Angewandte Chemie International Edition,
Год журнала:
2022,
Номер
62(5)
Опубликована: Ноя. 24, 2022
Abstract
C−F
insertion
of
carbon‐atom
units
is
underdeveloped
although
it
poses
significant
potential
applications
in
both
drug
discovery
and
development.
Herein,
we
report
a
photocatalytic
protocol
for
late‐stage
modification
trifluoromethyl
aromatic
drugs
involving
formal
abundant
alkene
feedstocks
into
benzylic
bond
selectively.
This
redox‐neutral
transformation
features
mild
conditions
extraordinary
functional
group
tolerance.
Preliminary
studies
are
consistent
with
this
radical‐polar
crossover
pathway.
Additionally,
offers
an
alternative
strategy
difunctionalization
alkenes
via
quenching
the
carbocation
intermediate
nucleophiles
other
than
external
fluoride.
ACS Catalysis,
Год журнала:
2023,
Номер
13(24), С. 15991 - 16011
Опубликована: Ноя. 28, 2023
Carbon
dioxide
radical
anion
(CO2•–)
is
a
highly
reactive
nucleophilic
species
that
has
recently
emerged
in
organic
chemistry
as
strong
single
electron
donor
(reductant)
and
reactant
for
the
synthesis
of
carboxylic
acids.
In
general,
CO2•–
can
be
generated
by
either
direct
reduction
CO2
or
HAT
formate
salts.
Achievements
reactions
involving
have
been
witnessed
recent
years.
This
Review
summarizes
advances
highlighting
some
challenges
identifying
potential
areas
improvement,
which
may
offer
inspiration
future
studies.
ACS Catalysis,
Год журнала:
2023,
Номер
13(4), С. 2482 - 2488
Опубликована: Фев. 3, 2023
The
radical
anion
of
CO2
(CO2•–)
is
a
strongly
nucleophilic
species
with
rapidly
emerging
applications
in
contemporary
organic
chemistry.
This
exhibits
high
reactivity
single-electron
reduction
reactions
due
to
the
concomitant
release
stable
CO2,
or
Giese-type
reactions,
especially
for
electron-deficient
alkenes
and
styrene
derivatives.
In
contrast
previous
reports,
we
herein
disclose
development
robust
method
introduction
CO2•–,
which
can
be
generated
from
cesium
formate
under
photoredox/hydrogen
atom
transfer
(HAT)
catalysis,
into
heteroaromatics
such
as
benzofuran,
benzothiophene,
indole
derivatives
afford
synthetically
useful
α-oxy,
α-thio,
α-amino
acid
moderate
yield.
addition,
when
using
naphthalene
derivatives,
both
addition
occur
simultaneously
produce
carboxylated
tetrahydronaphthalene
good
Moreover,
one
tetrahydronaphthalenes
that
bear
cyano
group
was
transformed
corresponding
γ-butyrolactam
via
functionality
through
hydrogenation
followed
by
cyclization.
To
best
our
knowledge,
these
dearomative
carboxylation
metal
formates
photoredox/HAT
conditions
are
unprecedented,
thus
providing
synthetic
option
C1
source
(hetero)aromatics.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Янв. 10, 2024
Abstract
Bioisosteric
design
has
become
an
essential
approach
in
the
development
of
drug
molecules.
Recent
advancements
synthetic
methodologies
have
enabled
rapid
adoption
this
strategy
into
discovery
programs.
Consequently,
conceptionally
innovative
practices
would
be
appreciated
by
medicinal
chemistry
community.
Here
we
report
expeditous
method
for
synthesizing
aryl
difluoromethyl
bicyclopentane
(ADB)
as
a
bioisostere
benzophenone
core.
This
involves
merger
light-driven
C−F
bond
activation
and
strain-release
under
catalysis
newly
designed
N
-anionic-based
organic
photocatalyst.
defluorinative
coupling
methodology
enables
direct
conversion
wide
variety
commercially
available
trifluoromethylaromatic
bonds
(more
than
70
examples)
corresponding
bicyclo[1.1.1]pentanes
(BCP)
arenes/difluoromethyl
BCP
boronates
single
step.
The
can
also
applied
to
[3.1.1]and
[4.1.1]propellane
systems,
providing
access
analogues
with
different
geometries.
Moreover,
successfully
used
protocol
rapidly
prepare
ADB-substituted
bioactive
molecule
Adiporon.
Biological
testing
shown
that
ADB
scaffold
potential
enhance
pharmacological
properties
benzophenone-type
candidates.
Organic Letters,
Год журнала:
2022,
Номер
24(22), С. 4075 - 4080
Опубликована: Июнь 1, 2022
We
describe
a
catalytic
strategy
for
direct
single
C(sp3)-F
bond
alkylation
of
trifluoromethylbenzimidazoles
under
photoinduced
thiol
catalysis
process.
The
CO2
radical
anion
(CO2•-)
proved
to
be
the
most
efficient
single-electron
reductant
realize
such
transformation.
spin-center
shift
generated
intermediate
is
key
step
in
realizing
C-F
activation
mild
conditions
with
high
efficiency.
Chemical Society Reviews,
Год журнала:
2023,
Номер
53(1), С. 263 - 316
Опубликована: Дек. 7, 2023
The
employment
of
light
and/or
electricity
-
alternatively
to
conventional
thermal
energy
unlocks
new
reactivity
paradigms
as
tools
for
chemical
substrate
activations.
This
leads
the
development
synthetic
reactions
and
a
vast
expansion
spaces.
review
summarizes
recent
developments
in
photo-
electrochemical
activation
strategies
functionalization
strong
bonds
particularly
carbon-heteroatom
(C-X)
Organic Letters,
Год журнала:
2022,
Номер
24(46), С. 8542 - 8546
Опубликована: Ноя. 14, 2022
An
aryl
disulfide
mediated
C-F
bond
activation
of
the
trifluoromethyl
group
to
generate
valuable
gem-difluoroalkylindoles
is
described.
This
method
relies
on
readily
available
commodity
reagents
under
mild
reaction
conditions
and
represents
first
transition-metal-free
redox-neutral
strategy.
The
employs
various
substituted
indoles
α-fluoro-substituted
esters.
Further,
this
mode
was
also
amenable
trifluoromethylated
arenes
for
preparation
bis-benzylic
gem-difluoromethylenes
between
indole
arene
substructures,
providing
access
a
unique
chemical
space.
