Digital Discovery,
Journal Year:
2023,
Volume and Issue:
2(6), P. 1900 - 1910
Published: Jan. 1, 2023
Bond
dissociation
energetics
underpin
the
thermodynamics
of
chemical
transformations
where
bonds
are
broken
or
formed
and
can
also
be
used
to
predict
reaction
rates
selectivities.
Chemical Science,
Journal Year:
2022,
Volume and Issue:
13(40), P. 11721 - 11737
Published: Jan. 1, 2022
A
flurry
of
reports
for
preparing,
functionalizing,
and
using
bicyclo[1.1.0]butanes
(BCBs)
have
positioned
them
to
be
powerful
synthons
with
numerous
applications.
This
review
discusses
the
recent
developments
regarding
this
strained
carbocycle.
Journal of the American Chemical Society,
Journal Year:
2023,
Volume and Issue:
145(5), P. 3092 - 3100
Published: Jan. 25, 2023
The
replacement
of
aryl
rings
with
saturated
carbocyclic
structures
has
garnered
significant
interest
in
drug
discovery
due
to
the
potential
for
improved
pharmacokinetic
properties
upon
substitution.
In
particular,
1,3-difunctionalized
bicyclo[1.1.1]pentanes
(BCPs)
have
been
widely
adopted
as
bioisosteres
parasubstituted
arene
rings,
appearing
a
number
lead
pharmaceutical
candidates.
However,
despite
value
2-substituted
BCPs
replacements
ortho-
or
meta-substituted
general
and
rapid
syntheses
these
scaffolds
remain
elusive.
Current
approaches
rely
on
installation
bridge
substituent
prior
BCP
core
construction,
leading
lengthy
step
counts
often
nonmodular
sequences.
While
challenging,
direct
functionalization
strong
C-H
bonds
would
offer
more
streamlined
pathway
diverse
BCPs.
Here,
we
report
generalizable
synthetic
linchpin
strategy
via
radical
abstraction
core.
Through
mild
generation
hydrogen
atom
abstractor,
rapidly
synthesize
novel
linchpins
one
pot.
These
then
serve
common
precursors
complex
BCPs,
allowing
one-step
access
previously
inaccessible
electrophile
nucleophile
fragments
at
2-position
two
new
metallaphotoredox
protocols.
Altogether,
this
platform
enables
expedient
synthesis
four
analogues,
all
which
show
similar
compared
their
aryl-containing
equivalents,
demonstrating
development.
Chemical Science,
Journal Year:
2024,
Volume and Issue:
15(28), P. 10823 - 10829
Published: Jan. 1, 2024
Bicyclo[4.1.1]octanes
(BCOs)
were
synthesized
in
up
to
quantitative
yields
through
the
formal
[4+2]
cycloaddition
of
aryl
and
alkyl
bicyclobutane
(BCB)
ketones
with
dienol
silyl
ethers
using
Al(OTf)
3
as
a
Lewis
acid
catalyst.
Nature Communications,
Journal Year:
2022,
Volume and Issue:
13(1)
Published: June 11, 2022
Abstract
Sulfonyl
fluorides
have
attracted
considerable
and
growing
research
interests
from
various
disciplines,
which
raises
a
high
demand
for
novel
effective
methods
to
access
this
class
of
compounds.
Radical
flurosulfonylation
is
recently
emerging
as
promising
approach
the
synthesis
sulfonyl
fluorides.
However,
scope
applicable
substrate
reaction
types
are
severely
restricted
by
limited
known
radical
reagents.
Here,
we
introduce
solid
state,
redox-active
type
fluorosulfonyl
reagents,
1-fluorosulfonyl
2-aryl
benzoimidazolium
triflate
(FABI)
salts,
enable
fluorosulfonylation
olefins
under
photoredox
conditions.
In
comparison
with
precursor,
gaseous
FSO
2
Cl,
FABI
salts
bench-stable,
easy
handle,
affording
yields
in
before
challenging
substrates.
The
advantage
FABIs
further
demonstrated
development
an
alkoxyl-fluorosulfonyl
difunctionalization
olefins,
forges
facile
useful
β-alkoxyl
related
compounds,
would
thus
benefit
study
context
chemical
biology
drug
discovery
future.
Chemistry - A European Journal,
Journal Year:
2022,
Volume and Issue:
28(19)
Published: Feb. 11, 2022
Physico-chemical
properties
important
to
drug
discovery
(pKa
,
LogP,
and
aqueous
solubility),
as
well
metabolic
stability,
were
studied
for
a
series
of
functionalized
gem-difluorinated
cycloalkanes
compared
those
non-fluorinated
acyclic
counterparts
evaluate
the
impact
fluorination.
It
was
found
that
influence
CF2
moiety
on
acidity/basicity
corresponding
carboxylic
acids
amines
defined
by
inductive
effect
fluorine
atoms
nearly
same
cyclic
aliphatic
compounds.
Lipophilicity
solubility
followed
more
complex
trends
affected
position
atoms,
ring
size,
even
nature
functional
group
present;
also,
significant
differences
series.
Also,
gem-difluorination
either
did
not
affect
or
slightly
improved
stability
model
derivatives.
The
presented
results
can
be
used
guide
rational
design
employing
establish
first
chapter
in
catalog
key
vitro
fluorinated
cycloalkanes.
ChemMedChem,
Journal Year:
2022,
Volume and Issue:
17(21)
Published: Aug. 29, 2022
The
review
covers
various
aspects
of
fluorinated
cycloalkyl
(C3
-C7
)
building
blocks
for
drug
discovery,
including
their
synthesis,
key
physicochemical
properties,
and
biological
medicinal
applications
derivatives.
discussed
synthetic
methods
include
classical
nucleophilic
fluorinations
substrates,
the
addition
fluorine
another
heteroatom
to
double
bonds,
cycloadditions
other
transformations
fluorine-containing
as
well
some
newer
reactions
like
fluorination
non-activated
remotely
activated
C-H
decarboxylative
deborylative
fluorinations,
etc.
known
data
on
effect
introducing
groups
compound's
in
vitro
parameters
(such
acidity/basicity,
lipophilicity,
conformational
behavior,
short
contact
capabilities)
are
surveyed.
Finally,
block
derivatives
design
biologically
active
compounds
(including
marketed
drugs
Maraviroc,
Ivosidenib,
Sitafloxacin)
covered,
with
a
focus
impact.
ChemCatChem,
Journal Year:
2022,
Volume and Issue:
14(24)
Published: Aug. 11, 2022
Abstract
gem
‐Difluorocyclopropanes
(F
2
CPs)
have
aroused
considerable
attention
not
only
from
the
structural
perspective
but
also
due
to
their
ability
participate
in
various
valuable
transformations.
This
Review
summarizes
advances
catalytic
ring‐opening
reactions
of
‐F
CPs,
especially
emphasizing
reactivities
and
applications
those
non‐activated
ones
under
transition‐metal
catalysis.
Their
achievements,
synthetic
limitations
are
discussed
with
aim
stimulate
enthusiasm
for
further
development.
RSC Advances,
Journal Year:
2023,
Volume and Issue:
13(24), P. 16619 - 16629
Published: Jan. 1, 2023
Tetronic
acid,
a
versatile
synthon,
has
been
extensively
investigated
by
numerous
researchers
in
synthetic
chemistry
due
to
its
crucial
role
synthesizing
heterocycles
which
makes
this
compound
particularly
advantageous
both
pharmaceutical
and
biological
fields.
Chemical Science,
Journal Year:
2023,
Volume and Issue:
14(30), P. 8070 - 8075
Published: Jan. 1, 2023
Identification
of
rigid
counterparts
for
common
flexible
scaffolds
is
crucial
to
the
advancement
medicinal
chemistry.
Here
we
showcase
a
new
class
building
blocks,
2,5-disubstituted
bicyclo[2.1.1]hexanes
that
can
act
as
rigidified
Angewandte Chemie International Edition,
Journal Year:
2023,
Volume and Issue:
62(21)
Published: March 24, 2023
Herein
we
reported
a
transition
metal-free
deborylative
cyclization
strategy,
based
on
which
two
routes
have
been
developed,
generating
racemic
and
enantioenriched
cyclopropylboronates.
The
of
geminal-bis(boronates)
bearing
leaving
group
was
highly
diastereoselective,
tolerating
few
functional
groups
applicable
to
heterocycles.
When
optically
active
epoxides
were
used
as
the
starting
materials,
cyclopropylboronates
could
be
efficiently
prepared
with
>99
%
stereospecificity.
Mechanistic
studies
showed
that
at
γ-position
played
crucial
role
significantly
promoted
activation
gem-diboron
moiety.