TEMPO-catalyzed decarboxylation reactions for the synthesis of 1,2-unsubstituted indolizines

Article abstract of DOI:10.1002/jhet.3766

An efficient synthesis of 1,2-unsubstituted indolizines was developed via 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)–catalyzed decarboxylation reaction. A series of target products were successfully prepared with the tolerance of a variety of functional

Full text of DOI:10.1002/jhet.3766

Received: 10 May 2019
DOI: 10.1002/jhet.3766
Revised: 6 September 2019
Accepted: 12 September 2019
A R T I C L E
TEMPO‐catalyzed decarboxylation reactions for the
synthesis of 1,2‐unsubstituted indolizines
Yuxuan Zhang1 | Wenhui Wang1 | Jinwei Sun1,2 | Yun Liu1,2
1 School of Chemistry and Material
Abstract
Science, Jiangsu Normal University,
An efficient synthesis of 1,2‐unsubstituted indolizines was developed via
Xuzhou, China
2 Jiangsu Collaborative Innovation Center
of Atmospheric Environment and
2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO)–catalyzed decarboxylation reac-
tion. A series of target products were successfully prepared with the tolerance
of a variety of functional groups. This protocol features advantages such as eas-
ily available substrates, broad substituent scope, and eco‐friendly conditions.
Equipment Technology, Jiangsu Key
Laboratory of Atmospheric Environment
Monitoring and Pollution Control,
Nanjing University of Information Science
& Technology, Nanjing, China
Correspondence
Jinwei Sun and Yun Liu, Jiangsu
Collaborative Innovation Center of
Atmospheric Environment and
Equipment Technology, Jiangsu Key
Laboratory of Atmospheric Environment
Monitoring and Pollution Control,
Nanjing University of Information Science
& Technology, Nanjing 210044, Jiangsu,
China.
Email: gysunjinwei@126.com;
liu__yun3@sina.com
Funding information
Natural Science Foundation of Jiangsu
Province, Grant/Award Number:
BK20170939; Natural Science Research of
Jiangsu Higher Education Institutions of
China, Grant/Award Number:
17KJB150016
1 | INTRODUCTION
picolinaldehyde with alkynes (Scheme 1a) [14]; Cu(I)‐
catalyzed transannulation reaction of pyridotriazoles with
Indolizines are basic structural motifs in many biologi-
terminal alkynes (Scheme 1b) [15]; cyclization of 2‐
vinylpyridine with chlorocarbenes (Scheme 1c) [16]; and
Cr(VI)‐promoted oxidative decarboxylation reaction of
[1–3]
cally active molecules
and have exhibited significant
biological activities [4–8] and fluorescence properties .[9–11]
Consequently, there are great demands for the synthesis
of indolizines with different substitution patterns .[12,13]
As a class of important indolizine derivatives, 1,2‐
pyridines,
bromides
and
maleic
anhydride
(Scheme 1d) .[17] Among these synthetic routes, oxidative
decarboxylation reaction is very attractive because of its
easily available substrates and high yields. However, this
reaction generally proceeds with excess amount of metal
oxidant, which leads to environmental pollution. Besides,
1,2‐unsubstituted indolizines are likely to undergo C–H
unsubstituted indolizines also drew much effort for their
[14–17]
syntheses.
The existing synthetic protocols to these
mainly include Co(II)‐catalyzed
transannulation reaction of
compounds
denitrogenative
J Heterocyclic Chem. 2019;1–8.
wileyonlinelibrary.com/journal/jhet
© 2019 Wiley Periodicals, Inc.
1

2
ZHANG ET AL.
SCHEME 1 Synthesis of indolizines
TABLE 1 Optimization of reaction conditionsa,b
functionalization under transition metal–catalyzed
[18]
conditions (Scheme 1e).
Hence, we wish to find new
reaction conditions to assemble 1,2‐unsubstituted
indolizines via oxidative decarboxylation reaction, espe-
cially under metal‐free conditions.
In the past decade, 2,2,6,6‐tetramethylpiperidine‐1‐
Entry
Solvent
Oxidant, equiv
T, °C
Yield, %a
oxyl (TEMPO) has been developed to be an efficient oxi-
[19–23]
1
DMF
TEMPO (0.5)
TEMPO (0.5)
TEMPO (0.5)
TEMPO (0.5)
TEMPO (0.5)
TEMPO (0.5)
TBHP (0.5)
90
76
53
32
30
82
27
36
28
23
21
82
63
dant in many organic reactions.
Recently, we also
2
Dioxane
Benzene
Toluene
CH3CN
THF
90
reported a TEMPO‐promoted reaction of pyridines,
methyl ketones, and alkenoic esters to prepare multi‐
3
Reflux
90
[24]
substituted indolizines.
However, to the best of our
4
knowledge, TEMPO has rarely been applied to oxidative
5
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
[25]
decarboxylation reaction.
Herein, we described a
6
TEMPO‐catalyzed three‐component reaction for the syn-
thesis of 1,2‐unsubstituted indolizines (Scheme 1f).
7
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
8
DTBP (0.5)
9
K2S2O8 (0.5)
PhI(OAc)2 (0.5)
TEMPO (0.2)
TEMPO (0.1)
2 | RESULTS AND DISCUSSION
10
11
12
To begin our work, we employed methyl isonicotinate 1a,
bromoketone 2a, and maleic anhydride 3 as the model
reactants. Solvent effect was first investigated by heating
1a (1.5 mmol), 2a (0.5 mmol), 3 (0.5 mmol), and TEMPO
(0.25 mmol) with different solvents. It is found that aceto-
nitrile provided the highest yields (Table 1, entries 1‐6).
With acetonitrile as the solvent, we then screened differ-
ent oxidants including TBHP, DTBP, K2S2O8, and
PhI(OAc)2 but found no oxidant that performs better
than TEMPO (Table 1, entries 7‐10). Further research
Note. Conditions: 1a (1.5 mmol), 2a (0.5 mmol), 3a (0.5 mmol), and oxidant,
heating in solvent for 6 h.
Abbreviations: DMF, dimethylformamide; THF, tetrahydrofuran.
aIsolated yields.
showed the loading of TEMPO could be reduced to
0.2 equiv in the air (Table 1, entry 11‐12). Therefore, the

ZHANG ET AL.
3
optimal conditions were refluxing the mixture of 1a
(1.5 mmol), 2a (0.5 mmol), 3 (0.5 mmol), and TEMPO
(0.1 mmol) in acetonitrile in a round bottle for 6 hours.
With the optimal condition in hand, we then turned
our attention to expand the reactant scope (Table 2). Ini-
tially, we focused on the kind of bromides and used dif-
ferent bromides 2 to react with isonicotinate (1a or 1b)
and maleic anhydride 3. It showed that bromoketone
(2b, 2c, 2f), bromonitrile (2i), and bromoester (2 h) all
performed well, giving 1,2‐unsubstituted indolizines
4a‐4h in 72% to 85% yields. Then we investigated the
scope of pyridine derivatives 1. By employing 4‐
cyanopyridines 1c and 4‐acylpyridine 1d as the starting
materials, we obtained products 4i‐4j in good yields.
TABLE 2 Synthesis of indolizines 4a,b
Note. Conditions: 1 (1.5 mmol), 2 (0.5 mmol), 3 (0.5 mmol), and TEMPO (0.1 mmol), refluxing in acetonitrile (10 mL) for 6 h.
aIsolated yields.

4
ZHANG ET AL.
SCHEME 2 Plausible reaction
mechanism
When pyridine 1e without substituent was used in this
reaction, we isolated product 4k and 4l in moderate
yields. Furthermore, high regioselectivity was observed
when methyl nicotinate 1f was used as substrate, and
products 4m‐4n were formed in 73% and 75% yields,
respectively. Besides, annulated pyridines 1g and 1h
afforded the target products 4o‐4t in 82% to 88% yields
under the optimal condition. All the products were char-
acterized by NMR and high‐resolution mass spectrometry
(HRMS), and the data of the known compounds were in
uses only catalytic amount of TEMPO with molecular
oxygen as the terminal oxidant. Various functional
groups could be well tolerated under this mild reaction
condition. This work represents a valuable example of
TEMPO‐catalyzed decarboxylation reaction.
4 | EXPERIMENTAL
4.1 | General
[17]
accordance with our previous report.
1
On the basis of these experimental results, a plausible
mechanism was suggested, as shown as Scheme 2. Ini-
tially, the reaction of 1a and 2a formed intermediate I,
which underwent cycloaddition with maleic anhydride
3, leading to intermediate II. Subsequently, II was con-
verted to III via a hydrolysis, TEMPO oxidation [26], and
decarboxylation cascade. Finally, the desired product 4a
was given from intermediate III by aromatization. In
the reaction process, TEMPO was regenerated from
TEMPOH by the oxidation of molecular oxygen in the
air [24,27–30], and TEMPO could be used in catalytic
amount.
Melting points are uncorrected. H NMR spectra were
measured at 400 MHz with CDCl3 as solvent. The chem-
ical shifts (δ) are reported in parts per million relative to
the residual deuterated solvent signal, and coupling con-
stants (J) are given in hertz. 13C NMR spectra were mea-
sured at 100 MHz with CDCl3 as solvent.
4.2 | General procedure for the
preparation of 4
The mixture of pyridines 1 (1.5 mmol), acyl bromides 2
(0.5 mmol), maleic anhydride 3 (0.5 mmol), and TEMPO
(0.1 mmol) was refluxed in acetonitrile (10 ml) for 6 hours
in a round bottle. After the reaction was completed, the
solvent was removed under reduced pressure, and the
residue was separated by flash chromatography on a sil-
ica gel column with ethyl acetate/petroleum as eluent to
give the products 4.
3 | CONCLUSIONS
In conclusion, an efficient synthetic protocol was devel-
oped to assemble 1,2‐unsubstituted indolizines under
metal‐free conditions. This TEMPO‐mediated reaction

ZHANG ET AL.
5
4.2.1 | Methyl
3‐benzoylindolizine‐7‐carboxylate (4a)
4.2.5 | Ethyl
3‐benzoylindolizine‐7‐carboxylate (4e)
Yield: 82%. Yellow solid, mp 132‐134°C. 1H NMR
(400 MHz, CDCl3): δ 3.97 (s, 3H), 6.76 (d, J = 4.4 Hz,
1H), 7.40 (d, J = 4.4 Hz, 1H), 7.45‐7.57 (m, 4H), 7.81
(dd, J = 8.4, 1.6 Hz, 2H), 8.32 (d, J = 0.8 Hz, 1H), 9.89
(d, J = 7.2 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ
185.4, 165.7, 140.3, 137.8, 131.4, 129.1, 128.3, 127.9,
126.9, 124.9, 124.1, 121.6, 112.5, 106.0, 52.5. HRMS
(electrospray ionization [ESI]) m/z calcd for C17H14NO3
[M + H]+ 280.0974, found 280.0975.
Yield: 80%. Yellow solid, mp 128‐130°C. 1H NMR
(400 MHz, CDCl3): δ 1.44 (t, J = 7.2 Hz, 3H), 4.43 (q,
J = 7.2 Hz, 2H), 6.76 (d, J = 4.8 Hz, 1H), 7.41 (d,
J = 4.8 Hz, 1H), 7.47‐7.57 (m, 4H), 7.82 (d, J = 7.2 Hz,
2H), 8.33 (s, 1H), 9.89 (d, J = 7.2 Hz, 1H). 13C NMR
(100 MHz, CDCl3): δ 185.7, 165.5, 140.6, 138.2, 131.7,
129.4, 128.7, 128.3, 127.3, 125.6, 124.4, 121.9, 112.9,
106.2, 61.9, 14.8. HRMS (ESI) m/z calcd for C18H16NO3
[M + H]+ 294.1130, found 294.1128.
4.2.6 | Ethyl 3‐(4‐bromobenzoyl)
indolizine‐7‐carboxylate (4f)
4.2.2 | Methyl 3‐(4‐methoxybenzoyl)
indolizine‐7‐carboxylate (4b)
Yield: 85%. Yellow solid, mp 154‐155°C. 1H NMR
(400 MHz, CDCl3): δ 1.44 (t, J = 7.2 Hz, 3H), 4.43 (q,
J = 7.2 Hz, 2H), 6.77 (d, J = 4.8 Hz, 1H), 7.36 (d,
J = 4.8 Hz, 1H), 7.48 (dd, J = 7.2, 1.6 Hz, 1H), 7.63‐7.71
(m, 4H), 8.32 (s, 1H), 9.86 (d, J = 7.6 Hz, 1H). 13C NMR
(100 MHz, CDCl3): δ 183.9, 165.1, 139.0, 138.2, 131.6,
130.6, 127.9, 126.7, 126.1, 125.6, 123.7, 121.5, 112.8,
106.1, 100.0, 61.6, 14.4. HRMS (ESI) m/z [M + H]+ calcd
for C18H15BrNO3 [M + H]+ 372.0235, found 372.0241.
Yield: 78%. Yellow solid, mp 148‐150°C. 1H NMR
(400 MHz, CDCl3): δ 3.90 (s, 3H), 3.97 (s, 3H), 6.76 (d,
J = 4.4 Hz, 1H), 7.00 (d, J = 8.8 Hz, 2H), 7.40‐7.43 (m,
2H), 7.82‐7.85 (m, 2H), 8.30 (s, 1H), 9.81 (d, J = 7.6 Hz,
1H). 13C NMR (100 MHz, CDCl3): δ 184.3, 165.7, 162.4,
137.4, 132.6, 131.2, 127.7, 126.2, 124.4, 121.6, 113.6,
112.2, 105.6, 55.4, 52.4. HRMS (ESI) m/z calcd for
C18H16NO4 [M + H]+ 310.1079, found 310.1085.
4.2.7 | Ethyl 3‐(4‐methoxybenzoyl)
indolizine‐7‐carboxylate (4g)
4.2.3 | Methyl 3‐(2‐naphthoyl)indolizine‐7‐
carboxylate (4c)
Yield: 80%. Yellow solid, mp 112‐114°C. 1H NMR
(400 MHz, CDCl3): δ 1.44 (t, J = 7.2 Hz, 3H), 3.90 (s,
3H), 4.42 (q, J = 7.2 Hz, 2H), 6.75 (d, J = 4.8 Hz, 1H),
7.00 (d, J = 8.8 Hz, 2H), 7.40‐7.44 (m, 2H), 7.84 (d,
J = 8.8 Hz, 2H), 8.31 (s, 1H), 9.81 (d, J = 7.6 Hz, 1H).
13C NMR (100 MHz, CDCl3): δ 184.3, 165.2, 162.4,
137.5, 132.7, 131.3, 127.7, 126.3, 124.8, 124.1, 121.5,
113.6, 112.2, 105.6, 61.4, 55.5, 14.3. HRMS (ESI) m/z
[M + H]+ calcd for C19H18NO4 [M + H]+ 324.1236, found
324.1241.
Yield: 83%. Yellow solid, mp 160‐162°C. 1H NMR
(400 MHz, CDCl3): δ 3.98 (s, 3H), 6.79 (d, J = 4.4 Hz,
1H), 7.46‐7.49 (m, 2H), 7.56‐7.60 (m, 2H), 7.91‐7.97 (m,
4H), 8.32 (d, J = 9.2 Hz, 2H), 9.92 (d, J = 7.2 Hz, 1H).
13C NMR (100 MHz, CDCl3): δ 185.2, 165.6, 137.8,
137.4, 134.7, 132.4, 129.9, 129.1, 128.2, 127.9, 127.8,
127.7, 127.0, 126.7, 125.6, 124.8, 124.2, 121.6, 112.5,
106.0, 52.5. HRMS (ESI) m/z calcd for C21H16NO3
[M + H]+ 330.1130, found 330.1132.
4.2.8 | Diethyl indolizine‐3,7‐dicarboxylate
(4h)
4.2.4 | Methyl
3‐cyanoindolizine‐7‐carboxylate (4d)
Yield: 78%. White solid, mp 63‐65°C. 1H NMR (400 MHz,
CDCl3): δ 1.39‐1.44 (m, 6H), 4.37‐4.43 (m, 4H), 6.71 (d,
J = 4.4 Hz, 1H), 7.34 (dd, J = 7.6, 2.0 Hz, 1H), 7.55 (d,
J = 4.8 Hz, 1H), 8.26 (s, 1H), 9.39 (d, J = 7.6 Hz, 1H).
13C NMR (100 MHz, CDCl3): δ 165.4, 161.2, 136.5,
126.5, 122.9, 122.2, 121.9, 116.3, 111.5, 105.1, 61.3, 60.2,
14.5, 14.3. HRMS (ESI) m/z calcd for C14H16NO4
[M + H]+ 262.1079, found 262.1078.
Yield: 72%. White solid, mp 153‐155°C. 1H NMR
(400 MHz, CDCl3): δ 3.96 (s, 3H), 6.74 (d, J = 4.4 Hz,
1H), 7.37 (d, J = 4.8 Hz, 1H), 7.39 (dd, J = 7.2, 1.6 Hz,
1H), 8.26‐8.28 (m, 2H). 13C NMR (100 MHz, CDCl3): δ
165.4, 135.0, 124.7, 123.4, 123.3, 122.7, 112.2, 105.4, 52.6.
HRMS (ESI) m/z calcd for C11H9N2O2 [M + H]+
201.0664, found 201.0678.

6
ZHANG ET AL.
4.2.9 | Methyl
7‐cyanoindolizine‐3‐carboxylate (4i)
4.2.13 | Methyl
3‐benzoylindolizine‐6‐carboxylate (4m)
Yield: 75%. White solid, mp 135‐137°C. 1H NMR
(400 MHz, CDCl3): δ 3.94 (s, 3H), 6.75 (d, J = 4.8 Hz,
1H), 6.88 (dd, J = 7.2, 1.6 Hz, 1H), 7.59 (d, J = 4.4 Hz,
1H), 7.90 (d, J = 1.2 Hz, 1H), 9.45 (d, J = 7.2 Hz, 1H).
13C NMR (100 MHz, CDCl3): δ 161.3, 135.3, 127.5,
125.4, 122.8, 118.1, 112.2, 105.4, 104.0, 51.6. HRMS (ESI)
m/z [M + H]+ calcd for. C11H9N2O2 [M + H]+
201.0664, found 201.0668.
Yield: 73%. Yellow solid, mp 118‐120°C. 1H NMR
(400 MHz, CDCl3): δ 3.97 (s, 3H), 6.59 (d, J = 4.4 Hz,
1H), 7.45‐7.52 (m, 3H), 7.55‐7.59 (m, 2H), 7.72 (d,
J = 9.2 Hz, 1H), 7.81‐7.83 (m, 2H), 10.62 (s, 1H). 13C
NMR (100 MHz, CDCl3): δ 184.8, 165.8, 140.1, 139.6,
132.7, 131.3, 129.0, 128.7, 128.3, 123.5, 123.4, 118.1,
117.5, 112.5, 104.3, 103.2, 52.4. HRMS (ESI) m/z calcd
for C17H14NO3 [M + H]+ 280.0974, found 280.0980.
4.2.10 | Indolizine‐3,7‐
diylbis(phenylmethanone) (4j)
4.2.14 | Methyl 3‐(4‐chlorobenzoyl)
indolizine‐6‐carboxylate (4n)
Yield: 81%. Yellow solid, mp 143‐145°C. 1H NMR
(400 MHz, CDCl3): δ 6.77 (d, J = 4.8 Hz, 1H), 7.42 (dd,
J = 7.2, 2.0 Hz, 2H), 7.49‐7.64 (m, 6H), 7.82‐7.85 (m,
4H), 8.02 (s, 1H), 9.94 (d, J = 7.6 Hz, 1H). 13C NMR
(100 MHz, CDCl3): δ 194.3, 185.4, 140.1, 137.4, 137.1,
132.6, 131.7, 131.4, 129.8, 129.0, 128.5, 128.3, 128.1,
127.0, 124.1, 122.6, 113.1, 106.4. HRMS (ESI) m/z
[M + H]+ calcd for C22H16NO2 [M + H]+ 326.1181, found
326.1193.
Yield: 75%. Yellow solid, mp 162‐164°C. 1H NMR
(400 MHz, CDCl3): δ 3.97 (s, 3H), 6.60 (d, J = 4.4 Hz,
1H), 7.42 (d, J = 4.8 Hz, 1H), 7.48 (d, J = 8.8 Hz, 2H),
7.59 (dd, J = 9.2, 0.4 Hz, 1H), 7.72‐7.78 (m, 3H), 10.58
(s, 1H). 13C NMR (100 MHz, CDCl3): δ 183.3, 165.7,
139.8, 138.5, 137.5, 132.6, 130.4, 130.3, 128.6, 128.5,
123.7, 118.1, 117.7, 103.4, 52.4. HRMS (ESI) m/z calcd
for C17H13ClNO3 [M + H]+ 314.0584, found 314.0597.
4.2.15 | Phenyl (pyrrolo[2,1‐a]isoquinolin‐
3‐yl)methanone (4o)
4.2.11 | (4‐Chlorophenyl)(indolizin‐3‐yl)
methanone (4k)
Yield: 86%. Yellow solid, mp 140‐141°C (lit.17 140‐142°C).
1H NMR (400 MHz, CDCl3): δ 7.05 (d, J = 4.4 Hz, 1H),
7.12 (d, J = 7.6 Hz, 1H), 7.31 (d, J = 4.4 Hz, 1H), 7.48‐
7.58 (m, 5H), 7.73 (dd, J = 7.2, 1.6 Hz, 1H), 7.84‐7.86
(m, 2H), 8.16‐8.19 (m, 1H), 9.61 (d, J = 7.6 Hz, 1H). 13C
NMR (100 MHz, CDCl3): δ 185.4, 140.6, 136.9, 131.1,
129.1, 128.9, 128.2, 128.0, 127.7, 126.9, 126.0, 125.8,
124.6, 123.6, 113.4, 101.9.
Yield: 62%. Yellow solid, mp 121‐122°C (lit.17 123‐125°C).
1H NMR (400 MHz, CDCl3): δ 6.54 (d, J = 4.8 Hz, 1H),
6.97 (td, J = 7.2, 0.8 Hz, 1H), 7.21 (td, J = 7.6, 1.2 Hz,
1H), 7.30 (d, J = 4.4 Hz, 1H), 7.46 (d, J = 8.4 Hz, 2H),
7.57 (d, J = 8.8 Hz, 1H), 7.75 (d, J = 8.4 Hz, 2H), 9.94
(d, J = 7.2 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ
182.9, 139.7, 139.1, 137.0, 130.3, 128.8, 128.4, 126.6,
124.6, 122.3, 118.7, 114.0, 102.8.
4.2.12 | (3,4‐Dichlorophenyl)(indolizin‐3‐
yl)methanone (4l)
4.2.16 | (4‐Methoxyphenyl)(pyrrolo[2,1‐a]
isoquinolin‐3‐yl)methanone (4p)
Yield: 65%. Yellow solid, mp 157‐159°C. 1H NMR
(400 MHz, CDCl3): δ 6.56 (d, J = 4.4 Hz, 1H), 6.98 (td,
J = 7.2, 1.2 Hz, 1H), 7.23 (dd, J = 8.4, 0.8 Hz, 1H), 7.31
(d, J = 4.8 Hz, 1H), 7.55‐7.65 (m, 3H), 7.89 (d,
J = 2.0 Hz, 1H), 9.93 (d, J = 7.2 Hz, 1H). 13C NMR
(100 MHz, CDCl3): δ 181.2, 140.6, 135.1, 132.7, 130.9,
130.3, 128.9, 128.1, 126.7, 125.1, 118.8, 114.3, 103.3.
HRMS (ESI) m/z calcd for C15H10Cl2NO [M + H]+
290.0139, found 290.0139.
Yield: 82%. Yellow solid, mp 185‐186°C (lit.17 187‐189°C).
1H NMR (400 MHz, CDCl3): δ 3.89 (s, 3H), 6.99 (d,
J = 8.8 Hz, 2H), 7.04 (d, J = 4.4 Hz, 1H), 7.08 (d,
J = 7.6 Hz, 1H), 7.31 (d, J = 4.4 Hz, 1H), 7.53‐7.56 (m,
2H), 7.70 (dd, J = 8.4, 1.6 Hz, 1H), 7.86 (d, J = 8.4 Hz,
2H), 8.16 (d, J = 7.2 Hz, 1H), 9.53 (d, J = 7.6 Hz, 1H).
13C NMR (100 MHz, CDCl3): δ 184.4, 162.2, 136.6,
133.1, 131.3, 128.8, 127.8, 127.6, 126.9, 125.8, 125.2,
124.8, 123.5, 113.5, 113.1, 101.6, 55.4.

ZHANG ET AL.
7
China (17KJB150016) and the Natural Science Founda-
tion of Jiangsu Province (BK20170939).
4.2.17 | Methyl pyrrolo[2,1‐a]isoquinoline‐
3‐carboxylate (4q)
Yield: 85%. White solid, mp 110‐112°C. 1H NMR
(400 MHz, CDCl3): δ 3.92 (s, 3H), 6.99‐7.02 (m, 2H),
7.48‐7.54 (m, 3H), 7.66 (dd, J = 7.6, 1.2 Hz, 1H), 8.11
(dd, J = 8.0, 0.8 Hz, 1H), 9.21 (d, J = 7.6 Hz, 1H). 13C
NMR (100 MHz, CDCl3): δ 161.8, 135.4, 127.8, 127.6,
127.3, 126.8, 125.1, 124.9, 123.1, 120.6, 116.2, 112.7,
101.1, 51.2. HRMS (ESI) m/z [M + H]+ calcd for
C14H12NO2 226.0868, found 226.0877.
ORCID
Yun Liu https://orcid.org/0000-0001-5783-4848
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carboxylate (4r)
1
Yield: 83%. White solid, mp 94‐96°C (lit.17 95‐97°C). H
[6] A. Hazra, S. Mondal, A. Maity, S. Naskar, P. Saha, R. Paira, K.
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NMR (400 MHz, CDCl3): δ 1.42 (t, J = 7.2 Hz, 3H), 4.39
(q, J = 7.2 Hz, 2H), 6.99‐7.01 (m, 2H), 7.48‐7.53 (m,
3H), 7.66 (d, J = 7.6 Hz, 1H), 8.11 (d, J = 8.0 Hz, 1H),
9.22 (d, J = 7.2 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ
161.5, 135.4, 127.8, 127.6, 127.3, 126.8, 125.1, 124.9,
123.1, 120.5, 116.6, 112.6, 101.0, 60.0, 14.6.
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4.2.19 | Phenyl (pyrrolo[1,2‐a]quinolin‐1‐
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1
Yield: 88%. Yellow solid, mp 93‐95°C (lit.17 93‐95°C). H
NMR (400 MHz, CDCl3): δ 6.54 (d, J = 4.4 Hz, 1H), 7.20
(d, J = 4.4 Hz, 1H), 7.39‐7.43 (m, 3H), 7.49‐7.54 (m,
3H), 7.61 (t, J = 7.6 Hz, 1H), 7.72 (dd, J = 8.0, 1.2 Hz,
1H), 8.06 (dd, J = 8.0, 1.2 Hz, 2H), 8.17 (d, J = 8.4 Hz,
1H). 13C NMR (100 MHz, CDCl3): δ 184.3, 139.5, 139.4,
133.7, 132.2, 130.1, 128.9, 128.6, 128.5, 128.2, 128.0,
125.7, 125.0, 124.7, 120.1, 117.9, 104.1.
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4.2.20 | (4‐Chlorophenyl)(pyrrolo[1,2‐a]
quinolin‐1‐yl)methanone (4t)
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Yield: 85%. Yellow solid, mp 108‐110°C (lit.17 110‐112°C).
1H NMR (400 MHz, CDCl3): δ 6.54 (d, J = 4.4 Hz, 1H),
7.18 (d, J = 4.4 Hz, 1H), 7.41‐7.43 (m, 3H), 7.48‐7.53 (m,
3H), 7.72 (dd, J = 8.0, 1.6 Hz, 1H), 8.00 (dd, J = 6.8,
2.0 Hz, 2H), 8.14 (d, J = 8.4 Hz, 1H). 13C NMR
(100 MHz, CDCl3): δ 182.8, 139.7, 138.5, 137.9, 133.7,
131.4, 128.9, 128.7, 128.5, 128.1, 128.0, 126.0, 125.0,
124.8, 120.0, 117.8, 104.3.
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ACKNOWLEDGMENTS
This work was supported by the Natural Science
Research of Jiangsu Higher Education Institutions of
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8
ZHANG ET AL.
[26] The oxidation of the carboxylate anion by TEMPO is thermody-
namically feasible, considering that the oxidation potentials of
carboxylate anion are in the range of 1~1.3 V (SCE) [See, for
exampleL. Capaldo, L. Buzzetti, D. Merli, M. Fagnoni, D.
Ravelli, J. Org. Chem. 2016, 81, 7102. while the reduction
potential of TEMPO is 1.48 V (SCE) [Mancheño, O. G., Stopka,
T. Synthesis 2013, 45, 1602–1611.]
How to cite this article: Zhang Y, Wang W, Sun
J, Liu Y. TEMPO‐catalyzed decarboxylation
reactions for the synthesis of 1,2‐unsubstituted
indolizines. J Heterocyclic Chem. 2019;1–8. https://
doi.org/10.1002/jhet.3766
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Lett. 2019, 21, 3332.
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SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of the
article.