The
'escape
from
flatland'
concept
has
gained
significant
traction
in
modern
drug
discovery,
emphasizing
the
importance
of
three-dimensional
molecular
architectures,
which
serve
as
saturated
bioisosteres
benzenoids.
Bicyclo[1.1.0]butanes
(BCBs),
known
for
their
high
ring
strain
and
numerous
reactivities,
offer
a
simple
yet
effective
method
synthesizing
these
bicyclic
frameworks.
Although
(3
+
2)
annulations
involving
BCBs
have
been
extensively
studied,
1,3-dipolar
cycloaddition
leading
to
3)
annulation
received
limited
attention.
Herein,
we
report
Lewis
acid-catalyzed
with
isatogens
allowing
synthesis
biologically
relevant
tetracyclic
2-oxa-3-azabicyclo[3.1.1]heptanes.
Moreover,
reaction
can
be
performed
one-pot
process
by
situ
generation
2-alkynylated
nitrobenzenes.
Additionally,
preliminary
mechanistic
photophysical
studies
annulated
products
experiments
toward
asymmetric
version
this
are
also
provided.
Chemical Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 1, 2025
We
disclose
a
method
for
silver-enabled
formal
[4π
+
2
σ
]
cycloaddition
reactions
between
bicyclobutanes
and
nitrile
imines
(generated
from
hydrazonyl
chlorides)
to
furnish
diverse
array
of
2,3-diazo-BCHepes.
ACS Catalysis,
Год журнала:
2024,
Номер
unknown, С. 17837 - 17849
Опубликована: Ноя. 18, 2024
The
investigation
into
the
synthesis
of
azabicyclo[3.1.1]heptanes
(azaBCHeps)
as
bioisosteres
to
flat
aza-aromatics
has
garnered
increasing
attention,
while
it
encounters
significant
challenges.
Herein,
we
have
demonstrated
In(OTf)3-catalyzed
(3
+
3)
dipolar
cyclization
bicyclo[1.1.0]butanes
(BCBs)
with
hydrazones
and
π-allyl-iridium
1,3-dipoles,
engendering
a
diverse
array
azaBCHeps.
BCBs
furnished
densely
substituted
2,3-diazabicyclo[3.1.1]heptanes
2,3-diazabicyclo[3.1.1]heptenes
under
nitrogen
oxygen
atmospheres,
respectively.
A
combination
experimental
computational
investigations
lends
robust
support
for
proton-transfer-interposed
sequential
mechanism.
More
importantly,
by
integrating
In(OTf)3/iridium
relay
catalysis,
enantiopure
2-azabicyclo[3.1.1]heptanes
were
constructed
through
aza-π-allyl-iridium
in
situ
generated
from
N-allyl
carbonates.
Both
methodologies
exhibit
mild
reaction
conditions
good
tolerance
various
functional
groups.
Moreover,
copious
derivatization
products
highlights
utility
newly
synthesized
heterobicyclic
motifs
versatile
building
blocks
synthetic
chemistry.
The Journal of Organic Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 27, 2025
Organic
selenium
compounds
are
important
molecules
with
a
wide
range
of
applications
in
pharmaceuticals,
organic
materials,
catalysis,
and
other
fields.
Herein,
we
report
the
synthesis
α-selenomethylketones
through
reaction
vinyl
azides
arylselenols
benzylselenol.
This
protocol
has
advantages
releasing
only
nitrogen
as
benign
byproduct,
using
air
an
environmentally
friendly
initiator,
very
short
duration,
mild
conditions,
broad
substrate
compatibility.
The
results
exploratory
studies
show
that
oxygen
is
used
initiator
to
promote
this
radical
cascade
reaction.
Journal of the American Chemical Society,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 28, 2025
The
cycloaddition
reactions
of
bicyclo[1.1.0]butanes
with
alkenes,
imines,
nitrones,
or
aziridines
have
served
as
an
efficient
platform
to
create
conformationally
restricted
saturated
bicyclic
scaffolds.
However,
the
use
readily
available
aromatics
in
such
reactions,
especially
asymmetric
manner,
remains
underexplored.
Herein,
we
report
a
highly
regio-
and
enantioselective
dearomative
[2π
+
2σ]
photocycloaddition
reaction
between
naphthalene
derivatives
bicyclo[1.1.0]butanes,
enabled
by
Gd(III)
catalysis.
Bicyclo[1.1.0]butanes
naphthalenes
adorned
diverse
array
functional
groups
are
well-tolerated
under
mild
conditions,
affording
enantioenriched
pharmaceutically
important
bicyclo[2.1.1]hexanes
30–96%
yields
81–93%
ee
12:1
→
>20:1
rr.
synthetic
versatility
this
is
further
demonstrated
facile
removal
directing
group
derivatizations
dearomatized
product.
UV–vis
absorption
spectroscopy
studies
suggest
involvement
excited
species
process.
Cycloadditions
of
bicyclobutanes
with
two-
or
three-atom
reaction
partners
have
been
widely
exploited
to
access
bicyclo[2.1.1]hexanes
and
bicyclo[3.1.1]heptanes.
However,
their
application
the
synthesis
bicyclo[4.1.1]octane
derivatives
has
remained
elusive.
Herein,
we
report
silver-catalyzed
formal
(4+3)
cycloadditions
between
simple
benzodithioloimines,
establishing
a
new
method
for
synthesizing
previously
inaccessible
2,5-dithia-bicyclo[4.1.1]octanes,
which
two
sulfur
atoms
in
frameworks.
This
mild
tolerates
bicyclobutane
substrates
wide
range
substituents.
The
synthetic
utility
this
was
demonstrated
via
various
transformations
products
yield
valuable
sulfur-containing
bridged
bicyclic
scaffolds.
Multiply
substituted
cyclobutanols
are
pivotal
synthetic
intermediates
for
constructing
complex
molecular
architectures
via
ring-opening
strategies.
The
development
of
efficient
methods
these
valuable
building
blocks
has
garnered
significant
interest
in
the
chemical
community.
In
this
work,
we
have
described
a
novel
silver(I)-catalyzed
tandem
cyclization–cycloaddition–isomerization
sequence
with
bicyclobutanes
and
2-alkynylbenzaldoximes,
which
offered
an
effective
route
to
multiply
cyclobutanols.
This
protocol
features
mild
conditions,
remarkable
stereospecificity,
broad
substrate
scope,
excellent
functional
group
tolerance.
addition,
application
potential
reaction
was
readily
proven
by
its
high
efficiency
reactants
bearing
biological
moieties
scale-up
experiments.
Higher-order
cycloadditions
are
a
simple
and
effective
strategy
for
constructing
significant
medium-sized
architectures.
Azaheptafulvenes
reacting
with
readily
accessible
bicyclo[1.1.0]butanes
(BCBs)
through
FeCl3-promoted
intermolecular
formal
[8π+2σ]
cycloaddition
reactions
to
access
cycloheptatriene-fused
2-azabicyclo[3.1.1]heptanes
have
been
developed.
This
new
reaction
tolerated
wide
range
of
azaheptafulvenes
BCBs.
Furthermore,
the
amplification
experiment
synthetic
transformations
adducts,
including
modifications
marketed
drugs,
further
highlighted
their
practicalities.
Control
experiments
DFT
calculations
suggest
that
diastereoselective
product
formation
may
involve
stepwise
pathway.
A
palladium-catalyzed
[2π
+
2σ]
cycloaddition
of
vinyl
bicyclo[1.1.0]butanes
with
methyleneindolinones
has
been
developed.
The
reaction
enables
the
construction
spirobicyclo[2.1.1]hexanes
bearing
an
all-carbon
quaternary
center
in
moderate
to
good
yields
excellent
diastereoselectivities.
This
method
features
a
broad
substrate
scope
functional
group
compatibility.
practical
utility
this
protocol
was
further
demonstrated
by
gram-scale
synthesis
and
postsynthetic
transformations
desired
product.
