Journal of the American Chemical Society,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 12, 2024
Enantioenriched
unnatural
amino
acids
represent
a
prevalent
motif
in
organic
chemistry,
with
profound
applications
biochemistry,
medicinal
and
materials
science.
Herein,
we
report
cobalt-catalyzed
aza-Barbier
reaction
of
dehydroglycines
unactivated
alkyl
halides
to
afford
α-amino
esters
high
enantioselectivity.
This
catalytic
reductive
alkylative
addition
protocol
circumvents
the
use
moisture-,
air-sensitive
organometallic
reagents,
stoichiometric
chiral
auxiliaries,
enabling
conversion
variety
primary,
secondary,
even
tertiary
α-alkyl-amino
under
mild
conditions,
thus
leading
broad
functional
group
tolerance.
The
expedient
access
biologically
active
motifs
demonstrates
practicality
this
by
reducing
number
synthetic
steps
enhancing
efficiency.
ACS Catalysis,
Год журнала:
2024,
Номер
14(6), С. 3812 - 3844
Опубликована: Фев. 23, 2024
Chiral
skeletons
with
multiple
stereogenic
centers
widely
reside
in
nature
and
drugs,
their
relative
absolute
configuration
often
determine
physiological
or
pharmacological
properties.
Stereodivergent
synthesis
of
chiral
molecules
is
not
only
great
significance,
but
also
highly
challenging
since
the
formation
one
diastereomers
inherently
preferred
most
asymmetric
reactions.
dual
catalysis,
introduced
2013
by
Carreira
group,
perfectly
catered
to
all
requirements
for
full
stereoselectivity
control
given
reactions
two
catalysts
are
utilized
a
synergistic
way
act
independently,
has
now
been
arguably
efficient
strategy
realize
stereodivergent
synthesis.
This
comprehensive
review
presents
an
overview
development
enabled
catalysis
past
ten
years,
providing
readers
fundamental
attributes
as
well
ability,
scope,
mechanism,
limitations
this
strategy.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(13), С. 9241 - 9251
Опубликована: Март 19, 2024
Much
attention
has
been
focused
on
the
catalytic
asymmetric
creation
of
single
chiral
centers
or
two
adjacent
stereocenters.
However,
construction
nonadjacent
stereocenters
is
significant
importance
but
challenging
because
lack
remote
induction
models.
Herein,
based
a
C═C
bond
relay
strategy,
we
report
synergistic
Pd/Cu-catalyzed
1,5-double
model.
All
four
stereoisomers
target
products
bearing
1,5-nonadjacent
involving
both
allenyl
axial
and
central
chirality
could
be
obtained
divergently
by
simply
changing
combination
catalysts
with
different
configurations.
Control
experiments
DFT
calculations
reveal
novel
mechanism
1,5-oxidative
addition,
contra-thermodynamic
η3-allyl
palladium
shift,
conjugate
nucleophilic
substitution,
which
play
crucial
roles
in
control
reactivity,
regio-,
enantio-,
diastereoselectivity.
It
expected
that
this
strategy
may
provide
general
protocol
for
synthesis
structural
motifs
distant
Angewandte Chemie International Edition,
Год журнала:
2023,
Номер
62(31)
Опубликована: Июнь 1, 2023
The
skeletons
of
chiral
tetrasubstituted
allenes
bearing
a
vicinal
all-carbon
quaternary
stereocenter
are
importance
but
still
challenging
to
synthesize.
Herein,
we
report
enantio-
and
diastereoselective
γ-additions
1-alkynyl
ketimines
with
dual-copper-catalysis
under
mild
conditions,
affording
α-amino
allenoates
in
high
yields
(up
99
%
yield)
excellent
enantioselectivities
ee)
diastereoselectivities
>20
:
1
dr).
Importantly,
the
stereodivergent
synthesis
products
was
realized
by
asymmetric
γ-addition
reaction
Grignard
reagent
promoted
epimerization.
Moreover,
dual-copper-catalyzed
reactions
were
smoothly
applied
gram-scale
adopted
introduce
allenyl
moieties
into
bioactive
molecules.
Mechanistic
experiments
density
functional
theory
(DFT)
calculations
demonstrated
that
catalyzed
double
copper
catalysts.
Angewandte Chemie International Edition,
Год журнала:
2023,
Номер
63(7)
Опубликована: Дек. 29, 2023
Abstract
An
atom‐
and
step‐economical
redox‐neutral
cascade
reaction
enabled
by
asymmetric
bimetallic
relay
catalysis
merging
a
ruthenium‐catalyzed
borrowing‐hydrogen
with
copper‐catalyzed
Michael
addition
has
been
realized.
A
variety
of
highly
functionalized
2‐amino‐5‐hydroxyvaleric
acid
esters
or
peptides
bearing
1,4‐non‐adjacent
stereogenic
centers
have
prepared
in
high
yields
excellent
enantio‐
diastereoselectivity.
Judicious
selection
rational
modification
the
Ru
catalysts
careful
tuning
conditions
played
pivotal
role
stereoselectivity
control
as
well
attenuating
undesired
α‐epimerization,
thus
enabling
full
complement
all
four
stereoisomers
that
were
otherwise
inaccessible
previous
work.
Concise
stereodivergent
synthesis
key
intermediates
for
biologically
important
chiral
molecules
further
showcases
synthetic
utility
this
methodology.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(21)
Опубликована: Март 21, 2024
Abstract
The
construction
of
two
distal
stereocenters
through
a
single
catalytic
process
is
great
interest
in
organic
synthesis.
While
there
are
some
successful
reports
regarding
stereodivergent
preparation
1,3‐
or
1,4‐stereocenters,
the
more
challenged
1,5‐nonadjacent
have
never
been
achieved
fashion.
Herein
we
describe
synergistic
palladium/copper
catalysis
for
1,4‐difunctionalization
reactions
1,3‐dienes,
providing
access
to
quaternary
stereocenters.
Because
each
catalysts
separately
controlled
one
newly
formed
stereocenters,
synthesis
all
four
diastereomers
products
could
readily
be
simply
by
choosing
an
appropriate
combination
chiral
catalysts.
Experimental
and
computational
studies
supported
mechanism
involving
Heck/Tsuji–Trost
cascade
reaction,
origins
stereoselectivity
were
elucidated.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(23)
Опубликована: Фев. 27, 2024
A
novel
enantioselective
Tsuji-Trost-type
cross
coupling
reaction
between
gem-difluorinated
cyclopropanes
and
N-unprotected
amino
acid
esters
enabled
by
synergistic
Pd/Ni/chiral
aldehyde
catalysis
is
presented
herein.
This
transformation
streamlined
the
diversity-oriented
synthesis
(DOS)
of
optically
active
α-quaternary
α-amino
bearing
a
linear
2-fluoroallylic
motif,
which
served
as
an
appealing
platform
for
construction
other
valuable
enantioenriched
compounds.
The
key
intermediates
were
confirmed
HRMS
detection,
while
DFT
calculations
revealed
that
excellent
enantioselectivity
was
attributed
to
stabilizing
non-covalent
interactions
Pd(II)-π-fluoroallyl
species
Ni(II)-Schiff
base
complex.
Abstract
Asymmetric
sequential
hydrogenations
of
α
‐methylene
γ
‐
or
δ
‐keto
carboxylic
acids
are
established
in
one‐pot
using
a
bimetallic
Ru/Ru
catalyst
system,
achieving
the
stereodivergent
synthesis
all
four
stereoisomers
both
chiral
and
‐lactones
with
two
non‐vicinal
carbon
stereocenters
high
yields
(up
to
99%)
excellent
stereoselectivities
>99%
ee
>20:1
dr).
The
compatibility
Ru
systems
is
investigated
detail,
it
found
that
basicity
reaction
system
plays
key
role
hydrogenation
processes.
protocol
can
be
performed
on
gram‐scale
low
loading
11000
S/C)
resulting
products
allow
for
many
transformations,
particularly
several
intermediates
useful
preparation
drugs
natural
products.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(35)
Опубликована: Май 16, 2024
Abstract
The
construction
of
chiral
motifs
containing
nonadjacent
stereocenters
in
an
enantio‐
and
diastereoselective
manner
has
long
been
a
challenging
task
synthetic
chemistry,
especially
with
respect
to
their
stereodivergent
synthesis.
Herein,
we
describe
protocol
that
enables
the
1,5/1,7‐nonadjacent
tetrasubstituted
through
Pd/Cu‐cocatalyzed
Heck
cascade
reaction.
Notably,
C=C
bond
relay
strategy
involving
shift
π‐allyl
palladium
intermediate
was
successfully
applied
asymmetric
1,7‐nonadjacent
stereocenters.
current
method
allows
for
efficient
preparation
molecules
bearing
two
privileged
scaffolds,
oxindoles
non‐natural
α‐amino
acids,
good
functional
group
tolerance.
full
complement
four
stereoisomers
products
could
be
readily
accessed
by
simple
combination
metal
catalysts
different
enantiomers.
