Organic Letters,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 26, 2024
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.
Organic Letters,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 20, 2025
The
bicyclo[1.1.0]butyl
scaffold
has
emerged
as
a
valuable
bioisostere
in
drug
discovery
programs.
Here,
we
present
streamlined
approach
for
the
generation
of
bicyclo[1.1.0]butyllithium
and
its
functionalization
with
various
classes
electrophiles
one-flow
process,
eliminating
need
intermediate
isolation.
In
comparison
to
traditional
batch
processes,
flow
method
allows
use
single
organolithium
reagent
instead
two
operates
at
significantly
higher
temperatures
(0
°C
versus
−78
°C),
enhancing
both
practicality
scalability.
Organic Letters,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 30, 2025
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.
Organic Letters,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 1, 2025
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.
Organic Letters,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 8, 2025
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.
Journal of the American Chemical Society,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 23, 2025
Bicyclo[2.1.1]hexane
is
an
emerging
scaffold
in
various
pharmaceutical
settings,
but
the
scarcity
of
approaches
to
target
different
regioisomers
from
a
common
starting
material
prevents
targeting
broader
range
chemical
space.
Herein,
we
demonstrate
new
design
for
photocatalyst-controlled
regiodivergent
synthesis
this
scaffold.
Of
particular
interest
that
two
distinct
substitution
patterns
was
achieved
under
photochemical
conditions
with
catalyst
control.
This
possible
due
activating
group,
N-methylimidazole,
not
only
playing
important
role
guiding
divergent
pathways
also
enabling
transformation
functional
groups.
Transient
absorption
spectroscopy
discerned
between
mechanisms,
as
assignable
bands
consistent
electron
transfer
and
energy
processes
were
distinctively
observed,
depending
on
identity
photocatalyst.
The Journal of Organic Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown
Published: May 18, 2025
The
Alder-ene
reaction
of
the
C-C
bond
in
bicyclo[1.1.0]butanes
would
provide
a
unique
and
efficient
synthesis
route
for
cyclobutene
frameworks.
Herein,
we
report
regio-
diastereoselective
with
β-fluoroalkyl-α,β-unsaturated
ketones,
giving
wide
variety
cyclobutenes
two
contiguous
centers
diene
products.
features
atoms
step
economies
exhibits
broad
substrate
scope.
Several
downstream
transformations
these
were
performed.
JACS Au,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 19, 2024
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.
