Synthesis of pyrrolo[2,3-a]pyrrolizidino derivatives through intramolecular 1,3-dipolar cycloaddition in ionic liquid medium

Article abstract of DOI:10.1080/00397911.2011.594545

An ecofriently method for the synthesis of pyrrole-fused polycyclic heterocycles through intramolecular 1,3-dipolar cycloaddition reaction of azomethine ylides derived from pyrrole-2-carbaldehyde and secondary amino acids in ionic liquid [bmim][BF₄] as green solvent is reported. Copyright Taylor & Francis Group, LLC.

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Synthesis of Pyrrolo[2,3-a]pyrrolizidino
Derivatives Through Intramolecular 1,3-
Dipolar Cycloaddition in Ionic Liquid
Medium
Subban Kathiravan a & Raghavachary Raghunathan a
a Department of Organic Chemistry, University of Madras, Chennai,
India
Accepted author version posted online: 01 Feb 2012.Version of
record first published: 05 Sep 2012.
To cite this article: Subban Kathiravan & Raghavachary Raghunathan (2013): Synthesis of Pyrrolo[2,3-
a]pyrrolizidino Derivatives Through Intramolecular 1,3-Dipolar Cycloaddition in Ionic Liquid Medium,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 43:1, 147-155
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Synthetic Communications1, 43: 147–155, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.594545
SYNTHESIS OF PYRROLO[2,3-a]PYRROLIZIDINO
DERIVATIVES THROUGH INTRAMOLECULAR
1,3-DIPOLAR CYCLOADDITION IN IONIC LIQUID
MEDIUM
Subban Kathiravan and Raghavachary Raghunathan
Department of Organic Chemistry, University of Madras, Chennai, India
GRAPHICAL ABSTRACT
Abstract An ecofriently method for the synthesis of pyrrole-fused polycyclic heterocycles
through intramolecular 1,3-dipolar cycloaddition reaction of azomethine ylides derived from
pyrrole-2-carbaldehyde and secondary amino acids in ionic liquid [bmim][BF4] as green
solvent is reported.
Keywords Azomethine ylide; cycloaddition; heterocycles; ionic liquid; green solvents
INTRODUCTION
In recent years, ionic liquids as alternative reaction media have been frequently
reported in the literature.[1–3] Molten salts at ambient temperature that contain only
ions and no solvent are referred to as ‘‘ionic liquids.’’ They have been successfully
used in a variety of catalytic reactions as environmentally benign solvents and cata-
lysts because of their relatively low viscosities, low vapor pressure, and high thermal
and chemical stability.[4,5] Their nonvolatile nature can reduce the emission of toxic
organic compounds and facilitate the separation of products and=or catalysts from
the reaction solvents. They are used as green solvents for the immobilization of
transition-metal-based catalysts, Lewis acids, and enzymes.[6–8] Much attention
has been focused on the organic reactions with ionic liquids as catalysts or
solvents.[9–12] Many reactions such as Friedel–Crafts reactions,[13] arene
Received March 9, 2011.
Address correspondence to Raghavachary Raghunathan, Department of Organic Chemistry,
University of Madras, Guindy Campus, Chennai 600025, India. E-mail: ragharaghunathan@yahoo.com
147

148
S. KATHIRAVAN AND R. RAGHUNATHAN
Figure 1. Biologically active pyrrole alkaloids.
hydrogenation,[14] dimerizations of alkenes,[15] allylations of aldehydes,[16] Heck
reactions,[17] and Diels–Alder reactions[18] have been reported with good results,
indicating that use of ionic liquids as catalysts may be possible for those traditionally
important reactions. To our knowledge, there is no report in the literature on the
intramolecular 1,3-dipolar azomethine ylide cycloaddition reaction in ionic liquid
medium for the synthesis of pyrrolo[2,3-a]-pyrrolidines, pyrrolizidines, indolizidines
and isoquinolines. Herein, we report a simple and efficient protocol for the synthesis
of pyrrolo[2,3-a]pyrrolizidino derivatives using [bmim][BF4] as ionic liquid.
Nitrogen-containing heterocycles form the basic skeleton of numerous alka-
loids and physiologically active compounds.[19] The syntheses of polysubstituted
and fused pyrrolidines, pyrrolizidines, indazolidines, and isoquinoline ring systems
have received attention over the because since these heterocycles form the structural
subunits of biologically important alkaloids[20] and pharmaceutically important
compounds.[21]
1,3-Dipolar cycloaddition reaction is one of the most useful methods for the
preparation of five-membered heterocycles, and consequently, it has been extensively
studied.[22] In particular, the reaction of azomethine ylides[23] with alkenes provides
pyrrolidine ring systems that are the central skeleton of numerous alkaloids[24] and
physiologically active compounds.[25] The intramolecular version of this reaction
results in the formation of fused or bridged nitrogen-containing bicyclic systems
and generally occurs with high regio- and stereocontrol.[26–28]
In continuation of our research in cycloaddition chemistry,[29] we have
developed a simple method for the synthesis of pyrrolo[2,3-a]pyrrolidines, pyrrolizi-
dines, indolizidines, and isoquinolines using [bmim][BF4] as green solvent through
intramolecular 1,3-dipolar cycloaddition reactions from N-alkenyl pyrrole-2-
carbaldehyde. These systems are of interest because they are related to alkaloids such
as mirmicarin (1 and 2) and polyavolensin (3)[30] (Fig. 1)
RESULTS AND DISCUSSION
N-Alkenyl carboxaldehyde 5 was prepared from pyrrole-2-carbaldehyde by the
reported procedure as outlined in Scheme 1.[31]

PYRROLO[2,3-a]PYRROLIZIDINES
149
Scheme 1. Synthesis of N-cinnamyl pyrrole-2-carbaldehyde.
N-Alkenyl pyrrole-2-carbaldehyde (5), when treated with sarcosine (9) in
[Bmim][BF4] medium at 85–95 ꢀC for about 3 h, forms pyrrolopyrrolidines in good
yield (Scheme 2).
1
The formation of the product was established by spectroscopic data. The H
NMR spectrum of 6 exhibited a singlet at d 2.46 corresponding to N-methyl group.
The two –NCH2 protons appeared as multiplets in the ranges d 3.25–3.40 and d
3.42–3.51. The benzylic proton appeared as a triplet at d 4.11 with the coupling con-
stant value 9.6 Hz. A peak at d 3.92 was observed as a doublet with the coupling con-
stant value 4.8 Hz for the N-CH proton. The small value of the coupling constant
suggested a cis fusion at the ring junction. The pyrrole and aromatic ring protons
appeared in the regions d 5.92–6.49 and d 7.15–7.29 respectively. The 13C NMR
spectrum of 6 showed carbon signals at 50.45, 51.40, and 53.93 ppm for methylene
carbons. The pyrrole and aromatic carbons appeared at 98.94, 111.40, 112.08,
113.04, and 127.66, 128.16, 128.69 ppm respectively. To demonstrate the generality
of this reaction, we carried out the reaction of pyrrole-2-carbaldehyde with cyclic
secondary amino acids such as proline, pipecolinic acid, and isoquinolinic acid to
give the corresponding linearly fused pyrrolizidine, indolizidine, and isoquinoline
derivatives (Scheme 3).
The structures of all the products were determined by spectroscopic techniques
and confirmed by x-ray crystal analysis of one of the products (10).[32] The results
are tabulated in Table 1.
To compare the efficiency of this method, we carried out the reaction in various
organic solvents such as toluene, methanol, and acetonitrile. The reaction was slow
in organic solvents and afforded lesser yields of the desired products.
Scheme 2. Synthesis of N-methyl pyrrolo[2,3-a]pyrrolizidine.

150
S. KATHIRAVAN AND R. RAGHUNATHAN
Scheme 3. Synthesis of pyrrolo[2,3-a]pyrrolizidine, indolizidine, thiapyrrolizidine, and isoquinoline.
Figure 2. X-ray crystal structure of compound 10. (Figure is provided in color online.)
In conclusion, we have demonstrated that it is possible to carry out intramol-
ecular 1,3-dipolar cycloaddition in ionic liquid [bmim][BF4] as green and reusable
reaction medium. Separation of the final products could be done by simple extrac-
tion with organic solvents. In addition, the work described here has furnished a num-
ber of products of biological interest and offers a promising step for a synthetic
approach to natural products.

PYRROLO[2,3-a]PYRROLIZIDINES
151
Table 1. Synthesis of pyrrolo-[2,3-a]pyrrolizidino derivatives
N-Cinnamyl
pyrrole-2-
carbaldehyde
Time
(h)
Yieldb
(%)
Entry
Amino acid
Cycloadductsa
1
5
5
5
5
3.0
3.0
3.5
3.0
92
2
3
4
88
85
90
5
5
4.0
80
aIsolated products were characterized by 1H NMR, 13C NMR, mass spectra, and x-ray analysis.
EXPERIMENTAL
All melting points are uncorrected. Infrared (IR) spectra were recorded on a
Shimadzu Fourier transform (FT)–IR 8300 instrument. Mass spectra were recorded
1
on a Jeol DX 303 HF spectrometer with Maspec System (msw=9629). H and 13C
NMR were recorded in CDCl3 using tetramethylsilane (TMS) as internal standard
on a Bruker spectrometer at 300 and 75 MHz, respectively. Elemental analyses were
carried out on a Perkin-Elmer 2400 B instrument.
Representative Experimental Procedure for the Synthesis of
Cycloadducts 6–10
A mixture of N-cinnamyl pyrrole-2-carbaldehyde (0.2 g, 1 mmol) and the sec-
ondary amino acid (0.08 g, 1.1 mmol) in [bmim][BF4] (0.5 g) was placed in a
round-bottom flask (50 mL). The flask was then dipped in a oil bath preheated at
85–95 ꢀC. The homogenous mixture was stirred for about 3 h. After completion of
the reaction as evidenced by thin-layer chromatographic (TLC) analysis, the mixture

152
S. KATHIRAVAN AND R. RAGHUNATHAN
was cooled to rt and extracted with Et2O (2 ꢁ 10 mL). The ether layer was dried over
Na2SO4 and concentrated under reduced pressure. The residue obtained was
subjected to column chromatography using hexane and ethyl acetate as eluent.
Cycloadduct 6
1
Rf ¼ 0.6 (hexane–ethylacetate 95:5), light yellow liquid, yield 92%. H NMR
(300 MHz, CDCl3): d 2.46 (s, 3H), 2.56–2.64 (m, 1H), 3.25–3.40 (m, 2H), 3.42, 3.51
(m, 1H), 3.85–3.90 (m, 1H), 3.92 (d, J ¼ 4.8 Hz, 1H), 4.11(t, J ¼ 9.6 Hz, 1H), 5.92 (d,
J ¼ 3.6 Hz, 1H), 6.19 (d, J ¼ 2.4 Hz, 1H), 6.48 (t, J ¼ 1.2 Hz, 1H), 7.15–7.29 (m, 5H);
13C NMR (75 MHz, CDCl3): d 39.23, 50.45, 51.40, 53.93, 64.25, 67.06, 98.94, 112.08,
113.04, 125.74, 126.38, 127.66, 135.61, 141.30; m=z 237.5(Mþ). Elemental anal. calcd.
for C16H18N2: C, 80.67; H, 7.56; N, 11.76. Found: C, 80.53; H, 7.51; N, 11.82.
Cycloadduct 7
1
Rf ¼ 0.6 (hexane–ethylacetate 95:5), light yellow liquid, yield 88%. H NMR
(300 MHz, CDCl3): d 1.68–1.85 (m, 2H), 2.03–2.08 (m, 1H), 2.44 (s, 1H),
2.96–3.04 (m, 1H), 3.27–3.35 (m, 1H), 3.56–3.73(m, 2H), 3.81–3.84 (m, 2H),
4.04–4.07 (m, 1H), 4.09 (d, J ¼ 4.8 Hz, 1H), 6.04 (s, 1H), 6.27 (d, J ¼ 2.7 Hz, 1H),
6.50 (s, 1H), 7.26–7.35 (m, 5H); 13C NMR (75 MHz, CDCl3): d 25.63, 27.37,
48.01, 49.38, 52.17, 56.54, 69.16, 72.18, 99.78, 113.19, 113.61, 126.70, 127.99,
128.54, 139.14, 139.57; m=z 215.4 (Mþ). Elemental anal. calcd. for C18H20N2: C,
81.81; H, 7.57; N, 11.76. Found: C, 81.76; H, 7.50; N, 11.80.
Cycloadduct 8
Rf ¼ 0.6, (hexane–ethylacetate 95:5), light yellow solid, mp 95 ꢀC, yield 85%.
1H NMR (300 MHz, CDCl3); d 2.42–2.47 (m, 2H), 3.81–3.96 (m, 4H), 4.09–4.15
(m, 2H), 4.28–4.38 (m, 2H), 5.91 (s, 1H), 6.21 (s, 1H), 6.45 (s, 1H), 7.15–7.29 (m,
5H); 13C NMR (75 MHz, CDCl3): d 32.82, 47.78, 50.99, 52.99, 60.08, 64.08, 99.28,
109.93, 113.92, 114.08, 117.16, 127.24, 127.66, 128.62, 137.75, 138.57; m=z 281.3
(Mþ). Elemental anal. calcd. for C17H18N2S: C, 72.34; H, 8.38; N, 11.76. Found:
C, 72.21; H, 8.31; N, 11.79.
Cycloadduct 9
Rf ¼ 0.6 (hexane–ethylacetate 95:5), light yellow crystal, mp 110 ꢀC, yield 90%.
1H NMR (300 MHz, CDCl3): d 0.45–0.49 (m, 1H), 1.14–1.27 (m, 1H), 0.92–0.97 (m,
1H), 1.43–1.46 (m, 1H), 2.35–2.468 (m, 2H), 2.92–2.65 (m, 2H), 3.07–3.11 (m, 1H),
3.37–3.43 (m, 1H), 3.79 (d, J ¼ 3.0 Hz, 1H), 3.82 (d, J ¼ 3.0 Hz, 1H), 4.11 (q,
J ¼ 8.5 Hz, 1H), 4.74 (d, J ¼ 7.5 Hz, 1H), 5.85 (d, J ¼ 3.3 Hz, 1H), 6.19 (t, J ¼ 1.9 Hz,
Hz, 1H), 6.49 (q, J ¼ 1.2 Hz, 1H), 7.11–7.22 (m, 5H); 13C NMR (75 MHz, CDCl3): d
23.97, 25.30, 28.07, 48.88, 52.07, 53.40, 57.12, 62.63, 64.97, 102.22, 112.93, 114.06,
126.33, 128.04, 128.95, 134.34, 143.36; m=z 277.6 (Mþ). Elemental anal. calcd. for
C19H22N2: C, 82.01; H, 7.91; N, 11.76. Found: C, 81.91; H, 7.82; N, 11.84.

PYRROLO[2,3-a]PYRROLIZIDINES
153
Cycloadduct 10
Rf ¼ 0.6 (hexane–ethylacetate 95:5), light yellow crystal, mp 116 ꢀC, yield 80%. 1H
NMR (300MHz, CDCl3): d 1.17 (s, 1H), 1.61 (s, 1H), 2.60 (d, J ¼ 4.2 Hz, 1H), 2.31 (d,
J ¼ 4.2 Hz, 1H), 3.03–3.08 (m, 1H), 3.22–3.25 (m, 1H), 3.57–3.62 (m, 1H), 3.86–4.23 (m,
1H), 4.91 (d, J ¼ 7.2 Hz, 1H), 5.02 (d, J ¼ 5.7 Hz, 1H), 6.00 (s, 1H), 6.34 (s, 1H), 6.55 (s,
1H), 7.00–7.25 (m, 9H); 13C NMR (75 MHz, CDCl3): d 30.33, 49.63, 51.39, 51.99, 54.88,
58.48, 63.33, 101.80, 108.97, 111.98, 113.36, 125.62, 126.88, 127.34, 129.84, 131.77,
132.85, 132.91, 133.52, 135.21, 141.02. m=z 335.8 (Mþ). Elemental anal. calcd. for
C23H22N2: C, 85.11; H, 6.54; N, 11.76. Found: C, 85.02; H, 6.50; N, 11.83.
ACKNOWLEDGMENTS
S. K. thanks the Council of Scientific Industrial and Research for a senior
research fellowship. S. K. and R. R. thank for the Department of Science and
Technology–Funding for Infrastructure in Science and Technology for the NMR
facility and financial assistance.
REFERENCES
1. Earle, M. J.; McCormac, P. B.; Seddon, K. R. Diels–Alder reactions in ionic liquids: A
safe recyclable alternative to lithium perchlorate–diethyl ether mixtures. Green Chem.
1999, 1, 23–25.
2. Kitazume, T.; Kasai, K. The synthesis and reaction of zinc reagents in ionic liquids. Green
Chem. 2001, 3, 30–32.
3. Owens, G. S.; Abu-Omar, M. M. Methyltrioxorhenium-catalyzed epoxidations in ionic
liquids. Chem. Commun. 2000, 1165–1166.
4. Ranu, B. C.; Banerjee, S. Ionic liquid as catalyst and reaction medium: The dramatic inf-
lence of a task-specific ionic liquid [bmim]OH in Michael addition of active methylene
compounds to conjugated ketones, carboxylic esters and nitriles. Org. Lett. 2005, 7,
3049–3052.
5. Predel, T.; Schlucker, E.; Wasserscheid, P.; Gerhard, D.; Arlt, W. Ionic liquids as operat-
ing fluids in high pressure applications. Chem. Eng. Technol. 2007, 30, 1475–1480.
6. Dubreuil, J. F.; Bazureau, J. P. Rate accelerations of 1,3-dipolar cycloaddition reactions
in ionic liquids. Tetrahedron Lett. 2000, 41, 7351–7355.
7. Kragl, U.; Eckstein, M.; Kaftzik, N. Enzyme catalysis in ionic liquids. Curr. Opin.
Biotechnol. 2002, 13, 565–571.
8. Dubreuil, J. F.; Bourahla, K.; Rahmouni, M.; Bazureau, J. P.; Hamelin, J. Catalysed
esterifications in room temperature ionic liquids with acidic counteranion as recyclable
reaction media. Catal. Commun. 2002, 3, 185–190.
9. Carmichael, A. J.; Earle, M. J.; Holbrey, J. D.; McCormac, P. B.; Seddon, K. R.
The Heck reaction in ionic liquids: A multiphasic catalyst system. Org. Lett. 1999, 1,
997–1000.
10. Gordon, C. M. New developments in catalysis using ionic liquids. Appl. Catal. A 2001,
222, 101–117.
11. Zimmerman, H. E.; Wang, P. A. The regioselectivity of the Birch reduction. J. Am.Chem.
Soc. 1993, 115, 2205–2216.
12. Li, S.; Lin, Y.; Xie, H.; Zhang, S.; Xu, J. Bronsted guanidine acid–base ionic liquids: Novel
reaction media for the palladium-catalyzed Heck reaction. Org. Lett. 2006, 8, 391–394.

154
S. KATHIRAVAN AND R. RAGHUNATHAN
13. Boon, J. A.; Levisky, J. A.; Pflug, J. L.; Wilkes, J. S. Friedel–Crafts reactions in ambient
temperature molten salts. J. Org. Chem. 1986, 51, 480–483.
14. Anderson, K.; Goodrich, P.; Hardacre, C.; Rooney, D. W. Heterogeneously catalysed
selective hydrogenation reactions in ionic liquids. Green Chem. 2003, 5, 448–453.
15. Ellis, B.; Keim, W.; Wasserscheid, P. Linear dimerisation of but-1-ene in biphasic mode
using buffered chloroaluminate ionic liquid solvents. Chem. Commun. 1999, 337–338.
16. Gordon, C. M.; McCluskey, A. Ionic liquids, a convenient solvent for environmentally
friendly allylation reactions with tetraallylstannane. Chem. Commun. 1999, 1431–1432.
17. Bohm, V. P. W.; Herrmann, W. A. Nonaqueous ionic liquids: Superior reaction media for
the catalytic Heck vinylation of chloroarenes. Chem. Eur. J. 2000, 6, 1017–1025.
18. Fischer, T.; Sethi, A.; Welton, T.; Woolf, J. Diels–Alder reactions in room-temperature
ionic liquids. Tetrahedron Lett. 1999, 40, 793–796.
19. (a) Southen, J. W.; Buckingham, J. (Eds.). Dictionary of Alkaloids; Chapman & Hall: New
York, 1980.
20. (a) Daly, J. W.; Garro, H. M.; Spande, T. F. In Alkaloids: Chemical and Biological
Perspectives; S. W. Pelletier (Ed.); Pergamon Press: New York, 1999; Vol. 13, p. 1. (b)
Daly, J. W. In The Alkaloids; G. A. Cordell (Ed.); Academic Press: New York, 1998;
Vol. 50, p. 141; (c) Denes, F.; Beaufils, F.; Renaud, P. Thiophenol-mediated 1,5-hydrogen
transfer for the preparation of pyrrolizidines, indolizidines, and related compounds. Org.
Lett. 2007, 9, 4375–4378; (d) Broggini, G.; Zecchi, G. Pyrrolizidine and indolizidine synth-
eses involving 1,3-dipolar cycloadditions Synlett. 1999, 905–917.
21. Sternfeld, F.; Guiblin, A. R.; Jelley, R. A.; Matassa, V. G.; Reeve, A. J.; Hunt, P. A.; Beer,
M. S.; Heald, A.; Stanton, J. A.; Sohal, B.; Watt, A. P.; Street, L. J. Synthesis and sero-
tonergic activity of 3-f2-(pyrrolidine-1-yl)ethyl]indoles: Potnet agonists for the h5-HT1D
receptor with high selectivity over the h5-HT1B. J. Med. Chem. 1999, 42, 677–690.
22. (a) Curruthers, W. In Cycloaddition Reaction in Organic Synthesis; Pergamon Press:
Oxford, 1990; vol. 8, p. 269; (b) Padwa, A. In Comprehensive Organic Synthesis; Pergamon
Press: Oxford, 1991; vol. 4, p. 1069.
23. (a) Cravoto, G.; Giovenzana, G. B.; Pilati, T.; Sisti, M.; Palmisano, G. Azomethine ylide
cycloaddition=reductive heterocyclization approach to oxindole alkaloids—Asymmetric
synthesis of (ꢂ)-horsfiline. J. Org. Chem. 2001, 66, 8447–8453; (b) Pandey, G.; Banerjee,
P.; Kumar, R.; Puranik, V. G. Stereospecific route to 5,11-methanomphanathridine alka-
loids via intramolecular 1,3-dipolar cycloaddition of nonstabilized azomethine ylide:
Formal total synthesis of pancracine. Org. Lett. 2005, 7, 3173–3176.
24. Southon, I. W.; Buckingham, J. (Eds.); Dictionary of Alkaloids; Chapman and Hall:
New York, 1989.
25. Jensen, K. B.; Roberson, M.; Jorgensen, K. A. Catalytic enantioselective 1,3-dipolar
cycloaddition reactions of cyclic nitrones: A simple approach for the formation of opti-
cally active isoquinoline derivatives. J. Org. Chem. 2000, 65, 9080–9084.
26. Wade, P. A. In Comprehensive Organic Synthesis; Pergamon Press: Oxford, 1991; vol. 4,
p. 1111.
27. DeShong, P.; Kell, D. A. R. Intermolecular and intramolecular azomethine ylide [3 þ 2]
dipolar cycloadditions for the synthesis of highly functionalized pyrroles and pyrrolidines.
J. Org. Chem. 1985, 50, 2309–2315.
28. Overman, L. E.; Tellew, J. E. Synthesis of 2-azatricyclo[5.2.1.04,10]decanes and 2,5-diaza-
tricyclo[5.2.1.04,10] decanes by intramolecular azomethine ylide cycloadditions. J. Org.
Chem. 1996, 61, 8338–8340.
29. (a) Kathiravan, S.; Raghunathan, R. Synthesis of macrocyclic bis-imidazolidine deriva-
tives through [3 þ 2] cycloaddition reaction. Synlett. 2009, 1126–1129; (b) Suresh Babu,
A. R.; Raghunathan, R.; Satiskumar, B. K. A facile synthesis of ferrocene grafted N-
methyl-spiropyrrolidines through 1,3-dipolar cycloaddition of azomethine ylides. Tetra-

PYRROLO[2,3-a]PYRROLIZIDINES
155
hedron Lett. 2009, 50, 2818–2821; (c) Poornachandran, M.; Raghunathan, R. Synthesis of
pyrrolo[3,4-b]pyrroles and perhydrothiazolo[30,40-2,3]pyrrolo[4,5-c]pyrroles. Tetrahedron
2008, 64, 6461–6474; (d) Poornachandran, M.; Raghunathan, R. A novel diastereoselec-
tive 1,3-dipolar cycloaddition approach to cis-fused bispyrrolidines. Tetrahedron: Asym-
metry 2008, 19, 2177–2183; (e) Kathiravan, S.; Ramesh, E.; Raghunathan, R. Synthesis
of pyrrolo[2,3-a]pyrrolizine and pyrrolizine[2,3-a]pyrrolizine derived from allyl derivatives
of Baylis–Hillman adducts through intramolecular 1,3-dipolar cycloaddition. Tetrahedron
Lett. 2008, 50, 2389–2391.
30. Schro¨der, F.; Franke, S.; Francke, W.; Baumann, H.; Kaib, M.; Pasteels, J. M.; Daloze,
D. A new family of tricyclic alkaloids from Myrmicaria ants. Tetrahedron 1996, 52, 13539–
13546.
31. (a) Falshaw, C. P.; Kinf, T. J.; Okorie, D. A. Revised structure of polyavolensin and its
analogues. Tetrahderon 1982, 38, 2311–2313; (b) Broggini, G.; Rosa, C. L.; Pilati, T.;
Terraneo, A.; Zecchi, G. Regiochemical aspects of intramolecular cycloadditions of
nitrones derived from N-(2-alkenyl)2-pyrrolecarbaldehydes: Competitive entries to pyrro-
lizidine and indolizidine derivatives. Tetrahedron 2001, 57, 8323–8332.
32. Gunasekaran, B.; Kathiravan, S.; Raghunathan, R.; Renuga, V.; Manivannan, V.
6-Phenyl-5a,6,6a,7,12,13a-hexahydro-5H-benzo[6,7]indolizino[3,2-a]pyrrolizine. Acta Cryst.
2009, E65, o1454.