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.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(16)
Published: Jan. 29, 2024
Abstract
We
highlight
key
contributions
in
the
field
of
direct
radical
C
Ar
−
H
(hetero)aromatic
functionalization
involving
fluorinated
radicals.
A
compilation
Functional
Group
Transfer
Reagents
and
their
diverse
activation
mechanisms
leading
to
release
radicals
are
discussed.
The
substrate
scope
for
each
is
analyzed
classified
into
three
categories
according
electronic
properties
substrates.
Density
functional
theory
computational
analysis
provides
insights
chemical
reactivity
several
through
electrophilicity
nucleophilicity
parameters.
Theoretical
reduction
potentials
also
highlights
remarkable
correlation
between
oxidizing
ability.
It
established
that
highly
(e.g.
⋅OCF
3
)
capable
engaging
single‐electron
transfer
(SET)
processes
rather
than
addition,
which
good
agreement
with
experimental
literature
data.
scale,
based
on
barrier
addition
these
benzene
elaborated
using
high
accuracy
DLPNO‐(U)CCSD(T)
method.
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(2), P. 1276 - 1281
Published: Jan. 5, 2024
The
first
efficient
access
to
N-difluoromethyl
amides,
carbamates,
thiocarbamates,
ureas,
formamides,
and
their
derivatives
is
reported
herein.
synthetic
strategy
relies
on
the
initial
synthesis
straightforward
derivatization
of
N-CF2H
carbamoyl
fluorides,
which
were
prepared
through
a
desulfurization–fluorination
thioformamides
(─NH─C(H)═S)
coupled
with
carbonylation.
newly
made
carbonyl
compounds
proved
be
highly
robust
compatible
numerous
chemical
transformations
downstream
derivatizations,
underscoring
potential
this
novel
motif
as
building
block
in
complex
functional
molecules.
Organic Letters,
Journal Year:
2024,
Volume and Issue:
26(17), P. 3661 - 3666
Published: April 24, 2024
Considering
the
ubiquitous
presence
of
pyridine
moieties
in
pharmaceutical
compounds,
it
holds
immense
value
to
develop
practical
and
straightforward
methodologies
for
accessing
heterocyclic
aromatic
hydrocarbons.
In
recent
years,
N-alkoxypyridinium
salts
have
emerged
as
convenient
radical
precursors,
enabling
generation
corresponding
alkoxy
radicals
through
single-electron
transfer.
Herein,
we
present
first
report
on
visible-light-mediated
intermolecular
alkoxypyridylation
alkenes
employing
N-alkoxylpyridinium
bifunctional
reagents
with
an
exceptionally
low
catalyst
loading
(0.5
mol
%).
Chemical Reviews,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 22, 2025
Fluorine
and
nitrogen
form
a
successful
partnership
in
organic
synthesis,
medicinal
chemistry,
material
sciences.
Although
fluorine-nitrogen
chemistry
has
long
rich
history,
this
field
received
increasing
interest
made
remarkable
progress
over
the
past
two
decades,
driven
by
recent
advancements
transition
metal
organocatalysis
photochemistry.
This
review,
emphasizing
contributions
from
2015
to
2023,
aims
update
state
of
art
synthesis
applications
nitrogen-based
organofluorine
functional
molecules
chemistry.
In
dedicated
sections,
we
first
focus
on
fluorine-containing
reagents
organized
according
type
groups
attached
nitrogen,
including
N-F,
N-RF,
N-SRF,
N-ORF.
review
also
covers
nitrogen-linked
building
blocks,
catalysts,
pharmaceuticals,
agrochemicals,
underlining
these
components'
broad
applicability
growing
importance
modern
The Journal of Organic Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 22, 2025
A
visible-light-driven
intermolecular
tandem
α-amidotrifluoroethylation/cyclization
of
enaminones
using
a
previously
unreported
N-trifluoroethylaminopyridinium
salt
was
achieved
in
the
absence
transition
metal
catalysts
or
bases.
Notable
features
this
synthetic
method
include
mild
conditions,
high
selectivity,
excellent
functional
group
compatibility,
and
satisfactory
yields.
Preliminary
mechanistic
studies
indicate
that
reaction
proceeds
via
radical
pathway,
involving
an
situ
generated
N-trifluoroethyl
radical,
followed
by
1,2-H
shift.
ACS Catalysis,
Journal Year:
2024,
Volume and Issue:
14(16), P. 12082 - 12092
Published: July 29, 2024
Sulfur(VI)
fluoride
exchange
(SuFEx)
is
a
second-generation
click
chemistry
reaction
that
relies
on
the
unique
reactivities
of
SVI–F
bonds.
The
development
efficient
methods
for
incorporating
S(VI)–F
motif
into
molecules
great
significance.
Sulfamoyl
fluorides
(R1R2NSO2F),
serving
as
versatile
SuFExable
hubs,
are
typically
synthesized
by
using
"+SO2F"
reagents
to
establish
N-SO2F
In
this
study,
we
report
N-fluorosulfamoyl
pyridium
salts
(NFSAPs)
radical
fluorosulfonamidation
readily
accessible
and
bench-stable.
By
employing
NFSAPs
essential
fluorosulfamoyl
(•NSO2F)
precursors,
direct
installation
NSO2F
group
onto
(hetero)arenes
alkenes
achieved
through
distinct
C–N
bond
formation
reactions.
This
platform
facilitates
collective
synthesis
highly
functionalized
N-aryl,
N-alkyl,
N-alkenyl
sulfamoyl
(R1R2NSO2F)
under
mild
photocatalytic
conditions
has
been
applied
in
late-stage
functionalization
pharmaceuticals
peptides.
Beilstein Journal of Organic Chemistry,
Journal Year:
2025,
Volume and Issue:
21, P. 189 - 199
Published: Jan. 20, 2025
The
CF
2
H
group
can
act
as
a
hydrogen
bond
donor,
serving
potential
surrogate
for
OH
or
SH
groups
but
with
weaker
donation
ability.
Here,
we
describe
series
of
group-containing
moieties
that
facilitate
interactions.
We
survey
ability
using
several
established
methods,
including
1
NMR-based
acidity
determination,
UV–vis
spectroscopy
titration
Reichardt's
dye,
and
NMR
tri-
n
-butylphosphine
oxide
acceptor.
Our
experiments
reveal
the
direct
attachment
to
cationic
aromatic
systems
significantly
enhances
its
ability,
result
consistent
theoretical
calculations.
anticipate
this
chemistry
will
be
valuable
designing
functional
molecules
chemical
biology
medicinal
applications.
The Journal of Organic Chemistry,
Journal Year:
2023,
Volume and Issue:
89(1), P. 644 - 655
Published: Dec. 13, 2023
A
photoredox-catalyzed
intermolecular
tandem
sulfonamination/cyclization
of
enaminones
was
realized
by
using
N-aminopyridinium
salts
as
the
sulfonaminated
reagents
without
transition-metal
catalysts
or
bases.
The
reaction
exhibits
a
broad
scope
and
good
functional
group
tolerance,
yields,
regioselectivity.
Preliminary
mechanistic
studies
support
radical
property
involvement
N-centered
intermediates.
Angewandte Chemie,
Journal Year:
2024,
Volume and Issue:
136(16)
Published: Jan. 29, 2024
Abstract
We
highlight
key
contributions
in
the
field
of
direct
radical
C
Ar
−
H
(hetero)aromatic
functionalization
involving
fluorinated
radicals.
A
compilation
Functional
Group
Transfer
Reagents
and
their
diverse
activation
mechanisms
leading
to
release
radicals
are
discussed.
The
substrate
scope
for
each
is
analyzed
classified
into
three
categories
according
electronic
properties
substrates.
Density
functional
theory
computational
analysis
provides
insights
chemical
reactivity
several
through
electrophilicity
nucleophilicity
parameters.
Theoretical
reduction
potentials
also
highlights
remarkable
correlation
between
oxidizing
ability.
It
established
that
highly
(e.g.
⋅OCF
3
)
capable
engaging
single‐electron
transfer
(SET)
processes
rather
than
addition,
which
good
agreement
with
experimental
literature
data.
scale,
based
on
barrier
addition
these
benzene
elaborated
using
high
accuracy
DLPNO‐(U)CCSD(T)
method.
