Preparation of Ruthenium Olefin Metathesis Catalysts Immobilized

catalysts

Article Preparation of Ruthenium Oleﬁn Metathesis Catalysts Immobilized on MOF, SBA-15, and 13X for Probing Heterogeneous Boomerang Eﬀect

Artur Chołuj † , Wojciech Noga´s † , Michał Patrzałek †, Paweł Krzesi ´nski †, Michał J. Chmielewski , Anna Kajetanowicz * and Karol Grela * Biological and Chemical Research Centre, Faculty of Chemistry, University of Warsaw, Zwirki˙ i Wigury Street 101, 02-089 Warsaw, Poland; [email protected] (A.C.); [email protected] (W.N.); [email protected] (M.P.); [email protected] (P.K.); [email protected] (M.J.C.) * Correspondence: [email protected] (A.K.); [email protected] (K.G.) These authors contributed equally. † Received: 15 March 2020; Accepted: 15 April 2020; Published: 17 April 2020

Abstract: Promoted by homogeneous Ru-benzylidene complexes, the olefin metathesis reaction is a powerful methodology for C-C double bonds formation that can find a number of applications in green chemical production. A set of heterogeneous olefin metathesis pre-catalysts composed of ammonium-tagged Ru-benzylidene complexes 4 (commercial FixCat™ catalyst) and 6 (in-house made) immobilized on solid supports such as 13X zeolite, metal-organic framework (MOF), and SBA-15 silica were obtained and tested in catalysis. These hybrid materials were doped with various amounts of ammonium-tagged styrene derivative 5—a precursor of a spare benzylidene ligand—in order to enhance pre-catalyst regeneration via the so-called release-return “boomerang effect”. Although this effect was for the first time observed inside the solid support, we discovered that non-doped systems gave better results in terms of the resulting turnover number (TON) values, and the most productive were hybrid catalysts composed of 4@MOF, 4@SBA-15, and 6@SBA-15.

Keywords: oleﬁn metathesis; ruthenium; supported catalysts; metal organic frameworks; SBA-15; − microporous materials; boomerang eﬀect

1. Introduction It is well established that the initiation step in oleﬁn metathesis reaction catalyzed by the so-called Hoveyda–Grubbs catalyst (1) involves the dissociation of the 2-(isopropoxy)benzylidene ligand and the release of 2-(isopropoxy)styrene 2 (Figure1a) [ 1,2]. In 1999, Hoveyda showed that after the metathesis reaction, the released styrene 2 can react back with propagating (and unstable) 14 e– ruthenium species to re-create the pre-catalyst (1). He called it the release-return (or boomerang) mechanism [3]. Since in many synthetic studies it was found that catalyst 1 can be recovered after the metathesis reaction [3–6] (at least in a good part), many accepted the existence of the boomerang mechanism. In addition, various early labeling studies provided evidence that this mechanism is operative. For example, in 2008 we executed a study showing that during the metathesis reaction conducted in the presence of one equivalent of deuterium labeled styrene 2, up to 50% of Hoveyda pre-catalyst isolated after the reaction contained the labeled benzylidene ligand, thus the release-return mechanism may be operational [7]. However, since these experiments used relatively high catalyst loading (5 mol %), the relevance of the boomerang mechanism in truly catalytic reaction conditions ( 1 mol % ≤ of catalyst loading) was later questioned. Plenio investigated this matter in a scholarly way using a ﬂuorophore-tagged Hoveyda complex [8]. Using a small amount of the catalyst (0.2 mol %), he did not

Catalysts 2020, 10, 438; doi:10.3390/catal10040438 www.mdpi.com/journal/catalysts Catalysts 2020, 10, 438 2 of 18 Catalysts 2019, 9, x FOR PEER REVIEW 2 of 18 ﬁnd evidence of a release-return mechanism in the studied ring-closing metathesis (RCM) reactions. evidenceIt shall of bea release-return noted that the complex mechanism used in in histhe studystudied formally ring-closing belonged metathesis to a class of(RCM) fast-activating reactions. It shallEWG-substituted be noted that the Hoveyda–Grubbs complex used in complexes his study [ 9formally]. belonged to a class of fast-activating EWG- substituted Hoveyda–Grubbs complexes [9].

FigureFigure 1. a) 1. Widely(a) Widely accepted accepted dissociative dissociative mechanism mechanism of of initiation of of a a Ru Ru pre-catalyst pre-catalyst (black (black arrows) arrows) and suggestedand suggested pre-catalyst pre-catalyst regeneration regeneration via via the the “boomerang” mechanism mechanism (red (red arrows). arrows). (b,c )b Problems,c) Problems in a Ruin a catalyst Ru catalyst immobilization immobilization caused caused by by ligand ligand dissociation.dissociation. For For Hoveyda–Grubbs Hoveyda–Grubbs catalysts catalysts1 L = 1 L = SIMes (1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene). SIMes (1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene). Fogg undertook another study revisiting our old labeling experiments and addressing their deﬁcienciesFogg undertook [10]. The another initial experiments study revisiting showed our that old even labeling a small experiments amount of 2-(isopropoxy)styrene and addressing their deficiencies2 can inhibit [10]. aThe model initial metathesis experiments reaction, showed indicating that even that thea small reaction amount between of 2-(isopropoxy)styrene propagating 14 e- 2 canruthenium inhibit a speciesmodel andmetathesis2 is rapid reaction, in both its indicating early and latethat stages. the reaction Next, the between cross-over propagating studies with 14 e– rutheniumthe 13C-labeled species and styrene 2 is2 rapidshowed in both a very its e ﬃearlycient and formation late stages. of 13C-labeled Next, the1 cross-overin a near theoretical studies with the 13equilibriumC-labeled amountstyrene (47%),2 showed further a supporting very efficient therelease-return formation of mechanism 13C-labeled [10 ].1 in a near theoretical equilibriumAlthough amount no (47%), consensus further has been supporting reached on the the release-return existence or lack mechanism of the release-return [10]. mechanism underAlthough “practical” no consensus metathesis conditions has been typically reached applied on the in organic existence synthesis, or lack in the of context the of release-return catalysts immobilization one can anticipate the apparent problems caused by unavoidable benzylidene ligand mechanism under “practical” metathesis conditions typically applied in organic synthesis, in the dissociation during initiation of a supported Hoveyda–Grubbs catalyst (Figure1a). context of catalysts immobilization one can anticipate the apparent problems caused by unavoidable Basically, the immobilization can be made via a dissociating benzylidene ligand (Figure1b) or via benzylidenea non-dissociating ligand dissociation ligand L (Figure during1c). initiation Both these of approaches a supported are notHoveyda–Grubbs free from potential catalyst problems (Figure 1a). that can lead to two extremes: Basically, the immobilization can be made via a dissociating benzylidene ligand (Figure 1b) or via a non-dissociating ligand L (Figure 1c). Both these approaches are not free from potential problems that can lead to two extremes: (i) For systems where the support is connected via a dissociating ligand (Figure 1b), initiation of the catalysts must lead to leaching metal out of the support. Despite some spectacular failures of such systems in continuous flow experiments [11], this mode of immobilization was surprisingly popular in the early years of the metathesis research [12,13];

Catalysts 2020, 10, 438 3 of 18

(i) For systems where the support is connected via a dissociating ligand (Figure1b), initiation of the catalysts must lead to leaching metal out of the support. Despite some spectacular failures of such systems in continuous flow experiments [11], this mode of immobilization was surprisingly popular in the early years of the metathesis research [12,13]; (ii) For systems where the support is connected to a non-dissociating ligand (Figure1b) the situation is seemingly better because usually there is no heavy leaching observed with such systems. However, as the initiation step leaves the catalysts stripped off the stabilizing alkylidene ligand, the remaining fragile 14 e− Ru complexes are totally exposed to harmful factors such as oxygen or impurities from solvents and reagents. As a result, such immobilized complexes quickly die, and as their cadavers stay attached to the support, usually there is no strong leaching of metal to the organic products [14]. Interestingly, many of these immobilized systems were reported to work well in batch and even enabled the catalysts recycling from 3 to 10 times (however, usually applied at relatively large loading, such as 5 mol %). In this context, it was often suggested that the presence of the release-return ≥ boomerang mechanism may help to regenerate the pre-catalysts on the support [12,13]. Despite the lack of a general consensus regarding the existence of the release-return process, the boomerang mechanism has already been applied to improve the outcome of heterogeneous metathesis reactions involving immobilized Hoveyda–Grubbs type catalysts. While Hoveyda has unambiguously shown [3] that the participation of the release-return mechanism in the case of 1 bounded to glass-sol pellets in a batch is not high (measured as the propagating 14 e− species cross-over between two separate pellets, Figure2a), other trials were continued. Skowerski [ 15] very elegantly utilized the boomerang effect to prolong the length of life of commercial FixCat™ catalyst 4 immobilized on SBA-15 under batch and continuous flow conditions (Figure2b). In the initial experiment in batch, it was shown that the addition of the benzylidene ligand precursor 3 (100 ppm, 1 equiv. relative to the Ru catalyst used) to the solution of a metathesis substrate resulted in the reduction of immobilized catalyst 4 activity, which is in full accordance with the results obtained earlier by Fogg [10]. At the same time, a visible stabilization of 4@SBA-15 system was observed in continuous flow when styrene derivative 3 was added to the substrate feed (Figure2b). Although the catalyst initiated more slowly, it maintained reasonable activity longer, which allowed it to more than double the resulting total turnover number (TON) (from 9149 to 21,660) [15]. We hypothesized that the release-return mechanism can be one of the contributors to higher productivity of immobilized Hoveyda–Grubbs catalysts. Owing to the ease of initiation and possibility of regeneration in the presence of styrene 2, the immobilized Hoveyda pre-catalyst can be viewed as the resting state which protects the active propagating species from decomposition and readily re-enters the catalytic cycle. For obvious reasons, both interacting elements (i.e., the pre-catalyst and the benzylidene ligand precursor) have to be immobilized on the support close to each other and with flexibility allowing for their subsequent mating. In the present report we disclose our results on testing the validity of such “boomerang inside support’s pores” idea (Figure2c). For grafting of Ru pre-catalysts and their benzylidene ligand precursor on solid supports we decided to use a non-covalent immobilization strategy utilizing quaternary ammonium groups as anchors [16]. Next, the reaction between 5 and activated 6 should re-create the stable pre-catalyst form. At the same time, the tagged styrene derivative 5 will not be washed out from the support and contaminate the product (contrary to Skowerski’s approach). Catalysts 2019, 9, x FOR PEER REVIEW 3 of 18

(ii) For systems where the support is connected to a non-dissociating ligand (Figure 1b) the situation is seemingly better because usually there is no heavy leaching observed with such systems. However, as the initiation step leaves the catalysts stripped off the stabilizing alkylidene ligand, the remaining fragile 14 e− Ru complexes are totally exposed to harmful factors such as oxygen or impurities from solvents and reagents. As a result, such immobilized complexes quickly die, and as their cadavers stay attached to the support, usually there is no strong leaching of metal to the organic products [14]. Interestingly, many of these immobilized systems were reported to work well in batch and even enabled the catalysts recycling from 3 to 10 times (however, usually applied at relatively large Catalysts 2020, 10, 438 4 of 18 loading, such as ≥5 mol %). In this context, it was often suggested that the presence of the release- return boomerang mechanism may help to regenerate the pre-catalysts on the support [12,13]. a) Cl Cl Cl Cl O Ru L O Ru L O Ru L O Ru L' Cl Cl Cl Cl

R Pellet 1 substrate Pellet 1 only 2% +olefin metathesis + crossover Cl Cl & pellets recovery Cl Cl O Ru L' O Ru L' O Ru L' O Ru L Cl Cl Cl Cl

Pellet 2 Pellet 2 [Ref. 3] (SIMes) D D D D

L = N N L' =N N or N N

b) R product substrate (contaminated with 2, 3 – and probably secondary + Cl O N N metathesis products)

+ N 3 N N ≡ N added to allow Cl Ammonium anchor immobilized 4 Ru for immobilization regeneration Cl via boomerang O 4 (FixCat) mechanism immobilized on SBA-15 [Ref. 15]

c) support with well-defined immobilized 5 – pores to allow catalyst 2 × Cl – 6 regeneration Cl inside support + N N pores + N O

5 N N product Cl (free of 5) Ru Cl + N O R substrate 6 This work

Figure 2. (a) Cross-over experiment by Hoveyda showing some (2%) existence of the boomerang eﬀect in the case of pellet-immobilized catalysts under batch conditions [3]. (b) Skowerski’s approach to extending the lifetime of non-covalently immobilized catalyst 4 in continuous ﬂow [15]. (c) Idea of “boomerang inside support’s pores” explored in this work. Catalysts 2020, 10, 438 5 of 18

2. Results and Discussion

2.1. Tagged Ligand Precursor and Catalyst Synthesis Tagged catalyst 4 is commercially available (Apeiron Synthesis FixCat™)[17]. However, in order to study the boomerang eﬀect in solid supports, a tagged benzylidene ligand precursor (styrene derivative 5) and a double-tagged catalyst 6 were prepared. Using a method previously developed in our laboratory [18], known 2-propenyl-phenol 7 [19] was converted into ether 8, a common starting material for the synthesis of tagged ligand precursor 5 and tagged catalyst 6. To obtain the latter, salt 9 [18] was deprotonated using potassium tert-amylate to form in situ the free N-heterocyclic carbene (NHC), which later in the sequence of one-pot transmetalation reactions was transformed into Ru complex 11 in 34% overall yield starting from 9. The ﬁnal quaternization with MeCl in a glass ampule led to the formation of new double-tagged complex 6 in 65% yield (Scheme1). Interestingly, contrary to the commercially available FixCat™ catalyst 4 [17], which is not soluble in water (0.45 mg/mL), theCatalysts double-tagged 2019, 9, x FOR complexPEER REVIEW6 exhibited high water solubility, exceeding 100 mg/mL. 5 of 18

Scheme 1. 1. Synthesis of of double-tagged pre-catalyst 6 and tagged benzylidene ligand precursor 5 designed for testing the “boomerang insideinside support’ssupport's pores” idea.idea.

Single crystals of 6 suitablesuitable for XRD were obtainedobtained by layeringlayering a MeOHMeOH/MeCN/MeCN solution of the tert complex withwith anan EtEt22OO/MTBE/MTBE (methyl (methyl tert-butyl-butyl ether) ether) solvent solvent mixture mixture and and allowing allowing the the precipitated precipitated oil tooil recrystallizeto recrystallize over over two two weeks weeks (Figure (Figure3). Remarkably,3). Remarkably, the formedthe formed needle-like needle-like crystals crystals were were stable stable for severalfor several months months in the in motherthe mother liquor liquor in a closedin a closed flask flask without without deoxygenation. deoxygenation. To our To knowledge, our knowledge, this is thethis firstis the measured first measured crystal structurecrystal structure of a double of a ammonium-taggeddouble ammonium-tagged olefin metathesis olefin metathesis catalyst [catalyst15]. [15].

Catalysts 2019, 9, x FOR PEER REVIEW 5 of 18

Scheme 1. Synthesis of double-tagged pre-catalyst 6 and tagged benzylidene ligand precursor 5 designed for testing the “boomerang inside support's pores” idea.

Single crystals of 6 suitable for XRD were obtained by layering a MeOH/MeCN solution of the complex with an Et2O/MTBE (methyl tert-butyl ether) solvent mixture and allowing the precipitated oil to recrystallize over two weeks (Figure 3). Remarkably, the formed needle-like crystals were stable for several months in the mother liquor in a closed flask without deoxygenation. To our knowledge, Catalysts 2020, 10, 438 6 of 18 this is the first measured crystal structure of a double ammonium-tagged olefin metathesis catalyst [15].

Figure 3. Solid-state structure of 6. Ellipsoids are drawn at the 50% probability level. Hydrogen atoms are omitted for clarity. Approximate molecular dimensions of 6 molecule: 1.7 1.2 0.9 nm (height × × × width depth). × 2.2. Supports and Catalysts Immobilization

Three different types of porous materials for immobilization purposes: 13X, (Al)MIL-101-NH3Cl, and SBA-15 were used in this study (Figure4). Support 13X is a representative of molecular sieves (aluminosilicates);Catalysts 2019, 9, x FOR it PEER is crystalline REVIEW and has micropores 0.8 to 1.0 nm in diameter [20]. A metal-organic 6 of 18 framework (MOF) coded (Al)MIL-101-NH3Cl is a crystalline hybrid organic-inorganic material bearing two typesFigure of 3.di Solid-statefferently-sized structure mesopores, of 6. Ellipsoids 2.6 nmare drawn and 3.2 atnm the 50% in diameter probability [21 level.]. SBA-15 Hydrogen is a crystalline, atoms mesoporousare omitted siliceous for clarity. material Approximate with 8 nmmolecular mesopores dimensions [22]. The of 6 (Al)MIL-101-NHmolecule: 1.7 × 1.2 3×Cl 0.9 and nm SBA-15(height × have alreadywidth proved × depth). to be effective supports for olefin metathesis catalyst [15,23,24].

FigureFigure 4. SolidSolid supports supports selected selected for for this this study: study: a) 13X, (a) b zeolite) metal-organic 13X, (b) metal-organicframework (MOF), framework and c) (Al)MIL-101-NH3Cl,SBA-15 (drawings are and not ( cin) mesoporousthe same scale). silica SBA-15).

2.2. SupportsThe immobilization and Catalysts of Immobilization Ru complexes 4 or 6 was accomplished by sorption from dichloromethane (DCM) solution under an argon atmosphere. Stirring of a catalyst solution with any of the three sorbents for 1Three hour resulted different in types quantitative of porous adsorption materials offor the immobilization catalyst, as conﬁrmed purposes: by 13X, UV–Vis (Al)MIL-101-NH spectroscopy3Cl, of theand supernatant SBA-15 were (see used Supplementary in this study Materials). (Figure 4). Subsequent Support 13X removal is a representative of the solvent of by molecular decantation sieves and drying(aluminosilicates); under vacuum it is producedcrystalline heterogeneous and has micropores catalysts 0.8 asto greenish1.0 nm in powders. diameter [20]. A metal-organic framework (MOF) coded (Al)MIL-101-NH3Cl is a crystalline hybrid organic-inorganic material bearing two types of differently-sized mesopores, 2.6 nm and 3.2 nm in diameter [21]. SBA-15 is a crystalline, mesoporous siliceous material with 8 nm mesopores [22]. The (Al)MIL-101-NH3Cl and SBA-15 have already proved to be effective supports for olefin metathesis catalyst [15,23,24]. The immobilization of Ru complexes 4 or 6 was accomplished by sorption from dichloromethane (DCM) solution under an argon atmosphere. Stirring of a catalyst solution with any of the three sorbents for 1 hour resulted in quantitative absorption of the catalyst, as confirmed by UV–Vis spectroscopy of the supernatant (see Supporting Information). Subsequent removal of the solvent by decantation and drying under vacuum produced heterogeneous catalysts as greenish powders. It shall be noted that the immobilization procedure is easily scalable, and large amounts of adsorbed ruthenium complexes can be stored in a freezer under an argon atmosphere for at least a month without losing catalytic activity. Materials containing 1.0–0.05 wt % of ruthenium complexes were characterized by nitrogen sorption analysis which showed that the specific surface areas of these materials were not significantly decreased.

2.3. Optimization of Metathesis Reaction Conditions Using a popular model ring-closing metathesis (RCM) reaction of diethyl 2,2-diallylmalonate (12) (DEDAM) [25] we established the optimal application regimes for the studied hybrid catalysts (Scheme 2).

Scheme 2. Model ring-closing metathesis reaction of 12 (DEDAM) used in this study.

First, to set up a benchmark for further comparisons, we outlined the activity of the commercial FixCat™ catalyst (4) in the above RCM reaction under homogeneous conditions (in dichloroethane (DCE) solution at 50 °C, 24 h) and obtained a turnover number (TON) of 12,400. The same reaction conducted in toluene (4 is insoluble in this solvent, so the catalyst was dissolved in a minimal volume

Catalysts 2019, 9, x FOR PEER REVIEW 6 of 18

Figure 4. Solid supports selected for this study: a) 13X, b) metal-organic framework (MOF), and c) SBA-15 (drawings are not in the same scale).

2.2. Supports and Catalysts Immobilization

Three different types of porous materials for immobilization purposes: 13X, (Al)MIL-101-NH3Cl, and SBA-15 were used in this study (Figure 4). Support 13X is a representative of molecular sieves (aluminosilicates); it is crystalline and has micropores 0.8 to 1.0 nm in diameter [20]. A metal-organic framework (MOF) coded (Al)MIL-101-NH3Cl is a crystalline hybrid organic-inorganic material bearing two types of differently-sized mesopores, 2.6 nm and 3.2 nm in diameter [21]. SBA-15 is a crystalline, mesoporous siliceous material with 8 nm mesopores [22]. The (Al)MIL-101-NH3Cl and SBA-15 have already proved to be effective supports for olefin metathesis catalyst [15,23,24]. The immobilization of Ru complexes 4 or 6 was accomplished by sorption from dichloromethane (DCM) solution under an argon atmosphere. Stirring of a catalyst solution with any of the three Catalystssorbents2020 for, 10 1, 438 hour resulted in quantitative absorption of the catalyst, as confirmed by UV–Vis7 of 18 spectroscopy of the supernatant (see Supporting Information). Subsequent removal of the solvent by decantation and drying under vacuum produced heterogeneous catalysts as greenish powders. It shall be noted that the immobilization procedure is easily scalable, and large amounts of It shall be noted that the immobilization procedure is easily scalable, and large amounts of adsorbed ruthenium complexes can be stored in a freezer under an argon atmosphere for at least a adsorbed ruthenium complexes can be stored in a freezer under an argon atmosphere for at least a month without losing catalytic activity. Materials containing 1.0–0.05 wt % of ruthenium complexes month without losing catalytic activity. Materials containing 1.0–0.05 wt % of ruthenium complexes were characterized by nitrogen sorption analysis which showed that the speciﬁc surface areas of these were characterized by nitrogen sorption analysis which showed that the specific surface areas of these materials were not signiﬁcantly decreased. materials were not significantly decreased. 2.3. Optimization of Metathesis Reaction Conditions 2.3. Optimization of Metathesis Reaction Conditions Using a popular model ring-closing metathesis (RCM) reaction of diethyl 2,2-diallylmalonate Using a popular model ring-closing metathesis (RCM) reaction of diethyl 2,2-diallylmalonate (12) (DEDAM) [25] we established the optimal application regimes for the studied hybrid catalysts (12) (DEDAM) [25] we established the optimal application regimes for the studied hybrid catalysts (Scheme2). (Scheme 2).

Scheme 2. 12 Scheme 2. ModelModel ring-closing ring-closing metathesis metathesis reaction reaction of 12 (DEDAM)(DEDAM) used used in this study. First, to set up a benchmark for further comparisons, we outlined the activity of the commercial First, to set up a benchmark for further comparisons, we outlined the activity of the commercial FixCat™ catalyst (4) in the above RCM reaction under homogeneous conditions (in dichloroethane FixCat™ catalyst (4) in the above RCM reaction under homogeneous conditions (in dichloroethane (DCE) solution at 50 ◦C, 24 h) and obtained a turnover number (TON) of 12,400. The same reaction (DCE) solution at 50 °C, 24 h) and obtained a turnover number (TON) of 12,400. The same reaction conducted in toluene (4 is insoluble in this solvent, so the catalyst was dissolved in a minimal volume of conducted in toluene (4 is insoluble in this solvent, so the catalyst was dissolved in a minimal volume DCM (25 µL) and added to the solution of 12 in toluene (1 mL)) gave a TON of 9000. The double-tagged highly polar 6 under homogeneous conditions (in DCE solution) gave a TON of 8800, while in toluene the obtained TON was only 600. It should be noted that the use of an ammonium-tagged Ru catalyst as a ﬁne suspension in toluene was previously proposed by the authors of this study as a simple and eﬃcient quasi-heterogeneous method to obtain organic products with a low ruthenium contamination level [14]. Next, in a set of experiments, we checked the optimal temperature in the application of heterogeneous catalysts based on 4. To do so, the RCM reaction of 12 was run at temperatures varying from 30 to 110 ◦C. Interestingly, while non-immobilized 4 showed maximum reactivity at 80 ◦C, the immobilized systems were the most active in 40–60 ◦C window (Figure5).

Figure 5. Eﬀect of temperature on catalyst productivity. Conditions: 0.5 M 12 in toluene, 50 ppm or 35 ppm for MOF, 24 h, 0.5 wt % on support. Lines are a visual aid only.

Catalysts 2020, 10, 438 8 of 18

Finally, we repeated the model RCM reaction using various amounts of 4 immobilized on a support (given in wt %, see Table1 and Figure6). As before, the temperature for the RCM test reactions was set at 50 ◦C. In general, we found that 0.5 wt % of catalyst loading on the support gives the best results in the context of RCM productivity. Despite the fact that MOF seemed to work even better at lower loading values (see Table1 and Figure6), we decided to use 0.5 wt % of Ru on the support because this loading was optimal for the majority of tested systems. Lower loading values were excluded from further tests because using such materials would lead to signiﬁcantly larger volumes of the support (and then the solvent), which may be problematic from a practical point of view.

Table 1. Eﬀect of catalyst 4 loading (wt % with respect to the support) on productivity of the heterogeneous system in ring-closing metathesis (RCM) of 12. 1

Catalyst Loading on Support (wt %) Catalyst/Support 1.0 0.5 0.1 0.05 4@13X 9 400 10 000 7 500 4 400 4@SBA-15 8 000 12 800 12 800 12 800 4@MOF 17 800 19 700 21 600 24 100 1 Test RCM reaction conditions: substrate 12 in toluene (0.5 M), 50 ◦C, 50 ppm of catalyst for 13X and SBA-15 or 35 Catalystsppm 2019 for, MOF9, x FOR (relative PEER to REVIEW substrate 12). 8 of 18

Figure 6. Effect of catalyst 4 loading on the support (wt %) on productivity of the heterogeneous system inFigure RCM 6. of Effect12. Lines of catalyst are a visual 4 loading aid only. on Forthe thesupport RCM (wt reaction %) on conditions, productivity see Table of the1. heterogeneous system in RCM of 12. Lines are a visual aid only. For the RCM reaction conditions, see Table 1. Having established the basic set of conditions for an application of FixCat™ catalyst (4) immobilized on variousHaving supports, established we decided the basic to studyset of the conditions effect of extrafor an added application benzylidene of FixCat™ ligand precursor catalyst (45) onimmobilized the productivity on various of the supports, resulting we hybrid decided system. to study We the believed effect thatof extra the propagatingadded benzylidene 14 e− species ligand resultedprecursor upon 5 on initiationthe productivity of Ru pre-catalyst of the resulting (4 or hybrid6) could system. perhaps We reboundbelieved tothat molecules the propagating of 5 present 14 e− inspecies the support resulted cavities, upon initiation thus increasing of Ru pre-catalyst the lifetime (4 of or the 6) hybridcould perhaps catalyst rebound (this concept to molecules is explained of 5 inpresent Figure in2c). the Atsupport the same cavities, time, thus one increasing can expect the that lifetime this process of the willhybrid compete catalyst with (this RCM concept of 12 is, thusexplained slowing in Figure down the2c). productiveAt the same metathesis time, one can process. expect To that test this these process speculations, will compete a number with ofRCM RCM of experiments12, thus slowing were down performed the productive utilizing 0.5 metathesis wt % catalyst process. immobilized To test these on supports speculations, impregnated a number with of variousRCM experiments amounts of were5 (0–100 performed equiv. relativeutilizing to 0.5 Ru). wt Using% catalyst the prepared immobilized catalysts on supports for RCM impregnated of DEDAM 12with(50 various ppm of Ruamounts relative of to 512 (0–100, 0.5 M equiv. of 12 inrelative toluene, to 50 Ru).◦C, Using 24 h), wetheexpected prepared to catalysts quantify for the RCM effect ofof theDEDAM additional 12 (50 ligand ppm of precursor Ru relative present to 12 in, 0.5 the M support. of 12 in toluene, 50 °C, 24 h), we expected to quantify the effectTheimpregnation of the additional ofthe ligand support precursor with 5presentand 4 orin the6 was support. done as before: a stock solution of Ru catalystThe in impregnation dry dichloromethane of the support was addedwith 5to and a solid4 or 6 support was done placed as before: in a dry a stock vial (insolution an amount of Ru requiredcatalyst in to obtaindry dichloromethane 0.5 wt % of catalyst was relativeadded to thea solid mass support of a support). placed Afterin a dry 30 min vial of (in stirring, an amount 1, 10, required to obtain 0.5 wt % of catalyst relative to the mass of a support). After 30 min of stirring, 1, 10, or 20 equiv. of 5 were added as a stock solution and the suspension was stirred for an additional 30 min. Then the solvent was evaporated and the resulting solid dried under high vacuum at 30 °C for 2 h. The obtained heterogeneous systems were thus used in the model RCM reaction of 12 (Scheme 2) and the results are compiled in Table 2.

Table 2. Effect of ligand precursor 5 co-immobilized on a support on productivity of the model heterogeneous systems.1

Conversion Turnover Entry Catalyst@support 5 (equiv.) (%) number (TON) 0 50 10,000 1 15 3000 1 4@13X 10 27 5400 20 21 4200 0 41 8200 1 42 8400 2 6@13X 10 30 6000 20 25 5000 0 64 12,800 3 4@SBA-15 1 40 8000

Catalysts 2020, 10, 438 9 of 18 or 20 equiv. of 5 were added as a stock solution and the suspension was stirred for an additional 30 min. Then the solvent was evaporated and the resulting solid dried under high vacuum at 30 ◦C for 2 h. The obtained heterogeneous systems were thus used in the model RCM reaction of 12 (Scheme2) and the results are compiled in Table2.

Table 2. Eﬀect of ligand precursor 5 co-immobilized on a support on productivity of the model heterogeneous systems. 1

Entry Catalyst@support 5 (equiv.) Conversion (%) Turnover Number (TON) 0 50 10,000 1 15 3000 1 4@13X 10 27 5400 20 21 4200 0 41 8200 1 42 8400 2 6@13X 10 30 6000 20 25 5000 0 64 12,800 1 40 8000 3 4@SBA-15 10 30 6000 20 15 3000 0 70 14,000 1 68 13,600 4 6@SBA-15 10 49 9800 20 31 6200 0 91 18,200 1 90 18,000 5 4@MOF 10 83 16,600 20 81 16,200 60 57 11,400 0 33 6600 6 6@MOF 20 13 2600 100 4 800 1 Test RCM reaction conditions: 0.5 wt % catalyst and 0–100 equiv. 5 (relative to catalyst) immobilized on diﬀerent supports, 50 ppm Ru used relatively to substrate 12 in toluene (0.5 M), 50 ◦C, 24 h.

Results compiled in Table2 show that in all cases the presence of ligand precursor 5 on a support resulted in a decrease of the hybrid catalyst’s productivity. Interestingly, this inhibiting effect was the strongest in the case of 13X support. For MOF and SBA-15, the increase in the amount of 5 decreases the activity proportionally, and the presence of just one equivalent of 5 seems to have only a small effect on catalyst activity. We speculate that this result can be explained by different support morphologies. In the case of 13X, the bonding of the Ru catalyst, as well as catalysis itself, takes place preferentially at the surface of the support, so the increase in the amount of 5 does not lead to a proportional decrease of activity because it can be adsorbed inside of the pores support. For MOF and SBA-15, the catalytic activity of the resulting system decreases proportionally with the amount of the tagged styrene derivative added, because the internal channels and voids in these porous materials are clogged by numerous molecules of 5, thus blocking the access of substrate 12 to the catalyst molecules immobilized inside. Since the MOF used in this study had a better developed internal surface in comparison with SBA-15, the latter material needed relatively smaller amounts of 5 to be “saturated” (e.g., Table2 entry 3 versus entry 5). In addition, the relative mobility of tagged polar molecules of 4, 6, and 5 inside the support pores may be different in the case of SBA-15 and MOF. Specifically, for the MOF support which has rather cramped narrowing (1.6 nm) between the voids, the mobility of molecules can be limited in contrast to SBA-15 containing huge and straight 8 nm channels. While Catalysts 2020, 10, 438 10 of 18 the sum of all these subtle effects translates into the observed differences in reactivity of the tested Ru catalysts, the involvement of Ru catalyst molecules into non-productive metathesis with 5 is obviously responsible for visible hampering of catalytic activity of all the systems.

2.4. Reuse of Heterogeneous Catalysts To test the longevity of the SBA-15 and MOF-based heterogeneous systems, a number of recycling experiments were performed in batch (13X was not included in these tests due to its inferiority noted in previous experiments). Supports bearing Ru pre-catalysts (500 ppm relative to the substrate) impregnated with various amounts of 5 were used in a series of RCM reactions of 12 (0.5 M solution in toluene, 50 ◦C, 1 h). The solid catalysts were recovered after each cycle using a centrifuge (the clear supernatant solution was decanted, and the conversion of 12 was determined by gas chromatography (GC) analysis) and washed with anhydrous toluene (4 ) by repeating the centrifugation-decantation × procedure. Then a new portion of substrate 12 solution was added, and the RCM reaction was repeated until the final cycle. The results varied depending on the catalyst and support used. It turned out that adding the benzylidene ligand precursor 5 to the system with FixCat 4 on MOF had no visible effect on the catalyst productivity. Interestingly in the case of 6 on MOF, the presence of 5 seems to reduce the hybrid catalyst productivity (Figure7a). In the case of SBA-15, the productivity of the system also Catalysts 2019, 9, x FOR PEER REVIEW 10 of 18 decreases with increasing the amount of 5 (Figure7b). We also see that the double-tagged catalyst 6 on SBA-15that is the slightly double-tagged more stable catalyst than 6 on4, SBA-15 reaching is slightly a TON more of 8900 stable for than6 versus 4, reaching 8800 a for TON4. of The 8900 recycling for experiment6 versus clearly 8800 for shows 4. The that recycling the double-tagged experiment clearly6 in MOF shows is definitelythat the double-tagged less active (we 6 in have MOF no is clear explanationdefinitely of less this active effect). (we The have addition no clear ofexplanation the benzylidene of this effect). ligand The precursor addition of to the6 on benzylidene MOF leads to even strongerligand precursor hampering to 6 on of MOF catalyst leads activity, to even thus stronger suggesting hampering that of the catalyst catalyst activity, is mostly thus engagedsuggesting in the non-productivethat the catalyst boomerang is mostly cycles engaged with 5 ininstead the non-productive of converting boomerang substrate cycles12 into with product 5 instead13. of converting substrate 12 into product 13.

Figure 7. Eﬀect of catalysts 4 and 6 and benzylidene ligand precursor 5 (n equivalents) on recycling and reuseFigure of immobilized 7. Effect of catalyst catalysts in 4 RCMand 6 ofand12 benzylidene.(a) Catalyst ligand4 or 6precursorand styrene 5 (n derivativeequivalents)5 onimmobilized recycling on MOF.and (b) Catalysts reuse of immobilized4 or 6 and styrene catalyst derivative in RCM of5 12immobilized. a) Catalyst on 4 SBA-15. or 6 and Conditions styrene derivative for each 5 run: immobilized on MOF. b) Catalysts 4 or 6 and styrene derivative 5 immobilized on SBA-15. Conditions 500 ppm of Ru relative to 12 in toluene (0.5 M), 50 ◦C, 1 h. for each run: 500 ppm of Ru relative to 12 in toluene (0.5 M), 50 °C, 1 h.

2.5. Substrate Scope and Limitations Study The most promising catalysts based on MOF and SBA-15 supports were then tested in a number of metathesis reactions presented in Scheme 3, including more challenging self-cross metathesis of α- olefins [26–28] and RCM. The progress of each reaction was monitored by gas chromatography (GC). To start, the model RCM of 12 leading to product 13 was repeated once again, using only 50 ppm of Ru at optimized conditions (Table 3, entry 1), and reaching TON values up to 19,000. In addition, another diene 14 (entry 2) underwent RCM reactions using as low as 20 ppm of Ru with good results (TON up to 27,000).

Catalysts 2020, 10, 438 11 of 18

NTs NTs

14 15

( )6 ( )6 ( )6 16 17

18 19

OBn BnO BnO 20 21 Scheme 3. Scheme 3. MoreMore advancedadvanced metathesismetathesis reactionsreactionsstudied. studied. Conditions:Conditions: substratesubstrate (1(1 M)M) inin toluene,toluene, 5050 ◦C,C, 24 h. 24 h. To start, the model RCM of 12 leading to product 13 was repeated once again, using only 50 ppm Next, the industrially relevant self-cross metathesis (self-CM) reaction of α-olefins—substrates of Ru at optimized conditions (Table3, entry 1), and reaching TON values up to 19,000. In addition, particularly susceptible to migration of double bond—was attempted (Table 3) [26–29]. It is known another diene 14 (entry 2) underwent RCM reactions using as low as 20 ppm of Ru with good results that many homogeneous Ru catalysts lead to severe isomerization (shifting of double bond position) (TON up to 27,000). of C-C double bonds in this reaction [29,30]. We were therefore curious whether the new hybrid Next, the industrially relevant self-cross metathesis (self-CM) reaction of α-olefins—substrates catalysts would show good selectivity in this challenging reaction. Firstly, the self-CM reaction of 1- particularly susceptible to migration of double bond—was attempted (Table3)[ 26–29]. It is known decene (16), a good representative of the Fischer–Tropsch class of α-olefins, was conducted at 50 °C that many homogeneous Ru catalysts lead to severe isomerization (shifting of double bond position) of with 50 to 100 ppm of Ru (entry 3). Pleasingly, both 4 and 6 at MOF and SBA-15 provided the expected C-C double bonds in this reaction [29,30]. We were therefore curious whether the new hybrid catalysts product—an internal olefin 17—in conversion not exceeding 50%, but with very good selectivity of would show good selectivity in this challenging reaction. Firstly, the self-CM reaction of 1-decene ≥98%. However, it should be noted that the obtained numbers do not outperform the results obtained (16), a good representative of the Fischer–Tropsch class of α-olefins, was conducted at 50 C with with homogeneous catalysts especially designed for this transformation [26–29]. The next challenging◦ 50 to 100 ppm of Ru (entry 3). Pleasingly, both 4 and 6 at MOF and SBA-15 provided the expected substrate, 18, also underwent self-CM with perfect selectivity, and 100 ppm of Ru on SBA-15 led to a product—an internal olefin 17—in conversion not exceeding 50%, but with very good selectivity complete conversion (entry 4). Interestingly, when a fragile O-allyl [31] that substituted substrate 20 of 98%. However, it should be noted that the obtained numbers do not outperform the results was≥ used in the self-CM reaction with 50–100 ppm of Ru carried out at 50 °C no significant obtained with homogeneous catalysts especially designed for this transformation [26–29]. The next isomerization (selectivity 96%) was noted only for the MOF-based catalysts, while almost complete challenging substrate, 18, also underwent self-CM with perfect selectivity, and 100 ppm of Ru on isomerization was observed for SBA-15 systems (entry 5). As self-CM of O-allyl decorated substrates SBA-15 led to a complete conversion (entry 4). Interestingly, when a fragile O-allyl [31] that substituted is used in preparation of “dimers” of biologically active substrates and active pharmaceutical substrate 20 was used in the self-CM reaction with 50–100 ppm of Ru carried out at 50 C no significant ingredients (APIs), and a number of problems caused by the C-C double bond migration◦ during isomerization (selectivity 96%) was noted only for the MOF-based catalysts, while almost complete metathesis has been reported in these studies [31], the exceptionally high selectivity exhibited by isomerization was observed for SBA-15 systems (entry 5). As self-CM of O-allyl decorated substrates is Ru@MOF in self-CM of 20 is interesting and will be studied further in due course. used in preparation of “dimers” of biologically active substrates and active pharmaceutical ingredients (APIs), and a number of problems causedTable by 3. the Substrate C-C double scope. bond1 migration during metathesis has been reported in these studies [31], the exceptionally high selectivity exhibited by Ru@MOF in self-CM Conv. (selec.)2 E/Z TOF ofEntry20 is interesting Substrate and will be Catalyst studied (loading) further in due course. TON (%) ratio (min−1)3 4@MOF (50 ppm) 95 (>99) - 19 000 370 6@MOF (50 ppm) 47 (>99) - 9 400 93 1 4@SBA-15 (50 ppm) 83 (>99) - 16 600 209 6@SBA-15 (50 ppm) 79 (>99) - 15 800 99 4@MOF (50 ppm) 86 (>99) - 17 200 320 6@MOF (50 ppm) 58 (>99) - 11 600 160 2 4@SBA-15 (20 ppm) 54 (>99) - 27 000 1498 6@SBA-15 (20 ppm) 51 (>99) - 25 500 1528 4@SBA (50 ppm) 29 (99) 3.3 5 800 116 6@SBA (50 ppm) 27 (99) 3.2 5 600 77 3 4@MOF (100 ppm) 65 (99) 4.6 6 500 203 6@MOF (100 ppm) 60 (99) 4.1 6 000 93

Catalysts 2019, 9, x FOR PEER REVIEW 11 of 18 CatalystsCatalysts 2019 2019, 9, ,9 x, xFOR FOR PEER PEER REVIEW REVIEW 11 11 of of 18 18

NTs NTs NTsNTs NTsNTs 14 15 1414 1515

( )6 ( )6 ( )6 ( () 6)6 ( () )6 ( () )6 16 6 17 6 1616 1717

18 19 1818 1919 OBn BnO BnO OBnOBn BnOBnO BnOBnO 20 21 20 21 20 21 Scheme 3. More advanced metathesis reactions studied. Conditions: substrate (1 M) in toluene, 50 C, SchemeScheme 3. 3. More More advanced advanced metathesis metathesis reactions reactions studied. studied. Conditions: Conditions: substrate substrate (1 (1 M) M) in in toluene, toluene, 50 50  C,C, 24 h. 2424 h. h. Next, the industrially relevant self-cross metathesis (self-CM) reaction of α-olefins—substrates Next,Next, the the industrially industrially relevant relevant self-cross self-cross metathesis metathesis (self-CM) (self-CM) reaction reaction of of α-olefins—substrates α-olefins—substrates particularly susceptible to migration of double bond—was attempted (Table 3) [26–29]. It is known particularlyparticularly susceptible susceptible to to migration migration of of double double bond—was bond—was attempted attempted (Table (Table 3) 3) [26–29]. [26–29]. It It is is known known that many homogeneous Ru catalysts lead to severe isomerization (shifting of double bond position) thatthat many many homogeneous homogeneous Ru Ru catalysts catalysts lead lead to to severe severe isomerization isomerization (shifting (shifting of of double double bond bond position) position) of C-C double bonds in this reaction [29,30]. We were therefore curious whether the new hybrid ofof C-C C-C double double bonds bonds in in this this reaction reaction [29,30]. [29,30]. We We were were therefore therefore curious curious whether whether the the new new hybrid hybrid catalysts would show good selectivity in this challenging reaction. Firstly, the self-CM reaction of 1- catalystscatalysts would would show show good good selectivity selectivity in in this this challenging challenging reaction. reaction. Firstly, Firstly, the the self-CM self-CM reaction reaction of of 1- 1- decene (16), a good representative of the Fischer–Tropsch class of α-olefins, was conducted at 50 °C decenedecene ( 16(16),), a agood good representative representative of of the the Fischer–Tropsch Fischer–Tropsch class class of of α-olefins, α-olefins, was was conducted conducted at at 50 50 °C °C with 50 to 100 ppm of Ru (entry 3). Pleasingly, both 4 and 6 at MOF and SBA-15 provided the expected withwith 50 50 to to 100 100 ppm ppm of of Ru Ru (entry (entry 3). 3). Pleasingly, Pleasingly, both both 4 4and and 6 6at at MOF MOF and and SBA-15 SBA-15 provided provided the the expected expected product—an internal olefin 17—in conversion not exceeding 50%, but with very good selectivity of product—anproduct—an internal internal olefin olefin 17 17—in—in conversion conversion not not exceeding exceeding 50%, 50%, but but with with very very good good selectivity selectivity of of ≥98%. However, it should be noted that the obtained numbers do not outperform the results obtained ≥98%.≥98%. However, However, it it should should be be noted noted that that the the obtained obtained numbers numbers do do not not outperform outperform the the results results obtained obtained with homogeneous catalysts especially designed for this transformation [26–29]. The next challenging withwith homogeneous homogeneous catalysts catalysts especially especially designed designed for for this this transformation transformation [26–29]. [26–29]. The The next next challenging challenging substrate, 18, also underwent self-CM with perfect selectivity, and 100 ppm of Ru on SBA-15 led to a substrate,substrate, 18 18, also, also underwent underwent self-CM self-CM with with perfect perfect selectivity, selectivity, and and 100 100 ppm ppm of of Ru Ru on on SBA-15 SBA-15 led led to to a a complete conversion (entry 4). Interestingly, when a fragile O-allyl [31] that substituted substrate 20 completecomplete conversion conversion (entry (entry 4). 4). Interestingly, Interestingly, when when a afragile fragile O O-allyl-allyl [31] [31] that that substituted substituted substrate substrate 20 20 was used in the self-CM reaction with 50–100 ppm of Ru carried out at 50 °C no significant waswas used used in in the the self-CM self-CM reaction reaction with with 50–100 50–100 ppm ppm of of Ru Ru carried carried out out at at 50 50 °C °C no no significant significant isomerization (selectivity 96%) was noted only for the MOF-based catalysts, while almost complete isomerizationisomerization (selectivity (selectivity 96%) 96%) was was noted noted only only for for the the MOF-based MOF-based catalysts, catalysts, while while almost almost complete complete isomerization was observed for SBA-15 systems (entry 5). As self-CM of O-allyl decorated substrates isomerizationisomerization was was observed observed for for SBA-15 SBA-15 systems systems (entry (entry 5). 5). As As self-CM self-CM of of O O-allyl-allyl decorated decorated substrates substrates is used in preparation of “dimers” of biologically active substrates and active pharmaceutical isis used used in in preparation preparation of of “dimers” “dimers” of of biologically biologically active active substrates substrates and and active active pharmaceutical pharmaceutical ingredients (APIs), and a number of problems caused by the C-C double bond migration during ingredientsingredients (APIs), (APIs), and and a anumber number of of problems problems caused caused by by the the C-C C-C double double bond bond migration migration during during metathesis has been reported in these studies [31], the exceptionally high selectivity exhibited by metathesismetathesis has has been been reported reported in in these these studies studies [31], [31], the the exceptionally exceptionally high high selectivity selectivity exhibited exhibited by by Ru@MOF in self-CM of 20 is interesting and will be studied further in due course. Ru@MOFCatalystsRu@MOF2020 in in, self-CM10 self-CM, 438 of of 20 20 is is interesting interesting and and will will be be studied studied further further in in due due course. course. 12 of 18

Table 3. Substrate scope.1 TableTable 3. 3. Substrate Substrate scope. scope.1 1 Table 3. Substrate scope 1. Conv. (selec.)2 E/Z TOF Entry Substrate Catalyst (loading) Conv.Conv. (selec.) (selec.)2 2 EE/Z/Z TON TOFTOF EntryEntry Substrate Substrate Catalyst Catalyst (loading) (loading) (%) 2 ratio TONTON (min−1)3 1 3 Entry Substrate Catalyst (Loading) Conv. (Selec.)(%)(%) (%) Eratio/ratioZ Ratio TON (min(min−1TOF−1)3) 3 (min − ) 4@MOF (50 ppm) 95 (>99) - 19 000 370 4@MOF4@MOF4@MOF (50 (50 ppm)(50 ppm) ppm) 95 95( 95> (>99)99) (>99) - - - 19 19 000 000 19 000 370 370 370 6@MOF6@MOF (50 (50 ppm) ppm) 47 47 (> 99)(>99) - - 9 400 9 400 93 93 11 6@MOF6@MOF (50 (50 ppm) ppm) 47 47 (>99) (>99) - - 9 9400 400 93 93 1 1 4@SBA-154@SBA-15 (50 (50 ppm) ppm) 83 83 (> 99)(>99) - - 16 600 16 600 209 209 4@SBA-154@SBA-15 (50 (50 ppm) ppm) 83 83 (>99) (>99) - - 16 16 600 600 209 209 6@SBA-156@SBA-15 (50 (50 ppm) ppm) 79 79 (> 99)(>99) - - 15 800 15 800 99 99 6@SBA-156@SBA-15 (50 (50 ppm) ppm) 79 79 (>99) (>99) - - 15 15 800 800 99 99 4@MOF4@MOF (50 (50 ppm) ppm) 86 86 (> 99)(>99) - - 17 200 17 200 320 320 4@MOF4@MOF (50 (50 ppm) ppm) 86 86 (>99) (>99) - - 17 17 200 200 320 320 6@MOF6@MOF (50 (50 ppm) ppm) 58 58 (> 99)(>99) - - 11 600 11 600 160 160 22 6@MOF6@MOF (50 (50 ppm) ppm) 58 58 (>99) (>99) - - 11 11 600 600 160 160 2 2 4@SBA-154@SBA-15 (20 (20 ppm) ppm) 54 54 (> 99)(>99) - - 27 000 27 000 1498 1498 6@SBA-154@SBA-154@SBA-15 (20 (20 ppm)(20 ppm) ppm) 51 54( 54> (>99)99) (>99) - - - 27 27 000 000 25 500 1498 1498 1528 6@SBA-15 (20 ppm) 51 (>99) - 25 500 1528 6@SBA-156@SBA-15 (20 (20 ppm) ppm) 51 51 (>99) (>99) - - 25 25 500 500 1528 1528 4@SBA4@SBA (50 (50 ppm) ppm) 29 29 (99) (99) 3.3 3.3 5 800 5 800 116 116 Catalysts 2019, 9, x FOR PEER REVIEW6@SBA4@SBA4@SBA (50 (50 ppm)(50 ppm) ppm) 27 29 (99)29 (99) (99) 3.3 3.3 3.2 5 5800 800 5 600 116 116 12 of 18 77 Catalysts 2019, 9, x FOR PEER REVIEW4@MOF6@SBA6@SBA (100 (50 (50 ppm) ppm) ppm) 65 27 (99)27 (99) (99) 3.2 3.2 4.6 5 5 600 600 6 500 77 1277 of 18 203 33 6@SBA (50 ppm) 27 (99) 3.2 5 600 77 3 3 6@MOF4@MOF (100 (100 ppm) ppm) 60 65 (99) (99) 4.6 4.1 6 500 6 000 203 93 4@MOF4@SBA4@MOF (100(100 (100 ppm)ppm) ppm) 6548 65 (99)(98) (99) 4.64.5 4.6 64 6500800 500 203 nd 203 4@SBA6@MOF4@SBA (100 (100 (100 ppm) ppm) ppm) 48 48 60 (98) (98)(99) 4.5 4.1 4.5 4 6 800000 4 800 nd 93 nd 6@MOF6@SBA6@MOF (100(100 (100 ppm)ppm) ppm) 6044 60 (99)(98) (99) 4.14.3 4.1 64 6000400 000 nd93 93 6@SBA6@SBA (100 (100 ppm) ppm) 44 44 (98) (98) 4.3 4.3 4 400 4 400 nd nd 4@MOF (50 ppm) 57 (>99) 3.8 11 400 207 4@MOF (50 ppm) 57 (>99) 3.8 11 400 207 4@MOF6@MOF (50 (50 ppm) ppm) 57 46 (> (>99)99) 3.2 3.8 9 200 11 400 33 207 6@MOF6@MOF (50 (50 ppm) ppm) 46 46 (> (>99)99) 3.2 3.2 9 200 9 200 33 33 4@SBA (50 ppm) 50 (>99) 3.2 10 000 242 4@SBA (50 ppm) 50 (>99) 3.2 10 000 242 44 4@SBA (50 ppm) 50 (>99) 3.2 10 000 242 4 6@SBA6@SBA (50 (50 ppm) ppm) 51 51 (> (>99)99) 3.2 3.2 10 500 10 500 211 211 6@SBA (50 ppm) 51 (>99) 3.2 10 500 211 4@SBA4@SBA (100 (100 ppm) ppm) 100 100 (> 99)(>99) 3.9 3.9 10 000 10 000 nd nd 4@SBA (100 ppm) 100 (>99) 3.9 10 000 nd 6@SBA6@SBA (100 (100 ppm) ppm) 100 100 (> 99)(>99) 4.0 4.0 10 000 10 000 nd nd 6@SBA (100 ppm) 100 (>99) 4.0 10 000 nd 4@MOF4@MOF (250 (250 ppm) ppm) 70 70 (96) (96) 11.8 11.8 2 800 2 800 87 87 6@MOF4@MOF (250 (250 ppm) ppm) 68 70 (95) (96) 11.8 10.1 2 800 2 700 87 40 5 6@MOF (250 ppm) 68 (95) 10.1 2 700 40 5 46@MOF@SBA (250 (250 ppm) ppm) 38 68 (4) (95) 10.1 6.1 2 700 750 40 5 5 4@SBA (250 ppm) 38 (4) 6.1 750 5 6@SBA4@SBA (250 (250 ppm) ppm) 34 38 (3) (4) 6.1 5.3 750 670 5 6 6@SBA (250 ppm) 34 (3) 5.3 670 6 1 Conditions: substrate (16@SBA M) in (250 toluene, ppm) 50 C, 24 h. 342 (3)Conversions 5.3and yields 670 were calculated 6 based on 1 Conditions: substrate (1 M) in toluene, 50 C, 24◦ h. 2 Conversions and yields were calculated based 1internal Conditions: standard substrate (1,2,4,5-tetramethylbenzene, (1 M) in toluene, 50 C, durene) 24 h. 2 Conversions using theoretical and response yields were gas chromatographycalculated based (GC) factors onmethod internal [32]. standard Selectivity (1,2,4,5-tetramethylbenzene,= yield/conversion 100%. 3 durene)Turnover using frequency theoretical (TOF) was response measured gas after 30 min. on internal standard (1,2,4,5-tetramethylbenzene, durene) using theoretical response gas chromatographynd = not determined. (GC) factors method [32].× Selectivity = yield/conversion × 100%. 3 Turnover chromatography (GC) factors method [32]. Selectivity = yield/conversion × 100%. 3 Turnover frequency (TOF) was measured after 30 minnd = not determined. frequency (TOF) was measured after 30 minnd = not determined. 2.6. Probing the Boomerang Existence 2.6. Probing the Boomerang Existence 2.6. ProbingTo understand the Boomerang the processesExistence ongoing inside the solid support during the course of metathesis, we To understand the processes ongoing inside the solid support during the course of metathesis, To understand the processes ongoing inside the solid support during the course of metathesis, performedwe performed the the following following experiment experiment (Figure (Figure 8).8). Using Using a ahybrid hybrid catalyst catalyst composed composed of 4 (5 of wt4 (5%) wt %) and we performed the following experiment (Figure 8). Using a hybrid catalyst composed of 4 (5 wt %) 10and equiv. 10 equiv. of 5ofimmobilized 5 immobilized in in MOF, MOF, thethe RCMRCM reaction reaction of of 1212 (1 (1mol mol % of % Ru, of Ru, toluene, toluene, 50 °C, 50 1 ◦h)C, 1 h) was and 10 equiv. of 5 immobilized in MOF, the RCM reaction of 12 (1 mol % of Ru, toluene, 50 °C, 1 h) wasconducted. conducted. This This RCM RCM reaction reaction was was repeated repeated twice twice (with (with 33 mLmL toluenetoluene wash between cycles), cycles), then the was conducted. This RCM reaction was repeated twice (with 3 mL toluene wash between cycles), thenMOF-adsorbed the MOF-adsorbed organometallic organometallic complexes complexes were washed were washed out from out the from support the support using using methanol, and then the MOF-adsorbed organometallic complexes were washed out from the support using methanol,the collected and solutionthe collected was solution concentrated was concentrated and analyzed and directlyanalyzed bydirectly HPLC. by TheHPLC. same The experiment same was methanol, and the collected solution was concentrated and analyzed directly by HPLC. The same experiment was repeated using an SBA-154 supported 4 containing 10 5equiv. of 5. The composition of experimentrepeated using was repeated an SBA-15 using supported an SBA-15 supportedcontaining 4 containing 10 equiv. of10 equiv.. The of composition 5. The composition of organometallics of organometallics washed out from SBA-15 was also analyzed by HPLC and the results are presented washedorganometallics out from washed SBA-15 out was from also SBA-15 analyzed was also by HPLCanalyzed and by the HPLC results and are the presented results are inpresented Figure9 . It seems in Figure 9. It seems that in the RCM reaction in MOF some ligand scrambling took place, as the inthat Figure in the 9. RCMIt seems reaction that in in the MOF RCM some reaction ligand in scramblingMOF some ligand took place, scrambling as the took material place, washed as the out from material washed out from the support consisted of ca. 1:1 mixture of 4 and 6 (so: 4 + 5 → 6, Figure materialthe support washed consisted out from of the ca. support 1:1 mixture consisted of of4 andca. 1:16 (so:mixture4 + of5 4 and6, Figure6 (so: 49 +b), 5 → while 6, Figure initially only 9b), while initially only complex 4 and styrene 5 were loaded on the support.→ HPLC analysis of the 9b), while initially only complex 4 and styrene 5 were loaded on the support. HPLC analysis of the organometalliccomplex 4 and material styrene washed5 were out loaded from the on theSBA-15 support. hybrid HPLC catalyst analysis divulged of 4 theand organometallic6 in proportion material organometallic material washed out from the SBA-15 hybrid catalyst divulged 4 and 6 in proportion washed5:95. This out result from shows the SBA-15that almost hybrid all 4 catalystinitially present divulged in the4 and support6 in proportion was converted 5:95. during This the result shows 5:95. This result shows that almost all 4 initially present in the support was converted during the coursethat almost of metathesis all 4 initially reaction present into in 6 the (Figure support 9c), was thus converted strongly suggesting during the the course existence of metathesis of the reaction course of metathesis reaction into 6 (Figure 9c), thus strongly suggesting the existence of the boomeranginto 6 (Figure process.9c), thus strongly suggesting the existence of the boomerang process. boomerang process. We were, of course, aware of the possibility that 6 may be prepared during the impregnation of the support with a solution of 4 and 10 equiv. of 5 in DCM, before the RCM reaction shown in Figure8 was made, thus forming a false positive. A clariﬁcation experiment was therefore conducted consisting of washing out the organometallic complexes from the support with methanol 30 min after the impregnation. Analysis of the extracts showed no formation of 6 in both cases (for MOF and for SBA-15). In the second blind test, the material consisting of 4 and 10 equiv. of 5 immobilized on the support was heated in toluene at 50 ◦C for 3 h (so, under the same conditions as the RCM reaction, but in the absence of diene 12). After washing out organometallic complexes from the support, again, 6 was not observed in the extract (so: 4 + 5 9 6; see Supplementary Materials for details). Finally,

Figure 8. Ligand scrambling during the course of olefin metathesis: (1) RCM reactions carried out Figure 8. Ligand scrambling during the course of olefin metathesis: (1) RCM reactions carried out with hybrid catalyst composed of 4 and 10 equiv. of 5 on MOF. (2) Ru complexes are washed out from with hybrid catalyst composed of 4 and 10 equiv. of 5 on MOF. (2) Ru complexes are washed out from MOF after RCM reactions are done. The same experiment was also done with (4 + 5)@SBA-15 system, MOF after RCM reactions are done. The same experiment was also done with (4 + 5)@SBA-15 system, see discussion in the text. see discussion in the text.

Catalysts 2019, 9, x FOR PEER REVIEW 12 of 18

4@SBA (100 ppm) 48 (98) 4.5 4 800 nd 6@SBA (100 ppm) 44 (98) 4.3 4 400 nd 4@MOF (50 ppm) 57 (>99) 3.8 11 400 207 6@MOF (50 ppm) 46 (>99) 3.2 9 200 33 4@SBA (50 ppm) 50 (>99) 3.2 10 000 242 4 6@SBA (50 ppm) 51 (>99) 3.2 10 500 211

4@SBA (100 ppm) 100 (>99) 3.9 10 000 nd 6@SBA (100 ppm) 100 (>99) 4.0 10 000 nd 4@MOF (250 ppm) 70 (96) 11.8 2 800 87 6@MOF (250 ppm) 68 (95) 10.1 2 700 40 5 4@SBA (250 ppm) 38 (4) 6.1 750 5 6@SBA (250 ppm) 34 (3) 5.3 670 6 1 Conditions: substrate (1 M) in toluene, 50 C, 24 h. 2 Conversions and yields were calculated based on internal standard (1,2,4,5-tetramethylbenzene, durene) using theoretical response gas chromatography (GC) factors method [32]. Selectivity = yield/conversion × 100%. 3 Turnover frequency (TOF) was measured after 30 minnd = not determined.

2.6. Probing the Boomerang Existence To understand the processes ongoing inside the solid support during the course of metathesis, we performed the following experiment (Figure 8). Using a hybrid catalyst composed of 4 (5 wt %) and 10 equiv. of 5 immobilized in MOF, the RCM reaction of 12 (1 mol % of Ru, toluene, 50 °C, 1 h) was conducted. This RCM reaction was repeated twice (with 3 mL toluene wash between cycles), then the MOF-adsorbed organometallic complexes were washed out from the support using methanol, and the collected solution was concentrated and analyzed directly by HPLC. The same experiment was repeated using an SBA-15 supported 4 containing 10 equiv. of 5. The composition of Catalysts 2020, 10, 438 13 of 18 organometallics washed out from SBA-15 was also analyzed by HPLC and the results are presented in Figure 9. It seems that in the RCM reaction in MOF some ligand scrambling took place, as the materialwe considered washed the out possibility from the thatsupport the exchangeconsisted betweenof ca. 1:14 mixtureand 5 might of 4 and occur 6 during(so: 4 + the5 → prolonged 6, Figure 9b),handling while ofinitially the methanol only complex solutions 4 and of washed-out styrene 5 were organometallic loaded on the complexes support. after HPLC the analysis RCM reaction of the organometallic(Figure8). To check material this possibility, washed out we from mixed the4 SBA-15and 10 hybrid equiv. ofcatalyst5 in methanol divulged and 4 and stirred 6 in the proportion resulting 5:95.solution This for result 3 h atshows room that temperature almost all followed 4 initially by evaporationpresent in the of thesupport solvent. was Once converted again, thisduring process the coursedid not of yield metathesis any amount reaction of complex into 66 . (Figure 9c), thus strongly suggesting the existence of the boomerang process. Catalysts 2019, 9, x FOR PEER REVIEW 13 of 18

We were, of course, aware of the possibility that 6 may be prepared during the impregnation of the support with a solution of 4 and 10 equiv. of 5 in DCM, before the RCM reaction shown in Figure 8 was made, thus forming a false positive. A clarification experiment was therefore conducted consisting of washing out the organometallic complexes from the support with methanol 30 min after the impregnation. Analysis of the extracts showed no formation of 6 in both cases (for MOF and for SBA-15). In the second blind test, the material consisting of 4 and 10 equiv. of 5 immobilized on the support was heated in toluene at 50 °C for 3 h (so, under the same conditions as the RCM reaction, but in the absence of diene 12). After washing out organometallic complexes from the support, again, 6 was not observed in the extract (so: 4 + 5 ↛ 6; see SI for details). Finally, we considered the possibility that the exchange between 4 and 5 might occur during the prolonged handling of the methanol solutions of washed-out organometallic complexes after the RCM reaction (Figure 8). To check this possibility, we mixed 4 and 10 equiv. of 5 in methanol and stirred the resulting solution for 3 h at room temperature followed by evaporation of the solvent. Once again, this process did not yield any amountFigureFigure of complex8. LigandLigand 6scrambling scrambling. during during the the course course of of olefin oleﬁn metathesis: (1) (1) RCM RCM reactions reactions carried carried out out withwithAlthough hybrid hybrid we catalyst catalyst have composed composed no direct of definite 44 andand 10 10 proofequiv. equiv. offor of 55 theonon MOF. MOF.boomerang (2) (2) Ru Ru complexes complexes inside pores are are washed washed of the out outsupport, from from we thinkMOFMOF that after afterthe RCMabove RCM reactions reactions experiments are done. suggest The The same same the experiment experimentexistence ofwas was the also also ligand done done withexchange ( 4 + 55)@SBA-15 )@SBA-15ongoing system, system,exclusively duringseesee thediscussion discussion catalysis. in in the the text. text.

Figure 9. HPLC analysis of mixtures washed-out from supports after RCM reactions. (a) Reference Figure 9. HPLC analysis of mixtures washed-out from supports after RCM reactions. a) Reference mixture of 6 and 4 showing its separation on HPLC column; (b) Chromatogram of mixture washed mixture of 6 and 4 showing its separation on HPLC column; b) Chromatogram of mixture washed out from MOF-based catalyst used in RCM reactions; (c) Chromatogram of mixture washed out from out from MOF-based catalyst used in RCM reactions; c) Chromatogram of mixture washed out from SBA-15-based catalyst used in RCM reactions. SBA-15-based catalyst used in RCM reactions. Although we have no direct deﬁnite proof for the boomerang inside pores of the support, we think 3.that Materials the above and experiments Methods suggest the existence of the ligand exchange ongoing exclusively during the catalysis. 3.1. General Reactions requiring the use of a protective atmosphere were conducted using Schlenk technique in either Schlenk flasks or 4 mL vials, which were dried in 130 °C for at least 12 h prior to use. All metathesis reactions and sorption of the catalysts were carried out in vials equipped with magnetic stirrers. Purging vials with argon was performed after closing them with a screw cap with a septum and piercing it with a needle connected to a Schlenk line. Commercially available (HPLC grade) dichloromethane (DCM), tetrahydrofuran (THF), diethyl ether, toluene, and n-hexane were purified using solvent purification system MBRAUN SPS-800 and stored in ampules under argon over activated 4 Å molecular sieves for at least 12 h prior to use. Water content was measured with Karl Fisher apparatus (Titroline® 7500 KF trace) and did not exceeded 2

Catalysts 2020, 10, 438 14 of 18

3. Materials and Methods

3.1. General Reactions requiring the use of a protective atmosphere were conducted using Schlenk technique in either Schlenk flasks or 4 mL vials, which were dried at 130 ◦C for at least 12 h prior to use. All metathesis reactions and sorption of the catalysts were carried out in vials equipped with magnetic stirrers. Purging vials with argon was performed after closing them with a screw cap with a septum and piercing it with a needle connected to a Schlenk line. Commercially available (HPLC grade) dichloromethane (DCM), tetrahydrofuran (THF), diethyl ether, toluene, and n-hexane were purified using solvent purification system MBRAUN SPS-800 and stored in ampules under argon over activated 4 Å molecular sieves for at least 12 h prior to use. Water content was measured with Karl Fisher apparatus (Titroline® 7500 KF trace) and did not exceeded 2 ppm in each case. DMF (anhydrous), pyridine (anhydrous), n-heptane, and MeOH were purchased from Sigma Aldrich and used as received. n-Hexane, EtOAc, and DCM for column chromatography were purchased from Avantor Performance Materials Poland S.A. and distilled prior to use. Substrates 12 [33], 14 [34], 18 [35], and 20 [36] were prepared according to literature procedures. Substrate 16 was supplied by Sigma Aldrich. All substrates were freeze-pump-thaw degassed and stored under argon over activated 4 Å molecular sieves for at least 12 h prior to use. MOF (Al)MIL-101-NH2 was synthesized according to literature procedure [23], activated in 130 ◦C under the reduced pressure of an oil pump and stored in a Schlenk flask in an argon atmosphere. Ruthenium catalysts were prepared using a known literature procedure [15] or stated in Section 3.2, stored in argon atmosphere, and refrigerated at 4 ◦C. Unless otherwise noted, all common laboratory reagents (NaOH, KOH, Na2SO4, MgSO4, KI, NaCl, NH4Cl, HCl, H2SO4, Na2CO3, NaHCO3) were purchased from Avantor Performance Materials Poland S.A. and used as received. Aluminum oxide (Neutral, Brockmann grade I) was purchased from Sigma Aldrich and activated by heating for at least 3 days TM at 200 ◦C prior to use. SnatchCat metal scavenger was synthesized according to known literature procedure [37] and used as 4.5 mM solution in DCM. Silica gel 60 (230–400 mesh) was purchased from Merck and used as received. Sodium hydride (60% in mineral oil) was purchased from TCI Chemicals and used as received. Molecular sieve 13X and mesoporous SBA-15, <150 µm particle size, pore size 8 nm, hexagonal pore morphology were purchased from Sigma Aldrich and activated by heating for 24 h at 200 ◦C under the reduced pressure of an oil pump and stored in an argon atmosphere. GC analyses were performed by means of PerkinElmer Clarus 580 chromatograph with FID detector and GL Sciences InertCap 5MS/Sil Capillary Column (inner diameter 0.25 mm, length 30 m, df 0.50 µm). GC-MS analyses were performed by means of PerkinElmer Clarus 680 chromatograph with Mass Spectrometer Clarus SQ 8C detector and GL Sciences InertCap 5MS/Sil Capillary Column (inner diameter 0.25 mm, length 30 m, df 0.50 µm). NMR spectra were recorded on an Agilent 400-MR DD2 400 MHz spectrometer. NMR chemical shifts are reported in ppm with solvent residual peak as a reference (7.26 and 77.16 ppm for 1H and 13 1 13 C in CDCl3, respectively; 4.87 and 49.00 ppm for H and C in CD3OD, respectively). Deuterated solvents (chloroform, methanol) were purchased from Euroisotop, stored over molecular sieves and used without further purification. The following abbreviations were used in reporting NMR data: s (singlet), d (doublet), t (triplet), q (quartet), quint (quintet), sex (sextet), sep (septet), m (multiplet), br (broad). 1H NMR signals were given followed by multiplicity, coupling constants J in Hertz, and integration in parentheses. Elemental analyses (EA) were provided by the EA analytical laboratory at the Institute of Organic Chemistry, Polish Academy of Sciences (PAS). High-resolution mass spectra (HRMS) were provided by the Faculty of Chemistry at the University of Warsaw or the analytical laboratory at the Institute of Organic Chemistry, PAS. Catalysts 2020, 10, 438 15 of 18

UV–Vis spectra were collected with Thermo Fisher Scientific Evolution 300 UV–Vis spectrometer in 10.00 mm QS cuvettes with scan speed 600 nm/min, range 300–500 nm, bandwidth 1 nm, and data interval 1 nm. All powder X-ray diffraction (PXRD) patterns were recorded on a Bruker D8 Discover X-ray diffractometer (CuKα radiation, parallel beam formed by Goebel mirror) equipped with a VANTEC 1 position sensitive detector. All measurements were performed on standard aluminum holders. For measurement of N2 sorption isotherms, samples were thermally activated and degassed immediately prior to the N2 physisorption measurements for at least 12 h at 80 ◦C. The nitrogen sorption isotherms were determined at liquid nitrogen temperature (77 K) using Micrometrics ASAP 2020 or Quantachrome Autosorb-IQ-MP sorption analyzer. The specific surface areas were calculated according to the Brunauer–Emmett–Teller (BET) method using P/P0 values in the range 0.05–0.2.

3.2. Synthesis of Complexes 11 and 6 Synthesis of complex 11: NHC precursor 9 (466 mg, 0.771 mmol, 1.15 equiv.) was dried under vacuum at 60 ◦C for 1 h, suspended in toluene (2 mL), and treated with potassium tert-amylate in toluene (1.7 M, 200 µL, 0.704 mmol, 1.05 equiv). A turbid carbene adduct solution was formed over 10 min at ambient temperature. Then Grubbs 1st Generation Catalyst (551 mg, 0.67 mmol, 1 equiv.) was added and the mixture was stirred at 80 ◦C. The solution turned dark red over 20 min and then 8 (341 mg, 1.47 mmol, 2.2 equiv.) was added in toluene (2 mL) followed by the addition of CuCl (168 mg, 1.68 mmol, 2.5 equiv.). The solution turned dark green over 15 min with the formation of brown precipitate. The mixture was then cooled down to RT, filtered through a celite pad, evaporated, and the product was isolated using column chromatography (silica, 0–5% gradient of NEt3/EtOAc). The green fractions were evaporated yielding dark green oil, which was again purified by column chromatography (neutral alumina, 5–20% EtOAc/hexane). The pure fractions were combined and evaporated, yielding crude green crystalline product (205 mg, 0.23 mmol, 34%) which was immediately used in the next step without further purification. Synthesis of complex 6: At 78 C an excess of liquid MeCl was transferred into a glass − ◦ pressure-resistant ampule previously cooled down to 78 C. Then complex 11 (205 mg, 0.23 mmol, − ◦ 1 equiv.) was added and dissolved. The vessel was closed and put in a heated bath at 60 ◦C for 48 h. During the process, a precipitation was observed. After 48 h the ampule was cooled down to ambient temperature and excess MeCl was evaporated. The crude product was purified by column chromatography (acidic activated alumina, gradient 0–5% MeOH/DCM). The pure fractions were combined, evaporated, and dried under vacuum, yielding green hygroscopic product (149 mg, 0.15 mmol, 65%).

3.3. Catalysts and Ligand Immobilization In an oven-dried and purged with argon vial, closed with a screw cap containing a magnetic stirrer, MOF (Al)MIL-101-NH2 was weighted (100 mg). Then 1 M solution of HCl in anhydrous diethyl ether was added (2 mL). The suspension was sonicated and then stirred at RT for 0.5 h. After that, the vial was centrifuged, the solvent was removed, and the MOF was left to dry for several minutes under vacuum. Mass of the MOF increased to 120 mg because of HCl accumulation. After that, the stock solution of catalyst in DCM was added (0.59 mg of the catalyst, concentration 1 mg/mL). In the case of experiments with the addition of 5, the previous was followed by the addition of a stock solution of 5 (concentration 10 mg/mL, quantity dependent on the catalyst/5 ratio). The vial was sonicated and stirred for 1 h. Then it was centrifuged, the solvent was removed, and the catalytic material was left to dry under vacuum overnight. Catalyst@MOF was obtained as yellow powder (ca. 120 mg, 0.5 wt % of the catalyst). The same procedure was used for SBA-15 and 13X and supports omitting the HCl treatment. Prepared materials with catalyst can be stored refrigerated under argon atmosphere for at least a month without a signiﬁcant decrease in catalytic activity. Catalysts 2020, 10, 438 16 of 18

3.4. Catalysis Homogeneous reactions: In a 4 mL vial covered with a septum cap and purged with argon (3 ), × 0.5 M solution of substrate with internal standard (0.05 M durene) in toluene or DCE (1 mL) was placed followed by the addition of a stock solution of the catalyst (concentration 1 mg/mL, ca. 50 µL, the amount corresponding to 50 ppm loading of the catalyst). The reaction was stirred at 50 ◦C for 24 h. After that, 1 mL of 4.5 mM solution of SnatchCatTM in DCM was added, and the conversion was measured by GC. Heterogeneous reactions: to a 4 mL vial, equipped with a magnetic stirrer, catalytic material (the mass of the material was determined by catalyst to substrate ratio; catalyst loading on the support was 0.5 wt %)was weighted (on air). The vial was purged with Ar (3 ) which was realized by closing it × with a screw cap with a septum and piercing it with a needle connected to a Schlenk line. Then 1 mL of 1 M substrate solution in toluene (1 mmol) with internal standard (0.1 M durene) was added and mixed at 50 ◦C for 24 h. The catalytic material was ﬁltered oﬀ and the conversion determined by GC analysis. TOF was calculated after 30 min by taking a sample from the reaction and SnachCatTM was added to stop the reaction.

4. Conclusions Two ammonium-tagged homogeneous Ru-benzylidene catalysts: the commercially available FixCat™ (4) and new double-tagged 6 were immobilized on solid supports such as 13X, metal organic framework (MOF), and SBA-15. Such obtained heterogeneous systems were tested in a model ring-closing metathesis (RCM) reaction of diene 12 (DEDAM). The initial results showed that the 13X-based catalyst is the least productive in oleﬁn metathesis. Two remaining hybrid materials, based on MOF and SBA-15, were doped with various amounts of an ammonium-tagged styrene derivative 5—a precursor of a benzylidene ligand—in order to enhance pre-catalyst regeneration via the so-called release-return “boomerang” mechanism. The ligand scrambling experiments suggested, indeed, that during the RCM reaction the boomerang eﬀect can exist inside a solid support. At the same time, it was observed that non-doped catalysts give better results in terms of resulting turnover number (TON) values than systems loaded with additional amounts of ligand precursor 5. The most productive were the hybrid catalysts composed of 4@MOF, 4@SBA-15, and 6@SBA-15. Using these heterogeneous catalysts, a small set of model metathesis substrates were transformed reaching TON values up to 27,000.

Supplementary Materials: The following are available online at http://www.mdpi.com/2073-4344/10/4/438/s1. Author Contributions: Investigation, MOF preparation, visualization, supervision, A.C.; investigation, synthesis of compounds 5 and 6, model experiments with MOF, W.N.; investigation, model reactions with SBA-15 and 13X, M.P.; investigation, optimization, boomerang studies, visualization, P.K.; discussion and review, M.J.C.; supervision, writing—original draft preparation, review and editing, A.K. and K.G. All authors have read and agreed to the published version of the manuscript. Funding: A.C., W.N., M.P., P.K., A.K., and K.G. are grateful to the “Catalysis for the Twenty-First Century Chemical Industry” project carried out within the TEAM-TECH programme of the Foundation for Polish Science co-financed by the European Union from the European Regional Development under the Operational Programme Smart Growth. M.J.C. thanks the Polish Ministry of Science and Higher Education for IDEAS PLUS grant no. IdP 2012/0002/62. The study was carried out at the Biological and Chemical Research Centre, University of Warsaw, established within the project co-financed by European Union from the European Regional Development Fund under the Operational Programme Innovative Economy, 2007–2013. Acknowledgments: We are very grateful to the Referees for their fair and helpful comments, particularly for the suggestion of additional blind experiments regarding experiments shown in Figure8. Conflicts of Interest: The authors declare no conflict of interest. K.G. is an advisory board member of the Apeiron Synthesis company, the producer of catalyst 4. Catalysts 2020, 10, 438 17 of 18

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