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.
Science,
Journal Year:
2023,
Volume and Issue:
381(6653), P. 75 - 81
Published: July 6, 2023
Skeletal
ring
enlargement
is
gaining
renewed
interest
in
synthetic
chemistry
and
has
recently
focused
on
insertion
of
one
or
two
atoms.
Strategies
for
heterocyclic
expansion
through
small-ring
remain
elusive,
although
they
would
lead
to
the
efficient
formation
bicyclic
products.
Here,
we
report
a
photoinduced
dearomative
thiophenes
by
bicyclo[1.1.0]butanes
produce
eight-membered
rings
under
mild
conditions.
The
value,
broad
functional-group
compatibility,
excellent
chemo-
regioselectivity
were
demonstrated
scope
evaluation
product
derivatization.
Experimental
computational
studies
point
toward
photoredox-induced
radical
pathway.
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.
Journal of the American Chemical Society,
Journal Year:
2022,
Volume and Issue:
144(48), P. 22309 - 22315
Published: Nov. 28, 2022
A
method
for
the
conversion
of
pyrimidines
into
pyrazoles
by
a
formal
carbon
deletion
has
been
achieved
guided
computational
analysis.
The
pyrimidine
heterocycle
is
most
common
diazine
in
FDA-approved
drugs,
and
are
diazole.
An
efficient
to
convert
would
therefore
be
valuable
leveraging
chemistries
unique
access
diversified
pyrazoles.
One
known,
though
it
proceeds
low
yields
requires
harsh
conditions.
transformation
reported
here
under
milder
conditions,
tolerates
wide
range
functional
groups,
enables
simultaneous
regioselective
introduction
N-substitution
on
resulting
pyrazole.
Key
success
this
one-carbon
room-temperature
triflylation
core,
followed
hydrazine-mediated
skeletal
remodeling.
Chemistry - A European Journal,
Journal Year:
2023,
Volume and Issue:
29(42)
Published: May 26, 2023
Abstract
(Hetero)arenes
continue
to
prove
their
indispensability
in
pharmaceuticals,
materials
science,
and
synthetic
chemistry.
As
such,
the
controllable
modification
of
biologically
significant
(hetero)arenes
towards
diverse
more‐potent
complex
molecular
scaffolds
through
peripheral
skeletal
editing
has
been
considered
a
challenging
goal
organic
Despite
many
excellent
reviews
on
(
i.
e
.,
C−H
functionalization)
(hetero)arenes,
editings
via
single
atom
insertion,
deletion,
or
transmutations
have
received
less
attention
review
literature.
In
this
review,
we
systematically
summarize
state‐of‐the‐art
reactions
using
carbenes,
with
focus
general
mechanistic
considerations
applications
natural
product
syntheses.
The
potential
opportunities
inherent
challenges
encountered
while
developing
these
strategies
are
also
highlighted.
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(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(7), P. 4301 - 4308
Published: Feb. 9, 2024
The
development
of
divergent
methods
to
expedite
structure–activity
relationship
studies
is
crucial
streamline
discovery
processes.
We
developed
a
rare
example
regiodivergent
ring
expansion
access
two
regioisomers
from
common
starting
material.
To
enable
this
regiodivergence,
we
identified
distinct
reaction
conditions
for
transforming
oxindoles
into
quinolinone
isomers.
presented
proved
be
compatible
with
variety
functional
groups,
which
enabled
the
late-stage
diversification
bioactive
as
well
facilitated
synthesis
drugs
and
their
derivatives.
Journal of the American Chemical Society,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 2, 2025
We
recently
reported
a
chiral
phosphoric
acid
(CPA)
catalyzed
enantioselective
photomediated
ring
contraction
of
piperidines
and
other
saturated
heterocycles.
By
extruding
single
heteroatom
from
ring,
this
transformation
builds
desirable
C(sp3)–C(sp3)
bonds
in
the
contracted
products;
however,
origins
enantioselectivity
remain
poorly
understood.
In
work,
has
been
explored
across
an
expanded
structurally
diverse
substrate
scope,
revealing
wide
range
enantioselectivities
(0–99%)
using
two
distinct
CPA
catalysts.
Mechanistic
investigations
support
rate-determining
excitation
that
generates
short-lived
achiral
intermediates
are
intercepted
by
enantiodetermining
closure.
The
effects
competitive
uncatalyzed
reactivity
light-driven
reversibility
closure
on
have
elucidated.
Statistical
models
were
built
regressing
scope
against
key
structural
features
products
for
both
resultant
suggested
factors
influence
response
each
catalyst
enabled
rational
modification
pharmaceutically
relevant
target
molecule
to
improve
enantioselectivity.
Finally,
density
functional
theory
(DFT)-based
transition
state
analysis
identified
noncovalent
interactions
with
correlated
unique
selectivity-relevant
uncovered
through
statistical
modeling.
Our
findings
not
only
offer
comprehensive
insight
into
system
but
should
also
aid
future
development
related
CPA-catalyzed
reactions.