of 8
A Carborane-Derived
Proton-Coupled
Electron
Transfer
Reagent
Enric
H. Adillon
and Jonas
C. Peters
*
Cite This:
J. Am. Chem.
Soc.
2024,
146, 30204−30211
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Supporting
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ABSTRACT:
Reagents
capable
of
concerted
proton
−
electron
transfer
(CPET)
reactions
can
access
reaction
pathways
with
lower
reaction
barriers
compared
to
stepwise
pathways
involving
electron
transfer
(ET)
and
proton
transfer
(PT).
To
realize
reductive
multielectron/proton
transformations
involving
CPET,
one
approach
that
has
shown
recent
promise
involves
coupling
a
cobaltocene
ET
site
with
a protonated
arylamine
Brønsted
acid
PT
site.
This
strategy
colocalizes
the
electron/proton
in
a
matter
compatible
with
a CPET
step
and
net
reductive
electrocatalysis.
To
probe
the
generality
of
such
an
approach
a class
of
C,C
′
-diaryl-
o
-
carboranes
is
herein
explored
as
a
conceptual
substitute
for
the
cobaltocene
subunit,
with
an
arylamine
linkage
still
serving
as
a
colocalized
Brønsted
base
suitable
for
protonation.
The
featured
o
-
carborane
(Ph
Cb
Ph
N
) can
be
reduced
and
protonated
to
generate
an
N
−
H
bond
with
a weak
effective
bond
dissociation
free
energy
(BDFE
eff
) of
31
kcal/mol,
estimated
with
measured
thermodynamic
data.
This
N
−
H
bond
is
among
the
lowest
measured
element
−
H
bonds
for
analyzed
nonmetal
compounds.
Distinct
solid-state
crystal
structures
of
the
one-
and
two-electron
reduced
forms
of
diaryl-
o
-carboranes
are
disclosed
to
gain
insight
into
their
well-behaved
redox
characteristics.
The
singly
reduced,
protonated
form
of
the
diaryl-
o
-carborane
can
mediate
multi-ET/PT
reductions
of
azoarenes,
diphenylfumarate,
and
nitrotoluene.
In
contrast
to
the
aforementioned
cobaltocene
system,
available
mechanistic
data
disclosed
herein
support
these
reactions
occurring
by
a rate-limiting
ET
step
and
not
a CPET
step.
A
relevant
hydrogen
evolution
reaction
(HER)
reaction
was
also
studied,
with
data
pointing
to
a PT/
ET/PT
mechanism,
where
the
reduced
carborane
core
is
itself
highly
stable
to
protonation.
■
INTRODUCTION
Proton-coupled
electron
transfer
(PCET)
reagents
can
facilitate
challenging
substrate
reductions
via
pathways
that
are
efficient
compared
with
stepwise
ET-PT
pathways.
1
Such
reagents
have
been
demonstrated
to
be
useful
tools
for
selective
hydrogen
atom
delivery
(or
abstraction)
with
organic
and
inorganic
substrates.
2
Systems
that
mediate
reductive
PCET
transformations
have
largely
utilized
the
well-behaved
redox
properties
of
transition
metal
and
lanthanide
complexes
(Scheme
1A).
3
−
7
To
access
PCET
reactivity,
the
reduced
form
of
these
systems
(e.g.,
Co(II)
or
Sm(II))
can
be
coupled
to
a
Brønsted
acid
via
covalent
linkage,
coordination,
or
substrate
preorganization
to
form
a
reactive
net
hydrogen
atom
equivalent
that
can
be
delivered
to
substrates.
Redox
potential
and
acid
p
K
a
govern
the
effective
X
−
H
bond
dissociation
free
energy
(BDFE
X
−
H
, X
=
C,
N,
O)
as
in
eq
1,
8
allowing
H
atom
reactivity
to
be
measured
and
tuned
via
the
individual
proton
and
electron
transfer
equilibria
(p
K
a
and
E
°
,
respectively,
where
C
g
is
a
solvent-dependent
constant).
E
K
C
BDFE
23
.06
1.37p
eff
a
g
=
+
+
(1)
While
weakening
the
BDFE
X
−
H
can
promote
net
H
atom
transfer
reactivity,
it
can
in
turn
predispose
a reagent
toward
the
hydrogen
evolution
reaction
(HER);
the
latter
is
thermodynamically
favorable
when
the
BDFE
X
−
H
is
less
than
half
that
of
the
dihydrogen
bond
(BDFE
H
−
H
= 104
kcal/mol).
3
Strategies
for
mitigating
HER
are
central
to
reductive
PCET
reagent
design.
4,9
One
strategy
for
promoting
PCET
reactions
in
a
fashion
compatible
with
electrocatalysis
involves
covalent
tethering
of
a Brønsted
acid
to
a reductant,
as
illustrated
in
Scheme
1B.
10
Our
lab
has
shown
that
attaching
an
anilinium
fragment
to
cobaltocene
(left)
yields
Cp
Co
Cp
NH+
(right),
a complex
with
a
weak
BDFE
N
−
H
. This
species
operates
as
an
electrocatalytic
PCET
(
e
PCET)
mediator
under
controlled
potential
elec-
trolysis
conditions,
effecting
ketone
and
olefin
reductions,
11
ketyl-olefin
cyclizations,
12
and
with
transition
metal
cocatalysts,
alkyne
semihydrogenation
13
and
nitrogen
reduction
to
ammonia.
14
The
turnover-limiting
PCET
step
can
be
concerted,
as
evidenced
by
zero
order
acid
concentration
Received:
July
3,
2024
Revised:
October
11,
2024
Accepted:
October
14,
2024
Published:
October
28,
2024
Article
pubs.acs.org/JACS
© 2024
The Authors.
Published
by
American
Chemical
Society
30204
https://doi.org/10.1021/jacs.4c09007
J. Am. Chem.
Soc.
2024,
146, 30204
−
30211
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dependence
on
the
catalytic
rate
but
still
a substantial
primary
kinetic
isotope
effect
(KIE).
Given
the
observed
PCET
reactivity
of
aniline-modified
cobaltocene,
we
sought
to
explore
an
alternative
system
wherein
the
cobaltocene
redox
relay
is
replaced
by
another
redox
subunit,
focusing
herein
on
a
main
group
cluster.
We
selected
the
o
-carborane
platform
for
its
synthetic
malleability
and
its
compatibility
with
strongly
reducing
anionic
states.
15,16
In
particular,
o
-carboranes
�
icosahedral
clusters
comprised
of
ten
boron
atoms
and
two
adjacent
carbon
atoms
�
are
reported
to
have
two
one-electron
redox
features
between
−
1
and
−
3
V
(all
potentials
reported
in
acetonitrile
referenced
to
the
ferrocene/ferrocenium
couple).
17
Whereas
the
potentials
of
o
-carboranes
can
be
modulated
by
over
2
V
by
changing
the
carbon
substituents,
the
use
of
reduced
carboranes
as
stoichiometric
reductants
(whether
in
ET
or
PCET
steps)
has
not
to
our
knowledge
been
previously
explored.
■
RESULTS
AND DISCUSSION
Structure
of Reduced
Carboranes.
As
an
entry
point
for
reductive
carborane
chemistry,
we
first
determined
the
structures
of
diaryl-
o
-carboranes
following
one-
and
two-
electron
reduction.
Samples
of
the
anionic
and
dianionic
compounds
were
generated
according
to
prior
reports
by
reducing
diphenyl-
o
-carborane
(Ph
2
Cb
)
with
potassium
metal;
one
equivalent
yields
the
radical
anion
(Ph
2
Cb
−
) and
excess
affords
the
closed-shell
dianion
(Ph
2
Cb
2
−
).
18
The
radical
nature
of
[Ph
2
Cb
]K
is
supported
by
Evans
method
and
a CW-
EPR
spectrum
featuring
a broad
resonance
with
no
resolvable
hyperfine
interactions
centered
at
g
=
2.026
(Figure
S36).
[Ph
2
Cb
]K
2
has
diagnostic
1
H,
11
B,
and
13
C
NMR
signals
consistent
with
the
formation
of
a closed-shell
species
(Figure
S2
−
S4).
The
mono-
and
dianions
were
characterized
by
single
crystal
XRD
as
their
respective
K(18-crown-6)
salts
(crown
=
c
hereafter).
The
structure
of
[Ph
2
Cb
]K(18-
c
-6)
is
shown
in
Figure
1
(top)
with
the
neutral
Ph
2
Cb
for
reference
and
counterions
omitted
for
clarity.
19
Comparing
these
two
structures,
the
largest
change
is
a
lengthening
of
the
C
−
C
bond
between
the
two
adjacent
carbon
atoms
of
the
icosahedron
core
(which
lengthens
from
1.733
to
2.374
Å).
Scheme
1. (A) Widely
Adopted
PCET
Reagents
Derived
from
Metal
Reductants;
(B) An Aniline-Appended
Cobaltocene
e
PCET
Mediator;
(C) Exploring
the Reactivity
of a Main-Group
Reductant
with An Appended
Brønsted-Acid
Figure
1.
X-ray
Crystal
Structures
of
Ph
2
Cb
and
[Ph
2
Cb]K(18-
crown-6)
with
a
cartoon
of
the
SOMO
highlighting
its
σ
*
and
π
bonding
character.
Journal
of the American
Chemical
Society
pubs.acs.org/JACS
Article
https://doi.org/10.1021/jacs.4c09007
J. Am. Chem.
Soc.
2024,
146, 30204
−
30211
30205
In
addition,
the
C
−
C
bond
length
between
the
core
carbon
atoms
and
the
aryl
ipso-
atoms
shortens
considerably
(1.504
to
1.470
Å).
20
The
lengthening
of
C
−
C
bond
is
consistent
with
previous
theoretical
studies
and
related
structures.
15,21
−
27
The
structural
parameters
suggest
that
the
SOMO
is
chiefly
comprised
of
the
tangential
p-orbitals
of
the
two
adjacent
carbon
atoms
of
the
cluster
(Figure
1,
bottom).
The
cluster
carbon
atoms
engage
in
a
σ
*
interaction
leading
to
the
observed
breaking
of
the
C
−
C
bond
upon
reduction
to
the
radical
anion.
Because
the
carbon
p-orbitals
are
aligned
with
the
aryl
π
*
orbitals,
they
form
a partial
π
bond
that
distributes
negative
charge
away
from
the
o
-carborane
core.
For
the
dianionic
Ph
2
Cb
2
−
, the
structure
follows
the
Wade’s
rules
prediction
of
a
nido
-icosahedron
(Figure
S52).
28
Thermochemistry
of PhCbPh
NH
.
Through
incorporation
of
a
Brønsted
base
on
the
aryl
substituents,
we
envisaged
forming
a compound
which
could
be
reduced
at
the
carborane
core
and
protonated
at
the
base
to
yield
a net
H
atom
donor.
1-(4-N,N-dimethylaniline)-2-phenyl-
o
-carborane
(Ph
Cb
Ph
N
)
is
a previously
reported
carborane
which
contains
an
appended
base
and
was
readily
prepared.
15
Chemical
reduction
of
Ph
Cb
Ph
N
with
one
equivalent
of
potassium
metal
and
two
equivalents
of
benzo-15-c-5
yielded
the
radical
anion
as
red
needles.
XRD
analysis
provides
a
structure
featuring
an
icosahedron
core
structure
similar
to
Ph
2
Cb
−
(Figure
2A).
UV
−
vis
spectroscopy
was
used
to
study
the
protonation
of
Ph
Cb
Ph
N
to
furnish
Ph
Cb
Ph
NH
. [Ph
Cb
Ph
N
]K(b-15-
c
-5)
2
(b-
15-c-5
=
benzo-15-crown-5)
(blue
trace)
in
THF
solution
cooled
to
−
80
°
C
was
protonated
by
addition
of
up
to
one
equivalent
of
4-cyanoanilinium
triflate
([
4
‑
CN
PhNH
3
]OTf),
forming
a
new
species
assigned
as
Ph
Cb
Ph
NH
(Figure
2B).
Addition
of
triazabicyclodecene
(TBD)
as
base
produces
a
spectrum
consistent
with
Ph
Cb
Ph
N
−
,
suggesting
that
the
protonation
is
reversible
(Figure
2B,
inset
).
Addition
of
the
same
acid
to
Ph
2
Cb
−
does
not
yield
any
new
features,
suggesting
that
incorporation
of
the
aniline
moiety
allows
for
reversible
protonation
of
the
carborane
species
(Figure
S68).
Next,
we
set
out
to
determine
the
effective
BDFE
N
−
H
of
Ph
Cb
Ph
NH
by
measuring
the
PT
and
ET
equilibria
depicted
along
the
edges
of
the
square
scheme
in
Figure
2A.
Ph
Cb
Ph
N
was
analyzed
by
cyclic
voltammetry
to
determine
its
reduction
potential
and
the
shift
in
potential
upon
protonation
(Figure
2C).
First,
the
voltammogram
of
Ph
Cb
Ph
N
(blue
trace)
shows
two
reversible
features
at
−
1.67
and
−
1.80
V
corresponding
to
the
formation
of
the
radical
anionic
and
dianionic
carboranes.
Upon
addition
of
acid
to
generate
Ph
Cb
Ph
NH
, we
observe
an
anodically
shifted
irreversible
multielectron
wave
(gray
trace),
suggesting
that
formation
of
Ph
Cb
Ph
NH
is
coupled
to
a
fast
chemical
step.
To
estimate
the
reduction
potential
of
[Ph
Cb
Ph
NH
]
+/0
, the
N
-methylated
analog
1-(4-N,N,N-trime-
thylanilinium)-2-phenyl-
o
-carborane
triflate
([Ph
Cb
Ph
NMe3
]
-
OTf)
was
prepared
and
isolated
by
addition
of
methyl
triflate
to
Ph
Cb
Ph
N
. Its
voltammogram
(red
trace)
contains
two
reversible
features
at
−
1.43
and
−
1.59
V
which
are
anodically
shifted
relative
to
Ph
Cb
Ph
N
. Since
the
onset
of
the
cathodic
waves
corresponding
to
reduction
of
[Ph
Cb
Ph
NMe3
]
+/0
and
[Ph
Cb
Ph
NH
]
+/0
overlay,
we
deduce
that
the
([Ph
Cb
Ph
NMe3
]
+/0
E
1/2
is
a good
approximation
of
the
[Ph
Cb
Ph
NH
]
+/0
E
1/2
.
The
p
K
a
of
Ph
Cb
Ph
NH+
was
determined
by
titration
with
2-
chloroanilinium
triflate
in
CD
3
CN
and
quantification
of
the
equilibrium
constant
by
1
H
NMR
spectroscopy
(see
S8).
The
p
K
a
was
measured
to
be
8.6
�
much
lower
than
N,N-
dimethylaniline
(p
K
a
=
11.5)
�
demonstrating
the
strong
electron-withdrawing
nature
of
neutral
o
-carborane.
29
Figure
2.
(A)
square
scheme
of
Ph
Cb
Ph
NH
with
the
X-ray
crystal
structure
of
[Ph
Cb
Ph
N
]K(b-15-
c
-5)
2
(bottom
left).
(B)
UV
−
vis
spectra
of
[Ph
Cb
Ph
N
]K(b-15-
c
-5)
2
(1
mM)
in
THF
at
−
80
°
C
with
[
4
‑
CN
PhNH
3
]OTf
titrant
(0
−
1
eq
in
0.2
eq
increments)
and
(
inset
)
TBD
titrant
(0
−
1
eq
in
0.2
eq
increments).
(C)
Cyclic
voltammograms
of
Ph
Cb
Ph
N
(1
mM,
blue
)
with
[
4
‑
CN
PhNH
3
]OTf
(10
mM,
gray
)
and
[Ph
Cb
Ph
NMe3
]OTf
(1
mM,
red
)
in
acetonitrile
with
n
Bu
4
PF
6
(200
mM)
supporting
electrolyte.
The
scans
are
swept
cathodic,
then
anodic
at
100
mV/s.
Journal
of the American
Chemical
Society
pubs.acs.org/JACS
Article
https://doi.org/10.1021/jacs.4c09007
J. Am. Chem.
Soc.
2024,
146, 30204
−
30211
30206
With
the
[Ph
Cb
Ph
NH
]
+/0
E
1/2
and
the
Ph
Cb
Ph
NH+
p
K
a
in
hand,
the
Ph
Cb
Ph
NH
BDFE
N
−
H
can
be
estimated
to
be
31
kcal/mol.
This
is
a
very
low
BDFE
N
−
H
,
especially
for
a
nonmetal
compound.
To
our
knowledge,
only
one
nonmetal
compound,
the
nicotinamide
radical
cation,
has
a
weaker
experimentally
measured
value
for
a condensed
phase
element-
hydrogen
BDFE
(BDFE
C
−
H
=
26
kcal/mol).
3,30,31
Akin
to
the
nicotinamide
radical
cation,
the
o
-carborane’s
driving
force
for
H
atom
loss
can
be
linked
to
restoring
aromaticity
upon
oxidation
by
reforming
the
icosahedral
core
and
breaking
C
cluster
−
C
aryl
π
-bond.
Relatedly,
restoring
aromaticity
has
been
invoked
by
our
laboratory
to
rationalize
the
very
weak
C
−
H
bond
of
ring-protonated
cobaltocenes.
32
Reactivity
of PhCbPh
NH
.
The
weak
BDFE
N
−
H
of
Ph
Cb
Ph
NH
indicates
that
it
should
serve
as
a potent
H
atom
donor
but
may
also
be
disposed
to
HER.
To
probe
its
reactivity,
we
first
studied
its
stability
in
solution
in
the
absence
of
a substrate.
Ph
Cb
Ph
NH
was
generated
in
THF
at
−
40
°
C
by
protonation
of
[Ph
Cb
Ph
N
]K(b-15-
c
-5)
2
with
[Ph
3
PH]OTf.
Its
concentration
was
monitored
by
UV
−
vis
spectroscopy
(Figure
S71).
The
behavior
of
its
absorbance
at
550
nm
reflects
first-
order
decay
with
t
1/2
=
7.9
min
which
we
ascribe
to
HER
(
vide
infra
).
Next,
we
studied
the
reactivity
of
Ph
Cb
Ph
NH
toward
model
organic
substrates.
To
do
so,
Ph
Cb
Ph
NH
was
preformed
by
mixing
[Ph
Cb
Ph
N
]K(b-15-
c
-5)
2
and
[Ph
3
PH]OTf
in
THF
solution
at
−
40
°
C,
followed
by
substrate
addition.
We
chose
the
substrates
acetophenone
and
diphenylfumarate
as
they
had
been
previously
shown
to
react
with
Cp
Co
Cp
NH+
, in
addition
to
azoarenes
which
may
also
be
reduced
via
PCET
path-
ways.
33
−
35
The
results
are
summarized
in
Scheme
2.
In
each
case,
the
only
observed
boron-containing
product
by
11
B
NMR
spectroscopy
is
Ph
Cb
Ph
N
, as
expected
if Ph
Cb
Ph
NH
serves
as
a
net
H
atom
donor
(Figure
S13).
Diphenylfumarate,
nitrotoluene,
and
azobenzene
were
reduced
in
good
yield
to
diphenyl
succinate,
toluidine,
and
diphenylhydrazine,
respectively,
suggesting
that
the
transfer
of
reducing
equivalents
from
Ph
Cb
Ph
NH
to
these
substrates
can
outcompete
HER.
However,
for
acetophenone
and
electron-
rich
azoarenes
(Ar
=
p
-tolyl,
p
-MeOPh),
little
to
none
of
the
reduced
products
were
formed
despite
the
substantial
driving
force
for
the
first
net
H
atom
transfer.
We
note
that
similar
substrate
classes
have
been
assessed
for
reactions
with
bismuth-
and
phosphorus-derived
reductants.
36,37
To
probe
the
mechanism
through
which
reduction
by
Ph
Cb
Ph
NH
operates,
we
performed
a competition
experiment
between
azobenzene
and
para
-substituted
azoarenes,
extracting
the
relative
rates
from
starting
material
conversion
to
generate
linear
free-energy
relationships
(Figure
3).
Should
azoarene
Scheme
2. Reduction
of model
organic
substrates
by PhCbPh
NH
plotted
as a function
of their
calculated
redution
potential
Figure
3.
(A)
Azoarene
reduction
competition
experiment
using
Ph
Cb
Ph
NH
as
the
reductant.
(B)
Rate-driving
force
analysis
for
an
ET
step.
Journal
of the American
Chemical
Society
pubs.acs.org/JACS
Article
https://doi.org/10.1021/jacs.4c09007
J. Am. Chem.
Soc.
2024,
146, 30204
−
30211
30207
reduction
by
Ph
Cb
Ph
NH
be
occurring
through
a
CPET
step
rather
than
ET-PT
steps,
we
would
expect
that
the
relative
rate
(k
x
/k
H
)
should
be
fairly
insensitive
to
substitution
on
the
azoarenes.
Previous
Hammett
analyses
of
reactions
occurring
through
CPET
steps
returned
shallow
slopes,
implying
that
a
decrease
in
ET-driving
force
is
compensated
by
an
increase
in
PT-driving
force.
10,11,38,39
Plotting
the
relative
rates
against
the
substituent
Hammett
parameter,
a large
positive
slope
(
ρ
=
2.5
or
2.8
for
σ
+
and
σ
,
respectively)
is
observed
(Figure
S61
−
S62).
For
general
comparison,
in
this
case
ρ
is
substantially
larger
than
that
observed
for
reductive
CPET
from
Cp
Co
Cp
NH+
to
acetophe-
none
(
ρ
=
−
0.55)
or
fumarate
(
ρ
=
0.44)
as
substrates.
40
These
analyses
support
a
rate-limiting
step
involving
a
substantial
negative
charge
accumulation
on
the
substrate
in
the
transition
state
relative
to
the
ground
state.
To
further
disentangle
whether
azoarene
reduction
occurs
through
a
rate-limiting
ET
or
CPET
step,
we
plotted
the
relative
rates
against
the
driving
force
for
ET
and
net
H
atom
transfer.
The
relative
rates
plotted
against
the
driving
force
(Marcus
plots)
for
ET
(
Δ
E
)
or
CPET
(
Δ
G
CPET
)
yield
excellent
(
R
2
=
0.99)
and
moderate
(
R
2
=
0.70)
correlations,
respectively
(Figure
3B,
S66).
41,42
These
plots
demonstrate
that
the
reduction
potential,
not
the
BDFE,
most
accurately
trends
with
the
observed
rates.
Also
considering
that
the
Hammett
analysis
yields
a large
and
positive
slope,
we
deduce
that
these
data
support
azoarene
reduction
by
Ph
Cb
Ph
NH
proceeding
by
a rate-limiting
ET
step
rather
than
a CPET
step.
The
stepwise
ET-PT
reactivity
of
Ph
Cb
Ph
NH
contrasts
the
apparent
CPET-type
reactivity
of
Cp
Co
Cp
NH+
studied
on
different
classes
of
substrates
(e.g.,
acetophenones,
fumarates,
as
well
as
N
2
and
phenylmethylpropriolate
via
tandem
catalysis).
10
−
14
This
difference
is
noted
despite
shared
thermochemical
properties
(they
have
the
same
p
K
a
(8.6,
in
MeCN
)
and
similar
shifts
in
potential
upon
protonation
(
Δ
E
=
+240
mV
vs
+140
mV,
respectively);
the
carborane
system
is
nevertheless
moderately
more
reducing
(
E
1/2
=
−
1.43
V
vs
−
1.21
V,
respectively).
The
absence
of
observed
CPET-type
reactivity
for
Ph
Cb
Ph
NH
may
be
due
to
the
large
degree
of
structural
reorganization
that
can
be
anticipated
between
Scheme
3. (A) Plausible
HER
Mechanisms
for Ph
2
Cb
−
with Relevant
Measured
and Computed
Thermochemical
Parameters
of Intermediates;
(B) Regioselectivity
of the Rate
Determining
PT Step for Ph
2
Cb
−
and Cp
*
2
Co
Journal
of the American
Chemical
Society
pubs.acs.org/JACS
Article
https://doi.org/10.1021/jacs.4c09007
J. Am. Chem.
Soc.
2024,
146, 30204
−
30211
30208