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Organic Letters
Letter
the formation of spirocyclopentene 3aa in a 2.5:1 ratio (Table
2, entry 1). Only the two annulation products (3aa and 14aa)
were observed as products in this competition reaction.
Switching to allyl(tri-isopropyl)silane 13b, a competition
experiment with 2a reversed selectivity with spirocyclopentane
14ab produced at a faster rate in a 2.4:1 ratio (entry 2). The
competition between allyl(tri-isopropyl)silane 13b and allenyl-
(tri-isopropyl)silane 2b also indicated enhanced nucleophil-
icity for the allylsilane, with product 14ab again forming at a
faster rate than 3ab in a 2.8:1 ratio (entry 3). The trend from
these initial data suggests that an allenylsilane is more
nucleophilic with a smaller silyl group (SiEt3), while an
allylsilane is more nucleophilic with a larger silyl group (Si(i-
Pr)3). Although not a large effect, the reversal in relative rates
may suggest a different mechanistic pathway is followed for the
allenylsilane and allylsilane in this reaction. While the
allylsilane annulation proceeds via formation of a β-stabilized
carbocation intermediate (via a 1,2-silyl shift),29a−c which is
favored for large silyl groups,29d the allenylsilane annulation
may proceed via a concerted cycloaddition that is more
favorable for the smaller silyl group.28
In conclusion, we have shown the utility of allenylsilanes to
access cyclopentene-spirooxindoles in high yield and selectivity
with a chiral scandium catalyst. This methodology favors the
annulation pathway (vs propargylation). Competition experi-
ments comparing the nucleophilicity of allenylsilanes and
allylsilanes demonstrate that both the π-system and the size of
the silyl group affect the relative rate and product distribution
for these annulation reactions and suggest that different
mechanistic pathways may be operative. The vinylsilane affords
a versatile functional group to further modify the spirooxindole
scaffold for potential applications in medicinal chemistry.
ACKNOWLEDGMENTS
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We acknowledge the American Chemical Society Petroleum
Research Fund, ACS-PRF (49I8I-DNI1 and 56230-ND1), for
partial support of this research. We acknowledge the National
Science Foundation (DBIO/722538) for funding the 800
MHz NMR spectrometer.
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ASSOCIATED CONTENT
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Accession Codes
CCDC 1941096−1941097 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
■
Corresponding Author
ORCID
James C. Fettinger: 0000-0002-6428-4909
Annaliese K. Franz: 0000-0002-4841-2448
Notes
The authors declare no competing financial interest.
D
DOI: 10.1021/acs.orglett.9b02852
Org. Lett. XXXX, XXX, XXX−XXX