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Coordination–driven encapsulation of transition metal complexes in molecular capsules andtheir application in hydroformylation and proton reduction catalysis

Nurttila, S.S.

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Citation for published version (APA):Nurttila, S. S. (2018). Coordination–driven encapsulation of transition metal complexes in molecular capsulesand their application in hydroformylation and proton reduction catalysis.

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Download date: 14 Jul 2020

Chapter 1

Introduction

* This chapter is in part adapted from: S. S. Nurttila, P. R. Linnebank, T. Krachko, and J. N. H. Reek, “Supramolecular Approaches to Control Activity and Selectivity in Hydroformylation Catalysis”, ACS Catal. 2018, 8, 3469-3488.

Chapter 1

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Homogeneous transition metal catalysisThe term ‘catalysis’ suggested by Swedish chemist Jöns Jacob Berzelius in 1835 originates from the Greek word kata (down) and lyein (loosen).1 Berze-lius elaborated on the meaning of the term by stating: “This new force, which was unknown until now, is common to organic and inorganic nature. I do not believe that this is a force entirely independent of the electrochemical affinities of matter; I believe, on the contrary, that it is only a new manifestation, but since we cannot see their connection and mutual dependence, it will be easier to designate it by a separate name. I will call this force catalytic force. Simi-larly, I will call the decomposition of bodies by this force catalysis, as one des-ignates the decomposition of bodies by chemical affinity analysis.” (Berzelius, 1835). The first example of the use of inorganic catalysts dates back to 1575 when Valerius Cordus used sulfuric acid as a catalyst for ether formation from alcohol. By the beginning of the 19th century a crude description of homoge-neous catalysis was proposed by Désormes and Clément when they presented a rational theory on the catalytic influence of nitrogen oxides in sulfuric acid production.

Modern synthetic chemistry relies on catalysis and 90% of all commercial chem-icals involve at minimum of one catalytic step in their production process.2 Ca-talysis enables the manufacture of chemicals in an atom economical and highly efficient fashion. Heterogeneous catalysis covers 75% of all industrial processes, but homogeneous catalysis is preferred for processes that require a high control of selectivity, such as hydroformylation, carbonylation, oxidation, hydrogenation and metathesis reaction. High selectivity equals reduced waste and work–up, and a more effective use of feedstock, in line with principles outlined by ‘green chemistry’. In the field of homogeneous catalysis, transition metal catalysis has without a doubt received the most attention in academic literature in the past decades. The traditional approach involves the use of metal–organic catalysts which are optimized by changing the metal or modifying the electronics and/or sterics of the surrounding ligands.3 Fine–tuning of the ligands provides a relatively easy platform to steer the catalytic reaction. The sophisticated inter-play between the central atom, the ligands and the bound substrate governs the activity and selectivity of the reaction. The importance of the ligands is evident as one metal can give multiple products depending on the used li-gand. For example, by changing the ligands around a nickel catalyst, products

Introduction

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ranging from polymers to cyclized structures are obtained (Scheme 1). The use of metal–organic complexes has yielded many beautiful examples of selective catalytic transformations, such as the Nobel prize awarded pal-ladium–catalyzed cross–coupling, ru-thenium–catalyzed olefin metathesis and rhodium–catalyzed asymmetric hydrogenation.

Still today many catalytic reactions suffer from insufficient control of the activity and/or selectivity and new concepts are required to overcome these limitations. In this respect, catalysts of nature, ‘enzymes’, serve

as a source of inspiration due their inherently high activity and selectivity in selected catalytic transformations. Enzymes use a larger toolbox to steer the outcome of reactions compared to traditional homogeneous catalysts. Confine-ment of the active site (catalyst) in a bulky second coordination sphere com-posed of interconnected peptides is key, resulting in a local microenvironment radically different from bulk solution.4 As the catalyst occupies the hydrophobic interior of the protein structure it is isolated from bulk solution. As a conse-quence, the local concentration of catalyst and substrate is increased, resulting in faster reaction kinetics.5 The substrate is also pre–organized close to the active site by multiple specific noncovalent interactions between the substrate and the amino acid residues of the cavity. This may lead to stabilization of transition states distinct from bulk solution and modified product selectivity.6 It is therefore no surprise that inspired by nature the field of homogeneous catalysis attempts to apply concepts of molecular encapsulation to synthetic transition metal catalysts, coined here ‘Homogeneous catalysis 2.0’ (Figure 1). In this fashion the activity and selectivity of the catalysts are not exclusively controlled by the first coordination sphere containing the metal complex but also by additional interactions with a synthetic second coordination sphere.

Two different approaches for cage–controlled catalysis can be distinguished: encapsulation of purely synthetic catalysts in synthetic cages and encapsula-tion of enzyme mimics in synthetic cages and apoproteins. Each concept will

Scheme 1. The effect of changing the li-gand in nickel–catalyzed reactivity of bu-tadiene.

Chapter 1

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be addressed in this review on the basis of one model reaction, that is hydroformylation catalysis (part I) and proton reduction catalysis (part II). Other cage–controlled metal–cat-alyzed transformations and organic transformations have been the topic of previous review articles7–11 and are beyond the scope of this review.

I Hydroformylation catalysisThe hydroformylation reaction is the formal addition of a formyl group to an alkene functional group, which in practice involves a metal–catalyzed addition of CO and H2 to the alkene. The reaction was serendipitously found by Roelen while working on a Fisher–Tropsch process in 1938.12 In the 20 years after this discovery, the hydroformylation reaction did not receive much attention, which changed from the mid–fifties. In the 60 years that followed, the hydroformyla-tion reaction was subject to intensive investigations, leading to many industrial applications. The first catalyst was a cobalt complex, and as a consequence the first bulk processes also applied cobalt complexes. Later it was found that rhodium forms far more active catalysts for this reaction, and as such the next generation of industrial processes applied rhodium catalysts, despite the fact that rhodium is more expensive. Other metals that can catalyze this reaction include palladium, platinum, ruthenium and iridium, but no commercial appli-cations are known based on these metals. So far rhodium complexes remain a favorite because of their superior activity, allowing processes at lower tem-perature and pressure, and the ability to control the selectivity of the reaction to a large extent by ligand variation. In volume, hydroformylation is still the largest industrial process in homogeneous catalysis, and several large compa-nies have plants including SHELL, BASF, Eastman, BP, DOW and Evonik. The aldehyde products generally also have a characteristic smell, and as such the hydroformylation reaction is also popular in the fragrance industry. Asym-metric hydroformylation leads to chiral compounds with an interesting alde-hyde function that can be used for further functionalization, and as such it is also a potentially interesting reaction for the fine chemical and pharmaceutical industry, however, it is so far a bit underexplored. The application of hydro-

Figure 1. Homogeneous catalysis 2.0.

Introduction

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formylation has recently been summarized by Börner in a review on applied hydroformylation13 and a beautiful review on hydroformylation of the flavor, fragrance and food industry.14

The hydroformylation reaction is also an important reaction for educational purposes, not only because of its rich history and plethora of applications, but also because it is well understood despite its complexity.3,15 Next to the alde-hyde products that are generally desired, there are several by–products that can form (Scheme 2). Under hydroformylation reaction conditions, hydrogen is always present and as such both the substrate and the products can be hy-

drogenated leading to alkanes and alcohols. In fact, alkene hydroge-nation is thermodynamically more favorable, and therefore the reac-tion should proceed under kinetic control. Next to this, the substrate can also isomerize under catalytic conditions, leading to a mixture of terminal and internal alkenes, which in turn can be hydroformy-lated. This isomerization can also be used as an advantage in cases where isomerization–hydroformyla-tion tandem reactions lead directly

to the desired product; for example, the production of linear aldehydes from internal alkenes.16 All these side reactions depend on the catalyst properties and the conditions that are applied, and can be qualitatively understood.

The mechanism originally proposed by Heck and Breslow17,18 is generally still valid, although more detailed insight has been obtained ever since.19–31 The general mechanism, displayed in Scheme 3, starts with the rhodium(I)hydrido complex 1, and for this example we use the bisphosphine biscarbonyl analogue. After decoordination of a CO ligand to create a vacant site, the alkene can coordinate to give common intermediate 3. In the next step hydride migration to the carbon atom leads to the rhodium alkyl species. Depending on the ori-entation of the alkene, the migration is to either C2 or C1 leading to the linear (4) or the branched alkyl species (8). These two enter separate but identical catalytic cycles. After CO coordination and subsequent alkyl migration to the CO, the rhodium acyl species (6 and 10) are formed. These four–coordinate

Scheme 2. The general reaction scheme of the hydroformylation reaction, converting alkenes into aldehydes, and potential side products.

Chapter 1

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species can directly coordinate CO to form 7 or 11, or directly react with molecular hydrogen to give the product and intermediate 2. Species 1, 7 and 11 are most often drawn as a part of the catalytic cycle, but recently Landis showed that part of the reaction can go directly from acyl–intermediate 6 to 2 without forming 7.32 As such, it is more accurate to draw these intermediates as off–cycle species. It is important to realize that all the steps except for the final hydrogenolysis are equilibria. As a consequence, the regio– and enantiose-lectivity could be determined by the hydride migration step from intermediate 3, but under certain conditions it could also be that intermediates 6 and 10 are in fast equilibrium and the relative rate of the final hydrogenolysis of these species is determining the selectivity. The reversibility of the hydride migration is the basis for the isomerization reaction, which can result in the formation of unwanted side products. For some applications, for example when a mixture of alkenes is offered as the feed, an isomerization–hydroformylation sequence is required.16

Over the years many different ligands have been explored for rhodium–cata-lyzed hydroformylation, some of which are displayed in Figure 2. Triphenyl-

Scheme 3. Mechanism of the rhodium–catalyzed hydroformylation.

Introduction

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phosphine (TPP) has without a doubt been studied the most, as it is a cheap and readily available ligand, and several large–scale processes started in the seventies using TPP. Also, water–soluble analogues have been developed, in-cluding monosulfonated TPP (TPPMS), and these have been used for aqueous phase hydroformylation. For these types of phosphine ligands, the rate limiting step is early in the catalytic cycle (1–4), often referred to as type I kinetics,3 and the use of more electron donating ligands such as alkyl phosphines results in very low activity. The use of more electron poor (or π–accepting) ligands such as phosphites results in much higher activities as CO dissociation is generally fast. As a consequence, the rate de-termining step can be later in the cycle, typically the hydrog-enolysis step, in which case one generally refers to type II ki-netics.3 As the CO ligands are much more weakly coordinated on these electron poor complex-es, the hydride migration reac-tion becomes more reversible, resulting in the formation of more isomerization side prod-ucts. If the phosphite ligands are very bulky, there is only space for one ligand to coordi-nate to rhodium, and this leads to the most active catalysts.33,34

A lot of attention has been devoted to control the regioselectivity of the re-action, with the main target being the linear aldehyde. It was found that the use of a large excess of TPP can already provide reasonably high selectivity for the linear product, albeit at the expense of the activity of the catalyst.20 Many bidentate ligands have been explored, and it was found that ligands with a large bite angle, i.e. P–Rh–P angle around 110–120°, give rhodium complexes that produce the linear aldehyde in very high selectivity.35–40 BISBI and Xant-phos are the most illustrative examples of such ligands (Figure 2). Catalysts that give very high selectivity for the branched aldehyde for aliphatic alkenes are unknown to date. For substrates such as styrene and vinyl acetate the for-

Figure 2. Some typical ligands that have been used in the rhodium–catalyzed hydroformylation.

Chapter 1

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mation of a stabilizing allyl intermediate directs the hydroformylation towards the branched product.13

The field of enantioselective hydroformylation is far from mature, which is strange if one considers the potential impact for the fine chemical and phar-maceutical industry. The main reason must be the challenges associated with asymmetric hydroformylation processes. Whereas lots of asymmetric hydrogena-tion processes were re-ported between the sev-enties and nineties, the contributions in that pe-riod on asymmetric hy-droformylation report-ed modest to good ee at best. This changed with the seminal work of Nozaki31,41–43 and later Landis,44–46 who reported BINAPHOS and diazaphospholanes, respectively, as novel bidentate ligands that gave high enantioselec-tivity in asymmetric hydroformylation. Sub-strates that have been mostly studied are those that typically give high branched selectivity, such as styrene deriva-tives and vinyl acetate. More recently, BOBphos was reported as a bidentate ligand that also gave relatively high branched selectivity and enantioselectivity in the hydroformylation of unfunctionalized 1–alkenes (Figure 3).47,48

It is clear that the hydroformylation reaction is a very powerful transformation for both the bulk, the fragrance, fine chemical and pharmaceutical industry. Al-though many selectivity and activity issues have been solved by now, there are still many challenges left that would, when solved, really expand the scope of possibilities of this reaction. These challenges mainly involve selectivity issues,

Figure 3. Some typical ligands that have successfully been used in asymmetric hydroformylation, typically of styrene derivatives.

Introduction

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including the branched selective hydroformylation, selective hydroformylation of internal alkenes and the selective hydroformylation of tri– and tetra–substitut-ed alkenes. Also, the asymmetric hydroformylation of terminal disubstituted alkenes is a largely unsolved issue. In this light, the development of novel concepts to control selectivity in hydroformylation catalysis is of utmost im-portance. In this review we will elaborate on the use of novel supramolecular strategies in hydroformylation, namely hydroformylation catalysis in cages.

Hydroformylation catalysis in confined spacesMany substrates of interest for hydroformylation do not have functional groups. To achieve selective hydroformylation for this class of substrates, the hydride migration step must be controlled in a manner that does not involve selective interactions between the substrate and the catalyst. One strategy that has been explored is the application of catalysts in confined spaces, and this will be discussed in this section.

For the sake of brevity, in this section solely the modulation of the activity and/or selectivity of rhodium–based hydroformylation catalysts as a result of confinement in a synthetic, molecular cage–like structure will be discussed. Or-ganic transformations and other metal–catalyzed reactions have recently been described elsewhere; excellent reviews on using molecular containers in multi-step reaction cascades and tandem enzymatic reactions,49 in reactivity modula-tion,50 in the context of enzyme mimics based upon supramolecular coordina-tion chemistry,51 along with transition metal and organo–catalysis in functional molecular flasks,7–11 have already been published.

Cyclodextrin–based systems

In pioneering work by Monflier and co–workers, cyclodextrins (CD) have been applied in combination with water–soluble rhodium phosphine–based catalysts for biphasic hydroformylation of higher olefins.52–57 The cyclodextrin cavity is essentially hydrophobic and can therefore host various organic molecules in water (Figure 4). Generally, the cyclodextrin host forms a water–soluble host–guest complex with the substrate, thereby increasing the water–solubil-

Chapter 1

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ity of the alkene. As such, it brings it in closer contact with the catalyst residing in the aqueous layer, typically resulting in increased catalytic rates (Scheme 4). In this re-gard, the cyclodextrin acts as a phase–transfer catalyst by facilitating the migration of a reactant from one phase into the phase where the reaction occurs. Furthermore, in most examples the regioselectivity is also affected as a direct consequence of confinement. Examples where the cyclodextrin acts exclusively as a phase–transfer catalyst will not be discussed in this review.

The first example reported along these lines was the application of partially methylated β–cyclodex-trins in the biphasic rho-dium 3,3’,3”–phosphine-triyltris(benzenesulfonate) (TPPTS) catalyzed hy-droformylation of various water–insoluble terminal and internal alkenes, en-abling efficient biphasic hydroformylation of higher alkenes.52 In the absence of cyclodextrins, only sub-strates with sufficient wa-ter–solubility, hence short-er carbon chain length, are efficiently converted under biphasic hydroformyla-tion conditions. Different substrates ranging from terminal and internal ali-phatic alkenes to aromatic styrene derivatives can be converted with the novel

Figure 4. Schematic representation of the α–, β– and γ–cyclodextrins that have a hydrophobic cavi-ty that can host organic guest molecules.

Scheme 4. Phase–transfer catalysis mediated by cy-clodextrins.

Introduction

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catalytic system. A significant increase in the catalytic rate was observed in the presence of methylated β–cyclodextrins, especially for the insoluble alkenes. For example, for 1–decene the conversion after 6 h was tenfold, and the in-crease in reaction rate is estimated to be 25. The effect of confinement is also clear in the hydroformylation of internal alkenes, although the overall conver-sions are rather low. This low reactivity is attributed to the lack of accessibility of the double bond of the substrate, which most likely resides too deep inside the hydrophobic cavity of the cyclodextrin host. The presence of the cyclo-dextrin also has an influence on the regioselectivity in the hydroformylation of 1–alkenes. For all substrates the selectivity for the linear aldehyde decreases in the presence of the cyclodextrin. This is explained by the fact that not only the alkene but also the water–soluble phosphine ligand interacts with the cavi-ty.53 By encapsulation of the phosphine ligand, the equilibria between different rhodium species are shifted to low–coordinate complexes which are generally more active and less selective, explaining the decrease in selectivity.

The group of Monflier extended the cyclodextrin–based catalytic system to fully solvent–free conditions.58 Substrate molecules and a rhodium phosphine–based catalyst were dispersed in a mixture of acyclic saccharides and cyclodex-trins, resulting in a heterogeneous mixture. The saccharides ensure complete

Scheme 5. Schematic representation of the effect of the depth of inclusion of the sub-strate in the cyclodextrin cavity on the observed aldehyde product selectivity.

Chapter 1

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dispersion of the substrates in the solid mixture, leading to increased catalytic rates. Exposure of this mixture to syngas in a mixing planetary ball mill, re-sults in the hydroformylation of various styrene derivatives, always with 100% chemoselectivity to provide the corresponding aldehydes. In the absence of cy-clodextrins the branched aldehyde is predominantly formed, which is typical for styrene derivatives. However, the presence of cyclodextrins results in a fivefold increase in the selectivity for the linear aldehyde product. This altered selec-tivity is due to the binding of the aromatic alkene in the hydrophobic cavity of the cyclodextrin, favoring hydroformylation at the less–hindered position of the vinyl function (Scheme 5). The substrate displays a stronger inclusion in the larger cyclodextrin (n = 7), which results in steric hindrance between the alkene functionality and the host. As a consequence, the formyl group will be transferred to the least hindered carbon atom which yields the linear aldehyde as the main product. For the smaller cyclodextrin (n = 6) the binding does not result in shielding as the substrate is less deep in the pocket, and as a result the selectivity is solely determined by the electronics of the substrate itself.

To prevent the earlier discussed inclusion of the phosphine ligand within the cavity of the cyclodextrin, bulkier mono– and bidentate ligands were subse-quently applied in search for catalytic systems that display a higher selectivity for the linear aldehyde product.54 Indeed, bulky water–soluble phosphine ligands such as 1,3,5–triaza–7–phosphaadamantane–based ligands55 (13) (Figure 5, top right) and 2–naphthylphosphines56 (14a–14c) (Figure 5, bottom) do not form strong inclusion complexes with cyclodextrins as compared to TPPTS, and thus a smaller decrease in regioselectivity is observed in the hydroformylation of 1–decene, and at the same time the conversions are much higher. The biden-tate sulfonated 4,5–bis(diphenylphosphino)–9,9–dimethylxanthene ligand (12) is of particular interest as it forms strong complexes with rhodium, preventing the formation of monoligated complexes and due to its large natural bite angle, it already favors the formation of the linear product (Figure 5, top left). Fur-thermore, due to its larger size compared to the previously employed TPPTS ligand, it does not form a strong inclusion complex with the cyclodextrin host, allowing more efficient substrate transportation. In the presence of β–cyclo-dextrin the catalytic system displays a fivefold increase in the conversion of 1–octene to nonanal under standard hydroformylation conditions. Interestingly, the selectivity for the linear aldehyde increased (linear–to–branched ratio; l/b = from 14 to 33) when cyclodextrin is present in the catalytic mixture. This enhanced selectivity is proposed to be due to the steric bulk around the co-ordination sphere of rhodium, forcing the hydride to preferentially migrate to

Introduction

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carbon atom C2 over C1.

As an alternative to the above de-scribed approach, systems relying on the direct covalent functionalization of the β–cyclodextrin with phosphine ligands have been reported.59,60 The group of Reetz reported on the appli-cation of rhodium complexes of various β–cyclodextrin–modified diphosphine li-gands in the biphasic hydroformylation of 1–octene. Interestingly, this catalyt-ic system converts not only terminal alkenes but also relatively unreactive internal alkenes. A proposed mode of action for the diphosphine–based cata-lyst is displayed in Scheme 6. The modified cyclodextrin–based catalysts dis-play a 150–fold increase in activity at 80°C compared to systems without cyclodextrin at 120°C in the conversion of 1–octene to nonanal. The catalyst converts the substrate with a selectivity for the linear product of 76%, which is typical for rhodium complexes based on small bite angle ligands.

A similar approach to the cyclodextrin system relies on the use of hemispher-ical rhodium calixarene–based phosphite and phosphine complexes. These sys-tems have shown to promote the formation of linear aldehyde products over branched ones in hydroformylation catalysis. While it has been postulated that the confined space around the catalytically active site plays a role in the prod-

Figure 5. Structures of the water–solu-ble ligands 12, 13 and 14a–14c.

Scheme 6. Proposed mode of action of the β–cyclodextrin–modified diphosphine–based catalytic system.

Chapter 1

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uct selectivity, more detailed mechanistic studies are needed to confirm this.61,62

Recently, Matt and co–workers described the use of rhodium monophosphine complexes for the hydroformylation of styrene.60 By covalent confinement of the phosphine ligand inside a chiral cyclodextrin cavity, exclusive formation of rhodium monophosphine complex 15b is observed, even in the presence of excess ligand (Scheme 7). This is a clear example in which the second coor-dination sphere around the catalytically active site controls the coordination mode of the metal. Remarkably, the catalyst converts styrene with both a high branched selectivity (98%) and enantioselectivity (up to 95%). It is interesting to note that the cyclodextrin is the only source of chirality, and as such the enantioselectivity is controlled by the chiral second coordination sphere around the metal complex.

Ligand–template approach

Reek and co–workers introduced a general strategy to encapsulate transi-tion metal complexes in an efficient way that involves a ligand–template ap-proach.63–65 In this strategy the ligand serves a dual role as it operates as a template for the self–assembly of the capsule and it coordinates to the catalyt-ically active metal center, hence it was coined ligand–template approach. The first example reported using this strategy was structure 16 (Figure 6), formed by the self–assembly of three zinc meso–tetraphenylporphyrin (ZnIITPP) units around the ligand–template tris–(meta–pyridyl)–phosphine (P(m–py)3), relying on the selective N–Zn coordination. The phosphine atom of the ligand–tem-plate is coordinated to rhodium and forms the active species (HRhP(CO)3) under syngas. The overall formed encapsulated complex is an efficient hydro-

Scheme 7. Formation of the active species 15b from the monophosphine rhodium complex 15a.

Introduction

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formylation catalyst that converts various terminal alkene substrates with enhanced activity and selec-tivity for the branched aldehyde. Importantly, due to the steric bulk imposed by the porphyrin moieties monoligation of the formed rhodi-um complexes is enforced. By vary-ing the structure of the template and the surrounding zinc building blocks, the effect of variations in the second coordination sphere on the activity and selectivity of the encapsulated rhodium catalyst has been further explored.

Application of 16 in 1–octene hy-droformylation at room temperature leads to a tenfold increase in the catalytic activity as compared to

the rhodium complex in absence of porphyrin under otherwise identical con-ditions.63,64 This rate enhancement can, at least partly, be explained by the higher reactivity of monophosphine complexes. Indeed, DFT calculations show that the catalytic pathway of the rhodium monophosphine catalyst has a lower free energy barrier than that of the bisphosphine analogue, leading to an inher-ently more active catalyst.66 Remarkably, the encapsulated catalyst dominantly forms the branched aldehyde product (l/b = 0.6), which is highly unusual for aliphatic, terminal alkenes. When generating the encapsulated catalysts based on ruthenium porphyrin building blocks instead of zinc, less dynamic capsules are formed which display even higher regioselectivity (l/b = 0.4), but at the cost of the catalytic activity. The orientation of the porphyrin with respect to the phosphine is crucial; the use of tris–(para–pyridyl)–phosphine (P(p–py)3)

Figure 6. Structure of HRh(CO)3 co-ordinated to the central phosphine of the first–generation assembly 16. (a) Molecular structure of the active rho-dium complex of cage 16. (b) Modelled structure of the active rhodium com-plex of cage 16.

Chapter 1

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ligand–templates in-stead of the meta ana-logue, results in a cat-alyst that displays the selectivity typical for rhodium bisphosphine

complexes.67 Indeed a more open structure is formed, allowing the formation of a bisphosphine coordinated rhodium complex that is encapsulated by six por-phyrins. In the solid state an unusual supramolecular structure is formed ac-cording to X–ray analysis, in which one zinc porphyrin unit acts as a bridging moiety between two capsules via an uncommon hexacoordinate zinc (Figure 7).

The generality of the ligand–template approach is demonstrated by the appli-cation of a variety of building blocks. The ligand template can be combined with zinc salphens (17a–17d) and zinc bis–(thiosemicarbazonato) complexes (18) (Figure 8),68–70 which both display a stronger supramolecular binding with pyridine than zinc porphyrins. As these building blocks are significantly small-er, the exclusive formation of encapsulated catalysts cannot be enforced. The smaller size allows considerable conformational flexibility in the self–assembled structures, resulting in a mixture of mono– and bisligated complexes. The catalysts encapsulated by 17a–17d display some selectivity for the branched aldehyde product when applied in 1–octene hydroformylation, but much lower than for the first–generation capsule 16. Moreover, these systems also show an increase in undesired isomerization. Similar results have been obtained for the capsules based on 18.

Following the promising results obtained with terminal alkene substrates, the more challenging internal alkenes were subjected to capsule–controlled hydro-formylation.71,72 Regioselective hydroformylation of internal alkenes is challeng-ing as the two carbon atoms of the double bond are electronically identical and sterically similar. In addition, the reactivity of internal alkenes is lower, and the application of harsher conditions leads in general to more side reactions such as isomerization. The rhodium complex of the first–generation capsule 16 con-

Figure 7. The highly unusual supramolecular structure containing a mixture of penta– and hexacoordinate zinc por-phyrins.

Introduction

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verts trans–2–oc-tene and trans–3–octene with very high regioselec-tivity, where the formyl group is installed on the innermost carbon atom, and also the activity is higher compared to that displayed by the un–encapsulated

catalyst. This selectivity is in line with the results obtained for 1–octene where a preference for the branched aldehyde is observed. Interestingly, a rather high selectivity could still be retained at 40°C, whereas at 80°C isomerization side products lead to a loss in regioselectivity. A combination of DFT calculations and detailed kinetic and mechanistic studies, demonstrate that the selectivity is determined in the hydride migration step (Figure 9).72 The path to the 3–alkyl-rhodium intermediate is considerably lower in energy compared to the 2–alkyl-rhodium intermediate. Signifi-cant structural rearrangements of the capsule would be neces-sary to arrive at the 2–alkyl-rhodium intermediate, resulting in a high energy penalty. Con-sequently, the 3–alkylrhodium intermediate is favored leading to a high selectivity towards the C3–aldehyde. This is relat-ed to the mechanism in which the selectivity is controlled by substrate orientation, with the difference that the rotation of the alkene associated with the hydride migration step is not controlled by hydrogen bonds, but by the sterics of the cage.

Figure 8. Molecular structures of the smaller building blocks 17a–17d and 18.

Figure 9. The energy profile for the hydride mi-gration step leading to the two possible interme-diates c and d. Image reprinted with permission from reference 72.

Chapter 1

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All these hydroformylation reactions were carried out at room temperature or at slightly elevated temperatures, as the supramolecular N–Zn coordinate bond was expected to weaken at elevated temperatures. To expand the application of the capsule to more industrially relevant conditions, catalytic experiments were conducted at 75°C.73 To retain the unusual branched selectivity in the hydroformylation of 1–octene at this temperature, a higher partial pressure of CO is required. Remarkably, when the reaction is performed at 75°C and at 80 bar of CO/H2 (2:1), a nearly identical selectivity (l/b = 0.7) is obtained as at room temperature. At these elevated temperatures the reaction is highly de-pendent on the partial CO pressure, at 20 bar the selectivity for the branched aldehyde was lost. In line with that, high pressure infrared measurements show the formation of bisphosphine coordinated rhodium complexes under these low–pressure conditions.

Next to temperature, the solvent scope was also investigated. As the zinc–pyr-idine interaction is strongest in apolar and non–coordinating solvents, these solvents were preferably applied in the initial experiments. As expected, upon using more polar solvents, the zinc–pyridine binding constant decreases and as a result the equilibrium shifts to the non–encapsulated catalyst, resulting in a loss in activity and selectivity. Interestingly, the oxidized analogues of ZnIITPP, zinc porpholactones, bind more strongly to pyridine by nearly an order of mag-nitude.74 Consequently, the application window of the ligand–template approach can be extended to industrially relevant more polar and coordinating solvents, such as dioctyl terephthalate, while retaining the typical branched selectivity in 1–octene hydroformylation. Furthermore, as the capsule 19 has a slightly smaller size and different shape, it also allows the branched–selective hydro-formylation of propene, which is inherently challenging (l/b = 0.84) (Figure 10). The assembly crystallized as the phosphine oxide complex.

While the regioselectivity is now controlled, these branched aldehydes are formed in racemic form as the catalyst is not chiral. Next, the ligand–template approach was extended to the enantioselective hydroformylation of internal alkenes and styrene derivatives.75–77 Replacing the ligand–template with a chiral pyridine–functionalized phosphoramidite ligand, while maintaining the original zinc porphyrin building blocks, results in novel chiral capsules. Interestingly, addition of the zinc porphyrin building blocks to the activated rhodium–phos-phoramidite hydride complex enforces a change from equatorial to axial coordi-nation mode for the ligand. This change in the coordination mode also changes the properties of the catalyst in the hydroformylation of trans–2–octene. Both

Introduction

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the conversion (56%) and the enantioselectivity (45%) increase in the presence of porphyrin leading to the capsule, and yet again a preference for the addi-tion of the formyl group to the innermost carbon atom was seen. The modest increase in enantioselectivity can be attributed to the dynamic nature of the capsule and therefore a more rigid capsule with less rotational freedom was explored.78 The same chiral ligand was also encapsulated in a metal–organic

coordination cage containing two zinc porphyrins.79 The supramolecular complex does not result in sig-nificant enantioselective induction in the asymmet-ric hydroformylation of 1–octene, however, it gives rise to a high chiral induction (ee up to 74%) in the hydroformylation of styrene compared to the non–encapsulated catalyst (ee < 10%).

The mixing of two bis–[ZnII(salphen)] building blocks with two chiral pyridine–functionalized phosphoramidite templates results in the forma-tion of a supramolecular “box” 20 with the ligands functioning as pillars (Figure 11).78 Modeling of the complex shows that the rhodium complex in-

Figure 10. (left) Comparison of the crystal structures of assemblies 16 and 19, formed by the self–assembly of three equivalents of ZnIITPP/ZnIITPPL and P(m–py)3 in tolu-ene. (right) Molecular structure of assembly 19 (right).

Figure 11. Bis–zinc(II) salphen templated supramo-lecular ”box’’ 20.

Chapter 1

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deed is embedded in a cage defined by the bis–[ZnII(salphen)] building blocks. The application of this supramolecular box in the hydroformylation of internal alkenes such as trans– and cis–2–octene, results in the formation of the alde-hyde product with high regioselectivity and enantioselectivity (ee up to 86%). This demonstrates that both the regioselectivity and enantioselectivity can be controlled by spatially confining the catalytically active site in a tight pocket.

II Site–isolated [FeFe]hydrogenase mimicsConversion of solar energy into hydrogen as the clean molecular fuel has at-tracted a great deal of attention in the past decades.80,81 The use of sunlight as the sole energy source and water as the proton source results in a carbon neutral energy cycle, often referred to as ‘hydrogen economy’ (Figure 12). Hy-drogen is particularly interesting as an alternative to fossil fuels as the only by–product formed during combustion is water. Importantly, to be considered a key green fuel for the future, hydrogen also has to be produced sustainably. Yet today the majority of hydrogen is produced by steam reforming or partial oxidation of methane with fossil fuels as the carbon source.82

Nature has already solved the issue of storing the energy from sunlight in chemical bonds through its sophisticated and highly optimized photosynthetic machinery. All plants use photosynthesis as a process to convert light energy into chemical energy stored in sugars, the fuel of plants. The field of ‘artificial photosynthesis’ tries to mimic the natural process and typically the captured

Figure 12. Schematic picture of envisioned hydrogen economy.83

Introduction

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energy is stored in a fuel such as hydrogen.84 As such, ‘photocatalytic water splitting’ in which water is split into hydrogen and oxygen using solar ener-gy is the major subfield of artificial photosynthesis. Typically, this process is studied as its half reactions: water oxidation to oxygen and protons and proton reduction to molecular hydrogen (Scheme 8). The focus of this review is on proton reduction catalysis.

The best catalyst for proton reduction is platinum that functions as a highly efficient heterogeneous proton reduction catalyst with nearly no overpotential.85 Due to its limited availability and high price, platinum is not a good candidate for large scale applications. Nature has evolved a competitor to platinum in the form of hydrogenase enzymes. These enzymes contain solely base metals in their structure and perform proton reduction catalysis at high rates (9·103 s–1) with overpotentials close to the thermodynamic limit.86 As such, it is no surprise that vast effort is dedicated to mimic the active site of these enzymes. Three types of hydrogenases are known, namely [NiFe], [FeFe] and [Fe]–only hydrogenases with the letters referring to the metals present in the active site. [FeFe] hydrogenases are generally the most active in proton reduction catalysis and as a result most artificial systems pursuit structural or functional resem-

blance of the active site of this specific enzyme type.87 Many synthetic [FeFe] hydrogenase mimics already outperform the natural [FeFe] system by nearly an order of magnitude in terms of catalytic rate; rates of up to 7.0·104 s–1 have been reported.87 However, all mimics still suffer from large overpotentials.88

Figure 13. Synthetic [FeFe] hydrogenase mimics with the lowest overpotentials in proton reduction catalysis reported to date.

Scheme 8. Half reactions of water splitting into molecular oxygen and hydrogen (pH 0, 298 K).

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Four synthetic [FeFe] hydrogenase mimics with the lowest overpotentials re-ported to date are presented in Figure 13. Still, 400 mV overpotential is need-ed to drive catalysis with these complexes, resulting in inherently inefficient systems.

Some strategies to overcome these limitations have been presented, including the installment of a basic site on the dithiolate fragment of the complex to assist proton delivery, often referred to as ‘proton relay’. For example, two synthetic diiron hexacarbonyl catalysts that differ only in the bridgehead atom (nitrogen vs carbon) of the dithiolate fragment already show a difference of 250 mV in reduction potential, clearly demonstrating the stabilizing effect of the basic site.89,90 Another strategy, which is the topic of this section, involves the confinement of synthetic mimics in soluble (supra)molecular architectures including apohydrogenases, membranes, micelles, polymersomes, liposomes, peptidic scaffolds, cyclodextrins and dendrimers, with the aim to study the influence of the second coordination sphere on the catalyst performance. Met-al organic frameworks,91 fibrous cellulose membranes92 and peptide hydrogels93 have also received some attention in this area, but as heterogeneous second coordination spheres they are beyond the scope of this review.

Cyclodextrins

As previously discussed, CDs form stable host–guest complexes with various hydrophobic molecules in aqueous solutions due to the hydrophobic nature of their internal cavities. This can address one of the key problems of hydrogenase mimics, that is their low solubility in water which is the favored solvent and proton source for proton reduction catalysis. Moreover, the hydrophilic rims of the structure enable hydrogen bonding with potential guests. The group of Darensbourg has made use of these advantageous properties by encapsulation of small molecular models of the [FeFe] hydrogenase active site in β–cyclo-dextrins.94,95 The first example involves complex 21 in which the bridgehead nitrogen atom is functionalized with an aryl sulfonate moiety which renders the complex more soluble in water in addition to driving its encapsulation by hydrogen bonding interactions with the rims of the cyclodextrin (Figure 14). The aryl sulfonate group is located in one cyclodextrin cavity and the diiron center in another one. The two cyclodextrin units are bridged by hydrogen bonding between the hydroxyl groups and ion–dipole interactions with the so-dium counter–ion.

Introduction

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Encapsulation of 21 results in an 80 mV negative shift of the reduction poten-tial of the catalyst.94 Also the catalytic proton reduction potential shifts more negative in the cyclodextrin as compared to bulk solution and is attributed to the hydrophobicity of the cavity. The system was extended to a series of sulfonated phosphine–substituted diiron complexes (22–25) that differ by their solubility in water (Figure 15).95 Inclusion of the complexes in the CD structure was confirmed by NMR studies in addition to solid state structures. In all cases inclusion of the complexes in the CD improved their stability in water, but hindered proton reduction catalysis. The impaired catalysis in the CD is assigned to the rigidity of the second coordination sphere not allowing structur-al rearrangements of the complex or the slow diffusion of protons into the CD. Further studies with these types of host–guest complexes for photocatalytic applications were undertaken by Sun and co–workers.96,97 Via host–guest com-plexation of complex 21 published by the Darensbourg group94 and the organic dye Eosin Y with a tenfold excess of γ–cyclodextrin, a 16–fold increase in the quantum efficiency was achieved in photocatalytic proton reduction catalysis

Figure 14. Schematic and X–ray crystal structure of the host–guest complex between 21 and two β–cyclodextrin units.

Chapter 1

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as compared to the same system in the absence of cyclodextrin.96 In presence of CD, the stability of the catalyst towards photodegradation also increased, further demonstrating the beneficial effect of the second coordination sphere around the active catalyst. Functionalization of the CD with a thiol group al-lowed simultaneous grafting of both the catalyst and CdSe quantum dots (QD) to the cyclodextrin (Figure 16).97 In photocatalytic proton reduction catalysis the hybrid system reduces protons to molecular hydrogen with a turnover num-ber (TON) of 2370, which is nearly a 7–fold improvement compared to in the absence of cyclodextrin.

Micelles and liposomes

Micelles are soluble aggregates formed by self–assembly of surfactant molecules such as sodium dodecyl sulfate (SDS). Typically, micelles are present in aque-ous solutions and the hydrophilic head of the surfactant molecule is in contact with the polar solution, leaving the aliphatic tails in the hydrophobic center of the micelle. Just as for cyclodextrins, the apolar cavity of micelles can host various hydrophobic molecules and thereby isolate them from bulk solution.

Figure 15. Molecular structures of a series of CD–encapsulated diiron complexes stud-ied by Darensbourg and co–workers.

Introduction

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The effects of encapsulation of [FeFe] hydrogenase mimics in SDS micelles in aqueous solutions have been thor-oughly studied by the groups of Glo-aguen98,99 and Wu100,101. The first ex-ample constituted the incorporation of water insoluble mimic 26 and rheni-um(I) phenantroline photosensitizer 27 into the hydrophobic core of SDS micelles (Figure 17).101 In the presence of the micelles a colored solution is obtained, suggesting that the water insoluble complex is indeed solubilized in water by encapsulation in the mi-celles. The photochemical reaction for hydrogen evolution was carried out with complex 26 in a degassed SDS

micelle solution with ascorbic acid as the sacrificial electron donor (SED) and 27 as the photosensitizer. A maximum TON of 0.13 was obtained, indicating that the process is not catalytic. For a similar diiron complex, 28, in SDS micelles Gloaguen and co–workers showed that the activity of the catalyst is markedly increased when operating in aqueous micellar solutions as opposed to organic solvents.99 Moreover, by exchanging two CO ligands of complex 28 by two trimethoxyphosphite ligands complex 29 was obtained, that also shows high activity as an electrochemical proton reduction catalyst when dis-solved in aqueous SDS micellar solution.98 Complex 29 slowly decomposes in aqueous micellar solution at pH values below 2. The presence of micelles in electrochemistry causes the width of the double layer close to the electrode to increase, making the electron transfer relatively slow.102 Surfactant monomers, on the other hand, arrange at the electrode such that the rate of electron transfer increases. Some studies with [FeFe] hydrogenase complexes in reversed micelles103 and polymersomes100 have also been reported.

Wright, Picket, Hunt and co–workers used steady state, ultrafast pump–probe and 2D–IR spectroscopy to gain a deeper understanding of the molecular en-vironment of diiron complex 30 encapsulated by heptane–dodecyltrimethylam-monium bromide (DTAB) micelles in water (Figure 18, top).104 The question the authors raised was if water can penetrate the self–assembled structure and whether this process serves a role in enhancing the catalytic activity of the

Figure 16. Schematic diagram of the photocatalytic hybrid system based on complex 21 encapsulated in a cyclodex-trin with a CdSe QD grafted to it.97

Chapter 1

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complex. By using a combination of different spectroscopic techniques, it was concluded that up to 40% of the encapsulated molecules are accessible to the water molecules. The authors speculate that this may provide a route for sub-strate molecules to reach the catalyst, thereby increasing the catalytic rate as compared to in the absence of micelles.

The group of König has taken the encapsulation of [FeFe] mimics one step further by utilizing lipid bilayers in the form of self–assembled liposomes as the second coordination sphere.105,106 A ruthenium photosensitizer functionalized with aliphatic alkyl tails (31) was embedded in the phospholipid membrane of a liposome and complex 21 adsorbed to the surface of the liposome, resulting in a high local concentration of photosensitizer and catalyst (Figure 18, mid-dle).105 As a consequence, the system functions as a photocatalyst for proton reduction catalysis in water with a TON of 35. In the absence of liposome low productivity (TON = 3) is observed which is only marginally increased by the addition of acetonitrile as co–solvent (TON = 9). By exchanging the photosen-sitizer to oleic acid capped CdSe QD’s and by functionalizing the catalyst with

Figure 17. (left) Molecular structures of the photosensitizer and diiron complexes used by Wu, Gloaguen and co–workers. (right) Schematic picture of photocatalytic proton reduction catalysis in SDS micelles mediated by complex 26 and Re(I) photosensitizer 27.99,101

Introduction

— 27 —

Figure 18. (top) Diiron complex 30 encapsulated in a DTAB micelle, showing how water molecules penetrate into the micellar structure. (middle) Schematic picture of photocatalytic proton reduction catalysis with [FeFe] mimic 21 and alkyl–functionalized photosensitizer 31 co–embedded in the liposome membrane. HA– = ascorbate. (bottom) Schematic picture of photocatalytic proton reduction catalysis with alkyl–functionalized [FeFe] hydrogenase mimic 32 and oleic acid capped QD’s co–embedded in the liposome membrane.104–106

Chapter 1

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an aliphatic alkyl tail (32) enabling inclusion in the membrane, the catalytic productivity (TON = 651) was greatly increased (Figure 18, bottom).106

Peptides and apohydrogenases

Synthetic [FeFe] hydrogenase mimics have also been incorportated into pep-tides to mimic the natural protein environment of the hydrogenase active site. The typical strategy is to covalently link the complex to a peptide scaffold through a suitable substituent on the dithiolate moiety (Figure 19).107

Jones and co–workers showed that on resin synthesis of a modified lysine res-idue allowed the formation of [(μ–SRS){Fe(CO)3}2], where the [FeFe] complex is linked to a peptide framework through an amide bond (strategy II, Figure 19).108 The synthetic approach was further extended to mono–substituted phos-phine complexes which due to their more electron rich structure display higher catalytic rates than their non–substituted analogues, but at the expense of a higher overpotential.87,109 For efficient catalysis both a low overpotential and high rates are required.110 The attachment of the peptide significantly increases the polarity of the [FeFe] complex, allowing electrochemical studies in wa-

ter mixtures. These demon-strate that the reduction of the peptide [FeFe] complex in water has a milder poten-tial and increased current as compared to the reduction in pure organic solvents, showing the beneficial effect of applying water as the sol-vent.

The group of Ghirlanda has demonstrated that an [FeFe] hydrogenase mimic can be anchored to a model helical peptide via an artificial dithiolate amino acid.111 The method allows for the catalyst to be anchored at any position in the peptide framework and it is shown to stabilize the secondary helical structure of the peptide. In the presence of ruthenium(I) photosensitizer and ascorbate as SED the catalyst–peptide assembly catalyzes the reduction of protons in aqueous solution with a TON of 84. Hayashi and co–workers reported on a hy-brid system formed by the inclusion of an [FeFe] hydrogenase mimic and a ru-

Figure 19. Three typical strategies to covalently anchor synthetic [FeFe] hydrogenase mimics to pep-tide scaffolds.107

Introduction

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thenium photosensitizer into a native peptide sequence of cytochrome c556 enzyme (Figure 20).112 Formation of the hybrid system was con-firmed by high resolution mass spectrometry and IR spectroscopy. The novel sys-tem reduces protons photo-catalytically, albeit with low efficiency (TON = 8). The low efficiency is ascribed to decomposition of the [FeFe] complex under the applied catalytic conditions.

In 2013 a beautiful study was published by Fontecave and co–workers in which full activation of an [FeFe] hydrogenase mimic was achieved by loading it into an apohydrogenase.88 The diiron complex was first assembled on the helper protein HydF, where after the diiron complex was transferred into the apohy-drogenase HydA (Figure 21). IR studies confirm that the complex is located inside the natural protein structure. Coupling constants obtained from EPR measurements are in line with one of the CN– ligands of the complex bridging to the [4Fe–4S] cluster of the hydrogenase. Remarkably, the system results in

Figure 20. Schematic picture of photocatalytic pro-ton reduction catalysis with an [FeFe] hydrogenase mimic and a ruthenium photosensitizer docked in a native peptide sequence of cytochrome c556.112

Figure 21. Full activation of a synthetic [FeFe] hydrogenase mimic complex by incor-poration in the apohydrogenase HydA1. The crystal structures of the proteins are taken from the protein data bank and correspond to PDB ID numbers 3QQ5 and 3LX4 and they are visualized with the software Pymol.

Chapter 1

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proton reduction catalytic activity comparable to a fully active native [FeFe] hydrogenase. Later the group of Happe showed that mimics can also be fully activated without helper proteins by direct incorporation of the diiron complex into an apohydrogenase.113 Both studies clearly demonstrate the crucial impor-tance of the secondary protein structure on the activity of diiron complexes.

Dendrimers

Dendrimers are highly branched macromolecules with a well–defined structure and they are also used as second coordination spheres for [FeFe] hydrogenase mimics. Zheng, Yang, Li and co–workers reported the first example of embed-ding the hydrogenase mimic [(µ–S2)Fe2(CO)6] in the core of dendrimers based on Fréchet–type dendrons (Figure 22, 33–36).114 The structures of the various complexes were confirmed by NMR and IR spectroscopy along with high res-olution mass spectrometry. When combined with photosensitizer [Ir(ppy)2(bpy)]PF6 (ppy = 2‐phenylpyridine, bpy = 2,2’‐bipyridine) in presence of triethyl-amine as SED in a 9:1 mixture of acetone and water as solvent, the system reduces protons photocatalytically with high efficiency. A maximum TON of 22,200 was obtained after having reached a plateau after 8 h irradiation for complex 36. The other complexes 33–35 are also highly efficient catalysts, and the trend is that the higher generation dendrimers give better performance. The diiron catalyst is highly stabilized by the dendritic structure and displays the highest TON obtained for [2Fe2S] catalysts in photocatalytic proton re-duction catalysis. This high efficiency is attributed to the increase in lifetime of the charge–separated state enabled by the dendrimer structure. The neutral photosensitizer penetrates into the hydrophobic dendrimer structure, and after electron transfer to the catalyst the cationic photosensitizer escapes the struc-ture and thereby decreases undesired charge recombination. Second generation dendritic hydrogenases were reported in which the iridium(I) photosensitizers were covalently attached to the rims of the dendrimers to mimic the light–har-vesting antennae of plants.115 However, the catalytic efficiency is much lower (TON = 74) than for the first noncovalent approach due to more easy charge recombination.

Clearly second coordination spheres provide a new means by which the activity of encapsulated [FeFe] hydrogenase mimics can be effectively controlled. Yet, all overpotentials are high apart from systems relying on the natural apohy-drogenase. To this end, in this thesis we aim to reduce the overpotential of

Introduction

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synthetic [FeFe] hydrogenase mimics by encapsulation in synthetic second co-ordination spheres and to understand the underlying principles governing the overpotentials of the encapsulated catalysts.

Figure 22. Molecular structures of the diiron mimics encapsulated by dendritic struc-tures.114

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Thesis scope and outlineThis thesis is the result of a research project with the topic of nature in-spired transition metal catalysis in supramolecular cages. The project focused on studying various effects of confinement on encapsulated transition metal catalysts, with the aim to control the activity, selectivity or stability of the catalyst by the surrounding second coordination sphere.

Chapter 2 reports on the encapsulation of a rhodium complex in a supra-molecular assembly based on a pyridine–functionalized phosphine ligand and zinc porpholactone moieties. The resulting supramolecular catalyst displays unprecedented branched selectivity in the hydroformylation of propene. The used porholactone units display strong binding with the pyridine groups of the phosphine ligand, resulting in a cage that is stable in polar and coordinating solvents. As a result, the cage–controlled hydroformylation reaction can be extended to industrially relevant polar solvents such as dioctyl terephthalate without compromising the regioselectivity.

Chapter 3 discusses the first example of substrate–selective hydroformylation of terminal alkenes by embedding a rhodium bisphosphine complex in a supra-molecular metal–organic cage that is formed by subcomponent self–assembly. The catalyst is bound in the cage via a template ligand approach in which pyridyl–zinc(II)porphyrin interactions lead to high association constants for the binding of the ligands and the corresponding rhodium complex. DFT calcu-lations confirm that the second coordination sphere forces the encapsulated active species to adopt the diequatorial coordination geometry, in line with in situ high pressure IR studies of the host–guest complex. The window aperture of the cage decreases slightly upon binding the catalyst. As a result, the diffu-sion of larger substrates into the cage is slower compared to smaller substrates. Consequently, the encapsulated rhodium catalyst displays substrate selectivity, converting smaller substrates faster to the corresponding aldehydes.

Chapter 4 describes the design of a biomimetic and fully base–metal photoca-talytic system for photocatalytic proton reduction in a homogeneous medium. A synthetic pyridylphosphole–appended [FeFe]hydrogenase mimic is encapsulated inside a supramolecular zinc porphyrin–based metal–organic cage structure. The binding is driven by the selective pyridine–zinc porphyrin interaction and results in the catalyst being bound strongly inside the hydrophobic cavity of the cage. Excitation of the capsule–forming porphyrin ligands with visible light,

Introduction

— 33 —

while probing the infrared spectrum, confirms that electron transfer takes pla-ce from the excited porphyrin cage to the catalyst residing inside the capsule. Light–driven proton reduction is achieved by irradiation of an acidic solution of the caged catalyst with visible light.

Chapter 5 reports a new tetrahedral porphyrin–based M4L6 cage with redox–innocent triazole corners that allows for it to be applied as a second coordina-tion sphere for reductive catalysis. The structure of the novel cage is confirmed by various spectroscopic techniques and high resolution mass spectrometry. Relying on the well–known pyridine–zinc porphyrin interaction, pyridine–func-tionalized synthetic [FeFe]hydrogenase mimic 1 is selectively encapsulated in-side the cage with a relatively high binding constant (>104 M–1). Electrochem-ical studies of encapsulated 1 reveal that its disproportionation, which occurs in bulk solution, is prevented by the surrounding second coordination sphere. In the presence of mild acid, the confined complex functions as a highly active (4.2·105 M–1s–1) electrocatalyst for proton reduction catalysis and it operates with a 150 mV lower overpotential than the same catalyst in bulk solution. Irradiation of the cage by visible light, while probing the IR spectrum, leads to electron transfer from the cage to the encapsulated catalyst confirming the formation of the mono–anion 1–. In the presence of trifluoroacetic acid under visible light irradiation, the novel system reduces protons photo–catalytically.

Chapter 6 shows the design and synthesis of a novel supramolecular cage-based functional rotaxane. Water–soluble M6L4 cage 1d functions as the mac-rocycle and tetraethylene glycol–substituted pyrene 20 operates as the rod–like structure. Bulky water–soluble β–cyclodextrin groups are installed at each end of the threaded rod to kinetically trap it inside the cage. Rod 20 is confirmed to thread through the cage to give a pseudorotaxane and this binding is driv-en by favorable π–π stacking interactions between the interior of the cage and the aromatic pyrene plane. Two rod molecules are shown to bind in a single cage, but the second binding is an order of magnitude weaker than the first. Alternatively, the rod co–encapsulates with ferrocene to give a stable ternary host–guest complex. In our design the co–encapsulation of the rod and ferro-cene will serve as a novel trigger for shuttling. By extraction of one guest from the interior of the cage, the binding of the second guest changes significantly, which may allow for shuttling when two stations are incorporated in the same rod structure.

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References(1) Wisniak, J. Educ. Química 2010, 21, 60–69.

(2) Zhou, Q.–L. Angew. Chem. Int. Ed. 2016, 55, 5352–5353.

(3) Van Leeuwen, P. W. N. M. In Homogeneous catalysis: Understand-ing the art; Kluwer Academic Publishers: Dordrecht, The Netherlands, 2004; pp 125–174.

(4) Ringe, D.; Petsko, G. A. Science 2008, 320, 1428–1429.

(5) Wang, Q.–Q.; Gonell, S.; Leenders, S. H. A. M.; Dürr, M.; Ivanović–Burmazović, I.; Reek, J. N. H. Nat. Chem. 2016, 8, 225–230.

(6) Rajagopalan, P. T. R.; Benkovic, S. J. Chem. Rec. 2002, 2, 24–36.

(7) Leenders, S. H. A. M.; Gramage–Doria, R.; de Bruin, B.; Reek, J. N. H. Chem. Soc. Rev. 2015, 44, 433–448.

(8) Brown, C. J.; Toste, F. D.; Bergman, R. G.; Raymond, K. N. Chem. Rev. 2015, 115, 3012–3035.

(9) Yoshizawa, M.; Klosterman, J. K. K.; Fujita, M. Angew. Chem. Int. Ed. 2009, 48, 3418–3438.

(10) Vriezema, D. M.; Comellas Aragonès, M.; Elemans, J. A. A. W.; Cor-nelissen, J. J. L. M.; Rowan, A. E.; Nolte, R. J. M. Chem. Rev. 2005, 105, 1445–1490.

(11) Hooley, R. J.; Rebek Jr., J. Chem. Biol. 2009, 16, 255–264.

(12) Roelen, O. (to Chemische Verwertungsgesellschaft Oberhausen m.b.H.) German Patent DE 849548, 1938/1952; US Patent 2327066, 1943; Chem. Abstr. 1944, 38, 3631.

(13) Franke, R.; Selent, D.; Börner, A. Chem. Rev. 2012, 112, 5675–5732.

(14) Gusevskaya, E. V.; Jiménez–Pinto, J.; Börner, A. ChemCatChem 2014, 6, 382–411.

(15) Cornils, B.; Herrmann, W. A. In Applied Homogeneous Catalysis with

Introduction

— 35 —

Organometallic Compounds: A Comprehensive Handbook in Three Volumes; Wiley–VCH Verlag GmbH & Co: Weinheim, Germany, 2002; Vol. 1, pp 31–194.

(16) Vilches–Herrera, M.; Domke, L.; Börner, A. ACS Catal. 2014, 4, 1706–1724.

(17) Heck, R. F.; Breslow, D. S. J. Am. Chem. Soc. 1961, 83, 4023–4027.

(18) Heck, R. F. Acc. Chem. Res. 1969, 2, 10–16.

(19) Agbossou, F.; Carpentier, J.–F.; Mortreux, A. Chem. Rev. 1995, 95, 2485–2506.

(20) Van Leeuwen, P. W. N. M.; Claver, C. Rhodium Catalyzed Hydro-formylation; Kluwer Academic Publishers: Dordrecht, The Nether-lands, 2000.

(21) Lazzaroni, R.; Settambolo, R.; Uccello–Barretta, G.; Caiazzo, A.; Scamuzzi, S. J. Mol. Catal. A Chem. 1999, 143, 123–130.

(22) Van der Slot, S. C.; Duran, J.; Luten, J.; Kamer, P. C. J.; Van Leeu-wen, P. W. N. M. Organomet. 2002, 21, 3873–3883.

(23) Watkins, A. L.; Landis, C. R. J. Am. Chem. Soc. 2010, 132 (30), 10306–10317.

(24) Wiese, K.–D.; Obst, D. In Catalytic Carbonylation Reactions; Beller, M., Ed.; Springer: Berlin, Germany, 2006; pp 1–33.

(25) Kubis, C.; Baumann, W.; Barsch, E.; Selent, D.; Sawall, M.; Ludwig, R.; Neymeyr, K.; Hess, D.; Franke, R.; Börner, A. ACS Catal. 2014, 4, 2097–2108.

(26) Kubis, C.; Sawall, M.; Block, A.; Neymeyr, K.; Ludwig, R.; Börner, A.; Selent, D. Chem. Eur. J. 2014, 20, 11921–11931.

(27) Kubis, C.; Ludwig, R.; Sawall, M.; Neymeyr, K.; Börner, A.; Wiese, K.–D.; Hess, D.; Franke, R.; Selent, D. ChemCatChem 2010, 2, 287–295.

(28) Kubis, C.; Selent, D.; Sawall, M.; Ludwig, R.; Neymeyr, K.; Baumann,

Chapter 1

— 36 —

W.; Franke, R.; Börner, A. Chem. – A Eur. J. 2012, 18, 8780–8794.

(29) Casey, C. P.; Petrovich, L. M. J. Am. Chem. Soc. 1995, 117, 6007–6014.

(30) Lazzaroni, R.; Uccello–Barretta, G.; Scamuzzi, S.; Settambolo, R.; Caiazzo, A. Organomet. 1996, 15, 4657–4659.

(31) Horiuchi, T.; Shirakawa, E.; Nozaki, K.; Takaya, H. Organomet. 1997, 16, 2981–2986.

(32) Brezny, A. C.; Landis, C. R. J. Am. Chem. Soc. 2017, 139, 2778–2785.

(33) Van Rooy, A.; de Bruijn, J. N. H.; Roobeek, K. F.; Kamer, P. C. J.; Van Leeuwen, P. W. N. M. J. Organomet. Chem. 1996, 507, 69–73.

(34) Kamer, P. C. J.; Van Rooy, A.; Schoemaker, G. C.; van Leeuwen, P. W. N. M. Coord. Chem. Rev. 2004, 248, 2409–2424.

(35) Casey, C. P.; Whiteker, G. T.; Melville, M. G.; Petrovich, L. M.; Gavney, J. A.; Powell, D. R. J. Am. Chem. Soc. 1992, 114, 5535–5543.

(36) Kranenburg, M.; van der Burgt, Y. E. M.; Kamer, P. C. J.; van Leeu-wen, P. W. N. M.; Goubitz, K.; Fraanje, J. Organometallics 1995, 14, 3081–3089.

(37) Van Der Veen, L. A.; Boele, M. D. K.; Bregman, F. R.; Kamer, P. C. J.; Van Leeuwen, P. W. N. M.; Goubitz, K.; Fraanje, J.; Schenk, H.; Bo, C. J. Am. Chem. Soc. 1998, 120, 11616–11626.

(38) Van der Veen, L. A.; Keeven, P. H.; Schoemaker, G. C.; Reek, J. N. H.; Kamer, P. C. J.; Van Leeuwen, P. W. N. M.; Lutz, M.; Spek, A. L. Organometallics 2000, 19, 872–883.

(39) Carbó, J. J.; Maseras, F.; Bo, C.; van Leeuwen, P. W. N. M. J. Am. Chem. Soc. 2001, 123, 7630–7637.

(40) Kumar, M.; Chaudhari, R. V.; Subramaniam, B.; Jackson, T. A. Or-ganometallics 2015, 34, 1062–1073.

Introduction

— 37 —

(41) Sakai, N.; Mano, S.; Nozaki, K.; Takaya, H. J. Am. Chem. Soc. 1993, 115, 7033–7034.

(42) Nozaki, K.; Sakai, N.; Nanno, T.; Takanori, H.; Mano, S.; Horiuchi, T.; Takaya, H. J. Am. Chem. Soc. 1997, 119, 4413–4423.

(43) Yan, Y.; Zhang, X. J. Am. Chem. Soc. 2006, 128, 7198–7202.

(44) Landis, C. R.; Jin, W.; Owen, J. S.; Clark, T. P. Angew. Chem. Int. Ed. 2001, 40, 3432–3434.

(45) Clark, T. P.; Landis, C. R.; Freed, S. L.; Klosin, J.; Abboud, K. A. J. Am. Chem. Soc. 2005, 127, 5040–5042.

(46) Klosin, J.; Landis, C. R. Acc. Chem. Res. 2007, 40, 1251–1259.

(47) Noonan, G. M.; Fuentes, J. A.; Cobley, C. J.; Clarke, M. L. Angew. Chem. Int. Ed. 2012, 124, 2527–2530.

(48) Dingwall, P.; Fuentes, J. A.; Crawford, L.; Slawin, A. M. Z.; Bühl, M.; Clarke, M. L. J. Am. Chem. Soc. 2017, 139, 15921–15932.

(49) Zarra, S.; Wood, D. M.; Roberts, D. A.; Nitschke, J. R. Chem. Soc. Rev. 2015, 44, 419–432.

(50) Breiner, B.; Clegg, J. K.; Nitschke, J. R. Chem. Sci. 2011, 2, 51–56.

(51) Wiester, M. J.; Ulmann, P. A.; Mirkin, C. A. Angew. Chem. Int. Ed. 2011, 50, 114–137.

(52) Monflier, E.; Tilloy, S.; Fremy, G.; Castanet, Y.; Mortreux, A. Tetra-hedron Lett. 1995, 36, 9481–9484.

(53) Mathivet, T.; Méliet, C.; Castanet, Y.; Mortreux, A.; Caron, L.; Tilloy, S.; Monflier, E. J. Mol. Catal. A 2001, 176, 105–116.

(54) Leclercq, L.; Hapiot, F.; Tilloy, S.; Ramkisoensing, K.; Reek, J. N. H.; Van Leeuwen, P. W. N. M.; Monflier, E. Organomet. 2005, 24, 2070–2075.

(55) Legrand, F.–X.; Hapiot, F.; Tilloy, S.; Guerriero, A.; Peruzzini, M.; Gonsalvi, L.; Monflier, E. Appl. Catal. A 2009, 362, 62–66.

Chapter 1

— 38 —

(56) Elard, M.; Denis, J.; Ferreira, M.; Bricout, H.; Landy, D.; Tilloy, S.; Monflier, E. Catal. Today 2015, 247, 47–54.

(57) Vanbésien, T.; Sayede, A.; Monflier, E.; Hapiot, F. Catal. Sci. Tech-nol. 2016, 6, 3064–3073.

(58) Cousin, K.; Menuel, S.; Monflier, E.; Hapiot, F. Angew. Chem. Int. Ed. 2017, 56, 10564–10568.

(59) Reetz, M. T.; Waldvogel, S. R. Angew. Chem. Int. Ed. 1997, 36, 865–867.

(60) Jouffroy, M.; Gramage–Doria, R.; Armspach, D.; Sémeril, D.; Ober-hauser, W.; Matt, D.; Toupet, L. Angew. Chem. Int. Ed. 2014, 53, 3937–3940.

(61) Van Leeuwen, P. W. N. M.; Kamer, P. C. J. Phosphorus (III) Li-gands in Homogeneous Catalysis Design and Synthesis; John Wiley & Sons: New Jersey, USA, 2012.

(62) Sémeril, D.; Matt, D. Coord. Chem. Rev. 2014, 279, 58–95.

(63) Slagt, V. F.; Reek, J. N. H.; Kamer, P. C. J.; Van Leeuwen, P. W. N. M. Angew. Chem. Int. Ed. 2001, 113, 4401–4404.

(64) Slagt, V. F.; Kamer, P. C. J.; Van Leeuwen, P. W. N. M.; Reek, J. N. H. J. Am. Chem. Soc 2004, 126, 1526–1536.

(65) Kleij, A. W.; Reek, J. N. H. Chem. Eur. J. 2006, 12, 4218–4227.

(66) Jacobs, I.; de Bruin, B.; Reek, J. N. H. ChemCatChem 2015, 7, 1708–1718.

(67) Kleij, A. W.; Kuil, M.; Tooke, D. M.; Spek, A. L.; Reek, J. N. H. In-org. Chem. 2005, 44, 7696–7698.

(68) Kleij, A. W.; Lutz, M.; Spek, A. L.; Van Leeuwen, P. W. N. M.; Reek, J. N. H. Chem. Commun. 2005, 0, 3661.

(69) Jacobs, I.; Van Duin, A. C. T.; Kleij, A. W.; Kuil, M.; Tooke, D. M.; Spek, A. L.; Reek, J. N. H. Catal. Sci. Technol. 2013, 3, 1955–1963.

Introduction

— 39 —

(70) Bocokić, V.; Lutz, M.; Spek, A. L.; Reek, J. N. H. Dalt. Trans. 2012, 41, 3740–3750.

(71) Kuil, M.; Soltner, T.; Van Leeuwen, P. W. N. M.; Reek, J. N. H. J. Am. Chem. Soc. 2006, 128, 11344–11345.

(72) Bocokić, V.; Kalkan, A.; Lutz, M.; Spek, A. L.; Gryko, D. T.; Reek, J. N. H. Nat. Comm. 2013, 4, 2670.

(73) Besset, T.; Norman, D. W.; Reek, J. N. H. Adv. Synth. Catal. 2013, 355, 348–352.

(74) Wang, X.; Nurttila, S. S.; Dzik, W. I.; Becker, R.; Rodgers, J.; Reek, J. N. H. Chem. Eur. J. 2017, 23, 14769–14777.

(75) Bellini, R.; Chikkali, S. H.; Berthon–Gelloz, G.; Reek, J. N. H. Angew. Chem. Int. Ed. 2011, 50, 7342–7345.

(76) Bellini, R.; Reek, J. N. H. Chem. Eur. J. 2012, 18, 7091–7099.

(77) Bellini, R.; Reek, J. N. H. Chem. Eur. J. 2012, 18, 13510–13519.

(78) Gadzikwa, T.; Bellini, R.; Dekker, H. L.; Reek, J. N. H. J. Am. Chem. Soc. 2012, 134, 2860–2863.

(79) García–Simón, C.; Gramage–Doria, R.; Raoufmoghaddam, S.; Parella, T.; Costas, M.; Ribas, X.; Reek, J. N. H. J. Am. Chem. Soc. 2015, 137, 2680–2687.

(80) Heyduk, A. F.; Nocera, D. G. Science 2001, 293, 1639–1641.

(81) Bolton, J. R. Science 1978, 202, 705–711.

(82) Haryanto, A.; Fernando, S.; Murali, N.; Adhikari, S. Energy Fuels 2005, 19, 2098–2106.

(83) Hydrogen Production In The Coming Hydrogen Economy https://newenergytreasure.com/2014/06/28/hydrogen–production–in–the–new–hydrogen–economy/ (accessed Jun 19, 2018).

(84) Styring, S. Faraday Discuss. 2012, 155, 357–376.

(85) Abe, T.; Hirano, K.; Shiraishi, Y.; Toshima, N.; Kaneko, M. Eur.

Chapter 1

— 40 —

Polym. J. 2001, 37, 753–761.

(86) Winkler, M.; Esselborn, J.; Happe, T. Biochim. Biophys. Acta – Bio-energ. 2013, 1827, 974–985.

(87) Watanabe, M.; Honda, Y.; Hagiwara, H.; Ishihara, T. J. Photochem. Photobiol. C Photochem. Rev. 2017, 33, 1–26.

(88) Berggren, G.; Adamska, A.; Lambertz, C.; Simmons, T. R.; Esselborn, J.; Atta, M.; Gambarelli, S.; Mouesca, J.–M.; Reijerse, E.; Lubitz, W.; Happe, T.; Artero, V.; Fontecave, M. Nature 2013, 499, 66–69.

(89) Capon, J.–F.; Ezzaher, S.; Gloaguen, F.; Pétillon, F. Y.; Schollhammer, P.; Talarmin, J.; Davin, T. J.; McGrady, J. E.; Muir, K. W. New J. Chem. 2007, 31, 2052.

(90) Ott, S.; Kritikos, M.; Åkermark, B.; Sun, L.; Lomoth, R. Angew. Chem. Int. Ed. 2004, 116, 1024–1027.

(91) Balestri, D.; Roux, Y.; Mattarozzi, M.; Mucchino, C.; Heux, L.; Braz-zolotto, D.; Artero, V.; Duboc, C.; Pelagatti, P.; Marchiò, L.; Gennari, M. Inorg. Chem. 2017, 56, 14801–14808.

(92) Zhu, D.; Xiao, Z.; Liu, X. Int. J. Hydrogen Energy 2015, 40, 5081–5091.

(93) Frederix, P. W. J. M.; Kania, R.; Wright, J. A.; Lamprou, D. A.; Ulijn, R. V.; Pickett, C. J.; Hunt, N. T. Dalt. Trans. 2012, 41, 13112–13119.

(94) Singleton, M. L.; Reibenspies, J. H.; Darensbourg, M. Y. J. Am. Chem. Soc. 2010, 132, 8870–8871.

(95) Singleton, M. L.; Crouthers, D. J.; Duttweiler III, R. P.; Reibenspies, J. H.; Darensbourg, M. Y. Inorg. Chem. 2011, 50, 5015–5026.

(96) Li, X.; Wang, M.; Zheng, D.; Han, K.; Dong, J.; Sun, L. Energy En-viron. Sci. 2012, 5, 8220–8224.

(97) Cheng, M.; Wang, M.; Zhang, S.; Liu, F.; Yang, Y.; Wan, B.; Sun, L. Faraday Discuss. 2017, 198, 197–209.

(98) Quentel, F.; Passard, G.; Gloaguen, F. Chem. Eur. J 2012, 18, 13473–

Introduction

— 41 —

13479.

(99) Quentel, F.; Passard, G.; Gloaguen, F. Energy Environ. Sci. 2012, 5, 7757–7761.

(100) Wang, F.; Wen, M.; Feng, K.; Liang, W.–J.; Li, X.–B.; Chen, B.; Tung, C.–H.; Wu, L.–Z. Chem. Commun. 2016, 52, 457–460.

(101) Wang, H.–Y.; Wang, W.–G.; Si, G.; Wang, F.; Tung, C.–H.; Wu, L.–Z. Langmuir 2010, 26, 9766–9771.

(102) Ko, Y.–C. Bull. Korean Chem. Soc. 2007, 28, 1857–1859.

(103) Hilhorst, R.; Laane, C.; Veeger, C. Proc. Natl. Acad. Sci. U. S. A. 1982, 79, 3927–3930.

(104) Fritzsch, R.; Brady, O.; Adair, E.; Wright, J. A.; Pickett, C. J.; Hunt, N. T. J. Phys. Chem. Lett. 2016, 7, 2838–2843.

(105) Troppmann, S.; Brandes, E.; Motschmann, H.; Li, F.; Wang, M.; Sun, L.; König, B. Eur. J. Inorg. Chem. 2016, 554–560.

(106) Troppmann, S.; König, B. ChemistrySelect 2016, 1, 1405–1409.

(107) Simmons, T. R.; Berggren, G.; Bacchi, M.; Fontecave, M.; Artero, V. Coord. Chem. Rev. 2014, 270–271, 127–150.

(108) Roy, S.; Shinde, S.; Hamilton, G. A.; Hartnett, H. E.; Jones, A. K. Eur. J. Inorg. Chem. 2011, 1050–1055.

(109) Roy, S.; Nguyen, T.–A. D.; Gan, L.; Jones, A. K. Dalt. Trans. 2015, 44, 14865–14876.

(110) Artero, V.; Saveant, J.–M. Energy Environ. Sci. 2014, 7, 3808–3814.

(111) Roy, A.; Madden, C.; Ghirlanda, G. Chem. Commun. 2012, 48, 9816–9818.

(112) Sano, Y.; Onoda, A.; Hayashi, T. J. Inorg. Biochem. 2012, 108, 159–162.

(113) Esselborn, J.; Lambertz, C.; Adamska–Venkatesh, A.; Simmons, T.; Berggren, G.; Noth, J.; Siebel, J.; Hemschemeier, A.; Artero, V.; Rei-

Chapter 1

— 42 —

jerse, E.; Fontecave, M.; Lubitz, W.; Happe, T. Nat. Chem. Biol. 2013, 9, 607–609.

(114) Yu, T.; Zeng, Y.; Chen, J.; Li, Y.–Y.; Yang, G.; Li, Y. Angew. Chem. Int. Ed 2013, 125, 5741–5745.

(115) Xun, Z.; Yu, T.; Zeng, Y.; Chen, J.; Zhang, X.; Yang, G.; Li, Y. J. Mater. Chem. A 2015, 3, 12965–12971.