Angewandte Chemie,
Journal Year:
2024,
Volume and Issue:
136(38)
Published: June 26, 2024
Abstract
Piperidines
are
widely
present
in
small
molecule
drugs
and
natural
products.
Despite
many
methods
have
been
developed
for
their
synthesis,
new
approaches
to
polysubstituted
piperidines
highly
desirable.
This
work
presents
a
radical
(4+2)
cycloaddition
reaction
synthesis
of
featuring
dense
substituents
at
3,4,5‐positions
that
not
readily
accessible
by
known
methods.
Using
commercially
available
diboron(4)
compounds
4‐phenylpyridine
as
the
catalyst
precursors,
boronyl
radical‐catalyzed
between
3‐aroyl
azetidines
various
alkenes,
including
previously
unreactive
1,2‐di‐,
tri‐,
tetrasubstituted
has
delivered
generally
high
yield
diastereoselectivity.
The
also
features
modularity,
atom
economy,
broad
substrate
scope,
metal‐free
conditions,
simple
catalysts
operation.
utilization
products
demonstrated
selective
transformations.
A
plausible
mechanism,
with
ring‐opening
azetidine
rate‐limiting
step,
proposed
based
on
experimental
computational
results.
Chemical Society Reviews,
Journal Year:
2024,
Volume and Issue:
53(12), P. 6600 - 6624
Published: Jan. 1, 2024
Dearomatization
has
emerged
as
a
powerful
tool
for
rapid
construction
of
3D
molecular
architectures
from
simple,
abundant,
and
planar
(hetero)arenes.
The
field
evolved
beyond
simple
dearomatization
driven
by
new
synthetic
technology
development.
With
the
renaissance
photocatalysis
expansion
activation
mode,
last
few
years
have
witnessed
impressive
developments
in
innovative
photochemical
methodologies,
enabling
skeletal
modifications
dearomatized
structures.
They
offer
truly
efficient
useful
tools
facile
highly
complex
structures,
which
are
viable
natural
product
synthesis
drug
discovery.
In
this
review,
we
aim
to
provide
mechanistically
insightful
overview
on
these
innovations
based
degree
alteration,
categorized
into
dearomative
functionalization
editing,
highlight
their
utilities.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(38)
Published: June 26, 2024
Piperidines
are
widely
present
in
small
molecule
drugs
and
natural
products.
Despite
many
methods
have
been
developed
for
their
synthesis,
new
approaches
to
polysubstituted
piperidines
highly
desirable.
This
work
presents
a
radical
(4+2)
cycloaddition
reaction
synthesis
of
featuring
dense
substituents
at
3,4,5-positions
that
not
readily
accessible
by
known
methods.
Using
commercially
available
diboron(4)
compounds
4-phenylpyridine
as
the
catalyst
precursors,
boronyl
radical-catalyzed
between
3-aroyl
azetidines
various
alkenes,
including
previously
unreactive
1,2-di-,
tri-,
tetrasubstituted
has
delivered
generally
high
yield
diastereoselectivity.
The
also
features
modularity,
atom
economy,
broad
substrate
scope,
metal-free
conditions,
simple
catalysts
operation.
utilization
products
demonstrated
selective
transformations.
A
plausible
mechanism,
with
ring-opening
azetidine
rate-limiting
step,
proposed
based
on
experimental
computational
results.
Synthesis,
Journal Year:
2024,
Volume and Issue:
56(23), P. 3621 - 3629
Published: Oct. 22, 2024
Abstract
A
rapid
and
convenient
method
for
the
synthesis
of
differently
substituted
spiro[cyclohexane-1,1′-isochromane]-2,5-dien-4-one
derivatives
via
phenyliodine(III)
bis(trifluoroacetate)
(PIFA)-promoted
intramolecular
oxidative
dearomatization
at
para
position
is
disclosed,
with
aim
building
a
library
new
spirocyclohexadienone
scaffolds.
Subsequently,
this
strategy
modified
to
access
novel
cyclohexanedienone-containing
polycyclic
compounds.
Organic Letters,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 10, 2025
A
three-component
cascade
boronation–dearomatization
reaction
of
alkenes,
a
diboron
compound,
and
pyridinium
salt
is
diclosed,
affording
chiral
boron-containing
1,4-dihyropyridines
in
high
yields
(≤98%)
diastereoselectivity
(≤10:1
dr),
along
with
excellent
enantioselectivity
(typically
>99%
ee).
The
catalytic
system
performs
efficiently
at
low
catalyst
loadings
(1
mol
%)
was
tested
>50
examples,
including
some
biologically
active
molecules.
Chemical Communications,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 1, 2025
A
divergent
denitrogenation/recyclization
of
1,2,3,4-benzothiatriazine-1,1-dioxides
is
disclosed,
including
C(sp
2
)-alkyl
transposition
and
aniline
dearomatization.
Accounts of Chemical Research,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 11, 2025
ConspectusDearomatization
of
simple
aromatics
serves
as
one
the
most
direct
strategies
for
converting
abundant
chemical
feedstocks
into
three-dimensional
value-added
products.
Among
such
transformations,
cycloadditions
between
arenes
and
alkenes
have
historically
offered
effective
means
to
construct
complex
polycyclic
architectures.
However,
traditionally
harsh
conditions,
high-energy
UV
light
irradiation,
greatly
limited
scope
this
transformation.
Nevertheless,
recent
progress
has
led
development
visible-light-promoted
dearomative
photocycloadditions
with
expanded
capable
preparing
bicyclic
structures.A
fundamentally
distinct
approach
involves
visible-light
activation
arenophiles,
which
undergo
para-photocycloaddition
various
aromatic
compounds
produce
arene-arenophile
cycloadducts.
While
only
transiently
stable
subject
retro-cycloaddition,
further
functionalization
photocycloadducts
allowed
a
wide
collection
dearomatization
methodologies
that
access
products
orthogonal
existing
biological
processes.
Central
strategy
was
observation
photocycloaddition
reveals
π-system
can
be
functionalized
through
traditional
olefin
chemistry.
Coupled
subsequent
[4
+
2]-cycloreversion
arenophile,
process
acts
effectively
isolate
single
from
an
ring.
We
developed
several
transformations
bias
methodology
perform
single-atom
insertion
π-extension
reactions
prepare
unique
cannot
prepared
easily
means.Through
application
epoxidation,
we
were
able
develop
method
epoxidation
pyridines
arene-oxides
pyridine-oxides,
respectively.
Notably,
when
arenophile
chemistry
is
applied
arenes,
transposed
site
native
olefinic
reactivity,
enabling
site-selectivity
functionalization.
As
result,
oxygen
(aza)arenes
3-benzoxepines.
When
applying
in
context
cyclopropanations,
accomplish
cyclopropanation
yield
benzocycloheptatrienes
upon
cycloreversion.
while
Buchner
ring
expansion
powerful
carbon
corresponding
does
not
ring-expanded
Furthermore,
could
utilized
synthesis
novel
nanographenes
M-region
annulative
(M-APEX)
reaction.
Traditionally,
methods
rely
on
reactivity
at
K-
bay-region.
arenophiles
activate
reactivity.
arenophile-mediated
diarylation,
followed
by
cycloreversion,
deliver
π-extended
exclusive
selectivity.
Abstract
Dearomatizations
have
long
been
recognized
as
an
important
class
of
reactions,
with
significant
progress
achieved;
however,
the
utilization
simple
and
nonactivated
arenes
remains
a
challenging
endeavor
due
to
their
inherent
inertness
difficulty
achieving
selective
transformations.
This
review
highlights
emerging
dearomatization
approach
that
enables
conversion
such
under
mild
conditions:
arenophile-mediated
photochemical
dearomative
functionalization.
methodology
provides
efficient
access
alicyclic
structures,
offering
both
functional
stereochemical
complexity,
including
C—C,
C—B,
C—N,
C—O,
C—H
bond
formations.
Applications
in
synthesis
complex
bioactive
compounds
are
also
presented
demonstrate
unique
versatility
this
strategy.
Organic Letters,
Journal Year:
2025,
Volume and Issue:
unknown
Published: May 12, 2025
The
use
of
simple
raw
materials
to
construct
complex
piperidine
scaffolds
via
multicomponent
reactions
is
highly
desirable
from
the
perspectives
atom
and
step-economy.
In
this
Letter,
we
present
a
photoinduced
copper-catalyzed
three-
or
four-component
[3
+
2
1]
radical
cyclization,
utilizing
inexpensive
readily
available
feedstock
amines,
alkynes,
aldehydes,
synthesize
multisubstituted
bicyclic
spirocyclic
tetrahydropyridines.
This
method
notable
for
its
mild
conditions,
atom-economic
approach,
excellent
regio-
diastereoselectivity,
simultaneous
activation
two
α-amino
C(sp3)-H
bonds,
resulting
in
formation
three
C-C
bonds
one
C-N
bond
single
step.
Mechanistic
studies
suggest
that
α-aminoalkyl
key
intermediate
reaction,
which
undergoes
sequential
addition,
1,5-HAT,
6-exo-trig-type
cyclization.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
64(1)
Published: Sept. 16, 2024
The
rapid
construction
of
three-dimensional
(3D)
heterocyclic
frameworks
is
a
key
challenge
in
contemporary
medicinal
chemistry.
molecules
with
complexity
hold
greater
probability
to
improve
clinical
outcomes,
solubility,
selectivity
for
target
proteins,
and
metabolic
stability.
However,
the
prevalence
flat
persists
among
new
drug
candidates,
primarily
owing
multitude
chemical
methods
available
their
synthesis.
In
principle,
dearomative
functionalization
N-heteroarene
allows
conversion
readily
planar
into
partially
or
fully
saturated
nitrogen
heterocycles,
which
are
most
significant
structural
motifs
pharmaceuticals
natural
products.
Unfortunately,
these
reactions
very
rare
because
inherent
imposed
by
heteroarenes'
poor
reactivity,
rendering
process
thermodynamically
unfavorable.
Herein,
we
report
modular
approach
accessing
3D
space
translating
heteroarenes
valuable
heterocycles
via
installation
highly
versatile
cyano
group
as
vector.
This
enabled
situ
generation
reactive,
non-symmetric
iodane
combining
cyanide
anion
bench-stable
PhI(OAc)
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(17), P. 11610 - 11615
Published: April 15, 2024
Despite
much
progress
in
the
area
of
dearomatization,
enantioselective
dearomatization
heterocycles
is
limited
to
those
with
a
single
heteroatom.
Here
we
report
highly
copper-catalyzed
pyrazine,
diazine,
leading
chiral
C-substituted
piperazines.
When
exposed
chloroformate
and
an
alkyne
presence
catalyst
derived
from
copper
salt
ligand
StackPhos,
pyrazine
readily
dearomatized
provide
2,3-disubstituted
dihydropyrazine
as
diastereomer
high
enantiomeric
excess.
Mechanistic
studies
support
noninnocent
involvement
chloride
ion
preventing
second
iminium
alkynylation,
thus
enabling
subsequent
functionalization
at
reactive
site.
The
synthetically
useful
products,
obtained
up
95%
yield
99%
ee,
can
be
further
manipulated
form
optically
active
piperazines
