10.1002/anie.202004441
Angewandte Chemie International Edition
RESEARCH ARTICLE
employing the classical Parr-Knorr procedures,[31] 22a could be
distinctive reaction mechanism, which involves a C–H activation
event prior to the oxidative addition step, in clear contrast to the
previously reported mechanisms that usually commence with the
generation of an acyl nickel species by oxidative addition. This
work will serve as a key starting point to further investigate the
cross-sections of amide catalysis and C(sp3)–H bond activation,
enabling novel functionalization reactions which are inaccessible
by traditional approaches.
transformed into
a
series of 2,5-diaryl 5-membered
heteroaromatics in good yields (24–26), of which the utilities
span over various fields of chemistry.[32] Furthermore, double
aldol condensation with phthalaldehyde furnished the naphthyl-
o-diketone product 27, which is a basic building block in
naphtho[c]thiophene synthesis used for photochemical and
electronic materials.[33] To our delight, the direct, selective
syntheses of valuable α-amino ketone derivatives (23a, 16a)
were also enabled in high yields (Scheme 6b) by applying the
reaction to readily available N,N-dimethylacetamide (DMA) and
tert-butoxycarbonyl (Boc) protected pyrrolidine. The developed
method, compared to the classical methods such as employing
the organometallic addition to the Weinreb amide generated
from the α-amino acid after protection,[34] could serve as an
economical and convenient alternative to synthesize biologically
relevant α-amino ketone products.
Acknowledgements
This work was gratefully supported by the Samsung Science
and Technology Foundation (SSTF-BA1601-12) and the Institute
for Basic Science in Korea (IBS-R10-A1). We thank Prof.
Sukbok Chang for insightful comments and discussions.
Keywords: C–H activation • acylation • amides • nickel •
photocatalysis
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In conclusion, an acyl transfer reaction from amides to
unactivated C(sp3)–H bonds was developed for the first time.
Significant thermodynamic challenges to activate both inert
bonds were overcome by careful orchestration of photoredox
and Ni catalysis strategies, leading to the first merger of C(sp3)–
H functionalization and amide C–N bond cleavage. As a result,
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user-friendly
amides
and
simple
C–H
substrates.
Comprehensive mechanistic studies revealed that the
proficiency of the N-acylsuccinimide substrate is rooted in the
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