Angewandte Chemie,
Journal Year:
2024,
Volume and Issue:
136(32)
Published: May 24, 2024
Abstract
Synthesis
of
bicyclic
scaffolds
has
gained
significant
attention
in
drug
discovery
due
to
their
potential
mimic
benzene
bioisosteres.
Here,
we
present
a
mild
and
scalable
Sc(OTf)
3
‐catalyzed
[3+2]
cycloaddition
bicyclo[1.1.0]butanes
(BCBs)
with
ynamides,
yielding
diverse
array
polysubstituted
2‐amino‐bicyclo[2.1.1]hexenes
good
excellent
yields.
These
products
offer
valuable
starting
materials
for
the
construction
novel
functionalized
bicyclo[1.1.0]butanes.
Preliminary
mechanistic
studies
indicate
that
reaction
involves
nucleophilic
addition
ynamides
bicyclo[1.1.0]butanes,
followed
by
an
intramolecular
cyclization
situ
generated
enolate
keteniminium
ion.
We
expect
these
findings
will
encourage
utilization
complex
bioisosteres
foster
further
investigation
into
BCB‐based
chemistry.
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(27), P. 18565 - 18575
Published: June 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
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(29)
Published: May 11, 2024
Abstract
The
exploration
of
the
complex
chemical
diversity
bicyclo[n.1.1]alkanes
and
their
use
as
benzene
bioisosteres
has
garnered
significant
attention
over
past
two
decades.
Regiodivergent
syntheses
thiabicyclo[4.1.1]octanes
(S‐BCOs)
highly
substituted
bicyclo[2.1.1]hexanes
(BCHs)
using
a
Lewis
acid‐catalyzed
formal
cycloaddition
bicyclobutanes
(BCBs)
3‐benzylideneindoline‐2‐thione
derivatives
have
been
established.
first
hetero‐(4+3)
BCBs,
catalyzed
by
Zn(OTf)
2
,
was
achieved
with
broad
substrate
scope
under
mild
conditions.
In
contrast,
less
electrophilic
BCB
ester
undergoes
Sc(OTf)
3
‐catalyzed
[2π+2σ]
reaction
1,1,2‐trisubstituted
alkenes,
yielding
BCHs
spirocyclic
quaternary
carbon
center.
Control
experiments
preliminary
theoretical
calculations
suggest
that
diastereoselective
product
formation
may
involve
concerted
between
zwitterionic
intermediate
E
‐1,1,2‐trisubstituted
alkenes.
Additionally,
nucleophilic
ring‐opening
mechanism.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(32)
Published: May 24, 2024
Abstract
Synthesis
of
bicyclic
scaffolds
has
gained
significant
attention
in
drug
discovery
due
to
their
potential
mimic
benzene
bioisosteres.
Here,
we
present
a
mild
and
scalable
Sc(OTf)
3
‐catalyzed
[3+2]
cycloaddition
bicyclo[1.1.0]butanes
(BCBs)
with
ynamides,
yielding
diverse
array
polysubstituted
2‐amino‐bicyclo[2.1.1]hexenes
good
excellent
yields.
These
products
offer
valuable
starting
materials
for
the
construction
novel
functionalized
bicyclo[1.1.0]butanes.
Preliminary
mechanistic
studies
indicate
that
reaction
involves
nucleophilic
addition
ynamides
bicyclo[1.1.0]butanes,
followed
by
an
intramolecular
cyclization
situ
generated
enolate
keteniminium
ion.
We
expect
these
findings
will
encourage
utilization
complex
bioisosteres
foster
further
investigation
into
BCB‐based
chemistry.
Organic Letters,
Journal Year:
2024,
Volume and Issue:
26(19), P. 4104 - 4110
Published: May 3, 2024
Herein,
a
B(C6F5)3-catalyzed
formal
(n
+
3)
=
5
and
6)
cycloaddition
of
bicyclo[1.1.0]butanes
(BCBs)
with
imidazolidines/hexahydropyrimidines
is
described.
The
reaction
provides
modular,
atom-economical,
efficient
strategy
to
two
libraries
synthetically
challenging
medium-bridged
rings,
2,5-diazabicyclo[5.1.1]nonanes
2,6-diazabicyclo[6.1.1]decanes,
in
moderate
excellent
yields.
This
also
features
simple
operation,
mild
conditions,
broad
substrate
scope.
A
scale-up
experiment
various
synthetic
transformations
products
further
highlight
the
utility.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(48)
Published: Sept. 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.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: July 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,
Journal Year:
2024,
Volume and Issue:
unknown
Published: May 31, 2024
Bridged
cyclobutanes
and
sulfur
heterocycles
are
currently
under
intense
investigation
as
building
blocks
for
pharmaceutical
drug
design.
Two
formal
cycloaddition
modes
involving
bicyclobutanes
(BCBs)
pyridinium
1,4-zwitterionic
thiolate
derivatives
were
described
to
rapidly
expand
the
chemical
space
of
sulfur-containing
bridged
cyclobutanes.
By
using
Ni(ClO
Organic Chemistry Frontiers,
Journal Year:
2024,
Volume and Issue:
11(16), P. 4539 - 4545
Published: Jan. 1, 2024
Rapid
access
to
diverse
spiro[benzofuran-2,2′-bicyclo[2.1.1]hexanes]
via
BF
3
·Et
2
O-catalyzed
[2π
+
2σ]
cycloaddition
of
bicyclo[1.1.0]butanes
with
readily
available
benzofuran-derived
oxa(aza)dienes.
