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Formation of Spiroindolinone–Isoindolinone
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Conclusions
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In summary, we have demonstrated an efficient Pd-cata-
lyzed Buchwald–Hartwig addition–elimination sequence for
the construction of the spiroindolinone–isoindolinone
framework. The reaction occurred under relatively mild
conditions with a broad substrate scope and good to excel-
lent yields. The control experiments provide support for the
proposed mechanism. Further, application of this protocol
for cascade cyclization by using dehydrogenative coupling
is under investigation (Scheme 2b).[9]
Experimental Section
General Procedure for the Pd-Catalyzed Cascade Cyclization: To a
screw-cap vial were added Ugi product 5a–v (0.2 mmol), Pd(OAc)
(5 mol-%), Xantphos (5 mol-%), and Cs2CO3 (2 equiv.), along
2
with dry toluene (3 mL). The reaction vial was then evacuated and
back-filled with N2 (five times), and the reaction mixture was
stirred at 120 °C for 15–20 h. After completion of the reaction, the
mixture was diluted with EtOAc (100 mL) and extracted with water
(50 mL). The organic layer was washed with brine (50 mL), dried
with magnesium sulfate, and concentrated under reduced pressure
to obtain a residue, which was subjected to silica gel column
chromatography (20–40% ethyl acetate in heptane) to afford the
desired product 6a–v.
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2, 632.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures, spectroscopic data, and copies of
1
the H NMR and 13C NMR spectra.
Acknowledgments
Support was provided by the research fund of the University of
Leuven (KU Leuven) and the Fund for Scientific Research-Flan-
ders, Belgium (FWO). D. D. V. thanks KU Leuven for providing a
post-doctoral scholarship. H. H. B. thanks Erasmus Mundus Ex-
perts 2 for providing a visiting doctoral fellowship.
[1] For selected reviews on the spirooxindole core as a privileged
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[9] Employment of the Ugi adduct 5v, derived from the electron
deficient 4-nitrobenzoic acid, yielded 15% of the desired prod-
uct 6v. This might point to a Pd-catalyzed ring closure em-
ploying C-H activation for the upper spiro ring. This work is
under current investigation.
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Received: July 11, 2014
Published Online:
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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