Copper-catalyzed formation of indolizine derivatives via one-pot reactions of chalcones, benzyl bromides and pyridines

Article abstract of DOI:10.1016/j.tet.2020.131347

The one-pot cascade reaction for the preparation of indolizine from a wide range of chalcone, pyridine and benzyl bromide via [3 + 2] cycloaddition/oxidative aromatization promoted by Cu(OAc)₂ has been developed. This convenient method don't need to isolate the intermediates and the desired products indolizines were obtained in moderate to high yield catalyzed by Cu(OAc)₂ in the presence of oxygen.

Full text of DOI:10.1016/j.tet.2020.131347

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Copper-catalyzed formation of indolizine derivatives via one-pot reactions of
chalcones, benzyl bromides and pyridines
Chao-dong Li, Xue Tang, Xiao-long He, Shuai Xue, Jiang-hong Xu, Yu-jin Li
PII:
S0040-4020(20)30502-0
https://doi.org/10.1016/j.tet.2020.131347
TET 131347
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 30 January 2020
Revised Date: 12 June 2020
Accepted Date: 16 June 2020
Please cite this article as: Li C-d, Tang X, He X-l, Xue S, Xu J-h, Li Y-j, Copper-catalyzed formation of
indolizine derivatives via one-pot reactions of chalcones, benzyl bromides and pyridines, Tetrahedron
(2020), doi: https://doi.org/10.1016/j.tet.2020.131347.
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Copper-Catalyzed Formation of Indolizine Derivatives
via One-Pot Reactions of Chalcones, Benzyl bromides
and Pyridines
Chao-dong Li, Xue Tang, Xiao-long He, Shuai Xue, Jiang-hong Xu, Yu-jin Li*
College of Chemical Engineering, Zhejiang University of Technology. Hangzhou 310014, P. R. of China
Fonts or abstract dimensions should not be changed or altered
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1
Tetrahedron
journal homepage: www.elsevier.com
Copper-Catalyzed Formation of Indolizine Derivatives via One-Pot Reactions of
Chalcones, Benzyl bromides and Pyridines
Chao-dong Li, Xue Tang, Xiao-long He, Shuai Xue, Jiang-hong Xu, Yu-jin Li*
College of Chemical Engineering, Zhejiang University of Technology. Hangzhou 310014, P. R. of China
ARTICLE INFO
ABSTRACT
The one-pot cascade reaction for the preparation of indolizine from a wide range of chalcone,
pyridine and benzyl bromide via [3+2] cycloaddition/oxidative aromatization promoted by
Cu(OAc)2 has been developed. This convenient method don’t need to isolate the intermediates
and the desired products indolizines were obtained in moderate to high yield catalyzed by
Cu(OAc)2 in the presence of oxygen.
Article history:
Received
Received in revised form
Accepted
Available online
Keywords:
Copper-catalyzed
indolizine
1,3-dipolar cycloadditions
one-pot reaction
2018 Elsevier Ltd. All rights
reserved
.
1. Introduction
Me
N
O
O
Indolizines constitute a class of heteroaromatic compounds
containing two condensed rings and a bridging nitrogen atom,1
which were found in numerous natural products, pharmaceuticals
and microbes.2 Indolizines derivatives exhibit a broad array of
bioactivities,3 for example, as antiemetics the 5-
hydroxytryptamine receptor antagonists,4 a potential inhibitor of
growth factor VEGF,5 tumor necrosis factor (TNF) inhibitors,6 as
well as phosphodiesterase inhibitors.7 In addition, most of
indolizines with conjugated substituents on the ring have bright
colors, so it also has a very good application prospects in the
fields of dyes and materials.8
O
CN
R
F
N
H
N
N
O
N
N
N
N
N
O
Cl
N
O
H
OMe
O
Ph
VEGF inhibitor
Antiemetics
TNF inhibitor
PDESA inhibitor
Figure. 1 Some examples of biologically active compounds
Therefore, it is highly desirable to establish a simple and
efficient domino reaction in one-pot manner for synthesis of
indolizines derivatives from cheap, readily available starting
materials.17 When several reactions are conducted in a single
reactor, without purifying or isolating the intermediates, it can
simplify practical aspects and reduce chemical waste.18 Herein,
Based on the development of heterocyclic synthesis19 and copper
promoted reaction20 in our laboratory, we report a straightforward
and effective method for the synthesis of indolizine from a wide
range of chalcones, pyridine and benzyl bromide via the
[3+2]cycloaddition/oxidative aromatization cascade reaction
promoted by Cu(OAc)2. This protocol was accomplished in a
one-pot domino manner and no additional separation process was
required.
Due to their important bioactive and therapeutic properties,
indolizines derivatives have attracted much attention from the
organic chemistry community.9 A variety of efficient methods
have been reported for their synthesis, such as the tschitschibabin
reaction,10 1,3-dipolar cyclization,11 1,5-dipolar cyclizations,12
transition metal catalyzed intramolecular cyclization and
intermolecular cyclization,13 etc. Among them, 1,3-dipolar
cycloadditions of pyridinium ylides with unsaturated
hydrocarbons are one of the most convergent and straightforward
methods of the synthesis of functionalize indolizines.14 However,
the reported reactions have several drawbacks at present, such as
these reaction needs to be carried out in steps and each step
requires a different solvent, catalyst, and temperature. In
addition, the intermediate pyridinium ylides need to be isolated.
Obviously, these methods suffer from drawbacks in an atom- or
step-economic.15,16
2. Results and discussion
The reaction of chalcone (3a) with benzyl bromide (2a) and
pyridine (1a) was chosen as the model reaction to screen the
optimal reaction conditions (Table1).
Corresponding author
*. Tel.: +86 0571 88320891; fax: +86 0571
88320544; e-mail address: lyjzjut@zjut.edu.cn (Y.-J. Li).

2
Tetrahedron
Table 1. Optimization of the reaction conditionsa
with 2a in the presence of pyridine under the optimized
conditions (Table 2).
Table 2. Reaction substrate scope of chalconea
Entry
Catalysts (equiv)
Base
Temp Solvent
(°C )
Yield b
(%)
10
25
62
44
85
58
62
66
76
46
NR
49
59
Trace
15
19
45
1c
2
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
NaOH
TEA
Cs2CO3
NaHCO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
120
120
120
120
120
120
120
120
120
120
120
120
120
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
3c
4c
5
Cu(OAc)2 (0.5)
Cu(OAc)2 (0.25)
Cu(OAc)2 (0.25)
Cu(OAc)2 (0.125)
CuI (0.25)
6
7
8
9
CuBr (0.25)
CuCl2 (0.25)
10
11
12
13
14
15
16
17
18
19
Cu(OAc)2 (0.25)
Cu(OAc)2 (0.25)
Cu(OAc)2 (0.25)
Cu(OAc)2 (0.25)
Cu(OAc)2 (0.25)
Cu(OAc)2 (0.25)
Cu(OAc)2 (0.25)
Cu(OAc)2 (0.25)
Cu(OAc)2 (0.25)
Cu(OAc)2 (0.25)
reflux toluene
reflux
reflux
THF
EtOH
reflux DMSO
100
140
DMF
DMF
71
75
aReactions for entries:1a (0.2 mmol), 2a (0.2 mmol), 3a (0.1 mmol) and base
(0.2 mmol) in solvent (1.0 mL) under O2 atmosphere for 8 h.
bIsolated yield.
cReactions for entries: under air atmosphere.
The desired product 4a was isolated in 10% yield in DMF at
120 °C under air condition (Table 1, entry 1). Encouraged by this
result, we continued to explore the optimal conditions. To our
surprised, Cu(OAc)2 can be used as the good promoter to
facilitate the transformation process with DMF as the solvent at
120 °C under air condition and the yield of 4a was increased to
44% and 62% in the presence of 0.25 eq and 0.5 eq Cu(OAc)2
(entries 3 and 4). When the reaction was under O2 atmosphere,
the yield was increased to 25% even if without Cu(OAc)2 (entry
2). The control experiment revealed that copper and oxygen had
the function of promotion in this transformation. To our delight,
the yield of 4a was increased to 85% when the reaction was
conducted under O2 atmosphere catalyzed by 0.25eq Cu(OAc)2
(entry 5). Unfortunately, the yield was decreased to 58% when
Cu(OAc)2 was further reduced to 0.125eq (entry 6). It showed
that oxygen and 0.25eq Cu(OAc)2 were necessary for this
transformation. Next, several copper salt catalysts were
investigated such as CuI, CuBr and CuCl2 and the poor yields
were afforded (entries 7−9). A variety of base, including NaOH,
TEA, Cs2CO3 and NaHCO3 were screened to investigate their
effect on the reaction, but there was no further improvement for
obtaining 4a (entries 10−13). Solvent screening indicated that
DMF was the most effective solvent. Compared to the reaction in
DMF, the reactions in THF and EtOH gave obviously low yields
of 15% and 19%, respectively (entries 15 and 16). DMSO was
also less effective solvent than DMF (entry 17).Notably, by
studying the temperature, the best temperature was 120 °C.
Whether increasing or decreasing the reaction temperature, a
decreasing yield of the product 4a was caused (entries 18 and
19). Through the above experimental results, the optimum
reaction conditions were found to be 1a (0.2 mmol), 2a (0.2
mmol) and 3a (0.1 mmol) induced by Cu(OAc)2 (0.25 equiv.) in
DMF (1 mL) under O2 atmosphere for 8 h.
aReaction conditions: 1a (0.2 mmol), 2a (0.2 mmol), 3 (0.1 mmol),
Cu(OAc)2 (0.025 mmol) and K2CO3 (0.2 mmol) in DMF (1 mL) at 120 °C for
8 h under O2 atmosphere. bIsolated yield based on 3.
The results indicated that most of the chalcone derivatives
reacted smoothly with benzyl bromide and pyridine to obtain the
corresponding substituted indolizines in moderate to good yields
(4a-4j). It should be noted that the substituents on the aromatic
ring of chalcone such as halogen (Fuoro-, chloro-, bromo-) or
electron-donating groups (methoxy, methyl) could all be well
tolerated and the corresponding substituted indolizines 4 were
obtained in good yields 75~85% (4a-4g, 4m-4q). When the
substituents on the aromatic ring of chalcone were the strong
electron-withdrawing groups such as nitro- or trifluoromethyl
group, the yields of indolizines 4 were reduced to 55% (4h), 66%
(4i) and 51% (4j), respectively. The steric effect was observed
from the methyl substitution at different positions on the
aromatic ring of chalcone. The substrate produced 4m with 80%
yield with methyl-substituent on the para-position, while methyl-
substituent in the meta-position gave 75% yield of 4l and methyl-
substituent in the ortho-position gave 62% yield of 4k because of
Steric hindrance. Further experiments involved the evaluation of
heteroaryl and fused-aromatic chalcones under the optimal
reaction conditions. It was found that 2-naphthyl could be
effectively transformed to the desired product 4r in 80% yield
and heteroaryl chalcones including 2-furyl and 2-thienyl could
also react, but the yields of the products were reduced to 49%
(4s) and 59% (4t).
With the optimized conditions in hand, the substrate scope of
this transformation was investigated and the result was shown in
Table 2. At the outset, a series of substituted chalcone were tested

3
Table 3. Reaction substrate scope of pyridine and bromidea
R3
N
R4
R3
O
Cu(OAc)2, K2CO3
O
R4
+
+
Br
Scheme 2. Reaction of 3-penten-2-one 5 with pyridine 1a
and benzyl bromide 2a
DMF, O2, 120oC
N
1
2
3a
4
A mechanistic rationalization for the formation of product 4u
was given in Scheme 3. Presumably, the initial event 2a attacked
by isoquinoline to afford pyridinium salt (7), which is converted
into nitrogen ylide 8 in the presence of base. Then, it undergoes
1,3-dipolar cycloaddition reaction with 3a to form intermediate 9
(which can be detected by GC-MS, see the Supporting
Information for details). The intermediate 9 is easily converted
into intermediate 10 confirmed by GC-MS and NMR in air
atmosphere. Finally, the corresponding indolizine (4u) is
afforded by the co-oxidation with O2 and Cu(OAc)2.
Scheme 3. Mechanistic rationalization for the formation of
product 4u
3. Conclusion
aReaction conditions: 1 (0.2 mmol), 2 (0.2 mmol), 3a (0.1 mmol), Cu(OAc)2
(0.025 mmol) and K2CO3 (0.2 mmol) in DMF (1 mL) at 120 °C for 8 h under
O2 atmosphere. bIsolated yield based on 3a.
In summary, we have developed a novel and efficient method
for the synthesis of functionalized indolizine derivatives through
the one-pot [3+2] cycloaddition / oxidative aromatization
reaction under the catalysis of Cu(OAc)2 in the presence of
oxygen. This protocol exhibits a wide range of applications for
various easily accessible chalcones, pyridine and benzyl bromide
under mild reaction conditions, and the corresponding products
were obtained in good to excellent yields. These results will offer
considerable applications to complex targets in organic and
medicinal chemistry.
The substrate scope of pyridine derivatives and bromide
derivatives were also studied under the optimal reaction
conditions (Table 3). Isoquinoline as a substrate delivers the
corresponding product 4u was yielded in 88%. Benzyl bromides
containing electron-withdrawing groups delivered the
corresponding products (4v in 82% yield and 4w in 47% yield),
while benzyl bromides with electron-donating groups afforded
the corresponding products (4x with methyl group in 69% yield
and 4y with methoxy group in 44% yield). It is noteworthy that
pyridine with a 3-methyl substituted substrate reacted well for
producing product 4 in 77% total yield with the isomers 4z (42%)
and 4z′ (35%), respectively (Scheme 1). Besides, a series of alkyl
bromides show good reactivities, affording the corresponding
products (4aa-4ad) in 23~55% yields. It was also found that 3-
penten-2-one 5 as a substrate delivers the corresponding product
6 in 60% yield (Scheme 2).
4. Experimental section
4.1. General information
All chemicals were purchased from commercial vendors and
were used as received without further purification; any
exceptions are noted within the text and the vendors are noted
1
within the context of use. The H and 13C NMR spectra were
recorded at 500 and 125 MHz, respectively, in CDCl3 using TMS
as internal standard with a Bruker AM 500 spectrometer.
Chemical shifts (δ) were reported as parts per million (ppm) and
the following abbreviations were used to identify the
multiplicities: s=singlet, d=doublet, t=triplet, q=quartet,
m=multiplet, b=broad and all combinations thereof can be
explained by their integral parts. The GC-MS was taken on
Agilent (GC431-MS210), HRMS were recorded on a Bruker
MicroTOF-QII mass instrument (ESI).
Scheme 1. Reaction of chalcone 3a with 3-methylpyridine 1b
and benzyl bromide 2a

4
Tetrahedron
1
4.2 General procedure for the synthesis of 4a
Yellow solid. 78% yield. Mp 176-178 ℃. H NMR (500 MHz,
CDCl3) δ 8.12 (d, J = 9.0 Hz, 1H), 8.07 (d, J = 7.0 Hz, 1H), 7.57
(d, J = 7.2 Hz, 2H), 7.41 (ddd, J = 10.2, 7.7, 2.4 Hz, 3H), 7.31 –
7.27 (m, 3H), 7.15 (t, J = 7.7 Hz, 2H), 7.10 (dd, J = 8.9, 6.8 Hz,
1H), 6.94 – 6.89 (m, 4H), 6.73 (t, J = 6.8 Hz, 1H). 13C NMR (126
MHz, CDCl3) δ 192.05, 140.37, 136.67, 132.85, 132.33, 132.21,
131.16, 131.00, 129.89, 129.39, 129.13, 128.83, 128.55, 127.64,
127.60, 124.38, 123.43, 123.16, 120.04, 113.40, 112.06. HRMS
(ESI) m/z calcd for C27H18ClNONa [M+Na]+ 430.09691, found
430.09631.
Pyridine 1a (0.2 mmol), benzyl bromide 2a (0.2 mmol),
chalcones 3a (0.1 mmol), Copper acetate (0.025 mmol) and
Potassium carbonate (0.2 mmol）were dissolved in DMF (1.0
mL) in a thick-wall tube (10 mL) with screw cap. The reaction
was stirred at 120 °C for 8 h under O2 atmosphere. After reaction
was completed with detected by TLC, the mixture was cooled to
room temperature, the solution was then poured into water (10
mL) and extracted with EtOAc (3 × 10 mL). The acquired
organic phase was then dried over anhydrous Na2SO4, after
removing the volatile solvent, the product 4a was obtained in
85% yield by isolation with silica column chromatography.
4.2.6. (4-bromophenyl)(2,3-diphenylindolizin-1-yl)methanone
(4f)
4.2.1. (2,3-diphenylindolizin-1-yl)(phenyl)methanone (4a)
1
Yellow solid. 85% yield. Mp 172-174 ℃. H NMR (500 MHz,
1
Yellow solid. 85% yield. Mp 173-175 ℃. H NMR (500 MHz,
CDCl3) δ 8.26 (d, J = 9.0 Hz, 1H), 8.10 (d, J = 7.0 Hz, 1H), 7.43
– 7.36 (m, 5H), 7.32 – 7.28 (m, 2H), 7.21 – 7.14 (m, 3H), 7.02 –
6.98 (m, 1H), 6.97 – 6.92 (m, 4H), 6.76 (td, J = 6.9, 1.0 Hz, 1H).
13C NMR (126 MHz, CDCl3) δ 191.00, 139.24, 136.89, 133.97,
131.20, 131.19, 130.92, 130.54, 130.06, 129.98, 129.01, 128.41,
127.52, 126.31, 125.31, 124.32, 123.72, 123.21, 120.06, 113.52,
111.80. HRMS (ESI) m/z calcd for C27H18BrNONa [M+Na]+
474.04640, found 474.04581.
CDCl3) δ 8.19 (d, J = 9.0 Hz, 1H), 8.09 (d, J = 7.0 Hz, 1H), 7.60
– 7.54 (m, 2H), 7.43 – 7.36 (m, 3H), 7.31 (dd, J = 7.9, 1.4 Hz,
2H), 7.25 – 7.20 (m, 1H), 7.15 – 7.08 (m, 3H), 7.00 – 6.93 (m,
5H), 6.74 (td, J = 6.9, 1.1 Hz, 1H). 13C NMR (126 MHz, CDCl3)
δ 192.35, 140.37, 136.67, 134.17, 131.20, 130.75, 130.29, 130.10,
129.43, 128.94, 128.28, 127.36, 126.12, 124.17, 123.11, 120.06,
113.19, 112.17. HRMS (ESI) m/z calcd for C27H19NONa
[M+Na]+ 396.13589, found 396.13510.
4.2.7. (2-(4-bromophenyl)-3-phenylindolizin-1-
4.2.2. (2,3-diphenylindolizin-1-yl)(4-fluorophenyl)methanone
(4b)
yl)(phenyl)methanone (4g)
Yellow solid. 81% yield. Mp 145-147 ℃. 1H NMR (500 MHz,
CDCl3) δ 8.25 (d, J = 9.0 Hz, 1H), 8.10 (d, J = 7.0 Hz, 1H), 7.58
– 7.53 (m, 2H), 7.44 – 7.36 (m, 3H), 7.32 – 7.29 (m, 2H), 7.15
(ddd, J = 9.0, 6.6, 0.9 Hz, 1H), 6.99 – 6.93 (m, 5H), 6.78 – 6.72
(m, 3H). 13C NMR (126 MHz, CDCl3) δ 190.83, 165.20, 163.20,
136.77, 136.59, 136.57, 134.05, 131.82, 131.74, 131.21, 130.15,
129.90, 128.99, 128.37, 127.46, 126.30, 124.18, 123.45, 123.13,
120.01, 114.43, 114.25, 113.38, 111.90. HRMS (ESI) m/z calcd
for C27H18FNONa [M+Na]+ 414.12646, found 414.12582.
1
Yellow solid. 79% yield. Mp 183-185 ℃. H NMR (500 MHz,
CDCl3) δ 8.11 (d, J = 9.1 Hz, 1H), 8.06 (d, J = 7.0 Hz, 1H), 7.60
– 7.54 (m, 2H), 7.43 – 7.36 (m, 3H), 7.31 – 7.27 (m, 3H), 7.15 (t,
J = 7.7 Hz, 2H), 7.08 (dd, J = 12.5, 6.0 Hz, 3H), 6.88 – 6.83 (m,
2H), 6.72 (td, J = 6.9, 0.8 Hz, 1H). 13C NMR (126 MHz, CDCl3)
δ 191.99, 140.38, 136.67, 133.34, 132.75, 132.67, 131.21,
131.16, 131.01, 130.61, 130.55, 129.85, 129.45, 129.39, 129.16,
128.83, 128.58, 127.68, 124.34, 123.45, 123.18, 120.53, 120.03,
113.42, 112.02. HRMS (ESI) m/z calcd for C27H18BrNONa
[M+Na]+ 474.04640, found 474.0605.
4.2.3. (2-(4-fluorophenyl)-3-phenylindolizin-1-
yl)(phenyl)methanone (4c)
4.2.8. (2,3-diphenylindolizin-1-yl)(4-nitrophenyl)methanone (4h)
Yellow solid. 78% yield. Mp 158-160 ℃. 1H NMR (500 MHz,
CDCl3) δ 8.17 (d, J = 9.1 Hz, 1H), 8.09 (d, J = 7.0 Hz, 1H), 7.58
– 7.52 (m, 2H), 7.44 – 7.37 (m, 3H), 7.29 (ddd, J = 8.8, 5.6, 2.5
Hz, 3H), 7.15 – 7.11 (m, 3H), 6.95 – 6.91 (m, 2H), 6.75 (td, J =
6.9, 1.2 Hz, 1H), 6.67 – 6.62 (m, 2H). 13C NMR (126 MHz,
CDCl3) δ 192.19, 162.38, 160.42, 140.36, 136.68, 132.64,
132.58, 131.17, 130.92, 130.25, 130.22, 130.03, 129.39, 129.06,
129.02, 128.44, 127.54, 124.29, 123.40, 123.12, 120.06, 114.46,
114.29, 113.35, 112.12. HRMS (ESI) m/z calcd for
C27H18FNONa [M+Na]+ 414.12646, found 414.12576.
1
Yellow solid. 55% yield. Mp 207-209 ℃. H NMR (500 MHz,
CDCl3) δ 8.48 (d, J = 9.0 Hz, 1H), 8.13 (d, J = 7.0 Hz, 1H), 7.85
(d, J = 8.8 Hz, 2H), 7.55 (d, J = 8.8 Hz, 2H), 7.42 – 7.35 (m, 3H),
7.31 – 7.26 (m, 3H), 6.92 – 6.83 (m, 6H). 13C NMR (126 MHz,
CDCl3) δ 189.76, 148.19, 146.20, 137.42, 133.70, 131.17,
131.04, 129.92, 129.70, 129.59, 128.95, 128.50, 127.44, 126.50,
124.83, 124.74, 123.41, 122.34, 120.20, 114.07, 111.40. HRMS
(ESI) m/z calcd for C27H18N2O3Na [M+Na]+ 441.12096, found
441.12027.
4.2.4. (4-chlorophenyl)(2,3-diphenylindolizin-1-yl)methanone
4.2.9. (2-(4-nitrophenyl)-3-phenylindolizin-1-
(4d)
yl)(phenyl)methanone (4i)
1
1
Yellow solid. 76% yield. Mp 170-172 ℃. H NMR (500 MHz,
Yellow solid. 66% yield. Mp 193-195 ℃. H NMR (500 MHz,
CDCl3) δ 8.26 (d, J = 9.0 Hz, 1H), 8.10 (d, J = 7.0 Hz, 1H), 7.50
– 7.44 (m, 2H), 7.42 – 7.35 (m, 3H), 7.30 (dd, J = 7.8, 1.4 Hz,
2H), 7.15 (ddd, J = 8.9, 6.7, 0.6 Hz, 1H), 7.05 – 7.01 (m, 2H),
6.98 (s, 1H), 6.97 – 6.92 (m, 4H), 6.76 (td, J = 6.9, 1.1 Hz, 1H).
13C NMR (126 MHz, CDCl3) δ 190.89, 138.81, 136.87, 136.71,
134.00, 131.21, 131.19, 130.99, 130.78, 130.07, 129.96, 129.01,
128.41, 127.58, 127.51, 126.32, 124.29, 123.67, 123.19, 120.05,
113.51, 111.84. HRMS (ESI) m/z calcd for C27H18ClNONa
[M+Na]+ 430.09691, found 430.09613.
CDCl3) δ 8.06 (dd, J = 9.6, 8.7 Hz, 2H), 7.82 (d, J = 8.8 Hz, 2H),
7.61 – 7.55 (m, 2H), 7.43 (dd, J = 7.8, 4.4 Hz, 3H), 7.31 – 7.26
(m, 3H), 7.18 – 7.10 (m, 5H), 6.77 (dd, J = 9.8, 3.8 Hz, 1H). 13C
NMR (126 MHz, CDCl3) δ 191.49, 145.92, 141.78, 140.32,
136.71, 131.63, 131.23, 131.06, 129.24, 128.90, 127.73, 124.97,
123.74, 123.24, 122.48, 120.03, 113.64, 112.00. HRMS (ESI)
m/z calcd for C27H18N2O3Na [M+Na]+ 441.12096, found
441.12024.
4.2.10. (2,3-diphenylindolizin-1-yl)(4-
4.2.5. (2-(4-chlorophenyl)-3-phenylindolizin-1-
(trifluoromethyl)phenyl)methanone (4j)
yl)(phenyl)methanone (4e)

5
1
Yellow solid. 51% yield. Mp 183-185 . H NMR (500 MHz,
– 7.37 (m, 3H), 7.34 – 7.30 (m, 2H), 7.15 – 7.09 (m, 4H), 7.08
CDCl3) δ 8.43 (d, J = 9.0 Hz, 1H), 8.13 (d, J = 7.0 Hz, 1H), 7.54
(d, J = 8.0 Hz, 2H), 7.43 – 7.36 (m, 3H), 7.30 (dd, J = 12.8, 4.8
Hz, 4H), 7.26 – 7.21 (m, 1H), 6.95 – 6.87 (m, 5H), 6.82 (td, J =
6.9, 1.0 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 190.94, 143.78,
137.26, 133.84, 131.77, 131.51, 131.19, 131.16, 130.19, 129.92,
129.26, 128.98, 128.45, 127.41, 126.40, 124.89, 124.59, 124.33,
124.22, 124.20, 124.16, 123.33, 122.72, 120.29, 113.82, 111.70.
HRMS (ESI) m/z calcd for C28H18F3NONa [M+Na]+ 464.12327,
found 464.12283.
(ddd, J = 7.4, 3.7, 1.8 Hz, 3H), 6.75 (dd, J = 3.5, 0.5 Hz, 1H),
6.71 (td, J = 6.9, 1.2 Hz, 1H), 6.19 (dd, J = 3.5, 1.7 Hz, 1H). 13C
NMR (126 MHz, CDCl3) δ 178.79, 153.29, 144.88, 136.37,
134.64, 131.20, 130.55, 130.18, 129.14, 128.92, 128.30, 127.59,
126.11, 124.00, 122.98, 119.63, 117.49, 113.16, 111.61, 111.39.
4.2.16. (2-(4-methoxyphenyl)-3-phenylindolizin-1-
yl)(phenyl)methanone (4p)
1
Yellow solid. 82% yield. Mp 184-186 . H NMR (500 MHz,
4.2.11. phenyl(3-phenyl-2-(o-tolyl)indolizin-1-yl)methanone (4k)
CDCl3) δ 8.14 (d, J = 9.0 Hz, 1H), 8.08 (d, J = 7.0 Hz, 1H), 7.58
– 7.55 (m, 2H), 7.44 – 7.36 (m, 3H), 7.33 – 7.30 (m, 2H), 7.25 (t,
J = 7.4 Hz, 1H), 7.12 (dd, J = 12.3, 4.6 Hz, 3H), 6.90 – 6.85 (m,
2H), 6.73 (td, J = 6.9, 1.2 Hz, 1H), 6.51 – 6.47 (m, 2H), 3.66 (s,
3H). 13C NMR (126 MHz, CDCl3) δ 192.39, 158.02, 140.44,
136.63, 132.21, 131.22, 130.72, 130.48, 129.83, 129.46, 128.96,
128.21, 127.44, 126.51, 123.98, 123.00, 119.99, 113.08, 113.03,
112.18, 55.09. HRMS (ESI) m/z calcd for C28H21NO2Na
[M+Na]+ 426.14645, found 426.14487.
1
Yellow solid. 62% yield. Mp 176-178 . H NMR (500 MHz,
CDCl3) δ 8.22 (d, J = 7.0 Hz, 1H), 8.17 (d, J = 9.0 Hz, 1H), 7.57
– 7.47 (m, 2H), 7.38 – 7.29 (m, 3H), 7.23 (ddd, J = 8.6, 3.1, 1.4
Hz, 3H), 7.15 – 7.09 (m, 3H), 6.98 (dd, J = 7.4, 1.2 Hz, 1H), 6.92
(td, J = 7.4, 1.4 Hz, 1H), 6.85 (dd, J = 15.0, 7.5 Hz, 2H), 6.76 (td,
J = 6.9, 1.3 Hz, 1H), 1.97 (s, 3H). 13C NMR (126 MHz, CDCl3) δ
192.33, 140.57, 136.64, 136.62, 134.00, 131.93, 130.48, 130.33,
130.30, 129.60, 129.30, 128.82, 128.78, 128.00, 127.21, 126.88,
124.77, 124.62, 123.24, 123.05, 120.25, 113.13, 112.80. HRMS
(ESI) m/z calcd for C28H21NONa [M+Na]+ 410.15154, found
410.15106.
4.2.17. (2,3-diphenylindolizin-1-yl)(4-methoxyphenyl)methanon
(4q)
1
Yellow solid. 79% yield. Mp 203-205 . H NMR (500 MHz,
4.2.12. phenyl(3-phenyl-2-(m-tolyl)indolizin-1-yl)methanone (4l)
CDCl3) δ 8.07 (d, J = 8.9 Hz, 2H), 7.66 – 7.57 (m, 2H), 7.44 –
7.34 (m, 3H), 7.34 – 7.29 (m, 2H), 7.09 – 6.94 (m, 6H), 6.68 (td,
J = 6.8, 1.4 Hz, 1H), 6.63 (d, J = 8.8 Hz, 2H), 3.73 (s, 3H). 13C
NMR (126 MHz, CDCl3) δ 190.96, 161.87, 136.02, 134.22,
132.86, 132.33, 131.63, 131.09, 131.04, 130.31, 129.67, 129.44,
128.83, 128.47, 128.30, 128.12, 127.32, 126.42, 126.01, 123.78,
122.81, 122.33, 119.76, 113.48, 112.77, 112.70, 112.35, 55.13.
HRMS (ESI) m/z calcd for C28H21NO2Na [M+Na]+ 426.14645,
found 426.14587.
1
Yellow solid. 75% yield. Mp 183-185 . H NMR (500 MHz,
CDCl3) δ 8.23 (dt, J = 9.1, 1.1 Hz, 1H), 8.09 (dt, J = 6.9, 0.9 Hz,
1H), 7.58 – 7.52 (m, 2H), 7.43 – 7.36 (m, 3H), 7.34 – 7.31 (m,
2H), 7.24 – 7.19 (m, 1H), 7.14 – 7.07 (m, 3H), 6.83 (t, J = 7.5
Hz, 1H), 6.78 – 6.72 (m, 4H), 2.02 (s, 3H). 13C NMR (126 MHz,
CDCl3) δ 192.44, 140.56, 136.66, 136.62, 133.85, 132.40,
131.17, 130.56, 130.35, 130.20, 129.14, 128.86, 128.20, 127.96,
127.23, 127.17, 126.77, 124.00, 123.08, 123.01, 120.04, 113.14,
112.17, 20.97. HRMS (ESI) m/z calcd for C28H21NONa [M+Na]+
410.15154, found 410.15100.
4.2.18. (2,3-diphenylindolizin-1-yl)(naphthalen-2-yl)methanone
(4r)
4.2.13. phenyl(3-phenyl-2-(p-tolyl)indolizin-1-yl)methanone (4m)
1
Yellow solid. 80% yield. Mp 168-170 . H NMR (500 MHz,
1
Yellow solid. 80% yield. Mp 172-174 . H NMR (500 MHz,
CDCl3) δ 8.22 (d, J = 9.0 Hz, 1H), 8.13 (d, J = 7.0 Hz, 1H), 8.09
(s, 1H), 7.82 (dd, J = 8.5, 1.5 Hz, 1H), 7.73 (d, J = 8.1 Hz, 1H),
7.66 (dd, J = 12.2, 8.4 Hz, 2H), 7.48 – 7.33 (m, 7H), 7.12 – 7.08
(m, 1H), 7.08 – 7.03 (m, 2H), 6.84 (t, J = 7.6 Hz, 2H), 6.73 (dd, J
= 13.4, 6.9 Hz, 2H). 13C NMR (126 MHz, CDCl3) δ 191.86,
137.42, 136.47, 134.30, 134.12, 131.92, 131.02, 130.94, 130.86,
130.09, 128.80, 128.14, 127.31, 127.19, 127.17, 127.08, 125.84,
125.72, 125.48, 124.09, 122.99, 122.94, 119.86, 113.07, 112.35.
HRMS (ESI) m/z calcd for C31H21NONa [M+Na]+ 446.15154,
found 446.15094.
CDCl3) δ 8.12 (d, J = 9.0 Hz, 1H), 8.08 (d, J = 7.0 Hz, 1H), 7.61
– 7.57 (m, 2H), 7.43 – 7.36 (m, 3H), 7.35 – 7.31 (m, 2H), 7.24
(dd, J = 10.6, 4.2 Hz, 1H), 7.14 – 7.06 (m, 3H), 6.87 (d, J = 8.0
Hz, 2H), 6.76 (d, J = 7.9 Hz, 2H), 6.71 (td, J = 6.9, 1.2 Hz, 1H),
2.16 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 192.30, 140.43,
136.50, 135.60, 131.18, 131.05, 130.96, 130.58, 130.42, 130.15,
129.42, 128.90, 128.18, 128.06, 127.38, 124.01, 122.99, 122.86,
119.93, 113.00, 112.22, 20.96. HRMS (ESI) m/z calcd for
C28H21NONa [M+Na]+ 410.15154, found 410.15115.
4.2.14. (2,3-diphenylindolizin-1-yl)(p-tolyl)methanone (4n)
4.2.19. (2,3-diphenylindolizin-1-yl)(thiophen-2-yl)methanone (4s)
1
Yellow solid. 76% yield. Mp 188-190 . H NMR (500 MHz,
1
Yellow solid. 49% yield. Mp 152-154 . H NMR (500 MHz,
CDCl3) δ 8.12 – 8.05 (m, 2H), 7.51 (d, J = 8.1 Hz, 2H), 7.44 –
7.35 (m, 3H), 7.34 – 7.30 (m, 2H), 7.09 – 7.04 (m, 1H), 7.02 –
6.95 (m, 5H), 6.93 (d, J = 7.9 Hz, 2H), 6.71 (td, J = 6.7, 1.4 Hz,
1H), 2.26 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 192.00, 141.24,
137.62, 136.29, 134.24, 131.17, 131.10, 130.36, 129.98, 129.63,
128.90, 128.20, 128.11, 127.32, 125.96, 124.01, 122.95, 122.63,
119.94, 112.92, 112.42, 21.39. HRMS (ESI) m/z calcd for
C28H21NONa [M+Na]+ 410.15154, found 410.15120.
CDCl3) δ 8.11 (d, J = 9.1 Hz, 1H), 8.05 (d, J = 7.1 Hz, 1H), 7.43
– 7.35 (m, 4H), 7.34 – 7.31 (m, 2H), 7.13 – 7.09 (m, 3H), 7.08 –
7.03 (m, 4H), 6.69 (td, J = 6.0, 2.9 Hz, 2H). 13C NMR (126 MHz,
CDCl3) δ 183.59, 145.63, 135.89, 134.23, 133.38, 131.50,
131.09, 130.86, 130.14, 128.89, 128.85, 128.21, 127.51, 126.86,
126.20, 123.86, 122.82, 122.46, 119.52, 112.91, 112.23. HRMS
(ESI) m/z calcd for C25H17NOSNa [M+Na]+ 402.09231, found
402.09158.
4.2.15. (2-(3,5-dichlorophenyl)-3-phenylindolizin-1-
4.2.20. (2,3-diphenylindolizin-1-yl)(furan-2-yl)methanone (4t)
yl)(phenyl)methanone (4o)
1
Yellow solid. 59% yield. Mp 167-169 . H NMR (500 MHz,
1
CDCl3) δ 8.17 (d, J = 9.0 Hz, 1H), 8.04 (d, J = 7.0 Hz, 1H), 7.44
Yellow solid. 76% yield. Mp 169-171 . H NMR (500 MHz,
– 7.37 (m, 3H), 7.34 – 7.29 (m, 2H), 7.16 – 7.09 (m, 4H), 7.09 –
CDCl3) δ 8.18 (d, J = 9.0 Hz, 1H), 8.05 (d, J = 7.0 Hz, 1H), 7.44

6
Tetrahedron
7.05 (m, 3H), 6.75 (d, J = 3.5 Hz, 1H), 6.71 (t, J = 6.8 Hz, 1H),
1.6 Hz, 1H), 6.74 (td, J = 6.9, 1.2 Hz, 1H), 3.67 (s, 3H). 13C
NMR (126 MHz, CDCl3) δ 192.29, 159.87, 140.40, 136.66,
134.24, 131.49, 131.12, 130.73, 130.10, 129.91, 129.41, 127.39,
127.34, 126.13, 124.01, 123.32, 123.20, 123.12, 120.06, 116.52,
114.17, 113.19, 112.18 , 55.40, 55.17. HRMS (ESI) m/z calcd for
C28H21NO2Na [M+Na]+ 426.14645, found 426.14560.
6.19 (dd, J = 3.4, 1.6 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ
178.79, 153.32, 144.88, 136.37, 134.66, 131.21, 130.56, 130.19,
129.16, 128.92, 128.30, 127.59, 126.12, 124.01, 122.99, 122.97,
119.65, 117.48, 113.16, 111.63, 111.39. HRMS (ESI) m/z calcd
for C25H17NO2Na [M+Na]+ 386.11515, found 386.11450.
4.2.21. (2,3-diphenylpyrrolo[2,1-a]isoquinolin-1-
4.2.26. (6-methyl-2,3-diphenylindolizin-1-yl)(phenyl)methanone
yl)(phenyl)methanone (4u)
(4z)
1
Yellow liquid. 88% yield. 1H NMR (500 MHz, CDCl3) δ 8.10 (d,
J = 8.1 Hz, 1H), 7.92 (dd, J = 8.2, 1.2 Hz, 2H), 7.88 (d, J = 7.5
Hz, 1H), 7.62 – 7.58 (m, 1H), 7.43 (t, J = 2.5 Hz, 1H), 7.41 (d, J
= 3.4 Hz, 1H), 7.39 (dq, J = 6.1, 4.5 Hz, 5H), 7.37 – 7.31 (m,
2H), 7.28 (d, J = 3.7 Hz, 1H), 7.11 – 7.06 (m, 2H), 7.05 – 6.98
(m, 3H), 6.86 (d, J = 7.5 Hz, 1H).13C NMR (126 MHz, CDCl3) δ
196.65, 138.98, 134.02, 132.66, 131.17, 130.44, 130.33, 129.97,
128.81, 128.25, 128.16, 128.11, 128.04, 127.61, 127.50, 127.11,
126.97, 126.54, 126.16, 125.24, 125.08, 124.10, 121.67, 116.24,
112.47.
Yellow solid. 42% yield. Mp 161-163 . H NMR (500 MHz,
CDCl3) δ 8.11 (d, J = 9.1 Hz, 1H), 7.86 (s, 1H), 7.55 (d, J = 7.3
Hz, 2H), 7.44 – 7.36 (m, 3H), 7.33 – 7.29 (m, 2H), 7.21 (t, J =
7.4 Hz, 1H), 7.08 (t, J = 7.7 Hz, 2H), 7.00 (d, J = 9.2 Hz, 1H),
6.97 – 6.90 (m, 5H), 2.27 (s, 3H). 13C NMR (126 MHz, CDCl3) δ
192.21, 140.56, 135.63, 134.36, 131.29, 131.21, 130.60, 130.55,
129.96, 129.41, 128.91, 128.19, 127.35, 127.27, 126.38, 126.01,
123.92, 122.87, 120.74, 119.57, 111.93, 18.47. HRMS (ESI) m/z
calcd for C28H21NONa [M+Na]+ 410.15154, found 410.15094.
4.2.27. (8-methyl-2,3-diphenylindolizin-1-yl)(phenyl)methanone
4.2.22. (3-(4-bromophenyl)-2-phenylindolizin-1-
(4z′)
yl)(phenyl)methanone (4v)
1
Yellow solid. 35% yield. Mp 166-168 . H NMR (500 MHz,
1
Yellow solid. 82% yield. Mp 163-165 . H NMR (500 MHz,
CDCl3) δ 7.99 (d, J = 7.0 Hz, 1H), 7.82 – 7.77 (m, 2H), 7.42 –
7.34 (m, 5H), 7.33 – 7.30 (m, 1H), 7.20 (dd, J = 10.7, 4.7 Hz,
2H), 7.08 – 7.04 (m, 2H), 7.00 – 6.94 (m, 3H), 6.75 (dd, J = 5.9,
0.9 Hz, 1H), 6.59 (t, J = 6.9 Hz, 1H),2.36 (s, 3H). 13C NMR (126
MHz, CDCl3) δ 194.81, 139.92, 134.25, 132.56, 131.99, 131.17,
130.75, 130.58, 130.09, 129.07, 128.82, 128.72, 128.01, 127.66,
127.46, 126.13, 122.92, 121.53, 120.93, 113.92, 111.85, 20.72.
HRMS (ESI) m/z calcd for C28H21NONa [M+Na]+ 410.15154,
found 410.15100.
CDCl3) δ 8.17 (d, J = 9.0 Hz, 1H), 8.06 (d, J = 7.0 Hz, 1H), 7.54
(dd, J = 10.5, 8.3 Hz, 4H), 7.24 – 7.09 (m, 6H), 6.96 (s, 5H), 6.76
(t, J = 6.8 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 192.21,
140.20, 136.75, 133.82, 132.67, 132.21, 131.06, 130.82, 130.36,
129.34, 129.21, 127.47, 127.40, 126.31, 123.28, 122.74, 122.71,
122.41, 120.13, 113.42, 112.30. HRMS (ESI) m/z calcd for
C27H18BrNONa [M+Na]+ 474.04640, found 474.04575.
4.2.23. (3-(4-nitrophenyl)-2-phenylindolizin-1-
4.2.28. (3-ethyl-2-phenylindolizin-1-yl)(phenyl)methanone (4aa)
Liquid. 55% yield. H NMR (500 MHz, CDCl3) δ 8.17 (dt, J =
yl)(phenyl)methanone (4w)
1
1
Yellow solid. 47% yield. Mp 204-206 . H NMR (500 MHz,
9.0, 1.1 Hz, 1H), 7.97 – 8.00 (m, 1H), 7.49 – 7.58 (dt, J = 8.3, 1.4
Hz, 3H), 7.23 – 7.17 (m, 2H), 7.13 – 7.07 (m, 6H), 6.85 (td, J =
6.8, 1.3 Hz, 1H), 2.91 (q, J = 7.5 Hz, 2H), 1.27 (t, J = 3.7 Hz,
3H). 13C NMR (126 MHz, CDCl3) δ 192.07, 149.50, 140.64,
136.65, 134.99, 133.73, 130.71, 130.49, 129.74, 129.29, 128.68,
128.33, 127.60, 127.27, 126.36, 123.96, 122.63, 122.37, 120.40,
113.20, 111.78, 22.70, 14.12. HRMS (ESI) m/z calcd for
C23H19NONa [M+Na]+ 348.13589, found 348.13571.
CDCl3) δ 8.23 (d, J = 8.8 Hz, 2H), 8.19 (t, J = 7.3 Hz, 2H), 7.56 –
7.51 (m, 2H), 7.47 (d, J = 8.8 Hz, 2H), 7.24 (t, J = 7.4 Hz, 1H),
7.18 (dd, J = 8.9, 6.9 Hz, 1H), 7.10 (t, J = 7.7 Hz, 2H), 7.02 –
6.96 (m, 3H), 6.94 (dd, J = 7.9, 1.5 Hz, 2H), 6.83 (dd, J = 10.2,
4.4 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 192.19, 146.98,
140.00, 137.29, 137.25, 133.40, 131.57, 131.51, 131.06, 129.32,
128.83, 127.76, 127.51, 126.82, 124.14, 123.86, 122.47, 121.52,
120.42, 113.99, 113.03.
4.2.29. phenyl(2-phenyl-3-propylindolizin-1-yl)methanone (4ab)
Liquid. 36% yield. H NMR (500 MHz, CDCl3) δ 8.17 (dt, J =
1
4.2.24. phenyl(2-phenyl-3-(m-tolyl)indolizin-1-yl)methanone (4x)
9.0, 1.1 Hz, 1H), 7.99 – 7.96 (m, 1H), 7.50 (dt, J = 8.3, 1.4 Hz,
2H), 7.23 – 7.17 (m, 2H), 7.13 – 7.07 (m, 8H), 6.85 (td, J = 6.8,
1.3 Hz, 1H), 2.90 – 2.85 (m, 2H), 1.69 (dt, J = 15.3, 7.5 Hz, 2H),
0.90 (t, J = 7.3 Hz,3H). 13C NMR (126 MHz, CDCl3) δ 192.07,
140.61, 136.56, 135.04, 130.76, 130.44, 129.68, 129.26, 128.65,
128.28, 128.08, 127.55, 127.22, 126.29, 123.98, 122.76, 122.35,
120.30, 113.13, 111.81, 29.68, 25.92, 13.92. HRMS (ESI) m/z
calcd for C24H21NONa [M+Na]+ 362.15154, found 362.15121.
Yellow solid. 69% yield. Mp 147-149 . 1H NMR (500 MHz,
CDCl3) δ 8.20 (d, J = 9.0 Hz, 1H), 8.08 (d, J = 7.0 Hz, 1H), 7.62
– 7.57 (m, 2H), 7.29 – 7.26 (m, 1H), 7.24 – 7.20 (m, 1H), 7.20 –
7.15 (m, 2H), 7.12 – 7.07 (m, 4H), 7.03 – 6.99 (m, 2H), 6.95 (dd,
J = 6.6, 3.4 Hz, 3H), 6.74 – 6.69 (m, 1H), 2.34 (s, 3H). 13C NMR
(126 MHz, CDCl3) δ 192.18, 140.34, 138.45, 136.49, 134.16,
131.54, 131.05, 130.61, 130.04, 129.85, 129.31, 129.00, 128.72,
128.24, 127.28, 127.19, 125.97, 124.26, 123.09, 122.95, 119.87,
113.01, 112.02, 21.29. HRMS (ESI) m/z calcd for C28H21NONa
[M+Na]+ 410.15154, found 410.15060.
4.2.30. (3-isobutyl-2-phenylindolizin-1-yl)(phenyl)methanone
(4ac)
Liquid. 34% yield. 1H NMR (500 MHz, CDCl3) δ 8.18 (dt, J =
9.0, 1.1 Hz, 1H), 7.98 (d, J = 7.1 Hz, 1H), 7.49 – 7.46 (m, 2H),
7.21 – 7.18 (m, 1H), 7.12 – 7.05 (m, 8H), 6.85 (td, J = 6.8, 1.3
Hz, 1H), 2.82 (d, J = 7.4 Hz, 2H), 1.97 (dt, J = 13.6, 6.9 Hz, 1H),
0.76 (d, J = 6.6 Hz, 6H). 13C NMR (126 MHz, CDCl3) δ 192.23,
136.63, 135.20, 131.00, 130.44, 129.77, 129.27, 128.29, 128.11,
127.54, 127.25, 126.25, 123.99, 123.39, 123.08, 122.39, 120.29,
4.2.25. (3-(4-methoxyphenyl)-2-phenylindolizin-1-
yl)(phenyl)methanone(4y)
1
Yellow solid. 44% yield. Mp 165-167 . H NMR (500 MHz,
CDCl3) δ 8.22 – 8.11 (m, 2H), 7.59 – 7.55 (m, 2H), 7.33 (dd, J =
14.2, 6.3 Hz, 1H), 7.25 – 7.20 (m, 1H), 7.11 (td, J = 7.6, 1.3 Hz,
3H), 7.02 – 6.98 (m, 2H), 6.97 – 6.89 (m, 5H), 6.80 (dd, J = 2.4,

7
Joseph-McCarthy, S.Y. Tam, R. Hotchandani, J. Wu, A. Huang, Q.
113.07, 112.06, 32.70, 29.71, 26.85, 22.47. HRMS (ESI) m/z
calcd for C25H23NONa [M+Na]+ 376.16719, found 376.16681.
Wang, L. Leung, J. Pelker, S. Marusic, S. Hsu, J.-B. Telliez, J.P. Hall,
J.W. Cuozzo and L.-L. Lin, J. Med. Chem. 2007, 50, 4728-4745.
F. Svensson, A. Bender and D. Bailey, J. Med. Chem. 2018, 61, 1415-
1424.
(a) D.T. Yang, J. Radtke, S.K. Mellerup, K. Yuan, X. Wang, M. Wagner
and S. Wang, Org. Lett. 2015, 17, 2486-2489. (b) Y. Segawa, T.
Maekawa and K. Itami, Angew. Chem. Int. Ed. 2015, 54, 66-81. (c) D.
Liu, Z. Zhang, H. Zhang and Y. Wang, Chem. Commun. 2013, 49,
10001-10003. (d) B. Liu, Z. Wang, N. Wu, M. Li, J. You and J. Lan,
Chem. Eur. J. 2012, 18, 1599–1603.
7.
8.
4.2.31. (3-butyl-2-phenylindolizin-1-yl)(phenyl)methanone (4ad)
Liquid. 23% yield. 1H NMR (500 MHz, CDCl3) δ 8.17 (d, J = 9.0
Hz, 1H), 7.98 (t, J = 7.3 Hz, 1H), 7.51 – 7.48 (m, 2H), 7.22 –
7.18 (m, 1H), 7.13 – 7.06 (m,8H), 6.86 (td, J = 6.8, 1.2 Hz, 1H),
2.92 – 2.84 (m, 2H), 1.66 – 1.61 (m, 2H), 1.28 (dd, J = 15.9, 8.4
Hz, 16H), 0.90 (t, J = 7.0 Hz, 3H). 13C NMR (126 MHz, CDCl3)
δ 192.07, 140.63, 136.57, 135.06, 130.76, 130.44, 129.53,
129.28, 127.56, 127.30, 126.29, 124.22, 122.74, 122.33, 120.33,
113.14, 111.80, 31.91, 29.87 – 29.22, 29.15, 27.52, 23.84, 22.67,
14.10. HRMS (ESI) m/z calcd for C32H37NONa [M+Na]+
474.27674, found 474.27625.
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4.2.32. 1-(2-methyl-3-phenylindolizin-1-yl)ethan-1-one (6)
Liquid. 60% yield. 1H NMR (500 MHz, CDCl3) δ 8.42 (d, J = 9.1
Hz, 1H), 7.94 (d, J = 6.9 Hz, 1H), 7.55 (t, J = 7.5 Hz, 3H), 7.48
(t, J = 5.7 Hz, 1H), 7.44 – 7.40 (m, 1H), 7.13 (dd, J = 8.5, 7.2 Hz,
1H), 6.68 (t, J = 6.8 Hz, 1H), 2.64 (s, 3H), 2.47 (s, 3H). 13C NMR
(126 MHz, CDCl3) δ 193.60, 130.98 , 130.30, 129.19, 128.73,
128.51, 124.61, 123.60, 123.16, 120.12, 112.77, 77.29, 77.03,
76.78, 29.70, 13.35.
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3718-3721.
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4.2.33. (3-butyl-2-phenylindolizin-1-yl)(phenyl)methanone (10)
1
Liquid. H NMR (500 MHz, CDCl3) δ 8.92 (d, J = 8.3 Hz, 1H),
7.58 – 7.51 (m, 1H), 7.43 – 7.35 (m, 6H), 7.32 – 7.11 (m, 11H),
6.74 (d, J = 7.0 Hz, 1H), 6.42 (d, J = 7.0 Hz, 1H), 5.08 (d, J = 5.0
Hz, 1H), 4.45 (d, J = 5.0 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ
189.61, 152.88, 145.01, 143.09, 140.88, 136.37, 132.10, 131.57,
129.26, 129.00, 128.58, 127.72, 127.48, 127.19, 126.62, 126.15,
125.94, 123.20, 109.56, 106.28, 75.69, 58.84.
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Acknowledgements
We gratefully acknowledge the financial supported by the
Natural Science Foundation of China (21606201)，the National
Natural Science Foundation of Zhejiang (LY13B020016) and
Technological Innovation Program in Zhejiang Province(Zhejian
g Xinmiao Talents Program) (2017R403066).
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3690-3693. (b) Y. Li, H. M. Huang, J. Ju, L. Han, Q. Ye, RSC
Advances. 2013, 3, 25840-25848. (c) Y.J. Li, H.M. Huang, H.Q. Dong,
J.H. Jia, L. Han, Q. Ye, J. R. Gao, J. Org. Chem. 2013, 78, 9424-9430.
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Supplementary data
Supplementary data related to this article can be found at
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Dear Editor:
We would like to submit the enclosed manuscript entitled “Copper-catalyzed
formation of indolizine derivatives via the one-pot reaction of chalcone, benzyl
bromide and pyridine”, which we wish to be considered for publication in
Tetrahedron. We believe the paper will make it interesting to general readers of
Tetrahedron.
The following are some highlights.
1): a one-pot manner for synthesis of indolizines derivatives, without purifying
or isolating the intermediates.
2): the reaction don’t requires the addition of starting materials stage by stage
and no additional separation process was required.
3): the desired products indolizines were obtained in high yield catalyzed by
Cu(OAc)2 in the presence of oxygen. This method is new, neither the entire paper nor
any part of its content has been published or has been accepted elsewhere.
Sincerely yours
Corresponding author:
Name: Yujin Li
E-mail: lyjzjut@zjut.edu.cn
Tel: +86-0571-88320891
Fax: ++86-0571-8832054

Declaration of interests
☒ 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.
☐The authors declare the following financial interests/personal relationships which may be considered
as potential competing interests:
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.