Synlett,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 26, 2024
Abstract
Recent
developments
in
the
isotopic
labeling
of
heteroarenes
may
prove
to
be
useful
realms
biomedical
science,
materials
chemistry,
and
fundamental
organic
chemistry.
The
use
age-old
Zincke
reaction,
or
tactical
variants
thereof,
has
become
particularly
utilitarian
effecting
single-atom
nitrogen
replacement
various
azines
generate
their
desired
isotopologues.
This
chemistry
can
synthetically
leveraged
at
an
early
stage
for
diversity-oriented
heterocyclic
pharmaceuticals
and/or
natural
products.
Additionally,
given
prevalence
saturated
azacycles
biologically
relevant
molecules,
access
these
isotopologues
becomes
through
dearomative
retrosynthetic
analysis
from
corresponding
15N-labeled
heteroarenes.
1
Introduction
2
Our
Lab’s
Development
15NRORC
Reaction
3
Other
Azine-Labeling
Methods
4
Expanded
ANRORC
Utilization
5
Conclusion
Outlook
Synthesis,
Journal Year:
2024,
Volume and Issue:
56(24), P. 3793 - 3814
Published: Aug. 20, 2024
Abstract
Considering
the
importance
of
heterocycles,
significantly
represented
in
medicinal
chemistry
and
drug
development,
single-atom
insertion
technique
transmutation
strategy
provide
productive
approaches
towards
complicated
molecular
structures
through
heterocycle
diversification.
It
shows
a
potentially
powerful
approach
for
modifying
complex
substrates
concisely
chemospecifically.
Although
skeletal
editing
applies
to
cyclic
acyclic
compounds,
this
review
focuses
on
diversification
carbo-
heterocyclic
compounds
synthesizing
various
medicinally
important
molecules
via
technique.
The
classification
system
is
based
recent
critical
historical
methods
as
applied
aromatic
rings.
1
Introduction
2
Skeletal
Editing
Carbon-Atom
Insertion
2.1
Indoles
Pyrroles
Derivatives:
into
C=C
Bond
2.2
Pyrazole
Indazole
an
N–N
2.3
CF3
Group
Heteroarenes
2.4
Imidazole
C–N
2.5
Atom-to-Atom
Transmutation
3
N-Atom
3.1
Nitrogen-Atom
Carbocycles
3.2
Heterocycles
3.3
Carbon
Nitrogen
Molecular
Isotopic
4
Conclusion
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Aug. 28, 2024
Regioselective
C-H
functionalization
of
pyridines
remains
a
persistent
challenge
due
to
their
inherent
electronically
deficient
properties.
In
this
report,
we
present
strategy
for
the
selective
pyridine
C3-H
thiolation,
selenylation,
and
fluorination
under
mild
conditions
via
classic
N-2,4-dinitrophenyl
Zincke
imine
intermediates.
Radical
inhibition
trapping
experiments,
as
well
DFT
theoretical
calculations,
indicated
that
thiolation
selenylation
proceeds
through
radical
addition-elimination
pathway,
whereas
two-electron
electrophilic
substitution
pathway.
The
pre-installed
electron-deficient
activating
N-DNP
group
plays
crucial
positive
role,
with
additional
benefit
recyclability.
practicability
protocol
was
demonstrated
in
gram-scale
synthesis
late-stage
modification
pharmaceutically
relevant
pyridines.
Chemical Science,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 1, 2025
Isotopically
chiral
molecules
have
drawn
much
attention
due
to
their
practical
applications
in
drug
discovery.
However,
existing
studies
this
area
are
mainly
limited
centrally
and
H/D
exchange.
Herein,
we
report
a
phosphoric
acid-catalyzed
atroposelective
[4+1]
annulation
of
ketoaldehydes
1H-indol-1-amines.
By
means
strategy,
series
D-
18O-labeled
atropisomers
featuring
both
central
axial
chiralities
synthesized
with
high
enantioselectivities
diastereoselectivities
good
excellent
isotopic
incorporation.
Experimental
density
functional
theory
suggest
that
the
reaction
involves
sequential
condensation,
cyclization
isomerization
cascade,
which
second
step
is
enantio-determining
process.
Journal of Medicinal Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 7, 2025
Heteroaromatics
are
the
basis
for
many
pharmaceuticals.
The
ability
to
modify
these
structures
through
selective
core-atom
transformations,
or
"skeletal
edits",
can
dramatically
expand
landscape
drug
discovery
and
development.
However,
despite
importance
of
modifications,
quantitative
impact
such
transformations
on
accessible
chemical
space
remains
undefined.
Here,
we
report
a
cheminformatic
platform
analyze
which
skeletal
edits
would
most
increase
access
novel
space.
This
study
underscores
significance
emerging
single
multiple
heteroaromatics
in
enhancing
diversity,
example,
at
late-stage
campaign.
Our
findings
provide
framework
prioritizing
modifications
heteroaromatic
structural
motifs,
calling
development
new
methods
achieve
types
transformations.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(38)
Published: June 27, 2024
Herein
we
report
the
development
of
an
oxidative
amination
process
for
streamlined
synthesis
pyridones
from
cyclopentenones.
Cyclopentenone
building
blocks
can
undergo
in
situ
silyl
enol
ether
formation,
followed
by
introduction
a
nitrogen
atom
into
carbon
skeleton
with
successive
aromatisation
to
yield
pyridones.
The
reaction
sequence
is
operationally
simple,
rapid,
and
carried
out
one
pot.
proceeds
under
mild
conditions,
exhibits
broad
functional
group
tolerance,
complete
regioselectivity,
well
scalable.
developed
method
provides
facile
access
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: July 18, 2024
Abstract
Isotopic
labeling
is
at
the
core
of
health
and
life
science
applications
such
as
nuclear
imaging,
metabolomics
plays
a
central
role
in
drug
development.
The
rapid
access
to
isotopically
labeled
organic
molecules
sine
qua
non
condition
support
these
societally
vital
areas
research.
Based
on
rationally
driven
approach,
this
study
presents
an
innovative
solution
pyridines
by
nitrogen
isotope
exchange
reaction
based
Zincke
activation
strategy.
technology
conceptualizes
opportunity
field
labeling.
15
N-labeling
other
relevant
heterocycles
pyrimidines
isoquinolines
showcases
large
set
derivatives,
including
pharmaceuticals.
Finally,
we
explore
nitrogen-to-carbon
strategy
order
13
C-labeled
phenyl
derivatives
deuterium
mono-substituted
benzene
from
pyridine-
2
H
5
.
These
results
open
alternative
avenues
for
multiple
aromatic
cores.
The
transformation
of
pyridines
into
benzene
derivatives
is
described,
using
a
one-pot
ANRORC
process
with
soft
nucleophiles
such
as
malonate.
Triflic
anhydride
activates
the
pyridine
to
synthesis
carbocyclic
β-aminoester
intermediate,
which
aromatizes
on
heating.
reaction
has
been
exemplified
room
temperature
protocol,
along
direct
syntheses
biologi-cally
active,
tertiary-alkylated
and
isotopically-labelled
benzoates.
