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.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(48)
Published: Sept. 2, 2024
Abstract
The
cycloaddition
reaction
involving
bicyclo[1.1.0]butanes
(BCBs)
offers
a
versatile
and
efficient
synthetic
platform
for
producing
C(sp
3
)‐rich
rigid
bridged
ring
scaffolds,
which
act
as
phenyl
bioisosteres.
However,
there
is
scarcity
of
catalytic
asymmetric
cycloadditions
BCBs
to
fulfill
the
need
enantioenriched
saturated
bicycles
in
drug
design
development.
In
this
study,
an
synthesis
valuable
azabicyclo[2.1.1]hexanes
(aza‐BCHs)
by
enantioselective
zinc‐catalyzed
(3+2)
with
imines
reported.
proceeds
effectively
novel
type
BCB
that
incorporates
2‐acyl
imidazole
group
diverse
array
alkynyl‐
aryl‐substituted
imines.
target
aza‐BCHs,
consist
α‐chiral
amine
fragments
two
quaternary
carbon
centers,
are
efficiently
synthesized
up
94
%
96.5:3.5
er
under
mild
conditions.
Experimental
computational
studies
reveal
follows
concerted
nucleophilic
ring‐opening
mechanism
This
distinct
from
previous
on
Lewis
acid‐catalyzed
BCBs.
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 25, 2024
The
selective
construction
of
bridged
bicyclic
scaffolds
has
garnered
increasing
attention
because
their
extensive
use
as
saturated
bioisosteres
arene
in
pharmaceutical
industry.
However,
sharp
contrast
to
racemic
counterparts,
assembling
chiral
structures
an
enantioselective
and
regioselective
manner
remains
challenging.
Herein,
we
describe
our
protocol
for
constructing
2-oxa-3-azabicyclo[3.1.1]heptanes
(BCHeps)
by
[4π
+
2σ]
cycloadditions
bicyclo[1.1.0]butanes
(BCBs)
nitrones
taking
advantage
a
copper(II)
complex
Lewis
acid
catalyst.
This
method
features
mild
conditions,
good
functional
group
tolerance,
high
yield
(up
99%),
excellent
enantioselectivity
99%
ee).
Density
theory
(DFT)
calculation
elucidates
the
origin
reaction's
mechanism
BCB
activation
Cu(II)
complex.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: July 20, 2024
Abstract
Saturated
three-dimensional
carbocycles
have
gained
increasing
prominence
in
synthetic
and
medicinal
chemistry.
In
particular,
bicyclo[2.1.1]hexanes
(BCHs)
been
identified
as
the
molecular
replacement
for
benzenes.
Here,
we
present
facile
access
to
a
variety
of
BCHs
via
stepwise
two-electron
formal
(3
+
2)
cycloaddition
between
silyl
enol
ethers
bicyclo[1.1.0]butanes
(BCBs)
under
Lewis
acid
catalysis.
The
reaction
features
wide
functional
group
tolerance
ethers,
allowing
efficient
construction
two
vicinal
quaternary
carbon
centers
silyl-protected
tertiary
alcohol
unit
streamlined
fashion.
Interestingly,
with
conjugated
dienol
can
provide
bicyclo[4.1.1]octanes
(BCOs)
equipped
that
facilitate
further
transformation.
utilities
this
methodology
are
demonstrated
by
late-stage
modification
natural
products,
transformations
units
on
bicyclo[2.1.1]hexane
frameworks,
derivatization
bicyclo[4.1.1]octanes,
delivering
functionalized
bicycles
traditionally
inaccessible.
Chemical Science,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 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.
Chemical Science,
Journal Year:
2024,
Volume and Issue:
15(31), P. 12473 - 12479
Published: Jan. 1, 2024
Bicyclo[1.1.0]butanes
(BCBs),
featuring
two
fused
cyclopropane
rings,
have
found
widespread
application
in
organic
synthesis.
Their
versatile
reactivity
towards
radicals,
nucleophiles,
cations,
and
carbenes
makes
them
suitable
for
various
reactions,
including
ring-opening
annulation
strategies.
Despite
this
versatility,
their
potential
as
enophiles
an
ene
reaction
remains
underexplored.
Considering
given
the
challenges
of
achieving
diastereoselectivity
reactions
BCBs,
herein,
we
present
a
unique
method
utilizing
BCBs
mild
diastereoselective
Sc(OTf)
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(48)
Published: Aug. 22, 2024
Over
the
past
few
years,
there
has
been
a
surge
of
interest
in
chemistry
bicyclobutanes
(BCBs).
Although
BCBs
have
used
to
synthesize
bicyclo[2.1.1]hexanes
and
bicyclo[3.1.1]heptanes,
synthesis
bicyclo[4.1.1]octanes
remained
elusive.
Herein,
we
report
first
Lewis
acid-catalyzed
unexpected
(4+3)
annulation
para-quinonemethides
(p-QMs)
with
allowing
oxabicyclo[4.1.1]octanes
proceeding
under
mild
conditions.
With
5
mol
%
Bi(OTf)
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 30, 2024
Achieving
structural
and
stereogenic
diversity
from
the
same
starting
materials
remains
a
fundamental
challenge
in
organic
synthesis,
requiring
precise
control
over
selectivity.
Here,
we
report
divergent
catalytic
methods
that
selectively
yield
either
cycloaddition
or
addition/elimination
products
bicyclo[1.1.0]butanes
α,β-unsaturated
ketones.
By
employing
chiral
Lewis
acid
Brønsted
catalysts,
achieved
excellent
regio-,
diastereo-,
enantioselectivity
across
all
three
distinct
transformations,
affording
diverse
array
of
synthetically
valuable
bicyclo[2.1.1]hexanes
cyclobutenes.
The
outcomes
are
controlled
by
differential
activation
substrates
specific
catalyst
with
reaction
conditions
dictating
pathway
This
strategy
demonstrates
power
catalysis
creating
molecular
complexity
diversity,
offering
tool
for
synthesis
enantioenriched
building
blocks.
