Iodine-promoted synthesis of 1-alkyl-3-aroylindolizines from N-(Aroylmethyl)pyridinium salts and aliphatic aldehydes

Article abstract of DOI:10.1002/hc.21137

An effective and practical method has been developed for the diversity-oriented synthesis of 1-alkyl-3-aroylindolizines via the 1,3-dipolar cycloaddition of pyridinium ylides and aliphatic aldehydes in the presence of molecular iodine and a catalytic amount of MnO₂. The synthesis proceeds by tandem reactions involving [3+2] cycloaddition, dehydration of the cycloadduct, and dehydroaromatization. Molecular iodine served both as a catalyst and a dehydroaromatization reagent in the reaction.

Full text of DOI:10.1002/hc.21137

Heteroatom Chemistry
Volume 25, Number 1, 2014
Iodine-Promoted Synthesis of 1-Alkyl-3-
aroylindolizines from N-(Aroylmethyl)
pyridinium Salts and Aliphatic Aldehydes
Chen Tan,1 Peiyun Yan,1 Weijian Ye,1 Juan Yao,1 Weiming Wu,2
and Cunde Wang1
1School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou 225002, Peiple’s
Republic of China
2Department of Chemistry and Biochemistry, San Francisco State University, San Francisco, CA
94132, USA
Received 8 September 2013; revised 14 November 2013
[1]. Indolizine derivatives have been a rich source
ABSTRACT: An effective and practical method has
of molecules with potential pharmaceutical applica-
been developed for the diversity-oriented synthesis of
tions [2]. Furthermore, substituted indolizines can
1-alkyl-3-aroylindolizines via the 1,3-dipolar cycload-
also serve as versatile building blocks for the synthe-
dition of pyridinium ylides and aliphatic aldehydes
sis of novel classes of dyes, biological markers, and
in the presence of molecular iodine and a catalytic
electroluminescent [3, 4]. Therefore, the develop-
amount of MnO2. The synthesis proceeds by tandem
ment of efficient and convergent methods for rapid
reactions involving [3+2] cycloaddition, dehydration
construction of indolizines has stimulated consider-
of the cycloadduct, and dehydroaromatization. Molec-
able interest.
ular iodine served both as a catalyst and a dehy-
Many substituted indolizines have been syn-
ꢀC
droaromatization reagent in the reaction.
2013
thesized by various methods such as the Scholtz
reaction, the Tschitschibabin reaction, 1,3-dipolar
cycloadditions of pyridinium methylides with
electron-deficient alkynes or alkenes, 1,5-dipolar cy-
clizations, and metal-catalyzed intramolecular cy-
cloisomerizations of pyridines with specific C-2
functionalization [5–7]. The recently developed syn-
thesis of indolizines using 1,3-dipolar cycloaddi-
tions of pyridinium ylide is especially noteworthy
due to its simplicity, efficiency, and convenience
[5i,8]. However, the 1,3-dipolar cycloadditions re-
quire the olefinic or acetylenic dipolarophiles to have
one or two electron-withdrawing substituents, thus
limiting its applicability. We report here the con-
venient synthesis of 1-alkyl-3-aroylindolizine ana-
logues from the 1,3-dipolar cycloaddition of pyri-
dinium ylide with aliphatic aldehydes.
Wiley Periodicals, Inc. Heteroatom Chem. 25:72–
81, 2014; View this article online at wileyonlineli-
brary.com. DOI 10.1002/hc.21137
INTRODUCTION
The indolizine ring is a key structural unit for numer-
ous natural products, synthetic pharmaceuticals,
and a wide variety of biologically active compounds
Correspondence to: Cunde Wang; e-mail: wangcd@yzu.edu.cn.
Contract grant sponsor: National Natural Science Foundation
of China
Contract grant number: NNSFC 21173181.
Contract grant sponsor: Priority Academic Program Develop-
ment of Jiangsu Higher Education Institutions.
Supporting Information is available in the online issue at
www.wileyonlinelibrary.com.
More recently, molecular iodine has been used
as a mild and efficient promoter for various
ꢀC
2013 Wiley Periodicals, Inc.
72

Iodine-Promoted Synthesis of 1-Alkyl-3-aroylindolizines from N-(Aroylmethyl)pyridinium Salts and Aliphatic Aldehydes 73
organic transformations [9] through its usage from
the stoichiometric level to a catalytic amount to af-
ford the corresponding products in excellent yields
with high selectivity. It has also been reported as a
mild, cheap, and easily available oxidizing reagent
for the fundamental organic reactions, and, more-
over, owing to numerous advantages associated with
this ecofriendly element and its solid form and is less
toxic than molecular bromine or chlorine, iodine has
been explored as a powerful catalyst for various or-
ganic transformations. We report here a convenient
synthesis of 1-alkyl-3-aroylindolizine analogues by
the more general 1,3-dipolar cycloaddition reactions
of pyridinium ylide by using aliphatic aldehydes as
the olefinic substrate. This strategy has overcome the
inherent shortcomings of the 1,3-dipolar cycloaddi-
tions using conventional alkynes and alkenes in ac-
cessing the 1-alkyl indolizines by taking advantage of
the novel dehydrogenation reaction of the primary
cycloadducts under the action of the mild oxidant
molecular iodine in the presence of catalyst man-
ganese dioxide.
sented in Table 1. When the reaction was carried out
using pyridine as both a base and a solvent with-
out any catalyst or promoter at 80◦C for 40 h, the
product was obtained but the yield was very low (en-
try 1). Considering that molecular iodine as a mild
Lewis acid can promote the keto–enol tautomerism
of aldyhydes and ketones [10], a catalytic amount of
molecular iodine (0.1 equiv) was introduced into the
reaction mixture. As a result, the yield was improved
to 32% (entry 2).
Although dehydroaromatization of many hetero-
cycles containing nitrogen can occur spontaneously
in air, mild oxidants such as (Tetrakis-pyridino-
cobalt (II) dichromate, Py4Co(HCrO4)2), MnO2, and
I2 are used to facilitate the reaction. Therefore, the
test reaction was carried out using 1 equiv of io-
dine as both a catalyst for the keto–enol tautomerism
and a reagent for the aromatization of B to 3. The
yield was thus improved to a reasonable 49%, which
was further increased to 52% upon addition of cat-
alytic amount of MnO2 (entries 3 and 4). In an effort
to optimizing the reaction conditions, the reactions
were tested in different temperature, time, base, and
solvent, and the results are summarized in Table 1
(entries 5–10). The optimal reaction conditions were
found to be 120◦C and 40 h in pyridine with 1 equiv
of iodine and 0.05 equiv of MnO2, which gave a yield
of 59%.
The side reaction in the present reaction is
α-iodonation of aliphatic aldehydes in basic condi-
tions. However, HI also partly reduces it to alde-
hyde together with molecular iodine. Some of α-
iodoaldehyde may react further under the present
conditions. Therefore, excess aldehyde was required.
Yields for 1-alkyl-3-aroylindolizines were found
to be good when the reactions were run with
various pyridinium salts and aliphatic aldehyde
(Table 2). It was found that C4–C12 aliphatic
aldehydes reacted equally well and different
subsituted aryl groups (both electron donating and
electron withdrawing) had no significant effect.
Therefore, the reaction described proves to be a
general and convenient method for the synthesis of
the previously unknown 1-alkyl-3-aroylindolizines.
The structure of (4-bromophenyl)(1-octylindolizin-
3-yl)methanone (3h) was determined by X-ray crys-
tallographic analysis (Fig. 1). Crystallographic data
for 3h have been deposited with the Cambridge Crys-
tallographic Data Centre with the deposition num-
ber CCDC 933729. These data can be obtained free
of charge on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK [fax (+44) 1223 336033,
e-mail: deposit@ccdc.cam.ac.uk].
RESULTS AND DISCUSSION
A fraction of aldehyde molecules exist in the enol
form, and the enol–aldehyde interconversion is cat-
alyzed by acid or base. We thought to explore the
reaction of the enol with pyridinium ylides (struc-
ture 1 in Scheme 1) in the synthesis of indolizine.
The 1,3-dipolar cycloaddition of the ylide and enol
(structure 2 in Scheme 1) will give the initial adduct
A. Base-catalyzed elimination of water from adduct
A will yield dihydroindolizine B, which is expected
to undergo spontaneous aromatization to form in-
dolizine 3.
The reaction was then tested with 1-phenacyl
pyridinium with butanal, and the results are pre-
The title reaction is proposed to proceed by a
mechanism as shown in Scheme 2.
SCHEME 1
Heteroatom Chemistry DOI 10.1002/hc

74 Tan et al.
TABLE 1 Optimization of Bases, Solvents, and Temperature in the Synthesis of 3j
Entry
Selected Conditions
Yield (%)
1
2
3
4
5
6
7
8
9
Pyridine/80◦C/40 h
19
32
49
52
59
52
50
54
52
59
I2 (0.1 equiv)/pyridine/80◦C/40 h
I2 (1 equiv)/pyridine/80◦C/40 h
I2 (1 equiv)/MnO2(0.05 equiv)/pyridine/80◦C/40 h
I2 (1 equiv)/MnO2(0.05 equiv)/pyridine/120◦C/40 h
I2 (1 equiv)/MnO2(0.05 equiv)/K2CO2(1 equiv)/toluene/120◦C/40 h
I2 (1 equiv)/MnO2(0.05 equiv)/DBU(1 equiv)/toluene/120◦C/40 h
I2 (1 equiv)/MnO2(0.05 equiv)/piperidine(1 equiv)/toluene/120◦C/40 h
I2 (1 equiv)/MnO2(0.05 equiv)/pyridine(1 equiv)/toluene/120◦C/40 h
I2 (1 equiv)/MnO2(0.05 equiv)/pyridine/120◦C/45 h
10
FIGURE 1 Molecular structure of indolizine 3h.
First, molecular iodine is capable of binding with
the carbonyl oxygen increasing the reactivities of
parent carbonyl as it behaves as a mild Lewis acid
[10], the keto–enol tautomerism of aliphatic alde-
hyde gave an intermediate enol in the presence of
molecular iodine. Next, the N-ylide generated by de-
protonation of the pyridinium salt with pyridine as
a base took part in a 1,3-dipolar cycloaddition with
enol to give the primary product C. Dehydration of C
in the solvent formed the dihydroindolizine D. Fur-
ther dehydroaromatization of D oxidized by molec-
ular iodine led to the 1-alkyl-3-aroylindolizine 3j.
CONCLUSIONS
In summary, 1-alkyl-3-aroylindolizines have been
synthesized by the reaction of the pyridinium ylide
with aliphatic aldehydes in the presence of molec-
ular iodine and a catalytic amount of MnO2. The
reaction proceeds via tandem reactions involving
Heteroatom Chemistry DOI 10.1002/hc

Iodine-Promoted Synthesis of 1-Alkyl-3-aroylindolizines from N-(Aroylmethyl)pyridinium Salts and Aliphatic Aldehydes 75
TABLE 2 Preparation of the 1-Alkyl-3-aroylindolizines
Entry
X
R
Product
Yield (%)
1
2
3
4
5
6
7
8
p-Br
p-Br
p-Br
p-Br
p-Br
p-Br
p-Br
p-Br
H
H
H
H
H
H
H
H
p-CH3O
p-CH3O
p-CH3O
p-CH3O
p-CH3O
p-CH3O
p-CH3O
p-CH3O
o-CH3
o-O2N
CH3
C2H5
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
57
56
67
71
66
60
58
59
58
59
75
72
64
66
57
58
51
50
53
65
54
53
64
67
71
72
n-C3H7
n-C4H9
n-C5H11
n-C6H13
n-C7H15
n-C8H17
CH3
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
C2H5
n-C3H7
n-C4H9
n-C5H11
n-C6H13
n-C7H15
n-C8H17
CH3
C2H5
n-C3H7
n-C4H9
n-C5H11
n-C6H13
n-C7H15
n-C8H17
n-C4H9
n-C4H9
3s
3t
3u
3v
3w
3x
3y
3z
[3+2] cycloaddition, dehydration of the cycloadduct,
and further dehydroaromatization of the dihydroin-
dolizines. Molecular iodine served both as a cata-
lyst and a dehydroaromatization reagent in the re-
action. Pyridine was used both as a base reagent and
a solvent in the reaction. The operational simplic-
ity, ready availability of starting materials, and good
yields make this reaction a potentially useful method
in the diversity-oriented synthesis of indolizines.
in CDCl3 solutions. The J values are given in hertz.
Only discrete or characteristic signals for the 1H
NMR are reported. The MS spectra were obtained
on a ZAB-HS mass spectrometer with 70 eV. The el-
emental analyses were performed in a Perkin–Elmer
240C instrument. Flash chromatography was per-
formed on silica gel (230–400 mesh) eluting with
an ethyl acetate–hexanes mixture. All reactions were
monitored by thin layer chromatography (TLC). All
reagents and solvents were purchased from commer-
cial sources and purified commonly before used.
EXPERIMENTAL
General
General Procedure for Preparation of 1-Alkyl-3-
aroylindolizines 3a–z. A mixture of 1-arylacyl pyri-
dinium salt (4 mmol), aliphatic aldehyde (6 mmol),
MnO2 (18 mg, 0.2 mmol), and molecular iodine
(1.02 g, 4 mmol) in pyridine (7 mL) was heated at
120◦C for 40 h with magnetic stirring. The reaction
course was monitored by TLC. After the reaction
was completed, solid MnO2 was filtered away, then
All melting points were determined in a SGW X-
4B melting point apparatus and are uncorrected. IR
spectra were recorded in a Nicolet FT-IR 5DX spec-
trometer. The 1H NMR (600 MHz) and 13C NMR
(151 MHz) spectra were recorded in a Bruker AV-
600 spectrometer with TMS as an internal reference
Heteroatom Chemistry DOI 10.1002/hc

76 Tan et al.
SCHEME 2 Tentative reaction mechanism.
the solvent was removed under reduced pressure,
and the residue was dissolved with dichloromethane
(20 mL). The resultant mixture was washed with
20% sodium thiosulfate solution (10 mL), water
(10 mL), and brine (10 mL). The organic phase
was dried over anhydrous sodium sulfate, the sol-
vent was removed under reduced pressure, and the
residue was separated by flash chromatography on
a silica gel column with petroleum ether (bp 60–
90◦C)/dichloromethane/ethyl acetate (16/4/1) as an
eluent to give the products 3.
(4-Bromophenyl)(1-ethylindolizin-3-yl)metha-
none (3b). mp 131.2–132.9◦C (PE/EA); 1H NMR
(600 MHz, CDCl3) δ (ppm): 8.41 (d, J = 9.0 Hz,
1H), 7.84 (d, J = 7.0 Hz, 1H), 7.63 (d, J = 8.4 Hz,
2H), 7.54 (d, J = 8.4 Hz, 2H), 7.14 (dd, J = 8.4 and
7.2 Hz, 1H), 6.83 (td, J = 6.8 and 1.1 Hz, 1H), 6.74
(s, 1H), 2.74 (q, J = 7.4 Hz, 2H), 1.32 (t, J = 7.5 Hz,
3H); 13C NMR (151 MHz, CDCl3) δ (ppm): 187.8,
139.2, 136.2, 130.3(2C), 129.5(2C), 126.6, 124.1,
122.6, 121.7, 119.9, 113.8, 112.8, 110.02, 18.0, 10.3;
IR (KBr, cm−1): 3057, 2964, 1678, 1632, 1589, 1555,
1490, 1292, 1239, 935, 873, 838, 762, 684; MS(EI)
(m/z): 325 [(M – 2)+] (75%), 326 [(M – 1)+] (55%),
329 [(M + 2)+] (100%); Anal. calcd. for C17H14BrNO:
C, 62.21; H, 4.30; N, 4.27; Found: C, 62.01; H, 4.39;
N, 4.22.
(4-Bromophenyl)(1-methylindolizin-3-yl)metha-
none (3a). mp 125.5–126.3◦C (PE/EA); 1H NMR
(600 MHz, CDCl3) δ (ppm): 8.41 (d, J = 9.0 Hz,
1H), 7.79 (d, J = 6.9 Hz, 1H), 7.61 (d, J = 8.4 Hz,
2H), 7.52 (d, J = 8.3 Hz, 2H), 7.13 (dd, J = 8.3 and
7.1 Hz, 1H), 6.84 (td, J = 6.8 and 1.0 Hz, 1H), 6.74
(s, 1H), 2.39 (s, 3H); 13C NMR (151 MHz, CDCl3) δ
(ppm): 187.7, 139.1, 136.0, 130.3 (2C), 129.5 (2C),
124.1, 122.5, 121.8, 120.4, 119.8, 115.7, 112.8, 109.9,
10.5; IR (KBr, cm−1): 2974, 1678, 1609, 1583, 1495,
1419, 1325, 874, 844, 762; MS(EI) (m/z): 312 [(M –
1)+] (10%), 313 [M+] (100%), 315 [(M + 2)+] (35%);
Anal. calcd. for C16H12BrNO: C, 61.17; H, 3.85; N,
4.46; Found: C, 61.02; H, 3.98; N, 4.20.
(4-Bromophenyl)(1-propylindolizin-3-yl)metha-
1
none (3c). mp 114.9–115.0◦C (PE/DCM); H NMR
(600 MHz, CDCl3) δ (ppm): 8.41 (d, J = 9.0 Hz, 1H),
7.85 (d, J = 6.9 Hz, 1H), 7.63 (d, J = 8.4 Hz, 2H),
7.54 (d, J = 8.4 Hz, 2H), 7.13 (dd, J = 8.4 and 7.2 Hz,
1H), 6.82 (td, J = 6.8 and 1.2 Hz, 1H), 6.74 (s, 1H),
2.71 (t, J = 7.6 Hz, 2H), 1.75–1.65 (m, 2H), 0.97 (t,
J = 7.3 Hz, 3H); 13C NMR (151 MHz, CDCl3) δ
(ppm): 187.8, 139.2, 136.1, 130.3(2C), 129.5(2C),
Heteroatom Chemistry DOI 10.1002/hc

Iodine-Promoted Synthesis of 1-Alkyl-3-aroylindolizines from N-(Aroylmethyl)pyridinium Salts and Aliphatic Aldehydes 77
125.0, 124.1, 122.5, 121.8, 119.9, 114.7, 112.7, 110.0,
26.7, 19.2, 12.9; IR (KBr, cm−1): 2960, 2929, 2869,
1674, 1602, 1555, 1498, 1276, 1236, 876, 832, 763;
MS(EI) (m/z): 341 [(M)+] (72%), 342 [(M + 1)+]
(100%), 343 [(M + 2)+] (35%); Anal. calcd. for
C18H16BrNO: C, 63.17; H, 4.71; N, 4.09; Found: C,
63.02; H, 4.89; N, 4.12.
2858, 1634, 1608, 1551, 1524, 1498, 1448, 1421,
1244, 1218, 1153, 877, 833, 763; MS(EI) (m/z): 383
[(M + 1)+] (100%), 384 [(M + 1)+] (75%); Anal.
calcd. for C21H22BrNO: C, 65.63; H, 5.77; N, 3.64;
Found: C, 65.58; H, 5.68; N, 3.50.
(4-Bromophenyl)(1-heptylindolizin-3-yl)metha-
none (3g). mp 89.8–91.5◦C (PE); 1H NMR
(600 MHz, CDCl3) δ (ppm): 8.40 (d, J = 8.9 Hz,
1H), 7.84 (d, J = 6.9 Hz, 1H), 7.62 (d, J = 8.4 Hz,
2H), 7.53 (d, J = 8.3 Hz, 2H), 7.12 (dd, J = 8.4 and
7.2 Hz, 1H), 6.81 (td, J = 6.8 and 0.9 Hz, 1H), 6.72
(s, 1H), 2.72 (t, J = 7.6 Hz, 2H), 1.68–1.61 (m, 2H),
1.38–1.31 (m, 2H), 1.30–1.26 (m, 2H), 1.24–1.18 (m,
4H), 0.81 (t, J = 6.9 Hz, 3H); 13C NMR (151 MHz,
CDCl3) δ (ppm): 187.8, 139.2, 136.1, 130.3 (2C),
129.5 (2C), 125.2, 124.1, 122.5, 121.8, 119.9, 114.6,
112.7, 110.0, 30.7 , 28.4, 28.0, 25.8, 24.7, 21.6, 13.1;
IR (KBr, cm−1): 2924, 2852, 1632, 1602, 1562, 1523,
1496, 1250, 1237, 931, 872, 828, 763; MS(EI) (m/z):
398 [(M + 1)+] (100%), 399 [(M + 2)+] (72%); Anal.
calcd. for C22H24BrNO: C, 66.33; H, 6.07; N, 3.52;
Found: C, 66.10; H, 6.22; N, 3.30.
(4-Bromophenyl)(1-butylindolizin-3-yl)metha-
none (3d). mp 79.1–80.0◦C (PE/DCM); 1H NMR
(600 MHz, CDCl3) δ (ppm): 8.40 (d, J = 8.9 Hz,
1H), 7.84 (d, J = 6.9 Hz, 1H), 7.64 (d, J = 8.4 Hz,
2H), 7.53 (d, J = 8.4 Hz, 2H), 7.12 (dd, J = 8.4 and
7.2 Hz, 1H), 6.81 (td, J = 6.8 and 1.0 Hz, 1H), 6.72
(s, 1H), 2.72 (t, J = 7.6 Hz, 2H), 1.68–1.61 (m, 2H),
1.47–1.30 (m, 2H), 0.89 (t, J = 7.4 Hz, 3H); 13C NMR
(151 MHz, CDCl3) δ (ppm): 187.7, 139.2, 136.1,
130.3 (2C), 129.5 (2C), 125.2, 124.1, 122.5, 121.8,
119.9, 114.6, 112.7, 110.0, 28.0, 24.4, 21.5, 12.8; IR
(KBr, cm−1): 2952, 2927, 2868, 1638, 1603, 1555,
1497, 1298, 1251, 875, 832, 763, 684; MS(EI) (m/z):
356 [(M + 1)+] (15%), 358 [(M + 3)+] (100%); Anal.
calcd. for C19H18BrNO: C, 64.06; H, 5.09; N, 3.93;
Found: C, 63.89; H, 5.17; N, 3.69.
(4-Bromophenyl)(1-octylindolizin-3-yl)methanone
(3h). mp 96.5–97.1◦C (PE); 1H NMR (600 MHz,
CDCl3) δ (ppm): 8.40 (d, J = 8.9 Hz, 1H), 7.84 (d,
J = 6.9 Hz, 1H), 7.62 (d, J = 8.4 Hz, 2H), 7.53 (d,
J = 8.3 Hz, 2H), 7.12 (dd, J = 8.3 and 7.2 Hz, 1H),
6.81 (td, J = 6.9 and 0.8 Hz, 1H), 6.72 (s, 1H), 2.71
(t, J = 7.6 Hz, 2H), 1.68–1.61 (m, 2H), 1.39–1.30 (m,
2H), 1.31–1.10 (m, 8H), 0.80 (t, J = 7.0 Hz, 3H);
13C NMR (151 MHz, CDCl3) δ (ppm): 187.6, 139.2,
136.1, 130.3 (2C), 129.5 (2C), 125.2, 124.1, 122.5,
121.8, 119.9, 114.6, 112.7, 110.0, 30.8, 28.5, 28.3,
28.2, 25.8, 24.7, 21.6, 13.1; IR (KBr, cm−1): 2923,
2854, 1601, 1557, 1498, 1424, 1295, 1253, 873, 830,
764; MS(EI) (m/z): 412 [(M + 1)+] (55%), 413 [(M +
2)+] (100%); Anal. calcd. for C23H26BrNO: C, 66.99;
H, 6.36; N, 3.40; Found: C, 66.70; H, 6.46; N, 3.52.
(4-Bromophenyl)(1-pentylindolizin-3-yl)metha-
none (3e). Mp 90.8–91.9◦C (PE/DCM); 1H NMR
(600 MHz, CDCl3) δ (ppm): 8.40 (d, J = 9.0 Hz, 1H),
7.84 (d, J = 6.9 Hz, 1H), 7.61 (d, J = 8.4 Hz, 2H), 7.53
(d, J = 8.4 Hz, 2H), 7.11 (dd, J = 8.4 and 7.0 Hz, 1H),
6.81 (td, J = 6.8 and 1.0 Hz, 1H), 6.72 (s, 1H), 2.71
(t, J = 7.6 Hz, 2H), 1.68-1.61 (m, 2H), 1.38-1.24 (m,
4H), 0.84 (t, J = 7.1 Hz, 3H); 13C NMR (151 MHz,
CDCl3) δ (ppm): 187.7, 139.2, 136.1, 130.3(2C),
129.5(2C), 125.2, 124.1, 122.5, 121.8, 119.9, 114.6,
112.7, 110.0, 30.6, 25.5, 24.7, 21.4, 12.9; IR (KBr,
cm−1): 2953, 2925, 2861, 1632, 1607, 1586, 1558,
1524, 1501, 1452, 1425, 1290, 1249, 1223, 878, 833,
762, 735, 686; MS(EI) (m/z): 369 [M+] (46%), 370
[(M + 1)+] (75%), 371 [(M + 2)+] (100%), 373 [(M +
4)+] (42%); Anal. calcd. for C20H20BrNO: C, 64.87;
H, 5.44; N, 3.78; Found: C, 64.92; H, 5.32; N, 3.82.
(1-Methylindolizin-3-yl)(phenyl)methanone (3i).
mp 93.0–94.1◦C (PE/EA); 1H NMR (600 MHz, CDCl3)
δ (ppm): 8.50 (d, J = 8.6 Hz, 1H), 7.86 (d, J = 6.8 Hz,
1H), 7.74 (d, J = 7.8 Hz,, 2H), 7.43 (t, J = 7.2 Hz, 1H),
7.38 (t, J = 7.2 Hz, 2H), 7.11 (t, J = 7.2 Hz, 1H), 6.82
(t, J = 6.8 Hz, 1H), 6.80 (s, 1H), 2.39 (s, 3H); 13C NMR
(151 MHz, CDCl3) δ (ppm) 189.2, 140.4, 135.9, 129.5,
127.8 (2C), 127.0 (2C), 122.1, 121.7, 120.1, 119.9,
116.0, 112.6, 110.3, 10.4; IR (KBr, cm−1): 2918, 1714,
1604, 1554, 1494, 1421, 1248, 932, 872, 747, 710;
MS(EI) (m/z): 234 [(M – 1)+] (100%), 237 [(M + 2)+]
(15%); Anal. calcd. for C16H13NO: C, 81.68; H, 5.57;
N, 5.95; Found: C, 81.49; H, 5.60; N, 5.72.
(4-Bromophenyl)(1-hexylindolizin-3-yl)metha-
none (3f). mp 92.3–93.0◦C (PE); 1H NMR
(600 MHz, CDCl3) δ (ppm): 8.41 (d, J = 9.0 Hz,
1H), 7.85 (d, J = 6.9 Hz, 1H), 7.62 (d, J = 8.4 Hz,
2H), 7.53 (d, J = 8.3 Hz, 2H), 7.12 (dd, J = 8.4 and
7.2 Hz, 1H), 6.82 (td, J = 6.8 and 0.9 Hz, 1H), 6.73
(s, 1H), 2.72 (t, J = 7.6 Hz, 2H), 1.68–1.61 (m, 2H),
1.41–1.29 (m, 2H), 1.30–1.19 (m, 4H), 0.82 (t, J =
7.0 Hz, 3H); 13C NMR (151 MHz, CDCl3) δ (ppm):
187.8, 139.2, 136.1, 130.2 (2C), 129.5 (2C), 125.2,
124.1, 122.5, 121.8, 119.9, 114.6, 112.7, 110.0, 30.5,
28.1, 25.8, 24.7, 21.5, 13.0; IR (KBr, cm−1): 2921,
Heteroatom Chemistry DOI 10.1002/hc

78 Tan et al.
(1-Ethylindolizin-3-yl)(phenyl)methanone (3j).
J = 7.6 Hz, 2H), 1.71–1.63 (m, 2H), 1.37–1.29 (m,
4H), 0.85 (t, J = 7.1 Hz, 3H); 13C NMR (151 MHz,
CDCl3) δ (ppm) 190.3, 141.5, 137.0, 130.6, 128.9 (2C),
128.1 (2C), 126.0, 123.2, 122.7, 121.0, 115.9, 113.5,
111.4, 31.7, 26.6, 25.7, 22.4, 14.0; IR (KBr, cm−1):
2925, 2860, 1602, 1572, 1548, 1526, 1496, 1444, 1293,
1248, 1222, 873, 790, 749; MS(EI) (m/z): 290 [(M –
1)+] (100%), 291 [M+] (23%), 292 [(M + 1)+] (15%);
Anal. calcd. for C20H21NO: C, 82.44; H, 7.26; N, 4.81;
Found: C, 82.32; H, 7.22; N, 4.78.
mp 65.0–66.7◦C (PE/EA); 1H NMR (600 MHz), δ
(ppm): 8.42 (d, J = 8.9 Hz, 1H), 7.84 (d, J = 6.9 Hz,
1H), 7.75 (d, J = 7.2 Hz, 2H), 7.44 (t, J = 7.2 Hz,
1H), 7.41 (t, J = 7.2 Hz, 2H), 7.12 (dd, J = 8.5 and
7.2 Hz, 1H), 6.82 (t, J = 6.8 Hz, 1H), 6.79 (s, 1H),
2.75 (q, J = 7.2 Hz, 2H), 1.38 (t, J = 7.2 Hz, 3H);
13C NMR (151 MHz, CDCl3) δ (ppm) 190.3, 141.5,
137.1, 130.6, 128.9 (2C), 128.1 (2C), 127.3, 123.3,
122.7, 121.0, 115.2, 113.6, 111.4, 19.0, 11.4; IR (KBr,
cm−1): 2969, 2935, 1608, 1497, 1291, 1238, 872, 796,
746; MS(EI) (m/z): 248 [(M – 1)+] (24%), 250 [(M +
1)+] (100%); Anal. calcd. for C17H15NO: C, 81.90; H,
6.06; N, 5.62; Found: C, 81.72; H, 6.26; N, 5.88.
(1-Hexylindolizin-3-yl)(phenyl)methanone (3n).
mp 83.5–84.9◦C (PE/EA); 1H NMR (600 MHz, CDCl3)
δ (ppm): 8.49 (d, J = 9.0 Hz, 1H), 7.92 (d, J = 6.9 Hz,
1H), 7.82 (d, J = 7.0 Hz, 2H), 7.52 (t, J = 7.2 Hz, 1H),
7.48 (t, J = 7.8 Hz, 2H), 7.18 (dd, J = 8.5 and 7.0 Hz,
1H), 6.88 (t, J = 6.8 Hz, 1H), 6.86 (s, 1H), 2.80 (t,
J = 7.6 Hz, 2H), 1.78–1.72 (m, 2H), 1.46-1.42 (m,
2H), 1.35–1.30 (m, 4H), 0.90 (t, J = 7.0 Hz, 3H); 13C
NMR (151 MHz, CDCl3) δ (ppm) 189.2, 140.5, 136.0,
129.5, 127.9 (2C), 127.0 (2C), 125.0, 122.1, 121.7,
120.0, 114.9, 112.5, 110.4, 30.5, 28.1, 25.8, 24.7, 21.5,
13.0; IR (KBr, cm−1): 2921, 2856, 1672, 1601, 1494,
1417, 1357, 1246, 1159, 871, 780, 743, 697; MS(EI)
(m/z): 204 [(M – 1)+] (100%), 205 [M+] (14%), 306
[(M + 1)+] (9%); Anal. calcd. for C21H23NO: C, 82.58;
H, 7.59; N, 4.59; Found: C, 82.43; H, 7.72; N, 4.66
Phenyl(1-propylindolizin-3-yl)methanone (3k).
mp 79.0–80.0◦C (PE/EA); 1H NMR (600 MHz,
CDCl3) δ (ppm): 8.49 (d, J = 8.9 Hz, 1H), 7.92 (d,
J = 6.9 Hz, 1H), 7.82 (d, J = 7.2 Hz, 2H), 7.45 (t, J =
7.2 Hz, 1H), 7.41 (t, J = 7.2 Hz, 2H), 7.18 (dd, J =
8.4 and 7.1 Hz, 1H), 6.82 (t, J = 6.8 Hz, 1H), 6.81
(s, 1H), 2.79 (t, J = 7.6 Hz, 2H), 1.84–1.75 (m, 2H),
1.05 (t, J = 7.3 Hz, 3H); 13C NMR (151 MHz, CDCl3)
δ (ppm) 189.2, 140.5, 135.9, 129.5, 127.9 (2C), 127.0
(2C), 124.8, 122.1, 121.7, 119.9, 115.0, 112.5, 110.4,
26.7, 19.2, 13.0; IR (KBr, cm−1): 2951, 2924, 2867,
1630, 1600, 1570, 1546, 1495, 1421, 1374, 1309,
1276, 1233, 874, 831, 794, 751; MS(EI) (m/z): 263
[M+] (100%), 264 [(M + 1)+] (35%); Anal. calcd.
for C18H17NO: C, 82.10; H, 6.51; N, 5.32; Found: C,
82.02; H, 6.50; N, 5.60.
(1-Heptylindolizin-3-yl)(phenyl)methanone (3o).
mp 46.5–47.1◦C (PE/DCM); 1H NMR (600 MHz,
CDCl3) δ (ppm): 8.41 (d, J = 8.9 Hz, 1H), 7.83 (d,
J = 7.0 Hz, 1H), 7.74 (d, J = 7.0 Hz, 2H), 7.44 (t, J
= 7.2 Hz, 1H), 7.39 (t, J = 7.8 Hz, 2H), 7.08 (dd, J
= 8.5 and 7.0 Hz, 1H), 6.78 (t, J = 6.8 Hz, 1H), 6.70
(s, 1H), 2.70 (t, J = 7.6 Hz, 2H), 1.69–1.62 (m, 2H),
1.35–1.30 (m, 2H), 1.29–1.24 (m, 2H), 1.23–1.18 (m,
4H), 0.81 (t, J = 7.0 Hz, 3H); 13C NMR (151 MHz,
CDCl3) δ (ppm) 190.2, 141.5, 137.0, 130.6, 128.9
(2C), 128.1 (2C), 126.0, 123.2, 122.7, 121.0, 115.9,
113.5, 111.4, 31.8, 29.5, 29.1, 26.9, 25.7, 22.6, 14.1;
IR (KBr, cm−1): 2917, 2852, 1694, 1600, 1563, 1495,
1418, 1294, 1242, 868, 755; MS(EI) (m/z): 318 [(M –
1)+] (100%), 319 [M+] (38%), 320 [(M + 1)+] (15%);
Anal. calcd. for C22H25NO: C, 82.72; H, 7.89; N, 4.38;
Found: C, 82.88; H, 7.90; N, 4.32.
(1-Butylindolizin-3-yl)(phenyl)methanone (3l).
mp 97.9–98.0◦C (PE/EA); 1H NMR (600 MHz,
CDCl3) δ (ppm): 8.42 (d, J = 8.9 Hz, 1H), 7.85 (d,
J = 7.0 Hz, 1H), 7.82 (d, J = 7.2 Hz, 2H), 7.44 (t,
J = 7.2 Hz, 1H), 7.41 (t, J = 7.2 Hz, 2H), 7.11 (dd,
J = 8.2 and 6.9 Hz, 1H), 6.82 (t, J = 6.8 Hz, 1H),
6.79 (s, 1H), 2.73 (t, J = 7.6 Hz, 2H), 1.70–1.64 (m,
2H), 1.42–1.36 (m, 2H), 0.90 (t, J = 7.4 Hz, 3H); 13C
NMR (151 MHz, CDCl3) δ (ppm) 189.2, 140.5, 136.0,
129.5, 127.9 (2C), 127.1 (2C), 124.9, 122.1, 121.7,
120.0, 114.9, 112.5, 110.4, 28.0, 24.4, 21.5, 12.8; IR
(KBr, cm−1): 2919, 2859, 1677, 1601, 1538, 1495,
1416, 1296, 1237, 930, 869, 780; MS(EI) (m/z): 277
[M+] (50%), 278 [(M + 1)+] (100%); Anal. calcd.
for C19H19NO: C, 82.28; H, 6.90; N, 5.05; Found: C,
82.04; H, 6.82; N, 5.01.
(1-Octylindolizin-3-yl)(phenyl)methanone (3p).
mp 75.1–76.8◦C (PE/DCM); 1H NMR (600 MHz,
CDCl3) δ (ppm): 8.43 (d, J = 8.9 Hz, 1H), 7.82 (d,
J = 7.0 Hz, 1H), 7.74 (d, J = 7.0 Hz, 2H), 7.41 (t,
J = 7.2 Hz, 1H), 7.39 (t, J = 7.8 Hz, 2H), 7.09 (dd,
J = 8.5 and 7.0 Hz, 1H), 6.78–6.70 (m, 2H), 2.71
(t, J = 7.2 Hz, 2H), 1.67–1.54 (m, 2H), 1.34–1.28
(m, 2H), 1.22–1.10 (m, 8H), 0.80 (d, J = 6.6 Hz,
3H); 13C NMR (151 MHz, CDCl3) δ (ppm) 190.2,
(1-Pentylindolizin-3-yl)(phenyl)methanone (3m).
mp 74.0–75.1◦C (PE/EA); 1H NMR (600 MHz, CDCl3)
δ (ppm): 8.42 (d, J = 8.4 Hz, 1H), 7.85 (d, J = 7.2 Hz,
1H), 7.76 (d, J = 6.6 Hz, 2H), 7.45 (t, J = 7.2 Hz, 1H),
7.41 (t, J = 7.8 Hz, 2H), 7.11 (dd, J = 8.6 and 7.2 Hz,
1H), 6.82 (t, J = 6.8 Hz, 1H), 6.79 (s, 1H), 2.73 (t,
Heteroatom Chemistry DOI 10.1002/hc

Iodine-Promoted Synthesis of 1-Alkyl-3-aroylindolizines from N-(Aroylmethyl)pyridinium Salts and Aliphatic Aldehydes 79
141.5, 137.0, 130.6, 128.9(2C), 128.1(2C), 126.0,
123.1 122.7, 121.0, 115.9, 113.5, 111.4, 31.8, 29.5,
29.4, 29.2, 26.9, 25.8, 22.7; IR (KBr, cm−1): 2917,
2849, 1688, 1600, 1562, 1494, 1418, 1374, 1297,
1239, 870, 754; MS(EI)(m/z): 332[(M – 1)+] (31%),
333[M+] (100%), 334 [(M + 1)+] (38%); Anal. calcd.
for C22H25NO: C, 82.84; H, 8.16; N, 4.20; Found: C,
82.67; H, 8.10; N, 4.29.
(1-Butylindolizin-3-yl)(4-methoxyphenyl)metha-
none (3t). mp 75.1–76.8◦C (PE/DCM); 1H NMR
(600 MHz, CDCl3) δ (ppm) 8.38 (d, J = 8.9 Hz, 1H),
7.82 (d, J = 6.9 Hz, 1H), 7.77 (d, J = 8.6 Hz, 2H),
7.06 (t, J = 7.2 Hz, 1H), 6.90 (d, J = 8.6 Hz, 2H), 6.81
(s, 1H), 6.76 (t, J = 6.7 Hz, 1H), 3.89 (s, 3H), 2.72 (q,
J = 7.2 Hz, 2H), 1.69–1.62 (m, 2H), 1.42–1.34 (m,
2H), 0.89 (t, J = 7.4 Hz, 3H); 13C NMR (151 MHz,
CDCl3) δ (ppm) 188.2, 160.7, 135.8, 132.9, 130.0
(2C), 124.7, 121.8, 121.6, 119.9, 114.7, 112.4, 112.3
(2C), 110.5, 54.4, 27.9, 24.4, 21.5, 12.9; IR (KBr,
cm−1): 2931, 2870, 2838, 1677, 1604, 1497, 1461,
1249, 966, 902, 878, MS(EI) (m/z): 305 [(M – 2)+]
(92%), 307 [M+] (100%); Anal. calcd. for C20H21NO2:
C, 78.15; H, 6.89; N, 4.56; Found: C, 78.02; H, 6.98;
N, 4.50.
(4-Methoxyphenyl)(1-methylindolizin-3-yl)metha-
none (3q). mp 128.3–129.1◦C (PE/EA); 1H NMR
(600 MHz, CDCl3) δ (ppm) 8.39 (d, J = 9.0 Hz, 1H),
7.99 (d, J = 9.0 Hz, 1H), 7.77 (d, J = 8.4 Hz, 2H), 7.09
(dd, J = 6.6 and 8.4 Hz, 1H), 6.90 (d, J = 8.4 Hz, 2H),
6.82 (s, 1H), 6.80 (t, J = 6.8 Hz, 1H), 3.81 (s, 3H),
2.40 (s, 3H); 13C NMR (151 MHz, CDCl3) δ (ppm)
188.2, 160.7, 135.7, 132.9, 131.3, 130.1(2C), 121.7,
121.6, 119.9, 115.8, 112.7, 112.4, 112.2(2C), 54.40,
10.46; IR (KBr, cm−1): 2980, 2903, 2841, 1685, 1601,
1499, 1247, 929, 877, 844; MS(EI) (m/z): 266 [(M +
1)+] (100%); Anal. calcd. for C17H15NO2: C, 76.96;
H, 5.70; N, 5.28; Found: C, 76.88; H, 5.86; N, 5.02.
(4-Methoxyphenyl)(1-pentylindolizin-3-yl)metha-
none (3u). mp 69.1–70.5◦C (PE/DCM); 1H NMR
(600 MHz, CDCl3) δ (ppm): 8.46 (d, J = 8.9 Hz, 1H),
7.91 (d, J = 6.0 Hz, 1H), 7.85 (d, J = 7.2 Hz, 2H),
7.14 (t, J = 7.2 Hz, 1H), 6.99 (d, J = 8.5 Hz, 2H), 6.89
(s, 1H), 6.86 (t, J = 6.7 Hz, 1H), 3.89 (s, 3H), 2.80 (d,
J = 7.2 Hz, 2H), 1.79–1.74 (m, 2H), 1.45–1.35 (m,
4H), 0.92 (t, J = 6.9 Hz, 3H). 13C NMR (151 MHz,
CDCl3) δ (ppm): 189.3, 161.8, 136.8, 134.0, 131.1
(2C), 125.8, 122.7, 122.0, 121.0, 115.7, 113.3 (2C),
112.9, 111.5, 55.4, 31.7, 26.6, 25.7, 22.5, 14.0; IR
(KBr, cm−1): 2955, 2930, 2858, 1675, 1604, 1496,
1461, 1422, 1249, 1170, 966, 903, 878; MS(EI) (m/z):
321 [M+] (24%), 322 [(M + 1)+] (100%), 323 [(M +
2)+] (65%); Anal. calcd. for C21H23NO2: C, 78.47; H,
7.21; N, 4.36; Found: C, 78.24; H, 7.20; N, 4.52.
(1-Ethylindolizin-3-yl)(4-methoxyphenyl)metha-
1
none (3r). mp 104.5–105.3◦C (PE/DCM); H NMR
(600 MHz, CDCl3) δ (ppm): 8.46 (d, J = 8.7 Hz,
1H), 7.90 (d, J = 6.7 Hz, 1H), 7.85 (d, J = 8.4 Hz,
2H), 7.16 (dd, J = 6.6 and 8.4 Hz, 1H), 6.99 (d, J =
8.4 Hz, 2H), 6.91 (s, 1H), 6.87 (t, J = 6.5 Hz, 1H),
3.89 (s, 3H), 2.83 (q, J = 7.2 Hz, 2H), 1.40 (t, J =
7.2 Hz, 3H); 13C NMR (151 MHz, CDCl3) δ (ppm):
189.3, 161.8, 136.9, 134.0, 132.1, 131.1(2C), 128.3,
127.1, 122.7, 121.0, 114.9, 113.4(2C), 111.6, 55.4,
19.0, 11.4; IR (KBr, cm−1): 2968, 2934, 2872, 2843,
1669, 1597, 1566, 1497, 1424, 1377, 1248, 1169, 943,
876, 842; MS(EI) (m/z): 278 [(M – 1)+] (23%), 279
[M+] (56%), 280 [(M + 1)+] (100%), 281 [(M + 2)+]
(92%); Anal. calcd. for C18H17NO2: C, 77.40; H, 6.13;
N, 5.01; Found: C, 77.26; H, 6.10; N, 5.24.
(1-Hexylindolizin-3-yl)(4-methoxyphenyl)metha-
none (3v). mp 58.4–59.6◦C (PE/DCM); 1H NMR
(600 MHz, CDCl3) δ (ppm): 8.38 (d, J = 8.8 Hz, 1H),
7.83 (d, J = 6.7 Hz, 1H), 7.78 (d, J = 8.4 Hz, 2H),
7.07 (t, J = 7.2 Hz, 1H), 6.91 (d, J = 8.4 Hz, 2H), 6.81
(s, 1H), 6.78 (t, J = 6.6 Hz, 1H), 3.82 (s, 3H), 2.72
(t, J = 7.2 Hz, 2H), 1.73–1.61 (m, 2H), 1.40–1.35 (m,
2H), 1.29–1.24 (m, 4H), 0.83 (d, J = 6.6 Hz, 3H); 13C
NMR (151 MHz, CDCl3) δ (ppm): 188.2, 160.7,
135.8, 133.0, 130.0(2C), 124.7, 121.6, 121.5, 120.0,
114.7, 112.3 (2C), 112.0 110.5, 54.4, 30.6, 28.1, 25.9,
24.7, 21.6, 13.0; IR (KBr, cm−1): 2925, 2858, 1670,
1599, 1497, 1278, 1242, 958, 934, 832, 797; MS(EI)
(m/z): 334[(M – 1)+] (45%), 335[M+] (46%), 336 [(M
+ 1)+] (100%); Anal. calcd. for C22H25NO2: C, 78.77;
H, 7.51; N, 4.18; Found: C, 78.68; H, 7.70; N, 4.29.
(4-Methoxyphenyl)(1-propylindolizin-3-yl)metha-
none (3s). mp 83.2–84.5◦C (PE/DCM); 1H NMR
(600 MHz, CDCl3) δ (ppm): 8.46 (d, J = 8.7 Hz, 1H),
7.91 (d, J = 6.7 Hz, 1H), 7.85 (d, J = 8.3 Hz, 2H),
7.14 (t, J = 7.2 Hz, 1H), 6.99 (d, J = 8.4 Hz, 2H),
6.90 (s, 1H), 6.85 (t, J = 6.6 Hz, 1H), 3.89 (s, 3H),
2.79 (t, J = 7.4 Hz, 2H), 1.85–1.75 (m, 2H), 1.05 (t,
J = 7.2 Hz, 3H); 13C NMR (151 MHz, CDCl3) δ
(ppm): 189.3, 161.8, 136.9, 134.0, 131.1(2C), 125.5,
124.5, 122.7, 122.0, 121.0, 115.9, 113.3(2C), 111.6,
55.4, 27.8, 20.3, 14.1; IR (KBr, cm−1): 32930, 2871,
2841, 1647, 1599, 1497, 1460, 1277, 1247, 902, 877,
847, 773; MS(EI) (m/z): 294 [(M + 1)+] (100%);
Anal. calcd. for C19H19NO2: C, 77.79; H, 6.53; N,
4.77; Found: C, 77.63; H, 6.50; N, 4.88.
(1-Heptylindolizin-3-yl)(4-methoxyphenyl)metha-
none (3w). mp 62.0–63.4◦C (PE/EA); 1H NMR
(600 MHz, CDCl3) δ (ppm): 8.46 (d, J = 8.8 Hz, 1H),
7.91 (d, J = 6.7 Hz, 1H), 7.85 (d, J = 8.6 Hz, 2H),
Heteroatom Chemistry DOI 10.1002/hc

80 Tan et al.
= 7.4 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ (ppm):
186.4, 147.7, 146.0, 136.4, 128.5, 125.8, 123.4, 122.4,
122.0, 119.9, 114.4, 113.2, 109.7, 27.9, 24.3, 21.5,
12.8; IR (KBr, cm−1) ν: 2934, 1737, 1525, 1497,
1425, 1348, 1232, 841, 745; MS(EI) (m/z): 323.59
[(M + 1)+] (100%); Anal. calcd. for C19H18N2O3: C,
70.79; H, 5.63; N, 8.69; Found: C, 70.88; H, 5.82; N,
8.78.
7.15 (t, J = 7.2 Hz, 1H), 6.99 (d, J = 8.6 Hz, 2H), 6.89
(s, 1H), 6.86 (t, J = 6.8 Hz, 1H), 3.89 (s, 3H), 2.72
(t, J = 7.2 Hz, 2H), 1.81–1.71 (m, 2H), 1.49–1.19 (m,
8H), 0.89 (t, J = 6.8 Hz, 3H); 13C NMR (151 MHz,
CDCl3) δ (ppm): 188.2, 160.7, 135.8, 132.9, 130.1
(2C), 124.7, 121.7, 121.6, 119.9, 114.7, 112.4, 112.2
(2C), 110.5, 54.4, 30.7, 28.4, 28.0, 25.9, 24.7, 21.6,
13.1; IR (KBr, cm−1): 2925, 2854, 2830, 1648, 1598,
1497, 1465, 1249, 927, 876, 799; MS(EI) (m/z): 348
[(M – 1)+] (58%), 349 [M+] (30%), 350 [(M + 1)+]
(100%); Anal. calcd. for C23H27NO2: C, 79.05; H,
7.79; N, 4.01; Found: C, 79.12; H, 7.88; N, 4.28.
REFERENCES
[1] (a) Katritzky, A. R.; Rees, C. W. (Eds.). Comprehen-
sive Heterocyclic Chemistry: The Structure, Reac-
tions, Synthesis, and Uses of Heterocyclic Com-
pounds; Pergamon Press: Oxford, UK, 1984; Vols. 18;
(b) Andersen, R. J.; Faulkner, D. J.; Cun-heng, H.; Van
Duyne, G. D.; Clardy, J. J Am Chem Soc 1985, 107,
5492; (c) Katritzky, A. R.; Rees, C. W.; Scriven, E. F.
V. (Eds.). Comprehensive Heterocyclic Chemistry II;
Pergamon: Oxford, UK 1996, Vols. 18; (d) Micheal, J.
P. Alkaloids, 2001, 55, 91; (e) Micheal, J. P. Nat Prod
Rep 2002, 19, 742; (f) Lourenco, A. M.; Maximo, P.;
Ferreira, L. M.; Pereira, M. M. A. Bioactive Natural
Products (Part H), Stud Nat Prod Chem 2002, 27,
233.
(4-Methoxyphenyl)(1-octylindolizin-3-yl)metha-
none (3x). mp 64.5–65.6◦C (PE/EA); 1H NMR
(600 MHz, CDCl3) δ (ppm): 8.39 (d, J = 8.9 Hz, 1H),
7.83 (d, J = 6.7 Hz, 1H), 7.78 (d, J = 8.5 Hz, 2H),
7.08 (t, J = 7.2 Hz, 1H), 6.92 (d, J = 8.5 Hz, 2H),
6.82 (s, 1H), 6.79 (t, J = 6.7 Hz, 1H), 3.82 (s, 3H),
2.73 (t, J = 7.5 Hz, 2H), 1.75–1.63 (m, 2H), 1.40–1.31
(m, 2H), 1.30–1.25 (m, 2H), 1.25–1.16 (m, 6H), 0.81
(t, J = 6.6 Hz, 3H); 13C NMR (151 MHz, CDCl3)
δ (ppm): 188.2, 162.7, 140.6, 135.8, 134.0, 133.0,
132.2, 130.1 (2C), 124.7, 121.7, 121.6, 120.0, 114.7,
112.3 (2C), 54.4, 30.8, 28.5, 28.3, 28.2, 25.9, 24.7,
21.6; IR (KBr, cm−1): 2954, 2913, 2852, 1651, 1608,
1545, 1497, 1288, 1247, 956, 924, 880, 770; MS(EI)
(m/z): 362 [(M – 1)+] (100%), 363 [M+] (24%), 364
[(M + 1)+] (25%), 365 [(M + 2)+] (55%); Anal. calcd.
for C24H29NO2: C, 79.30; H, 8.04; N, 3.85; Found: C,
79.38; H, 8.26; N, 3.68.
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(1-Butylindolizin-3-yl)(o-tolyl)methanone (3y).
mp 64.0–65.0◦C (PE/EA); 1H NMR (600 MHz,
CDCl3) δ (ppm): 8.39 (d, J = 8.9 Hz, 1H), 7.81 (d,
J = 6.9 Hz, 1H), 7.66 (d, J = 8.0 Hz, 2H), 7.19 (d, J
= 7.9 Hz, 2H), 7.06 (dd, J = 8.1, 7.5 Hz, 1H), 6.79
(s, 1H), 6.78 – 6.74 (m, 1H), 2.70 (t, J = 7.7 Hz, 2H),
2.35 (s, 3H), 1.71–1.60 (m, 2H), 1.43–1.31 (m, 2H),
0.88 (t, J = 7.4 Hz, 3H); 13C NMR (150 MHz, CDCl3)
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124.7, 121.8, 121.6, 119.9, 114.8, 112.3, 110.5, 27.9,
24.3, 21.5, 20.4, 12.8; IR (KBr, cm−1) ν: 2920, 1602,
1496, 1420, 1356, 1295, 1253, 1227, 1156, 876, 764;
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(1-Butylindolizin-3-yl)(2-nitrophenyl)methanone
(3z). mp 82.0–84.0◦C (PE/EA); 1H NMR (600 MHz,
CDCl3) δ (ppm): 8.45 (d, J = 8.9 Hz, 1H), 8.25 (d,
J = 6.8 Hz, 2H), 7.89 (d, J = 6.9 Hz, 1H), 7.85 (d,
J = 7.9 Hz, 2H), 7.19 (dd, J = 10.2, 5.3 Hz, 1H), 6.88
(t, J = 6.8 Hz, 1H), 6.66 (s, 1H), 2.73 (t, J = 7.7 Hz,
2H), 1.71–1.59 (m, 2H), 1.45–1.30 (m, 2H), 0.90 (t, J
Heteroatom Chemistry DOI 10.1002/hc

Iodine-Promoted Synthesis of 1-Alkyl-3-aroylindolizines from N-(Aroylmethyl)pyridinium Salts and Aliphatic Aldehydes 81
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Heteroatom Chemistry DOI 10.1002/hc