ORGANIC
LETTERS
2012
Vol. 14, No. 18
4810–4813
Synthesis of Enantiomerically Enriched
3‑Amino-2-oxindoles through a
Palladium-Mediated Asymmetric
Intramolecular Arylation of
r‑Ketimino Amides
€
Paivi Tolstoy, Samantha X. Y. Lee, Christof Sparr, and Steven V. Ley*
Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW,
United Kingdom
Received July 31, 2012
ABSTRACT
A highly efficient and enantioselective synthesis of 3-amino-2-oxindoles through a palladium-catalyzed asymmetric intramolecular arylation of
R-ketimino amides using (R)-DiFluorPhos as the coordinating ligand is reported. This report constitutes the first enantioselective palladium-
catalyzed arylation of ketimines.
Oxindoles bearing a tetrasubstituted carbon stereocenter
at the 3-position are common motifs in natural products
and in pharmaceutically interesting lead compounds.1
Recently, 3-amino-2-oxindoles have been reported to be
biologically active against a variety of targets including
anxiety and depression (SSR149415)2 as well as a gastrin/
CCK-B receptor agonist (AG-041R)3 and an antimalarial
agent (NITD609)4 (Figure 1). Although this subclass is
clearly important, relatively few methods have been de-
scribed to construct enantiomerically enriched 3-amino-2-
oxindoles.5 While the catalytic enantioselective R-amina-
tion of prochiral isatins catalyzed by chiral scandium
complexes,6 chiral Schiff baseÀnickel complexes,7 and
cinchona alkaloid analogs8 have been reported to proceed
with high enantioselectivity, further routes are needed to
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10.1021/ol302119j
Published on Web 09/04/2012
2012 American Chemical Society