Organic Letters
Letter
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reaction with a salicylamide compound as the substrate. The
salicylamide demonstrated difficulty in forming the enone
intermediate in the reaction, but it does not hinder forming the
C−O bond, providing an up to 80% isolated yield of the
cyclized product (see Scheme 1D). This reaction has been
reported by the Maiti group using a Cu/O2 catalytic system, but
it failed to proceed under N2.10
The results presented clearly show that the hydrogen of
electron-rich C−H bonds may be viewed as leaving group
equivalents and can be substituted by nucleophilic reagents in
the presence of palladium(0). These findings provide new
access to C−H functionalization directly through C−H bond
hydrogen substitution without oxidants, hydrogen acceptors,
and substrate prefunctionalization. Furthermore, these reac-
tions being without oxidants and hydrogen acceptors circum-
vent the intrinsic reaction complications normally associated
with oxidative C−H functionalization and also avoid the
byproducts from oxidants, hydrogen acceptors, and C−H bond
coupling partners. The novel use of palladium(0) in place of
high valence state palladium as the catalyst and the realization
of ζ-hydride elimination play crucial roles in this trans-
formation. These reactions for flavonoid synthesis exhibit
high isolated yields, functional-group tolerance, and atom
economy. Taken together, the broad substrate scope and
applications and the use of minimum quantities of additives as
well as a simple and recycled catalyst in these transformations
make the substitution C−H functionalization strategy for
organic synthesis intrinsically easy for industrial applications. As
an effective complement to the current dehydrogenative
synthetic methods, the protocol represents a significant step
forward in the constant search for more streamlined and
greener chemical synthesis.
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ASSOCIATED CONTENT
* Supporting Information
■
S
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The Supporting Information is available free of charge on the
Experimental details for chemical synthesis of all
compounds, materials, supplementary text, and NMR
AUTHOR INFORMATION
■
Corresponding Author
ORCID
Author Contributions
†X.Z. and J.Z. contributed equally to this work.
(10) Modak, A.; Dutta, U.; Kancherla, R.; Maity, S.; Bhadra, M.;
Mobin, S. M.; Maiti, D. Org. Lett. 2014, 16, 2602.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We gratefully acknowledge the National Natural Science
Foundation of China (Grants 21072055) for financial support.
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