Angewandte Chemie,
Год журнала:
2024,
Номер
136(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.
A
palladium-catalyzed
[2π
+
2σ]
cycloaddition
of
vinyl
bicyclo[1.1.0]butanes
with
methyleneindolinones
has
been
developed.
The
reaction
enables
the
construction
spirobicyclo[2.1.1]hexanes
bearing
an
all-carbon
quaternary
center
in
moderate
to
good
yields
excellent
diastereoselectivities.
This
method
features
a
broad
substrate
scope
functional
group
compatibility.
practical
utility
this
protocol
was
further
demonstrated
by
gram-scale
synthesis
and
postsynthetic
transformations
desired
product.
Abstract
In
recent
years,
formal
cycloaddition
reactions
involving
bicyclo[1.1.0]butanes
(BCBs)
have
furnished
an
array
of
innovative
methodologies
and
strategies
for
the
efficient
synthesis
bicyclo[2.1.1]hexanes
(BCHs).
Most
methods
can
be
broadly
classified
into
two
main
modes:
radical
pathway
two-electron
pathway.
This
Synpacts
article
will
summarize
advancements
in
Lewis
acid
catalyzed
BCBs
with
alkenes,
dipolar
molecules,
alkynes,
spanning
period
from
2022
to
2024.
Additionally,
we
introduce
reaction
ynamides,
by
Sc(OTf)3,
which
has
been
recently
developed
our
group.
approach
offers
a
novel
method
polysubstituted
2-amino-bicyclo[2.1.1]hexenes.
1
Introduction
2
Acid
Catalyzed
Formal
Cycloaddition
Alkenes
Dipoles
3
Alkynes
4
Conclusion
Angewandte Chemie,
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
).
Angewandte Chemie,
Год журнала:
2024,
Номер
136(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.
