Electrocatalytic Reduction of C-C π-Bonds via a Cobaltocene-Derived Concerted Proton-Electron Transfer Mediator: Fumarate Hydrogenation as a Model Study

Article abstract of DOI:10.1021/jacs.1c03335

Reductive concerted proton-electron transfer (CPET) is poorly developed for the reduction of C-C π-bonds, including for activated alkenes that can succumb to deleterious pathways (e.g., a competing hydrogen evolution reaction or oligomerization) in a standard electrochemical reduction. We demonstrate herein that selective hydrogenation of the C-C π-bond of fumarate esters can be achieved via electrocatalytic CPET (eCPET) using a CPET mediator comprising cobaltocene with a tethered Br?nsted base. High selectivity for electrocatalytic hydrogenation is observed only when the mediator is present. Mechanistic analysis sheds light on two distinct kinetic regimes based on the substrate concentration: low fumarate concentrations operate via rate-limiting CPET followed by an electron-transfer/proton-transfer (ET/PT) step, whereas high concentrations operate via CPET followed by a rate-limiting ET/PT step.

Full text of DOI:10.1021/jacs.1c03335

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Electrocatalytic Reduction of C−C π‑Bonds via a Cobaltocene-
Derived Concerted Proton−Electron Transfer Mediator: Fumarate
Hydrogenation as a Model Study
Joseph Derosa,† Pablo Garrido-Barros,† and Jonas C. Peters*
Cite This: J. Am. Chem. Soc. 2021, 143, 9303−9307
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ABSTRACT: Reductive concerted proton−electron transfer (CPET) is poorly developed for the reduction of C−C π-bonds,
including for activated alkenes that can succumb to deleterious pathways (e.g., a competing hydrogen evolution reaction or
oligomerization) in a standard electrochemical reduction. We demonstrate herein that selective hydrogenation of the C−C π-bond
of fumarate esters can be achieved via electrocatalytic CPET (eCPET) using a CPET mediator comprising cobaltocene with a
tethered Brønsted base. High selectivity for electrocatalytic hydrogenation is observed only when the mediator is present.
Mechanistic analysis sheds light on two distinct kinetic regimes based on the substrate concentration: low fumarate concentrations
operate via rate-limiting CPET followed by an electron-transfer/proton-transfer (ET/PT) step, whereas high concentrations operate
via CPET followed by a rate-limiting ET/PT step.
Scheme 1. Representative Reagents in Chemical CPET with
C−C π-Bonds and Our Strategy to Extend eCPET to C−C
π-Bond Reduction
oncerted proton−electron transfer (CPET) steps are
Cadvantageous in catalyst design schemes as a strategy to
enhance reaction kinetics.1 Reductive CPET strategies are of
interest toward the reduction of unsaturated substrates,2 for
example with respect to carbonyl functionalities.3 Reductive
CPET with C−C π-bonds, however, remains an opportunity
for chemical synthesis but is underexplored, an inherent
obstacle being the large structural reorganization (sp2-to-sp3
hybridization) associated with CPET to the carbon atom of a
C−C π-bond.4 Nevertheless, representative reports include
mechanistic investigations of SmI2·H2O used in the reduction
of anthracene or enamines, as reported by the Flowers and
Mayer groups, respectively (Scheme 1A).5,6 Relatedly, studies
of metal−hydride (M−H)-mediated hydrogen atom transfer
(HAT/MHAT) have pointed to CPET from M−H
intermediates to C−C π-bonds,7,8 a strategy that can be
rendered catalytic when stoichiometric silane or H2 regenerates
the active catalyst.9−12
Electrocatalytic CPET (eCPET) (Scheme 1B) may offer an
attractive complementary approach toward C−C π-bond
reductions, especially if competitive hydrogen evolution
reaction (HER) and/or substrate polymerization pathways,
both of which may be problematic in canonical electrode-
mediated reductions,13 can be mitigated. Toward this end, our
group has begun exploring molecular mediators that can
transfer a stored H-atom equivalent, derived from an acid in
solution and an electrode, to unsaturated substrates.14
Accordingly, we modified a cobaltocenium redox mediator
homolytically weak N−H bond (N−H bond dissociation free
energy (BDFEN−H) = 39 kcal·mol−1; Figure 1). This state of
the mediator is highly reactive and was shown to reduce
acetophenone via a net H-atom (H·) (Scheme 1B), with
with N,N-dimethylaniline as a Brønsted base ([CpCoCpNMe ]-
2
Received: March 29, 2021
Published: June 17, 2021
[OTf]) in order to decouple the redox and protonation sites to
minimize undesired HER15,16 while allowing for electro-
reductive cycling of the mediator.
Reduction from CoIII to CoII in this system induces bond
weakening of the protonated dimethylaniline to furnish a
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© 2021 American Chemical Society
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Figure 1. Thermochemical square scheme for CPET reduction of
diphenyl fumarate, including PT (blue) and ET (red) pathways.
Experimental and calculated values in MeCN are reported.
associated mechanistic data confirming a CPET process. With
acetophenone, the overall reaction is selective for C−C
(pinacol-type) coupling of the ketyl radical; further reduction
to the alcohol (i.e., Ph(Me)CH(OH)) is not observed. To
probe whether a net 2H+/2e− (2H·) transfer can instead be
catalyzed by this Co-derived mediator, here we focus on C−C
π-bonded fumarate esters as suitable candidates, noting their
associated challenges (e.g., oligomerization and competitive
HER) in traditional electrode-mediated reductions.17,18
The BDFEC−H for the succinyl radical derived from diphenyl
fumarate (DPF) was calculated to be 48 kcal·mol−1 via DFT
using MeCN as the solvent, providing a substantial driving
force (ΔG° = −9 kcal·mol−1) with respect to a CPET step
from the protonated Co(II) state of the mediator. DPF
reduction should preferably occur via CPET using the
Figure 2. (A) Cyclic voltammograms of reaction components using
diphenyl fumarate as the substrate at 100 mV/s. (B) Optimized
controlled-potential coulometry (CPC) conditions for eCPET
reduction of diphenyl fumarate and dicyclohexyl fumarate.
[CpCoCpNMe ][OTf] mediator, as supported by thermody-
2
namic considerations compared with initial proton transfer
(PT) (ΔpKa(MeCN, calc) = 25; ΔG° = 33 kcal·mol−1) or
electron transfer (ET) (ΔE1/2 = 0.5 V; ΔG° = 12.5 kcal·mol−1)
(Figure 1).
that at high concentration a rate term dominates that is not
dependent on [DPF].
ipl = 2FSCc0at
D
kobs
Cyclic voltammetry (CV) at 100 mV/s with 1 mM
cat
(1)
[CpCoCpNMe ][OTf] in the presence of 50 mM [4‑CNPhNH3]-
2
[OTf] and 50 mM diphenyl fumarate at a boron-doped
diamond (BDD) working electrode resulted in an electro-
catalytic wave at −1.21 V vs Fc+/0. Gratifyingly, controlled-
potential coulometry (CPC) with TsOH in an undivided cell
at −1.30 V vs Fc+/0 furnished diphenyl succinate in 86%
isolated yield after 20 h (Figure 2). The reaction is efficient in
acid because of dramatic HER attenuation. In the absence of
In the low-[DPF] regime, the reaction is first-order in [Co],
as evidenced by a linear relationship observed between icat and
[Co] with a kobs value that remains constant (see the
Supporting Information (SI)). We further observe an
approximately zeroth-order dependence on [H+] (slope ≈
0.1); these observations intimate a kinetically dominant rate-
limiting step involving CPET from the mediator
+
[CpCoCpNMe ][OTf], the desired product was detected in just
[CpCoCpNHMe ] to DPF at low [DPF]. A second-order rate
2
2
24% yield with only 26% of the starting material remaining.
constant kCPET of 14.20 M−1 s−1 was obtained in this regime,
with kobs = kCPET[DPF].
Using 1 mM Cp2Co in place of [CpCoCpNMe ][OTf] gave the
2
product in just 9% yield with only 32% of the starting material
remaining (and substantial HER). Dicyclohexyl fumarate
By contrast, at higher [DPF], where the dependence of the
rate on the substrate concentration begins to plateau, a
stronger dependence on [H+] is observed, with an approximate
initial slope of 0.4 in the linear fit between log(kobs) and
log([H+]); an eventual decrease in slope is noted at the highest
[H+] studied. These observations suggest a larger kinetic
influence of an acid-dependent step in the regime where
[DPF] ≥ [H+].22
delivered a 78% yield with 2 mM [CpCoCpNMe ][OTf] but
2
only a 2% yield of the product without the mediator.
Collectively, these data underscore the utility of the catalytic
mediator compared with low-yielding electrode-mediated
reductions;19 undesired reactivity is attenuated, and the
electrocatalytic reduction occurs at lower overpotentials.
́
Following the analytical methods of Saveant and co-workers,
An observed shift in the kinetic dependence on the relative
[DPF] and [H+] is also evident from an examination of the
kinetic isotope effect (KIE) using [4‑CNPhND3][OTf] at both
high and low [DPF] concentrations (Figure 3B). In the low-
[DPF] regime (20 mM), a large KIE of 4.1 0.6 is observed
that is similar to our previously reported KIE for O−H bond
formation using acetophenone substrate via eCPET (4.9
kobs in eq 1 reflects the rate of kinetically limiting steps in a
2H+/2e− process.20,21 Curiously, variation of [DPF] reveals
two kinetic regimes, indicative of the interplay between two
rate-determining steps (rds) (Figure 3A). At low [DPF] (5−30
mM), log(kobs) increases linearly with log([DPF]) with a slope
of ∼1, revealing the reaction to be first-order with respect to
[DPF]. However, at higher [DPF] (40−80 mM), this
dependence begins to plateau toward zeroth-order, suggesting
0.7).14 Alternatively, a much smaller KIE of 1.3
0.1 is
observed at high [DPF], providing further support that a
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Communication
1
1/2
(kobs
)
=
1
1
+
kCPETCs0ubstrate
kPTC0
+
(2)
H
An ECEC mechanism (Figure 4A), whose kobs is provided
by the rate law in eq 2, accommodates the collective data.
Figure 3. (A) Analyses of the dependence of the rate on (left) the
substrate (DPF) concentration and (right) the acid ([4‑CNPhNH3]-
[OTf]) concentration in two substrate concentration regimes. Linear
fits correspond to highlighted points. (B) Kinetic isotope effect
studies using [4‑CNPhND3][OTf] at (left) 20 mM and (right) 50 mM
DPF. (C) Hammett analysis and rate−driving force relationship with
various para-substituted diaryl fumarates at a substrate concentration
of 50 mM.
Figure 4. (A) Plausible mechanism via a catalytic ECEC pathway with
a DFT-derived structure showing intermolecular association of
+
succinyl anion with [CpCoCpNMe ] . (B) EC pathway following
2
initial catalytic CPET.
change in the relative rate contributions of distinct steps is
operative in this system.23
Following initial CPET to DPF and subsequent reduction of
the resulting radical (presumably faster than protonation of the
generated Co(III) species), an intermediate involving the
Co(III) mediator and the succinyl anion is formed; the latter is
then protonated (kPT) to release the product and regenerate
the CPET mediator via protonation/reduction. The catalytic
current and the value of kobs are determined by both the rate of
CPET (kCPET) and the rate of protonation (kPT), thus
accounting for the observed kinetic behavior. At low [DPF],
To account for the onset of an acid dependence at higher
[DPF], we have considered several scenarios. One could
involve a kinetically limiting change from an initial CPET step
+
between [CpCoCpNHMe
]
and DPF to a multisite proton-
2
coupled electron transfer (MS-PCET)24−26 involving net
HAT, with the mediator as an electron source and exogenous
acid as the proton source. We disfavor this scenario since a
first-order dependence on both [DPF] and [H+] would be
expected. Additionally, CPET from the mediator should
kinetically outcompete a proton-dependent MS-PCET at
high [DPF] because of the expected higher kobs, which is
inconsistent with the plateau behavior observed in Figure 3.
We instead posit that a second elementary step, involving acid
instead of DPF, becomes kinetically relevant as [DPF]
increases.
k
CPET[DPF] ≪ kPT[H+]. Therefore, a first-order dependence
on [DPF] and a zeroth-order dependence on [H+] is observed.
For kCPET[DPF] > kPT[H+], which occurs at higher [DPF], a
positive order in [H+] arises as the [DPF] dependence is
diminished.
Rate-determining protonation of the Co(III) mediator
would also account for the acid dependence observed.
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Communication
However, on the basis of measurements of the rate of
net hydrogenation (2e−/2H+) at −1.30 V vs Fc+/0. This
reactivity profile contrasts with the previously reported
reactivity of ketones with this mediator (1e−/1H+ followed
by C−C coupling) and demonstrates that cobaltocene can be
repurposed from a competent HER (electro)catalyst to a net
hydrogenation (electro)catalyst via tethering of a Brønsted
base.
protonation of [CpCoCpNMe ] (2.7 × 10 M s−1) using
different acid concentrations, following Dempsey and co-
workers,27,28 we disfavor this scenario. Such a high rate
compared with kobs is inconsistent with protonation of the
CPET mediator being rate-limiting. This observation also
disfavors a second CPET from the mediator to furnish the
product, as such a pathway should not show a dependence on
the acid concentration (see the SI). A catalytic EC pathway
(Figure 4B), akin to that proposed previously for acetophe-
none,14 is also unlikely because one would expect a zeroth-
order dependence on the acid and/or detectable hydro-
dimerization products via radical homocoupling or radical/
anion addition (Figure 4A),17,18 inconsistent with the available
data. Reduction of the succinyl radical at the electrode is
sufficiently facile (Ecalc = −0.78 V vs Fc+/0) at the working
potential of −1.30 V vs Fc+/0 that subsequent protonation
would not be expected to influence the rate of electrocatalysis.
The shift in relative rate contributions to the overall catalysis
between initial CPET and the downstream protonation step is
evident at high [DPF], where the positive [H+] dependence
decreases at the highest [H+] concentrations examined because
of enhancement of kPT[H+] relative to kCPET[DPF] (i.e.,
kPT[H+] ≫ kCPET[DPF]). Accordingly, reevaluation of the
DPF substrate order at a very high acid concentration (150
mM), where the downstream protonation step is not predicted
to be rate-limiting, displays a first-order dependence on the
substrate throughout the entire [DPF] range examined (Figure
3A).29
+
7
−1
2
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/jacs.1c03335.
■
sı
Synthesis and characterization of compounds, electro-
chemical data and procedures, thermochemical consid-
erations, details of DFT calculations, and Cartesian
coordinates (PDF)
AUTHOR INFORMATION
Corresponding Author
■
Jonas C. Peters − Division of Chemistry and Chemical
Engineering, California Institute of Technology (Caltech),
Pasadena, California 91125, United States; orcid.org/
0000-0002-6610-4414; Email: jpeters@caltech.edu
Authors
Joseph Derosa − Division of Chemistry and Chemical
Engineering, California Institute of Technology (Caltech),
Pasadena, California 91125, United States; orcid.org/
0000-0001-8672-4875
The collective kinetic data and facile reduction of the
succinyl radical at our working potential suggest an interaction
between the succinyl anion and Co(III) mediator. A DFT
calculation (see the SI for details) supports the exergonic
formation of such an intermediate (ΔGassoc = −4.4 kcal·mol−1),
where intermolecular π−π stacking can be identified (Figure
4A). Additionally, an electrostatic attraction may contribute to
such an associated intermediate considering the relatively low
polarity of the medium.30,31 As inferred from the optimized
structure, protonation of the succinyl anion, with a
concomitant change from C(sp2) to C(sp3) hybridization, is
sterically hindered by the interaction with the Co(III)
mediator, providing a barrier for this step.
Pablo Garrido-Barros − Division of Chemistry and Chemical
Engineering, California Institute of Technology (Caltech),
Pasadena, California 91125, United States; orcid.org/
0000-0002-1489-3386
Complete contact information is available at:
https://pubs.acs.org/10.1021/jacs.1c03335
Author Contributions
†J.D. and P.G.-B. contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Hammett analysis of 4-CF3-, 4-Cl-, 4-H-, and 4-OMe-
substituted diaryl fumarates (50 mM)32 with 1 mM
The authors are grateful to the U.S. Department of Energy,
Office of Basic Energy Sciences, for support via Grant DE-
SC0019136 and also to the American Chemical Society
Petroleum Research Fund (61951-ND3). J.D. thanks the
Arnold and Mabel Beckman Foundation for a postdoctoral
fellowship, and P.G.-B thanks the Ramón Areces Foundation
for a postdoctoral fellowship. J.C.P. is grateful to the Resnick
Sustainability Institute. We thank a reviewer for helpful
feedback regarding proposed intermediates.
[CpCoCpNMe ][OTf] and 50 mM [4‑CNPhNH3][OTf] (see
2
Figure 3C) shows a clear trend in reaction rate with increasing
driving force, contrasting with our previous data for aryl
ketones14 but consistent with other examples of reductive
CPET transformations.33−36 The obtained slope value of 0.83
(the Brønsted α value) is higher than the theoretical slope
predicted by Marcus theory for the low driving force regime
(0.5), suggesting a late transition state along the reaction
coordinate. According to this relationship (Figure 3C, right,
linear fit), a thermoneutral CPET to a C−C π-bond should
occur with kobs = 1.5 × 10−4 s−1. This is approximately 3 orders
of magnitude lower than the calculated kobs of a thermoneutral
CPET to the C−O π bond in acetophenone,14 supporting the
notion of significantly slower CPET to a C−C π-bond because
of substantial reorganization at carbon.37
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