Metallaphotoredox
cross-coupling
is
a
well-established
strategy
for
generating
clinically
privileged
aliphatic
scaffolds
via
open-shell
reactivity.
The
introduction
of
new
C(sp3)-coupling
partners
within
this
paradigm
can
provide
entry
to
novel,
medicinally-relevant
chemical
space.
Alkenes
are
abundant,
bench-stable
and
undergo
facile
C(sp3)-radical
reactivity
metal-hydride
hydrogen
atom
transfer
(MHAT),
yet
metallaphotoredox
methodologies
invoking
remain
underdeveloped.
Importantly,
the
merger
MHAT
activation
with
catalysis
could
enable
olefins
feedstock
radical
only
activated
photocatalysis,
such
as
alcohols.
Herein,
we
report
first
C(sp3)–C(sp3)
coupling
MHAT-activated
alkenes
alcohols
(i.e.
deoxygenative
hy-droalkylation)
triple
co-catalysis.
Through
synergistic
Ir
Mn
Ni
sorting
pathways,
branch-selective
protocol
pairs
diverse
methanol
or
primary
alcohols,
displays
remarkable
functional
group
tolerance,
enables
rapid
construction
complex
frameworks.
Functional
group
interconversions
of
abundant
substructures
that
accommodate
the
often-complex
molecular
architectures
seen
in
pharmaceuticals
are
particularly
sought
after
by
medicinal
chemists
as
a
means
to
enable
both
lead
optimization
and
library
diversification.
Here,
we
report
conceptually
new
strategy
enables
net
SO
2
-insertion
into
C–N
bond
primary
amines,
enabling
direct
synthesis
sulfonamides
without
pre-activation
effectively
inverting
nitrogen’s
properties
(acidity,
hydrogen
bonding,
etc.).
The
key
realizing
this
overall
transformation
is
implementation
an
anomeric
amide
dual-function
reagent
which
serves
cleave
initial
deliver
nitrogen
atom
product
incorporation.
process
tolerates
wide
array
functionalities
can
be
run
automated
fashion
thus
allowing
libraries
amines
viable
progenitors
highly
desirable
sulfonamides.
Mechanistic
studies
support
isodiazene
radical
chain
mechanism
generates
intermediate
sulfinate
reacts
with
forge
S–N
bond.
As
proof
concept,
our
protocol
was
used
conduct
high-throughput
diversification
campaign,
applied
modification
approved
active
pharmaceutical
ingredients
CO-to-SO
“isosteric
replacement”
approach.
Conceptually,
successful
translation
originally
developed
for
deletion
insertion
has
important
implications
skeletal
editing.
Organic Letters,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 27, 2024
Herein,
aryl
decarboxylative
allylation,
thiolation,
and
bromination
reactions
via
photoinduced
ligand-to-copper
charge
transfer
are
described.
Utilizing
inexpensive
copper
metal,
the
transformations
of
various
carboxylic
acids
enable
rapid
synthesis
corresponding
alkene,
thioether,
bromide
derivatives
under
visible
light
irradiation,
which
offers
significant
synthetic
value.
The
reaction
conditions
mild
straightforward,
exhibiting
a
broad
substrate
compatibility.
Furthermore,
this
method
can
be
applied
for
late-stage
modification
complex
drug
molecules.
Chinese Journal of Chemistry,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 2, 2024
Comprehensive
Summary
Herein,
we
report
a
rare
example
of
three‐component
net‐oxidative
sulfonylation
SO
2
surrogate
with
an
oxidatively
activated
radical
precursor
under
mild
and
metal‐
external‐oxidant‐free
conditions.
The
mildness
sustainability
the
reaction
are
enabled
by
photoelectrocatalysis,
3‐aza‐1,5‐dienes,
organotrifluoroborates
1,4‐diazabicyclo[2.2.2]octane
bis(sulfur
dioxide)
adduct
(DABSO)
undergo
sulfonylative
cyclization
to
afford
sulfono
4‐pyrrolin‐2‐ones
in
atom‐economical
manner
broad
substrate
scope
good
functional‐group
tolerance.
protocol
is
amenable
late‐stage
diversification
complex
molecular
architectures
as
well
gram‐scale
synthesis.
Sunlight
could
be
used
light
source,
conducted
all‐solar
mode
using
commercially
available
photovoltaic
panel
generate
electricity
situ
.
Mechanistic
studies
reveal
that
generated
(DABCO),
which
was
generally
innocent
previous
reactions,
functions
electron
shuttle
between
photocatalytic
cycle
reactants.
Metallaphotoredox
cross-coupling
is
a
well-established
strategy
for
generating
clinically
privileged
aliphatic
scaffolds
via
open-shell
reactivity.
The
introduction
of
new
C(sp3)-coupling
partners
within
this
paradigm
can
provide
entry
to
novel,
medicinally-relevant
chemical
space.
Alkenes
are
abundant,
bench-stable
and
undergo
facile
C(sp3)-radical
reactivity
metal-hydride
hydrogen
atom
transfer
(MHAT),
yet
metallaphotoredox
methodologies
invoking
remain
underdeveloped.
Importantly,
the
merger
MHAT
activation
with
catalysis
could
enable
olefins
feedstock
radical
only
activated
photocatalysis,
such
as
alcohols.
Herein,
we
report
first
C(sp3)–C(sp3)
coupling
MHAT-activated
alkenes
alcohols
(i.e.
deoxygenative
hy-droalkylation)
triple
co-catalysis.
Through
synergistic
Ir
Mn
Ni
sorting
pathways,
branch-selective
protocol
pairs
diverse
methanol
or
primary
alcohols,
displays
remarkable
functional
group
tolerance,
enables
rapid
construction
complex
frameworks.
