Abstract
The
difluoromethyl
group
(CF2H)
can
function
as
a
lipophilic
hydrogen-bond
donor,
and
is
regarded
bioisostere
of
functional
groups
such
hydroxy
(-OH),
thiol
(-SH),
amino
(-NH2).
unique
physicochemical
properties
this
make
difluoromethylation
hot
topic
in
the
field
synthetic
organic
chemistry,
recent
decades,
various
methods
have
been
developed
for
constructing
C(sp3)—CF2H,
C(sp2)—CF2H,
C(sp)
—CF2H,
X—CF2H
(X
=
N,
O,
S,
Se,
B,
P,
etc.)
bonds.
This
review
summarizes
currently
available
reagents
performing
reactions,
well
other
approaches
installing
unit.
Chemical Communications,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 1, 2025
We
present
a
highly
efficient
and
versatile
nickel-catalyzed
protocol
for
the
reductive
cross-coupling
of
unactivated
CF2H-substituted
electrophiles
with
wide
variety
aryl
alkenyl
halides.
This
novel
approach
offers
high
catalytic
reactivity
broad
functional
group
compatibility,
enabling
late-stage
fluoroalkylation
drug
molecules.
The Journal of Organic Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 28, 2025
The
synthesis
of
perfluoroalkylated
fullerenes
(PFAFs)
holds
significant
importance
due
to
their
enhanced
molecular
stability,
increased
lipophilicity,
and
high
electron
affinity.
Herein,
we
report
a
copper-catalyzed
multicomponent
reaction
conducted
under
aerobic
conditions,
which
enables
the
production
highly
soluble
PFAFs
with
half-wave
reduction
potentials
similar
those
C60.
Furthermore,
challenges
posed
by
C-F
coupling
in
carbon
signal
assignment
were
addressed
through
fluorine-decoupled
spectroscopy,
facilitating
precise
structural
characterization
perfluoroalkyl
moieties.
Nature Communications,
Год журнала:
2025,
Номер
16(1)
Опубликована: Фев. 13, 2025
Abstract
Positron
emission
tomography
(PET)
is
an
advanced
biomedical
imaging
modality
that
relies
on
well-designed
radiotracers
to
report
specific
protein
targets
and
processes
occurring
in
living
animals
humans.
Cyclotron-produced
short-lived
fluorine-18
(
t
1/2
=
109.8
min)
widely
used
radiolabel
tracers
for
PET.
Herein
we
aim
expand
the
chemical
space
available
PET
tracer
development
include
structures
with
18
F-labeled
α,α-difluoromethylalkyl
groups.
We
efficient
broad-scope
method
labeling
such
groups
high
molar
activities
based
a
single-step
radiofluorination
of
α-bromo-α-fluoroalkanes.
The
applicable
bioactive
compounds
drug-like
molecules,
readily
automated
radiotracer
production.
unique
physical
biochemical
features
α,α-difluoromethyl
group
can
now
be
exploited
design
new
tracers.
Molecules,
Год журнала:
2025,
Номер
30(11), С. 2305 - 2305
Опубликована: Май 24, 2025
This
perspective
highlights
current
trends
and
recent
advances
in
the
introduction
of
fluorine
fluoroalkyl
moieties
into
furanic
core
biobased
furfural-derived
furans.
Existing
potential
applications
these
fluorinated
building
blocks
development
pharmaceuticals
advanced
materials
are
also
discussed.
The Chemical Record,
Год журнала:
2023,
Номер
23(9)
Опубликована: Май 17, 2023
Due
to
its
unique
physical
and
electrophilic
properties,
the
difluoromethyl
group
(-CF2
H)
has
been
playing
an
irreplaceable
role
in
field
of
pharmaceutical
agrochemical
industry.
Methods
that
could
efficiently
incorporate
into
target
molecules
are
increasing
recent
years.
Developing
a
stable
efficient
difluoromethylating
reagent
is
thus
highly
attractive.
In
this
review,
we
describe
development
nucleophilic
difluoromethylation
[(SIPr)Ag(CF2
H)],
including
elemental
reaction,
reaction
with
different
types
electrophiles,
application
synthesis
difluoromethylthiolating
reagent.
The Journal of Organic Chemistry,
Год журнала:
2023,
Номер
88(24), С. 17134 - 17143
Опубликована: Дек. 6, 2023
It
is
significant
to
develop
novel
difluoromethylation
methods
because
of
the
important
roles
difluoromethyl
groups
in
medicinal
chemistry
and
material
industries.
Here,
we
developed
a
difluoromethylation–carboxylation
difluoromethylation–deuteration
method
triggered
by
radical
generated
electroreduction
stable
easily
available
difluoromethyltriphenylphosphonium
bromide.
Various
molecules
containing
carboxyl
or
deuterium
can
be
synthesized
through
this
method.
The
establishment
will
provide
an
alternative
reactions.
Fluoroalkyl
fragments
have
played
a
critical
role
in
the
design
of
pharmaceutical
and
agrochemical
molecules
recent
years
due
to
enhanced
biological
properties
fluorinated
compared
their
non-fluorinated
analogues.
Despite
potential
advantages
conferred
by
incorporating
difluoromethyl
group
organic
compounds,
industrial
adoption
difluoromethylation
methods
lags
be-hind
fluorination
trifluoromethylation.
This
is
part
challenges
applying
common
sources
towards
indus-trial
applications.
We
report
here
nickel-catalyzed
cross-electrophile
coupling
(hetero)aryl
bromides
with
2-pyridyl
sulfone,
sustainably
sourced,
crystalline
reagent.
The
scope
this
reaction
demonstrated
24
examples
(67
±
16%
average
yield)
including
diverse
array
heteroaryl
precursors
difluoromethyl-containing
preclinical
pharmaceuti-cals.
can
be
applied
small-scale
parallel
synthesis
benchtop
scale-up
under
mild
conditions.
As
sulfone
reagents
are
uncommon
electrophiles
coupling,
mechanism
process
was
investigated.
Studies
confirmed
formation
•CF2H
instead
difluorocarbene.
A
series
modified
sulfones
revealed
that
reactivity
does
not
correlate
ex-clusively
reduction
coordination
cations
or
nickel
pyridyl
essential
reactivity,
setting
out
pa-rameters
for
matching
coupling.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(46)
Опубликована: Авг. 9, 2024
Abstract
Given
the
prevalence
of
pyridine
motifs
in
FDA‐approved
drugs,
selective
fluoroalkylation
pyridines
and
quinolines
is
essential
for
preparing
diverse
bioisosteres.
However,
challenges
are
often
faced
with
conventional
Minisci
reactions
achieving
precise
regioselectivity
owing
to
competing
reaction
sites
limited
availability
fluoroalkyl
radical
sources.
Herein,
we
present
a
light‐driven,
C4‐selective
azines
utilizing
N‐aminopyridinium
salts
readily
available
sulfinates.
Our
approach
employs
electron
donor‐acceptor
complexes,
highly
under
mild
conditions
without
an
external
photocatalyst.
This
practical
method
not
only
enables
installation
CF
2
H
groups
but
also
allows
incorporation
‐alkyl
functional
entities,
surpassing
limitations
previous
methods.
The
versatility
pathway
further
demonstrated
through
straightforward
three‐component
involving
alkenes
[1.1.1]propellane.
Detailed
experimental
computational
studies
have
elucidated
origins
regioselectivity,
providing
profound
insights
into
mechanistic
aspects.
