Organic Letters
Letter
Scheme 5. Plausible Mechanism
migratory insertion of alkene−1,4-Pd shift−relay Heck manner.
In this transformation, allyl alcohol could proceed smoothly,
providing 5a in 67% isolated yield. In addition, the length of the
chain between the alcohol and alkene minimally affects the
efficiency of the relay Heck reaction. Excellent yields could be
obtained with an increased chain length (5b and 5c). Next, the
electronic effect on the phenyl group linked to the alkene was
also evaluated. Electron-withdrawing group CF3 accelerated the
reaction, while electron-donating substituent OMe provided a
slightly decreased yield of the desired product (5d and 5e).
Synthetically versatile substituents on the oxindole backbones
such as F, Cl, and Br groups were examined in this
transformation. All of these groups could be employed to give
the desired products in moderate to good yields (5f−5h,
respectively); the fluorine group vicinal to the tethered alkene
might affect the first insertion step, while the modest yield of 5f
is likely due to disfavored steric hindrance.
proceed through different pathways depending on the nature of
the ingredient to afford 3,3-disubstituted oxindoles bearing an
all-carbon quaternary center alkene and aldehyde functional
group. This tranformation is distinguished by its multiple
reactivities and broad functional group tolerance, which might
establish a complementary approach to the synthesis of some
useful pharmaceutical scaffolds.
ASSOCIATED CONTENT
* Supporting Information
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The Supporting Information is available free of charge at
Detailed experimental procedures, characterization data,
and copies of NMR spectra (PDF)
FAIR data, including the primary NMR FID files, for
compounds 1b−1n, 1′b, 1′f−1′h, 3a−3u, 4a−4k, 5a−
On the basis of the experimental results, we propose the
following reaction pathways (Scheme 5). First, oxidative
addition of carbamoyl chloride to Pd(0) formed A, which
subsequently proceeded via the intramolecular migratory
insertion into the tethered alkene to generate alkylpalladium
species B. When the R group on B was an alkyl substituent, the
existence of another olefinic counterpart led to the sequential
intermolecular migratory insertion, followed by the β-H
elimination to provide the oxindole product 3, and the reactive
Pd(0) intermediate was regenerated via the reductive
elimination step (circle I). Moreover, when the R group on
intermediate B was an aromatic ring, the reaction proceeded via
path II. Intramolecular C−H activation of alkylpalladium with a
phenyl group on an alkene resulted in a 1,4-Pd migration to
afford intermediate C, which then could be trapped by alkene
via intermolecular Heck reaction to furnish product 4.
Alternatively, when alkenols were used as the olefin counterpart
to participate in this reaction, intermediate E was originally
formed from species D, which then proceeded via the fast
reinsertion of the Pd−H reactive intermediate to initiate the
final relay Heck process. Aldehyde 5 was obtained to finish the
whole domino process.
AUTHOR INFORMATION
Corresponding Authors
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Jingping Qu − Key Laboratory for Advanced Materials and Joint
International Research Laboratory of Precision Chemistry and
Molecular Engineering, Feringa Nobel Prize Scientist Joint
Research Center, Frontiers Science Center for Materiobiology and
Dynamic Chemistry, School of Chemistry and Molecular
Engineering, East China University of Science & Technology,
Yifeng Chen − Key Laboratory for Advanced Materials and Joint
International Research Laboratory of Precision Chemistry and
Molecular Engineering, Feringa Nobel Prize Scientist Joint
Research Center, Frontiers Science Center for Materiobiology and
Dynamic Chemistry, School of Chemistry and Molecular
Engineering, East China University of Science & Technology,
Authors
In summary, we have developed an efficient and intriguing
protocol for the construction of various useful oxindole
scaffolds via a Pd-catalyzed cascade intramolecular cyclization
and versatile intermolecular Heck reaction of easily accessible
carbamoyl chlorides with simple alkenes. The reaction can
Xianqing Wu − Key Laboratory for Advanced Materials and
Joint International Research Laboratory of Precision Chemistry
and Molecular Engineering, Feringa Nobel Prize Scientist Joint
Research Center, Frontiers Science Center for Materiobiology
and Dynamic Chemistry, School of Chemistry and Molecular
D
Org. Lett. XXXX, XXX, XXX−XXX