Joe Derosa Proton-Coupled Electron Transfer with Metal ComplexesEngle Group
Meeting04/11/19
Selection of reviews/resources for topics beyond scope of this review:• Photochemical reactions, see: Hoffmann, N. Eur. J. Org. Chem. 2017, 15, 1982.• Biological systems, see: Reece, S. Y.; Nocera, D. G. Annu. Rev. Biochem. 2009, 78, 673.• High-level theory (Marcus-Type), see: Hammes-Schiffer, S. Acc. Chem. Res. 2009, 42, 1859.
For general review, see: Huynh, M. H. V.; Meyer, T. J. Chem. Rev. 2007, 107, 5004.
History and Definitions of Proton-Coupled Electron Transfer (PCET)• In 1981, the term proton-coupled electron transfer (PCET) was first used to describe a process in which electrons and protons transferred together – specifically in a concerted e- / H+ transfer process.• Meyer and coworkers invented the term to distinguish the following process from a hydrogen atom transfer (HAT) mechanism, in which the proton and electron are delivered from the same bond.
[RuIV(bpy)2(py)(O)]2+ + [RuII(bpy)2(py)(OH2)]2+ 2 [RuIII(bpy)2(py)(OH)]2+2.1 x 105 M-1 s-1
3 x 105 M-1 s-1
JACS 1981, 103, 2897.• The mechanism is thought to be simultaneous transfer of a proton from H2O and an electron from RuII via c comproportionation.
LnRuIV O RuIILnOH
H
protonation
electron transfer
LnRuIII O RuIIILnOH
HPCET
proton and electron transferred from two distinct sources
• Despite the original definition of PCET being born out of differentiating from HAT, the terminology has evolved to include the general reaction paradigm of transfer of protons and electrons. In general, PCET can occur through several processes/elementary steps defined accordingly in the context of this review, such as:
a) Hydrogen atom transfer (HAT) - simultaneous proton/electron transfer from same underlying X–H σ orbital or bond
b) Concerted electron-proton transfer (EPT) - simultaneous (relative to period of coupled vibration, ~ 10 fs) proton/electron transfer from different and independent sources
Note: Other terms do exist, but for the purpose of this review will not be defined (i.e. concerted proton-electron transfer (CPET), electron transfer proton transfer (ET-PT), concerted electron-proton transfer (CEP)).
LnRuIV O RuIILnOH
H
protonation
electron transfer
LnRuIV O RuIILnOH
H
protonation
electron transfer
HAT EPTPCET
• In the example shown, EPT occurs at a single site – both the proton and electron are delivered from a single donor to a single acceptor (complex to complex transfer)• Another class of EPT reactions are multiple site electron-proton transfer (MS-EPT) in which concerted electron-proton transfer occurs to different acceptors or from different donors.
NH3+
O
O-
OHB
B = base
+
Os(bpy)33+
MS-EPT
NH3+
O
O-
O
Os(bpy)32++
+ BH
• MS-EPT is more common in biological systems involving enzymes or cofactors that can stabilize key reactive intermediates
JACS 2007, 129,15462.
Mechanistic Insights - EPT
• In general, the sequence of transfer events can occur in a variety of multistep mechanisms that are highly dependent on reaction conditions such as temperature or pH.
2 [RuIII(bpy)2(py)(OH)]2+
EPT
Δ G* = + 0.44 eVΔ Gº' = - 0.11 eV
Δ Gº' > + 0.55 eV
Δ Gº' > + 0.59 eV
[RuII] OH22+[RuIV] O2+ +
[RuIII][RuIII] +
in pH = 7 (ligands are bpy + py)
O+ OH3+
[RuII][RuIV] +OH3+ OH+
electron transfer
(ET)
protontransfer
(PT)
proton transfer(PT)
electron transfer(ET)
• At a neutral pH, comproportionation via EPT dominates because it avoids high energy intermediates that would result from ET-PT or PT-ET – the energy required exceeds the experimental free energy of activation.• At a low pH, PT-ET becomes more favorable through stabilization of [Ru]=OH3+.Other related processes
a) Atom-proton transfer (APT) b) Hydride-proton transfer (HPT)
[RuV] O3+ OH
H
B
JACS 2010, 132, 17670.
Angew. Chem. Int. Ed. 2002, 41, 3870.
JACS 2010, 132, 16318.
Joe Derosa Proton-Coupled Electron Transfer with Metal ComplexesEngle Group Meeting
04/11/19
Organic PCET - Phenol Case Study
• Phenols are considered to be one of the more commonly encountered organic molecules that engages in PCET.• Mechanistic studies have shown that three distinct PCET pathways can be viable for phenol-based reagents: HAT, EPT, and PT-ET.• The precise mechanism of phenol-based PCET depends on: (a) hydrogen-bond-accepting and anion-solvating effects of solvent; (b) electron affinities and bond-dissociation enthalpies of initially formed radicals; (c) electronic influence of substituents on phenol ring.
O
O
OHOH
HO
OHOH
O
O
OHOH
O
OHOH
O
O
OHOH
•O
OHOH
- H+ ET
rapid
HAT
O
O
OO•
HO
OHOH
- H+ O
O
OO•
O
OHOH
O
O
OO
•O
OHOH
- H+HAT
HHH
polar solvents
non-polar solvents
• In addition to solvent polarity accelerating specific steps in the PCET of phenols, acids can be added with peroxides to generate highly reactive peroxy radical cations to facillitate 16 fold increase in the rate of the reaction.
RO
O• + AcOH RO
OH+
OH
RO
OH
OH+
Metal-mediated PCET Processes
• PCET mechanisms are important processes in the context of metal complex reactivity because of potential insights toward biochemically mediated processes.• In general, harnessing PCET with metal-mediated paradigms is a powerful tool for studying fundamental mechanisms and enabling reactivity.
a) Water oxidation• Photosystem II is considered to be the active component in water oxidation, specifically the Mn4Ca cluster that is a part of the oxygen-evolving complex.• Most common approach toward a biomimetic Mn-cluster is photosensitized oxidation.• Ru-based catalytic studies provide evidence for a synergistic PCET and APT sequence.
RuN N
OH2N
N N N
N
2+
[RuII–OH2]2+
[RuII–OH2]2+ 2 Ce(IV)
2 Ce(III)
[RuIV=O]2+
Ce(IV)
Ce(III)
[RuV=O]3+[RuIII–OOH]2+
Ce(IV)
Ce(III) + H+
H2OH+
[RuIV–OO]2+
H2O
O2
atom-proton transfer
electrontransfer
electrontransfer
electrontransfer
• Complementary studies by Thummel and coworkers illustrating that a dinuclear catalyst could improve the turnover number (TON)
Inorg. Chem. 2010, 49, 2202.
• Burlinguette and coworkers reported a series of electronically diverse complexes and measured the turnover number – both strongly electron-donating and -withdrawing substituents generally gave lower TN due to catalyst instability, while halide substitutents performed the best. • It is hypothesized that O2 evolution catalysts require a balance between electron density on the metal and π-back bonding to the most labile ligand
RuN N
OH2
N N
N
2+
RuN N
OH2
N N
N
2+
RuN N
OH2
N N
N
2+
MeO
MeO Cl
Cl
HO2C
HO2C
TON = 200 TON = 480 TON = 210
RuCl Ru
N N NNN N
N
N
N
N
Me Me
Me Me
TON = 538
* when Me is substituted for CF3, TON = 116
proximity of Ru centersfacilitates PCET
Inorg. Chem. 2008, 47, 1793.
t-BuNH
Joe Derosa Proton-Coupled Electron Transfer with Metal ComplexesEngle Group Meeting
04/11/19
b) Oxidation of organic molecules
• Despite organic PCET processes being thermodynamically favored, the initially oxidized intermediates can often react unpredictably with the proton/electron donating reagents• In the context of PCET involving organic oxidation reactions, metal oxo species can often serve as engines for oxygen atom transfer
FeII
NN
NN
N
2+
FeIV
NN
NN
N
2+
O
Ce(IV) Ce(III)H2O +
AB
A B TON
thioansiole
benzylalcohol
cyclohexene
sulfoxide
benzaldehyde
adipicacid
10
10
5.6
Angew. Chem. Int. Ed. 2009, 48, 1803.
• In an interesting series of reports by Borovik and coworkers, Mn-oxo complexes were shown to act as bases in a PCET pathway to oxidize dihydroanthracene via C–H bond cleavage
MnIII
O-
N
NNN
HN
O
t-BuNHO
t-Bu
O
2-
[MnIIIH3buea(O)]2-
t-BuNH
MnIV
O
N
NNN
HN
O
t-BuNHO
t-Bu
O
[MnIVH3buea(O)]-
-
• The mechanism of oxidation differs based on the identity of the Mn-oxo species that is employed• The pKa difference between the two species results in a two-step or concerted mechanism
for preparation of complexes, see: JACS 2006, 128, 8728.
t-BuNH
MnIII
O-
N
NNN
HN
O
t-BuNHO
t-Bu
O
2-
[MnIIIH3buea(O)]2-
+
protontransfer
t-BuNH
MnIII
OH
N
NNN
HN
O
t-BuNHO
t-Bu
O
-
+
electrontransfer
t-BuNH
MnII
OH
N
NNN
HN
O
t-BuNHO
t-Bu
O
2-
+•
t-BuNH
MnIV
O
N
NNN
HN
O
t-BuNHO
t-Bu
O
[MnIVH3buea(O)]-
-
H
HAT /EPTmechanism
KIE > 2xthat of
[MnIIIH3buea(O)]2-
JACS 2009, 131, 2762.
• Tuning of the ligand sphere can also influence the type of reactivity that is observed, including site-selectivity, chemoselectivity, and the transformation itself• An assortment of hybrid guanadine ligands bound to a dimeric copper complex resulted in interesting divergent reactivity
CuIIIO
CuIIIO
N
N
Me2NNMe2
Me2N NMe2
N
N
NMe2Me2N
NMe2Me2N
unreactive
sterically encumberedlow oxidation potential
CuIIIO
CuIIIO
N
NMe2
Me2N NMe2Me2N
N
NMe2Me2N
• fast phenolate oxidation •• slow homodimerization •
moderate steric bulkmoderate oxidation potential
CuIIIO
CuIIIO
Me2N
NMe2
Me2N
NMe2
• fast phenolate oxidation •• fast homodimerization •
flexible ligand spherehigher oxidation potential
JACS 2009, 131, 1155.
• Several studies have focused on the effect of PCET on relatively mild C–H bond activation pathways.
R
N N
N
CuII
H
H HH
2+
triazomacrocylicligand
MeCN0 ºC
minutesseconds
TEMPO0 ºC
R
N N
N
CuIII
H
H H
2+
+TEMPO–H
+1/2
R
N N
N
CuIII
H
H H
2+
1/2
protonatedtriazomacrocylic
ligand+ Cu(MeCN)4
+1/2
• In an effort to probe the mechanism of this C–H activation step, the authors carry out EPR, DFT, and UV-Vis kinetic data that supports a PCET pathway.
JACS 2010, 132, 12299.
optimized structure shows C–H–Cu bond distances consistent with
three-centered three-electron bond
HYSCORE EPR pulse experiment consistent withcomplex having electronic ground state with unpaired
electron localized in copper dx2–y2
N N
Joe Derosa Proton-Coupled Electron Transfer with Metal ComplexesEngle Group Meeting
04/11/19
• Key step thought to be a rate-limiting PCET step involved in a binuclear copper-mediated C–H cleavage step.• Interestingly, the analogous nickel complex exhibits very different behavior under the same reaction conditions.R
N N
N
CuII
H
HH
H
2+
proposed σ-complex
N N
N
NiII
H
HH
H
2+
MeCN
base
N N
N
NiII
H
H H
+
proposed agostic interaction Ni(II)-aryl species
• The precise mechanism of this C–Ni bond formation is still debated, as there is no evidence to support a simple base assisted deprotonation mechanism and Ni(II)/(IV) oxidative addition to a C–H bond of this class has no substantial precedence.
c) Oxidation and Reduction of Hydrogen
• Hydrogen oxidation and reduction is highly sought out because of the multifaceted utility of harnessing hydrogen in ammonia production, fuel cells, and organic synthesis.
Fe Fe
S S
OC CO
Ph2P
PPh2
Ph2P
PPh2
H+
Fe Fe
S S
CO
CO
Ph2P
PPh2
Ph2P
PPh2
+
He-
Fe Fe
S S
CO
CO
Ph2P
PPh2
Ph2P
PPh2
H
H+
H2
Fe Fe
S S
CO
CO
Ph2P
PPh2
Ph2P
PPh2
+e-
terminal hydride neutral hydridic species (enhanced Fe–H hydricity)
• Hydrogen evolution complex (HEC) is thought to utilize PCET to reduce a proton to hydrogen – model systems that invoke a terminal hydride can catalyze proton reduction at 200 mV less than isomeric bridging hydride.
Coord. Chem. Rev. 2009, 253, 1476.
• The opposite process, dihydrogen oxidation, is also a fundamentally important sequence that sheds light on various modes of action in hydrogenase systems.
NiII
Ph2P
PPh2
PhP
NPPh
Bz
NBz 2+
NiP4-N
NiIIPhP
NPPh
Bz
NBz 2+
NiP4-N2
PhP
N PPh
Bz
NBz
H Hdifference in mechanism of H2 oxidation
depending on ligand sphere – NiP4-N2 20x faster!
H H
Proposed PCET cycle:
Ni
Ph2P
PPh2
PhP
NPPh
Bz
NBz 2+
H2
Ni
Ph2P
PPh2
PhP
NPPh
Bz
NBz 2+
H H
Ni
Ph2P
PPh2
PhP
NPPh
Bz
NBz 2+
H
H
Ni
Ph2P
PPh2
PhP
NPPh
Bz
NBz 2+
H
H
NiIIPh2P
PPh2
PhP
NPPh
Bz
NBz +
H
- e-
NiIIPh2P
PPh2
PhP
NPPh
Bz
NBz 2+
H- 0.6 V
B
BH
Ni
Ph2P
PPh2
PhP
NPPh
Bz
NBz 2+
- e-
base
- 0.51 V1 atm H2, pH = 8.5
JACS 2009, 131, 5935.
d) Reduction of Oxygen
• Strategies for reducing dioxygen include both primary- and secondary-sphere coordination involvement, particularly with iron, manganese, and copper catalysts.
NN
N
NNHN PhNHPh
N4Py2PhNH
(5 steps from 2-aminopicoline)
+ Fe(OTf)2(CH3CN)2N N
NHFeIIOTf
N
PhNH
Ph
THF
N N
N N
NHFeIIOTf
N
PhNH
Ph
ascorbic acid
O2N N
N N
NHFeIIIO
N
PhNH
Ph
H
+
+ 2+
AgOTf
Cp2CoN N
N N
NHFeIIO
N
PhNH
Ph
H+
20% NaOH
HOTf
• Unique stability derived from significant hydrogen bond donor/acceptor potential – complex remains intact in presence of strong acids.• Catalyst can be regenerated in many ways through a variety of redox manipulations and O2 can be reduced efficiently due to secondary sphere interactions.
2
Inorg. Chem. 2009, 48, 10024.
Joe Derosa Proton-Coupled Electron Transfer with Metal ComplexesEngle Group Meeting
04/11/19
• The stabilization effect of secondary-sphere hydrogen bond interactions in the context of oxygen reduction was qualitatively assessed in a series of cobalt oxo complexes.
CoII
N
NN
NHN
O
t-BuNHO
t-Bu
O
-
NHt-Bu
CoII
N
NN
N i-Pr
NHO
t-Bu
O
-
NHt-Bu
i-Pr CoII
N
NN
N i-Pr
NHO
t-Bu- -
i-Pr CoII
N
NN
N i-Pr
i-Pr
0.5 equiv O2DMA, rt, 1h
0.5 equiv O2DMA, rt, 1h
xs O2
xs O2
0.5 equiv O2
or
CoIII
N
NN
NHN
O
t-BuNHO
t-Bu
O
-
NHt-Bu OH
CoIII
N
NN
N i-Pr
NHO
t-Bu
O
-
NHt-Bu OH
i-Pr CoIII
N
NN
N i-Pr
NHO
t-Bu-
OHno reaction
stable > 24h stable up to 13h stable up to 5h
[M]
N
NN
NN
O
RNO
R
O
NR X H
H
H
hydrogen bond networkstabilizes intermediate
steric bulk exposes metal center for coordination
to small molecules
Inorg. Chem. 2010, 49, 3646.
e) Oxidation and Reduction of Metals
• In the context of small molecule activation, PCET is a powerful approach, but it can also be used to manipulate redox states of the metal complex itself in oxidation or reduction.• This area is heavily mechanistic in nature and does not include many synthetic applications, but there could be space for developing robust redox cycling in an organometallic catalytic process.
NFeIII
Ntetraphenylporphyrin
N
HN
Me
Me
H+N
FeIII
N
NH
HN
Me
Me
+
e-N
FeII
N
NH
HN
Me
Me
• This is another example of simple pH modularity in accessing various oxidation states of a metal species via PCET.
JACS 2008, 130, 2774.
O
Me
MeO
OMe
Me
O
RuIIN
N NH
+ NO•
MeMe
MeMe
O
Me
MeO
OMe
Me
O
RuIIIN
N N
+ NOH
MeMe
MeMe
KIE = 23
JACS 2008, 130, 14745.
• Interesting mechanistic studies have been conducted regarding the effect of distance between electron and proton transfer sites in PCET systems.• This line of inquiry has high impact on various subfields such as the understanding of complex biological systems (i.e. PSII or ribonucleotide reductases) and potential applications in charge injection semiconducting materials.
N
OO
O O
RuIII
N
N
N
O
On
+ NO
MeMe
MeMe N
OO
O O
RuII
N
N
N
O
OH
NO•
MeMe
MeMe
+
11.2 Å distance (n = 1)
seconds
H
• Based on cyclic volatammetry measurements, the two species exhibit almost identical chemically reversible oxidations.• Thermodynamic and spectroscopic measurements suggest that there is little to no interaction between redox and basic sites despite a CPET mechanism still being viable – reduction potentials of reactants can be used to calculate the energy barriers for PT and ET, thus ruling out a stepwise mechanism.
JACS 2009, 131, 9874.
Joe Derosa Proton-Coupled Electron Transfer with Metal ComplexesEngle Group Meeting
04/11/19
Applications of PCET in Other Processes• Based on the operative mechanism of PCET, there are opprotunities to discover new reactivity while also improving the energetic efficiency of existing processes.
a) PCET as lower driving force for N2 reduction
• Several groups have been interested in the catalytic reduction of N2 to NH3 using a combination of chemical oxidants and reductants
BP(i-Pr)2Fe(i-Pr)2P
(i-Pr)2P
-N2xs HBArF
4•2Et2Oxs KC8
1 atm N2
-78 ºC, Et2O
NH3
> 7 turnovers
HBArF4•2Et2O
very strong acid
pKa < 0
KC8
very strong reductant
< - 3.0 VΔΔHf > 156 kcal/mol
• Despite the elegance of acheiving this process, the corresponding redox manifold is very harsh and has an extremely high enthalpic driving force.• Peters and coworkers turned to the development of a novel PCET reagent for the direct reduction of N2 to NH3.
Cp*2Co [Cp*Co(η4-C5Me5H)]+
"H+"
"H+" ΔGcalc
Ph2NH2+
PhNH3+
-21 kcal/mol
-13 kcal/mol
[Cp*Co(η4-C5Me5H)]+
X-ray structure (exo)
JACS 2019, 141, 4721.
BP(i-Pr)2Fe(i-Pr)2P
(i-Pr)2P
+
1 atm N2
-78 ºC, Et2ONH3
~ 13 turnovers
xs Cp*2Co
xs Ph2NH2+
weaker acid
pKa = 3.2
weakerreductant
- 1.96 VΔΔHf = 77 kcal/mol
Ph2NH2+ Cp*
2Co
ACS Cent. Sci. 2017, 3, 217.
• An alternative to PCET chemical redox is photochemical PCET, which will not be covered in detail in this review, but elegant work can be found in the following review: Acc. Chem. Res. 2016, 49, 1546.
O
N N
OMn
N H+ / e-O
N N
OMn
N H+ / e-O
N N
OMn
N
H+ / e-
O
N N
OMn
NNH3
Mn-nitride
H HH
H HH
per Mn-nitride
NH
dihydroacridinestoichiometric reductant
NMe3H+BF4-
catalytic acid
NN
RuII
NN
N
N
Ru(bpy)3(PF6)2
2PF6-
O
N N
OMn
N15 5 mol% Ru(bpy)3(PF6)210 mol% NMe3H+BF4
-
DCM, blue LED, rtNH
+ 15NH3
65%
+ [Mn]red + acridine
[Mn]red
CO
TMEDA
15NH3
30%
15NH3
42%
remaining mystery complex can still produce ammonia
t-Bu
t-Bu
t-Bu
t-Bu
JACS 2019, 141, 4795.
Joe Derosa Proton-Coupled Electron Transfer with Metal ComplexesEngle Group Meeting
04/11/19
Summary of Key Concepts
reaction coordinate
ener
gy
General mechanism of PCET of metal complexes:
[Mn] X H B [Mn+1] X + B Hconcerted
PCET
PT
PT
ETET
concerted mechanism allows for milderreagents and effective, kinetically rapid
redox events to occur
reaction mechanism can be modulatedbased on pKa, ligand sphere (primary or secondary
interactions), metal identity
Important Players in PCET Chemistry
Prof. Thomas J. Meyer Prof. Jillian L. Dempsey Prof. Daniel Nocera
Prof. Robert R. Knowles Prof. James Mayer Prof. Sharon Hammes-Schiffer