Electron-rich phenoxyl mediators improve thermodynamic performance of electrocatalytic alcohol oxidation with an iridium pincer complex

Article abstract of DOI:10.1021/jacs.0c09605

Electron-rich phenols, including α-rac-tocopherol Ar1OH, 2,4,6,-tri-tert-butylphenol Ar3OH, and butylated hydroxy-toluene Ar4OH, are effective electrochemical mediators for the electrocatalytic oxidation of alcohols by an iridium amido dihyride complex (PNP)Ir(H)2 (IrN 1, PNP = bis[2-diisopropylphosphino)ethyl]amide). Addition of phenol mediators leads to a decrease in the onset potential of catalysis from -0.65 V vs Fc+/0 under unmediated conditions to -1.07 V vs Fc+/0 in the presence of phenols. Mechanistic analysis suggests that oxidative turnover of the iridium amino trihydride (PNHP)Ir(H)3 (IrH 2, PNHP = bis[2-diisopropylphosphino)ethyl]amine) to IrN 1 proceeds through two successive hydrogen atom transfers (HAT) to 2 equiv of phenoxyl that are generated transiently at the anode. Isotope studies and comparison to known systems are consistent with initial homolysis of an Ir-H bond being rate-determining. Turnover frequencies up to 14.6 s-1 and an average Faradaic efficiency of 93% are observed. The mediated system shows excellent chemoselectivity in bulk oxidations of 2-propanol and 1,2-benzenedimethanol in THF and is also viable in neat 2-propanol.

Full text of DOI:10.1021/jacs.0c09605

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Article
Electron-Rich Phenoxyl Mediators Improve Thermodynamic
Performance of Electrocatalytic Alcohol Oxidation with an Iridium
Pincer Complex
Conor M. Galvin and Robert M. Waymouth*
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ABSTRACT: Electron-rich phenols, including α-rac-tocopherol
Ar1OH, 2,4,6,-tri-tert-butylphenol Ar3OH, and butylated hydroxy-
toluene Ar4OH, are effective electrochemical mediators for the
electrocatalytic oxidation of alcohols by an iridium amido dihyride
c o m p l e x ( P N P ) I r ( H ) 2 ( I r N 1 , P N P
= b i s [ 2 -
diisopropylphosphino)ethyl]amide). Addition of phenol mediators
leads to a decrease in the onset potential of catalysis from −0.65 V
vs Fc+/0 under unmediated conditions to −1.07 V vs Fc+/0 in the
presence of phenols. Mechanistic analysis suggests that oxidative
turnover of the iridium amino trihydride (PNHP)Ir(H)3 (IrH 2,
PNHP = bis[2-diisopropylphosphino)ethyl]amine) to IrN 1
proceeds through two successive hydrogen atom transfers (HAT)
to 2 equiv of phenoxyl that are generated transiently at the anode. Isotope studies and comparison to known systems are consistent
with initial homolysis of an Ir−H bond being rate-determining. Turnover frequencies up to 14.6 s−1 and an average Faradaic
efficiency of 93% are observed. The mediated system shows excellent chemoselectivity in bulk oxidations of 2-propanol and 1,2-
benzenedimethanol in THF and is also viable in neat 2-propanol.
mediators can be employed to mediate critical electron and/or
proton transfer steps. The use of mediators in electrochemical
reactions has a long history in electrosynthesis,11−14 including
bioinspired mediators such as quinones15−17 and NAD+,13 as
well as nitroxyls.14 Nitroxyls can function both as alcohol
oxidation electrocatalysts18−20 and mediators that operate by
hydrogen atom abstraction (e.g., Cu-coordinated alco-
hols).14,21−23 Ferrocene, flavins, and polypyridyl complexes
of ruthenium and osmium mediate the transfer of electrons
from glucose oxidases to anodes in glucose-detection
technologies and fuel cells.6,24,25 Typically, mediators are
two-electron/two-proton shuttles or agents that mediate
electron transfer.
INTRODUCTION
■
Electrocatalytic oxidations are important for energy conversion
and selective chemical synthesis.1−3 Alcohol electrooxidation
strategies enable the direct utilization of biofeedstock polyols
as fuels1,4−7 and can also provide an alternative to
stoichiometric and unselective chemical oxidants.1,8,9 Although
heterogeneous electrocatalysts1,10 have been explored exten-
sively, homogeneous molecular electrocatalysts provide oppor-
tunities to interrogate the key chemical or electrochemical
steps that influence the rate, selectivity, and thermodynamics
of key intermediates and to tune these properties through
rational synthetic design. Ideal catalysts should not only exhibit
high rates but should optimally operate with 100% Faradaic
efficiency (FE) at or near the thermodynamically reversible
potential of alcohol and carbonyl interconversion. The
difference between the reversible potential and the catalyst
operating potential is the overpotential and is a measure of the
reaction’s thermodynamic efficiency. The overpotential is
principally dictated by the electrochemical properties (pKa
and E0) of the catalyst (or electrode composition for
heterogeneous electrocatalysts1,10).
Our studies with Ru26,27 and Fe pincer28 compounds
revealed that complexes active for transfer hydrogenation or
acceptorless alcohol oxidation are good candidates for alcohol
electrooxidation catalysts. As these and many other electro-
catalytic processes involve metal hydrides as key intermedi-
ates,26,28−30 strategies to improve both the rate and efficiency
Received: September 14, 2020
One of the major challenges in the design of new
electrocatalysts is that both the electrochemical properties
and chemical properties of the catalysts (and intermediates)
need to be optimized to simultaneously achieve fast rates at the
appropriate electrochemical potential and pH. Electrochemical
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of electro-oxidation of metal hydrides are critical. The
electrooxidation of transition metal hydrides typically involves
stepwise electron transfer (ET) and proton transfer (PT) steps
(Figure 1, red steps). As discrete ET and PT pathways can be
Figure 2. Phenol thermochemical cycle.
potential decreases as electron-donating groups are added.
Generally, the phenol BDFE increases as electron-withdrawing
groups are added, but even the most electron-rich phenols
(excluding hydroquinones and catechols) have BDFEs in
excess of 73 kcal/mol in organic solvents.38
Phenoxyl-mediated alcohol electrooxidation also requires a
catalyst that rapidly dehydrogenates alcohols, tolerates electro-
chemical conditions, and is susceptible to oxidation by HAT.
These requirements directed us to the Ir(III) amido pincer
complex IrN 1, which was first reported as an active
bifunctional catalyst for the fast transfer hydrogenation of
ketones with 2-propanol (Figure 3).47 The mechanism of
Figure 1. Unmediated (red) and mediated (blue) approaches to
electrocatalytic alcohol oxidation with bifunctional metal hydride
catalysts.
associated with high kinetic barriers,31,32 we targeted mediators
that can intercept metal hydrides to bypass thermodynamically
costly ET and PT steps.27 Many metal hydrides have relatively
low bond dissociation free energies (BDFEs),33,34 and this
makes them susceptible to interception by hydrogen atom
transfer (HAT),35−37 a subclass of proton-coupled electron
transfer (PCET) reactions.38−40 If the hydrogen atom acceptor
were electrochemically regenerable, a transition from un-
mediated to mediated electrocatalytic alcohol oxidation could
be envisioned (Figure 1, blue steps).
There are specific thermochemical criteria that are necessary
for this class of electrochemical mediators. First, the mediator
must be a strong enough hydrogen atom acceptor to remove a
hydrogen atom from the metal hydride; the resulting A−H
bond in the mediator must therefore have a BDFE similar to or
greater than the M−H BDFE (Figure 1).
To afford a thermodynamic improvement over direct
electrocatalysis with the metal hydride catalyst, the mediator
must be electrochemically regenerable at potentials cathodic of
the direct electrocatalysis onset potential. Lastly, the mediator
should be sufficiently acidic to be deprotonated by bases used
in the unmediated process so that a reliable comparison of
overpotentials can be made between the mediated and
unmediated systems.
With these considerations in mind, we investigated phenoxyl
radicals as mediators for electrocatalytic alcohol oxidation. Due
to their importance as antioxidants and their roles as hydrogen
atom acceptors in enzyme catalysis, electron-rich phenoxyl
radicals and their thermochemistry have been studied
extensively.38,41−46 Phenoxyls can be readily generated through
deprotonation of the parent phenol with base and subsequent
one-electron oxidation of the resulting phenoxide at the anode
(Figure 2).38 The thermochemical parameters of the phenol/
phenoxide/phenoxyl cycle are tunable by varying the aryl
substituents. Phenol pKa increases and phenoxide oxidation
Figure 3. Transfer hydrogenation of ketones with an iridium pincer
catalyst.
transfer hydrogenation was proposed to proceed through the
reversible dehydrogenation of secondary alcohols by 1 to
generate the Ir(III) trihydride IrH 2.47 This isolable
intermediate is the quantitative product when 1 is treated
with 2-propanol.47 There is precedent for electrocatalytic
activity in this class of PNP pincer catalysts, as a related iron
complex catalyzes alcohol electrooxidation, and IrH 2 itself
performs CO2 electroreduction.28,48 Two additional properties
of 2 make it an attractive target for interception by HAT in an
electrochemical setting. First, both 1 and 2 tolerate strong
bases because transfer hydrogenation is still viable in the
presence of a 10-fold excess of KOtBu.47 Second, we expected
the Ir−H bonds of 2 to be weak because similar octahedral
bis(phosphine) Ir(III) hydrides have low bond dissociation
enthalpies (BDEs) (58−64 kcal/mol).33,34,49 This iridium
system is therefore an excellent candidate for phenoxyl-
mediated alcohol electrooxidation because it rapidly dehydro-
genates alcohols, tolerates strong bases, and has weak Ir−H
bonds that are likely susceptible to HAT to phenoxyl radicals.
Herein we demonstrate that electron-rich phenoxyl radicals
are competent mediators for the electrocatalytic oxidation of
alcohols to carbonyls by IrH 2. The addition of phenoxyl
mediators affords a substantial thermodynamic benefit by
lowering the onset potential of catalysis from −0.65 V vs Fc+/0
under unmediated conditions to −1.07 V vs Fc+/0 in the
presence of the phenol and a base.
B
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1 readily generates IrH 2 in the presence of excess 2-propanol
(Figures 6A, S10). That the electrocatalytic peak occurs at a
RESULTS AND DISCUSSION
■
On the basis of prior studies with Ru26,27 and Fe28 transfer
hydrogenation catalysts, we anticipated that IrH 2 might be a
viable candidate as an alcohol electrooxidation catalyst. To test
this hypothesis, we investigated the electrochemistry of IrH 2
by cyclic voltammetry and carried out a bulk electrolysis of 2-
propanol with 2 as a soluble electrocatalyst. Cyclic
voltammetry (CV) of IrH 2 in THF shows two irreversible
oxidative features with onsets at −0.65 V vs Fc+/0 and 0.04 V vs
Fc+/0 (Figure S2). These features are unchanged upon addition
of 350 mM 2-propanol. However, upon addition of the
phosphazene base 1-ethyl-2,2,4,4,4-pentakis(dimethylamino)-
2λ5,4λ5-catenadi(phosphazene) (P2-Et) (pKa(THF) = 25.3,
pKa(MeCN) = 32.9) to this solution, the current at −0.65 V vs
Fc+/0 increases significantly, consistent with electrocatalytic
turnover (Figure 4).50 To confirm this, bulk oxidations of 2-
Figure 6. Speciation of the iridium catalyst in the presence of excess
alcohol (A) and base (B).
similar potential to that of oxidation of IrH 2 suggests that
oxidation of 2 is a key step. Stoichiometric studies reveal that
IrH 2 does not react with excess base P2-Et (Figures 6B, S11−
S13), consistent with electron transfer as the initial step in the
oxidation of 2 to 1, as proposed for the analogous Fe pincer
complex.28
To assess the role of the phenoxide on electrocatalytic
alcohol oxidation, we investigated changes in the cyclic
voltammetry of α-rac-tocopherol Ar1OH (pKa(MeCN) = 30,
BDFE(MeCN) = 75.2 kcal/mol)38,42,51 upon addition of IrH 2
in THF in the presence of excess P2-Et and 2-propanol. In the
absence of IrH 2 (Figure 7, green trace), the quasi-reversible
Figure 4. Titration of IrH 2 with P2-Et in the presence of excess 2-
propanol in THF (0.4 mM IrH 2, 350 mM 2-propanol, 100 mM
NBu4BF4, ν = 25 mV/s).
propanol with 2 and P2-Et were carried out at −0.355 V vs
Fc+/0 in a divided H-cell (Figure S3) for 6.5 h. Analysis of the
reaction mixture revealed acetone as the product with an
average Faradaic efficiency of 78% based on the ratio of
acetone generated to the current passed (Figures S4 and S5).
Although the catalytic wave is close in potential to the
background oxidation of P2-Et (Figure S1), the reasonably high
Faradaic efficiency with respect to acetone rules out 2-
catalyzed oxidation of P2-Et and background P2-Et oxidation as
possible causes of the increase in current observed in Figure 4.
These observations are consistent with an electrocatalytic
alcohol oxidation (ECAT) mediated by IrN 1 and IrH 2
(Figure 5). Stoichiometric NMR experiments indicate that IrN
Figure 7. Comparison of Ar1O−/Ar1O· quasi-reversible oxidation
(green, 0.8 mM Ar1OH + 23 mM P2-Et), unmediated ECAT (orange,
0.4 mM IrH 2 + 7 mM P2-Et), and mediated ECHAT (blue, 0.4 mM
IrH 2 + 0.8 mM Ar1OH + 23 mM P2-Et) in THF with 100 mM
NBu4BF4 and 400 mM 2-propanol (ν = 25 mV/s).
peak-shaped wave of the phenoxide/phenoxyl Ar1O−/Ar1O·
couple is apparent. When IrH 2 is added, this feature is
replaced by an irreversible, plateau-shaped wave of greater
maximum current at the same onset potential (Figure 7, blue
trace). These characteristics are consistent with the electro-
catalytic turnover of Ar1OH, presumably through net HAT
from IrH 2 to the phenoxyl Ar1O·.52−54 Most importantly, this
new electrocatalytic process, which we refer to as electro-
catalytic hydrogen atom transfer (ECHAT), occurs with Eonset
= −1.07 V vs Fc+/0 whereas unmediated ECAT (Figure 7,
,
Figure 5. Direct electrocatalytic alcohol oxidation with IrH 2.
orange trace) has Eonset = −0.65 V vs Fc+/0. The operating
C
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potential of electrocatalysis decreased by 420 mV simply by
adding the Ar1OH mediator.
We screened several other electron-rich phenoxyls (Figure
8) for their performance as electrochemically regenerable HAT
electrocatalytic oxidation of 2-propanol with IrH 2, we
investigated the catalytic oxidation of 2-propanol with a stable
phenoxyl radical as the terminal oxidant (Figure 9A).
When a stirred solution of the persistent and isolable
phenoxyl 2,4,6-tri-tert-butylphenoxyl Ar3O· (BDFE (MeCN) =
77.1 kcal/mol)38 in deuterated toluene was treated with 0.37%
IrH 2 and a slight excess of 2-propanol, the vibrant deep blue
color of the phenoxyl radical disappeared within 15 s to afford
a light yellow solution. Subsequent 1H NMR analysis showed a
2:1 ratio of the corresponding phenol Ar3OH and acetone in
76% yield (Figure 9A). This result demonstrates that phenoxyl
radicals are competent terminal oxidants for the oxidation of 2-
propanol by IrH 2 and suggests that the oxidation of IrH 2 to
give IrN 1 can be mediated by the consecutive homolyses of
the Ir−H and the N−H bonds of IrH 2 by 2 equiv of phenoxyl.
To provide further evidence that hydrogen atom transfer is a
viable oxidative process, the stoichiometric reaction of IrH 2
with a weaker hydrogen atom acceptor was investigated. When
treated with 2 equiv of the persistent nitroxyl radical TEMPO
((2,2,6,6-tetramethylpiperidin-1-yl)oxyl) (BDFE(MeCN) =
66.5 kcal/mol),38 IrH 2 is slowly oxidized to IrN 1, reaching
29% conversion over 16 h (Figure 9B). This observation
provides further evidence that IrN 1 can be generated through
successive HATs from IrH 2. An analogous stoichiometric
experiment was carried out with 2 equiv of Ar3O·, but the
results were less conclusive (Figures S19 and S20). Although
the blue color of the Ar3O· was quenched almost immediately
upon addition to a solution of IrH 2 in toluene-d8, only partial
conversion of IrH 2 to IrN 1 was observed. Several new and
Figure 8. Candidate electron-rich phenols.
mediators by cyclic voltammetry. The screening process
identified 2,2,5,7,8-pentamethylchromanol Ar2OH, 2,4,6-tri-
tert-butylphenol Ar3OH, and butylated hydroxytoluene Ar4OH
as effective mediators, as in each of these cases, titration with
IrH 2 was concomitant with marked increases in the peak
current of the ArxO−/ArxO· wave and a transformation from
reversible or quasi-reversible peak-shaped signals to irreversible
catalytic plateau-shaped ones (Figures S24−S26) in the range
of −0.95 V to −1.1 V vs Fc+/0. Hydroquinone Ar5OH and 4-
aminophenol Ar6OH did not appear to be effective in these
screens and the CVs exhibited multielectron/multiproton
behavior (Figures S27 and S28). 2,6-Dimethoxyphenol
Ar7OH and 3,5-dimethoxyphenol Ar8OH were also ineffective,
as the ArxO−/ArxO· couples were insufficiently cathodic
(Figures S29 and S30) and overlapped with the oxidation of
IrH 2. We used Ar1OH for all subsequent electrochemical
experiments because it had the lowest onset potential and the
greatest increase in plateau current in response to IrH 2
titration (Figures S31−S33).
1
unidentified metal hydride signals were detected by H NMR.
Treatment of IrN 1 with 1.8 equiv of Ar3O· results in the
formation of Ar3OH (Figures S21 and S22), which suggests
that poor mixing in combination with overoxidation of IrN 1
may be the causes of the complex product mixture and
incomplete conversion observed in the stoichiometric reaction
of IrH 2 and Ar3O·.
Under the conditions of kinetically limited (Zone KS)
electrocatalysis,53 the plateau current, and therefore the
turnover frequency, are limited only by the rate of
homogeneous chemical reactions and not by the mass
transport of chemical species.52 The plateau-shaped wave of
Figure 7 and experiments demonstrating that the plateau
current of Ar1OH-mediated electrocatalytic 2-propanol
oxidation with 2 remains constant between scan rates of 25
and 1600 mV/s (Figures S34 and S35) indicate that under
these experimental conditions, the reaction is in the kinetically
Having established that electron-rich phenoxyl mediators
can substantially reduce the potential of electrocatalytic alcohol
oxidation with IrH 2, we conducted additional electrochemical
experiments, scan rate studies, CV titrations, and isotope effect
studies to provide further insights on the mechanism of this
tandem electrocatalytic process. To assess if hydrogen atom
transfer by a phenoxyl radical is a plausible step in the
Figure 9. Catalytic (A) and stoichiometric (B) HAT from IrH 2 to persistent radicals.
D
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Figure 10. kobs vs iridium concentration (0.75 mM Ar1OH, 23 mM P2-Et, 400 mM 2-propanol, 100 mM NBu4BF4 in THF, ν = 25 mV/s).
Figure 11. Plateau current vs Ar1OH concentration (1.1 mM 1, 45 mM P2-Et, 400 mM 2-propanol, 100 mM NBu4BF4 in THF, ν = 25 mV/s).
Figure 12. Plateau current squared vs 2-propanol concentration (1.1 mM IrH 1, 0.4 mM Ar1OH, 42 mM P2-Et, 100 mM NBu4BF4 in THF, ν = 25
mV/s).
limited regime where the magnitude of the plateau current
depends only on the rates of homogeneous chemical reactions.
Under the assumption that the phenol is the key
electrocatalytic intermediate, the formula for plateau current
for the kinetically limited catalytic wave can be written as
Here υ is the voltammetric scan rate, R is the gas constant, and
T is the temperature. Division of eq 1 by eq 2 and subsequent
rearrangement enables the tabulation of kobs by comparing the
catalytic plateau currents in the presence of substrate to the
noncatalytic peak current in the absence of substrate:
2
iplateau = FA[Ar1OH]total 2Dkobs
i
j
y
z
iplateau
Fv
(1)
1
j
j
j
z
z
z
kobs
=
0.4463
2
j
j
z
z
ipeak RT
(3)
k
{
where F is the Faraday constant, A is the electrode surface area,
[Ar1OH]total and D are the total concentration and diffusion
coefficient of the Ar1OH, and kobs is the catalytic turnover
frequency.52,54 A complete derivation of eq 1 is presented in
Supporting Information. In the absence of IrH 2, the maximum
current of the noncatalytic peak-shaped Ar1O−/Ar1O· wave is
governed by the Randles−Sevcik equation:
Titration of IrH 2 into a cell containing Ar1OH, P2-Et, and 2-
propanol and analysis of the corresponding plateau currents
(eqs 1−3) by cyclic voltammetry reveals that kobs shows a
linear dependence on Ir concentration (Figure 10), indicating
a first-order dependence on Ir. Turnover frequencies up to
14.6 s−1 were observed. When this experiment is repeated with
2-propanol-d8 in place of protiated 2-propanol, the plot of kobs
vs [Ir] also shows a linear dependence but with a slope that
decreases by a factor of 4.2, corresponding to a primary kinetic
FvD
RT
ipeak = 0.4463FA[Ar1OH]total
(2)
E
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Figure 13. Plateau current squared vs P2-Et concentration (1.1 mM IrH 1, 0.4 mM Ar1OH, 420 mM 2-propanol, 100 mM NBu4BF4 in THF, ν =
25 mV/s).
isotope effect (KIE) of 4.2 (Figures S37 and S38). Foot-of-the-
wave analysis52,55 of the same voltammograms in Figure 10
affords a value of kobs/[Ir] that is within 10% of that calculated
from the catalytic plateau analysis (Figures S39 and S40).
Analysis of the plateau current vs [Ar1OH] reveals the linear
relationship (Figure 11) predicted by eq 2, which indicates that
kobs is independent of phenol concentration.
Analysis of the square of the plateau current as a function of
2
2-propanol concentration (eq 1) reveals that iplateau increases
as the concentration of 2-propanol is increased up to about
200 mM but does not change at concentrations above 200 mM
2-propanol (Figure 12). These data indicate that the kobs is
independent of 2-propanol concentration for [iPrOH]0 > 200
mM, concentrations at which the other titrations and the bulk
electrolyses were performed.
Figure 14. Proposed elementary steps of electrocatalytic hydrogen
atom transfer (ECHAT).
Analogous studies carried out as a function of [P2-Et] reveal
that iplateau is independent of the concentration of P2-Et, but
2
d[acetone]
= kobs[Ar1O·]0
(5)
(6)
dt
the catalytic wave is plateau-shaped only for concentrations
greater than 5 mM (Figure 13). Below this limit, the wave is
peak-shaped. This behavior is consistent with a transition from
mass-transport limited catalysis (zone K) at low base
concentrations to kinetically limited catalysis (zone KS) at
high base concentrations.52,53 Foot-of-the-wave analysis of
these same voltammograms reveals that the rate of catalysis
remains independent of base concentration even when the
waves are peak-shaped due to mass-transport limitation
(Figures S41 and S42). Thus, the experimental data are
consistent with eq 4:
kobs = k1[IrH]0
where [Ar1O·]0 and [IrH]0 are the concentrations of Ar1O·
and IrH at the anode surface. The plateau shape of the
ECHAT waves dictates that the substrate concentration at the
anode surface [IrH]0 is essentially the same as that in the bulk
52
solution, so [IrH]0 = [IrH]total
.
If the net hydrogen atom
transfer (HAT) of step 1 is assumed to be slow relative to
deprotonation and heterogeneous electron transfer, the
phenoxyl Ar1O· is the predominant resting state of the phenol
mediator at the anode and [Ar1O·]0 ≈ [Ar1OH]total. Steady-
state assumptions on the concentrations of 3, Ar1OH, and
Ar1O− leads to a predicted rate law for the mechanism of
Figure 14 in terms of the known total bulk concentrations of
phenol and iridium:
kobs(exp) = k[IrH]0
(4)
where kobs is first-order with respect to iridium and zero-order
with respect to Ar1OH, P2-Et, and 2-propanol.
On the basis of this mechanistic investigation and the known
reactivities of phenols and the iridium complex 2, a mechanism
consisting of the elementary steps of Figure 14 can be
proposed. Step 1 is the first net HAT from IrH 2 to Ar1O·,
which generates Ar1OH and an iridium radical species 3. Step
2 is the second net HAT event from 3 to Ar1O·, which
regenerates IrN 1. Step 3 is the acid−base reaction of P2-Et
and Ar1OH, step 4 is heterogeneous electron transfer from
Ar1O− to the anode, and step 5 is the dehydrogenation of 2-
propanol by IrN 1 to yield acetone and IrH 2.
d[acetone]
= kobs[Ar1OH]total
(7)
(8)
dt
kobs = k1[IrH]total
This rate law is in agreement with that determined
experimentally (eq 4). Substituting the slope of the plot of
k
obs vs [IrH]total concentration (Figure 10) for kobs/[IrH]total in
eq 8 gives a value of k1 = 4650 M−1 s−1 for protiated 2-
propanol and k1‑d = 1100 M−1 s−1 for 2-propanol-d8. According
to the proposed mechanism of Figure 14, this corresponds to
the second-order rate constant for the reaction of Ar1O· with
IrH(D) 2.
If hydrogen atom transfer from IrH 2 to the phenoxyl Ar1O·
is assumed to be turnover limiting, this mechanism would
predict that the rate should conform to eq 5 with kobs defined
as in eq 6:
The kinetics and mechanistic studies (Figure 9) suggest that
the reaction of Ar1O· with the IrH 2 is the key turnover-
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Figure 15. Proposed mechanism for the tandem electrocatalytic oxidation of 2-propanol with phenols as electrocatalytic hydrogen atom transfer
(ECHAT) mediators.
limiting step in the tandem catalytic cycle ([iPrOH] > 200
mM). The mechanism of this net hydrogen atom transfer
could proceed by a concerted hydrogen atom transfer, or by
stepwise electron and proton transfers. Although it is difficult
to experimentally discriminate between concerted HAT and
ET-PT or PT-ET,38,56 several lines of evidence argue against
the stepwise processes. A putative ET-PT pathway would
involve an endergonic (+9.7 kcal/mol) electron transfer from
IrH 2 to Ar1O· followed by deprotonation of the resulting
iridium cation by Ar1O− or P2-Et (Figure S43). A significant
primary KIE of 4.2 is observed experimentally, which is
consistent with Ir−H bond breaking in the rate-determining
step. Large KIEs and unfavorable electron transfers have been
used previously to rule out discrete ET-PT pathways in the
oxidation of toluenes by permanganate, the comproportiona-
tion of ruthenium oxo and aquo complexes,57,58 and the
oxidation of ascorbate by Ar1O·, where initial ET was
calculated to be endergonic by +12.2 kcal/mol.59 The
observation that the rate of the electrocatalytic oxidation is
independent of P2-Et concentration (Figure 13) argues against
a rapid ET preequilibrium followed by proton transfer.60−62
A stepwise PT-ET mechanism is also unlikely, as this would
occur via initial deprotonation of IrH 2 by P2-Et, which we
have shown is unfavorable (Figures 6 B, S36). Therefore, the
rapid oxidation of IrH 2 by Ar3O· in Figure 8A, which occurs
in the absence of a base, is unlikely to proceed by an initial PT,
and the oxidation of IrH 2 by phenoxyl mediators under
ECHAT conditions is most likely a concerted, rather than
stepwise, HAT event. Similar logic applies to the slow
oxidation of IrH 2 by TEMPO (Figure 8B).
oxidation of the metal hydrides HMn(CO)5 and H2Os(CO)4
by tris(p-tert-butylphenyl)methyl radical 4.63
Shown in Figure 15 is a proposed mechanism that is
consistent with the experimental evidence to date. Following
the rapid dehydrogenation of 2-propanol by IrN 1, oxidation of
IrH 2 back to IrN 1 proceeds through two successive hydrogen
atom transfer events to 2 equiv of Ar1O·. The kinetic data
suggest that the first hydrogen atom transfer from IrH 2 to
Ar1O· is turnover-limiting (k1 = 4650 M−1 s−1). Subsequent
hydrogen atom abstraction of the intermediate 3 by Ar1O·
generates IrN 1. The 2 equiv of Ar1OH are then turned over
through fast deprotonation by P2-Et and heterogeneous single
electron transfer. Significantly, as the oxidation of the
phenoxide Ar1O− occurs with Eonset = −1.07 V vs Fc+/0, 420
mV cathodic of Eonset for IrH 2, the addition of the phenol
mediator results in a significant decrease in the operating
potential of the tandem electrocatalytic process relative to that
for the electroxidation with IrH 2 alone.
The observations that (1) the stable phenoxyl radical Ar3O·
is a competent terminal oxidant for the oxidation of 2-propanol
with IrH 2 (Figure 9) and (2) that the reaction of IrH 2 with
the nitroxyl radical TEMPO affords the amido complex IrN 1
support this proposed mechanism. We have no direct evidence
for the intermediacy of the Ir(II) dihydride 3 nor information
regarding its redox potential and/or pKa; thus, the data to date
do not allow us to rule out that the proposed interconversion
of 3 to IrN 1 occurs by stepwise proton and electron (ET-PT
or PT-ET) processes. Furthermore, while the kinetic isotope
effect observed is consistent with the initial abstraction of a
hydride from IrH 2, we cannot rule out that the N−H bond of
IrH 2 is homolyzed first. Stable rhodium aminyl complexes
have been synthesized through the deprotonation and
oxidation of the corresponding rhodium secondary amino
complex with N−H homolytic BDEs as low as 76 kcal/
mol.64−66 Related iridium aminyl species have been detected in
situ and invoked as key intermediates in catalytic alcohol
dehydrogenation.67,68 Nevertheless, the rate constant of k1 =
The primary KIE of 4.2 observed for the electrocatalytic
reaction in the presence of phenol is also consistent with metal
hydride homolysis, as this value is similar to the maximum KIE
of 4.4 estimated from the previously reported IR spectrum of
IrH 2 (see Supporting Information).47 Similar reasoning was
used by Norton and co-workers in their studies of the
G
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Figure 16. Bulk electrocatalytic alcohol oxidations. FE for A and B are the averages of two runs, and C and D were each performed once. The error
for FE is 10% for any one experiment.
4650 M−1 s−1 calculated for the turnover-limiting step
involving the reaction of IrH 2 with Ar1O· is similar to
previously reported rate constants for bimolecular HAT from
Rh(III) (1170 M−1 s−1), Co(I) (1600 M−1 s−1), and Fe(II)
(12000 M−1 s−1) hydrides to the trityl radical 4 (BDE (4) = 74
kcal/mol, BDE (Ar1OH) = 80.4 kcal/mol).36,37
as supporting electrolyte) and the changes induced upon the
addition of base (P2-Et) and phenol Ar1OH (Figure 17). In
To corroborate the results obtained by CV, controlled-
potential electrocatalytic alcohol oxidations with IrH 2 were
carried out under both unmediated and phenol-mediated
conditions in a divided glass H-cell with a disposable
reticulated vitreous carbon (RVC) working electrode. Bulk
electrocatalytic oxidation of 2-propanol (0.41 M in THF) with
2 (3.1 mM) in the absence of Ar1OH was performed at −355
mV vs Fc+/0 (Figure 16A). Acetone was detected as the sole
product with a modest average Faradaic efficiency of 78% and
turnover number (TON) up to 4. The analogous controlled
potential electrocatalytic oxidation in the presence of Ar1OH
(2.5 mM in THF) was performed at −735 mV vs Fc+/0 (Figure
16B). Acetone was the only product detected and the average
Faradaic efficiency improved to 93%. Turnover numbers up to
8 with respect IrH 2 and 10 with respect to Ar1OH were
calculated based on the yield of acetone. These data reveal that
the addition of the phenol mediator noticeably improves
turnover number and Faradaic efficiency at an operating
potential 380 mV more cathodic than that of the unmediated
electrocatalytic oxidation with IrH 2 alone. The presence of
the phenoxyl mediator is imperative to the success of low-
potential mediated electrocatalytic oxidation, as no appreciable
catalysis was observed in a control electrolysis performed at
−735 mV vs Fc+/0 in the absence of Ar1OH (Figure 16C).
Controlled potential electrocatalytic oxidation of 1,2-
benzenedimethanol under similar conditions resulted in
exclusive conversion to phthalide (Figure 16D), which
demonstrates the system’s capacity for selective polyol
oxidation. Esterificative coupling of primary alcohols, thought
to result from the dehydrogenation of hemiacetal intermedi-
ates, is frequently observed in related bifunctional pincer
catalysts.69−71
Figure 17. Comparison of IrH 2 oxidation (red, 1.1 mM IrH 2),
unmediated ECAT (orange, 1.1 mM IrH 2 + 71 mM P2-Et), and
mediated ECHAT (blue, 1.1 mM IrH 2 + 1.8 mM Ar1OH + 71 mM
P2-Et) in 100 mM NBu4BF4 neat 2-propanol (ν = 25 mV/s).
the absence of base, the CV of IrH 2 (1.1 mM) exhibits an
irreversible oxidation at approximately −0.63 V vs Fc+/0 in 2-
propanol, comparable to that observed in THF (Figure 4). An
increase in current at −0.63 V is observed upon addition of 71
mM P2-Et, consistent with an electrocatalytic current. When a
similar experiment is carried out with the addition of 1.8 mM
Ar1OH, a plateau-shaped wave is observed with an onset of
−0.81 V vs Fc+/0. The addition of Ar1OH as a mediator lowers
the onset potential of catalysis in neat 2-propanol by 180 mV
(Eonset(unmediated) = −0.63 V vs Fc+/0 vs Eonset(ArOH mediated)
=
−0.81 V vs Fc+/0, Figure 17). For Ar1OH-mediated oxidation
in 2-propanol, turnover frequencies up to 9.6 s−1 are observed.
The electrocatalytic rate law derived from the cyclic
voltammetry is comparable to that observed in THF (Figures
S45−S50), although the rates are slightly slower in 2-propanol
than in THF (k1(iPrOH) = 2960 M−1 s−1 vs k1(THF) = 4650 M−1
s−1). These data suggest that electrocatalytic alcohol oxidation
with phenol mediators is not limited to polar aprotic solvents
such as THF, but might be profitably carried out in a variety of
solvents. Further studies along these lines are in progress.
To assess whether electrocatalytic alcohol oxidation might
be extended to other solvents, we briefly examined the cyclic
voltammetry of IrH 2 in neat 2-propanol (100 mM NBu4BF4
H
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CONCLUSIONS
■
Herein we demonstrated that electron-rich phenols function as
effective mediators for the electrocatalytic oxidation of alcohols
catalyzed by IrH 2. The addition of phenol mediators results in
a significant decrease in the onset potential (420 mV in THF,
180 mV in neat 2-propanol) relative to that of the unmediated
electrocatalytic oxidations. Mechanistic studies, voltammetric
titrations, and KIE studies are consistent with a tandem
electrocatalytic process in the presence of phenol mediators
(Figure 15). The phenol functions as an electrochemically
regenerable hydrogen atom acceptor to facilitate the
reoxidation of transition metal hydrides generated in the
course of the Ir-mediated oxidation of the alcohol. Turnover
frequencies up to 14.6 s −1 and 9.6 s−1 were observed by CV in
THF and neat 2-propanol, respectively. Bulk oxidations of 2-
propanol in the presence of IrH 2 and phenol Ar1OH afforded
acetone selectively, with an average Faradaic efficiency of 93%.
This study demonstrates the capacity of electron-rich
phenoxyls to improve thermodynamic performance in electro-
oxidative catalysis by providing an alternative to stepwise
proton and electron transfer steps for the oxidation of
transition metal hydrides.
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
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■
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AUTHOR INFORMATION
Corresponding Author
Robert M. Waymouth − Department of Chemistry, Stanford
University, Stanford, California 94305, United States;
orcid.org/0000-0001-9862-9509; Email: waymouth@
stanford.edu
■
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Author
Conor M. Galvin − Department of Chemistry, Stanford
University, Stanford, California 94305, United States;
orcid.org/0000-0002-7678-5647
Complete contact information is available at:
https://pubs.acs.org/10.1021/jacs.0c09605
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This material is based on work supported by the National
Science Foundation (CHE-1565947, initial studies) and the
Department of Energy (DE-SC0018168).
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