Organometallics,
Год журнала:
2024,
Номер
43(20), С. 2403 - 2412
Опубликована: Май 8, 2024
Oxidative
addition
complexes
play
a
crucial
role
in
Pd-catalyzed
transformations.
They
are
not
only
key
catalytic
intermediates
but
also
powerful
and
robust
precatalysts,
effective
reactants
for
late-stage
functionalization
of
complex
molecules.
However,
accessing
given
oxidative
is
often
challenging
due
to
lack
stable
palladium
sources
with
the
correct
reactivity.
Herein,
we
report
an
easily
prepared
bench-stable
Pd(II)
dialkyl
complex,
DMPDAB–Pd–BTSM
(DMPDAB
=
N,N′-bis(2,6-dimethylphenyl)diazabutadiene;
BTSM
bis(trimethylsilylmethyl)),
that
versatile
precursor
generating
highly
active
as
Pd
source
situ
catalyst
formation
cross-coupling
reactions.
A
aspect
this
structure
absence
alkene-based
stabilizing
ligands
common
other
precursors.
We
demonstrate
utility
several
complexes,
including
phosphine
diimine-ligated
high-turnover-number
catalysis
C–O,
Suzuki,
Heck
coupling
Angewandte Chemie International Edition,
Год журнала:
2023,
Номер
62(49)
Опубликована: Авг. 22, 2023
Abstract
Much
progress
has
been
made
in
the
development
of
methods
to
both
create
compounds
that
contain
C−F
bonds
and
functionalize
bonds.
As
such,
are
becoming
common
versatile
synthetic
functional
handles.
This
review
summarizes
advantages
defluorinative
functionalization
reactions
for
small
molecule
synthesis.
The
coverage
is
organized
by
type
carbon
framework
fluorine
attached
mono‐
polyfluorinated
motifs.
main
challenges,
opportunities
advances
discussed
each
class
organofluorine.
Most
text
focuses
on
case
studies
illustrate
how
defluorofunctionalization
can
improve
routes
targets
or
properties
enable
unique
mechanisms
reactions.
broader
goal
showcase
incorporating
exploiting
design
routes,
improvement
specific
advent
new
methods.
Chemical Science,
Год журнала:
2022,
Номер
13(12), С. 3477 - 3488
Опубликована: Янв. 1, 2022
Making
accurate,
quantitative
predictions
of
chemical
reactivity
based
on
molecular
structure
is
an
unsolved
problem
in
synthesis,
particularly
for
complex
molecules.
We
report
approach
to
prediction
catalytic
reactions
structure-reactivity
models
a
key
step
common
many
mechanisms.
demonstrate
this
with
mechanistically
model
the
oxidative
addition
(hetero)aryl
electrophiles
palladium(0),
which
myriad
processes.
This
links
simple
descriptors
relative
rates
79
substrates,
including
chloride,
bromide
and
triflate
leaving
groups.
Because
often
controls
rate
and/or
selectivity
palladium-catalyzed
reactions,
can
be
used
make
about
reaction
outcomes.
Demonstrated
applications
include
multivariate
linear
initial
Sonogashira
coupling
successful
site-selectivity
Suzuki,
Buchwald-Hartwig,
Stille
multihalogenated
substrates
relevant
synthesis
pharmaceuticals
natural
products.
Organic Process Research & Development,
Год журнала:
2023,
Номер
27(7), С. 1160 - 1184
Опубликована: Март 20, 2023
Earth-abundant
metal
(EAM)
catalysis
can
have
profound
impact
in
the
pharmaceutical
industry
terms
of
sustainability
and
cost
improvements
from
replacing
precious
metals
like
palladium
as
well
harnessing
differential
reactivity
first-row
that
allows
for
novel
transformations
to
enable
more
efficient
routes
clinical
candidates.
The
strategy
building
these
capabilities
within
process
group
at
Bristol
Myers
Squibb
is
described
herein,
with
general
plan
a
reaction
screening
platform,
demonstrating
scalability,
increasing
mechanistic
understanding
catalyst
activation.
development
catalytic
utilizing
nickel,
cobalt,
iron
while
highlighting
importance
collaboration
internal
external
groups
advance
EAM
our
portfolio.
challenges
benefits
working
transition
metals,
including
metrics
implementation
catalysis,
such
cost,
mass
intensity,
commercial
availability
catalysts
ligands,
are
discussed.
Journal of the American Chemical Society,
Год журнала:
2023,
Номер
145(14), С. 7729 - 7735
Опубликована: Март 30, 2023
We
report
a
fully
orthogonal
C-O
bond
formation
strategy,
which
involves
the
selective
coupling
of
arylgermanes
with
alkyl
alcohols
(primary,
secondary
and
tertiary)
as
well
carboxylic
acids,
tolerating
otherwise
widely
employed
handles,
such
aromatic
(pseudo)halogens
(C-I,
C-Br,
C-Cl,
C-F,
C-OTf,
C-OFs),
silanes
boronic
acid
derivatives.
This
unprecedented
[Ge]-based
construction
is
rapid
(15
min
to
few
hours
reaction
time),
air-tolerant,
operationally
simple
mild,
it
base-free
proceeds
at
room
temperature.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(14), С. 9755 - 9767
Опубликована: Март 26, 2024
Hydroxylated
(hetero)arenes
are
valued
in
many
industries
as
both
key
constituents
of
end
products
and
diversifiable
synthetic
building
blocks.
Accordingly,
the
development
reactions
that
complement
address
limitations
existing
methods
for
introduction
aromatic
hydroxyl
groups
is
an
important
goal.
To
this
end,
we
apply
base-catalyzed
halogen
transfer
(X-transfer)
to
enable
direct
C–H
hydroxylation
mildly
acidic
N-heteroarenes
benzenes.
This
protocol
employs
alkoxide
base
catalyze
X-transfer
from
sacrificial
2-halothiophene
oxidants
aryl
substrates,
forming
SNAr-active
intermediates
undergo
nucleophilic
hydroxylation.
Key
process
use
2-phenylethanol
inexpensive
hydroxide
surrogate
that,
after
substitution
rapid
elimination,
provides
hydroxylated
arene
styrene
byproduct.
Use
simple
2-halothiophenes
allows
6-membered
1,3-azole
derivatives,
while
a
rationally
designed
2-halobenzothiophene
oxidant
extends
scope
electron-deficient
benzene
substrates.
Mechanistic
studies
indicate
reversible,
suggesting
deprotonation,
halogenation,
steps
operate
synergy,
manifesting
unique
selectivity
trends
not
necessarily
dependent
on
most
position.
The
utility
method
further
demonstrated
through
streamlined
target
molecule
syntheses,
examples
regioselectivity
contrast
alternative
methods,
scalable
recycling
thiophene
oxidants.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(28), С. 19249 - 19260
Опубликована: Июль 3, 2024
Two
limiting
mechanisms
are
possible
for
oxidative
addition
of
(hetero)aryl
(pseudo)halides
at
Pd(0):
a
3-centered
concerted
and
nucleophilic
displacement
mechanism.
Until
now,
there
has
been
little
understanding
about
when
each
mechanism
is
relevant.
Prior
investigations
to
distinguish
between
these
pathways
were
limited
few
specific
combinations
the
substrate
ligand.
Here,
we
computationally
evaluated
over
180
transition
structures
in
order
determine
mechanistic
trends
based
on
substrate,
ligand(s),
coordination
number.
Natural
abundance
The Journal of Organic Chemistry,
Год журнала:
2025,
Номер
90(5), С. 1895 - 1904
Опубликована: Янв. 24, 2025
Multipalladium
clusters
possess
peculiar
structures
and
synergistic
effects
for
reactivity
selectivity.
Herein,
C3-symmetric
tripalladium
(1,
0.5
mol
%)
afford
C2-regioselective
SMCC
of
2,4-dibromopyridine
with
phenylboronic
acids
or
pinacol
esters
(C2:C4
up
to
98:1),
in
contrast
Pd(OAc)2
ligand-free
conditions.
In
addition,
similar
C2-selectivity
was
achieved
Sonogashira,
Negishi,
Kumada
coupling
reactions.
This
method
highlights
their
powerful
catalytic
ability,
exclusive
C2-selectivity,
broad
substrate
scope,
efficient
amplification,
multiple
ligand-exchange
feasibility
demonstrates
that
the
conventional
sites
could
be
successfully
regulated
even
reversed
by
catalysts.
ACS Catalysis,
Год журнала:
2022,
Номер
12(15), С. 8822 - 8828
Опубликована: Июль 8, 2022
In
cross-coupling
reactions,
dihaloheteroarenes
are
usually
most
reactive
at
C─halide
bonds
adjacent
to
a
heteroatom.
This
selectivity
has
been
previously
rationalized.
However,
no
mechanistic
explanation
exists
for
anomalous
reports
in
which
specific
ligands
effect
inverted
with
dihalopyridines
and
-pyridazines.
Here
we
provide
evidence
that
these
uniquely
promote
oxidative
addition
12e-
Pd(0).
Computations
indicate
14e-
Pd(0)
can
favor
different
mechanisms
due
differences
their
HOMO
symmetries.
These
shown
lead
site
preferences,
where
an
atypical
distal
nitrogen.
Organic Letters,
Год журнала:
2022,
Номер
24(2), С. 762 - 766
Опубликована: Янв. 10, 2022
Enantioselective
Cu-catalyzed
C–O
cross
coupling
reactions
yielding
atropisomeric
resorcinol-bearing
quinazolinones
have
been
developed.
Utilizing
a
new
guanidinylated
dimeric
peptidic
ligand,
set
of
products
were
generated
in
good
yields
with
excellent
stereocontrol.
The
transformation
was
readily
scalable,
and
range
product
derivatizations
performed.