Science Advances,
Journal Year:
2024,
Volume and Issue:
10(19)
Published: May 10, 2024
Atropisomeric
indoles
defined
by
a
N─N
axis
are
an
important
class
of
heterocycles
in
synthetic
and
medicinal
chemistry
material
sciences.
However,
they
remain
heavily
underexplored
due
to
limited
methods
challenging
stereocontrol
over
the
short
bonds.
Here,
we
report
highly
atroposelective
access
axially
chiral
via
asymmetric
Larock
reaction.
This
protocol
leveraged
powerful
role
phosphoramidite
ligand
attenuate
common
dissociation
original
reaction,
forming
with
excellent
functional
group
tolerance
high
enantioselectivity
palladium-catalyzed
intermolecular
annulation
between
readily
available
o
-iodoaniline
alkynes.
The
multifunctionality
prepared
allowed
diverse
post-coupling
transformations,
affording
broad
array
functionalized
indoles.
Experimental
computational
studies
have
been
conducted
explore
reaction
mechanism,
elucidating
enantio-determining
rate-limiting
steps.
Angewandte Chemie International Edition,
Journal Year:
2023,
Volume and Issue:
62(15)
Published: Feb. 7, 2023
This
study
establishes
the
first
organocatalytic
enantioselective
synthesis
of
axially
chiral
N,N'-bisindoles
via
phosphoric
acid-catalyzed
formal
(3+2)
cycloadditions
indole-based
enaminones
as
novel
platform
molecules
with
2,3-diketoesters,
where
de
novo
indole-ring
formation
is
involved.
Using
this
new
strategy,
various
were
synthesized
in
good
yields
and
excellent
enantioselectivities
(up
to
87
%
yield
96
ee).
More
importantly,
class
exhibited
some
degree
cytotoxicity
toward
cancer
cells
was
derived
into
phosphine
ligands
high
catalytic
activity.
provides
a
strategy
for
using
asymmetric
organocatalysis
realize
applications
such
scaffolds
medicinal
chemistry
catalysis.
Angewandte Chemie International Edition,
Journal Year:
2022,
Volume and Issue:
61(44)
Published: Sept. 15, 2022
N-N
Atropisomers
are
a
common
motif
in
natural
products
and
represent
significant
dimension
for
exploration
modern
pharmaceutical
medicinal
chemistry.
However,
the
catalytic
atroposelective
synthesis
of
such
molecules
remains
challenging,
hampering
meaningful
development.
In
particular,
an
enantioselective
bisindole
atropisomers
is
unprecedented.
Herein,
first
via
palladium-catalyzed
de
novo
construction
one
indole
skeleton
presented.
A
wide
variety
axially
chiral
bisindoles
were
generated
good
yields
with
excellent
enantioselectivities
cascade
condensation/N-arylation
reaction.
Structurally
diverse
indole-pyrrole,
indole-carbazole,
non-biaryl-indole
possessing
axis
accessed
using
this
protocol.
Moreover,
investigations
density
functional
theory
(DFT)
calculations
provided
insight
into
reaction
mechanism
enantiocontrol.
Accounts of Chemical Research,
Journal Year:
2023,
Volume and Issue:
56(18), P. 2537 - 2554
Published: Sept. 11, 2023
ConspectusAtropisomers
bearing
a
rotation-restricted
axis
are
common
structural
units
in
natural
products,
chiral
ligands,
and
drugs;
thus,
the
prevalence
of
asymmetric
synthesis
has
increased
recent
decades.
Research
into
atropisomers
featuring
an
N-containing
(N-X
atropisomers)
remains
its
infancy
compared
with
well-developed
C-C
atropisomer
analogue.
Notably,
N-X
could
offer
divergent
scaffolds,
which
extremely
important
bioactive
molecules.
The
is
recognized
as
both
appealing
challenging.
Recently,
we
devoted
our
efforts
to
catalytic
atropisomers,
benzimidazole-aryl
N-C
indole-aryl
hydrogen-bond-assisted
pyrrole-pyrrole
N-N
pyrrole-indole
indole-indole
atropisomers.
To
obtain
Buchwald-Hartwig
reaction
amidines
or
enamines
was
employed.
Using
Pd(OAc)2/(S)-BINAP
Pd(OAc)2/(S)-Xyl-BINAP
catalyst
system,
were
readily
obtained.
address
issue
reduced
stability
diarylamine
axis,
six-membered
intramolecular
N-H-O
hydrogen
bond
introduced
scaffold.
A
tandem
N-arylation/oxidation
process
used
for
phosphoric
acid
(CPA)-catalyzed
N-aryl
quinone
For
copper-mediated
Friedel-Crafts
alkylation/arylation
developed.
desymmetrization
completed
successfully
via
Cu(OTf)2/chiral
bisoxazoline
(CuOTf)·Tol/bis(phosphine)
dioxide
thereby
achieving
first
N/N
bipyrrole
Asymmetric
amination
utilized
provide
bisindole
excellent
stereogenic
control.
This
scaffold
using
de
novo
indole
construction
strategy.
heterobiaryl
substantially
facilitated
palladium-catalyzed
transient
directing
group
(TDG)-mediated
C-H
functionalization.
Atropisomeric
alkenylation,
allylation,
alkynylation
accomplished
Pd(OAc)2/l-tert-leucine
system.
Herein,
summarize
work
on
palladium-,
copper-,
CPA-catalyzed
syntheses
Furthermore,
application
molecule
analogues
axially
ligands
demonstrated.
Subsequently,
briefly
discussed
terms
single
crystals
obtained
rotational
barriers.
Finally,
outlook
provided.
Angewandte Chemie International Edition,
Journal Year:
2023,
Volume and Issue:
62(37)
Published: May 4, 2023
Abstract
Enantioselective
synthesis
of
N−N
biaryl
atropisomers
is
an
emerging
area
but
remains
underexplored.
The
development
efficient
in
great
demand.
Herein,
the
construction
through
iridium‐catalyzed
asymmetric
C−H
alkylation
reported
for
first
time.
In
presence
readily
available
Ir
precursor
and
Xyl‐BINAP,
a
variety
axially
chiral
molecules
based
on
indole‐pyrrole
skeleton
were
obtained
good
yields
(up
to
98
%)
with
excellent
enantioselectivity
99
%
ee).
addition,
bispyrrole
could
also
be
synthesized
enantioselectivity.
This
method
features
perfect
atom
economy,
wide
substrate
scope,
multifunctionalized
products
allowing
diverse
transformations.
Angewandte Chemie International Edition,
Journal Year:
2023,
Volume and Issue:
62(21)
Published: March 21, 2023
The
catalytic
asymmetric
construction
of
N-N
atropisomeric
biaryls
remains
a
formidable
challenge.
Studies
them
lag
far
behind
studies
the
more
classical
carbon-carbon
biaryl
atropisomers,
hampering
meaningful
development.
Herein,
first
palladium-catalyzed
enantioselective
C-H
activation
pyrroles
for
synthesis
atropisomers
is
presented.
Structurally
diverse
indole-pyrrole
possessing
chiral
axis
were
produced
with
good
yields
and
high
enantioselectivities
by
alkenylation,
alkynylation,
allylation,
or
arylation
reactions.
Furthermore,
kinetic
resolution
trisubstituted
heterobiaryls
sterically
demanding
substituents
was
also
achieved.
Importantly,
this
versatile
functionalization
strategy
enables
iterative
exquisite
selectivity,
expediting
formation
valuable,
complex,
atropisomers.
Nature Communications,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: Aug. 29, 2023
The
N-N
atropisomer,
as
an
important
and
intriguing
chiral
system,
was
widely
present
in
natural
products,
pharmaceutical
lead
compounds,
advanced
material
skeletons.
anisotropic
structural
characteristics
caused
by
its
special
axial
rotation
have
always
been
one
of
the
challenges
that
chemists
strive
to
overcome.
Herein,
we
report
efficient
method
for
enantioselective
synthesis
axially
frameworks
via
a
cobalt-catalyzed
atroposelective
C-H
activation/annulation
process.
reaction
proceeds
under
mild
conditions
using
Co(OAc)2·4H2O
catalyst
with
salicyl-oxazoline
(Salox)
ligand
O2
oxidant,
affording
variety
products
high
yields
enantioselectivities.
This
protocol
provides
approach
facile
construction
atropisomers
further
expands
range
derivatives.
Additionally,
electrocatalysis,
desired
were
also
successfully
achieved
good
excellent
efficiencies
Angewandte Chemie International Edition,
Journal Year:
2023,
Volume and Issue:
62(14)
Published: Feb. 10, 2023
Axially
chiral
diaryl
ethers
are
a
type
of
unique
atropisomers
bearing
two
potential
axes,
which
have
applications
in
variety
research
fields.
However,
the
catalytic
enantioselective
synthesis
these
ether
is
largely
underexplored
when
compared
to
asymmetric
biaryl
or
other
types
atropisomers.
Herein,
we
report
highly
efficient
through
an
organocatalyzed
desymmetrization
protocol.
The
phosphoric
acid-catalyzed
electrophilic
aromatic
aminations
symmetrical
1,3-benzenediamine
substrates
afforded
series
excellent
yields
and
enantioselectivities.
facile
construction
heterocycles
by
utilizations
1,2-benzenediamine
moiety
products
provided
access
structurally
diverse
novel
azaarene-containing
Angewandte Chemie International Edition,
Journal Year:
2023,
Volume and Issue:
62(31)
Published: April 25, 2023
Axially
chiral
compounds
have
been
always
considered
a
laboratory
curiosity
with
rare
prospects
of
being
applied
in
asymmetric
synthesis.
Things
changed
very
quickly
the
last
twenty
years
when
it
was
understood
important
role
and
enormous
impact
that
these
medicinal,
biological
material
chemistry.
The
synthesis
atropisomers
became
rapidly
expanding
field
recent
reports
on
development
N-N
strongly
prove
how
this
research
is
hot
topic
open
to
new
challenges
frontiers
This
review
focuses
advances
enantioselective
highlighting
strategies
breakthroughs
obtain
novel
stimulating
atropisomeric
framework.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Jan. 15, 2024
Abstract
The
construction
of
N–N
axially
chiral
motifs
is
an
important
research
topic,
owing
to
their
wide
occurrence
in
natural
products,
pharmaceuticals
and
ligands.
One
efficient
method
the
atroposelective
dihydropyrimidin-4-one
formation.
We
present
herein
a
direct
catalytic
synthesis
atropisomers
with
simultaneous
creation
contiguous
axial
central
chirality
by
oxidative
NHC
(
N
-heterocyclic
carbenes)
catalyzed
(3
+
3)
cycloaddition.
Using
our
method,
we
are
able
synthesize
structurally
diverse
pyrroles
indoles
vicinal
or
bearing
2,3-dihydropyrimidin-4-one
moiety
moderate
good
yields
excellent
enantioselectivities.
Further
synthetic
transformations
obtained
derivative
products
demonstrated.
reaction
mechanism
origin
enantioselectivity
understood
through
DFT
calculations.