A
Pd-catalyzed
asymmetric
Heck
cascade
reaction
involving
the
intramolecular
carbopalladation
of
unsaturated
hydrocarbons,
followed
by
nucleophilic
trapping
resulting
palladium
species,
is
a
powerful
approach
for
constructing
chiral
N-heterocycles.
However,
use
prochiral
nucleophiles
in
these
reactions
remains
significantly
underexplored.
Herein,
we
report
novel
Pd/Cu
catalytic
system
Heck/Tsuji–Trost
allenamides
and
aldimine
esters.
This
robust
method
allows
rapid
synthesis
wide
range
enantiopure
non-natural
α-substituted
tryptophans
high
yields
(up
to
99%
yield)
with
excellent
enantioselectivities
98%
ee).
Additionally,
synthetic
utility
this
protocol
demonstrated
through
scale-up
experiments
diverse
valuable
transformations.
The
stereodivergent
synthesis
of
δ-lactones,
which
are
prevalent
in
natural
product
frameworks,
from
simple
starting
materials
via
a
single
transformation
remains
significant
challenge.
Herein,
we
report
an
enantio-
and
diastereodivergent
cascade
reaction
for
the
modular
chiral
δ-lactones
bearing
two
nonadjacent
quaternary
tertiary
carbon
stereocenters.
This
approach
employs
bimetallic
Ru/Cu
relay
catalysis
between
allylic
alcohols
azaaryl
acetates.
method
integrates
Ru-catalyzed
asymmetric
borrowing
hydrogen
reaction,
Cu-catalyzed
Michael
addition,
rapid
lactonization
into
one-pot
process,
with
all
catalysts
substrates
introduced
at
outset.
By
orthogonal
permutation
metal
catalysts,
precise
control
over
relative
absolute
configurations
newly
formed
stereocenters
is
achieved,
allowing
selective
access
to
stereoisomers
δ-lactone
products
predictable
efficient
manner.
Bulletin of the Korean Chemical Society,
Год журнала:
2025,
Номер
unknown
Опубликована: Июнь 4, 2025
Abstract
The
catalytic
synthesis
of
chiral
azaarenes
has
become
a
focal
point
research
due
to
their
signifi`1cant
applications
across
various
fields,
including
medicinal
chemistry
and
materials
science.
α‐Azaaryl
carbonyl
compounds,
featuring
both
an
electron‐withdrawing
C=N
moiety
within
azaarene
core
functional
group,
have
proven
be
versatile
precursors
in
the
stereochemically
intricate
azaaryl
molecules.
In
particular,
generation
α‐azaaryl
enolate
intermediates,
catalyzed
by
Lewis
acids,
enabled
precise
construction
α‐stereogenic
azaarenes.
This
review
explores
recent
advances
stereodivergent
transformations
derivatives
with
array
carbon
electrophiles,
emphasizing
efficiency
systems
involving
copper
acids
combined
Ir,
Pd,
Ni,
amine,
or
Ru
catalysts.
These
strategies
offer
control
over
stereochemical
outcome,
facilitating
access
all
stereoisomers
multi‐stereogenic
Additionally,
we
discuss
sequence‐dependent
approach
that
allows
for
controlled
stereodivergence
reactions
derivatives.
Through
detailed
exploration
advancements,
mechanistic
insights,
practical
applications,
this
underscores
potential
unlock
new
avenues
compounds.
By
presenting
diverse
expanding
opportunities
controlling
stereochemistry,
it
fosters
further
development
design
structurally
complex
azaarene‐based
frameworks.
Journal of the American Chemical Society,
Год журнала:
2025,
Номер
unknown
Опубликована: Июнь 5, 2025
Olefins
are
fundamental
functional
groups
present
in
numerous
molecules,
and
the
geometrical
configuration
of
C═C
bonds
often
plays
a
critical
role
determining
properties
these
compounds.
Alkenyl
isomerization
is,
principle,
one
most
efficient
approaches
for
accessing
stereodefined
olefins.
While
some
progress
has
been
made
achieving
unidirectional
Z
→
E
or
conversion
via
olefin
isomerization,
there
remains
strong
demand
controllable,
bidirectional
bonds.
Herein,
we
method
Z/E
mutual
alkenyl
by
using
Pd/Cu
catalytic
system.
This
process
involves
Pd-mediated
π-σ-π
interconversion
followed
selective
trapping
π-allyl-Pd
intermediates
with
N-metalated
azomethine
ylides
generated
chiral
Cu-catalyst.
The
reaction
enables
synthesis
non-natural
amino
acid
derivatives
bearing
Z-
E-alkenyl
an
enantio-
Z/E-divergent
manner,
yields
up
to
92%,
>
20:1
E/Z,
>99%
ee.
Furthermore,
is
scalable
gram
quantities,
resulting
products
can
be
transformed
into
valuable
molecules
adorned
groups.
Computational
studies
show
that
bimetallic
system
better
distinguishes
among
eight
stereoisomers
than
monometallic
system,
which
results
exceptional
Z/E-selectivity
products.
offers
robust
protocol
synthesizing
E-trisubstituted
olefins
motif
utilizing
readily
available
Z/E-mixture
substrates.
Advanced Science,
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 25, 2024
The
development
of
efficient
methodologies
for
the
controlled
manufacture
specific
stereoisomers
bearing
quaternary
stereocenters
has
prompted
advances
in
a
variety
scientific
disciplines
including
pharmaceutical
chemistry,
materials
science,
and
chemical
biology.
However,
complete
control
absolute
relative
stereochemical
configurations
alkyne
derivatives
remains
an
unmet
synthetic
challenge.
Herein,
Ni/Cu
dual-catalyzed
asymmetric
propargylic
substitution
reaction
is
presented
to
produce
propargylated
products
with
all-carbon
high
yields
significant
diastereo-
enantioselectivities
(up
>20:1
dr,
>99%
ee).
synthesis
all
variants
methohexital,
widely
used
sedative-hypnotic
drug,
exemplifies
efficacy
stereodivergent
propargylation.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 2, 2024
Understanding
the
nature
of
a
transition-metal-catalyzed
process,
including
catalyst
evolution
and
real
active
species,
is
rather
challenging
yet
great
importance
for
rational
design
development
novel
catalysts,
this
even
more
difficult
bimetallic
catalytic
system.
Pd(0)/carboxylic
acid
combined
system-catalyzed
allylic
alkylation
reaction
alkynes
has
been
used
as
an
atom-economical
protocol
synthesis
products.
However,
asymmetric
version
still
limited,
in-depth
understanding
Pd
species
elusive.
Herein
we
report
enantioselective
coupling
between
readily
available
aldimine
esters
using
synergistic
Cu/Pd
system,
affording
diverse
set
α-quaternary
allyl
amino
ester
derivatives
in
good
yields
with
excellent
enantioselectivities.
Mechanistic
studies
indicated
that
it
most
likely
molecular
Cu
catalysis
nanoparticle
catalysis.
The
precursor
transformed
to
soluble
nanoparticles
Organic Letters,
Год журнала:
2024,
Номер
26(44), С. 9598 - 9603
Опубликована: Окт. 28, 2024
A
photoinduced
three-component
radical
addition-aminalization
cascade
was
accomplished,
enabling
rapid
assembly
of
a
wide
range
densely
functionalized
γ-lactams.
Key
to
this
transformation
is
the
electron-donor-acceptor
(EDA)
generation
enamine
and
in
situ
trapping
an
iminium
intermediate
with
bromodifluoroacetamide.
This
rationally
designed
protocol
fully
takes
advantage
polarity
crossover
(enamine-iminium)
process,
providing
modular
previously
inaccessible
scaffolds.
The
reaction
proceeds
under
mild
conditions
excellent
regio-
diastereoselectivity,
which
amenable
structurally
varied
substrates
pharmaceuticals.
