Azepines
and
their
saturated
azepane
counterparts
are
important
moieties
in
bioactive
molecules
but
underrepresented
current
drug
screening
libraries.
Herein,
we
report
a
mild
efficient
azepine
formation
via
silver-catalyzed
dearomative
nitrene
transfer.
A
2,2,2-trichloroethoxysulfonyl
(Tces)-protected
carbamimidate
precursor,
coupled
with
the
appropriate
ligand
for
silver,
is
essential
achieving
unexpected
chemoselectivity
between
arene
dearomatization
benzylic
C(sp3)–H
amination.
Potential
applications
late-stage
diversification
of
azepines
to
complex
molecular
scaffolds
diastereoselective
hydrogenations
high
Fsp3
azepanes
also
highlighted.
Chemistry - A European Journal,
Год журнала:
2024,
Номер
30(16)
Опубликована: Янв. 11, 2024
Abstract
Given
the
prevalence
of
heterocyclic
scaffolds
in
drug‐related
molecules,
converting
these
highly
modular
into
structural
diversified
and
dearomatized
analogs
is
an
ideal
strategy
for
improving
their
physicochemical
pharmacokinetic
properties.
Here,
we
described
efficient
method
silver
carbene‐mediated
dearomative
N−N
bond
cleavage
leading
to
skeletal
hopping
between
indazole
1,2‐dihydroquinazoline
via
a
selective
single‐carbon
insertion
procedure.
Using
this
methodology,
series
dihydroquinazoline
analogues
with
diarylmethylene‐substituted
quaternary
carbon
centers
were
constructed
excellent
yields
good
functional
group
compatibility,
which
was
further
illustrated
by
late‐stage
diversification
important
pharmaceutically
active
ingredients.
DFT
calculations
indicated
that
catalyst
not
only
induces
formation
carbene,
but
also
activates
diazahexatriene
intermediate,
plays
crucial
role
C−N
bond.
Chemistry - A European Journal,
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 24, 2024
Hypervalent
iodine
reagents
are
versatile
and
readily
accessible
that
have
been
extensively
applied
in
contemporary
synthesis
modern
organic
chemistry.
Among
them,
iodonitrene
(ArI=NR),
is
a
powerful
reactive
species,
widely
used
for
single-nitrogen-atom
insertion
reaction,
skeletal
editing
to
construct
N-heterocycles.
Skeletal
with
components
has
recently
emerged
as
an
exciting
approach
chemical
transformation.
These
produce
biologically
relevant
heterocycles
functionalized
molecular
architectures.
Recently,
the
of
nitrogen-atom
into
hydrocarbons
generate
N-heterocyclic
compounds
using
hypervalent
significant
focus
field
reactions.
In
this
review,
we
discuss
rapidly
emerging
nitrene
insertion,
including
nitrogen
access
nitrogen-containing
heterocycles,
current
mechanistic
understanding
these
processes.
Chemical Communications,
Год журнала:
2024,
Номер
60(26), С. 3571 - 3574
Опубликована: Янв. 1, 2024
Herein,
a
novel
Pd-catalyzed
denitrogenation/vinylation
of
benzotriazinones
using
vinylene
carbonate
as
the
vinylation
reagent
is
reported.
This
transformation
demonstrates
an
unprecedented
skeletal
editing
approach,
effectively
converting
NN
to
CC
fragments
Synthesis,
Год журнала:
2024,
Номер
56(24), С. 3793 - 3814
Опубликована: Авг. 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
Organic Letters,
Год журнала:
2024,
Номер
26(23), С. 4910 - 4915
Опубликована: Май 31, 2024
A
silver-catalyzed
aminative
dearomatization
of
naphthols
has
been
developed
and
integrated
into
a
stepwise
approach
for
subsequent
skeletal
diversifications
including
ring
expansion,
opening,
contraction,
atom
transmutation
aryl
scaffolds.
This
enables
the
synthesis
diverse
array
azepinones,
unsaturated
amides,
isoquinolines,
indenones
from
naphthol
substrates.
Its
application
in
bioactive
functional
molecules
as
well
conversion
complex
molecular
skeletons
underscores
its
broad
potential
applicability.
Mechanistic
investigations
suggest
intermediacy
dearomatized
intermediates.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(31), С. 22085 - 22092
Опубликована: Июль 25, 2024
Azepines
and
their
saturated
azepane
counterparts
are
important
moieties
in
bioactive
molecules
but
under-represented
current
drug
screening
libraries.
Herein,
we
report
a
mild
efficient
azepine
formation
via
silver-catalyzed
dearomative
nitrene
transfer.
A
2,2,2-trichloroethoxysulfonyl
(Tces)-protected
carbamimidate
precursor,
coupled
with
the
appropriate
ligand
for
silver,
is
essential
achieving
unexpected
chemoselectivity
between
arene
dearomatization
benzylic
C(sp3)–H
amination.
Potential
applications
late-stage
diversification
of
azepines
to
complex
molecular
scaffolds
diastereoselective
hydrogenations
sp3-rich
derivatives
also
highlighted.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(17)
Опубликована: Март 9, 2024
Abstract
The
molecular
structure‐editing
through
selective
C−C
bond
cleavage
allows
for
the
precise
modification
of
structures
and
opens
up
new
possibilities
in
chemical
synthesis.
By
strategically
cleaving
bonds
editing
structure,
more
efficient
versatile
pathways
synthesis
complex
compounds
could
be
designed,
which
brings
significant
implications
drug
development
materials
science.
o
‐Aminophenethyl
alcohols
amines
are
essential
key
motifs
bioactive
functional
material
molecules.
traditional
these
usually
requires
multiple
steps
generate
inseparable
isomers
induce
low
efficiencies.
leveraging
a
strategy,
we
herein
reported
ring‐opening
amination
isochromans
tetrahydroisoquinolines
‐aminophenethyl
amines.
This
innovative
chemistry
under
mild
transition
metal‐free
conditions.
Notably,
further
synthetic
application
demonstrated
that
our
method
provide
an
approach
to
components
diverse
Journal of the American Chemical Society,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 25, 2025
Dearomative
skeletal
editing
of
benzenoids
represents
a
promising
yet
challenging
strategy
for
the
rapid
construction
high-value
carbon
frameworks
from
readily
accessible
starting
materials.
Büchner
reaction
is
unique
type
expansive
that
transforms
into
functionalized
cycloheptatrienes.
However,
due
to
challenges
in
compatibility
and
selectivity,
achieving
seamless
integration
this
with
dearomative
cycloaddition
within
unified
system
remains
undeveloped.
Here,
we
demonstrated
an
energy-transfer-induced
intermolecular
range
electronically
diverse
alkynes.
This
protocol
employed
N-acylimines
as
diradical
precursors
efficiently
construct
various
structurally
polycyclic
high
chemo-,
regio-,
diastereoselectivities
have
been
previously
inaccessible.
The
related
general
reactivity
selectivity
issues
were
circumvented
through
smooth
merging
photoinduced
cycloaddition.
Experimental
computational
studies
performed
support
mechanism
interpret
origins
observed
diastereoselectivities.
Organic Chemistry Frontiers,
Год журнала:
2024,
Номер
11(17), С. 4779 - 4784
Опубликована: Янв. 1, 2024
A
novel
and
unique
nitrogen
atom
insertion
into
naphthoquinone
rings
to
construct
structurally
valuable
polycyclic
heterocycles
at
room
temperature
under
transition-metal-free
conditions
has
been
described.
