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.
Chinese Journal of Chemistry,
Journal Year:
2022,
Volume and Issue:
40(11), P. 1346 - 1358
Published: Feb. 12, 2022
Comprehensive
Summary
Cyclobutane
derivatives
have
been
recognized
as
useful
structural
motifs
in
organic
synthesis
and
drug
design.
With
the
revival
of
photochemistry,
enantioselective
cyclobutane
using
[2
+
2]‐cycloadditions
has
garnered
numerous
attentions.
On
other
hand,
functionalization
preformed
four‐membered
carbocycles
is
emerging
an
important
complementary
approach
to
access
chiral
with
versatile
patterns.
Herein,
we
summarize
recent
advances
this
field
from
2012.
To
avoid
undesired
C—C
bond
cleavage
driven
by
strain‐releasing,
it
crucial
choose
compatible
methods
for
meanwhile
preserving
intact
ring
skeleton.
Guided
calculated
hydrogenation
enthalpies,
which
are
used
evaluate
strain
energy
indicated
bond,
a
clear
picture
developed
methodologies
on
combining
enhanced
reactivity
presented.
Angewandte Chemie International Edition,
Journal Year:
2022,
Volume and Issue:
61(25)
Published: April 21, 2022
A
new
strategy
for
the
synthesis
of
highly
versatile
cyclobutylboronates
via
photosensitized
[2+2]-cycloaddition
alkenylboronates
and
alkenes
is
presented.
The
process
mechanistically
different
from
other
processes
in
that
energy
transfer
occurs
with
alkenylboronate
as
opposed
to
alkene.
This
allows
an
array
diverse
cyclobutylboronates.
conversion
these
adducts
compounds
well
their
utility
melicodenine
C
demonstrated.
Journal of the American Chemical Society,
Journal Year:
2023,
Volume and Issue:
145(6), P. 3588 - 3598
Published: Feb. 3, 2023
Catalytic
enantioselective
functionalization
of
cyclobutenes
constitutes
a
general
and
modular
strategy
for
construction
enantioenriched
complex
cyclobutanes
bearing
multiple
stereogenic
centers,
as
chiral
four-membered
rings
are
common
motifs
in
biologically
active
molecules
versatile
intermediates
organic
synthesis.
However,
synthesis
through
such
remained
significantly
limited.
Herein,
we
report
series
unprecedented
cobalt-catalyzed
carbon-carbon
bond
forming
reactions
that
initiated
carbometalation.
The
protocols
feature
diastereo-
introduction
allyl,
alkynyl,
functionalized
alkyl
groups.
Mechanistic
studies
indicated
an
unusual
1,3-cobalt
migration
subsequent
β-carbon
elimination
cascade
process
occurred
the
allyl
addition.
These
new
discoveries
established
elementary
cobalt
catalysis
extension
diversity
nucleophiles
transformations
cyclobutenes.
Science,
Journal Year:
2024,
Volume and Issue:
386(6717)
Published: Oct. 3, 2024
Kinases
are
critical
regulators
of
cellular
function
that
commonly
implicated
in
the
mechanisms
underlying
disease.
Most
drugs
target
kinases
molecules
inhibit
their
catalytic
activity,
but
here
we
used
chemically
induced
proximity
to
convert
kinase
inhibitors
into
activators
therapeutic
genes.
We
synthesized
bivalent
link
ligands
transcription
factor
B
cell
lymphoma
6
(BCL6)
cyclin-dependent
(CDKs).
These
relocalized
CDK9
BCL6-bound
DNA
and
directed
phosphorylation
RNA
polymerase
II.
The
resulting
expression
pro-apoptotic,
BCL6-target
genes
caused
killing
diffuse
large
cells
specific
ablation
BCL6-regulated
germinal
center
response.
Genomics
proteomics
corroborated
a
gain-of-function
mechanism
which
global
activity
was
not
inhibited
rather
redirected.
Thus,
can
be
context-specifically
activate
transcription.
ACS Catalysis,
Journal Year:
2021,
Volume and Issue:
11(20), P. 12815 - 12820
Published: Oct. 6, 2021
A
method
to
achieve
the
synthesis
of
highly
substituted
spirocyclic
cyclobutanes
is
disclosed.
The
reaction
involves
catalytic
arylboration
cyclobutenes.
Depending
on
substitution
pattern
cyclobutene,
either
a
Cu/Pd-
or
Ni-catalyzed
was
utilized.
In
case
Cu/Pd
catalyzed
reactions,
identification
Cu-complex
for
crucial
observe
high
selectivity.
synthetic
utility
products
demonstrated,
and
mechanistic
details
are
discussed.
Angewandte Chemie International Edition,
Journal Year:
2022,
Volume and Issue:
61(46)
Published: Oct. 17, 2022
Two
catalytic
systems
have
been
developed
for
the
arylboration
of
endocyclic
enecarbamates
to
deliver
synthetically
versatile
borylated
saturated
N-heterocycles
in
good
regio-
and
diastereoselectivities.
A
Cu/Pd
dual
reaction
enables
synthesis
borylated,
α-arylated
azetidines,
while
a
Ni-catalysed
efficiently
functionalizes
5-,
6-,
7-membered
enecarbamates.
In
case
Cu/Pd-system,
remarkable
additive
effect
was
identified
that
allowed
broader
scope.
The
products
are
useful,
as
demonstrated
by
manipulations
boronic
ester
access
biologically
active
compounds.
Molecules,
Journal Year:
2023,
Volume and Issue:
28(5), P. 2252 - 2252
Published: Feb. 28, 2023
Borylation
has
become
a
powerful
method
to
synthesize
organoboranes
as
versatile
building
blocks
in
organic
synthesis,
medicinal
chemistry,
and
materials
science.
Copper-promoted
borylation
reactions
are
extremely
attractive
due
the
low
cost
non-toxicity
of
copper
catalyst,
mild
reaction
conditions,
good
functional
group
tolerance,
convenience
chiral
induction.
In
this
review,
we
mainly
updated
recent
advances
(from
2020
2022)
synthetic
transformations
C=C/C≡C
multiple
bonds,
C=E
bonds
mediated
by
boryl
systems.
Chemical Science,
Journal Year:
2023,
Volume and Issue:
14(6), P. 1575 - 1581
Published: Jan. 1, 2023
Herein,
we
describe
the
catalytic
enantioselective
cross-coupling
of
1,2-bisboronic
esters.
Prior
work
on
group
specific
cross
coupling
is
limited
to
use
geminal
bis-boronates.
This
desymmetrization
provides
a
novel
approach
prepare
enantioenriched
cyclopropyl
boronates
with
three
contiguous
stereocenters,
that
could
be
further
derivatized
through
selective
functionalization
carbon-boron
bond.
Our
results
suggest
transmetallation,
which
enantiodetermining
step,
takes
place
retention
stereochemistry
at
carbon.
Angewandte Chemie International Edition,
Journal Year:
2023,
Volume and Issue:
62(13)
Published: Feb. 2, 2023
Complex
cyclobutanes
are
important
motifs
in
both
bioactive
molecules
and
natural
products,
yet
their
enantioselective
preparation
has
not
been
widely
explored.
In
this
work,
we
describe
rhodium-catalyzed
additions
of
aryl
vinyl
boronic
acids
to
cyclobutenone
ketals.
This
transformation
involves
carbometalation
give
cyclobutyl-rhodium
intermediates,
followed
by
β-oxygen
elimination
afford
enantioenriched
enol
ethers.
Overall,
addition
serves
as
a
surrogate
for
Rh-catalyzed
1,4-additions
cyclobutenone.
