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
Angewandte Chemie International Edition,
Год журнала:
2023,
Номер
62(48)
Опубликована: Окт. 12, 2023
Bicyclo[2.1.1]hexanes
(BCHs)
are
becoming
ever
more
important
in
drug
design
and
development
as
bridged
scaffolds
that
provide
underexplored
chemical
space,
but
difficult
to
access.
Here
a
silver-catalyzed
dearomative
[2π+2σ]
cycloaddition
strategy
for
the
synthesis
of
indoline
fused
BCHs
from
N-unprotected
indoles
bicyclobutane
precursors
is
described.
The
strain-release
operates
under
mild
conditions,
tolerating
wide
range
functional
groups.
It
capable
forming
with
up
four
contiguous
quaternary
carbon
centers,
achieving
yields
99
%.
In
addition,
scale-up
experiment
synthetic
transformations
cycloadducts
further
highlighted
utility.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(29), С. 19621 - 19628
Опубликована: Май 13, 2024
For
nearly
60
years,
significant
research
efforts
have
been
focused
on
developing
strategies
for
the
cycloaddition
of
bicyclobutanes
(BCBs).
However,
higher-order
and
catalytic
asymmetric
BCBs
long-standing
formidable
challenges.
Here,
we
report
Pd-catalyzed
ligand-controlled,
tunable
cycloadditions
divergent
synthesis
bridged
bicyclic
frameworks.
The
dppb
ligand
facilitates
formal
(5+3)
vinyl
oxiranes,
yielding
valuable
eight-membered
ethers
with
scaffolds
in
100%
regioselectivity.
Cy-DPEphos
promotes
selective
hetero-[2σ+2σ]
to
access
pharmacologically
important
2-oxabicyclo[3.1.1]heptane
(O-BCHeps).
Furthermore,
corresponding
O-BCHeps
94–99%
ee
has
achieved
using
chiral
(S)-DTBM-Segphos,
representing
first
cross-dimerization
two
strained
rings.
obtained
are
promising
bioisosteres
ortho-substituted
benzenes.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(21)
Опубликована: Март 5, 2024
Abstract
Synthesis
of
bicyclic
scaffolds
has
emerged
as
an
important
research
topic
in
modern
drug
development
because
they
can
serve
saturated
bioisosters
to
enhance
the
physicochemical
properties
and
metabolic
profiles
candidates.
Here
we
report
a
remarkably
simple
silver‐enabled
strategy
access
polysubstituted
3‐azabicyclo[3.1.1]heptanes
single
operation
from
readily
accessible
bicyclobutanes
(BCBs)
isocyanides.
The
process
is
proposed
involve
formal
(3+3)/(3+2)/retro‐(3+2)
cycloaddition
sequence.
This
novel
protocol
allows
for
rapid
generation
molecular
complexity
starting
materials,
products
be
easily
derivatized,
further
enriching
BCB
chemistry
growing
set
valuable
sp
3
‐rich
building
blocks.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(27), С. 18565 - 18575
Опубликована: Июнь 27, 2024
Bridged
bicyclic
scaffolds
are
emerging
bioisosteres
of
planar
aromatic
rings
under
the
concept
"escape
from
flatland".
However,
adopting
this
into
exploration
pyridines
remains
elusive
due
to
challenge
incorporating
a
N
atom
such
bridged
structures.
Herein,
we
report
practical
routes
for
divergent
synthesis
2-
and
3-azabicyclo[3.1.1]heptenes
(aza-BCHepes)
as
potential
readily
accessible
vinyl
azides
bicyclo[1.1.0]butanes
(BCBs)
via
two
distinct
catalytic
annulations.
The
reactivity
tailored
with
BCBs
is
key
achieving
transformations.
Ti
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Май 23, 2024
Abstract
Natural
stilbenes
have
shown
significant
potential
in
the
prevention
and
treatment
of
diseases
due
to
their
diverse
pharmacological
activities.
Here
we
present
a
mild
effective
Ti-catalyzed
intermolecular
radical-relay
[2σ
+
2π]
cycloaddition
bicyclo[1.1.0]-butanes
1,3-dienes.
This
transformation
enables
synthesis
bicyclo[2.1.1]hexane
(BCH)
scaffolds
containing
aryl
vinyl
groups
with
excellent
regio-
trans
-selectivity
broad
functional
group
tolerance,
thus
offering
rapid
access
structurally
stilbene
bioisosteres.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(48)
Опубликована: Сен. 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.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 19, 2024
Saturated
nitrogen
heterocycles
are
among
the
most
significant
structural
components
in
small-molecule
pharmaceuticals.
Herein,
a
protocol
for
construction
of
enantiopure
2-azabicyclo[3.1.1]heptane
derivatives
by
stereospecific
intermolecular
formal
cycloaddition
aziridines
with
bicyclo[1.1.0]butanes
is
described.
The
reaction
run
using
B(C
