Journal of the American Chemical Society,
Journal Year:
2023,
Volume and Issue:
145(50), P. 27810 - 27820
Published: Dec. 7, 2023
Bicyclic
amines
are
important
motifs
for
the
preparation
of
bioactive
materials.
These
species
have
well-defined
exit
vectors
that
enable
accurate
disposition
substituents
toward
specific
areas
chemical
space.
Of
all
possible
skeletons,
2-azabicyclo[3.2.0]heptane
framework
is
virtually
absent
from
MedChem
libraries
due
to
a
paucity
synthetic
methods
its
preparation.
Here,
we
report
modular
strategy
utilizes
nitroarenes
as
flat
and
easy-to-functionalize
feedstocks
assembly
these
sp3-rich
Mechanistically,
this
approach
exploits
two
concomitant
photochemical
processes
sequentially
ring-expand
nitroarene
into
an
azepine
then
fold
it
rigid
bicycle
pyrroline
by
means
singlet
nitrene-mediated
nitrogen
insertion
excited-state-4π
electrocyclization.
A
following
hydrogenolysis
provides,
with
full
diastereocontrol,
desired
bicyclic
amine
derivatives
whereby
aromatic
substitution
pattern
has
been
translated
one
three-dimensional
heterocycle.
molecules
can
be
considered
pyrrolidine
analogues
orientation
their
substituents.
Furthermore,
unsupervised
clustering
expansive
virtual
database
saturated
N-heterocycles
revealed
effective
isosteres
rigidified
piperidines.
Overall,
platform
enables
conversion
complex
heterocycles
potential
interest
drug
development.
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.
Science,
Journal Year:
2023,
Volume and Issue:
381(6665), P. 1474 - 1479
Published: Sept. 28, 2023
Nitrogen
scanning
in
aryl
fragments
is
a
valuable
aspect
of
the
drug
discovery
process,
but
current
strategies
require
time-intensive,
parallel,
bottom-up
synthesis
each
pyridyl
isomer
because
lack
direct
carbon-to-nitrogen
(C-to-N)
replacement
reactions.
We
report
site-directable
C-to-N
reaction
allowing
unified
access
to
various
pyridine
isomers
through
nitrene-internalization
process.
In
two-step,
one-pot
procedure,
azides
are
first
photochemically
converted
3
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
