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.
Chemical Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 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.
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.
Chemical Communications,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 1, 2025
Herein
we
report
a
simple
BF
3
-catalyzed
cycloaddition
of
dihydropyridines
with
bicyclobutanes
for
the
expedient
synthesis
novel
three-dimensional
azacycle-fused
bicyclo[2.1.1]hexane
scaffolds.
The
bicyclo[1.1.0]butyl
scaffold
has
emerged
as
a
valuable
bioisostere
in
drug
discovery
programs.
Here,
we
present
streamlined
approach
for
the
generation
of
bicyclo[1.1.0]butyllithium
and
its
functionalization
with
various
classes
electrophiles
one-flow
process,
eliminating
need
intermediate
isolation.
In
comparison
to
traditional
batch
processes,
flow
method
allows
use
single
organolithium
reagent
instead
two
operates
at
significantly
higher
temperatures
(0
°C
versus
−78
°C),
enhancing
both
practicality
scalability.
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.
