Advanced Synthesis & Catalysis,
Journal Year:
2024,
Volume and Issue:
366(20), P. 4219 - 4227
Published: Aug. 7, 2024
Abstract
Cascade
dearomative
functionalization
is
a
robust
protocol
to
convert
flat
arenes
into
medicinally
relevant
three‐dimensional
architectures
with
added
new
functionality.
Herein,
cycloaddition
for
synthesizing
tetrahydroquinoline‐embedded
α‐tertiary
amine
scaffolds
has
been
developed
employing
quinolinium
salts
and
sulfonyl
azides
under
metal‐free
conditions.
An
underexplored
mechanistically
distinct
pathway
unveiled,
creating
quaternary‐center‐bearing
skeletons
by
an
group
migration
during
the
transfer
hydrogenation
cascade
reaction.
This
approach
provided
broad
substrate
scope
of
from
plethora
C3‐substituted
azides.
The
post‐synthetic
modifications
have
further
diversified
core
interesting
scaffolds.
Preliminary
mechanistic
studies
suggested
involvement
aziridine
ring
formation
C‐3
position
quinoline
generate
core.
Chemical Reviews,
Journal Year:
2024,
Volume and Issue:
124(3), P. 1122 - 1246
Published: Jan. 2, 2024
Dearomatization
reactions
have
become
fundamental
chemical
transformations
in
organic
synthesis
since
they
allow
for
the
generation
of
three-dimensional
complexity
from
two-dimensional
precursors,
bridging
arene
feedstocks
with
alicyclic
structures.
When
those
processes
are
applied
to
pyridines,
quinolines,
and
isoquinolines,
partially
or
fully
saturated
nitrogen
heterocycles
formed,
which
among
most
significant
structural
components
pharmaceuticals
natural
products.
The
inherent
challenge
lies
low
reactivity
heteroaromatic
substrates,
makes
dearomatization
process
thermodynamically
unfavorable.
Usually,
connecting
event
irreversible
formation
a
strong
C–C,
C–H,
C–heteroatom
bond
compensates
energy
required
disrupt
aromaticity.
This
aromaticity
breakup
normally
results
1,2-
1,4-functionalization
heterocycle.
Moreover,
combination
these
subsequent
tandem
stepwise
protocols
allows
multiple
heterocycle
functionalizations,
giving
access
complex
molecular
skeletons.
aim
this
review,
covers
period
2016
2022,
is
update
state
art
nucleophilic
dearomatizations
showing
extraordinary
ability
dearomative
methodology
indicating
their
limitations
future
trends.
Journal of the American Chemical Society,
Journal Year:
2022,
Volume and Issue:
144(32), P. 14463 - 14470
Published: Aug. 1, 2022
Herein,
we
report
a
method
for
C3-selective
C–H
tri-
and
difluoromethylthiolation
of
pyridines.
The
relies
on
borane-catalyzed
pyridine
hydroboration
generation
nucleophilic
dihydropyridines;
these
intermediates
react
with
trifluoromethylthio
difluoromethylthio
electrophiles
to
form
functionalized
dihydropyridines,
which
then
undergo
oxidative
aromatization.
can
be
used
late-stage
functionalization
drugs
the
new
drug
candidates.
Chemical Science,
Journal Year:
2022,
Volume and Issue:
13(48), P. 14213 - 14225
Published: Jan. 1, 2022
This
Perspective
outlines
the
myriad
of
products
that
can
be
obtained
by
dearomatisation
and
functionalization
heteroarene
substrates.
Complex
3D
molecules
often
prepared
in
one
step
from
simple
arene
starting
materials.
Journal of the American Chemical Society,
Journal Year:
2023,
Volume and Issue:
unknown
Published: May 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.
Angewandte Chemie International Edition,
Journal Year:
2023,
Volume and Issue:
62(34)
Published: July 3, 2023
Abstract
Herein,
we
report
a
one‐pot
method
for
enantioselective
C−H
allylation
of
pyridines
at
C3
via
tandem
borane
and
palladium
catalysis.
This
involves
borane‐catalyzed
pyridine
hydroboration
to
generate
dihydropyridines,
then
palladium‐catalyzed
the
dihydropyridines
with
allylic
esters,
finally
air
oxidation
allylated
afford
products.
enables
introduction
an
group
excellent
regio‐
enantioselectivities.
Angewandte Chemie International Edition,
Journal Year:
2022,
Volume and Issue:
62(6)
Published: Dec. 15, 2022
Methods
for
C-H
cyanation
of
pyridines
are
rare.
Here,
we
report
a
method
C3-selective
by
tandem
process
with
the
reaction
an
in
situ
generated
dihydropyridine
cyano
electrophile
as
key
step.
The
is
suitable
late-stage
functionalization
pyridine
drugs.
low
reduction
potential
and
effective
transfer
nitrile
group
were
found
to
be
essential
success
this
method.
We
studied
mechanism
detail
means
control
experiments
theoretical
calculations
that
combination
electronic
steric
factors
determined
regioselectivity
reactions
involving
C2-substituted
pyridines.
Angewandte Chemie International Edition,
Journal Year:
2021,
Volume and Issue:
60(34), P. 18454 - 18460
Published: June 7, 2021
Herein,
we
report
a
KIO4
-mediated,
sustainable
and
chemoselective
approach
for
the
one-pot
C(sp2
)-H
bond
hydroxymethylation
or
methylenation
of
imidazo-heteroarenes
with
formaldehyde,
generated
in
situ
via
oxidative
cleavage
ethylene
glycol
glycerol
(renewable
reagents)
through
Malaprade
reaction.
In
presence
glycol,
series
3-hydroxymethyl-imidazo-heteroarenes
was
obtained
good
to
excellent
yields.
These
compounds
are
important
intermediates
access
pharmaceutical
drugs,
e.g.,
Zolpidem.
Furthermore,
by
using
glycerol,
bis(imidazo[1,2-a]pyridin-3-yl)methane
derivatives
were
selectively
Angewandte Chemie International Edition,
Journal Year:
2022,
Volume and Issue:
61(27)
Published: May 13, 2022
Herein
we
disclose
a
mild
protocol
for
the
reductive
functionalisation
of
quinolinium
and
isoquinolinium
salts.
The
reaction
proceeds
under
transition-metal-free
conditions
as
well
rhodium
catalysis
with
very
low
catalyst
loadings
(0.01
mol
%)
uses
inexpensive
formic
acid
terminal
reductant.
A
wide
range
electrophiles,
including
enones,
imides,
unsaturated
esters
sulfones,
β-nitro
styrenes
aldehydes
are
intercepted
by
in
situ
formed
enamine
species
forming
large
variety
substituted
tetrahydro(iso)quinolines.
Electrophiles
incorporated
at
C-3
C-4
position
quinolines
isoquinolines
respectively,
providing
access
to
substitution
patterns
which
not
favoured
electrophilic
or
nucleophilic
aromatic
substitution.
Finally,
this
reactivity
was
exploited
facilitate
three
types
annulation
reactions,
giving
rise
complex
polycyclic
products
formal
[3+3]
[4+2]
cycloaddition.
Chemical Communications,
Journal Year:
2023,
Volume and Issue:
59(27), P. 4051 - 4054
Published: Jan. 1, 2023
Dearomatization
reactions
provide
a
rapid
approach
to
construct
complicated
molecules
that
are
difficult
synthesize
by
traditional
methods
from
simple
aromatic
compounds.
Herein,
we
report
an
efficient
dearomative
[3+2]
cycloaddition
reaction
of
2-alkynyl
pyridines
with
diarylcyclopropenones,
leading
the
synthesis
densely
functionalized
indolizinones
in
moderate
good
yields
under
metal-free
conditions.
In
addition,
this
strategy
can
also
be
employed
cyclization
isoquinolines
access
variety
benzo-fused
indolizinones.
Density
functional
theory
(DFT)
calculations
revealed
appropriate
substituent
at
2-position
pyridine
is
crucial
dearomatization
process.
