Angewandte Chemie,
Journal Year:
2024,
Volume and Issue:
136(42)
Published: July 24, 2024
Abstract
The
homolysis
of
chemical
bonds
represents
one
the
most
fundamental
reactivities
excited
molecules.
Historically,
it
has
been
exploited
to
generate
radicals
under
ultraviolet
(UV)
light
irradiation.
However,
unlike
contemporary
radical‐generating
mechanisms,
direct
excitation
homolyze
and
produce
aliphatic
carbon‐centered
visible
remains
rare,
especially
in
metallaphotoredox
cross
couplings.
Herein,
we
present
our
design
dihydropyrimidoquinolinone
(DHPQ)
reagents
derived
from
ketones,
which
can
undergo
formal
deacylation
homolytic
C−C
bond
cleavage
release
alkyl
without
external
photocatalysts.
Spectroscopic
computational
analysis
reveal
unique
optical
structural
features
DHPQs,
rationalizing
their
faster
kinetics
radical
generation
than
a
structurally
similar
but
visible‐light
transparent
precursor.
Such
capability
allows
DHPQ
facilitate
wide
range
Ni‐metallaphotoredox
couplings
with
aryl,
alkynyl
acyl
halides.
Other
catalytic
non‐catalyzed
alkylative
transformations
DHPQs
are
also
feasible
various
acceptors.
We
believe
this
work
would
be
broad
interest,
aiding
synthetic
planning
simplified
operation
expanding
reach
photocatalyst‐free
approaches
cutting‐edge
research.
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(32), P. 22829 - 22839
Published: Aug. 1, 2024
The
molecular
editing
of
ketones
represents
an
appealing
strategy
due
to
its
ability
maximize
the
structural
diversity
ketone
compounds
in
a
straightforward
manner.
However,
developing
efficient
methods
for
arbitrary
modification
ketonic
molecules,
particularly
those
integrated
within
complex
skeletons,
remains
significant
challenge.
Herein,
we
present
unique
recasting
that
involves
radical
acylation
Science Advances,
Journal Year:
2024,
Volume and Issue:
10(17)
Published: April 26, 2024
Ketones
are
ubiquitous
in
bioactive
natural
products,
pharmaceuticals,
chemical
feedstocks,
and
synthetic
intermediates.
Hence,
deacylative
coupling
reactions
enable
the
versatile
elaboration
of
a
plethora
chemicals
to
access
complex
drug
candidates
products.
Here,
we
present
arylation
alkynylation
strategies
for
synthesis
wide
range
alkyl-tethered
arenes
alkynes
from
cyclic
ketones
methyl
under
dual
nickel/photoredox
catalysis.
This
reaction
begins
by
generating
pre-aromatic
intermediate
(PAI)
through
condensation
ketone
Organic Letters,
Journal Year:
2024,
Volume and Issue:
26(32), P. 6915 - 6920
Published: Aug. 8, 2024
Ketones,
as
essential
functional
group
skeletons,
have
garnered
significant
interest
due
to
their
diverse
transformations.
Herein,
we
describe
a
versatile
photoredox
catalyzed
deacylation-aroylation
strategy
that
enables
the
direct
transformation
of
alkyl
ketones
aryl
ketones.
This
process
involves
deacylation
dihydroquinazolinones
derived
from
generate
radicals,
followed
by
subsequent
NHC-catalyzed
or
NHC-mediated
radical
aroylation.
Journal of the American Chemical Society,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 7, 2025
The
homolytic
cleavage
of
C–C
bonds
adjacent
to
specific
functional
groups
has
lately
emerged
as
a
versatile
approach
for
molecular
diversification.
Despite
the
ubiquity
and
synthetic
utility
ketones,
radical
fragmentation
their
α-C–C
proven
be
formidable
challenge.
Here,
we
present
broadly
applicable
deacylative
strategy
designed
homolytically
cleave
aliphatic
ketones
various
complexities,
including
transformations
cycloalkanones
into
carboxylic
acids
tethered
C-centered
free
radicals
that
can
engaged
in
diverse
radical-based
processes.
method
involves
ketone
activation
through
treatment
with
hydrogen
peroxide,
yielding
gem-dihydroperoxides.
Subsequent
single-electron-transfer
reduction
mediated
by
low-valent
metal
complex
generates
alkyl
captured
selectively
radicophile
choice,
catalytic
cross-coupling.
logic
our
functionalization
is
exemplified
total
synthesis
14
natural
products,
one
analogue,
two
drugs
starting
from
readily
available
showcasing
its
transformative
power
settings.
This
obviates
need
reagents
allows
controlled
conversion
reconstructed
making
process
highly
across
spectrum
domains.
The Journal of Organic Chemistry,
Journal Year:
2024,
Volume and Issue:
89(15), P. 10987 - 10997
Published: July 22, 2024
Herein,
visible
light-induced,
nickel-catalyzed
direct
functionalization
of
the
Hantzsch
esters
(HEs)
with
readily
accessible
alkyl
bromides
has
been
successfully
achieved
by
taking
advantage
HE
as
reductant
and
substrate
through
an
aromatization-dearomatization
process.
In
this
strategy,
single
electron
reduction
reactive
Ni(I)
species
is
essential
for
success
late-stage
transformation.
A
wide
range
4-alkyl-1,4-dihydropyridines
were
rapidly
assembled
in
moderate
to
good
yields
under
mild
conditions,
rendering
photoinduced
approach
attractive
synthetic
medicinal
chemistry.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
unknown
Published: July 24, 2024
Abstract
The
homolysis
of
chemical
bonds
represents
one
the
most
fundamental
reactivities
excited
molecules.
Historically,
it
has
been
exploited
to
generate
radicals
under
ultraviolet
(UV)
light
irradiation.
However,
unlike
contemporary
radical‐generating
mechanisms,
direct
excitation
homolyze
and
produce
aliphatic
carbon‐centered
visible
remains
rare,
especially
in
metallaphotoredox
cross
couplings.
Herein,
we
present
our
design
dihydropyrimidoquinolinone
(DHPQ)
reagents
derived
from
ketones,
which
can
undergo
formal
deacylation
homolytic
C−C
bond
cleavage
release
alkyl
without
external
photocatalysts.
Spectroscopic
computational
analysis
reveal
unique
optical
structural
features
DHPQs,
rationalizing
their
faster
kinetics
radical
generation
than
a
structurally
similar
but
visible‐light
transparent
precursor.
Such
capability
allows
DHPQ
facilitate
wide
range
Ni‐metallaphotoredox
couplings
with
aryl,
alkynyl
acyl
halides.
Other
catalytic
non‐catalyzed
alkylative
transformations
DHPQs
are
also
feasible
various
acceptors.
We
believe
this
work
would
be
broad
interest,
aiding
synthetic
planning
simplified
operation
expanding
reach
photocatalyst‐free
approaches
cutting‐edge
research.
Organic Letters,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 21, 2025
Conventional
synthetic
organic
chemistry
typically
relies
on
site-centered
reactivity
for
the
reaction
discovery.
Herein,
skeleton-chaperoned
is
exploited
development,
with
skeleton
utilized
as
a
structural
scaffold
assisting
functional
group
activation
into
proper
sequence.
A
Co(III)
catalytic
method
has
been
developed
N-amino-directed
C-H
coupling
4-hydroxy-2-alkynoates,
allowing
convenient
access
to
2-alkene-3-carboxylic
acid
type
indole
derivatives.
This
features
phenyl/pyrrole/lactone
skeleton-chaperone
and
simultaneous
conversion
of
five
groups.
Synlett,
Journal Year:
2023,
Volume and Issue:
35(10), P. 1072 - 1088
Published: Oct. 24, 2023
Abstract
The
recent
prominence
of
ketones
as
handles
for
sp3-rich
radicals
has
expanded
the
paradigm
synthetic
utility
ketones,
putting
ubiquitous
functional
group
once
again
into
spotlight
in
years.
One
emerging
strategy
arose
through
ketone-derived
pro-aromatic
reagents
form
dihydrobenzothiazoline
(BTZ),
dihydroquinazolinone
(DHQZ),
dihydropyrazole
(DHP),
and
dihydro-1,2,4-triazole
(DHT)
key
intermediates
aromaticity-promoted
C–C
bond
homolytic
fission.
formed
sp3-radicals
could
then
participate
various
radical
functionalizations,
including
alkylations,
arylations,
olefination,
alkynylation,
silylations,
amination,
thiolation,
deuteration,
among
others,
either
photocatalytic,
thermal,
or
oxidative
conditions.
In
this
review,
we
highlight
implications
advances
using
these
transfer
reactions
deconstructive
functionalization.
1
Introduction
2
Aromatization-Driven
Bond
Scission
Ketones
3
Photochemical
Reactions
Ketone-Derived
Pro-aromatic
Reagents
4
Non-photochemical
5
Conclusion
Future
Outlook
Hydrogen
atom
transfer
(HAT)
from
a
metal-hydride
is
reliable
and
powerful
method
for
functionalizing
unsaturated
C–C
bonds
in
organic
synthesis.
Cobalt
hydrides
(Co–H)
have
garnered
significant
attention
this
field,
where
the
weak
Co–H
are
most
commonly
generated
catalytic
fashion
through
mixture
of
stoichiometric
amounts
peroxide
oxidant
silane
reductant.
Here
we
show
that
reverse
process
HAT
to
an
alkene,
i.e.
hydrogen
abstraction
C–H
adjacent
radical,
can
be
leveraged
generate
catalytically
active
species
new
application
shuttle
catalysis
coined
HAT.
This
obviates
need
reductant/oxidant
mixtures
thereby
greatly
simplifying
generation
under
exceedingly
mild
reaction
conditions.
approach
opens
door
introduction
functional
handles
(e.g.,
iodides)
were
previously
inaccessible
other
approaches,
paves
way
reagent
design
which
incorporates
platform.
To
demonstrate
generality
platform,
five
different
manifolds
shown,
including
late-stage
C(sp3)
iodination
structurally
diverse
FDA
approved
drugs.
