Angewandte Chemie International Edition,
Год журнала:
2023,
Номер
62(51)
Опубликована: Ноя. 2, 2023
Evaluation
of
the
relative
rates
cobalt-catalyzed
C(sp2
)-C(sp3
)
Suzuki-Miyaura
cross-coupling
between
neopentylglycol
ester
4-fluorophenylboronic
acid
and
N-Boc-4-bromopiperidine
established
that
smaller
N-alkyl
substituents
on
phenoxyimine
(FI)
supporting
ligand
accelerated
overall
rate
reaction.
This
trend
inspired
design
optimal
cobalt
catalysts
with
phenoxyoxazoline
(FOx)
phenoxythiazoline
(FTz)
ligands.
An
air-stable
cobalt(II)
precatalyst,
(FTz)CoBr(py)3
was
synthesized
applied
to
an
indole-5-boronic
nucleophile
a
piperidine-4-bromide
electrophile
is
relevant
synthesis
reported
toll-like
receptor
(TLR)
7/8
antagonist
molecules
including
afimetoran.
Addition
excess
KOMe⋅B(Oi
Pr)3
improved
catalyst
lifetime
due
attenuation
alkoxide
basicity
otherwise
resulted
in
demetallation
FI
chelate.
A
first-order
dependence
precatalyst
saturation
regime
were
observed,
turnover-limiting
transmetalation
origin
observed
trends
N-imine
substitution.
The
Suzuki-Miyaura
cross-coupling
reaction
is
a
cornerstone
in
organic
synthesis,
enabling
the
formation
of
carbon–carbon
bonds
with
high
efficiency
and
selectivity.
This
study
represents
groundbreaking
advancement
field
by
pioneering
first
enantioselective
Ni-catalyzed
Suzuki–Miyaura
reactions
for
synthesis
biaryl
atropisomers.
Employing
data-driven
approach,
we
have
crafted
novel
N-protected
Xiao-Phos
ligand,
which,
conjunction
commercially
available
Ni(COD)2,
delivered
unparalleled
enantioselectivity
reactivity
under
mild
conditions.
ligand
design
was
meticulously
guided
an
extensive
examination
existing
literature
on
Pd-catalyzed
asymmetric
reactions,
directing
virtual
screening
subsequent
experimental
verification
synthesized
ligands
single
iteration.
innovative
N-Bn-Xiao-Phos
exhibited
impressive
enantioselectivities
coupled
exceptional
yields,
showcasing
versatility
diverse
array
functional
groups
aryl
boronic
acids,
accomplishing
successful
gram-scale
synthesis.
DFT
computational
studies
provided
profound
insights
into
mechanism
roots
enantioselectivity,
elucidating
dynamic
coordination
modes
chiral
steric
induction.
breakthrough
not
only
broadens
horizons
but
also
highlights
immense
potential
machine
learning
judicious
Recent
global
events
have
led
to
the
cost
of
platinum
group
metals
(PGMs)
reaching
unprecedented
heights.
Many
chemical
companies
are
therefore
starting
seriously
consider
and
evaluate
if,
where,
they
can
substitute
PGMs
for
non-PGMs
in
their
catalytic
processes.
This
review
covers
recent
large-scale
applications
non-PGM
catalysts
modern
pharmaceutical
industry.
By
highlighting
these
selected
successful
examples
non-PGM-catalyzed
processes
from
literature,
we
hope
emphasize
enormous
potential
catalysis
inspire
further
development
within
this
field
enable
technology
progress
towards
manufacturing
We
also
present
some
historical
context
perceived
advantages
challenges
implementing
environment.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(14), С. 10124 - 10141
Опубликована: Апрель 1, 2024
Phenoxyimine
(FI)–nickel(II)(2-tolyl)(DMAP)
compounds
were
synthesized
and
evaluated
as
precatalysts
for
the
C(sp2)–C(sp3)
Suzuki–Miyaura
cross
coupling
of
(hetero)arylboronic
acids
with
alkyl
bromides.
With
5
mol
%
optimal
(MeOMeFI)Ni(Aryl)(DMAP)
precatalyst,
scope
cross-coupling
reaction
was
established
included
a
variety
bromides
(>50
examples,
33–97%
yield).
A
β-hydride
elimination–reductive
elimination
sequence
from
potassium
isopropoxide
base,
yielding
(FI)nickel(0)ate,
identified
catalyst
activation
pathway
that
is
responsible
halogen
atom
abstraction
bromide.
combination
NMR
EPR
spectroscopies
(FI)nickel(II)–aryl
complexes
resting
state
during
catalysis
no
evidence
long-lived
organic
radical
or
odd-electron
nickel
intermediates.
These
data
establish
chain
short-lived
undergoes
facile
termination
also
support
"recovering
chain"
process
whereby
compound
continually
(re)initiates
chain.
Kinetic
studies
rate
product
formation
proportional
to
concentration
captures
propagation.
The
proposed
mechanism
involves
two
key
concurrently
operating
catalytic
cycles;
first
involving
nickel(I/II/III)
propagation
cycle
consisting
capture
at
(FI)nickel(II)–aryl,
reductive
elimination,
bromine
C(sp3)–Br,
transmetalation;
second
an
off-cycle
recovery
by
slow
→
(FI)nickel(0)ate
conversion
nickel(I)
regeneration.
