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treated in acidic medium (Lewis and Brønsted acids), and provided
spiro-oxindolopyrroloisoquinolines via stable N-acyliminium spe-
cies with high stereocontrol.
Finally, we anticipate that the transformations developed in this
project, particularly the access to spiro-oxindoles containing c-lac-
tams, will find further applications in total synthesis of bioactive
alkaloids. These systems are currently under investigation in our
group, and the results will be reported soon in full account.
16. For
a recent and elegant use of o-nitrofluorobenzene derivatives for the
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18. Unreacted starting materials 6a and 6b were recovered in all the cases.
19. Wiseman, E. H.; Chiaini, J.; McManus, J. M. J. Med. Chem. 1973, 16, 131–134.
20. Full crystallographic data have been deposited at the Cambridge
Crystallographic Data Center (CCDC reference number 698963 for spiro-
oxindole product 2c. Copies of the data can be obtained free of charge at the
Acknowledgments
The authors are grateful to the Syrian Government and the
Pharmaceutical University of Damascus for the Graduate Fellow-
ship (2006–2009) attributed to one of us, Iyad Allous. Financial
support by the Slovak Grant Agency No. 1/0629/08 is also grate-
fully acknowledged. We also wish to thank our colleague Morgane
Sanselme from the University of Rouen in France for the X-ray
analysis of compound 2c. We would also like to thank our col-
league Dawn Hallidy for her technical contribution throughout
the course of this work.
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706–715.
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26. Typical procedure for the synthesis of pentacyclic spiro-oxindoles 8 and 9: BF3ꢁOEt2
(50 lL, 0.36 mmol) or TFA (70 lL, 0.7 mmol) was added at rt to a solution of
hydroxy-lactam 14 or 15 (0.18 mmol) in CH2Cl2 (2 mL). After 12 h of the
reaction, the solution was cooled to 0 °C and quenched carefully by addition of
an aqueous saturated solution of NaHCO3 (10 mL). The aqueous layer was
extracted with CH2Cl2 (3 ꢂ 10 mL), the organic layers were combined, dried
over MgSO4, and evaporated to dryness. The residue was then purified by
chromatography on silica gel column using a mixture of AcOEt/cyclohexane as
eluent. Data for a representative pentacyclic spiro-oxindole product 9d: 1H
NMR (200 MHz, CDCl3): 2.61–2.85 (m, 1H), 2.75 (d, 1H, J = 16.4 Hz), 3.01 (s,
3H), 2.86–3.21 (m, 2H), 3,01 (d, 1H, J = 16.4 Hz), 4.50 (dd, 1H, J = 3.3 and
12.5 Hz), 5.21 (s, 1H), 6.06 (d, 1H, J = 7.0 Hz), 6.83 (d, 2H, J = 7.8 Hz), 7.07 (d, 2H,
J = 3.9 Hz), 7.17–7.46 (m, 3H). 13C NMR (50 MHz, CDCl3): 25.8, 28.9, 37.3, 41.3,
53.9, 64.0, 108.5, 122.9, 123.3, 123.6, 126.1, 127.4, 128.9, 129.5, 131.9, 135.4,
144.3, 170.5, 176.1.
27. NMR spectra were recorded on an INOVA 600 Varian spectrometer in CDCl3
solution. Chemical shifts (d) are quoted in ppm, and are referenced to the
tetramethylsilane (TMS) as the internal standard. The COSY and NOESY-1D
techniques were used for the assignment of 1H–1H relationships and the
determination of relative configuration. The HSQC and HMBC techniques were
used throughout for the assignment of the 1H–13C relationships.
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