In
this
study,
we
present
the
first
cobalt(III)-catalyzed
direct
synthesis
of
isoquinolones
from
readily
available
primary
arylamides
and
internal
alkynes
through
a
controlled
oxidative
C-H/N-H
annulation
reaction.
This
innovative
protocol
eliminates
need
for
expensive
transition
metal
salts
external
auxiliaries,
producing
desired
mono-annulated
product
exclusively
while
accommodating
wide
range
substrates.
Preliminary
mechanistic
studies
highlight
critical
role
copper
oxide
in
facilitating
transformation.
Additionally,
peripheral
modifications
core
isoquinolone
rings
have
been
performed
to
synthesize
complex
heterocyclic
systems.
Chemical Communications,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Jan. 1, 2024
Herein,
an
overview
of
the
evolution
electrochemical
C–H
annulations
with
alkynes
for
construction
heterocycles
is
provided,
a
topical
focus
on
underlying
mechanism
manifolds.
ACS Catalysis,
Journal Year:
2024,
Volume and Issue:
unknown, P. 17556 - 17570
Published: Nov. 14, 2024
The
mechanism
of
the
quinoline
transfer
hydrogenation
(TH)
by
aqueous
HCOOH
under
action
[Cp*Co(quinNH2)I]+
(A*;
quinNH2
=
8-aminoquinoline)
has
been
investigated
a
combination
experiments
and
density
functional
theory
(DFT)
calculations.
Variable-temperature
(−40
to
20
°C)
1H
NMR
in
absence
substrate
shows
rapid
equilibration
between
A*
formate
complex
[Cp*Co(quinNH2)(O2CH)]+
(B*)
upon
addition
HCOOH/NEt3
MeOH,
yielding
ΔH°
1.49
±
0.03
kcal
mol–1
ΔS°
1.92
0.06
cal
K–1.
This
equilibrium
mixture
slowly
converts
decarboxylation
deprotonation
paramagnetic
(S
1)
[Cp*Cp(quinNH2)]
(C*),
indirectly
identified
derivatization
[Cp*Co(CNtBu)2]
further
I2
oxidation
[Cp*Co(CNtBu)2I](I3).
rate
law
[Cp*Co(quinNH2)I]+-catalyzed
8-methylquinoline
(8MQ)
TH
with
D2O
at
80
°C
order
one
for
catalyst
zero
HCOOH,
constant
k
(1.52
0.05)
×
10–2
s–1
L.
(Q)
(k
(2.04
L)
selectively
yields
tetrahydroquinoline
doubly
D-labeled
C3
position
([3,3-D2]-THQ).
Under
same
conditions,
DCOOD
[2,3,3,4-D4]-THQ
(6.6
0.6)
10–3
L
(KIE
kH/kD
3.1
0.5),
while
H2O
[2,4-D2]-THQ.
DFT
calculations
Cp
model
system
point
catalytic
cycle
both
diamagnetic
intermediates.
A
key
aspect
is
that
H
atom
as
hydride
metal
center,
converting
[CpCo(quinNH2)(O2CH)]+
(B)
[CpCo(quinNH2)H]+
(D),
faster
than
its
proton
yield
[CpCp(quinNH2)]
(C).
variance
closely
related
8-hydroxyquinoline
ligand
(ACS
Catal.
2021,
11,
11906–11920),
underlining
decisive
roles
reaction
medium
selection
dehydrogenation
pathway.
Angewandte Chemie,
Journal Year:
2024,
Volume and Issue:
136(40)
Published: June 19, 2024
Abstract
In
this
study,
we
unveil
a
novel
method
for
the
asymmetric
dearomatization
of
indoles
under
cobalt/photoredox
catalysis.
By
strategically
activating
C−H
bonds
amides
and
subsequent
migratory
insertion
π‐bonds
present
in
indole
as
reactive
partner,
achieve
syn
‐selective
tetrahydro‐5
H
‐indolo[2,3‐
c
]isoquinolin‐5‐one
derivatives
with
excellent
yields
enantiomeric
excesses
up
to
>99
%.
The
developed
operates
without
metal
oxidant,
relying
solely
on
oxygen
oxidant
employing
an
organic
dye
photocatalyst
irradiation.
Control
experiments
stoichiometric
studies
elucidate
reversible
nature
enantiodetermining
activation
step,
albeit
not
being
rate‐determining.
This
study
only
expands
horizon
cobalt‐catalyzed
bond
functionalization,
but
also
showcases
potential
synergy
between
cobalt
photoredox
catalysis
enabling
synthesis
complex
molecules.
In
this
study,
we
present
the
first
cobalt(III)-catalyzed
direct
synthesis
of
isoquinolones
from
readily
available
primary
arylamides
and
internal
alkynes
through
a
controlled
oxidative
C-H/N-H
annulation
reaction.
This
innovative
protocol
eliminates
need
for
expensive
transition
metal
salts
external
auxiliaries,
producing
desired
mono-annulated
product
exclusively
while
accommodating
wide
range
substrates.
Preliminary
mechanistic
studies
highlight
critical
role
copper
oxide
in
facilitating
transformation.
Additionally,
peripheral
modifications
core
isoquinolone
rings
have
been
performed
to
synthesize
complex
heterocyclic
systems.
