Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(29), С. 19660 - 19666
Опубликована: Июль 12, 2024
Late-stage
derivatization
of
drug-like
functional
groups
can
accelerate
drug
discovery
efforts
by
swiftly
exchanging
hydrogen-bond
donors
with
acceptors,
or
modulating
key
physicochemical
properties
like
logP,
solubility,
polar
surface
area.
A
proven
strategy
to
improve
ligand
potency
is
extend
the
displace
water
molecules
that
are
mediating
interactions
a
receptor.
Inspired
this
application,
we
developed
method
regioselectively
transmute
nitrogen
atom
from
pyridine
into
carbon
bearing
an
ester,
flexible
group
handle.
We
applied
variety
substituted
pyridines,
as
well
late-stage
transformation
FDA-approved
drugs.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(4), С. 2845 - 2854
Опубликована: Янв. 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,
Год журнала:
2024,
Номер
146(5), С. 2950 - 2958
Опубликована: Янв. 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,
Год журнала:
2024,
Номер
146(32), С. 22829 - 22839
Опубликована: Авг. 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
Chem,
Год журнала:
2024,
Номер
10(6), С. 1940 - 1949
Опубликована: Июнь 1, 2024
The
skeletal
editing
of
heteroarenes
introduces
new
disconnections
to
the
chemistry
lexicon,
enabling
interconversion
ring
systems
via
selective
breaking/re-making
carbon
framework.
We
describe
one-pot
transformation
pyridines
into
benzene
derivatives,
using
a
nucleophilic
addition
ring-opening/ring-closing
(ANRORC)
process
with
soft
nucleophiles
such
as
malonate.
Triflic
anhydride
activates
pyridine
ANRORC
synthesis
an
isolable
amine
intermediate,
which
aromatizes
on
simple
heating.
reaction
has
been
exemplified
room
temperature
protocol,
along
direct
syntheses
drug-like,
tertiary-alkylated,
and
isotopically
labeled
benzoates.
Chemical Science,
Год журнала:
2024,
Номер
15(16), С. 5938 - 5943
Опубликована: Янв. 1, 2024
Cyclopropyl-substituted
sulfonium
salts
are
obtained
by
Rh-catalysed
addition
of
α-diazo
dibenzothiophenium
to
olefins.
When
indenes
used
as
substrates,
initially
formed
cyclopropyl
rings
open
with
concomitant
elimination
dibenzothiophene,
enabling
access
2-substituted
naphthalenes.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(24)
Опубликована: Апрель 10, 2024
Abstract
The
skeletal
editing
of
azaarenes
through
insertion,
deletion,
or
swapping
single
atoms
has
recently
gained
considerable
momentum
in
chemical
synthesis.
Here,
we
describe
a
practical
strategy
using
vinylcarbenes
situ
generated
from
trifluoromethyl
vinyl
N
‐triftosylhydrazones,
leading
to
the
first
dearomative
pyrroles
carbon‐atom
insertion.
Furthermore,
depending
on
used
catalyst
and
substrate,
three
types
peripheral
reactions
are
also
disclosed:
α‐
γ‐selective
C−H
[3+2]
cycloaddition.
These
controllable
molecular
provide
powerful
platform
for
accessing
medicinally
relevant
CF
3
‐containing
‐heterocyclic
frameworks,
such
as
2,5‐dihydropyridines,
piperidines,
azabicyclo[3.3.0]octadienes,
allylated
readily
available
pyrroles.
Mechanistic
insights
experiments
density
functional
theory
(DFT)
calculations
shed
light
origin
substrate‐
catalyst‐controlled
chemo‐
regioselectivity
well
reaction
mechanism.
