Angewandte Chemie,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 14, 2024
Abstract
Cyclobutanes
are
prominent
structural
components
in
natural
products
and
drug
molecules.
With
the
advent
of
strain‐release‐driven
synthesis,
ring‐opening
reactions
bicyclo[1.1.0]butanes
(BCBs)
provide
an
attractive
pathway
to
construct
these
three‐dimensional
structures.
However,
stereoselective
difunctionalization
central
C−C
σ‐bonds
remains
challenging.
Reported
herein
is
a
covalent‐based
organocatalytic
strategy
that
exploits
radical
NHC
catalysis
achieve
diastereoselective
acylfluoroalkylation
BCBs
under
mild
conditions.
The
Breslow
enolate
acts
as
single
electron
donor
provides
NHC‐bound
ketyl
with
appropriate
steric
hindrance,
which
effectively
distinguishes
between
two
faces
transient
cyclobutyl
radicals.
This
operationally
simple
method
tolerates
various
fluoroalkyl
reagents
common
functional
groups,
providing
straightforward
access
polysubstituted
cyclobutanes
(75
examples,
up
>19
:
1
d.r.).
combined
experimental
theoretical
investigations
this
system
confirm
formation
NHC‐derived
understanding
how
radical‐radical
coupling
occurs.
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.
Chemistry - A European Journal,
Journal Year:
2024,
Volume and Issue:
30(68)
Published: Aug. 23, 2024
Abstract
We
reported
herein
a
visible
light
mediated
de
Mayo‐type
reaction
between
1,3‐diketones
and
BCB.
The
proceeds
through
[2π+2σ]
cycloaddition
retro‐aldol
sequence,
producing
cis‐difunctionalized
cyclobutanes
in
high
yields
with
good
regio‐
diastereoselectivity.
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.
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.
ACS Catalysis,
Journal Year:
2024,
Volume and Issue:
14(24), P. 18799 - 18809
Published: Dec. 11, 2024
Transition-metal-catalyzed
cycloaddition
reactions
of
strained
small-ring
compounds
are
powerful
methods
for
constructing
carbo-
and
heterocyclic
structures
medicinal
interest.
However,
the
application
this
strategy
to
bicyclo[1.1.0]butanes
(BCBs),
which
among
most
carbocycles
known,
remains
underdeveloped.
Herein,
we
report
vinylbicyclo[1.1.0]butane
(VBCB)
as
a
platform
synthon
palladium-catalyzed
formal
[2σ+2π]
with
various
2π-components,
enabling
synthesis
BCHs,
oxa-BCHs,
aza-BCHs
under
identical
reaction
conditions.
The
zwitterionic
π-allyl-Pd
species
generated
through
activation
VBCBs
is
key
circumventing
potential
carbene
reactivity
serves
common
intermediate
cycloadditions
diverse
2π-systems,
including
alkenes,
aldehydes,
ketones,
imines.
Notably,
by
utilizing
Pd2(dba)3
an
anthracene-derived
Trost
ligand,
wide
array
BCHs
bearing
two
vicinal
chiral
centers
has
been
prepared
in
highly
diastereo-,
enantioselective
manner.
generality
practicality
method
have
demonstrated
broad
substrate
scope,
scale-up
reactions,
versatile
transformation
multiple
functional
groups
into
BCH
scaffolds.
Preliminary
mechanistic
studies
support
formation
species.
Organic Letters,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 26, 2024
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.
