Abstract
The
construction
of
trifluoromethylated
quaternary
carbon
centers
and
tertiary
alcohols
is
realized
by
organo-photoredox
catalysis.
process
proceeds
via
visible-light-induced
C(sp3)–Si
bond
cleavage
for
the
generation
α-trifluoromethylated
benzyl
radicals,
which
are
readily
trapped
electron-deficient
alkenes
with
excellent
regioselectivity
all-carbon
centers.
α-difluoromethyl
counterparts
also
suitable
this
radical
conjugate
addition.
Furthermore,
in
situ
oxidation
these
radicals
O2
from
air
affords
high
yields,
extends
Fleming–Tamao
reaction
to
systems.
Nature Communications,
Год журнала:
2025,
Номер
16(1)
Опубликована: Янв. 11, 2025
The
difluoromethyl
group
is
a
crucial
fluorinated
moiety
with
distinctive
biological
properties,
and
the
synthesis
of
chiral
CF₂H-containing
analogs
has
been
recognized
as
powerful
strategy
in
drug
design.
To
date,
most
established
method
for
accessing
enantioenriched
compounds
involves
enantioselective
functionalization
nucleophilic
electrophilic
CF₂H
synthons.
However,
this
approach
limited
by
lower
reactivity
reduced
enantioselectivity.
Leveraging
unique
fluorine
effect,
we
design
synthesize
radical
synthon
incorporating
isoindolinone
into
alkyl
halides
asymmetric
transformation.
Here,
report
an
efficient
construction
carbon
stereocenters
featuring
via
nickel-catalyzed
Negishi
cross-coupling.
This
demonstrates
mild
reaction
conditions
excellent
Given
that
optically
pure
difluoromethylated
amines
isoindolinones
are
key
structural
motifs
bioactive
compounds,
offers
practical
solution
drug-like
molecules.
moiety,
screening.
authors
The
development
of
robust
and
readily
available
carbon
electrophiles
for
cross-electrophile
coupling
(XEC)
is
important
highly
desirable.
Herein,
we
report
a
cobalt-catalyzed
chemoselective
XEC
between
alkynyl
sulfides
various
alkyl
halides,
which
tolerates
otherwise
widely
employed
handles
such
as
series
aromatic
(pseudo)halogens
(Ar-I/Br/Cl/OTf/OTs/SMe)
provides
an
easy
efficient
method
synthesizing
internal
alkynes
(>60
examples
achieving
up
to
96%
yields).
Mechanistic
studies
have
revealed
that
the
leaving
sulfide
anion
adjusts
reactivity
alkynyl-Co
intermediates,
enabling
excellent
chemoselectivity.
Chinese Journal of Chemistry,
Год журнала:
2024,
Номер
42(20), С. 2479 - 2484
Опубликована: Июнь 21, 2024
Comprehensive
Summary
Traditional
reduction
coupling
reactions
of
two
bromides
typically
rely
on
transition
metal
catalysis.
Here,
we
introduce
the
development
a
visible‐light
catalytic
direct
reaction
between
α
‐CF
3
‐alkyl
and
alkynyl
to
access
valuable
organic
frameworks.
Our
research
confirms
excellent
compatibility
this
with
various
functional
groups,
which
could
be
used
modify
substrate
biologically
active
molecular
fragments.
Mechanistic
investigations,
including
control
experiments,
fluorescence
quenching
studies,
light‐switching
have
provided
insights
into
mechanism.
This
study
paves
way
for
application
catalysis
in
diverse
synthetic
transformations,
offering
sustainable
efficient
approach
synthesis.
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.
ACS Catalysis,
Год журнала:
2024,
Номер
14(21), С. 15879 - 15907
Опубликована: Окт. 11, 2024
Partially
fluorinated
alkyl
groups
other
than
methyl
are
increasingly
playing
crucial
roles
in
the
development
of
drugs
with
diverse
biological
activities,
thus
creating
an
innovative
chemical
space
within
organofluorine
chemistry.
For
studies
structure–activity
relationships,
late-stage
modification
such
or
substituents
into
substrates
that
bear
activity
is
essential.
This
perspective
will
study
catalytic
protocols
for
direct
introduction
partially
monofluoroalkylated
(−CHFR,
–CH2CH2F),
difluoroalkylated
(−CF2Me,
–CH2CF2H),
trifluoroalkylated
(−CHR(CF3),
–CH2CF3,
–CH2CH2CF3,
–CH(Me)CF3,
–C(Me)2CF3),
and
pentafluoropropylated
(−CH2C2F5)
onto
(hetero)aromatic
compounds,
double
bonds,
isonitriles,
halides,
N,
O,
S
atoms.
Organic Letters,
Год журнала:
2024,
Номер
26(35), С. 7398 - 7402
Опубликована: Авг. 23, 2024
α-Amino-CF3
compounds
are
widely
employed
in
bio-
and
pharmaceutical
chemistry
for
improved
stability
bioactivities.
Traditional
methods
often
face
challenges
with
functional
group
tolerance
lack
a
general
approach
late-stage
functionalization.
Herein,
we
report
new
type
of
redox-active
α-amino-CF3
reagents,
easily
prepared
from
trifluoro
acetaldehyde
hydrates.
These
reagents
can
serve
as
versatile
building
blocks
coupling
alkynyl
bromides,
aryl
enol
triflates
under
nickel
catalysis.
Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 29, 2024
Abstract
The
difluoromethyl
group
(CF₂H)
is
a
crucial
fluorinated
moiety
with
distinctive
biological
properties,
and
the
synthesis
of
chiral
CF₂H-containing
analogs
has
been
recognized
as
powerful
strategy
in
drug
design
screening.
To
date,
most
established
method
for
accessing
enantioenriched
compounds
involves
enantioselective
functionalization
nucleophilic
electrophilic
CF₂H
synthons.
However,
this
approach
limited
by
reaction
scope,
lower
reactivity,
reduced
enantioselectivity.
Leveraging
unique
fluorine
effect,
we
designed
synthesized
novel
radical
synthon
incorporating
isoindolinone
into
alkyl
halides
asymmetric
transformation.
Here,
report
an
efficient
construction
carbon
stereocenters
featuring
via
nickel-catalyzed
Negishi
cross-coupling.
This
demonstrates
mild
conditions,
broad
substrate
excellent
Given
that
optically
pure
difluoromethylated
amines
isoindolinones
are
key
structural
motifs
bioactive
compounds,
offers
practical
solution
drug-like
molecules
pharmaceutical
research
development.
