Organic Letters,
Год журнала:
2023,
Номер
25(38), С. 6964 - 6968
Опубликована: Сен. 14, 2023
A
nickel-catalyzed
asymmetric
decarboxyarylation
of
NHP
esters
via
reductive
cross-coupling
has
been
established.
Utilizing
the
amino
acid
as
radical
precursors
furnishes
a
new
protocol
in
which
structurally
diverse
chiral
benzylamines
could
be
accessible.
This
method
demonstrated
excellent
catalytic
efficiency,
high
enantioselective
control,
mild
conditions,
and
good
functional
group
tolerance,
thus
enabling
late-stage
modification
bioactive
molecules
pharmaceuticals.
Angewandte Chemie,
Год журнала:
2024,
Номер
136(25)
Опубликована: Янв. 22, 2024
Abstract
β‐Tertiary
amino
acid
derivatives
constitute
one
of
the
most
frequently
occurring
units
in
natural
products
and
bioactive
molecules.
However,
efficient
asymmetric
synthesis
this
motif
still
remains
a
significant
challenge.
Herein,
we
disclose
cobalt‐catalyzed
enantioselective
reductive
addition
reaction
ketimine
using
α‐chloro
carbonyl
compound
as
radical
precursor,
providing
expedient
access
to
diverse
array
enantioenriched
β‐quaternary
analogues.
This
protocol
exhibits
outstanding
enantioselectivity
broad
substrate
scope
with
excellent
functional
group
tolerance.
Preliminary
mechanism
studies
rule
out
possibility
Reformatsky‐type
confirm
involvement
species
stereoselective
process.
The
synthetic
utility
has
been
demonstrated
through
rapid
assembly
iterative
oligopeptide,
showcasing
its
versatile
platform
for
late‐stage
modification
drug
candidates.
Chiral
alpha-amino
ketones
have
found
extensive
applications
as
functional
molecules.
A
nickel-catalyzed,
enantioselective,
and
fully
intermolecular
three-component
1,2-alkylacylation
of
N-acyl
enamides
has
been
realized
with
tertiary
alkyl
bromides
carboxylic
acid-derived
electrophiles
the
coupling
reagents.
This
reductive
strategy
is
operationally
simple,
exhibiting
broad
substrate
scope
excellent
group
tolerance
using
readily
available
starting
materials
allowing
rapid
access
to
structurally
complex
α-amino
ketone
derivatives
in
high
enantioselectivity.
suitable
chiral
biimidazoline
ligand
together
additional
chelation
amide
carbonyl
a
Ni
intermediate
facilitates
enantioselective
control
by
suppressing
background
reaction,
accounting
for
Mechanistic
studies
indicated
intermediacy
radical
species.
Organic Chemistry Frontiers,
Год журнала:
2024,
Номер
11(22), С. 6311 - 6318
Опубликована: Янв. 1, 2024
Co-catalyzed
asymmetric
reductive
addition
of
ketimine
with
cyclopropyl
chloride
has
been
realized
to
access
diverse
chiral
amino
esters
bearing
fragments
broad
functional
group
tolerance
and
excellent
enantioselectivities.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 19, 2024
The
development
of
effective
synthetic
methods
to
construct
γ-lactams
bearing
a
chiral
α-quaternary
carbon
from
relatively
inert
C(O)–H
bonds
with
alkenes
has
been
an
elusive
challenge.
Herein,
we
used
naphthylamine-derived
phosphine
oxide
ligating
Ni
and
Al
bimetallic
catalyst
realize
carbonylative
cyclization
formyl
C–H
alkenes,
highly
regio-
enantioselectively
constructing
in
up
99%
yield
98%
ee.
These
proved
be
versatile
precursors
for
many
biologically
active
molecules.
Organic Letters,
Год журнала:
2023,
Номер
25(38), С. 6964 - 6968
Опубликована: Сен. 14, 2023
A
nickel-catalyzed
asymmetric
decarboxyarylation
of
NHP
esters
via
reductive
cross-coupling
has
been
established.
Utilizing
the
amino
acid
as
radical
precursors
furnishes
a
new
protocol
in
which
structurally
diverse
chiral
benzylamines
could
be
accessible.
This
method
demonstrated
excellent
catalytic
efficiency,
high
enantioselective
control,
mild
conditions,
and
good
functional
group
tolerance,
thus
enabling
late-stage
modification
bioactive
molecules
pharmaceuticals.
