Angewandte Chemie,
Год журнала:
2023,
Номер
136(3)
Опубликована: Ноя. 28, 2023
Abstract
A
general
one‐pot
approach
to
diverse
N
‐acylsulfenamides
from
a
common
S
‐phenethylsulfenamide
starting
material
is
reported.
This
was
demonstrated
by
C−S
bond
formation
utilizing
commercially
abundant
(hetero)aryl
iodides
and
boronic
acids
provide
sulfilimine
intermediates
that
undergo
thermal
elimination
of
styrene.
In
contrast,
all
prior
approaches
rely
on
thiol
inputs
introduce
sulfenamide
‐substituents.
broad
scope
reaction
including
for
approved
drugs
drug
precursors
with
dense
display
functionality.
Several
different
types
sulfur
functionalization
were
performed
derived
complex
precursor
the
blockbuster
anticoagulant
apixaban,
highlighting
utility
this
introduction
high
oxidation
state
groups
in
bioactive
compounds.
Mechanistic
studies
established
key
styrene
step
proceeds
concerted
does
not
require
reagents
or
catalysts,
therefore,
should
be
applicable
synthesis
electrophiles
conditions
formation.
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.
Angewandte Chemie International Edition,
Год журнала:
2023,
Номер
63(3)
Опубликована: Ноя. 28, 2023
Abstract
A
general
one‐pot
approach
to
diverse
N
‐acylsulfenamides
from
a
common
S
‐phenethylsulfenamide
starting
material
is
reported.
This
was
demonstrated
by
C−S
bond
formation
utilizing
commercially
abundant
(hetero)aryl
iodides
and
boronic
acids
provide
sulfilimine
intermediates
that
undergo
thermal
elimination
of
styrene.
In
contrast,
all
prior
approaches
rely
on
thiol
inputs
introduce
sulfenamide
‐substituents.
broad
scope
reaction
including
for
approved
drugs
drug
precursors
with
dense
display
functionality.
Several
different
types
sulfur
functionalization
were
performed
derived
complex
precursor
the
blockbuster
anticoagulant
apixaban,
highlighting
utility
this
introduction
high
oxidation
state
groups
in
bioactive
compounds.
Mechanistic
studies
established
key
styrene
step
proceeds
concerted
does
not
require
reagents
or
catalysts,
therefore,
should
be
applicable
synthesis
electrophiles
conditions
formation.
The Journal of Organic Chemistry,
Год журнала:
2024,
Номер
89(12), С. 9043 - 9050
Опубликована: Июнь 6, 2024
A
mild
and
metal-free
approach
has
been
developed
for
1,2-difunctionalization
of
aryne
using
sulfenamides
as
a
nucleophile
halogen
source
(CX4)
an
electrophile
to
synthesize
S-(o-halo)aryl
sulfilimines.
The
late-stage
functionalizations
halide
handles
via
Suzuki–Miyaura
Buchwald–Hartwig
reactions
exhibit
the
synthetic
utilities
products.
chemoselectivity,
regioselectivity,
rapidity,
use
economical
CCl4
are
advantages
this
protocol.
The
functionalization
of
N-acylsulfenamides
is
a
research
focus
in
organosulfur
chemistry,
as
the
N-S
array
has
unique
properties
and
versatile
applications.
Although
great
progress
been
made
S-functionalization,
N-functionalization,
especially
N-arylation
N-acylsulfenamides,
rarely
explored
because
lower
nucleophilicity
N-site.
Herein,
we
report
Brønsted
acid-catalyzed
regioselective
reaction
with
o-quinone
diimides.
Under
mild
metal-free
conditions,
wide
range
N-arylated
have
prepared
good
yields
excellent
regioselectivity.
ease
gram-scale
synthesis
transformations
into
useful
sulfonamides
demonstrates
their
synthetic
practicality.
Chiral
sulfilimines,
aza
analogues
of
sulfoxides,
are
essential
in
natural
products
and
pharmaceuticals,
highlighting
the
importance
their
synthesis
asymmetric
catalysis.
However,
efficient
approaches
for
synthesizing
chiral
diaryl
sulfilimines
still
rare
challenging,
particularly
those
with
two
sterically
similar
aryl
groups.
Herein,
we
present
a
mild
protocol
generating
diverse
enantioenriched
alkyl
via
copper-catalyzed
enantioselective
S-arylation
N-acyl
sulfenamides
diaryliodonium
salts.
A
bulky
PyBox
ligand
is
crucial
stereocontrol,
delivering
various
up
to
95%
ee
(51
examples).
The
site-selective
incorporation
of
sulfilimine
functionalities
into
aromatic
compounds
provides
a
vital
strategy
for
drug
discovery
in
medicinal
chemistry.
However,
green
and
sustainable
methods
realizing
the
goal
are
still
limited.
Here,
we
report
copper-catalyzed
S-arylation
sulfenamides
with
aryl
thianthrenium
salts
irradiated
by
visible
light
without
photocatalyst,
which
exhibited
fine
functional-group
compatibility
gave
desired
products
high
yields.
Mechanistic
investigations
revealed
that
key
to
achieving
these
results
is
generation
an
electron
donor-acceptor
(EDA)
complex
between
under
basic
conditions.
The Journal of Organic Chemistry,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 18, 2024
An
iron-catalyzed
nitrene
transfer
reaction
for
the
rapid
synthesis
of
sulfinamidines
from
readily
available
sulfenamides
is
reported.
This
method
features
mild
conditions,
short
times,
and
a
broad
substrate
scope,
allowing
preparation
variety
in
good
to
excellent
yields.
The
synthetic
utility
sulfinamidine
products
was
further
demonstrated
through
their
conversion
other
valuable
sulfur(VI)
compounds,
such
as
sulfondiimidoyl
fluorides,
sulfinamidiate
esters,
sulfonimidamides.
Preliminary
efforts
development
an
asymmetric
variant
showed
moderate
enantioselectivity.
Sulfilimines
and
their
derivatives
have
garnered
considerable
interest
in
both
synthetic
medicinal
chemistry.
Photochemical
nitrene
transfer
to
sulfides
is
known
as
a
conventional
approach
sulfilimines.
However,
the
existing
methods
limited
substrate
scope
stemming
from
incompatibility
of
singlet
intermediates
with
nucleophilic
functional
groups.
Herein,
we
report
general
for
synthesis
N-sulfonyl
sulfilimines
enabled
by
visible-light-mediated
energy
sulfonyl
azides,
uncovering
neglected
reactivity
triplet
nitrenes
sulfides.
The
unprecedented
mechanism
involving
single
electron
broad
group
tolerance,
water
compatibility,
amenability
use
late-stage
functionalization
drugs.
