Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(47)
Опубликована: Авг. 10, 2024
Abstract
The
functionalization
of
pyridines
is
crucial
for
the
rapid
construction
and
derivatization
agrochemicals,
pharmaceuticals,
materials.
Conventional
approaches
have
primarily
focused
on
ortho
‐
para
‐positions,
while
achieving
precise
meta‐selective
functionalization,
particularly
at
C5
position
in
substituted
pyridines,
remains
a
formidable
challenge
due
to
intrinsic
electronic
properties
pyridines.
Herein,
we
present
new
strategy
meta
C5‐selective
C−H
sulfonylation
N
‐amidopyridinium
salts,
which
employs
transient
enamine‐type
intermediate
generated
through
nucleophilic
addition
salts.
This
process
harnesses
power
electron
donor‐acceptor
complexes,
enabling
high
selectivity
broad
applicability,
including
complex
bearing
valuable
sulfonyl
functionalities
under
mild
conditions
without
need
an
external
photocatalyst.
remarkable
selectivity,
combined
with
applicability
late‐stage
significantly
expands
toolbox
pyridine
unlocking
access
previously
unattainable
‐sulfonylated
Chemical Reviews,
Год журнала:
2023,
Номер
123(12), С. 7655 - 7691
Опубликована: Май 3, 2023
Azines,
such
as
pyridines,
quinolines,
pyrimidines,
and
pyridazines,
are
widespread
components
of
pharmaceuticals.
Their
occurrence
derives
from
a
suite
physiochemical
properties
that
match
key
criteria
in
drug
design
is
tunable
by
varying
their
substituents.
Developments
synthetic
chemistry,
therefore,
directly
impact
these
efforts,
methods
can
install
various
groups
azine
C–H
bonds
particularly
valuable.
Furthermore,
there
growing
interest
late-stage
functionalization
(LSF)
reactions
focus
on
advanced
candidate
compounds
often
complex
structures
with
multiple
heterocycles,
functional
groups,
reactive
sites.
Because
factors
electron-deficient
nature
the
effects
Lewis
basic
N
atom,
distinct
arene
counterparts,
application
LSF
contexts
difficult.
However,
have
been
many
significant
advances
reactions,
this
review
will
describe
progress,
much
which
has
occurred
over
past
decade.
It
possible
to
categorize
radical
addition
processes,
metal-catalyzed
activation
transformations
occurring
via
dearomatized
intermediates.
Substantial
variation
reaction
within
each
category
indicates
both
rich
reactivity
heterocycles
creativity
approaches
involved.
Science,
Год журнала:
2022,
Номер
378(6621), С. 779 - 785
Опубликована: Ноя. 17, 2022
Carbon-hydrogen
(C−H)
functionalization
of
pyridines
is
a
powerful
tool
for
the
rapid
construction
and
derivatization
many
agrochemicals,
pharmaceuticals,
materials.
Because
inherent
electronic
properties
pyridines,
selective
meta
-C−H
challenging.
Here,
we
present
protocol
highly
regioselective
trifluoromethylation,
perfluoroalkylation,
chlorination,
bromination,
iodination,
nitration,
sulfanylation,
selenylation
through
redox-neutral
dearomatization-rearomatization
process.
The
introduced
dearomative
activation
mode
provides
diversification
platform
meta-selective
reactions
on
other
azaarenes
radical
as
well
ionic
pathways.
broad
scope
high
selectivity
these
catalyst-free
render
processes
applicable
late-stage
drugs.
Science,
Год журнала:
2022,
Номер
378(6621), С. 773 - 779
Опубликована: Ноя. 17, 2022
Pyridine
halogenation
reactions
are
crucial
for
obtaining
the
vast
array
of
derivatives
required
drug
and
agrochemical
development.
However,
despite
more
than
a
century
synthetic
endeavors,
processes
that
selectively
functionalize
carbon-hydrogen
bond
in
3-position
broad
range
pyridine
precursors
remain
largely
elusive.
We
report
reaction
sequence
pyridyl
ring
opening,
halogenation,
closing
whereby
acyclic
Zincke
imine
intermediates
undergo
highly
regioselective
under
mild
conditions.
Experimental
computational
mechanistic
studies
indicate
nature
halogen
electrophile
can
modify
selectivity-determining
step.
Using
this
method,
we
produced
diverse
set
3-halopyridines
demonstrated
late-stage
complex
pharmaceuticals
agrochemicals.
Nature Chemistry,
Год журнала:
2024,
Номер
16(5), С. 741 - 748
Опубликована: Янв. 18, 2024
Abstract
Skeletal
editing
is
a
straightforward
synthetic
strategy
for
precise
substitution
or
rearrangement
of
atoms
in
core
ring
structures
complex
molecules;
it
enables
quick
diversification
compounds
that
not
possible
by
applying
peripheral
strategies.
Previously
reported
skeletal
common
arenes
mainly
relies
on
carbene-
nitrene-type
insertion
reactions
rearrangements.
Although
powerful,
efficient
and
applicable
to
late-stage
heteroarene
structure
modification,
these
strategies
cannot
be
used
pyridines.
Here
we
report
the
direct
pyridines
through
atom-pair
swap
from
CN
CC
generate
benzenes
naphthalenes
modular
fashion.
Specifically,
use
sequential
dearomatization,
cycloaddition
rearomatizing
retrocycloaddition
one-pot
sequence
transform
parent
into
bearing
diversified
substituents
at
specific
sites,
as
defined
reaction
components.
Applications
pyridine
cores
several
drugs
are
demonstrated.
Angewandte Chemie International Edition,
Год журнала:
2023,
Номер
62(42)
Опубликована: Апрель 4, 2023
The
pyridine
moiety
is
an
important
core
structure
for
a
variety
of
drugs,
agrochemicals,
catalysts,
and
functional
materials.
Direct
functionalization
C-H
bonds
in
pyridines
straightforward
approach
to
access
valuable
substituted
pyridines.
Compared
the
direct
ortho-
para-functionalization,
meta-selective
far
more
challenging
due
inherent
electronic
properties
entity.
This
review
summarizes
currently
available
methods
meta-C-H
using
directing
group,
non-directed
metalation,
temporary
dearomatization
strategies.
Recent
advances
ligand
control
are
highlighted.
We
analyze
advantages
as
well
limitations
current
techniques
hope
inspire
further
developments
this
area.
Journal of the American Chemical Society,
Год журнала:
2023,
Номер
unknown
Опубликована: Май 17, 2023
Asymmetric
intermolecular
C–H
functionalization
of
pyridines
at
C3
is
unprecedented.
Herein,
we
report
the
first
examples
such
transformations:
specifically,
C3-allylation
via
tandem
borane
and
iridium
catalysis.
First,
borane-catalyzed
pyridine
hydroboration
generates
nucleophilic
dihydropyridines;
then,
dihydropyridine
undergoes
enantioselective
iridium-catalyzed
allylation;
finally,
oxidative
aromatization
with
air
as
oxidant
gives
C3-allylated
pyridine.
This
protocol
provides
direct
access
to
excellent
enantioselectivity
(up
>99%
ee)
suitable
for
late-stage
pyridine-containing
drugs.
The Journal of Organic Chemistry,
Год журнала:
2023,
Номер
88(6), С. 3359 - 3371
Опубликована: Фев. 16, 2023
Two
types
of
electrophilic
trifluoromethylthiolating
reagents
were
developed
in
the
past
10
years
our
laboratory.
The
development
first
type
reagent,
trifluoromethanesulfenate
I,
which
is
highly
reactive
toward
a
variety
nucleophiles,
was
based
on
an
unexpected
discovery
initial
design
for
reagent
with
hypervalent
iodine
skeleton.
A
structure–activity
study
disclosed
that
α-cumyl
(reagent
II)
without
iodo
substituent
equally
effective.
Subsequent
derivatization
let
us
develop
bromodifluoromethanesulfenate
III
could
be
used
preparation
[18F]ArSCF3.
To
remediate
low
reactivity
I
Friedel–Crafts
trifluoromethylthiolation
electron-rich
(hetero)arenes,
we
designed
and
prepared
N-trifluoromethylthiosaccharin
IV,
exhibits
broad
various
including
arenes.
comparison
structure
IV
N-trifluoromethylthiophthalimide
showed
replacement
one
carbonyl
group
sulfonyl
made
much
more
electrophilic.
Thus,
both
carbonyls
two
groups
would
further
increase
electrophilicity.
Such
rationale
prompted
to
current
most
N-trifluoromethylthiodibenzenesulfonimide
V,
its
higher
than
IV.
We
optically
pure
(1S)-(−)-N-trifluoromethylthio-2,10-camphorsultam
VI,
active
trifluoromethylthio-substituted
carbon
stereogenic
centers.
Reagents
I–VI
now
constitute
powerful
toolbox
introduction
trifluoromethylthio
into
target
molecules.
European Journal of Organic Chemistry,
Год журнала:
2023,
Номер
26(16)
Опубликована: Фев. 21, 2023
Abstract
Late‐Stage
Functionalisation
(LSF)
is
an
innovative
technique
that
has
been
successfully
applied
to
the
C−H
diversification
of
pharmaceuticals.
However,
LSF
pyridine
ring
in
drug‐like
molecules
often
unselective.
As
a
result,
mixture
structurally
related
products
obtained,
thus
making
purification
tedious
and
time‐consuming.
This
review
shines
light
on
recent
strategies
addressing
selectivity
issue
complex
natural
or
drugs
containing
moiety.
Specifically,
we
have
reviewed
efforts
reported
both
academia
industries
with
hope
providing
guide
for
elaborated
pyridines.