We
unveil
a
novel
strategy
that
leverages
cost-effective
fluorine-containing
sources
for
rapid
synthesis
of
fluorinated
com-pounds
through
multicomponent
reactions.
Our
study
introduces
visible
light-driven
palladium-catalyzed
1,4-difluoromethyl
difunctionalization
conjugated
dienes,
capitalizing
on
the
abundant
industrial
resource
chlorodifluoro-methane
(ClCF2H,
Freon-22).
Illuminated
by
blue
LED
light,
palladium
catalyst
orchestrates
efficient
single
electron
reduction
Freon-22's
C-Cl
bond,
yielding
CF2H
radicals.
This
versatile
protocol
accommodates
an
extensive
array
amines,
sulfinates,
and
enolates
as
nucleophiles,
delivering
regioselective
products
via
SN2'
substitution
allylic
intermediate.
Redox-neutral
in
nature,
this
transformation
finds
utility
late-stage
functionalization
drug
molecules,
while
broad
compatibility
with
diverse
functional
groups
dienes
underscores
its
versa-tility.
Initial
insights
suggest
involvement
difluoromethyl
radical
intermediate,
unveiling
direct
mild
avenue
to
harness
radicals
from
Freon-22.
Journal of the American Chemical Society,
Journal Year:
2022,
Volume and Issue:
144(31), P. 14288 - 14296
Published: July 27, 2022
The
application
of
abundant
and
inexpensive
fluorine
feedstock
sources
to
synthesize
fluorinated
compounds
is
an
appealing
yet
underexplored
strategy.
Here,
we
report
a
photocatalytic
radical
hydrodifluoromethylation
unactivated
alkenes
with
industrial
chemical,
chlorodifluoromethane
(ClCF2H,
Freon-22).
This
protocol
realized
by
merging
tertiary
amine-ligated
boryl
radical-induced
halogen
atom
transfer
(XAT)
organophotoredox
catalysis
under
blue
light
irradiation.
A
broad
scope
readily
accessible
featuring
variety
functional
groups
drug
natural
product
moieties
could
be
selectively
difluoromethylated
good
efficiency
in
metal-free
manner.
Combined
experimental
computational
studies
suggest
that
the
key
XAT
process
ClCF2H
both
thermodynamically
kinetically
favored
over
hydrogen
pathway
owing
formation
strong
boron–chlorine
(B–Cl)
bond
low-lying
antibonding
orbital
carbon–chlorine
(C–Cl)
bond.
Angewandte Chemie International Edition,
Journal Year:
2021,
Volume and Issue:
60(48), P. 25477 - 25484
Published: Sept. 7, 2021
The
sigma
(σ)-hole
effect
has
emerged
as
a
promising
tool
to
construct
novel
architectures
endowed
with
new
properties.
A
simple
yet
effective
strategy
for
the
generation
of
monofluoromethyl
radicals
is
continuing
challenge
within
synthetic
community.
Fluoromethylphosphonium
salts
are
easily
available,
air-
and
thermally
stable,
well
simple-to-handle.
Herein,
we
report
ability
σ-hole
facilitate
visible-light-triggered
photolysis
phosphonium
iodide
salts,
charge-transfer
complex,
selectively
giving
fluoromethyl
radicals.
usefulness
versatility
this
protocol
demonstrated
through
mono-,
di-,
trifluoromethylation
variety
alkenes.
Angewandte Chemie International Edition,
Journal Year:
2020,
Volume and Issue:
60(8), P. 4300 - 4306
Published: Nov. 16, 2020
Abstract
A
silver‐mediated
oxidative
difluoromethylation
of
styrenes
and
vinyl
trifluoroborates
with
TMSCF
2
H
is
reported
for
the
first
time.
This
method
enables
direct
facile
access
to
CF
H‐alkenes
from
abundant
alkenes
excellent
functional‐group
compatibility.
Moreover,
this
Ag/TMSCF
protocol
could
further
enable
a
series
radical
reactions
wide
array
substrates,
offering
generic
complementary
platform
construction
diversified
C−CF
bonds.
Expert Opinion on Drug Discovery,
Journal Year:
2021,
Volume and Issue:
16(11), P. 1261 - 1286
Published: June 2, 2021
Introduction
There
continues
to
be
an
exponential
rise
in
the
number
of
small
molecule
drugs
that
contain
either
a
fluorine
atom
or
fluorinated
fragment.
While
unique
properties
enable
precise
modulation
molecule's
physicochemical
properties,
strategic
bioisosteric
replacement
fragments
with
moieties
represents
area
significant
growth.Areas
covered
This
review
discusses
employment
substitution
design
and
development
bioisosteres
medicinal
chemistry.
In
addition,
classic
exploitation
trifluoroethylamine
group
as
amide
bioisostere
is
discussed.
each
case
studies
presented,
emphasis
placed
on
context-dependent
influence
fragment
overall
properties/binding
compound
interest.Expert
opinion
Whereas
utilization
replacements
modify
molecular
structures
commonplace
within
drug
discovery,
overarching
lesson
learned
chances
success
this
strategy
significantly
increase
knowledge
structure/environment
biological
target
grows.
Coupled
this,
breakthroughs
learnings
achieved
using
specific
program
are
context-based,
though
may
helpful
guiding
future
intuition,
will
not
necessarily
directly
translated
programs.
Another
important
point
bear
mind
what
implications
structural
change
based
have
candidate
molecule.
Finally,
new
methods
reagents
for
controlled
regioselective
introduction
into
biologically
relevant
compounds
particularly
discovery
remains
contemporary
challenge
organic
Organic Letters,
Journal Year:
2022,
Volume and Issue:
24(20), P. 3721 - 3725
Published: May 12, 2022
With
the
continued
interest
in
properties
of
difluoromethyl
(CF2H)
group,
small
molecules
with
alkyl-CF2H
motifs
have
gained
increasing
attention.
However,
concise
and
efficient
synthetic
protocols
to
achieve
these
structures
are
still
urgently
needed.
Herein,
we
report
a
new
acyldifluoromethylation
inert
alkenes
via
synergistic
NHC-photoredox
catalysis
featuring
broad
substrate
scope
good
functional
group
tolerance.
Organic Letters,
Journal Year:
2020,
Volume and Issue:
22(23), P. 9313 - 9318
Published: Nov. 16, 2020
Here
we
present
a
novel
annulation
of
pyridinium
salts
with
BrCF2CO2Et
to
access
the
indolizine
derivatives
high
efficiency.
The
α
substitution
pyridine
plays
key
role
in
determining
reaction
pathways.
Various
types
indolizines
can
be
conveniently
accessed
from
easily
available
under
mild
and
simple
conditions.
