1,5-Disubstituted
bicyclo[2.1.1]hexanes
are
bridged
scaffolds
with
well-defined
exit
vectors
that
becoming
increasingly
popular
building
blocks
in
medicinal
chemistry
since
they
saturated
bioisosteres
of
orthosubstituted
phenyl
rings.
Here
we
have
developed
the
first
enantioselective
catalytic
strategy
based
on
a
Lewis
acid-catalyzed
[2+2]
photocycloaddition
to
obtain
these
motifs
as
enantioenriched
scaffolds,
providing
an
efficient
approach
for
their
incorporation
variety
drug
analogues.
The
bioisostere-containing
drugs
been
evaluated
cancer
cell
viability
studies,
observing
some
cases
biological
activity
two
enantiomers
is
highly
different.
This
showcases
control
absolute
configuration
and
tridimensionality
analogue
has
large
impact
its
bioactivity,
highlighting
need
stereoselective
methods
towards
construction
bicyclo[2.1.1]hexane
core.
Chemical Science,
Год журнала:
2022,
Номер
14(4), С. 963 - 969
Опубликована: Дек. 21, 2022
There
is
an
increasing
interest
in
cyclobutanes
within
the
medicinal
chemistry
community.
Therefore,
methods
to
prepare
that
contain
synthetic
handles
for
further
elaboration
are
of
interest.
Herein,
we
report
a
new
approach
synthesis
3-borylated
cyclobutanols
via
formal
[3
+
1]-cycloaddition
using
readily
accessible
1,1-diborylalkanes
and
epihalohydrins
or
epoxy
alcohol
derivatives.
1-Substituted
epibromohydrin
starting
materials
provide
access
borylated
containing
substituents
at
three
four
positions
on
cyclobutane
core,
enantioenriched
epibromohydrins
lead
with
high
levels
enantiospecificity
(>98%).
Finally,
derivatization
studies
demonstrate
utility
both
OH
Bpin
handles.
Chemical Science,
Год журнала:
2024,
Номер
15(9), С. 3249 - 3254
Опубликована: Янв. 1, 2024
A
one-step
approach
to
borylated
cyclobutanes
from
amides
of
carboxylic
acids
and
vinyl
boronates
is
elaborated.
The
reaction
proceeds
via
the
thermal
[2
+
2]-cycloaddition
in
situ
-generated
keteniminium
salts.
Journal of the American Chemical Society,
Год журнала:
2023,
Номер
145(33), С. 18591 - 18597
Опубликована: Авг. 8, 2023
Herein,
we
demonstrate
the
use
of
E/Z
mixtures
α,α-disubstituted
crotylhydrazones
to
obtain
spirocyclic
vinylcyclobutanes
in
a
diastereoselective
fashion.
We
show
24
examples
1,1-insertion/4-exo-trig
tandem
process
produce
these
motifs.
Additionally,
alkylidene
cyclobutanes
can
be
obtained
by
using
allylated
hydrazones
(11
examples).
In
this
study,
that
aryl
migrating
group
has
dramatic
impact
on
course
reaction.
Specifically,
allylic
C-H
insertion
products
good
yields
bromoenones
as
reaction
partners.
When
Pd(0)
is
used
with
no
or
alkenyl
bromide,
an
intramolecular
cyclopropanation
takes
place
afford
[2.1.0]-bicycles.
European Journal of Organic Chemistry,
Год журнала:
2022,
Номер
2022(41)
Опубликована: Окт. 5, 2022
Abstract
The
1,2‐metallate
rearrangement
occurring
with
boronate
complexes
is
a
strategy
of
choice
for
the
synthesis
organoboron
compounds,
giving
direct
access
to
highly
functionalized
molecules.
Lately,
significant
progress
has
been
made
in
use
this
reaction
opening,
functionalization,
and
formation
strained
cycles.
In
review,
we
will
highlight
these
recent
advances,
focusing
on
cycloalkanes
oxygen‐
or
nitrogen‐containing
1,5-Disubstituted
bicyclo[2.1.1]hexanes
are
bridged
scaffolds
with
well-defined
exit
vectors
that
becoming
increasingly
popular
building
blocks
in
medicinal
chemistry
since
they
saturated
bioisosteres
of
orthosubstituted
phenyl
rings.
Here
we
have
developed
the
first
enantioselective
catalytic
strategy
based
on
a
Lewis
acid-catalyzed
[2+2]
photocycloaddition
to
obtain
these
motifs
as
enantioenriched
scaffolds,
providing
an
efficient
approach
for
their
incorporation
variety
drug
analogues.
The
bioisostere-containing
drugs
been
evaluated
cancer
cell
viability
studies,
observing
some
cases
biological
activity
two
enantiomers
is
highly
different.
This
showcases
control
absolute
configuration
and
tridimensionality
analogue
has
large
impact
its
bioactivity,
highlighting
need
stereoselective
methods
towards
construction
bicyclo[2.1.1]hexane
core.
