LETTER
Synthesis of Functionalized 3-Spiropyrrolidines and 3-Spiropyrrolizidines
1017
Hz), 4.78 (t, 1 H, J = 5.4 Hz), 5.29 (s, 1 H), 6.72–7.52 (m, 10 H).
13C NMR (75 MHz, CDCl3): d = 25.04, 27.69, 48.50, 59.23, 65.28,
69.60, 73.67, 104.73, 110.22, 122.73, 125.31, 126.25, 128.33,
128.96, 129.43, 130.01, 131.79, 141.40, 178.87. MS: m/z = 380
[M+ + 1]. Anal. Calcd for C21H21N3O4: C, 66.48; H, 5.58; N, 11.08.
Found: C, 66.42; H, 5.49; N, 11.16.
O
Hb
Ha
N
NH
O2N
HO
7d
Acknowledgment
Figure 4
We thank DST (New Delhi) for the financial support under fast
track scheme for the young scientists. We thank DST-FIST for the
funding program at the Department of Organic Chemistry, Univer-
sity of Madras, Chennai.
Typical Experimental Procedure of 6a
A mixture of (E)-2-nitro-3-phenylprop-2-en-1-ol (5a, 2 mmol, 0.36
g), isatin (2 mmol, 0.29 g), and sarcosine (2 mmol, 0.18 g) in MeCN
(8 mL) was refluxed for 5 h. After the completion of the reaction as
indicated by TLC, the reaction mixture was concentrated, and the
resulting crude mass was diluted with H2O (10 mL) and extracted
with EtOAc (3 × 10 mL). The combined organic layers were
washed with brine (2 × 10 mL) and dried over anhyd Na2SO4. The
organic layer was concentrated and the residue purified by column
chromatography on SiO2 (Acme 100–200 mesh), using EtOAc–
hexanes (2:8) to afford 6a as a colorless solid in 82% (0.58g) yield.
References and Notes
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8001.
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Ed.; Wiley: New York, 1997, 201–350.
(6) Jossang, A.; Jossang, P.; Hadi, H. A.; Sevenet, T.; Bodo, B.
J. Org. Chem. 1991, 56, 6527.
Typical Experimental Procedure of 7a and 8a
A mixture of (E)-2-nitro-3-phenylprop-2-en-1-ol (5a, 2 mmol, 0.36
g), isatin (2 mmol, 0.29 g), and L-proline (2 mmol, 0.23 g) in MeCN
(8 mL) was refluxed for 2 h. After the completion of the reaction as
indicated by TLC, the reaction mixture was concentrated, and the
resulting crude mass was diluted with H2O (20 mL) and extracted
with EtOAc (3 × 10 mL). The combined organic layer obtained was
washed with brine (3 × 10 mL) and dried over anhyd Na2SO4. The
organic layers were concentrated and purified by column chroma-
tography on SiO2 (Acme 100–200 mesh), using EtOAc–hexanes
(3:7) to provide 7a as a colorless solid in 52% (0.11 g) yield and 8a
as a colorless solid (Acme 100–200 mesh), using EtOAc–hexanes
(4:6) in 33% (0.07 g) yield.
(7) James, M. N. G.; Williams, G. J. B. Can. J. Chem. 1972, 50,
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J. Antibiot. 1996, 49, 527.
(10) (a) De Amici, M.; De Michelli, C.; Sani, V. M. Tetrahedron
1990, 46, 1975. (b) Early, W. G.; Oh, T.; Overman, L. E.
Tetrahedron Lett. 1988, 29, 3785. (c) Kozikowski, A. P.
Acc. Chem. Res. 1984, 17, 410. (d) Ban, Y.; Taga, N.; Oishi,
T. Chem. Pharm. Bull. 1976, 24, 736. (e) Van Tamlen,
E. E.; Yardley, J. P.; Miyano, M.; Hinshaw, W. B. Jr. J. Am.
Chem. Soc. 1969, 26, 7333. (f) Howe, R. K.; Shelton, B. R.
J. Org. Chem. 1990, 55, 4603. (g) Cohen, V. L.; Kleinman,
E. E. WO 24, 398, 1995; Chem. Abstr. 1995, 122, 20667j.
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1974, 15, 187. (j) Caroll, W. A.; Grieco, P. A. J. Am. Chem.
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Spectroscopic Data for Selected Compounds
Compound 6a
Mp 160–162 °C. IR (KBr): 3484, 3227, 1717, 1544, 1337 cm–1. 1H
NMR (300 MHz, CDCl3): d = 2.18 (s, 3 H), 2.89 (dd, 1 H, J = 2.7,
9.0 Hz), 3.53 (t, 1 H, J = 9.0 Hz), 3.78 (dd, 1 H, J = 3.0, 10.5 Hz),
3.90–4.07 (m, 2 H), 4.97 (t, 1 H, J = 9.0 Hz), 6.82–7.57 (m, 9 H),
7.74 (s, 1 H). 13C NMR (75 MHz, CDCl3): d = 34.77, 49.40, 56.78,
64.17, 77.23, 105.05, 110.15, 123.38, 124.46, 125.20, 128.18,
128.78, 129.99, 130.48, 134.75, 141.55, 176.06. MS: m/z = 354 [M+
+ 1]. Anal. Calcd for C19H19N3O4: C, 64.58; H, 5.42; N, 11.89.
Found: C, 64.56; H, 5.39; N, 11.94.
(11) Ding, K.; Lu, Y.; Nikolovska-Coleska, Z.; Wang, G.; Qiu,
S.; Shangary, S.; Gao, W.; Qin, D.; Stuckey, J.; Krajewski,
K.; Roller, P. P.; Wang, S. J. Med. Chem. 2006, 49, 3432.
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Lett. 2000, 2, 2639.
Compound 7a
Mp 148–150 °C. IR (KBr): 3463, 3197, 1709, 1540, 1336 cm–1. 1H
NMR (300 MHz, CDCl3): d = 1.50–1.62 (m, 1 H), 1.87–2.10 (m, 3
H), 2.48–2.56 (m, 1 H), 2.69–2.76 (m, 1 H), 3.87 (t, 1 H, J = 12.0
Hz), 4.27 (d, 1 H, J = 10.2 Hz), 4.39–4.56 (m, 2 H), 4.95 (dd, 1 H,
J = 3.6, 8.1 Hz), 6.87–7.81 (m, 10 H). 13C NMR (75 MHz, CDCl3):
d = 27.88, 32.74, 47.89, 56.59, 64.51, 69.88, 78.03, 105.54, 111.22,
122.96, 124.98, 125.52, 127.99, 128.56, 130.70, 130.88, 134.19,
140.86, 179.78. MS: m/z = 380 [M+ + 1]. Anal. Calcd for
C21H21N3O4: C, 66.48; H, 5.58; N, 11.08. Found: C, 66.41; H, 5.46;
N, 11.14.
(13) Zeni, G.; Larock, R. C. Chem. Rev. 2006, 106, 4644.
(14) Basavaiah, D.; Roy, S. Org. Lett. 2008, 10, 1819.
(15) Savitha, G.; Niveditha, S. K.; Muralidharan, D.; Perumal,
P. T. Tetrahedron Lett. 2007, 48, 2943.
(16) (a) Muthusamy, S.; Gunanathan, C.; Babu, S. A.
Tetrahedron Lett. 2001, 42, 523. (b) Shanmugam, P.;
Viswambharan, B.; Madhavan, S. Org. Lett. 2007, 9, 4095.
(17) Coldham, I.; Hufton, R. Chem. Rev. 2005, 105, 2765.
(18) (a) Pandey, G.; Banerjee, P.; Gadre, S. R. Chem. Rev. 2006,
106, 4484. (b) Petrovskaia, O.; Taylor, B. M.; Hauze, D. B.;
Carroll, P. J.; Joullie, M. M. J. Org. Chem. 2001, 66, 7666.
(c) Fokas, D.; Ryan, W. J.; Casebier, D. S.; Coffen, D. L.
Tetrahedron Lett. 1998, 39, 2235. (d) Ghandi, M.; Rezaei,
S. J. T.; Yari, A.; Taheri, A. Tetrahedron Lett. 2008, 49,
5899. (e) Panja, S. K.; Karmakar, P.; Chakraborty, J.;
Compound 8a
Mp 170–172 °C. IR (KBr): 3467, 3185, 1709, 1535, 1345 cm–1. 1H
NMR (300 MHz, CDCl3): d = 1.38–1.50 (m, 1 H), 1.80–2.05 (m, 2
H), 2.71–2.31 (m, 2 H), 2.67 (td, 1 H, J = 2.4, 5.4 Hz), 3.26 (q, 1 H,
J = 8.4 Hz), 4.15 (dd, 1 H, J = 4.5, 8.7 Hz), 4.49 (t, 1 H, J = 10.5
Synlett 2009, No. 6, 1014–1018 © Thieme Stuttgart · New York