ACS Catalysis,
Journal Year:
2023,
Volume and Issue:
13(19), P. 12692 - 12699
Published: Sept. 14, 2023
Accomplished
herein
is
a
rearrangement
strategy
for
the
highly
efficient
assembly
of
synthetically
cumbersome
while
medicinally
significant
2-amino-3-formyl
chromones
via
palladium-catalyzed
ring-opening,
rearrangement,
and
cyclization
process.
Such
sequence
enables
formation
one
C(sp2)–O
bond
C(sp2)–C(sp2)
bond,
reconstruction
benzo-γ-pyrone
moiety
in
single
operation,
thus
producing
difunctionalized
chromone-incorporated
derivatives.
The
reaction
proceeds
shorter
time
(30
min
3-iodochromones
most
cases)
atom-
step-economical
manner.
synthetic
application
current
protocol
further
demonstrated
by
late-stage
modification
pharmaceuticals
their
intermediates,
gram-scale
reactions,
transformations
functional
groups,
as
well
synthesis
bioactive
molecules
drugs.
Mechanistic
studies
indicate
that
nucleophilic
ring-opening
process
moiety,
phenoxy
anion
intermediate,
an
intramolecular
might
be
involved
present
system.
Helvetica Chimica Acta,
Journal Year:
2023,
Volume and Issue:
106(3)
Published: Jan. 13, 2023
Abstract
Skeletal
editing
involves
making
specific
point‐changes
to
the
core
of
a
molecule
through
selective
insertion,
deletion
or
exchange
atoms.
It
thus
represents
potentially
powerful
strategy
for
step‐economic
modification
complex
substrates
and
is
perfect
complement
methods
such
as
C−H
functionalization
that
target
molecular
periphery.
Given
their
ubiquity
in
biologically
active
compounds,
ability
perform
skeletal
on
–
therefore
interconvert
between
aromatic
heterocycles
especially
valuable.
This
review
summarizes
both
recent
key
historical
examples
applied
interconversion
rings;
we
anticipate
it
will
serve
highlight
not
only
innovative
enabling
nature
current
methods,
but
also
tremendous
opportunities
still
exist
field.
Nature Chemistry,
Journal Year:
2024,
Volume and Issue:
16(5), P. 741 - 748
Published: Jan. 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.
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(5), P. 2950 - 2958
Published: Jan. 29, 2024
The
selective
modification
of
nitrogen
heteroaromatics
enables
the
development
new
chemical
tools
and
accelerates
drug
discovery.
While
methods
that
focus
on
expanding
or
contracting
skeletal
structures
are
emerging,
for
direct
exchange
single
core
atoms
remain
limited.
Here,
we
present
a
method
14N
→
15N
isotopic
several
aromatic
heterocycles.
This
isotope
transmutation
occurs
through
activation
heteroaromatic
substrate
by
triflylation
atom,
followed
ring-opening/ring-closure
sequence
mediated
15N-aspartate
to
effect
atom.
Key
success
this
transformation
is
formation
an
isolable
15N-succinyl
intermediate,
which
undergoes
elimination
give
isotopically
labeled
heterocycle.
These
transformations
occur
under
mild
conditions
in
high
yields.
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(4), P. 2845 - 2854
Published: Jan. 18, 2024
In
this
report,
we
developed
a
unified
and
standardized
one-pot
sequence
that
converts
pyridine
derivatives
into
1,2-diazepines
by
inserting
nitrogen
atom.
This
skeletal
transformation
capitalizes
on
the
in
situ
generation
of
1-aminopyridinium
ylides,
which
rearrange
under
UV
light
irradiation.
A
thorough
evaluation
key
parameters
(wavelength,
reaction
conditions,
activating
agent)
allowed
us
to
elaborate
simple,
mild,
user-friendly
protocol.
The
model
was
extrapolated
more
than
40
examples,
including
drug
derivatives,
affording
unique
7-membered
structures.
Mechanistic
evidence
supports
transient
presence
diazanorcaradiene
species.
Finally,
pertinent
transformations
products,
ring
contraction
reactions
form
pyrazoles,
were
conducted
paved
way
broad
application
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(5), P. 2939 - 2943
Published: Jan. 12, 2024
A
practical
method
for
the
synthesis
of
15N-labeled
azines
with
a
high
degree
isotopic
enrichment
is
described.
Activation
azine
heterocycles
an
electron-deficient
arene
allows
facile
substitution
nitrogen
atom
specifically
designed
reagent
that
undergoes
canonical
ANRORC-type
mechanism.
wide
range
can
be
converted
to
their
corresponding
15N
isotopologs
using
this
method,
and
it
also
dearomative
access
reduced
heterocyclic
congeners.
short
formal
15N-solifenacin
accomplished
as
well
demonstrate
application
generating
labeled
pharmaceuticals.
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
Science,
Journal Year:
2025,
Volume and Issue:
387(6729), P. 102 - 107
Published: Jan. 2, 2025
Given
the
prevalence
of
nitrogen-containing
heterocycles
in
commercial
drugs,
selectively
incorporating
a
single
nitrogen
atom
is
promising
scaffold
hopping
approach
to
enhance
chemical
diversity
drug
discovery
libraries.
We
harness
distinct
reactivity
sulfenylnitrenes,
which
insert
transform
readily
available
pyrroles,
indoles,
and
imidazoles
into
synthetically
challenging
pyrimidines,
quinazolines,
triazines,
respectively.
Our
additive-free
method
for
skeletal
editing
employs
easily
accessible,
benchtop-stable
sulfenylnitrene
precursors
over
broad
temperature
range
(−30
150°C).
This
compatible
with
diverse
functional
groups,
including
oxidation-sensitive
functionalities
such
as
phenols
thioethers,
has
been
applied
various
natural
products,
amino
acids,
pharmaceuticals.
Furthermore,
we
have
conducted
mechanistic
studies
explored
regioselectivity
outcomes
through
density
theory
calculations.
