Chemical Science,
Год журнала:
2023,
Номер
14(48), С. 14124 - 14130
Опубликована: Янв. 1, 2023
We
have
developed
a
general
process
for
the
formation
of
enantioenriched
benzylic
stereocenters
via
stereospecific
Pd-catalyzed
cross-coupling
reactions
tricyclohexyltin
nucleophiles.
This
proceeds
with
excellent
stereospecificity
remarkably
broad
scope
electrophilic
coupling
partners
including
aryl
and
heteroaryl
halides
triflates,
acid
chlorides,
thioesters,
chloroformates,
carbamoyl
chlorides.
Thus,
1,1-diarylalkanes
as
well
formal
products
asymmetric
enolate
arylation
are
readily
accessed
using
this
approach.
additionally
provide
first
demonstration
Sn-selective
reaction
vicinal
alkylborylstannane
nucleophile.
In
these
reactions,
presence
cyclohexyl
spectator
ligands
on
tin
is
essential
to
ensure
selective
transfer
secondary
unit
from
palladium.
We
report
a
Cu-catalysed
oxidative
coupling
of
aliphatic
amines
with
benzylic
and
boronic
esters
to
give
high
value
alkyl
amines,
products
found
widely
in
applications
from
medicinal
chemistry
materials
science.
This
operationally
simple
reaction,
which
can
be
performed
on
gram
scale,
runs
under
mild
conditions
exhibits
broad
functional
group
tolerance.
The
terminal
oxidant
the
reaction
is
O2
air,
avoiding
need
for
additional
chemical
oxidants.
Investigation
into
mechanism
suggests
that
ester
activated
by
an
aminyl
radical,
formed
through
oxidation
amine
Cu
catalyst,
key
radical
intermediate.
To
demonstrate
its
utility
potential
late-stage
functionalization,
we
showcase
method
as
final
step
total
synthesis
TRPV1
antagonist.
Chemical Science,
Год журнала:
2023,
Номер
14(48), С. 14124 - 14130
Опубликована: Янв. 1, 2023
We
have
developed
a
general
process
for
the
formation
of
enantioenriched
benzylic
stereocenters
via
stereospecific
Pd-catalyzed
cross-coupling
reactions
tricyclohexyltin
nucleophiles.
This
proceeds
with
excellent
stereospecificity
remarkably
broad
scope
electrophilic
coupling
partners
including
aryl
and
heteroaryl
halides
triflates,
acid
chlorides,
thioesters,
chloroformates,
carbamoyl
chlorides.
Thus,
1,1-diarylalkanes
as
well
formal
products
asymmetric
enolate
arylation
are
readily
accessed
using
this
approach.
additionally
provide
first
demonstration
Sn-selective
reaction
vicinal
alkylborylstannane
nucleophile.
In
these
reactions,
presence
cyclohexyl
spectator
ligands
on
tin
is
essential
to
ensure
selective
transfer
secondary
unit
from
palladium.
