Accounts of Chemical Research,
Год журнала:
2023,
Номер
56(18), С. 2537 - 2554
Опубликована: Сен. 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,
Год журнала:
2023,
Номер
62(15)
Опубликована: Фев. 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,
Год журнала:
2022,
Номер
61(20)
Опубликована: Март 5, 2022
In
recent
years,
asymmetric
catalysis
of
ynamides
has
attracted
much
attention,
but
these
reactions
mostly
constructed
central
chirality,
except
for
a
few
examples
on
the
synthesis
axially
chiral
compounds
which
exclusively
relied
noble-metal
catalysis.
Herein,
facile
access
to
N-heterocycles
enabled
by
Brønsted
acid-catalyzed
5-endo-dig
cyclization
is
disclosed,
represents
first
metal-free
protocol
construction
from
ynamides.
This
method
allows
practical
and
atom-economical
valuable
N-arylindoles
in
excellent
yields
with
generally
enantioselectivities.
Moreover,
organocatalysts
ligands
based
such
N-arylindole
skeletons
are
demonstrated
be
applicable
Angewandte Chemie International Edition,
Год журнала:
2022,
Номер
61(44)
Опубликована: Сен. 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,
Год журнала:
2023,
Номер
56(18), С. 2537 - 2554
Опубликована: Сен. 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.