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
Science,
Journal Year:
2024,
Volume and Issue:
386(6717), P. 99 - 105
Published: Oct. 3, 2024
The
identity
of
a
heteroatom
within
an
aromatic
ring
influences
the
chemical
properties
that
heterocyclic
compound.
Systematically
evaluating
effect
single
atom,
however,
poses
synthetic
challenges,
primarily
as
result
thermodynamic
mismatches
in
atomic
exchange
processes.
We
present
photocatalytic
strategy
swaps
oxygen
atom
furan
with
nitrogen
group,
directly
converting
into
pyrrole
analog
intermolecular
reaction.
High
compatibility
was
observed
various
derivatives
and
nucleophiles
commonly
used
drug
discovery,
late-stage
functionalization
furnished
otherwise
difficult-to-access
pyrroles
from
naturally
occurring
furans
high
molecular
complexity.
Mechanistic
analysis
suggested
polarity
inversion
through
electron
transfer
initiates
redox-neutral
processes
at
room
temperature.
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(32), P. 22829 - 22839
Published: Aug. 1, 2024
The
molecular
editing
of
ketones
represents
an
appealing
strategy
due
to
its
ability
maximize
the
structural
diversity
ketone
compounds
in
a
straightforward
manner.
However,
developing
efficient
methods
for
arbitrary
modification
ketonic
molecules,
particularly
those
integrated
within
complex
skeletons,
remains
significant
challenge.
Herein,
we
present
unique
recasting
that
involves
radical
acylation
Accounts of Chemical Research,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 26, 2025
ConspectusN-Heterocycles
are
essential
in
pharmaceutical
engineering,
materials
science,
and
synthetic
chemistry.
Recently,
skeletal
editing,
which
involves
making
specific
point
changes
to
the
core
of
a
molecule
through
single-atom
insertion,
deletion,
or
transmutation,
has
gained
attention
for
its
potential
modify
complex
substrates.
In
this
context,
insertion
nitrogen
atoms
into
carbocycles
form
N-heterocycles
emerged
as
significant
research
focus
modern
chemistry
owing
novel
logic.
This
distinctive
retrosynthetic
approach
enables
late-stage
modification
molecular
skeletons
provides
different
pathway
synthesizing
multiply
substituted
N-heterocycles.
Nevertheless,
atom
proven
challenging
because
inherent
inertness
carbon-based
difficulty
cleaving
C-C
bonds.
Therefore,
selective
editing
remains
growing
field
Account
primarily
highlights
contributions
our
laboratory
active
acknowledges
key
from
other
researchers.
It
is
organized
two
sections
based
on
type
carbocycle.
The
first
section
explores
cycloalkenes.
Recent
Co-catalyzed
oxidative
azidation
strategies
have
enabled
cyclobutenes,
cyclopentenes,
cyclohexenes,
facilitating
synthesis
polysubstituted
pyridines,
been
conventionally
pyridine
cross-coupling.
subsequent
discovery
realm
arenes.
site-selective
stable
arenes
We
developed
method
intramolecular
benzene
rings
2-amino
biaryls
by
suppressing
competing
C-H
process
using
paddlewheel
dirhodium
catalyst.
addition,
address
issues
we
employed
arenols
substrates,
could
act
controlling
elements
editing.
reported
Cu-catalyzed
arenols,
proceeds
dearomative
azidation/aryl
migration
process,
enabling
incorporation
Inspired
result,
recently
extended
reaction
model
Fe-catalyst
facilitate
ring
contraction
nitrogen-inserted
product,
achieving
carbon-to-nitrogen
transmutation
arenols.
Various
polyaromatic
effectively
undergo
desired
atom's
presenting
considerable
various
applications
Account,
present
an
overview
achievements
reactions,
with
scopes,
mechanistic
features,
applications.
anticipate
that
will
provide
valuable
insights
propel
development
innovative
methodologies
both
N-heterocycle
synthesis.
Organic Letters,
Journal Year:
2024,
Volume and Issue:
26(33), P. 7078 - 7082
Published: Aug. 9, 2024
Multicomponent
reactions
hold
the
potential
to
maximize
synthetic
efficiency
in
preparation
of
diverse
and
complex
molecular
scaffolds.
An
unprecedented
formal
[3+1+1+1]
annulation
approach
for
one-step
synthesis
fluoroalkylated
2-H-pyrimidines
commencing
from
perfluoroalkyl
alkenes,
paraformaldehyde,
ammonium
carbonate
is
described.
By
harnessing
readily
accessible
(CH2O)n
cheap
(NH4)2CO3
as
a
formamidine
surrogate,
this
method
effectively
replaces
traditionally
preformed
amidines
with
pyrimidine
assembly.
The
multicomponent
reaction
proceeds
step-economical,
operationally
simple,
metal-free,
additive-free
manner,
featuring
broad
substrate
scope,
excellent
functional
group
compatibility,
scalability.
elaboration
obtained
2-H-pyrimidine
further
demonstrated
alkylation
vinylation
its
C2
position.
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.
Chemical Science,
Journal Year:
2024,
Volume and Issue:
15(37), P. 15205 - 15211
Published: Jan. 1, 2024
The
targeted
and
selective
replacement
of
a
single
atom
in
an
aromatic
system
represents
powerful
strategy
for
the
rapid
interconversion
molecular
scaffolds.
Herein,
we
report
pyridine-to-benzene
transformation
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.
