The
undirected
functionalization
of
pyridines
at
positions
remote
to
the
N-atom
remains
an
outstanding
problem
in
organic
synthesis.
inherent
challenges
associated
with
overriding
strong
directing
influence
embedded
within
pyridine
was
overcome
through
use
n-butylsodium
which
provided
us
avenue
generate
4-sodiopyridine
over
traditionally
observed
2-metalated
products
when
organolithium
bases
are
utilized.
freshly
generated
4-
sodiopyrdine
found
undergo
transition
metal
free
alkylation
reactions
directly
a
variety
primary
halides
bearing
diverse
functional
groups.
In
addition,
after
transmetalation
zinc
chloride
simple
and
efficient
Negishi
cross-coupling
protocol
formulated
for
aromatic
heteroaromatic
halides.
robustness
this
demonstrated
late-stage
installation
4-pyridyl
fragments
into
complex
active
pharmaceutical
ingredients
including
loratadine
prochlorperazine.
This
not
only
unlocks
new
prepare
4-subsituted
but
highlights
preparative
advantages
differences
organosodium
their
lithium
counterparts.
Chemical Science,
Год журнала:
2024,
Номер
15(31), С. 12442 - 12450
Опубликована: Янв. 1, 2024
A
practical
and
general
C-4
functionalization
strategy
of
unbiased
pyridines
is
developed
by
identifying
a
readily
synthesized
substituted
urea
as
the
pyridine
activation
reagent.
Organic Letters,
Год журнала:
2023,
Номер
25(28), С. 5366 - 5371
Опубликована: Июль 11, 2023
A
multicomponent
dearomative
difluoroalkylation
of
isoquinolines
has
been
developed
with
difluorinated
silyl
enol
ethers
serving
as
poor
nucleophiles
without
an
additional
transition-metal
or
organic
catalyst.
The
sequential
oxidative
rearomatization
under
different
alkaline
conditions
provides
a
controllable
formal
C-H
and
difluoromethylation
method
for
peroxide
metal
oxidant.
series
including
pharmaceutical,
phenanthridine,
quinolines,
were
suitable
substrates
to
construct
gem-difluorinated
heterocycles.
inexpensive
starting
materials,
mild
reaction
conditions,
simple
operation
also
show
practical
environmentally
benign
advantages.
Chemistry - A European Journal,
Год журнала:
2024,
Номер
31(2)
Опубликована: Ноя. 28, 2024
The
pyridine
core
is
a
crucial
component
in
numerous
FDA-approved
drugs
and
Environmental
Protection
Agency
(EPA)
regulated
agrochemicals.
It
also
plays
significant
role
ligands
for
transition
metals,
alkaloids,
catalysts,
various
organic
materials
with
diverse
properties,
making
it
one
of
the
most
important
structural
frameworks.
However,
despite
its
significance,
direct
selective
functionalization
still
relatively
underdeveloped
due
to
electron-deficient
nature
strong
coordinating
ability
nitrogen.
Among
variety
synthetic
transformation,
C-H
bond
straightforward
atom
economical
approach
it's
advantageous
late-stage
containing
drugs.
In
recent
years,
innovative
strategies
regioselective
pyridines
azines
have
emerged,
offering
benefits
such
as
high
regioselectivity,
mild
conditions,
enabling
transformations
that
were
challenging
traditional
methods.
This
review
emphasizes
latest
advancements
meta
para-C-H
through
approaches,
including
phosphonium
salts,
photocatalytic
methods,
temporary
de-aromatization,
Minisci-type
reactions,
metal-catalyzed
activation
techniques.
We
discuss
advantages
limitations
these
current
methods
aim
inspire
further
progress
this
field.
Angewandte Chemie International Edition,
Год журнала:
2021,
Номер
60(39), С. 21283 - 21288
Опубликована: Авг. 3, 2021
Abstract
Methods
to
synthesize
alkylated
pyridines
are
valuable
because
these
structures
prevalent
in
pharmaceuticals
and
agrochemicals.
We
have
developed
a
distinct
approach
construct
4‐alkylpyridines
using
dearomatized
pyridylphosphonium
ylide
intermediates
Wittig
olefination‐rearomatization
sequence.
Pyridine
N
‐activation
is
key
this
strategy,
‐triazinylpyridinium
salts
enable
coupling
between
wide
variety
of
substituted
aldehydes.
The
alkylation
protocol
viable
for
late‐stage
functionalization,
including
methylation
pyridine‐containing
drugs.
This
represents
an
alternative
metal‐catalyzed
sp
2
‐
3
cross‐coupling
reactions
Minisci‐type
processes.
Angewandte Chemie International Edition,
Год журнала:
2021,
Номер
61(9)
Опубликована: Дек. 13, 2021
Strong
and
confined
imidodiphosphorimidate
(IDPi)
catalysts
enable
highly
enantioselective
substitutions
of
cyclic,
aliphatic
hemiaminal
ethers
with
enol
silanes.
2-Substituted
pyrrolidines,
piperidines,
azepanes
are
obtained
high
enantioselectivities,
the
method
displays
a
broad
tolerance
various
silane
nucleophiles.
Several
natural
products
can
be
accessed
using
this
methodology.
Mechanistic
studies
support
intermediacy
non-stabilized,
cyclic
N-(exo-acyl)iminium
ions,
paired
chiral
counteranion.
Computational
suggest
transition
states
that
explain
observed
enantioselectivity.
The Journal of Organic Chemistry,
Год журнала:
2024,
Номер
89(18), С. 13450 - 13456
Опубликована: Авг. 28, 2024
Aminated
nitrogen
heterocycles
are
valuable
motifs
across
numerous
chemical
industries,
perhaps
most
notably
in
small
molecule
drug
discovery.
While
strategies
for
installing
atoms
onto
azaarenes
exist,
require
prefunctionalization
and
methods
direct
C-H
amination
almost
entirely
limited
to
position
C2.
Herein,
we
report
a
method
the
C2
C4
of
fused
via
Herein,
we
report
a
method
for
the
regioselective
alkylation
and
phosphonation
of
quinoline
C4–H
via
B3H7-mediated
nucleophilic
addition
Turbo
Grignard
reagents
phosphine
oxide
anions
to
quinolines
bearing
different
substituents,
affording
4-alkyl
4-phosphoryl
tetrahydroquinolines
after
one-pot
oxidation
or
reduction.
The
results
indicate
that
coordination
B3H7
group
can
activate
substrates
toward
potential
1,4-dearomative
subtly
control
regioselectivity
by
preventing
1,2-dearomative
addition.
The Journal of Organic Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 3, 2025
We
report
the
photocatalyzed
three-component
alkene
1,2-alkylpyridylation
reaction
between
alkylboronic
acids,
4-cyanopyridine,
and
an
olefin
to
achieve
pyridination
alkylation
of
synthesis
structurally
diversified
4-alkylpyridines.
The
readily
available
easily
manipulated
acids
were
used
as
alkyl
radical
precursors.
reactions
take
place
under
mild
conditions
with
a
broad
substrate
scope
are
easy
scale
up
gram
level,
they
therefore
potential
practical
value
for
structural
modification
biologically
active
alkylpyridine
derivatives.
Chemical Reviews,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 22, 2025
Fluorine
and
nitrogen
form
a
successful
partnership
in
organic
synthesis,
medicinal
chemistry,
material
sciences.
Although
fluorine-nitrogen
chemistry
has
long
rich
history,
this
field
received
increasing
interest
made
remarkable
progress
over
the
past
two
decades,
driven
by
recent
advancements
transition
metal
organocatalysis
photochemistry.
This
review,
emphasizing
contributions
from
2015
to
2023,
aims
update
state
of
art
synthesis
applications
nitrogen-based
organofluorine
functional
molecules
chemistry.
In
dedicated
sections,
we
first
focus
on
fluorine-containing
reagents
organized
according
type
groups
attached
nitrogen,
including
N-F,
N-RF,
N-SRF,
N-ORF.
review
also
covers
nitrogen-linked
building
blocks,
catalysts,
pharmaceuticals,
agrochemicals,
underlining
these
components'
broad
applicability
growing
importance
modern
Organic Chemistry Frontiers,
Год журнала:
2023,
Номер
10(9), С. 2324 - 2331
Опубликована: Янв. 1, 2023
Metal-free
selective
C–H
thiolation
of
quinoline,
including
trifluoromethyl
thiolation,
aryl
alkyl
and
phenyl
selenylation,
using
N
-arylmethyl
activation
strategies
is
reported
applicable
to
quinoline-based
biologically
active
complex
molecules.
