Angewandte Chemie,
Год журнала:
2024,
Номер
136(37)
Опубликована: Июнь 27, 2024
Abstract
Sulfur‐containing
functional
groups
have
garnered
considerable
attention
due
to
their
common
occurrence
in
ligands,
pharmaceuticals,
and
insecticides.
Nevertheless,
enantioselective
synthesis
of
sulfilimines,
particularly
diaryl
sulfilimines
remains
a
challenging
persistent
goal.
Herein
we
report
highly
enantio‐
chemoselective
cross–coupling
sulfenamides
with
aryl
diazonium
salt
construct
diverse
S(IV)
stereocenters
by
Pd
catalysis.
Bisphosphine
ligands
bearing
sulfinamide
play
crucial
role
achieving
high
reactivity
selectivity.
This
approach
provides
general,
modular
divergent
framework
for
quickly
synthesizing
chiral
sulfoximines
that
are
otherwise
access.
In
addition,
the
origins
chemoselectivity
enantioselectivity
were
extensively
investigated
using
density
theory
calculations.
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.
Organic Letters,
Год журнала:
2023,
Номер
25(27), С. 5157 - 5161
Опубликована: Июль 5, 2023
An
efficient
and
metal-free
approach
for
the
synthesis
of
sulfilimines
from
sulfenamides
with
aryne
cyclohexyne
precursors
has
been
developed.
The
reaction
proceeds
through
unusual
S–C
bond
formation,
which
offers
a
novel
practical
entry
to
access
wide
range
in
moderate
good
yields
excellent
chemoselectivity.
Moreover,
this
protocol
is
amenable
gram-scale
applicable
transformation
products
into
useful
sulfoximines.
Organic Letters,
Год журнала:
2023,
Номер
25(25), С. 4759 - 4764
Опубликована: Июнь 20, 2023
Sulfur-(hetero)arylation
of
sulfenamides
with
commercially
abundant
(hetero)aryl
iodides
by
Ullmann-type
coupling
inexpensive
copper(I)
iodide
as
the
catalyst
is
reported.
A
broad
scope
reaction
inputs
was
demonstrated,
including
both
aryl
and
alkyl
highly
sterically
hindered
5-
6-membered
ring
heteroaryl
iodides.
Relevant
to
many
bioactive
high
oxidation
state
sulfur
compounds,
(hetero)arylation
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(37)
Опубликована: Июнь 27, 2024
Abstract
Sulfur‐containing
functional
groups
have
garnered
considerable
attention
due
to
their
common
occurrence
in
ligands,
pharmaceuticals,
and
insecticides.
Nevertheless,
enantioselective
synthesis
of
sulfilimines,
particularly
diaryl
sulfilimines
remains
a
challenging
persistent
goal.
Herein
we
report
highly
enantio‐
chemoselective
cross–coupling
sulfenamides
with
aryl
diazonium
salt
construct
diverse
S(IV)
stereocenters
by
Pd
catalysis.
Bisphosphine
ligands
bearing
sulfinamide
play
crucial
role
achieving
high
reactivity
selectivity.
This
approach
provides
general,
modular
divergent
framework
for
quickly
synthesizing
chiral
sulfoximines
that
are
otherwise
access.
In
addition,
the
origins
chemoselectivity
enantioselectivity
were
extensively
investigated
using
density
theory
calculations.
Angewandte Chemie International Edition,
Год журнала:
2023,
Номер
63(6)
Опубликована: Дек. 21, 2023
Sulfilimines,
the
aza-variants
of
sulfoxides,
are
key
structural
motifs
in
natural
products,
pharmaceuticals,
and
agrochemicals;
sulfilimine
synthesis
is
therefore
important
organic
chemistry.
However,
methods
for
radical
sulfilimination
remain
elusive,
as
a
result,
diversity
currently
available
sulfilimines
limited.
Herein,
we
report
first
protocol
decarboxylative
reactions
between
sulfenamides
N-hydroxyphthalimide
esters
primary,
secondary,
tertiary
alkyl
carboxylic
acids,
which
were
achieved
via
combination
photoredox,
copper,
Brønsted
base
catalysis.
This
novel
provided
wide
variety
sulfilimines,
addition
to
serving
an
efficient
route
S-alkyl/S-aryl
homocysteine
S-(4-methylphenyl)
sulfoximine.
Moreover,
it
could
be
used
late-stage
introduction
group
into
structurally
complex
molecules,
thereby
avoiding
need
preserve
labile
organosulfur
moieties
through
multistep
synthetic
sequences.
A
mechanism
involving
photocatalytic
substrate
transformation
copper-mediated
C(sp
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 26, 2024
Abstract
A
general
phase‐transfer
catalyst
(PTC)
mediated
enantioselective
alkylation
of
N
‐acylsulfenamides
is
reported.
Essential
to
achieving
high
selectivity
was
the
use
triethylacetyl
sulfenamide
protecting
group
along
with
aqueous
KOH
as
base
under
biphasic
conditions
enable
reaction
be
performed
at
−40
°C.
With
these
key
parameters,
enantiomeric
ratios
up
97.5
:
2.5
newly
generated
chiral
sulfur
center
were
achieved
an
inexpensive
cinchona
alkaloid
derived
PTC.
Broad
scope
and
excellent
functional
compatibility
observed
for
a
variety
S
‐(hetero)aryl
branched
unbranched
‐alkyl
sulfenamides.
Moreover,
achieve
opposite
enantiomer,
pseudoenantiomeric
designed
synthesized
from
cinchonidine.
Given
that
sulfoximines
are
bioactive
pharmacophore
ever‐increasing
interest,
selected
product
sulfilimines
oxidized
corresponding
subsequent
reductive
cleavage
affording
free‐NH
in
yields.
The
utility
disclosed
method
further
demonstrated
by
efficient
asymmetric
synthesis
atuveciclib,
phase
I
clinical
candidate
which
only
HPLC
separation
had
previously
been
reported
isolation
desired
(
R
)‐sulfoximine
stereoisomer.
Organic Letters,
Год журнала:
2024,
Номер
26(18), С. 3906 - 3910
Опубликована: Апрель 29, 2024
Sulfilimines
are
valuable
compounds
in
both
organic
synthesis
and
pharmaceuticals.
In
this
study,
we
present
a
copper-catalyzed
sulfur
alkylation
of
sulfenamides
with
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.
Organic Letters,
Год журнала:
2023,
Номер
25(39), С. 7192 - 7197
Опубликована: Сен. 21, 2023
Sulfilimines,
the
aza
analogues
of
sulfoxides,
are
increasing
interest
in
medicinal
and
agrochemical
research
programs.
However,
development
efficient
routes
for
their
synthesis
has
remained
relatively
unexplored.
In
this
study,
we
report
a
transition
metal-free,
selective
S-arylation
reaction
between
sulfenamides
arynes,
enabling
facile
preparation
structurally
diverse
sulfilimines
under
mild
redox-neutral
conditions
good
yields.
The
application
value
our
method
was
further
demonstrated
by
scale-up
synthesis,
downstream
derivatization,
robustness
screen.
