ACS Catalysis,
Год журнала:
2023,
Номер
13(24), С. 16195 - 16206
Опубликована: Дек. 5, 2023
Synthesis
of
α-branched
aryl
amines
is
a
continuing
challenge
in
synthetic
and
medicinal
chemistry.
Although
transition-metal-promoted
C–N
cross-coupling
desirable
approach
to
the
synthesis
amines,
there
are
limited
examples
methods
that
demonstrate
broad
generality
applicability
using
structurally
complex
substrates.
Herein,
we
report
method
cross-couple
halides
promoted
by
Cu
an
oxamate
ligand
system.
The
compatible
with
many
druglike
can
be
executed
miniaturized
high-throughput
experimentation
(HTE)
techniques
enable
rapid
production
high-quality,
consistent
data
sets.
In
addition
exploring
substrate
scope
executing
late-stage
library
active
pharmaceutical,
used
HTE
interrogate
performance
ligands
across
multiple
combinations
parallel
at
time
points.
were
build
statistical
models
provided
insight
as
what
features
important
for
function,
which
further
enabled
design
improved
reaction
performance.
Data
science
is
assuming
a
pivotal
role
in
guiding
reaction
optimization
and
streamlining
experimental
workloads
the
evolving
landscape
of
synthetic
chemistry.
A
discipline-wide
goal
development
workflows
that
integrate
computational
chemistry
data
tools
with
high-throughput
experimentation
as
it
provides
experimentalists
ability
to
maximize
success
expensive
campaigns.
Here,
we
report
an
end-to-end
data-driven
process
effectively
predict
how
structural
features
coupling
partners
ligands
affect
Cu-catalyzed
C–N
reactions.
The
established
workflow
underscores
limitations
posed
by
substrates
while
also
providing
systematic
ligand
prediction
tool
uses
probability
assess
when
will
be
successful.
This
platform
strategically
designed
confront
intrinsic
unpredictability
frequently
encountered
deployment.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(19)
Опубликована: Фев. 15, 2024
Abstract
We
disclose
the
development
of
a
Cu‐catalyzed
C−O
coupling
method
utilizing
new
N
1
,
2
‐diarylbenzene‐1,2‐diamine
ligand,
L8
.
Under
optimized
reaction
conditions,
structurally
diverse
aryl
and
heteroaryl
bromides
underwent
efficient
with
variety
alcohols
at
room
temperature
using
an
‐based
catalyst.
Notably,
‐derived
catalyst
exhibited
enhanced
activity
when
compared
to
L4
system
previously
disclosed
for
C−N
coupling,
namely
ability
functionalize
containing
acidic
functional
groups.
Mechanistic
studies
demonstrate
that
⋅
Cu
involves
rate‐limiting
alkoxide
transmetallation,
resulting
in
mechanism
bond
formation
is
distinct
from
described
Pd‐,
Cu‐,
or
Ni‐based
systems.
This
lower
energy
pathway
leads
rapid
formation;
7‐fold
increase
relative
what
seen
other
ligands.
The
results
presented
this
report
overcome
limitations
methods
introduce
ligand
we
anticipate
may
be
useful
C‐heteroatom
bond‐forming
reactions.
Science,
Год журнала:
2023,
Номер
381(6662), С. 1079 - 1085
Опубликована: Сен. 7, 2023
Copper
complexes
are
widely
used
in
the
synthesis
of
fine
chemicals
and
materials
to
catalyze
couplings
heteroatom
nucleophiles
with
aryl
halides.
We
show
that
cross-couplings
catalyzed
by
some
most
active
catalysts
occur
a
mechanism
not
previously
considered.
Copper(II)
[Cu(II)]
oxalamide
ligands
Ullmann
coupling
form
C–O
bond
ethers
concerted
oxidative
addition
an
halide
Cu(II)
high-valent
species
is
stabilized
radical
character
on
ligand.
This
diverges
from
those
involving
Cu(I)
Cu(III)
intermediates
have
been
posited
for
other
Ullmann-type
couplings.
The
stability
state
leads
high
turnover
numbers,
>1000
phenoxide
chloride
electrophiles,
as
well
ability
run
reactions
air.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(27), С. 18616 - 18625
Опубликована: Июнь 26, 2024
We
report
a
general
and
functional-group-tolerant
method
for
the
Cu-catalyzed
amination
of
base-sensitive
aryl
bromides
including
substrates
possessing
acidic
functional
groups
small
five-membered
heteroarenes.
The
results
presented
herein
substantially
expand
scope
C–N
coupling
reactions.
combination
L8,
an
anionic
N1,N2-diarylbenzene-1,2-diamine
ligand,
along
with
mild
base
NaOTMS
leads
to
formation
stable
yet
reactive
catalyst
that
resists
deactivation
from
coordination
heterocycles
or
charged
intermediates.
This
system
enables
use
low
ligand
loadings.
Exploiting
differences
in
nucleophile
deprotonation
C–O
reactions
catalyzed
by
Cu·L8
we
developed
chemoselectively
N-
O-arylate
variety
amino
alcohol
substrates.
Employing
NaOt-Bu
as
resulted
exclusively
when
alcohols
featured
primary
more
hindered
amines
aniline
groups.
Utilizing
enabled
ability
override
steric-based
selectivity
these
completely
promoted
regardless
structure
alcohol.
invert
observed
chemoselectivity
is
distinct
previously
described
methods
require
protecting
group
manipulations
rely
entirely
on
steric
effects
control
reactivity.
These
improve
using
ligands
introduce
new
chemoselective
arylate
alcohols.
Materials Horizons,
Год журнала:
2024,
Номер
11(10), С. 2494 - 2505
Опубликована: Янв. 1, 2024
We
present
a
new
type
of
core–shell
copper
nanocluster,
[Cu
29
(S
t
Bu)
13
Cl
5
(PPh
3
)
4
H
10
]
BuSO
,
that
has
multiple
active
sites
on
its
surface.
This
nanocluster
serves
as
versatile
heterogeneous
catalyst
for
various
C-heteroatom
(C–O,
C–N
and
C–S)
bond-forming
reactions.
Chemical Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 1, 2025
A
multiligand-involved
Cu
catalysis
offers
an
efficient
Hiyama
coupling
of
arylsilanes
with
unactivated
alkyl
halides,
where
copper
NHC
and
phenanthroline
ligands
were
account
for
C(sp
2
)–Si
activation
)–C(sp
3
)
formation,
respectively.
JACS Au,
Год журнала:
2024,
Номер
4(2), С. 680 - 689
Опубликована: Фев. 12, 2024
Sustainable
technology
for
constructing
Pd-catalyzed
C–N
bonds
involving
aliphatic
amines
is
reported.
A
catalytic
system
that
relies
on
low
levels
of
recyclable
precious
metal,
a
known
and
commercially
available
ligand,
aqueous
medium
are
combined,
leading
to
newly
developed
procedure.
This
new
can
be
used
in
ocean
water
with
equal
effectiveness.
Applications
highly
challenging
reaction
partners
constituting
late-stage
functionalization
documented,
as
short
but
efficient
synthesis
the
drug
naftopidil.
Comparisons
existing
aminations
highlight
many
advances
being
offered.
ACS Sustainable Chemistry & Engineering,
Год журнала:
2024,
Номер
12(5), С. 1997 - 2008
Опубликована: Янв. 22, 2024
A
general
protocol
employing
heterogeneous
catalysis
has
been
developed
that
enables
ppm
of
Pd-catalyzed
C-N
cross-coupling
reactions
under
aqueous
micellar
catalysis.
new
nanoparticle
catalyst
containing
specifically
ligated
Pd,
in
combination
with
nanoreactors
composed
the
designer
surfactant
Savie,
a
biodegradable
amphiphile,
catalyzes
bond
formations
recyclable
water.
variety
coupling
partners,
ranging
from
highly
functionalized
pharmaceutically
relevant
APIs
to
educts
Merck
Informer
Library,
readily
participate
these
environmentally
responsible,
sustainable
reaction
conditions.
Other
key
features
associated
this
report
include
low
levels
residual
Pd
found
products,
recyclability
medium,
use
ocean
water
as
an
alternative
source
options
for
pseudohalides
and
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(13), С. 8839 - 8846
Опубликована: Март 25, 2024
Aryl
amines
are
highly
useful
organic
chemicals,
but
large-scale,
transition-metal-free
syntheses
of
aryl
surprisingly
underdeveloped.
A
mild
and
scalable
(up
to
500
mmol)
amine
synthesis
from
benzyne
chemistry
was
invented
using
easily
accessible
chlorides
as
precursors,
NaH
a
stoichiometric
base,
new
type
sodium
alkoxide
cluster,
X@RONa,
catalyst.
The
cluster
catalyst
X@RONa
featured
an
externally
hydrophobic
dodecameric
shell
housing
encapsulated
center
anion.
made
methoxy-tert-butanol
found
be
the
most
effective.
intramolecular
version
this
reaction
allowed
indolines
indoles.
Experimental
computational
mechanistic
studies
revealed
that
rate-determining
step
likely
transport
solid
into
in
phase.
