Journal of the American Chemical Society,
Journal Year:
2025,
Volume and Issue:
unknown
Published: June 5, 2025
Selective
fluorination
of
C(sp3)-H
bonds
is
a
highly
valuable
transformation
in
organic
synthesis
and
drug
discovery.
However,
achieving
methylene
C-H
native
substrates
remains
significant
challenge,
as
it
typically
requires
external
directing
groups
to
facilitate
catalyst-substrate
binding.
Herein,
we
report
ligand-accelerated
Pd-catalyzed
β-C-H
amides
using
bidentate
neutral
amide-pyridone
ligand.
This
ligand
design
features
the
enhancement
interactions
via
stabilization
cationic
palladium
center
acceleration
activation,
enabling
stereo-
site-selective
under
relatively
mild
conditions.
Notably,
Pd(II)-catalyzed
activation
weakly
coordinating
has
not
been
reported
date.
method
compatible
with
derived
from
selected
molecules
Weinreb
amides,
demonstrating
potential
utility
discovery
other
applications.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(19)
Published: Feb. 29, 2024
Abstract
In
2001,
our
curiosity
to
understand
the
stereochemistry
of
C−H
metalation
with
Pd
prompted
first
studies
in
Pd(II)‐catalyzed
asymmetric
activation
(RSC
Research
appointment:
020
7451
2545,
Grant:
RG
36873,
Dec.
2002).
We
identified
four
central
challenges:
1.
poor
reactivity
simple
salts
native
substrates;
2.
few
strategies
control
site
selectivity
for
remote
bonds;
3.
lack
chiral
catalysts
achieve
enantioselectivity
via
metalation,
and
4.
low
practicality
due
limited
coupling
partner
scope
use
specialized
oxidants.
These
challenges
necessitated
new
catalyst
reaction
development.
For
,
we
developed
approaches
enhance
substrate–catalyst
affinity
together
novel
bifunctional
ligands
which
participate
accelerate
cleavage
step.
site‐selectivity
introduced
concept
systematically
modulating
distance
geometry
between
a
directing
template,
catalyst,
substrate
selectively
access
bonds.
devised
predictable
stereomodels
catalyst‐controlled
enantioselective
based
on
participation
ligands.
Finally,
have
varied
catalytic
manifolds
Pd(II)
accommodate
diverse
partners
while
employing
practical
oxidants
such
as
peroxides.
advances
culminated
numerous
reactions,
setting
stage
broad
industrial
applications.
Chemical Society Reviews,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Jan. 1, 2024
Differentiating
between
two
highly
similar
C-H
bonds
in
a
given
molecule
remains
fundamental
challenge
synthetic
organic
chemistry.
Directing
group
assisted
strategies
for
the
functionalisation
of
proximal
has
been
known
last
few
decades.
However,
distal
bond
is
strenuous
and
requires
distinctly
specialised
techniques.
In
this
review,
we
summarise
advancement
Pd-catalysed
C(sp
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(48)
Published: Aug. 7, 2024
Abstract
Deuterated
and
tritiated
analogs
of
drugs
are
valuable
compounds
for
pharmaceutical
medicinal
chemistry.
In
this
work,
we
present
a
novel
hydrogen
isotope
exchange
reaction
using
non‐directed
homogeneous
Pd‐catalysis.
Aromatic
C−H
activation
is
achieved
by
commercially
available
pyridine
ligand.
Using
the
most
convenient
cheapest
deuterium
source,
D
2
O,
as
only
solvent
39
pharmaceuticals
were
labelled
with
clean
profiles
high
uptakes.
Additionally,
describe
first
application
Pd‐catalysis
H/T
on
three
different
T
O
isotopic
demonstrating
applicability
to
synthesis
radiotracers.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Feb. 19, 2024
Abstract
Aliphatic
allylic
amines
are
common
in
natural
products
and
pharmaceuticals.
The
oxidative
intermolecular
amination
of
C(sp
3
)-H
bonds
represents
one
the
most
straightforward
strategies
to
construct
these
motifs.
However,
utilization
widely
internal
alkenes
with
this
transformation
remains
a
synthetic
challenge
due
inefficient
coordination
metals
excessive
aliphatic
aromatic
amines,
resulting
decreasing
reactivity
catalyst.
Here,
we
present
regioselective
Cu-catalyzed
olefins
azodiformates
problems.
A
removable
bidentate
directing
group
is
used
control
regiochemistry
stabilize
π-allyl-metal
intermediate.
Noteworthy
dual
role
as
both
nitrogen
source
an
electrophilic
oxidant
for
C-H
activation.
This
protocol
features
simple
conditions,
remarkable
scope
functional
tolerance
evidenced
by
>40
examples
exhibits
high
regioselectivity
excellent
E/Z
selectivity.
Organic Letters,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 13, 2025
A
visible-light-mediated
photoredox
catalysis
for
β-C(sp3)–H
alkylation
of
1-(o-iodoaryl)alkan-1-ones
with
alkenes
via
1,5-hydrogen
atom
transfer
and
alkene
alkylarylation
to
produce
diverse
β-alkyl
arylalkanones
containing
a
quaternary
carbon
center
is
presented.
This
method
applicable
wide
range
activated
alkenes.
Mechanistic
studies
suggest
that
the
reaction
involves
radical
process.
