Angewandte Chemie,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 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
).
Journal of the American Chemical Society,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 28, 2025
Asymmetric
synthesis
presents
many
challenges,
with
the
selective
formation
of
chiral
bridged
polyheterocycles
being
a
notable
example.
Cycloadditions
using
bicyclo[1.1.0]butanes
(BCB)
offer
promising
solution
along
those
lines,
yet,
despite
significant
advances
in
that
emerging
area,
asymmetric
control
has
remained
limited
thus
far.
Here,
we
describe
an
organocatalytic,
enantioselective
formal
(3
+
3)-cycloaddition
BCBs
1H-indol-3-yl((hetero)aryl)methanol
derivatives.
This
approach
enables
rapid
and
efficient
tetrahydro-1H-1,3-methanocarbazole
derivatives
(34
examples)
from
readily
available
starting
materials,
very
good
stereochemical
(up
to
98:2
er).
Successful
scale-up
experiments
product
modification
demonstrated
potential
this
methodology.
Control
DFT
calculations
provide
insights
into
mechanistic
pathway.
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 30, 2024
Achieving
structural
and
stereogenic
diversity
from
the
same
starting
materials
remains
a
fundamental
challenge
in
organic
synthesis,
requiring
precise
control
over
selectivity.
Here,
we
report
divergent
catalytic
methods
that
selectively
yield
either
cycloaddition
or
addition/elimination
products
bicyclo[1.1.0]butanes
α,β-unsaturated
ketones.
By
employing
chiral
Lewis
acid
Brønsted
catalysts,
achieved
excellent
regio-,
diastereo-,
enantioselectivity
across
all
three
distinct
transformations,
affording
diverse
array
of
synthetically
valuable
bicyclo[2.1.1]hexanes
cyclobutenes.
The
outcomes
are
controlled
by
differential
activation
substrates
specific
catalyst
with
reaction
conditions
dictating
pathway
This
strategy
demonstrates
power
catalysis
creating
molecular
complexity
diversity,
offering
tool
for
synthesis
enantioenriched
building
blocks.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 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
).
Chemical Science,
Journal Year:
2024,
Volume and Issue:
15(46), P. 19488 - 19495
Published: Jan. 1, 2024
We
present
the
first
enantioselective
dearomative
(3+3)
cycloadditions
of
bicyclobutanes
(BCBs)
utilizing
a
chiral
Lewis
acid
catalyst
and
bidentate
chelating
BCB
substrates.
Chemical Communications,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 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.
European Journal of Organic Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 11, 2025
Abstract
Zinc
has
been
an
overlooked
metal
in
catalysis
for
many
years.
However,
this
situation
begun
to
change
the
last
two
decades
with
a
number
of
contributions
demonstrating
that
zinc
salts
and
complexes
are
able
catalyze
transformations
typically
accomplished
catalysts
based
on
precious
transition
metals.
The
development
such
zinc‐catalyzed
methodologies
is
highly
appealing
because,
general,
easily
available,
inexpensive
less
toxic.
This
review
aims
present
most
recent
relevant
examples
use
formation
carbon‐heteroatom
bonds,
which
very
important
process
synthetic
organic
chemistry.
ACS Catalysis,
Journal Year:
2025,
Volume and Issue:
unknown, P. 5825 - 5834
Published: March 25, 2025
Rigid
three-dimensional
scaffolds
such
as
2-azabicyclo[2.1.1]hexanes
(aza-BCHs)
and
bicyclo[1.1.1]pentanes
(BCPs)
serve
unique
saturated
isosteres
of
arenes,
offering
distinct
substitution
patterns
due
to
their
differing
molecular
exit
vectors.
This
study
introduces
a
skeletal
editing
strategy
that
efficiently
transforms
multisubstituted
aza-BCHs
into
BCPs
via
an
O-diphenylphosphinylhydroxylamine-promoted
N-atom
deletion
process.
method
effectively
addresses
the
challenge
creating
sterically
hindered
(2°)C–C(3°)
bonds
by
removing
nitrogen
atom
encased
within
bulky
alkyl
groups,
reconstructing
strained
aza-BCH
structure
more
BCP
without
generating
undesired
ring-opening
diene
byproducts.
The
used
can
be
prepared
from
modified
intermolecular
[3
+
2]
cycloaddition
between
bicyclo[1.1.0]butanes
imines,
making
this
practical.
approach
achieves
remarkable
efficiency,
with
yields
up
99%
scalability
decagram
quantities.
resulting
carboxylates
further
functionalized
through
decarboxylation,
highlighting
potential
for
programmed
divergent
synthesis
BCPs.
broad
substrate
scope
high
functional
group
tolerance
protocol
emphasize
its
versatility,
it
particularly
valuable
late-stage
contained
peptides,
natural
products,
pharmaceuticals.
Journal of the American Chemical Society,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 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.
