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,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 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,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 30, 2025
A
post-transition
state
surface
intersection
(PTSSI)
between
radical
and
zwitterionic
states
that
causes
a
bifurcation
in
the
reaction
pathway
was
discovered
through
density
functional
theory
calculations
on
potential
energy
surfaces
ab
initio
molecular
dynamics
simulations
of
cycloadditions
bicyclobutane
triazolinedione
(BCB-TAD).
It
predicted
changes
to
solvent
polarity
would
enable
control
over
dynamic
selectivity
this
system;
indeed,
experimental
evidence
supported
prediction.
This
work
not
only
provides
new
insights
into
an
unusual
type
bifurcation,
but
also
demonstrates
how
nonstatistical
effects
for
such
reactions
can
be
manipulated
rationally
increase
yields
synthetically
useful
reactions.
Bicyclic
carbocycles
containing
a
high
fraction
of
Csp3
have
become
highly
attractive
synthetic
targets
because
the
multiple
applications
they
found
in
medicinal
chemistry.
The
formal
cycloaddition
bicyclobutanes
(BCB)
has
recently
been
extensively
explored
for
construction
both
bicyclohexanes
and
bicycloheptanes.
Adopting
this
approach
synthesis
medium-sized
bridged
instead
remained
more
limited.
We
report
herein
(4π+2σ)
BCB
ketones
with
silyl
dienol
ethers.
reaction
occurred
presence
aluminium
triflate
as
Lewis
acid
catalyst.
Upon
acidic
hydrolysis
enol
ether
intermediates,
rigid
bicyclo[4.1.1]octanes
(BCOs)
diketones
could
be
easily
accessed
good
to
very
yields.
This
convenient
scalable
procedure
was
tolerant
towards
range
aromatic
aliphatic
substituents
on
substrates
dienes.
obtained
BCO
products
smoothly
functionalized
through
reduction
cross-coupling
reactions.
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,
Год журнала:
2024,
Номер
15(46), С. 19488 - 19495
Опубликована: Янв. 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,
Год журнала:
2024,
Номер
15(28), С. 11092 - 11098
Опубликована: Янв. 1, 2024
A
concise
protocol
for
the
synthesis
of
constrained
bicycloalkanes
has
been
developed,
using
easily
obtainable
α-silyl
alcohols
and
alkenes
through
a
bibase-promoted
brook
rearrangement/radical-polar
crossover
cyclization
(RPCC)
process.
ACS Catalysis,
Год журнала:
2025,
Номер
unknown, С. 5825 - 5834
Опубликована: Март 25, 2025
Rigid
three-dimensional
scaffolds
such
as
2-azabicyclo[2.1.1]hexanes
(aza-BCHs)
and
bicyclo[1.1.1]pentanes
(BCPs)
serve
unique
saturated
isosteres
of
arenes,
offering
distinct
substitution
patterns
due
to
their
differing
molecular
exit
vectors.
This
study
introduces
a
skeletal
editing
strategy
that
efficiently
transforms
multisubstituted
aza-BCHs
into
BCPs
via
an
O-diphenylphosphinylhydroxylamine-promoted
N-atom
deletion
process.
method
effectively
addresses
the
challenge
creating
sterically
hindered
(2°)C–C(3°)
bonds
by
removing
nitrogen
atom
encased
within
bulky
alkyl
groups,
reconstructing
strained
aza-BCH
structure
more
BCP
without
generating
undesired
ring-opening
diene
byproducts.
The
used
can
be
prepared
from
modified
intermolecular
[3
+
2]
cycloaddition
between
bicyclo[1.1.0]butanes
imines,
making
this
practical.
approach
achieves
remarkable
efficiency,
with
yields
up
99%
scalability
decagram
quantities.
resulting
carboxylates
further
functionalized
through
decarboxylation,
highlighting
potential
for
programmed
divergent
synthesis
BCPs.
broad
substrate
scope
high
functional
group
tolerance
protocol
emphasize
its
versatility,
it
particularly
valuable
late-stage
contained
peptides,
natural
products,
pharmaceuticals.
New Journal of Chemistry,
Год журнала:
2024,
Номер
48(25), С. 11360 - 11365
Опубликована: Янв. 1, 2024
The
mechanism,
role
of
catalyst
and
origin
stereoselectivity
for
the
isomerization
reaction
BCB
catalyzed
by
a
chiral
Brønsted
acid
(CBA)
have
been
revealed
in
detail
using
DFT
calculations.
