Angewandte Chemie,
Год журнала:
2024,
Номер
136(35)
Опубликована: Май 15, 2024
Abstract
Sulfinamidines
are
promising
aza‐S
IV
chiral
building
blocks
in
asymmetric
synthesis
and
drug
discovery.
However,
no
report
has
documented
their
enantioselective
synthesis.
Here
we
present
an
of
sulfinamidines
via
electrophilic
amination
sulfenamides
using
enantiopure
N−H
oxaziridine.
The
resulting
enantiomerically
enriched
primary
configurationally
stable
at
90
°C
solution
show
remarkable
stability
against
organic
acids
bases
under
non‐aqueous
conditions.
We
also
demonstrate
a
one‐pot,
three‐component,
sulfinamides
oxaziridine
reagents.
Journal of Medicinal Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 9, 2025
While
sulfoximines
are
nowadays
a
well
established
functional
group
for
medicinal
chemistry,
the
properties
of
sulfilimines
significantly
less
studied,
and
no
sulfilimine
has
progressed
to
clinic
date.
In
this
account,
physicochemical
in
vitro
reported
compared
those
other
more
traditional
groups.
Furthermore,
impact
on
real
drug
scaffolds
is
studied
two
series
sulfilimine-containing
analogs
imatinib
hNE
inhibitors.
We
show
that
can
be
chemically
configurationally
stable
under
physiologically
relevant
conditions
they
basic
highly
polar
thus
often
beneficial
solubility
metabolic
stability,
although
at
cost
reduced
permeability.
conclude
S-cyclopropyl,S-(hetero)aryl
S,S-di(hetero)aryl
so
far
neglected
but
potentially
valuable
S(IV)
based
pharmacophores
deserve
considered
as
part
chemistry
toolbox.
Journal of the American Chemical Society,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 2, 2025
Asymmetric
catalysis
involving
a
sulfoxide
electrophile
intermediate
presents
an
efficient
methodology
for
accessing
stereogenic-at-sulfur
compounds,
such
as
sulfinate
esters,
sulfinamides,
etc.,
which
have
garnered
increasing
attention
in
modern
pharmaceutical
sciences.
However,
the
aza-analog
of
electrophiles,
asymmetric
issues
about
electrophilic
sulfinimidoyl
species
remain
largely
unexplored
and
represent
significant
challenge
sulfur
stereochemistry.
Herein,
we
exhibit
anionic
stereogenic-at-cobalt(III)
complex-catalyzed
synthesis
chiral
sulfinamides
via
iodide
intermediates.
Mechanistic
investigations
reveal
that
catalytic
cycle
is
initiated
by
oxidative
iodination,
generating
iodides.
These
active
intermediates
subsequently
undergo
enantiospecific
nucleophilic
substitution
with
water,
affording
diverse
array
enantioenriched
sulfinamides.
Notably,
these
promising
antifungal
activities
against
Sclerotinia
sclerotiorum
serve
ideal
platform
molecules
facilitating
stereospecific
transformation
into
various
stereogenic
aza-sulfur
compounds.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Июнь 4, 2024
Abstract
The
unique
features
of
the
sulfenamides’
S(II)-N
bond
lead
to
interesting
stereochemical
properties
and
significant
industrial
functions.
Here
we
present
a
chemoselective
Chan–Lam
coupling
sulfenamides
prepare
N
-arylated
sulfenamides.
A
tridentate
pybox
ligand
governs
chemoselectivity
favoring
C–N
formation,
overrides
competitive
C-S
formation
by
preventing
S,N-bis-chelation
copper
center.
Cu(II)-derived
resting
state
catalyst
is
captured
UV-Vis
spectra
EPR
technique,
key
intermediate
confirmed
isotope
response
using
15
N-labeled
sulfenamide.
computational
mechanistic
study
reveals
that
-arylation
both
kinetically
thermodynamically
favorable,
with
deprotonation
sulfenamide
nitrogen
atom
occurring
prior
reductive
elimination.
origin
ligand-controlled
explored,
interaction
between
substrate
controlling
energy
S
corresponding
product
distribution,
in
agreement
studies
kinetic
results.
A
copper-catalyzed
Ullmann-type
cross-coupling
reaction
of
sulfenamides
with
aryl
iodides
is
developed.
The
key
to
success
the
use
a
2-methylnaphthalen-1-amine-derived
amide
ligand,
which
enables
formation
an
S-C
bond
access
functionalized
sulfilimines
in
good
excellent
yields
at
room
temperature.
This
method
has
advantages
mild
conditions,
broad
substrate
scope,
functional
group
compatibility,
and
high
chemoselectivity.
utility
this
protocol
highlighted
through
late-stage
modification
drug-relevant
molecules
sulfilimine
product
derivatization.
Sulfilimines
are
versatile
synthetic
intermediates
and
important
moieties
in
bioactive
molecules.
However,
their
applications
drug
discovery
underexplored,
efficient
asymmetric
methods
highly
desirable.
Here,
we
report
a
transition
metal–free
pentanidium-catalyzed
sulfur
alkylation
of
sulfenamides
with
exclusive
chemoselectivity
over
nitrogen
high
enantioselectivity.
The
reaction
conditions
were
mild,
wide
range
enantioenriched
aryl
alkyl
sulfilimines
obtained.
utility
practicability
this
robust
protocol
further
demonstrated
through
gram-scale
reactions
late-stage
functionalization
drugs.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(33)
Опубликована: Май 31, 2024
Abstract
gem
‐Diborylalkanes
are
highly
valuable
building
blocks
in
organic
synthesis
and
pharmaceutical
chemistry
due
to
their
ability
participate
multi‐step
cross‐coupling
transformations,
allowing
for
the
rapid
generation
of
molecular
complexity.
While
progress
has
been
made
synthetic
metholodology,
construction
β‐tertiary
C(sp
3
)‐rich
‐diborylalkanes
remains
a
challenge
substrate
limitations
steric
hindrance
issues.
An
approach
is
presented
that
utilizes
synergistic
photoredox
copper
catalysis
achieve
efficient
)−C(sp
)
alkyl
N
‐hydroxyphthalimide
esters,
which
can
easily
be
obtained
from
carboxylic
acids,
with
diborylmethyl
species,
providing
series
1°,
2°,
even
3°
β
positions.
Furthermore,
this
also
applied
complex
medicinal
compounds
natural
products,
offering
access
complexity
late‐stage
functionalization
drug
candidates.
Mechanistic
experiments
revealed
Cu(I)
species
participated
both
process
key
bond‐forming
step.
Abstract
Sulfur-containing
compounds
are
found
in
myriad
applications.
Sulfones
and
sulfonamides
the
most
common
functional
groups
used
medicinal
agrochemical
endeavours.
Isosteres
of
these
groups,
for
example,
sulfoximines
sulfonimidamides,
emerging
functionalities,
they
increasingly
relevant
patent
literature.
However,
general,
associated
synthetic
routes
still
have
limitations,
including
use
harsh
reaction
conditions
highly
reactive
reagents.
A
variety
catalytic
reactions
that
employ
a
diverse
range
substrate
classes
been
developed
to
address
issues.
This
short
review
highlights
recent
syntheses
aza-sulfur
compounds,
which
we
hope
will
open
new
directions
discovery
chemistry.
1
Introduction
2
Reactions
N-Sulfinylamines
3
with
Sulfenamides
4
Sulfinates
5
Sulfinamides
6
Other
Aza-Sulfur
Compounds
7
Conclusion
