Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
unknown
Published: June 8, 2024
Abstract
Cross‐electrophile
coupling
(XEC)
between
aryl
halides
and
alkyl
is
a
streamlined
approach
for
C(sp
2
)−C(sp
3
)
bond
construction,
which
highly
valuable
in
medicinal
chemistry.
Based
on
key
Ni
II
amido
intermediate,
we
developed
selective
scalable
Ni‐catalyzed
electrochemical
XEC
reaction
(hetero)aryl
primary
secondary
halides.
Experimental
computational
mechanistic
studies
indicate
that
an
amine
ligand
slows
down
the
oxidative
addition
process
of
Ni‐polypyridine
catalyst
to
bromide
intermediate
formed
situ
during
process.
The
relatively
slow
beneficial
enhancing
selectivity
reaction.
stabilizes
–aryl
species
prevent
aryl–aryl
homo‐coupling
side
reactions
acts
as
activate
substrates.
This
electrosynthesis
system
provides
facile,
practical,
platform
formation
(hetero)aryl–alkyl
bonds
using
standard
catalysts
under
mild
conditions.
insights
from
this
work
could
serve
great
foundation
future
cross‐couplings.
Journal of the American Chemical Society,
Journal Year:
2023,
Volume and Issue:
145(11), P. 6270 - 6279
Published: March 7, 2023
An
electrochemically
driven
nickel-catalyzed
enantioselective
reductive
cross-coupling
of
aryl
aziridines
with
alkenyl
bromides
has
been
developed,
affording
enantioenriched
β-aryl
homoallylic
amines
excellent
E-selectivity.
This
electroreductive
strategy
proceeds
in
the
absence
heterogeneous
metal
reductants
and
sacrificial
anodes
by
employing
constant
current
electrolysis
an
undivided
cell
triethylamine
as
a
terminal
reductant.
The
reaction
features
mild
conditions,
remarkable
stereocontrol,
broad
substrate
scope,
functional
group
compatibility,
which
was
illustrated
late-stage
functionalization
bioactive
molecules.
Mechanistic
studies
indicate
that
this
transformation
conforms
stereoconvergent
mechanism
aziridine
is
activated
through
nucleophilic
halide
ring-opening
process.
Angewandte Chemie International Edition,
Journal Year:
2023,
Volume and Issue:
62(45)
Published: June 16, 2023
Abstract
Electrochemistry
utilizes
electrons
as
a
potent,
controllable,
and
traceless
alternative
to
chemical
oxidants
or
reductants,
typically
offers
more
sustainable
option
for
achieving
selective
organic
synthesis.
Recently,
the
merger
of
electrochemistry
with
readily
available
electrophiles
has
been
recognized
viable
increasingly
popular
methodology
efficiently
constructing
challenging
C−C
C‐heteroatom
bonds
in
manner
complex
molecules.
In
this
mini‐review,
we
have
systematically
summarized
most
recent
advances
electroreductive
cross‐electrophile
coupling
(eXEC)
reactions
during
last
decade.
Our
focus
on
electrophiles,
including
aryl
alkyl
(pseudo)halides,
well
small
molecules
such
CO
2
,
SO
D
O.
Chemical Society Reviews,
Journal Year:
2023,
Volume and Issue:
52(23), P. 8106 - 8125
Published: Jan. 1, 2023
This
tutorial
review
delves
into
the
unique
advantages
of
electrochemistry
in
context
asymmetric
catalysis,
first
providing
a
brief
introduction
to
electrosynthesis,
then
exploring
representative
case
studies
with
mechanistic
focus.
Angewandte Chemie International Edition,
Journal Year:
2023,
Volume and Issue:
62(45)
Published: Sept. 12, 2023
Despite
widespread
use
of
the
deuterium
isotope
effect,
selective
labeling
chemical
molecules
remains
a
major
challenge.
Herein,
facile
and
general
electrochemically
driven,
organic
mediator
enabled
deuteration
styrenes
with
oxide
(D2
O)
as
economical
source
was
reported.
Importantly,
this
transformation
could
be
suitable
for
various
electron
rich
mediated
by
triphenylphosphine
(TPP).
The
reaction
proceeded
under
mild
conditions
without
transition-metal
catalysts,
affording
desired
products
in
good
yields
excellent
D-incorporation
(D-inc,
up
to
>99
%).
Mechanistic
investigations
means
experiments
cyclic
voltammetry
tests
provided
sufficient
support
transformation.
Notably,
method
proved
powerful
tool
late-stage
biorelevant
compounds.
Organic Process Research & Development,
Journal Year:
2024,
Volume and Issue:
28(2), P. 338 - 366
Published: Jan. 18, 2024
This
review
summarizes
examples
of
organic
electrosynthesis
from
the
peer-reviewed
literature
2000
to
2023
that
have
been
conducted
on
scales
20
g
or
above.
A
significant
portion
these
were
a
≤100
scale,
while
detailed
reports
kilogram-scale
remain
scarce
in
pharmaceutical
industry.
In
addition
chemical
transformation,
this
also
highlights
type
reactor
used
and
projected
productivity
metric
as
ways
compare
different
reports.
The
selected
scale-ups
described
herein
illustrate
remaining
challenges
currently
preventing
routine
use
large-scale
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(5), P. 3043 - 3051
Published: Jan. 26, 2024
Cross-electrophile
coupling
has
emerged
as
an
attractive
and
efficient
method
for
the
synthesis
of
C(sp2)–C(sp3)
bonds.
These
reactions
are
most
often
catalyzed
by
nickel
complexes
nitrogenous
ligands,
especially
2,2′-bipyridines.
Precise
prediction,
selection,
design
optimal
ligands
remains
challenging,
despite
significant
increases
in
reaction
scope
mechanistic
understanding.
Molecular
parameterization
statistical
modeling
provide
a
path
to
development
improved
bipyridine
that
will
enhance
selectivity
existing
broaden
electrophiles
can
be
coupled.
Herein,
we
describe
generation
computational
ligand
library,
correlation
observed
outcomes
with
features
silico
Ni-catalyzed
cross-electrophile
coupling.
The
new
nitrogen-substituted
display
5-fold
increase
product
formation
versus
homodimerization
when
compared
current
state
art.
This
yield
was
general
several
couplings,
including
challenging
aryl
chloride
N-alkylpyridinium
salt.
Organic Process Research & Development,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 7, 2025
A
scalable
electrochemical
process
to
synthesize
iminophosphorane
ligands
is
reported.
The
application
of
these
iminophosphoranes
was
recently
reported
in
Ni-catalyzed
cross-electrophile
and
C–N
cross-couplings.
use
parallel
plate
flow
reactors
enables
the
synthesis
on
a
multigram
scale,
with
selected
examples
up
0.6
kg
scale.
Direct
crystallization
from
end
reaction
mixture
for
provides
facile
isolation
processes.
This
article
also
details
improvements
our
capabilities
across
scales,
including
addressing
material
compatibility
issues,
increasing
accessible
range
rates,
integration
analytical
technology
tools.
Journal of the American Chemical Society,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 14, 2025
Ni-catalyzed
asymmetric
reductive
cross-coupling
reactions
provide
rapid
and
modular
access
to
enantioenriched
building
blocks
from
simple
electrophile
precursors.
Reductive
coupling
that
can
diverge
through
a
common
organometallic
intermediate
two
distinct
families
of
products
are
particularly
versatile
but
underdeveloped.
Here,
we
describe
the
development
bis(oxazoline)
ligand
enables
desymmetrization
meso-anhydrides.
When
secondary
benzylic
electrophiles
employed,
doubly
stereoselective
acyl
proceeds
give
ketone
with
catalyst
control
over
three
newly
formed
stereogenic
centers.
Alternatively,
use
primary
alkyl
halides
in
presence
an
additional
halogen
atom
transfer
results
decarbonylative
alkylation
β-alkyl
acids.
Analysis
reaction
rates
for
range
both
catalysts
substrates
supports
notion
tuning
different
activation
steps
is
required
enhanced
performance.
These
studies
illustrate
how
design
Ni-acyl
either
or
highlight
dual
systems
be
used
engage
unactivated
coupling.
