Trimethylsilyl iodide as a multifunctional agent in the one-pot synthesis of 9-(1 H -Indol-3-yl)xanthen-4-(9 H)-ones from O -methyl protected salicylaldehydes, indoles, and β-dicarbonyl compounds

Article abstract of DOI:10.1055/s-0033-1338633

Trimethylsilyl iodide (TMSI) is introduced as an efficient reagent for the one-pot synthesis of 9-(1H-indol-3-yl)xanthen-4-(9H)-ones using the reaction of 2-methoxybenzaldehydes (as O-methyl protected salicylaldehydes), indoles, and β-dicarbonyl compounds. In this protocol, a set of TMSI reactions involving silylation, silyl enol ether formation, methyl deprotection, and nucleophilic substitution/cyclization are performed to furnish the target product. The key step in this protocol is the deprotection of the methoxy group by TMSI. Georg Thieme Verlag Stuttgart, New York.

Full text of DOI:10.1055/s-0033-1338633

PAPER
▌2071
pTaprerimethylsilyl Iodide as a Multifunctional Agent in the One-Pot Synthesis of
-(1H-Indol-3-yl)xanthen-4-(9H)-ones from O-Methyl Protected Salicylaldehydes,
9
Indoles, and β-Dicarbonyl Compounds
Synthesis of 9-(1H-Indol-3-yl)xanthen-4-(9H)-ones Using TMSI
Ali Khalafi-Nezhad,* Maryam Nourisefat, Farhad Panahi*
Department of Chemistry, College of Sciences, Shiraz University, Shiraz, 71454, Iran
E-mail: khalafi@chem.susc.ac.ir; E-mail: panahi@shirazu.ac.ir; Fax +98(711)2280926
Received: 05.02.2014; Accepted after revision: 04.04.2014
another report, TMSI has been used to promote the reac-
tion between salicylaldehydes and ketones for the con-
Abstract: Trimethylsilyl iodide (TMSI) is introduced as an effi-
cient reagent for the one-pot synthesis of 9-(1H-indol-3-yl)xanthen-
struction of benzopyranic[2,3-b]ketals and spiroketals in a
4-(9H)-ones using the reaction of 2-methoxybenzaldehydes (as O-
12
one-step procedure.
methyl protected salicylaldehydes), indoles, and β-dicarbonyl com-
pounds. In this protocol, a set of TMSI reactions involving si-
lylation, silyl enol ether formation, methyl deprotection, and
nucleophilic substitution/cyclization are performed to furnish the
target product. The key step in this protocol is the deprotection of
the methoxy group by TMSI.
In a continuation of our previous studies on multicompo-
1
3
nent reactions, herein, we report a novel and practical
synthetic method for the synthesis of 9-(1H-indol-3-
yl)xanthen-4-(9H)-ones through the reaction of O-methyl
protected salicylaldehydes, indoles, and β-dicarbonyl
compounds by using TMSI as a multifunctional agent. It
is noteworthy that the 9-(1H-indol-3-yl)xanthen-4-(9H)-
ones are a class of xanthenes with versatile biological ac-
Key words: trimethylsilyl iodide, xanthenes, salicylaldehydes, in-
doles, multicomponent reactions
1
4
tivities. Consequently, the synthesis of new derivatives
and the development of new methodologies for the con-
Trimethylsilyl iodide (TMSI) is a proficient reagent that
has been used for a range of specific organic transforma-
1
5
1
struction of this class of materials is of clear interest.
tions such as ring opening of cyclopropyl ketones, spiro-
2
cyclization of amines, dealkylation of alkyl esters and
alkyl ethers, conversion of alkyl carbamates into Table 1 Optimization of the Reaction Conditionsa
3
4
amines, and transformation of α,β-unsaturated sulfoxides
NH
5
into carbonyl compounds. It has been widely applied for
the silylation of alcohols and amines, and used for silyl
enol ether formation of ketones or dicarbonyl com-
O
CHO
O
TMSCl/NaI
+
+
O
solvent
O
N
6
pounds. This reagent can also efficiently promulgate the
Me
H
temperature
O
7
methyl-deprotection of methoxy groups. Furthermore, as
24 h
1
a
2a
3a
4a
a reducing agent, TMSI has been used for the reduction of
8
unsaturated compounds and aldehydes. Nucleophilic ad- Entry
dition reaction of TMSI to aldehydes results in the pro-
duction of a reactive intermediate (A), which undergoes
TMSCl/NaI Solvent
Temp
(°C)
Yield of 4a
(%)
b
(
equiv)
1
2
3
4
5
6
7
8
9
0
0
1
5
5
5
8
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
CHCl3
THF
r.t.
r.t.
r.t.
50
80
50
50
50
50
r.t.
50
0
trace
18
55
39
78
86
63
67
32
0c
9
subsequent reaction with other nucleophiles (Scheme 1).
Nu
I
Nu
TMSI
TMS
I
TMS
R
O
R
O
R
Nu/I/OTMS
R
O
A
Scheme 1 Nucleophilic addition reaction of TMSI to aldehydes
1
0
Through the use of TMSI as a multifunctional agent one
can design a protocol in which all or a set of its transfor-
mations can be accomplished in a one-pot procedure. In
fact, this protocol allows the preparation of a highly com-
plex product in a single-step process. Recently, TMSI has
been used to promote a reaction of salicylaldehydes and β-
10
10
10
10
10
1
MeCN
MeCN
1
1
dicarbonyl compounds to prepare 4H-benzopyrans. In 11
a
Reaction conditions: 2-methoxybenzaldehyde (1 mmol), dimedone
1 mmol), indole (1 mmol).
Isolated yield.
SYNTHESIS 2014, 46, 2071–2078
Advanced online publication: 14.05.2014
(
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
b
c
DOI: 10.1055/s-0033-1338633; Art ID: SS-2014-z0089-OP
Georg Thieme Verlag Stuttgart · New York
Only TMSCl (10 equiv) was used.
©

2072
A. Khalafi-Nezhad et al.
PAPER
The current design of this study was based on the use of substrate under a range of conditions. The results of the
TMSI transformations to obtain the target product 9-(1H- optimization study are summarized in Table 1.
indol-3-yl)xanthen-4-(9H)-ones in a single-step process.
It was envisioned that the product could be obtained by si-
lylation, silyl enol ether formation, methyl deprotection,
and nucleophilic substitution and cyclization reactions,
which are all promoted by TMSI.
When the reaction was conducted without any reagent in
MeCN, no product was observed (Table 1, entry 1). When
5
equivalents of TMSI (generated in situ from TMSCl and
16
NaI) was used, 18% 4a produced (Table 1, entry 3). The
product yield was enhanced to 55% when the reaction was
To achieve appropriate conditions for the synthesis of 9- performed at 50 °C, however, upon increasing the temper-
1H-indol-3-yl)xanthen-4-(9H)-one derivatives using ature to 80 °C, the product yield decreased to 39%, dem-
TMSI, we tested the reaction of 2-methoxybenzaldehyde onstrating that temperature plays a significant role in the
(
(1a), dimedone (2a), and indole (3a) as a simple model progress of the reaction (Table 1, entries 4 and 5). We also
investigated the amount of TMSI required for the reac-
R2
N
O
CHO
R3
R4
TMSCl/NaI (10 equiv)
MeCN
O
+
R3
+
R1
O
N
R2
O
R4
Me
5
0 °C, 24 h
O
1
2
3
R1
4
a–p
NH
NH
NH
NH
Br
O
O
O
O
O
O
O
HO
O
4a 86%
4b 85%
4c 78%
4d 82%
Me
Me
N
N
NH
NH
O
O
O
O
HO
O
O
O
O
4e 81%
4f 87%
4g 84%
4h 84%
Me
NH
N
NH
NH
Br
O
O
O
O
NH
HO
O
HO
O
O
O
N
O
H
4i 82%
4j 81%
4k 80%
4l 80%
Me
N
NH
NH
NH
O
O
O
O
NH
NH
NH
O
N
O
O
N
H
S
O
N
O
X
O
H
H
4m 78%
4n 79%
4o 75%
4p X = OMe 51%
q X = OH 29%
4
NH
NH
NH
O
O
O
NH
NH
Br
O
N
H
O
Br
O
2
O N
O
N
H
O
4
r 75%
4s 78%
4t 70%
Scheme 2 Products of reaction between 2-methoxybenzaldehydes (1 mmol), indoles (1 mmol), and β-dicarbonyl compounds (1 mmol) in the
presence of TMSI reagent. All yields are isolated yields.
Synthesis 2014, 46, 2071–2078
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of 9-(1H-Indol-3-yl)xanthen-4-(9H)-ones Using TMSI
2073
tion, and 10 equivalents of TMSI were established as op- ide group afforded 4l, 4m, and 4n in good yields. A
timal (Table 1, entries 4, 6, and 7). Subsequently, the further extension of this new multicomponent coupling
effect of solvent was examined, however, CHCl and tet- sequence was demonstrated by the preparation of 10-(1H-
3
rahydrofuran (THF) showed no superiority to MeCN (Ta- indol-3-yl)-2-thioxo-1,2,3,10-tetrahydro-9-oxa-1,3-diaza-
ble 1, entries 8 and 9). The reaction yield decreased anthracen-4-one (4o) using thiobarbituric acid. Overall,
significantly at r.t., which can be attributed to the methyl- the yield of barbituric acids was less than those of dime-
deprotection step, because higher temperature is neces- done and cyclohexane-1,3-dione. Interestingly, the struc-
1
6
sary for this stage (Table 1, entry 10). In the absence of tural diversity of this process was further increased by
NaI (for the generation of TMSI in situ) no product was using 2,4-dimethoxybenzaldehyde, which resulted in the
observed, suggesting TMSI is also a key reagent for this formation of compound 4p with 51% yield; this reaction
process. The result of this experiment also suggests that was accompanied by the formation of 7-demethylated
TMSCl does not promote this reaction alone (Table 1, en- product 4q in 29% yield.
try 11). Thus, a simple system including TMSI (10 equiv)
and MeCN at 50 °C was chosen as the optimized reaction
conditions.
Although, the reactions of salicyladehydes, 1,3-diketones,
and indoles have been well established, we developed an
efficient strategy to improve the scope of this reaction by
17
The scope of the reaction was investigated with a selec- using 2-methoxybenzaldehydes as O-methyl protected
tion of commercially available salicylaldehydes, indoles, salicylaldehydes. This protocol also demonstrated a new
and dicarbonyl compounds; the results are summarized in approach to TMSI-catalyzed multicomponent reactions
Scheme 2. A variety of dicarbonyl compounds and in- containing more TMSI-transformations.
doles were applicable to the reaction, affording the prod-
ucts in good to excellent yields.
Although the mechanism of the current reaction has not
been fully established at the present stage, a possible reac-
The structural diversity of this process was increased by tion pathway is shown in Scheme 3. Addition of TMSI to
using different indoles, leading to the formation of new in- the C=O bond in the aldehyde results in the formation of
dole-based xanthene derivatives. Another important fea- intermediate A. TMSI can also convert the 1,3-diketone
ture of this method is the use of different salicylaldehydes into the corresponding silyl enol ether. Nucleophilic at-
to generate the desired derivatives, however, the electron- tack of the silyl enol ether/enol form of 1,3-diketone on A
ic properties of the substituents on the salicylic aldehydes resulted in the production of intermediate B. Subsequent-
had a significant influence on the reaction yield. The ap- ly, nucleophilic addition of indole to B with the elimina-
plication of β-dicarbonyl compounds (dimedone, cyclo- tion of TMSOH/HI affords intermediate C. It should be
hexane-1,3-dione, and barbituric acids) provided a handle noted that the latter intermediate can also be generated
with which to introduce other groups at the xanthene ring through a second pathway (dashed line). In the latter path-
by using this multicomponent reaction. Under the opti- way, the indole first adds to A to produce intermediate D,
mized reaction conditions, barbituric acid having an am- and then nucleophilic addition of β-dicarbonyl compound
R
N
O
O
2
H O
TMSI
O
O
Me
R
O
N
R
3
OTMS
N
I
O
2
I/TMSO
A
O HO
Me
O
OTMS
E
Me
MeI
R
O
D
N
O
O
OTMS/I
O
TMSI
TMSI
O
O
O
O
Me
R
Me
B
N
C
O
2
3
Scheme 3 Proposed reaction mechanism for one-pot synthesis of 9-(1H-indol-3-yl)xanthen-4-(9H)-ones through reaction of salicyladehydes,
indoles, and β-dicarbonyl compounds in the presence of TMSI
©
Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 2071–2078

2074
A. Khalafi-Nezhad et al.
PAPER
(either in the enol or silyl enol ether form) to D results in Interestingly, under the optimized reaction conditions, in-
the production of C. Subsequently, methyl deprotection of dole reacts with 2-methoxybenzaldehyde to produce
2
0
intermediate C can be performed by TMSI to give inter- bis(indolyl)methane 7a and 7a′, suggesting that in the
mediate E. Finally, intramolecular condensation of E presence of indole (as a nucleophile) the reduction process
gives the desired product.
is not accomplished (Scheme 5).
Further experiments were conducted to obtain a deeper in- It is worth mentioning that this protocol is highly depen-
sight into the reaction mechanism. When 2-methoxybenz- dent on the strength of the nucleophile used. For example,
aldehyde and dimedone were used in the reaction, the by the use of 5-nitro-1H-indole the obtained product was
prominent product was 4H-benzopyran 6a11 (Scheme 4). 6a, demonstrating that, in the presence of a weak nucleo-
This experiment demonstrates that TMSI has three impor- phile, reduction is the prominent process (Scheme 6).
1
8
tant roles in this reaction: (1) silyl enol ether formation,
2) methyl deprotection, and (3) reduction. It is known
In summary, we have developed a new and efficient meth-
od for the synthesis of 9-(1H-indol-3-yl)xanthen-4-(9H)-
one derivatives in high yields by using TMSI as a multi-
functional agent. A set of reactions involving, silylation,
silyl enol ether formation, methyl deprotection, and nu-
cleophilic substitution/cyclization are proposed to be me-
diated by the TMSI reagent to furnish the target product.
Further studies on this reaction are expected to lead to new
multicomponent reactions for the synthesis of new com-
pounds using TMSI as a multifunctional agent.
(
that TMSI acts as a reducing agent through HI forma-
tion.19
O
O
O
O
TMSCl/NaI (10 equiv)
Me
+
MeCN, 50 °C
24 h
O
O
1
mmol
1 mmol
6a
73%
OTMS
Chemicals were purchased from Fluka and Aldrich and used with-
1
13
out further purification. H and C NMR spectra were recorded
with a Bruker Avance 250 MHz spectrometer in DMSO solution
with TMS as internal standard. Chemical shifts are given in the δ
scale in parts per million (ppm) and the bonds are assigned as singlet
I
I/OTMS
O
Me
O
O
Me
O
O
Me
A
reduction
(
s), doublet (d), triplet (t), and multiplet (m). FTIR spectroscopy
O
(Shimadzu FT-IR 8300 spectrophotometer) was employed for the
characterization of compounds. Melting points were determined in
open capillary tubes in a Barnstead Electrothermal 9100 BZ circu-
lating oil melting point apparatus. The reactions were monitored by
TLC on silica gel PolyGram SILG/UV254 plates.
O
O
F
G
OTMS
methyl deprotection
then cyclization
E
General Procedure
To a stirring solution of 2-methoxybenzaldehydes (1 mmol) in
MeCN (5 mL) containing TMSCl (10 mmol) and NaI (10 mmol)
were added diketone (1 mmol) and indole (1 mmol), and the result-
ing mixture was vigorously stirred for 24 h at 50 °C (reaction mon-
itored by TLC). The mixture was then extracted with EtOAc (3 × 10
mL), the combined extract was washed with brine (2 × 3 mL) and
dried (Na SO ). Removal of the solvent under reduced pressure
6
a
Scheme 4 Synthesis of 4H-benzopyrans by using the reaction of 2-
methoxybenzaldehyde and dimedone under the optimized conditions.
Both the reduction and methyl-deprotection roles of TMSI are needed
to form 4H-benzopyran product.
2
4
HN
HN
O
TMSCl/NaI (10 equiv)
HN
+
+
HN
HN
MeCN, 50 °C
4 h
O
Me
mmol
2
O
HO
Me
1
2.2 mmol
7
a'
7
a
3
7%
5
1%
HN
HN
HN
A
+
7a
I/OTMS
Me
methyl deprotection
O
(
D)
7
a'
Scheme 5 Reaction of indole with 2-methoxybenzaldehyde in the presence of TMSI under optimized conditions results in the production of
bis(indolyl)methanes 7a and 7a′. This reaction confirms the nucleophilic addition of indole to intermediate A and D.
Synthesis 2014, 46, 2071–2078
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of 9-(1H-Indol-3-yl)xanthen-4-(9H)-ones Using TMSI
2075
O
O
NH
TMSCl/NaI (10 equiv)
MeCN, 50 °C
+
+
6a
1%
O
O
7
Me
2
4 h
NO
2
Me
O
O
I/OTMS
O
Me
methyl deprotection
then cyclization
O
6
a
O
reduction
O
F
NO
HN
2
HN
HN
NO
2
NO
2
3
H C
O
O
O
methyl deprotection
then cyclization
O
O
G
4
v
Scheme 6 Reaction of 2-methoxybenzaldehyde, dimedone, and 5-nitro-1H-indole under the optimized conditions resulted in the production
of 4H-benzopyran 6a. This reaction confirms that TMSI acts as a reducing agent in the presence of weak nucleophiles.
gave almost pure products, which were further purified by recrys-
tallization from EtOH.
IR (KBr): 3463, 3193, 2954, 2869, 2360, 1643, 1589, 1488, 1380,
1311, 1234, 1149, 1026, 756, 655, 578, 478 cm .
–1
1
H NMR (250 MHz, DMSO-d , TMS): δ = 0.89 (s, 3 H, CH ), 1.02
6
3
9
-(1H-Indol-3-yl)-3,3-dimethyl-3,4-dihydro-2H-xanthen-
(9H)-one (4a)
(
5
1
s, 3 H, CH ), 2.02–2.29 (m, 2 H, CH ), 2.50–2.67 (m, 2 H, CH ),
.16 (s, 1 H, CH), 7.00–7.25 (m, 7 H, ArH), 7.57 (s, 1 H, ArH),
1.03 (br s, 1 H, NH).
1
3
2
2
Yield: 0.29 g (86%); white solid; mp 190–193 °C.
–1
IR (KBr): 3410, 2878, 1643, 1373, 1227, 1180, 741 cm .
13
C NMR (62.5 MHz, DMSO-d , TMS): δ = 26.3, 28.2, 28.7, 31.5,
1
6
H NMR (250 MHz, DMSO-d , TMS): δ = 0.91 (s, 3 H, CH ), 1.03
6
3
5
1
0.0, 111.1, 111.8, 113.5, 116.1, 119.5, 120.6, 123.2, 124.3, 124.8,
25.3, 126.9, 127.5, 129.72, 134.8, 148.8, 164.3, 196.2.
(
1
7
s, 3 H, CH ), 2.03–2.29 (m, 2 H, CH ), 2.61 (s, 2 H, CH ), 5.17 (s,
H, CH), 6.87 (t, J = 7.5 Hz, 1 H, ArH), 6.94–7.02 (m, 2 H, ArH),
.13 (s, 3 H, ArH), 7.24 (t, J = 5.0 Hz, 2 H, ArH), 7.41 (d,
3
2
2
MS: m/z (%) = 422 (31) [M]+.
J = 7.7 Hz, 1 H, ArH), 10.81 (br s, 1 H, NH).
Anal. Calcd for C H BrNO (422.3): C, 65.41; H, 4.77; N, 3.32.
Found: C, 65.47; H, 4.81; N, 3.39.
2
3
20
2
13
C NMR (62.5 MHz, DMSO-d , TMS): δ = 31.9, 33.8, 34.0, 36.8,
6
5
5.4, 116.7, 117.2, 121.3, 123.5, 123.6, 124.8, 126.0, 127.8, 129.9,
6
-Hydroxy-9-(1H-indol-3-yl)-3,3-dimethyl-3,4-dihydro-2H-
130.4, 131.0, 132.6, 135.0, 141.6, 154.2, 169.4, 201.2.
xanthen-1(9H)-one (4d)
+
MS: m/z (%) = 343 (36) [M] , 344 (28) [M + 1].
Yield: 0.29 g (82%); white solid; mp 126–129 °C.
Anal. Calcd for C H NO (343.4): C, 80.44; H, 6.16; N, 4.08.
Found: C, 80.52; H, 6.19; N, 4.14.
IR (KBr): 3818, 3749, 3386, 2692, 1627, 1458, 1373, 1218, 1172,
1095, 1033, 964.3, 840.9, 740.6, 424.3 cm .
2
3
21
2
–
1
1
H NMR (250 MHz, DMSO-d , TMS): δ = 0.64 (s, 3 H, CH ), 0.78
6
3
3
,3-Dimethyl-9-(2-methyl-1H-indol-3-yl)-3,4-dihydro-2H-xan-
(
s, 3 H, CH ), 1.77–2.02 (m, 2 H, CH ), 2.23–2.33 (m, 2 H, CH ),
.81 (s, 1 H, CH), 6.25 (s, 2 H, ArH), 6.62–6.86 (m, 4 H, ArH), 7.00
then-1(9H)-one (4b)
3
2
2
4
Yield: 0.30 g (85%); white solid; mp 247–250 °C.
(s, 1 H, ArH), 7.11 (s, 1 H, ArH), 9.30 (s, 1 H, OH), 10.51 (s, 1 H,
IR (KBr): 3294, 2962, 2322, 1632, 1458, 1380, 1226, 1180, 1149,
NH).
–1
1018, 933, 871, 632.6 cm .
13
C NMR (62.5 MHz, DMSO-d , TMS): δ = 26.6, 27.9, 28.7, 31.5,
1
6
H NMR (250 MHz, DMSO-d , TMS): δ = 0.80 (s, 3 H, CH ), 1.02
6
3
5
1
0.1, 102.?, 111.4, 112.2, 112.3, 116.0, 118.2, 118.3, 119.9, 120.6,
22.3, 125.2, 130.2, 136.3, 149.4, 156.4, 163.9, 196.0.
(s, 3 H, CH ), 1.96–2.25 (m, 2 H, CH ), 2.47–2.60 (m, 5 H, CH ,
3
2
2
CH ), 5.10 (s, 1 H, CH), 6.73 (t, J = 7.5 Hz, 1 H, ArH), 6.84 (t,
J = 7.5 Hz, 1 H, ArH), 6.93–7.15 (m, 6 H, ArH), 10.74 (br s, 1 H,
3
MS: m/z (%) = 359 (27) [M]+.
NH).
Anal. Calcd for C H NO (359.4): C, 76.86; H, 5.89; N, 3.90.
Found: C, 76.91; H, 5.92; N, 3.96.
2
3
21
3
13
C NMR (62.5 MHz, DMSO-d , TMS): δ = 11.5, 26.4, 27.6, 28.8,
6
3
1
1.4, 50.1, 110.4, 111.6, 114.9, 115.8, 117.0, 118.0, 119.5, 124.6,
25.2, 126.3, 127.3, 130.0, 131.4, 135.0, 148.9, 163.4, 196.0.
6
-Hydroxy-3,3-dimethyl-9-(1-methyl-1H-indol-3-yl)-3,4-di-
hydro-2H-xanthen-1(9H)-one (4e)
MS: m/z (%) = 357 (23) [M]+.
Yield: 0.30 g (81%); white solid; mp 272–275 °C.
Anal. Calcd for C H NO (357.45): C, 80.64; H, 6.49; N, 3.92.
Found: C, 81.68; H, 6.49; N, 4.81.
IR (KBr): 3155, 3055, 2954, 2360, 1627, 1589, 1512, 1473, 1373,
1218, 1141, 1095, 1033, 964, 856, 732 cm .
24
23
2
–
1
1
H NMR (250 MHz, DMSO-d , TMS): δ = 0.88 (s, 3 H, CH ), 1.00
6
3
9
-(5-Bromo-1H-indol-3-yl)-3,3-dimethyl-3,4-dihydro-2H-xan-
(
3
s, 3 H, CH ), 2.02–2.26 (m, 2 H, CH ), 2.55 (s, 2 H, CH ), 3.63 (s,
then-1(9H)-one (4c)
3
2
2
H, CH ), 5.06 (s, 1 H, CH), 6.46–6.55 (m, 2 H, ArH), 6.89–7.10
Yield: 0.32 g (78%); white solid; mp 205–208 °C.
3
©
Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 2071–2078

2076
A. Khalafi-Nezhad et al.
PAPER
(
1
m, 4 H, ArH), 7.27 (d, J = 8.0 Hz, 1 H, ArH), 7.40 (d, J = 7.7 Hz,
H, ArH), 9.67 (br s, 1 H, OH).
6-Hydroxy-9-(1H-indol-3-yl)-3,4-dihydro-2H-xanthen-1(9H)-
one (4i)
Yield: 0.27 g (82%); yellow solid; mp >300 °C (dec.).
13
C NMR (62.5 MHz, DMSO-d , TMS): δ = 26.6, 27.8, 28.7, 31.5,
6
IR (KBr): 3755, 3379, 3301, 2569, 1635, 1589, 1512, 1373, 1226,
3
1
2.0, 50.2, 102.3, 109.5, 112.1, 112.4, 115.9, 118.3, 118.5, 119.2,
20.7, 125.5, 126.7, 130.2, 136.6, 149.42, 156.5, 163.9, 196.1.
–
1
1
180, 1002, 856, 786, 756, 524, 424 cm .
1
+
H NMR (250 MHz, DMSO-d , TMS): δ = 1.83–1.92 (m, 2 H,
MS: m/z (%) = 373 (25) [M] , 374 (23) [M + 1], 375 (8) [M + 2].
6
CH ), 2.23 (s, 2 H, CH ), 2.67 (s, 2 H, CH ), 5.06 (s, 1 H, CH),
2
2
2
Anal. Calcd for C H NO (373.4): C, 77.19; H, 6.21; N, 3.75.
Found: C, 77.24; H, 6.23; N, 3.78.
2
4
23
3
6
.42–6.48 (m, 2 H, ArH), 6.86–7.08 (m, 4 H, ArH), 7.24 (s, 1 H,
ArH), 7.39 (s, 1 H, ArH), 9.54 (s, 1 H, OH), 10.76 (s, 1 H, NH).
1
3
9
-(1H-Indol-3-yl)-3,4-dihydro-2H-xanthen-1(9H)-one (4f)
C NMR (62.5 MHz, DMSO-d , TMS): δ = 20.0, 27.0, 27.8, 36.5,
6
Yield: 0.27 g (87%); white solid; mp 255–258 °C.
102.2, 111.4, 112.3, 113.4, 116.1, 118.3, 119.9, 120.9, 122.4, 125.2,
30.1, 136.3, 149.4, 156.46, 156.9, 196.2.
1
IR (KBr): 3749, 3332, 3055, 2947, 2360, 1766, 1635, 1581, 1481,
MS: m/z (%) = 331 (18) [M]+.
1
6
1
458, 1427, 1380, 1226, 1180, 1134, 1091, 995, 918, 864, 794, 748,
24, 555.5, 424 cm .
–
1
Anal. Calcd for C H NO (331.4): C, 76.12; H, 5.17; N, 4.23.
Found: C, 76.07; H, 5.13; N, 4.29.
2
1
17
3
H NMR (250 MHz, DMSO-d , TMS): δ = 1.62–1.71 (m, 2 H,
6
CH ), 2.01–2.02 (m, 2 H, CH ), 2.36–2.56 (m, 2 H, CH ), 4.98 (s,
2
2
2
1
H, CH), 6.63–6.78 (m, 3 H, ArH), 6.89 (s, 3 H, ArH), 7.04 (d,
6-Hydroxy-9-(1-methyl-1H-indol-3-yl)-3,4-dihydro-2H-xan-
then-1(9H)-one (4j)
Yield: 0.27 g (81%); yellow solid; mp >300 °C (dec.).
J = 8.0 Hz, 2 H, ArH), 7.24 (d, J = 7.5 Hz, 1 H, ArH), 10.58 (s, 1 H,
NH).
1
3
IR (KBr): 3433, 3155, 2931, 2823, 2707, 1627, 1581, 1512, 1458,
C NMR (62.5 MHz, DMSO-d , TMS): δ = 20.0, 27.0, 28.4, 36.5,
6
–1
1
380, 1226, 1180, 1134, 1095, 1064, 1002, 964, 848, 740 cm .
1
1
11.5, 113.1, 116.0, 118.2, 118.4, 119.5, 120.7, 122.6, 124.6, 125.2,
25.8, 127.3, 129.6, 136.4, 148.96, 166.0, 196.1.
1
H NMR (250 MHz, DMSO-d , TMS): δ = 1.88–1.89 (m, 2 H,
6
+
CH ), 2.22 (s, 2 H, CH ), 2.65 (s, 2 H, CH ), 3.62 (s, 3 H, CH ), 5.05
MS: m/z (%) = 315 (43) [M] , 316 (29) [M + 1].
2
2
2
3
(
s, 1 H, CH), 6.47 (s, 2 H, ArH), 7.03 (s, 4 H, ArH), 7.25 (s, 1 H,
Anal. Calcd for C H NO (315.4): C, 79.98; H, 5.43; N, 4.44.
Found: C, 80.02; H, 5.45; N, 4.49.
2
1
17
2
ArH), 7.42 (s, 1 H, ArH), 9.55 (br s, 1 H, OH).
13
C NMR (62.5 MHz, DMSO-d , TMS): δ = 20.0, 27.0, 27.6, 32.0,
6
9
-(1-Methyl-1H-indol-3-yl)-3,4-dihydro-2H-xanthen-1(9H)-one
36.5, 102.2, 109.5, 112.3, 113.4, 116.0, 118.4, 118.5, 120.7, 122.8,
126.7, 130.0, 136.5, 149.27, 156.4, 165.9, 196.1.
MS: m/z (%) = 345 (29) [M]+.
(4g)
Yield: 0.27 g (84%); white solid; mp 212–215 °C.
IR (KBr): 3340, 2877, 2360, 1643, 1488, 1373, 1326, 1234, 1134,
Anal. Calcd for C H NO (345.4): C, 76.50; H, 5.54; N, 4.06.
–
1
22 19
3
1064, 995, 748, 555 cm .
Found: C, 76.44; H, 5.57; N, 4.14.
1
H NMR (250 MHz, DMSO-d , TMS): δ = 1.87–1.95 (m, 2 H,
6
CH ), 2.26–2.31 (m, 2 H, CH ), 2.71–2.72 (m, 2 H, CH ), 3.64 (s,
9-(5-Bromo-1H-indol-3-yl)-3,4-dihydro-2H-xanthen-1(9H)-one
2
2
2
(
4k)
3
H, CH ), 5.18 (s, 1 H, CH), 6.93–7.13 (m, 6 H, ArH), 7.26 (s, 2 H,
3
Yield: 0.31 g (80%); white solid; mp 244–247 °C.
ArH), 7.45–7.51 (m, 1 H, ArH).
1
3
IR (KBr): 3379, 2885, 2360, 1643, 1581, 1450, 1337, 1234, 1180,
C NMR (62.5 MHz, DMSO-d , TMS): δ = 20.0, 27.0, 28.1, 32.1,
6
–
1
1
103, 995, 918, 879, 794, 756, 624, 424 cm .
3
1
6.5, 109.6, 113.0, 116.0, 118.5, 118.5, 118.8, 120.8, 124.6, 125.5,
25.7, 126.9, 127.8, 129.58, 136.6, 148.8, 166.1, 196.1.
1
H NMR (250 MHz, DMSO-d , TMS): δ = 1.85–1.99 (m, 2 H,
6
+
CH ), 2.20–2.31 (m, 2 H, CH ), 2.67–2.76 (m, 2 H, CH ), 5.21 (s,
MS: m/z (%) = 329 (32) [M] , 330 (16) [M + 1].
2
2
2
1
H, CH), 6.98–7.05 (m, 1 H, ArH), 7.10–7.15 (m, 4 H, ArH),7.24–
Anal. Calcd for C H NO (329.4): C, 80.22; H, 5.81; N, 4.25.
Found: C, 80.28; H, 5.83; N, 4.29.
2
2
19
2
7.28 (m, 2 H, ArH), 7.69 (s, 1 H, ArH), 11.08 (br s, 1 H, NH).
13
C NMR (62.5 MHz, DMSO-d , TMS): δ = 20.0, 27.0, 28.0, 36.4,
6
9
-(2-Methyl-1H-indol-3-yl)-3,4-dihydro-2H-xanthen-1(9H)-one
111.2, 113.1, 113.4, 116.0, 119.7, 120.6, 123.2, 124.5, 124.7, 125.6,
127.1, 1275, 129.6, 134.91, 148.9, 166.1, 196.1.
(4h)
Yield: 0.27 g (84%); white solid; mp 237–240 °C.
+
MS: m/z (%) = 394 (65) [M] , 395 (80) [M + 1], 396 (35) [M + 2].
IR (KBr): 3355, 2877, 2360, 1635, 1581, 1458, 1373, 1234, 1180,
Anal. Calcd for C H BrNO (394.3): C, 63.97; H, 4.09; N, 3.55.
–
1
21 16
2
1118, 995, 918, 864, 748, 617, 570, 524 cm .
Found: C, 63.91; H, 4.13; N, 3.42.
1
H NMR (250 MHz, DMSO-d , TMS): δ = 1.72–1.97 (m, 2 H,
6
CH ), 2.17–2.32 (m, 2 H, CH ), 2.53 (s, 3 H, CH ), 2.67–2.69 (m,
2
J = 7 Hz, 1 H, ArH), 6.93–7.17 (m, 6 H, ArH), 10.74 (br s, 1 H,
5-(1H-Indol-3-yl)-1H-chromeno[2,3-d]pyrimidine-2,4(3H,5H)-
dione (4l)
Yield: 0.26 g (80%); white solid; mp 247–250 °C.
2
2
3
H, CH ), 5.12 (s, 1 H, CH), 6.77 (t, J = 7.5 Hz, 1 H, ArH), 6.87 (t,
2
NH).
IR (KBr): 3818, 3749, 3502, 3402, 3278, 3224, 3031, 2862, 2515,
1697, 1651, 1581, 1519, 1488, 1458, 1380, 1280, 1226, 1103, 1041,
13
C NMR (62.5 MHz, DMSO-d , TMS): δ = 11.5, 20.1, 26.9, 27.6,
6
–
1
887, 763, 663, 594, 540, 509 cm .
3
1
6.5, 110.4, 112.6, 114.9, 115.8, 116.8, 118.2, 119.5, 124.6, 125.2,
26.4, 127.3, 129.9, 131.50, 134.9, 148.8, 165.4, 196.2.
1
H NMR (250 MHz, DMSO-d , TMS): δ = 4.69 (s, 1 H, CH), 6.52
6
MS: m/z (%) = 329 (35) [M]+.
(s, 1 H, ArH), 6.74–7.34 (m, 8 H, ArH), 10.98 (s, 1 H, NH), 11.18
(s, 1 H, NH), 11.97 (s, 1 H, NH).
Anal. Calcd for C H NO (329.4): C, 80.22; H, 5.81; N, 4.25.
2
2
19
2
13
C NMR (62.5 MHz, DMSO-d , TMS): δ = 33.5, 53.2, 85.1, 116.4,
Found: C, 80.17; H, 5.79; N, 4.32.
6
120.7, 125.5, 127.9, 129.1, 149.0, 149.4, 150.4, 155.3, 163.4, 168.8,
1
69.5.
Synthesis 2014, 46, 2071–2078
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of 9-(1H-Indol-3-yl)xanthen-4-(9H)-ones Using TMSI
2077
+
13
MS: m/z (%) = 331 (37) [M] , 332 (22) [M + 1], 333 (9) [M + 2].
C NMR (62.5 MHz, DMSO-d , TMS): δ = 26.6, 28.0, 28.7, 31.5,
6
5
1
0.2, 55.2, 100.9, 111.3, 111.4, 112.2, 117.6, 118.2, 119.7, 120.6,
22.4, 125.1, 130.2, 136.3, 149.5, 158.3, 163.8, 196.0.
Anal. Calcd for C H N O (331.3): C, 68.88; H, 3.95; N, 12.68.
Found: C, 68.94; H, 3.88; N, 12.72.
1
9
13
3
3
MS: m/z (%) = 373 (38) [M]+.
5
-(1-Methyl-1H-indol-3-yl)-1H-chromeno[2,3-d]pyrimidine-
,4(3H,5H)-dione (4m)
Anal. Calcd for C H NO (373.5): C, 77.19; H, 6.21; N, 3.75.
Found: C, 77.11; H, 6.15; N, 3.68.
2
24 23
3
Yield: 0.26 g (78%); white solid; mp 219–222 °C.
IR (KBr): 3494, 3224, 2862, 2360, 1697, 1651, 1519, 1496, 1458,
6
-Hydroxy-9-(1H-indol-3-yl)-3,3-dimethyl-3,4-dihydro-2H-
–
1
1380, 1326, 1280, 1226, 1064, 871, 748, 663, 424 cm .
xanthen-1(9H)-one (4q)
1
Yield: 0.10 g (29%); white solid; mp 126–129 °C.
H NMR (250 MHz, DMSO-d , TMS): δ = 3.65 (s, 3 H, CH ), 4.70
6
3
(
1
s, 1 H, CH, ArH), 6.61–7.35 (m, 9 H, ArH), 10.99 (s, 1 H, NH),
1.97 (s, 1 H, NH).
IR (KBr): 3818, 3749, 3386, 2692, 1627, 1458, 1373, 1218, 1172,
1095, 1033, 964.3, 840.9, 740.6, 424.3 cm .
–
1
13
1
C NMR (62.5 MHz, DMSO-d , TMS): δ = 32.1, 33.5, 85.1, 109.4,
H NMR (250 MHz, DMSO-d , TMS): δ = 0.64 (s, 3 H, CH ), 0.78
6
6
3
116.4, 117.2, 118.1, 119.0, 120.8, 125.5, 127.7, 127.9, 129.1, 136.8,
(s, 3 H, CH ), 1.77–2.02 (m, 2 H, CH ), 2.23–2.33 (m, 2 H, CH ),
3
2
2
149.5, 150.5, 163.4, 168.9, 169.5.
4.81 (s, 1 H, CH), 6.25 (s, 2 H, ArH), 6.62–6.86 (m, 4 H, ArH), 7.00
MS: m/z (%) = 345 (30) [M]+.
(s, 1 H, ArH), 7.11 (s, 1 H, ArH), 9.30 (s, 1 H, OH), 10.51 (s, 1 H,
NH).
Anal. Calcd for C H N O (345.4): C, 69.56; H, 4.38; N, 12.17.
2
0
15
3
3
13
C NMR (62.5 MHz, DMSO-d , TMS): δ = 26.6, 27.9, 28.7, 31.5,
6
Found: C, 69.48; H, 4.32; N, 12.09.
50.1, 102., 111.4, 112.2, 112.3, 116.0, 118.2, 118.3, 119.9, 120.6,
1
22.3, 125.2, 130.2, 136.3, 149.4, 156.4, 163.9, 196.0.
5
-(2-Methyl-1H-indol-3-yl)-1H-chromeno[2,3-d]pyrimidine-
,4(3H,5H)-dione (4n)
2
+
MS: m/z (%) = 359 (42) [M] , 360 (25) [M + 1], 361 (12) [M + 2].
Yield: 0.27 g (79%); white solid; mp >300 °C (dec.).
Anal. Calcd for C H NO (359.4): C, 76.86; H, 5.89; N, 3.90.
Found: C, 76.92; H, 5.93; N, 3.97.
2
3
21
3
IR (KBr): 3294, 2831, 2360, 1712, 1674, 1519, 1458, 1342, 1257,
–
1
1041, 756, 671, 547, 439.7 cm .
1
8-Bromo-5-(1H-indol-3-yl)-1H-chromeno[2,3-d]pyrimidine-
H NMR (250 MHz, DMSO-d , TMS): δ = 2.52 (s, 3 H, CH ), 5.15
s, 1 H, CH), 6.74 (t, J = 7.5 Hz, 1 H, ArH), 6.86 (t, J = 7.5 Hz, 1 H,
6
3
2
,4(3H,5H)-dione (4r)
(
Yield: 0.31 g (75%); yellow solid; mp 341–345 °C (dec.).
ArH), 6.95–7.23 (m, 6 H, ArH), 10.78 (br s, 1 H, NH), 10.90 (br s,
1
H, NH), 11.90 (br s, 1 H, NH).
IR (KBr): 3494, 3402, 3016, 2908, 2360, 1681, 1589, 1458, 1334,
13
1265, 1234, 1134, 1080, 1041, 941, 817, 748.3, 671.2, 594, 547,
C NMR (62.5 MHz, DMSO-d , TMS): δ = 11.5, 27.9, 87.9, 110.6,
6
–1
4
16 cm .
1
1
13.9, 115.7, 116.4, 118.2, 119.6, 124.7, 125.3, 126.2, 127.8, 130.1,
32.0, 134.9, 148.2, 149.6, 153.2, 163.1.
1
H NMR (250 MHz, DMSO-d , TMS): δ = 4.69 (s, 1 H, CH), 6.52
6
MS: m/z (%) = 345 (44) [M]+.
(s, 1 H, ArH), 6.74–7.34 (m, 7 H, ArH), 9.85 (s, 1 H, NH), 10.18 (s,
1
H, NH), 10.90 (s, 1 H, NH).
Anal. Calcd for C H N O (345.3): C, 69.56; H, 4.38; N, 12.17.
2
0
15
3
3
13
C NMR (62.5 MHz, DMSO-d , TMS): δ = 23.0, 27.8, 45.4, 58.9,
6
Found: C, 69.64; H, 4.46; N, 12.26.
8
0.1, 88.89, 150.0, 151.0, 152.7, 165.2, 165.3, 170.5.
5
-(1H-Indol-3-yl)-2-thioxo-2,3-dihydro-1H-chromeno[2,3-
MS: m/z (%) = 410 (21) [M]+.
d]pyrimidin-4(5H)-one (4o)
Anal. Calcd for C H BrN O (410.23): C, 55.63; H, 2.95; N,
Yield: 0.26 g (75%); yellow solid; mp >300 °C (dec.).
19 12
3
3
10.24. Found: C, 55.54; H, 2.88; N, 10.18.
IR (KBr): 3494, 3402, 3016, 2908, 2360, 1681, 1589, 1458, 1334,
1
4
1
265, 1234, 1134, 1080, 1041, 941, 817, 748.3, 671.2, 594, 547,
16 cm .
6
-Bromo-9-(1H-indol-3-yl)-3,3-dimethyl-3,4-dihydro-2H-xan-
–1
then-1(9H)-one (4s)
Yield: 0.33 g (78%); white solid; mp 269–273 °C.
H NMR (250 MHz, DMSO-d , TMS): δ = 4.69 (s, 1 H, CH), 6.08
6
(
6
s, 1 H), 6.51–6.55 (m, 2 H, ArH), 6.77 (t, J = 7.2 Hz, 1 H, ArH),
.88–6.97 (m, 3 H, ArH), 7.24 (t, J = 7.5 Hz, 2 H, ArH), 10.44 (s,
IR (KBr): 3463, 3193, 2954, 2869, 2360, 1643, 1589, 1488, 1380,
1311, 1234, 1149, 1026, 756, 655, 578, 478 cm .
–1
1
H, NH), 11.18 (s, 1 H, NH), 11.97 (s, 1 H, NH).
1
H NMR (250 MHz, DMSO-d , TMS): δ = 0.71 (s, 3 H, CH ), 0.78
6
3
13
C NMR (62.5 MHz, DMSO-d , TMS): δ = 33.5, 53.2, 110.8,
(s, 3 H, CH ), 1.80–2.09 (m, 2 H, CH ), 2.25–2.31 (m, 2 H, CH ),
6
3
2
2
1
1
11.0, 115.2, 117.9, 118.2, 119.1, 120.2, 125.7, 126.9, 129.4, 130.2,
36.8, 136.8, 154.4.
4.78 (s, 1 H, CH), 6.46–6.55 (m, 2 H, ArH), 6.89–7.10 (m, 4 H,
ArH), 7.27 (d, J = 8 Hz, 1 H, ArH), 7.40 (d, J = 7.7 Hz, 1 H), 10.34
(s, 1 H, NH).
MS: m/z (%) = 347 (22) [M]+.
13
C NMR (62.5 MHz, DMSO-d , TMS): δ = 25.1, 26.0, 27.5, 29.1,
6
Anal. Calcd for C H N O S (347.4): C, 65.69; H, 3.77; N, 12.10.
Found: C, 65.75; H, 3.82; N, 12.17.
1
9
13
3
2
31.5, 50.2, 110.3, 115.3, 117.6, 128.2, 129.6, 130.5, 148.8, 164.3,
1
95.5.
6
-Methoxy-9-(1H-indol-3-yl)-3,3-dimethyl-3,4-dihydro-2H-
MS: m/z (%) = 422 (27) [M]+.
xanthen-1(9H)-one (4p)
Anal. Calcd for C H BrNO (422.32): C, 65.41; H, 4.77; N, 3.32.
Yield: 0.19 g (51%); white solid; mp 192–198 °C.
23 20
2
Found: C, 65.32; H, 4.71; N, 3.25.
–
1
IR (KBr): 3309, 2962, 2353, 1627, 1496, 1373, 1218, 740 cm .
1
5-(1H-Indol-3-yl)-8-nitro-1H-chromeno[2,3-d]pyrimidine-
H NMR (250 MHz, DMSO-d , TMS): δ = 0.90 (s, 3 H, CH ), 1.02
6
3
2
,4(3H,5H)-dione (4t)
(
3
s, 3 H, CH ), 2.03–2.28 (m, 2 H, CH ), 2.59 (s, 2 H, CH ), 3.68 (s,
3
2
2
Yield: 0.26 g (70%); white solid; mp 219–222 °C.
H, CH ), 5.11 (s, 1 H, CH), 6.59 (d, J = 8.2 Hz, 1 H, ArH), 6.71
3
(
1
7
s, 1 H, ArH), 6.87 (t, J = 7.2 Hz, 1 H, ArH), 6.98 (t, J = 7.7 Hz,
H, ArH), 7.09–7.13 (m, 2 H, ArH), 7.27 (d, J = 8 Hz, 1 H, ArH),
.39 (d, J = 7.7 Hz, 1 H, ArH), 10.79 (s, 1 H, NH).
IR (KBr): 3818, 3749, 3502, 3402, 3278, 3224, 3031, 2862, 2515,
1697, 1651, 1581, 1519, 1488, 1458, 1380, 1280, 1226, 1103, 1041,
887, 763, 663, 594, 540, 509 cm .
–
1
©
Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 2071–2078

2078
A. Khalafi-Nezhad et al.
PAPER
1
H NMR (250 MHz, DMSO-d , TMS): δ = 4.97 (s, 1 H, CH), 6.56–
(8) Sakai, T.; Miyata, K.; Tsuboi, S.; Utaka, M. Bull. Chem. Soc.
Jpn. 1989, 62, 4072.
(9) Jung, M. E.; Mossman, A. B.; Lyster, M. A. J. Org. Chem.
1978, 43, 3698.
6
6
.66 (m, 2 H, ArH), 6.77 (t, J = 7 Hz, 1 H, ArH), 6.94–7.08 (m, 3 H,
ArH), 7.64–7.89 (m, 2 H, ArH), 9.74 (s, 1 H, NH), 10.03 (s, 1 H,
NH), 10.60 (s, 1 H, NH).
1
3
(10) Handbook of Reagents for Organic Synthesis: Reagents for
Silicon-Mediated Organic Synthesis; Fuchs, P. L., Ed.;
Wiley: Chichester, 2011.
C NMR (62.5 MHz, DMSO-d , TMS): δ = 23.3, 28.3, 45.2, 59.7,
6
8
1
8.9, 117.9, 118.0, 118.5, 123.8, 125.1, 135.8, 137.0, 149.9, 165.3,
70.0.
(11) Wang, F.; Qu, M.; Chen, F.; Li, L.; Shi, M. Chem. Commun.
MS: m/z (%) = 376 (16) [M]+.
2
012, 48, 437.
Anal. Calcd for C H N O (376.33): C, 60.64; H, 3.21; N, 14.89.
Found: C, 60.55; H, 3.16; N, 14.80.
(12) Wang, F.; Qu, M.; Lu, X.; Chen, F.; Chen, F.; Shi, M. Chem.
Commun. 2012, 48, 6259.
19
12
4
5
(
(
(
13) (a) Khalafi-Nezhad, A.; Panahi, F. Synthesis 2011, 984.
(
b) Khalafi-Nezhad, A.; Haghighi, S. M.; Purkhosrow, A.;
Acknowledgment
Panahi, F. Synlett 2012, 920. (c) Khalafi-Nezhad, A.;
Sarikhani, S.; Shahidzadeh, S. E.; Panahi, F. Green Chem.
Financial support from the research councils of Shiraz University is
gratefully acknowledged.
2
012, 14, 2876. (d) Khalafi-Nezhad, A.; Panahi, F.;
Golesorkhi, B. Helv. Chim. Acta 2013, 96, 1155. (e) Khalafi-
Nezhad, A.; Divar, M.; Panahi, F. Tetrahedron Lett. 2013,
5
4, 220.
Supporting Information for this article is available online
14) (a) Huang, H.; La, D. S.; Cheng, A. C.; Whittington, D. A.;
Patel, V. F.; Chen, K.; Dineen, T. A.; Epstein, O.; Graceffa,
R.; Hickman, D.; Kiang, Y.-H.; Louie, S.; Luo, Y.; Wahl, R.
C.; Wen, P. H.; Wood, S.; Fremeau, R. T. Jr. J. Med. Chem.
2012, 55, 9156. (b) Pasha, M. A.; Jayashankara, V. P.
Bioorg. Med. Chem. Lett. 2007, 17, 621. (c) Chen, X.;
Pradhan, T.; Wang, F.; Kim, J. S.; Yoon, J. Chem. Rev. 2012,
at
http://www.thieme-connect.com/products/ejournals/journal/
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0.1055/s-00000084.SunpfgIpi
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Synthesis 2014, 46, 2071–2078
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