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.
ACS Catalysis,
Год журнала:
2024,
Номер
14(18), С. 13557 - 13566
Опубликована: Авг. 28, 2024
The
incorporation
of
the
difluoromethyl
(CF2H)
group
into
arenes
has
increasingly
been
recognized
as
important
in
drug
discovery.
Herein,
we
report
a
divergent
cross-coupling
method
for
constructing
both
aryl
difluoromethanes
and
difluoroketones
from
thianthrenium
salts.
Site
selectivity
Negishi-type
coupling
C1
insertion
reactions
was
achieved
under
palladium
catalysis.
Both
transformations
proceed
with
broad
functional
tolerance,
enabling
late-stage
difluoromethylation
difluoromethylcarbonylation
complex
molecules.
synthetic
utility
this
demonstrated
by
synthesizing
four
pharmaceutical
analogues
same
precursor
applying
it
downstream
functionalization
difluoroketones.
ACS Omega,
Год журнала:
2024,
Номер
9(26), С. 28129 - 28143
Опубликована: Июнь 19, 2024
An
efficient
and
mild
protocol
for
the
visible
light-induced
radical
cascade
difluoromethylation/cyclization
of
imidazoles
with
unactivated
alkenes
using
easily
accessible
bench-stable
difluoromethyltriphenylphosphonium
bromide
as
precursor
-CF
Chinese Journal of Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 16, 2025
Comprehensive
Summary
Herein,
we
report
a
photo‐induced,
metal‐/additive‐free
protocol
for
the
difluoromethylation
of
N
‐heteroaromatics
with
[bis(difluoroacetoxy)iodo]benzene
as
reagent.
The
affords
difluoromethylated
in
moderate
to
good
yield
(up
91%).
transformation
is
compatible
wide
range
substrates
and
has
tolerance
towards
various
functional
groups.
Moreover,
synthetic
value
this
method
further
demonstrated
by
applications
gram‐scale
synthesis
late‐stage
functionalization
biologically
important
molecules.
ACS Catalysis,
Год журнала:
2025,
Номер
unknown, С. 4644 - 4653
Опубликована: Март 4, 2025
A
copper-catalyzed
fluoroalkylation
of
lithium
aryl
nbutyl
borates
with
electrophilic
fluoroalkylating
reagent
YlideFluor
for
the
preparation
di-,
trifluoromethyl-,
and
monofluoroalkyl-substituted
(hetero)arenes
under
mild
conditions
was
described.
Control
experiments
indicated
that
a
fluoroalkyl
radical,
rather
than
difluorocarbene
intermediate,
is
involved
in
catalytic
process.
In
addition,
stoichiometric
reactions
demonstrated
transmetalation
copper
catalyst
borate
takes
place
before
single-electron-transfer
(SET)
oxidation
an
ate-type
Cu(I)
intermediate
[CuI(Ar)(SCN)]−
by
YlideFluor.
Based
on
these
mechanistic
results,
reasonable
cycle
proposed.
A
class
of
sulfonium
ylide-based
reagents
for
electrophilic
deuteriodifluoromethylation
is
reported.
Thus,
a
wide
array
ubiquitous
O-nucleophiles
such
as
sulfonic
acid,
alcohol,
carboxyl
and
phosphoric
acid
are
deuteriodifluoromethylated,
providing
straightforward
approach
to
access
the
OCF2D-functionalizazed
scaffolds
that
otherwise
challenging
synthesize
using
conventional
methods.
This
base-free
protocol
also
displays
broad
functional
group
compatibility
amenable
effective
late-stage
modification
bioactive
molecules.
