Journal of the American Chemical Society,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 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.
ACS Catalysis,
Journal Year:
2024,
Volume and Issue:
unknown, P. 17837 - 17849
Published: Nov. 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.
Chemical Science,
Journal Year:
2024,
Volume and Issue:
15(46), P. 19488 - 19495
Published: Jan. 1, 2024
We
present
the
first
enantioselective
dearomative
(3+3)
cycloadditions
of
bicyclobutanes
(BCBs)
utilizing
a
chiral
Lewis
acid
catalyst
and
bidentate
chelating
BCB
substrates.
Organic Letters,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 10, 2025
A
novel
cascade
Pd-catalyzed
cross-coupling
reaction
of
cyclopropyl
alcohol-derived
ketone
homoenolate
with
2-Br-p-quinone
methides
and
2-Br-cinnamate
esters
followed
by
a
1,6-
1,4-conjugate
addition
is
disclosed.
This
protocol
converts
various
alcohols
into
homoenolate,
which
undergoes
C-C
bond
formation
2-Br
p-quinone
esters.
The
salient
features
this
methodology
include
its
operational
simplicity,
mild
conditions,
an
environmentally
benign
protocol,
high
efficiency,
good
to
excellent
yields,
wide
substrate
scope.
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.
The Journal of Organic Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 31, 2025
In
this
work,
we
studied
the
conjugated
additions
of
bis-trimethylsilylacetalketene
acetals
(bis-TMSKA)
to
para-quinone
methides
(p-QMs),
which
are
one
most
explored
molecules
for
study
and
gained
significant
attention
in
organic
chemistry
due
their
versatile
reactivity,
particularly
Michael
addition
reactions.
study,
trifluoromethanesulfonic
anhydride
(Tf2O)
was
used
as
an
activating
agent
p-QMs,
aiming
achieve
1,6-Michael
products
least
reported
1,8-Michael
with
pyridine
substituents.
The
reactivity
p-QMs
derived
from
demonstrated
distinct
reaction
pathways,
leading
formation
δ
γ
lactones.
investigation
also
involved
synthesizing
a
1-indanone
carboxylic
acids
obtained
1,6-addition.
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.
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.
