Crowned Macrocycles Containing Two Pyrrolo[1,2-a] Indoles Created By Intramolecular Fusion

Article abstract of DOI:10.1002/asia.202100799

Heterocyclic fused-ring systems are of utmost importance because of their presence in many natural products with biological activity. Pyrroloindoles are tricyclic heterocycles that are present in various bioactive and medicinally valuable compounds. Herein, we report the synthesis of phenylene-bridged bis-pyrrolo[1,2-a]indole crowned macrocycles 1–3 in which the pyrrolo[1,2-a]indole moieties were formed via intramolecular fusion. The macrocycles were thoroughly characterized by 1D and 2D NMR, HRMS and X-ray crystallographic studies. The X-ray structure revealed that the two pyrrolo[1,2-a]indole moieties were parallel to each other, and one pyrrolo[1,2-a]indole unit was deviated by an angle of 9.54° while the other pyrrolo[1,2-a]indole unit was deviated by an angle of 12.0° from the mean plane defined by 28 core atoms. The macrocycles 1–3 absorb in the visible region and readily undergo oxidations because of their electron rich nature. The macrocycles 1–3 upon treatment with trifluoroacetic acid (TFA) generates the corresponding cation radicals 1–3^.+ which were stable in the open air for a week. The cation radicals 1–3^.+ absorb strongly in the NIR region and the experimental observations on crowned macrocycles 1–3 were corroborated by DFT and TD-DFT studies.

Full text of DOI:10.1002/asia.202100799

doi.org/10.1002/asia.202100799
Full Paper
Crowned Macrocycles Containing Two Pyrrolo[1,2-a] Indoles
Created By Intramolecular Fusion
Belarani Ojha, Kandala Laxman, and Mangalampalli Ravikanth*[a]
°
Abstract: Heterocyclic fused-ring systems are of utmost
importance because of their presence in many natural
products with biological activity. Pyrroloindoles are tricyclic
heterocycles that are present in various bioactive and
medicinally valuable compounds. Herein, we report the
synthesis of phenylene-bridged bis-pyrrolo[1,2-a]indole
crowned macrocycles 1–3 in which the pyrrolo[1,2-a]indole
moieties were formed via intramolecular fusion. The macro-
cycles were thoroughly characterized by 1D and 2D NMR,
HRMS and X-ray crystallographic studies. The X-ray structure
revealed that the two pyrrolo[1,2-a]indole moieties were
parallel to each other, and one pyrrolo[1,2-a]indole unit was
deviated by an angle of 9.54 while the other pyrrolo[1,2-a]
°
indole unit was deviated by an angle of 12.0 from the mean
plane defined by 28 core atoms. The macrocycles 1–3 absorb
in the visible region and readily undergo oxidations because
of their electron rich nature. The macrocycles 1–3 upon
treatment with trifluoroacetic acid (TFA) generates the
*
+
corresponding cation radicals 1–3 which were stable in the
*
+
open air for a week. The cation radicals 1–3 absorb strongly
in the NIR region and the experimental observations on
crowned macrocycles 1–3 were corroborated by DFT and TD-
DFT studies.
Introduction
oxidation step of the reaction. In continuation of our work on
pyrrolo[1,2-a]indole containing macrocycles, herein we report
the synthesis of a new type of crowned macrocycles 1–3 that
contain two pyrrolo[1,2-a] moieties as a part of the macrocyclic
framework.
Heterocyclic fused-ring systems with ring junction nitrogen
atom(s) are of interest because they constitute an important
class of natural products, many of which exhibit useful bio-
logical activity.[1–8] Pyrrolo[1.2-a]indole is one such class of
heterocyclic fused ring systems with utmost importance in
biology and medicine.[9–14] These tricyclic indole derivatives are Results and Discussion
found in many natural products and pharmaceuticals and
proved to be valuable intermediates for synthesizing more
complex alkaloids. Pyrrolo[1.2-a]indole scaffolds present in
numerous bioactive compounds such as mitomycin A and C,
which acts as anti-tumor agents, antiparasitic isoborreverine,
antimalarial alkaloid Flinderole C and Isatisine A which acts as
anti-HIV agent to name a few.[11,15–18] Because of their significant
importance as bioactive and medicinally important compounds,
many synthetic pathways have been developed to synthesize
pyrrolo[1,2-a]indoles and their derivatives. Pyrrolo[1,2-a]indole
scaffold exists as three structural isomers, namely, 9H-pyrrolo
[1,2-a]indole I, 1H-pyrrolo[1,2-a]indole II and 3H-pyrrolo[1,2-a]
indole III, depending on conjugation and position of the sp3
carbon (Scheme 1).[19] A perusal of literature reveals very few
reports on macrocycles that contain pyrrolo[1,2-a]indole moiety
as a part of the macrocyclic framework. Recently, we reported
the synthesis of crowned 3H-pyrrolo[1,2-a]indole fluorophore
macrocycles IV using readily available precursors under acid-
catalyzed reaction conditions.[20] In crowned fluorophore macro-
cycles, the pyrrolo[1,2-a]indole unit was created during the
The phenylene bridged bis-pyrrolo[1,2-a]indole crowned macro-
cycles 1–3 were synthesized as shown in Scheme 2. The desired
key precursors 5 and 6 were synthesized by adopting literature
procedures.[21,22] The p-hydroxy benzaldehyde was treated with
bis (2-chloroethyl) ether at reflux for two days to afford 7. In the
subsequent step, the compound 7 was subjected to Grignard
reaction with two different ArMgBr to afford diols 5a and 5b in
45–48% yields. On the other hand, terephthalaldehyde was
treated with two different ArMgBr under Grignard reaction
conditions to afford diols 8, which were then treated with
excess pyrrole under mild acid-catalyzed conditions to afford
benzitripyrranes 6a and 6b in 60–65% yields. The phenylene
bridged bis-pyrrolo[1,2-a]indole crowned macrocycles 1–3 were
synthesized by condensing one equivalent of appropriate diol
5a/5b with one equivalent of benzitripyrrane 6a/6b in CH2Cl2
in the presence of a catalytic amount of BF3.OEt2 under inert
atmosphere at room temperature for 10 min followed by
oxidation with DDQ in the open air for an additional 30 min.
TLC analysis showed one less polar major spot corresponding
to the desired crowned macrocycle 1–3, and a more polar
minor spot corresponding to our earlier reported macrocycle IV
and one or two more polar unidentified minor spots. The
formation of compound IV during the condensation was due to
[a] B. Ojha, Dr. K. Laxman, Prof. Dr. M. Ravikanth
Department of Chemistry
Indian Institute of Technology Bombay
Powai, Mumbai 400076 (India)
E-mail: ravikanth@chem.iitb.ac.in
scrambling in presence acid catalyst which is
a known
phenomenon in porphyrinoid chemistry.[23,24] Column chromato-
graphic purification on basic alumina afforded crowned macro-
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/asia.202100799
Chem Asian J. 2021, 16, 1–10
1
© 2021 Wiley-VCH GmbH
��
These are not the final page numbers!

Full Paper
Scheme 1. Structures of various pyrrolo[1,2-a]indole scaffolds and pyrrolo[1,2-a]indole based macrocycles.
cycles 1–3 as violet solids in 10–15% yields. The condensation
of diol 5a/5b and benzitripyrrane 6a/6b were also carried out
by using the other acid catalysts such as TFA and PTSA under
different reaction conditions, but the best yields of crowned
macrocycles 1–3 were obtained only with 0.1 equivalent of
BF3.OEt2 as an acid catalyst. The macrocycles 1–3 are highly
soluble in common organic solvents like CH2Cl2, CHCl3, THF, and
HR-MS analysis showed four mass units less than the expected
macrocycle 4 indicating the occurrence of two intramolecular
fusion reactions between pyrrolic “N” and benzene “C” to create
two pyrrolo[1,2-a]indole units as a part of the macrocyclic
skeleton to form macrocycles 1–3 as we noted previously with
macrocycle IV.[20] The formation of macrocycles 1–3 with two
pyrrolo[1,2-a]indole moieties was later confirmed by obtaining
crystal structure of macrocycle 2 (vide-infra). The compounds
1–3 were further characterized by detailed 1D and 2D NMR, and
highly distorted, we noted two resonances at 2.28 and
2.41 ppm for meso-tolyl À CH3 protons; a bunch of resonances in
the region of 3.6–4.4 ppm corresponding to À OCH2 protons of
crown ether moiety and a singlet resonance at 4.43 ppm for
anisyl À OCH3 protons. The four pyrrole protons of two pyrrolo
[1,2-a]indole moieties have appeared as three resonances at
6.57, 6.77 and 6.22 ppm; the four outer protons of benzene
rings (type d, g, e, h) of pyrrolo[1,2-a]indole moieties appeared
at 6.54, 6.77, 7.51–7.64 ppm, whereas the two inner protons
(type f and c) appeared as two doublets at 5.45 and 6.09 ppm.
The four protons resonances of p-phenylene ring of the
macrocycle overlapped with meso-aryl protons. The other two
macrocycles 1 and 3 have also shown similar NMR features.
Since the macrocycles 1–3 showed unsymmetric 1H NMR
spectra, we recorded the 1H NMR of compound 2 in pyridine-d5
°
°
at higher temperatures ( 55 C and 85 C), but the spectra
remained unsymmetric (Figure S10) suggesting a high remark-
able conformational stability of compound 2. Thus, NMR studies
helped to deduce the molecular structure of macrocycles 1–3.
the H NMR, H-1H COSY and NOESY and the selected region of
macrocycle 2 are presented in Figure 1. We made an attempt to
identify the resonances in 1H NMR based on their location,
integration, coupling constant, cross-peak connectivities ob-
served in COSY and NOESY spectra. However, due to the
overlap of resonances, we identified and assigned few
resonances, as shown in Figure 1. Since the macrocycle was
1
1
Chem Asian J. 2021, 16, 1–10
www.chemasianj.org
2
© 2021 Wiley-VCH GmbH
��
These are not the final page numbers!

Full Paper
Scheme 2. Synthesis of phenylene bridged bis-pyrrolo[1,2-a]indole crowned macrocycles 1–3.
Crystallographic Studies
crystalized in a triclinic system with P-1 space group, and the
important crystallographic parameters are given in supporting
information (Table S1–S3). The crystal structure of compound 2
presented in Figure 2 revealed that macrocycle 2 contained two
pyrrolo[1,2-a]indole moieties, one p-phenylene ring, two meso
The diffraction quality single crystals of macrocycle 2 were
grown by slow diffusion of n-hexane into chloroform solution
at room temperature over a period of 7 days. The macrocycle 2
Chem Asian J. 2021, 16, 1–10
www.chemasianj.org
3
© 2021 Wiley-VCH GmbH
��
These are not the final page numbers!

Full Paper
Figure 1. (a) Partial 1H NMR (b) partial 1H-1H COSY and (c) partial 1H-1H NOESY spectra of compound 2 recorded in CDCl3.
Figure 2. X-ray crystal structures of the compound 2 (a) top view; and (b) side view. The meso groups were omitted for the clarity of the side view.
carbon atoms and a long ether chain connected to each other
in a cyclic fashion. The pyrrole ring C fused with the benzene
ring A, creating a pyrrolo[1,2-a]indole unit A-B-C whereas the
pyrrole ring F fused with the benzene ring D generating
another pyrrolo[1,2-a]indole unit D-E-F. Thus, in compound 2,
the two pyrrolo indole units (A-B-C and D-E-F) were connected
by a long-distorted ether chain containing three oxygen atoms
(O1, O2, O3), four carbon atoms (C25–C28) at one side and a
benzene ring I with two meso carbon atoms (C6, C13) on the
other side. The mean plane is defined by considering both the
Chem Asian J. 2021, 16, 1–10
www.chemasianj.org
4
© 2021 Wiley-VCH GmbH
��
These are not the final page numbers!

Full Paper
°
pyrrolo[1,2-a]indole units, two meso-carbons and 1,4-carbon
atoms of phenylene moiety consisting of 28 atoms in total. The
pyrrolo[1,2-a]indole unit A-B-C (12 atoms) was deviated from
mean plane by an angle of 66.9 . The two tolyl groups on the
meso carbon atoms were anti-parallel to each other. The tolyl
ring H at C6 meso carbon was oriented towards the macrocyclic
°
°
the mean plane by an angle of 9.54 , whereas the pyrrolo[1,2-a]
indole unit D-E-F (12 atoms) was deviated by an angle of
core by making an angle of 55.3 with the mean plane. In
contrast, the tolyl ring G at C13 meso carbon was away from
°
°
12.01 . However, the two pyrrolo[1,2-a]indole units were almost
the core of the macrocycle by making an angle of 59.3 . Overall,
parallel to each other. The benzene ring I deviated from the
the X-ray crystallographic studies revealed non-planarity in the
macrocyclic structure.
Table 1. Photophysical and Electrochemical Data of compounds 1–3.
Absorption and electrochemical studies
Compounds
Absorption data
Electrochemical data
λabs[nm]
[logɛ]
λabs[nm]
[logɛ]
E1/2ox
[V]
E1/2ox
[V]
E1/2ox
[V]
E1/2Rdx
[V]
The absorption and redox potentials of macrocycles 1–3 were
measured, and the relevant data are tabulated in Table 1. The
comparison of absorption spectra of macrocycles 1–3 along
with macrocycle IV recorded in CHCl3 is presented in Figure 3a.
In general, the macrocycles 1–3 showed one sharp band at
300 nm and a broad band at ~550 nm with a shoulder at
~400 nm. The absorption spectra of compounds 1–3 were red
shifted compared to that of the contracted macrocycle IV by
~100 nm, which was attributed to the extended π-conjugation
in macrocycles 1–3. The macrocycles 1–3 were non-fluorescent,
unlike fluorescent macrocycle IV in spite of the presence of two
pyrrolo[1,2-a]indole moieties in macrocycles 1–3, which was
tentatively attributed to higher vibrational relaxations in macro-
1
285
[4.87]
285
[4.84]
285
[4.80]
280
[4.85]
533
[5.00]
478
[4.74]
529
[4.78]
381
[2.73]
551
[4.71]
551
[4.70]
552
[4.67]
469
[4.27]
1144
[4.27]
1109
[4.28]
1112
[4.17]
628
0.621
0.557
0.556
0.79
–
0.770
0.688
0.679
1.25
–
1.20
1.16
1.06
–
À 1.27
2
À 1.35
3
À 1.31
IV
À 1.61
*
+
1
–
–
–
–
–
*
+
2
–
–
–
*
+
3
–
–
–
*
+
IV
–
–
–
[4.50]
Figure 3. (a) Comparison of absorption spectra of the compounds 1–3 and IV (2×10À 5 M) recorded in CHCl3 at room temperature, (b) Comparison of cyclic
voltammograms of the compounds 1 and IV recorded in CH2Cl2 using saturated calomel electrode as reference electrode and 0.1 M TBAP as supporting
electrolyte. (c) Change in the absorption spectra and colour of the compounds 1 (2×10À 5 M) upon systematic addition of TFA (1–8% v/v) recorded in CHCl3 at
*
+
room temperature (d) EPR spectra of 1–3 recorded in CHCl3.
Chem Asian J. 2021, 16, 1–10
www.chemasianj.org
5
© 2021 Wiley-VCH GmbH
��
These are not the final page numbers!

Full Paper
cycles 1–3.[25,26] To further understand the electronic properties
of macrocycles 1–3, cyclic voltametric and differential pulse
voltametric studies were performed on macrocycles 1–3 (Fig-
ure S11). The comparison of oxidation waves of macrocycles 1
and IV is shown in Figure 3b, and the data is included in
Table 1. The cyclic voltametric studies revealed that the macro-
cycles 1–3 have three reversible oxidations and one quasi-
reversible reduction whereas macrocycle IV showed two
reversible oxidations and one irreversible reduction. For exam-
ple, the macrocycle 1 showed three reversible oxidations at
0.62 V, 0.77 V, 1.2 V, and one quasi-reversible reduction at
À 1.27 V. In comparison to compound IV, compounds 1–3 have
lower oxidation potentials and higher reduction potentials
(Table 1), suggesting that compounds 1–3 were easier to
oxidize and reduce compared to compound IV. Among macro-
cycles 1–3, macrocycles 2 and 3 were easier to oxidize
compared to macrocycle 1 due to the presence of electron-
donating meso-anisyl groups. Thus, macrocycles 1–3 were
electron-rich and easier to oxidize.
atmospheric conditions (Figure S15). Similar observation of
formation of cation radicals were also noted when compound 1
was treted with AgSbF6 and CuCl2 (Figure S13).
DFT Studies
To further understand the electronic structure of macrocycle 1–
*
3 and their cation radicals 1–3 +, density functional theory
(DFT)[28] and TD-DFT[29–31] calculations were carried out at
uB3LYP/6-31G (d,p)[32,33] level of theory, and the ground state
optimized structures along with the structural parameters have
been given in Figure S16 and Table S4–9. The ground state
optimized structure of macrocycle 2 closely matched with the
X-ray crystal structure of 2 where the aryl groups on two
pyrrolo[1,2-a]indole moieties were oriented away from the
macrocyclic core. However, one of the aryl group present at the
meso carbon bridging the pyrrolo[1,2-a]indole moiety and
phenylene moiety was oriented away from the core whereas
the other meso-aryl group was oriented towards the macro-
cyclic core. The frontier molecular orbital (FMO) analysis of the
macrocycle 1–3 showed that the HOMO and LUMO were
present all over the macrocycle with a negligible contribution
from crowned moiety with a HOMO-LUMO gap of 2.22 eV,
2.19 eV, 2.17 eV, respectively, for macrocycles 1, 2 and 3
(Figure S17). As we move from macrocycle 1 to 3, all the FMO
orbitals were slightly destabilized. HOMO and LUMO of
compound 3 were relatively destabilized compared to that of
compound 2, which were further destabilized compared to that
of compound 1. This upward trend of destabilization of HOMO
and LUMO led to lower oxidation as well as reduction potential
for compound 3 compared to compounds 1 and 2, which is in
agreement with data obtained from electrochemical experi-
ments (Figure S11). It was noted that as the number of anisyl
groups at the meso position of the macrocycle was increased,
the macrocycle became relatively easier to oxidize and reduce.
TD-DFT studies showed that these macrocycles 1–3 absorb in
visible region with peak absorption corresponds to HOMO-
LUMO transition at ~660 nm which is in line with the observed
absorption spectra of macrocycles 1–3 (Figure S18–20).
Formation of cation radical
Since the macrocycles 1–3 are highly electron rich and our
earlier study on similar kind of macrocycle IV, which is
contracted compared to the compounds 1–3 showed that these
types of compounds can easily form cation radicals, so we have
oxidized these macrocycles 1–3 by treating them with TFA as
well as AgSbF6 and CuCl2.[20] The macrocycles 1–3 upon treat-
*
+
ment with TFA readily formed cation radicals 1–3 as evident
from clear colour change from violet to blue and confirmed by
electron paramagnetic resonance and spectral absorption
studies.[27] The electron paramagnetic resonance spectrum of
*
+
generated cation radicals 1–3 showed one sharp resonance
with a g value of ~2.005 (Figure 3d). The formation of cation
radical was also evident from spectral absorption studies. The
absorption spectral changes upon systematic titration of macro-
cycle 1 with increasing amounts of TFA is presented in
Figure 3c. Upon increasing the amounts of TFA to macrocycle 1,
the absorption band at 550 nm was hypsochromically shifted to
533 nm with increasing intensity along with the appearance
new broad band in the region of 850–1400 nm with a peak
Since the macrocycles 1–3 are electronically rich and easily
*
oxidized to their corresponding cation radicals 1–3 +, DFT, as
*
+
maxima of 1144 nm due to the formation of cation radical 1
.
well as TD-DFT calculations, were performed on corresponding
cation radicals to get further insights into their electronic
These observations were in line with our previous studies on
*
+
macrocycle IV. However, the lower energy absorption band of
structures. The ground state optimized structures of 1–3
showed no visible changes in the structural parameters of the
macrocycles, but the SOMO and LUMO orbitals were highly
stabilized compared to the HOMO-LUMO of the parent macro-
cycles 1–3 (Figure 4a, S18–20). The SOMO and LUMO were
*
+
1–3 was 500 nm bathochromically shifted compared to cation
*
+,
radical IV which was observed at 628 nm. (Figure S12) Thus,
the significant red shift in the absorption band of cation radical
*
*
+
+
1
compared to IV
was attributed to the enhanced π-
*
+
*
1
+
conjugation in macrocycle 1. The H NMR spectrum of 1 is
broadened, and very few resonances appeared supporting the
paramagnetic nature of the compound (Figure S14). Further-
present all over the structures 1–3 with negligible contribu-
tion from crowned moiety similar to that of the macrocycles 1–
*
+
3. The LUMO was highly stabilized in cation radicals 1–3
compared to SOMO, leading to a significant decreasing of the
SOMO-LUMO gap (~0.85 eV), which is almost half of that of the
HOMO-LUMO gap (~2.2 eV) of macrocycles 1–3. Furthermore,
*
+
more, a stability study on the generated cation radical 1 was
performed by recording the absorption and EPR spectra of the
*
+
solution of 1 stored under an open atmosphere over a period
of 1 week. The studies indicated that the cation radical was
stable for up to one week at room temperature in open
*
+
TD-DFT studies on cation radicals 1–3 showed a new intense
transition in the NIR region at ~1050 nm corresponding to S!
Chem Asian J. 2021, 16, 1–10
www.chemasianj.org
6
© 2021 Wiley-VCH GmbH
��
These are not the final page numbers!

Full Paper
*
*
*
+
Figure 4. (a) Energy level diagrams of compound 2 and 2 +, (b) overlay of absorption and TD-DFT spectra of 2 +, (c) Spin density plot of 2
.
L+1 and S-1!L electronic transitions, which indicates that the
radicals absorb in the NIR region, and the experimental
observations were further validated by DFT and TD-DFT studies.
absorption band experienced massive bathochromic shift (~
*
+
500 nm) upon formation of cation radicals 1–3 which is in
agreement with the experimental observations (Figure 4b, S18–
*
+
20). The longest absorption predicted for 1–3 was found to Experimental Section
be for S-1!L (~2100 nm) transition which is typical for radical
General Information. The chemicals, such as BF3 ·Et2O and 2,3-
cations. Further, spin density analysis was performed on the
dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), were used as ob-
tained from Aldrich. All other chemicals used for the synthesis were
reagent grade unless otherwise specified. Column chromatography
*
+
cation radicals 1–3 to ascertain the paramagnetic spin local-
ization on the macrocyclic core and corresponding spin density
plots are presented in Figure 4c, S21. The studies revealed that
the paramagnetic spin was highly delocalized on the macro-
cyclic core consisting of two pyrrol[1,2-a]indole moieties along
with the phenylene bridge and no contribution from crowned
moiety. Overall, the DFT as well as TD-DFT studies corroborate
with the experimental observations.
1
was performed on silica gel (100–200) and basic alumina. The H
and 13C NMR spectra were recorded in CDCl3 on Bruker 400 and
500 MHz instruments. The frequencies for the 13C nucleus are
100.06 and 125.77 MHz for 400 and 500 MHz instruments, respec-
tively. Tetramethylsilane [Si(CH3)4] was used as an internal standard
for 1H and 13C NMR. Absorption and steady-state fluorescence
spectra were obtained with PerkinElmer Lambda-35. Cyclic voltam-
metry (CV) studies were carried out with BAS electrochemical
system utilizing the three-electrode configuration consisting of
glassy carbon (working electrode), platinum wire (auxiliary elec-
trode) and saturated calomel (reference electrode) electrodes. The
experiments were done in dry dichloromethane using tetrabuty-
lammonium perchlorate as a supporting electrolyte. EPR spectra
were recorded on a JEOL model FA200 electron spin resonance
spectrometer. The HR-mass spectra were recorded with a Q-TOF
micro mass spectrometer.
Conclusions
In conclusion, we synthesized phenylene-bridged bis-pyrrolo
[1,2-a]indole crowned macrocycles 1–3 using readily synthe-
sized precursors under mild reaction conditions. The X-ray
structure revealed that the two pyrrolo[1,2-a]indole moieties
were parallel to each other, and the pyrrolo[1,2-a]indole
moieties were deviated by an angle which are in the range of
Computational Details: All the calculations were performed using
the Gaussian 09 program package.[28] The density functional theory
(DFT) method, hybrid functional uB3LYP with basis set 6–31G
(d,p),[32,33] was used to optimizes the geometries of the phenylene
bridged bis- pyrrolo[1,2-a]-indol crowned macrocycle 1–3 and their
°
°
9.50 –12.0 from the mean plane defined by 28 macrocyclic
core atoms. The pyrrolo[1,2-a]indole containing macrocycles 1–
3 absorbs strongly in the visible region, electron-rich and
undergoes oxidations readily. The macrocycles 1–3 readily
*
+
oxidized forms 1–3 in their ground (S0) states. The minimum
*
+
energies surface of the optimized geometries of 1–3 and 1–3
were verified by vibrational analyses, and no imaginary frequencies
were found. The vertical excitation energies and oscillator strengths
*
+
formed stable cation radicals 1–3 upon treatment with TFA,
which are stable for about a week in open air. The cation
Chem Asian J. 2021, 16, 1–10
www.chemasianj.org
7
© 2021 Wiley-VCH GmbH
��
These are not the final page numbers!

Full Paper
were obtained for the 50 lowest S0!Sn transitions at the optimized
S0 state equilibrium geometries using the time-dependent density
functional theory (TDDFT) method that was carried out at the same
level of theory.[29–31] All the computations in the chloroform media
were carried out using the self-consistent reaction field (SCRF)
under the polarizable continuum model (PCM).[30,31] The electronic
absorption spectra, including wavelengths, were systematically
investigated using TDDFT with the PCM model based on the
optimized ground structure.
(m, 5H), 6.55 (dd, J=14.0, 3.9 Hz, 2H), 6.21 (d, 1H), 5.45 (d, J=
1.7 Hz, 1H), 4.16–3.95 (m, 2H), 3.88 (s, 9H), 3.78 (s, 3H), 3.69–3.34 (m,
6H). 13C NMR (126 MHz, CDCl3) δ 155.71, 154.72, 144.01, 143.44,
141.14, 140.64, 139.13, 139.05, 138.46, 137.96, 137.54, 136.32,
136.23, 135.32, 134.95, 134.78, 132.98, 132.84, 132.43, 132.22,
132.12, 132.04, 131.94, 131.87, 131.69, 131.15, 130.85, 129.84,
129.14, 128.30, 128.09, 126.83, 125.58, 124.48, 124.27, 121.79,
121.25, 120.85, 113.14, 112.15, 111.64, 108.22, 101.29, 98.26, 70.62,
69.14, 68.16, 64.93, 21.51. HRMS (ESI-TOF), m/z calculated for
C62H50N2O5 [M]+ 934.3617, found 934.3615.
Synthesis of compound 1: A sample of diol 5a (100 mg,0.20 mmol)
and benzitripyrrane 6a (84 mg, 0.20 mmol) was dissolved in 150 ml
of CH2Cl2 taken in a 250 ml of one necked round-bottom flask and
purged nitrogen for 5 min. The condensation reaction was initiated
by addition of BF3.OEt2 (2.5 μl, 0.02 mmol). After 10 minutes, the
reaction mixture was oxidized by adding DDQ (114 mg, 0.50 mmol)
and the reaction mixture was stirred in open air for additional
30 minutes. The solvent was removed under reduced pressure and
the crude compound was purified by basic alumina column
chromatography using petroleum ether-CH2Cl2 (40:60) and af-
forded pure macrocycle 1 as a violet solid in 15% yield (26 mg,
0.029 mmol). 1H NMR (400 MHz, CDCl3) δ 7.64 (d, J=8.6 Hz, 2H),
7.59–7.44 (m, 8H), 7.30 (dd, J=10.8, 4.5 Hz, 7H), 7.23–7.17 (m, 3H),
7.14 (dd, J=8.2, 1.6 Hz, 1H), 7.03 (d, J=7.5 Hz, 1H), 6.83 (dd, J=
13.1, 5.6 Hz, 2H), 6.81–6.75 (m, 2H), 6.58 (d, J=5.8 Hz, 1H), 6.54 (dd,
J=8.7, 2.2 Hz, 1H), 6.08 (d, J=2.1 Hz, 1H), 5.44 (d, J=2.0 Hz, 1H),
4.13–3.98 (m, 2H), 3.95–3.81 (m, 1H), 3.61 (dd, J=18.3, 9.2 Hz, 3H),
3.56–3.48 (m, 1H), 3.44–3.35 (m, 1H), 2.42 (s, 9H), 2.29 (s, 3H) 13C
NMR (126 MHz, CDCl3) δ 155.4, 154.4, 143.7, 143.2, 140.8, 140.3,
138.8, 138.8, 138.2„ 137.7, 137.3, 136.0, 135.0, 134.7, 134.5, 132.7,
132.5, 132.1, 131.9, 131.7, 131.6, 131.6, 131.4, 130.9, 130.6, 129.5,
129.4, 128.8, 128.0, 127.8, 126.5, 125.3, 124.2, 124.0, 121.5, 121.0,
120.6, 112.8, 111.9, 111.3, 107.9, 101.0, 98.0, 70.38, 68.8,
67.9,64.6,31.6,29.4,21.2.HRMS (ESI-TOF), m/z calculated for
C62H50N2O3[[M]+ 870.3817, found 870.3817.
Supporting Information
Supporting information contains characterization data (HRMS,
1H, 13C NMR spectra), EPR, DFT calculation data and crystallo-
graphic characterization.
Acknowledgements
M.R. thanks Science and Engineering Research Board, Government
of India for funding the project (CRG/2020/000088). B.O thanks
the CSIR India for the research fellowship and K.L thanks IIT
Bombay for IPDF fellowship.
Conflict of Interest
The authors declare no conflict of interest.
Synthesis of compound 2: Compound 2 was synthesized under
similar reaction conditions used for compound 1 using the crown
diol 5b (100 mg,0.188 mmol), benzitripyrrane 6a (78 mg,
0.187 mmol), BF3.OEt2 (2.3 μl, 0.018 mmol) and DDQ (107 mg,
0.47 mmol). The crude compound was purified by basic alumina
column chromatography using petroleum ether-CH2Cl2 (30:70) and
Keywords: Pyrrolo[1-2-a]indole
Oxidation · Cation radical · Crowned macrocycles
· Intra molecular fusion ·
[1] M. M. Heravi, V. Zadsirjan, RSC Adv. 2020, 10, 44247–44311.
afforded compound
2
as
a
violet solid in 12% yield
[2] F. Salehian, H. Nadri, L. Jalili-Baleh, L. Youseftabar-Miri, S. N. Abbas Bu-
khari, A. Foroumadi, T. Tüylü Küçükkilinç, M. Sharifzadeh, M. Khoobi, Eur.
J. Med. Chem. 2021, 212, 113034–113099.
[3] K. R. A. Abdellatif, R. B. Bakr, Med. Chem. Res. 2021, 30, 31–49.
[4] M. Tanaka, S. Sagawa, J. ichi Hoshi, F. Shimoma, K. Yasue, M. Ubukata, T.
Ikemoto, Y. Hase, M. Takahashi, T. Sasase, N. Ueda, M. Matsushita, T.
Inaba, Bioorg. Med. Chem. 2006, 14, 5781–5794.
[5] K. A. Koo, N. D. Kim, Y. S. Chon, M. S. Jung, B. J. Lee, J. H. Kim, W. J. Song,
Bioorg. Med. Chem. Lett. 2009, 19, 2324–2328.
[6] N. K. Kaushik, N. Kaushik, P. Attri, N. Kumar, C. H. Kim, A. K. Verma, E. H.
Choi, Molecules 2013, 18, 6620–6662.
(19 mg,0.021 mmol). 1H NMR (500 MHz, CDCl3) δ 7.55 (dddd, J=
34.0, 15.6, 8.1, 1.7 Hz, 9H), 7.33–7.27 (m, 5H), 7.23–7.16 (m, 3H), 7.13
(dd, J=8.2, 1.7 Hz, 1H), 7.02 (dd, J=8.7, 2.0 Hz, 4H), 6.82 (q, J=
5.6 Hz, 2H), 6.79–6.75 (m, 2H), 6.57 (d, J=5.8 Hz, 1H), 6.53 (dd, J=
8.7, 2.3 Hz, 1H), 6.08 (d, J=2.1 Hz, 1H), 5.44 (d, J=2.1 Hz, 1H), 4.14–
4.05 (m, 1H), 4.01 (d, J=2.2 Hz, 1H), 3.97–3.88 (m, 1H), 3.87 (d, J=
0.8 Hz, 6H), 3.63 (dd, J=21.8, 6.1 Hz, 3H), 3.56–3.46 (m, 1H), 3.45–
3.33 (m, 1H), 2.42 (s, 3H), 2.29 (s, 3H). 13C NMR (126 MHz, CDCl3) δ
158.3, 155.4, 154.5, 143.5, 142.9, 140.9, 140.4, 138.8, 137.7, 137.2,
135.3,134.8, 134.9, 134.6, 134.5, 132.7, 132.4, 132.0, 131.4, 130.9,
130.6, 129.4, 129.2, 129.0, 128.9, 127.1, 126.6, 125.3, 123.9, 121.4,
120.9, 120.5, 114.4, 112.6, 111.8, 111.5, 111.3, 107.9, 101.0, 98.0,
70.3, 68.9, 67.9, 64.7, 55.3, 29.7, 21.3. HRMS (ESI-TOF), m/z calculated
for C62H50N2O5 [M]+ 902.3714, found 902.3719.
[7] J. Jampilek, Molecules 2019, 24, 3839–3843.
[8] S. Tahlan, S. Kumar, B. Narasimhan, BMC Chem. Biol. 2019, 13, 1–21.
[9] M. Toyota, M. Ihara, Nat. Prod. Rep. 1998, 15, 327–340.
[10] T. R. Sutariya, B. M. Labana, N. J. Parmar, R. Kant, V. K. Gupta, G. B. Plata,
J. M. Padrón, New J. Chem. 2015, 39, 2657–2668.
[11] L. S. Fernandez, M. S. Buchanan, A. R. Carroll, Y. J. Feng, R. J. Quinn, V. M.
Avery, Org. Lett. 2009, 11, 329–332.
[12] M. B. Johansen, M. A. Kerr, Org. Lett. 2008, 10, 3497–3500.
[13] B. M. Trost, B. M. O’Boyle, W. Torres, M. K. Ameriks, Chem. A Eur. J. 2011,
17, 7890–7903.
Synthesis of compound 3: Compound 3 was synthesized under
similar reaction conditions used for compound 1 using the crown
diol
5b
(100 mg,0.188 mmol)
and
compound
6b
[14] S. A. Samsoniya, D. O. Kadzhrishvili, I. S. Chikvaidze, Pharm. Chem. J.
2011, 45, 22–25.
[15] W. T. Bradner, Cancer Treat. Rev. 2001, 27, 35–50.
[16] J. E. C. Tejeda, B. K. Landschoot, M. A. Kerr, Org. Lett. 2016, 18, 2142–
2145.
[17] D. A. Gubler, R. M. Williams, Tetrahedron Lett. 2009, 50, 4265–4267.
[18] J. F. Liu, Z. Y. Jiang, R. R. Wang, Y. T. Zheng, J. J. Chen, X. M. Zhang, Y. B.
Ma, Org. Lett. 2007, 9, 4127–4129.
(85 mg,0.189 mmol), BF3.OEt2 (2.3 μl, 0.018 mmol) and DDQ
(107 mg, 0.47 mmol). The crude compound was purified by basic
alumina column chromatography using petroleum ether-CH2Cl2
(20:80) and afforded macrocycle 3 as a violet solid in 10% yield
(17 mg, 0.018 mmol). 1H NMR (400 MHz, CDCl3) δ 7.59 (ddd, J=31.3,
13.2, 9.0 Hz, 9H), 7.47 (d, J=8.3 Hz, 1H), 7.36–7.29 (m, 3H), 7.13 (d,
J=8.2 Hz, 1H), 7.02 (d, J=7.0 Hz, 4H), 6.97–6.87 (m, 3H), 6.86–6.72
Chem Asian J. 2021, 16, 1–10
www.chemasianj.org
8
© 2021 Wiley-VCH GmbH
��
These are not the final page numbers!

Full Paper
[19] C. Lorton, A. Voituriez, Eur. J. Org. Chem. 2019, 2019, 5133–5150.
[20] B. Ojha, K. Laxman, M. Ravikanth, Asian J. Org. Chem. 2021, 10, 857–867.
[21] B. Ojha, A. Kumar, K. G. Thorat, M. Ravikanth, Tetrahedron 2019, 75,
130574.
[29] J. Tomasi, B. Mennucci, R. Cammi, Chem. Rev. 2005, 105, 2999–3094.
[30] R. Bauernschmitt, R. Ahlrichs, Chem. Phys. Lett. 1996, 256, 454–464.
[31] M. Cossi, V. Barone, R. Cammi, J. Tomasi, Chem. Phys. Lett. 1996, 255,
327–335.
[22] R. Sengupta, K. G. Thorat, M. Ravikanth, J. Org. Chem. 2018, 83, 11794–
[32] W. J. Hehre, Acc. Chem. Res. 1976, 9, 399–406.
11803.
[33] O. Treutler, R. Ahlrichs, J. Chem. Phys. 1995, 102, 346–354.
[23] A. N. Cammidge, O. Öztürk, Tetrahedron Lett. 2001, 42, 355–358.
[24] F. R. Kooriyaden, S. Sujatha, C. Arunkumar, Polyhedron 2017, 128, 85–94.
[25] N. Nijegorodov, P. V. C. Luhanga, J. S. Nkoma, D. P. Winkoun, Spectro-
chim. Acta Part A 2006, 64, 1–5.
[26] N. I. Nijegorodov, W. S. Downey, J. Phys. Chem. 2002, 98, 5639–5643.
[27] L. Eberson, F. Radner, Acta Chem. Scand. 1991, 45, 1093–1095.
[28] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R.
Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson,
Gaussian 09, Revis. A. 02; Gaussian, Inc Wallingford, CT, 2009 2009.
Manuscript received: July 14, 2021
Revised manuscript received: August 17, 2021
Accepted manuscript online: August 17, 2021
Version of record online: ■■■, ■■■■
Chem Asian J. 2021, 16, 1–10
www.chemasianj.org
9
© 2021 Wiley-VCH GmbH
��
These are not the final page numbers!

Full Paper
FULL PAPER
B. Ojha, Dr. K. Laxman, Prof. Dr. M.
Ravikanth*
1 – 10
Crowned Macrocycles Containing
Two Pyrrolo[1,2-a] Indoles
Created By Intramolecular Fusion
A facile synthesis of electronically
rich phenylene-bridged bis-pyrrolo
[1,2-a]indole crowned macrocycles 1–
3 is reported via intramolecular fusion
under oxidation conditions and
formation of corresponding cation
radicals in the presence of TFA with
huge bathochromic shift (~500 nm),
leading to NIR (850–1400 nm) absorp-
tion.