ACS Organic & Inorganic Au,
Journal Year:
2024,
Volume and Issue:
4(4), P. 424 - 431
Published: May 15, 2024
Parallel
Minisci
reactions
of
nonfluorinated
and
gem-difluorinated
C4–C7
cycloalkyl
building
blocks
(trifluoroborates
carboxylic
acids)
with
a
series
electron-deficient
heterocycles
were
studied.
A
comparison
the
reaction's
outcome
revealed
better
product
yields
in
case
acids
as
radical
precursors
most
cases,
albeit
these
reagents
used
three-fold
excess
under
optimized
conditions.
The
nature
heterocyclic
core
was
found
to
be
important
for
successful
incorporation
fragment.
impact
CF2
moiety
on
oxidation
potential
fluorinated
trifluoroborates
reaction
outcome,
general,
also
evaluated.
Angewandte Chemie International Edition,
Journal Year:
2023,
Volume and Issue:
62(32)
Published: June 20, 2023
Direct
synthesis
of
gem-difluorinated
carbocyclic
molecules
represents
a
longstanding
challenge
in
organic
chemistry.
Herein,
Rh-catalyzed
[3+2]
cycloaddition
reaction
between
readily
available
cyclopropanes
(gem-DFCPs)
and
internal
olefins
has
been
developed,
enabling
the
efficient
cyclopentanes
with
good
functional
group
compatibility,
excellent
regioselectivity
diastereoselectivity.
The
resulting
products
can
undergo
downstream
transformations
to
access
various
mono-fluorinated
cyclopentenes
cyclopentanes.
This
demonstrates
use
gem-DFCPs
as
type
"CF2
"
C3
synthon
for
under
transition
metal
catalysis,
which
provides
potential
strategy
synthesizing
other
molecules.
Chemical Communications,
Journal Year:
2024,
Volume and Issue:
60(28), P. 3764 - 3773
Published: Jan. 1, 2024
This
feature
article
summarizes
our
efforts
towards
developing
Rh-catalyzed
reactions
of
gem
-difluorinated
cyclopropanes,
briefly
discussing
the
design,
selectivity,
mechanisms
and
future
research
prospects.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(23)
Published: April 2, 2024
The
diversified
synthesis
of
chiral
fluorinated
cyclobutane
derivatives
has
remained
a
difficult
task
in
synthetic
chemistry.
Herein,
we
present
an
approach
for
asymmetric
hydroboration
and
formal
hydrodefluorination
gem-difluorinated
cyclobutenes
through
rhodium
catalysis,
providing
α-boryl
cyclobutanes
monofluorinated
with
excellent
regio-
enantioselectivity,
respectively.
key
to
the
success
two
transformations
relies
on
efficient,
mild
highly
selective
rhodium-catalyzed
HBPin
(pinacolborane),
which
subsequent
addition
base,
catalytic
amount
palladium
some
cases,
results
formation
products
four-membered
ring
retained.
obtained
are
versatile
building
blocks
that
provide
platform
enantioenriched
great
diversity.
Nature Communications,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: June 2, 2023
Partially
saturated,
fluorine-containing
rings
are
ubiquitous
across
the
drug
discovery
spectrum.
This
capitalises
upon
biological
significance
of
native
structure
and
physicochemical
advantages
conferred
by
fluorination.
Motivated
aryl
tetralins
in
bioactive
small
molecules,
a
reaction
cascade
has
been
validated
to
generate
novel
gem-difluorinated
isosteres
from
1,3-diaryl
cyclobutanols
single
operation.
Under
Brønsted
acidity
catalysis
conditions,
an
acid-catalysed
unmasking/fluorination
sequence
generates
homoallylic
fluoride
situ.
species
serves
as
substrate
for
I(I)/I(III)
cycle
is
processed,
via
phenonium
ion
rearrangement,
(isolable)
1,3,3-trifluoride.
A
final
C(sp3)-F
bond
activation
event,
enabled
HFIP,
forges
difluorinated
tetralin
scaffold.
The
highly
modular,
enabling
intermediates
be
intercepted:
this
provides
expansive
platform
generation
structural
diversity.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(22)
Published: March 14, 2024
Abstract
Cyclic
β,β‐difluoro‐carbonyl
compounds
have
a
venerable
history
as
drug
discovery
leads,
but
limitations
in
the
synthesis
arsenal
continue
to
impede
chemical
space
exploration.
This
challenge
is
particularly
acute
arena
of
fluorinated
medium
rings
where
installing
difluoromethylene
unit
subtly
alters
ring
conformation
by
expanding
internal
angle
(∠C−CF
2
−C>∠C−CH
−C):
this
provides
handle
modulate
physicochemistry
(e.g.
p
K
).
To
reconcile
disparity,
highly
modular
expansion
has
been
devised
that
leverages
simple
α,β‐unsaturated
esters
and
amides,
processes
them
one‐carbon
homologated
with
concomitant
geminal
difluorination
(6
10
membered
rings,
up
95
%
yield).
process
rare
example
formal
an
alkene
enabled
sequential
I(III)‐enabled
O
‐activation.
Validation
enantioselective
catalysis
generation
unprecedented
scaffolds
reported
(up
93
:
7
e.r
.)
together
X‐ray
structural
analyses
product
derivatization.
The Journal of Organic Chemistry,
Journal Year:
2023,
Volume and Issue:
88(18), P. 12935 - 12948
Published: Sept. 6, 2023
An
electrochemical
or
photoelectrochemical
regioselective
polyfluoroalkylation/cyclization
cascade
of
3-aza-1,5-dienes
with
sodium
fluoroalkanesulfinates
is
presented.
This
protocol
proceeds
a
broad
substrate
scope
and
good
functional
group
tolerance
under
mild,
oxidant-free,
transition-metal-free,
electrolyte-free
conditions
to
provide
3-polyfluoroalkylated
4-pyrrolin-2-ones
in
one
step
from
readily
available
N-vinylacrylamides,
it
scalable
the
Gram
scale.
Chemical Science,
Journal Year:
2024,
Volume and Issue:
15(34), P. 13800 - 13806
Published: Jan. 1, 2024
Metathesis
reactions
have
been
established
as
a
powerful
tool
in
organic
synthesis.
While
great
advances
were
achieved
double-bond
metathesis,
like
olefin
metathesis
and
carbonyl
single-bond
has
received
less
attention
the
past
decade.
Herein,
we
describe
first
C(sp
Chemistry - A European Journal,
Journal Year:
2023,
Volume and Issue:
29(47)
Published: June 15, 2023
A
comprehensive
study
of
physicochemical
properties
(pKa
,
LogP,
and
intrinsic
microsomal
clearance)
within
the
series
mono-
difluorinated
azetidine,
pyrrolidine,
piperidine
derivatives
was
performed.
While
number
fluorine
atoms
their
distance
to
protonation
center
were
major
factors
defining
compound's
basicity,
both
pKa
LogP
values
affected
considerably
by
conformational
preferences
corresponding
derivatives.
For
example,
features
"Janus
face"
(facially
polarized)
cyclic
compounds
(i.
e.,
unusually
high
hydrophilicity)
identified
for
cis-3,5-difluoropiperidine,
preferring
a
diaxial
conformation.
Intrinsic
clearance
measurements
demonstrated
metabolic
stability
studied
(with
single
exception
3,3-difluoroazetidine
derivative).
According
-
plots,
title
provide
valuable
extension
fluorine-containing
(e.
g.,
fluoroalkyl-substituted)
saturated
heterocyclic
amine
as
building
blocks
rational
optimization
studies
in
early
drug
discovery.
