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.
Organic Chemistry Frontiers,
Год журнала:
2024,
Номер
11(5), С. 1388 - 1394
Опубликована: Янв. 1, 2024
Zn-catalyzed
stereoselective
hydrodefluorination
of
CF
3
-substituted
alkenes,
gem
-difluoroalkenes
and
polyfluoroarenes
by
hydride
ion
addition
has
been
realized
through
controlled
C(sp
)–F
and/or
2
bonds
cleavage.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(25)
Опубликована: Апрель 19, 2024
The
reaction
regioselectivity
of
gem-difluoroalkenes
is
dependent
on
the
intrinsic
polarity.
Thus,
reversal
addition
remains
a
formidable
challenge.
Herein,
we
described
an
unprecedented
hydrogen
atom
transfer
(HAT)
to
triggered
by
Fe-H
species
for
formation
difluoroalkyl
radicals.
Hydrogenation
in
situ
generated
radicals
gave
difluoromethylated
products.
Mechanism
experiments
and
theoretical
studies
revealed
that
kinetic
effect
irreversible
HAT
process
resulted
this
scenario,
leading
less
stable
α-difluoroalkyl
radical
regioisomer.
On
basis
new
gem-difluoroalkene,
iron-promoted
hydrohalogenation
efficient
synthesis
aliphatic
chlorodifluoromethyl-,
bromodifluoromethyl-
iododifluoromethyl-containing
compounds
was
developed.
Particularly,
novel
provided
large-scale
access
various
iododifluoromethylated
high
value
synthetic
application.
Organic Letters,
Год журнала:
2024,
Номер
26(23), С. 4953 - 4957
Опубликована: Май 30, 2024
Organofluorine
compounds
are
of
high
value
in
medicinal
and
agricultural
chemistry.
Herein,
we
report
a
palladium-catalyzed
fluoro-alkoxylation
gem-difluoroalkenes
for
the
synthesis
much
more
challenging
sterically
hindered
ethers.
This
reaction
represents
direct
method
α-trifluoromethyl
ethers
with
broad
functional
group
tolerance
excellent
regioselectivity.
system
employs
N-fluorobenzenesulfonimide
(NFSI)
as
an
electrophilic
fluorine
source
alcohols
nucleophilic
donors,
including
but
not
limited
to
tert-substituted
alcohols.
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.
Synthesis,
Год журнала:
2023,
Номер
55(18), С. 2833 - 2842
Опубликована: Янв. 26, 2023
Abstract
Selective
functionalization
via
cleavage
of
the
C–N
bond
amines
has
proven
to
be
challenging
partly
because
its
relatively
high
dissociation
energy,
even
though
are
abundant
and
readily
available.
To
meet
this
challenge,
many
new
transformations
based
on
pre-activation
before
have
been
developed.
Among
them,
conversion
into
quaternary
ammonium
salts
certain
advantages,
such
as
easy
preparation
from
primary,
secondary,
or
tertiary
amines,
well
stable
storage
usage.
Although
transition
metal
catalysis
frequently
applied
for
developing
oxidative
addition
salts,
recent
studies
shown
a
dimension
by
using
green
electro-
photochemical
tools.
In
short
review,
advances
in
electro-,
photo-,
photoelectrochemical
driven
synthetic
applications
summarized
discussed.
1
Introduction
2
Electrochemical
Driven
Transformations
3
Photochemical
4
Photoelectrochemical
5
Conclusion
Outlook
Organic & Biomolecular Chemistry,
Год журнала:
2023,
Номер
21(16), С. 3330 - 3334
Опубликована: Янв. 1, 2023
Catalyst-
and
metal-free
difluoroallylation
of
alkyl
precursors
with
trifluoromethyl
alkenes
for
the
synthesis
gem-difluoroalkenes
is
appealing
challenging.
We
herein
describe
a
visible
light-induced
approach
that
enables
deoxygenative
abundant
alcohols
via
xanthate
salts
alkenes,
where
work
as
photoreductant
an
alkylating
reagent,
avoiding
use
external
catalysts.
This
one-pot
method
can
accommodate
primary,
secondary
tertiary
good
functionality
tolerance
be
successfully
applied
to
late-stage
functionalization
natural
products
drugs.
Organic Chemistry Frontiers,
Год журнала:
2023,
Номер
11(1), С. 142 - 148
Опубликована: Ноя. 22, 2023
A
direct
electrolysis
protocol
for
difluorination
and
azo-fluorination
of
gem
-difluorostyrenes
was
achieved
involving
Et
3
N·3HF
as
fluorine
source.
The
electrochemical
reduction
the
benzyl
C–F
bond
also
achieved.
ACS Catalysis,
Год журнала:
2023,
Номер
13(19), С. 12960 - 12969
Опубликована: Сен. 20, 2023
The
enantioselective
synthesis
of
chiral
fluorinated
amines
is
great
importance
but
highly
challenging
in
synthetic
chemistry
and
the
pharmaceutical
industry.
Herein,
we
established
a
chemoenzymatic
cascade
for
α-mono-
difluoromethyl
from
easily
available
β-keto-acid
esters
water–oil–solid
multiphasic
systems
via
two
catalytic
modules,
i.e.,
organo-enzymatic
decarboxylative
fluorination
bienzymatic
reductive
amination.
An
efficient
continuous
system
was
constructed
by
stepwise
enzyme
immobilization,
biphasic
construction,
continuous-flow
operation
to
achieve
process
intensification.
flow
achieved
high
space-time
yield
up
19.7
g
L–1
h–1,
which
35-fold
enhancement
compared
batch
using
free
enzymes,
also
demonstrated
operational
stability,
maintaining
87%
production
activity
after
96
h
with
half-life
443.9
h.
