Catalysts for Oxygen Production
and Utilization
Closing the Oxygen Cycle: From Biomimetic Oxidation
to Artificial Photosynthesis
Erik Karlsson
c Erik Karlsson, Stockholm 2011
Cover picture: X-ray crystal structure of water oxidation catalyst 71.
ISBN 978-91-7447-289-9
Printed in Sweden by US-AB, Stockholm 2011
Distributor: Department of Organic Chemistry, Stockholm University
“Failure is always an option”
Adam Savage
Abstract
This thesis describes the development and study of catalysts for redox reactions, which either utilize oxygen or hydrogen peroxide for the purpose of
selectively oxidizing organic substrates, or produce oxygen as the necessary
byproduct in the production of hydrogen by artificial photosynthesis.
The first chapter gives a general introduction about the use of environmentally friendly oxidants in the field of organic synthesis, and about the field of
artificial photosynthesis.
The second chapter describes a computational study of the mechanism of
palladium-catalyzed oxidative carbohydroxylation of allene-substituted conjugated dienes. The proposed mechanism, which was supported by DFT calculations, involves an unusual water attack on a (π -allyl)palladium complex.
The third chapter describes a computational study of the oxidation of unfunctionalized hydrocarbons, ethers and alcohols with hydrogen peroxide, catalyzed by methyltrioxorhenium (MTO). The mechanism was found to proceed
via rate-limiting hydride abstraction followed by hydroxide transfer in a single concerted, but highly asynchronous, step as shown by intrinsic reaction
coordinate (IRC) scans.
The fourth chapter describes the use of a new hybrid (hydroquinone-Schiff
base)cobalt catalyst as electron transfer mediator (ETM) in the palladiumcatalyzed aerobic carbocyclization of enallenes. Covalently linking the two
ETMs gave a fivefold rate increase compared to the use of separate components.
The fifth chapter describes an improved synthetic route to the
(hydroquinone-Schiff base)cobalt catalysts. Preparation of the key
intermediate 5-(2,5-hydroxyphenyl)salicylaldehyde was improved by
optimization of the key Suzuki coupling and change of protecting groups
from methyl ethers to easily cleaved THP groups. The catalysts could thus be
prepared in good overall yield from inexpensive starting materials.
Finally, the sixth chapter describes the preparation and study of two catalysts for water oxidation, both based on ligands containing imidazole groups,
analogous to the histidine residues present in the oxygen evolving complex
(OEC) and in many other metalloenzymes. The first, ruthenium-based, catalyst was found to catalyze highly efficient water oxidation induced by visible
light. The second catalyst is, to the best of our knowledge, the first homogeneous manganese complex to catalyze light-driven water oxidation.
List of Publications
This thesis is based on the following papers, which are referred to in the text
by their roman numerals.
I
Mechanism of the Palladium-Catalyzed Carbohydroxylation
of Allene-Substituted Conjugated Dienes: Rationalization of
the Recently Observed Nucleophilic Attack by Water on a (π Allyl)palladium Intermediate
Karlsson, E. A.; Bäckvall, J.-E.
Chem. Eur. J. 2008, 14, 9175–9180.
Copyright 2008 Wiley-VCH Verlag GmbH & Co. KGaA.
Reproduced with permission.
II
Oxidation of Ethers, Alcohols, and Unfunctionalized Hydrocarbons by the Methyltrioxorhenium/H2 O2 System: A Computational Study on Catalytic C–H Bond Activation
Karlsson, E. A.; Privalov T.
Chem. Eur. J. 2009, 15, 1862–1869.
Copyright 2009 Wiley-VCH Verlag GmbH & Co. KGaA.
Reproduced with permission.
III
Efficient Reoxidation of Palladium by a Hybrid Catalyst in
Aerobic Palladium-Catalyzed Carbocyclization of Enallenes
Johnston, E. V.; Karlsson, E. A.; Lindberg, S. A.; Åkermark, B.;
Bäckvall, J.-E.
Chem. Eur. J. 2009, 15, 6799–6801.
Copyright 2009 Wiley-VCH Verlag GmbH & Co. KGaA.
Reproduced with permission.
IV
Efficient Synthesis of Hybrid (Hydroquinone-Schiff
base)cobalt Oxidation Catalysts
Johnston, E. V.; Karlsson, E. A.; Tran, L.-H.; Åkermark, B.;
Bäckvall, J.-E.
Eur. J. Org. Chem. 2009, 2009, 3973–3976.
Copyright 2009 Wiley-VCH Verlag GmbH & Co. KGaA.
Reproduced with permission.
V
Light-Induced Water Oxidation by a Ru-complex Containing
a Bio-Inspired Ligand
Kärkäs, M. D.; Johnston, E. V.; Karlsson, E. A.; Lee, B.-L.; Åkermark, T.; Shariatgorji, M.; Ilag, L.; Hansson, Ö.; Bäckvall, J.-E.;
Åkermark, B.
Accepted for publication in Chem. Eur. J.
VI
Photosensitized Water Oxidation Using a Bio-Inspired
Manganese Catalyst
Karlsson, E. A.; Lee, B.-L.; Åkermark, T.; Johnston, E. V.;
Kärkäs, M. D.; Sun, J.; Hansson, Ö.; Bäckvall, J.-E.;
Åkermark, B.
Submitted to Science.
Papers not included in this thesis:
VII
Efficient Aerobic Ruthenium-Catalyzed Oxidation of
Secondary Alcohols by the Use of a Hybrid Electron Transfer
Catalyst
Johnston, E. V.; Karlsson, E. A.; Tran, L.-H.; Åkermark, B.;
Bäckvall, J.-E.
Eur. J. Org. Chem. 2010, 2010, 1971–1976.
VIII
Efficient regioselective protection of myo-inositol via facile
protecting group migration
Nkambule, C. M.; Kwezi, N. W.; Kinfe, H. H.; Nokwequ, M. G.;
Gammon, D. W.; Oscarson, S.; Karlsson, E.
Tetrahedron 2011, 67, 618–623.
IX
Tuning of the Electronic Properties of a Cyclopentadienylruthenium Catalyst to Match Racemization of Electron-Rich
and Electron-Deficient Alcohols
Verho, O.; Johnston, E. V.; Karlsson, E.; Bäckvall, J.-E.
Submitted to Chem. Eur. J.
Contents
1
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
13
1.1 Use of Environmentally Friendly Oxidants . . . . . . . . . . . . . . . . . . . . . . . . .
13
13
14
16
17
19
20
1.1.1 Biomimetic Oxidation Using a Coupled Catalytic System . . . . . . . . . . .
1.1.2 Palladium-Catalyzed Oxidative Carbocyclization of Allenes . . . . . . . . .
1.1.3 Methyltrioxorhenium (MTO) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1.2 Artificial Photosynthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1.2.1 Water Oxidation Catalysts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1.2.2 Model Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2 Mechanism of the Palladium-Catalyzed Carbohydroxylation of
Allene-Substituted Conjugated Dienes: Rationalization of the Recently
Observed Nucleophilic Attack by Water on a π -Allyl)palladium
Intermediate (Paper I) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.2 Results and Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.3 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
23
24
26
3 Oxidation of Ethers, Alcohols and Unfunctionalized Hydrocarbons by the
Methyltrioxorhenium/H2 O2 System: A Computational Study on Catalytic
C–H Bond Activation (Paper II) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.2 Results and Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.2.1 Oxidation of Alcohols and Ethers . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.2.2 Solvent Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.3 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
31
32
35
37
37
4 Efficient Reoxidation of Palladium by a Hybrid Catalyst in Aerobic,
Palladium-Catalyzed Carbocyclization of Enallenes (Paper III) . . . . . 39
4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.2 Results and Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.3 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
39
40
42
5 Efficient Synthesis of Hybrid (Hydroquinone-Schiff base)cobalt Oxidation Catalysts (Paper IV) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.2 Results and Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.3 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
45
46
48
6 Water Oxidation Catalysts Based on Imidazole-Containing Ligands (Papers V, VI) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
49
6.2 Results and Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.2.1 Synthesis of Imidazole-Based Ligands . . . . . . . . . . . . . . . . . . . . . . .
6.2.2 Ruthenium Catalyst for Water Oxidation (Paper V) . . . . . . . . . . . . . . .
6.2.3 Manganese Catalyst for Water Oxidation (Paper VI) . . . . . . . . . . . . . .
6.3 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
49
49
51
52
56
59
61
Abbreviations
bpy
2,2’-bipyridine
BVS
bond valence sum
BQ
1,4-benzoquinone
CAN
ceric ammonium nitrate
Co(salmdpt) bis(salicylideniminato-3-propyl)methylaminocobalt(II)
DCM
dichloromethane
deeb
4,4’-bis(ethoxycarbonyl)-2,2’-bipyridine
DFT
density functional theory
DMDO
dimethyldioxirane
DMSO
dimethyl sulfoxide
DMF
N,N -dimethylformamide
EPR
electron paramagnetic resonance
ETM
electron transfer mediator
Fe(Pc)
iron(II) phthalocyanine
HQ
hydroquinone
IRC
intrinsic reaction coordinate
MS
mass spectrometry
MTO
methyltrioxorhenium
NHE
normal hydrogen electrode
NMR
nuclear magnetic resonance
OEC
oxygen evolving complex
PB-SCRF
Poisson-Boltzmann self-consistent reaction field
PPTS
pyridinium p-toluenesulfonate
QST
quadratic synchronous transit
TFA
trifluoroacetic acid
TFA –
trifluoroacetate
THF
tetrahydrofuran
THP
tetrahydropyranyl
TOF
turnover frequency
TON
turnover number
UV/Vis
ultraviolet-visible
1. Introduction
1.1 Use of Environmentally Friendly Oxidants
Oxidation reactions are of fundamental importance in organic chemistry. 1
Traditionally, oxidation reactions are performed using stoichiometric amounts
of high-valent transition metals such as chromium(VI) and manganese(VII).
These methods are still used in the production of a large number of organic
compounds. 2 The major drawback with these reagents is that a large amount
of metal waste is produced, and this also leads to poor atom economy. Other
drawbacks are the toxicity and cost of transition metal-based oxidants.
Ideally, an oxidant should be inexpensive, safe, non-toxic, and have a low
molecular weight per oxidation equivalent. Two oxidants that fulfill these criteria are molecular oxygen and hydrogen peroxide. Both are inexpensive, have
relatively low toxicity and low molecular weight, and the only byproduct
formed is water. There are, however, some safety issues, particularly on an
industrial scale. Molecular oxygen and hydrogen peroxide can form explosive
mixtures with organic compounds and hydrogen peroxide can decompose in
an explosive manner when exposed to heat or catalysts.
The main problem with the use of molecular oxygen and hydrogen peroxide
as oxidants in organic synthesis is that the activation energy for the reactions
with most organic substrates is high. Molecular oxygen has a triplet ground
state, which makes reactions with closed-shell organic molecules disfavored.
Catalysts are thus necessary to facilitate the reactions.
1.1.1 Biomimetic Oxidation Using a Coupled Catalytic System
In a catalytic oxidation, a substrate-specific catalyst oxidizes the substrate to
the desired product. The catalyst is then reoxidized by a stoichiometric oxidant. Direct reoxidation of the substrate-specific catalyst with molecular oxygen can occur, but is often difficult due to the high activation barrier for reaction of the reduced form of the catalyst with oxygen (Scheme 1.1). 3 Although
direct reoxidation is successful in many cases, it fails in others because the
reduced catalyst is reoxidized too slowly, which leads to deactivation of the
catalyst by competing pathways. 4 For example in palladium-catalyzed oxidations, precipitation of palladium metal from soluble Pd 0 species often competes with the reoxidation by O2 .
One way to overcome the high activation barrier for direct reoxidation is to
introduce electron transfer mediators (ETMs) between the substrate-specific
13
catox
Starting material
Oxidized product
catred
H2O
1/2 O2
Scheme 1.1: Direct reoxidation of substrate-specific catalyst with O2 .
catalyst and O2 or H2 O2 . The single high-barrier redox step is then broken
down into several steps with low barriers (Scheme 1.2). This is similar to the
respiratory chain, which is involved in many biological oxidation processes.
Starting material
Oxidized product
catox
catred
[Fe(Pc)]ox
HQ
BQ
Fe(Pc)
H2O
1/2 O2
Scheme 1.2: Catalytic oxidation with O2 facilitated by ETMs.
The use of coupled catalytic systems with ETMs (such as that in
Scheme 1.2) significantly extends the use of oxygen and H2 O2 as terminal
oxidants in metal-catalyzed reactions. 4 These types of systems have been
applied to several different aerobic oxidation reactions such as Pd-catalyzed
1,4-addition, 5 allylic acetoxylation, 5 oxidation of terminal olefins, 5
Pd-catalyzed enallene carbocyclization, 6 and Ru-catalyzed oxidations of
alcohols and amines to ketones 7 and imines, 8 respectively (Scheme 1.3).
One of the most well known examples of oxidation using a coupled catalytic
system is the Wacker oxidation of ethylene to acetaldehyde, where CuCl2
is used as an ETM to transfer electrons from PdCl2 to molecular oxygen
(Scheme 1.4). 9
1.1.2 Palladium-Catalyzed
Allenes
Oxidative
Carbocyclization
of
Previously, our research group has reported on a palladium-catalyzed oxidative carbocyclization of allene-substituted olefins. 10 Initially a stoichiometric
amount of 1,4-benzoquinone (BQ) was used to reoxidize the palladium catalyst. Use of a stoichiometric amount of BQ, however, causes some problems.
The hydroquinone (HQ) formed and the excess BQ have to be removed by extraction with sodium hydroxide, which is unsuitable for base-sensitive products. Byproducts can also be formed from a Diels-Alder reaction between BQ
and the product.
To avoid the use of BQ as stoichiometric oxidant, a new version of
the reaction was developed, in which a catalytic amount of BQ is used.
The HQ formed is then reoxidized with molecular oxygen using iron(II)
phthalocyanine (Fe(Pc)) as oxygen-activating catalyst (Scheme 1.5). 6 This is
14
[Pd]
AcO
O
[Pd]
OAc
R
R
OH
[Pd]
OAc
R1
R3
[Pd]
E
RO
OR
E
E
R2
E
[Ru]
R2
R1
N
R2
E
E
E
HO
[Pd]
Me
R2
R1
R3
NH
R1
E
O
[Ru]
[Pd]
Me
Me
Me
Me
Me
(E=CO2Me)
Scheme 1.3: Oxidation reactions using coupled catalytic systems, with O2 as terminal
oxidant.
CH2=CH2 + 1/2 O2
cat. PdCl2
cat. CuCl2
CH3CHO
H2O
H
H
H
PdII
2 CuI
1/2 O2
Pd0
2 CuII
H2O
+ H
H2O
O
H
Scheme 1.4: Wacker oxidation of ethylene to acetaldehyde.
E
E
n
+ 1/2 O2
R'
(E=CO2Me)
R
1 mol% of Pd(TFA)2
4 mol% of benzoquinone
1 mol% of Fe(Pc)
E
E
n
+ H2O
toluene, 95 oC
R'
R
(75-96%)
Scheme 1.5: Palladium-catalyzed aerobic carbocyclization of enallenes.
15
a coupled catalytic oxidation using Pd(TFA)2 as substrate-specific catalyst,
BQ and Fe(Pc) as ETMs, and O2 as terminal oxidant (Scheme 1.6).
E
E
OH
n
[Fe(Pc)]ox
PdII
R'
E
R
H2O
OH
O
E
Pd0
n
1/2 O2
Fe(Pc)
O
R
R'
(E = CO2Me)
Scheme 1.6: Coupled catalytic system for aerobic carbocyclization of enallenes.
1.1.3 Methyltrioxorhenium (MTO)
Methyltrioxorhenium (MTO, 1) 11 is a widely used catalyst for oxidation reactions with hydrogen peroxide as terminal oxidant. 12 Reaction of MTO with
H2 O2 affords monoperoxo complex 2, which reacts with a second equivalent
of H2 O2 to form the diperoxo complex 3 (Scheme 1.7). 13 In solution, in the
presence of an excess of H2 O2 , complex 3 is the most abundant species. Both
2 and 3 have been fully characterized by ultraviolet-visible (UV/Vis) and nuclear magnetic resonance (NMR) spectroscopy. 14,15 Complex 3 has also been
characterized by X-ray crystallography. 14
O
Me Re O
O
1
H2O2
H2O
O O
Me Re O
O
2
H2O2
H2O
O O
Me Re O
O O
3
Nu
O Nu
O O
Me Re O
O
O Nu
4
Scheme 1.7: General mechanism of MTO-catalyzed oxidation (Nu = R3 N, R3 P, R2 S).
Unlike other transition metal-based oxidants, the redox activity of Re is not
involved in the catalytic cycle. Instead the rhenium acts as a Lewis acid, activating the peroxo oxygens in complexes 2 and 3 towards nucleophilic attack.
16
The nucleophile, which could be the lone pair of a heteroatom (N, P, S) or the
π -bond of an olefin, attacks one of the peroxo oxygens leading to cleavage of
the O-O bond and formation of complex 4 (Scheme 1.7). Release of product
then regenerates complex 2.
MTO is particularly useful as a catalyst for epoxidation of olefins, reported
by Herrmann in 1991. 16 Initially, an anhydrous solution of H2 O2 in tertbutanol was used to minimize hydrolysis of the resulting epoxide, but significant hydrolysis still occurred in many cases due to the water formed as
byproduct and the Lewis acidity of MTO. This problem could be avoided
by addition of an amine in excess, however with the expense of severely
reduced catalytic activity. 17 Later, it was reported by Sharpless that a substoichiometric amount of pyridine as cocatalyst accelerates the reaction and
also prevents hydrolysis. 18 The solvent was also changed from tert-butanol to
dichloromethane (DCM). Thus, even hydrolytically sensitive epoxides could
be obtained, even though aqueous H2 O2 was used as oxidant.
1.2 Artificial Photosynthesis
The search for clean and renewable fuels is one of the greatest challenges of
the 21st century. 19,20 One of the many options proposed is the use of hydrogen, which is popularly known as the so called “hydrogen economy”. 21 In the
realization of this, however, there are still several major challenges to be overcome. First of all, hydrogen is a highly flammable gas, making safe handling
and storage difficult. Furthermore, as hydrogen is not naturally abundant, it
has to be produced synthetically, a process which requires the input of energy.
Hydrogen is thus properly classified as an energy carrier and not as an energy
source.
Nowadays, the most important process for hydrogen production is steam
reforming of natural gas (Eq 1.1). Coal could also be used in the water gas
reaction (Eq 1.2). The carbon monoxide produced as byproduct in both processes could either be utilized for other purposes, or be used to produce more
hydrogen, employing the water gas shift reaction (Eq 1.3). The bottom line
is thus that fossil fuels are used to make hydrogen, and as usual when utilizing fossil fuels, carbon dioxide (Eq 1.3) is obtained as a byproduct, which
according to common practice is released into the atmosphere. As such, until
those processes have been replaced, hydrogen should be considered a nonrenewable fuel.
The electrolysis of water (Eq 1.4), which as a matter of fact is the oldest technology for large-scale hydrogen production, provides hydrogen without simultaneous production of CO2 . Unfortunately, due do the large input of
electricity required, its use has, for economical reasons, been limited in favor
of the cheaper fossil fuel-based alternatives. Furthermore, the environmental
consequences of the electricity generation have to be taken into account.
17
CH4 + H2 O −−→ 3 H2 + CO
(1.1)
C + H2 O −−→ H2 + CO
(1.2)
CO + H2 O −−→ H2 + CO2
(1.3)
E −◦ =1.23 V
2 H2 O −−−−−−→ 2 H2 + O2
(1.4)
Sunlight is a promising source of renewable energy, but its use has so far
been severely limited by the high costs of the currently available technology. 20
The availability of sunlight also varies greatly over the day and the year, posing serious problems for the direct generation of electricity from sunlight,
unless technology for the large-scale storage of energy is available. The problem of solar energy utilization has, however, been solved hundreds of millions
of years ago by nature, in the form of the photosynthesis occurring in plants,
algae and many species of bacteria (Eq 1.5).
hν
n CO2 + n H2 O −→ C(H2 O)n + n O2
(1.5)
hν
2 H2 O −→ 2 H2 + O2
(1.6)
Photosynthesis leads to the generation of biomass, which could be burnt for
energy, subsequently used for hydrogen production, for example by the electrolysis of water. This is, unfortunately, a highly inefficient process due to the
great losses of heat at each stage. Another option is the chemical production
of hydrogen, by the means of biomass gasification, but that is also fairly inefficient. Conversely, by taking inspiration from nature, instead of exploiting it,
artificial photosynthesis could be accomplished. This has been envisioned to
efficiently afford hydrogen by the direct splitting of water using solar energy
(Eq 1.6). 20
e-
e-
2 H 2O
H2
D
O2 + 4 H+
P
A
2 H+
Figure 1.1: Artificial photosynthesis (D = donor, P = photosensitizer, A = acceptor).
The basic principle of artificial photosynthesis is illustrated in Figure 1.1.
The system consists of a photosensitizer (P), an electron acceptor (A), and
an electron donor (D). After excitation by visible light the photosensitizer,
18
corresponding to chlorophyll in photosynthesis, transfers an electron to the
acceptor, where the electrons are used to reduce protons to hydrogen. The
photosensitizer, now in its oxidized state, then abstracts an electron from
the donor or water oxidation catalyst, corresponding to the oxygen evolving
complex (OEC) in photosystem II. After absorption of four photons, the water
oxidation catalyst has lost four electrons, enabling it to oxidize two molecules
of water to one molecule of oxygen, thus returning to its reduced state, ready
to deliver more electrons to the photosensitizer.
1.2.1 Water Oxidation Catalysts
One of the major challenges in the realization of artificial photosynthesis is the
development of an efficient and inexpensive catalyst for water oxidation. The
difficulties arise from the complicated nature of the four-electron oxidation of
water to oxygen, and from the strongly oxidizing conditions necessary, under
which many of the organic ligands commonly used are readily degraded.
3+
4+
OH2
N
N
O
Ru
N
N
N
Ru
N
N
N
R
N
N
N
N N
N
N
H2O
R
Ru
Ru
Cl
N
N
R
R
N
N
N
R = CH3, CF3, NMe2
5
6
Figure 1.2: Ruthenium-based catalysts for water oxidation.
The first homogeneous catalyst for water oxidation (5) was reported by
Meyer et al. in 1982. 22 Catalyst 5, which is based on ruthenium, was shown to
oxidize water with a turnover number (TON) of ca 13 using ceric ammonium
nitrate (CAN) as the oxidant. 23 After the initial breakthrough, however, the
progress in the field was slow for more than twenty years, until 2005 when
Thummel et al. reported a series of ruthenium-based catalysts (6) that are
able to catalyze water oxidation with greatly improved TONs of up to about
500, also using CAN as oxidant. 24 Since then, a variety of ruthenium-based
catalysts have been reported, ranging from mononuclear to multinuclear complexes. 25–36 In addition, a few catalysts based on iridium 37,38 and cobalt 39,40
have been reported.
19
Despite the relatively high efficiency of the recently reported ruthenium catalysts, the high cost and low natural abundance of ruthenium makes their use
in large scale applications questionable. On the contrary, manganese, which
is present in the active site of the OEC as an oxo-bridged Mn4 Ca cluster, 41 is
both inexpensive and readily available, being after iron and titanium the third
most abundant transition metal in Earth’s crust. 42 Inspired by the OEC, many
attempts have been made to develop manganese-based catalysts for water oxidation. Several homogeneous manganese complexes have been prepared and
studied as models of the OEC, 43–46 but none of these have so far succeeded in
oxidizing water catalytically, using a one-electron oxidant as required for application in a system for artificial photosynthesis. Two of the most well-known
model complexes are shown in Figure 1.3. 43,44
3+
N
N
N Mn
H2O
O
O
OH2
Mn N
N
N
2+
N
OH2
N Mn
N
N
7
O
N
N
Mn N
O
H2O
O
N
O
8
Figure 1.3: Manganese complexes as models for the OEC.
1.2.2 Model Systems
Since a complete system for artificial photosynthesis is fairly complicated,
simpler model systems are necessary for testing the performance of water oxidation catalysts. The most simple model involves the use of a one-electron
oxidant in stoichiometric amounts. Most commonly, CAN has been used for
this purpose, but this is not a very realistic model in the context of artificial
photosynthesis, owing to the fact that CAN has a very high redox potential
of +1.61 V vs normal hydrogen electrode (NHE), 47 hardly achievable using
visible light in combination with a photosensitizer. Additionally, CAN only
works under strongly acidic conditions (pH ∼ 1), limiting the scope to catalysts that are acid stable, thus excluding most complexes of first row transition
metals, such as manganese.
On the contrary, Ru(bpy)32+ (bpy = 2,2’-bipyridine), a commonly used photosensitizer, has a significantly lower redox potential (+1.26 V vs NHE). 36
The oxidized form, Ru(bpy)33+ , which is the oxidant formed in situ when
Ru(bpy)32+ is used as photosensitizer, could thus be used as a one-electron
oxidant in a more realistic model system. 28,36,40 Despite being highly reac20
Scheme 1.8: Model system using Ru(bpy)32+ as photosensitizer and S2 O82 – as electron
acceptor (WOC = water oxidation catalyst).
tive, Ru(bpy)33+ is easily prepared by oxidation of Ru(bpy)32+ with PbO2 in
aqueous H2 SO4 , followed by precipitation as the hexafluorophosphate salt. 48
One step further towards the system shown in Figure 1.1 is to use visible
light and a photosensitizer instead of a stoichiometric oxidant. The acceptor
part (A) is still omitted, and replaced by a chemical electron acceptor, such as
persulfate (S2 O82 – ), present in stoichiometric amounts (Scheme 1.8). 29,34–36
The distinction between an oxidant and an electron acceptor is somewhat subtle though. In this work, a compound reactive enough to directly oxidize the
water oxidation catalyst is referred to as an oxidant, while a less reactive compound, which needs the aid of light and a photosensitizer, is referred to as an
acceptor.
21
2. Mechanism of the PalladiumCatalyzed Carbohydroxylation of
Allene-Substituted Conjugated
Dienes: Rationalization of the
Recently Observed Nucleophilic
Attack by Water on a π -Allyl)palladium
Intermediate (Paper I)
2.1 Introduction
In the previously reported palladium-catalyzed carbohydroxylation
of allene-substituted dienes, 49 allene-diene 9 reacts with water in the
presence of BQ (10) and Pd(TFA)2 to form the product 11 (Scheme 2.1).
The BQ could either be used in stoichiometric amounts, or in catalytic
amounts in combination with Fe(Pc) and O2 as terminal oxidant, in a
triple-catalytic system similar to that shown in Scheme 1.6. The reaction,
which occurs in water, is suggested to involve water attack on an intermediate
(π -allyl)palladium complex.
E E
O
·
H E
HO
+ H2O +
OH
E
+
O
9
Pd(TFA)2
(1 mol%)
H2O/THF
(4:1)
10
H
OH
11
12
(E = CO2Me)
Scheme 2.1: Carbocyclization of allene-substituted dienes.
Since water attack on (π -allyl)palladium complexes is unusual, 50 it was of
interest to elucidate the mechanism of the reaction in Scheme 2.1. This was
investigated by the means of density functional theory (DFT) calculations.
The calculations are based on the proposed mechanism shown in Scheme 2.2.
23
E E
E E
Pd(TFA)2
E E
.
.
TS13-14
H2O Pd
O
O
9
O
H2O
O
Pd
H2O
O H
CF3
CF3
13
14
E E
E E
H2O
E E
H2O
-TFA
Pd
OH2
15
TS15-16
OMe
E
O
E E
BQ
TS17-18
H2O Pd
OH2
Pd
OH2
O
OH2
16
17
E E
E E
E E
H2O Pd
OH2
18
19
TS16-17
H2O Pd
HO
HO
TFA
H2O
O
TS20-21
Pd
H
O
Pd
11
+ Pd(II) + hydroquinone
H2O
O
20
H2O
O
21
Scheme 2.2: Mechanism of the Pd(II)-catalyzed oxidative carbocyclization of allenediene 9 (E = CO2 Me).
2.2 Results and Discussion
All stable intermediates and transition states in the proposed mechanism above
were optimized by DFT calculations using the B3LYP functional 51 and the
lacvp**/6-31G(d,p) basis set 52,53 in the gas phase. The gas phase structures
were then used for solvent calculations using the Poisson-Boltzmann selfconsistent reaction field (PB-SCRF) method 54 with water and tetrahydrofuran
(THF) as solvents.
The reaction starts by formation of complex 13 (Figure 2.1(a)) between the
substrate 9 and Pd(TFA)2 followed by allylic C−H activation via the transition state TS13-14 (Figure 2.1(b)) to form the vinyl-palladium complex 14
(Figure 2.2(a)). The trifluoroacetic acid (TFA) ligand is then exchanged for
water to give the more stable complex 15 (Figure 2.2(b)), followed by migratory insertion to give σ -allylpalladium 16 (Figure 2.3(b)) via the transition
state TS15-16 (Figure 2.3(a)).
The σ -allylpalladium complex 16 is subsequently isomerized, via the intermediate 17 and transition states TS16-17 and TS17-18 , to the more stable π allylpalladium complex 18, where the palladium is bound to the carbons C2,
24
(a) Structure of complex 13.
(b) Structure of transition state TS13-14 .
Figure 2.1
C3 and C4 (Figure 2.4(a)). The bond lengths to the terminal carbons Pd−C2
(2.16 Å) and Pd−C4 (2.20 Å) are similar. In the next step complex 18 should
be attacked by water to form product 11. Water is, however, too poor a nucleophile to react with unactivated π -allylpalladium complexes such as 18. 50
The water attack requires the presence of BQ, which is assumed to coordinate
to palladium forming complex 19 (Figure 2.4(b)).
The terminal double bond in 19 could then coordinate to palladium forming the chelated complex 20. In complex 20 the Pd−C4 distance (2.72 Å) is
significantly longer than the Pd−C2 distance (2.16 Å), suggesting a high reactivity towards nucleophilic attack at C4. Indeed a transition state (TS20-21 ,
Figure 2.5(b)) for the attack of water on complex 20 was found with an activation energy of 10.7 kcal/mol in water with respect to 20 (Figure 2.8). Complex
21 (Figure 2.6) is then formed, which after decomplexation releases the product 11.
The calculated energy profile for the entire reaction sequence in the gas
phase is given in Figure 2.7 and the energy profile in water, obtained from
PB-SCRF calculations of the gas phase geometries is given in Figure 2.8. The
energy profile in THF is similar to that in water. We have not calculated the
transition states for the ligand exchanges converting 14 −−→ 15, 18 −−→ 19 and
19 −−→ 20, since these transition states are supposed to be quite low and will
not change the overall energy profile.
The first two steps, allylic C−H activation (13 −−→ 15) and migratory insertion (15 −−→ 16) are expected to be fast and exothermic. After that the energy
surface is essentially flat, giving an equilibrating mixture of allylpalladium
complexes 16, 17, 18, 19 and 20. The most stable species in water is 18 at
−43 kcal/mol with respect to 13, and the most stable species in the gas phase
25
(a) Structure of complex 14.
(b) Structure of complex 15
Figure 2.2
is 19 at −45 kcal/mol. The rate-determining step is the water attack which
occurs through TS20-21 . The total barrier is 23 kcal/mol with respect to 18 in
water (Figure 2.8) and 27 kcal/mol with respect to 19 in the gas phase (Figure 2.7).
2.3 Conclusions
We have found that the palladium-catalyzed reaction of allene-substituted
dienes in water proceeds via the pathway proposed in our previous
experimental work. Coordination of a carbon-carbon double bond in
the endo-(π -allyl)palladium complex 19, obtained from intramolecular
syn-carbopalladation of a 1,3-cyclohexadiene, is a highly likely intermediate
according to DFT calculations. The calculations predict the formation of
intermediate 20 which is attacked by water on the allylic carbon. The
transition state of the water attack is, according to the PB-SCRF calculations
in water, 23 kcal/mol above the most stable species 18.
26
(a) Structure of transition state TS15-16 .
(b) Structure of complex 16.
Figure 2.3
(a) Structure of complex 18.
(b) Structure of complex 19.
Figure 2.4
(a) Structure of complex 20.
(b) Structure of transition state TS20-21 .
Figure 2.5
27
Figure 2.6: Structure of complex 21.
20
TS13-14
9
10
14
−1
Energy (kcal/mol)
0
-10
-20
-30
13
0
TS15-16
−10
TS20-21
−18
15
−16
TS16-17
−33
-40
-50
16
−40
TS17-18
−34
17
−36
-60
Figure 2.7: Energy profile of the reaction in the gas phase.
28
19
−45
18
−44
20
−36
21
−47
20
TS13-14
10
10
Energy (kcal/mol)
0
-10
-20
-30
13
0
14
3
TS15-16
−9
TS20-21
−20
15
−15
TS16-17
−33
-40
-50
16
−38
TS17-18
−34
17
−37
19
−37
20
−31
18
−43
21
−41
-60
Figure 2.8: Energy profile for the reaction in water.
29
3. Oxidation of Ethers, Alcohols
and Unfunctionalized Hydrocarbons
by the Methyltrioxorhenium/H2O2
System: A Computational Study
on Catalytic C–H Bond Activation
(Paper II)
3.1 Introduction
Methyltrioxorhenium (MTO) has been reported to catalyze oxidation of unfunctionalized tertiary hydrocarbons to alcohols using hydrogen peroxide as
terminal oxidant. 55,56 The mechanism of this reaction is intriguing, because
hydrocarbons do not have any obvious nucleophilic site that could attack the
peroxide oxygen in MTO. It has also been shown that the reaction does not
proceed via radical intermediates. 57 Instead, based on an analogy with the oxidation of hydrocarbons using dimethyldioxirane (DMDO), 58 it was proposed
that the reaction proceeds via a side-on insertion of the oxygen atom into the
C−H bond (Scheme 3.1). 56 However, there is no experimental evidence for
the side-on insertion. Furthermore, it is highly unlikely due to the great steric
hindrance when a tertiary C−H bond is approached from the side.
O O
Me Re O
O O
H
R
O O
Me Re O
H
O
O
R
Scheme 3.1: Side-on insertion mechanism.
Another option is hydride abstraction, which implies the presence of a carbocationic intermediate (Scheme 3.2). However, according to experimental
data, 55 there is complete retention of stereochemistry, and when an alcohol
is used as solvent no ether resulting from reaction of the carbocation with
the solvent is formed. The stereospecific cleavage and lack of ether formation
speak against the existence of a stable carbocationic intermediate. However, if
the intermediate ion pair collapses rapidly to the product via hydroxide ion abstraction, before it has time to rearrange or dissociate, the hydride abstraction
mechanism could still be valid. In order to further investigate if a hydride ab31
straction mechanism is possible, a DFT-based (B3LYP 51 /lacvp** 52,53 ) computational study was performed.
O O
Me Re O
O O
H R
O O
Me Re O
O O H
R
O O
Me Re O
H
O
O
R
Scheme 3.2: Hydride abstraction mechanism.
3.2 Results and Discussion
The calculated structures of the catalytically active species MeRe(O)(O2 )2 (3)
and MeRe(O)2 (O2 ) (2) are shown in Figure 3.1. All geometries were optimized in the gas phase.
(a) Complex 3.
(b) Complex 2.
Figure 3.1: Optimized structures of the catalytically active species MeRe(O)(O2 )2 (3)
and MeRe(O)2 (O2 ) (2). All distances are in Å.
Initially, the reaction between the diperoxo species 3 and cis-1,2-dimethylcyclohexane (22) was investigated (Scheme 3.3). 55 Transition states were located for abstraction of the equatorial (TS3-23 ) and axial (TS3-24 ) hydrogens
(Figure 3.2), using the quadratic synchronous transit (QST) method in the
gas phase. The transition states have almost equal potential energy barriers of
23 kcal/mol with respect to starting materials. In both transition states there
is an elongation of the C−H bond and a linear arrangement of C, H, and O,
which is in accordance with a hydride abstraction mechanism. The O−O bond
is also elongated, which suggests that the other oxygen acts as a leaving group
in an SN 2-type reaction where the electrons from the hydride enter the O−O
antibonding orbital.
Whereas the transition state structures clearly show that the reaction starts
with hydride abstraction, it is not obvious how the reaction proceeds from
the transition states towards the product complexes 23 and 24. To investigate
this, intrinsic reaction coordinate (IRC) scans were performed from TS3-23
and TS3-24 towards the products. Selected frames from the IRC scan starting
32
TS
3-2
eq
3
ua
tor
ial
CH
O O
O Re Me
O O
H
al
CH
4
-2
TS 3
22
3
a xi
H
H
H
H
2
OH
23
H
25
O
Me
O
Re
O
O
O
H 24
H
2
OH
25
Scheme 3.3: Oxidation of cis-1,2-dimethylcyclohexane by diperoxo complex 3.
(a) Transition state TS3-23 .
(b) Transition state TS3-24 .
Figure 3.2: Transition states for the oxidation of the equatorial and axial C−H bonds
of cis-1,2-dimethylcyclohexane by complex 3. All distances are in Å.
from TS3-23 are shown in Figure 3.3. The results of the IRC scan from TS3-24
are similar. The IRC scan shows that the reaction proceeds from TS3-23 to the
product complex 23 in a concerted fashion without any intermediates. Even
though the reaction is concerted, it is still highly asynchronous. First the hydride is transferred from carbon to oxygen, while the electrons populate the
O−O antibonding orbital leading to cleavage of the O−O bond and formation of a Re-bound OH-group and a carbocation. The OH-group, which now
has its partially positively charged hydrogen oriented towards the carbocation,
then rotates around the Re−O bond to orient the negatively charged oxygen
towards the carbocation. The OH-group then transfers from rhenium to carbon
leading to the product complex 23. The fact that no cationic intermediate is
formed is in agreement with the observed stereospecificity of the reaction and
the absence of ether products resulting from reaction with alcoholic solvents.
For example, it has been demonstrated that oxidation of 22 in tert-butanol
as solvent affords the corresponding alcohol (25) as a single diastereoisomer
with retention of configuration in 98 % yield (Scheme 3.3). 55
For completeness, the oxidation of 22 by the monoperoxo complex 2, was
subsequently modeled. The transition state (TS2-26 ) is shown in Figure 3.4,
and the potential energy barrier is 30 kcal/mol, which is 7 kcal/mol higher
33
(a) Frame 05: 20.5 kcal/mol
(b) Frame 10: 15.5 kcal/mol
(c) Frame 15: 4.1 kcal/mol
(d) Frame 20: −11.5 kcal/mol
(e) Frame 25: −25.9 kcal/mol
(f) Frame 30: −38.7 kcal/mol
(g) Frame 35: −50.8 kcal/mol
(h) Frame 40: −60.8 kcal/mol
(i) Frame 45: −65.7 kcal/mol
(j) Frame 50: −67.4 kcal/mol
Figure 3.3: Selected frames from IRC scan from the transition state TS3-23 towards
23. All distances are in Å. The OH-transfer is clearly seen starting from Frame 30
onwards.
34
Figure 3.4: Transition state (TS2-26 ) for the oxidation of the equatorial C−H bond of
cis-1,2-dimethylcyclohexane by monoperoxo complex 2. All distances are in Å.
than for oxidation by complex 3. As comparison, the hypothetical oxidation
of toluene to benzyl alcohol was also modeled. The transition state (TS3-27 ),
which is shown in Figure 3.5, has a barrier of 27 kcal/mol. The IRC scans
from TS2-26 and TS3-27 towards the corresponding products are both similar
to the one from TS3-23 .
Figure 3.5: Transition state (TS3-27 ) for the oxidation of toluene by complex 3. All
distances are in Å.
3.2.1 Oxidation of Alcohols and Ethers
MTO has also been shown to catalyze oxidation of secondary alcohols to
ketones. 55–57 Interestingly, methyl ethers of secondary alcohols are also
oxidized to ketones under the same reaction conditions. 55,57 Attempts to
model the classical mechanism of alcohol oxidation, involving alkoxide
formation with subsequent C−H bond cleavage, were unsuccessful.
Re-alkoxide and Re-carbonyl intermediates could be found, but their energies
are 10 and 18 kcal/mol above the starting material, respectively. The barrier
for formation of the Re-carbonyl intermediate was found to be as high as
40 kcal/mol, with respect to the starting materials.
Instead, for the oxidation of 1-phenylethanol (29), a transition state (TS3-28 )
involving hydride abstraction, similar to those obtained for oxidation of hydrocarbons, was located with an activation energy of 20 kcal/mol (Figure 3.6).
The transition state has the same linear arrangement of C, H, and O as those of
35
Figure 3.6: Transition state (TS3-28 ) for the oxidation of 1-phenylethanol by complex
3. All distances are in Å.
hydrocarbon oxidation, and there is no interaction between the alcohol oxygen
and rhenium. An IRC scan resulted in a ketone hydrate (28), in the same manner as an alcohol is produced from TS3-23 . Decomplexation and elimination
of water would then generate the ketone (Scheme 3.4). The deuterium kinetic
isotope effect (kH /kD ) was calculated to be 2.9, which is in good agreement
with the experimental value of 3.2. 57
H OH
TS3-28
Ph
29
3
O O
Me Re O
H
O
O
Ph
OH
28
O
HO OH
Ph
Ph
30
2
H 2O
31
Scheme 3.4: Oxidation of 1-phenylethanol by complex 3.
The absence of O−H bond cleavage in TS3-28 could explain why the reaction also works with ethers. Indeed, a similar transition state (TS3-32 ) for
the oxidation of 1-phenylethyl methyl ether (33) was found (Figure 3.7), with
an activation energy of 21 kcal/mol. Analogously, the IRC scan resulted in
a hemiacetal (32), which after decomplexation and elimination of methanol
would afford the corresponding ketone (Scheme 3.5).
Figure 3.7: Transition state (TS3-32 ) for the oxidation of 1-phenylethyl methyl ether
by complex 3. All distances are in Å.
36
H OMe TS3-32
Ph
33
3
O O
Me Re O
H
O
O
Ph
OMe
32
O
HO OMe
Ph
Ph
34
MeOH
2
31
Scheme 3.5: Oxidation of 1-phenylethyl methyl ether by complex 3.
3.2.2 Solvent Effects
The gas phase structures were used to calculate solution phase energies using
the PB-SCRF method. 54 The barriers for all transition states in the gas phase,
and in toluene, acetonitrile, and water are given in Table 3.1. Only minor solvent effects were observed. This further contradicts the formation of an ionic
intermediate.
Table 3.1: Calculated barriers in the gas phase and in solution with respect to starting
materials. All energies are raw potential energies in kcal/mol.
∆E ‡ (gas)
∆E ‡ (toluene)
∆E ‡ (MeCN)
∆E ‡ (H2 O)
TS3-23
22.7
21.9
21.4
20.2
TS3-24
23.0
22.3
22.1
21.0
TS2-26
29.9
29.2
28.6
27.9
TS3-27
26.7
26.1
24.9
23.1
TS3-28
20.7
20.6
22.4
20.0
TS3-32
19.8
21.7
23.2
22.3
3.3 Conclusions
A new mechanism for the MTO-catalyzed oxidation of tertiary hydrocarbons,
alcohols, and ethers using hydrogen peroxide has been proposed and supported by DFT calculations. All reactions proceed through an initial hydride
abstraction followed by hydroxide transfer in a single concerted step without
formation of ionic intermediates, as shown by IRC scans. For tertiary hydrocarbons, alcohols are formed directly. For alcohols and methyl ethers, hydrates
and hemiacetals are formed, respectively, which after elimination of water or
methanol afford the corresponding ketone.
37
4. Efficient Reoxidation of Palladium
by a Hybrid Catalyst in Aerobic,
Palladium-Catalyzed Carbocyclization
of Enallenes (Paper III)
4.1 Introduction
In the palladium-catalyzed aerobic carbocyclization of enallenes (Scheme 1.5,
Scheme 1.6), 6 a triple-catalytic system consisting of Pd(TFA)2 , BQ and
Fe(Pc) was used to transfer electrons from the substrate to molecular oxygen.
The reaction was, however, slow and required elevated temperature (95 ◦C).
Slow addition of the substrate was also necessary to avoid non-oxidative
side-reactions due to the inefficient electron transfer. The solvent was also
changed from THF in the original stoichiometric reaction 10 to toluene in
order to accommodate the required temperature. This is far from optimal due
to the insolubility of Pd(TFA)2 in toluene.
One way to improve the election transfer would be to covalently link BQ to
the oxygen-activating catalyst. The electron transfer then becomes intramolecular instead of intermolecular. This had been done previously in the group by
linking HQ to a porphyrin. 59 Although the use of this catalyst led to improved
electron transfer it is difficult to synthesize and furthermore it is sensitive to
degradation. More recently, attempts were made to link HQ to Fe(Pc), both directly and with a tether, without any success. The problem could have been the
very limited solubility of Fe(Pc) derivatives in most solvents. Whereas Fe(Pc)
works efficiently as a heterogeneous catalyst in the aerobic oxidation of HQ,
it seems that the molecule containing the BQ moiety has to be in solution to
efficiently reoxidize the palladium catalyst.
The attention was therefore turned towards cobalt Schiff base complexes
instead, which finally led to development of the hybrid catalysts 35 and 36
(Scheme 4.1). Their synthesis and application in the palladium-catalyzed diacetoxylation of conjugated dienes was previously reported in a communication. 60 A preliminary study on the application of catalyst 36 in the carbocyclization of enallenes was also reported. Unfortunately, there were only minor
improvements compared to the triple-catalytic system. The reason is probably
that catalyst 36 has very low solubility in toluene.
While studying the reaction with stoichiometric amounts of BQ, it was discovered that the presence of protic solvents, such as methanol, led to a sig39
OH
OH
O
N
OH
N
Co
N
HO
Co
O N N
HO
HO
O
HO
35
O
OH
36
Scheme 4.1: Hybrid catalysts 35 and 36.
nificant acceleration of the reaction. In mixtures of THF and methanol the
reaction went to completion within 5 minutes. The study also suggested that
palladium acetate is more efficient than Pd(TFA)2 . Thus, we decided to study
the aerobic carbocyclization of enallenes in the presence of protic solvents, using palladium acetate and hybrid catalyst 35, which is more soluble in organic
solvents than 36.
4.2 Results and Discussion
Initially the carbocyclization was investigated using substrate 37, Pd(OAc)2
and hybrid catalyst 35 under pure oxygen at atmospheric pressure, by varying
solvents, temperature and catalytic loadings (Scheme 4.2, Table 4.1). When
THF/MeOH (4:1) was used with 5 mol% Pd(OAc)2 and 5 mol% of 35 at room
temperature, 95 % conversion was achieved within 24 h (Table 4.1, Entry 1).
When the solvent was changed to pure methanol the reaction time decreased
to 5 h and the reaction also went to completion (Table 4.1, Entry 2). On the
contrary, when pure THF was used, only 47 % conversion was obtained after
24 h (Table 4.1, Entry 3). This is in accordance with the previous observation
that the reaction with stoichiometric amounts of BQ is accelerated by protic
solvents.
Pd(OAc)2 (cat)
35 or 36 (cat)
E E
·
solvent
O2 (1 atm)
37
HE E
H
38
Scheme 4.2: Aerobic carbocyclization of substrate 37.
By increasing the temperature to 40 ◦C, the loadings of Pd(OAc)2 and 35
could be lowered to 2.5 mol% for both catalysts, giving full conversion in 3 h
(Table 4.1, Entry 4). Changing the solvent to ethanol gave identical results
(Table 4.1, Entry 5). In ethanol, the reaction time could be shortened even
40
Table 4.1: Aerobic carbocyclization of substrate 37.
T
Time
Conversionb
(◦C)
(h)
(%)
THF/MeOH (4:1)
23
24
95
35 (5.0)
MeOH
23
5
100
5.0
35 (5.0)
THF
23
24
47
4
2.5
35 (2.5)
MeOH
40
3
100
5
2.5
35 (2.5)
EtOH
40
3
100
6
2.5
35 (2.5)
EtOH
75
0.3
100
7
1.0
35 (1.0)
EtOH
75
2
100
8c
1.0
35 (1.0)
EtOH
75
0.8
100
9
2.5
36 (2.5)
EtOH
75
4
100
Pd(OAc)2
Catalyst
(mol%)
(mol%)
1
5.0
35 (5.0)
2
5.0
3
Solvent
a All
reactions were performed at 1 mmol scale in 5 ml solvent under O2 (1 atm).
were determined by 1H NMR after filtration through a silica plug.
c 2 ml of solvent was used.
b Conversions
further to 0.3 h by increasing the temperature to 75 ◦C (Table 4.1, Entry 6).
When the catalytic loadings of Pd(OAc)2 and 35 were lowered to 1 mol% the
reaction time increased to 2 h (Table 4.1, Entry 7). The rate could also be
improved by increasing the concentration (Table 4.1, Entry 8). When catalyst
36 was used instead of 35, the reaction time increased from 0.3 h (Table 4.1,
Entry 6) to 4 h (Table 4.1, Entry 9). This is probably due to the low solubility
of catalyst 36 in ethanol.
To estimate the efficiency of catalyst 35, the reaction in Table 4.1, Entry 6
was repeated using separate bis(salicylideniminato-3-propyl)methylaminocobalt(II) (Co(salmdpt)) (2.5 mol%) and BQ (5 mol%) instead of catalyst
35. The reaction time was then increased from 0.3 h to 1.5 h. Covalently
linking BQ to Co(salmdpt) thus gave a fivefold rate increase due to the faster
intramolecular electron transfer.
The substrate scope was investigated by performing the reaction using the
conditions described above (Table 4.1, Entry 7) with various substrates (Table 4.2). In all cases excellent yields were obtained. The reactions were also
highly selective, with no significant byproducts detected. Pure products could
thus be obtained by simply diluting the reaction mixture with diethyl ether,
filtering through a plug of silica gel to remove catalysts and concentrating the
solution. For the acyclic substrate 39, however, the reaction was significantly
slower, requiring 11 h to reach completion (Table 4.2, Entry 2).
To show that hybrid catalyst 35 is necessary to achieve reoxidation of palladium(0), substrate 37 was reacted in the presence of Pd(OAc)2 (2.5 mol%) in
41
ethanol under O2 at 75 ◦C without any hybrid catalyst. In this reaction, none of
the oxidation product 38 was detected. Instead significant amounts of byproducts were formed showing that, for this reaction, direct reoxidation of palladium(0) by O2 is not possible. Electron transfer mediators are thus required.
4.3 Conclusions
The use of hybrid catalyst 35 gives approximately a fivefold increase in reaction rate compared to the use of separate BQ and Co(salmdpt) in ethanol.
Changing the solvent from toluene to ethanol also led to significant improvements. In the absence of catalyst 35 or any other electron transfer mediations
the aerobic carbocyclization is several orders of magnitude slower and side
reactions take over. The use of catalyst 35 is thus an important complement to
the systems that are already used for reoxidation of Pd 0 by O2 . 4
42
Table 4.2: Aerobic carbocyclization of different substrates using catalyst 35.
Entry
Substrate
E
Product
1
38
E
Yieldb
(h)
(%)
0.8
97
11
94
2–3
96
2–3
94
2–3
96
HE E
E
37
Time
H
E E
E
2
40
39
E
HE E
E
3
H
41
42
E
E
E E
4
43
44
E
HE E
E
5
H
45
46
a The
reactions were carried out on a 1 mmol scale with Pd(OAc)2 (1 mol%),
hybrid catalyst 35 (1 mol%) in EtOH (2 ml) at 75 ◦C under O2 (1 atm).
b Isolated yield of pure product.
43
5. Efficient Synthesis of Hybrid
(Hydroquinone-Schiff base)cobalt
Oxidation Catalysts (Paper IV)
5.1 Introduction
Hybrid catalysts 35 and 36 were recently prepared and were found to increase
the rate of electron transfer in biomimetic oxidation reactions. 60 However, the
practical use of hybrid catalysts 35 and 36 in oxidation has been held back
by the inefficient preparation of the key intermediate 47, which is required for
their preparation (Scheme 5.1).
OH
OH
O
N
OH
N
Co
OH
OH
HO
Co
O N N
HO
N
HO
O
HO
35
CHO
O
OH
36
OH
47
Scheme 5.1: Hybrid catalysts 35, 36 and key intermediate 47.
In the original synthetic route, 60 the key intermediate 47 was prepared in a
two-step sequence from commercially available starting materials 48 and 49
(Scheme 5.2). The aryl bromide 48 was first connected with the boronic acid
49 in a Suzuki cross-coupling using a catalyst formed in situ from palladium
acetate and triphenylphosphine. The methyl ethers were then cleaved using
boron tribromide to afford intermediate 47.
OMe
OMe
CHO
Br
Pd(OAc)2
PPh3
OMe
OMe
CHO
+
OMe
B(OH)2
48
49
K2CO3
DMF
50 %
BBr3, DCM
OH
OH
CHO
-78 °C to rt
49 %
OMe
50
OH
47
Scheme 5.2: Original route to intermediate 47.
The intermediate 47 was then condensed with N -(3-aminopropyl)-N methylpropane-1,3-diamine (51) and 1,2-penylenediamine (52) respectively
to form ligand 53 (Scheme 5.3) and ligand 54 (Scheme 5.4). Ligands 53 and
54 were subsequently allowed to react with cobalt acetate to afford hybrid
catalysts 35 and 36 in high yields from intermediate 47.
45
N
N
OH
OH
N
CHO
NH2
51
EtOH
OH
47
NH2
N
OH HO
HO
OH
94 %
53
OH
95 %
HO
Co(OAc)2
MeOH
OH
OH
O
N
Co
O N N
HO
HO
35
Scheme 5.3: Preparation of hybrid catalyst 35.
Even though the route to intermediate 47 is short and seemingly easy, it has
some major drawbacks. First, the starting materials 48 and 49 are expensive.
The second drawback is the moderate yield of the Suzuki coupling. The reaction is also producing significant amounts of byproducts, requiring lengthy
chromatographic purification. Finally, deprotection of the methyl ethers requires the use of boron tribromide, which is a harsh and expensive reagent.
This leads to partial decomposition of the product, thus lowering the yield and
requiring chromatographic purification.
Therefore, we decided to develop a new synthetic route to intermediate 47.
The objectives were to use inexpensive starting materials, improve the yield
and selectivity of the Suzuki coupling and change the methyl ethers to protective groups that can be cleaved off cleanly under mild conditions, thus improving the yield and avoiding chromatographic purification in the deprotection
step.
5.2 Results and Discussion
The newly developed route to intermediate 47 is shown in Scheme 5.5.
In the first step HQ is protected using 3,4-dihydro-2H -pyran (55) and
0.1 mol% of pyridinium p-toluenesulfonate (PPTS) as catalyst to obtain
tetrahydropyranyl (THP) protected HQ (56) after recrystallization from ethyl
46
OH
OH
NH2
CHO
52
OH
NH2
47
70 %
N
HO
OH HO
EtOH
OH
N
HO
OH
54
Co(OAc)2
MeOH
95 %
OH
N
N
HO
Co
O
HO
O
36
OH
Scheme 5.4: Preparation of hybrid catalyst 36.
acetate. THP groups were chosen for protection of HQ because they can be
cleaved off easily under weakly acidic conditions.
In the next step 56 was ortho-lithiated by treatment with n-butyllithium, followed by quenching with triisopropyl borate and hydrolysis to obtain boronic
acid 57. In this reaction the THP group promotes the ortho-lithiation by coordinating to n-butyllithium. However, the purification of the boronic acid
proved to be difficult. It could be purified by silica gel chromatography, but
due to partial decomposition on the column, the recovery was low. Recrystallization was not possible since the compound is an oil. Attempts were also
made to remove the THP groups prior to isolation, but that only resulted in
decomposition.
Finally, the crude boronic acid 57 was used directly in a Suzuki crosscoupling with unprotected 5-bromosalicyladehyde (58) under phase-transfer
conditions using a catalyst formed in situ from palladium acetate and triphenylphosphine affording 59 in 94 % yield after column chromatography. The
major improvement arises from the change of solvent from N,N -dimethylformamide (DMF) to a mixture of toluene, ethanol and water. When THP
protected boronic acid 57 was used in the original Suzuki conditions with
DMF as solvent, complex mixtures were obtained.
There were some difficulties in the deprotection of 59 due to the acid sensitivity of intermediate 47. Initial attempts using p-toluenesulfonic acid resulted
in decomposition. Finally, deprotection was achieved with PPTS in ethanolwater (9:1) at 60 ◦C. Pyridine was added prior to concentration of the reaction
mixture to avoid decomposition and reversal of the reaction. The intermediate
47
OH
CHO
OTHP 1) n-BuLi, rt
2) B(Oi-Pr)3
-78 °C to rt
OH
O
55
OH
12
3) H2O
PPTS
DCM
97 %
OTHP
57
OH
CHO
PPTS
EtOH/H2O (9:1)
60 °C
59
OH
OH
98 %
58
Br
Pd(OAc)2, PPh3
BnEt3NCl, Na2CO3
toluene-EtOH-H2O
100 °C
OTHP
56
OTHP
OTHP
OTHP
B(OH)2
94 %
CHO
OH
47
Scheme 5.5: New route to intermediate 47.
47 could then be isolated in 98 % yield and excellent purity by simple precipitation with chloroform. The rest of the synthesis was then performed as
previously reported.
5.3 Conclusions
A new synthetic route to hybrid catalysts 35 and 36 has been developed. By
changing the protecting groups on HQ from methyl ethers to THP and optimizing the Suzuki coupling the catalysts could be prepared in good overall
yields from inexpensive starting materials.
48
6. Water Oxidation Catalysts Based
on Imidazole-Containing Ligands
(Papers V, VI)
6.1 Introduction
In the search for a catalyst for water oxidation, ruthenium complex 60 has recently been prepared and studied in the group. 61 A manganese complex of the
same ligand (61) has also been prepared previously. 62 Unfortunately, none of
these succeeded in catalyzing water oxidation. The failure has been attributed
to the benzylic amines present in ligand 61, which are oxididatively sensitive
and could readily be degraded under the strongly oxidative conditions required
for water oxidation.
+
O
OO
O
Ru
Ru
O
N
N
HO
OH
O
O
N
N
N
OH
N
60
N
N
61
Figure 6.1: Ruthenium complex 60 and ligand 61.
In order to obtain complexes which are more stable towards oxidative
degradation, a replacement for the sensitive benzylic amines was searched
for. One such possibility is imidazole, which also is commonly found in
metalloenzymes, such as the OEC, in the form of histidine residues which act
as ligands for the metal(s). A modified ligand (62) was thus designed, where
the benzylic amines have been replaced by imidazole groups.
6.2 Results and Discussion
6.2.1 Synthesis of Imidazole-Based Ligands
The synthesis of ligand 62 starts with the preparation of the diester 63 from
diacid 64 and bromoketone 65 (Scheme 6.1). The ketoester functionalities
49
were then transformed into imidazole groups by refluxing in xylene together
with ammonium acetate, according to a modification of a published procedure
for similar substrates. 63 The rather moderate yield (33 %) could be attributed
to the formation of significant quantities of byproducts containing oxazole
groups instead of the desired imidazoles. Demethylation of the protected ligand 66 was first attempted using BBr3 in DCM, but this resulted in a complex mixture from which ligand 62 was isolated in low yield (∼ 20 %) by a
tedious purification procedure involving multiple recrystallizations. In contrast, when 66 was refluxed in concentrated HI, the demethylation proceeded
smoothly and cleanly, and the deprotected ligand 62 was isolated in good yield
and excellent purity as the hydroiodide salt by a simple recrystallization from
methanol/acetone.
OMe
O
OMe O
1) Cs2CO3, EtOH
HO
MeO
O
O
OMe O
O
OH
O
2) OMe O
O
Br
64
65
63
DMF
92 %
OH
N
HO
OH
N
H
OMe
HI (conc)
reflux
N
N
H
1.5 HI
62
NH4OAc
xylene
reflux
33 %
64 %
N
MeO
OMe N
N
H
N
H
66
Scheme 6.1: Synthesis of ligand 62.
Despite being relatively short, the synthesis of ligand 62 still involves multiple steps and suffers from the low yield and difficult purification of the protected ligand 66. Based on a recently published procedure for the preparation
of benzimidazoles, 64 a similar ligand (67) was thus designed and synthesized.
Ligand 67 was prepared in a single step from dialdehyde 68 and o-nitroaniline
69, via a reductive cyclization reaction utilizing Na2 S2 O4 as the reducing
agent (Scheme 6.2). Gratifyingly, the product precipitated directly from the
reaction mixture, affording ligand 67 in good yield and purity without the
need for further purification.
50
COOH
OH
replacements
OHC
COOH
NH2
CHO
Na2S2O4
EtOH, H2O
70 °C
OH HN
NH
+
N
NO2
68
HOOC
N
71 %
69
67
Scheme 6.2: Synthesis of ligand 67.
6.2.2 Ruthenium Catalyst for Water Oxidation (Paper V)
Since ligand 62 failed to give a stable manganese complex, our work was
initially directed towards making ruthenium complexes. When ligand 62 was
treated with Ru(DMSO)4 Cl2 in methanol at reflux, followed by addition of
4-picoline and continued reflux, a ruthenium complex (70) was obtained
(Scheme 6.3). Characterization of the complex, however, proved to be very
difficult. We have so far been unable to obtain crystals suitable for single
crystal X-ray diffraction, and furthermore, due to the paramagnetic nature of
the complex no 1H NMR signals could be observed, even at temperatures as
low as −90 ◦C. Surprisingly, the elemental analysis showed that the ratio
between ligand 62 and ruthenium was actually 1 : 1 and not the expected 1 : 2
ratio. Based on the elemental analysis and mass spectrometry (MS) data, a
highly speculative structure, consisting of two mononuclear units bridged by
an iodide, was thus suggested (see Paper V for a more detailed discussion).
L= N
H
N
N
OH
N
1) Ru(DMSO)4Cl2
Et3N, MeOH,
reflux
HO
OH
N
H
Ru
O
N
N
H
62
L
N
1.5 HI
2) 4-picoline
reflux
L
N
3) H2O, rt
quant.
OH
HO
N
O
I L
O
Ru
O
L
N
N
H
N
H
70
Scheme 6.3: Preparation of ruthenium complex 70.
Despite the ambiguity about the structure of complex 70, testing for water oxidation activity was conducted, initially employing Ru(bpy)3 (PF6 )3 as
a stoichiometric one-electron oxidant in aqueous phosphate buffer (0.1 M,
pH = 7.2). This resulted in oxygen evolution with a TON of ca 100, as measured by MS. Encouraged by this result, we decided to study light-driven water oxidation, initially using Ru(bpy)3 (PF6 )2 as photosensitizer and Na2 S2 O8
as electron acceptor. When the light was switched on, oxygen evolution could
51
be detected with a TON of ca 30. Substituting the sensitizer, however, for
the more strongly oxidizing Ru(bpy)2 (deeb)(PF6 )2 (deeb = 4,4’-bis(ethoxycarbonyl)-2,2’-bipyridine), increasing the redox potential from +1.26 V 36 to
+1.40 V 35 vs NHE, greatly improved the water oxidation, resulting in a TON
of ca 250 (Figure 6.2). To show that the formed oxygen originates from water, the light-driven oxidation with Ru(bpy)2 (deeb)(PF6 )2 was repeated with
18O-labeled water (4.5 % H 18 O). The ratio 16,18O / 16,16O in the evolved oxy2
2
2
gen was determined to be 0.094, which corresponds to the theoretical ratio
(2 · 0.045/(1 − 0.045) = 0.094) when all oxygen is derived from water (Figure 6.3).
Figure 6.2: Light-driven oxygen evolution catalyzed by complex 70 (5.4 µ M), in
an aqueous phosphate buffer solution (0.1 M, pH = 7.2, 1.0 ml), in the presence of
Ru(bpy)2 (deeb)(PF6 )2 (A) or Ru(bpy)3 (PF6 )2 (B) (99 µ M) as photosensitizer and
Na2 S2 O8 (20 mM) as electron acceptor.
6.2.3 Manganese Catalyst for Water Oxidation (Paper VI)
In contrast to the results with ligand 62, a manganese complex (71) could
be obtained when ligand 67 was treated with Mn(OAc)2 and Na(OAc)2 in
methanol at reflux (Scheme 6.4). The X-ray crystal structure (Figure 6.4)
shows that complex 71 is present as an S2 -symmetric dimer (Figure 6.5), at
least in the solid state. Interestingly, the dimeric structure has four manganese
atoms in close proximity, bridged by oxygens, a structure reminiscent of the
Mn4 Ca cluster in the OEC. Based on bond valence sum (BVS) calculations,
the oxidation states of the two unique Mn atoms were assigned as Mn II and
52
Figure 6.3: Light-driven water oxidation catalyzed by complex 70 (4.8 µ M), in an
aqueous phosphate buffer solution (0.1 M, pH = 7.2, 0.46 ml) containing 4.5 % 18O,
in the presence of Ru(bpy)2 (deeb)(PF6 )2 (110 µ M) as photosensitizer and Na2 S2 O8
(21 mM) as electron acceptor.
Mn III . BVS calculations in combination with the analysis of hydrogen bonds
also showed that N3 is protonated while N2 is not, thus further confirming the
oxidation states, based on the neutrality of complex 71, since no counterions
could be observed.
COOH
NH
HOOC
Mn(OAc)2
NaOAc
MeOH
O
N
N
67
Mn
Mn
O
N
N
H
N
L = MeOH
O
O
O
N
OH HN
79 %
L
L
O
71
Scheme 6.4: Preparation of manganese complex 71.
When complex 71 was treated with Ru(bpy)3 (PF6 )3 in phosphate buffer
(0.1 M, pH = 7.2), oxygen evolution was detected with an initial turnover
frequency (TOF) of ca 0.027 s−1 , lasting for about one hour, giving a
TON of ca 25 (Figure 6.6). This is, to the best of our knowledge, the
first water oxidation catalyzed by a homogeneous manganese complex,
using a one-electron oxidant. That the evolved oxygen indeed originates
from water was shown by using 18O-labeled water (5.8 % H218 O). The
53
Figure 6.4: X-ray crystal structure of complex 71 at 50 % probability level.
H
N
O
O
O
N
N
N
N L O L
Mn Mn N
O
O
O
O
O
O
O
Mn Mn
L O L N
N
H
L = MeOH
Figure 6.5: Dimeric structure of complex 71.
observed ratio 16,18O2 / 16,16O2 was 0.10, which is close to the theoretical
ratio (2 · 0.058/(1 − 0.058) = 0.12), when all oxygen originates from
water. Light-induced water oxidation was also investigated, first using
Ru(bpy)3 (PF6 )2 , resulting in oxygen formation with a TON of ca 1. Changing
to the more strongly oxidizing Ru(bpy)2 (deeb)(PF6 )2 led to an increase of the
TON to ca 4 (Figure 6.7).
The properties of complex 71 in solution were studied by 1H NMR spectroscopy and X-band electron paramagnetic resonance (EPR) spectroscopy, in
D2 O and H2 O, respectively, in the presence of K3 PO4 . The relatively narrow
chemical shift range in combination with the absence of any EPR signal at
77 K indicate the presence of an antiferromagnetically coupled Mn2III,III complex with a singlet ground state, i.e. the Mn2II,III complex 71 has been oxidized
in solution to Mn2III,III . The broadening of the NMR signals could be attributed
54
Figure 6.6: Oxygen evolution using Ru(bpy)33+ as stoichiometric oxidant. A solution
of complex 71 (0.5 ml, 84 µ M) in phosphate buffer (0.1 M, pH = 7.2) was injected to
Ru(bpy)3 (PF6 )3 (20 mg, 20 µ mol) at t = 0. The jump at t = 45 min is due to bursting
of gas bubbles.
to the population of excited spin states at ambient temperature. The EPR spectrum recorded in dimethyl sulfoxide (DMSO) at 77 K, however, shows a broad
(100 mT) signal at g = 2.0, indicative of a Mn2II,III complex. 65
The NMR spectra recorded at 25 ◦C and low concentrations of complex
71 show three broad signals with chemical shifts at 7.52, 7.31, and 6.69 ppm
(Figure 6.8). The chemical shifts were shown to be essentially independent
of the concentration of complex 71, suggesting that the ligand backbone of
complex 71 is intact in solution, under conditions similar to those used in the
water oxidation experiments, i.e. there is no rapid equilibrium between the
complex and the uncoordinated ligand. However, at higher concentrations a
set of three new, very broad signals was observed. This could be attributed
to an equilibrium between the monomeric and dimeric forms of complex 71
in solution. At low concentration the monomer should be favored, giving rise
to the initial set of three signals, while at higher concentrations a mixture of
monomer and dimer could be observed. In addition, NMR spectra recorded at
different temperatures (5, 25, 50, and 80 ◦C) indicate that the dimerization is
favored at higher temperatures, possibly due to entropy effects as coordinated
solvent molecules are released into solution.
55
Figure 6.7: Light-driven oxygen evolution catalyzed by complex 71. A solution of
complex 71 (1.0 ml, 84 µ M) in phosphate buffer (0.1 M, pH = 7.2) was injected to
Na2 S2 O8 (4.7 mg, 20 µ mol) and Ru(bpy)2 (deeb)(PF6 )2 in acetonitrile (50 µ l, 10 mM).
Light was switched on at t = 0.
6.3 Conclusions
Two new catalysts for water oxidation have been developed. The first,
ruthenium-based, catalyst was shown to catalyze highly efficient water
oxidation with a TON of ca 250, induced by visible light. The second,
manganese-based, catalyst having a tetranuclear structure reminiscent
of the Mn4 Ca cluster in the OEC is, to the best of of our knowledge,
the first homogeneous manganese complex to catalyze water oxidation
using a one-electron oxidant, and more importantly, using visible light in
combination with a photosensitizer.
56
10
9
8
7
6
5
4
3
2
1
0
−1 ppm
Figure 6.8: 1H NMR spectrum of 71 (1.0 mg) in D2 O (0.5 ml) containing K3 PO4
(1.0 mg) at 25 ◦C.
57
Acknowledgements
I would like to thank the following people:
• My supervisors Prof. Björn Åkermark and Prof. Jan-Erling Bäckvall.
• My former supervisor Prof. Stefan Oscarson.
• Bao-Lin Lee, Docent Timofei Privalov, Dr. Torbjörn Åkermark, Dr. Junliang
Sun, Docent Örjan Hansson, Markus Kärkäs, and Eric Johnston for fruitful
collaboration.
• Bao-Lin Lee for proofreading of the thesis.
• Past and present members of the BÅ, JEB and SO groups.
• All the people at the Department of Organic Chemistry.
• C F Liljevalch J:ors stipendiefond, stiftelsen Bengt Lundqvist Minne, Ångpanneföreningens Forskningsstiftelse, and AstraZeneca for traveling scholarships.
59
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