Nature Communications,
Год журнала:
2021,
Номер
12(1)
Опубликована: Июнь 1, 2021
Abstract
Organic
molecules
that
contain
alkyl-difluoromethyl
moieties
have
received
increased
attention
in
medicinal
chemistry,
but
their
synthesis
a
modular
and
late-stage
fashion
remains
challenging.
We
report
herein
an
efficient
copper-catalyzed
radical
relay
approach
for
the
carbo-difluoromethylation
of
alkenes.
This
simultaneously
introduces
CF
2
H
groups
along
with
complex
alkyl
or
aryl
into
alkenes
regioselectivity
opposite
to
traditional
addition.
demonstrate
broad
substrate
scope
wide
functional
group
compatibility.
scalable
protocol
is
applied
functionalization
analogues
bioactive
molecules.
Mechanistic
studies
density
theory
calculations
suggest
unique
ligand
effect
on
reactivity
Cu-CF
species.
Chemical Society Reviews,
Год журнала:
2021,
Номер
50(11), С. 6308 - 6319
Опубликована: Янв. 1, 2021
Radical
trifluoromethylation
has
been
emerging
as
a
versatile
tool
for
the
synthesis
of
trifluoromethylated
compounds
that
play
increasingly
important
roles
in
pharmaceuticals,
agrochemicals
and
materials
science.
ACS Catalysis,
Год журнала:
2021,
Номер
11(3), С. 1640 - 1683
Опубликована: Янв. 20, 2021
The
past
decade
has
witnessed
the
emergence
of
N-(acyloxy)phthalimides
(NHPI
esters)
and
its
derivatives
at
forefront
synthetic
methods
facilitating
construction
diverse
molecular
frameworks
from
readily
available
carboxylic
acid
feedstock.
NHPI
esters
are
predisposed
to
undergo
reductive
fragmentation
via
a
single
electron
transfer
(SET)
process
under
thermal,
photochemical,
or
electrochemical
conditions
generate
corresponding
carbon-
nitrogen-centered
radicals
that
participate
in
multitude
transformations
forge
carbon–carbon
carbon–heteroatom
bonds.
chemistry
involving
received
broad
applicability
not
only
well-designed
cascade
annulations
but
also
medicinal
natural
product
synthesis.
This
comprehensive
Review,
broadly
categorized
according
nature
bond
formation,
details
progress
made
this
field
since
initial
discovery
by
providing
representative
examples
with
mechanistic
details,
an
emphasis
on
challenges
future
directions.
Nature Communications,
Год журнала:
2020,
Номер
11(1)
Опубликована: Янв. 31, 2020
Abstract
The
discovery
of
modern
medicine
relies
on
the
sustainable
development
synthetic
methodologies
to
meet
needs
associated
with
drug
molecular
design.
Heterocycles
containing
difluoromethyl
groups
are
an
emerging
but
scarcely
investigated
class
organofluoro
molecules
potential
applications
in
pharmaceutical,
agricultural
and
material
science.
Herein,
we
developed
organophotocatalytic
direct
difluoromethylation
heterocycles
using
O
2
as
a
green
oxidant.
C–H
oxidative
obviates
need
for
pre-functionalization
substrates,
metals
additives.
operationally
straightforward
method
enriches
efficient
synthesis
many
difluoromethylated
moderate
excellent
yields.
pharmaceutical
moleculars
demonstrates
practicability
this
methodology
late-stage
development.
Moreover,
2′-deoxy-5-difluoromethyluridine
(F
TDR)
exhibits
promising
activity
against
some
cancer
cell
lines,
indicating
that
might
provide
assistance
discovery.
Green Chemistry,
Год журнала:
2020,
Номер
22(15), С. 4849 - 4870
Опубликована: Янв. 1, 2020
Herein,
electrochemical
annulations
involving
mediators
and
mediator-free
conditions
have
been
discussed.
Also,
the
use
of
sacrificial
electrodes
has
explored.
Journal of the American Chemical Society,
Год журнала:
2019,
Номер
141(50), С. 19941 - 19949
Опубликована: Ноя. 22, 2019
We
report
herein
the
first
catalytic
strategy
to
harness
amidyl
radicals
derived
from
N-chloroamides
for
C–C
bond
formation,
allowing
discovery
of
benzylic
C–H
difluoromethylation.
Under
copper-catalyzed
conditions,
a
wide
variety
N-chlorocarboxamides
and
N-chlorocarbamates
direct
selective
difluoromethylation
with
nucleophilic
difluoromethyl
source
at
room
temperature.
This
scalable
protocol
exhibits
broad
substrate
scope
functional
group
tolerance,
enabling
late-stage
bioactive
molecules.
copper-catalyzed,
chloroamide-directed
has
also
been
extended
pentafluoroethylation
trifluoromethylation.
Mechanistic
studies
on
reactions
support
that
involve
formation
via
intramolecular
activation,
followed
by
copper-mediated
transfer
groups
radicals.
Chemical Society Reviews,
Год журнала:
2021,
Номер
50(10), С. 6094 - 6151
Опубликована: Янв. 1, 2021
Decarboxylation
strategy
has
been
emerging
as
a
powerful
tool
for
the
synthesis
of
fluorine-containing
organic
compounds
that
play
important
roles
in
various
fields
such
pharmaceuticals,
agrochemicals,
and
materials
science.
Considerable
progress
decarboxylation
made
over
past
decade
towards
construction
diverse
valuable
fluorinated
fine
chemicals
which
part
can
be
brought
two
ways.
The
first
way
is
described
reaction
non-fluorinated
carboxylic
acids
(and
their
derivatives)
with
fluorinating
reagents,
well
building
blocks.
second
dedicated
to
exploration
use
decarboxylative
transformations.
This
review
aims
provide
comprehensive
summary
development
applications
radical,
nucleophilic
cross-coupling
strategies
organofluorine
chemistry.
Journal of the American Chemical Society,
Год журнала:
2021,
Номер
143(26), С. 9952 - 9960
Опубликована: Июнь 28, 2021
Given
their
ubiquity
in
natural
products
and
pharmaceuticals,
alcohols
represent
one
of
the
most
attractive
starting
materials
for
construction
C–C
bonds.
We
report
herein
first
catalytic
strategy
to
harness
reactivity
aryl
radicals
activation
C–O
bonds
alcohol-derived
xanthate
esters,
allowing
discovery
deoxygenative
difluoromethylation
reaction.
Under
copper-catalyzed
conditions,
a
wide
variety
alkyl
readily
synthesized
from
alcohol
feedstocks,
were
activated
by
catalytically
generated
converted
alkyl-difluoromethane
via
radical
intermediates.
This
scalable
protocol
exhibits
broad
substrate
scope
functional
group
tolerance,
enabling
late-stage
modification
complex
pharmaceutical
agents.
A
one-pot
has
been
developed
that
allows
direct
use
free
without
purification
esters.
Mechanistic
studies
are
consistent
with
hypothesis
being
formed
initiating
cleavage
generate
as
key
approach
represents
new
cross-coupling
partners.
