Organic Letters,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 4, 2024
A
structure-dependent,
palladium-catalyzed
switchable
alder-ene/[2π
+
2σ]
cycloaddition
of
VBCBs
with
α-ketoesters
has
been
reported.
variety
cyclobutenes
and
2-oxabicyclo[2.1.1]hexanes
have
efficiently
achieved
in
good
to
excellent
yields
through
strain-release-driven
alder-ene
reactions
[2π
cycloadditions,
respectively.
The
potential
this
method
is
illustrated
by
the
scale-up
reaction
diverse
postsynthetic
transformations
obtained
cyclic
scaffolds.
Additionally,
mechanism
origins
chemoselectivity
probed
computational
studies.
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.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 13, 2024
Abstract
The
synthesis
of
bicyclic
scaffolds
has
garnered
considerable
interest
in
drug
discovery
because
their
ability
to
mimic
benzene
bioisosteres.
Herein,
we
introduce
a
new
approach
that
utilizes
Lewis
acid
(Sc(OTf)
3
)‐catalyzed
σ‐bond
cross‐exchange
reaction
between
the
C−C
bond
bicyclobutanes
and
C−N
diaziridines
produce
multifunctionalized
medicinally
interesting
azabicyclo[3.1.1]heptane
derivatives.
proceeds
well
with
different
broad
range
aryl‐
as
alkenyl‐,
but
also
alkyl‐substituted
(up
98
%
yield).
Conducting
scale‐up
experiment
exploring
synthetic
transformations
cycloadducts
emphasized
practical
application
synthesis.
Furthermore,
zinc‐based
chiral
catalytic
system
was
developed
for
enantioselective
version
this
96
ee
).
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.
Synlett,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Aug. 28, 2024
Abstract
The
synthesis
of
bicyclo[3.1.1]heptane
(BCHeps)
derivatives,
which
serve
as
three-dimensional
(3D)
bioisosteres
benzenes
and
are
the
core
skeleton
several
terpene
natural
products,
is
garnering
growing
interest.
(3+3)
cycloadditions
bicyclobutanes
(BCBs)
represent
an
attractive
method
for
efficiently
accessing
(hetero)BCHep
skeletons
with
100%
atom
economy.
Herein,
we
give
a
brief
summary
recent
achievements
in
this
approach
diverse
BCHep
emphasizing
our
progress
initial
palladium-catalyzed
vinyl
oxiranes.
1
Introduction
2
Radical
Cycloaddition
Reaction
3
Polar
4
Palladium-Catalyzed
Enantioselective
5
Conclusion
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.
Chemical Science,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 13, 2024
This
manuscript
presents
a
photoredox-catalyzed
defluorinative
(4
+
3)
annulation
of
bicyclo[1.1.0]butanes
with
gem
-difluoroalkenes,
providing
practical
and
straightforward
access
to
the
fluorine-containing
bicyclo[4.1.1]octenes.
