European Journal of Organic Chemistry,
Год журнала:
2023,
Номер
27(3)
Опубликована: Ноя. 28, 2023
Abstract
A
visible
light
photoreductive
dearomatizative
alkylation
of
N
‐alkyl
pyridinium
salts
for
producing
4‐alkyl‐1,4‐dihydropyridines
is
described.
The
reaction
harnesses
both
as
the
alkyl
radical
precursors
to
initiate
and
1,4‐dihydropyridin‐4‐yl‐based
alkylating
reagents
terminate
reaction.
In
contrast
reported
electroreductive
procedure
via
key
dihydropyridine
intermediates,
mechanistic
studies
demonstrate
that
this
proceeds
directly
addition
across
ring
followed
by
single
electron
oxidant
(SEO)
dearomatization.
Organic Process Research & Development,
Год журнала:
2024,
Номер
28(2), С. 338 - 366
Опубликована: Янв. 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,
Год журнала:
2024,
Номер
146(5), С. 3043 - 3051
Опубликована: Янв. 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.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(10), С. 6947 - 6954
Опубликована: Март 1, 2024
Although
screening
technology
has
heavily
impacted
the
fields
of
metal
catalysis
and
drug
discovery,
its
application
to
discovery
new
catalyst
classes
been
limited.
The
diversity
on-
off-cycle
pathways,
combined
with
incomplete
mechanistic
understanding,
means
that
screens
potential
ligands
have
thus
far
guided
by
intuitive
analysis
binding
potential.
This
resulted
in
ligands,
but
low
hit
rates
limited
use
this
strategy
because
large
require
considerable
cost
effort.
Here,
we
demonstrate
a
method
identify
promising
directions
via
simple
scalable
computational
linear
regression
tools
leads
substantial
improvement
rate,
enabling
smaller
find
ligands.
approach
particular
example
Ni-catalyzed
cross-electrophile
coupling
aryl
halides
alkyl
revealed
previously
overlooked
trend:
reactions
more
electron-poor
amidine
result
higher
yield.
Focused
utilizing
trend
were
successful
than
serendipity-based
led
two
types
pyridyl
oxadiazoles
oximes.
These
are
especially
effective
for
couplings
bromo-
chloroquinolines
isoquinolines,
where
they
now
state
art.
simplicity
these
models
parameters
derived
from
metal-free
ligand
structures
should
make
widely
accessible.
Beilstein Journal of Organic Chemistry,
Год журнала:
2024,
Номер
20, С. 2500 - 2566
Опубликована: Окт. 9, 2024
With
the
resurgence
of
electrosynthesis
in
organic
chemistry,
there
is
a
significant
increase
number
routes
available
for
late-stage
functionalization
(LSF)
drugs.
Electrosynthetic
methods,
which
obviate
need
hazardous
chemical
oxidants
or
reductants,
offer
unprecedented
control
reactions
through
continuous
variation
applied
potential
and
possibility
combination
with
photochemical
processes.
This
capability
substantial
advantage
performing
electrochemical
photoelectrochemical
LSF.
Ultimately,
these
protocols
are
poised
to
become
vital
component
medicinal
chemist's
toolkit.
In
this
review,
we
discuss
that
have
been
demonstrated
be
applicable
LSF
pharmaceutical
drugs,
their
derivatives,
natural
substrates.
We
present
analyze
representative
examples
illustrate
electrochemistry
photoelectrochemistry
valuable
molecular
scaffolds.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
64(1)
Опубликована: Окт. 9, 2024
Abstract
Etherification
and
amination
of
aryl
halide
scaffolds
are
commonly
used
reactions
in
parallel
medicinal
chemistry
to
rapidly
scan
structure–activity
relationships
with
abundant
building
blocks.
Electrochemical
methods
for
etherification
demonstrate
broad
functional
group
tolerance
extended
nucleophile
scope
compared
traditional
methods.
Nevertheless,
there
is
a
need
robust
scale‐transferable
workflows
electrochemical
compound
library
synthesis.
Herein
we
describe
platform
automated
synthesis
C−X
arylation
(X=NH,
OH)
flow
access
libraries.
A
comprehensive
Design
Experiment
(DoE)
study
identifies
an
optimal
protocol
which
generates
high
yields
across>30
scaffolds,
diverse
amines
(including
electron‐deficient
sulfonamides,
sulfoximines,
amides,
anilines)
alcohols
serine
residues
within
peptides).
Reaction
sequences
on
commercially
available
equipment
generate
libraries
anilines
ethers.
The
unprecedented
application
potentiostatic
alternating
polarity
essential
avoid
accumulating
electrode
passivation.
Moreover,
it
enables
be
performed
air,
without
supporting
electrolyte
reproducibility
over
consecutive
runs.
Our
method
represents
powerful
means
independent
using
electrochemistry.
Chemical Communications,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 1, 2025
This
review
summarizes
recent
advancements
in
radical-mediated
deaminative
transformations,
focusing
on
the
mechanisms,
substrate
compatibility,
and
emerging
applications
synthetic
organic
chemistry.
Organic Chemistry Frontiers,
Год журнала:
2023,
Номер
11(2), С. 477 - 483
Опубликована: Дек. 1, 2023
An
environmentally
benign
electrochemical
approach
has
been
developed
for
the
construction
of
β-sulfonylated
BODIPYs
by
using
sulfonylhydrazide
as
sulfonyl
source.
