Dual organic dyes as a pseudo-redox mediation system to promotion of tandem oxidation /[3+2] cycloaddition reactions under visible light

Article abstract of DOI:10.1016/j.tet.2021.132166

An atom- and step-economy protocol has been developed to synthesize some new biologically active pyrrolo[2,1-a]isoquinoline alkaloids via redox mediation system under visible light irradiation. A vast variety of double and triple bonds, as dipolarophiles, treated with in situ generated azomethine ylides to prepare corresponding products in good to excellent yields. This metal-free method effectively promoted oxidation/[3 + 2] cycloaddition/oxidative/aromatization domino reaction without further oxidant using dual organic dyes as pseudo-redox mediation system. Besides, for most of the products, product precipitate was readily separated from reaction media. To the best of our knowledge, this is the first report of dual dyes as a pseudo-redox mediation system.

Full text of DOI:10.1016/j.tet.2021.132166

Tetrahedron xxx (xxxx) xxx
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Dual organic dyes as a pseudo-redox mediation system to promotion
of tandem oxidation /[3þ2] cycloaddition reactions under visible light
Mehdi Koohgard, Zeinab Hosseinpour, Mona Hosseini-Sarvari*
Nano Photocatalysis Lab, Department of Chemistry, Shiraz University, Shiraz, 7194684795, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
An atom- and step-economy protocol has been developed to synthesize some new biologically active
pyrrolo[2,1-a]isoquinoline alkaloids via redox mediation system under visible light irradiation. A vast
variety of double and triple bonds, as dipolarophiles, treated with in situ generated azomethine ylides to
prepare corresponding products in good to excellent yields. This metal-free method effectively promoted
oxidation/[3 þ 2] cycloaddition/oxidative/aromatization domino reaction without further oxidant using
dual organic dyes as pseudo-redox mediation system. Besides, for most of the products, product pre-
cipitate was readily separated from reaction media. To the best of our knowledge, this is the first report of
dual dyes as a pseudo-redox mediation system.
Received 30 January 2021
Received in revised form
9 April 2021
Accepted 13 April 2021
Available online xxx
Keywords:
Dual organic dyes photocatalyst
[3þ2] Cycloaddition
© 2021 Elsevier Ltd. All rights reserved.
Pyrrolo[2,1-a]isoquinoline
Redox mediation system
1. Introduction
Pyrrolo[2,1-a]isoquinoline scaffolds have proved to be very
important building blocks in natural and synthetic compounds for
Photo-induced trends have been typically used as an alternative
in synthetic chemistry through advantageous bond formations of
organic compound scaffolds [1e11]. Whereas transition-metal
photoredox catalysts usually suffer from high cost, toxicity, weak
absorption of visible light (e ˂ 20 000 Mꢀ1 cmꢀ1 at 450 nm for
Ru(bpy)3Cl2 that bpy stands for 2,20-bipyridine) and short triplet
their various spectrum of biological activities such as antidepres-
sant [18] and cardiotonics [19e21]. Some alkaloids containing
pyrrolo[2,1 a]isoquinoline moieties such as cryptaustoline and
cryptowoline adequately show antitumor and antileukemia activ-
ities and act as tubulin polymerization inhibitors [22,23]. Further-
more, other pyrrolo [2, 1-a] isoquinoline scaffolds are in charge of
the properties of the marine natural products, lamellarin alkaloids;
accordingly, a family of about 30 members of them exhibits
outstanding pharmacological properties [24e26]. In this context,
several methodologies for the preparation of pyrrolo[2,1-a]iso-
quinoline scaffolds have been applied up to now. Early methodol-
ogies have gone forward based on multistep routes and typically
require harsh reaction conditions [27e34]. More importantly,
cascade reactions as a straightforward way of synthetic method-
ologies for the synthesis of pyrrolo[2,1-a]isoquinoline scaffolds
have attracted great attention because of a high facility, atom
economy, and easy handling [35e40]. Dipolar [3 þ 2] cycloaddi-
tions between azomethines and active alkenes are highly efficient
strategies for the rapid synthesis of pyrrolo[2,1-a]isoquinoline
scaffolds. In this regard, several strategies by employing copper salt
[41], rhodium complex [42], [Ru(bpy)3]2þ 43, N-heterocyclic carbine
[44], C60-Bodipy hybrids [13], and iodo-Bodipy immobilized on the
support [45] have been investigated. Besides, two commercial
organophotocatalyst have been successfully applied in this meth-
odology [46,47]. Despite significant advances in these tandem
state lifetime (tT ¼ 0.89
ms for Ru(bpy)3Cl2), the organic dyes are
becoming very attractive alternative photosensitizers because of
relatively low cost, amenable handling and environmentally benign
property. However, not all organic dyes have long excited state
lifetime [4,12e16].
Redox mediation is one of the versatile technique in dual pho-
tocatalyst systems. The redox mediator (RM), also known as redox
photosensitizer, is a cooperative quencher that involves in the
redox processes with both the substrate and photocatalyst in the
distinct electron-transfer path [17]. Mechanistically, there are
several main routes in which a redox mediator may accelerate the
rate of a photoinduced electron transfer (PET) reaction [17]. How-
ever, the typical pathway for redox mediation of an oxidative
transformation is depicted in Scheme 1 in which "A" stands for an
electron acceptor and "sub" stands for a substrate.
* Corresponding author.
E-mail address: hossaini@shirazu.ac.ir (M. Hosseini-Sarvari).
https://doi.org/10.1016/j.tet.2021.132166
0040-4020/© 2021 Elsevier Ltd. All rights reserved.
Please cite this article as: M. Koohgard, Z. Hosseinpour and M. Hosseini-Sarvari, Dual organic dyes as a pseudo-redox mediation system to
promotion of tandem oxidation /[3þ2] cycloaddition reactions under visible light, Tetrahedron, https://doi.org/10.1016/j.tet.2021.132166

M. Koohgard, Z. Hosseinpour and M. Hosseini-Sarvari
Tetrahedron xxx (xxxx) xxx
we envision to use organic dye with high oxidation potential
(Alizarin red S [50], Ered ¼ ꢀ0.28 V vs. SCE) alongside low oxidation
potential (Eosin Y [51], Ered ¼ ꢀ1.14 vs. SCE) (See SI, Table S1) for the
highly efficient synthesis of pyrrolo[2,1-a]isoquinoline scaffolds.
2. Results and discussion
At the outset, tetrahydroisoquinoline ester 1a and N-phenyl
maleimide 2a were selected as the substrates in the model reaction
(Table 1). At ambient temperature, ARS was applied as high
oxidation potential dye along with other dyes to proceed reaction
through pseudo-redox mediation system under air atmosphere and
blue LED (15 W). Delightfully, compared with Indigo carmine (IC),
Fluorescein (Fl) and Rhodamine B (RB), combining Eosin Y (EY)
with ARS exhibited high efficacy in the conversion of 1a and 2a to
dihydropyrrolo[2,1-a]isoquinoline 3a with 87% yield in acetonitrile,
upon isolation (entries 1e4). Notably, all of the 4a byproduct could
be converted to 3a by adding 1.2 equiv. NBS to the reaction vessel
and stirring for 1 h. Indeed, most of the previous reports applied
NBS to afford dihydropyrrolo[2,1-a]isoquinoline scaffolds
[43,45,46]. Driven by these results, the dual dyes system was sur-
veyed in other organic solvents such as acetone, and better results
were achieved for the combination of EY and ARS in excellent yield
(entry 5). The continued solvent investigation indicated that ARS
and EY as a redox mediation system show very good activity in THF
(75%) and CHCl3 (80%) (entries 7, 9), yet DMF, EtOAc and EtOH led to
a much lower desired product than other solvents (entries 6, 8, 10).
The impact of single dye in the reaction improvement can be also
found from entries 11 and 12. To gain further investigation on the
photocatalyst effect in this tandem reaction, EY and ARS were
separately used into the reaction vessel and afforded low corre-
sponding product with 32% and 19% yields, respectively. Thereafter,
the different molar ratios of reactants were studied and the best
Scheme 1. Redox mediation of an oxidative transformation.
methodologies in comparison with early methods, most of them
suffer from one of the following drawbacks: extra oxidation steps
such as the stoichiometric amount of N-bromosuccinimide (NBS)
which is a toxic additive, using unsafe material such as I2 as co-
catalyst, using toxic and expensive catalysts, limited scope, pro-
longed reaction time and low yield.
To address these challenges, we wish to apply dual dyes as
pseudo-redox mediation system to afford tandem reaction of N-
substituted tetrahydroisoquinolines with double and triple bonds
bearing electron-withdrawing substituents without further
oxidant, hoping this unprecedented method represents a rather
inexpensive, environmentally friendly and efficient protocol under
visible light and ambient aerobic conditions. While similar trans-
formations have been reported previously, there are some merits to
this new procedure. In particular, the methodology appears to be
operationally simple and high yielding across a wide range of
substrate combinations.
One of the neglected organic dye in the photocatalytic reactions
is Alizarin red S (ARS). We previously reported the application of
ARS in the sensitization of TiO2 toward CeC bond formation [48],
thiocyanation, and cyclization reactions [49]. In the current report,
Table 1
Optimization of reaction conditions for 1a and 2a a
.
Entry
Photocatalyst
Solvent
Yield 3a/4a (%)b
1
2
3
4
5
6
7
8
ARS/IC
ARS/FL
ARS/RhB
ARS/EY
ARS/EY
ARS/EY
ARS/EY
ARS/EY
ARS/EY
ARS/EY
EY
CH3CN
CH3CN
CH3CN
CH3CN
Acetone
DMF
THF
EtOAc
CHCl3
EtOH
39/0
21/44
17/57
87/trace
91/0
32/11
75/13
43/12
80/trace
12/11
32/10
19/14
93/0
9
10
11c
12c
13d
14e
Acetone
Acetone
Acetone
Acetone
ARS
ARS/EY
ARS/EY
86/0
a
Reaction conditions: Tetrahydroisoquinoline ester 1a (1.0 mmol), N-phenyl maleimide 2a (1.0 mmol), and catalyst (1.0 mol % of each dye) in solvent (6 mL) were irradiated
by 15 W Blue LED for 18 h at ambient temperature (28 ꢁC).
b
Isolated product.
2.0 mol % of dye.
c
d
1.2 mmol 1a and 1.0 mmol 2a.
1.0 mmol 1a and 1.2 mmol 2a. IC: Indigo carmine; FL: Fluorescein; RhB: Rhodamine B.
e
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M. Koohgard, Z. Hosseinpour and M. Hosseini-Sarvari
Tetrahedron xxx (xxxx) xxx
Table 2
Optimization of light, atmosphere and amount of photocatalysta.
Entry
Light
Amount of photocatalyst (EY/ARS)
Yield of 3a (%)b
1
2
3
4
5
6
7
8
Blue LED
Green LED
Red LED
White LED
Sunlight
Dark
Blue LED
Blue LED
Blue LED
Blue LED
Blue LED
Blue LED
1 mol%/1 mol%
1 mol%/1 mol%
1 mol%/1 mol%
1 mol%/1 mol%
1 mol%/1 mol%
1 mol%/1 mol%
2 mol%/2 mol%
3 mol%/3 mol%
2 mol%/4 mol%
4 mol%/2 mol%
2 mol%/4 mol%
2 mol%/4 mol%
93
62
23
88
91
0
95
95
97
94
trace
trace
9
10
11c
12d
a
Reaction conditions: Tetrahydroisoquinoline ester 1a (1.2 mmol), N-phenyl maleimide 2a (1.0 mmol) and catalyst (EY/ARS) in acetone (6 mL) were irradiated by 15 W LED
for 18 h at ambient temperature (all reactions at 28 ꢁC except for reaction under sunlight).
b
Yield of the isolated product.
Under Ar atmosphere (1atm, ballon).
With 1.5 equiv. of TEMPO.
c
d
result was tabulated for 1.2 equiv. of 1a and 1.0 equiv. of 2a
furnishing the respective product in 93% yield (entries 13 and 14).
In comparison to the previous reports [13,43], in the optimized
condition, the target product can be obtained without the addition
of NBS as an external oxidant.
double and triple bonds bearing electron-withdrawing substituents
(Tables 3 and 4). According to Table 3, a vast majority of N-
substituted maleimides such as N-aryl and N-alkyl maleimide
bearing electron-withdrawing and electron-donating groups pro-
ceeded in the reaction condition and gave corresponding products
in good to excellent yields. Moreover, this protocol could tolerate
different functional groups for example eCF3, eNO2, eCN, eOCH3
(3i, 3g, 3h, 3d, 3e), and halogens (3b, 3f). Notably, these results
imply that the substituents on the nitrogen atom of maleimide
showed little effect on the yields of the reaction.
Moreover, to investigate the electronic impact of substitutions
on 1, two tetrahydroisoquinolines bearing MeO or Br were exam-
ined under optimized condition. The reaction condition well
tolerated these substrates and provided 89% and 91% of corre-
sponding products, respectively (3n and 3o). So, the electronic
modification of tetrahydroisoquinoline can be accomplished.
Interestingly, for nearly all of the products, the precipitate of the
target product which is insoluble in acetone is collected at the
bottom of the reaction vessel after completing the reaction (for
example 3a, as shown in Table 2).
Then, we tested other dipolarophiles with N-substituted tetra-
hydroisoquinolines bearing nitrile, ester, ketone, nitro, and propyl.
In this context, we kept the previous optimized procedure except in
some cases we replaced acetone with acetonitrile to achieve higher
product yields. Satisfactory yields were obtained and the results
have been highlighted in Table 4. In the same way, in this procedure
air was also used as the terminal oxidant to represent this method
as a versatile and environmentally benign strategy. Notably, sym-
metrical and unsymmetrical alkynes were applicable in this pro-
tocol and led to the final pyrrolo[2,1-a]isoquinoline scaffold along
with regiospecificity (3be, 3ae and 3df). Notably, the substrate
bearing the nitro group did not work well under the reaction
condition, resulted in side reactions instead of the corresponding
product (3fa). Also, the presence of electron-withdrawing groups
on N-substituted tetrahydroisoquinolines is essential for the
Encouraged by these results, we embarked upon a study on light
sources, atmosphere, and amount of photocatalyst in the reaction,
and the results are summarized in Table 2. Entries 1e4 demon-
strated blue LED turned out to be the best light for this oxidation/
[3 þ 2] cycloaddition cascade reaction. Importantly, the reaction
under sunlight at ambient temperature and atmospheric oxygen
proceeded with excellent yield (entry 5). This result was gathered
in two consecutive clear days at Shiraz University (July. 15,16 2018,
29ꢁ590 north latitude and 52ꢁ580 east longitude, 1500 m above the
sea level). Notably, no desired product could be found in the
absence of visible light (entry 6). After examining the ratio of
photocatalysts and their amount, we have further found that the
best yield was achieved when 2 mol % of EYand 4 mol% of ARS were
applied (entries 7e10). In this condition, the corresponding product
yielded up to 97% (entry 9). Gratifyingly, the precipitate of the
target product is insoluble in acetone and was deposited at the
bottom of the reaction vessel (as shown in Table 2). To shed light on
investigating the reaction pathway, the reaction was carried out
under the Ar gas atmosphere and a trace amount of dihydropyrrolo
[2,1-a]isoquinoline 3a was obtained (entry 11). This result implies
that the reaction needs molecular oxygen as a terminal oxidant. To
gain more mechanistic evidence via diagnostic test, 2,2,6,6-
tetramethyl piperidine-1-yl)oxidanyl (TEMPO) was added to the
reaction. It was further found that the addition of TEMPO to reac-
tion resulted in a trace amount of target product (entry 12). It is
probably implied this reaction proceeds through a radical mecha-
nistic scenario.
To unfold the merit of the foregoing method, we proceeded to
explore the scope of the reaction. To address this issue, N-
substituted tetrahydroisoquinolines treated with a variety of
3

M. Koohgard, Z. Hosseinpour and M. Hosseini-Sarvari
Tetrahedron xxx (xxxx) xxx
Table 3
Evaluation of the substrate scope with maleimidesa.
progress of this reaction (3ga). Finally, acrylonitrile, (2-nitrovinyl)
benzene and 1,4-naphthoquinone were successfully applied in the
reaction providing 86%, 69% and 84% of the corresponding products
(3 ab, 3ad and 3 dg), respectively. Noteworthy, a comparison be-
tween some obtained results with methylene blue-catalyzed (e.g.,
3j, 3dc and 3df) [3 þ 2] cycloaddition reaction [47] revealed that
this dual photocatalytic system provides high efficiency in this
reaction.
intensity of EY were plotted against the different concentration of
1a and 2a, also in the absence of 1a and 2a. Fig. 1 shows that the
fluorescence intensity of EY, in the presence of ARS, increased
significantly after the addition of 1a and it has a linear correlation
with a concentration of 1a. However, 2a did not affect the intensity
of EY fluorescence. In contrast to 1a, the emission intensity of EY*
did not show a dramatically change in the presence of 2a. Hence,
SET can be attributed to 1a, not 2a.
To survey the synthetic utility of this protocol, we performed a
gram-scale reaction under optimized condition, as demonstrated in
Scheme 2. Accordingly, the reaction keeps the efficiency even on a
larger scale providing 93% of the corresponding product.
Moreover, the redox potential of 1a measured versus silver
quasi-reference electrode (Ag/AgNO3, see Supporting Information,
Fig. S2) and converted to saturated calomel electrode (þ1.24 V vs.
SCE) according to a reported literature [52].
Afterward, we performed the fluorescence quenching experi-
ments to gain more insight into the mechanism. Accordingly, EY
was efficiently quenched by ARS. Also, it was found that the
emission intensity of dual dyes mixture dramatically enhanced in
the presence of 1a. On the other hand, there is no significant effect
when 2a was added (see Supporting Information, Fig. S3, and
Fig. S4). Besides, we studied the difference in fluorescence intensity
of EY in the presence of ARS, also, diꢀff2erent concentrations of 1a and
Also, the possibility of oxidation in the last step was surveyed
through the transformation of 4a to 3a in the presence and absence
of visible light. While the corresponding product 3a was isolated in
94% yield under visible light, the conversion was shut down in dark
(Scheme 3).
Finally, based on previous reports [13,43], and our control ex-
periments, we proposed
a plausible reaction mechanism as
depicted in Scheme 4. Notably, in the catalytic circle EY/EY* has
redox potential between the excited states of ARS and N-
2a in the range of 0.0e3.75 ꢂ 10
M. The ratio of fluorescence
4

M. Koohgard, Z. Hosseinpour and M. Hosseini-Sarvari
Tetrahedron xxx (xxxx) xxx
Table 4
Evaluation of the substrate scope with other N-substituted tetrahydroisoquinolines and dipolarophilesa.
5

M. Koohgard, Z. Hosseinpour and M. Hosseini-Sarvari
Tetrahedron xxx (xxxx) xxx
Scheme 2. Oxidation/[3 þ 2]cycloaddition/aromatization cascade reaction, a gram-
scale reaction.
substituted tetrahydroisoquinoline substrates (Table S1). Typically,
ARS was excited under visible light; then, an electron transfer took
place between ARS* (E*red (ARS*/ARSꢃe) ¼ þ1.32 V vs. SCE) and EY
Fig. 1. The calibration curve for the response of EY and ARS mixture to different
concentration of 1a and 2a. EY (5.0 * 10ꢀ5 M), ARS (1.0 * 10ꢀ4 M), EY excitation
wavelength at 540 nm and emission wavelength at 580 nm, in acetone.
(Eox (EY/EYꢃþ) ¼ þ 0.72 V vs. SCE) resulted in cation radical of EYꢃþ
.
Returning EYꢃþ to the cycle of photocatalytic reaction can be
assigned to SET between EYꢃþ (E* (EY*/EYꢃþ) ¼ ꢀ1.60 V vs. SCE) and
the tetrahydroisoquinoline derivative 1 (e.g., þ1.24 V vs. SCE for 1a)
which afforded cation radical I. These electron transfers (ARS, EY, 1)
are in accord with their redox potentials (See SI, Table S1). Next, the
resulting cation radical I underwent two steps (probably Hꢃ
abstraction followed by deprotonation in the presence of super-
oxide anion radical [53]) generating azomethine ylide III. Subse-
quently, the azomethine ylide reacted with dipolarophile through
[3 þ 2] cycloaddition reaction to afford cycloadduct 4. Afterward,
these intermediate oxidized to the corresponding pyrrolo[2,1-a]
isoquinoline derivative 3.
3. Conclusion
In conclusion, we have reported an unprecedented visible light-
6

M. Koohgard, Z. Hosseinpour and M. Hosseini-Sarvari
Tetrahedron xxx (xxxx) xxx
purified by hand-made column chromatography: short columns of
SiO2 60 (230e400 mesh) in glass columns (1.0e1.5 cm); 10e20 g of
SiO2 per nearly 0.4 g crude mixture. The reactions were monitored
by thin-layer chromatography (TLC): silica gel PolyGram SIL G/UV
254 plates.
4.1.1. Synthesis of maleimides
N-aryl maleimides and N-alkyl maleimides were synthesized
respectively, according to the modified previously reported pro-
cedures [54,55].
4.1.2. Synthesis of N-aryl maleimides
5 mmol of maleic anhydride was put into to 50 mL three-necked
round-bottom flask and dissolved in 10 mL of diethyl ether upon
stirring. The flask was equipped with a dropping funnel and reflux
condenser. Then, 5 mmol of the given aniline was dissolved in 3 mL
diethyl ether and added to the flask through the dropping funnel.
The reaction mixture was stirred at room temperature for 1 h. Next,
the reaction mixture was cooled to the room temperature, was
filtered off and washed with diethyl ether to separate N-substituted
maleic acid. Afterward, the dried product added to the flask and
mixed with anhydrous sodium acetate (0.16 g, 2 mmol) and acetic
anhydride (2 mL) then stirred for 1 h at 80 ꢁC. The reaction mixture
was cooled to the room temperature and poured into an ice-water
mixture. The product washed with 20 mL of ice-cold water 3 times.
The dried crude was recrystallized from n-hexane or n-hexane/
acetone to obtain the corresponding product.
Scheme 3. Transformation of 4a to 3a.
4.1.3. Synthesis of N-alkyl maleimides
5 mmol of maleic anhydride was put into to 50 mL three-necked
round-bottom flask and dissolved in 10 mL of dichloromethane
upon stirring. The flask was kept at 0e5 ꢁC and equipped by a
dropping funnel. Then, 5 mmol of the given amine was dissolved in
3 mL dichloromethane and added to the flask through the dropping
funnel within 20 min. The reaction mixture was stirred at room
temperature for 1 h. Next, the reaction mixture was cooled to room
temperature, filtered off, and washed with diethyl ether to separate
N-substituted maleic acid. Afterward, the dried product was added
to the flask and mixed with triethylamine (0.28 mL, 2 mmol) and
acetic anhydride (2 mL) in 10 mL acetone. The reaction was refluxed
for 2 h. The reaction mixture was cooled to room temperature and
poured into an ice-water mixture. The product was washed with
20 mL ice-cold water for 3 times. The dried product was purified
using silica gel column chromatography with petroleum ether/
ethyl acetate as eluents.
Scheme 4. The proposed reaction mechanism.
mediated procedure to the promotion of tandem oxidation/[3 þ 2]
cycloaddition reactions. This facile pseudo-redox mediation system
afforded a one-pot synthesis of some new pyrrolo[2,1-a]isoquino-
line derivatives using the synergic effect of ARS high oxidation
potential dye and EY as low oxidation potential dye. High product
yields, mild and sustainable reaction conditions, and easily purifi-
cation of corresponding products are the main advantages of this
method.
4.1.4. Synthesis of N-substituted tetrahydroisoquinolines
Tetrahydroisoquinoline (5 mmol), appropriate compounds
bearing ester and carbonyl motifs (6 mmol) and K2CO3 or trie-
thylamine (10 mmol) was dissolved in THF (25 mL), the mixture
was stirred at ambient temperature for 24 h. The N-substituted
tetrahydroisoquinoline bearing nitrile and nitro was synthesized
through the following procedure. Tetrahydroisoquinoline
(5 mmol), chloroacetonitrile (6 mmol) and K2CO3 (10 mmol) were
added in toluene (25 mL) at room temperature. The reaction vessel
was heated at 80 ꢁC for 4 h and cooled. After the completion of all
reactions, the reaction mixture was poured into water (50 mL), and
extracted with CH2Cl2 or EtOAc and dried over MgSO4. The solvent
was removed under reduced pressure. The reaction mixture was
purified by column chromatography (silica gel, petroleum ether/
dichloromethane).
4. Experimental
4.1. General
Unless otherwise noted, starting materials were purchased from
Acros and Merck chemical companies and used without further
purification. Fluorescence spectra were obtained using a Perki-
nElmer LS50B fluorescence spectrophotometer. UVeVis absorp-
tions were recorded using a Hewlett-Packard Model 8452 A diode-
array spectrophotometer. Elemental analysis was performed on a
2400 series PerkinElmer analyzer. 1H NMR and 13C NMR spectra
were recorded in DMSO‑d6 or CDCl3 as solvent using Bruker Avance
DPX FT 250 MHz and Bruker Ultrashield 400 MHz spectrometry
respectively, with TMS as an internal standard (multiplicity:
s ¼ singlet, d ¼ doublet, t ¼ triplet, dd ¼ doublet of doublets,
m ¼ multiplet), coupling constants: Hz). (FT-IR) spectra were ob-
tained by a Shimadzu FT-IR 8300 spectrophotometer. The products
4.1.5. General procedure for the synthesis of Pyrrolo[2,1-a]
isoquinoline derivatives
Typically,
a mixture of tetrahydroisoquinoline ester 1a
7

M. Koohgard, Z. Hosseinpour and M. Hosseini-Sarvari
Tetrahedron xxx (xxxx) xxx
(1.2 mmol), maleimides 2a (1 mmol), and photocatalyst (EY- ARS,
2 mol%: 4 mol %) in acetone (6 mL) was added to a flask under air
atmosphere. Then, the mixture was stirred under the irradiation of
a 15 W blue LED lamp (distance app. 5.0 cm) for 20 h at ambient
temperature (28 ꢁC). After completion of the reaction (monitored
by TLC), the reaction mixture concentrated in a rotary evaporator,
and the residue was purified just by washing with acetone or by
flash column chromatography on silica gel with petroleum ether/
ethyl acetate as eluent. Other Pyrrolo[2,1-a]isoquinoline derivatives
were prepared by a similar method except the solvent was changed
to acetonitrile, respectively (in some cases prolonged time were
applied) as well as the eluent ratio of flash column chromatography
was changed regarding target products.
J ¼ 6.9 Hz), 3.11 (t, 2H, J ¼ 6.7 Hz), 3.91 (s, 3H), 4.70 (t, 2H,
J ¼ 6.7 Hz), 7.19e7.27 (m, 5H)), 7.29e7.37 (m, 2H), 8.49e8.52 (m,
1H). 13CNMR (101 MHz, CDCl3)
d (ppm) 24.0, 28.3, 33.9, 43.4, 52.3,
116.4, 118.1, 125.4, 125.5, 126.9, 127.0, 127.7, 128.0, 128.0, 130.1, 130.4,
132.4, 133.6, 148.5, 160.1, 161.8, 163.2. IR (KBr)
n
¼ 2954, 1760, 1705,
1512, 1481, 1434, 1350, 1280, 1203, 771, 740, 699 cmꢀ1. EA Requires
for C25H22N2O4: C 72.45, H 5.35, N 6.67. Found: C 72.38, H 5.39, N
6.59.
4.1.11. Methyl-10-(4-methoxyphenyl)-9,11-dioxo-5,9,10,11-
tetrahydro-6H-pyrrolo[30,4’:3,4]pyrrolo[2,1-a]isoquinoline-8-
carboxylate (3 d) [57]
White solid; yield: 365.9 mg (91%); mp 194e195 ꢁC (lit. mp
192e193 ꢁC). 1HNMR (250 MHz, CDCl3)
d (ppm) 3.11 (t, 2H,
4.1.6. Electrochemical measurement
J ¼ 7.1 Hz), 3.77 (s, 3H), 3.91 (s, 3H), 4.70 (t, 2H, J ¼ 7.1 Hz), 6.92 (d,
Cyclic voltammogram was collected using glassy carbon (as
working electrode), coiled platinum (as counter electrode), a piece
of silver wire (inserted into concentrated HNO3 then allow the wire
to dry) as a quasi-reference electrode and tetrabutylammonium
perchlorate (as electrolyte). 0.1 mmol of electrolyte (previously
dried on the vacuum oven) was weighed out and placed into the
flask and 5.0 mL dried CH3CN added. This solution was used for
0.05 mmol of sample and the final solution was completely
degassed with nitrogen gas. Data recorded at a scan rate of 100 mV/
s at ambient temperature (28 ꢁC) and the midpoint redox potential
converted to saturated calomel electrode (SCE) according to re-
ported literature [52].
2H, J ¼ 9.0), 7.23 (d, 2H, J ¼ 9.0), 7.30e7.34 (m, 3H), 8.48e8.52 (m,
1H). 13CNMR (101 MHz, CDCl3)
d (ppm) 28.3, 43.4, 52.4, 55.5, 114.2,
116.3, 118.1, 125.3, 125.4, 125.5, 127.7, 128.0, 128.0, 128.4, 130.4,
132.4, 159.0, 160.1, 162.0, 163.3. IR (KBr)
¼ 1758, 1712, 1519, 1434,
1380, 1257, 1195, 1080, 948, 817, 740, 678 cmꢀ1
n
.
4.1.12. Methyl-10-(3-methoxyphenyl)-9,11-dioxo-5,9,10,11-
tetrahydro-6H-pyrrolo[30,4’:3,4]pyrrolo[2,1-a]isoquinoline-8-
carboxylate (3e)
Yellowish oil; yield: 350.0 mg (87%). 1HNMR (250 MHz, CDCl3)
d
(ppm) 3.17 (t, 2H, J ¼ 7.0 Hz), 3.82 (s, 3H), 3.97 (s, 3H), 4.76 (t, 2H,
J ¼ 7.0 Hz), 6.91e6.97 (m, 3H), 7.26e7.29 (d, 1H, J ¼ 8.1 Hz),
7.36e7.40 (m, 3H), 8.55e8.58 (m, 1H). 13CNMR (101 MHz, CDCl3)
4.1.7. Fluorescence quenching studies
d
(ppm) 28.3, 43.5, 52.4, 55.4, 112.7, 114.0, 116.3, 118.2, 119.4, 125.3,
All Eosin Y (EY) solutions were excited at 540 nm and the
emission intensity at 580 nm was observed. Typically, appropriate
125.5, 127.7, 128.0, 128.0, 129.5, 130.4, 132.5, 133.6, 133.7, 159.9,
160.1, 161.6, 162.9. IR (KBr)
n
¼ 1759, 1712, 1604, 1542, 1434, 1350,
amounts of quencher in acetone were mixed with 5.0 * 10ꢀ5
M
1272, 1234, 1041, 956, 740, 686 cmꢀ1. EA Requires for C23H18N2O5: C
68.65, H 4.51, N 6.96. Found: C 68.61, H 4.57, N 6.89.
solution (solvent: acetone) of EY in a quartz cuvette under open-air
condition. After 4 min, the emission intensity was collected. Then,
the fluorescence intensity of EY, in the presence of ARS, after the
addition of a given amount of 1a or 2a was plotted.
4.1.13. Methyl-10-(3-chlorophenyl)-9,11-dioxo-5,9,10,11-
tetrahydro-6H-pyrrolo[30,4’:3,4]pyrrolo[2,1-a]isoquinoline-8-
carboxylate (3f)
4.1.8. Methyl-9,11-dioxo-10-phenyl-5,9,10,11-tetrahydro-6H-
pyrrolo[30,4’:3,4]pyrrolo[2,1-a]isoquinoline-8-carboxylate (3a) [56]
White solid; yield: 361.1 mg (97%); mp 218e219 ꢁC (lit.
White solid; yield: 322.8 mg (79%); mp 214e215 ꢁC. 1HNMR
(250 MHz, CDCl3)
d
(ppm) 3.11 (t, 2H, J ¼ 6.7 Hz), 3.91 (s, 3H), 4.70 (t,
2H, J ¼ 6.7 Hz), 7.19e7.40 (m, 7H), 8.46e8.49 (m, 1H). 13CNMR
217e218 ꢁC). 1HNMR (250 MHz, CDCl3)
d
(ppm) 3.18 (t, 2H,
(101 MHz, CDCl3) d (ppm) 28.4, 43.3, 51.8, 55.6, 109.5, 115.3, 119.8,
J ¼ 6.7 Hz), 3.98 (s, 3H), 4.77 (t, 2H, J ¼ 6.7 Hz), 7.26e7.30 (m, 1H),
123.1, 124.6, 127.4, 127.7, 127.7, 128.0, 128.7, 130.2, 132.7, 135.2, 135.9,
7.34e7.52 (m, 7H), 8.56e8.59 (m, 1H). 13CNMR (101 MHz, CDCl3)
137.8, 158.9, 163.2, 164.6, 165.4. IR (KBr)
n
¼ 1758, 1704, 1542, 1481,
d
(ppm) 28.3, 43.4, 52.4, 116.3, 118.2, 125.3, 125.5, 127.0, 127.7, 127.8,
128.0, 128.0, 128.9, 130.4, 132.4, 132.6, 133.7, 160.1, 161.6, 163.0. IR
(KBr)
¼ 2954, 1759, 1720, 1542, 1481, 1334, 1280, 1203, 1149, 756,
694 cmꢀ1
1434, 1280, 1157, 964, 740, 686 cmꢀ1. EA Requires for C22H15ClN2O4:
C 64.95, H 3.72, N 6.89. Found: C 64.99, H 3.66, N 6.91.
n
.
4.1.14. Methyl-10-(4-nitrophenyl)-9,11-dioxo-5,9,10,11-tetrahydro-
6H-pyrrolo[30,4’:3,4]pyrrolo[2,1-a]isoquinoline-8-carboxylate (3 g)
[58]
4.1.9. Methyl-10-(4-bromophenyl)-9,11-dioxo-5,9,10,11-tetrahydro-
6H-pyrrolo[30,4’:3,4]pyrrolo[2,1-a]isoquinoline-8-carboxylate (3 b)
White solid; yield: 378.9 mg (84%); mp 237e238 ꢁC. 1HNMR
Yellowish solid; yield: (72% using 1HNMR); mp 219e220 ꢁC.
1HNMR (250 MHz, CDCl3)
d
(ppm) 3.14 (t, 2H, J ¼ 7.1 Hz), 3.94 (s,
(250 MHz, CDCl3)
d
(ppm) 3.11 (t, 2H, J ¼ 6.8 Hz), 3.91 (s, 3H), 4.70 (t,
3H), 4.73 (t, 2H, J ¼ 7.1 Hz), 7.19e7.41 (m, 3H), 7.64 (d, 2H, J ¼ 9.1),
2H, J ¼ 6.8 Hz), 7.18e7.26 (m, 3H), 7.30-7-35 (m, 2 h), 7.52 (d, 2H,
8.27 (d, 2H, J ¼ 9.1), 8.45e8.48 (m, 1H). 13CNMR (101 MHz, CDCl3)
J ¼ 8.7 Hz), 8.45e8.49 (m, 1H). 13CNMR (101 MHz, CDCl3)
d
(ppm)
d (ppm) 28.3, 43.6, 52.6, 124.2, 124.6,125.2, 126.7, 127.8, 128.1, 128.8,
28.4, 43.3, 51.8, 119.6, 121.1, 124.3, 127.6, 127.6, 127.7, 127.7, 128.0,
128.7, 130.2, 132.5, 133.2, 135.9, 137.8, 158.9, 164.5, 165.3. IR (KBr)
130.8, 130.9, 132.5, 134.3, 138.5, 146.0, 159.8, 160.7, 162.1. IR (KBr)
n
¼ 1720, 1540, 1519, 1342, 1272, 1071, 740 cmꢀ1
.
n
¼ 1759, 1712, 1543, 1488, 1342, 1280, 1110, 810, 790 cmꢀ1. EA
Requires for C22H15BrN2O4: C 58.55, H 3.35, N 6.21. Found: C 58.61,
H 3.37, N 6.32.
4.1.15. Methyl-10-(3-cyanophenyl)-9,11-dioxo-5,9,10,11-
tetrahydro-6H-pyrrolo[30,4’:3,4]pyrrolo[2,1-a]isoquinoline-8-
carboxylate (3 h)
4.1.10. Methyl-10-(4-isopropylphenyl)-9,11-dioxo-5,9,10,11-
tetrahydro-6H-pyrrolo[30,4’:3,4]pyrrolo[2,1-a]isoquinoline-8-
carboxylate (3c)
White solid; yield: 310.0 mg (78%); mp 190e191 ꢁC. 1HNMR
(250 MHz, CDCl3)
d
(ppm) 3.19 (t, 2H, J ¼ 6.9 Hz), 4.0 (s, 3H), 4.78 (t,
2H, J ¼ 6.9 Hz), 7.29e7.32 (m. 1H), 7.40e7.43 (m, 2H), 7.55e7.63 (m,
White solid; yield: 368.8 mg (89%); mp 232e233 ꢁC. 1HNMR
2H), 7.72e7.80 (m, 2H), 8.51e8.55 (m, 1H). 13CNMR (101 MHz,
(250 MHz, CDCl3)
d
(ppm) 1.20 (d, 6H, J ¼ 6.9 Hz), 2.88 (sept, 1H,
CDCl3) d (ppm) 28.3, 43.6, 52.5, 113.1, 115.7, 118.1, 118.7, 124.7, 125.3,
8

M. Koohgard, Z. Hosseinpour and M. Hosseini-Sarvari
Tetrahedron xxx (xxxx) xxx
127.8, 128.0,128.1, 129.7, 130.1, 130.7, 130.9, 131.0, 132.5,133.6, 134.2,
4.1.21. Ethyl2-bromo-9,11-dioxo-10-phenyl-5,9,10,11-tetrahydro-
6H-pyrrolo[30,4’:3,4]pyrrolo[2,1-a]isoquinoline-8-carboxylate (3n)
[41]
159.9, 160.9, 162.3. IR (KBr)
1350, 1272, 1195, 956, 786, 740, 678 cmꢀ1. EA Requires for
23H15N3O4: C 69.52, H 3.80, N 10.57. Found: C 69.61, H 3.73, N
n
¼ 2237, 1766, 1720, 1538, 1481, 1434,
C
White solid; yield: 414.1 mg (89%); mp 217e218 ꢁC. 1H NMR
10.49.
(400 MHz, CDCl3)
d
(ppm) 1.37 (t, J ¼ 6.3 Hz, 3H) 3.07 (t, J ¼ 5.8, 2H),
4.41 (q, J ¼ 6.4 Hz, 2H), 4.52e4.68 (m, 2H), 7.14 (d, J ¼ 8.4, 1H), 7.36
(d, J ¼ 8.3, 1H), 7.39e7.53 (m, 5H), 7.72 (d, J ¼ 2.6 Hz, 1H). 13CNMR
4.1.16. Methyl-9,11-dioxo-10-(2-(trifluoromethyl)phenyl)-5,9,10,11-
tetrahydro-6H-pyrrolo[30,4’:3,4]pyrrolo[2,1-a]isoquinoline-8-
carboxylate (3i)
(101 MHz, CDCl3)
d (ppm) 14.3, 28.3, 43.4, 60.6, 118.0, 119.8, 122.8,
125.5, 126.8, 127.2, 128.4, 129.0, 129.0, 129.6, 131.0, 132.0, 134.8,
136.4, 158.5, 164.3, 165.4. IR (KBr)
¼ 2909, 1726, 1651, 1511, 1468,
1317, 1275, 738, 711 cmꢀ1
White solid, yield: 339.0 mg (77%); mp 239e240 ꢁC. 1HNMR
n
.
(250 MHz, CDCl3)
d
(ppm) 3.20 (t, 2H, J ¼ 6.8 Hz), 3.97 (s, 3H),
4.69e4.89 (m, 2H), 7.26e7.30 (m, 1H), 7.37e7.40 (m, 3H), 7.57e7.73
(m, 2H), 7.83 (d, 1H, J ¼ 7.7), 8.51e8.55 (m, 1H). 13CNMR (101 MHz,
4.1.22. Ethyl2,3-dimethoxy-9,11-dioxo-10-phenyl-5,9,10,11-
tetrahydro-6H-pyrrolo[30,4’:3,4]pyrrolo[2,1-a]isoquinoline-8-
carboxylate (3ꢁ) [56]
CDCl3) d (ppm) 28.3, 43.5, 52.4, 116.3, 118.4, 121.8, 124.5, 125.4, 127.4
(q, 1C, J ¼ 12 Hz) 127.7, 129.8, 130.0, 130.5, 130.8, 132.0, 132.5, 133.0,
Yellow solid; yield: 406.3 mg (91%); mp 229e230 ꢁC (lit.
133.9. IR (KBr)
n
¼ 1765, 1721, 1550, 1357, 1319, 1126, 879, 748,
230e231 ꢁC). 1H NMR (400 MHz, CDCl3)
d
1.37 (t, J ¼ 6.3 Hz, 3H),
624 cmꢀ1. EA Requires for C23H15F3N2O4: C 62.73, H 3.43, N 6.36.
Found: C 62.78, H 3.37, N 6.31.
3.10 (t, J ¼ 5.7, 2H), 3.85 (s, 3H), 3.86 (s, 3H), 4.41 (q, J ¼ 6.4 Hz, 2H),
4.57e4.64 (m, 2H), 6.94 (t, J ¼ 1.0 Hz, 1H), 7.15 (s, 1H), 7.39e7.52 (m,
4H), 8.15 (s, 1H). 13CNMR (101 MHz, CDCl3)
d (ppm) 14.3, 28.1, 43.5,
4.1.17. Ethyl-9,11-dioxo-10-phenyl-5,9,10,11-tetrahydro-6H-pyrrolo
[30,4’:3,4]pyrrolo[2,1-a]isoquinoline-8-carboxylate (3j) [35]
White solid; yield: 363.2 mg (94%); mp 192e193 ꢁC (lit.
56.0, 56.1, 60.6, 109.9, 111.2, 120.1, 121.9, 122.8, 125.4, 126.8, 128.4,
129.0, 129.0, 132.5, 134.5, 148.1, 148.6, 158.5, 164.5, 165.2. IR (KBr)
n
¼ 2952, 1723, 1698, 1549, 1345, 1265, 1186, 1033, 912, 734,
190e191 ꢁC). 1HNMR (250 MHz, CDCl3)
d (ppm) 1.39 (t, 3H,
646 cmꢀ1
.
J ¼ 7.1 Hz), 3.11 (t, 2H, J ¼ 6.7 Hz), 4.35 (q, 2H, J ¼ 7.1 Hz), 4.70 (t, 2H,
J ¼ 6.7 Hz), 7.19e7.23 (m,1H), 7.30e7.45 (m, 6H), 8.49e8.53 (m, 1H).
4.1.23. Methyl 1-cyano-5,6-dihydropyrrolo[2,1-a]isoquinoline-3-
carboxylate (3 ab)
13CNMR (101 MHz, CDCl3)
d 14.2, 28.4, 43.4, 61.7, 125.2, 125.6, 127.2,
127.7, 127.8, 128.0, 128.0, 129.0, 130.4, 132.5, 132.6, 133.5, 159.7,
161.7, 163.1, 177.7. IR (KBr)
¼ 1761, 1705, 1553, 1481, 1342, 1280,
1195, 756, 694, 617 cmꢀ1
White solid; yield: 216.8 mg (86%); mp 97e98 ꢁC. 1HNMR
n
(250 MHz, CDCl3)
d
(ppm) 3.03 (t, 2H, J ¼ 6.7 Hz), 3.79 (s, 3H), 4.58
.
(t, 2H, J ¼ 6.7 Hz), 7.18e7.34 (m, 3H), 8.10e8.14 (m, 1H). 13CNMR
(101 MHz, CDCl3)
d (ppm) 28.3, 43.0, 51.1, 87.1, 114.8, 119.4, 123.4,
4.1.18. Methyl-10-isobutyl-9,11-dioxo-5,9,10,11-tetrahydro-6H-
pyrrolo[30,4’:3,4]pyrrolo[2,1-a]isoquinoline-8-carboxylate (3 k)
White solid; yield: 320.7 mg (91%); mp 172e173 ꢁC. 1HNMR
124.7, 127.9, 128.7, 130.1, 133.3, 136.6, 141.2, 163.1. IR (KBr)
1712, 1450, 1257, 1195, 1095, 763, 717 cmꢀ1. EA Requires for
15H12N2O2: C 71.42, H 4.79, N 11.10. Found: C 71.48, H 4.71, N 11.15.
n
¼ 2221,
C
(250 MHz, CDCl3)
d
(ppm) 0.84 (d, 6H, J ¼ 6.7 Hz), 2.01 (sept, 1H,
J ¼ 6.7 Hz), 3.05 (t, 2H, J ¼ 7.0 Hz), 3.31 (d, 2H, J ¼ 7.2 Hz), 3.87 (s,
3H), 4.62 (t, 2H, J ¼ 7.0 Hz), 7.14e7.32 (m, 3H), 8.39e8.43 (m, 1H).
4.1.24. 9,11-Dioxo-10-phenyl-5,9,10,11-tetrahydro-6H-pyrrolo
[30,4’:3,4]pyrrolo[2,1-a]isoquinoline-8-carbonitrile (3ba)
White solid; yield: 271.4 mg (80%); mp 288e289 ꢁC. 1HNMR
(250 MHz, CDCl3)
J ¼ 6.6 Hz), 7.26 (t, 2H, J ¼ 1.5 Hz), 7.32e7.53 (m, 6H), 8.48e8.52 (m,
1H). 13CNMR (101 MHz, CDCl3)
(ppm) 28.0, 43.8,101.1,113.6,120.5,
124.7, 126.8, 127.0, 127.8, 127.8, 128.4, 128.5, 129.0, 129.0, 130.2,
13CNMR (101 MHz, CDCl3)
d (ppm) 20.2, 27.9, 28.2, 43.2, 45.6, 52.3,
116.5, 117.4, 125.5, 125.7, 127.6, 127.8, 127.9, 130.1, 132.3, 132.9, 160.0,
d
(ppm) 3.28 (t, 2H, J ¼ 6.6 Hz), 4.39 (t, 2H,
162.9, 164.1. IR (KBr)
n
¼ 1751, 1697, 1542, 1481, 1342, 1280, 1203,
1041, 748, 624 cmꢀ1. EA Requires for C20H20N2O4: C 68.17, H 5.72, N
7.95. Found: C 68.14, H 5.79, N 7.88.
d
137.1, 139.5, 164.1, 165.1. IR (KBr)
n
¼ 2221, 1757, 1712, 1473, 1350,
1141, 1087, 763, 694 cmꢀ1. EA Requires for C21H13N3O2: C 74.33, H
3.86, N 11.10. Found: C 74.27, H 3.77, N 11.06.
4.1.19. Methyl-10-cyclohexyl-9,11-dioxo-5,9,10,11-tetrahydro-6H-
pyrrolo[30,4’:3,4]pyrrolo[2,1-a]isoquinoline-8-carboxylate (3 l) [46]
White solid; yield: 351.9 mg (93%); mp 188e189 ꢁC. 1HNMR
(250 MHz, CDCl3)
d (ppm) 1.18e1.36 (m, 4H), 1.65 (d, 2H,
4.1.25. Methyl-9,11-dioxo-5,9,10,11-tetrahydro-6H-pyrrolo
[30,4’:3,4]pyrrolo[2,1-a]isoquinoline-8-carboxylate (3ac)
Yellowish solid; yield: 272.5 mg (92%); mp 168e169 ꢁC. 1HNMR
J ¼ 10.0 Hz), 1.78 (d, 2H, J ¼ 12.0 Hz), 2.08e2.23 (m, 2H), 3.07 (t, 2H,
J ¼ 7.0 Hz), 3.91 (s, 3H), 3.94e4.04 (m, 1H), 4.65 (t, 2H, J ¼ 7.0 Hz),
7.18e7.21 (m, 1H), 7.25e7.37 (m, 2H), 8.45e8.48 (m, 1H). 13CNMR
(250 MHz, DMSO‑d6)
4.61 (t, 2H, J ¼ 6.7 Hz), 7.38e7.42 (m, 3H), 8.31e8.34 (m, 1H), 10.71
(s, 1H). 13CNMR (101 MHz, DMSO‑d6)
(ppm) 27.2, 43.0, 52.0, 116.9,
117.1, 125.0, 125.8, 126.6, 127.3, 127.9, 130.1, 131.7, 133.0, 159.2, 162.9,
d
(ppm) 3.13 (t, 2H, J ¼ 6.7 Hz), 3.82 (s, 3H),
(101 MHz, CDCl3)
116.3, 124.6, 124.7,126.6,126.8,126.9,129.1,131.3, 131.9, 159.2,161.9,
163.1. IR (KBr)
¼ 2939, 1755, 1697, 1550, 1427, 1380, 1334, 1280,
1195, 1033, 748 cmꢀ1
d (ppm) 24.2, 25.1, 27.3, 28.8, 42.2, 50.0, 51.2,115.7,
d
n
.
164.6. IR (KBr)
n
¼ 3440, 1712, 1658, 1365, 1280, 1226, 763,
624 cmꢀ1. EA Requires for C16H12N2O4: C 64.86, H 4.08, N 9.46.
Found: C 64.82, H 4.04, N 9.30.
4.1.20. Methyl-10-benzyl-9,11-dioxo-5,9,10,11-tetrahydro-6H-
pyrrolo[30,4’:3,4]pyrrolo[2,1-a]isoquinoline-8-carboxylate (3 m)
[46]
4.1.26. Methyl-1-nitro-2-phenyl-5,6-dihydropyrrolo[2,1-a]
isoquinoline-3-carboxylate (3ad)
White solid; yield: 328.4 mg (85%); mp 208e209 ꢁC. 1HNMR
(250 MHz, CDCl3)
2H, J ¼ 6.8 Hz), 4.77 (s, 2H), 7.21e7.39 (m, 6H), 7.42e7.46 (m, 2H),
8.48e8.52 (m, 1H). 13CNMR (101 MHz, CDCl3)
(ppm) 28.3, 41.09,
43.3, 52.4, 116.5, 117.8, 125.5, 125.7, 127.6, 127.6, 127.9, 128.0, 128.6,
130.3, 132.3, 133.2, 137.1, 160.1, 162.4, 163.7. IR (KBr)
¼ 2939, 1759,
1705, 1550, 1481, 1427, 1334, 1280, 1195, 1056, 910, 748, 624 cmꢀ1
d
(ppm) 3.12 (t, 2H, J ¼ 6.8 Hz), 3.97 (s, 3H), 4.70 (t,
Yellowish solid; yield: 240.3 mg (69%); mp 167e168 ꢁC. 1HNMR
(250 MHz, CDCl3)
3H, J ¼ 6.7 Hz), 7.11e7.19 (m, 3H), 7.25e7.40 (m, 5H), 8.0 (m, 1H).
13CNMR (101 MHz, CDCl3)
(ppm) 28.1, 43.4, 51.8, 120.1, 125.2,
126.8, 128.0, 128.2, 129.2, 129.5, 129.8, 130.1, 132.0, 132.4, 132.9,
133.1, 137.0, 159.4. IR (KBr)
¼ 2916, 1738, 1651, 1509, 1481, 1434,
d
(ppm) 3.0 (t, 2H, J ¼ 6.7 Hz), 3.69 (s, 3H), 4.63 (t,
d
d
n
.
n
9

M. Koohgard, Z. Hosseinpour and M. Hosseini-Sarvari
Tetrahedron xxx (xxxx) xxx
1311, 1265, 1218, 748, 702 cmꢀ1. EA Requires for C20H16N2O4: C
68.96, H 4.63, N 8.04. Found: C 68.92, H 4.68, N 8.09.
126.22, 126.89, 127.42, 128.37, 130.57, 131.92, 133.25, 158.96, 163.12,
164.88. IR (KBr)
n
¼ 3117, 2971, 1761, 1709, 1608, 1521, 1349, 1311,
1161, 769, 761 cmꢀ1
.
4.1.27. Diethyl 3-cyano-5,6-dihydropyrrolo[2,1-a]isoquinoline-1,2-
dicarboxylate (3be)
Declaration of competing interest
White solid; yield: 290.9 mg (86%); mp 134e135 ꢁC. 1HNMR
(250 MHz, CDCl3)
4.17 (t, 3H, J ¼ 6.7 Hz), 4.26e4.40 (m, 4H), 7.19e7.26 (m, 3H),
7.58e7.62 (m, 1H). 13CNMR (101 MHz, CDCl3)
(ppm) 14.1, 28.6,
29.7, 43.4, 61.4, 62.1, 105.9, 111.4, 115.2, 122.9, 125.2, 125.8, 127.9,
128.4, 129.4, 132.3, 132.4, 161.1, 165.4. IR (KBr)
¼ 2923, 2224, 1720,
1463, 1296, 1240, 1180, 1103, 1056, 765 cmꢀ1. EA Requires for
19H18N2O4: C 67.45, H 5.36, N 8.28. Found: C 67.40, H 5.38, N 8.31.
d
(ppm) 1.28e1.35 (m, 6H), 3.07 (t, 2H, J ¼ 6.7 Hz),
The authors declare that they have no known competing
financial interests or personal relationships that could have
appeared to influence the work reported in this paper.
d
n
Acknowledgments
C
We gratefully thank the support of this work by the Shiraz
University Research Council. We also thank Dr Mohammad Mahdi
Bordbar and Mr. Hossein Ashrafi for their kindly helps.
4.1.28. 1,2-Diethyl-3-methyl-5,6-dihydropyrrolo[2,1-a]
isoquinoline-1,2,3-tricarboxylate (3ae)
White solid; yield: 278.4 mg (75%); mp 93e94 ꢁC. 1HNMR
Appendix A. Supplementary data
(250 MHz, CDCl3)
3.76 (s, 3H), 4.18e4.36 (m, 4H), 4.44 (t, 2H, J ¼ 7.1 Hz), 7.14e7.24 (m,
3H), 8.08e8.12 (m, 1H). 13CNMR (101 MHz, CDCl3)
(ppm) 14.0,
14.3, 29.3, 42.6, 51.9, 60.8, 61.5, 110.7, 118.7, 126.3, 126.9, 127.1, 127.3,
128.4, 129.3, 134.2, 136.8, 160.2, 163.4, 166.1. IR (KBr)
¼ 2977, 1713,
1512, 1465, 1296, 1211, 1110, 1026, 879, 771 cmꢀ1. EA Requires for
20H21NO6: C 64.68, H 5.70, N 3.77. Found: C 64.61, H 5.75, N 3.68.
d
(ppm) 1.21e1.35 (m, 6H), 2.91 (t, 2H, J ¼ 7.1 Hz),
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tet.2021.132166.
d
n
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(ppm) 28.4,
30.8, 43.8, 116.0, 117.1, 125.3, 127.1, 127.7, 128.0, 128.0, 128.3, 129.0,
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1471, 1376, 1347, 1280, 1103, 1149, 756, 694 cmꢀ1. EA Requires for
22H16N2O3: C 74.15, H 4.53, N 7.86. Found: C 74.11, H 4.47, N 7.82.
d
(ppm) 2.90 (s, 3H), 3.16 (t, 2H, J ¼ 7.0 Hz), 4.80 (t,
d
n
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ꢀ
ꢀ
ꢀ
}
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11