMR (CDCl ): δ = 30.30, 30.66, 51.54, 66.61, 110.60, 118.80,
3
Brown solid; yield: 347 mg (89%); mp 68–72 °C.
1
1
20.98, 122.34, 124.40, 125.02, 127.13, 127.55, 134.00, 148.19,
49.34, 152.39.
IR (KBr): 617 (w), 756 (w), 794 (w), 864 (m), 1010 (m), 1110 (s),
1
211 (m), 1257 (m), 1380 (s), 1450 (s), 1627 (m), 2808 (w), 2854
+
+
+
MS: m/z (%) = 351 (M + 2, 4.6), 350 (M + 1, 11.2), 349 (M ,
2.8), 234 (10.4), 218 (10.7), 147 (32.8), 121 (100.0), 91 (13.2), 73
13.2), 57 (33.0).
–1
(w), 2910 cm (m).
1
(
1
H NMR (CDCl ): δ = 1.52–1.54 (m, 2 H), 1.63–1.69 (m, 4 H), 2.36
3
(
(
1
t, J = 4.5 Hz, 4 H), 3.05 (t, J = 5 Hz, 4 H), 3.48 (s, 2 H), 3.62–3.66
m, 4 H), 4.07 (s, 2 H), 6.96–7.22 (m, 7 H), 7.46–7.49 (m, 1 H).
Anal. Calcd for C H NO (349.471): C, 79.05; H, 7.79; N, 4.01.
Found: C, 79.07; H, 7.77; N, 4.05.
2
3
27
2
3
C NMR (CDCl ): δ = 24.29, 26.83, 32.54, 53.60, 53.75, 63.63,
3
1
-[2-(4-tert-Butylbenzyl)-1-benzofuran-3-yl]-4-phenylpiper-
67.04, 111.14, 120.63, 124.61, 126.32, 126.59, 128.47, 128.56,
130.14, 131.20, 138.54, 149.22, 152.84.
azine (5h)
White solid; yield: 360 mg (85%); mp 128–131 °C.
+
+
+
MS: m/z (%) = 393 (M + 3, 11.1), 392 (M + 2, 31.2), 391 (M + 1,
5
1
IR (KBr): 524 (w), 563 (w), 694 (m), 756 (s), 810 (w), 840 (w), 894
+
0.5), 390 (M , 96.7), 339 (14.8), 305 (86.1), 292 (13.1), 231 (40.6),
78 (14.7), 149 (31.5), 133 (65.7), 112 (53.5), 86 (100.0), 57 (73.1).
(
(
1
w), 933 (m), 1026 (s), 1134 (s), 1226 (s), 1265 (m), 1334 (w), 1373
m), 1450 (s), 1496 (s), 1596 (s), 2815 (w), 2954 (m), 3031 cm (w).
–1
Anal. Calcd for C H N O (390.523): C, 76.89; H, 7.74; N, 7.17.
25
30
2
2
H NMR (CDCl ): δ = 1.30 (s, 9 H), 3.36 (s, 8 H), 4.16 (s, 2 H),
3
Found: C, 76.92; H, 7.77; N, 7.15.
6.91–7.41 (m, 12 H), 7.98–7.71 (m, 1 H).
1
3
4-{[2-Benzyl-3-(4-phenylpiperazin-1-yl)-1-benzofuran-5-
yl]methyl}morpholine (5l)
C NMR (CDCl ): δ = 31.47, 31.90, 34.48, 50.27, 52.49, 111.74,
3
1
1
16.44, 120.02, 120.06, 122.12, 123.48, 125.56, 126.34, 128.31,
28.83, 129.26, 135.24, 149.33, 150.25, 151.63, 153.56.
Brown oil; yield: 415 mg (89%).
IR (KBr): 524 (w), 694 (s), 756 (s), 864 (w), 1026 (m), 1118 (s),
+
+
+
MS: m/z (%) = 427 (M + 2, 1.6), 426 (M + 1, 4.0), 425 (M , 7.1),
2
5
1
1
1
226 (s), 1257 (m), 1334 (m), 1380 (m), 1450 (s), 1496 (s), 1596 (s),
643 (m), 2815 (m), 3031 cm (w).
91 (3.8), 234 (11.2), 161 (2.6), 132 (33.0), 105 (14.1), 83 (100.0),
7 (10.8).
–1
H NMR (CDCl ): δ = 2.36–2.39 (m, 4 H), 3.27 (s, 8 H), 3.47 (s, 2
3
Anal. Calcd for C H N O (424.584): C, 82.04; H, 7.60; N, 6.60.
Found: C, 82.09; H, 7.63; N, 6.57.
2
9
32
2
H), 3.63 (t, J = 4.75 Hz, 4 H), 4.1 (s, 2 H), 6.78–7.27 (m, 12 H),
7.54–7.55 (m, 1 H).
1
3
4
-[2-Benzyl-7-(morpholin-4-ylmethyl)-1-benzofuran-3-yl]mor-
C NMR (CDCl ): δ = 32.40, 50.23, 52.42, 53.54, 63.55, 66.95,
3
pholine (5i)
111.32, 116.41, 116.57, 120.06, 120.63, 124.92, 126.16, 126.47,
1
Brown solid; yield: 309 mg (79%); mp 84–91 °C.
26.91, 128.57, 129.20, 131.41, 138.23, 150.47, 151.53, 152.93.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 2489–2498

PAPER
2,3-Disubstituted 1-Benzofurans Using Cu O Nanoparticles
2497
2
+
+
MS: m/z (%) = 469 (M + 1, 0.5), 468 (M , 2.8), 325 (2.3), 280
19.1), 161 (17.8), 132 (100), 91 (47.0), 56 (51.8).
J. Comb. Chem. 2010, 12, 696. (c) Patil, S. S.; Patil, S. V.;
Bobade, V. D. Synlett 2011, 2379.
(
(
6) (a) Nguyen, R. V.; Li, C.-J. Synlett 2008, 1897. (b) Sakai,
Anal. Calcd for C H N O (467.609): C, 77.06; H, 7.11; N, 8.99.
Found: C, 77.09; H, 7.10; N, 8.96.
30
33
3
2
N.; Uchida, N.; Konakahara, T. Tetrahedron Lett. 2008, 49,
3437. (c) Zhang, X.; Li, D.; Jia, X.; Wang, J.; Fan, X. Catal.
4
-{2-Benzyl-5-[(4-{[2-benzyl-3-(morpholin-4-yl)-1-benzofuran-
-yl]methyl}piperazin-1-yl)methyl]-1-benzofuran-3-yl}mor-
Commun. 2011, 12, 839.
(7) For a recent monograph, see: Multicomponent Reactions;
Zhu, J.; Bienayme, H., Eds.; Wiley-VCH: Weinheim, 2005.
5
pholine (5m)
Brown solid; yield: 416 mg (80%); mp 155–157 °C.
(
8) For reviews, see: (a) Sunderhaus, J. D.; Martin, S. F. Chem.
Eur. J. 2009, 15, 1300. (b) Isambert, N.; Lavilla, R. Chem.
Eur. J. 2008, 14, 8444. (c) Domling, A. Chem. Rev. 2006,
106, 17. (d) Orru, R. V. A.; de Greef, M. Synthesis 2003,
1471. (e) Bienayme, H.; Hulme, C.; Oddon, G.; Schmitt, P.
Chem. Eur. J. 2000, 6, 3321. (f) Domling, A.; Ugi, I. Angew.
Chem. Int. Ed. 2000, 39, 3168. (g) Ugi, I.; Domling, A.;
Werner, B. J. Heterocycl. Chem. 2000, 37, 647. (h) Weber,
L.; Illgen, K.; Almstetter, M. Synlett 1999, 366.
IR (KBr): 547 (w), 702 (s), 794 (w), 918 (w), 1010 (m), 1110 (s),
1211 (m), 1265 (m), 1373 (m), 1450 (s), 1612 (m), 2815 (m), 2954
–1
cm (m).
1
H NMR (CDCl ): δ = 2.52 (s, 8 H), 3.16 (t, J = 4.5 Hz, 8 H), 3.59
3
(s, 4 H), 3.85 (t, J = 4.5 Hz, 8 H), 4.15 (s, 4 H), 7.16–7.31 (m, 14 H),
7.57 (s, 2 H).
13
C NMR (CDCl ): δ = 32.33, 52.55, 52.90, 63.05, 6769, 111.25,
3
1
1
20.50, 125.01, 125.93, 126.45, 128.52, 128.69, 131.68, 138.17,
50.45, 152.85.
(i) Armstrong, R. W.; Combs, A. P.; Tempest, P. A.; Brown,
S. D.; Keating, T. A. Acc. Chem. Res. 1996, 29, 123. (j) Ugi,
I.; Domling, A.; Horl, W. Endeavour 1994, 18, 115.
(k) Posner, G. H. Chem. Rev. 1986, 86, 831. (l) Choudhury,
L. H.; Parvin, T. Tetrahedron 2011, 67, 8213.
+
+
+
MS: m/z (%) = 698 (M + 2, 0.8), 697 (M + 1, 1.5), 696 (M , 4.9),
09 (12.1), 391 (45.3), 350 (10.1), 307 (98.6), 242 (60.6), 176
15.4), 142 (80.2), 91 (83.3), 56 (100.0).
5
(
(
9) (a) Denmark, S. E.; Smith, R. C.; Chang, W.-T. T.; Muhuhi,
J. M. J. Am. Chem. Soc. 2009, 131, 3104. (b) Wang, S.; Li,
P.; Yu, L.; Wang, L. Org. Lett. 2011, 13, 5968. (c) Zhou, L.;
Shi, Y.; Xiao, Q.; Liu, Y.; Ye, F.; Zhang, Y.; Wang, J. Org.
Lett. 2011, 13, 968. (d) Wang, J.-R.; Manabe, K. J. Org.
Chem. 2010, 75, 5340. (e) Pei, T.; Chen, C.-Y.; DiMichele,
L.; Davies, I. W. Org. Lett. 2010, 12, 4972. (f) Maimone, T.
J.; Buchwald, S. L. J. Am. Chem. Soc. 2010, 132, 9990.
Anal. Calcd for C H N O (696.886): C, 75.84; H, 6.94; N, 8.04.
Found: C, 75.89; H, 6.97; N, 8.01.
44
48
4
4
Acknowledgment
We gratefully acknowledge the support of this work by the Shiraz
University Research Council.
(
g) Nakamura, I.; Mizushima, Y.; Yamamoto, Y. J. Am.
Chem. Soc. 2005, 127, 15022. (h) Anderson, K. W.; Ikawa,
T.; Tundel, R. E.; Buchwald, S. L. J. Am. Chem. Soc. 2006,
Supporting Information for this article is available online
at
http://www.thieme-connect.com/products/ejournals/journal/
1
28, 10694. (i) De Luca, L.; Giacomelli, G.; Nieddu, G.
1
0.1055/s-00000084.SunpfgIpi
o
nr
i
o
J. Org. Chem. 2007, 72, 3955. (j) Shibata, T.; Hashimoto,
Y.-K.; Otsuka, M.; Tsuchikama, K.; Endo, K. Synlett 2011,
2
2
075. (k) Yue, D.; Yao, T.; Larock, R. C. J. Org. Chem.
005, 70, 10292. (l) Hirano, K.; Satoh, T.; Miura, M. Org.
References
(
1) (a) Moss, G. P. Pure Appl. Chem. 2000, 72, 1493.
Lett. 2011, 13, 2395. (m) Duan, X.-F.; Shen, G.; Zhang, Z.-
B. Synthesis 2010, 2547. (n) Fiandanese, V.; Bottalico, D.;
Marchese, G.; Punzi, A.; Quarta, M. R. Synthesis 2009,
3853.
(
b) Zareba, K. M. Drugs Today 2006, 42, 75. (c) Kumar, V.;
Ackerman, J. H.; Alexander, M. D.; Bell, M. R.;
Christiansen, R. G.; Dung, J. S.; Jaeger, E. P.; Herrmann, J.
L. Jr.; Krolski, M. E.; McKloskey, P.; Batzold, F. H.;
Juniewicz, P. E.; Reel, J.; Snyder, B. W.; Winneker, R. C.
J. Med. Chem. 1994, 37, 4227. (d) Ohemeng, K. A.;
Appollina, M. A.; Nguyen, V. N.; Schwender, C. F.; Singer,
M.; Steber, M.; Ansell, J.; Argentieri, D.; Hageman, W.
J. Med. Chem. 1994, 37, 3663. (e) Zacchino, S.; Rodriguez,
G.; Pezzenati, G.; Orellana, G.; Enriz, R.; Gonzalez Sierra,
M. J. Nat. Prod. 1997, 60, 659.
(10) (a) Tang, B.-X.; Wang, F.; Li, J.-H.; Xie, Y.-X.; Zhang, M.-
B. J. Org. Chem. 2007, 72, 6294. (b) Li, J.-H.; Tang, B.-X.;
Tao, L.-M.; Xie, Y.-X.; Liang, Y.; Zhang, M.-B. J. Org.
Chem. 2006, 71, 7488. (c) Chanda, K.; Rej, S.; Huang, M. H.
Chem. Eur. J. 2013, 19, 16036. (d) Sharghi, H.; Aberi, M.
Synlett 2014, 25, 1111.
(11) (a) Sharghi, H.; Hosseini-Sarvari, M.; Moeini, F.; Khalifeh,
R. Helv. Chim. Acta 2010, 93, 435. (b) Sharghi, H.;
(
2) (a) Flynn, B. L.; Hamel, E.; Jung, M. K. J. Med. Chem. 2002,
Hosseini-Sarvari, M.; Moeini, F. Can. J. Chem. 2008, 86,
1044. (c) Sharghi, H.; Khoshnood, A.; Khalifeh, R. Iran. J.
Sci. Technol. 2012, A1, 25. (d) Sharghi, H.; Khoshnood, A.;
Doroodmand, M. M.; Khalifeh, R. J. Iran. Chem. Soc. 2012,
9, 231. (e) Sharghi, H.; Aberi, M.; Doroodmand, M. M.
J. Iran. Chem. Soc. 2012, 9, 189. (f) Sharghi, H.; Khalifeh,
R.; Mansouri, S. G.; Aberi, M.; Eskandari, M. M. Catal. Lett.
2011, 141, 1845. (g) Sharghi, H.; Khalifeh, R.; Moeini, F.;
Beyzavi, M. H.; Salimi Beni, A.; Doroodmand, M. M.
J. Iran. Chem. Soc. 2011, 8, S89. (h) Sharghi, H.; Jokar, M.;
Doroodmand, M. M.; Khalifeh, R. Adv. Synth. Catal. 2010,
352, 3031. (i) Sharghi, H.; Khalifeh, R.; Salimi Beni, A.
J. Iran. Chem. Soc. 2010, 7, 275. (j) Sharghi, H.; Beyzavi,
M. H.; Safavi, A.; Doroodmand, M. M.; Khalifeh, R. Adv.
Synth. Catal. 2009, 351, 2391. (k) Sharghi, H.; Khalifeh, R.;
Doroodmand, M. M. Adv. Synth. Catal. 2009, 351, 207.
(l) Sharghi, H.; Aberi, M.; Doroodmand, M. M. Adv. Synth.
4
5, 2670. (b) Lambert, J. D.; Meyers, R. O.; Timmermann,
B. N.; Dorr, R. T. Cancer Lett. 2001, 171, 47. (c) Thompson,
L. U.; Rickard, S. E.; Orcheson, L. J.; Seidl, M. M.
Carcinogenesis 1996, 17, 1373. (d) Navarro, E.; Alonso, S.
J.; Trujillo, J.; Jorge, E.; Perez, C. J. Nat. Prod. 2001, 64,
134. (e) Gangjee, A.; Devraj, R.; McGuire, J. J.; Kisliuk, R.
L. J. Med. Chem. 1995, 38, 3798.
(
3) (a) Silva, D. H. S.; Pereira, F. C.; Zanoni, M. V. B.; Yoshida,
M. Phytochemistry 2001, 57, 437. (b) Maeda, S.; Masuda,
H.; Tokoroyama, T. Chem. Pharm. Bull. 1994, 42, 2500.
4) (a) Borsato, M. L. C.; Grael, C. F. F.; Souza, G. E. P.; Lopes,
N. P. Phytochemistry 2000, 55, 809. (b) Day, S. H.; Chiu, N.
Y.; Tsao, L. T.; Wang, J. P.; Lin, C. N. J. Nat. Prod. 2000,
(
6
3, 1560.
(5) (a) Yan, B.; Liu, Y. Org. Lett. 2007, 9, 4323. (b) Bai, Y.;
Zeng, J.; Ma, J.; Liu, W.; Gorityala, B. K.; Liu, X.-W.
©
Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 2489–2498

2498
H. Sharghi et al.
PAPER
Catal. 2008, 350, 2380. (m) Sharghi, H.; Khalifeh, R. Can.
J. Chem. 2008, 86, 426. (n) Sharghi, H.; Asemani, O.;
Khalifeh, R. Synth. Commun. 2008, 38, 1128. (o) Sharghi,
H.; Khalifeh, R. Heterocycles 2007, 71, 1601. (p) Sharghi,
H.; Salimi Beni, A. Helv. Chim. Acta 2007, 90, 1373.
Curran, K.; Brooijmans, N.; Bennett, E. M.; Toral-Barza, L.;
Hollander, I.; Ayral-Kaloustian, S.; Yu, K. J. Med. Chem.
2009, 52, 7942.
(14) (a) Ramu, E.; Varala, R.; Sreelatha, N.; Adapa, S. R.
Tetrahedron Lett. 2007, 48, 7184. (b) Sreedhar, B.; Suresh
Kumar, A.; Surendra Reddy, P. Tetrahedron Lett. 2010, 51,
1891. (c) Bhatte, K. D.; Sawant, D. N.; Deshmukh, K. M.;
Bhanage, B. M. Catal. Commun. 2011, 16, 114. (d) Yoo,
W.-J.; Zhao, L.; Li, C.-J. Aldrichimica Acta 2011, 44, 43.
(e) Li, C.-J. Acc. Chem. Res. 2010, 43, 581.
(
(
12) Shen, G.; Lv, X.; Qian, W.; Bao, W. Tetrahedron Lett. 2008,
9, 4556.
4
13) (a) Sammons, M.; Jennings, S. M.; Herr, M.; Hulford, C. A.;
Wei, L.; Hallissey, J. F.; Kiser, E. J.; Wright, S. W.;
Piotrowski, D. W. Org. Process Res. Dev. 2013, 17, 934.
(b) Zask, A.; Kaplan, J.; Verheijen, J. C.; Richard, D. J.;
(15) Kooti, M.; Matouri, L. Sci. Iran. 2010, 17, 73.
Synthesis 2014, 46, 2489–2498
© Georg Thieme Verlag Stuttgart · New York