Angewandte Chemie,
Journal Year:
2024,
Volume and Issue:
136(23)
Published: April 4, 2024
Abstract
The
present
study
reports
an
unprecedented
protocol
for
the
phosphonylation
of
unactivated
C(sp
3
)−H
bonds.
By
utilizing
1
mol
%
4DPAIPN
(1,2,3,5‐tetrakis(diphenylamino)‐4,6‐dicyanobenzene)
as
catalyst,
satisfactory
yields
γ‐phosphonylated
amides
are
obtained
through
a
visible‐light‐induced
reaction
between
N
‐((4‐cyanobenzoyl)oxy)alkanamides
and
9‐fluorenyl
o
‐phenylene
phosphite
at
room
temperature.
This
demonstrates
broad
substrate
scope
wide
functional
group
compatibility.
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(12), P. 7942 - 7949
Published: March 12, 2024
Here
we
report
the
design
of
a
general,
redox-switchable
organophosphorus
alkyl
radical
trap
that
enables
synthesis
broad
range
C(sp3)–P(V)
modalities.
This
"plug-and-play"
approach
relies
upon
in
situ
activation
alcohols
and
O═P(R2)H
motifs,
two
broadly
available
inexpensive
sources
molecular
complexity.
The
mild,
photocatalytic
deoxygenative
strategy
described
herein
allows
for
direct
conversion
sugars,
nucleosides,
complex
pharmaceutical
architectures
to
their
analogs.
includes
facile
incorporation
medicinally
relevant
phosphonate
ester
prodrugs.
ACS Catalysis,
Journal Year:
2023,
Volume and Issue:
13(24), P. 16105 - 16113
Published: Dec. 5, 2023
Despite
remarkable
progress
in
photocatalytic
hydrogen
atom
transfer
(HAT)-induced
C(sp3)–H
functionalization,
achieving
to
C(sp3)–P
transformation
by
the
HAT
process
remains
highly
challenging
due
P-reagents'
compatibility
issues.
α-Aminophosphonic
acids
have
shown
great
potential
medicinal
chemistry,
yet
their
synthesis
is
hindered
limited
substrate
scopes,
poor
functional
group
tolerance,
and
reliance
on
prefunctionalized
substrates,
restricting
broad
applications.
Herein,
we
report
HAT-induced
α-C(sp3)–H
phosphonylation
of
aliphatic
amines,
providing
rapid
access
structurally
diverse
α-aminophosphonates
from
abundant
amines.
Leveraging
intramolecular
HAT,
radical
polar
crossover,
an
Arbuzov-type
cascade,
challenges
associated
with
were
overcome.
This
protocol
features
base-free,
redox-neutral,
mild
conditions
employing
amines
as
limiting
reagents,
allows
for
late-stage
complex
drug
molecules
possessing
amine
moieties.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(8)
Published: Jan. 5, 2024
Abstract
Reported
herein
is
an
unprecedented
protocol
for
C(sp
3
)‐phosphinylation.
With
1
mol
%
4CzIPN
(1,2,3,5‐tetrakis(carbazol‐9‐yl)‐4,6‐dicyanobenzene)
as
the
catalyst,
visible
light
induced
reaction
of
redox‐active
esters
aliphatic
carboxylic
acids
with
dimethyl
arylphosphonites
or
diethyl
alkylphosphonites
at
room
temperature
provides
corresponding
decarboxylative
phosphinylation
products
in
satisfactory
yields.
The
exhibits
broad
substrate
scope
and
wide
functional‐group
compatibility,
enabling
late‐stage
modification
complex
molecules
rapid
synthesis
bioactive
phosphinic
such
glutamine
synthetase
phosphinothricin
a
kynureninase
inhibitor.
A
radical‐polar
crossover
mechanism
involving
formation
subsequent
oxidation
phosphoranyl
radicals
followed
by
nucleophilic
demethylation
(or
deethylation)
proposed.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(17)
Published: Feb. 15, 2024
Abstract
A
general
approach
to
the
direct
deoxygenative
transformation
of
primary,
secondary,
and
tertiary
alcohols
has
been
developed.
It
undergoes
through
phosphoranyl
radical
intermediates
generated
by
addition
exogenous
iodine
trivalent
alkoxylphosphanes.
Since
these
alkoxylphosphanes
are
readily
in
situ
obtained
from
commercially
available,
inexpensive
chlorodiphenylphosphine,
a
diverse
range
with
various
functional
groups
can
be
utilized
proceed
cross‐couplings
alkenes
or
aryl
iodides.
The
selective
polyhydroxy
substrates
rapid
synthesis
complex
organic
molecules
also
demonstrated
this
method.
Journal of the American Chemical Society,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 11, 2025
Synthetic
protein/peptide
modification
is
a
powerful
strategy
for
the
development
of
new
therapeutics
and
tools
chemical
biology.
Accordingly,
synthetic
variant
biological
tyrosine
phosphorylation,
cornerstone
post-translational
landscape,
could
find
widespread
application
in
study
this
fundamental
biochemical
signal.
This
work
describes
mechanistically
novel,
redox-neutral,
photocatalytic
phosphorylation
reaction
via
radical
Arbuzov-type
mechanism.
The
proceeds
with
good
selectivity
di-,
tri-,
oligopeptides
under
mild
conditions
near
neutral
pH,
tolerating
potentially
problematic
functionality.
As
first
reaction,
represents
major
advance
toward
goal
phosphorylation.
Nature Communications,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: Oct. 31, 2023
Chemical
modification
of
nucleotides
can
improve
the
metabolic
stability
and
target
specificity
oligonucleotide
therapeutics,
alkylphosphonates
have
been
employed
as
charge-neutral
replacements
for
naturally-occurring
phosphodiester
backbones
in
these
compounds.
However,
at
present,
alkyl
moieties
that
be
attached
to
phosphorus
atoms
compounds
are
limited
methyl
groups
or
primary/secondary
alkyls,
such
alkylphosphonate
degrade
during
synthesis.
The
present
work
demonstrates
tertiary
alkylation
phosphites
bearing
two
2'-deoxynuclosides.
This
process
utilizes
a
carbocation
generated
via
light-driven
radical-polar
crossover
mechanism.
protocol
provides
structures
difficult
synthesize
using
existing
methods.
conversion
species
oligonucleotides
having
linkages
through
phosphoramidite-based
approach
was
also
confirmed
this
study.
Organic Chemistry Frontiers,
Journal Year:
2024,
Volume and Issue:
11(17), P. 4882 - 4894
Published: Jan. 1, 2024
This
review
focuses
on
the
synthesis
of
C–P
bonds
using
carbon-centered
radicals
with
phosphorous
compounds
different
valence
states
(P
III
,
P
V
4
)
under
photocatalysis.
Science,
Journal Year:
2024,
Volume and Issue:
385(6716), P. 1471 - 1477
Published: Sept. 26, 2024
The
excitation
of
carbonyl
compounds
by
light
to
generate
radical
intermediates
has
historically
been
restricted
ketones
and
aldehydes;
carboxylic
acids
have
overlooked
because
high
energy
requirements
low
quantum
efficiency.
A
successful
activation
strategy
would
necessitate
a
bathochromic
shift
in
the
absorbance
profile,
an
increase
triplet
diradical
lifetime,
ease
further
functionalization.
We
present
single-flask
transformation
acyl
phosphonates
that
can
access
synthetically
useful
diradicals
under
visible
or
near-ultraviolet
irradiation.
use
phosphorus
circumvents
unproductive
Norrish
type
I
processes,
promoting
selectivity
enables
hydrogen-atom
transfer
reactivity.
Use
this
promotes
efficient
scaffold
remodeling
through
various
annulation,
contraction,
expansion
manifolds.
Organic Letters,
Journal Year:
2024,
Volume and Issue:
26(11), P. 2197 - 2201
Published: March 7, 2024
In
this
study,
we
present
an
N-heterocyclic
carbene-catalyzed
method
for
the
radical
acylphosphorylation
of
alkenes.
Electrochemical
investigations
were
employed
to
identify
appropriate
class
oxime
phosphonates
capable
undergoing
a
single-electron
transfer
(SET)
with
Breslow
enolates.
The
resulting
phosphoryl
radicals
effectively
coupled
diverse
styrenes
and
aldehydes
yield
variety
γ-oxo-phosphonates.
Both
clock
experiments
electrochemical
studies
support
our
reaction
design,
plausible
mechanism
organocatalytic
transformation
is
proposed.
