Iodine mediated intramolecular C2-amidative cyclization of indoles: A facile access to indole fused tetracycles

Article abstract of DOI:10.1039/c5ob02449h

A novel and metal-free I₂-mediated intramolecular C2 amidation of indoles under mild reaction conditions is developed. This methodology affords various indole fused tetracyclic compounds, such as benzo[4,5]imidazo[1,2-a]indoles by intramolecular C2 amidation of N-aryl substituted indoles. This C2 sulfonamidative cyclization also offers convenient access to indolo[2,3-b]indoles and dihydroindolo[2,3-b]quinoline from C3 aryl substituted indoles in good to excellent yields. Indolo[2,3-b]quinolines are also synthesized by the domino cyclization-detosylation-aromatization reaction sequence.

Full text of DOI:10.1039/c5ob02449h

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Iodine mediated intramolecular C2-amidative cyclization of
indoles: A facile access to indole fused tetracycles
Received 00th January 20xx,
Accepted 00th January 20xx
Sindhura Badigenchala, Venkatachalam Rajeshkumar and Govindasamy Sekar*
A novel and metal-free I2-mediated intramolecular C2 amidation of indoles under mild reaction conditions is developed.
This methodology affords various indole fused tetracyclic compounds such as benzo[4,5]imidazo[1,2-a]indoles by
intramolecular C2 amidation of N-aryl substituted indoles. This C2 sulfonamidative cyclization also offers convenient
access to indolo[2,3-b]indoles and dihydroindolo[2,3-b]quinoline from C3 aryl substituted indoles in good to excellent
yields. Indolo[2,3-b]quinolines are also synthesized by the domino cyclization-detosylation-aromatization reaction
sequence.
DOI: 10.1039/x0xx00000x
www.rsc.org/
promoted cyclization,10 gold catalyzed intramolecular
cyclization,7g,11 double C-H functionalization,12 transition metal
Introduction
catalyzed
annulation,7d-f,8a
intramolecular
coupling
The nitrogen-containing heterocycles are widespread in
various natural products1 and bioactive molecules.2 Among
these, indole is a most privileged structural motif3 found in
various biologically and pharmaceutically active molecules,4
agrochemicals, dyes and essential oils (Figure 1).5 Owing to its
importance, indole and its derivatives have been the choice of
research and much attention has been paid to synthesize and
study their properties.6a Consequently, development of new
synthetic strategies for functionalization of indole has always
been the area of interest.6
reactions.7c,9c
Fig. 2 Indole fused tetracycles 1, 2 and 3.
As part of our on-going research towards metal free C-N bond
formation and C-H functionalization reactions,13 we herein
report iodine mediated intramolecular C2 amidative cyclization
of suitably substituted indoles for the synthesis of tetracyclic
indoles (Scheme 1).
Fig. 1 Selected biologically active naturally occurring indole derivatives.
Various methodologies have been developed for the synthesis
of highly functionalized indole molecules7 and were utilized in
total synthesis as well.8 Fascinated by the importance of indole
fused heterocycles, we were interested in developing a new
strategy to synthesize indole fused heterocycles such as
benzo[4,5]imidazo[1,2-a]indoles, indolo[2,3-b]indoles (which
are very less explored in the literature)9 and indolo[2,3-
b]quinolones9e-f (Figure 2). These type of indole fused
heterocyclic moieties have been generally synthesized by C-H
functionalization,7h Cu mediated cyclization,9b halogen
Scheme 1 Intramolecular cyclization by C2-amidation of indoles.
Results and Discussion
Compared with C3-functionalization of indoles, C2-
functionalization is less explored and only few reports are
available for C2-amination of indoles. Initially, Pd/Cu catalyzed
methodologies have been developed for C2-amination of
Indole.14 Complimentary to these metal catalyzed reactions,
Liang et al., reported iodine mediated C2-amination of
indoles15 and recent report in this area is NIS mediated C2-
amidation, by Nagarajan et al.16 However, these are
intermolecular reactions and only few literature reports are
available for intramolecular C2-amination of indoles. Recently,
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transition metal catalysts7c-e,8a were also employed for this conditions in hand, we have investigated the substrate scope
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transformation. Ghosh et al. described NCS mediated cascade of the methodology and the results are summarized in Table 2.
cyclization in which C2 amination took place.10c Neverthless, All the substrates gave very good to satisfactory yields of the
synthesis
of
the
benzo[4,5]imidazo[2,3-b]indoles,9a,9b products. Electron releasing groups such as 5-methoxy, 5-
indolo[2,3-b]indoles9c,9d seldom appeared in literature. methyl, 3-methyl, 5-phenyl and 5-p-tolyl attached to indole
Therefore, development of a simple methodology which could gave benzo[4,5]imidazo[1,2-a]indoles in moderate to good
give facile access to these heterocycles is desirable. To yield (entries 2, 3, 5, 7 and 8). Presence of electron
establish the intramolecular C2-amidation of indoles, initially, withdrawing fluoro, cyano groups also provided the C2-
we treated indole derivative 1a with 2 equiv. of iodine and 2 cyclized products 2d and 2i in 72 and 45% yield respectively
equiv. of Cs2CO3 in MeCN at room temperature. This (entries 4 and 9). 7-Azaindole derivative also rendered the
intramolecular C2-sulfonamidative cyclization gave product corresponding product 2e in 70% yield (entry 6).
benzo[4,5]imidazo[1,2-a]indole 2a in 49% isolated yield after 6
Table 2 Substrate scope of I2 mediated C2-amidative cyclization.a
hours and considerable amount of side product was also
formed (Table 1, entry 1). Suspecting the side product formed
might be iodinated compound of product 2a (as excess iodine
is present in reaction medium), the quantity of I2 was reduced
to 1.5 equivalents and the reaction gave 58% of 2a (entry 2).
However, reducing the amount of iodine to 1 equivalent
reduced the yield of 2a to 29% and lot of starting material was
left unreacted (entry 3). Increasing the reaction temperature
to 60 oC increased the yield to 57% (entry 4).
Table 1 Optimization of reaction conditions for C2 amidative cyclizationa
To increase the efficiency of this intramolecular C2-amidation
reaction, the quantity of iodine was increased to 1.5
equivalent, and the reaction yielded only 50% of 2a (entry 5).
When the reaction was carried out using 1.2 equivalent of
o
iodine at 60 C, the yield was increased to 62% and the side
product was considerably reduced (entry 6). Addition of iodine
in two equal portions resulted in 75% of 2a (entry 7) without
formation of any side products. Further changing the reaction
conditions did not increase the yield of 2a (Table 1). Use of
solvents such as CCl4, toluene, THF, DMSO and ethanol failed
to increase the yield of the product (entries 8-12) and MeCN
was found to be the best solvent. Similarly, Cs2CO3 turned out
to be the choice of base compared with bases such as K2CO3,
KOH, NaOtBu, K3PO4 etc. From the optimization studies, the
best reaction condition for this C2-sulfonamidative cyclization
was found to be, iodine (1.2 equiv.), Cs2CO3 (2 equiv.) in 2 mL
MeCN at 60 oC (entry 7). With the optimized reaction
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When the tosyl protection on nitrogen was replaced with In order to explore the generality of this methodology, C3
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brosyl group, corresponding indole derivative was also readily arylated indole 3a was subjected to the optimized reaction
underwent for cyclization to yield 62% of the product (entry condition. To our delight, this reaction afforded 95% yield of
10).
indolo[2,3-b]indole 4a in 5 hours (Table 3). Encouraged with
this result, we explored the substrate scope of this type of
compounds and all the substrates gave good to excellent yields
of the indolo[2,3-b]indoles (Table 3). Substrates bearing N-
ethyl, N-isopropyl, N-propyl and N-butyl substituents gave
excellent yields of cyclized products (entry 2-5). 5-Methoxy
and 5-cyano substituted N-methyl indoles gave 80% and 82%
yields of products (entries 6 and 8). N-methyl 7-azaindole
derivative also yielded 78% of the product 4g (entry 7). In this
context to further extend scope of this cyclization, compounds
3i and 3j were also cyclized to give corresponding products,
dihydroindolo[2,3-b]quinolines 4i and 4j respectively (entries 9
and 10). In the cyclization reaction of 3i, trace amount of
Table 3 Substrate scope of I2 mediated C2-amidaitve cyclization.a
another product was also isolated which was analysed as 5a
.
This compound was expected to have formed by the
detosylation and aromatization sequence of 4i. Prolonging the
reaction time in case of substrates 3i and 3j resulted in
cyclization followed by detosylation and aromatization,
affording indolo[2,3-b]quinolines 5a and 5b respectively
(Scheme 2). In contrast, subtrates with 5-methoxy N-ethyl and
N-isopropyl substituents (3k
aromatized indoloquinolines (5c
,
3l and 3m) gave exclusively the
5d and 5e) and not even
,
trace amount of dihydroindoloquinolines were detected
(Scheme 2).
Scheme 2 I2-mediated domino C2 amidative cyclization followed by detosylation and
aromatization.
To examine which substrate is more facile for the C-N bond
forming cyclization reaction, the intermolecular competitive
reaction between 1a and 3a has been performed. As expected,
the reaction resulted selectively in 95% of 4a in 5 hours and
only trace amount of 2a was detected (Scheme 3).
Scheme 3 Intermolecular competitive reaction between 1a and 3a.
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This shows that the C2 amidaton of substrate 3a, where aryl a]indoles and indolo[2,3-b]quinolines. Under the optimized
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group is tethered to C3 is more facile yielding major quantity reaction conditions, C2 position is amidated than the more
of the product. Further to carry out the intramolecular reactive C3 position. The competitive intermolecular reaction
competitive cyclization reaction, compound 6a has been shows that indole substrate with aryl group tethered to C3
prepared and subjected to the reaction conditions. Surprisingly position (3a) is more reactive than corresponding indole
this reaction afforded 42% of novel indole fused hexacyclic substrate with aryl group tethered to nitrogen of indole.
compound 7a, which was formed by double cyclization and Further Indolo[2,3-b]quinolines were also synthesized by the
further nucleophilic substitution of iodine at C3 by hydroxy ion domino cyclization-detosylation-aromatization sequence.
(Scheme 4). This reaction also yielded 38% of monocyclized–
detosylated compound 7b. Structure of compound 7a is
unambiguously established by XRD analysis (Figure 3).
Experimental Section
General considerations:
All reactions were carried out in reaction tubes closed with
stoppers and in an undistilled solvents. All the solvents used
for the reactions were obtained from Fischer Scientific, India
Pvt. Ltd. Reactions were monitored by thin-layer
chromatography (TLC) using Merck silica gel 60 F254 precoated
Scheme 4 Intramolecular competitive reaction.
plates (0.25 mm) and visualized by UV fluorescence quenching
using appropriate mixture of ethyl acetate and hexanes. Silica
gel (particle size: 100-200 mesh) was purchased from Avra and
used for column chromatography using hexanes and ethyl
acetate mixture as eluent. Cs2CO3 was purchased from Sigma-
Aldrich Company. Other reagents such as Indole, Iodine were
purchased from Spectrochem, India Pvt. Ltd., 2-fluoro
nitrobenzene and 2-bromo nitrobenzene were obtained from
Avra synthesis Pvt. Ltd. India. Various substituted indoles were
obtained from Spectrochem India Pvt. Ltd and Alfa Aesar
Company. All the reactions were carried out in temperature
1
controlled IKA magnetic stirrers. H and 13C NMR spectra were
Fig. 3 ORTEP diagram of compound 7a (CCDC 142079). Ellipsoids represent 30%
probability.
1
recorded on a Bruker 400 instrument. H NMR spectra were
reported relative to Me4Si (δ 0.0 ppm) or residual CDCl3 (δ 7.26
ppm). 13C NMR were reported relative to CDCl3 (δ 77.16 ppm).
FTIR spectra were recorded on a Nicolet 6700 spectrometer
and were reported in frequency of absorption (cm-1). High
resolution mass spectra (HRMS) were recorded on Q-Tof Micro
mass spectrometer. Melting points were measured either on a
It is expected that the reaction may proceed via formation of
cyclic iodonium ion which may undergo intramolecular
cyclization by nucleophilic attack of amine to open iodonium
ion (Scheme 5). Subsequent elimination of HI in presence of
base may yield corresponding cyclized products.
Toshniwal melting point apparatus or on
Heizitschmikroskop apparatus.
a
Kofler-
General procedure for Iodine mediated intramolecular C2
amidative cyclization of compounds 1a-j:
Indole derivative
1 (0.5 mmol) was taken in a clean, dry
reaction tube. To this iodine (0.3 mmol), Cs2CO3 ( 1.0 mmol)
and acetonotrile (2 mL) were added. Reaction tube was
stoppered and the resulting reaction mixture was stirred at 60
oC. After 4 h the second portion of iodine (0.3 mmol) was
added and reaction was allowed to stir at 60 oC. Upon
completion of reaction was monitored by TLC, then the solvent
was removed under vacuum in rotary evaporator and DCM
was added. The crude reaction mixture was washed with
Na2S2O3 solution (2 × 10 mL) and extracted with DCM. The
organic layer was washed water (1 × 10 mL). Combined organic
layers were concentrated using rotary evaporator and residue
was purified by column chromatography on silica gel using
Scheme 5. Proposed reaction mechanism for intramolecular amidation of indoles.15
Conclusions
In conclusion, we have developed a novel, metal-free and
efficient, iodine mediated intramolecular sulfonamidation of
indoles to give general access to different indole fused
heterocycles like indolo[2,3-b]indoles, benzo[4,5]imidazo[1,2-
hexanes/ethyl acetate as the eluent to afford pure product 2.
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10-Tosyl-10H-benzo[4,5]imidazo[1,2-a]indole (2a): White J=8, 1.5 Hz, 1H), 7.36 (dt, J=5, 1 Hz, 1H), 7.79 (d, J=8.5 Hz, 2H),
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o
DOI: 10.1039/C5OB02449H
solid, mp 148-150 C; Rf 0.50 (15% ethyl acetate in hexanes); 7.98 (dd, J=8, 1.5 Hz, 1H), 8.02 (d, J=7.5 Hz, 1H), 8.12 (d, J=8 Hz,
1H NMR (CDCl3, 400 MHz) δ 2.28 (s, 3H), 6.57 (d, J=0.4 Hz, 1H), 1H), 8.32 (dd, J=4.5, 1.5 Hz, 1H); 13C NMR (CDCl3, 125 MHz) δ
7.22 (m, 3H), 7.33 (dt, J=8, 1.2 Hz, 1H), 7.59 (dd, J=1., 0.4 Hz, 21.7, 112.8, 114.8, 117.7, 124.0, 125.5, 127.1, 128.6, 128.8,
1H), 7.68-7.72 (m, 2H), 7.79 (d, J=8.4 Hz, 2H), 8.04 (dd, J=8, 0.4 130.0, 133.4, 133.5, 139.0, 140.9, 146.0; FTIR (KBr) 3060, 2923,
Hz, 1H) ; 13C NMR (CDCl3, 100 MHz) δ 21.7, 82.1, 110.5, 110.7, 2851, 1599, 1553, 1496, 1428 cm-1; HRMS (m/z): [M+H]+ calcd.
115.1, 120.7, 121.2, 121.7, 123.1, 125.1, 127.0, 127.1, 129.8, for C20H16N3O2S: 362.0963; found: 362.0975.
130.0, 132.5, 133.6, 138.9, 145.7; FTIR (KBr) 2922, 2856, 1578, 2-Phenyl-10-tosyl-10H-benzo[4,5]imidazo[1,2-a]indole (2g):
1492, 1377, 1177, 1019 cm-1; HRMS (m/z): [M+H]+ calcd. for White solid, mp 173-175 oC; Rf 0.41 (15% ethyl acetate in
1
C21H17N2O2S: 361.1011; found: 361.0999.
hexanes); H NMR (CDCl3, 400 MHz) δ 2.19, (s, 3H), 6.52 (s,
2-Methoxy-10-tosyl-10H-benzo[4,5]imidazo[1,2-a]indole (2b): 1H), 7.05 (d, J=8 Hz, 2H), 7.14-7.19 (m, 1H), 7.22-7.28 (m, 2H),
o
Pale brown solid, mp 142-144 C; Rf 0.51 (20% ethyl acetate in 7.35-7.41 (m, 3H), 7.51 (d, J=8 Hz, 1H), 7.56-7.60 (m, 2H), 7.64
hexanes); 1H NMR (CDCl3, 400 MHz) δ 2.28 (s, 3H), 3.89 (s, 3H), (d, J=8.4 Hz, 1H), 7.72 (d, J=8.4 Hz, 2H), 7.81 (d, J=1.2 Hz, 1H),
6.49 (s, 1H), 6.87 (dd, J=8.8 Hz, 1H), 7.13 (d, J=8 Hz, 2H), 7.17 7.96 (d, J=8 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 21.7, 110.5,
(d, J=2.4 Hz, 1H), 7.22 (dt, J=8, 1.2 Hz, 1H), 7.31 (dt, J=7.6, 1.2 110.9, 115.1, 119.7, 120.4, 123.1, 125.2, 126.4, 126.8, 127.1,
Hz, 1H), 7.52 (d, J=8 Hz, 1H), 7.56 (d, J=8.8 Hz, 1H), 7.79 (d, 127.6, 128.9, 129.7, 130.0, 133.1, 133.6, 135.3, 139.4, 142.3;
J=8.4 Hz, 2H), 8.02 (dd, J=8, 0.8 Hz, 1H); 13C NMR (CDCl3, 100 FTIR (KBr) 3059, 2923, 2856, 1602, 1574, 1489, 1468 cm-1;
MHz) δ 21.7, 56.0, 103.7, 110.0, 110.1, 111.3, 115.0, 122.1, HRMS (m/z): [M+H]+ calcd. for C27H21N2O2S: 437.1324; found:
122.7, 125.1, 127.1, 128.3, 130.0, 133.3, 133.4, 133.7, 139.4, 437.1340.
145.7, 155.5; FTIR (KBr) 3065, 2924, 2854, 1598, 1577, 1490 2-(p-Tolyl)-10-tosyl-10H-benzo[4,5]imidazo[1,2-a]indole (2h):
cm-1; HRMS (m/z): [M+H]+ calcd. for C22H19N2O3S: 391.1116; Light brown solid, mp 165-167 oC; Rf 0.43 (15% ethyl acetate in
found: 391.1102.
hexanes); 1H NMR (CDCl3, 400 MHz) δ 2.19 (s, 3H), 2.33 (s, 3H),
2-Methyl-10-tosyl-10H-benzo[4,5]imidazo[1,2-a]indole (2c): 6.51 (s, 1H), 7.05 (d, J=8.4 Hz, 2H), 7.15-7.21 (m, 3H), 7.24 (dt,
White solid, mp 155-158 oC; Rf 0.52 (15% ethyl acetate in J=7.6, 1.2 Hz, 1H), 7.37 (dd, J=8.4, 2.0 Hz, 1H), 7.45-7.55 (m,
hexanes); 1H NMR (CDCl3, 400 MHz) δ 2.27 (s, 3H), 2.49 (s, 3H), 3H), 7.63 (d, J=8.4 Hz, 1H), 7.71 (d, J=8.4 Hz, 2H), 7.79 (d, J=1.2
6.48 (s, 1H), 7.06 (dd, J=8.4, 1.2 Hz, 1H), 7.12 (d, J=8 Hz, 2H), Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 21.2, 21.7, 82.3, 110.5,
7.22 (dt, J=8, 1.2 Hz, 1H), 7.31 (dt, J=7.8, 1.2 Hz, 1H), 7.49 (s, 110.8, 115.1, 119.5, 120.3, 123.1, 125.2, 126.3, 127.1, 127.4,
1H), 7.53-7.58 (m, 2H), 7.78 (d, J=8.4 Hz, 2H), 8.02 (d, J=8 Hz, 129.6, 129.7, 130.0, 133.0, 133.5, 133.5, 135.2, 136.5, 139.3,
1H); 13C NMR (CDCl3, 100 MHz) δ 21.7, 21.8, 81.7, 110.3, 115.1, 145.7; FTIR (KBr) 3029, 2921, 2856, 1602, 1575, 1490, 1458,
121.0, 122.1, 122.8, 125.1, 125.3, 127.1, 128.3, 129.9, 129.9, 1375, 1317 cm-1; HRMS (m/z): [M+H]+ calcd. for C28H23N2O2S:
131.2, 132.8, 133.5, 133.6, 139.0, 145.6; FTIR (KBr) 3061, 2923, 451.1480; found: 451.1461.
2858, 1600, 1575, 1495, 1457, 1377cm-1.
10-Tosyl-10H-benzo[4,5]imidazo[1,2-a]indole-2-carbonitrile
2-Fluoro-10-tosyl-10H-benzo[4,5]imidazo[1,2-a]indole (2d): (2i): Pale brown solid, mp 220-222 oC; Rf 0.50 (50% ethyl
Pale yellow solid, mp 162-165 oC; Rf 0.50 (15% ethyl acetate in acetate in hexanes); H NMR (CDCl3, 400 MHz) δ 2.30 (s, 3H),
1
hexanes); 1H NMR (CDCl3, 400 MHz) δ 2.29 (s, 3H), 6.53 (s, 1H), 6.61 (s, 1H), 7.17 (d, J=8.4 Hz, 2H), 7.31-7.40 (m, 2H), 7.47 (dd,
6.97 (dt, J=9.2, 2.4 Hz, 1H), 7.15 (q, J=8.8 Hz, 3H), 7.31-7.37 (m, J=8.2, 1.2 Hz, 1H), 7.61-7.65 (m, 1H), 7.74 (d, J=8.4 Hz, 1H),
2H), 7.56 (d, J=7.8 Hz, 1H), 7.59 (dd, J=8.8, 8.4 Hz, 1H), 7.80 (d, 7.80 (d, J=8.4 Hz, 2H), 8.01 (d, J=1.2 Hz, 1H), 8.04-8.09 (m, 1H);
J=8.4 Hz, 2H), 8.04 (d, J=8 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 13C NMR (CDCl3, 100 MHz) δ 21.7, 82.1, 104.9, 111.1, 111.4,
21.7, 82.1, 106.4, 106.6, 108.5, 108.8, 110.2, 111.2, 111.3, 115.2, 120.4, 123.6, 124.4, 125.3, 126.0, 127.1, 128.2, 128.7,
115.1, 123.2, 125.1, 127.1, 127.8, 128.3, 129.5, 130.0, 133.3, 130.1, 132.2, 133.4, 133.6, 140.4, 146.2; FTIR (KBr) 2922, 2854,
145.9; 19F NMR (C6F6, 500 MHz) δ -124.47; FTIR (KBr) 2923, 2221, 1603, 1566, 1490, 1375 cm-1.
2855, 1568, 1489, 1466, 1458 cm-1.
10-((4-Bromophenyl)sulfonyl)-10H-benzo[4,5]imidazo[1,2-
o
11-Methyl-10-tosyl-10H-benzo[4,5]imidazo[1,2-a]indole (2e): a]indole (2j): Pale green solid, mp 148-150 C; Rf 0.46 (10%
White solid, mp 158-160 oC; Rf 0.45 (10% ethyl acetate in ethyl acetate in hexanes); H NMR (CDCl3, 400 MHz) δ 6.48 (s,
1
hexanes); 1H NMR (CDCl3, 400 MHz) δ 2.14 (s, 3H), 2.60 (s, 3H), 1H), 7.15-7.21 (m, 3H), 7.26 (dt, J=8, 0.8 Hz, 1H), 7.39 (d, J=8.8
6.93 (d, J=8 Hz, 2H), 7.10 (dt, J=8, 1.2 Hz, 1H), 7.16-7.24 (m, Hz, 2H), 7.52 (d, J=8 Hz), 7.60-7.64 (m, 2H), 7.66 (d, J=8.8 Hz,
3H), 7.35-7.42 (m, 3H), 7.49-7.55 (m, 1H), 7.57-7.62 (m, 1H), 2H), 7.93 (d, J=8 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 21.7,
8.01 (dd, J=8, 0.4 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 9.3, 82.1, 110.5, 110.7, 115.1, 120.7, 121.2, 121.7, 123.1, 125.1,
21.6, 94.8, 109.8, 110.4, 117.6, 119.6, 121.1, 121.4, 122.5, 127.0, 127.1, 129.8, 130.0, 132.5, 133.6, 138.9, 145.7; FTIR
125.9, 126.8, 127.3, 129.7, 130.6, 133.6, 135.0, 145.1; FTIR (KBr) 3062, 1605, 1572, 1494, 1457, 1385 cm-1. HRMS (m/z):
(KBr) 3057, 2923, 2859, 1603, 1499, 1365, 1242, 1176 cm-1; [M+H]+ calcd. for C20H14N2O2SBr: 424.9959; found:424.9980
HRMS (m/z): [M+H]+ calcd. for C22H19N2O2S: 375.1167; found: (HRMS data for 79Br isotope).
375.1176.
General procedure for C2 amidative cyclization of compounds
3a-i:
6-Tosyl-6H-benzo[4',5']imidazo[1',2':1,5]pyrrolo[2,3-
b]pyridine (2f): White solid, mp 140-142 oC; Rf 0.48 (20% ethyl Indole derivative
3 (0.5 mmol) was taken in a clean and dry
1
acetate in hexanes); H NMR (CDCl3, 500 MHz) δ 2.29 (s, 3H), reaction tube. To this iodine (0.6 mmol), Cs2CO3 ( 1.0 mmol)
6.51 (s, 1H), 7.15 (d, J=8 Hz, 2H), 7.21 (dd, J=8 Hz, 1H), 7.29 (dt, and acetonotrile (2 mL) was added. Reaction tube is stoppered
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and the resulting reaction mixture was stirred at 60 C. After 4 1H NMR (CDCl3, 400 MHz) δ 0.96 (t, J=7.6 Hz, 3H),V1ie.w3A5rti(csleeOxntelinte,
DOI: 10.1039/C5OB02449H
h the second portion of iodine (0.3 mmol) was added and J=7.6 Hz, 2H), 1.94 (quintet, J=7.6 Hz, 2H) 2.19 (s, 3H), 4.74 (t,
reaction was allowed to stir at 60 oC. Upon completion of J=7.6 Hz, 2H), 6.94 (d, J=8.0 Hz, 2H), 7.19 (dt, J=8.0, 1.2 Hz, 1H),
reaction as monitored by TLC, solvent was removed under 7.23-7.29 (m, 2H), 7.32 (d, J=8.4 Hz, 3H), 7.52 (d, J=8.4 Hz, 1H),
vacuum in rotary evaporator and DCM was added. The crude 7.58 (d, J=7.6 Hz, 1H), 7.80 (d, J=7.6 Hz, 1H), 8.16 (d, J=8.4 Hz,
reaction mixture was washed with saturated Na2S2O3 solution 1H); 13C NMR (CDCl3, 100 MHz) δ 14.0, 20.2, 21.6, 31.6, 46.5,
(2 × 10 mL) and extracted with DCM. The organic layer was 109.5, 111.4, 118.0, 118.4, 119.5, 120.7, 120.8, 122.1, 122.4,
washed water (1 × 10 mL). Combined organic layers were 125.6, 126.9, 127.3, 129.3, 132.3, 140.7, 141.1, 142.5, 144.9;
concentrated using rotary evaporator and residue is purified FTIR (KBr) 3058, 2965, 2927, 2865, 1604, 1511, 1457, 1373,
by column chromatography on silica gel using hexanes/ethyl 1176 cm-1.
acetate as an eluent to afford pure product
4
.
2-Methoxy-5-methyl-6-tosyl-5,6-dihydroindolo[2,3-b]indole
5-Methyl-6-tosyl-5,6-dihydroindolo[2,3-b]indole (4a)10: White (4f): Pale green solid, mp 162-164 oC; Rf 0.43 (15% ethyl
o
o
1
solid, mp 164-166 C [lit. 162 C]10; Rf 0.56 (10% ethyl acetate acetate in hexanes); H NMR (CDCl3, 400 MHz) δ 2.11 (s, 3H),
1
in hexanes); H NMR (CDCl3, 400 MHz) δ 2.11 (s, 3H), 4.13 (s, 3.82 (s, 3H), 4.08 (s, 3H), 6.83-6.92 (m, 3H), 7.10 (dt, J=8.4, 1.2
3H), 6.86 (d, J=8.4 Hz, 2H), 7.11 (dt, J=7.6, 1.2 Hz, 1H), 7.15- Hz, 1H), 7.15-7.21 (m, 2H), 7.23 (d, J=8.4 Hz, 2H), 7.28 (d, J=8.8
7.30 (m, 5H), 7.41 (d, J=8 Hz, 1H), 7.50 (dd, J=7.6, 0.8 Hz, 1H), Hz, 1H), 7.47 (d, J=7.4 Hz, 1H), 8.05 (d, J=8.4 Hz, 1H); 13C NMR
7.71 (d, J=7.6 Hz, 1H), 8.07 (dd, J=8.4, 0.8 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 21.6, 34.0, 56.1, 102.5, 108.8, 111.3, 111.6,
(CDCl3, 100 MHz) δ 21.6, 34.0, 111.0, 118.0, 118.5, 119.5, 117.9, 118.3, 120.9, 122.2, 125.6, 127.0, 127.3, 129.4, 132.5,
120.5, 121.0, 122.3, 122.4, 125.6, 127.0, 129.4, 132.5, 140.7, 136.7, 140.5, 143.5, 144.9, 155.1; FTIR (KBr) 3060, 2927, 2845,
141.7, 143.0, 145.0; FTIR (KBr) 3057, 2923, 2853, 1600, 1528, 1623, 1527, 1466, 1433, 1369, 1177 cm-1; HRMS (m/z): [M+H]+
1505, 1436, 1396, 1368, 1175 cm-1; HRMS (m/z): [M+H]+ calcd. calcd. for C23H21N2O3S: 405.1273; found: 405.1264.
for C22H19N2O2S: 375.1167; found: 375.1166.
10-Methyl-9-tosyl-9,10-dihydropyrido[3',2':4,5]pyrrolo[2,3-
o
5-Ethyl-6-tosyl-5,6-dihydroindolo[2,3-b]indole (4b): Pale b]indole (4g): White solid, mp 160-162 C; Rf 0.46 (20% ethyl
brown solid, mp 156-158 oC; Rf 0.55 (10% ethyl acetate in acetate in hexanes); H NMR (CDCl3, 400 MHz) δ 2.21 (s, 3H),
1
1
hexanes); H NMR (CDCl3, 400 MHz) δ 1.48 (t, J=7.2 Hz, 3H), 4.33 (s, 3H), 6.98 (d, J=8.4 Hz, 2H), 7.20(dd, J=7.6 Hz, 1H), 7.22-
2.11 (s, 3H), 4.70 (q, J=7.2 Hz, 2H), 6.86 (d, J=8.4 Hz, 2H), 7.11 7.27 (m, 1H), 7.31 (t, J=8.4 Hz, 1H), 7.39 (d, J=8.4 Hz, 2H), 7.58
(dt, J=7.6, 1.2 Hz, 1H), 7.15-7.21 (m, 2H), 7.21-7.29 (m, 3H), (d, J=7.6 Hz, 1H), 8.05 (dd, J=7.6, 0.8 Hz, 1H), 8.22 (d, J=8.4 Hz,
7.45 (d, J=8 Hz, 1H), 7.49 (td, J=7.6, 0.8 Hz, 1H), 7.72dd, J=7.4, 1H), 8.40 (dd, J=4.8, 1.2 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ
0.8 Hz, 1H), 8.07 (dd, J=8.2, 0.8 Hz, 1H); 13C NMR (CDCl3, 100 21.6, 32.5, 106.1, 113.9, 117.0, 117.6, 118.5, 122.9, 125.6,
MHz) δ 15.0, 21.6, 41.8, 109.6, 111.3, 117.9, 118.4, 119.6, 126.6, 126.9, 127.0, 129.6, 132.9, 139.9, 142.4, 145.2, 151.5;
120.9, 122.3, 125.6, 127.0, 127.3, 129.4, 132.5, 140.8, 141.0, FTIR (KBr) 3056, 2926, 1609, 1514, 1435 cm-1; HRMS (m/z):
142.5, 144.9; FTIR (KBr) 3056, 2926, 2859, 1604, 1515, 1453, [M+H]+ calcd. for C21H12N3O2S: 376.1120; found: 376.1131.
1370, 1251, 1176 cm-1; HRMS (m/z): [M+H]+ calcd. for 5-Methyl-6-tosyl-5,6-dihydroindolo[2,3-b]indole-2-
o
C23H21N2O2S: 389.1324; found: 389.1313.
5-Isopropyl-6-tosyl-5,6-dihydroindolo[2,3-b]indole
carbonitrile (4h): White solid, mp 223-225 C; Rf 0.43 (20%
1
(4c): ethyl acetate in hexanes); H NMR (CDCl3, 400 MHz ppm) δ
White solid, mp 138-140 oC; Rf 0.46 (20% ethyl acetate in 2.13 (s, 3H), 4.16 (s, 3H), 6.89 (d, J=8 Hz, 2H), 7.15-7.28 (m,
hexanes); H NMR (CDCl3, 400 MHz) δ 1.74 (d, J=7.2 Hz, 6H), 4H), 7.42-7.52 (m, 3H), 8.00 (s, 1H), 8.08 (d, J=8Hz, 1H); 13C
1
2.17 (s, 3H), 5.64 (septet, J=7.2 Hz, 1H), 6.88 (s, 1H), 6.89 (d, NMR (CDCl3, 100 MHz) δ 21.7, 34.4, 104.2, 109.2, 111.7, 118.0,
J=8 Hz 2H), 7.15-7.22 (m, 3H), 7.23-7.29 (m, 3H), 7.49 (dd, 118.9, 120.2, 120.5, 124.5, 125.4, 126.0, 126.2, 127.0, 129.6,
J=7.6, 0.8 Hz, 1H), 7.73-7.79 (m, 2H), 8.11 (d, J=8 Hz, 1H); 13C 132.4, 140.8, 143.0, 144.2, 145.5; FTIR (KBr) 2923, 2855, 2217,
NMR (CDCl3, 100 MHz) δ 21.6, 21.7, 51.8, 114.5, 118.3, 118.8, 1614, 1515, 1466, 1439, 1169 cm-1.
120.0, 120.7, 121.6, 122.1, 122.3, 125.9, 127.2, 128.1, 129.1, 6-Methyl-5-tosyl-6,11-dihydro-5H-indolo[2,3-b]quinoline (4i):
131.3, 139.4, 141.4, 143.7, 144.8; FTIR (KBr) 3058, 2973, 2927, Pale red solid, mp 97-99 oC; Rf 0.46 (10% ethyl acetate in
1
2854, 1604, 1531, 1504, 1457, 1172 cm-1.
hexanes); H NMR (CDCl3, 400 MHz) δ 2.21 (d, J=18.6 Hz, 1H),
5-propyl-6-tosyl-5,6-dihydroindolo[2,3-b]indole (4d): White 2.27 (s, 3H), 3.41 (d, J=18.6 Hz, 1H), 3.86 (s, 3H), 6.89 (s, 3H),
o
solid, mp 138-140 C; Rf 0.46 (20% ethyl acetate in hexanes); 6.93 (d, J=8.4 Hz, 1H), 7.03 (dt, J=7.2, 0.8 Hz, 1H), 7.11 (dt,
1H NMR (CDCl3, 400 MHz) δ 0.94 (t, J=7.6 Hz, 3H), 2.01 (sextet, J=7.6, 1.2 Hz, 1H), 7.15-7.25 (m, 2h), 7.28 (d, J=8.4 Hz, 1H),
J=7.6 Hz, 2H), 2.19 (s, 3H), 4.69 (t, J=7.6 Hz, 2H), 6.93 (d, J=8.0 7.32 (dd, J=7.6, 0.8 Hz, 1H), 7.77 (dd, J=8, 1.2 Hz, 1H); 13C NMR
Hz, 2H), 7.19 (dt, J=8.4, 1.2 Hz, 1H), 7.21-7.29 (m, 2H), 7.30- (CDCl3, 100 MHz) δ 21.8, 25.3, 30.8, 106.2, 110.0, 118.2, 119.6,
7.35 (m, 3H), 7.52 (d, J=8.0 Hz, 1H), 7.58 (dd, J=3.6, 0.8 Hz, 1H), 122.1, 124.1, 126.6, 127.3, 128.2, 128.7, 128.9, 129.1, 131.7,
7.80 (d, J=7.2 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 11.4, 21.6, 133.5, 136.3, 136.4, 138.2, 144.8; FTIR (KBr) 3054, 2925, 2855,
22.9, 48.2, 109.5, 111.4, 117.9, 118.4, 119.5, 120.6, 120.8, 1636, 1608, 1516, 1483, 1428 cm-1; HRMS (m/z): [M+H]+ calcd.
122.1, 122.4, 125.5, 126.9, 127.3, 129.3, 132.3, 140.7, 141.2, for C23H21N2O2S: 389.1324; found: 389.1327.
142.5, 144.9; FTIR (KBr) 3058, 2965, 2927, 2865, 1604, 1511, 9-bromo-6-methyl-5-tosyl-6,11-dihydro-5H-indolo[2,3-
1454, 1176 cm-1.
b]quinoline (4j): White solid, mp 154-156 oC; Rf 0.52 (10%
1
5-butyl-6-tosyl-5,6-dihydroindolo[2,3-b]indole (4e): White ethyl acetate in hexanes); H NMR (CDCl3, 400 MHz, ppm) δ
solid, mp 138-140 C; Rf 0.46 (20% ethyl acetate in hexanes); 2.23 (d, J=18.4 Hz, 1H), 2.38 (s, 3H), 3.44 (d, J=18.4 Hz, 1H),
o
6 | J. Name., 2012, 00, 1-3
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3.93 (s, 3H), 6.93 (d, J= 8.4 Hz, 2H), 7.02 (d, J=8.0 Hz, 3H), 7.21- MHz, ppm) δ 1.52 (t, J=7.2 Hz, 3H), 4.61 (q, J=7.2VHiezw,A2rtHic)le,O7n.l3in0e
DOI: 10.1039/C5OB02449H
7.26 (m, 2H), 7.30-7.36 (m, 2H), 7.53 (d, J=0.8 Hz, 1H), 7.85 (dd, (dt, J= 7.2, 0.8 Hz, 1H), 7.42-7.49 (m, 2H), 7.58 (dt, J= 7.6, 1.2
J= 8, 0.8 Hz, 1H); 13C NMR (CDCl3, 100 MHz, ppm) δ 21.8, 25.1, Hz, 1H), 7.73 (dt, J= 7.6, 1.6 Hz, 1H), 8.00 (dd, J= 8.2, 1.6 Hz,
31.0, 105.8, 111.6, 112.9, 120.8, 124.9, 125.6, 126.3, 126.8, 1H), 8.17 (t, J= 8.4 Hz, 2H), 8.71 (s, 1H) ; 13C NMR (CDCl3, 125
127.5, 128.2, 128.7, 128.8, 129.3, 131.5, 135.0, 135.9, 138.0, MHz, ppm) δ 13.8, 36.4, 109.0, 118.5, 120.0, 120.7, 121.7,
145.1; FTIR (KBr) 3060, 2953, 2853, 1606, 1596, 1567, 1491, 123.0, 124.2, 127.5, 127.8, 128.2, 128.6, 129.0, 142.0, 146.7,
1468, 1362, 1280 cm-1. HRMS (m/z): [M+Na]+ calcd. for 152.1; FTIR (KBr) 3056, 2926, 2853, 1605, 1571, 1481, 1450,
C23H19N2O2NaSBr: 489.0248; found:489.0219 (HRMS data for 1349, 1229 cm-1.
79Br isotope).
6-Isopropyl-6H-indolo[2,3-b]quinoline (5e): Pale yellow solid,
o
1
General procedure for C2 amidative cyclization followed by mp 83-87 C; Rf 0.42 (10% ethyl acetate in hexanes); H NMR
detosylation and aromatization: Indole derivative 3f-i (0.5 (CDCl3, 500 MHz) δ 1.66 (d, J=7.0 Hz, 6H), 5.56 (septet, J=7.0
mmol) was taken in a clean and dry reaction tube. To this Hz, 1H), 7.17 (t, J=7.5 Hz, 1H), 7.34 (t, J=8 Hz, 1H), 7.43 (t, J=7.5
iodine (0.6 mmol), Cs2CO3 ( 1.0 mmol) and acetonotrile (2 mL) Hz, 1H), 7.49 (d, J=8.5 Hz, 1H), 7.60 (t, J=7.5 Hz, 1H), 7.88 (d,
were added. The reaction tube was stoppered and the J=8.5 Hz, 1H), 8.02 (d, J=8.5 Hz, 1H), 8.59 (s, 1H); 13C NMR
o
resulting reaction mixture was stirred at 60 C. After 4 h the (CDCl3, 125 MHz) δ 21.0, 44.9, 110.7, 118.3, 119.5, 121.1,
second portion of iodine (0.3 mmol) was added and reaction is 121.5, 122.7, 124.1, 127.0, 127.2, 127.6, 128.3, 128.7, 141.3,
allowed to stir at 60 oC. Upon completion of reaction as 146.8, 152.3; FTIR (KBr) 3058, 2969, 2854, 1604, 1569, 1461,
monitored by TLC, solvent was removed under vacuum in 1365, 1234 cm-1.
rotary evaporator and DCM was added. The crude reaction General procedure for iodine mediated intramolecular
mixture was washed with saturated Na2S2O3 solution (2 × 10 competitive experiment:
mL) and extracted with DCM. The organic layer was washed Compound 6a (0.5 mmol) was taken in a clean and dry
with water (1 × 10 mL). Combined organic layers were reaction tube. To this iodine (0.6 mmol), Cs2CO3 ( 1.0 mmol)
concentrated using rotary evaporator and residue is purified and acetonotrile (2 mL) were added. The reaction tube was
by column chromatography on silica gel using hexanes/ethyl stoppered and the resulting reaction mixture was stirred at 60
acetate as an eluent to afford pure product 5a-d
.
oC. After 4 h the second portion of iodine (0.3 mmol) was
6-Methyl-6H-indolo[2,3-b]quinoline (5a): Pale yellow solid, added and reaction is allowed to stir at 60 oC. Upon
o
1
mp 83-87 C; Rf 0.42 (10% ethyl acetate in hexanes); H NMR completion of reaction as monitored by TLC, solvent was
(CDCl3, 500 MHz) δ 4.02 (s, 3H), 7.32 (d, J=7.2 Hz, 1H), 7.41 (d, removed under vacuum in rotary evaporator and DCM was
J=8 Hz, 1H), 7.47 (dt, J=7, 1 Hz, 1H), 7.57-7.62 (m, 1H), 7.71- added. The crude reaction mixture was washed with saturated
7.76 (m, 1H), 8.00 (d, J=8 Hz, 1H), 8.14 (d, J=7.5 Hz, 1H), 8.22 Na2S2O3 solution (2 × 10 mL) and extracted with DCM. The
(d, J=8.5 Hz, 1H), 8.70 (s, 1H) ; 13C NMR (CDCl3, 125 MHz) δ organic layer was washed with water (1 × 10 mL). Combined
28.2, 109.0, 118.6, 120.4, 120.4, 121.6, 123.3, 124.0, 127.0, organic layers were concentrated using rotary evaporator and
128.1, 128.4, 128.7, 129.4, 142.9, 146.0, 152.3; FTIR (KBr) residue is purified by column chromatography on silica gel
3053, 2928, 1607, 1579, 1483, 1430 cm-1.
9-bromo-6-methyl-6H-indolo[2,3-b]quinoline (5b): Yellow products 7a and 7b
using hexanes/ethyl acetate as an eluent to afford pure
.
o
solid, mp 132-134 C; Rf 0.46 (20% ethyl acetate in hexanes); 14,15-ditosyl-15H-benzo[4,5]imidazo[1,2-a]indolo[2,3-
1H NMR (CDCl3, 400 MHz, ppm) δ 3.86 (s, 3H), 7.07 (1:1 q, b]indol-(14H)-ol (7a): White solid, mp 198-200 oC; Rf 0.41
J=7.2 Hz, 1H), 7.14-7.19 (m, 1H), 7.39 (t, J= 7.2 Hz, 1H), 7.56 (20% ethyl acetate in hexanes); 1H NMR (CDCl3, 500 MHz, ppm)
(dd, J= 8.4, 2.4 Hz, 1H), 7.65 (dt, J= 7.6, 1.2 Hz, 1H), 7.89 (d, J= δ 2.21 (s, 3H), 2.45 (s, 3H), 6.61 (d, J=7.6 Hz, 1H), 6.93 (d, J=8
8.0 Hz, 1H), 8.07 (d, J=8.8 Hz, 1H), 8.11 (s, 1H), 8.52 (s, 1H); 13C Hz, 2H), 6.96 (dd, J=7.4, 1.2 Hz, 1H), 7.02 (dt, J=7.6, 1.6 Hz, 1H),
NMR (CDCl3, 100 MHz, ppm) δ 28.1, 110.3, 112.9, 117.2, 122.2, 7.07-7.10 (m, 2H), 7.27 (d, J=8.0 Hz, 3H), 7.39 (d, J=8 Hz, 4H),
123.5, 124.1, 124.3, 127.4, 127.8, 128.2, 128.4, 128.8, 129.6, 7.71 (dd, J=8, 1.6 Hz, 1H), 7.77 (dd, J=7.6, 1.2 Hz, 1H), 7.83 (d,
130.9, 141.5; FTIR (KBr) 2923, 2852, 1603, 1572, 1477, 1458, J=8.0 Hz, 1H), 7.87 (d, J=8.8 Hz, 2H); 13C NMR (CDCl3, 125 MHz,
1325, 1254 cm-1. HRMS (m/z): [M+H]+ calcd. for C16H12N2Br: ppm) δ 21.4, 21.9, 87.5, 110.8, 111.9, 113.6, 113.7, 123.2,
311.0184; found:311.0172 (HRMS data for 79Br isotope).
123.4, 123.7, 124.6, 125.1, 125.3, 126.1, 128.0, 129.0, 129.8,
9-Methoxy-6-methyl-6H-indolo[2,3-b]quinoline (5c): Yellow 129.9, 132.6, 132.8, 134.4, 135.3, 138.9, 141.3, 143.5, 144.4,
o
solid, mp 110-112 C; Rf 0.46 (20% ethyl acetate in hexanes); 145.2; FTIR (KBr) 3061, 2923, 2857, 1597, 1487, 1169 cm-1.
1H NMR (CDCl3, 400 MHz) δ 3.95 (s, 3H), 3.96 (s, 3H), 7.20 (dd, 2-(6-tosylindolo[2,3-b]indol-5(6H)-yl)aniline (7b): Pale yellow
o
J=8.6, 2.4 Hz, 1H), 7.31 (d, J=8.8 Hz, 1H), 7.44 (dd, J=7.4, 1.2 Hz, solid, mp 105-107 C; Rf 0.56 (20% ethyl acetate in hexanes);
1H), 7.66 (d, J=2.4 Hz, 1H), 7.71 (dt, J=7.6, 1.6 Hz, 1H), 7.98 (dd, 1H NMR (CDCl3, 500 MHz, ppm) δ 2.24 (s, 3H), 6.89 (t, J=7.6 Hz,
J=8.4, 1.2 Hz, 1H), 8.15 (d, J=8.4 Hz, 1H), 8.66 (s, 1H); 13C NMR 1H), 7.12-7.20 (m, 2H), 7.23-7.27 (m, 1H), 7.28-7.32 (m, 2H),
(CDCl3, 100 MHz) δ 28.0, 56.3, 105.7, 109.5, 116.3, 118.5, 7.33-7.40 (m, 2H), 7.46 (d, J=8.4 Hz, 2H), 7.76 (d, J= 7.2 Hz,
120.9, 122.9, 123.9, 127.4, 127.7, 127.8, 128.3, 128.7, 129.1, 1H), 7.89 (d, J=7.6 Hz, 1H), 8.21 (d, J= 8.0 Hz, 1H); 13C NMR
137.7, 154.5; FTIR (KBr) 3055, 2927, 2855, 1615, 1576, 1392, (CDCl3, 125 MHz, ppm) δ 21.6, 112.4, 116.8, 116.9, 118.8,
1285 cm-1.
118.9, 119.3, 120.9, 121.9, 122.8, 122.8, 125.1, 126.0, 127.1,
6-ethyl-6H-indolo[2,3-b]quinoline (5d): White solid, mp 93-95 129.1, 129.5, 129.8, 134.0, 139.9, 141.6, 141.7, 143.9, 144.9;
oC; Rf 0.56 (10% ethyl acetate in hexanes); 1H NMR (CDCl3, 500
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J. Name., 2013, 00, 1-3 | 7
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ARTICLE
Journal Name
Int. Ed., 2001, 40, 4461; (c) A. K. Ghosh and Z.-VHie.wCAhrteicnle,OOnrlinge.
FTIR (KBr) 3472, 3382, 3056, 2925, 2857, 1615, 1509, 1456,
1375, 1262 cm-1.
Biomol. Chem., 2014, 12, 3567.
DOI: 10.1039/C5OB02449H
11 Y. Tokimizu, S. Oishi, N. Fujii and H. Ohno, Org. Lett., 2014,
16, 3138.
12 H. Ohno, M. Iuchi, N. Kojima, T. Yoshimitsu, N. Fujii and T.
Tanaka, Chem. - Eur. J., 2012, 18, 5352.
Acknowledgements
13 (a) V. Rajeshkumar, S. Chandrasekar and G. Sekar, Org.
Biomol. Chem., 2014, 12, 8512; (b) S. Guha, V. Rajeshkumar,
S. S. Kotha and G. Sekar, Org. Lett., 2015, 17, 406; (c) I.
Karthikeyan, D. Arunprasath and G. Sekar, Chem. Commun.,
2015, 51, 1701.
We thank DST (SB/S1/OC-72/2013) for funding. V.R. thanks
DST for funding fast track project (Project No. SB/FT/CS-
167/2013). B.S. thanks UGC, New Delhi for SRF. We thank IIT-
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