Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 18, 2024
Abstract
The
absence
of
catalytic
asymmetric
methods
for
synthesizing
chiral
(hetero)bicyclo[n.1.1]alkanes
has
hindered
their
application
in
new
drug
discovery.
Here
we
demonstrate
the
achievability
an
polar
cycloaddition
BCB
using
a
Lewis
acid
catalyst
and
bidentate
chelating
substrate,
as
exemplified
by
current
enantioselective
formal
[4π+2σ]
BCBs
with
nitrones.
In
addition
to
diverse
incorporating
acyl
imidazole
group
or
pyrazole
moiety,
wide
array
nitrones
are
compatible
this
catalysis,
successfully
assembling
two
congested
quaternary
carbon
centers
aza-trisubstituted
center
pharmaceutically
important
hetero-bicyclo[3.1.1]heptane
product
up
99%
yield
>99%
ee.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Июль 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.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(48)
Опубликована: Авг. 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,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 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,
Год журнала:
2024,
Номер
unknown, С. 17837 - 17849
Опубликована: Ноя. 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.
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
unknown
Опубликована: Дек. 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.
Angewandte Chemie,
Год журнала:
2024,
Номер
136(48)
Опубликована: Авг. 22, 2024
Abstract
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)
3
,
reaction
afforded
annulated
product
high
regioselectivity
good
functional
group
compatibility
via
simultaneous
acid
activation
‐QMs.
The
is
likely
initiated
by
1,6‐addition
activated
‐QMs
followed
C2‐selective
intramolecular
addition
phenol
moiety
generated
cyclobutyl
cation
intermediate.
Moreover,
detailed
mechanistic
studies
provided
insight
into
mechanism
reaction.
