Synthesis of Pyrrolo[2,1,5- cd]indolizine Rings via Visible-Light-Induced Intermolecular [3+2] Cycloaddition of Indolizines and Alkynes

Article abstract of DOI:10.1021/acs.joc.0c01253

A range of indolizine smoothly underwent visible-light-induced intermolecular [3+2] annulations with internal alkynes to afford pyrrolo[2,1,5-cd]indolizine in good to excellent yields with high regioselectivity. Through this cascade reaction, a series of fluoroactive fused indolizines with a large π-system were conveniently synthesized. The usage of visible light as energy source with air as a stoichiometric oxidant under simple conditions makes this process attractive and practical.

Full text of DOI:10.1021/acs.joc.0c01253

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Article
Synthesis of Pyrrolo[2,1,5-cd]indolizine Rings via Visible-Light-
Induced Intermolecular [3+2] Cycloaddition of Indolizines and Alkynes
Yu Zhang, Yue Yu, Bing-bing Liang, Yong-yan Pei, Xiang Liu, Hua-Gang Yao, and Hua Cao
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c01253 • Publication Date (Web): 14 Jul 2020
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Synthesis of Pyrrolo[2,1,5-cd]indolizine Rings via
Visible-Light-Induced Intermolecular [3+2] Cycloaddition
of Indolizines and Alkynes
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Yu Zhang, Yue Yu, Bing-bing Liang, Yong-yan Pei, Xiang Liu, Hua-gang Yao* and
Hua Cao*
School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University,
Zhongshan, 528458, P.R. of China
Email: caohua@gdpu.edu.cn
A range of indolizine underwent visible-light-induced intermolecular [3+2] cycloaddition with
internal alkynes to afford pyrrolo[2,1,5-cd]indolizine.
R1
RB, air
blue LED
R1
R2
R2
N
N
R3
EWG
+
KI, DMSO
H
R3
H
EWG
transition-metal-free
organo photocatalysis
air as oxidant
32 examples
58-91% yeilds
green condition
ABSTRACT: A range of indolizine smoothly underwent visible-light-induced
intermolecular [3+2] annulations with internal alkynes to afford
pyrrolo[2,1,5-cd]indolizine in good to excellent yields with high regioselectivity.
Through this cascade reaction, a series of fluoroactive fused indolizines with a
large π-system were conveniently synthesized. The usage of visible-light as
energy source with air as stoichiometric oxidant under simple conditions
makes this process attractive and practical.
INTRODUCTION
Owing to their unique structures and long wavelength fluorescence in the visible light region,
the fused indolizines are ubiquitous skeletons in synthetic pharmaceuticals1 and fluorescent
materials2. In light of this, the development of more efficient and straightforward synthetic
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methods for the construction of fused indolizines is highly desirable. To date, considerable
attentions have been devoted to the synthesis of such compounds.3,4 Among these methods,
the [3+2]-cycloaddition of indolizines with unsaturated hydrocarbons was undoubtedly the
most concise strategy.5,6 In 2015, Hu’s group7 have reported a highly regioselective
palladium-catalyzed dehydrogenative Heck annulation of indolizine with diaryl acetylene,
affording a wide range of diarylpyrrolo[2,1,5-cd]indolizines with high atom economy
(Scheme 1a). Recently, photocatalytic transformations have been considered to be a green
alternative in synthetic chemistry.8,9 Therefore, our group10 have developed a metal-free,
visible-light-induced intermolecular [3+2] cycloaddition strategy in 2019. A broad range of
pyrrolo[2,1,5-cd]indolizine derivatives were conveniently synthesized under simple
conditions, thus providing a novel green synthetic route (Scheme 1b). However, this method
is unable to synthesize 2-substituted pyrrolo[2,1,5-cd]indolizine11, which limits the diversity
of these compounds to some degree.
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To overcome the above issue, as a continuation of our interest in the synthesis of
photocatalytic transformations and heterocyclic compounds, we herein report another highly
efficient strategy for the green construction of pyrrolo[2,1,5-cd]indolizine rings via
visible-light induced intermolecular [3+2] annulation of indolizines with alkynes, bearing a
series of versatile functional groups such as formyl, ester or carbonyl groups (Scheme 1c).
Scheme 1. Synthesis of Pyrrolo[2,1,5-cd]indolizine from Indolizine and Unsaturated
Hydrocarbon
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a) Hu's work: Org. Lett.
2015, 17, 1114-1117.
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R1
Pd(OAc)2, O2, DMSO
Ar1
R2
R1
R2
Ar2
+
N
N
8
9
Ar1
R1
Ar2
b) Our previous work: Green Chem.
, 2019, 21, 4025-4029.
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R2
rose bengal, blue LED
N
R1
R2
EWG
+
N
EWG = ester, amido, pyridyl
GWE
R2
c) This work:
R1
R1
+
N
R2
R3
EWG
N
EWG = formyl, ester, carbonyl
R3
GWE
RESULTS AND DISCUSSION
At the outset of our studies, we attempted the reaction of 2-phenylindolizine (1a)
with 3-phenylpropiolaldehyde (2a) in the presence of an organic photocatalyst. To
optimize the con-ditions, the above reaction was performed using an organic
photocatalyst in the presence of rose bengal (RB) in MeCN at room temperature for
10 h under 20 W blue LED (455nm) . The desired product 3a was obtained in 68%
yield under these reaction conditions (entry 1, Table 1). Encouraged by this result, we
tried to optimized the reaction by using other organ-ic photocatalysts at first. Eosin Y,
eosin B, rhodamine 6G and fluorescein were then tested, while none of them
catalyzed this reaction better than RB under blue light-emitting diode (LED)
irradiation, mainly due to the unmatched solvent (Table 1, entries 2-5). Therefore, we
next turned our attention to exam-ined the effect of various solvents, such as DMSO,
DCM, Toluene, EtOH, Dioxane (Table 1, entries 6-10). Among them, DMSO gave
the best result, obtaining the target product in 91% yield (Table 1, entry 7).
Alternatively, DCE was also found to be equally effective for this conversion (Table 1,
entry 8). Notably, only trace amount of product obtained when the reaction was
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performed in the absence of KI (Table 1, en-try 11). Subsequently, the influence of
additives was investi-gated by adding TFA, DABCO or t-Bu4NI to the reaction
mixture to take the place of KI. It was found that the presence of organic acid, base or
other iodized salt all improved the yield of 3a, mainly due to their promotion of the
oxidation of free radicals (Table 1, entries 12-14). In addition, we verified that the
product was not obtained without photosensitizer or in the dark (Table 1, entries
15-16). Finally, the optimal reaction conditions were achieved that adding 3 mol% of
RB and 20 mol% of KI in DMSO at room temperature for 10 h under 20 W blue LED
(Table 1, entry 7).
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Table 1. Optimization of Reaction Conditionsa
Ph
photocatalyst, additive
solvent, air
N
Ph + Ph
CHO
N
Ph
O
H
H
1a
2a
3a
entry
photocatalyst
additive
solvent
yield (%)b
1
2
RB
eosin Y
eosin B
rhodamine 6G
fluorescein
RB
KI
KI
KI
KI
KI
KI
KI
KI
KI
KI
-
MeCN
MeCN
MeCN
MeCN
MeCN
DCM
68
56
3
44
4
5
48
48
6
7
72
RB
DMSO
DCE
91
8
9
10
11
RB
78
RB
EtOH
NRc
25
RB
Dioxane
DMSO
RB
trace
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RB
RB
RB
-
TFA
DABCO
t-Bu4NI
KI
DMSO
DMSO
DMSO
DMSO
DMSO
70
87
14
15
85
NR
NR
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16d
RB
KI
aReaction conditions: 1a (0.3 mmol), 2a (0.3 mmol), photocatalyst (3 mol%), additive (0.06
b
mmol) and solvent (3 mL), carried out in air, and irradiation with a 20 W blue LED for 8 h;
Determined by GC-MS analysis. c No reaction. d In the dark.
Scheme 2. Substrate Scope of Indolizines a
R1
CHO
R1
RB, KI, air
R2
R2
+
N
DMSO, 8 h
20 W blue LED
N
Ph
Ph
OHC
1
2a
3
O
R1
R
Cl
O
N
N
N
N
R
Cl
Ph
87%
Ph
, R= OCH3,
, R= Cl,
OHC
Ph
OHC
3j
3k
OHC
Ph
OHC
84%
58%
3l 78%
3m 67%
1
3a
3b
3c
3d
3e
, R = Ph,
1
, 80%
, R = 4-Me-Ph
COOMe
Ph
1
70%
, R = 4-OMe-Ph,
O
1
58%
, R = 4-NO2-Ph,
1
N
64%
N
, R = 4-Br-Ph,
N
1
3f
81%
, R = 4-F-Ph,
1
Ph
3g
3h
71%
63%
, R = 4-CF3-Ph,
Ph
OHC
O
OHC
OHC
1
3o 62%
, R = 3-Me-Ph,
3n 60%
3p 59%
1
3i
73%
, R = 2-F-Ph,
Ph
Ph
N
Ph
Ph
N
Et
N
N
Ph
3q 61%
OHC
Ph
3r 73%
OHC
Ph
3t 61%
Ph
OHC
OHC
3s 70%
a Isolated yields
With a set of optimized reaction conditions in hand, we next examined the
substrate scope with respect to various indolizines derivatives, and the results were
reported in the Scheme 2. Gratifyingly, a broad spectrum of aryl indolizines bearing
diverse substituents, including electron-donating or electron-withdrawing groups
(such as methyl, methoxy, nitro, fluoro, chloro, bromo or trifluoromethyl), all
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smoothly underwent the transformation to produce the corresponding
2-phenylpyrrolo[2,1,5-cd]indolizine-1-carbaldehydes in fair to good yields (3a-3l).
Remarkably, our protocol could be applied to other specific aryl indolizines in
60-67% yields (3m-3o). In addition, 3-ester indolizine 1p was also suitable substrate
to perform in this transformation, giving the corresponding product 3p in 59% yields.
Meanwhile, substrates with a substituent on the indolizine ring were well-tolerated
under the standard conditions and afforded the desired products in 61-73%
yields(3q-3t).
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Scheme 3. Substrate Scope of Other Electron-Deficient Alkynea
R3
RB, KI, air
Ph
Ph
N
+
N
DMSO, 8 h
20 W blue LED
R4
R3
R4
1a
2
4
Ph
Ph
Ph
Ph
N
N
N
N
OHC
OHC
OHC
OHC
MeOC
N
Cl
4a 79%
4d 57%
4c 77%
4b 58%
Ph
Ph
Ph
Ph
N
N
N
S
OHC
OHC
OHC
O
R
O
4h,
70%
88%
R=Me
4f 66%
4g 61%
4e 59%
4i
, R=Et
Ph
Ph
Ph
Ph
N
N
N
N
O
O
Ph
Ph
4m 0%
O
Ph
O
O
O
O
O
O
Ph
4j 70%
4l 58%
4k 77%
a Isolated yields
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To further improve the synthetic value of this green method for the formation of
pyrrolo[2,1,5-cd]indolizines, the substrate scope of alkynes were subsequently
explored, as shown in Scheme 3. It was found that phenylpropiolaldehydes with
chlorine-, methyl-, or carbonyl-substitutes on the phenyl ring all reacted well under
the standard reaction conditions to afford the corresponding products in good yields
(4a-4d). To our delight, naphthyl, thienyl and alkyl alkynaldehydes also participated
well in the reaction to give the pyrrolo[2,1,5-cd]indolizines 4e-4g, albeit in low yields
of 59-66%. Furthermore, acetyenic esters or ketone reacted with 2-phenylindolizine
(1a) smoothly, affording the corresponding products 4h-4l in 58-88% yields. We also
tried to used 1,2-diphenylethyne as substrate under similar conditions but failed (4m).
We supposed that alkynes with electron-withdrawing group were more beneficial to
improve the conversion and yield of this transformation (4h-4k).
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We next investigated the effect of the solvents on its photophysical properties in air
at room temperature by taking compound 3b as an example. These results were
summarized in Table 2, Figure 2 and Figure 3. It was shown that compound 3b
equilibrated DMSO, DMF, MeCN, EtOH, and tBuOH all have absorption (λabs) in the
purple region (420-422 nm), and have their emission (λem) in the blue region (442-446
nm). When dissolved in tBuOH, 3b has the strongest absorbance in absorption spectra
and the strongest fluorescence intensity in emission spectra.
Figure 1. Absorption spectra of compound 3b
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Table 2. Spectroscopic Data of Compound 3b in Different Solvent
solvent
DMSO
DMF
EtOH
MeCN
tBuOH
a
λabs
422
422
421
420
422
(nm)
b
λem
446
447
443
442
444
(nm)
a Longest wavelength absorption maximum. b Excited at the longest wavelength absorption
maximum.
Figure 2. Emission spectra of compound 3b
To further probe the details of the mechanism, two mechanistic experiments were
conducted in Scheme 4. When 3.0 equiv. of 2,2,6,6-tetramethylpiperidin-1-oxyl
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(TEMPO) or butylated hydroxytoluene (BHT) was added to the mixture of
2-phenylindolizine (1a) and 3-phenylpropiolaldehyde (2a) in standard conditions,
only trace amount of product or no target product was observed, respectively. These
results hints that radical intermediates may be involved in this mechanism.
Scheme 4. Control experiments.
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Ph
standard conditions
N
+
Ph
Ph
CHO
N
Ph
O
1a
2a
3a
trace
no product
a) with the adding of TEMPO (3 equiv.)
b) with the adding of BHT (3 equiv.)
Figure 3. The quenching of RB fluorescence emission with 1a
Figure 4. Stern-Volmer plot.
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I0 is the inherent fluorescence intensity of RB. I is the fluorescence intensity of RB in the
presence of 1a.
Following these control experiments, we then probed the potential route of
energy transfer in the photocatalytic reaction. Thus, the effect of 2-phenylindolizine
1a on the fluorescence intensity of RB catalyst was measured at different
concentrations. As outlined in Figure 3 and 4, the results indicated that the
fluorescence emission of RB is quenched by 1a obviously because the fluorescence
emission intensity of RB decreases with the increase of 1a. Therefore, we deduced
that 1a was the energy receptor of the activated RB in this reaction.
On the basis of the experiments described above and previous report12, a
plausible mechanism for this visible-light-induced intermolecular [3+2] cycloaddition
reaction was proposed in Scheme 5. Firstly, the ground state of RB is converted to its
excited state RB* under visible light irradiation, which then interact with 1a to
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produce the radical intermediate A and RB•−. Under air atmosphere, intermediate
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•−
RB•− combined with oxygen to generate superoxide radical anion (O2 ) and
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regenerate RB to complete the photoredox cycle. Subsequently, the intermolecular
addition of intermediate B (radical resonance structure of intermediate A) to internal
alkyne 2a furnishes the radical intermediate C, which further underwent sequential
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•−
dehydrogenation oxidation by the superoxide anion radical (O2 ) to give intermediate
D and E. Finally, the target product 3a was obtained under aromatization.
Scheme 5. Possible Mechanism.
hv
RB
standard conditions
O2
O2
1a
3a
RB
Ph
Ph
Ph
N
N
A
Ph
OHC
HO2
E
N
H2O2
B
Ph
Ph
N
N
H
Ph
Ph
OHC
D
O
O2
HO2
C
In summary, we have developed a highly efficient strategy for the synthesis of
2-substituted pyrrolo[2,1,5-cd]indolizines via visible-light induced intermolecular
[3+2] annulation of indolizines with alkynes. This approach is environmentally
benign by using visible-light as energy source and air as oxi-dizing reagent. Further
biological activity study of pyr-rolo[2,1,5-cd]indolizines is ongoing and will be
reported in the near future.
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EXPERIMENTAL SECTION
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General Methods
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All reactions were performed in the sealed tube (SYNTHWARE GLASS F580852,
borosilicate glass) 10cm from the visible light source otherwise noted. The blue
lightemitting diode (LED) (20W, 450-460nm) purchased from JIADENG (LS) was
used for blue light irradiation. A fan attached to the apparatus was used to maintain
the reaction temperature at room temperature. Analytical thin layer chromatography
was carried out using silica gel GF254, visualized under UV light (at 254 nm). Proton
NMR (1H) were recorded at 400 MHz, and Carbon NMR (13C) at 100 MHz NMR
spectrometer. 1H and 13C NMR spectra were recorded using a Bruker DRX-400
spectrometer using Chloroform-d as solvent. Multiplicities are abbreviated as: s, singlet; d,
doublet; t, triplet; q, quartet; m, multiplet. The data of HRMS was carried out on a
high-resolution mass spectrometer (LCMS-IT-TOF). IR spectra were obtained either
as potassium bromide pellets or as liquid films between two potassium bromide
pellets with a Bruker TENSOR 27 spectrometer. Fluorescence analysis was
performed with Thermo Scientific Lumina and ultraviolet absorption analysis was
Shimazu UV2600.
General procedure
Synthesis of 1a according to the following procedure:
A solution of 2-picoline (0.93 g, 10 mmol, 1.0 equiv.) and 2 bromoacetophenone
(1.99 g, 10 mmol, 1.0 equiv) in acetone (50 mL) were added to a 100 mL round
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bottom flask and heated at 60 °C in an oil bath for 5 hours. The precipitate obtained
by filtration separation was redissolved in 20 mL of water (60 °C in an oil bath). Then,
K2CO3 (1.38 g, 10 mmol, 1.0 equiv) was added and heated at 60 °C in an oil bath for
5 hours. After filtration and drying in vacuo, a white solid compound 1a was obtained
in 50% overall yield (965 mg, 5 mmol) without further purification.
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Synthesis of 2a according to the following procedure:
Step 1: A mixture of iodobenzene (816 mg) and prop-2-yn-1-ol (336 mg) was treated
with Pd(PPh3)2Cl2 (140 mg) and CuI (76 mg) in 8 mL Et3N under N2 at room
temperature for 10 h. The solvent was removed and the mixture was purified by
column chromatography (eluted with petroleum ether : ethyl acetate = 4:1) to give 2aa
in 87% yield (459.9 mg).
Step 2: 2-phenylethyn-1-ol was treated with NaNO2 (24 mg) and DDQ (79 mg) in 6
mL mixed solvent (DCM : AcOH = 10:1) under O2 at room temperature for 10 h. The
solvent was removed and the mixture was purified by column chromatography (eluted
with petroleum ether : ethyl acetate = 8:1) to give 3-phenylpropiolaldehyde 2a in 73%
yield (330.6 mg).
Synthesis of 3a according to the following procedure:
A 25 mL tube was charged with a stirring bar, and added 2-phenylindolizine 1a
(0.058g, 1.0 equiv), 3-phenylpropiolaldehyde 2a (0.039g, 1.0 equiv), KI (0.01g, 0.2
equiv), rose bengal (0.006g, 0.03 equiv), DMSO (3 mL). The reaction was irradiated
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with a 20W blue LED at room temperature stirring for 8 h and monitored by TLC.
The reaction mixture was then diluted with EtOAc and water, extracted with EtOAc.
The organic layers were washed with brine and dried over MgSO4, evaporated under
reduced pressure. The crude mixture was purified by Thin layer chromatography
silica gel plate (eluted with petroleum ether : ethyl acetate = 15 : 1) to give 3a in 87%
yield (83.9 mg).
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Gram-scale experiment
An oven-dried 25 mL Schlenk flask with a stir bar was evacuated and back-filled with
nitrogen three times. To a solution of 2-phenylindolizine 1a (0.193g, 1mmol),
3-phenylpropiolaldehyde 2a (0.130g, 1mmol), KI (0.033g, 0.2 equiv),and
photocatalyst rose bengal (0.031g, 0.003 equiv) were added in DMSO (15 mL). The
reaction was irradiated with a 20W blue LED at room temperature stirring for 16h and
monitored by TLC. The reaction mixture was then diluted with EtOAc and water,
extracted with EtOAc. The combined organic extracts were dried over anhydrous
Na2SO4, filtered, and concentrated. The solvent was removed with a rotary evaporator.
The residue was purified by flash column chromatography (eluted with petroleum
ether : ethyl acetate = 15 : 1) to give product 3a (0.219g, 68% yield).
2,3-Diphenylpyrrolo[2,1,5-cd]indolizine-1-carbaldehyde (3a)
Yellow solid (83.9 mg, 87%); m.p. 62-64 °C. IR (KBr): 2969, 1554, 1462, 1221, 1132,
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782 cm−1; H NMR (400 MHz, Chloroform-d) δ 10.14 (s, 1H), 8.52 (d, J = 8.5 Hz,
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1H), 7.94 (d, J = 4.1 Hz, 2H), 7.52 (d, J = 6.7 Hz, 2H), 7.47 – 7.44 (m, 2H), 7.40 (t, J
= 7.1 Hz, 4H), 7.28 (d, J = 7.3 Hz, 1H), 7.22 (t, J = 7.3 Hz, 2H); 13C{1H} NMR (100
MHz, Chloroform-d) δ 187.6, 138.7, 137.9, 133.4, 132.2, 131.5, 131.4, 129.3, 129.2,
128.7, 128.3, 128.2, 126.2, 123.3, 120.6, 115.1, 113.7, 112.2; HRMS ESI (m/z): calcd
for C23H15NO [M + H]+: 322.1226, found: 322.1226.
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2,3-Diphenylpyrrolo[2,1,5-cd]indolizine-1-carbaldehyde (3b)
Green solid (80.4 mg, 80%); m.p. 139-140 °C. IR (KBr): 2918, 1649, 1490, 1287, 972,
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743 cm−1; H NMR (400 MHz, Chloroform-d) δ 10.11 (s, 1H), 8.50 (dd, J = 6.3, 2.2
Hz, 1H), 7.93 (d, J = 6.3 Hz, 2H), 7.53 (dd, J = 8.0, 1.4 Hz, 2H), 7.48 (t, J = 7.3 Hz,
1H), 7.45 – 7.39 (m, 3H), 7.29 (d, J = 8.1 Hz, 2H), 7.02 (d, J = 7.9 Hz, 2H), 2.35 (s,
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3H); C{1H} NMR (100 MHz, Chloroform-d) δ 187.6, 138.7, 138.2, 138.1, 132.3,
131.6, 131.4, 130.5, 129.3, 129.1, 129.0, 128.7, 128.3, 126.3, 123.4, 120.6, 114.9,
113.5, 111.8, 21.2; HRMS ESI (m/z): calcd for C24H17NO [M + Na]+: 358.1201,
found: 358.1201.
3-(4-Methoxyphenyl)-2-phenylpyrrolo[2,1,5-cd]indolizine-1-carbaldehyde (3c)
Yellow solid (73.7 mg, 70%); m.p. 161-163 °C. IR (KBr): 2932, 1651, 1493, 1292,
1250, 745 cm−1; 1H NMR (400 MHz, Chloroform-d) δ 10.11 (s, 1H), 8.48 (d, J = 7.1
Hz, 1H), 7.91 (q, J = 7.7 Hz, 2H), 7.53 (d, J = 6.4 Hz, 2H), 7.49 – 7.41 (m, 3H), 7.37
(s, 1H), 7.32 (d, J = 8.8 Hz, 2H), 6.75 (d, J = 8.8 Hz, 2H), 3.81 (s, 3H); 13C{1H} NMR
(100 MHz, Chloroform-d) δ 187.7, 159.7, 138.5, 137.9, 132.3, 131.7, 131.4, 130.4,
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129.3, 128.7, 128.4, 126.2, 126.0, 123.3, 120.5, 114.7, 113.8, 113.2, 111.3, 55.3;
HRMS ESI (m/z): calcd for C24H17NO2 [M + Na]+: 374.1151, found: 374.1152.
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3-(4-Nitrophenyl)-2-phenylpyrrolo[2,1,5-cd]indolizine-1-carbaldehyde (3d)
Brown solid (63.7 mg, 58%); m.p. 133-134 °C. IR (KBr): 2924, 1657, 1516, 1340,
976, 743 cm−1; 1H NMR (400 MHz, Chloroform-d) δ 10.15 (s, 1H), 8.60 (dd, J = 7.6,
0.7 Hz, 1H), 8.07 (d, J = 8.9 Hz, 2H), 8.05 – 7.98 (m, 2H), 7.58 (s, 1H), 7.55 – 7.51
(m, 5H), 7.47 – 7.43 (m, 2H); 13C{1H} NMR (100 MHz, Chloroform-d) δ 187.5,
147.3, 140.1, 138.8, 134.7, 131.9, 131.9, 131.2, 131.1, 129.8, 129.3, 128.7, 126.5,
123.7, 123.0, 121.3, 116.3, 114.8, 113.2; HRMS ESI (m/z): calcd for C24H17NO2 [M
+ H]+: 367.1077, found: 367.1077.
3-(4-Bromophenyl)-2-phenylpyrrolo[2,1,5-cd]indolizine-1-carbaldehyde (3e)
Yellow solid (76.6 mg, 64%); m.p. 152-154 °C. IR (KBr): 2917, 1656, 1492, 1298,
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977, 772 cm−1; H NMR (400 MHz, Chloroform-d) δ 10.13 (s, 1H), 8.54 (d, J = 8.5
Hz, 1H), 7.98 – 7.95 (m, 2H), 7.50 (t, J = 8.2 Hz, 4H), 7.45 (t, J = 3.8 Hz, 3H), 7.34
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(d, J = 8.4 Hz, 2H), 7.24 (s, 1H); C{1H} NMR (100 MHz, Chloroform-d) δ 187.6,
138.7, 136.5, 132.4, 132.1, 131.5, 131.3, 131.3, 130.8, 130.6, 129.4, 129.0, 128.5,
126.3, 122.5, 120.8, 115.4, 114.0, 112.1; HRMS ESI (m/z): calcd for C23H15NO [M +
H]+: 400.0330, found: 400.0331.
3-(4-Fluorophenyl)-2-phenylpyrrolo[2,1,5-cd]indolizine-1-carbaldehyde (3f)
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Yellow solid (82.4 mg, 81%); m.p. 157-159 °C. IR (KBr): 2918, 1655, 1490, 1290,
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972, 738 cm−1; H NMR (400 MHz, Chloroform-d) δ 10.13 (s, 1H), 8.53 (d, J = 3.8
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Hz, 1H), 7.94 (d, J = 3.3 Hz, 2H), 7.50 (t, J = 8.1 Hz, 3H), 7.42 – 7.40 (m, 3H), 7.37 –
7.33 (m, 2H), 6.94 – 6.88 (m, 2H); 13C{1H} NMR (100 MHz, Chloroform-d) δ 187.6,
162.7 (d, J = 207.0 Hz), 138.5, 136.8, 131.5 (d, J = 68.0 Hz), 131.4, 130.9 (d, J = 8.0
Hz), 129.6 (d, J = 3.0 Hz), 129.4, 128.8, 128.4, 126.3, 123.2, 120.7, 115.5, 115.3,
115.2, 113.7, 112.0; HRMS ESI (m/z): calcd for C23H15NO [M + Na]+: 362.0949,
found: 362.0952.
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2-Phenyl-3-(4-(trifluoromethyl)phenyl)pyrrolo[2,1,5-cd]indolizine-1-carbaldehyd
e (3g)
Green solid (82.9 mg, 71%); m.p. 146-150 °C. IR (KBr): 2916, 1657, 1491, 1292,
1120, 748 cm−1; 1H NMR (400 MHz, Chloroform-d) δ 10.14 (s, 1H), 8.55 (d, J = 7.1
Hz, 1H), 7.96 (d, J = 7.9 Hz, 2H), 7.51 – 7.47 (m, 8H), 7.44 – 7.40 (m, 2H); 13C{1H}
NMR (100 MHz, Chloroform-d) δ 187.6, 138.7, 137.0, 135.9, 131.9, 131.3, 131.2,
129.9 (d, J = 32.0 Hz), 129.4, 129.3, 129.1, 128.5, 126.3, 125.2 (m, J = 4.0 Hz), 124.0
(m, J = 271.0 Hz), 123.1, 121.0, 115.7, 114.3, 112.8; HRMS ESI (m/z): calcd for
C23H15NO [M + H]+: 390.1101, found: 390.1100.
2-Phenyl-3-(m-tolyl)pyrrolo[2,1,5-cd]indolizine-1-carbaldehyde (3h)
Green solid (63.3 mg, 63%); m.p. 118-120 °C. IR (KBr): 2920, 1688, 1510, 1338, 974,
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743 cm−1; H NMR (400 MHz, Chloroform-d) δ 10.13 (s, 1H), 8.52 (d, J = 8.5 Hz,
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1H), 7.94 (d, J = 4.9 Hz, 2H), 7.54 (d, J = 6.7 Hz, 2H), 7.48 (d, J = 7.2 Hz, 2H), 7.43
(d, J = 7.4 Hz, 2H), 7.32 (d, J = 7.6 Hz, 1H), 7.17 (t, J = 7.7 Hz, 1H), 7.09 (d, J = 7.9
Hz, 2H), 2.09 (s, 3H); 13C{1H} NMR (100 MHz, Chloroform-d) δ 187.6, 138.7, 138.1,
137.9, 133.1, 132.4, 131.6, 131.5, 130.5, 129.3, 128.9, 128.7, 128.3, 126.2, 125.8,
123.5, 120.7, 115.0, 113.6, 111.8, 21.2; HRMS ESI (m/z): calcd for C23H15NO [M +
H]+: 336.1381, found: 336.1383.
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3-(2-Fluorophenyl)-2-phenylpyrrolo[2,1,5-cd]indolizine-1-carbaldehyde (3i)
Yellow solid (74.2 mg, 73%); m.p. 145-147 °C.IR (KBr): 2913, 1647, 1489, 1288,
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974, 745 cm−1; H NMR (400 MHz, Chloroform-d) δ 10.18 (s, 1H), 8.54 (d, J = 7.2
Hz, 1H), 7.96 (t, J = 8.7 Hz, 2H), 7.55 (s, 1H), 7.48 (d, J = 6.9 Hz, 2H), 7.42 (d, J =
7.3 Hz, 1H), 7.36 (t, J = 7.3 Hz, 2H), 7.28 (d, J = 7.7 Hz, 1H), 7.21 (t, J = 7.6 Hz, 1H),
7.09 – 7.02 (m, 1H), 6.93 (t, J = 7.5 Hz, 1H); 13C{1H} NMR (100 MHz, Chloroform-d)
δ 187.6, 159.9 (J = 248.0 Hz), 138.7, 132.2 (J = 3.0 Hz), 132.18, 131.2, 131.1, 130.5,
129.8 (d, J = 8.0 Hz), 129.3, 128.6, 128.3, 126.1, 123.8 (d, J = 4.0 Hz), 123.8, 121.6
(d, J = 13.0 Hz), 120.5, 115.8 (d, J = 22.0 Hz), 115.4, 114.5 (d, J = 22.0 Hz), 114.1;
HRMS ESI (m/z): calcd for C23H15NO [M + H]+: 340.1131, found: 340.1132.
3-(3,4-Dimethoxyphenyl)-2-phenylpyrrolo[2,1,5-cd]indolizine-1-carbaldehyde
(3j)
Yellow solid (96.1 mg, 84%); m.p. 172-175 °C. IR (KBr): 2934, 1664, 1466, 1279,
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974, 745 cm−1; H NMR (400 MHz, Chloroform-d) δ 10.11 (s, 1H), 8.50 (d, J = 6.9
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Hz, 1H), 7.96 – 7.90 (m, 2H), 7.56 (dd, J = 7.4, 2.0 Hz, 2H), 7.46 – 7.39 (m, 4H),
7.22 (dd, J = 8.3, 2.0 Hz, 1H), 6.86 (d, J = 8.3 Hz, 1H), 6.75 (d, J = 2.0 Hz, 1H), 3.91
(s, 3H), 3.28 (s, 3H); 13C{1H} NMR (100 MHz, Chloroform-d) δ 187.6, 149.1, 148.4,
138.2, 138.1, 132.5, 131.6, 129.4, 128.8, 128.5, 126.3, 123.1, 121.0, 120.6, 114.8,
113.4, 112.8, 111.6, 111.1, 55.9, 55.0; HRMS ESI (m/z): calcd for C23H15NO [M +
H]+: 382.1434, found: 382.1438.
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3-(3,4-Dichlorophenyl)-2-phenylpyrrolo[2,1,5-cd]indolizine-1-carbaldehyde (3k)
Yellow solid (67.9 mg, 58%); m.p. 145-147 °C. IR (KBr): 2916, 1659, 1489, 1279,
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972, 741 cm−1; H NMR (400 MHz, Chloroform-d) δ 10.11 (s, 1H), 8.52 (d, J = 8.5
Hz, 1H), 7.96 – 7.91 (m, 2H), 7.53 – 7.44 (m, 5H), 7.42 (s, 1H), 7.37 (d, J = 2.0 Hz,
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1H), 7.27 (d, J = 9.4 Hz, 1H), 7.20 (dd, J = 8.3, 2.1 Hz, 1H); C{1H} NMR (100
MHz, Chloroform-d) δ 187.4, 138.60, 134.8, 133.4, 132.5, 132.2, 131.8, 131.1, 131.0,
130.9, 130.2, 129.3, 129.1, 128.6, 128.0, 126.3, 122.9, 121.0, 115.6, 114.2, 112.2;
HRMS ESI (m/z): calcd for C23H15NO [M + H]+: 390.0447, found: 390.0447.
3-(2,4-Dichlorophenyl)-2-phenylpyrrolo[2,1,5-cd]indolizine-1-carbaldehyde (3l)
Yellow solid (91.0 mg, 78%); m.p. 109-111 °C.IR (KBr): 2918, 1649, 1474, 1277,
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982, 744 cm−1; H NMR (400 MHz, Chloroform-d) δ 10.23 (s, 1H), 8.58 (d, J = 7.4
Hz, 1H), 8.04 – 7.95 (m, 2H), 7.49 (s, 1H), 7.43 – 7.37 (m, 4H), 7.33 (dd, J = 8.0, 6.9
Hz, 2H), 7.21 (d, J = 8.3 Hz, 1H), 7.10 (dd, J = 8.3, 2.0 Hz, 1H). 13C{1H} NMR (100
MHz, Chloroform-d) δ 187.5, 138.7, 134.6, 134.2, 133.2, 132.4, 131.9, 131.6, 131.1,
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130.8, 129.7, 129.6, 128.8, 128.4, 126.8, 126.2, 123.9, 120.4, 115.8, 115.1, 114.5.
HRMS ESI (m/z): calcd for C23H15NO [M + H]+: 390.0447, found: 390.0447.
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3-(Benzo[d][1,3]dioxol-5-yl)-2-phenylpyrrolo[2,1,5-cd]indolizine-1-carbaldehyde
(3m)
Yellow solid (73.4 mg, 67%); m.p. 131-134 °C. IR (KBr): 2918, 1657, 1489, 1242,
1038, 746 cm−1; 1H NMR (400 MHz, Chloroform-d) δ 10.11 (s, 1H), 8.49 (d, J = 7.0
Hz, 1H), 7.91 (q, J = 7.7 Hz, 2H), 7.55 – 7.41 (m, 5H), 7.34 (s, 1H), 6.90 – 6.79 (m,
2H), 6.62 (d, J = 8.0 Hz, 1H), 5.96 (s, 2H); 13C{1H} NMR (100 MHz, Chloroform-d)
δ 187.6, 147.7, 147.7, 138.5, 137.8, 132.2, 131.5, 131.4, 129.3, 128.8, 128.4, 127.4,
126.3, 123.4, 123.3, 120.6, 114.9, 113.4, 111.5, 109.36, 108.2, 101.2; HRMS ESI
(m/z): calcd for C23H15NO [M + H]+: 366.1123, found: 366.1125.
3-(Naphthalen-2-yl)-2-phenylpyrrolo[2,1,5-cd]indolizine-1-carbaldehyde (3n)
Yellow solid (66.8 mg, 60%); m.p. 140-142 °C. IR (KBr): 2947, 1663, 1516, 1344,
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976, 743 cm−1; H NMR (400 MHz, Chloroform-d) δ 10.14 (s, 1H), 8.54 (d, J = 8.5
Hz, 1H), 7.98 – 7.95 (m, 2H), 7.80 (d, J = 8.0 Hz, 1H), 7.74 (d, J = 8.4 Hz, 2H), 7.65
(d, J = 10.3 Hz, 1H), 7.61 – 7.57 (m, 3H), 7.51 – 7.44 (m, 2H), 7.41 (t, J = 7.4 Hz,
3H), 7.35 (d, J = 7.9 Hz, 1H); 13C{1H} NMR (100 MHz, Chloroform-d) δ 187.7,
138.8, 137.9, 133.1, 133.0, 132.5, 131.6, 131.4, 130.5, 129.3, 129.0, 128.8, 128.5,
128.3, 128.0, 127.5, 126.4, 126.4, 126.3, 123.6, 120.9, 115.2, 113.7, 112.2, 100.0;
HRMS ESI (m/z): calcd for C23H15NO [M + Na]+: 394.1202, found: 394.1202.
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Yellow solid (57.8 mg, 62%); m.p. 150-152 °C. IR (KBr): 2953, 1715, 1526, 1300,
1186, 1049, 739 cm−1; 1H NMR (400 MHz, Chloroform-d) δ 10.01 (s, 1H), 8.47 (d, J
= 8.4 Hz, 1H), 7.90 (d, J = 6.1 Hz, 2H), 7.65 (dd, J = 6.5, 2.9 Hz, 2H), 7.56 – 7.53 (m,
4H), 7.41 (d, J = 1.4 Hz, 1H), 6.33 (dd, J = 3.4, 1.8 Hz, 1H), 5.98 (d, J = 3.4 Hz, 1H);
13C{1H} NMR (100 MHz, Chloroform-d) δ 187.5, 148.7, 143.0, 138.1, 132.4, 131.6,
131.0, 129.1, 128.9, 128.3, 126.5, 126.4, 122.3, 121.1, 115.1, 113.7, 111.9, 110.6,
109.5; HRMS ESI (m/z): calcd for C23H15NO [M + H]+: 312.1019, found: 312.1015.
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Methyl 1-formyl-2-phenylpyrrolo[2,1,5-cd]indolizine-4-carboxylate (3p)
Yellow solid (53.6 mg, 59%); m.p. 158-161 °C. IR (KBr): 2380, 1687, 1543, 1338,
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933, 698 cm−1; H NMR (400 MHz, Chloroform-d) δ 10.37 (s, 1H), 8.55 (d, J = 7.8
Hz, 1H), 8.42 (d, J = 8.0 Hz, 1H), 8.27 (s, 1H), 8.10 – 8.04 (m, 1H), 7.84 (d, J = 6.7
Hz, 2H), 7.64 – 7.56 (m, 3H), 4.03 (s, 3H); 13C{1H} NMR (100 MHz, Chloroform-d)
δ 187.2, 164.5, 140.8, 131.9, 130.9, 130.6, 130.6, 129.7, 129.3, 128.1, 125.2, 122.8,
121.9, 118.5, 116.2, 116.2, 100.0, 51.8; HRMS ESI (m/z): calcd for C23H15NO [M +
H]+: 304.0968, found: 304.0964.
5-Methyl-2,3-diphenylpyrrolo[2,1,5-cd]indolizine-1-carbaldehyde (3q)
Yellow solid (63.8 mg, 61%); m.p. 113-115 °C. IR (KBr): 2922, 1649, 1493, 1298,
978, 700 cm−1; 1H NMR (400 MHz, Chloroform-d) δ 10.11 (s, 1H), 7.89 (d, J = 7.9
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– 7.08 (m, 4H), 3.67 (q, J = 7.0 Hz, 2H), 1.44 (t, J = 7.4 Hz, 3H). ; C{1H} NMR
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(100 MHz, Chloroform-d) δ 186.9, 139.4, 136.3, 134.2, 133.6, 132.8, 131.5, 130.2,
129.0, 128.4, 128.2, 128.1, 127.8, 127.3, 124.1, 121.4, 113.9, 111.9, 27.4, 17.51;
HRMS ESI (m/z): calcd for C23H15NO [M + H]+: 348.1383, found: 348.1388.
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6-Methyl-2,3-diphenylpyrrolo[2,1,5-cd]indolizine-1-carbaldehyde (3r)
Yellow solid (73.4 mg, 73%); m.p. 143-146 °C. IR (KBr): 3055, 1649, 1489, 1263,
981, 743 cm−1; 1H NMR (400 MHz, Chloroform-d) δ 10.01 (s, 1H), 8.28 (s, 1H), 7.66
(s, 1H), 7.43 (d, J = 6.7 Hz, 2H), 7.37 (d, J = 7.2 Hz, 1H), 7.32 (dd, J = 10.4, 7.2 Hz,
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4H), 7.19 (d, J = 5.2 Hz, 1H), 7.13 (t, J = 7.2 Hz, 2H), 2.73 (s, 3H); C{1H} NMR
(100 MHz, Chloroform-d) δ 187.6, 138.5, 138.2, 137.8, 133.5, 132.3, 131.4, 131.3,
129.2, 129.1, 128.6, 128.3, 128.1, 122.9, 119.8, 115.8, 114.5, 111.5, 22.6; HRMS ESI
(m/z): calcd for C23H15NO [M + H]+: 336.1382, found: 336.1383.
6-Methoxy-2,3-diphenylpyrrolo[2,1,5-cd]indolizine-1-carbaldehyde (3s)
Yellow solid (73.7 mg, 70%); m.p. 191-193 °C. IR (KBr): 3011, 1650, 1489, 1293,
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954, 743 cm−1; H NMR (400 MHz, Chloroform-d) δ 10.04 (s, 1H), 8.08 (d, J = 1.8
Hz, 1H), 7.50 – 7.36 (m, 8H), 7.28 (d, J = 6.4 Hz, 2H), 7.20 (t, J = 7.3 Hz, 2H), 4.09
(s, 3H); 13C{1H} NMR (100 MHz, Chloroform-d) δ 187.4, 160.6, 139.5, 138.5, 133.3,
132.3, 132.3, 131.4, 130.3, 129.1, 128.6, 128.3, 122.1, 119.7, 111.8, 102.3, 100.1,
56.6; HRMS ESI (m/z): calcd for C23H15NO [M + H]+: 352.1332, found: 352.1338.
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5,7-Dimethyl-2,3-diphenylpyrrolo[2,1,5-cd]indolizine-1-carbaldehyde (3t)
Green solid (63.9 mg, 61%); m.p. 130-132 °C. IR (KBr): 2916, 1655, 1487, 1379, 914,
694 cm−1; 1H NMR (400 MHz, Chloroform-d) δ 9.97 (s, 1H), 7.46 (s, 1H), 7.38 (dd, J
= 7.9, 6.3 Hz, 4H), 7.31 (d, J = 7.5 Hz, 2H), 7.24 (d, J = 7.0 Hz, 2H), 7.15 (d, J = 7.2
Hz, 1H), 7.09 (t, J = 7.3 Hz, 2H), 3.10 (s, 3H), 2.76 (s, 3H); 13C{1H} NMR (100 MHz,
Chloroform-d) δ 186.9, 138.7, 135.0, 133.7, 132.8, 131.5, 130.4, 129.8, 129.6, 129.0,
128.4, 128.2, 128.1, 127.7, 127.4, 124.6, 124.3, 121.6, 110.7, 20.7, 17.1; HRMS ESI
(m/z): calcd for C23H15NO [M + H]+: 350.1539, found: 350.1539.
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2-(3-Chlorophenyl)-3-phenylpyrrolo[2,1,5-cd]indolizine-1-carbaldehyde (4a)
Brown solid (84.1 mg, 79%); m.p. 142-145 °C. IR (KBr): 2923, 1688, 1501, 1388,
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974, 776 cm−1; H NMR (400 MHz, Chloroform-d) δ 10.15 (s, 1H), 8.53 (d, J = 8.5
Hz, 1H), 7.95 (d, J = 4.2 Hz, 2H), 7.50 – 7.31 (m, 9H), 7.27 (t, J = 8.3 Hz, 1H);
13C{1H} NMR (100 MHz, Chloroform-d) δ 187.0, 137.9, 136.3, 134.3, 133.9, 133.2,
131.5, 131.3, 129.6, 129.5, 129.3, 129.1, 128.7, 128.4, 128.4, 126.4, 123.3, 120.4,
115.3, 113.9, 112.5; HRMS ESI (m/z): calcd for C23H15NO [M + H]+: 356.0837,
found: 356.0837.
2-(3-Acetylphenyl)-3-phenylpyrrolo[2,1,5-cd]indolizine-1-carbaldehyde (4b)
Yellow solid (63.2 mg, 58%); m.p. 124-126 °C. IR (KBr): 2924, 1688, 1508, 1288,
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974, 777 cm−1; H NMR (400 MHz, Chloroform-d) δ 10.19 (s, 1H), 8.54 (d, J = 8.5
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Hz, 1H), 8.06 (d, J = 7.9 Hz, 1H), 8.01 – 7.96 (m, 3H), 7.80 (d, J = 7.6 Hz, 1H), 7.56
(t, J = 7.7 Hz, 1H), 7.46 (s, 1H), 7.37 (d, J = 7.1 Hz, 2H), 7.28 (t, J = 7.3 Hz, 1H),
7.22 (t, J = 7.3 Hz, 2H), 2.29 (s, 3H); 13C{1H} NMR (100 MHz, Chloroform-d) δ
197.5, 186.8, 137.9, 136.9, 136.8, 135.7, 133.4, 132.4, 132.2, 131.6, 129.5, 129.3,
128.8, 128.4, 128.4, 128.1, 126.5, 123.3, 120.3, 115.4, 114.1, 112.8, 26.3; HRMS ESI
(m/z): calcd for C23H15NO [M + H]+: 364.1332, found: 364.1332.
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2-(3-Acetylphenyl)-3-phenylpyrrolo[2,1,5-cd]indolizine-1-carbaldehyde (4c)
Green solid (77.4 mg, 77%); m.p. 108-110 °C. IR (KBr): 3030, 1690, 1550, 1410.
1037, 694 cm−1; 1H NMR (400 MHz, Chloroform-d) δ 10.13 (s, 1H), 8.51 (d, J = 8.5
Hz, 1H), 7.95 – 7.93 (m, 2H), 7.46 – 7.40 (m, 5H), 7.33 – 7.28 (m, 2H), 7.24 – 7.20
(m, 3H), 2.45 (s, 3H); 13C{1H} NMR (100 MHz, Chloroform-d) δ 187.8, 138.8, 138.0,
133.6, 131.5, 131.4, 129.5, 129.3, 129.1, 129.2, 128.3, 128.2, 126.2, 120.6, 114.9,
113.6, 112.2, 21.4; HRMS ESI (m/z): calcd for C23H15NO [M + H]+: 336.1382, found:
336.1383.
2-(3,4-Dimethylphenyl)-3-phenylpyrrolo[2,1,5-cd]indolizine-1-carbaldehyde (4d)
Yellow solid (59.7 mg, 57%); m.p. 128-131 °C. IR (KBr): 2922, 1688, 1489, 1338,
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974, 775 cm−1; H NMR (400 MHz, Chloroform-d) δ 10.13 (s, 1H), 8.51 (d, J = 8.5
Hz, 1H), 7.95 – 7.93 (m, 2H), 7.46 – 7.40 (m, 5H), 7.33 – 7.28 (m, 2H), 7.24 – 7.20
(m, 3H), 2.45 (s, 3H); 13C{1H} NMR (100 MHz, Chloroform-d) δ 188.0, 139.3, 138.0,
137.4, 136.6, 133.7, 132.9, 131.4, 129.6, 129.5, 129.4, 129.3, 129.0, 128.2, 128.1,
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126.1, 123.3, 120.4, 114.9, 113.5, 112.2, 19.7, 19.6; HRMS ESI (m/z): calcd for
C23H15NO [M + H]+: 350.1539, found: 350.1539.
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2-(Naphthalen-2-yl)-3-phenylpyrrolo[2,1,5-cd]indolizine-1-carbaldehyde (4e)
Green solid (65.7 mg, 59%); m.p. 131-135 °C. IR (KBr): 3030, 1551, 1412, 1288,
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1029, 745 cm−1; H NMR (400 MHz, Chloroform-d) δ 9.89 (s, 1H), 8.60 – 8.55 (m,
1H), 8.00 (d, J = 4.5 Hz, 3H), 7.92 (d, J = 8.3 Hz, 1H), 7.76 (d, J = 8.5 Hz, 1H), 7.63
(d, J = 6.9 Hz, 1H), 7.54 (d, J = 10.0 Hz, 2H), 7.42 (d, J = 7.5 Hz, 1H), 7.24 (d, J =
7.8 Hz, 1H), 7.17 (d, J = 7.6 Hz, 2H), 7.05 (t, J = 7.4 Hz, 1H), 6.91 (t, J = 7.5 Hz, 2H);
13C{1H} NMR (100 MHz, Chloroform-d) δ 187.7, 138.1, 136.3, 133.4, 133.1, 132.9,
131.7, 130.1, 129.8, 129.3, 129.2, 128.4, 128.1, 127.9, 126.7, 126.3, 126.2, 125.9,
125.0, 124.9, 122.1, 115.1, 113.8, 111.5; HRMS ESI (m/z): calcd for C23H15NO [M +
H]+: 372.1382, found: 372.1383.
3-Phenyl-2-(thiophen-2-yl)pyrrolo[2,1,5-cd]indolizine-1-carbaldehyde (4f)
Green solid (64.7 mg, 66%); m.p. 125-127 °C. IR (KBr): 2922, 2018, 1659, 1508,
1288, 972, 775 cm−1; 1H NMR (400 MHz, Chloroform-d) δ 10.32 (s, 1H), 8.51 (d, J =
8.5 Hz, 1H), 7.93 (d, J = 4.2 Hz, 2H), 7.48 (dd, J = 12.6, 6.5 Hz, 3H), 7.42 (s, 1H),
7.35 – 7.29 (m, 3H), 7.19 (d, J = 3.5 Hz, 1H), 7.12 (dd, J = 5.1, 3.6 Hz, 1H); 13C{1H}
NMR (100 MHz, Chloroform-d) δ 187.4, 138.0, 133.5, 132.4, 131.4, 130.8, 130.2,
129.3, 129.2, 128.5, 128.4, 128.3, 127.6, 126.4, 123.7, 121.0, 115.3, 114.0, 112.7;
HRMS ESI (m/z): calcd for C23H15NO [M + H]+: 328.0790, found: 328.0791.
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2-Pentyl-3-phenylpyrrolo[2,1,5-cd]indolizine-1-carbaldehyde (4g)
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Brown solid (57.6 mg, 61%); m.p. 110-113 °C. IR (KBr): 2922, 1649, 1528, 1339,
1257, 772 cm−1; 1H NMR (400 MHz, Chloroform-d) δ 10.44 (s, 1H), 8.33 (d, J = 8.5
Hz, 1H), 7.90 – 7.86 (m, 2H), 7.77 (d, J = 7.0 Hz, 2H), 7.54 (t, J = 7.9 Hz, 2H), 7.47
(d, J = 7.4 Hz, 1H), 7.35 (s, 1H), 3.40 – 3.35 (m, 2H), 1.76 – 1.70 (m, 2H), 1.37 –
1.31 (m, 2H), 1.28 – 1.24 (m, 2H), 0.81 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100 MHz,
Chloroform-d) δ 185.2, 140.5, 137.9, 134.8, 131.2, 130.4, 128.9, 128.8, 128.3, 125.6,
124.5, 120.5, 113.1, 112.9, 112.0, 32.5, 31.8, 26.2, 22.2, 13.9; HRMS ESI (m/z):
calcd for C23H15NO [M + H]+: 316.1695, found: 316.1696.
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Methyl 3-phenylpyrrolo[2,1,5-cd]indolizine-1-carboxylate (4h)
Yellow solid (57.8 mg, 70%); m.p. 100-101 °C. IR (KBr): 3054, 2969, 1554, 1221,
1132, 782 cm−1; 1H NMR (400 MHz, Chloroform-d) δ 8.40 – 8.26 (m, 2H), 8.02 (d, J
= 8.2 Hz, 2H), 7.84 (d, J = 12.5 Hz, 2H), 7.55 – 7.49 (m, 3H), 7.41 (t, J = 7.4 Hz, 1H),
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4.03 (s, 3H); C{1H} NMR (100 MHz, Chloroform-d) δ 165.5, 135.7, 134.1, 132.1,
129.8, 129.1, 128.5, 127.6, 124.4, 124.4, 119.6, 114.8, 114.0, 113.0, 109.1, 51.4;
HRMS ESI (m/z): calcd for C23H15NO [M + H]+: 276.1019, found: 276.1017.
Ethyl 3-phenylpyrrolo[2,1,5-cd]indolizine-1-carboxylate (4i)
Yellow solid (76.3 mg, 88%); m.p. 93-94 °C. IR (KBr): 2924, 1610, 1505, 1256, 1097,
772 cm−1; 1H NMR (400 MHz, Chloroform-d) δ 8.41 – 8.29 (m, 2H), 8.03 (d, J = 7.4
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Hz, 2H), 7.85 (dt, J = 15.3, 7.5 Hz, 2H), 7.58 – 7.49 (m, 3H), 7.41 (t, J = 7.4 Hz, 1H),
4.51 (q, J = 7.1 Hz, 2H), 1.51 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (100 MHz,
Chloroform-d) δ 165.2, 135.6, 134.1, 131.9, 129.9, 129.1, 128.4, 127.6, 124.4, 119.6,
114.8, 114.5, 113.0, 109.0, 60.2, 14.6; HRMS ESI (m/z): calcd for C23H15NO [M +
H]+: 290.1119, found: 290.1117.
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Dimethyl 3-phenylpyrrolo[2,1,5-cd]indolizine-1,2-dicarboxylate (4j)
Yellow solid (69.9 mg, 70%); m.p. 135-136 °C. IR (KBr): 2924, 1617, 1487, 1256,
1067, 772 cm−1; 1H NMR (400 MHz, Chloroform-d) δ 8.32 (d, J = 7.6 Hz, 1H), 7.87 –
7.81 (m, 2H), 7.77 (d, J = 8.1 Hz, 2H), 7.49 (t, J = 7.6 Hz, 2H), 7.42 (d, J = 9.0 Hz,
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2H), 4.00 (d, J = 12.1 Hz, 6H); C{1H} NMR (100 MHz, Chloroform-d) δ 166.7,
164.2, 136.9, 133.7, 131.9, 128.8, 128.6, 128.5, 128.4, 125.2, 124.6, 122.1, 115.9,
113.9, 111.8, 111.2, 52.8, 51.7; HRMS ESI (m/z): calcd for C23H15NO [M + H]+:
334.34, found: 334.34.
Diethyl 3-phenylpyrrolo[2,1,5-cd]indolizine-1,2-dicarboxylate (4k)
Yellow solid (83.4 mg, 77%); m.p. 127-128 °C. IR (KBr): 2924, 1616, 1515, 1467,
1246, 1087, 774 cm−1; 1H NMR (400 MHz, Chloroform-d) δ 8.39 (d, J = 7.7 Hz, 1H),
7.98 – 7.87 (m, 2H), 7.81 (d, J = 7.7 Hz, 2H), 7.53 – 7.46 (m, 3H), 7.42 (d, J = 7.7 Hz,
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1H), 4.53 – 4.41 (m, 4H), 1.47 (t, J = 7.1 Hz, 3H), 1.30 (t, J = 7.1 Hz, 3H); C{1H}
NMR (100 MHz, Chloroform-d) δ 166.3, 163.9, 137.0, 133.9, 132.0, 128.9, 128.8,
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128.5, 128.5, 125.2, 125.1, 122.1, 116.0, 114.0, 111.7, 111.5, 62.1, 60.5, 14.4, 14.0;
HRMS ESI (m/z): calcd for C23H15NO [M + H]+: 362.3919, found: 362.3917.
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(2,3-Diphenylpyrrolo[2,1,5-cd]indolizin-1-yl)(phenyl)methanone (4l)
Yellow solid (69.1 mg, 58%); m.p. 128-130 °C. IR (KBr): 3057, 1628, 1489, 1387,
991, 696 cm−1; 1H NMR (400 MHz, Chloroform-d) δ 8.04 (d, J = 7.9 Hz, 1H), 7.95 (d,
J = 7.7 Hz, 1H), 7.85 (t, J = 7.9 Hz, 1H), 7.68 (d, J = 7.0 Hz, 2H), 7.47 (s, 1H), 7.38 –
7.34 (m, 3H), 7.28 (d, J = 6.8 Hz, 4H), 7.21 – 7.15 (m, 5H), 7.09 (t, J = 7.3 Hz, 2H);
13C{1H} NMR (100 MHz, Chloroform-d) δ 192.9, 139.8, 137.5, 136.1, 133.8, 133.8,
131.5, 131.3, 131.2, 131.1, 129.7, 129.4, 128.2, 127.9, 127.7, 127.7, 127.6, 124.6,
123.5, 120.1, 114.7, 113.0, 111.6; HRMS ESI (m/z): calcd for C23H15NO [M + H]+:
398.1538, found: 398.1539.
SUPPORTING INFORMATION
1
Copies of H and 13CNMR spectra. This material is available free of charge via
theInternet at http://pubs.acs.org
ACKNOWLEDGMENT
This work was supported by the Outstanding Youth Project of Guangdong Natural
Science Foundation (2020B1515020026), the Innovation and Strong School Project of
Guangdong Pharmaceutical University (2015cxqx212, 2018KQNCX131), the Science
and Technology Planning Project of Guangdong Province (201806040009,
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201804010349), the National Special Fund for Agro-scientific Research in the Public
Interest of China (201503112-8), the national key research and development project
(2017YFD0201600) and Provincial Experimental Teaching Demonstration Center of
Chemistry & Chemical Engineering, Guangdong Cosmetics Engineering &
Technology Research Center, and Provincial Experimental Teaching Demonstration
Center of Chemistry & Chemical Engineering. Special funds of key disciplines
construction from Guangdong and Zhongshan cooperating.
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